Sample records for agents sarin gb

  1. Sarin (GB, O-isopropyl methylphosphonofluoridate) neurotoxicity: critical review

    PubMed Central

    Abou-Donia, Mohamed B.; Siracuse, Briana; Gupta, Natasha; Sokol, Ashly Sobel

    2017-01-01

    Sarin (GB, O-isopropyl methylphosphonofluoridate) is a potent organophosphorus (OP) nerve agent that inhibits acetylcholinesterase (AChE) irreversibly. The subsequent build-up of acetylcholine (ACh) in the central nervous system (CNS) provokes seizures and, at sufficient doses, centrally-mediated respiratory arrest. Accumulation of ACh at peripheral autonomic synapses leads to peripheral signs of intoxication and overstimulation of the muscarinic and nicotinic receptors, which is described as “cholinergic crisis” (i.e. diarrhea, sweating, salivation, miosis, bronchoconstriction). Exposure to high doses of sarin can result in tremors, seizures, and hypothermia. More seriously, build-up of ACh at neuromuscular junctions also can cause paralysis and ultimately peripherally-mediated respiratory arrest which can lead to death via respiratory failure. In addition to its primary action on the cholinergic system, sarin possesses other indirect effects. These involve the activation of several neurotransmitters including gamma-amino-butyric acid (GABA) and the alteration of other signaling systems such as ion channels, cell adhesion molecules, and inflammatory regulators. Sarin exposure is associated with symptoms of organophosphate-induced delayed neurotoxicity (OPIDN) and organophosphate-induced chronic neurotoxicity (OPICN). Moreover, sarin has been involved in toxic and immunotoxic effects as well as organophosphate-induced endocrine disruption (OPIED). The standard treatment for sarin-like nerve agent exposure is post-exposure injection of atropine, a muscarinic receptor antagonist, accompanied by an oxime, an AChE reactivator, and diazepam. PMID:27705071

  2. Efficacy of the Tertiary Oxime Monoisonitrosoacetone (MINA) Against Lethal Sarin Intoxication in the Guinea Pig

    DTIC Science & Technology

    2007-10-01

    Sarin 5a. CONTRACT NUMBER Intoxication in the Guinea Pig 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) Koplovitz, I and...efficacy of MINA as a treatment for lethal sarin (GB) intoxication in guinea pigs . Male animals were challenged subcutaneously (s.c.) with 2 LD50s...oximes that are readily able to enter the brain. 15. SUBJECT TERMS oximes, brain, sarin, reactivation, nerve agents, guinea pigs 16. SECURITY

  3. Dissociation of sarin on a cement analogue surface: Effects of humidity and confined geometry

    DOE PAGES

    O’Brien, Christopher J.; Greathouse, Jeffery A.; Tenney, Craig M.

    2016-11-22

    Here, first-principles molecular dynamics simulations were used to investigate the dissociation of sarin (GB) on the calcium silicate hydrate (CSH) mineral tobermorite (TBM), a surrogate for cement. CSH minerals (including TBM) and amorphous materials of similar composition are the major components of Portland cement, the binding agent of concrete. Metadynamics simulations were used to investigate the effect of the TBM surface and confinement in a microscale pore on the mechanism and free energy of dissociation of GB. Our results indicate that both the adsorption site and the humidity of the local environment significantly affect the sarin dissociation energy. In particular,more » sarin dissociation in a low-water environment occurs via a dealkylation mechanism, which is consistent with previous experimental studies.« less

  4. Human Carboxylesterase 1 Stereoselectively Binds the Nerve Agent Cyclosarin and Spontaneously Hydrolyzes the Nerve Agent Sarin

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Hemmert, Andrew C.; Otto, Tamara C.; Wierdl, Monika

    Organophosphorus (OP) nerve agents are potent toxins that inhibit cholinesterases and produce a rapid and lethal cholinergic crisis. Development of protein-based therapeutics is being pursued with the goal of preventing nerve agent toxicity and protecting against the long-term side effects of these agents. The drug-metabolizing enzyme human carboxylesterase 1 (hCE1) is a candidate protein-based therapeutic because of its similarity in structure and function to the cholinesterase targets of nerve agent poisoning. However, the ability of wild-type hCE1 to process the G-type nerve agents sarin and cyclosarin has not been determined. We report the crystal structure of hCE1 in complex withmore » the nerve agent cyclosarin. We further use stereoselective nerve agent analogs to establish that hCE1 exhibits a 1700- and 2900-fold preference for the P{sub R} enantiomers of analogs of soman and cyclosarin, respectively, and a 5-fold preference for the P{sub S} isomer of a sarin analog. Finally, we show that for enzyme inhibited by racemic mixtures of bona fide nerve agents, hCE1 spontaneously reactivates in the presence of sarin but not soman or cyclosarin. The addition of the neutral oxime 2,3-butanedione monoxime increases the rate of reactivation of hCE1 from sarin inhibition by more than 60-fold but has no effect on reactivation with the other agents examined. Taken together, these data demonstrate that hCE1 is only reactivated after inhibition with the more toxic P{sub S} isomer of sarin. These results provide important insights toward the long-term goal of designing novel forms of hCE1 to act as protein-based therapeutics for nerve agent detoxification.« less

  5. Microfluidic chip with optical sensor for rapid detection of nerve agent Sarin in water samples

    NASA Astrophysics Data System (ADS)

    Tan, Hsih Yin; Nguyen, Nam-Trung; Loke, Weng Keong; Tan, Yong Teng

    2007-12-01

    The chemical warfare agent Sarin is an organophosphate that is highly toxic to humans as they can act as cholinesterase inhibitors, that disrupts neuromuscular transmission. As these nerve agents are colorless, odorless and highly toxic, they can be introduced into drinking water as a means of terrorist sabotage. Hence, numerous innovative devices and methods have been developed for rapid detection of these organophosphates. Microfluidic technology allows the implementation of fast and sensitive detection of Sarin. In this paper, a micro-total analysis systems (TAS), also known as Lab-on-a-chip, fitted with an optical detection system has been developed to analyze the presence of the nerve agent sarin in water samples. In the present set-up, inhibition of co-introduced cholinesterase and water samples containing trace amounts of nerve agent sarin into the microfluidic device was used as the basis for selective detection of sarin. The device was fabricated using polymeric micromachining with PMMA (poly (methymethacrylate)) as the substrate material. A chromophore was utilized to measure the activity of remnant cholinesterase activity, which is inversely related to the amount of sarin present in the water samples. Comparisons were made between two different optical detection techniques and the findings will be presented in this paper. The presented measurement method is simple, fast and as sensitive as Gas Chromatography.

  6. In vivo microdialysis and electroencephalographic activity in freely moving guinea pigs exposed to organophosphorus nerve agents sarin and VX: analysis of acetylcholine and glutamate.

    PubMed

    O'Donnell, John C; McDonough, John H; Shih, Tsung-Ming

    2011-12-01

    Organophosphorus nerve agents such as sarin (GB) and VX irreversibly inhibit acetylcholinesterase, causing a buildup of acetylcholine (ACh) in synapses and neuromuscular junctions, which leads to excess bronchial secretions, convulsions, seizures, coma, and death. Understanding the unique toxic characteristics of different nerve agents is vital in the effort to develop broad spectrum medical countermeasures. To this end, we employed a repeated measure multivariate design with striatal microdialysis collection and high-performance liquid chromatography analysis to measure changes in concentrations of several neurotransmitters (ACh, glutamate, aspartate, GABA) in the same samples during acute exposure to GB or VX in freely moving guinea pigs. Concurrent with microdialysis collection, we used cortical electrodes to monitor brain seizure activity. This robust double multivariate design provides greater fidelity when comparing data while also reducing the required number of subjects. No correlation between nerve agents' propensity for causing seizure and seizure-related lethality was observed. The GB seizure group experienced more rapid and severe cholinergic toxicity and lethality than that of the VX seizure group. Seizures generated from GB and VX exposure resulted in further elevation of ACh level and then a gradual return to baseline. Glutamate levels increased in the GB, but not in the VX, seizure group. There were no consistent changes in either aspartate or GABA as a result of either nerve agent. These observations reinforce findings with other nerve agents that seizure activity per se contributes to the elevated levels of brain ACh observed after nerve agent exposure.

