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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



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…

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



Fatal motor vehicle collisions while Gamma hydroxybutyrate (GHB)-intoxicated  

Microsoft Academic Search

Data from six fatal gamma hydroxybutyrate (GHB)-associated motor vehicle collisions (MVC's) is presented, including three pedestrians and three drivers; data was collected as part of a larger case series of 226 GHB-associated fatalities. Postmortem blood GHB levels in the six MVC deaths ranged from 53-240 mg\\/L. Blood GHB levels (± confidence intervals (CI)) in four MVC deaths with GHB confirmed

Coon Rapids



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.

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




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.

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



Discriminative stimulus effects of gamma-hydroxybutyrate (GHB) in rats discriminating GHB from baclofen and diazepam.  


Gamma-hydroxybutyrate (GHB) is a drug of abuse with actions at GHB and GABA receptors. This study tried to increase the selectivity of the discriminative stimulus effects of GHB by training animals to discriminate GHB from compounds that share pharmacological mechanisms with GHB. In comparison with a previous GHB versus saline discrimination (group 1), rats were trained to discriminate GHB (200 mg/kg) either from saline and the GABA(B) agonist baclofen (3.2 mg/kg) (group 2) or from saline, baclofen, and the positive GABA(A) modulator diazepam (1 mg/kg) (group 3). In all groups, GHB produced more than 80% GHB-appropriate responding. Baclofen produced 84% GHB-appropriate responding in group 1 but less than 30% in groups 2 and 3. Diazepam produced 68% GHB-appropriate responding in group 1, 30% in group 2, and only 5% in group 3. The GABA(B) receptor antagonists CGP35348 [3-[aminopropyl(diethoxymethyl)phosphinic acid] and CGP52432 [3-[[[((3,4-dichlorophenyl)methyl]amino]propyl]diethoxymethyl)phosphinic acid] attenuated the discriminative stimulus effects of GHB; CGP35348 did so with similar potency in all groups, but CGP52432 was significantly less potent in groups 2 and 3 than in group 1. In all groups, the GHB antagonist NCS-382 [(2E)-(5-hydroxy-5,7,8,9-tetrahydro-6H-benzo[a][7]annulen-6-ylidene ethanoic acid] partially attenuated the discriminative stimulus effects of GHB. The selective GHB receptor ligand UMB86 (4-hydroxy-4-napthylbutanoic acid sodium) tended to attenuate the discriminative stimulus effects of GHB more in group 3 than in the other groups. The finding that animals can discriminate GHB from baclofen is further evidence that the effects of GHB and baclofen are not identical. Effects that GHB does not share with baclofen may involve GHB receptors or differential interactions with GABA(B) receptors. PMID:15774716

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



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.  


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



The presence of gamma-hydroxybutyric acid (GHB) and gamma-butyrolactone (GBL) in alcoholic and non-alcoholic beverages.  


Gamma-hydroxybutyric acid (GHB) and its precursor gamma-butyrolactone (GBL) are regularly implicated in instances of surreptitious drug administration, particularly in beverages (so-called "spiked drinks"). In order to assist in the interpretation of cases where analysis of the actual beverage is required, over 50 beverages purchased in the UK were analysed for the presence of GHB and GBL. It was found that naturally occurring GHB and GBL were detected in those beverages involving the fermentation of white and particularly red grapes. No GHB or GBL was detected in other drinks such as beer, juice, spirits or liqueurs. GHB/GBL was detected in red wine vermouth (8.2 mg/L), sherry (9.7 mg/L), port (GBL), red wine (4.1-21.4 mg/L) and white wine (<3-9.6 mg/L). The presence of GHB/GBL did not appear to be influenced by the alcohol content or the pH of the beverage. In addition, the concentration in wines did not appear to be related to the geographical origin of the grape type. This is believed to be the first published data concerning the endogenous presence of GHB and GBL in the beverages described. PMID:15939164

Elliott, Simon; Burgess, Victoria



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

PubMed Central

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

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



Effects of gamma-hydroxybutyrate (GHB) on schedule-controlled responding in rats: role of GHB and GABAB receptors.  


Gamma-hydroxybutyrate (GHB), a metabolite of gamma-aminobutyric acid (GABA), is an increasingly popular drug of abuse and was recently approved for the treatment of narcolepsy (Xyrem). GHB and GABA receptors have been implicated in mediating effects of GHB; however, the relative importance of each of these receptors is unclear. This study evaluated the effects of selective antagonists in combination with GHB and related compounds on schedule-controlled responding. Eight male Sprague-Dawley rats responded under a fixed-ratio schedule of food presentation. Cumulative dose-effect curves were generated and ED50 values calculated to evaluate the relative potency at decreasing responding. The rank-order potency was as follows: diazepam = baclofen > gamma-butyrolactone (GBL) > 1,4-butanediol (1,4-BDL) = GHB. All compounds decreased responding 20 min after administration. The duration of action of diazepam, GHB, and GBL was shorter than that of 1,4-BDL and baclofen. p-3-Aminopropyl-p-diethoxymethyl phosphinic acid (CGP 35348) antagonized the rate-decreasing effects of baclofen and not GHB; flumazenil antagonized the effects of diazepam and not GHB. The GHB receptor antagonist (2E)-(5-hydroxy-5,7,8,9-tetrahydro-6H-benzo[a][7]annulen-6-ylidene ethanoic acid (NCS-382) did not attenuate the rate-decreasing effects of GHB, baclofen, or diazepam; larger doses of NCS-382 further decreased rate of responding when given in combination with each of these compounds. These studies show that GBL, 1,4-BDL, and GHB differ significantly in potency and duration of action. The ability of CGP 35348 to antagonize the rate-decreasing effects of baclofen may be limited by the involvement of multiple GABAB receptor subtypes and the lack of antagonism of GHB by NCS-382 may be due to its own GHB-like effects. PMID:14569056

Carter, Lawrence P; Wu, Huifang; Chen, Weibin; Cruz, Christopher M; Lamb, R J; Koek, Wouter; Coop, Andy; France, Charles P



Intravenous self-administration of gamma-hydroxybutyrate (GHB) in baboons  

PubMed Central

Background Abuse of gamma-hydroxybutyrate (GHB) poses a public health concern. In previous studies, intravenous (IV) self-administration of GHB doses up to 10 mg/kg was not maintained in non-human primates under limited-access conditions, which was inconsistent with the usual good correspondence between drugs abused by humans and those self-injected by laboratory animals. Methods Self-administration of GHB was studied in 10 baboons using procedures standard for our laboratory to assess drug abuse liability. Each self-injection depended on completion of 120 or 160 lever responses. Sessions ran continuously; a 3-h timeout limited the number of injections per 24 h to 8. Self-injection was established at 6–8 injections/day with cocaine (0.32 mg/kg/injection) prior to substitution of each GHB dose (3.2–178 mg/kg/injection) or vehicle for 15 days. Food pellets were available 24 h/day. Results GHB maintained significantly greater numbers of injections when compared to vehicle in 6 of the 9 baboons that completed GHB evaluations that included 32 mg/kg/injection or higher. The baboons that self-administered GHB at high rates were ones for which GHB was the first drug each had tested under the 24-hr/day cocaine baseline procedure. Self-injection of the highest doses of GHB decreased food-maintained responding. Conclusions High-dose GHB can function as a reinforcer in non-human primates under 24-h access, but self-administration history may be important. The findings are consistent with the demonstrated abuse liability of GHB in humans, and remove GHB as an exception to the typical good correspondence between those drugs abused by humans and those self-administered by nonhuman primates.

Goodwin, Amy K.; Kaminski, Barbara J.; Griffiths, Roland R.; Ator, Nancy A.; Weerts, Elise M.



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



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


According to available information, GHB and its precursors--gamma-butyrolactone (GBL) and 1,4-butanediol (1,4BD)--are used especially in a nightlife scene characterized by the search for amplified sensations through the combination of electronic music, marathon dancing, and substance abuse. Evidence indicates that GHB/GHL is used particularly in some subpopulations and in places, such as in gay nightclubs. Commonly known as Gorliquid ecstasy, it was misused in the 1980s for its bodybuilding effects and in the 1990s as a recreational drug at music venues. In the same period, media coverage of the use of GHB in sexual assault (often referred to as date rape) brought the drug into the spotlight. GHB/GHL addiction is a recognized clinical entity evidenced by severe withdrawal symptoms when the drug is abruptly discontinued after regular or chronic use. There is evidence that negative health and social consequences may occur in recreational and chronic users. Nonfatal overdoses and deaths related to GHB have been reported. These undesirable effects and especially the deaths appear to have prompted campaigns to limit the use of GHB. Clinicians must also be aware of GBL, which is being sold and used as a substitute for GHB. PMID:19762202

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



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


Anecdotal evidence links the initial phase of fasting or a low-carbohydrate diet with feelings of well-being and mild euphoria. These feelings have often been attributed to ketosis, the production of ketone bodies which can replace glucose as an energy source for the brain. One of these ketone bodies, beta-hydroxybutyrate (BHB), is an isomer of the notorious drug of abuse, GHB (gamma-hydroxybutyrate). GHB is also of interest in relation to its potential as a treatment for alcohol and opiate dependence and narcolepsy-associated cataplexy. Here I hypothesize that, the mild euphoria often noted with fasting or low-carbohydrate diets may be due to shared actions of BHB and GHB on the brain. Specifically, I propose that BHB, like GHB, induces mild euphoria by being a weak partial agonist for GABA(B) receptors. I outline several approaches that would test the hypothesis, including receptor binding studies in cultured cells, perception studies in trained rodents, and psychometric testing and functional magnetic resonance imaging in humans. These and other studies investigating whether BHB and GHB share common effects on brain chemistry and mood are timely and warranted, especially when considering their structural similarities and the popularity of ketogenic diets and GHB as a drug of abuse. PMID:17011713

Brown, Andrew J



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



Evaluation for the withdrawal syndrome from gamma-hydroxybutyric acid (GHB), gamma-butyrolactone (GBL), and 1,4-butanediol (1,4-BD) in different rat lines.  


A severe and life-threatening gamma-hydroxybutyric acid (GHB) withdrawal syndrome, clinically similar to the alcohol withdrawal syndrome, is increasingly being reported in GHB addicts. We investigated for the occurrence of withdrawal in Wistar and Sprague-Dawley rats, and in the selectively bred lines of GHB-sensitive (GHB-S) and Sardinian alcohol-preferring (sP) rats, following chronic administration of GHB, gamma-butyrolactone (GBL), and/or 1,4-butanediol (1,4-BD). Using validated rodent alcohol withdrawal scoring scales, little to no spontaneous or pharmacologically precipitated withdrawal effects were observed in Wistar, Sprague-Dawley, or GHB-S rats. Conversely, sP rats displayed both spontaneous and precipitated audiogenic seizures following abrupt cessation of chronic GHB or 1,4-BD administration and following pharmacological challenge with the GABA(B) receptor-selective antagonist, SCH 50911, respectively. PMID:17105952

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



Determination of gamma-hydroxybutyric acid (GHB) in plasma and urine by headspace solid-phase microextraction and gas chromatography/positive ion chemical ionization mass spectrometry.  


A new method for the qualitative and quantitative analysis of gamma-hydroxybutyric acid (GHB) in plasma and urine samples is described. It involves the conversion of GHB to gamma-butyrolactone (GBL), its subsequent headspace solid-phase microextraction (SPME), and detection by gas chromatography/positive ion chemical ionization mass spectrometry (GC/PICI-MS), using D(6)-GBL as internal standard. The assay is linear over a plasma GHB range of 1-100 microg/mL (n = 5, r = 0.999) and a urine GHB range of 5-150 microg/mL (n = 5, r = 0. 998). Relative intra- and inter-assay standard deviations, determined for plasma and urine samples at 5 and 50 microg/mL, are all below 5%. The method is simple, specific and reasonably fast. It may be applied for clinical and forensic toxicology as well as for purposes of therapeutic drug monitoring. PMID:11114057

Frison, G; Tedeschi, L; Maietti, S; Ferrara, S D



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



Analysis of biofluids for gamma-hydroxybutyrate (GHB) and gamma-butyrolactone (GBL) by headspace GC-FID and GC-MS.  


The past few years have seen a dramatic increase in the abuse of gamma-hydroxybutyrate (GHB) and gamma-butyrolactone (GBL) in the United States. The abuse stems primarily from their euphoric and sedative properties, but these substances are also misused by bodybuilders as steroid alternatives. Recently there has been an alarming increase in the use of GHB and GBL in crimes of drug-facilitated sexual assault. A rapid and sensitive procedure was developed for the analysis of biofluids containing GHB and GBL. Two separate aliquots of a biological specimen were spiked with an alpha-methylene-gamma-butyrolactone internal standard solution. One of the aliquots was treated with concentrated sulfuric acid for cyclization of GHB to GBL and the other remained untreated. Both aliquots were extracted with methylene chloride and concentrated. Extracts were screened using automated headspace gas chromatography-flame-ionization detection (GC-FID). Qualitative findings were quantitated and confirmed in a manner similar to the GC-FID procedure with some modifications. A calibrated solution of GHB-d6 (or GBL-d6, when warranted) was added to the aliquots at a concentration approximating the level determined by the GC-FID screen. The extraction was as described with conversion of GHB to GBL, but analysis was by full-scan gas chromatography-mass spectrometry (El). Quantitation was performed by comparison of the area of the molecular ion of the parent drug (m/z 86) to that of the calibrated deuterated analogue (m/z 92). This analytical procedure allows for the rapid detection of GHB and GBL in biofluids. Its sensitivity has proven useful for the toxicological investigation of cases of drug-facilitated sexual assault. PMID:10999347

LeBeau, M A; Montgomery, M A; Miller, M L; Burmeister, S G



Gamma-hydroxybutyric acid (GHB) and gamma-aminobutyric acidB receptor (GABABR) binding sites are distinctive from one another: molecular evidence.  


gamma-Hydroxybutyric Acid (GHB) is thought to be a weak partial agonist at the gamma-aminobutyric acid(B) Receptor (GABA(B)R), but the precise relationship of the GHB receptor (GHBR) to the GABA(B)R remains unclear. In order to test the hypothesis that the GHBR is not identical to the GABA(B)R, we conducted two groups of experiments. First, GABA(B)R subtype 1 (R1) and/or subtype 2 (R2) were over expressed in HEK 293 cells and membrane binding studies on the transfected cells done using [(3)H]GHB and [(3)H] (2E)-(5-hydroxy-5,7,8,9-tetrahydro-6H-benzo[a][7]annulen-6-ylidene) ethanoic acid ([(3)H]NCS-382). The latter is a specific antagonist at the GHB binding site. Second, [(3)H]GHB and [(3)H]NCS-382 autoradiographic binding studies were done on the brains of mice in which the gene for GABA(B)R1a was deleted. Such mice do not have a functioning GABA(B)R. There was no detectable specific [(3)H]GHB or [(3)H]NCS-382 binding in HEK 293 cells transfected with GABA(B)R1, R2, or R1/R2. Binding to [(3)H]CGP54626A, a high affinity GABA(B)R antagonist, was absent in GABA(B)R1a(-/-) mice. There was no difference in [(3)H]NCS-382 binding observed in the brains of GABA(B)R1a(-/-), GABA(B)R1a(+/-) or GABA(B)R1a(+/+) mice. Specific [(3)H]GHB binding was observed in the brain of GABA(B)R1a(-/-) mice but was significantly lower than in wild type mice. These data support the hypothesis that the GHB binding site is separate and distinct from the GABA(B)R. PMID:15567424

Wu, Ying; Ali, Saima; Ahmadian, Gholamreza; Liu, Chun Che; Wang, Yu Tian; Gibson, K Michael; Calver, Andrew R; Francis, Joseph; Pangalos, Menelas N; Carter Snead, O



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



Gamma hydroxybutyrate is not a GABA agonist.  


Gamma hydroxybutyrate (GHB) is primarily known and used as a relatively specific inhibitor of central DA release. However, it is also widely assumed to be an agonist or prodrug of gamma-aminobutyric acid (GABA) and its central activity has been attributed to an action exerted at GABA receptors. Nevertheless, there is compelling evidence that: (1) GHB formation may occur independently of GABA; (2) GHB is behaviorally, biochemically and physiologically distinct from GABA in many ways, and does not consistently effect GABAA or GABAB agonist induced responses; (3) GHB has little effect on either GABAA or GABAB receptors at less than millimolar concentrations. Consequently, GHB does not appear to be either a GABA prodrug or a GABA agonist. However, the GHB metabolite gamma butyrolactone (GBL) may possess some limited GABA agonist activity. PMID:8931105

Feigenbaum, J J; Howard, S G



The role of GABAB receptors in the discriminative stimulus effects of gamma-hydroxybutyrate in rats: time course and antagonism studies.  


gamma-Hydroxybutyrate (GHB) is a neurotransmitter in brain and an emerging drug of abuse, although its mechanism of action is poorly understood. This study characterized the role of GABA(A), GABA(B), and other receptors in the discriminative stimulus effects of GHB. Eight rats reliably discriminated 200 mg/kg GHB from saline after a median of 35 (range: 23-41) training sessions. GHB, a metabolic precursor 1,4-butanediol (1,4-BDL), and the GABA(B) agonist (+/-)baclofen all occasioned greater than 83% responding on the GHB lever. The onset of action was similar for GHB and 1,4-BDL; however, 1,4-BDL exhibited a longer duration of action than GHB. The GHB precursor gamma-butyrolactone, the benzodiazepine diazepam, the neuroactive steroid pregnanolone, the opioid agonist morphine, and the N-methyl-d-aspartate antagonist ketamine elicited substantial GHB-appropriate responding, although none occasioned greater than 66% drug-lever responding. The barbiturate pentobarbital and the GABA(A) receptor agonist muscimol did not occasion greater than 17% drug-lever responding at any dose tested. The benzodiazepine antagonist flumazenil attenuated GHB-lever responding occasioned by diazepam, but not GHB. The GABA(B) receptor antagonist CGP 35348 antagonized GHB-lever responding occasioned by baclofen or GHB. Small doses of the purported GHB receptor antagonist (2E)-(5-hydroxy-5,7,8,9-tetrahydro-6H-benzo[a][7]annulen-6-ylidene ethanoic acid (NCS-382) attenuated partially the effects of GHB, whereas larger doses of NCS-382 alone occasioned partial GHB-lever responding. These results implicate GABA(B) mechanisms in the discriminative stimulus effects of GHB and further suggest that the effects of 1,4-BDL under these conditions result from its conversion to GHB. That NCS-382 shares effects with GHB could explain the lack of antagonism reported for NCS-382 in some studies. PMID:12606639

Carter, Lawrence P; Flores, Lauren R; Wu, Huifang; Chen, Weibin; Unzeitig, Andrew W; Coop, Andy; France, Charles P



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  

Microsoft Academic Search

?-Hydroxybutyric acid (GHB) is an endogenous short-chain fatty acid popular as a recreational drug due to sedative and euphoric\\u000a effects, but also often implicated in drug-facilitated sexual assaults owing to disinhibition and amnesic properties. Whilst\\u000a discrimination between endogenous and exogenous GHB as required in intoxication cases may be achieved by the determination\\u000a of the carbon isotope content, such information has

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



Discriminative stimulus effects of gamma-hydroxybutyrate: role of training dose.  


gamma-Hydroxybutyrate (GHB) is a drug of abuse with actions at GHB and GABA receptors. This study examined whether the relative importance of GABA(A), GABA(B), and GHB receptors in the discriminative stimulus effects of GHB depends on the training dose. In comparison with a previous 100 mg/kg GHB-saline discrimination, pigeons were trained to discriminate either 178 or 56 mg/kg GHB from saline. Increasing the training dose shifted the GHB gradient to the right, and decreasing it shifted the gradient to the left. Similar shifts occurred with the GHB precursor gamma-butyrolactone, which substituted for GHB, and with the GABA(B) agonists baclofen and 3-aminopropyl(methyl)phosphinic acid hydrochloride (SKF97541) and the benzodiazepine diazepam, each of which produced at most 54 to 68% GHB-appropriate responding. The benzodiazepine antagonist flumazenil, the benzodiazepine inverse agonist ethyl 8-azido-6-dihydro-5-methyl-6-oxo-4H-imidazo[1,5-alpha]-[1,4]-benzodiazepine-3-carboxylate (Ro 15-4513), and the GHB receptor antagonist (2E)-5-hydroxy-5,7,8,9-tetrahydro-6H-benzo[a][7]annulen-6-ylidene ethanoic acid (NCS-382) produced a maximum of 66 to 97% GHB-appropriate responding in animals discriminating 56 or 100 mg/kg GHB and a maximum of 1 to 49% in animals discriminating 178 mg/kg. NCS-382 did not attenuate the effects of GHB. The GABA(B) antagonist 3-aminopropyl(diethoxymethyl)phosphinic acid (CGP35348) blocked GHB at all training doses. The results suggest that increasing the training dose of GHB increases the pharmacological selectivity of its discriminative stimulus effects. At a high training dose, diazepam-insensitive GABA(A) receptors, for which flumazenil and Ro 15-4513 have affinity, may no longer be involved. Diazepam-sensitive GABA(A) receptors and GABA(B) receptors appear to play a similar role at all training doses. There was no evidence for GHB receptor involvement. PMID:16330491

Koek, Wouter; Chen, Weibin; Mercer, Susan L; Coop, Andrew; France, Charles P



Quantitative autoradiographic analysis of the new radioligand [(3)H](2E)-(5-hydroxy-5,7,8,9-tetrahydro-6H-benzo[a][7]annulen-6-ylidene) ethanoic acid ([(3)H]NCS-382) at gamma-hydroxybutyric acid (GHB) binding sites in rat brain.  


(2E)-(5-Hydroxy-5,7,8,9-tetrahydro-6H-benzo[a][7]annulen-6-ylidene) ethanoic acid (NCS-382) is an antagonist for gamma-hydroxybutyric acid (GHB) at GHB receptor sites. Advantages of using [(3)H]NCS-382 over [(3)H]GHB in radioligand binding studies are that unlike GHB, NCS-382 does not appear to bind to, activate, or interfere with the functioning of GABA(B) or GABA(A) receptors, either directly or indirectly. Herein we establish a protocol for use of [(3)H]NCS-382 by quantitative autoradiography. GHB was used to define non-specific binding, since it displaced [(3)H]NCS-382 to an extent equivalent to NCS-382. Among many areas of brain examined, two regions in which high specific binding of [(3)H]NCS-382 occurred were the hippocampus and cerebral cortex. Areas such as the striatum and nucleus accumbens exhibited intermediate levels of specific binding. No or very low binding was observed in other areas such as the cerebellum and dorsal raphe nucleus. The distribution of GHB binding sites as defined by [(3)H]NCS-382 suggests that GHB may play a role in neuromodulation or neurotransmission in frontal brain areas. PMID:12850570

Gould, Georgianna G; Mehta, Ashok K; Frazer, Alan; Ticku, Maharaj K



GC/MS profiling of gamma-hydroxybutyrate and precursors in various animal tissues using automatic solid-phase extraction. Preliminary investigations of its potential interest in postmortem interval determination.  


To quantify gamma-hydroxybutyrate (GHB) and its physiological metabolites, gamma-aminobutyric acid (GABA), 1,4-butanediol (1,4-BD), and gamma-butyrolactone (GBL) in various animal tissues (kidney, muscle, heart, liver, blood, brain cortex, thalamus, hypothalamus, hippocampus, or pons), an original gas chromatographic/mass spectrometric method with a automated solid-phase extraction by Oasis MCX cartridges on a Gilson Aspec Xli was developed. Using such apparatus allowed the limit of detection (LOD) of target compounds to be significantly lowered (LOD: 0.027, 0.025, and 5.7 microg/mL for GHB, 1,4-BD, and GABA, respectively, in 200 microL or microg of sample). After validation of each analytical step, the satisfactory performances of the apparatus in conjunction with the rapidity and ease of the extraction step make it suitable for simultaneous assay of GHB, 1,4-BD, GBL, and GABA. The method was used to test the correlation between GHB levels in tissues obtained at different times after death of male Sprague-Dawley rats and the postmortem interval. Preliminary results show a linear increase of GHB levels in relation to time of death in thoracic blood and central nervous system of animals kept at 15 and 20 degrees C. PMID:15732918

Richard, Damien; Ling, Bing; Authier, Nicolas; Faict, Thierry W; Eschalier, Alain; Coudoré, François



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


Gamma-hydroxybutyrate (GHB) is a naturally occurring GABA-like drug used illicitly by bodybuilders. Although there are reports of several cases of GHB abuse, with a variety of nervous system complications, we present the first case associated with a Wernicke-Korsakoff syndrome. PMID:8614515

Friedman, J; Westlake, R; Furman, M



A tertiary alcohol analog of gamma-hydroxybutyric acid as a specific gamma-hydroxybutyric acid receptor ligand.  


gamma-Hydroxybutyric acid (GHB) shows great promise as a treatment for sleeping disorders but is also increasingly abused. The exact mechanism of action of GHB is yet to be delineated, but it is known to interact with specific GHB binding sites or receptors, to act as a weak agonist at GABA(B) receptors, and that GHB undergoes metabolism to GABA. In drug discrimination studies, GABA(B) agonists, and to a lesser extent GABA(A)-positive modulators, substitute for GHB. To delineate the relative contributions of each receptor system to the profile of GHB, tertiary alcohol analogs of GHB and its homolog, 5-hydroxypentanoic acid (UMB58), were prepared (UMB68 and UMB75, respectively), which cannot be metabolized to GABA-active compounds. Binding studies against [(3)H]NCS-382 [(2E)-(5-hydroxy-5,7,8,9-tetrahydro-6H-benzo[a][7]annulen-6-ylidene) ethanoic acid] showed that the tertiary alcohol analog of GHB (UMB68) has similar affinity to GHB, with the longer chain analogs possessing lower affinity. Against [(3)H]GABA, UMB68 showed no affinity (IC(50) >100 microM) at GABA(A) or GABA(B) receptors. In vivo studies showed that, at behaviorally active doses, rats trained to discriminate GHB did not recognize the novel ligands as GHB. Thus, UMB68 is a selective GHB receptor ligand in binding assays, will not undergo metabolism to GABA-active compounds, and does not show the same effects as GHB in vivo. These data suggest that, although UMB68 binds to the GHB receptor, it does not have the observed GABA receptor-mediated effects of GHB in vivo and could provide a novel tool for studying the pharmacology of the GHB receptor in the absence of complicating GABAergic effects. PMID:12606613

Wu, Huifang; Zink, Nick; Carter, Lawrence P; Mehta, Ashok K; Hernandez, R Jason; Ticku, Maharaj K; Lamb, Richard; France, Charles P; Coop, Andrew



Tolerance to the hypnotic and electroencephalographic effect of gamma-hydroxybutyrate in the rat: pharmacokinetic and pharmacodynamic aspects.  


Tolerance to gamma-hydroxybutyrate (GHB) has been suggested in illicit users and has been described for the hypnotic effect in the rat. The aim of this study was to investigate whether tolerance is also observed for the EEG effect, and whether the EEG can give insight into the pharmacodynamic aspects of GHB tolerance. In three series of experiments, rats were pre-treated with either the GHB precursor gamma-butyrolactone (GBL) or saline intraperitoneally twice daily. In the first series, a reduction in sleeping time was observed in the GBL pre-treated rats compared with controls. In the second series, a fast infusion of GHB (300 mg kg(-1) over 5 min) was given after 10 days pre-treatment. The GHB plasma concentration-time curves showed a slightly faster decrease in GHB concentration in the GBL pre-treated rats, suggesting a small induction of the GHB metabolism (V(max) = 2882 +/- 457 microg min(-1) kg(-1) vs 2205 +/- 315 microg min(-1) kg(-1), P < 0.01). In contrast to controls, GBL pre-treated rats did not lose righting reflex. In the third series, a slow infusion of 480 mg kg(-1) h(-1) was given after 7 days pre-treatment, which allowed fitting a sigmoid E(max) model to the EEG amplitude versus GHB plasma concentration curve. This showed reduced end-organ sensitivity to GHB in the GBL pre-treated rats (EC50 (concentration required to obtain 50% depression of the baseline effect) = 653+/- 183 microg mL(-1) vs 323 +/- 68 microg mL(-1), P < 0.001). In conclusion, chronic pre-treatment with gamma-butyrolactone in the rat results in a reduced sleeping time and this tolerance is reflected by the EEG. This can mainly be explained by reduced end-organ sensitivity. PMID:12831503

Van Sassenbroeck, Diederik K; De Paepe, Peter; Belpaire, Frans M; Boon, Paul A; Buylaert, Walter A



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



Hazardous use of gamma hydroxybutyrate: driving under the influence.  


Focus group discussions elicited descriptive experiences of driving under the influence of gamma hydroxybutyrate (GHB), and uncovered motivations that led participants to decide whether to get behind the wheel after ingesting this illegal psychoactive substance. Of the 51 current and past users interviewed, average age 31.1 +/- 7.7 years, 40% were female. All were recruited from the San Francisco Bay Area, in 2004. Factors making users vulnerable to adverse complications of driving while under the influence of GHB are also examined. Study limitations were noted. Implications for various law enforcement agencies and health professionals are derived from the data. PMID:18752156

Barker, Judith C; Karsoho, Hadi



[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



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



Coma in a 20-month-old child from an ingestion of a toy containing 1,4-butanediol, a precursor of gamma-hydroxybutyrate.  


Ingestion of plastic toys is common in children and usually does not result in harm. We report a case of coma in a 20-month-old child after an ingestion of a toy containing 1,4-butanediol, an industrial solvent used to manufacture plastics. When ingested, 1,4-butanediol is metabolized to gamma-hydroxybutyrate, which can have significant systemic effects including death. Health care providers should suspect the possibility of a toxic component when a presumed nontoxic object causes unusual symptoms. PMID:19915428

Ortmann, Laura A; Jaeger, Matthew W; James, Laura P; Schexnayder, Steve M



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


Gamma hydroxybutyrate (GHB) is a psychoactive substance with complex neurophysiological activity and significant potential for abuse, addiction, and dangerous toxicity. In this study, a semistructured interview was administered to 17 subjects to investigate GHB use, including: manner of use; setting; positive and negative consequences; other drug history; and sexual practices. Respondents were overwhelmingly male, but otherwise had a broad demographic background. Settings varied from nightclubs to private use at home. There was significant variability in the drug obtained, which subjects found problematic because of the narrow therapeutic window and ease of accidental overdose. Common positive experiences included increased sexual desire, decreased sexual inhibitions, and decreased anxiety. Common negative consequences included oversedation, loss of consciousness, motor incoordination, and mental confusion. Nine subjects reported that they would use GHB again, some despite severe negative consequences. Although most subjects reported negative experiences, only three felt their use was problematic, and none sought treatment for GHB abuse or addiction. Subjects were highly drug-experienced, most commonly using MDMA, ketamine, cocaine, alcohol, and methamphetamine. Some reported that GHB could cause poor decision making in sexual situations. This effect has significant ramifications for issues such as date rape and control of sexually transmitted diseases, such as HIV. PMID:19004416

Lee, Steven J; Levounis, Petros



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



Specific gamma-hydroxybutyrate-binding sites but loss of pharmacological effects of gamma-hydroxybutyrate in GABA(B)(1)-deficient mice.  


gamma-Hydroxybutyrate (GHB), a metabolite of gamma-aminobutyric acid (GABA), is proposed to function as a neurotransmitter or neuromodulator. gamma-Hydroxybutyrate and its prodrug, gamma-butyrolactone (GBL), recently received increased public attention as they emerged as popular drugs of abuse. The actions of GHB/GBL are believed to be mediated by GABAB and/or specific GHB receptors, the latter corresponding to high-affinity [3H]GHB-binding sites coupled to G-proteins. To investigate the contribution of GABAB receptors to GHB actions we studied the effects of GHB in GABAB(1)-/- mice, which lack functional GABAB receptors. Autoradiography reveals a similar spatial distribution of [3H]GHB-binding sites in brains of GABAB(1)-/- and wild-type mice. The maximal number of binding sites and the KD values for the putative GHB antagonist [3H]6,7,8,9-tetrahydro-5-hydroxy-5H-benzocyclohept-6-ylidene acetic acid (NCS-382) appear unchanged in GABAB(1)-/- compared with wild-type mice, demonstrating that GHB- are distinct from GABAB-binding sites. In the presence of the GABAB receptor positive modulator 2,6-di-tert-butyl-4-(3-hydroxy-2,2-dimethyl-propyl)-phenol GHB induced functional GTPgamma[35S] responses in brain membrane preparations from wild-type but not GABAB(1)-/- mice. The GTPgamma[35S] responses in wild-type mice were blocked by the GABAB antagonist [3-[[1-(S)-(3,4dichlorophenyl)ethyl]amino]-2-(S)-hydroxy-propyl]-cyclohexylmethyl phosphinic acid hydrochloride (CGP54626) but not by NCS-382. Altogether, these findings suggest that the GHB-induced GTPgamma[35S] responses are mediated by GABAB receptors. Following GHB or GBL application, GABAB(1)-/- mice showed neither the hypolocomotion, hypothermia, increase in striatal dopamine synthesis nor electroencephalogram delta-wave induction seen in wild-type mice. It, therefore, appears that all studied GHB effects are GABAB receptor dependent. The molecular nature and the signalling properties of the specific [3H]GHB-binding sites remain elusive. PMID:14656321

Kaupmann, Klemens; Cryan, John F; Wellendorph, Petrine; Mombereau, Cedric; Sansig, Gilles; Klebs, Klaus; Schmutz, Markus; Froestl, Wolfgang; van der Putten, Herman; Mosbacher, Johannes; Bräuner-Osborne, Hans; Waldmeier, Peter; Bettler, Bernhard



GABAA receptor function in the gamma-hydroxybutyrate model of generalized absence seizures.  


gamma-Hydroxybutyric acid (GHB) produces absence-like seizures when given to animals. One of the distinguishing characteristics of experimental generalized absence seizures is that they are exacerbated by GABAA agonists. Therefore, the hypothesis that GHB-induced absence seizures result from an interaction between GHB and the GABAA receptor complex was tested. The effect of GHB on the function of various components of the GABAA receptor complex in the cortex of the rat, was determined in a series of in vitro experiments. Similar studies were carried out at various times following systemic administration of the prodrug of GHB, gamma-butyrolactone (GBL) and changes in the GABAA receptor were correlated with electrographic and behavioral changes. gamma-Hydroxybutyric acid had no effect on the binding of [3H]muscimol, [3H]flunitrazepam and [35S]t-butylbicyclophosphorothionate (TBPS) or on the uptake of 36Cl- into synaptoneurosomes in the in vitro studies. Nor were changes observed after the administration of GBL before the onset of GHB-induced absence seizures. However, at the onset of GHB-induced spike wave discharge, there was a significant (P < 0.04) decrease in the binding of [35S]TBPS, associated with a significant decrease in muscimol-stimulated uptake of 36Cl- with no other biochemical change. One minute after onset of GHB-induced absence seizure, a significant (P < 0.05) increase in the binding of [3H]muscimol was noted. Ten minutes later the decrease in muscimol-stimulated uptake of 36Cl- had normalized, while the changes in binding of [3H]muscimol and [35S]TBPS persisted. Because GABAA function remained unchanged in the in vitro studies, as well as prior to the onset of GHB-induced absence seizures in the in vivo experiments, these studies do not support the hypothesis that GHB interacts directly with the GABAA receptor complex to produce absence-like seizures. PMID:8388552

Snead, O C; Liu, C C



GHB: a new and novel drug of abuse  

Microsoft Academic Search

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

Katherine L. Nicholson; Robert L. Balster



Acute poisoning from gamma-hydroxybutyrate in California.  


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



Effects of gamma hydroxybutyric acid on inhibition and excitation in rat neocortex.  


The mechanism by which the sedative and amnestic recreational drug gamma hydroxybutyric acid (GHB) acts is controversial. Some studies indicate that it acts at its unique receptor, while others demonstrate effects mediated through the GABAB receptor. We examined the effect of GHB on evoked GABAA receptor-mediated mono- and polysynaptic inhibitory postsynaptic currents (IPSCs) as well as on N-methyl-d-aspartate (NMDA) and AMPA-mediated excitatory postsynaptic currents (EPSCs) in layers II/III pyramidal cells of the frontal cortex of rat brain. One millimolar (mM) GHB suppressed monosynaptic IPSCs by 20%, whereas polysynaptic IPSCs were reduced by 56%. GHB (1 mM) also produced a significant suppression of NMDA-mediated EPSCs by 53% compared with 27% suppression of AMPA-mediated EPSCs. All effects of GHB on IPSCs and EPSCs were reversed by the specific GABAB antagonist CGP 62349, but not by the GHB receptor antagonist (2E)-5-hydroxy-5,7,8,9-tetrahydro-6H-benzo[a][7]annulen-6-ylidene ethanoic acid. Consistent with a presynaptic site of action, GHB reduced the frequency but not the amplitude of AMPA receptor-mediated mEPSCs and had no effect on postsynaptic currents evoked by direct application of NMDA. Finally, even though GHB appeared to be acting at presynaptic GABAB receptors, GHB and the GABAB agonist baclofen appeared to have opposite potencies for depression of NMDA- vs. AMPA-mediated EPSCs. GHB showed a preference for depressing NMDA responses while baclofen more potently suppressed AMPA responses. The suppression of NMDA more than AMPA responses by GHB at intoxicating doses may make it attractive as a recreational drug and may explain why GHB is abused and baclofen is not. PMID:17904295

Li, Q; Kuhn, C M; Wilson, W A; Lewis, D V



Effects of Gamma Hydroxybutyric Acid on Inhibition and Excitation in Rat Neocortex  

PubMed Central

The mechanism by which the sedative and amnestic recreational drug gamma hydroxybutyric acid (GHB) acts is controversial. Some studies indicate that it acts at its unique receptor, while others demonstrate effects mediated through the GABAB receptor. We examined the effect of GHB on evoked GABAA receptor mediated mono- and polysynaptic IPSCs as well as on NMDA and AMPA mediated EPSCs in layers II/III pyramidal cells of the frontal cortex of rat brain. One millimolar (mM) GHB suppressed monosynaptic IPSCs by 20%, whereas polysynaptic IPSCs were reduced by 56%. GHB (1mM) also produced a significant suppression of NMDA-mediated EPSCs by 53% compared to 27% suppression of AMPA-mediated EPSCs. All effects of GHB on IPSCs and EPSCs were reversed by the specific GABAB antagonist CGP62349, but not by the GHB receptor antagonist NCS 382. Consistent with a presynaptic site of action, GHB reduced the frequency but not the amplitude of AMPA receptor mediated mEPSCs and had no effect on postsynaptic currents evoked by direct application of NMDA. Finally, even though GHB appeared to be acting at presynaptic GABAB receptors, GHB and the GABAB agonist baclofen appeared to have opposite potencies for depression of NMDA vs AMPA mediated EPSCs. GHB showed a preference for depressing NMDA responses while baclofen more potently suppressed AMPA responses. The suppression of NMDA more than AMPA responses by GHB at intoxicating doses may make it attractive as a recreational drug and may explain why GHB is abused and baclofen is not.