  7. A Rapid and Sensitive Strip-Based Quick Test for Nerve Agents Tabun, Sarin, and Soman Using BODIPY-Modified Silica Materials.

    PubMed

    Climent, Estela; Biyikal, Mustafa; Gawlitza, Kornelia; Dropa, Tomáš; Urban, Martin; Costero, Ana M; Martínez-Máñez, Ramón; Rurack, Knut

    2016-08-01

    Test strips that in combination with a portable fluorescence reader or digital camera can rapidly and selectively detect chemical warfare agents (CWAs) such as Tabun (GA), Sarin (GB), and Soman (GD) and their simulants in the gas phase have been developed. The strips contain spots of a hybrid indicator material consisting of a fluorescent BODIPY indicator covalently anchored into the channels of mesoporous SBA silica microparticles. The fluorescence quenching response allows the sensitive detection of CWAs in the μg m(-3) range in a few seconds. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  8. Nerve agent analogues that produce authentic soman, sarin, tabun, and cyclohexyl methylphosphonate-modified human butyrylcholinesterase.

    PubMed

    Gilley, Cynthia; MacDonald, Mary; Nachon, Florian; Schopfer, Lawrence M; Zhang, Jun; Cashman, John R; Lockridge, Oksana

    2009-10-01

    The goal was to test 14 nerve agent model compounds of soman, sarin, tabun, and cyclohexyl methylphosphonofluoridate (GF) for their suitability as substitutes for true nerve agents. We wanted to know whether the model compounds would form the identical covalent adduct with human butyrylcholinesterase that is produced by reaction with true nerve agents. Nerve agent model compounds containing thiocholine or thiomethyl in place of fluorine or cyanide were synthesized as Sp and Rp stereoisomers. Purified human butyrylcholinesterase was treated with a 45-fold molar excess of nerve agent analogue at pH 7.4 for 17 h at 21 degrees C. The protein was denatured by boiling and was digested with trypsin. Aged and nonaged active site peptide adducts were quantified by matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry of the tryptic digest mixture. The active site peptides were isolated by HPLC and analyzed by MALDI-TOF-TOF mass spectrometry. Serine 198 of butyrylcholinesterase was covalently modified by all 14 compounds. Thiocholine was the leaving group in all compounds that had thiocholine in place of fluorine or cyanide. Thiomethyl was the leaving group in the GF thiomethyl compounds. However, sarin thiomethyl compounds released either thiomethyl or isopropyl, while soman thiomethyl compounds released either thiomethyl or pinacolyl. Thiocholine compounds reacted more rapidly with butyrylcholinesterase than thiomethyl compounds. Labeling with the model compounds resulted in aged adducts that had lost the O-alkyl group (O-ethyl for tabun, O-cyclohexyl for GF, isopropyl for sarin, and pinacolyl for soman) in addition to the thiocholine or thiomethyl group. The nerve agent model compounds containing thiocholine and the GF thiomethyl analogue were found to be suitable substitutes for true soman, sarin, tabun, and GF in terms of the adduct that they produced with human butyrylcholinesterase. However, the soman and sarin thiomethyl compounds

  9. Indoor sorption of surrogates for sarin and related nerve agents.

    PubMed

    Singer, Brett C; Hodgson, Alfred T; Destaillats, Hugo; Hotchi, Toshifumi; Revzan, Kenneth L; Sextro, Richard G

    2005-05-01

    Sorption rate parameters were determined for three organophosphorus (OP) compounds [dimethyl methylphosphonate (DMMP), diethyl ethylphosphonate (DEEP), and triethyl phosphate (TEP)] as surrogates for the G-type nerve agents sarin (GB), soman (GD), and tabun (GA). OP surrogates were injected and vaporized with additional volatile organic compounds into a 50 m3 chamber finished with painted wallboard. Experiments were conducted at two furnishing levels: (i) chamber containing only hard surfaces including a desk, a bookcase, tables, and chairs and (ii) with the addition of plush materials including carpet with cushion, draperies, and upholstered furniture. Each furnishing level was studied with aged and new painted wallboard. Gas-phase concentrations were measured during sealed chamber adsorb and desorb phases and then fit to three mathematical variations of a previously proposed sorption model having a surface sink and allowing for an embedded sink. A four-parameter model allowing unequal transport rates between surface and embedded sinks provided excellent fits for all conditions. To evaluate the potential effect of sorption, this model was incorporated into an indoor air quality simulation model to predict indoor concentrations of a G-type agent and a nonsorbing agent for hypothetical outdoor releases with shelter-in-place (SIP) response. Sorption was simulated using a range of parameters obtained experimentally. Simulations considered outdoor Gaussian plumes of 1- and 5-h duration and infiltration rates of 0.1, 0.3, and 0.9 h(-1). Indoor toxic loads (TL) for a 10-h SIP were calculated as integral C2 dt for a G-type agent. For the 5-h plume, sheltering reduced TLs for the nonsorbing agent to approximately 10-65% of outdoor levels. Analogous TLs for a G-type agent were 2-31% or 0.3-12% of outdoor levels assuming slow or moderate sorption. The relative effect of sorption was more pronounced for the longer plume and higher infiltration rates.

  10. Efficacy of human serum butyrylcholinesterase against sarin vapor.

    PubMed

    Saxena, Ashima; Sun, Wei; Dabisch, Paul A; Hulet, Stanley W; Hastings, Nicholas B; Jakubowski, Edward M; Mioduszewski, Robert J; Doctor, Bhupendra P

    2008-09-25

    Human serum butyrylcholinesterase (Hu BChE) is currently under advanced development as a pretreatment drug for organophosphate (OP) poisoning in humans. It was shown to protect mice, rats, guinea pigs, and monkeys against multiple LD(50) challenges of OP nerve agents by i.v. or s.c. bolus injections. Since inhalation is the most likely route of exposure to OP nerve agents on the battlefield or in public places, the aim of this study was to evaluate the efficacy of Hu BChE against whole-body inhalation exposure to sarin (GB) vapor. Male Göttingen minipigs were subjected to one of the following treatments: (1) air exposure; (2) GB vapor exposure; (3) pretreatment with 3 mg/kg of Hu BChE followed by GB vapor exposure; (4) pretreatment with 6.5 mg/kg of Hu BChE followed by GB vapor exposure; (5) pretreatment with 7.5 mg/kg of Hu BChE followed by GB vapor exposure. Hu BChE was administered by i.m. injection, 24h prior to whole-body exposure to GB vapor at a concentration of 4.1 mg/m(3) for 60 min, a dose lethal to 99% of untreated exposed pigs (LCt99). EEG, ECG, and pupil size were monitored throughout exposure, and blood drawn from a surgically implanted jugular catheter before and throughout the exposure period, was analyzed for acetylcholinesterase (AChE) and BChE activities, and the amount of GB present in plasma. All animals exposed to GB vapor alone or pretreated with 3 or 6.5 mg/kg of Hu BChE, died following exposure to GB vapor. All five animals pretreated with 7.5 mg/kg of Hu BChE survived the GB exposure. The amount of GB bound in plasma was 200-fold higher compared to that from plasma of pigs that did not receive Hu BChE, suggesting that Hu BChE was effective in scavenging GB in blood. Additionally, pretreatment with 7.5 mg/kg of Hu BChE prevented cardiac abnormalities and seizure activity observed in untreated animals and those treated with lower doses of Hu BChE.

  11. Natural Detoxification Capacity to Inactivate Nerve Agents Sarin and VX in the Rat Blood.

    PubMed

    Bajgar, Jiří; Cabal, Jiří; Kassa, Jiří; Pavlík, Michal

    2015-01-01

    The method of continual determination of the rat blood cholinesterase activity was developed to study the changes of the blood cholinesterases following different intervetions. The aim of this study is registration of cholinesterase activity in the rat blood and its changes to demonstrate detoxification capacity of rats to inactivate sarin or VX in vivo. The groups of female rats were premedicated (ketamine and xylazine) and cannulated to a. femoralis. Continual blood sampling (0.02 ml/min) and monitoring of the circulating blood cholinesterase activity were performed. Normal activity was monitored 1-2 min and then the nerve agent was administered i.m. (2×LD50). Using different time intervals of the leg compression and relaxation following the agent injection, cholinesterase activity was monitored and according to the inhibition obtained, detoxification capacity was assessed. Administration of sarin to the leg, then 1 and 5 min compression and 20 min later relaxation showed that further inhibition in the blood was not observed. On the other hand, VX was able to inhibit blood cholinesterases after this intervention. The results demonstrated that sarin can be naturally detoxified on the contrary to VX. Described method can be used as model for other studies dealing with changes of cholinesterases in the blood following different factors.

  12. Rotational Spectrum of Sarin

    NASA Astrophysics Data System (ADS)

    Walker, A. R. Hight; Suenram, R. D.; Samuels, Alan; Jensen, James; Ellzy, Michael W.; Lochner, J. Michael; Zeroka, Daniel

    2001-05-01

    As part of an effort to examine the possibility of using molecular-beam Fourier-transform microwave spectroscopy to unambiguously detect and monitor chemical warfare agents, we report the first observation and assignment of the rotational spectrum of the nerve agent Sarin (GB) (Methylphosphonofluoridic acid 1-methyl-ethyl ester, CAS #107-44-8) at frequencies between 10 and 22 GHz. Only one of the two low-energy conformers of this organophosphorus compound (C4H10FO2P) was observed in the rotationally cold (Trot<2 K) molecular beam. The experimental asymmetric-rotor ground-state rotational constants of this conformer are A=2874.0710(9) MHz, B=1168.5776(4) MHz, C=1056.3363(4) MHz (Type A standard uncertainties are given, i.e., 1σ), as obtained from a least-squares analysis of 74 a-, b-, and c-type rotational transitions. Several of the transitions are split into doublets due to the internal rotation of the methyl group attached to the phosphorus. The three-fold-symmetry barrier to internal rotation estimated from these splittings is 677.0(4) cm-1. Ab initio electronic structure calculations using Hartree-Fock, density functional, and Moller-Plesset perturbation theories have also been made. The structure of the lowest-energy conformer determined from a structural optimization at the MP2/6-311G** level of theory is consistent with our experimental findings.

  13. Chemical Warfare Agent Operational Exposure Hazard Assessment Research: FY07 Report and Analysis

    DTIC Science & Technology

    2010-07-01

    of the nerve agents sarin, soman, cyclohexylsarin, VX, and Russian VX in human urine using isotope-dilution gas chromatography-tandem mass...Needham L.L.; Barr, D.B. Quantitation of organophosphorous nerve agent metabolites in human urine using isotope dilution gas chromatography-tandem mass... nerve agents , VX, GB, or GF, and to determine lethal percutaneous (PC) levels of VX. Calibration of Physiologically-based pharmacokinetic biomarkers

  14. Low Dose Sarin Leads To Murine Cardiac Dysfunction

    DTIC Science & Technology

    2010-03-01

    work directly supported a grant held by Wright State University, grant # GW060050, from the United States Army Medical Research Acquisition Activity ...GB), acts as an irreversible AChE inhibitor. Sarin reacts with the serine hydroxyl residue in the active site of AChE to form a phosphate or...United States Air Force has become increasingly engaged with terrorist groups and other elusive enemies. As these activities increase, the potential for

  15. Identification of chemical warfare agents using a portable microchip-based detection device

    NASA Astrophysics Data System (ADS)

    Petkovic-Duran, K.; Swallow, A.; Sexton, B. A.; Glenn, F.; Zhu, Y.

    2011-12-01

    Analysis of chemical warfare agents (CWAs) and their degradation products is an important verification component in support of the Chemical Weapons Convention and urgently demanding rapid and reliable analytical methods. A portable microchip electrophoresis (ME) device with contactless conductivity (CCD) detection was developed for the in situ identification of CWA and their degradation products. A 10mM MES/His, 0.4mM CTAB - based separation electrolyte accomplished the analysis of Sarin (GB), Tabun( GA) and Soman (GD) in less than 1 min, which is the fastest screening of nerve agents achieved with portable ME and CCD based detection methods to date. Reproducibility of detection was successfully demonstrated on simultaneous detection of GB (200ppm) and GA (278ppm). Reasonable agreement for the four consecutive runs was achieved with the mean peak time for Sarin of 29.15s, and the standard error of 0.58s or 2%. GD and GA were simultaneously detected with their degradation products methylphosphonic acid (MPA), pinacolyl methylphosphonic acid (PMPA) and O-Ethyl Phosphorocyanidate (GAHP and GAHP1) respectively. The detection limit for Sarin was around 35ppb. To the best of our knowledge this is the best result achieved in microchip electrophoresis and contactless conductivity based detection to date.

  16. Rotational Spectrum of Sarin.

    PubMed

    Walker, A. R. Hight; Suenram, R. D.; Samuels, Alan; Jensen, James; Ellzy, Michael W.; Lochner, J. Michael; Zeroka, Daniel

    2001-05-01

    As part of an effort to examine the possibility of using molecular-beam Fourier-transform microwave spectroscopy to unambiguously detect and monitor chemical warfare agents, we report the first observation and assignment of the rotational spectrum of the nerve agent Sarin (GB) (Methylphosphonofluoridic acid 1-methyl-ethyl ester, CAS #107-44-8) at frequencies between 10 and 22 GHz. Only one of the two low-energy conformers of this organophosphorus compound (C(4)H(10)FO(2)P) was observed in the rotationally cold (T(rot)<2 K) molecular beam. The experimental asymmetric-rotor ground-state rotational constants of this conformer are A=2874.0710(9) MHz, B=1168.5776(4) MHz, C=1056.3363(4) MHz (Type A standard uncertainties are given, i.e., 1sigma), as obtained from a least-squares analysis of 74 a-, b-, and c-type rotational transitions. Several of the transitions are split into doublets due to the internal rotation of the methyl group attached to the phosphorus. The three-fold-symmetry barrier to internal rotation estimated from these splittings is 677.0(4) cm(-1). Ab initio electronic structure calculations using Hartree-Fock, density functional, and Moller-Plesset perturbation theories have also been made. The structure of the lowest-energy conformer determined from a structural optimization at the MP2/6-311G(**) level of theory is consistent with our experimental findings. Copyright 2001 Academic Press.