Li, Qiang; Kuhn, Cynthia M.; Wilson, Wilkie A.; Lewis, Darrell V.



GHB in Sydney, Australia, 2000–2006: A case study of the EDRS as a strategic early warning system  

Microsoft Academic Search

BackgroundThis paper documents the operation of Australia's Ecstasy and Related Drugs Reporting System (EDRS), using multiple data sources to document trends in gamma-hydroxybutyrate (GHB) use in Sydney, Australia between the years 2000–2006.

Matthew Dunn; Libby Topp; Louisa Degenhardt



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

NASA Astrophysics Data System (ADS)

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

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



Development and characterization of an enzymatic method for the rapid determination of gamma hydroxybutyric acid.  


Gamma hydroxybutyric acid (GHB) is a regulated therapeutic drug, which naturally occurs in mammalian brain tissues as an intermediate of the GABA (gamma aminobutyric acid) neurotransmitter metabolism. The increasing misuse of GHB as a narcotic or abusing drug in recent years calls for the development of a simple and rapid screening method as an alternative to the currently available, technically demanding diagnostic methods. We have developed a rapid enzymatic assay based on the GHB dehydrogenase of Ralstonia eutropha. The enzyme is expressed as a recombinant protein in Escherichia coli and characterized in terms of reaction mechanism and kinetic parameters for the catalysis of conversion of GHB into succinic semialdehyde (SSA). The concomitant NADH production enables spectrophotometric monitoring of the reaction and the quantification of GHB in physiological fluids depending on initial velocities. We have tested a panel of twelve serum and urine samples containing GHB concentrations from 0.0 to 2.1 mmol/L. GHB dehydrogenase activity obeys a non classical bi bi ping pong mechanism exhibiting substrate inhibition by NAD+. With an optimal NAD+ concentration of 3.7 mmol/L in the reaction, the enzyme yields a K(M) of 1.0 mmol/L for GHB and a Vmax of 3.37 mmol/min/mg. The assay shows a linear standard curve from 0.1 to at least 1 mmol/L of GHB. Spiking experiments result in mean recoveries of 92% for urine and 114% for serum, respectively. The comparison to an ion chromatographic reference method exhibits a mean difference of 10% divergence from the target values in urine and 9% in serum, respectively. PMID:21197843

Sciotti, Michel A; Hasan, Lara; Scholer, Andre; Jermann, Thomas M; Weber, Jakob M; Gygax, Daniel



Case Report of a Multi-drug Intoxication Fatality Involving GHB  

Microsoft Academic Search

Xyrem® (gamma-hydroxybutyrate or GHB) is a therapeutic agent used for the treatment of daytime sleepiness or cataplexy associated with narcolepsy. In addition to illicit uses, GHB is an endogenous compound that can be artifactually elevated during the post-mortem interval, thus complicating interpretation. This is a report of a case of a 53 year old woman undergoing treatment with Xyrem® for

Brianne E. Akins; Estuardo Miranda; J. Matthew Lacy; Ann Marie Gordon


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.

Molnar, Tunde; Heja, Laszlo; Emri, Zsuzsa; Simon, Agnes; Nyitrai, Gabriella; Pal, Ildiko; Kardos, Julianna



Therapeutic concepts in succinate semialdehyde dehydrogenase (SSADH; ALDH5a1) deficiency (gamma-hydroxybutyric aciduria). Hypotheses evolved from 25 years of patient evaluation, studies in Aldh5a1-/- mice and characterization of gamma-hydroxybutyric acid pharmacology.  


We overview the pathophysiological bases, clinical approaches and potential therapeutic options for succinate semialdehyde dehydrogenase (SSADH; EC1.2.1.24) deficiency (gamma-hydroxybutyric aciduria, OMIM 271980, 610045) in relation to studies on SSADH gene-deleted mice, outcome data developed from 25 years of patient evaluation, and characterization of gamma-hydroxybutyric acid (GHB) pharmacology in different species. The clinical picture of this disorder encompasses a wide spectrum of neurological and psychiatric dysfunction, such as psychomotor retardation, delayed speech development, epileptic seizures and behavioural disturbances, emphasizing the multifactorial pathophysiology of SSADH deficiency. The murine SSADH-/- (e.g. Aldh5a1-/-) mouse model suffers from epileptic seizures and succumbs to early lethality. Aldh5a1-/- mice accumulate GHB and gamma-aminobutyric acid (GABA) in the central nervous system, exhibit alterations of amino acids such as glutamine (Gln), alanine (Ala) and arginine (Arg), and manifest disturbances in other systems including dopamine, neurosteroids and antioxidant status. Therapeutic concepts in patients with SSADH deficiency and preclinical therapeutic experiments are discussed in light of data collected from research in Aldh5a1-/- mice and animal studies of GHB pharmacology; these studies are the foundation for novel working approaches, including pharmacological and dietary trials, which are presented for future evaluation in this disease. PMID:17457693

Knerr, I; Pearl, P L; Bottiglieri, T; Snead, O Carter; Jakobs, C; Gibson, K M



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

Microsoft Academic Search

The objective of this study was the development of an accurate and sensitive method for the determination of gamma-hydroxybutyric\\u000a acid (GHB) in dried whole blood samples using a GC-MS method. The complete procedure was optimized, with special attention\\u000a on the sample pretreatment, and validated. Therefore, dried blood spots of only 50 ?l were prepared and, after the addition\\u000a of internal standard

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



The role of aldehyde reductase AKR1A1 in the metabolism of gamma-hydroxybutyrate in 1321N1 human astrocytoma cells  

Microsoft Academic Search

The role of the aldehyde reductase AKR1A1 in the biosynthesis of gamma-hydroxybutyrate (GHB) has been investigated in cell lines using a specific double stranded siRNA designed to knock down expression of the enzyme. This enzyme, along with the aldo-keto reductase AKR7A2, has been proposed previously to be one of the major succinic semialdehyde reductases in brain. The AKR1A1 siRNA was

Samar Alzeer; Elizabeth M. Ellis



gamma-hydroxybutyrate increases a potassium current and decreases the H-current in hippocampal neurons via GABAB receptors.  


gamma-Hydroxybutyrate (GHB) is used for the treatment of alcoholism and to induce absence seizures in animals, but it has also recently emerged as a drug of abuse. In hippocampal neurons, GHB may activate its own putative receptor as well as GABA(B) receptors to affect synaptic transmission. We used voltage-clamp recordings of rat CA1 pyramidal neurons to characterize the postsynaptic conductances affected by GHB and to further clarify the site of GHB action. Low concentrations of GHB (0.1-1 mM) did not affect postsynaptic properties, but 10 mM GHB elicited an outward current at resting potential by augmenting an inwardly rectifying potassium current and concomitantly decreased the hyperpolarization-activated H-current (I(h)). Like GHB, the selective GABA(B)-receptor agonist baclofen (20 microM) increased a potassium current and decreased I(h). In the presence of 10 mM GHB, the baclofen effects were largely occluded. The selective GABA(B) receptor antagonist CGP 55845 [3-N[1-(S)-(3,4-dichlorophenyl)ethyl]amino-2-(S)-hydroxypropyl-p-benzyl-phosphinic acid] blocked the effects of both GHB and baclofen, whereas the putative GHB receptor antagonist NCS-382 [(2E)-(5-hydroxy-5,7,8,9-tetrahydro-6H-benzo[a][7]annulen-6-ylidene ethanoic acid] was ineffective. The GHB and baclofen effects were prevented in the presence of 200 microM barium, indicating that GHB augments a K(+) conductance, probably a G protein-coupled inwardly rectifying K(+) (GIRK) current. The decrease of I(h) by GHB and baclofen was also prevented by barium, suggesting that the diminution of I(h) is secondary to GIRK augmentation. Our results indicate that high GHB levels, which can be reached during abuse or intoxication, activate only GABA(B) receptors and not GHB receptors at the postsynaptic level to augment an inwardly rectifying K(+) current and decrease I(h). PMID:15152029

Schweitzer, Paul; Roberto, Marisa; Madamba, Samuel G; Siggins, George Robert



Detection of gamma-hydroxybutyrate in striatal microdialysates following peripheral 1,4-butanediol administration in rats.  


The illicit use and abuse of 1,4-butanediol (1,4-BD) results from its presumed conversion to gamma-hydroxybutyrate (GHB) and subsequent pharmacological effects via action on GABA-B and GHB-specific receptors. Using in vivo microdialysis we measured the appearance of GHB in the striata of rats after peripheral 1,4-BD administration. We developed and utilized an HPLC-UV (215 nm) detection of GHB that yielded a limit of quantification (S/N=10) of 2.0 micro g/mL (40 ng/injection) and a limit of detection (S/N=3) of 0.75 micro g/mL (15 ng/injection). GHB appeared in the striatal microdialysates within 20 min after intraperitoneal (i.p.) administration of varying doses of 1,4-BD. GHB concentrations reached dose-dependent maxima 80-100 min post-1,4-BD administration, with peak values of 10.6+/-2.9, 25.3+/-3.4 and 48.1+/-7.1 micro g/mL (mean+/-S.E.M.), corresponding to 1,4-BD doses of 250, 500 and 750 mg/kg, respectively. The conversion of 1,4-BD to GHB was completely prevented by the alcohol dehydrogenase inhibitor 4-methylpyrazole (4MP), administered prior to 1,4-BD, as evidenced by the failure of GHB to appear in the striatal microdialysates. Sleep times in animals were similarly correlated with GHB concentrations in the microdialysates. PMID:17188717

Kapadia, Roopa; Böhlke, Mark; Maher, Timothy J



Simultaneous stimulation of slow-wave sleep and growth hormone secretion by gamma-hydroxybutyrate in normal young Men.  

PubMed Central

The aim of this study was to investigate, in normal young men, whether gamma-hydroxybutyrate (GHB), a reliable stimulant of slow-wave (SW) sleep in normal subjects, would simultaneously enhance sleep related growth hormone (GH) secretion. Eight healthy young men participated each in four experiments involving bedtime oral administration of placebo, 2.5, 3.0, and 3.5 g of GHB. Polygraphic sleep recordings were performed every night, and blood samples were obtained at 15-min intervals from 2000 to 0800. GHB effects were mainly observed during the first 2 h after sleep onset. There was a doubling of GH secretion, resulting from an increase of the amplitude and the duration of the first GH pulse after sleep onset. This stimulation of GH secretion was significantly correlated to a simultaneous increase in the amount of sleep stage IV. Abrupt but transient elevations of prolactin and cortisol were also observed, but did not appear to be associated with the concomitant stimulation of SW sleep. Thyrotropin and melatonin profiles were not altered by GHB administration. These data suggest that pharmacological agents that reliably stimulate SW sleep, such as GHB, may represent a novel class of powerful GH secretagogues.

Van Cauter, E; Plat, L; Scharf, M B; Leproult, R; Cespedes, S; L'Hermite-Baleriaux, M; Copinschi, G



Gamma-hydroxybutyrate does not maintain self-administration but induces conditioned place preference when injected in the ventral tegmental area.  


Gamma-hydroxybutyric acid (GHB) is an endogenous brain substance that has diverse neuropharmacological actions, including rewarding properties in different animal species and in humans. As other drugs of abuse, GHB affects the firing of ventral tegmental neurons (VTA) in anaesthetized animals and hyperpolarizes dopaminergic neurons in VTA slices. However, no direct behavioural data on the effects of GHB applied in the VTA or in the target regions of its dopaminergic neurons, e.g. the nucleus accumbens (NAc), are available. Here, we investigated the effects of various doses of intravenous GHB in maintaining self-administration (from 0.001 to 10 mg/kg per infusion), and its ability to induce conditioned place preference (CPP) in rats when given orally (175-350 mg/kg) or injected directly either in the VTA or NAc (from 10 to 300 microg/0.5 microl per side). Our results indicate that while only 0.01 mg/kg per infusion GHB maintained self-administration, although not on every test day, 350 mg/kg GHB given orally induced CPP. CPP was also observed when GHB was injected in the VTA (30-100 microg/0.5 microl per side) but not in the NAc. Together with recent in-vitro findings, these results suggest that the rewarding properties of GHB mainly occur via disinhibition of VTA dopaminergic neurons. PMID:19573264

Watson, Jill; Guzzetti, Sara; Franchi, Carlotta; Di Clemente, Angelo; Burbassi, Silvia; Emri, Zsuzsa; Leresche, Nathalie; Parri, H Rheinallt; Crunelli, Vincenzo; Cervo, Luigi



Activation of astroglial calcium signaling by endogenous metabolites succinate and gamma-hydroxybutyrate in the nucleus accumbens.  


Accumulating evidence suggests that different energy metabolites play a role not only in neuronal but also in glial signaling. Recently, astroglial Ca(2+) 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 Ca(2+) transient constitute a subset of ATP-responsive astrocytes that are activated in a neuron-independent way. In this study we show that GHB-evoked Ca(2+) transients were also found to constitute a subset of ATP-responsive astrocytes in the NAc. Repetitive Ca(2+) dynamics evoked by GHB suggested that Ca(2+) 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 Ca(2+) signal remained in mice lacking GABA(B) 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 GABA(B) 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 Ca(2+) signaling in astrocytic networks. PMID:22180742

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



What is the role of the gamma-hydroxybutyrate receptor?  

Microsoft Academic Search

A possible functional role for endogenous gamma-hydroxybutyrate has been disputed. However, there are receptor sites for this molecule, which are highly enriched in the synaptosomal membrane fraction in the rat brain and are functionally linked to a guanosine triphosphate-binding protein. These data suggest that they play a neurological role. The binding sites recognize some drug molecules that bear no structural

C. D. Cash



Design, synthesis and pharmacological evaluation of alpha-substituted N-benzylamides of gamma-hydroxybutyric acid with potential GABA-ergic activity. Part 6. Search for new anticonvulsant compounds.  


In the recent study we have extended our investigations to the new anticonvulsant derivatives of alpha-substituted N-benzylamides of gamma-hydroxybutyric acid (GHB). Among the obtained compounds N-benzylamide of alpha-(1,2,3,4-tetrahydroisoquinoline)-GHB (9) has demonstrated activity against maximal electroshock (MES) induced seizures in mice (at 100 mg/kg ip) and in rats (at 30 mg/kg, po dose). Lactone 8 and amide 9 have possessed a weak effect on [3H]-muscimol binding. Molecular modeling studies have revealed that anticonvulsant activity of the alpha-substituted amides of GHB might partially be explained by the orientation of the terminal benzylamide fragment. PMID:17665862

Malawska, Barbara; Kulig, Katarzyna; Gajda, Justyna; Szczeblewski, Dominik; Musia?, Anna; Wieckowski, Krzysztof; Maciag, Dorota; Stables, James P


1H NMR analysis of GHB and GBL: further findings on the interconversion and a preliminary report on the analysis of GHB in serum and urine.  


A 1H nuclear magnetic resonance (1H NMR) method for the determination of gamma-hydroxybutyric acid (GHB) and gamma-hydroxybutyrolactone (GBL) in human serum and urine using spiked samples has been developed. The method gives linear responses (correlation coefficients of 0.99 or greater) over the concentration range 0.01 mg/mL to 4.0 mg/mL in urine and 0.3 mg/mL to 2.0 mg/mL in serum. No sample pretreatment is required. Studies of the chemical interconversion of GBL and GHB showed hydrolysis of GBL to be rapid at pH 11.54, slower and less complete (30% hydrolysis) at pH 2.54 and slowest at pH 7.0, reaching 30% hydrolysis in about 40 days. No esterification of GHB was observed at any pH. PMID:15831000

Del Signore, Anthony G; McGregor, Michael; Cho, Bongsup P



In vitro modulation of hippocampal pyramidal cell response by quinolones: effects of HA 966 and gamma-hydroxybutyric acid.  

PubMed Central

The influence of quinolones on electrically evoked pyramidal cell activity in the rat hippocampus in vitro was studied by using the slice technique. We hoped to learn more about the possible mechanisms for the development of side effects of different quinolones and to find a possible treatment. As reported earlier (W. Dimpfel, M. Spüler, A. Dalhoff, W. Hofmann, and G. Schlüter, Antimicrob. Agents Chemother. 35:1142-1146, 1991), the amplitude of the population spike increased in the presence of ciprofloxacin, lomefloxacin, or ofloxacin about twofold in comparison with reference values. This increase could be prevented in a concentration-dependent manner by the concomitant presence of 3-amino-1-hydroxy-2-pyrrolidone (HA 966), a compound acting at the so-called glycine site of the N-methyl-D-aspartate (NMDA) receptor, but not in the presence of aminophosphonovaleric acid (APV), which acts at a different recognition site of the NMDA receptor. Another tool, 6,7-dinitroquinoxaline-2,3-dione, an antagonist of the so-called AMPA receptor (named after the binding of L-alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid [AMPA] to this site), could not antagonize the effect induced by the quinolones. Activation of the glycine site of the NMDA receptor induced by the presence of D-serine in the superfusion medium also resulted in a concentration-dependent increase in the population spike amplitude. This response remained unchanged in the presence of ciprofloxacin, whereas lomefloxacin and ofloxacin led to further increases in the amplitude, especially in the presence of higher concentrations of D-serine. These results also point to an involvement of the glycine site of the central NMDA receptor in the development of side effects by different quinolones. A complete attenuation of the quinolone-induced effects was obtained in the presence of 2.5 microM gamma-hydroxybutyric acid (GHB), a physiological neuromodulator which is marketed in some countries of Europe as a sedative. It is therefore concluded that the excitatory adverse effects of quinolones might be treated by the administration of GHB.

Dimpfel, W; Dalhoff, A; von Keutz, E



In vitro modulation of hippocampal pyramidal cell response by quinolones: effects of HA 966 and gamma-hydroxybutyric acid.  


The influence of quinolones on electrically evoked pyramidal cell activity in the rat hippocampus in vitro was studied by using the slice technique. We hoped to learn more about the possible mechanisms for the development of side effects of different quinolones and to find a possible treatment. As reported earlier (W. Dimpfel, M. Spüler, A. Dalhoff, W. Hofmann, and G. Schlüter, Antimicrob. Agents Chemother. 35:1142-1146, 1991), the amplitude of the population spike increased in the presence of ciprofloxacin, lomefloxacin, or ofloxacin about twofold in comparison with reference values. This increase could be prevented in a concentration-dependent manner by the concomitant presence of 3-amino-1-hydroxy-2-pyrrolidone (HA 966), a compound acting at the so-called glycine site of the N-methyl-D-aspartate (NMDA) receptor, but not in the presence of aminophosphonovaleric acid (APV), which acts at a different recognition site of the NMDA receptor. Another tool, 6,7-dinitroquinoxaline-2,3-dione, an antagonist of the so-called AMPA receptor (named after the binding of L-alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid [AMPA] to this site), could not antagonize the effect induced by the quinolones. Activation of the glycine site of the NMDA receptor induced by the presence of D-serine in the superfusion medium also resulted in a concentration-dependent increase in the population spike amplitude. This response remained unchanged in the presence of ciprofloxacin, whereas lomefloxacin and ofloxacin led to further increases in the amplitude, especially in the presence of higher concentrations of D-serine. These results also point to an involvement of the glycine site of the central NMDA receptor in the development of side effects by different quinolones. A complete attenuation of the quinolone-induced effects was obtained in the presence of 2.5 microM gamma-hydroxybutyric acid (GHB), a physiological neuromodulator which is marketed in some countries of Europe as a sedative. It is therefore concluded that the excitatory adverse effects of quinolones might be treated by the administration of GHB. PMID:8913467

Dimpfel, W; Dalhoff, A; von Keutz, E



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



The drug of abuse gamma-hydroxybutyrate is a substrate for sodium-coupled monocarboxylate transporter (SMCT) 1 (SLC5A8): characterization of SMCT-mediated uptake and inhibition.  


Gamma-hydroxybutyric acid (GHB), a drug of abuse, is a substrate of monocarboxylate transporters (MCTs). Sodium-coupled monocarboxylate transporter 1 (SMCT1; SLC5A8) is expressed in kidney, thyroid gland, neurons, and intestinal tract and exhibits substrate specificity similar to that of the proton-dependent MCT (SLC16A) family. The role of SMCT1 in GHB disposition has not been determined. In this study we characterized the driving force, transport kinetics, and inhibitors of GHB uptake, as well as expression of SMCT and MCT isoforms, in rat thyroid follicular (FRTL-5) cells. GHB, as well as the monocarboxylates butyrate and d-lactate, exhibited sodium-dependent uptake at pH 7.4, which could be described with a simple Michaelis-Menten equation plus a diffusional component [K(m) 0.68 +/- 0.30 mM, V(max) 3.50 +/- 1.58 nmol . mg(-1) . min(-1), and diffusional clearance (P) 0.25 +/- 0.08 microl . mg(-1) . min(-1)]. In the absence of sodium, GHB uptake was significantly increased at lower pH, suggesting proton-gradient dependent transport. Reverse transcriptase-polymerase chain reaction and Western analyses demonstrated the expression of SMCT1, MCT1, and MCT2 in FRTL-5 cells, supporting the activity results. Sodium-dependent GHB uptake in FRTL-5 cells was inhibited by MCT substrates (d-lactate, l-lactate, pyruvate, and butyrate), nonsteroidal anti-inflammatory drugs (ibuprofen, ketoprofen, and naproxen), and probenecid. IC(50) values for l-lactate, ibuprofen, ketoprofen, and probenecid were 101, 31.6, 64.4, and 380 muM, respectively. All four inhibitors also significantly inhibited GHB uptake in rat MCT1 gene-transfected MDA/MB231 cells, suggesting they are not specific for SMCT1. Luteolin and alpha-cyano-4-hydroxycinnimate represent specific proton-dependent MCT inhibitors. Our findings indicate that GHB is a substrate for both sodium- and proton-dependent MCTs and identified specific inhibitors of MCTs. PMID:19389857

Cui, Dapeng; Morris, Marilyn E



[The radioprotective effect of GABA-tropic substances, gamma-hydroxybutyrate and piracetam].  


From experiments in mice, it is shown that with a radiation dose of 8 Gy (LD96) the radioprotective effect was exerted by gamma-aminobutyric acid (GABA), substances that increase its concentration in tissues (progabide and valproate), and synthetic agonists of both receptor types, particularly baclofen, a GABA-receptor agonist. The radioprotective effect is also exerted by gamma-hydroxybutyrate, not piracetam. PMID:8469734

Kulinski?, V I; Klimova, A D


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


The authors present the case of a 24-year-old girl who was sexually assaulted after administration of gamma-hydroxybutyrate (GHB) and morphine. She had been living in an international college for foreign students for about 1 year and often complained of a general unhealthy feeling in the morning. At the end of the college period she returned to Italy and received at home some video clips shot by a mobile phone camera. In these videos she was having sex with a boy she met when she was studying abroad. Toxicological analysis of her hair was done: the hair was 20-cm long. A 2/3-cm segmentation of all the length of the hair was performed. Morphine and GHB were detected in hair segments related to the period of time she was abroad. The analyses of hair segments were performed by gas chromatography/mass spectrometry (GC/MS) and the concentration of morphine and GHB were calculated. A higher value of GHB was found in the period associated with the possible criminal activity and was also associated with the presence of morphine in the same period. PMID:19261401

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



"Comparative abuse liability of GHB and ethanol in humans": Correction to Johnson and Griffiths (2013).  


Reports an error in "Comparative abuse liability of GHB and ethanol in humans" by Matthew W. Johnson and Roland R. Griffiths (Experimental and Clinical Psychopharmacology, 2013[Apr], Vol 21[2], 112-123). In the article, the concentration of GHB and sodium citrate solutions were misrepresented as "g/ml" rather than the correct "mg/ml". The online version of this article has been corrected. (The following abstract of the original article appeared in record 2013-05106-001.) 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 10g/70kg), ethanol (12, 24, 48, 72, 96, and 120g/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, whereas ethanol effects dissipated between 6 and 8 hours. Dose-related effects were observed for both drugs on a variety of measures assessing sedative drug effects, abuse liability, performance impairment, and physiological effects. Within-session measures of abuse liability were similar between the two drugs. However, postsession measures of abuse liability, including a direct preference test between the highest tolerated doses of each drug, suggested somewhat greater abuse liability for GHB, most likely as a result of the delayed aversive ethanol effects (e.g., headache). (PsycINFO Database Record (c) 2013 APA, all rights reserved). PMID:24000782

Johnson, Matthew W; Griffiths, Roland R



Binding characteristics of the gamma-hydroxybutyric acid receptor antagonist [(3)H](2E)-(5-hydroxy-5,7,8,9-tetrahydro-6H-benzo[a][7]annulen-6-ylidene) ethanoic acid in the rat brain.  


Radioligand binding studies with [(3)H](2E)-(5-hydroxy-5,7,8,9-tetrahydro-6H-benzo[a][7]annulen-6-ylidene) ethanoic acid ([(3)H]NCS-382), an antagonist of gamma-hydroxybutyric acid (GHB) receptor, revealed specific binding sites in the rat cerebral cortex and hippocampus. However, there was very little binding in the rat cerebellum, heart, kidney, liver, and lung membranes. Binding was rapid and reached equilibrium in about 5 min. Scatchard analysis of saturation isotherms revealed two different populations of binding sites in the rat cerebral cortex (K(d1), 795 nM, B(max1), 25.4 pmol/mg of protein; K(d2), 21 microM; B(max2), 178 pmol/mg of protein) as well as in the rat hippocampus (K(d1), 441 nM; B(max1), 16.2 pmol/mg of protein; K(d2), 9.8 microM; B(max2), 255 pmol/mg of protein). (+/-)Baclofen (500 microM) and gamma-aminobutyric acid (100 microM) inhibited the binding only partially, whereas (+)bicuculline, muscimol, picrotoxinin, and phaclofen did not modify the binding. Interestingly, potassium chloride (100-300 mM) inhibited [(3)H]NCS-382 binding (34-56%), and this inhibitory effect was not affected by picrotoxinin. GHB and NCS-382 completely inhibited the [(3)H]NCS-382 (16 nM) binding in the rat cerebrocortical and hippocampal membranes, and NCS-382 was found to be about 10 times more potent than GHB in this regard. A variety of ligands for other receptors did not modify the [(3)H]NCS-382 binding, thereby suggesting selectivity of this radioligand for the GHB receptor sites in the brain. Based on these observations, [(3)H]NCS-382 seems to be a better radioligand than [(3)H]GHB for investigating the role of the GHB receptors in various pharmacological actions. PMID:11714906

Mehta, A K; Muschaweck, N M; Maeda, D Y; Coop, A; Ticku, M K



[Anti-angiogenic activities of UFT and its metabolites, GHB and GBL, in the dorsal air sac (DAS) model in mice].  


We investigated the effects of UFT and its metabolites, GHB and GBL, on angiogenesis induced by tumor cells in a dorsal air sac (DAS) assay in mice. Five tumor cell lines (murine renal carcinoma; RENCA, human gastric cancer; 4-1ST, human small-cell lung carcinoma; LX-1, and human colon carcinoma; DLD-1, KM-20C) were used in the DAS assay. In this model, UFT demonstrated a significant anti-angiogenic activity in a dose-dependent manner while 5-FU (19 mg/kg/day) and 5'-DFUR (200 mg/kg/day) were less effective. Moreover, tegafur (FT), a component of UFT, and gamma-hydroxybutyric acid (GHB) and gamma-butyrolactone (GBL), in vivo metabolites of UFT, inhibited angiogenesis induced by RENCA cells. The inhibitory effects of 5-FU, GHB, and GBL on angiogenesis were increased with administration by continuous infusion, providing a suitable pharmacokinetic profile. These results suggest that GHB and GBL are involved in the expression of anti-angiogenic activity of UFT. PMID:10660738

Basaki, Y; Yonekura, K; Chikahisa, L; Okabe, S; Hashimoto, A; Miyadera, K; Aoyagi, K; Yamada, Y



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.

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



Club Drugs (GHB, Ketamine, and Rohypnol)  


... Is Club Drug Abuse? Monitoring the Future (MTF) Survey* MTF has reported consistently low levels of abuse ... club drugs since they were added to the survey. For GHB and ketamine, this occurred in 2000; ...


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.

Learning, Center F.



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



?-Hydroxybutyric acid (GHB) suppresses alcohol's motivational properties in alcohol-preferring rats  

Microsoft Academic Search

?-Hydroxybutyric acid (GHB) reduces alcohol drinking, promotes abstinence from alcohol, suppresses craving for alcohol, and ameliorates alcohol withdrawal syndrome in alcoholics. At preclinical level, GHB suppresses alcohol withdrawal signs and alcohol intake in rats. The present study was designed to investigate whether GHB administration was capable of affecting alcohol's motivational properties (the possible animal correlate of human craving for alcohol)

Paola Maccioni; Daniela Pes; Noemi Fantini; Mauro A. M. Carai; Gian Luigi Gessa; Giancarlo Colombo



Evaluation of the discriminative stimulus and reinforcing effects of gammahydroxybutyrate (GHB)  

Microsoft Academic Search

Gammahydroxybutyrate (GHB) satisfies many of the criteria for consideration as a neurotransmitter including having specific\\u000a receptor sites, endogenous synthesis, and heterogeneous CNS distribution. GHB has been reported to be illicitly used, to induce\\u000a physical dependence, and to relieve effects from alcohol and heroin withdrawal. GHB has also been shown to have antidopaminergic\\u000a activity to displace 3H[MK-801] binding in brain membranes,

Patrick M. Beardsley; Robert L. Balster; Louis S. Harris



GHB and synthetic cathinones: clinical effects and potential consequences.  


Designer drugs belong to a group of legally or illegally produced substances that are structurally and pharmacologically very similar to illicit drugs. In the past, designer drugs were often used during all-night dance parties, but they are now consumed in multiple settings from college bars to parks to private house parties. Most of these club drugs can be bought on legal websites and home-delivered for private parties. Recently, legal highs have once again become a burning media issue across the world. Our review will focus on GHB and synthetic cathinones. Literature searches were conducted for the period from 1975 to July 2010 using PubMed, EMBASE, PsycInfo, Internet underground and governmental websites using the following keywords alone or in combination: designer drugs, club drugs, party drugs, GHB, synthetic cathinones, mephedrone, methylone, flephedrone, MDAI, and MDVP. Available epidemiological, neurobiological, and clinical data for each compound are described. There is evidence that negative health and social consequences may occur in recreational and chronic users. The addictive potential of designer drugs is not weak. Non-fatal overdoses and deaths related to GHB/GBL or synthetic cathinones have been reported. Clinicians must be careful with GBL or synthetic cathinones, which are being sold and used as substitutes for GHB and MDMA, respectively. Interventions for drug prevention and harm reduction in response to the use of these drugs should be implemented on the Internet and in recreational settings. Prevention, Information, Action, and Treatment are the main goals that must be addressed for this new potentially addictive problem. PMID:21960540

Karila, Laurent; Reynaud, Michel



?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.

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



Gammahydroxybutyrate (GHB) receptor ligand effects on evoked synaptic field potentials in CA1 of the rat hippocampal slice.  


GHB produced a concentration-dependent depression of evoked synaptic field potentials (EFPs) recorded extracellularly in the CA1 region of the in vitro rat hippocampal slice. The concentration/response function revealed a threshold near 1 mM, with IC50 of 10.85 mM and a Hill coefficient of 1.29. The gamma-aminobutyric acid B-receptor (GABA-B) agonist baclofen also depressed the EFP, but even maximally effective concentrations of the GABA-B antagonist 2-hydroxy-saclofen (800 microM) could not completely block the GHB-induced EFP depression. Nor was GHB-induced EFP depression blocked by the GHB receptor "antagonist" NCS-382, which does not displace GABA-B receptor ligands. However, NCS-382 produced a concentration-dependent increase in EFP slope. The threshold concentration was about 100 microM but the maximally effective concentration, and thus the IC50, could not be determined in the perfusion slice system. NCS-382 may be an inverse agonist at hippocampal GHB receptors, or else endogenous hippocampal GHB receptor ligands medicate a tonic inhibition in CA1. At concentrations sufficient to induce EFP depression GHB did not alter pH. Although isosmotic sucrose did depress CA1 EFPs it was essentially ineffective at the IC50 for GHB. Gamma-butyrolactone, a prodrug of GHB, was only 1/20th as effective as GHB. This is consistent with previous data suggesting that GBL is freely permeable (does not substantially disturb tonicity) and that brain has very little capacity to either enzymatically convert the lactone to GHB or respond to the lactone itself. PMID:9503264

King, M A; Thinschmidt, J S; Walker, D W



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



A Colorimetric Sensor Array for the Detection of the Date-Rape Drug ?-Hydroxybutyric Acid (GHB): A Supramolecular Approach.  


?-Hydroxybutyric acid (GHB), a colourless, odourless and tasteless chemical, has become one of the most dangerous illicit drugs of abuse today. At low doses, this drug is a central nervous system depressant that reduces anxiety and produces euphoria and relaxation, sedating the recipient. There is an urgent need for simple, easy-to-use sensors for GHB in solution. Here, we present a colorimetric sensor array based on supramolecular host-guest complexes of fluorescent dyes with organic capsules (cucurbiturils) for the detection of GHB. PMID:20309968

Baumes, Laurent A; Buaki Sogo, Mireia; Montes-Navajas, Pedro; Corma, Avelino; Garcia, Hermenegildo



1,4-butanediol content of aqua dots children’s craft toy beads  

Microsoft Academic Search

Introduction  The U.S. Consumer Product Safety Commission announced a recall of Aqua Dots (Spin Master Ltd.; Toronto, Canada) on November\\u000a 7, 2007 due to children becoming ill after swallowing beads from these toy craft kits. Reports suggested that the beads contained\\u000a 1,4-butanediol (1,4-BD), a precursor to gamma-hydroxybutyrate (GHB), rather than the intended, but more expensive 1,5-pentanediol\\u000a (1,5-PD). We measured the 1,4-BD

Jeffrey R. Suchard; Sergey A. Nizkorodov; Stacy Wilkinson



Trends in the use of alcohol and other drugs in cases of sexual assault  

Microsoft Academic Search

Recent media coverage has raised awareness of the involvement of drugs, both licit and illicit, in the crime of 'date' or 'acquaintance' rape. The term 'date rape drug' has been coined and has been used to label a few specific drugs because of their alleged properties. These include flunitrazepam (Rohypnol), gamma hydroxybutyrate (GHB) and ketamine. Concerns over reports of flunitrazepam

Ian Hindmarch; Rüdiger Brinkmann



Quantitative autoradiographic analysis of the new radioligand [ 3H](2 E)-(5-hydroxy-5,7,8,9-tetrahydro-6H-benzo[ a][7]annulen-6-ylidene) ethanoic acid ([ 3H]NCS382) at ?-hydroxybutyric acid (GHB) binding sites in rat brain  

Microsoft Academic Search

(2E)-(5-Hydroxy-5,7,8,9-tetrahydro-6H-benzo[a][7]annulen-6-ylidene) ethanoic acid (NCS-382) is an antagonist for ?-hydroxybutyric acid (GHB) at GHB receptor sites. Advantages of using [3H]NCS-382 over [3H]GHB in radioligand binding studies are that unlike GHB, NCS-382 does not appear to bind to, activate, or interfere with the functioning of GABAB or GABAA receptors, either directly or indirectly. Herein we establish a protocol for use of [3H]NCS-382

Georgianna G. Gould; Ashok K. Mehta; Alan Frazer; Maharaj K. Ticku



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



Pharmacokinetics of gamma-hydroxybutylic acid (GHB) and gamma-butyrolactone (GBL), the anti-angiogenic metabolites of oral fluoropyrimidine UFT, in patients with gastric cancer.  


Gamma-hydroxybutylic acid (GHB) and gamma-butyrolactone (GBL), the metabolites of UFT, which is an oral fluoropyrimidine, have been reported to inhibit angiogenesis with IC50 values of 25.8 ng/ml. The pharmacokinetics of GHB and GBL were examined after the administration of UFT in patients with gastric cancer. The patients received 200 mg of UFT orally twice a day. Peripheral blood samples were collected at 0, 0.5, 1, 2 and 4 hr after the time of dosing on day 5. The baseline and endogenous GBL concentrations in plasma were 20.2 +/- 7.5 ng/ml for patients and 16.8 +/- 4.0 ng/ml for volunteers (P = 0.221). The values of C(max) for tegafur, uracil, 5-FU and GBL were 14.7 +/- 5.2 and 4.0 +/- 2.8 microg/ml, 191.2 +/- 115.3 and 147.5 +/- 57.3 ng/ml, respectively, and the values of Tmax were 1.0 +/- 0.6, 1.1 +/- 0.6, 0.9 +/- 0.6 and 1.2 +/- 0. 6 hr, respectively. The concentration of GBL was much higher than its IC50 value for angiogenesis. GBL is thus suggested to contribute to the anticancer effects of UFT in addition to that of 5-FU, which is continuously metabolized from UFT. PMID:18260367

Emi, Yasunori; Sumiyoshi, Yasushi; Oki, Eiji; Kakeji, Yoshihiro; Fukui, Yousuke; Maehara, Yoshihiko



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



rescue of lethal seizures in mice deficient in succinate semialdehyde dehydrogenase  

Microsoft Academic Search

Succinate semialdehyde dehydrogenase (ALDH5A1, encoding SSADH deficiency is a defect of 4-aminobutyric acid (GABA) degradation that manifests in humans as 4-hydroxybutyric (gamma-hydroxybutyric, GHB) aciduria. It is characterized by a non-specific neurological disorder including psychomotor retar- dation, language delay, seizures, hypotonia and ataxia. The cur- rent therapy, vigabatrin (VGB), is not uniformly successful1. Here we report the development of Aldh5a1-deficient mice.

Boris M. Hogema; Maneesh Gupta; Henry Senephansiri; Terry G. Burlingame; Melissa Taylor; Cornelis Jakobs; Ruud B. H. Schutgens; Wolfgang Froestl; O. Carter Snead; Ramon Diaz-Arrastia; Teodoro Bottiglieri; Markus Grompe; K. Michael Gibson; Bam HI


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


Clinical Pharmacology of 1,4Butanediol and Gammahydroxybutyrate After Oral 1,4Butanediol Administration to Healthy Volunteers  

Microsoft Academic Search

1,4-Butanediol (BD) is converted to gamma-hydroxybutyrate (GHB) after ingestion, and is associated with cases of dependence, coma, and death. The pharmacology of BD after oral ingestion has not been described in humans. Eight healthy volunteers (five men) were administered 25 mg\\/kg BD in a single oral dose after an overnight fast in a double-blinded, placebo-controlled, crossover study. Vital signs were

D Thai; J E Dyer; P Jacob; C A Haller



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



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

Code of Federal Regulations, 2013 CFR

21 Food and Drugs 9 2013-04-01...1304.26 Section 1304.26 Food and Drugs DRUG ENFORCEMENT ADMINISTRATION, DEPARTMENT OF JUSTICE RECORDS AND REPORTS OF REGISTRANTS...under section 505 of the Federal Food, Drug, and Cosmetic...