  17. Aerosolized scopolamine protects against microinstillation inhalation toxicity to sarin in guinea pigs.

    PubMed

    Che, Magnus M; Chanda, Soma; Song, Jian; Doctor, Bhupendra P; Rezk, Peter E; Sabnekar, Praveena; Perkins, Michael W; Sciuto, Alfred M; Nambiar, Madhusoodana P

    2011-07-01

    Sarin is a volatile nerve agent that has been used in the Tokyo subway attack. Inhalation is predicted to be the major route of exposure if sarin is used in war or terrorism. Currently available treatments are limited for effective postexposure protection against sarin under mass casualty scenario. Nasal drug delivery is a potential treatment option for mass casualty under field conditions. We evaluated the efficacy of endotracheal administration of muscarinic antagonist scopolamine, a secretion blocker which effectively crosses the blood-brain barrier for protection against sarin inhalation toxicity. Age and weight matched male Hartley guinea pigs were exposed to 677.4 mg/m³ or 846.5 mg/ m³ (1.2 × LCt₅₀) sarin by microinstillation inhalation exposure for 4 min. One minute later, the animals exposed to 846.5 mg/ m³ sarin were treated with endotracheally aerosolized scopolamine (0.25 mg/kg) and allowed to recover for 24 h for efficacy evaluation. The results showed that treatment with scopolamine increased the survival rate from 20% to 100% observed in untreated sarin-exposed animals. Behavioral symptoms of nerve agent toxicity including, convulsions and muscular tremors were reduced in sarin-exposed animals treated with scopolamine. Sarin-induced body weight loss, decreased blood O₂ saturation and pulse rate were returned to basal levels in scopolamine-treated animals. Increased bronchoalveolar lavage (BAL) cell death due to sarin exposure was returned to normal levels after treatment with scopolamine. Taken together, these data indicate that postexposure treatment with aerosolized scopolamine prevents respiratory toxicity and protects against lethal inhalation exposure to sarin in guinea pigs.

  18. Effects of low-level sarin and cyclosarin exposure on hippocampal subfields in Gulf War Veterans.

    PubMed

    Chao, Linda L; Kriger, Stephen; Buckley, Shannon; Ng, Peter; Mueller, Susanne G

    2014-09-01

    More than 100,000 US troops were potentially exposed to chemical warfare agents sarin (GB) and cyclosarin (GF) when an ammunition dump at Khamisiyah, Iraq was destroyed during the 1991 Gulf War (GW). We previously reported reduced hippocampal volume in GW veterans with suspected GB/GF exposure relative to matched, unexposed GW veterans estimated from 1.5T magnetic resonance images (MRI). Here we investigate, in a different cohort of GW veterans, whether low-level GB/GF exposure is associated with structural alterations in specific hippocampal subfields, estimated from 4T MRI. The Automatic Segmentation of Hippocampal Subfields (ASHS) technique was used to quantify CA1, CA2, CA3 and dentate gyrus (DG), and subiculum (SUB) subfields volumes from high-resolution T2-weighted images acquired on a 4T MR scanner in 56 GW veterans with suspected GB/GF exposure and 56 "matched" unexposed GW veterans (mean age 49±7 years). GB/GF exposed veterans had smaller CA2 (p=0.003) and CA3/DG (p=0.01) subfield volumes compared to matched, unexposed GW veterans. There were no group difference in total hippocampal volume, quantified with FreeSurfer, and no dose-response relationship between estimated levels of GB/GF exposure and total hippocampal or subfield volume. These findings extend our previous report of structural alterations in the hippocampi of GW veterans with suspected GB/GF exposure to volume changes in the CA2, CA3, and DG hippocampal subfields in a different cohort of GW veterans with suspected GB/GF exposure. Published by Elsevier B.V.

  19. Neuroprotective mechanisms activated in non-seizing rats exposed to sarin.

    PubMed

    Te, Jerez A; Spradling-Reeves, Kimberly D; Dillman, James F; Wallqvist, Anders

    2015-08-27

    Exposure to organophosphate (OP) nerve agents, such as sarin, may lead to uncontrolled seizures and irreversible brain injury and neuropathology. In rat studies, a median lethal dose of sarin leads to approximately half of the animals developing seizures. Whereas previous studies analyzed transcriptomic effects associated with seizing sarin-exposed rats, our study focused on the cohort of sarin-exposed rats that did not develop seizures. We analyzed the genomic changes occurring in sarin-exposed, non-seizing rats and compared differentially expressed genes and pathway activation to those of seizing rats. At the earliest time point (0.25 h) and in multiple sarin-sensitive brain regions, defense response genes were commonly expressed in both groups of animals as compared to the control groups. All sarin-exposed animals activated the MAPK signaling pathway, but only the seizing rats activated the apoptotic-associated JNK and p38 MAPK signaling sub-pathway. A unique phenotype of the non-seizing rats was the altered expression levels of genes that generally suppress inflammation or apoptosis. Importantly, the early transcriptional response for inflammation- and apoptosis-related genes in the thalamus showed opposite trends, with significantly down-regulated genes being up-regulated, and vice versa, between the seizing and non-seizing rats. These observations lend support to the hypothesis that regulation of anti-inflammatory genes might be part of an active and sufficient response in the non-seizing group to protect against the onset of seizures. As such, stimulating or activating these responses via pretreatment strategies could boost resilience against nerve agent exposures. Published by Elsevier B.V.

  20. Prophylaxis with human serum butyrylcholinesterase protects Göttingen minipigs exposed to a lethal high-dose of sarin vapor.

    PubMed

    Saxena, Ashima; Hastings, Nicholas B; Sun, Wei; Dabisch, Paul A; Hulet, Stanley W; Jakubowski, Edward M; Mioduszewski, Robert J; Doctor, Bhupendra P

    2015-08-05

    Serum-derived human butyrylcholinesterase (Hu BChE) is a stoichiometric bioscavenger that is being developed as a potential prophylactic nerve agent countermeasure. Previously, we reported the prophylactic efficacy of Hu BChE in Göttingen minipigs against a whole-body exposure to 4.1mg/m(3) of sarin (GB) vapor, which produced lethality over 60min. Since the toxicity of nerve agent is concentration-dependent, in the present study, we investigated the toxic effects of an almost 3-fold higher rate of GB vapor exposure and the ability of Hu BChE to protect minipigs against this exposure. Male minipigs were subjected to: (1) air exposure; (2) GB vapor exposure; or (3) pretreatment with 7.5mg/kg of Hu BChE by i.m. injection, 24h prior to whole-body exposure to 11.4mg/m(3) of GB vapor for 10min. Electrocardiogram, electroencephalogram, and pupil size were monitored throughout exposure. Blood drawn before and throughout exposure was analyzed for blood gases, electrolytes, metabolites, acetylcholinesterase and BChE activities, and amount of GB bound to red blood cells and plasma. A novel finding was that saline-treated animals exposed to GB vapor did not develop any seizures, but manifested a variety of cardiac and whole blood toxic signs and rapidly died due to respiratory failure. Strikingly, pre-treatment with 7.5mg/kg of Hu BChE not only prevented lethality, but also avoided all cardiac toxic signs manifested in the non-treated cohort. Thus, Hu BChE alone can serve as an effective prophylactic countermeasure versus a lethal high-dose exposure to GB vapor. Published by Elsevier Ireland Ltd.

  1. 2014 Review on the Extension of the AMedP-8(C) Methodology to New Agents, Materials, and Conditions

    DTIC Science & Technology

    2015-08-01

    chemical agents, five biological agents, seven radioisotopes , nuclear fallout, or prompt nuclear effects.1 Each year since 2009, OTSG has sponsored IDA...evaluated four agents: anthrax, botulinum toxin, sarin (GB), and distilled mustard (HD), first using the default parameters and methods in HPAC and...the IDA team then made incremental changes to the default casualty parameters and methods to control for all known data and methodological

  2. Developmental Toxic Effects of Exposure to Chemical Warfare Nerve Agents in Rats: Effects on Brain and Behavior

    DTIC Science & Technology

    2015-03-01

    Analysis of seizure activity and dendritic spine density following exposure to sarin during puberty Methods Female rats were surgically implanted...effects were observed in rats exposed to GB on PND 7 or 21. This study shows that nerve agent exposure during puberty results in severe and life

  3. Hydrolysis of DFP and the Nerve Agent (S)-Sarin by DFPase Proceeds along Two Different Reaction Pathways: Implications for Engineering Bioscavengers

    PubMed Central

    2015-01-01

    Organophosphorus (OP) nerve agents such as (S)-sarin are among the most highly toxic compounds that have been synthesized. Engineering enzymes that catalyze the hydrolysis of nerve agents (“bioscavengers”) is an emerging prophylactic approach to diminish their toxic effects. Although its native function is not known, diisopropyl fluorophosphatase (DFPase) from Loligo vulgaris catalyzes the hydrolysis of OP compounds. Here, we investigate the mechanisms of diisopropylfluorophosphate (DFP) and (S)-sarin hydrolysis by DFPase with quantum mechanical/molecular mechanical umbrella sampling simulations. We find that the mechanism for hydrolysis of DFP involves nucleophilic attack by Asp229 on phosphorus to form a pentavalent intermediate. P–F bond dissociation then yields a phosphoacyl enzyme intermediate in the rate-limiting step. The simulations suggest that a water molecule, coordinated to the catalytic Ca2+, donates a proton to Asp121 and then attacks the tetrahedral phosphoacyl intermediate to liberate the diisopropylphosphate product. In contrast, the calculated free energy barrier for hydrolysis of (S)-sarin by the same mechanism is highly unfavorable, primarily because of the instability of the pentavalent phosphoenzyme species. Instead, simulations suggest that hydrolysis of (S)-sarin proceeds by a mechanism in which Asp229 could activate an intervening water molecule for nucleophilic attack on the substrate. These findings may lead to improved strategies for engineering DFPase and related six-bladed β-propeller folds for more efficient degradation of OP compounds. PMID:24720808

  4. Aum Shinrikyo's Chemical and Biological Weapons: More Than Sarin.

    PubMed

    Tu, A T

    2014-07-01

    The radical religious group Aum Shinrikyo was founded in Japan in the 1980s and grew rapidly in the 1990s. Aum members perpetrated a mass murder in Matsumoto City in 1994, where they used sarin as a chemical weapon to poison approximately 500 civilians. On March 20, 1995, Aum deployed sarin in an even larger terrorist attack on the Tokyo Subway System, which poisoned some 6,000 people. After the Tokyo Subway attack, the Japanese Police arrested the sect's senior members. From 2005 through 2011, 13 of these senior members were sentenced to death. In this article, aspects of Aum's chemical and biological terrorism are reviewed. Sarin production efforts by the sect are described, including how the degradation product of sarin in soil, methylphosphonic acid, enabled the detection of sarin production sites. Also, Aum's chemical-warfare agents other than sarin are described, as are its biological weapons. The author was permitted by the Japanese government to interview Dr. Tomomasa Nakagawa, one of the senior members of Aum Shinrikyo. From Dr. Nakagawa the author obtained valuable inside information about Aum's chemical and biological weapons programs. Copyright © 2014 Central Police University.

  5. Hydrolysis of DFP and the Nerve Agent (S)-Sarin by DFPase Proceeds Along Two Different Reaction Pathways: Implica-tions for Engineering Bioscavengers

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Wymore, Troy W; Langan, Paul; Smith, Jeremy C

    Organophosphorus (OP) nerve agents such as (S)-sarin are among the most highly toxic compounds that have been synthesized. Engineering enzymes that catalyze the hydrolysis of nerve agents ( bioscavengers ) is an emerging prophylactic approach to diminishing their toxic effects. Although its native function is not known, diisopropyl fluorophosphatase (DFPase) from Loligo vulgaris catalyzes the hydrolysis of OP compounds. Here, we investigate the mechanisms of diisopropylfluorophosphate (DFP) and (S)-sarin hydrolysis by DFPase with quantum mechanical/molecular mechanical (QM/MM) umbrella sampling simulations. We find that the mechanism for hydrolysis of DFP involves nucleophilic attack by Asp229 on phosphorus to form a pentavalentmore » intermediate. P F bond dissociation then yields a phosphoacyl enzyme intermediate in the rate-limiting step. The simulations suggest that a water molecule, coordinated to the catalytic Ca2+, donates a proton to Asp121 and then attacks the tetrahedral phosphoacyl intermediate to liberate the diisopropylphosphate product. In contrast, the calculated free energy barrier for hydrolysis of (S)-sarin by the same mechanism is highly unfavorable, primarily due to the instability of the pentavalent phosphoenzyme species. Instead, simulations suggest that hydrolysis of (S)-sarin proceeds by a mechanism in which Asp229 could activate an intervening water molecule for nucleophilic attack on the substrate. These findings may lead to improved strategies for engineering DFPase and related six-bladed -propeller folds for more efficient degradation of OP compounds.« less

  6. Skin decontamination with mineral cationic carrier against sarin determined in vivo.

    PubMed

    Vucemilović, Ante; Hadzija, Mirko; Jukić, Ivan

    2009-06-01

    Our Institute's nuclear, biological, and chemical defense research team continuously investigates and develops preparations for skin decontamination against nerve agents. In this in vivo study, we evaluated skin decontamination efficacy against sarin by a synthetic preparation called Mineral Cationic Carrier (MCC) with known ion exchange, absorption efficacy and bioactive potential. Mice were treated with increasing doses of sarin applied on their skin, and MCC was administered immediately after contamination. The results showed that decontamination with MCC could achieve therapeutic efficacy corresponding to 3 x LD(50) of percutaneous sarin and call for further research.

  7. Blood and bronchoalveolar lavage fluid acetylcholinesterase levels following microinstillation inhalation exposure to sarin in Guinea pigs.

    PubMed

    Che, Magnus M; Conti, Michele; Boylan, Megan; Sciuto, Alfred M; Gordon, Richard K; Nambiar, Madhusoodana P

    2008-07-01

    We determined acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibition in the bronchoalveolar lavage fluid (BALF) following inhalation exposure to chemical threat nerve agent (CTNA) sarin. Age- and weight-matched male guinea pigs were exposed to five different doses of sarin (169.3, 338.7, 508, 677.4, and 846.5 mg/m(3)) using a microinstillation inhalation exposure technique for 4 min. The technique involves aerosolization of the agent in the trachea using a microcatheter with a center hole that delivers the agent and multiple peripheral holes that pumps air to aerosolize the agent at the tip. Animals exposed to higher doses of sarin occasionally developed seizures and succumbed to death within 15 min after exposure. The LCt(50) for sarin using the microinstillation technique was determined to be close to 677.4 mg/m(3). Ear blood AChE activity showed a dose-dependent inhibition at 15 min postexposure. The inhibition of blood AChE remained constant over 35 and 55 min after sarin exposure indicating that there was no lung depot effect. Cardiac blood AChE and butyrylcholinesterase (BChE) activity in surviving animals euthanized at 24 h postexposure showed a dose-dependent inhibition with an inhibition of 60% at 677.4 and 846.5 mg/m(3) sarin exposure. AChE and BChE activity in bronchoalveolar lavage fluid (BALF) showed a slight increase at 338.7 to 677.4 mg/m(3) sarin exposure but a marginal inhibition at 169.3 mg/m(3). In contrast, the AChE protein levels determined by immunoblotting showed an increase at 169.3 mg/m(3) in the BALF. The BALF protein level, a biomarker of lung injury, was increased maximally at 338.7 mg/m(3) and that increase was dropped with an increase in the dose of sarin. The BALF protein levels correlated with the AChE and BChE activity. These data suggest that sarin microinstillation inhalation exposure results in respiratory toxicity and lung injury characterized by changes in lavage AChE, BChE, and protein levels.