Shock precursor observations  

NASA Astrophysics Data System (ADS)

An experimental investigation has demonstrated that the previously observed wall-supported shock precursor, in high-explosive-driven argon-containing shock tubes, rapidly grows to a maximum length at a tube length-to-diameter ratio of 2. It then gradually decreases in length and grows in width as a steady-state configuration is apparently asymptotically approached. All experiments were done in 10.2-cm tubes varying in length from 10 to 80 cm. The explosive was Comp C-4, and the exterior surface of the tube was surrounded by a 4-mm-thick layer of Deta-sheet to minimize wave attenuation. The experimental assembly was tamped in sand. The precursor was observed with a smear camera as the wave system interacted with a thin aluminum foil covering the end of the tube.

Duff, Russell E.; Peterson, Frank I.



Shock precursor observations  

Microsoft Academic Search

An experimental investigation has demonstrated that the previously observed wall-supported shock precursor, in high-explosive-driven argon-containing shock tubes, rapidly grows to a maximum length at a tube length-to-diameter ratio of 2. It then gradually decreases in length and grows in width as a steady-state configuration is apparently asymptotically approached. All experiments were done in 10.2-cm tubes varying in length from 10

Russell E. Duff; Frank I. Peterson



Transsilylation Reactions of Phosphazene Precursors,  

National Technical Information Service (NTIS)

Me3SiN-P(OCH2CF3)Me2 (1) are useful precursors to poly-(alkyl/arylphosphazenes) via a thermally induced condensation polymerization process. Aside from this important thermolysis reaction, however, the chemistry of these phosphazene precursors has not bee...

U. G. Wettermark R. H. Neilson



Impulse buying: Modeling its precursors  

Microsoft Academic Search

A model of the precursors of impulse buying is presented and empirically tested with data drawn at two points in time (during pre- and post-shopping interviews) from a regional shopping mall setting. Analysis of the data, utilizing LISREL 8, supported most of the predictions. Situational variables (time available and money available) and individual difference variables (shopping enjoyment and impulse buying

M. Elizabeth Ferrell



Premarital Precursors of Marital Infidelity  

Microsoft Academic Search

Premarital precursors of infidelity were evaluated in a sample of 72 couples (N ¼144) who were taking part in a longitudinal study of marriage. Premarital self-report and observational data were compared for couples who experienced infidelity and those who did not experience infidelity in the first years of marriage. Couples in which the male engaged in marital infidelity were characterized,




Expression profiling of human glial precursors  

PubMed Central

Background We have generated gene expression databases for human glial precursors, neuronal precursors, astrocyte precursors and neural stem cells and focused on comparing the profile of glial precursors with that of other populations. Results A total of 14 samples were analyzed. Each population, previously distinguished from each other by immunocytochemical analysis of cell surface markers, expressed genes related to their key differentiation pathways. For the glial precursor cell population, we identified 458 genes that were uniquely expressed. Expression of a subset of these individual genes was validated by RT-PCR. We also report genes encoding cell surface markers that may be useful for identification and purification of human glial precursor populations. Conclusion We provide gene expression profile for human glial precursors. Our data suggest several signaling pathways that are important for proliferation and differentiation of human glial precursors. Such information may be utilized to further purify glial precursor populations, optimize media formulation, or study the effects of glial differentiation.

Campanelli, James T; Sandrock, Robert W; Wheatley, Will; Xue, Haipeng; Zheng, Jianhua; Liang, Feng; Chesnut, Jonathan D; Zhan, Ming; Rao, Mahendra S; Liu, Ying



Inhibition of 1,4-butanediol metabolism in human liver in vitro  

Microsoft Academic Search

The conversion of 1,4-butanediol (1,4-BD) to gamma-hydroxybutyric acid (GHB), a drug of abuse, is most probably catalyzed\\u000a by alcohol dehydrogenase, and potentially by aldehyde dehydrogenase. The purpose of this study was to investigate the degradation\\u000a of 1,4-BD in cytosolic supernatant of human liver in vitro, and to verify involvement of the suggested enzymes by means of\\u000a gas chromatography–mass spectrometry. The

Daniel Lenz; Martin Jübner; Katja Bender; Annette Wintermeyer; Justus Beike; Markus A. Rothschild; Herbert Käferstein



Whistler precursors on a VLF transmitter signal  

SciTech Connect

Whistler precursors are discrete emissions which are occasionally seen just before two-hop whistlers. Most theories of precursors assume they are triggered emissions and focus on creating a triggering signal with the proper time delay from the causative sferic. Whistler precursors have now been seen on a signal from the Siple VLF transmitter. Phase analysis shows that these precursors are caused by a rapid increase in growth activity, and not by a triggering signal.

Paschal, E.W. (Stanford Univ., CA (United States))



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




SciTech Connect

We carried out a systematic search of precursors on the sample of short gamma-ray bursts (GRBs) observed by Swift. We found that {approx}8%-10% of short GRBs display such early episodes 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.; Gehrels, N. [NASA, Goddard Space Flight Center, Greenbelt, MD 20771 (United States); Rosswog, S. [School of Engineering and Science, Jacobs University Bremen, Campus Ring 1, 28759 Bremen (Germany)



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.



Precursor lesions to prostatic adenocarcinoma  

Microsoft Academic Search

High-grade prostatic intraepithelial neoplasia (PIN) is the one well-documented precursor to adenocarcinoma of the prostate.\\u000a This review article defines both low- and high-grade PIN. Unusual variants of high-grade PIN are illustrated. Benign lesions\\u000a that may be confused with high-grade PIN, including central zone histology, clear cell cribriform hyperplasia, and basal cell\\u000a hyperplasia are described and illustrated. High-grade PIN is also

Jonathan I. Epstein



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.



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)




PubMed Central

Ribonucleoprotein (RNP) particles containing the precursors of ribosomal RNA were extracted from L cell nucleoli and analyzed under conditions comparable to those used in the characterization of cytoplasmic ribosomes. Using nucleoli from cells suitably labeled with 3H-uridine, we detected three basic RNP components, sedimenting at approximately 62S, 78S, and 110S in sucrose gradients containing magnesium. A fourth particle, sedimenting at about 95S, appears to be a dimer of the 62S and 78S components. When centrifuged in gradients containing EDTA, the 62S, 78S, and 110S particles sediment at about 55S, 65S, and 80S, respectively. RNA was extracted from RNP particles which were prepared by two cycles of zonal centrifugation. The 62S particles yielded 32S RNA and a detectable amount of 28S RNA, the 78S structures, 32S RNA and possibly some 36S RNA, and the 110S particles, a mixture of 45S, 36S, and 32S RNA's. When cells were pulsed briefly and further incubated in the presence of actinomycin D, there was a gradual shift of radioactivity from heavier to lighter particles. This observation is consistent with the scheme of maturation: 110S ? 78S ? 62S. The principal buoyant densities in cesium chloride of the 110S, 78S, and 62S particles are 1.465, 1.490, and 1.545, respectively. These densities are all significantly lower than 1.570, which is characteristic of the mature large subunit of cytoplasmic ribosomes, suggesting that the precursor particles have a relatively higher ratio of protein to RNA, and that ribosome maturation involves, in addition to decrease in the size of the RNA molecules, a progressive decrease in the proportion of associated protein.

Liau, Ming C.; Perry, Robert P.



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



Hydrologic precursors to earthquakes: A review  

Microsoft Academic Search

This review summarizes reports of anomalous flow rates or pressures of groundwater, oil, or gas that have been interpreted as earthquake precursors. Both increases and decreases of pressure and flow rate have been observed, at distances up to several hundred kilometers from the earthquake epicenter, with precursor times ranging from less than one day to more than one year. Although

Evelyn A. Roeloffs



The interrelationships of mathematical precursors in kindergarten.  


This study evaluated the interrelations among cognitive precursors across quantitative, linguistic, and spatial attention domains that have been implicated for math achievement in young children. The dimensionality of the quantity precursors was evaluated in 286 kindergarteners via latent variable techniques, and the contribution of precursors from each domain was established for small sums addition. Results showed a five-factor structure for the quantity precursors, with the major distinction being between nonsymbolic and symbolic tasks. The overall model demonstrated good fit and strong predictive power (R(2)=55%) for addition number combinations. Linguistic and spatial attention domains showed indirect relationships with outcomes, with their effects mediated by symbolic quantity measures. These results have implications for the measurement of mathematical precursors and yield promise for predicting future math performance. PMID:21194711

Cirino, Paul T



Do double 'SS precursors' mean double discontinuities?  

NASA Astrophysics Data System (ADS)

Stacks of SS precursors have been widely used in the past two decades to investigate the existence and characteristics of upper mantle discontinuities on a global scale as well as in several regional cases. Here, we present observations of SS precursors from an Mb 6.7 earthquake recorded at the US Transportable Array in 2010. In this particular case, the S660S precursors on the transverse component are strong enough to be identified on individual seismograms across the array without any stacking procedures. Two S660S precursors are observed, seeming to suggest double discontinuities around 660 km depth in the bounce point region. Through careful analysis of 1-D and 3-D synthetic seismograms, we however discover that, although they have arrival times and slownesses that are very close to the theoretical values of SS precursors, the apparent 'double precursors' are artefacts because of mantle heterogeneity in the upper mantle near the receivers away from the bounce point region. This suggests that caution must be taken about appropriate azimuthal coverage at the SS bounce point, before interpreting double SS or PP precursors in terms of complex mineralogical transitions.

Zheng, Zhao; Romanowicz, Barbara



Neural precursors of delayed insight.  


The solution of a problem left unresolved in the evening can sometimes pop into mind as a sudden insight after a night of sleep in the following morning. Although favorable effects of sleep on insightful behavior have been experimentally confirmed, the neural mechanisms determining this delayed insight remain unknown. Here, using fMRI, we characterize the neural precursors of delayed insight in the number reduction task (NRT), in which a hidden task structure can be learned implicitly, but can also be recognized explicitly in an insightful process, allowing immediate qualitative improvement in task performance. Normal volunteers practiced the NRT during two fMRI sessions (training and retest), taking place 12 hours apart after a night of sleep. After this delay, half of the subjects gained insight into the hidden task structure ("solvers," S), whereas the other half did not ("nonsolvers," NS). Already at training, solvers and nonsolvers differed in their cerebral responses associated with implicit learning. In future solvers, responses were observed in the superior frontal sulcus, posterior parietal cortex, and the insula, three areas mediating controlled processes and supporting early learning and novice performance. In contrast, implicit learning was related to significant responses in the hippocampus in nonsolvers. Moreover, the hippocampus was functionally coupled with the basal ganglia in nonsolvers and with the superior frontal sulcus in solvers, thus potentially biasing participants' strategy towards implicit or controlled processes of memory encoding, respectively. Furthermore, in solvers but not in nonsolvers, response patterns were further transformed overnight, with enhanced responses in ventral medial prefrontal cortex, an area previously implicated in the consolidation of declarative memory. During retest in solvers, before they gain insight into the hidden rule, significant responses were observed in the same medial prefrontal area. After insight, a distributed set of parietal and frontal areas is recruited among which information concerning the hidden rule can be shared in a so-called global workspace. PMID:20666600

Darsaud, Annabelle; Wagner, Ullrich; Balteau, Evelyne; Desseilles, Martin; Sterpenich, Virginie; Vandewalle, Gilles; Albouy, Geneviève; Dang-Vu, Thanh; Collette, Fabienne; Boly, Melanie; Schabus, Manuel; Degueldre, Christian; Luxen, Andre; Maquet, Pierre



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.




PubMed Central

1. Streptococcal proteinase is derived from an inactive precursor found in culture filtrates of proteinase-producing streptococci. 2. The precursor can be converted into the proteinase by low concentrations of trypsin but not by chymotrypsin. 3. In cultures grown in suitable media the conversion of precursor to proteinase is effected autocatalytically. This reaction occurs under reducing conditions and is initiated by active proteinase present in low concentrations with the precursor. 4. The autocatalytic reaction is suppressed or retarded by conditions which decrease the activity of the proteinase, e.g. by growing cultures at 22°C. instead of at 37°C. or by growing them under markedly aerobic conditions. It is also retarded in the presence of casein.

Elliott, Stuart D.; Dole, Vincent P.



Response of inorganic PM to precursor concentrations  

SciTech Connect

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 to sulfate and overall sensitivity to ammonia and nitric acid availability. The PM concentration level responds nonlinearly to sulfate and shows overall sensitivity to ammonia and nitric acid availability for specific atmospheric conditions and precursor concentrations. The generated diagrams are applied as a means of approximating the PM response to precursor concentrations for two urban polluted areas. In both cases, reductions in ammonia emissions have the most significant impact on the total PM level. However, such a reduction will result in significant increases in atmospheric acidity.

Ansari, A.S.; Pandis, S.N. [Carnegie Mellon Univ., Pittsburgh, PA (United States)



The Mars 2001 Athena Precursor Experiment (APEX)  

NASA Astrophysics Data System (ADS)

The Athena Precursor Experiment (APEX) is a suite of scientific instruments for the Mars 2001 lander mission. It includes a panoramic color imager, an IR spectrometer, an APX spectrometer, and a Mössbauer spectrometer.

Squyres, S. W.; Arvidson, R.; Bell, J. F., III; Carr, M.; Christensen, P.; Des Marais, D.; Economou, T.; Gorevan, S.; Klingelhöfer, G.; Haskin, L.; Herkenhoff, K.; Knoll, A.; Knudsen, J. M.; Malin, M.; McSween, H.; Morris, R.; Rieder, R.; Sims, M.; Soderblom, L.; Wänke, H.; Wdowiak, T.



Optical Precursor of a Single Photon  

NASA Astrophysics Data System (ADS)

We report the direct observation of optical precursors of heralded single photons with step- and square-modulated wave packets passing through cold atoms. Using electromagnetically induced transparency and the slow-light effect, we separate the single-photon precursor, which always travels at the speed of light in vacuum, from its delayed main wave packet. In the two-level superluminal medium, our result suggests that the causality holds for a single photon.

Zhang, Shanchao; Chen, J. F.; Liu, Chang; Loy, M. M. T.; Wong, G. K. L.; Du, Shengwang



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



Predicting Solar Cycle 24 With Geomagnetic Precursors  

NASA Astrophysics Data System (ADS)

We describe using a geomagnetic precursor to predict the amplitude of the upcoming solar cycle. The amplitude prediction for Solar Cycle 24 is 65 +/- 20 in smoothed sunspot number, indicating a below-average amplitude for Solar Cycle 24. Four precursor peaks are seen in the decline of Solar Cycle 23. The earliest is the most prominent but coincides with large levels of non-recurrent geomagnetic activity associated with the Halloween storms. The second and third peaks are for smaller amplitudes and show that a weak cycle precursor closely following a period of strong solar activity may be difficult to resolve. A fourth peak, in early 2008, which has recurrent activity similar to precursors of earlier solar cycles and appears to be the ``true" precursor peak for Solar Cycle 24, predicts the smallest amplitude for Solar Cycle 24. Several effects contribute to the smaller prediction when compared to other geomagnetic precursor predictions. During Solar Cycle 23 the correlation between sunspot number and F10.7 shows that F10.7 is greater than the equivalent sunspot number over most of the cycle, implying the sunspot number underestimates the solar activity component. During 2003 the correlation between aa and Ap shows that aa is much greater than the value predicted from Ap, leading to an overestimate of the aa precursor for that year. But the most important effect is the lack of recurrent geomagnetic activity until 2008. We conclude that Solar Cycle 24 will be no stronger than average and could be much weaker than average.

Pesnell, W. Dean



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


Cockayne syndrome b maintains neural precursor function.  


Neurodevelopmental defects are observed in the hereditary disorder Cockayne syndrome (CS). The gene most frequently mutated in CS, Cockayne Syndrome B (CSB), is required for the repair of bulky DNA adducts in transcribed genes during transcription-coupled nucleotide excision repair. CSB also plays a role in chromatin remodeling and mitochondrial function. The role of CSB in neural development is poorly understood. Here we report that the abundance of neural progenitors is normal in Csb(-/-) mice and the frequency of apoptotic cells in the neurogenic niche of the adult subependymal zone is similar in Csb(-/-) and wild type mice. Both embryonic and adult Csb(-/-) neural precursors exhibited defective self-renewal in the neurosphere assay. In Csb(-/-) neural precursors, self-renewal progressively decreased in serially passaged neurospheres. The data also indicate that Csb and the nucleotide excision repair protein Xpa preserve embryonic neural stem cell self-renewal after UV DNA damage. Although Csb(-/-) neural precursors do not exhibit altered neuronal lineage commitment after low-dose UV (1J/m(2)) in vitro, neurons differentiated in vitro from Csb(-/-) neural precursors that had been irradiated with 1J/m(2) UV exhibited defective neurite outgrowth. These findings identify a function for Csb in neural precursors. PMID:23245699

Sacco, Raffaele; Tamblyn, Laura; Rajakulendran, Nishani; Bralha, Fernando N; Tropepe, Vincent; Laposa, Rebecca R



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.



Turbulent wall jet in blast wave precursor  

Microsoft Academic Search

Numerical simulations of the turbulent dusty flow induced by an explosion over a ground surface were performed with a second-order Godunov code. Adaptive Mesh Refinement was used to capture the convective mixing processes on the computational grid. The most prominent feature of the flow was a turbulent wall jet that was induced by the precursor shock refraction into a thermal

A. L. Kuhl



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)



Inference or interaction: social cognition without precursors  

Microsoft Academic Search

In this paper I defend interaction theory (IT) as an alternative to both theory theory (TT) and simulation theory (ST). IT opposes the basic suppositions that both TT and ST depend upon. I argue that the various capacities for primary and secondary intersubjectivity found in infancy and early childhood should not be thought of as precursors to later developing capacities

Shaun Gallagher



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



Peer Review: a Precursor to Peer Assessment  

Microsoft Academic Search

This paper describes a two?year observation of peer review among first year undergraduates at Loughborough University of Technology. Peer review focuses on the learning benefits of small group work and the development of critical skills among students as a precursor to peer assessment of tutorial contributions. The paper outlines the methodology, design and pitfalls of the peer review process and

Keith Pond; Winnie Wade



Functional Analyses and Treatment of Precursor Behavior  

Microsoft Academic Search

Functional analysis has been demonstrated to be an effective method to identify environmental variables that maintain problem behavior. However, there are cases when conducting functional analyses of severe problem behavior may be contraindicated. The current study applied functional analysis procedures to a class of behavior that preceded severe problem behavior (precursor behavior) and evaluated treatments based on the outcomes of




Study of the precursor and non-precursor implosion regimes in wire array Z-pinches  

SciTech Connect

Star-like and closely spaced nested wire array configurations were investigated in precursor and non-precursor implosions. Closely spaced nested cylindrical arrays have inner and outer arrays with equal wire numbers, and inner and outer wires aligned to each other. The gap between the outer and inner wires is not more than 1 mm. Calculation of magnetic fields shows that the small gap results in a reversed, outward j Multiplication-Sign B force on the inner wires. Closely spaced arrays of 6-16 wires with outer diameter of 16 mm and with gaps of {Delta}R = 0.25-1 mm were tested. 6-8-wire arrays with a gap of {Delta}R = 0.4-1 mm imploded without precursor, but precursor was present in loads with 12-16 wires and {Delta}R = 0.25-1 mm. Implosion dynamics of closely spaced arrays was similar to that of star-like arrays. Implosion time was found to decrease with decreased wire numbers. Star array configurations were designed with a numerical scheme to implode with or without precursor. The lack of precursor resulted in a marginal improvement in total x-ray yield and power, and up to 20% increase in Al K-shell yield. The Al K-shell radiated energy was found to increase with decreasing the number of arrays in closely spaced and star-like wire arrays.

Papp, D.; Ivanov, V. V.; Anderson, A. A.; Altemara, S. D.; Talbot, B. R. [University of Nevada, Reno, Reno, Nevada 89507 (United States); Jones, B. [Sandia National Laboratories, P.O. Box 5800, Albuquerque, New Mexico 87185 (United States); Haboub, A. [Lawrence Berkeley National Laboratory, Berkeley, California 94720 (United States)



Precursors and pathogenesis of ovarian carcinoma.  


The ultimate goal of defining cancer specific precursors is to facilitate early detection and intervention before the development of invasive malignancy. Unlike other malignancies involving the female genital tract such as cervical or endometrial carcinomas, precursor lesions of ovarian carcinomas have not been well characterised, resulting in a failure to develop effective screening programs. Recent clinicopathological and molecular studies have provided new insight into the origin and pathogenesis of ovarian carcinomas. It has been shown that ovarian cancer is comprised of different tumour types differing not only in morphology, but also in pathogenesis, molecular alterations and clinical progression. A dualistic model of ovarian carcinogenesis has been proposed. Type I tumours which include low grade serous, low grade endometrioid, clear cell, mucinous carcinomas and Brenner tumours, are generally indolent and tend to be genetically stable, although clear cell carcinoma would probably belong to an intermediate category. They demonstrate a step-wise progression from a benign precursor such as a benign to borderline tumour or endometriosis and are characterised by genetic aberrations targeting specific cell signalling pathways. Type II tumours comprise high grade serous, high grade endometrioid, and undifferentiated carcinomas as well as malignant mixed mesodermal tumours. They are clinically aggressive and exhibit high genetic instability with frequent p53 mutations. Mounting evidence suggests that many high grade serous carcinomas originate from the epithelium of the distal fallopian tube, and that serous tubal intraepithelial carcinoma (STIC) represents the putative precursor of these neoplasms. Low grade serous carcinomas arise via transformation of benign and borderline serous tumours, thought to be derived from inclusion cysts originating from the ovarian surface or tubal epithelium. Recently it has been suggested that papillary tubal hyperplasia may be a putative precursor lesion for serous borderline tumours. Both endometrioid and clear cell carcinomas develop from endometriosis, via alterations affecting different genetic pathways. The origin of mucinous and transitional cell neoplasms is not well characterised, although new data suggest a possible origin from transitional cell nests present at the tubal-mesothelial junction. Likewise, the pathogenesis of carcinosarcomas is also not well established because of their rarity but there is accumulating evidence that the carcinomatous component determines the course of the disease and gives rise to the malignant mesenchymal component. This review discusses recent developments in the pathogenesis of ovarian carcinoma, with particular emphasis on the putative precursor lesions that give rise to the major histological subtypes. Recognition of these lesions is not only important in improving the understanding of ovarian carcinogenesis, but it will also influence our approach to prevent, detect and treat these tumours. PMID:23478230

Lim, D; Oliva, E



Amorphous precursors of crystallization during spinodal decomposition.  


A general Landau's free energy functional is used to study the dynamics of crystallization during liquid-solid spinodal decomposition (SD). The strong length scale selectivity imposed during the early stage of SD induces the appearance of small precursors for crystallization with icosahedral order. These precursors grow in densely packed clusters of tetrahedra through the addition of new particles. As the average size of the amorphous nuclei becomes large enough to reduce geometric frustration, crystalline particles with a body-centered cubic symmetry heterogeneously nucleate on the growing clusters. The volume fraction of the crystalline phase is strongly dependent on the depth of quench. At deep quenches, the SD mechanism produces amorphous structures arranged in dense polytetrahedral aggregates. PMID:21405846

Gómez, Leopoldo R; Vega, Daniel A



Deposition and Solidification of PPV Precursor  

NASA Astrophysics Data System (ADS)

Future high performance polymer films will be comprised of molecules oriented in the plane of the substrate. As a first step, a mixture of poly(p-xylene tetrahydrothiophenium chloride) in methanol was spun onto a sapphire substrate. These samples were fabricated over a range of spin-coating times, methanol solution concentrations, and number of drops of solution. Analysis with an ellipsometer revealed that layer thickness is independent of spinning period and applied solution volume, and decreases as the parts per volume of methanol increases. Furthermore, the samples were exposed to various wavelengths of UV-visible radiation to determine the optimal wavelength for driving these precursor molecules into a solid thin film, insoluble in methanol. Light from a mercury arc-lamp with a wavelength of 365 nm was found to solidify the precursor within five minutes of exposure most effectively.

Burdette, Edward; Hallen, Hans



Are there credible earthquake electromagnetic precursors?  

NASA Astrophysics Data System (ADS)

Ultra low frequency-ULF (1 Hz or lower), kHz and MHz electromagnetic (EM) anomalies were recorded prior to the L'Aquila catastrophic earthquake (EQ) that occurred on April 6, 2009. The detected anomalies followed this temporal scheme. (i) The MHZ EM anomalies were detected on March 26, 2009 and April 2, 2009. The kHz EM anomalies were emerged on April 4, 2009. The ULF EM anomaly was continuously recorded from March 29, 2009 up to April 2, 2009. Are EQs predictable is a question hotly debated in the science community. Its answer begs for another question: Are there credible EQ precursors? Despite fairly abundant circumstantial evidence pre-seismic EM signals have not been adequately accepted as real physical quantities. Therefore, the question effortlessly arises as to whether the observed anomalies before the L'Aquila EQ were seismogenic or not. The main goal of this work is to provide some insight into this issue. More precisely, the main aims of this contribution are threefold: (i) How can we recognize an EM observation as pre-seismic one? We wonder whether necessary and sufficient criteria have been established that permit the characterization of an EM observation as a precursor. (ii) How can we link an individual EM precursor with a distinctive stage of the EQ preparation process? (iii) How can we identify precursory symptoms in an individual EM precursor that indicate that the occurrence of the EQ is unavoidable? We emphasize that we attempt to specify not only whether or not a single EM anomaly is pre-seismic in itself, but mainly whether a combination of emergent ULF, MHz and kHz EM anomalies could be characterized as pre-earthquake.

Eftaxias, Konstantinos; Balasis, Georgios; Contoyiannis, Yiannis; Kalimeri, Maria; Papadimitriou, Constantinos; Athanasopoulou, Labrini; Kopanas, John; Antonopoulos, George



Biochar as a precursor of activated carbon  

Microsoft Academic Search

Biochar was evaluated as a precursor of activated carbon. This product was produced by chemical activation using potassium\\u000a hydroxide. The effects of operating conditions of activation process, such as temperature, activating agent to biochar mass\\u000a ratio, and nitrogen flow rate, on the textural and chemical properties of the product were investigated. Activated carbon\\u000a produced by this method has internal surface

R. Azargohar; A. K. Dalai



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)



Disc haemorrhages, precursors of open angle glaucoma  

Microsoft Academic Search

In a long-term study of 1270 patients with at least one of the findings, open-angle glaucoma, disc haemorrhages or retinal vein occlusions, disc haemorrhages were witnessed in approximately 20% of the cases with open-angle glaucoma, and were a precursor of glaucomatous disc changes and associated visual field defects. Disc haemorrhages also preceded a rising intraocular pressure (IOP) in the destructive

Bo Sonnsjö; Yvonne Dokmo; Torsten Krakau



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.

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



Procollagen I-expressing renin cell precursors.  


Renin-expressing cells in the kidney normally appear as mural cells of developing preglomerular vessels and finally impose as granulated juxtaglomerular cells in adult kidneys. The differentiation of renin-expressing cells from the metanephric mesenchyme in general and the potential role of special precursor stages in particular is not well understood. Therefore, it was the aim of this study to search for renin cell precursors in the kidney. As an experimental model, we used kidneys of aldosterone synthase-deficient mice, which display a prominent compensatory overproduction of renin cells that are arranged in multilayered perivascular cell clusters. We found that the perivascular cell clusters contained two apparently distinct cell types, one staining positive for renin and another one staining positive for type I procollagen (PC1). It appeared as if PC1 and renin expression were inversely related at the cellular level. The proportion of renin-positive to PC1-positive cells in the clusters was inversely linked to the rate of salt intake, as was overall renin expression. Our findings suggest that the cells in the perivascular cell clusters can reversibly switch between PC1 and renin expression and that PC1-expressing cells might be precursors of renin cells. A few of those PC1-positive cells were found also in adult wild-type kidneys in the juxtaglomerular lacis cell area, in which renin expression can be induced on demand. PMID:23761669

Karger, Christian; Kurtz, Felix; Steppan, Dominik; Schwarzensteiner, Ilona; Machura, Katharina; Angel, Peter; Banas, Bernhard; Risteli, Juha; Kurtz, Armin



Mathematical properties of ozone-precursor relationships in photochemical mechanisms  

Microsoft Academic Search

Ozone-precursor surfaces describe ozone's dependence on precursors for one set of conditions. When conditions change, surfaces are different, and such differences are important in developing ozone control strategies. Assessing cause and effect relationships between ozone-precursor surfaces and various conditions is difficult because of photochemical mechanism complexity and the current inability to easily describe surface changes with condition. To overcome these



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.



Osteogenic precursor cells in reparative osteogenesis  

SciTech Connect

The authors aim to discover osteogenic precursor cells in chinchilla rabbits appearing in the medullary cavity after removal of bone marrow. For this purpose the authors modified a model of medullary curettage. Pieces of tissue for electron-microscope autoradiography were incubated in medium with /sup 3/H-thymidine. To discover the proliferative properties of cells of the regenerating bone marrow tissue, an electron-microscopic autoradiographic investigation was carried out. It was found that DNA synthesis took place mainly in undifferentiated cells, endothelial cells, and differentiated cells.

Mikhailova, L.N.; Pal'tsyn, A.A.



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



Alendronate reduces osteoclast precursors in osteoporosis  

Microsoft Academic Search

Summary  This study evaluates the effect of alendronate on osteoclastogenesis, cytokine production, and bone resorption in postmenopausal\\u000a women. We suggest that it acts on mature bone resorbing osteoclasts after 3 months of treatment, whereas, after 1 year, it\\u000a diminishes their formation by reducing their precursors and serum RANKL.\\u000a \\u000a \\u000a \\u000a \\u000a Introduction  Osteoclasts are the target cells of bisphosphonates, though the most drug-sensitive steps of their formation

P. D’Amelio; A. Grimaldi; M. A. Cristofaro; M. Ravazzoli; P. A. Molinatti; G. P. Pescarmona; G. C. Isaia



On Verification of Earthquake Precursors (Invited)  

NASA Astrophysics Data System (ADS)

Although there are many claims of earthquake precursors, most of them should remain in the list of precursor candidates, which have never been tested in any rigorous way, and, in fact, are anecdotal cases of coincidental occurrence. To establish a precursory link between sequences of events of the same or different phenomena, it is necessary to accumulate enough statistics in a rigorous forecast/prediction test, which results, i.e. success-to-failure scores and space-time volume of alarms, must appeal for rejecting hypotheses of random coincidental appearance. We reiterate suggesting so-called “Seismic Roulette” null-hypothesis as the most adequate random alternative accounting for the empirical spatial distribution of earthquakes in question: (i) Consider a roulette wheel with as many sectors as the number of earthquake locations from a sample catalog, a sector per each location and (ii) make your bet according to prediction (i.e., determine, which locations are inside area of alarm, and put one chip in each of the corresponding sectors); (iii) Nature turns the wheel; (iv) accumulate statistics of wins and losses along with the number of chips spent. If a precursor in charge of prediction exposes an imperfection of Seismic Roulette then, having in mind optional “antipodal strategy”, one can make the predictions efficient, so that the wins will systematically outscore the losses. Sounds easy, we know! Seismology is juvenile and its appropriate statistical tools to-date may have a "medieval flavor" for those who hurry up to apply a fuzzy language of a highly developed probability theory and consider delicately-designed models as a full replacement of seismic phenomena. To become "quantitatively probabilistic" earthquake forecasts/predictions must be defined with a scientific accuracy. Following the most popular objectivists' viewpoint on probability, we cannot claim "probabilities" adequate without a long series of "yes/no" forecast/prediction outcomes. Without "antiquated binary language" of "yes/no" certainty we cannot judge an outcome ("success/failure"), and, therefore, quantify objectively a forecast/prediction method performance. The paper illustrates the complexity of seismic statistics based on a twenty years of experimental earthquake prediction in real time of extreme seismic events on the global and regional scales, along with a few outcomes of independent testing of earthquake precursors.

Kossobokov, V. G.



Optical precursors with self-induced transparency  

SciTech Connect

Optical Sommerfeld-Brillouin precursors significantly ahead of a main field of comparable amplitude have been recently observed in an opaque medium with an electromagnetically induced transparency window [Wei et al., Phys. Rev. Lett. 103, 093602 (2009)]. We theoretically analyze in this article the somewhat similar results obtained when the transparency is induced by the propagating field itself and we establish an approximate analytic expression of the time delay of the main-field arrival, which fits fairly well the result obtained by numerically solving the Maxwell-Bloch equations.

Macke, Bruno; Segard, Bernard [Laboratoire de Physique des Lasers, Atomes et Molecules (PhLAM), Centre d'Etudes et de Recherches Lasers et Applications, CNRS et Universite Lille 1, F-59655 Villeneuve d'Ascq (France)



Superhydrophobic silica aerogels based on methyltrimethoxysilane precursor  

Microsoft Academic Search

The experimental results on the synthesis and physicochemical properties of superhydrophobic silica aerogels, with the highest ever obtained contact angle (?173°), using methyltrimethoxysilane (MTMS) precursor, methanol (MeOH) solvent and ammonium hydroxide (NH4OH) catalyst, are reported. The molar ratios of NH4OH\\/MTMS (N), H2O\\/MTMS (H) and MeOH\\/MTMS (M) were varied from 4.25×10?2 to 3.5×10?1, 2 to 10 and 1.75 to 17, respectively.

A. Venkateswara Rao; Manish M. Kulkarni; D. P. Amalnerkar; Tanay Seth



[Two Mexican precursors of oral hydration (1833)].  


The use of oral rehydration to treat diarrhea was reported in the Children's Hospital of Mexico in 1956, and in the Jalisco highlands 23 years before its use was reported in Bangladesh. Reports have been found in the Historical Archives of the Palace of Medicine of two precursors of oral rehydration use dating to a deadly 1833 cholera epidemic. The 1833 publication entitled "Advice to the Mexican people on the most simple and easy methods to prevent and cure the Cholera Morbus epidemic" provides formulas for drinks rich in sodium, calcium, and other minerals to be administered at very frequent intervals. PMID:9789391

Quijano-Pitman, F; Rodríguez-de Romo, A C


Ascorbate as a Biosynthetic Precursor in Plants  

PubMed Central

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

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



Diagenesis and catagenesis of marine kerogen precursors  

SciTech Connect

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

Rafalska-Bloch, J.



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


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.

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



The assimilation of gamma-butyrolactone in Agrobacterium tumefaciens C58 interferes with the accumulation of the N-acyl-homoserine lactone signal.  


Agrobacterium tumefaciens C58 communicates using N-acyl-homoserine lactones (acyl-HSL) and contains two lactonase-encoding genes, attM and aiiB, the products of which are capable of inactivating the acyl-HSL signal. In A. tumefaciens A6, the expression of the attKLM operon is controlled by the transcriptional repressor encoded by an adjacent gene, attJ. An attJ::Tn5 mutant does not accumulate acyl-HSL because of the constitutive expression of the lactonase AttM, the activity of which inactivates acyl-HSL. In this work, the attKLM operon of A. tumefaciens C58 was shown to be involved in an assimilative pathway of gamma-butyrolactone (GBL), gamma-hydroxybutyrate (GHB), and succinate semialdehyde (SSA), in which AttM and AttL are key enzymes for GBL and GHB assimilation. The expression of the attKLM promoter was activated in the presence of GBL, GHB, and SSA. Under these conditions, A. tumefaciens C58 did not accumulate the acyl-HSL that it naturally synthesizes, and also became able to inactivate exogenous acyl-HSL signals. Therefore, in A. tumefaciens C58, the assimilative pathway of gamma-butyrolactone interferes with the acyl-HSL signaling. PMID:15384485

Carlier, Aurélien; Chevrot, Romain; Dessaux, Yves; Faure, Denis



Club drugs and sex on drugs are associated with different motivations for gay circuit party attendance in men.  


Data were collected from 1169 gay circuit party patrons in three North American circuit parties in three geographical locations in 1999. Questionnaires obtained reasons for attending circuit parties and drugs used at circuit parties. Factor analyses of the 10 major reasons for attending parties indicated that there were two significant moderately correlated dimensions: a social and celebratory one to be with friends and dance, and a sensation-seeking one, to have sex and drugs. Drug and sex on drugs predictors of the social dimension accounted for only 3.8% of its variance and included alcohol, ecstasy (methylenedioxymethamphetamine), GHB (gamma-hydroxybutyrate), and having sex while on alcohol as significant predictors. Drug predictors for the sensation-seeking dimension accounted for four times the variance of the first dimension and included poppers, alcohol, ecstasy, Special K, and GHB, and having sex while on methamphetamines and on GHB. Unsafe sex was significantly associated with the sensation-seeking dimension but not the social dimension. While 63% checked > or = 3 of the social reasons for attendance, only 13% checked > or = 3 of the sensation-seeking reasons for attendance. Age was significantly inversely associated with the social dimension. These data suggest that while drug use is significantly associated with both the sensation-seeking and social dimensions of circuit party attendance, a greater number of drugs, sexual activity while on drugs, and unsafe sex are more closely associated with the sensation-seeking dimension of attendance. PMID:12901454

Ross, Michael W; Mattison, Andrew M; Franklin, Donald R



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.

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



Gamma-aminobutyric acidB (GABAB)-receptor mediation of different in vivo effects of gamma-butyrolactone.  


The endogenous brain constituent, gamma-hydroxybutyric acid (GHB), as well as its prodrug, gamma-butyrolactone (GBL), have recently gained interest in the drug addiction field due to their abuse potential and fatalities caused by overdose. It is known that GHB has two sites of actions: the gamma-aminobutyric acid(B) (GABA(B)) receptor and a specific-GHB binding site. The present study was designed to extend to GBL the investigations on the contribution of the GABA(B) receptor and the specific-GHB binding site to its in vivo effects. To this aim, DBA mice were pretreated either with GABA(B)-receptor antagonists, (3-aminopropyl)(diethoxymethyl)phosphinic acid (CGP 35348) and (2S)(+)-5,5-dimethyl-2-morpholineacetic acid (SCH 50911), or a putative antagonist of the specific-GHB binding site, 6,7,8,9-tetrahydro-5-hydroxy-5H-benzocyclohept-6-ylideneacetic acid (NCS-382), prior to the administration of doses of GBL that induced hypothermia, motor-incoordination (measured as motor-impairment at the Rota-Rod task), and sedation/hypnosis. The capability of SCH 50911 and NCS-382 to protect against GBL-induced lethality was also investigated. Pretreatment with either GABA(B)-receptor antagonist completely prevented GBL-induced hypothermia, motor-incoordination, and sedation /hypnosis. SCH 50911 also provided complete protection against GBL-associated lethality. Vice versa, NCS-382 failed to exert any antagonistic or protective effect. These results suggest that the in vivo GBL effects tested in the present study are mediated by activation of the GABA(B) receptor. PMID:18270475

Carai, Mauro A M; Lobina, Carla; Maccioni, Paola; Cabras, Claudia; Colombo, Giancarlo; Gessa, Gian Luigi



Study of tectonic earthquake precursors by geodetic methods  

NASA Astrophysics Data System (ADS)

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 combination with geophysical and seismologic data to estimate the possible time of appearance of earthquake precursors.