  8. Pathways for the Oxidation of Sarin in Urban Atmospheres

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Gerald E. Streit; James E. Bossert; Jeffrey S. Gaffney

    1998-11-01

    Terrorists have threatened and carried out chemicalhiological agent attacks on targets in major cities. The nerve agent sarin figured prominently in one well-publicized incident. Vapors disseminating from open containers in a Tokyo subway caused thousands of casualties. High-resolution tracer transport modeling of agent dispersion is at hand and will be enhanced by data on reactions with components of the urban atmosphere. As a sample of the level of complexity currently attainable, we elaborate the mechanisms by which sarin can decompose in polluted air. A release scenario is outlined involving the passage of a gas-phase agent through a city locale inmore » the daytime. The atmospheric chemistry database on related organophosphorus pesticides is mined for rate and product information. The hydroxyl,radical and fine-mode particles are identified as major reactants. A review of urban air chernistry/rnicrophysics generates concentration tables for major oxidant and aerosol types in both clean and dirty environments. Organic structure-reactivity relationships yield an upper limit of 10-1' cm3 molecule-' S-* for hydrogen abstraction by hydroxyl. The associated midday loss time scale could be as little as one hour. Product distributions are difficult to define but may include nontoxic organic oxygenates, inorganic phosphorus acids, sarin-like aldehydes, and nitrates preserving cholinergic capabilities. Agent molecules will contact aerosol surfaces in on the order of minutes, with hydrolysis and side-chain oxidation as likely reaction channels.« less

  9. The effects of repeated low-dose sarin exposure

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Shih, T.-M.; Hulet, S.W.; McDonough, J.H.

    2006-09-01

    This project assessed the effects of repeated low-dose exposure of guinea pigs to the organophosphorus nerve agent sarin. Animals were injected once a day, 5 days per week (Monday-Friday), for 2 weeks with fractions (0.3x, 0.4x, 0.5x, or 0.6x) of the established LD{sub 5} dose of sarin (42 {mu}g/kg, s.c.). The animals were assessed for changes in body weight, red blood cell (RBC) acetylcholinesterase (AChE) levels, neurobehavioral reactions to a functional observational battery (FOB), cortical electroencephalographic (EEG) power spectrum, and intrinsic acetylcholine (ACh) neurotransmitter (NT) regulation over the 2 weeks of sarin exposure and for up to 12 days postinjection.more » No guinea pig receiving 0.3, 0.4 or 0.5 x LD{sub 5} of sarin showed signs of cortical EEG seizures despite decreases in RBC AChE levels to as low as 10% of baseline, while seizures were evident in animals receiving 0.6 x LD{sub 5} of sarin as early as the second day; subsequent injections led to incapacitation and death. Animals receiving 0.5 x LD{sub 5} sarin showed obvious signs of cholinergic toxicity; overall, 2 of 13 animals receiving 0.5 x LD{sub 5} sarin died before all 10 injections were given, and there was a significant increase in the angle of gait in the animals that lived. By the 10th day of injection, the animals receiving saline were significantly easier to remove from their cages and handle and significantly less responsive to an approaching pencil and touch on the rump in comparison with the first day of testing. In contrast, the animals receiving 0.4 x LD{sub 5} sarin failed to show any significant reductions in their responses to an approaching pencil and a touch on the rump as compared with the first day. The 0.5 x LD{sub 5} sarin animals also failed to show any significant changes to the approach and touch responses and did not adjust to handling or removal from the cage from the first day of injections to the last day of handling. Thus, the guinea pigs receiving

  10. Extraction Methodological Contributions Toward Ultra-Performance Liquid ChromatographyTime-of-Flight Mass Spectrometry: Quantification of Free GB from Various Food Matrices

    DTIC Science & Technology

    2016-02-01

    SPECTROMETRY: QUANTIFICATION OF FREE GB FROM VARIOUS FOOD MATRICES ECBC-TR-1351 Sue Y. Bae Mark D. Winemiller RESEARCH AND TECHNOLOGY DIRECTORATE...Flight Mass Spectrometry: Quantification of Free GB from Various Food Matrices 5a. CONTRACT NUMBER 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER...methylphosphonofluoridate (sarin, GB) in various food matrices. The development of a solid-phase extraction method using a normal-phase silica gel column for

  11. Pretreatment with human serum butyrylcholinesterase alone prevents cardiac abnormalities, seizures, and death in Göttingen minipigs exposed to sarin vapor.

    PubMed

    Saxena, Ashima; Sun, Wei; Dabisch, Paul A; Hulet, Stanley W; Hastings, Nicholas B; Jakubowski, Edward M; Mioduszewski, Robert J; Doctor, Bhupendra P

    2011-12-15

    Human serum butyrylcholinesterase (Hu BChE) is a stoichiometric bioscavenger that is being developed as a prophylactic countermeasure against organophosphorus nerve agents. This study was designed to evaluate the efficacy of Hu BChE against whole-body inhalation exposure to a lethal dose of sarin (GB) vapor. Male Göttingen minipigs were subjected to: air exposure, GB vapor exposure, or pretreatment with Hu BChE followed by GB vapor exposure. Hu BChE was administered by i.m. injection 24 h prior to exposure to 4.1 mg/m(3) of GB vapor for 60 min. Electrocardiograms (ECG), electroencephalograms (EEG), and pupil size were recorded throughout exposure. Blood drawn before and throughout exposure was analyzed for blood gases, electrolytes, metabolites, acetylcholinesterase and BChE activities, and amount of GB present. Untreated animals exposed to GB vapor exhibited cardiac abnormalities and generalized seizures, ultimately succumbing to respiratory failure. Pretreatment with 3.0 or 6.5 mg/kg of Hu BChE delayed blood gas and acid-base disturbances and the onset of cardiac and neural toxic signs, but failed to increase survivability. Pretreatment with 7.5 mg/kg of Hu BChE, however, completely prevented toxic signs, with blood chemistry and ECG and EEG parameters indistinguishable from control during and after GB exposure. GB bound in plasma was 200-fold higher than plasma from pigs that did not receive Hu BChE, suggesting that Hu BChE scavenged GB in blood and prevented it from reaching other tissues. Thus, prophylaxis with Hu BChE alone not only increased survivability, but also prevented cardiac abnormalities and neural toxicity in minipigs exposed to a lethal dose of GB vapor. Published by Elsevier Inc.

  12. A critical role of acute bronchoconstriction in the mortality associated with high-dose sarin inhalation: Effects of epinephrine and oxygen therapies

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Gundavarapu, Sravanthi; Zhuang, Jianguo; Barrett, Edward G.

    Sarin is an organophosphate nerve agent that is among the most lethal chemical toxins known to mankind. Because of its vaporization properties and ease and low cost of production, sarin is the nerve agent with a strong potential for use by terrorists and rouge nations. The primary route of sarin exposure is through inhalation and, depending on the dose, sarin leads to acute respiratory failure and death. The mechanism(s) of sarin-induced respiratory failure is poorly understood. Sarin irreversibly inhibits acetylcholine esterase, leading to excessive synaptic levels of acetylcholine and, we have previously shown that sarin causes marked ventilatory changes includingmore » weakened response to hypoxia. We now show that LD{sub 50} sarin inhalation causes severe bronchoconstriction in rats, leading to airway resistance, increased hypoxia-induced factor-1α, and severe lung epithelium injury. Transferring animals into 60% oxygen chambers after sarin exposure improved the survival from about 50% to 75% at 24 h; however, many animals died within hours after removal from the oxygen chambers. On the other hand, if LD{sub 50} sarin-exposed animals were administered the bronchodilator epinephrine, > 90% of the animals survived. Moreover, while both epinephrine and oxygen treatments moderated cardiorespiratory parameters, the proinflammatory cytokine surge, and elevated expression of hypoxia-induced factor-1α, only epinephrine consistently reduced the sarin-induced bronchoconstriction. These data suggest that severe bronchoconstriction is a critical factor in the mortality induced by LD{sub 50} sarin inhalation, and epinephrine may limit the ventilatory, inflammatory, and lethal effects of sarin. - Highlights: • Inhalation exposure of rats to LD{sub 50} sarin causes death through respiratory failure. • Severe bronchoconstriction is the major cause of sarin-induced respiratory failure. • Transfer of sarin exposed rats to 60% oxygen improves the mortality temporarily

  13. Acute effects of a sarin-like organophosphorus agent, bis(isopropyl methyl)phosphonate, on cardiovascular parameters in anaesthetized, artificially ventilated rats

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Watanabe, Yoshimasa; Itoh, Takeo, E-mail: titoh@med.nagoya-cu.ac.jp; Shiraishi, Hiroaki

    The organophosphorus compound sarin irreversibly inhibits acetylcholinesterase. We examined the acute cardiovascular effects of a sarin-like organophosphorus agent, bis(isopropyl methyl)phosphonate (BIMP), in anaesthetized, artificially ventilated rats. Intravenous administration of BIMP (0.8 mg/kg; the LD50 value) induced a long-lasting increase in blood pressure and tended to increase heart rate. In rats pretreated with the non-selective muscarinic-receptor antagonist atropine, BIMP significantly increased both heart rate and blood pressure. In atropine-treated rats, hexamethonium (antagonist of ganglionic nicotinic receptors) greatly attenuated the BIMP-induced increase in blood pressure without changing the BIMP-induced increase in heart rate. In rats treated with atropine plus hexamethonium, intravenous phentolaminemore » (non-selective α-adrenergic receptor antagonist) plus propranolol (non-selective β-adrenergic receptor antagonist) completely blocked the BIMP-induced increases in blood pressure and heart rate. In atropine-treated rats, the reversible acetylcholinesterase inhibitor neostigmine (1 mg/kg) induced a transient increase in blood pressure, but had no effect on heart rate. These results suggest that in anaesthetized rats, BIMP induces powerful stimulation of sympathetic as well as parasympathetic nerves and thereby modulates heart rate and blood pressure. They may also indicate that an action independent of acetylcholinesterase inhibition contributes to the acute cardiovascular responses induced by BIMP. - Highlights: • A sarin-like agent BIMP markedly increased blood pressure in anaesthetized rats. • Muscarinic receptor blockade enhanced the BIMP-induced increase in blood pressure. • Ganglionic nicotinic receptor blockade attenuated the BIMP-induced response. • Blockade of α- as well as β-receptors attenuated the BIMP-induced response.« less

  14. A System Dynamics Approach to the Efficacy of Oxime Therapy in Sub Lethal Exposure to Sarin Gas

    DTIC Science & Technology

    2015-06-18

    effective treatments , including antidotes, is considered to contribute to this high mortality rate (Buckley et al., 2004:1231). The efficacy of current...officials to reduce the risk associated with high -consequence threats”. Nerve agents, such as Sarin gas, are considered high consequence threats...The threat of use of agents such as Sarin is as much a threat today as any other time in our history. However, the suggested treatment protocol is

  15. Sarin Exposures in A Cohort of British Military Participants in Human Experimental Research at Porton Down 1945-1987.

    PubMed

    Keegan, Thomas J; Carpenter, Lucy M; Brooks, Claire; Langdon, Toby; Venables, Katherine M

    2017-12-15

    The effects of exposure to chemical warfare agents in humans are topical. Porton Down is the UK's centre for research on chemical warfare where, since WWI, a programme of experiments involving ~30000 participants drawn from the UK armed services has been undertaken. Our aim is to report on exposures to nerve agents, particularly sarin, using detailed exposure data not explored in a previous analysis. In this paper, we have used existing data on exposures to servicemen who attended the human volunteer programme at Porton Down to examine exposures to nerve agents in general and to sarin in particular. Six principal nerve agents were tested on humans between 1945 and 1987. Of all 4299 nerve agent tests recorded, 3511 (82%) were with sarin, most commonly in an exposure chamber, with inhalation being the commonest exposure route (85%). Biological response to sarin exposure was expressed as percentage change in cholinesterase activity and, less commonly, change in pupil size. For red blood cell cholinesterase, median inhibition for inhalation tests was 41% (interquartile range 28-51%), with a maximum of 87%. For dermal exposures the maximum inhibition recorded was 99%. There was a clear association between increasing exposure to sarin and depression of cholinesterase activity but the strength and direction of the association varied by exposure route and the presence of chemical or physical protection. Pupil size decreased with increased exposure but this relationship was less clear when modifiers, such as atropine drops, were present. These results, drawn from high quality experimental data, offer a unique insight into the effects of these chemical agents on humans. © The Author 2017. Published by Oxford University Press on behalf of the British Occupational Hygiene Society.

  16. Analysis of chemical warfare agents in food products by atmospheric pressure ionization-high field asymmetric waveform ion mobility spectrometry-mass spectrometry.

    PubMed

    Kolakowski, Beata M; D'Agostino, Paul A; Chenier, Claude; Mester, Zoltán

    2007-11-01

    Flow injection high field asymmetric waveform ion mobility spectrometry (FAIMS)-mass spectrometry (MS) methodology was developed for the detection and identification of chemical warfare (CW) agents in spiked food products. The CW agents, soman (GD), sarin (GB), tabun (GA), cyclohexyl sarin (GF), and four hydrolysis products, ethylphosphonic acid (EPA), methylphosphonic acid (MPA), pinacolyl methylphosphonic acid (Pin MPA), and isopropyl methylphosphonic acid (IMPA) were separated and detected by positive ion and negative ion atmospheric pressure ionization-FAIMS-MS. Under optimized conditions, the compensation voltages were 7.2 V for GD, 8.0 V for GA, 7.2 V for GF, 7.6 V for GB, 18.2 V for EPA, 25.9 V for MPA, -1.9 V for PinMPA, and +6.8 V for IMPA. Sample preparation was kept to a minimum, resulting in analysis times of 3 min or less per sample. The developed methodology was evaluated by spiking bottled water, canola oil, cornmeal, and honey samples at low microgram per gram (or microg/mL) levels with the CW agents or CW agent hydrolysis products. The detection limits observed for the CW agents in the spiked food samples ranged from 3 to 15 ng/mL in bottled water, 1-33 ng/mL in canola oil, 1-34 ng/g in cornmeal, and 13-18 ng/g in honey. Detection limits were much higher for the CW agent hydrolysis products, with only MPA being detected in spiked honey samples.

  17. Department of Defense Chemical, Biological, Defense Program, Annual Report to Congress, March 2005

    DTIC Science & Technology

    2005-03-01

    nerve agents ( GA , GB, GD, and GF), V type nerve agents , and H (mustard) type blister agents . M8 paper can identify agents through...The M21 RSCAAL is an automatic scanning, passive infrared sensor that detects nerve ( GA , GB, and GD) and blister (H and L) agent vapor clouds...Chief of Staff for Programs GA – tabun, a nerve agent GAO – General Accounting Office GBsarin, a nerve agent GD – soman, a nerve

  18. Synergistic Effects of Bacillus amyloliquefaciens (GB03) and Water Retaining Agent on Drought Tolerance of Perennial Ryegrass.