Sigalov, V. M.



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.



Time resolved spectral behavior of bright BATSE precursors  

NASA Astrophysics Data System (ADS)

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

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



The solution precursor plasma spray processing of nanomaterials  

Microsoft Academic Search

Solution precursor plasma spray (SPPS) synthesis is a simple, single-step, and rapid technique for synthesizing nano-ceramic\\u000a materials from solution precursors. This innovative method uses molecularly mixed precursors as liquids, avoiding a separate\\u000a processing method for the preparation of powders and enabling the synthesis of a wide range of metal oxide powders and coatings.\\u000a Also, this technique is considered to be

E. Brinley; K. S. Babu; S. Seal



Association between narcotic use and anabolic-androgenic steroid use among American adolescents.  


Drawing on the data gathered in the 2006 Monitoring the Future study of American youth, the present research examines associations between use of narcotics and use of anabolic-androgenic steroids (AASs) among high-school seniors (n = 2,489). With independent measures and controls including sex, race, media exposure, socializing with friends, participation in recreational and school-sponsored sports, perceptions of drug use among professional athletes, and perceptions of steroid use among close friends, binary logistic regression analyses revealed significant associations between AAS use and the use of alcohol, crack cocaine, Vicodin, gamma-hydroxybutyrate (GHB), Ketamine, and Rohypnol. While use of both AASs and the narcotic drugs generally did not eclipse 5% of the sample, the numbers extend to many thousands in larger populations. Implications for health practitioners and recommendations for future research are offered. The study's limitations are noted. PMID:20001694

Denham, Bryan E



[Drug facilitated sexual assault].  


In line with the fact that there is little information regarding drug facilitated sexual assault in national medical literature, the authors aimed to prepare a review of the phenomenon based on available international references. Therefore we offered a definition of the concept of sexual assault, and rape in particular. Consent and ability for valid consent for sexual intercourse were defined as well. A review contains discussion about the basic elements of a concept of drug-facilitated sexual assault. There is also available information in regard to pharmacology of common data rape drugs, i.e. flunitrazepam, gamma-hydroxybutyrate (GHB), and ketamine. We indicate the utmost importance of prompt collecting of biological samples for toxicological screening in patients who are suspected victims of drug facilitated sexual assault. PMID:17642470

Alempijevi?, Djordje; Savi?, Slobodan; Stojanovi?, Jovan; Spasi?, Andjelka


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.

Weir, E



Behavioral risk disparities in a random sample of self-identifying gay and non-gay male university students.  


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

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



Turbulent wall jet in blast wave precursor  

SciTech Connect

Numerical simulations of the turbulent dusty flow induced by an explosion over a ground surface were performed with a second-order Godunov code. Adaptive Mesh Refinement was used to capture the convective mixing processes on the computational grid. The most prominent feature of the flow was a turbulent wall jet that was induced by the precursor shock refraction into a thermal layer on the surface. Dust lofting occurred because the rotational structures of the boundary layer entrained dust from the ground surface. Scaling methods were defined in order to evaluate the mean and r.m.s. profiles of the wall jet. The profiles were shown to be similar to the profiles calculated for self-similar wall jets propagating over dust layers, and agreed with experimental profiles of a dusty boundary layer behind a shock. The Convective Mixing Model described here can be applied to a wide spectrum of fluid-dynamic mixing problems.

Kuhl, A.L.




SciTech Connect

Metallorganic chemical vapor deposition (MOCVD) was used to fabricate yttria-stabilized zirconia as a thermal barrier coating. The MOCVD precursors were Y(tmhd)3 and Zr(tmhd)4 (tmhd = 2, 2, 6, 6-tetramethyl-3, 5-heptanedianato) and delivered via aerosol assisted liquid delivery (AALD). The maximum tetragonal YSZ coating rate was 14.2 1.3 m h -1 (at 845oC) yielding a layered coating microstructure. The growth was first-order with temperature (T < 827oC) with an apparent activation energy (Ea) of 50.9 4.3 kJ mol -1. Coating efficiency was a maximum of approximately 10% at the highest growth rate.

Varanasi, Venu G [ORNL; Besmann, Theodore M [ORNL; Hyde, Robin L. [Oak Ridge National Laboratory (ORNL); Payzant, E Andrew [ORNL; Anderson, Timothy J [University of Florida



N-nitrosodimethylamine precursors in malt.  


NDMA is formed in malt because NOx reacts with certain amines in germinated barley when it is kilned. Hordenine is the major precursor of NDMA, although gramine and sarcosine can possibly contribute minor amounts. The hordenine is formed in the developing seedling. The amount of hordenine present in unkilned malts, made using a variety of malting techniques, is always much more than sufficient to account for NDMA formation. Malting techniques which inhibit hordenine breakdown during kilning decrease NDMA formation. Nitrosated intermediates formed from hordenine on treating with NOx at relatively low temperatures (ca 40 degrees C), can be separated by HPLC. They give NDMA on heating with additional NOx. The conditions under which the intermediates are formed and under which they are converted to NDMA correspond to the observed pattern of NDMA formation during kilning. The effects of sulfuring at different times can be explained by the effects on formation and breakdown of the intermediates. PMID:6183201

Wainwright, T; Slack, P T; Long, D E



Nanostructured carbonaceous materials from molecular precursors.  


Nanostructured carbonaceous materials, that is, carbon materials with a feature size on the nanometer scale and, in some cases, functionalized surfaces, already play an important role in a wide range of emerging fields, such as the search for novel energy sources, efficient energy storage, sustainable chemical technology, as well as organic electronic materials. Furthermore, such materials might offer solutions to the challenges associated with the on-going depletion of nonrenewable energy resources or climate change, and they may promote further breakthroughs in the field of microelectronics. However, novel methods for their preparation will be required that afford functional carbon materials with controlled surface chemistry, mesoscopic morphology, and microstructure. A highly promising approach for the synthesis of such materials is based on the use of well-defined molecular precursors. PMID:20661971

Hoheisel, Tobias N; Schrettl, Stephen; Szilluweit, Ruth; Frauenrath, Holger



Novel mediators of amyloid precursor protein signaling  

PubMed Central

Multiple recent reports implicate amyloid precursor protein (APP) signaling in the pathogenesis of Alzheimer's disease, but the APP-dependent signaling network involved has not been defined. Here we report a novel consensus sequence for interaction with the PDZ-1 and PDZ-2 domains of the APP-interacting proteins Mint1, Mint2, and Mint3 (X11?, X11?, and X11?), and multiple novel interactors for these proteins, with the finding that transcriptional co-activators are highly represented among these interactors. Furthermore, we show that Mint3 interaction with a set of the transcriptional co-activators leads to nuclear localization and transactivation, whereas interaction of the same set with Mint1 or Mint2 prevents nuclear localization and transactivation. These results define new mediators of the signal transduction network mediated by APP.

Swistowski, Andrzej; Zhang, Qiang; Orcholski, Mark E.; Crippen, Danielle; Vitelli, Cathy; Kurakin, Alexei; Bredesen, Dale E.



Disc haemorrhages, precursors of open angle glaucoma.  


In a long-term study of 1270 patients with at least one of the findings, open-angle glaucoma, disc haemorrhages or retinal vein occlusions, disc haemorrhages were witnessed in approximately 20% of the cases with open-angle glaucoma, and were a precursor of glaucomatous disc changes and associated visual field defects. Disc haemorrhages also preceded a rising intraocular pressure (IOP) in the destructive process among open-angle glaucoma cases. Similar glaucomatous development appears among cases independent of IOP or detection of exfoliation syndrome. Retinal vein occlusions and disc haemorrhages behave similarly with respect to glaucoma. The large number of transgressions is an argument against dividing glaucoma into different types. These findings support a vascular genesis to open-angle glaucoma, presented in earlier epidemiological studies. PMID:11906810

Sonnsjö, Bo; Dokmo, Yvonne; Krakau, Torsten



Diamond films grown from fullerene precursors  

SciTech Connect

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

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



Amyloid precursor protein interacts with notch receptors.  


The amyloid precursor protein (APP) must fulfill important roles based on its sequence conservation from fly to human. Although multiple functions for APP have been proposed, the best-known role for this protein is as the precursor of Abeta peptide, a neurotoxic 39-43-amino acid peptide crucial to the pathogenesis of Alzheimer's disease. To investigate additional roles for APP with an eye toward understanding the molecular basis of the pleiotropic effects ascribed to APP, we isolated proteins that interacted with the plasma membrane isoform of APP. We employed a membrane-impermeable crosslinker to immobilize proteins binding to transmembrane APP in human embryonic kidney (HEK)293 cells expressing APP751 (HEK275) or rat embryonic day 18 primary neurons infected with a virus expressing APP. Notch2 was identified as a potential APP binding partner based on mass spectrometry analysis of APP complexes immunopurified from neurons. To confirm the interaction between Notch2 and APP, we carried out immunoprecipitation studies in HEK275 cells transiently expressing full-length Notch2 using Notch2 antibodies. The results indicated that APP and Notch2 interact in mammalian cells, and confirmed our initial findings. Interestingly, Notch1 also coimmunoprecipitated with APP, suggesting that APP and Notch family members may engage in intermolecular cross talk to modulate cell function. Finally, cotransfection of APP/CFP and Notch2/YFP into COS cells revealed that these two proteins colocalize on the plasma membrane. Intracellularly, however, although some APP and Notch molecules colocalize, others reside in distinct locations. The discovery of proteins that interact with APP may aid in the identification of new functions for APP. PMID:16118793

Oh, Sun Young; Ellenstein, Aviva; Chen, Ci-Di; Hinman, Jason D; Berg, Eric A; Costello, Catherine E; Yamin, Rina; Neve, Rachael L; Abraham, Carmela R



Jaw bone marrow-derived osteoclast precursors internalize more bisphosphonate than long-bone marrow precursors.  


Bisphosphonates (BPs) are widely used in the treatment of several bone diseases, such as osteoporosis and cancers that have metastasized to bone, by virtue of their ability to inhibit osteoclastic bone resorption. Previously, it was shown that osteoclasts present at different bone sites have different characteristics. We hypothesized that BPs could have distinct effects on different populations of osteoclasts and their precursors, for example as a result of a different capacity to endocytose the drugs. To investigate this, bone marrow cells were isolated from jaw and long bone from mice and the cells were primed to differentiate into osteoclasts with the cytokines M-CSF and RANKL. Before fusion occurred, cells were incubated with fluorescein-risedronate (FAM-RIS) for 4 or 24h and uptake was determined by flow cytometry. We found that cultures obtained from the jaw internalized 1.7 to 2.5 times more FAM-RIS than long-bone cultures, both after 4 and 24h, and accordingly jaw osteoclasts were more susceptible to inhibition of prenylation of Rap1a after treatment with BPs for 24h. Surprisingly, differences in BP uptake did not differentially affect osteoclastogenesis. This suggests that jaw osteoclast precursors are less sensitive to bisphosphonates after internalization. This was supported by the finding that gene expression of the anti-apoptotic genes Bcl-2 and Bcl-xL was higher in jaw cells than long bone cells, suggesting that the jaw cells might be more resistant to BP-induced apoptosis. Our findings suggest that bisphosphonates have distinct effects on both populations of osteoclast precursors and support previous findings that osteoclasts and precursors are bone-site specific. This study may help to provide more insights into bone-site-specific responses to bisphosphonates. PMID:23962725

Vermeer, Jenny A F; Jansen, Ineke D C; Marthi, Matangi; Coxon, Fraser P; McKenna, Charles E; Sun, Shuting; de Vries, Teun J; Everts, Vincent



Dopamine depletion impairs precursor cell proliferation in Parkinson disease  

Microsoft Academic Search

Cerebral dopamine depletion is the hallmark of Parkinson disease. Because dopamine modulates ontogenetic neurogenesis, depletion of dopamine might affect neural precursors in the subependymal zone and subgranular zone of the adult brain. Here we provide ultrastructural evidence showing that highly proliferative precursors in the adult subependymal zone express dopamine receptors and receive dopaminergic afferents. Experimental depletion of dopamine in rodents

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



Mathematical properties of ozone-precursor relationships in photochemical mechanisms  

Microsoft Academic Search

The purpose of this research is to determine if a simple mathematical model adequately describes ozone-precursor surfaces in such a way that the model parameters can be related to specific chemical characteristics of the photochemical mechanisms used to generate the surfaces. To perform this research, a simple mathematical model whose parameters quantify specific portions of ozone-precursor surfaces was postulated. The



Mass spectral data of precursors of chemical warfare agents  

Microsoft Academic Search

Electron-impact mass spectral data of 50 possible precursors for the production of chemical warfare agents are presented in the form of an eight peak index. In addition to a brief description of the mass spectra of the precursors the relation with the agents is indicated.

Eric R. J. Wils



Polymer precursors for ceramic matrix composites. Annual contractor report  

Microsoft Academic Search

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

M. H. Litt; K. Kumar



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

National Technical Information Service (NTIS)

The focus of this study was on the autoxidation kinetics of deposit precursor formation in jet fuels. The objectives were: (1) to demonstrate that laser-induced fluorescence is a viable kinetic tool for measuring rates of deposit precursor formation in je...

D. W. Naegeli



Study of electromagnetic precursors in ionosphere (WARNING project)  

Microsoft Academic Search

The possibility of existence of ionospheric precursors of seismic hazards is more and more widely accepted. This is the reason why the importance of the WARNING project, declared by the National Space Agency of Ukraine (NSAU) [1], has been increased. Even some future projects have started to include, as an option, the instruments for electromagnetic earthquake precursors study [2]. This

V. Korepanov



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.



A Procedure for Identifying Precursors to Problem Behavior  

ERIC Educational Resources Information Center

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

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



Can a chondrule precursor survive a shock wave?  

NASA Astrophysics Data System (ADS)

In a shock-wave heating model, a chondrule is formed due to frictional heating between its precursor and gas. If the tensile stress inside the precursor derived from the gas dynamic pressure, is greater than the tensile strength of the precursor, the precursor is broken into smaller pieces. The yield (onset of plastic deformation) and breaking (onset of fracturing) strengths of the precursor when sintering is taken into account was calculated. The timescale of sintering is estimated. The model in Sirono & Greenberg (2000, Icarus 145, 230), in which agrain aggregate is assumed to comprise chains of spherical grains of uniform size was used. The critical packing fraction above which anaggregate can survive ashock wave is obtained. If the degree of sintering is low, the breaking strength of the aggregate decreases due to sintering. When sintering has sufficiently occurred, the aggregate can avoid breaking up. Sintering can proceed upstream of the shock wave before the passage of the shock wave.

Sirono, S.



Proinsulin: From Hormonal Precursor to Neuroprotective Factor  

PubMed Central

In the last decade, non-canonical functions have been described for several molecules with hormone-like activities in different stages of vertebrate development. Since its purification in the 1960s, proinsulin has been one of the best described hormonal precursors, though it has been overwhelmingly studied in the context of insulin, the mature protein secreted by the pancreas. Beginning with our discovery of the presence and precise regulation of proinsulin mRNA in early neurulation and neurogenesis, we uncovered a role for proinsulin in cell survival in the developing nervous system. We subsequently demonstrated the ability of proinsulin to prevent pathological cell death and delay photoreceptor degeneration in a mouse model of retinitis pigmentosa. In this review, we focus on the evolution of proinsulin/insulin, beginning with insulin-like peptides expressed in mainly the neurosecretory cells of some invertebrates. We summarize findings related to the regulation of proinsulin expression during development and discuss the possible effects of proinsulin in neural cells or tissue, and its potential as a neuroprotective molecule.

de la Rosa, Enrique J.; de Pablo, Flora



Cystic precursors to invasive pancreatic cancer  

PubMed Central

Improvements in the sensitivity and quality of cross-sectional imaging have led to increasing numbers of patients being diagnosed with cystic lesions of the pancreas. In parallel, clinical, radiological, pathological and molecular studies have improved the systems for classifying these cysts. Patients with asymptomatic serous cystic neoplasms can be managed conservatively with regular monitoring; however, the clinical management of patients with intraductal papillary mucinous neoplasms and mucinous cystic neoplasms is far more challenging, as it is difficult to determine whether these lesions will progress to malignancy. Fortunately, prospective studies have helped to establish that proposed clinical and radiological criteria (the Sendai guidelines) can be used to guide the care of patients with cystic lesions of the pancreas. Despite this progress in imaging and clinical guidelines, sensitive and specific tests have not yet been developed that can reliably predict the histology and biological properties of a cystic lesion. Such biomarkers are urgently needed, as noninvasive precursors of pancreatic cancer are curable, while the vast majority of invasive pancreatic adenocarcinomas are not.

Matthaei, Hanno; Schulick, Richard D.; Hruban, Ralph H.; Maitra, Anirban



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.



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)



Identification, Selection, and Enrichment of Cardiomyocyte Precursors  

PubMed Central

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.

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



A Fission-Powered Interstellar Precursor Mission  

SciTech Connect

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

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



Precursor and processing conditions to make dense ceramic coatings using the solution precursor plasma spraying process  

NASA Astrophysics Data System (ADS)

The objective of this research is to determine the precursor and processing conditions to produce nanograined ceramic coatings with high density and hardness using the Solution Precursor Plasma Spray (SPPS) process. These dense coatings would find potential applications as optical ceramics, wear resistant coatings and bioactive coatings. Basic operating principles needed to create relatively dense coatings using the SPPS process have been discovered. These principles were then used to produce two new precursors and associated processing methods. It has been shown that dense coatings can be best produced if deposits arriving at the substrate are fully Incited. Multiple factors have been experimentally identified that provide dense coatings, including: (1) high solution concentration: (2) low melting temperature compositions; (3) large diameter gun nozzles: (4) high gun power and low liquid feed rates, (5) better entrainment of the droplets in the hot part of the plasma jet. Based on these principles of dense coating formation, dense eutectic Al2O3-YSZ SPPS coatings were produced. The as-deposited coating has 95.6% density and hardness of 11.8 GPa. The thermal stability of as-sprayed dense eutectic Al2O3-7YSZ coatings was examined. High temperature heat treatments of the coating show that both the phase and nano-grain structure are very stable. The nanocomposite Al 2O3-7YSZ coatings are highly grain growth resistant due to the increased diffusion path of species along interphase boundaries. The reproducibility of the principles to make dense ceramic coatings was successfully demonstrated by deposition of a low melting point TiO 2 coating that has desirable biological properties. A dense TiO 2 coating (96%) with a hardness of 7.6 GPa was achieved. The conditions for making dense coatings have been identified. The discovery and demonstration of basic principles for making dense SPPS coatings is a fundamental advancement of the state of the art for SPPS coating technology.

Chen, Dianying


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

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



Rhodium pyrazolate complexes as potential CVD precursors.  


Reaction of 3,5-(CF(3))(2)PzLi with [Rh(?-Cl)(?(2)-C(2)H(4))(2)](2) or [Rh(?-Cl)(PMe(3))(2)](2) in Et(2)O gave the dinuclear complexes [Rh(?(2)-C(2)H(4))(2)(?-3,5-(CF(3))(2)-Pz)](2) (1) and [Rh(2)(?-Cl)(?-3,5-(CF(3))(2)-Pz) (PMe(3))(4)] (2) respectively (3,5-(CF(3))(2)Pz = bis-trifluoromethyl pyrazolate). Reaction of PMe(3) with [Rh(COD)(?-3,5-(CF(3))(2)-Pz)](2) in toluene gave [Rh(3,5-(CF(3))(2)-Pz)(PMe(3))(3)] (3). Reaction of 1 and 3 in toluene (1?:?4) gave moderate yields of the dinuclear complex [Rh(PMe(3))(2)(?-3,5-(CF(3))(2)-Pz)](2) (4). Reaction of 3,5-(CF(3))(2)PzLi with [Rh(PMe(3))(4)]Cl in Et(2)O gave the ionic complex [Rh(PMe(3))(4)][3,5-(CF(3))(2)-Pz] (5). Two of the complexes, 1 and 3, were studied for use as CVD precursors. Polycrystalline thin films of rhodium (fcc-Rh) and metastable-amorphous films of rhodium phosphide (Rh(2)P) were grown from 1 and 3 respectively at 170 and 130 °C, 0.3 mmHg in a hot wall reactor using Ar as the carrier gas (5 cc min(-1)). Thin films of amorphous rhodium and rhodium phosphide (Rh(2)P) were grown from 1 and 3 at 170 and 130 °C respectively at 0.3 mmHg in a hot wall reactor using H(2) as the carrier gas (7 cc min(-1)). PMID:22392449

Rivers, Joseph H; DePue Anderson, Lauren J; Starr, Cotton M N; Jones, Richard A



Metal Precursors and Reduction in Renazzo Chondrules  

NASA Astrophysics Data System (ADS)

The positive Co-Ni correlation and Cr, P contents of metal in CR chondrites have generally been taken to indicate their primitive nature, probably inherited from condensation [1,2]. Si in the metal of primitive chondrites has also been reported and interpreted as a condensation heritage [3,4]. However, Cr, P, and Si (dissolved or in the form of inclusions) in metal of any CR chondrule generally fall within a +-10% range, though large interchondrule variations exist [5]. We have shown that Cr and Si in metal are in equilibrium with Fo and En in silicates, due to the reducing conditions that prevailed during chondrule formation [6]. In the present paper, we show that the Co-Ni trend was also established during chondrule formation out of heterogeneous precursor material with a variable Co/Ni ratio. Chondrules in Renazzo are classified as highly molten (HM), in which metal has been expelled to form a mantle outside the chondrule, medium molten (MM), with metal inside and at the periphery, and with evidence for grain coalescence, and little melted (LM), in which metal is only present in the form of small blebs dispersed among the silicates. In HM chondrules, Ni and Co concentrations are extremely homogeneous, comparatively low and in the cosmic ratio. In LM chondrules, quite the opposite: Ni and Co spread over a large range and the amount of scatter increases with decreasing degree of melting of the chondrule. In addition, they do not correlate along the cosmic ratio, but show a negative correlation if any. This heterogeneity is present not only from grain to grain in these chondrules, but also in individual metal grains. Such a heterogeneity is also exhibited in Cr and P abundances that span a much larger range than the +-10% found in the other chondrules. These results indicate that chondrule formation is responsible for the homogenization of Co and Ni contents of metal grains through coalescence and mixing. The less melted objects give an idea of the nature of metal in chondrule precursors, extremely heterogeneous and fine grained (each small heterogeneous metal bleb might be the result of partial melting of one or of coalescence and imperfect mixing of a few such grains). Co and Ni in these individual grains were not in the cosmic ratio, but wide sampling of dust in each chondrule precursor insured that this ratio was attained after mixing and homogenization, as seen in HM chondrule metal grains and from mean values of Co and Ni in LM chondrules. In MM chondrules, scatter of Ni and Co data are, as expected, intermediate between those of HM and LM chondrules, but Co and Ni are close to the cosmic ratio. The scatter is mostly due to addition of variable quantities of iron in the reduction during chondrule formation, which is responsible for Cr and Si integration into metal. Further evidence of such a process can be found in the less molten of these objects, in which metal grain coalescence is limited and peripheral grains are still different from inside grains. In these cases, Co and Ni distributions are clearly bimodal, high in inside grains, low in peripheral grains. Co/Ni in these two populations are somewhat scattered around the cosmic ratio, but their means (Ni: 7.75 = +- 0.24, Co: 0.36 +- 0.04, and Ni: 4.39 +- 0.34, Co: 0.23 +- 0.02, e.g., in the case of chondrule AL1) are very close to the cosmic ratio. This is in good agreement with the low values found in the homogeneous mantle grains of HM chondrules and, as noted by Lee et al. [7], indicates that the reducing agent was external to the chondrule. Cr abundances of these peripheral metal grains, however, match Cr abundances of the interior ones in these chondrules. This indicates that the redox state of all these grains was attained simultaneously and controlled by equilibrium with chondrule silicates. Slightly more extensive reduction of the latter close to the chondrule surface that added more Fe to peripheral metal grains resulted in only a minor variation of the Cr partition coefficient: it consequently also induced Cr addition, the Cr/Fe ratio varying only marg

Zanda, B.; Hewins, R. H.; Bourot-Denise, M.



Search for GRB precursors in the Swift/BAT archive  

SciTech Connect

Some GRBs are characterized by emission episodes occurring before the main event, called precursors. Their emission intensity is usually weaker than the GRB and is often comparable to (or slightly greater than) the background noise, making their detection difficult. We developed a code to automatically detect such precursors and applied it to a sample of 281 Swift/BAT GRBs. The identification procedure of precursor candidates uses a detection algorithm based on the wavelet transforms, and relies on an accurate study of the BAT background noise properties. A rigorous statistical approach is used for detection threshold settings and detection significance evaluation. We show the preliminary results of the analysis.

Calderone, G. [DSFA-University of Palermo, via Archirafi 33, 90123 Palermo (Italy); Romano, P.; Mangano, V.; Cusumano, G.; Troja, E. [INAF-IASF, via Ugo La Malfa 153, 90146 Palermo (Italy)



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



Methods for forming particles from single source precursors  


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

Fox, Robert V. (Idaho Falls, ID); Rodriguez, Rene G. (Pocatello, ID); Pak, Joshua (Pocatello, ID)



40 CFR 93.164 - Inter-precursor mitigation measures and offsets.  

Code of Federal Regulations, 2012 CFR

... false Inter-precursor mitigation measures and offsets. 93.164 Section 93...164 Inter-precursor mitigation measures and offsets. Federal agencies must...Tribe may approve offsets or mitigation measures of different precursors of the...



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.



Chondrule Precursors and Cooling Paths: The Sulfur Evidence.  

National Technical Information Service (NTIS)

The behavior of moderately volatile elements (Na and S) is controversial but critical in understanding chondrule precursors and heating processes. Sulfide appeared to be present in most chondrules, but S should have been vaporized during chondrule formati...

B. Zanda Y. Yu M. Bourot-denise R. H. Hewins H. C. Connolly



Control of CVD precursor purity for integrated circuit manufacture  

NASA Astrophysics Data System (ADS)

Chemical vapor deposition, CVD, has assumed an increasing share of the processes utilized in the manufacture of submicron integrated circuits. In addition to the conventional CVD materials such as silicon oxide, nitride and polysilicon, an array of new materials for both dielectric and conductive material applications are in development. For films like BPSG or tungsten, convenient volatile precursor sources exist, however, in other cases temperature sensitive, lower volatility liquids and solids are utilized. The quality and consistency of these molecular precursors can have a marked impact on the film forming process. The application of SPC methodology to precursor manufacture provides an effective metric for controlling both the quality and the consistency of the precursors.

Roberts, David A.; Graf, Hans J.; Halberstadt, Michael J.



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 ion independent algorithm for top-down shotgun proteomics  

Microsoft Academic Search

We present a precursor ion independent top-down algorithm (PIITA) for use in automated assignment of protein identifications\\u000a from tandem mass spectra of whole proteins. To acquire the data, we utilize data-dependent acquisition to select protein precursor\\u000a ions eluting from a C4-based HPLC column for collision induced dissociation in the linear ion trap of an LTQ-Orbitrap mass\\u000a spectrometer. Gas-phase fractionation is

Yihsuan S. Tsai; Alexander Scherl; Jason L. Shaw; C. Logan MacKay; Scott A. Shaffer; Patrick R. R. Langridge-Smith; David R. Goodlett



The role of catalyst precursor anions in coal gasification  

SciTech Connect

The aims of the proposed project are to enrich our understanding of the roles of various aqueous soluble catalyst precursor anions on the surface electrical properties of coal and to ascertain the influence of the surface charge on the adsorption, dispersion, and activities of calcium and potassium. These goals will be achieved by impregnating a demineralized North Dakota lignite (PSOC 1482) with calcium or potassium catalyst precursors containing acetate (CH[sub 3]COO[sup [minus

Abotsi, G.M.K.



Senile Plaque Neurites in Alzheimer Disease Accumulate Amyloid Precursor Protein  

Microsoft Academic Search

Senile plaques are polymorphous beta-amyloid protein deposits found in the brain in Alzheimer disease and normal aging. This beta-amyloid protein is derived from a larger precursor molecule of which neurons are the principal producers in brain. We found that amyloid precursor protein (APP)-immunoreactive neurites were involved in senile plaques and that only a subset of these neurites showed markers for

Patrick Cras; Mitsuru Kawai; David Lowery; Patty Gonzalez-Dewhitt; Barry Greenberg; George Perry



Precursors for the polymer-assisted deposition of films  


A polymer assisted deposition process for deposition of metal oxide films is presented. The process includes solutions of one or more metal precursor and soluble polymers having binding properties for the one or more metal precursor. After a coating operation, the resultant coating is heated at high temperatures to yield metal oxide films. Such films can be epitaxial in structure and can be of optical quality. The process can be organic solvent-free.

McCleskey, Thomas M.; Burrell, Anthony K.; Jia, Quanxi; Lin, Yuan



Titanium–halide catalyst-precursors in sodium aluminum hydrides  

Microsoft Academic Search

The kinetics of absorption and desorption of hydrogen from NaAlH4 have previously been shown to improve upon the addition of a catalyst-precursor such as TiCl3. In this paper we demonstrate that TiCl2, TiF3, and TiBr4 all effectively improve sorption kinetics. Arrhenius data indicate that the catalyst precursors behave in essentially the same manner. Evidently the valency of Ti in the

E. H. Majzoub; K. J. Gross



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



Experimental observation of optical precursors in optically pumped crystals  

NASA Astrophysics Data System (ADS)

We experimentally observed optical precursors in optically pumped crystals using polarization-based interference. By switching the user-programmable medium among the fast light, slow light, and no-dispersion regimes, we observed an unchanged polarization state for the wave fronts. The robust polarization-encoded information carried by wave fronts suggests that precursors are the preferred carriers for both quantum and classical information in communication networks.

Zhou, Zong-Quan; Li, Chuan-Feng; Guo, Guang-Can



Global Observations of Mantle Discontinuities Using SS and PP Precursors  

Microsoft Academic Search

SS and PP precursors are currently the only body wave data types that have significant coverage in both oceanic and continental\\u000a regions to study the existence and characteristics of mantle discontinuities on a global scale. Here, the techniques used\\u000a by global seismologists to observe SS and PP precursors are reviewed. Seismograms, aligned on SS or PP, are stacked using\\u000a normal

Arwen Deuss



The Xyrem risk management program.  


Sodium oxybate, also known as gamma-hydroxybutyric acid (GHB), was discovered in 1960 and has been described both as a therapeutic agent with high medical value and, more recently, a substance of abuse. The naturally occurring form of this drug is found in various body tissues but has been studied most extensively in the CNS where its possible function as a neurotransmitter continues to be studied. Sodium oxybate has been approved in different countries for such varied uses as general anaesthesia, the treatment of alcohol withdrawal and addiction, and, most recently, cataplexy associated with narcolepsy. During the 1980s, easy access to GHB-containing products led to various unapproved uses, including weight loss, bodybuilding and the treatment of sleeplessness, sometimes with serious long-term effects. The availability of these unapproved and unregulated forms of the drug led to GHB and its analogues being popularised as substances of abuse and subsequent notoriety as agents used in drug-facilitated sexual assault, or 'date rape', eventually leading to the prohibition of GHB sales in the US. Legal efforts to control the sale and distribution of GHB and its analogues nearly prevented the clinical development of sodium oxybate for narcolepsy in the US. However, following extensive discussions with a variety of interested parties, a satisfactory solution was devised, including legislative action and the development of the Xyrem Risk Management Program. Amendments to the US Controlled Substances Act made GHB a schedule I drug, but also contained provisions that allow US FDA-approved products to be placed under schedule III. This unique, bifurcated schedule for sodium oxybate/GHB allowed the clinical development of sodium oxybate to proceed and, in July 2002, it was approved by the FDA as an orphan drug for the treatment of cataplexy in patients with narcolepsy as Xyrem(sodium oxybate) oral solution. To promote the safe use of sodium oxybate, as well as alleviate concerns over possible diversion and abuse following product approval, a proprietary restricted drug distribution system was created, called the Xyrem Success Program. Components of the programme include a centralised distribution and dispensing system, a physician and patient registry, compulsory educational materials for patients and physicians, a specially trained pharmacy staff, a method for tracking prescription shipments, and an initial post-marketing surveillance programme. The system has created a unique opportunity to provide both physician and patient education and ongoing patient counselling, promoting greater drug safety and enhanced patient compliance. PMID:15061684

Fuller, David E; Hornfeldt, Carl S; Kelloway, Judy S; Stahl, Pamela J; Anderson, Todd F



Active unfolding of precursor proteins during mitochondrial protein import.  


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



Detection of hydrogeochemical seismic precursors by a statistical learning model  

NASA Astrophysics Data System (ADS)

The problem of detecting the occurrence of an earthquake precursor is faced in the general framework of the statistical learning theory. The aim of this work is both to build models able to detect seismic precursors from time series of different geochemical signals and to provide an estimate of number of false positives. The model we used is k-Nearest-Neighbor classifier for discriminating "no-disturbed signal", "seismic precursor" and "co-post seismic precursor" in time series relative to thirteen different hydrogeochemical parameters collected in water samples from a natural spring in Kamchachta (Russia) peninsula. The measurements collected are ion content (Na, Cl, Ca, HCO3, H3BO3), parameters (pH, Q, T) and gases (N2, CO2, CH4, O2, Ag). The classification error is measured by Leave-K-Out-Cross-Validation procedure. Our study shows that the most discriminative ions for detecting seismic precursors are Cl and Na having an error rates of 15%. Moreover, the most discriminative parameters and gases are Q and CH4 respectively, with error rate of 21%. The ions result the most informative hydrogeochemicals for detecting seismic precursors due to the peculiarities of the mechanisms involved in earthquake preparation. Finally we show that the information collected some month before the event under analysis are necessary to improve the classification accuracy.

Castellana, L.; Biagi, P. F.



Altered Processing of Amyloid Precursor Protein in Cells Undergoing Apoptosis  

PubMed Central

Altered proteolysis of amyloid precursor protein is an important determinant of pathology development in Alzheimer's disease. Here, we describe the detection of two novel fragments of amyloid precursor protein in H4 neuroglioma cells undergoing apoptosis. Immunoreactivity of these 25–35 kDa fragments to two different amyloid precursor protein antibodies suggests that they contain the amyloid-? region and an epitope near the C-terminus of amyloid precursor protein. Generation of these fragments is associated with cleavage of caspase-3 and caspase-7, suggesting activation of these caspases. Studies in neurons undergoing DNA damage-induced apoptosis also showed similar results. Inclusion of caspase inhibitors prevented the generation of these novel fragments, suggesting that they are generated by a caspase-dependent mechanism. Molecular weight prediction and immunoreactivity of the fragments generated suggested that such fragments could not be generated by cleavage at any previously identified caspase, secretase, or calpain site on amyloid precursor protein. Bioinformatic analysis of the amino acid sequence of amyloid precursor protein revealed that fragments fitting the observed size and immunoreactivity could be generated by either cleavage at a novel, hitherto unidentified, caspase site or at a previously identified matrix metalloproteinase site in the extracellular domain. Proteolytic cleavage at any of these sites leads to a decrease in the generation of ?-secretase cleaved secreted APP, which has both anti-apoptotic and neuroprotective properties, and thus may contribute to neurodegeneration in Alzheimer's disease.

Fiorelli, Tina; Kirouac, Lisa; Padmanabhan, Jaya



The role of aldehyde reductase AKR1A1 in the metabolism of ?-hydroxybutyrate in 1321N1 human astrocytoma cells.  


The role of the aldehyde reductase AKR1A1 in the biosynthesis of gamma-hydroxybutyrate (GHB) has been investigated in cell lines using a specific double stranded siRNA designed to knock down expression of the enzyme. This enzyme, along with the aldo-keto reductase AKR7A2, has been proposed previously to be one of the major succinic semialdehyde reductases in brain. The AKR1A1 siRNA was introduced into the human astrocytoma cell line (1321N1) and AKR1A1 expression was monitored using quantitative reverse-transcriptase PCR and Western blots. Results show an 88% reduction in mRNA levels and a 94% reduction in AKR1A1 protein expression 72 h after transfection with the siRNA. Aldehyde reductase activity was examined in silenced cells by following the aldehyde-dependent conversion of NADPH to NADP at 340 nm. This revealed a 30% decrease in pNBA reductase activity in cell extracts after AKR1A1 silencing. Succinic semialdehyde reductase activity was significantly lower in silenced cells when measured using high concentrations (1mM) of succinic semialdehyde, but not with low concentrations (10 ?M). The effect of silencing on intracellular and extracellular GHB levels was measured using gas chromatography-mass spectrometry. Results show that AKR1A1 has little effect on the production of GHB, indicating that in this cell line alternative enzymes such as the AKR7A2 are likely to play a more significant role in GHB biosynthesis. PMID:21276435

Alzeer, Samar; Ellis, Elizabeth M



Characterizing precursors to stellar clusters with Herschel  

NASA Astrophysics Data System (ADS)

Context. Despite their profound effect on the universe, the formation of massive stars and stellar clusters remains elusive. Recent advances in observing facilities and computing power have brought us closer to understanding this formation process. In the past decade, compelling evidence has emerged that suggests infrared dark clouds (IRDCs) may be precursors to stellar clusters. However, the usual method for identifying IRDCs is biased by the requirement that they are seen in absorption against background mid-IR emission, whereas dust continuum observations allow cold, dense pre-stellar-clusters to be identified anywhere. Aims: We aim to understand what dust temperatures and column densities characterize and distinguish IRDCs, to explore the population of dust continuum sources that are not IRDCs, and to roughly characterize the level of star formation activity in these dust continuum sources. Methods: We use Hi-GAL 70 to 500 ?m data to identify dust continuum sources in the ? = 30° and ? = 59° Hi-GAL science demonstration phase (SDP) fields, to characterize and subtract the Galactic cirrus emission, and perform pixel-by-pixel modified blackbody fits on cirrus-subtracted Hi-GAL sources. We utilize archival Spitzer data to indicate the level of star-forming activity in each pixel, from mid-IR-dark to mid-IR-bright. Results: We present temperature and column density maps in the Hi-GAL ? = 30° and ? = 59° SDP fields, as well as a robust algorithm for cirrus subtraction and source identification using Hi-GAL data. We report on the fraction of Hi-GAL source pixels which are mid-IR-dark, mid-IR-neutral, or mid-IR-bright in both fields. We find significant trends in column density and temperature between mid-IR-dark and mid-IR-bright pixels; mid-IR-dark pixels are about 10 K colder and have a factor of 2 higher column density on average than mid-IR-bright pixels. We find that Hi-GAL dust continuum sources span a range of evolutionary states from pre- to star-forming, and that warmer sources are associated with more star formation tracers. Additionally, there is a trend of increasing temperature with tracer type from mid-IR-dark at the coldest, to outflow/maser sources in the middle, and finally to 8 and 24 ?m bright sources at the warmest. Finally, we identify five candidate IRDC-like sources on the far-side of the Galaxy. These are cold (~20 K), high column density (N(H2) > 1022 cm-2) clouds identified with Hi-GAL which, despite bright surrounding mid-IR emission, show little to no absorption at 8 ?m. These are the first inner Galaxy far-side candidate IRDCs of which the authors are aware. Herschel in an ESA space observatory with science instruments provided by European-led Principal Investigator consortia and with important participation by NASA.The FITS files discussed in the paper would be released publicly WITH the Hi-GAL data (on the Hi-GAL website) when the Hi-GAL data is released publicly.

Battersby, C.; Bally, J.; Ginsburg, A.; Bernard, J.-P.; Brunt, C.; Fuller, G. A.; Martin, P.; Molinari, S.; Mottram, J.; Peretto, N.; Testi, L.; Thompson, M. A.



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



A novel class of peptide pheromone precursors in ascomycetous fungi.  


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

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



Two-Dimensional Characterization of ELM Precursors in NSTX  

NASA Astrophysics Data System (ADS)

Gas Puff Imaging (GPI) has been used to capture the two-dimensional evolution of Edge Localized Mode (ELM) precursors. Precursor events were observed preceding ELMs and ELM-induced H-L back transitions in radio frequency (RF) heated H-mode plasmas, and the growth of the precursor mode through the ELM filamentation was imaged in the plane perpendicular to the local B-field. Strong edge intensity modulations appeared to propagate in the electron diamagnetic direction while steadily drifting radially outward. Intensity fluctuations were observed at frequencies around 20 kHz and wavenumbers of 0.05-0.2 cm-1. Edge intensity fluctuations are strongly correlated with magnetic signals from Mirnov coils, and toroidally distributed coils estimated toroidal mode numbers of n=5-10. Upon growing to a trigger point, precursor fluctuations were seen to form filamentary structures and move into the Scrape-Off Layer (SOL) explosively with radial velocities peaking at 8 km/s. Quantitatively similar precursors have been observed in Ohmic H-mode plasmas as well, though significantly fewer events are seen in the Ohmic cases and none were observed in similar near-threshold NBI shots studied.

Sechrest, Y.; Munsat, T.; Battaglia, D. J.; Zweben, S. J.



Two-dimensional characterization of ELM precursors in NSTX  

NASA Astrophysics Data System (ADS)

Gas puff imaging has been used to capture the two-dimensional evolution of edge-localized mode (ELM) precursors. Precursor events were observed preceding ELMs and ELM-induced H-L back-transitions in radio-frequency heated H-mode plasmas, and the growth of the precursor mode through the ELM filamentation was imaged in the plane perpendicular to the local B-field. Strong edge intensity modulations appeared to propagate in the electron diamagnetic direction while steadily drifting radially outwards. Intensity fluctuations were observed at frequencies around 20 kHz and wavenumbers of 0.05-0.2 cm-1. Upon growing to a trigger point, precursor fluctuations were seen to form filamentary structures and move into the scrape-off layer (SOL) explosively with radial velocities peaking at 8 km s-1. Once in the SOL, filaments reverse their propagation direction and travel in the ion diamagnetic direction. Edge intensity fluctuations are strongly correlated with magnetic signals from Mirnov coils, and toroidally distributed coils estimated toroidal mode numbers of n = 5-10. Quantitatively similar precursors have been observed in ohmic H-mode plasmas as well, though significantly fewer events are seen in the ohmic cases and none were observed in the near-threshold NBI H-modes studied.

Sechrest, Y.; Munsat, T.; Battaglia, D. J.; Zweben, S. J.



A novel class of peptide pheromone precursors in ascomycetous fungi  

PubMed Central

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

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



Plutonium Immobilization Project (PIP) Precursor Material Calcine Temperature  

SciTech Connect

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

Cozzi, A.D.



Time limited immunomodulatory functions of transplanted neural precursor cells.  


Fetal neural stem/precursor cells (NPCs) possess powerful immunomodulatory properties which enable them to protect the brain from immune-mediated injury. A major issue in developing neural stem/precursor cell (NPC) therapy for chronic neuroinflammatory disorders such as multiple sclerosis is whether cells maintain their immune-regulatory properties for prolonged periods of time. Therefore, we studied time-associated changes in NPC immunomodulatory properties. We examined whether intracerebrally-transplanted NPCs are able to inhibit early versus delayed induction of autoimmune brain inflammation and whether allogeneic NPC grafts continuously inhibit host rejection responses. In two experimental designs, intraventricular fetal NPC grafts attenuated clinically and pathologically brain inflammation during early EAE relapse but failed to inhibit the disease relapse if induced at a delayed time point. In correlation, long-term cultured neural precursors lost their capacity to inhibit immune cell proliferation in vitro. Loss of NPC immune functions was associated with transition into a quiescent undifferentiated state. Also, allogeneic fetal NPC grafts elicited a strong immune reaction of T cell and microglial infiltration and were rejected from the host brain. We conclude that long-term functional changes in transplanted neural precursor cells lead to loss of their therapeutic immune-regulatory properties, and render allogeneic grafts vulnerable to immunologic rejection. Thus, the immunomodulatory effects of neural precursor cell transplantation are limited in time. PMID:23001547

Fainstein, Nina; Einstein, Ofira; Cohen, Mikhal E; Brill, Livnat; Lavon, Iris; Ben-Hur, Tamir



Testosterone and its precursors and metabolites enhance guanylate cyclase activity.  

PubMed Central

Both testosterone and cyclic GMP stimulate DNA synthesis. Because cyclic GMP and testosterone seem to have similar actions, the objective of this investigation was to determine if testosterone and its precursors might have part of their mechanism of action through stimulation of guanylate cyclase [GTP pyrophosphate-lyase (cyclizing), EC], the enzyme that catalyzes the formation of cyclic GMP from GTP. The precursors--namely, progesterone, pregnenolone, 17 alpha-progesterone, 17 alpha-hydroxypregnenolone, androstenedione, and dehydroepiandrosterone--caused a 2- to 3 1/2-fold enhancement of guanylate cyclase activity in rat liver, kidney, skeletal muscle, and ventral prostate at a concentration of 1 microM. These precursors are generated from cholesterol, which had no effect itself on guanylate cyclase activity. Testosterone, 19-nortestosterone, 17-methyltestosterone, and 5 alpha-dihydrotestosterone enhanced guanylate cyclase activity 2- to 5-fold in the same tissues at 1 microM. Etiocholanolone, androsterone, and epiandrosterone, metabolites of testosterone metabolism, enhanced guanylate cyclase activity 1 1/2- to 2-fold at this same concentration. Dose-response relationships revealed that testosterone and its precursors and metabolites had their maximal effect at 1 microM but still had some effect at 0.001 microM. The data in this investigation suggest that the guanylate cyclase-cyclic GMP system plays a role in the mechanism of action of testosterone and its precursors.

Vesely, D L



TEM study of diamond films grown from fullerene precursors  

SciTech Connect

Transmission Electron Microscope (TEM) techniques are applied to study the microstructure of diamond films grown from fullerene precursors. Electron diffraction and electron energy loss spectra (EELS) collected from the diamond films correspond to that of bulk diamond. Microdiffraction, high resolution images and EELS help determine that the first diamond grains that nucleate from fullerene precursors generally form on a thin amorphous carbon interlayer and seldom directly on the silicon substrate. Grain size measurements reveal nanocrystalline diamond grains. Cross section TEM images show that the nanocrystalline diamond grains are equiaxed and not columnar nor dendritic. The microstructure of small equiaxed grains throughout the film thickness is believed responsible for the very smooth surfaces of diamond films grown from fullerene precursors.

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



Characteristics of oxide thin films from carboxylate precursors  

SciTech Connect

Oxide thin films on Si substrates were prepared from carboxylate precursors by the reaction of the metal nitrates and ammonium trimethylacetate. Precursor salts were characterized with respect to purity, structure, thermal pyrolysis, and phase development during calcination. A solvent system, based on carboxylic acid/amine mixture, was developed to dissolve the synthesized precursors, resulting in increased solubility, viscosity, and stability. Smooth, fine-grained ZrO{sub 2}, Y{sub 2}O{sub 3}, and YSZ films were obtained on Si wafers by spin-coating and subsequent heat treatment above 500 {degree}C. Films heat treated below 700 {degree}C were generally adherent, amorphous, or microcrystalline, while YSZ and ZrO{sub 2} showed (111) preferred orientation above 700 {degree}C. These oxide films show promise as protective or buffer layers on Si wafers.

Chu, P.; Buchanan, R.C. (Department of Materials Science and Engineering, University of Illinois at Urbana-Champaign, Urbana, Illinois (USA))



Mechanisms of Gravitational Sensitivity of Osteogenic Precursor Cells  

PubMed Central

This report is a detailed review of the current data on the mechanic and gravitational sensitivity of osteoblasts and osteogenic precursor cells in vitro. It summarizes the numerous responses of cells with an osteoblastic phenotype and osteogenic precursor cells and especially their responses to the alteration of their mechanic or gravitational surroundings. The review also discusses the osteogenic cell’s pathways of signal transduction and the mechanisms of gravitational sensitivity. It was shown that the earliest multipotent stromal precursor cells of an adult organism’s bone marrow can sense changes of intensity in a gravitational or mechanic field in model conditions, which may play a certain role in the development of osteopenia in microgravity.

Buravkova, L.B.; Gershovich, P.M.; Grigor?ev, A.I.



Testosterone precursors: use and abuse in pediatric athletes.  


The dietary supplements androstenedione, dehydroepiandrosterone, and androstenediol are precursors in the endogenous production of testosterone. The efficacy and safety of these prohormones are not well established but are promoted to have the same androgenic effects on building muscle mass and strength as anabolic-androgenic steroids. Studies have demonstrated repeatedly that acute and long-term administration of these oral testosterone precursors does not effectively increase serum testosterone levels and fails to produce any significant changes in lean body mass, muscle strength, or performance improvement compared with placebo. The Anabolic Steroid Control Act of 2004 lists androstenedione as a schedule III controlled substance, and it is regulated by the U.S. Food and Drug Administration. Testosterone precursors are banned by most major sports organizations. PMID:17723877

Smurawa, Troy M; Congeni, Joseph A




PubMed Central

The labile precursors of ribosomal RNA in mouse kidney are preserved when nuclei rapidly isolated after sieving through multiple screens are swollen and cleansed in the presence of an RNase inhibitor before digestion with DNase and phenol extraction. The kinetics of nucleolar labeling analyzed on polyacrylamide gels show that 36S RNA is the major intermediate product in the catabolism of the original 45S RNA precursor to 32S RNA, from which 28S RNA is derived. Each kidney nucleus contains about 200–600 molecules of 45S RNA; the turnover time of the 45S pool is about 3 ± 2 min. Compared with HeLa cells, kidney nuclei have a different major intermediate product and a much smaller and more rapidly turning-over pool of ribosomal precursor RNA.

Ab, Geert; Malt, Ronald A.



Effect of precursor solution dark incubation on gold nanorods morphology  

NASA Astrophysics Data System (ADS)

Gold nanorods were synthesized in an aqueous solution of hexadecyltrimethylammonium bromide via a combination of chemical reduction and UV photoirradiation. Gold ligand complexes, present in the stock solution, are initially reduced, by ascorbic acid as mild reducing agent. The gold ions nucleation and colloid growth proceeds then by subsequent UV irradiation of the so-obtained precursor solution. We present a systematic study of the effect of incubation of the precursor solution on the dispersion state and aspect ratio of the produced nanorods. Incubation of the precursor solution allows the synthesis of higher aspect ratio nanorods with narrower size distribution compared to those obtained without incubation. We propose a mechanism for the gold nanorods formation including two stages, a nucleation and a diffusive growth. This allows us to explain the synthesis improvement as a consequence of the increase in the size of the gold ligand complexes aggregates, leading to a decrease of the nanorods growth rate.

Abdelrasoul, Gaser N.; Scotto, Marco; Cingolani, Roberto; Diaspro, Alberto; Athanassiou, Athanassia; Pignatelli, Francesca



Neuroprotective Secreted Amyloid Precursor Protein Acts by Disrupting Amyloid Precursor Protein Dimers*S?  

PubMed Central

The amyloid precursor protein (APP) is implied both in cell growth and differentiation and in neurodegenerative processes in Alzheimer disease. Regulated proteolysis of APP generates biologically active fragments such as the neuroprotective secreted ectodomain sAPP? and the neurotoxic ?-amyloid peptide. Furthermore, it has been suggested that the intact transmembrane APP plays a signaling role, which might be important for both normal synaptic plasticity and neuronal dysfunction in dementia. To understand APP signaling, we tracked single molecules of APP using quantum dots and quantitated APP homodimerization using fluorescence lifetime imaging microscopy for the detection of Förster resonance energy transfer in living neuroblastoma cells. Using selective labeling with synthetic fluorophores, we show that the dimerization of APP is considerably higher at the plasma membrane than in intracellular membranes. Heparan sulfate significantly contributes to the almost complete dimerization of APP at the plasma membrane. Importantly, this technique for the first time structurally defines the initiation of APP signaling by binding of a relevant physiological extracellular ligand; our results indicate APP as receptor for neuroprotective sAPP?, as sAPP? binding disrupts APP dimers, and this disruption of APP dimers by sAPP? is necessary for the protection of neuroblastoma cells against starvation-induced cell death. Only cells expressing reversibly dimerized wild-type, but not covalently dimerized mutant APP are protected by sAPP?. These findings suggest a potentially beneficial effect of increasing sAPP? production or disrupting APP dimers for neuronal survival.

Gralle, Matthias; Botelho, Michelle Gralle; Wouters, Fred S.



Posttranslational processing of concanavalin A precursors in jackbean cotyledons  

PubMed Central

Metabolic labeling of immature jackbean cotyledons with 14C-amino acids was used to determine the processing steps involved in the assembly of concanavalin A. Pulse-chase experiments and analyses of immunoprecipitated lectin forms indicated a complex series of events involving seven distinct species. The structural relatedness of all of the intermediate species was confirmed by two-dimensional mapping of 125I-tryptic peptides. An initial glycosylated precursor was deglycosylated and cleaved into smaller polypeptides, which subsequently reannealed over a period of 10-27 h. NH2-terminal sequencing of the abundant precursors confirmed that the intact subunit of concanavalin A was formed by the reannealing of two fragments, since the alignment of residues 1-118 and 119-237 was reversed in the final form of the lectin identified in the chase and the precursor first labeled. When the tissue was pulse-chased in the presence of monensin, processing of the glycosylated precursor was inhibited. The weak bases NH4Cl and chloroquine were without effect. Immunocytochemical studies showed that monensin treatment caused the accumulation of immunoreactive material at the cell surface and indicated that the ionophore had induced the secretion of a component normally destined for deposition within the protein bodies. Consideration of the tertiary structure of the glycosylated precursor and mature lectin showed that the entire series of processing events could occur without significant refolding of the initial translational product. Proteolytic events included removal of a peptide from the surface of the precursor molecule that connected the NH2- and COOH-termini of the mature protein. This processing activated the carbohydrate-binding activity of the lectin. The chase data suggest the occurrence of a simultaneous cleavage and formation of a peptide bond, raising the possibility that annealment of the fragments to give rise to the mature subunit involves a transpeptidation event rather than cleavage and subsequent religation.



Thermal Conductivity of Porous Silicon Carbide Derived from Wood Precursors  

SciTech Connect

Biomorphic silicon carbide (bioSiC), a novel porous ceramic derived from natural wood precursors, has potential applicability at high temperatures, particularly when rapid temperature changes occur. The thermal conductivity of bioSiC from five different precursors was experimentally determined using flash diffusivity and specific heat measurements at temperatures ranging from room temperature to 1100 C. The results were compared with values obtained from object-oriented finite-element analysis (OOF). OOF was also used to model and understand the heat-flow paths through the complex bioSiC microstructures.

Pappacena, Kristen E [ORNL; Wang, Hsin [ORNL; Porter, Wallace D [ORNL; Faber, K. T. [Northwestern University, Evanston



Precursors of Parametric Oscillatory Instability in LIGO Interferometer  

NASA Astrophysics Data System (ADS)

The basis of undesirable effect of parametric oscillatory instability in optical interferometer is provided by excitation of the additional (Stokes) optical mode having frequency ?1, and the mirror elastic mode, having frequency ?m. It appears when optical energy stored in the main mode, with frequency ?0, exceeds a certain threshold and the frequencies are related as ?0 ? ?1 + ?m. We analyze time evolution of parametric instability which allows predicting the characteristics of precursors of parametric instability. Also we suggested device tranquilizer to dump the parametric instability. Observation of such precursors and the tranquilizer may help avoid parametric instability.

Polyakov, Ilya A.; Vyatchanin, S. P.



Aluminum titanium nitride films grown with multiple precursors  

Microsoft Academic Search

Metallorganic chemical vapor deposition (MOCVD) of AlxTi1?xN films was investigated at 200 to 400°C using terakis(dimethylamino)titanium (TDMAT), dimethylaluminum hydride (DMAH), triethylaluminum (TEA) and dimethylhydrazine (DMH). The film composition was examined by in-situ X-ray photoelectron spectroscopy. AlxTi1?xN and AlxTi1?xCN (CN designate to carbo-nitride) film growth was observed on SiO2\\/Si(100) using various combinations of above precursors. With TDMAT and either Al precursor,

Y.-M Sun; J. P Endle; J. G Ekerdt; N. M Russell; M. D Healy; J. M White



Expression cloning screen for modifiers of amyloid precursor protein shedding  

Microsoft Academic Search

Ectodomain shedding of the amyloid precursor protein (APP) is a key regulatory step in the generation of the amyloid ? peptide (A?), which is thought to provoke the pathogenesis of Alzheimer's disease. To better understand the cellular processes that regulate ectodomain shedding of APP we used human embryonic kidney 293 cells and applied a sib-selection expression cloning approach. In addition

Susanne Schöbel; Stephanie Neumann; Brian Seed; Stefan F. Lichtenthaler



Altered localization of amyloid precursor protein under endoplasmic reticulum stress  

Microsoft Academic Search

Recent reports have shown that the endoplasmic reticulum (ER) stress is relevant to the pathogenesis of Alzheimer disease. Following the amyloid cascade hypothesis, we therefore attempted to investigate the effects of ER stress on amyloid-? peptide (A?) generation. In this study, we found that ER stress altered the localization of amyloid precursor protein (APP) from late compartments to early compartments

Takashi Kudo; Masayo Okumura; Kazunori Imaizumi; Wataru Araki; Takashi Morihara; Hitoshi Tanimukai; Eiichiro Kamagata; Nobuhiko Tabuchi; Ryo Kimura; Daisuke Kanayama; Akio Fukumori; Shinji Tagami; Masayasu Okochi; Mikiko Kubo; Hisashi Tanii; Masaya Tohyama; Takeshi Tabira; Masatoshi Takeda



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.

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



Sol-gel processing of NASICON thin-film precursors  

Microsoft Academic Search

Metal-alkoxides have been used to produce Nasicon solid electrolyte thin-film precursors via sol-gel processing route. The influence of various processing parameters e.g., solvent type, temperature, acid or base catalysts, pH, chelating agents, etc., on the hydrolysis-polycondensation (gelation) behaviour of the metal-alkoxides is discussed.

A. Ahmad; C. Glasgow; T. A. Wheat



Panchromatic study of GRB 060124: from precursor to afterglow  

Microsoft Academic Search

We present observations of GRB 060124, the first event for which both the prompt and the afterglow emission could be observed simultaneously and in their entirety by the three Swift instruments. Indeed, Swift-BAT triggered on a precursor ~570 s before the main burst peak, and this allowed Swift to repoint the narrow field instruments to the burst position ~350 s

P. Romano; S. Campana; G. Chincarini; J. Cummings; G. Cusumano; S. T. Holland; V. Mangano; T. Mineo; K. L. Page; V. Pal'Shin; E. Rol; T. Sakamoto; B. Zhang; R. Aptekar; S. Barbier; S. Barthelmy; A. P. Beardmore; P. Boyd; D. N. Burrows; M. Capalbi; E. E. Fenimore; D. Frederiks; N. Gehrels; P. Giommi; M. R. Goad; O. Godet; S. Golenetskii; D. Guetta; J. A. Kennea; V. La Parola; D. Malesani; F. Marshall; A. Moretti; J. A. Nousek; P. T. O'Brien; J. P. Osborne; M. Perri; G. Tagliaferri



Bi2223 precursor billets for PIT wire production  

Microsoft Academic Search

High temperature superconductor precursor billets (feed rods) have been developed for loading into silver tubes. The billets are loaded prior to rolling or drawing operations in PIT wire manufacture. Investigations have shown that wires and tapes prepared from feed rod loaded tubes show enhanced uniformity of electrical transport properties when compared with conventional powder packing, especially in wires drawn to

Toru Yamashita; Jose A. Alarco; Alexander J. Ilyushechkin; Kelly Tomlins; Peter Talbot



Crystallographic Snapshot of Glycosylasparaginase Precursor Poised for Autoprocessing  

SciTech Connect

Glycosylasparaginase belongs to a family of N-terminal nucleophile hydrolases that autoproteolytically generate their mature enzymes from single-chain protein precursors. Previously, based on a precursor structure paused at pre-autoproteolysis stage by a reversible inhibitor (glycine), we proposed a mechanism of intramolecular autoproteolysis. A key structural feature, a highly strained conformation at the scissile peptide bond, had been identified and was hypothesized to be critical for driving autoproteolysis through an N-O acyl shift. To examine this 'twist-and-break' hypothesis, we report here a 1.9-{angstrom}-resolution structure of an autoproteolysis-active precursor (a T152C mutant) that is free of inhibitor or ligand and is poised to undergo autoproteolysis. The current crystallographic study has provided direct evidence for the natural conformation of the glycosylasparaginase autocatalytic site without influence from any inhibitor or ligand. This finding has confirmed our previous proposal that conformational strain is an intrinsic feature of an active precursor.

Wang, Y.; Guo, H



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...


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...


40 CFR 766.38 - Reporting on precursor chemical substances.  

Code of Federal Regulations, 2013 CFR

...formation under favorable reaction conditions when they are used to produce other chemicals or products. The following...made from precursor chemical substances identified...must report process and reaction condition data on Part...Form 7710-51 for each chemical product. A...



College Student Stress: A Predictor of Eating Disorder Precursor Behaviors  

ERIC Educational Resources Information Center

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

Shelton, Virginia L.; Valkyrie, Karena T.



Rheology of YBa2Cu3O(7-x) precursors.  

National Technical Information Service (NTIS)

Nitrate and acetate precursors to YBa(sub 2)Cu(sub 3)O(sub 7-x) (123) are prepared using a molten salt technique. The viscosity and shear stress of the paste are controlled by evaporation of water from the paste. The pastes contain (approximately) 20--80 ...

T. M. Green M. Akinc



ESA lunar study: precursor astronomy missions to the moon  

NASA Astrophysics Data System (ADS)

We give a summary of the areas identified by the ESA Lunar Study Steering Group for Scientific Exploration of the Moon in the ESA report ``Mission to the Moon''. We discuss the possible phased approach for different scientific areas and some potential Precursor Astronomy Missions. We give a short status of current related ESA studies.

Foing, B. H.



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...


Synthesis and Characterization of Nanocrystalline Magnetic Pigment via Coordinated Precursors  

Microsoft Academic Search

anocrystalline cobalt ferrite as a magnetic black pigment was synthesized via coordinated precursors with a significant decrease of the synthesis temperature using citric acid as a coordinating agent. The structure and properties of the cobalt ferrite powder were characterized by X-ray diffraction (XRD), colorimetric analysis (L * a * b * color parameters), diffuse reflectance spectroscopy and vibrating sample magnetometer

M. Gharagozlou


Hydroxyapatite formation from a hydrated calcium monohydrogen phosphate precursor  

Microsoft Academic Search

Hydrated calcium monohydrogen phosphate is proposed as the logical precursor in the formation of hydroxyapatite and a unifying theory for the formation of low calcium, or defect apatites, is presented. Structural relationships between calcium monohydrogen phosphate dihydrate and hydroxyapatite indicate that either material can provide the atomic arrangment for the epitaxial growth of one on the other. The formation of

Marion D. Francis; Ned C. Webb



Single-source precursors to ternary silver indium sulfide materials.  


Compounds of type [(Ph3P)2AgIn(SC(O)R)4] (R = Me (1), Ph (2)) are excellent single-source precursors for AgInS2 bulk materials by pyrolysis and AgIn5S8 films by aerosol assisted chemical vapour deposition (AACVD). PMID:12240047

Deivaraj, T C; Park, J H; Afzaal, M; O'Brien, P; Vittal, J J



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.



Elastic Scattering of Low-Energy Electron by Lignin Precursors  

NASA Astrophysics Data System (ADS)

We present cross sections for electron collisions with monolignol precursors obtained with the Schwinger Multichannel method. For Cs phenol system, ?* resonances are found in the A" irreducible representation. So, mechanisms for dissociative electron attachment could give rise if ?* resonances are found in the monolignols.

de Oliveira, Eliane M.; Bettega, Márcio H. F.; d'A Sanchez, Sergio; Lima, Marco A. P.; Varella, Márcio T. do N.



Anthraceno-perylene bisimides: the precursor of a new acene.  


A controlled synthesis strategy for a anthracene-fused perylene bisimide was developed from the cyclization of an anthracene unit pendant to a perylene diimide scaffold. The direct cyclization led to a zigzag molecule, while a Diels-Alder strategy influenced the regiochemistry of cyclization to afford the linear precursor of a new acene. PMID:21942870

Li, Yongjun; Xu, Liang; Liu, Taifeng; Yu, Yanwen; Liu, Huibiao; Li, Yuliang; Zhu, Daoben



How vegetation impacts affect climate metrics for ozone precursors  

Microsoft Academic Search

We examine the effect of ozone damage to vegetation as caused by anthropogenic emissions of ozone precursor species and quantify it in terms of its impact on terrestrial carbon stores. A simple climate model is then used to assess the expected changes in global surface temperature from the resulting perturbations to atmospheric concentrations of carbon dioxide, methane, and ozone. The

W. J. Collins; S. Sitch; O. Boucher



AIMStar: Antimatter initiated microfusion for pre-cursor interstellar missions  

Microsoft Academic Search

We address the challenge of delivering a scientific payload to 10,000 A.U. in 50 years. This mission may be viewed as a pre-cursor to later missions to Alpha Centauri and beyond. We consider a small, aneutronic nuclear fusion engine sparked by clouds of antiprotons, and describe the principle and operation of the engine and mission parameters.

G. Gaidos; R. A. Lewis; K. Meyer; T. Schmidt; G. A. Smith




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...



Technology Transfer Automated Retrieval System (TEKTRAN)

Osteoblasts are continually recruited from stem cell pools to maintain bone. Although their immediate precursor is a plastic-adherent mesenchymal stem cell able to generate tissues other than bone, increasing evidence suggests the existence of a more primitive cell that can differentiate to both hem...


Tashironin, a plausible biosynthetic precursor of anisatin-type sesquiterpenes  

Microsoft Academic Search

The structure of tashironin (1), isolated from the wood of Illicium tashiroi, has been elucidated by extensive analysis of spectroscopic data. Tashironin represents a presumed biosynthetic precursor of anisatintype sesquiterpenes which consists of a 2-oxatricyclo[,9]heptane skeleton.

Yoshiyasu Fukuyama; Naomi Shida; Mitsuaki Kodama



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




EPA Science Inventory

Aerometric data were examined to define relationships between atmospheric NO2 and its precursors. A descriptive and critical analysis of the nationwide data base of NO2 was carried out, followed by the formulation application and testing of empirical models relating ambient NO2 c...


Acenes generated from precursors and their semiconducting properties.  


Acenes are a class of aromatic hydrocarbons composed of linearly fused benzene rings. Noteworthy features of these molecules include their extended flat structure and the narrow gap between the HOMO and LUMO energy levels. However, the preparation of larger acenes, those that are larger than pentacene, has been challenging. These molecules are relatively unstable and have low solubility in typical solvents. Recently researchers have developed a new synthesis route for higher acenes using stable and soluble "precursors," which generate these structures on demand by either heating or irradiation of light. Using this method, nonsubstituted hexacene, heptacene, octacene, and nonacene were successfully prepared. In this Account, we summarize the preparation of nonsubstituted acenes from corresponding precursors, describe their physical properties, and discuss potential applications including potential usage in organic semiconductor devices. We first introduced the concept of using a precursor in the work with pentacene. Overall, we divide this methodology into two categories: masking pentacene itself with a dienophile to form a cycloadduct and the construction of higher acenes through conventional synthetic procedures. For the first category, a diverse array of dienophiles could be chosen, depending on the processing needs, especially for use in field-effect transistors (FETs). For the second category, researchers synthesized the pentacene precursor molecules using a multistep procedure. Upon proper activation, these molecules expel small fragments to generate pentacene readily. This strategy enabled the production of pentacene andunprepared higher acenes ranging from hexacene to nonacene. This new method provides a way to unravel the fascinating chemistry of higher acenes. PMID:23611137

Watanabe, Motonori; Chen, Kew-Yu; Chang, Yuan Jay; Chow, Tahsin J



Methionine as a Precursor of Ethylene—Commentary  

Technology Transfer Automated Retrieval System (TEKTRAN)

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


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



Oligodendrocyte precursor cells in the demyelinated multiple sclerosis spinal cord  

Microsoft Academic Search

Summary Lesions appearing in the CNS of patients in the chronic phase of the inflammatory, demyelinating disease mul- tiple sclerosis often fail to repair, resulting in neuro- logical dysfunction. This failure of remyelination appears, in many cases, to be due not to the destruction of the local oligodendrocyte precursor population, a source for new myelin-forming cells, but to the failure

Guus Wolswijk



Signaling via Immunoglobulin Fc Receptors Induces Oligodendrocyte Precursor Cell Differentiation  

Microsoft Academic Search

Dramatic changes in morphology and myelin protein expression take place during the differentiation of oligodendrocyte precursor cells (OPCs) into myelinating oligodendrocytes. Fyn tyrosine kinase was reported to play a central role in the differentiation process. Molecules that could induce Fyn signaling have not been studied. Such molecules are promising therapeutic targets in demyelinating diseases. We provide evidence that the common

Jin Nakahara; Kyoko Tan-Takeuchi; Chika Seiwa; Mari Gotoh; Tomonori Kaifu; Azusa Ujike; Masanori Inui; Takeshi Yagi; Masaharu Ogawa; Sadakazu Aiso; Toshiyuki Takai; Hiroaki Asou



Interactions between oligodendrocyte precursors control the onset of CNS myelination  

Microsoft Academic Search

The formation of CNS myelin is dependent on the differentiation of oligodendrocyte precursor cells (OPCs) and oligodendrocyte maturation. How the initiation of myelination is regulated is unclear, but it is likely to depend on the development of competence by oligodendrocytes and receptivity by target axons. Here we identify an additional level of control of oligodendrocyte maturation mediated by interactions between

Yan Yang; Rebecca Lewis; Robert H. Miller



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.



Multiple-Precursor ScenariosPredicting and Reducing Campus Violence  

Microsoft Academic Search

The objectives of this research were to identify an extensive set of precursors (risk and prevention) to interpersonal violence on campus and to develop a measure to predict patterns of violence potential on campus with greater specificity. The method involved a study of 451 college students on two campuses and tested the predictive capabilities of the Violence Risk Assessment measure.

Robert F. Marcus; Bruce Swett



Synthesis of yttrium iron garnet precursor particles by homogeneous precipitation  

Microsoft Academic Search

Yttrium iron garnet (YIG) precursor particles were obtained by homogeneous precipitation in a nitrate salt solution by a reaction involving the thermal decomposition of urea. Chemical analysis indicated that solid phases were initially precipitated with sequential iron ion content. The precipitate formed was an amorphous mixed iron oxide phase. The complex composition and the thermal decomposition of the precipitate were

Y. S. Ahn; M. H. Han; C. O. Kim



Drugs of abuse (Amfetamines, BZP, cannabis, cocaine, GHB)  

Microsoft Academic Search

The features of amfetamine poisoning are related predominantly to stimulation of central and peripheral adrenergic receptors, and in severe cases, excitability, agitation, paranoid delusions, hallucinations with violent behaviour, hypertonia and hyperreflexia develop. Convulsions, rhabdomyolysis, hyperthermia, intracerebral haemorrhage and cardiac arrhythmias are less common. In addition, hyperthermia and hyponatraemia are features of severe MDMA toxicity.Benzylpiperazine (BZP) has stimulant and amfetamine-like properties.

Allister Vale


Formation of refractory inclusions by evaporation of condensate precursors  

NASA Astrophysics Data System (ADS)

Berman's (1983) activity-composition model for CaO-MgO-Al 2O 3-SiO 2 liquids is used to calculate the change in bulk chemical and isotopic composition during simultaneous cooling, evaporation, and crystallization of droplets having the compositions of reasonable condensate precursors of Types A and B refractory inclusions in CV3 chondrites. The degree of evaporation of MgO and SiO 2, calculated to be faithfully recorded in chemical and isotopic zoning of individual melilite crystals, is directly proportional to evaporation rate, which is a sensitive function of PH 2, and inversely proportional to the droplet radius and cooling rate. When the precursors are partially melted in pure hydrogen at peak temperatures in the vicinity of the initial crystallization temperature of melilite, their bulk chemical compositions evolve into the composition fields of refractory inclusions, mass-fractionated isotopic compositions of Mg, Si, and O are produced that are in the range of the isotopic compositions of natural inclusions, and melilite zoning profiles result that are similar to those observed in real inclusions. For droplets of radius 0.25 cm evaporating at PH 2 = 10 -6 bar, precursors containing 8 to 13 wt.% MgO and 20 to 23% SiO 2 evolve into objects similar to compact Type A inclusions at cooling rates of 2 to 12 K/h, depending on the precise starting composition. Precursors containing 13 to 14 wt.% MgO and 23 to 26% SiO 2 evolve into objects with the characteristics of Type B1 inclusions at cooling rates of 1.5 to 3 K/h. The relatively SiO 2-poor members of the Type B2 group can be produced from precursors containing 14 to 16 wt.% MgO and 27 to 33% SiO 2 at cooling rates of <1 K/h. Type B2's containing 27 to 35 wt.% SiO 2 and <12% MgO require precursors with higher SiO 2/MgO ratios at MgO > 15% than are found on any condensation curve. The characteristics of fluffy Type A inclusions, including their reversely zoned melilite, can only be understood in the context of this model if they contain relict melilite.

Grossman, Lawrence; Ebel, Denton S.; Simon, Steven B.



Shock Wave Precursor Measurements. Part II. Experimental Apparatus and Air Test Results.  

National Technical Information Service (NTIS)

The pneumatic and electronic devices which have been used for precursor measurements are here described. Experiments are reported that were carried out in order to check the validity of the measure method. Finally, the precursor number densities, concentr...

A. Romiti



Can precursors improve the transmission of energy at optical frequencies?  

PubMed Central

The recent interest in precursors has been fuelled by the possibility of using them for the efficient transmission of information through absorbing media at radio or optical frequencies. Here we demonstrate that the low attenuation experienced by the Brillouin precursor is attributed to the inherently low absorption of dispersive media near DC, a characteristic already exploited with communications systems using the extremely low frequency (ELF) band. Pulses, regardless of their temporal width and carrier frequency, always obey Beer's law as long as they propagate in the linear time invariant regime. We conclude with an FDTD simulation of the Maxwell–Bloch equations that shows how optical coherent bleaching effects, which take place in the linear time variant regime of the Lorentz oscillator model, can cause sustained deviations from Beer's law over relatively long distances of water.

Lukofsky, David; Bessette, Jonathan; Jeong, Heejeong; Garmire, Elsa; Osterberg, Ulf



Synthesis and antiprotozoal activity of original porphyrin precursors and derivatives.  


Importance of heme in African trypanosomes, Leishmania sp. and Plasmodium sp. metabolisms justifies considering the potential of porphyrins and their precursors and derivatives as potential antiparasitic agents by interfering with heme metabolism. Consequently, twenty-four porphyrin precursors and derivatives were evaluated against Leishmania donovani, Trypanosoma brucei and Plasmodium sp. The best active compound against Trypanosoma brucei brucei was a new porphyrin derivative; compound 4i, with a MEC value of 6.25 ?M justifying further in vivo evaluation. Whereas these compounds were not active against intramacrophage amastigotes of L. donovani, another new porphyrin derivative, compound 4f was active in vitro against Plasmodium falciparum at 20 nM and a slight delay of mice survival was observed on the Plasmodium berghei/Swiss mice model at 50 ?mol/kg/day × 4. Pharmacomodulations should be further developed relying on a better knowledge on the porphyrin behaviour into the parasites comparatively to host cells. PMID:23851117

Abada, Zahra; Cojean, Sandrine; Pomel, Sébastien; Ferrié, Laurent; Akagah, Bernardin; Lormier, Anh Tuan; Loiseau, Philippe M; Figadère, Bruno



Solar microwave precursors and coronal mass ejection: Possible connection  

SciTech Connect

There are many results concerning the phenomena of preflare activity and coronal mass ejections (CME) formation. The situation is possible that the CME is the flare response or on the contrary the CME onset initiates the flare. In a number of recent papers R.A. Harrison and his coworkers have shown that CME initiation is associated with weak soft x-ray emission. We have studied a possible connection between the solar microwave precursors and CME. Following this goal, during the period of 1989, 36.5 hour observational samples preceding solar flares were investigated. There were 8 events among them which preceded proton flares. Data have been obtained at four wavelengths (3.2 cm, 10 cm, 30 cm, 46 cm) at the Zimenki Station near Nizhny Novgorod (Russia). To investigate the precursors we used the classification accepted for the description of radio emission bursts in Solar Geophysical Data.

Sheiner, O.A.; Durasova, M.S. [Radiophysical Research Institute, Nizhny Novgorod (Russian Federation)



Fission-Based Electric Propulsion for Interstellar Precursor Missions  

SciTech Connect

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




Mode structure of disruption precursors in TFTR - ERS discharges  

NASA Astrophysics Data System (ADS)

Two types of disruption precursor have been observed in TFTR-ERS (Enhanced Reversed Shear) high performance discharges, one with a finite frequency (2-10kHz) and the other with a purely growing amplitude and nearly-zero frequency. The internal mode structure of these precursors was determined with a common mesh analysis using two ECE polychromators separated by 126 degrees. This analysis both refines the radial mode structure and detects slowly varying n=1, 2, toroidally asymmetric phenomena leading toward the disruption. These structures have been compared with the ideal external kink structure using the PEST computer code. The observed radial displacement and the mode rotation frequency, corrected for the Doppler shift, are consistent with ideal MHD theory. A detailed comparison will be presented.

Okabayashi, M.; Chang, Z.; Fredrickson, E.; Jackson, J.; Leblanc, B.; Levinton, F.; Manickam, J.; Takahashi, H.; Taylor, G.; TFTR Team



Lack of replicative senescence in cultured rat oligodendrocyte precursor cells.  


Most mammalian somatic cells are thought to have a limited proliferative capacity because they permanently stop dividing after a finite number of divisions in culture, a state termed replicative cell senescence. Here we show that most oligodendrocyte precursor cells purified from postnatal rat optic nerve can proliferate indefinitely in serum-free culture if prevented from differentiating; various cell cycle-inhibitory proteins increase, but the cells do not stop dividing. The cells maintain high telomerase activity and p53- and Rb-dependent cell cycle checkpoint responses, and serum or genotoxic drugs induce them to acquire a senescence-like phenotype. Our findings suggest that some normal rodent precursor cells have an unlimited proliferative capacity if cultured in conditions that avoid both differentiation and the activation of checkpoint responses that arrest the cell cycle. PMID:11157165

Tang, D G; Tokumoto, Y M; Apperly, J A; Lloyd, A C; Raff, M C



Viral precursor polyproteins: keys of regulation from replication to maturation.  


Many viruses use a replication strategy involving the translation of a large polyprotein, which is cleaved by viral and/or cellular proteases. Several of these viruses severely impact human health around the globe, including HIV, HCV, Dengue virus, and West Nile virus. This method of genome organization has many benefits to the virus such as condensation of genetic material, as well as temporal and spatial regulation of protein activity depending on polyprotein cleavage state. The study of polyprotein precursors is necessary to fully understand viral infection, and identify possible new drug targets; however, few atomic structures are currently available. Presented here are structures of four recent polyprotein precursors from viruses with a positive sense RNA genome. PMID:23602469

Yost, Samantha A; Marcotrigiano, Joseph



Spatially correlated disorder in self-organized precursor magnetic nanostructures  

NASA Astrophysics Data System (ADS)

We study the scaling behavior of the characteristic length of precursor magnetic nanostructures above the Curie temperature with the correlation length of quenched-in disorder. We found that the modulation length of the nanostructures ? follows the scaling law ?˜ Dmacr , where Dmacr is the average size of the magnetized regions in the material. The scaling behavior of the average size of these regions, Dmacr , with the correlation length of the disorder, ? , depends on the properties of the disorder. For Gaussian disorder, we find that Dmacr scales with the disorder correlation length as Dmacr ˜?a/2 , where a is the exponent of the leading term of the pair correlation function of the disorder in the limit r?0 , ?(r)??[1-(1/a)(r/?)a] . These results are quite general and applicable to other systems, e.g., ferroelectric precursors, independent of the nature of the long-range dipolar forces.

Porta, Marcel; Castán, Teresa; Lloveras, Pol; Planes, Antoni; Saxena, Avadh



Ionospheric precursors for the crustal earthquakes in Italy  

NASA Astrophysics Data System (ADS)

Crustal earthquakes with moderate magnitude M=5.0-6.0 observed in Italy for the period 1995-2002 were used to check if the earlier obtained relationships for middle-term ionospheric precursors are valid for these type of earthquakes. The ionospheric precursors are based on the observed variations of the sporadic E-layer parameters (h'Es, fbEs, foEs) and foF2 at the ionospheric station Rome. Empirical dependencies for the seismo-ionospheric disturbances relating the earthquake magnitude and the epicentric distance are obtained and they have been shown to be similar to those obtained earlier in other seismic regions of the world.

Perrone, L.; Zolesi, B.; Korsunova, L.



Extrusion of Magnesium Tubes for Biodegradable Stent Precursors  

Microsoft Academic Search

Production of stent precursors in the form of small-size tubes has been evaluated by hot compression tests and extrusion trials on the AZ31B and ZM21 magnesium alloys. The investigation here presented mainly reports on the effects of extrusion parameters on microstructure and properties of the tubes. Processing at 410°C and at slow strain rate (2.78 · 10 s) by a laboratory hot-extrusion system

Q. Ge; M. Vedani; G. Vimercati



Formation of refractory inclusions by evaporation of condensate precursors  

Microsoft Academic Search

Berman’s (1983) activity-composition model for CaO-MgO-Al2O3-SiO2 liquids is used to calculate the change in bulk chemical and isotopic composition during simultaneous cooling, evaporation, and crystallization of droplets having the compositions of reasonable condensate precursors of Types A and B refractory inclusions in CV3 chondrites. The degree of evaporation of MgO and SiO2, calculated to be faithfully recorded in chemical and

Lawrence Grossman; DENTON S. EBEL; STEVEN B. SIMON



Ferrocene-containing polyphenylenes as precursors of magnetic nanomaterials  

Microsoft Academic Search

New magnetic nanomaterials based on ferrocene-containing polyphenylenes were obtained. The reaction of polycyclocondensation\\u000a of 1,1?-diacetylferrocene in the presence of triethyl orthoformate and p-toluenesulfonic acid within 20–200°C under common conditions and in supercritical carbon dioxide (scCO2) was carried out for the first time to give highly branched ferrocene-containing polyphenylenes as precursors of magnetic\\u000a nanomaterials. The heating of the polyphenylenes in the

R. A. Dvorikova; L. N. Nikitin; Yu. V. Korshak; M. I. Buzin; V. A. Shanditsev; A. A. Korlyukov; I. S. Bushmarinov; S. S. Abramchuk; A. L. Rusanov; A. R. Khokhlov



Myostatin imposes reversible quiescence on embryonic muscle precursors.  


We have previously shown that Myostatin, a member of the transforming growth factor beta (TFG-beta) family of signalling molecules, is expressed in developing muscle, and that treatment with recombinant Myostatin inhibited the expression of key myogenic transcription factors during chick embryogenesis. In this study, we followed the fate of muscle precursors after exposure to Myostatin. We report that in contrast to the down-regulation in expression of Pax-3, Myf-5, MyoD, and Myogenin, expression of Pax-7 was maintained. However, Myostatin completely inhibited cell division in the Pax-7-expressing cells. The inhibitory effect of Myostatin was reversible, as upon withdrawal myogenic cells re-initiated cell proliferation as well as expression of Pax-3 and MyoD. These results led us to investigate the temporal and spatial distribution of quiescent muscle precursors during development. To this end, we analysed distribution and mitotic behaviour of Pax-7-expressing cells during muscle development. Our studies revealed two populations of Pax-7-expressing cells, one that proliferated and incorporated BrdU, whilst the other did not. At early developmental stages, a high proportion of Pax-7-expressing cells proliferated, but there was a significant number of non-dividing Pax-7-expressing cells intermingled with differentiated muscle. Proliferating precursors became less frequent as development proceeded and at late fetal stages all Pax-7-expressing cells were mitotically quiescent. We suggest that Myostatin is an important signalling molecule responsible for imposing quiescence upon myogenic precursors during embryonic and foetal development. PMID:16425219

Amthor, Helge; Otto, Anthony; Macharia, Raymond; McKinnell, Iain; Patel, Ketan



Chromophore-bearing zeolite materials as precursors of colored ceramics  

Microsoft Academic Search

This work investigates the possibility to obtain colored ceramics by firing compacts of the synthetic zeolite A, pre-loaded with chromophore metal cations, and gives also a preliminary evaluation of their technical properties. Natural zeolite-bearing materials, i.e., clinoptilolite- and phillipsite-rich tuffs, which naturally contain chromofore agents, such as iron oxides and hydroxides, have also been considered as ceramic precursors. The results

B. Liguori; A. Cassese; C. Colella



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)



Burst strain disturbance — A new test study on fracture precursor  

Microsoft Academic Search

A multi-functional high-frequency seismometer, a new instrumental system, is used for recording multi-point strain variations\\u000a of rock samples in the process of fracture development. The results indicate that strain in each point appears burst disturbance\\u000a synchronously besides a tendency variation before main fracture. The burst disturbance could probably be one of the short-impending\\u000a precursors before great earthquake.

Zhao-Yong Xu; Run-Hai Yang; Bin Wang; Jin-Ming Zhao; Yu-Feng Yao; Pei-Zhong Hua; Shi-Rong Mei



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



Latest Developments in Suspension and Liquid Precursor Thermal Spraying  

Microsoft Academic Search

The interest to manufacture onto large surfaces thick (i.e., 10-20 ?m, average thickness) finely structured or nanostructured\\u000a layers is increasingly growing since the past 10 years. This explains the interest for suspension thermal spraying (STS) and\\u000a solution precursor thermal spraying (SPTS), both allowing manufacturing finely structured layers of thicknesses varying between\\u000a a few micrometers up to a few hundreds of micrometers. STS

Pierre Fauchais; Ghislain Montavon



Synthesis of Monodispersed Magnetite Particles From Different Organometallic Precursors  

Microsoft Academic Search

Magnetite (Fe3O4) nanoparticles with very narrow particle size distribution can be obtained by decomposition of an organometallic compound in the presence of oleic acid. It has been shown that the carboxylic acid catalyzes the reaction leading to decreased decomposition temperatures and, consequently, as the surfactant concentration increases, smaller particles are formed. Precursors such as Fe(CO)5, iron acetylacetonate, and iron-oleate complexes,

A. G. Roca; M. P. Morales; C. J. Serna



Crystallization of a coprecipitated mullite precursor during heat treatment  

Microsoft Academic Search

Powder of mullite composition (3Al2O3·2SiO2) has been made by a coprecipitation method. The evolution of mullite in this precursor powder during heat treatment has been studied using differential thermal analysis, electron microscopy and X-ray diffraction techniques. It is shown that during calcination below 1100°C the coprecipitate develops ?-Al2O3 and perhaps cristobalite crystallites within the basic grains, whose morphology is otherwise

S. Rajendran; H. J. Rossell; J. V. Sanders



AIMStar: Antimatter Initiated Microfusion For Precursor Interstellar Missions  

Microsoft Academic Search

We address the challenge of delivering a scientific payload to 10,000 A.U. in 50 years. This mission may be viewed as a pre-cursor to later missions to Alpha Centauri and beyond. We consider a small, nuclear fusion engine sparked by clouds of antiprotons, and describe the principle and operation of the engine and mission parameters. An R&D program currently in

Raymond A. Lewis; Kirby Meyer; Gerald A. Smith; Steven D. Howe


The miR-10 microRNA precursor family  

PubMed Central

The miR-10 microRNA precursor family encodes a group of short non-coding RNAs involved in gene regulation. The miR-10 family is highly conserved and has sparked the interest of many research groups because of the genomic localization in the vicinity of, coexpression with and regulation of the Hox gene developmental regulators. Here, we review the current knowledge of the evolution, physiological function and involvement in cancer of this family of microRNAs.



Axon-myelin transfer of phospholipids and phospholipid precursors  

Microsoft Academic Search

Previous studies have provided evidence for axon-to-myelin transfer of intact lipids and lipid precursors for reutilization\\u000a by myelin enzymes. Several of the lipid constituents of myelin showed significant contralateral\\/ipsilateral ratios of incorporated\\u000a radioactivity, indicative of axonal origin, whereas proteins and certain other lipids did not participate in this transfer-reutilization\\u000a process. The present study will examine the labeling of myelin phosphoinositides

Robert W. Ledeen; Francis Golly; James E. Haley



Hydroxycinnamic acid ethyl esters as precursors to ethylphenols in wine.  


A method for determining ethyl coumarate and ethyl ferulate in wine using GC-MS with deuterium-labeled analogues has been developed and used to measure the evolution of these two esters during the production of two commercial monovarietal red wines, cv. Grenache and Shiraz. During fermentation, the concentration of ethyl coumarate rose from low levels to 0.4 mg/L in Grenache and 1.6 mg/L in Shiraz wines. These concentrations then increased further during barrel aging to 1.4 and 3.6 mg/L, respectively. The concentration of ethyl ferulate was much lower, reaching a maximum of only 0.09 mg/L. Conversion of ethyl coumarate and ethyl ferulate to their corresponding ethylphenols was observed during fermentations of a synthetic medium with two strains of Dekkera bruxellensis (AWRI 1499 and AWRI 1608), while a third (strain AWRI 1613) produced no ethylphenols at all from these precursors. Strains AWRI 1499 and 1608 produced 4-ethylphenol from ethyl coumarate in 68% and 57% yields, respectively. The corresponding yields of 4-ethylguaiacol from ethyl ferulate were much lower, 7% and 3%. Monitoring of ethyl coumarate and ethyl ferulate concentration during the Dekkera fermentations showed that the selectivity for ethylphenol production according to yeast strain and the precursor was principally a result of variation in esterase activity. Consequently, ethyl coumarate can be considered to be a significant precursor to 4-ethylphenol in wines affected by these two strains of Brettanomyces/Dekkera yeast, while ethyl ferulate is not an important precursor to 4-ethylguaiacol. PMID:22324721

Hixson, Josh L; Sleep, Nicola R; Capone, Dimitra L; Elsey, Gordon M; Curtin, Christopher D; Sefton, Mark A; Taylor, Dennis K



Global tropospheric ozone dynamics. Part I: Tropospheric ozone precursors.  


An overview of the tropospheric ozone changes is presented focussing mainly on the tropospheric ozone precursors. The complexity of the problem is shown through the consideration of a great number of relevant substances, like nitrogen compounds, volatile organic compounds, peroxyacetyl nitrate, hydroxyl radical, carbon monoxide, alkyl nitrates. The up-to-date knowledge on the relevant numerical modelling is presented in Part II. PMID:11370655

Kondratyev, K Y; Varotsos, C A



Epidermal sphingomyelins are precursors for selected stratum corneum ceramides  

Microsoft Academic Search

Epidermal ceramides (Cer) comprise a heteroge- neous family of seven species, including two unique v -hydroxylated Cer, that are key components of the stratum corneum (SC) intercellular lamellar membranes responsi- ble for the epidermal permeability barrier. Although both glucosylceramide (GlcCer) and the phospho-sphingolipid sphingomyelin (SM) are potential precursors of SC Cer, based on reported chemical structures of epidermal GlcCer and

Yoshikazu Uchida; Mariko Hara; Hiroyuki Nishio; Ellen Sidransky; Shintaro Inoue; Fujio Otsuka; Akemi Suzuki; Peter M. Elias; Walter M. Holleran; Sumiko Hamanaka


Preparation of zinc sulfide nanocrystallites from single-molecule precursors  

Microsoft Academic Search

Zinc sulfide nanocrystallites were prepared using Zinc(II) thiosemicarbazone complexes of the types Zn(L)2 and ZnCl2(LH)2 (where, LH=thiosemicarbazones of cinnamaldehyde, 4-chlorobenzaldehyde, indol-3-carboxaldehyde and thiophene-2-carboxaldehyde) as single source precursors by solvothermal decomposition in ethylene glycol and ethylene diamine in few cases. The materials were characterized by powder X-ray diffraction (XRD), transmission electron microscopy (TEM), selected area electron diffraction, energy dispersive X-ray analysis

Anil M. Palve; Shivram S. Garje



Precursor transformation method for damage detection in structures  

NASA Astrophysics Data System (ADS)

In this paper, a new concept for damage detection and long- term health monitoring of structures is presented. The Precursor Transformation Method (PTM) is based on determining the causes (precursors) of change in the measured state of the structure under non-variable loading conditions (e.g. dead loads in bridges). The PTM concept addresses the inability of the current structural monitoring methods to discriminate, in structural behavior terms, the meaning of voluminous measured sensor data on a timely and cost effective basis. This method offers advantages in sensitivity and cost efficiency when compared to conventional vibration-based or parameter estimation methods. PTM was developed as part of a research project sponsored by the Federal Highway Administration on bridge stay cable condition assessment. Measured changes in the state of a structure (displacements, strains, internal forces) can be related to precursors through a transformation matrix. This matrix is formed by determining the patterns of change in the state of structure associated with externally imposed strains (temperatures) or displacements representing possible damage scenarios. A finite element model of the undamaged structure is used to calculate these patterns. The use of an undamaged model of the structure in determining damage patterns simplifies the calculation process significantly, while introducing some approximation in results. Theoretical derivations and special case studies indicate that these approximations are limited to second order effects, and in many cases well within measurement and calculation accuracies. Examples using simulated damages on two truss structures and a cable-stayed bridge are also presented.

Mehrabi, Armin B.; Tabatabai, Habib; Lotfi, Hamid R.



Multicomponent Assembly of Proposed DNA Precursors in Water  

PubMed Central

We propose a novel pathway for the prebiotic synthesis of 2?-deoxynucleotides. Consideration of the constitutional chemical relationships between glycolaldehyde and ?-mercapto-acetaldehyde, and the corresponding proteinogenic amino acids, serine and cysteine, led us to explore the consequences of the corresponding sulfur substitution for our previously proposed pathways leading to the canonical ribonucleotides. We demonstrate that just as 2-aminooxazole–an important prebiotic ribonucleotide precursor–is readily formed from glycolaldehyde and cyanamide, so is 2-aminothiazole formed from ?-mercapto-acetaldehyde and cyanamide in water at neutral pH. Indeed, both the oxazole and the thiazole can be formed together in a one-pot reaction, and can be co-purified by crystallization or sublimation. We then show that 2-aminothiazole can take part in a 3-component carbon–carbon bond-forming reaction in water that leads to the diastereoselective synthesis of masked 2?-thiosugars regiospecifically tethered to purine precursors, which would lead to 2?-deoxynucleotides upon desulfurization. The possibility of an abiotic route to the 2?-deoxynucleotides provides a new perspective on the evolutionary origins of DNA. We also show that 2-aminothiazole is able to sequester, through reversible aminal formation, the important nucleotide precursors glycolaldehyde and glyceraldehyde in a stable, crystalline form.



Prolactin Stimulates Precursor Cells in the Adult Mouse Hippocampus  

PubMed Central

In the search for ways to combat degenerative neurological disorders, neurogenesis-stimulating factors are proving to be a promising area of research. In this study, we show that the hormonal factor prolactin (PRL) can activate a pool of latent precursor cells in the adult mouse hippocampus. Using an in vitro neurosphere assay, we found that the addition of exogenous PRL to primary adult hippocampal cells resulted in an approximate 50% increase in neurosphere number. In addition, direct infusion of PRL into the adult dentate gyrus also resulted in a significant increase in neurosphere number. Together these data indicate that exogenous PRL can increase hippocampal precursor numbers both in vitro and in vivo. Conversely, PRL null mice showed a significant reduction (approximately 80%) in the number of hippocampal-derived neurospheres. Interestingly, no deficit in precursor proliferation was observed in vivo, indicating that in this situation other niche factors can compensate for a loss in PRL. The PRL loss resulted in learning and memory deficits in the PRL null mice, as indicated by significant deficits in the standard behavioral tests requiring input from the hippocampus. This behavioral deficit was rescued by direct infusion of recombinant PRL into the hippocampus, indicating that a lack of PRL in the adult mouse hippocampus can be correlated with impaired learning and memory.

Walker, Tara L.; Vukovic, Jana; Koudijs, Margaretha M.; Blackmore, Daniel G.; Mackay, Eirinn W.; Sykes, Alex M.; Overall, Rupert W.; Hamlin, Adam S.; Bartlett, Perry F.



Observations of electromagnetic whistler precursors at supercritical interplanetary shocks  

NASA Astrophysics Data System (ADS)

We present observations of electromagnetic precursor waves, identified as whistler mode waves, at supercritical interplanetary shocks using the Wind search coil magnetometer. The precursors propagate obliquely with respect to the local magnetic field, shock normal vector, solar wind velocity, and they are not phase standing structures. All are right-hand polarized with respect to the magnetic field (spacecraft frame), and all but one are right-hand polarized with respect to the shock normal vector in the normal incidence frame. They have rest frame frequencies fci < f ? fce and wave numbers 0.02 ? k?ce ? 5.0. Particle distributions show signatures of specularly reflected gyrating ions, which may be a source of free energy for the observed modes. In one event, we simultaneously observe perpendicular ion heating and parallel electron acceleration, consistent with wave heating/acceleration due to these waves. Although the precursors can have ?B/Bo as large as 2, fluxgate magnetometer measurements show relatively laminar shock transitions in three of the four events.

Wilson, L. B., III; Koval, A.; Szabo, A.; Breneman, A.; Cattell, C. A.; Goetz, K.; Kellogg, P. J.; Kersten, K.; Kasper, J. C.; Maruca, B. A.; Pulupa, M.



Multicomponent assembly of proposed DNA precursors in water.  


We propose a novel pathway for the prebiotic synthesis of 2'-deoxynucleotides. Consideration of the constitutional chemical relationships between glycolaldehyde and ?-mercapto-acetaldehyde, and the corresponding proteinogenic amino acids, serine and cysteine, led us to explore the consequences of the corresponding sulfur substitution for our previously proposed pathways leading to the canonical ribonucleotides. We demonstrate that just as 2-aminooxazole-an important prebiotic ribonucleotide precursor-is readily formed from glycolaldehyde and cyanamide, so is 2-aminothiazole formed from ?-mercapto-acetaldehyde and cyanamide in water at neutral pH. Indeed, both the oxazole and the thiazole can be formed together in a one-pot reaction, and can be co-purified by crystallization or sublimation. We then show that 2-aminothiazole can take part in a 3-component carbon-carbon bond-forming reaction in water that leads to the diastereoselective synthesis of masked 2'-thiosugars regiospecifically tethered to purine precursors, which would lead to 2'-deoxynucleotides upon desulfurization. The possibility of an abiotic route to the 2'-deoxynucleotides provides a new perspective on the evolutionary origins of DNA. We also show that 2-aminothiazole is able to sequester, through reversible aminal formation, the important nucleotide precursors glycolaldehyde and glyceraldehyde in a stable, crystalline form. PMID:22839703

Powner, Matthew W; Zheng, Shao-Liang; Szostak, Jack W



Precursor Effects in Different Cases of Forbush Decreases  

NASA Astrophysics Data System (ADS)

Over the last few years, the pre-decreases or pre-increases of the cosmic-ray intensity observed before a Forbush decrease, called the precursor effect and registered by the worldwide neutron monitor network, have been investigated for different cases of intense events. The Forbush decreases presented in this particular study were chosen from a list of events that occurred in the time period 1967 - 2006 and were characterized by an enhanced first harmonic of cosmic-ray anisotropy prior to the interplanetary disturbance arrival. The asymptotic longitudinal cosmic-ray distribution diagrams for the events under consideration were studied using the “Ring of Stations” method, and data on solar flares, solar-wind speed, geomagnetic indices, and interplanetary magnetic field were analyzed in detail. The results revealed that the use of this method allowed the selection of a large number of events with well-defined precursors, which could be separated into at least three categories, according to duration and longitudinal zone. Finally, this analysis showed that the first harmonic of cosmic-ray anisotropy could serve as an adequate tool in the search for precursors and could also be evidence for them.

Papailiou, M.; Mavromichalaki, H.; Belov, A.; Eroshenko, E.; Yanke, V.



Assigning probability gain for precursors of four large Chinese earthquakes  

SciTech Connect

We extend the concept of probability gain associated with a precursor (Aki, 1981) to a set of precursors which may be mutually dependent. Making use of a new formula, we derive a criterion for selecting precursors from a given data set in order to calculate the probability gain. The probabilities per unit time immediately before four large Chinese earthquakes are calculated. They are approximately 0.09, 0.09, 0.07 and 0.08 per day for 1975 Haicheng (M = 7.3), 1976 Tangshan (M = 7.8), 1976 Longling (M = 7.6), and Songpan (M = 7.2) earthquakes, respectively. These results are encouraging because they suggest that the investigated precursory phenomena may have included the complete information for earthquake prediction, at least for the above earthquakes. With this method, the step-by-step approach to prediction used in China may be quantified in terms of the probability of earthquake occurrence. The ln P versus t curve (where P is the probability of earthquake occurrence at time t) shows that ln P does not increase with t linearly but more rapidly as the time of earthquake approaches.

Cao, T.; Aki, K.



Assigning probability gain for precursors of four large Chinese earthquakes  

NASA Astrophysics Data System (ADS)

We extend the concept of probability gain associated with a precursor (Aki, 1981) to a set of precursors which may be mutually dependent. Making use of a new formula, we derive a criterion for selecting precursors from a given data set in order to calculate the probability gain. The probabilities per unit time immediately before four large Chinese earthquakes are calculated. They are approximately 0.09, 0.09, 0.07 and 0.08 per day for 1975 Haicheng (M = 7.3), 1976 Tangshan (M = 7.8), 1976 Longling (M = 7.6), and Songpan (M - 7.2) earthquakes, respectively. These results are encouraging because they suggest that the investigated precursory phenomena may have included the complete information for earthquake prediction, at least for the above earthquakes. With this method, the step-by-step approach to prediction used in China may be quantified in terms of the probability of earthquake occurrence. The ln P versus t curve (where P is the probability of earthquake occurrence at time t) shows that ln P does not increase with t linearly but more rapidly as the time of earthquake approaches.

Cao, Tianqing; Aki, Keiiti



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



Bridged Dithienylethylenes as Precursors of Small Bandgap Electrogenerated Conjugated Polymers.  


Bridged dithienylethylenes (DTEs) bearing solubilizing alkyl chains at various positions (2-5) have been synthesized by McMurry dimerization of cyclopenta[b]thiophen-6-ones. In order to introduce alkyl substituents at different positions of the DTE molecule, the precursor ketones have been prepared by different strategies based on a combination of Mannich or Wittig-Horner reaction and Friedel-Craft intramolecular cyclization. The position and the length of the alkyl substituents exert a strong effect on the ability of the precursor to undergo electrochemical polymerization. Thus, whereas substitution at the alpha-position of the ethylene linkage (3) results in a rapid inhibition of electropolymerization, introduction of alkyl chains at the beta-position (4, 5) greatly improves the efficiency of the polymerization process. The analysis of the electrochemical and optical properties of the polymers shows that rigidification of the DTE molecule leads to a significant decrease of the oxidation potential and bandgap. A comparative analysis of DTE and its bridged analogues by means of X-ray diffraction reveals, in agreement with experimental and theoretical results, that the observed reduction of both the HOMO-LUMO gap of the precursor and the bandgap of the corresponding polymers are related to a relaxation of bond length alternation in the DTE moiety. PMID:11671573

Blanchard, Philippe; Brisset, Hugues; Illien, Bertrand; Riou, Amédée; Roncali, Jean



Classification of breast cancer precursors through exhaled breath.  


Certain benign breast diseases are considered to be precursors of invasive breast cancer. Currently available techniques for diagnosing benign breast conditions lack accuracy. The purpose of this study was to deliver a proof-of-concept for a novel method that is based on breath testing to identify breast cancer precursors. Within this context, the authors explored the possibility of using exhaled alveolar breath to identify and distinguish between benign breast conditions, malignant lesions, and healthy states, using a small-scale, case-controlled, cross-sectional clinical trial. Breath samples were collected from 36 volunteers and were analyzed using a tailor-made nanoscale artificial NOSE (NA-NOSE). The NA-NOSE signals were analyzed using two independent methods: (i) principal component analysis, ANOVA and Student's t-test and (ii) support vector machine analysis to detect statistically significant differences between the sub-populations. The NA-NOSE could distinguish between all studied test populations. Breath testing with a NA-NOSE holds future potential as a cost-effective, fast, and reliable diagnostic test for breast cancer risk factors and precursors, with possible future potential as screening method. PMID:21190078

Shuster, Gregory; Gallimidi, Zahava; Reiss, Asnat Heyman; Dovgolevsky, Ekaterina; Billan, Salem; Abdah-Bortnyak, Roxolyana; Kuten, Abraham; Engel, Ahuva; Shiban, Ala; Tisch, Ulrike; Haick, Hossam



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)



Genetic Programming of Conventional Features to Detect Seizure Precursors.  


This paper presents an application of genetic programming (GP) to optimally select and fuse conventional features (C-features) for the detection of epileptic waveforms within intracranial electroencephalogram (IEEG) recordings that precede seizures, known as seizure-precursors. Evidence suggests that seizure-precursors may localize regions important to seizure generation on the IEEG and epilepsy treatment. However, current methods to detect epileptic precursors lack a sound approach to automatically select and combine C-features that best distinguish epileptic events from background, relying on visual review predominantly. This work suggests GP as an optimal alternative to create a single feature after evaluating the performance of a binary detector that uses: 1) genetically programmed features; 2) features selected via GP; 3) forward sequentially selected features; and 4) visually selected features. Results demonstrate that a detector with a genetically programmed feature outperforms the other three approaches, achieving over 78.5% positive predictive value, 83.5% sensitivity, and 93% specificity at the 95% level of confidence. PMID:19050744

Smart, Otis; Firpi, Hiram; Vachtsevanos, George



Precursors of primary nucleation induced by flow in isotactic polypropylene  

NASA Astrophysics Data System (ADS)

Small-angle X-ray scattering (SAXS) patterns of the sheared isotactic polypropylene (i-PP) melt at /175°C, above the nominal melting point of /162°C, showed development of oriented structures or aggregates of polymer molecules that did not disappear even after a long time relaxation (up to 2h). However, the corresponding wide-angle X-ray diffraction (WAXD) patterns did not show any visible Bragg reflections, suggesting that the induced structures are probably non-crystalline. The results suggest that metastable aggregates of polymer molecules are generated in the melt by assembly of bundle of oriented chain segments (especially in long chains). We speculate that the oriented aggregates of chain segments are precursors of primary nuclei. The spatial arrangement of these precursors showed a layer-like superstructure, evident by the appearance of the meridional maxima in SAXS. The spacing between the `layers' was estimated to be 430Å. A microstructural model of the orientation-induced precursors for primary nucleation is presented. An Avrami model was used to fit the evolution of the oriented structures in i-PP melt, which provided insights into the early stages of polymer crystallization.

Somani, Rajesh H.; Yang, Ling; Hsiao, Benjamin S.



Lineage-restricted neuronal precursors and methods of isolation  

US Patent & Trademark Office Database

A self-renewing restricted stem cell population has been identified in developing (embryonic day 13.5) spinal cords that can differentiate into multiple neuronal phenotypes, but cannot differentiate into glial phenotypes. This neuronal-restricted precursor (NRP) expresses highly polysialated or embryonic neural cell adhesion molecule (E-NCAM) and is morphologically distinct from neuroepithelial stem cells (NEP cells) and spinal glial progenitors derived from embryonic day 10.5 spinal cord. NRP cells self renew over multiple passages in the presence of fibroblast growth factor (FGF) and neurotrophin 3 (NT-3) and express a characteristic subset of neuronal epitopes. When cultured in the presence of RA and the absence of FGF, NRP cells differentiate into GABAergic, glutaminergic, and cholinergic immunoreactive neurons. NRP cells can also be generated from multipotent NEP cells cultured from embryonic day 10.5 neural tubes. Clonal analysis shows that E-NCAM immunoreactive NRP cells arise from an NEP progenitor cell that generates other restricted CNS precursors. The NEP-derived E-NCAM immunoreactive cells undergo self renewal in defined medium and differentiate into multiple neuronal phenotypes in mass and clonal culture. Thus, a direct lineal relationship exists between multipotential NEP cells and more restricted neuronal precursor cells present in vivo at embryonic day 13.5 in the spinal cord. Methods for treating neurological diseases are also disclosed.



Genetic Programming of Conventional Features to Detect Seizure Precursors  

PubMed Central

This paper presents an application of genetic programming (GP) to optimally select and fuse conventional features (C-features) for the detection of epileptic waveforms within intracranial electroencephalogram (IEEG) recordings that precede seizures, known as seizure-precursors. Evidence suggests that seizure-precursors may localize regions important to seizure generation on the IEEG and epilepsy treatment. However, current methods to detect epileptic precursors lack a sound approach to automatically select and combine C-features that best distinguish epileptic events from background, relying on visual review predominantly. This work suggests GP as an optimal alternative to create a single feature after evaluating the performance of a binary detector that uses: 1) genetically programmed features; 2) features selected via GP; 3) forward sequentially selected features; and 4) visually selected features. Results demonstrate that a detector with a genetically programmed feature outperforms the other three approaches, achieving over 78.5% positive predictive value, 83.5% sensitivity, and 93% specificity at the 95% level of confidence.

Smart, Otis; Firpi, Hiram; Vachtsevanos, George



A conserved threonine spring-loads precursor for intein splicing.  


Protein splicing is an autocatalytic process where an "intein" self-cleaves from a precursor and ligates the flanking N- and C-"extein" polypeptides. Inteins occur in all domains of life and have myriad uses in biotechnology. Although the reaction steps of protein splicing are known, mechanistic details remain incomplete, particularly the initial peptide rearrangement at the N-terminal extein/intein junction. Recently, we proposed that this transformation, an N-S acyl shift, is accelerated by a localized conformational strain, between the intein's catalytic cysteine (Cys1) and the neighboring glycine (Gly-1) in the N-extein. That proposal was based on the crystal structure of a catalytically competent trapped precursor. Here, we define the structural origins and mechanistic relevance of the conformational strain using a combination of quantum mechanical simulations, mutational analysis, and X-ray crystallography. Our results implicate a conserved, but largely unstudied, threonine residue of the Ssp DnaE intein (Thr69) as the mediator of conformational strain through hydrogen bonding. Further, the strain imposed by this residue is shown to position the splice junction in a manner that enhances the rate of the N-S acyl shift substantially. Taken together, our results not only provide fundamental understanding of the control of the first step of protein splicing but also have important implications in various biotechnological applications that require precursor manipulation. PMID:23423655

Dearden, Albert K; Callahan, Brian; Roey, Patrick Van; Li, Zhong; Kumar, Utsav; Belfort, Marlene; Nayak, Saroj K



Aqueous sol–gel synthesis of nanosized ceramic composite powders with metal-formate precursors  

Microsoft Academic Search

In the present investigation, a series of multicomponent silicate systems have been prepared by using an aqueous sol–gel method, where water-soluble metal formates were used as precursors. Tetraethoxy silane and metal formates were used as precursors and water was used as solvent. The gels prepared using these precursors were calcined at different temperatures and characterized by using XRD, IR, DTA,

N. N Ghosh; P Pramanik



Functional Analysis of Precursors for Serious Problem Behavior and Related Intervention  

ERIC Educational Resources Information Center

|Precursor behaviors are innocuous behaviors that reliably precede the occurrence of problem behavior. Intervention efforts applied to precursors might prevent the occurrence of severe problem behavior. We examined the relationship between precursor behavior and problem behavior in three individuals with developmental disabilities. First, a…

Langdon, Nancy A.; Carr, Edward G.; Owen-DeSchryver, Jamie S.



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.



Activated Notch2 Signaling Inhibits Differentiation of Cerebellar Granule Neuron Precursors by Maintaining Proliferation  

Microsoft Academic Search

In the developing cerebellar cortex, granule neuron precursors (GNPs) proliferate and commence differentiation in a superficial zone, the external granule layer (EGL). The molecular basis of the transition from proliferating precursors to immature differentiating neurons remains unknown. Notch signaling is an evolutionarily conserved pathway regulating the differentiation of precursor cells of many lineages. Notch2 is specifically expressed in proliferating GNPs

David J. Solecki; XiaoLin Liu; Toshifumi Tomoda; Yin Fang; Mary E. Hatten



Analysis of electrical brain waves in neurotoxicology: ?-hydroxybutyrate.  


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 alpha(1) 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 beta(2) 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



Precursors for liver gluconeogenesis in periparturient dairy cows.  


The review is based on a compiled data set from studies quantifying liver release of glucose concomitant with uptake of amino acids (AA) and other glucogenic precursors in periparturient dairy cows. It has become dogma that AAs are significant contributors to liver gluconeogenesis in early lactation, presumably accounting for the observed lack of glucogenic precursors to balance estimated glucose need. Until recently, there has been paucity in quantitative data on liver nutrient metabolism in the periparturient period. Propionate is the quantitatively most important glucogenic precursor throughout the periparturient period. However, the immediate post partum increment in liver release of glucose is not followed by an equivalent increment in propionate uptake, because of the lower rate of increment in feed intake compared with the rate of increment in requirements for milk synthesis. The quantitative data on liver metabolism of AA do not support the hypothesis that the rapid post partum increase in net liver release of glucose is supported by increased utilisation of AA for gluconeogenesis. Only alanine is likely to contribute to liver release of glucose through its role in the inter-organ transfer of nitrogen from catabolised AA. AAs seem to be prioritised for anabolic purposes, indicating the relevance of investigating effects of supplying additional protein to post partum dairy cows. Combining data from quantitative and qualitative experimental techniques on L-lactate metabolism point to the conclusion that the quantitatively most important adaptation of metabolism to support the increased glucose demand in the immediate post partum period is endogenous recycling of glucogenic carbon through lactate. This is mediated by a dual site of adaptation of metabolism in the liver and in the peripheral tissues, where the liver affinity for L-lactate is increased and glucose metabolism in peripheral tissues is shifted towards L-lactate formation over complete oxidation. PMID:23823867

Larsen, M; Kristensen, N B



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.

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



Precursor lesions and prognostic factors in primary peritoneal serous carcinoma.  


Primary peritoneal serous carcinoma (PPSC) is uncommon and precursor lesions and prognostic factors are incompletely understood or described. Charts of 22 women with PPSC were reviewed for clinical and pathology data. Glass slides were reviewed for areas of PPSC, ovarian surface epithelium (OSE), ovarian cortical inclusion cysts (OCICs), tubal epithelial atypia (TEA), and serous tubal intraepithelial carcinoma (STIC). p53 and p16 immunohistochemical staining was scored and expression between the sites was compared. PPSC outcome was correlated with biomarker expression and clinicopathologic variables. p53 and p16 scores were significantly higher among PPSC and tubes than OSE and OCICs. Approximately 64% of PPSC, 46% of fallopian tubes, and none of the OSE overexpressed both biomarkers. OCICs were more frequently negative. Tubal pathologies of STIC, TEA and/or p53 signatures were present in approximately 46% of PPSC cases and the association with tubal p53 overexpression was significant. Statistically significant associations between tubal pathologies, OSE and OCICs biomarker expression profiles and their PPSC expression profiles did not occur. The median overall survival was 53 months and low-grade tumors had a better prognosis (P=0.02). A role for p53 and p16 overexpression in the formation of some PPSC, and p53 overexpression in the generation of precursor tubal pathology was identified. The high frequency of tubal pathology overexpressing p53 and low frequency of OSE and OCICs expressing either biomarker highlights a possible precursor role for the tube in some PPSC. Tumor grade was the only significant prognostic factor. PMID:24071870

Lee, Sandra; Nelson, Gregg; Duan, Quili; Magliocco, Anthony M; Duggan, Máire A



3? processing of eukaryotic precursor tRNAs  

PubMed Central

Biogenesis of eukaryotic tRNAs requires transcription by RNA polymerase III and subsequent processing. 5? processing of precursor tRNA occurs by a single mechanism, cleavage by RNase P, and usually occurs before 3? processing although some conditions allow observation of the 3?-first pathway. 3? processing is relatively complex and is the focus of this review. Precursor RNA 3? end formation begins with pol III termination generating a variable length 3? oligo(U) tract that represents an underappreciated and previously unreviewed determinant of processing. Evidence that the pol III-intrinsic 3? exonuclease activity mediated by Rpc11p affects 3? oligo(U) length is reviewed. In addition to multiple 3? nucleases, pre-tRNA processing involves La and Lsm, distinct oligo(U)-binding proteins with proposed chaperone activities. 3? processing is performed by the endonuclease RNase Z or the exonuclease Rex1p (possibly others) along alternate pathways conditional on La. We review a S. pombe tRNA reporter system that has been used to distinguish two chaperone activities of La protein to its two conserved RNA binding motifs. Pre-tRNAs with structural impairments are degraded by a nuclear surveillance system that mediates polyadenylation by the TRAMP complex followed by 3? digestion by the nuclear exosome which appears to compete with 3? processing. We also try to reconcile limited data on pre-tRNA processing and Lsm proteins which largely affects precursors but not mature tRNAs. A pathway is proposed in which 3? oligo(U) length is a primary determinant of La binding with subsequent steps distinguished by 3? endo- vs. exo- nucleases, chaperone activities and nuclear surveillance.

Maraia, Richard J.; Lamichhane, Tek N.



Derivation of Glial Restricted Precursors from E13 mice  

PubMed Central

This is a protocol for derivation of glial restricted precursor (GRP) cells from the spinal cord of E13 mouse fetuses. These cells are early precursors within the oligodendrocytic cell lineage. Recently, these cells have been studied as potential source for restorative therapies in white matter diseases. Periventricular leukomalacia (PVL) is the leading cause of non-genetic white matter disease in childhood and affects up to 50% of extremely premature infants. The data suggest a heightened susceptibility of the developing brain to hypoxia-ischemia, oxidative stress and excitotoxicity that selectively targets nascent white matter. Glial restricted precursors (GRP), oligodendrocyte progenitor cells (OPC) and immature oligodendrocytes (preOL) seem to be key players in the development of PVL and are the subject of continuing studies. Furthermore, previous studies have identified a subset of CNS tissue that has increased susceptibility to glutamate excitotoxicity as well as a developmental pattern to this susceptibility. Our laboratory is currently investigating the role of oligodendrocyte progenitors in PVL and use cells at the GRP stage of development. We utilize these derived GRP cells in several experimental paradigms to test their response to select stresses consistent with PVL. GRP cells can be manipulated in vitro into OPCs and preOL for transplantation experiments with mouse PVL models and in vitro models of PVL-like insults including hypoxia-ischemia. By using cultured cells and in vitro studies there would be reduced variability between experiments which facilitates interpretation of the data. Cultured cells also allows for enrichment of the GRP population while minimizing the impact of contaminating cells of non-GRP phenotype.

Phillips, Andre W.; Falahati, Sina; DeSilva, Roshi; Shats, Irina; Marx, Joel; Arauz, Edwin; Kerr, Douglas A.; Rothstein, Jeffrey D.; Johnston, Michael V.; Fatemi, Ali



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



Cytoplasmic Incorporation of a Ribonucleic Acid Precursor in Amoeba proteus  

PubMed Central

The question of RNA synthesis in enucleate cytoplasm of Amoeba has been approached experimentally by incubating enucleate amoebae in a labelled RNA precursor and determining the incorporation into RNA autoradiographically. The results indicate that there is a cytoplasmic incorporation mechanism which can operate in the absence of the nucleus. A comparison is made between Acetabularia and Amoeba with respect to the origins of cytoplasmic RNA. It is concluded that the existing data are consistent with the assumption that some cytoplasmic RNA is of nuclear origin in both organisms.

Plaut, Walter; Rustad, Ronald C.



Survey of volatile oxylipins and their biosynthetic precursors in bryophytes.  


Oxylipins are metabolites which are derived from the oxidative fragmentation of polyunsaturated fatty acids. These metabolites play central roles in plant hormonal regulation and defense. Here we survey the production of volatile oxylipins in bryophytes and report the production of a high structural variety of C5, C6, C8 and C9 volatiles of mosses. In liverworts and hornworts oxylipin production was not as pronounced as in the 23 screened mosses. A biosynthetic investigation revealed that both, C18 and C20 fatty acids serve as precursors for the volatile oxylipins that are mainly produced after mechanical wounding of the green tissue of mosses. PMID:20079505

Croisier, Emmanuel; Rempt, Martin; Pohnert, Georg



Pseudogap Precursors in Optimal Doped EuBCO  

NASA Astrophysics Data System (ADS)

For the pseudogap phase, an important feature of cuprate superconductivity, Varma et al. predict the existence of loop currents. By means of Maximum Entropy analysis, we investigate transverse field ?SR data of optimal-doped EuBa2Cu3O7-? (Tc = 93 K). To search for precursor effects, and for predicted pseudogap loop currents, our focus is on a temperature interval between Tc and T*. An extra drop in normal-state frequency indicates demagnetization effects, possibly caused by short-living Cooper-pairs in the Cu-O2 planes. In sum, our results suggest magnetic roots of cuprate superconductivity.

Schwartz, R.



Rhizomucor miehei triglyceride lipase is synthesized as a precursor  

Microsoft Academic Search

ARhizomucor miehie cDNA library constructed inEscherichia coli was screened with synthetic oligonucleotides designed from knowledge of a partial amino acid sequence of the secreted triglyceride\\u000a lipase (triacyl-glycerol acylhydrolase EC from this fungus. Lipase-specific recombinants were isolated and their\\u000a insert sequenced. Unlike characterized bacterial and mammalian triglyceride lipases, the fungal enzyme is synthesized as a\\u000a precursor, including a 70 amino

Esper Boel; Birgitte Huge-Jensen; Mogens Christensen; Lars Thim; Niels P. Fiil



Transport of peroxisomal proteins synthesized as large precursors in plants  

Microsoft Academic Search

Plant peroxisomes contain at least four proteins, namely, citrate synthase, malate dehydrogenase, long-chain acyl-CoA oxidase,\\u000a and 3-ketoacyl-CoA thiolase, which are synthesized as large precursors with an N-terminal cleavable presequence. Each presequence\\u000a has a conserved domain (R[I\\/L.\\/Q]-X5-HL) that is homologous to peroxisomal targeting signal 2 from mammals and yeasts. In addition, a cysteine residue is found\\u000a at the C-terminal ends of

Akira Kato; Makoto Hayashi; Maki Kondo; Mikio Nishimura



The Search for Precursor and Aftershock Dynamics in Aqueous Foam  

NASA Astrophysics Data System (ADS)

We probe the dynamics of an aqueous foam sample using optical photon correlation spectroscopy. Using a multi-speckle detection scheme to record the changes in a coherent laser speckle pattern, we gain insight into the nature of the dynamics in the foam during the aging process. We introduce Temporal Contrast Analysis, an approach that couples to intermittent, ``avalanche''-like events, and enables us to study the magnitude, duration and temporal spacing of such events. We will discuss the application of Temporal Contrast Analysis to search for precursor and aftershock events that precede or succeed major structural rearrangements in the foam.

Folkerts, Michael M.; Stanwyck, Samuel W.; Shpyrko, Oleg G.



A payload diagnosis system for Columbus and Precursor Flights  

NASA Astrophysics Data System (ADS)

An expert system tool prototype termed COMPASS (computerized payload operations support system for Columbus), specially developed for the Columbus and Precursor Flights mission, is described. COMPASS provides: (1) know-how conservation for long-living payloads in a computerized knowledge base; (2) payload diagnosis (early warning, complete recovery by repair, complete recovery by command, and optimal recovery by appropriate continuation in degraded mode); (3) in-orbit integration/reconfiguration support; and (4) reactive science support (payload operations support, advice on operations in case of unusual results, and replanning advice in case of off-nominal situations or schedule changes). Block diagrams of COMPASS architecture are presented.

Heyland, D.; Kellner, A.; Timm, R.



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.

Baugh, Charles M.; Krumdieck, Carlos L.



Complete sets of monosubstituted ?-cyclodextrins as precursors for further synthesis.  


Regioselective alkylation of ?-cyclodextrin with allyl or propargyl bromide, using optimized reaction conditions, followed by peracetylation of the remaining hydroxyl groups and separation of isomers resulted in the set of peracetylated 2(I)-O-, 3(I)-O- and 6(I)-O-alkylated cyclodextrins in up to 19% yields. Ozonolysis or oxidative cleavage of peracetylated allyl derivatives resulted in a complete set of peracetylated 2(I)-O-, 3(I)-O-, and 6(I)-O-formylmethyl or -carboxymethyl derivatives. All of these derivatives are useful precursors for further preparation of regioselectively monosubstituted derivatives of ?-cyclodextrin. PMID:23205761

Bláhová, Markéta; Bedná?ová, Eva; ?ezanka, Michal; Jind?ich, Jind?ich



Precursor active galaxies and the cosmic x-ray background  

SciTech Connect

It is argued that the cosmic X-ray background (CXB) is not dominated by sources that are usual active galaxies or quasars. A comparable number of objects, young galaxies at z approximately 4 containing massive black holes surrounded by hot optically thin accretion disks, constitute the precursor active galaxies (PAG) postulated here for producing the thermal type spectrum required for the CXB. An evolutionary track for such PAG objects is described which would lead to the active galaxies observed as individual nonthermal sources. Unresolved emission from active galaxies at z 1 could then readily account for most of the nonthermal background observed in the gamma ray band.

Boldt, E.A.; Leiter, D.



Precursor active galaxies and the cosmic X-ray background  

NASA Astrophysics Data System (ADS)

It is argued that the cosmic X-ray background (CXB) is not dominated by sources that are usual active galaxies or quasars. A comparable number of objects, young galaxies at z approximately 4 containing massive black holes surrounded by hot optically thin accretion disks, constitute the precursor active galaxies (PAG) postulated here for producing the thermal type spectrum required for the CXB. An evolutionary track for such PAG objects is described which would lead to the active galaxies observed as individual nonthermal sources. Unresolved emission from active galaxies at z 1 could then readily account for most of the nonthermal background observed in the gamma ray band.

Boldt, E. A.; Leiter, D.



Precursor nanoscale modulations in ferromagnets: Modeling and thermodynamic characterization  

NASA Astrophysics Data System (ADS)

Using a Ginzburg-Landau model for the magnetic degrees of freedom with coupling to disorder, we demonstrate through simulations the existence of stripelike magnetic precursors recently observed in Co-Ni-Al alloys above the Curie temperature. We characterize these magnetic modulations by means of the temperature dependence of local magnetization distribution, magnetized volume fraction, and magnetic susceptibility. We also obtain a temperature-disorder strength phase diagram in which a magnetic tweed phase exists in a small region between the paramagnetic and dipolar phases.

Porta, Marcel; Castán, Teresa; Planes, Antoni; Saxena, Avadh



Spatially correlated disorder in striped precursor magnetic modulations  

NASA Astrophysics Data System (ADS)

We use a Ginzburg Landau model that includes long-range dipolar interactions and spatially correlated quenched-in disorder coupled to the local magnetization to study the properties of the precursor magnetic modulations as a function of the characteristics of the disorder. We find that although the modulation pattern is very robust and does not depend on details of the pair correlation function G(r), the scaling behaviour of the characteristic length of the striped magnetic modulations depends on the behaviour of G(r) for small values of r.

Porta, Marcel; Castán, Teresa; Lloveras, Pol; Planes, Antoni; Saxena, Avadh



Methods of making copper selenium precursor compositions with a targeted copper selenide content and precursor compositions and thin films resulting therefrom  

SciTech Connect

Precursor compositions containing copper and selenium suitable for deposition on a substrate to form thin films suitable for semi-conductor applications. Methods of forming the precursor compositions using primary amine solvents and methods of forming the thin films wherein the selection of temperature and duration of heating controls the formation of a targeted species of copper selenide.

Curtis, Calvin J. (Lakewood, CO); Miedaner, Alexander (Boulder, CO); van Hest, Marinus Franciscus Antonius Maria (Lakewood, CO); Ginley, David S. (Evergreen, CO); Leisch, Jennifer (Denver, CO); Taylor, Matthew (West Simsbury, CT); Stanbery, Billy J. (Austin, TX)



Calciothermic Preparation of Sm-Co From Nanostructured Precursor Oxides  

NASA Astrophysics Data System (ADS)

A calciothermic reduction/diffusion process has been developed for the preparation of Sm-Co alloys with good magnetic properties using nanostructured Co- and SmCo-oxide powders as precursors. The precursor oxides were obtained from an aqueous solution of Sm(NO3)36H2O, Co(NO3)26H2O, and citric acid which, after the removal of excess water, spontaneously reacts to form a fine mixture of Co3O4 and SmCoO3 nanoparticles. These nanoparticles were then mixed with metallic Ca granules, sealed under inert gas in Nb tubes, and heated to temperatures between 850 and 1000 ^oC for various lengths of time. The products of the reduction/diffusion reaction were studied by scanning electron microscopy with elemental analysis, vibrating sample magnetometry, and x-ray diffraction. These measurements revealed that (in addition to the oxidation product CaO) the products of the reduction/diffusion process were micron-sized particles of essentially single phase SmCo5 with a coercivity in excess of 40 kOe and a Curie temperature of about 950 ^oC.

Kelly, Brian; Poirier, Gerald; Unruh, Karl



Solution Structures of Chemoenzymatically Synthesized Heparin and Its Precursors  

PubMed Central

We report the first chemoenzymatic synthesis of the stable isotope-enriched heparin from a uniformly labeled [13C,15N]N-acetylheparosan (-GlcA(1,4)GlcNAc-) prepared from E. coli K5. Glycosaminoglycan (GAG) precursors and heparin were formed from N-acetylheparosan by the following steps: chemical N-deacetylation and N-sulfonation leading to N-sulfoheparosan (-GlcA(1,4)GlcNS-); enzyme-catalyzed C5-epimerization and 2-O-sulfonation leading to undersulfated heparin (-IdoA2S(1,4)GlcNS-); enzymatic 6-O-sulfonation leading to the heparin backbone (-IdoA2S(1,4)GlcNS6S-); and selective enzymatic 3-O-sulfonation leading to the anticoagulant heparin, containing the GlcNS6S3S residue. Heteronuclear, multidimensional nuclear magnetic resonance spectroscopy was employed to analyze the chemical composition and solution structure of [13C,15N]N-acetylheparosan, precursors, and heparin. Isotopic enrichment was found to provide well-resolved 13C spectra with the high sensitivity required for conformational studies of these biomolecules. Stable isotope-labeled heparin was indistinguishable from heparin derived from animal tissues and is a novel reagent for studying the interaction of heparin with proteins.

Zhang, Zhenqing; McCallum, Scott A.; Xie, Jin; Nieto, Lidia; Corzana, Francisco; Jimenez-Barbero, Jesus; Chen, Miao; Liu, Jian; Linhardt, Robert J.



Preparation of plutonium-bearing ceramics via mechanically activated precursor  

NASA Astrophysics Data System (ADS)

The problem of excess weapons plutonium disposition is suggested to be solved by means of its incorporation in stable ceramics with high chemical durability and radiation resistivity. The most promising host phases for plutonium as well as uranium and neutron poisons (gadolinium, hafnium) are zirconolite, pyrochlore, zircon, zirconia [1,2], and murataite [3]. Their production requires high temperatures and a fine-grained homogeneous precursor to reach final waste form with high quality and low leachability. Currently various routes to homogeneous products preparation such as sol-gel technology, wet-milling, and grinding in a ball or planetary mill are used. The best result demonstrates sol-gel technology but this route is very complicated. An alternative technology for preparation of ceramic precursors is the treatment of the oxide batch with high mechanical energy [4]. Such a treatment produces combination of mechanical (fine milling with formation of various defects, homogenization) and chemical (split bonds with formation of active centers-free radicals, ion-radicals, etc.) effects resulting in higher reactivity of the activated batch. .

Chizhevskaya, S. V.; Stefanovsky, S. V.



Heme regulates exocrine peptidase precursor genes in zebrafish.  


We previously determined that yquem harbors a mutation in the gene encoding uroporphyrinogen decarboxylase (UROD), the fifth enzyme in heme biosynthesis, and established zebrafish yquem (yqe(tp61)) as a vertebrate model for human hepatoery-thropoietic porphyria (HEP). Here we report that six exocrine peptidase precursor genes, carboxypeptidase A, trypsin precursor, trypsin like, chymotrypsinogen B1, chymotrypsinogen 1-like, and elastase 2 like, are downregulated in yquem/urod (-/-), identified initially by microarray analysis of yquem/urod zebrafish and, subsequently, confirmed by in situ hybridization. We then determined downregulation of these six zymogens specifically in the exocrine pancreas of sauternes (sau(tb223)) larvae, carrying a mutation in the gene encoding delta-amino-levulinate synthase (ALAS2), the first enzyme in heme biosynthesis. We also found that ptf1a, a transcription factor regulating exocrine zymogens, is downregulated in both yquem/urod (-/-) and sau/alas2 (-/-) larvae. Further, hemin treatment rescues expression of ptf1a and these six zymogens in both yquem/urod (-/-) and sauternes/alas2 (-/-) larvae. Thus, it appears that heme deficiency downregulates ptf1a, which, in turn, leads to downregulation of exocrine zymogens. Our findings provide a better understanding of heme deficiency pathogenesis and enhance our ability to diagnose and treat patients with porphyria or pancreatic diseases. PMID:17895525

Wang, Han; Zhou, Qingchun; Kesinger, Jason W; Norris, Chad; Valdez, Cammi



Hematopoietic precursor cells transiently reestablish permissiveness for X inactivation.  


Xist is the trigger for X inactivation in female mammals. The long noncoding Xist RNA localizes along one of the two female X chromosomes and initiates chromosome-wide silencing in the early embryo. In differentiated cells, Xist becomes dispensable for the maintenance of the inactive X, and its function for initiation of silencing is lost. How Xist mediates gene repression remains an open question. Here, we use an inducible Xist allele in adult mice to identify cells in which Xist can cause chromosome-wide silencing. We show that Xist has the ability to initiate silencing in immature hematopoietic precursor cells. In contrast, hematopoietic stem cells and mature blood cells are unable to initiate ectopic X inactivation. This indicates that pathways critical for silencing are transiently activated in hematopoietic differentiation. Xist-responsive cell types in normal female mice show a change of chromatin marks on the inactive X. However, dosage compensation is maintained throughout hematopoiesis. Therefore, Xist can initiate silencing in precursors with concomitant maintenance of dosage compensation. This suggests that Xist function is restricted in development by the limited activity of epigenetic pathways rather than by a change in the responsiveness of chromatin between embryonic and differentiated cell types. PMID:16980619

Savarese, Fabio; Flahndorfer, Katja; Jaenisch, Rudolf; Busslinger, Meinrad; Wutz, Anton



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



Illuminating Slab Remnants in the Lower Mantle Using PKP Precursors  

NASA Astrophysics Data System (ADS)

High quality recordings at the Yellowknife seismic array (YK) provide a good opportunity to locate the scatterers responsible for some of the observed PKP precursors, specifically those that appear well separated on the seismograms. Using data from high quality earthquake doublets, we have shown (Cao and Romanowicz, EPSL, 2007) that it is possible to precisely locate the scatterers responsible for these precursors, and determine whether they originate from the PKPbc or the PKPab phase, and on the source or receiver side. We have now expanded this dataset to non-doublet events. The most reliably measured individual scatterers delineate a region in the lowermost mantle where tomographic models indicate the presence of a transition from fast to slow velocities, likely associated with subducting slabs. To produce the scatterers, this transition should be sharper than seen in large scale tomographic models. This provides evidence for the penetration of slabs deep into the lower mantle beneath western North America and for the persistence of heterogeneity in composition during the slab's slow descent to the core-mantle boundary.

Romanowicz, B. A.; Cao, A.



Lunar precursor effects in the solar wind and terrestrial magnetosphere  

NASA Astrophysics Data System (ADS)

The two ARTEMIS probes observe significant precursor activity upstream from the Moon, when magnetically connected to the dayside lunar surface. The most common signature consists of high levels of whistler wave activity near half of the electron cyclotron frequency. This precursor activity extends to distances of many thousands of km, in both the solar wind and terrestrial magnetosphere. In the magnetosphere, electrons reflect from a combination of magnetic and electrostatic fields above the lunar surface, forming loss cone distributions. In the solar wind they generally form conics, as a result of reflection from an obstacle moving with respect to the plasma frame (just as at a shock). The anisotropy associated with these reflected electrons provides the free energy source for the whistlers, with cyclotron resonance conditions met between the reflected source population and Moonward-propagating waves. These waves can in turn affect incoming plasma, and we observe significant perpendicular electron heating and plasma density depletions in some cases. In the magnetosphere, we also observe broadband electrostatic modes driven by beams of secondary electrons and/or photoelectrons accelerated outward from the surface. We also occasionally see waves near the ion cyclotron frequency in the magnetosphere. These lower frequency waves, which may result from the presence of ions of lunar origin, modulate the whistlers described above, as well as the electrons. Taken together, our observations suggest that the presence of the Moon leads to the formation of an upstream region analogous in many ways to the terrestrial electron foreshock.

Halekas, J. S.; Poppe, A. R.; Farrell, W. M.; Delory, G. T.; Angelopoulos, V.; McFadden, J. P.; Bonnell, J. W.; Glassmeier, K. H.; Plaschke, F.; Roux, A.; Ergun, R. E.



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.

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



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.



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.



New morphologies of polyacetylene from the precursor polymer polybenzvalene  

SciTech Connect

The synthesis and properties of the polymer polybenzvalene and its conversion to polyacetylene are presented. This conversion is performed by treating polybenzvalene with Lewis acidic catalysts. The highest quality material was obtained from the isomerization with HgCl{sub 2}. The polyacetylene (PA) produced by this precursor route has a morphology that is considerably more amorphous than other forms of polyacetylene that have been previously reported. Orientation of the precursor polymer by stretching induced crystallinity and chain alignment as determined by X-ray diffraction. The unoriented PA exhibited a conductivity of 1 {Omega}{sup {minus}1} cm{sup {minus}1} and I{sub 2} doping. Materials stretched to elongations of l/l{sub 0} = 2.3 and l/l{sub 0} = 6 displayed conductivities of 13 {Omega}{sup {minus}1} cm{sup {minus}1} and 49 {Omega}{sup {minus}1} cm{sup {minus}1}, respectively. Block copolymers of polynorbornene and polybenzvalene were produced. These copolymers exhibited no phase separation as determined by DSC. The isomerization of these materials produced a polyacetylene-polynorbornene copolymer which exhibits a dominant x-ray diffraction peak with a d spacing of 4.7 {angstrom}. These results indicate that the interchain spacing of the block copolymer is significantly greater than that of the polyacetylene homopolymer due to the intimate mixing of the polyacetylene with the polynorbornene.

Swager, T.M.; Grubbs, R.H. (California Institute of Technology, Pasadena (USA))



Synthesis of the flavour precursor, alliin, in garlic tissue cultures.  


The path of synthesis of alkyl cysteine sulphoxides, or flavour precursors, in the Alliums is still speculative. There are two proposed routes for alliin biosynthesis, one is from serine and allyl thiol while the other is from glutathione and an allyl source via gamma glutamyl peptides. The routes have been investigated by exposing undifferentiated callus cultures of garlic and onion to potential pathway intermediates. After a period of incubation of 2 days the callus was extracted, and analysed for flavour precursors and related compounds by HPLC. Standards of alliin, isoallin and propiin were synthesised and their identity confirmed by HPLC and NMR. Putative intermediates selected included the amino acids serine and cysteine, as well as more complex intermediates such as allylthiol, allyl cysteine and glutathione. Both garlic and onion tissue cultures were able to synthesize alliin following incubation with allylthiol, and cysteine conjugates such as allyl cysteine. The ability of the tissue cultures to form alliin from intermediates was compatible with the proposed routes of synthesis of alliin. PMID:15652575

Hughes, J; Tregova, A; Tomsett, A B; Jones, M G; Cosstick, R; Collin, H A



Soot precursor measurements in benzene and hexane diffusion flames  

SciTech Connect

To clarify the mechanism of soot formation in diffusion flames of liquid fuels, measurements of soot and its precursors were carried out. Sooting diffusion flames formed by a small pool combustion equipment system were used for this purpose. Benzene and hexane were used as typical aromatic and paraffin fuels. A laser-induced fluorescence (LIF) method was used to obtain spatial distributions of polycyclic aromatic hydrocarbons (PAHs), which are considered as soot particles. Spatial distributions of soot in test flames were measured by a laser-induced incandescence (LII) method. Soot diameter was estimated from the temporal change of LII intensity. A region of transition from PAHs to soot was defined from the results of LIF and LII. Flame temperatures, PAH species, and soot diameters in this transition region were investigated for both benzene and hexane flames. The results show that though the flame structures of benzene and hexane were different, the temperature in the PAHs-soot transition region of the benzene flame was similar to that of the hexane flame. Furthermore, the relationship between the PAH concentrations measured by gas chromatography in both flames and the PAH distributions obtained from LIF are discussed. It was found that PAHs with smaller molecular mass, such as benzene and toluene, remained in both the PAHs-soot transition and sooting regions, and it is thought that molecules heavier than pyrene are the leading candidates for soot precursor formation. (author)

Kobayashi, Y.; Furuhata, T.; Amagai, K.; Arai, M. [Department of Mechanical System Engineering, Graduate School of Engineering, Gunma University, 1-5-1 Tenjin-cho, Kiryu-shi, Gunma 376-8515 (Japan)



A two-powder process for Bi-2223 precursors  

SciTech Connect

A two-powder process is described for the production of uniform, fine-grained Bi{sub 2}Sr{sub 2}Ca{sub 2}Cu{sub 3}O{sub {ital y}} (Bi-2223) powders. One powder is the Bi{sub 2.1{minus}{ital x}}Pb{sub {ital x}}Sr{sub 1.9{minus}{ital y}}Ca{sub {ital y}}O{sub {ital z}} (2:2 Cu-free) phase. The other is a multi-phase powder of approximate overall composition SrCaCu{sub 3}O{sub {ital y}}. The 2:2 Cu-free is one of the first Bi-containing phases to form from a nominal Bi-2223 mixture of oxides and carbonates. This precursor route was chosen for investigation because (1) powders have very similar particle morphologies and (2) the mixing volumes are closely matched. Both of these characteristics facilitate the milling and blending process. This precursor mix was found to be stable in that explosive grain growth of dundesirable phases was not observed during sintering. Critical current densities up to 26,900 A/cm{sup 2} in self field at 75 K were obtained in tapes. {copyright} {ital 1996 Materials Research Society.}

Holesinger, T.G.; Salazar, K.V.; Phillips, D.S.; Sargent, B.L.; Bremser, J.K.; Bingert, J.F.; Willis, J.O.; Peterson, D.E. [Superconductivity Technology Center, MS K763, Los Alamos National Laboratory, Los Alamos, New Mexico 87545 (United States)



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.



Magnetic and Density Spikes in Cosmic-Ray Shock Precursors  

NASA Astrophysics Data System (ADS)

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 Alfvén envelopes (solitons or breathers). As the conventional (undriven) solitons, the obtained magnetic spikes propagate at a speed C proportional to their amplitude, C=C_{A}B_{max}/\\sqrt{2}B_{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.; Sagdeev, R. Z.; Diamond, P. H.



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

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



Prediction of viral microRNA precursors based on human microRNA precursor sequence and structural features  

PubMed Central

MicroRNAs (small ~22 nucleotide long non-coding endogenous RNAs) have recently attracted immense attention as critical regulators of gene expression in multi-cellular eukaryotes, especially in humans. Recent studies have proved that viruses also express microRNAs, which are thought to contribute to the intricate mechanisms of host-pathogen interactions. Computational predictions have greatly accelerated the discovery of microRNAs. However, most of these widely used tools are dependent on structural features and sequence conservation which limits their use in discovering novel virus expressed microRNAs and non-conserved eukaryotic microRNAs. In this work an efficient prediction method is developed based on the hypothesis that sequence and structure features which discriminate between host microRNA precursor hairpins and pseudo microRNAs are shared by viral microRNA as they depend on host machinery for the processing of microRNA precursors. The proposed method has been found to be more efficient than recently reported ab-initio methods for predicting viral microRNAs and microRNAs expressed by mammals.

Kumar, Shiva; Ansari, Faraz A; Scaria, Vinod



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



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.



Comparative examination of titania nanocrystals synthesized by peroxo titanic acid approach from different precursors.  


Titanium dioxide nanocrystalline particles were synthesized by peroxo titanium acid (PTA) approach from titanium alkoxide and inorganic salt precursors, and their structural and surface properties, porosities, and photocatalytic activities were comparatively examined by XRD, TG/DTA, DRIFT, UV-vis, low temperature N(2) adsorption, and methyl orange (MO) degradation. It was found that nanoparticles with single anatase phase can be obtained from alkoxide precursor even near room temperature if synthesis conditions are appropriately controlled. PTA-derived anatase nanoparticles from titanium alkoxide precursor have smaller crystalline sizes and better porosities, and contain less amount of peroxo group and no organic impurities as compared to those from TiCl(4) precursor. The advantages in structural property, porosity, and surface properties (few deficiencies) lead to a much better photocatalytic activity for TiO(2) nanoparticles from titanium alkoxide precursor in comparison with those from TiCl(4) precursor. PMID:18406418

Liu, Yong-Jun; Aizawa, Mami; Wang, Zheng-Ming; Hatori, Hiroaki; Uekawa, Naofumi; Kanoh, Hirofumi



Precursor of PKKPbc: an Evidence for Core Rigidity Zone?  

NASA Astrophysics Data System (ADS)

As the boundary between solid mantle and liquid outer-core, Core Mantle Boundary (CMB) is one of the most important discontinuities in the deep interior of the Earth, controlling exchange of heat, angular moment and material. Usually, the mantle side of the CMB was regarded as a complex zone, as inferred from the observation of ultra low velocity zone (ULVZ) and etc, while the core side was regarded as less complicated. Recent studies showed that ScP phases in some regions can be modeled with a thin rigidity zone at the top of the core (Rost and Revenaugh, 2001), which called core rigidity zone (CRZ), which can also explain SPdKS waveform complexities. However, mantle side core phases such as ScP may be affected by complexities from the bottom of mantle. To get some evidence for CRZ from core side reflection phase from CMB, We observed PKKPbc occurred from events in Fiji-Tonga region recorded at US networks, and compared the waveforms with Hilbert transform of direct P as PKKP is a maximum arrival phase. The main phase of them fitted well, but there's a significant pulse arriving ~1s earlier in PKKPbc waveform. This precursor indicates the existence of CRZ at the bounce point region. Then we performed waveform modeling with Reflectivity Method (Kennett and Engdahl, 1991), and got a best-fit thickness of 1.0km when the Vp,Vs and density of CRZ accord with Rost's velocity model. Although this precursor can be also explained by a liquid layer at the uppermost outer core, the thickness of the layer must be greater than 5km. Helffrich et al has limited the thickness of the layer to less than 3km in a recent research (2004). Moreover, such distinct precursor if from liquid layer must have occurred from a discontinuity with large contrast, which may result in strong following phases of PcP at short distances where PcP direct phase is weak. Thus the anomaly layer is most likely a rigidity zone. Additionally, we analyzed S and ScS waveforms on models with CRZ or ULVZ, and found that the ScS behavior caused by 1km-thick CRZ can be also explained with 10km-thick ULVZ model with -30% anomalies in S velocity. However, ULVZ model should result in clear SdS phases between S and ScS arrivals. Anyway, ScS observations should be helpful in distinguishing CRZ and ULVZ.

Wan, K.; Huang, J.; Ni, S.



Real time validation of GPS TEC precursor mask for Greece  

NASA Astrophysics Data System (ADS)

It was established by earlier studies of pre-earthquake ionospheric variations that for every specific site these variations manifest definite stability in their temporal behavior within the time interval few days before the seismic shock. This self-similarity (characteristic to phenomena registered for processes observed close to critical point of the system) permits us to consider these variations as a good candidate to short-term precursor. Physical mechanism of GPS TEC variations before earthquakes is developed within the framework of Lithosphere-Atmosphere-Ionosphere Coupling (LAIC) model. Taking into account the different tectonic structure and different source mechanisms of earthquakes in different regions of the globe, every site has its individual behavior in pre-earthquake activity what creates individual "imprint" on the ionosphere behavior at every given point. Just this so called "mask" of the ionosphere variability before earthquake in the given point creates opportunity to detect anomalous behavior of electron concentration in ionosphere basing not only on statistical processing procedure but applying the pattern recognition technique what facilitates the automatic recognition of short-term ionospheric precursors of earthquakes. Such kind of precursor mask was created using the GPS TEC variation around the time of 9 earthquakes with magnitude from M6.0 till M6.9 which took place in Greece within the time interval 2006-2011. The major anomaly revealed in the relative deviation of the vertical TEC was the positive anomaly appearing at ~04PM UT one day before the seismic shock and lasting nearly 12 hours till ~04AM UT. To validate this approach it was decided to check the mask in real-time monitoring of earthquakes in Greece starting from the 1 of December 2012 for the earthquakes with magnitude more than 4.5. During this period (till 9 of January 2013) 4 cases of seismic shocks were registered, including the largest one M5.7 on 8 of January. For all of them the mask confirmed its validity and 6 of December event was predicted in advance.

Pulinets, Sergey; Davidenko, Dmitry



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.



Activated microporous materials through polymerization of microemulsion precursors  

NASA Astrophysics Data System (ADS)

Microemulsions have been well studied for their unique characteristics. They are isotropic, thermodynamically stable and microstructured mixtures of oil and water stabilized by one or more surfactant species. They are formed spontaneously and are thermodynamically stable. Microemulsion precursors can be polymerized to make microporous solids with controlled pore structure and sizes. These polymeric solids have been studied extensively in the past. Although the fundamental properties of the microporous solids have been studied in depth, the development of specific applications that will utilize the unique properties of these solids has not been exhaustively researched. The current work establishes the feasibility of making activated microporous solids from microemulsion precursors, by the use of a ligand that chelates metals and also attaches itself to the polymer monolith. It also uses a novel 'in-situ' incorporation by combining the formulation and incorporation steps into one. The research objectives are, to formulate a microemulsion system that can yield useful microporous solids upon polymerization and activation, to characterize these solids using existing techniques available for analysis of similar microporous solids, to identify and understand the effect of the variables in the system and to study the influence of these variables on the performance characteristics of this material. Characterization techniques like Differential Scanning Calorimetry, Thermogravimetric Analysis and Scanning Electron Microscopy were used. A hydroxyethylmethylmethacrylate/methylmethacrylate/aqueous phase containing 10% SDS' system was chosen as the precursor microemulsion and the corresponding microporous solids were made. A metal chelating ligand, Congo Red, was incorporated onto the microporous polymer using NaOH as a binding agent. The ability of the resultant 'activated' microporous solid to remove metal ions from solution, was evaluated. The metal ion chosen was chromium and the influence of variables such as NaOH loading, Congo Red loading, Cross linker content etc. were studied. It was found that the microporous solids were effective in removing chromium from solution. They outperformed similar polymeric solids with ligands (reported in literature) in chromium removal. A removal of about 1500 micro moles of chromium ions per gram of dry polymer from a solution of 5 mMol/L initial concentration of chromium was observed. This is much more than the removal of 340 micro moles/gram of dry polymer reported in literature for comparable non-microporous systems.

Venkatesan, Arunkumar


beta-Amyloid Precursor Protein Cleavage by a Membrane-Bound Protease  

Microsoft Academic Search

The principal component of amyloid plaques in Alzheimer disease is beta-amyloid protein, an ≈4-kDa peptide derived from amyloid precursor proteins. Previous studies have established that amyloid precursor proteins are secreted after proteolytic cleavage within the beta-amyloid peptide. The present investigation documents that, in cultured cells, amyloid precursor protein is cleaved on the plasma membrane by a membrane-bound endoprotease and that

Sangram S. Sisodia



Effect of the powder precursor characteristics in the reaction sintering of aluminum titanate  

Microsoft Academic Search

Aluminum titanate precursor powders, containing 2.5wt.% MgO additive, were prepared by two powder processing methods, the hydrolysis of alkoxides and coprecipitation of inorganic salts. The hydrolysis-derived precursor powder showed a higher chemical homogeneity than the coprecipitated-derived precursor powder. Dilatometric analysis, accomplished with XRD and microscopy, was a very good method to study both phase transformation and sintering processes. Different phase

Y. X. Huang; Ana M. R. Senos



Thermal transformations of akaganéite and lepidocrocite to hematite: assessment of possible precursors to Martian crystalline hematite  

Microsoft Academic Search

We examine the possibility that crystalline hematite (?-Fe2O3) deposits on Mars were derived from the precursor iron oxyhydroxide minerals akaganéite (?-FeOOH) or lepidocrocite (?-FeOOH)\\u000a and compare them to an earlier study of goethite (?-FeOOH) and magnetite (Fe3O4) precursors. Both the mid-infrared and visible\\/near infrared spectra of hematite are dependent upon the hematite precursor\\u000a mineral and the temperature of transformation. Laboratory

Timothy D. Glotch; Michael D. Kraft



Bioactive Glass-Ceramic Coatings Synthesized by the Liquid Precursor Plasma Spraying Process  

Microsoft Academic Search

In this study, the liquid precursor plasma spraying process was used to manufacture P2O5-Na2O-CaO-SiO2 bioactive glass-ceramic coatings (BGCCs), where sol and suspension were used as feedstocks for plasma spraying. The effect\\u000a of precursor and spray parameters on the formation and crystallinity of BGCCs was systematically studied. The results indicated\\u000a that coatings with higher crystallinity were obtained using the sol precursor,

Yanfeng Xiao; Lei Song; Xiaoguang Liu; Yi Huang; Tao Huang; Jiyong Chen; Yao Wu; Fang Wu



Mitochondrial protein import: Nucleoside triphosphates are involved in conferring import-competence to precursors  

Microsoft Academic Search

Summary The role of nucleoside triphosphates (NTPs) in mito- chondrial protein import was investigated with the precursors of N. crassa ADPlATP carrier, F1-ATPase subunit 9, F,-ATPase subunit 9, and fusion proteins between subunit 9 and mouse dihydrofolate reduc- tase. NTPs were necessary for the initial interaction of precursors with the mitochondria and for the comple- tion of translocation of precursors

Nikolaus Pfanner; Maximilian Tropschug; Walter Neupert



Biochemical Removal of HAP Precursors from Coal. Quarterly technical report, July 1-September 30, 1997  

SciTech Connect

This is the eighth and final phase 1 quarterly technical progress report on this project which is investigating the microbiological removal of 13 inorganic hazardous air pollutant (HAP) precursors and pyrite from four U.S. coals. Since most of the HAP precursors are associated with sulfides, at least in part, pyrite-oxidizing bacteria are being tested for their ability to remove HAP precursors from coal. This report documents the completion of the final (reporting) task.

Olson, G.L.



Interactions of Small Nuclear RNA's with Precursor Messenger RNA During in Vitro Splicing  

Microsoft Academic Search

Precursor messenger RNA splicing requires multiple factors including U1, U2, U4, U5, and U6 small nuclear RNA's. The crosslinking reagent psoralen was used to analyze the interactions of these RNA's with an adenovirus precursor messenger RNA in HeLa nuclear extract. An endogenous U2-U4-U6 crosslinkable complex dissociated upon incubation with precursor messenger RNA. During splicing, U1, U2, U5, and U6 became

David A. Wassarman; Joan A. Steitz



Application of evaluated fission-product delayed-neutron precursor data in reactor kinetics calculations  

SciTech Connect

Evaluated fission-product yield and decay data have been used to describe 105 delayed neutron precursors explicitly in point reactor kinetics calculations. Results calculated for /sup 235/U thermal fission show that rod-drop reactivity values obtained from kinetics calculations with 6-group precursor data are considerably higher than those calculated with explicit delayed-neutron precursor data. The calculated kinetics associated with positive reactivity steps are significantly different.

Perry, R.T.; Wilson, W.B.; England, T.R.; Brady, M.C.



Effect of post-spinning modification on the PAN precursors and resulting carbon fibers  

Microsoft Academic Search

The impregnation of a special grade PAN precursor fibers was carried out in a 8 wt% KMnO4 aqueous solution to obtain modified PAN precursor fibers. The effects of modification on the chemical structure and the mechanical\\u000a properties of precursor fibers thermally stabilized and their resulting carbon fibers were characterized by the combination\\u000a use of densities, wide-angle X-ray diffraction (WAXD), X-ray

Zhang Wangxi; Liu Jie



Specificity of leaf mitochondrial and chloroplast processing systems for nuclear-encoded precursor proteins  

Microsoft Academic Search

The specificity of the mitochondrial and chloroplast processing enzymes for the nuclear-encoded precursor proteins was investigated. Mitochondrial precursor proteins of the Nicotiana plumbaginifolia and the Neurospora crassa ß subunits of F1-ATPase and the Neurospora Rieske FeS precursor protein were processed to the correct mature size by matrix extracts isolated from spinach leaves, yeast, rat liver and beef heart. The mitochondrial

James Whelan; Carina Knorpp; Matthew A. Harmey; Elzbieta Glaser



Deposition of nanostructured photocatalytic zinc ferrite films using solution precursor plasma spraying  

Microsoft Academic Search

Deposition of pure spinet phase, photocatalytic zinc ferrite films on SS-304 substrates by solution precursor plasma spraying (SPPS) has been demonstrated for the first time. Deposition parameters such as precursor solution pH, concentration, film thickness, plasma power and gun-substrate distance were found to control physico-chemical properties of the film, with respect to their crystallinity, phase purity, and morphology. Alkaline precursor

Rekha Dom; G. Sivakumar; Neha Y. Hebalkar; Shrikant V. Joshi; Pramod H. Borse



Synthesis of polycrystalline yttrium iron garnet and yttrium aluminium garnet from organic precursors  

Microsoft Academic Search

Polycrystalline Y3Fe5O12 (YIG) and Y3Al5O12 (YAG) garnets have been prepared by the organic solution technique using a novel organic precursor. The thermal decomposition of the precursor and subsequent formation of the garnet phases was studied by thermal analysis, X-ray diffraction and Fourier transform infra red spectroscopy (FTIR) including diffuse reflectance FTIR (DRIFT). The precursor of YIG decomposes to give the

C. D. Veitch



Synthesis of S-doped graphene by liquid precursor.  


Doping is a common and effective approach to tailor semiconductor properties. Here, we demonstrate the growth of large-area sulfur (S)-doped graphene sheets on copper substrate via the chemical vapor deposition technique by using liquid organics (hexane in the presence of S) as the precursor. We found that S could be doped into graphene's lattice and mainly formed linear nanodomains, which was proved by elemental analysis, high resolution transmission microscopy and Raman spectra. Measurements on S-doped graphene field-effect transistors (G-FETs) revealed that S-doped graphene exhibited lower conductivity and distinctive p-type semiconductor properties compared with those of pristine graphene. Our approach has produced a new member in the family of graphene based materials and is promising for producing graphene based devices for multiple applications. PMID:22710561

Gao, Hui; Liu, Zheng; Song, Li; Guo, Wenhua; Gao, Wei; Ci, Lijie; Rao, Amrita; Quan, Weijin; Vajtai, Robert; Ajayan, Pulickel M



Molecular and polymeric ceramic precursors. Research progress report  

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.



Is there a field-theoretic explanation for precursor biopolymers?  


A Hu-Barkana-Gruzinov cold dark matter scalar field phi may enter a weak isospin invariant derivative interaction that causes the flow of right-handed electrons to align parallel to (inverted delta phi). Hence, in the outer regions of galaxies where (inverted delta phi) is large, as in galactic halos, the derivative interaction may induce a chirality-imbued quantum chemistry. Such a chirality-imbued chemistry would in turn be conducive to the formation of abundant precursor biopolymers on interstellar dust grains, comets and meteors in galactic halo regions, with subsequent delivery to planets in the inner galactic regions where phi and (inverted delta phi) are concomitantly near zero and left-right symmetric terrestrial quantum chemistry prevails. PMID:12458734

Rosen, Gerald



Precursors of order in aggregates of patchy particles.  


We study computationally the local structure of aggregated systems of patchy particles. By calculating the probability distribution functions of various rotational invariants we can identify the precursors of orientation order in amorphous phase. Surprisingly, the strongest signature of local order is observed for four-patch particles with tetrahedral symmetry, not for six-patch particles with the cubic one. This trend is exactly opposite to their known ability to crystallize. We relate this anomaly to the observation that a generic aggregate of patchy systems has a coordination number close to 4. Our results also suggest a significant correlation between rotational order in the studied liquids with the corresponding crystalline phases, making this approach potentially useful for a broader range of patchy systems. PMID:23944458

Vasilyev, Oleg A; Klumov, Boris A; Tkachenko, Alexei V



Phosphatidylglyceroylalkylamine, a novel phosphoglycolipid precursor in Deinococcus radiodurans  

SciTech Connect

We report here the structure of a previously uncharacterized phospholipid in the radiation-resistant bacterium Deinococcus radiodurans. This phospholipid, designated lipid 4, was shown by chemical analysis, HF hydrolysis, and nuclear magnetic resonance spectroscopy to be phosphatidylglyceroylalkylamine. Lipid 4 thus contains the unusual lipid constituents glyceric acid and alkylamines, which have previously been identified in two complex phosphoglycolipids from this organism. By ({sup 32}P)phosphate pulse-chase labeling techniques, lipid 4 was shown to be the precursor of the complex phosphoglycolipids alpha-galactosyl- and alpha-N-acetylglucosaminylphosphatidylglyceroylalkylamine. While phosphatidylglyceroylalkylamine is rapidly biosynthesized from Pi, its subsequent glycosylation occurs much more slowly. Therefore, we conclude that the final glycosylation step is the rate-limiting event in the biosynthesis of the complex phosphoglycolipids alpha-galactosyl- and alpha-N-acetylglucosaminyl-phosphatidylglyceroylalkylamine.

Huang, Y.; Anderson, R. (Univ. of Calgary, Alberta (Canada))



[Hybrid resistance to precursor cells of bone marrow stroma].  


A focusl of hemopoiesis appearing after the transplantation of a bone marrow fragment of C57BL mice to syngeneic mice (under the kidney capsule) contained more hemopoietic cells than in transplantation to the semisyngeneic (CBA X C57BL) FI recipient. Experiments were conducted with a secondary seeding by intravenous injection of hemopoietic cells of the C57BL transplant genotype into the transplant depopulated by irradiation; it was shown that these differences were caused by lesser dimensions of the hemopoietic microenvironment in the focus in the hybrid organism in comparison with such in the syngeneic system. Thus, the hybrid resistance was expressed not only to the hemopoietic cells, but also to the stromal precursors transferring the hemopoietic microenvironment. PMID:322765

Gurevich, O A; Chertkov, I L



Electrochemical behavior of carbon aerogels derived from different precursors  

SciTech Connect

The ability to tailor the structure and properties of porous carbons has led to their increased use as electrodes in energy storage devices. Our research focuses on the synthesis and characterization of carbon aerogels for use in electrochemical double layer capacitors. Carbon aerogels are formed from the sol-gel polymerization of (1) resorcinol-formaldehyde or (2) phenolic-furfural, followed by supercritical drying from carbon dioxide, and subsequent pyrolysis in an inert atmosphere. These materials can be produced as monoliths, composites, thin films, powders, or microspheres. In all cases, the areogels have an open-cell structure with an ultrafine pore size (<100 nm), high surface area (400-1 100 m{sup 2}/g), and a solid matrix composed of interconnected particles, fibers, or platelets with characteristic dimensions of 10 nm. This paper examines the effects of the carbon precursor and processing conditions on electrochemical performance in aqueous and organic electrolytes.

Pekala, R.W.; Alviso, C.T.; Nielson, J.K.; Tran, T.D. [Lawrence Livermore National Lab., CA (United States); Reynolds, G.M.; Dresshaus, M.S. [Massachusetts Inst. of Tech., Cambridge, MA (United States). Dept. of Physics



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 in the longer term they will provide the means to explore therapeutic methods of stimulating auditory hair cell regeneration.

Rivolta, M N; Grix, N; Lawlor, P; Ashmore, J F; Jagger, D J; Holley, M C



Oligodendrocyte precursor cell composition and methods of use  

US Patent & Trademark Office Database

The present invention provides a cell culture enriched for sphingolipid enhances neural stem cells (SENSe), particularly oligodendrocyte precursor cells (ODPCs), that do not form teratomas after transplanted in vivo. Methods for producing and use of the invention ODPCs or the cell culture enriched with these ODPCs for stem cell therapy are also provided. The invention method comprises culturing a stem cell culture with a cell culture medium comprising a ceramide compound and a S1P receptor agonist in sequence, overlapping intervals or concurrent manners. The present invention further provides a cellular or gene therapy using a composition comprising a ceramide compound in conjunction with a S1P.sub.1 agonist to proliferate or differentiate endogeneous neural stem cells to ODPCs and further to oligodendrocytes.



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)



Amyloid Precursor Protein Is Trafficked and Secreted via Synaptic Vesicles  

PubMed Central

A large body of evidence has implicated amyloid precursor protein (APP) and its proteolytic derivatives as key players in the physiological context of neuronal synaptogenesis and synapse maintenance, as well as in the pathology of Alzheimer's Disease (AD). Although APP processing and release are known to occur in response to neuronal stimulation, the exact mechanism by which APP reaches the neuronal surface is unclear. We now demonstrate that a small but relevant number of synaptic vesicles contain APP, which can be released during neuronal activity, and most likely represent the major exocytic pathway of APP. This novel finding leads us to propose a revised model of presynaptic APP trafficking that reconciles existing knowledge on APP with our present understanding of vesicular release and recycling.

Riedel, Dietmar; Hua, Yunfeng; Huve, Jana; Wilhelm, Benjamin G.; Klingauf, Jurgen



Idiopathic benign paroxysmal vertigo in children, a migraine precursor.  


Vertigo and dizziness are common conditions in the adult population that can be rarely seen during childhood; only a few articles describing vertigo in children can be found in literature. Although many causes of vertigo in adulthood occur also in childhood, their frequency may be different. A typical example is benign paroxysmal positional vertigo, the most common peripheral vestibular disorder in adults, which occurs quite uncommonly in children. Furthermore, many common diseases causing vertigo in children may be unique for this population, such as benign paroxysmal vertigo (BPV) of childhood. At present, BPV is defined as a migraine's equivalent, a precursor of migraine or a periodic syndrome of childhood. The International Headache Society also studied this form of vertigo and included the Benign Paroxysmal Vertigo in section 1.3.3. of the International Classification of Headaches (ICHD-2). The present review analyzes recent patho-physiological and clinical evidences regarding idiopathic BPV in children. PMID:20114149

Ralli, G; Atturo, F; de Filippis, C



Natural Modulators of Amyloid-Beta Precursor Protein Processing.  


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, C; Tanzi, R E



Mobile precursor mediated protein adsorption on solid surfaces  

NASA Astrophysics Data System (ADS)

The interaction between a protein molecule and a surface is ubiquitous to a number of important technologies, such as bio-sensing, biomaterials, and nanomedicine. This process is also essential to complex biological functions, such as protein-cell surface interactions. Here we explore the application of fundamental concepts developed in the field of surface science to the understanding of protein-surface interactions. In particular, we focus on the role of mobile precursor states in the reversible and irreversible adsorption of protein molecules. We attempt to apply these simple concepts to the analysis of the kinetics and thermodynamics of protein-surface interactions. We conclude by discussing how one may take advantage of these simple concepts in designing and controlling protein-surface interactions for various bio-interface based technologies.

Garland, Adam; Shen, Lei; Zhu, Xiaoyang



Ribosomal Precursors and Ribonucleic Acid Synthesis in Escherichia coli  

PubMed Central

Ribosomes and immature ribonucleoprotein particles were isolated from extracts of log-phase cells grown under various conditions. Quantitative measurements were made to determine the relative amounts of immature particles present in the extracts. The results indicate that the steady-state level of ribosomal precursors accounted for essentially a constant fraction of the total ribonucleic acid (RNA) of the cells. For cells with RNA-protein ratios between 0.43 and 0.65, about 1.6% of the total RNA occurred as immature ribonucleoprotein particles. Further, increased levels of immature particles were shown to be correlated with a reduced rate of RNA synthesis in cells recovering from chloramphenicol inhibition. The reduction was found to vary directly with the duration of pretreatment in chloramphenicol and, consequently, with the level of immature particles present in the cells.

Matchett, William H.



Energetic clues to pathways to biomineralization: Precursors, clusters, and nanoparticles  

PubMed Central

Nanoparticle and nanocluster precursors may play a major role in biomineralization. The small differences in enthalpy and free energy among metastable nanoscale phases offer controlled thermodynamic and mechanistic pathways. Clusters and nanoparticles offer concentration and controlled transport of reactants. Control of polymorphism, surface energy, and surface charge on nanoparticles can lead to morphological control and appropriate growth rates of biominerals. Rather than conventional nucleation and growth, assembly of nanoparticles may provide alternative mechanisms for crystal growth. The Ostwald step rule, based on a thermodynamic view of nucleation and growth, is supported by the observation that more metastable phases tend to have lower surface energies. Examples from nonbiological systems, stressing the interplay of thermodynamic and kinetic factors, illustrate features potentially important to biomineralization.

Navrotsky, Alexandra



Slippage of 4He Films and Precursor Phenomenon of Superfluidity  

NASA Astrophysics Data System (ADS)

We have carried out quartz crystal microbalance (QCM) experiments for 4He films on an exfoliated single-crystalline graphite using a 32 kHz tuning fork, and have measured the temperature dependence of the resonance frequency and the Q value for various areal densities and oscillation amplitudes. Comparing with the previous experiments for Grafoil, the decoupling of the films due to the slippage or the superfluidity was larger than that of Grafoil, and the competition between the slippage and the superfluidity was observed in three-atom thick films. Furthermore, it was found that the slippage is suppressed gradually at higher temperature than the superfluid onset T c , and that the relaxation time decreases at low temperatures while it obeys the Arrhenius law at high temperatures. These results suggest a precursor to the superfluidity of 4He films.

Noda, Kei; Okamura, Ko; Taniguchi, Junko; Suzuki, Masaru; Hieda, Mitsunori



Current development in isoprenoid precursor biosynthesis and regulation.  


Isoprenoids are one of the largest classes of natural products and all of them are constructed from two precursors, isopentenyl diphosphate (IPP) and its isomer dimethylallyl diphosphate (DMAPP). For decades, the mevalonic acid (MVA) pathway was proposed to be the only IPP and DMAPP biosynthetic pathway. This review summarizes the newly discovered IPP and DMAPP production pathways since late 1990s, their distribution among different kingdoms, and their roles in secondary metabolite production. These new IPP and DMAPP production pathways include the methylerythritol phosphate (MEP) pathway, a modified MVA pathway, and the 5-methylthioadenosine shunt pathway. Relative to the studies on the MVA pathway, information on the MEP pathway regulation is limited and the mechanistic details of several of its novel transformations remain to be addressed. Current status on both MEP pathway regulation and mechanistic issues is also presented. PMID:23891475

Chang, Wei-chen; Song, Heng; Liu, Hung-wen; Liu, Pinghua



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.

Mullighan, Charles G.



Pyrocystis lunula bioluminescence: physicochemical characterization of the luciferin precursor.  


The luminescence of the dinoflagellate Pyrocystis lunula is controlled by the reduction state of the luciferin precursor. This molecule (P630) is a chromopeptide more stable than luciferin in methanolic solutions at low temperature. Cations may oxidize P630 or cleave the bond between the peptidic chain and the extended tetrapyrrole. Reduction of P630 is performed enzymatically by a NAD(P)H-dependent oxidoreductase or chemically by 2-mercaptoethanol or dithiothreitol. The state of reduction is monitored by the absorption and fluorescence emission which reveal a conformational change of the chromopeptide depending on the pH. These data will be useful for forthcoming studies on intracellular reducing power regulation and luminescence rhythms of these cells. PMID:3415244

Fresneau, C; Arrio, B



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 effect of a precursor on growth of forward masking1  

PubMed Central

This study examined the effect of an on-frequency precursor on growth-of-masking (GOM) functions measured using an off-frequency masker. The signal was a 6-ms, 4-kHz tone. A GOM function was measured using a 40-ms, 2.8-kHz tone (the off-frequency masker). GOM functions were then measured with an on-frequency, fixed level precursor presented before the off-frequency masker. The precursor was 50 or 60 dB SPL, and 160 ms in duration. For the 60-dB SPL precursor, a 40-ms duration was also used. Two-line functions were fit to the GOM data to estimate the basilar membrane input-output function. The precursors reduced the gain of the input-output function, and this decrease was graded with precursor level. Both precursor durations had the same effect on gain. Changes in masking following a precursor were larger than would be predicted by additivity of masking. The observed decrease in gain may be consistent with activation of the medial olivocochlear reflex by the precursor.

Krull, Vidya; Strickland, Elizabeth A.



Variability in the precursor proteins of collagen I and III in different stages of COPD  

PubMed Central

Background Levels of precursor proteins of collagen I and III are increased in fibrotic pulmonary diseases. This study determined whether the expression of precursors of type I and III collagen proteins would be increased in small and large airways of COPD patients in various stages of the disease reflecting fibrogenesis. Methods The levels of precursor proteins of collagen I and III were studied by immunohistochemistry and quantified by image analysis in lung tissue of 16 non-smokers, 20 smokers with normal lung function, 20 smokers with stage I-II COPD and 8 ex-smokers with stage IV COPD. Results In large airways, the subepithelial layer which was positive for precursor proteins of collagen I and III was thicker in smokers and in stage I-II COPD compared to non-smokers. Large airways in stage IV COPD showed reduced expression of precursor protein of collagen I whereas precursor of collagen III was increased. The amount of precursor protein of collagen III was increased in small airways of smokers and stage I-II COPD but reduced in stage IV COPD. Conclusions Precursor proteins of collagen I and III revealed different expression profiles in large and small airways in various stages of COPD. Smoking enhanced expression of both precursors in large airways with a positive correlation with pack-years.



Residual gas analysis of volatile impurities in halide precursors for scintillator crystals  

NASA Astrophysics Data System (ADS)

Alkaline-earth halides can be made into bright scintillators if purity is maintained during synthesis and growth. In order to investigate precursor purity, beaded halide precursors were heated under vacuum and evolved gas was assessed by residual gas spectroscopy. These precursors included cesium chloride, lithium chloride, yttrium chloride, cerium chloride, strontium iodide, europium iodide, barium bromide, and europium bromide. Water and CO2 desorption, sulfur release, argon release, and halide dissociation was observed in samples. Triply-oxidized precursors showed multiple paths to decomposition. The data inform approaches toward purification and growth.

Swider, S.; Motakef, S.; Datta, A.; Higgins, W. M.



Amorphous Calcium Carbonate in Biomineralization: Stable and Precursor Phases  

NASA Astrophysics Data System (ADS)

The biological formation of the crystalline polymorphs of calcium carbonate, aragonite and calcite, is widespread. The less stable polymorphs, vaterite and monohydrocalcite are also formed by some organisms. Surprisingly, the highly unstable phase, amorphous calcium carbonate (ACC), is formed by a variety of organisms from different phyla. Most of these are stable at least within the lifetime of the organism. The stable forms all have a stoichiometry of CaCO3.H2O. Despite the fact that they do not diffract X-rays. Studies of their short range order by EXAFS, reveal species specific variations in the number and distances of atoms that surround the calcium ion. Proteins extracted from stable biogenic ACC are able to stabilize the phase in vitro. ACC has also been identified as a transient precursor phase during the formation of the calcitic larval spicule of the sea urchin and the formation of the larval shell of a bivalve. The transient form has little or no water associated with the CaCO3. Preliminary EXAFS data suggest that the short range order of the sea urchin spicule transient ACC resembles calcite. Proteins extracted from these spicules are able to stabilize ACC provided Mg is present in the solution. As the mollusks and the echinoderms are on two different branches of the animal phylogenetic tree, it is conceivable that the strategy of using ACC as a precursor phase at least for larval mineralization may be widespread. It has yet to be shown that it is used by adults of either phylum. The manner in which organisms precipitate, stabilize and destabilize if necessary, this highly metastable phase of calcium carbonate presents many fascinating and enigmatic questions, whose solutions could well contribute to a better understanding of basic processes in biomineralization. For more details and references, see Addadi, L., Raz, S. and Weiner, S. (2003). Taking advantage of disorder: Amorphous calcium carbonate and its roles in biomineralization. Adv. Mat.15, 959-970.

Weiner, S.



First results on GlioLab/GlioSat Precursors Missions  

NASA Astrophysics Data System (ADS)

Since 2009 GAUSS group is involved in a joint collaboration with Morehead State University (MSU) Space Science Center and IRCCS Casa Sollievo della Sofferenza (CSS) research labs with the aim to design a biomedical project in order to investigate if the combined effects of microgravity conditions and ionizing radiation increase or decrease the survival rate of cancer cells. The biological sample consists of Glioblastoma cancer cell line ANGM-CSS. Glioblastoma is a kind of cancer that can be treated after surgery only by radiotherapy using ionizing radiation. This treatment, anyway, results in a very low survival rate. This project uses different university space platforms: a CubeLab, named GlioLab, on board the International Space Station and the university microsatellite UniSat-5 designed by GAUSS. In addition a GlioLab/GlioSat precursor experiment has already flown two times with the Space Shuttle during the missions STS-134 and STS-135. The phase 0 or the precursor of GlioLab uses a COTS system, named Liquid Mixing Apparatus (LMA), to board the biological samples inside the Space Shuttle for thirty day . The LMA allows to board liquids inside a vial but is not equipped with environment control system. After landing the samples were investigated by researchers at CSS in Italy and at MSU in Kentucky. This paper deals with the experimental set up and the results obtained during the STS-134 and STS-135 missions and with the new evidences on the behavior of this kind of cancer. In particular the results obtained on the DNA analysis give a confirmation of the original idea of GLioLab/Gliosat project justifying the development of the two systems.

Cappelletti, Chantal; Notarangelo, Angelo; Demoss, Darrin; Carella, Massimo



Interactions between oligodendrocyte precursors control the onset of CNS myelination  

PubMed Central

The formation of CNS myelin is dependent on the differentiation of oligodendrocyte precursor cells (OPCs) and oligodendrocyte maturation. How the initiation of myelination is regulated is unclear but it is likely to depend on the development of competence by oligodendrocytes and receptivity by target axons. Here we identify an additional level of control of oligodendrocyte maturation mediated by interactions between the different cellular components of the oligodendrocyte lineage. During development oligodendrocyte precursors mature through a series of stages defined by labeling with monoclonal antibodies A2B5 and O4. Newly differentiated oligodendrocytes begin to express galactocerebroside recognized by O1 antibodies and subsequently mature to myelin basic protein (MBP) positive cells prior to formation of compact myelin. Using an in vitro brain slice culture system that supports robust myelination, the consequences of ablating cells at different stages of the oligodendrocyte lineage on myelination has been assayed. Elimination of all OPC lineage cells through A2B5+, O4+ and O1+ complement mediated cell lysis resulted in a delay in development of MBP cells and myelination. Selective elimination of early OPCs (A2B5+) also unexpectedly resulted in delayed MBP expression compared to controls suggesting early OPCs contribute to the timing of myelination onset. By contrast, elimination of differentiated (O1+) immature oligodendrocytes permanently inhibited the appearance of MBP+ cells suggesting that oligodendrocytes are critical to facilitate the maturation of OPCs. These data illuminate that the presence of intra-lineage feed-forward and feedback cues are important for timely myelination by oligodendrocytes.

Yang, Yan; Lewis, Rebecca; Miller, Robert H.



Regulation of Alzheimer beta-amyloid precursor trafficking and metabolism.  


Alzheimer's disease (AD) is characterized by the intracranial accumulation of the 4 kDa amyloid-beta peptide (Abeta), following proteolysis of a approximately 700-amino acid, integral membrane precursor, the Alzheimer amyloid precursor protein (APP). The best evidence causally linking APP to AD has been provided by the discovery of mutations within the APP coding sequence that segregate with disease phenotypes in autosomal dominant forms of familial AD (FAD). Though FAD is rare ( < 10% of all AD), the hallmark features (amyloid plaques, neurofibrillary tangles, synaptic and neuronal loss, neurotransmitter deficits and dementia) are indistinguishable when FAD is compared with typical, common, 'non-familial', or sporadic, AD (SAD). Studies of some clinically relevant mutant APP molecules from FAD families have yielded evidence that APP mutations can lead to the enhanced generation or aggregability of Abeta, consistent with a pathogenic role in AD. Other genetic loci for FAD have been discovered which are distinct from the immediate regulatory and coding regions of the APP gene, indicating that defects in molecules other than APP can also specify cerebral amyloidogenesis and FAD. To date, all APP and non-APP FAD mutations can be demonstrated to have the common feature of promoting amyloidogenesis of Abeta. Epidemiological studies indicate that postmenopausal women on estrogen replacement therapy (ERT) have their relative risk of developing SAD diminished by about one third as compared with age-matched women not receiving ERT [M.X. Tang, D. Jacobs, Y. Stern, K. Marder, P. Schofield, B. Gurland, H. Andrews, R. Mayeux, Effect of estrogen during menopause on risk and age at onset of Alzheimer's disease, Lancet 348 (2000) 429432]. Because of the key role of cerebral Abeta accumulation in initiating AD pathology, it is most attractive that estradiol might modulate SAD risk or age-at-onset by inhibiting Abeta accumulation. A possible mechanistic basis for such a scenario is reviewed here. PMID:10899430

Gandy, S; Petanceska, S



In silico identification of novel hevein-like peptide precursors.  


Lectins are proteins with ability to bind reversibly and non-enzymatically to a specific carbohydrate. They are involved in numerous biological processes and show enormous biotechnological potential. Among plant lectins, the hevein domain is extremely common, being observed in several kinds of lectins. Moreover, this domain is also observed in an important class of antimicrobial peptides named hevein-like peptides. Due to higher cysteine residues conservation, hevein-like peptides could be mined among the sequence databases. By using the pattern CX(4,5)CC[GS]X(2)GXCGX[GST]X(2,3)[FWY]C[GS]X[AGS] novel hevein-like peptide precursors were found from three different plants: Oryza sativa, Vitis vinifera and Selaginella moellendorffii. In addition, an hevein-like peptide precursor from the phytopathogenic fungus Phaeosphaeria nodorum was also identified. The molecular models indicate that they have the same scaffold as others, composed of an antiparallel ?-sheet and short helices. Nonetheless, the fungal hevein-like peptide probably has a different disulfide bond pattern. Despite this difference, the complexes between peptide and N,N,N-triacetylglucosamine are stable, according to molecular dynamics simulations. This is the first report of an hevein-like peptide from an organism outside the plant kingdom. The exact role of an hevein-like peptide in the fungal biology must be clarified, while in plants they are clearly involved in plant defense. In summary, data here reported clear shows that an in silico strategy could lead to the identification of novel hevein-like peptides that could be used as biotechnological tools in the fields of health and agribusiness. PMID:22981805

Porto, William F; Souza, Valéria A; Nolasco, Diego O; Franco, Octávio L



Interactions between oligodendrocyte precursors control the onset of CNS myelination.  


The formation of CNS myelin is dependent on the differentiation of oligodendrocyte precursor cells (OPCs) and oligodendrocyte maturation. How the initiation of myelination is regulated is unclear, but it is likely to depend on the development of competence by oligodendrocytes and receptivity by target axons. Here we identify an additional level of control of oligodendrocyte maturation mediated by interactions between the different cellular components of the oligodendrocyte lineage. During development oligodendrocyte precursors mature through a series of stages defined by labeling with monoclonal antibodies A2B5 and O4. Newly differentiated oligodendrocytes begin to express galactocerebroside recognized by O1 antibodies and subsequently mature to myelin basic protein (MBP)-positive cells prior to formation of compact myelin. Using an in vitro brain slice culture system that supports robust myelination, the consequences of ablating cells at different stages of the oligodendrocyte lineage on myelination have been assayed. Elimination of all OPC lineage cells through A2B5+, O4+, and O1+ complement-mediated cell lysis resulted in a delay in development of MBP cells and myelination. Selective elimination of early OPCs (A2B5+) also unexpectedly resulted in delayed MBP expression compared to controls suggesting that early OPCs contribute to the timing of myelination onset. By contrast, elimination of differentiated (O1+) immature oligodendrocytes permanently inhibited the appearance of MBP+ cells suggesting that oligodendrocytes are critical to facilitate the maturation of OPCs. These data illuminate that the presence of intra-lineage feed-forward and feedback cues are important for timely myelination by oligodendrocytes. PMID:21144846

Yang, Yan; Lewis, Rebecca; Miller, Robert H



Proconvertase proteolytic processing of an enzymatically active myeloperoxidase precursor.  


Optimal and efficient killing of ingested microbes by human neutrophils is mediated in large part by the action of hypochlorous acid produced by the myeloperoxidase-H(2)O(2)-chloride system in phagosomes. Myeloperoxidase gene transcription is limited to early myeloid precursors in the bone marrow, when myeloperoxidase is synthesized and stored in azurophilic granules for subsequent release from stimulated neutrophils. Promyeloperoxidase, the 90 kDa myeloperoxidase precursor synthesized in the endoplasmic reticulum (ER), contains a 125-amino acid pro-region whose function and fate during myeloperoxidase biosynthesis are unknown. Promyeloperoxidase has two fates during myeloperoxidase biosynthesis; the majority undergoes proteolytic processing to generate mature myeloperoxidase, while the remainder is constitutively secreted from the cells in bone marrow. We used a promyelocytic cell line that produces endogenous myeloperoxidase as well as human embryonic kidney cells stably expressing normal and mutant forms of myeloperoxidase to examine proteolytic processing of promyeloperoxidase. We demonstrated that CMK-RVKR, an inhibitor of subtilisin-like proteinases, blocked cleavage of the pro-peptide of promyeloperoxidase in a post-ER compartment. Mutants with alanine substitution of basic residues in the predicted proteinase cleavage site failed to undergo maturation to normal myeloperoxidase subunits and were arrested at the promyeloperoxidase stage. Whereas specific mutants varied as to their stability, secreted promyeloperoxidase from the mutants retained the capacity to generate hypochlorous acid. Taken together, these studies demonstrate proconvertase-dependent cleavage of promyeloperoxidase as an essential step in normal proteolytic processing and granule targeting of myeloperoxidase. Furthermore, although mutations in the proteinase cleavage site reduced intracellular stability of the mutants, the integrity of the heme group was not compromised, as chlorinating activity was retained in the secreted promyeloperoxidase. PMID:22902565

McCormick, Sally; Nelson, Angela; Nauseef, William M



Isolation of a Precursor and a Nascent Chain Form of Glucose-6-Phosphate Dehydrogenase from Rat Uterus and Regulation of Precursor Processing by Estradiol.  

National Technical Information Service (NTIS)

SDS-polyacrylamide gel electrophoresis of anti-glucose-6-phosphate dehydrogenase immunoprecipitates from radiolabeled uterine tissue extracts previously revealed three proteins: A, B and C, which were tentatively identified as a 60-64 kDa precursor form, ...

A. M. Cummings K. L. Barker



Effect of macrophage migration inhibition factor on the content of stromal precursor cells in mouse bone marrow and efficiency of bone marrow precursor cell cloning in vitro.  


The content of stromal precursor cells in the bone marrow of mice decreased 2-5.7 times 24 h after injection of macrophage migration inhibition factor in doses of 0.1-50 ng/kg, this reduction depending on the dose of inhibition factor. The content of precursor cells in the bone marrow of mice increased 2-fold 24 h after injection of S. typhimurium bacterial mass. One day after injection of S. typhimurium bacterial mass, the count of precursor cells in mouse spleen was 7-fold higher than 24 h after injection of macrophage migration inhibition factor. The efficiency of cloning of mouse bone marrow stromal precursor cells in vitro was suppressed 1.7-2.8 times in the presence of macrophage migration inhibition factor in doses of 0.1 to 50 ng/ml culture medium. The effect of cloning inhibition was preserved, if macrophage migration inhibition factor was added to the culture medium after 2 days of bone marrow cell culturing. In general, macrophage migration inhibition factor inhibits stromal precursor cells in vivo and in vitro. The data also indicate that macrophage migration inhibition factor is not responsible for rapid and sharp increase in the count of stromal precursor cells after immunization of animals. PMID:19513377

Gorskaya, U F; Tretyakov, O U; Suslov, A P; Nesterenko, V G



In vitro-Generated Neural Precursors Participate in Mammalian Brain Development  

Microsoft Academic Search

During embryogenesis, pluripotent stem cells segregate into daughter lineages of progressively restricted developmental potential. In vitro, this process has been mimicked by the controlled differentiation of embryonic stem cells into neural precursors. To explore the developmental potential of these cell-culture-derived precursors in vivo, we have implanted them into the ventricles of embryonic rats. The transplanted cells formed intraventricular neuroepithelial structures

Oliver Brustle; A. Cyril Spiro; Khalad Karram; Khalid Choudhary; Shigeo Okabe; Ronald D. G. McKay



Isolation and characterization of stem cell-like precursor cells from primary human anaplastic oligoastrocytoma  

Microsoft Academic Search

A small population of stem cell-like precursors in solid tumors are linked to histological composition, progression, angiogenesis, metastasis, recurrence and drug resistance of a variety of malignant tumors. Oligoastrocytoma is the most common brain mixed glioma composed of mixed cells of oligodendroglial and astrocytic phenotypes. Identification and characterization of stem cell-like precursors in oligoastrocytoma may shed light on the oncogenesis

Liang Yi; Zhi-hua Zhou; Yi-fang Ping; Jian-hong Chen; Xiao-hong Yao; Hua Feng; Jia-you Lu; Ji Ming Wang; Xiu-wu Bian



Carbothermal route for preparation of boron carbide powder from boric acid–citric acid gel precursor  

Microsoft Academic Search

Boron carbide (B4C) powder has been prepared by carbothermal process using boric acid and citric acid as raw materials. Aqueous solution of boric acid in presence of citric acid forms a stable gel under controlled pH condition. The gel on subsequent pyrolysis under vacuum yields a precursor powder consisting of boron oxide and carbon. The precursor is heated under vacuum

A. Sinha; T. Mahata; B. P Sharma



Vapor phase sorbent precursors for toxic metal emissions control from combustors  

Microsoft Academic Search

A bench scale system incorporating a high temperature flow reactor has been utilized to study the reaction of metallic species and sorbent compounds. The reaction and interaction between a lead precursor and a vapor phase silica precursor is studied. The effect of chlorine and the effect of sorbent to metal feed ratio on lead speciation and size distribution is determined.

Timothy M. Owens; Pratim Biswas



Isolation and Characterization of Tumorigenic, Stemlike Neural Precursors from Human Glioblastoma  

Microsoft Academic Search

Transformed stem cells have been isolated from some human cancers. We report that, unlike other brain cancers, the lethal glioblastoma mul- tiforme contains neural precursors endowed with all of the critical fea- tures expected from neural stem cells. Similar, yet not identical, to their normal neural stem cell counterpart, these precursors emerge as unipo- tent (astroglial) in vivo and multipotent

Rossella Galli; Elena Binda; Ugo Orfanelli; Barbara Cipelletti; Angela Gritti; Simona De Vitis; Roberta Fiocco; Chiara Foroni; Francesco Dimeco; Angelo Vescovi



Processing of YBa2Cu3O7 tapes from a molten salt precursor.  

National Technical Information Service (NTIS)

A novel process for forming a viscous nitrate precursor of the superconducting YBa(sub 2)Cu(sub 3)O(sub 7-x) material, without the use of binders or plasticizers, is described. The precursor material is formed at 90(degree)C from low melting salts such as...

R. P. Millis



Solder interconnection failure time estimation based on the embedded precursor behaviour modelling  

Microsoft Academic Search

This article presents a method for estimating solder interconnection failure times based on nonlinear parameter estimation techniques in conjunction with the Levenberg–Marquardt Algorithm (LMA). The LMA algorithm is applied to precursor measurements, from which failure time estimations are deduced using nonlinear estimation parameters. An electrical behavioural model is also proposed for precursors indicating weakening of solder interconnections. This model is

Juha-Veikko Voutilainen; Juha Häkkinen; Markku Moilanen



Precursors for the synthesis of citrulline in mice fed arginine free diets  

Technology Transfer Automated Retrieval System (TEKTRAN)

Dietary arginine (Arg) is the main dietary precursor for citrulline (Cit) synthesis. To test the hypothesis that the contribution of dietary proline (Pro) and glutamine (Gln) increases during the feeding of an Arg free diet, rates of appearance (Ra) and precursor-intermediate-product relationships w...