    PubMed

    Su, An-Yu; Niu, Shu-Qi; Liu, Yuan-Zheng; He, Ao-Lei; Zhao, Qi; Paré, Paul W; Li, Meng-Fei; Han, Qing-Qing; Ali Khan, Sardar; Zhang, Jin-Lin

    2017-12-11

    Water retaining agent (WRA) is widely used for soil erosion control and agricultural water saving. Here, we evaluated the effects of the combination of beneficial soil bacterium Bacillus amyloliquefaciens strain GB03 and WRA (the compound is super absorbent hydrogels) on drought tolerance of perennial ryegrass ( Lolium perenne L.). Seedlings were subjected to natural drought for maximum 20 days by stopping watering and then rewatered for seven days. Plant survival rate, biomass, photosynthesis, water status and leaf cell membrane integrity were measured. The results showed that under severe drought stress (20-day natural drought), compared to control, GB03, WRA and GB03+WRA all significantly improved shoot fresh weight, dry weight, relative water content (RWC) and chlorophyll content and decreased leaf relative electric conductivity (REC) and leaf malondialdehyde (MDA) content; GB03+WRA significantly enhanced chlorophyll content compared to control and other two treatments. Seven days after rewatering, GB03, WRA and GB03+WRA all significantly enhanced plant survival rate, biomass, RWC and maintained chlorophyll content compared to control; GB03+WRA significantly enhanced plant survival rate, biomass and chlorophyll content compared to control and other two treatments. The results established that GB03 together with water retaining agent promotes ryegrass growth under drought conditions by improving survival rate and maintaining chlorophyll content.

  19. Micromotor-based on-off fluorescence detection of sarin and soman simulants.

    PubMed

    Singh, Virendra V; Kaufmann, Kevin; Orozco, Jahir; Li, Jinxing; Galarnyk, Michael; Arya, Gaurav; Wang, Joseph

    2015-06-30

    Self-propelled micromotor-based fluorescent "On-Off" detection of nerve agents is described. The motion-based assay utilizes Si/Pt Janus micromotors coated with fluoresceinamine toward real-time "on-the-fly" field detection of sarin and soman simulants.

  20. The sources, fate, and toxicity of chemical warfare agent degradation products.

    PubMed Central

    Munro, N B; Talmage, S S; Griffin, G D; Waters, L C; Watson, A P; King, J F; Hauschild, V

    1999-01-01

    We include in this review an assessment of the formation, environmental fate, and mammalian and ecotoxicity of CW agent degradation products relevant to environmental and occupational health. These parent CW agents include several vesicants: sulfur mustards [undistilled sulfur mustard (H), sulfur mustard (HD), and an HD/agent T mixture (HT)]; nitrogen mustards [ethylbis(2-chloroethyl)amine (HN1), methylbis(2-chloroethyl)amine (HN2), tris(2-chloroethyl)amine (HN3)], and Lewisite; four nerve agents (O-ethyl S-[2-(diisopropylamino)ethyl] methylphosphonothioate (VX), tabun (GA), sarin (GB), and soman (GD)); and the blood agent cyanogen chloride. The degradation processes considered here include hydrolysis, microbial degradation, oxidation, and photolysis. We also briefly address decontamination but not combustion processes. Because CW agents are generally not considered very persistent, certain degradation products of significant persistence, even those that are not particularly toxic, may indicate previous CW agent presence or that degradation has occurred. Of those products for which there are data on both environmental fate and toxicity, only a few are both environmentally persistent and highly toxic. Major degradation products estimated to be of significant persistence (weeks to years) include thiodiglycol for HD; Lewisite oxide for Lewisite; and ethyl methyl phosphonic acid, methyl phosphonic acid, and possibly S-(2-diisopropylaminoethyl) methylphosphonothioic acid (EA 2192) for VX. Methyl phosphonic acid is also the ultimate hydrolysis product of both GB and GD. The GB product, isopropyl methylphosphonic acid, and a closely related contaminant of GB, diisopropyl methylphosphonate, are also persistent. Of all of these compounds, only Lewisite oxide and EA 2192 possess high mammalian toxicity. Unlike other CW agents, sulfur mustard agents (e.g., HD) are somewhat persistent; therefore, sites or conditions involving potential HD contamination should include an

  1. Simultaneous measurement of tabun, sarin, soman, cyclosarin, VR, VX, and VM adducts to tyrosine in blood products by isotope dilution UHPLC-MS/MS.

    PubMed

    Crow, Brian S; Pantazides, Brooke G; Quiñones-González, Jennifer; Garton, Joshua W; Carter, Melissa D; Perez, Jonas W; Watson, Caroline M; Tomcik, Dennis J; Crenshaw, Michael D; Brewer, Bobby N; Riches, James R; Stubbs, Sarah J; Read, Robert W; Evans, Ronald A; Thomas, Jerry D; Blake, Thomas A; Johnson, Rudolph C

    2014-10-21

    This work describes a new specific, sensitive, and rapid stable isotope dilution method for the simultaneous detection of the organophosphorus nerve agents (OPNAs) tabun (GA), sarin (GB), soman (GD), cyclosarin (GF), VR, VX, and VM adducts to tyrosine (Tyr). Serum, plasma, and lysed whole blood samples (50 μL) were prepared by protein precipitation followed by digestion with Pronase. Specific Tyr adducts were isolated from the digest by a single solid phase extraction (SPE) step, and the analytes were separated by reversed-phase ultra high performance liquid chromatography (UHPLC) gradient elution in less than 2 min. Detection was performed on a triple quadrupole tandem mass spectrometer using time-triggered selected reaction monitoring (SRM) in positive electrospray ionization (ESI) mode. The calibration range was characterized from 0.100-50.0 ng/mL for GB- and VR-Tyr and 0.250-50.0 ng/mL for GA-, GD-, GF-, and VX/VM-Tyr (R(2) ≥ 0.995). Inter- and intra-assay precision had coefficients of variation of ≤17 and ≤10%, respectively, and the measured concentration accuracies of spiked samples were within 15% of the targeted value for multiple spiking levels. The limit of detection was calculated to be 0.097, 0.027, 0.018, 0.074, 0.023, and 0.083 ng/mL for GA-, GB-, GD-, GF-, VR-, and VX/VM-Tyr, respectively. A convenience set of 96 serum samples with no known nerve agent exposure was screened and revealed no baseline values or potential interferences. This method provides a simple and highly specific diagnostic tool that may extend the time postevent that a confirmation of nerve agent exposure can be made with confidence.

  2. Effects of low-level exposure to sarin and cyclosarin during the 1991 Gulf War on brain function and brain structure in US veterans.

    PubMed

    Chao, Linda L; Rothlind, Johannes C; Cardenas, Valerie A; Meyerhoff, Dieter J; Weiner, Michael W

    2010-09-01

    Potentially more than 100,000 US troops may have been exposed to the organophosphate chemical warfare agents sarin (GB) and cyclosarin (GF) when a munitions dump at Khamisiyah, Iraq was destroyed during the Gulf War (GW) in 1991. Although little is known about the long-term neurobehavioral or neurophysiological effects of low-dose exposure to GB/GF in humans, recent studies of GW veterans from the Devens Cohort suggest decrements in certain cognitive domains and atrophy in brain white matter occur individuals with higher estimated levels of presumed GB/GF exposure. The goal of the current study is to determine the generalizability of these findings in another cohort of GW veterans with suspected GB/GF exposure. Neurobehavioral and imaging data collected in a study on Gulf War Illness between 2002 and 2007 were used in this study. We focused on the data of 40 GW-deployed veterans categorized as having been exposed to GB/GF at Khamisiyah, Iraq and 40 matched controls. Magnetic resonance images (MRI) of the brain were analyzed using automated and semi-automated image processing techniques that produced volumetric measurements of gray matter (GM), white matter (WM), cerebrospinal fluid (CSF) and hippocampus. GW veterans with suspected GB/GF exposure had reduced total GM and hippocampal volumes compared to their unexposed peers (p< or =0.01). Although there were no group differences in measures of cognitive function or total WM volume, there were significant, positive correlations between total WM volume and measures of executive function and visuospatial abilities in veterans with suspected GB/GF exposure. These findings suggest that low-level exposure to GB/GF can have deleterious effects on brain structure and brain function more than decade later. Copyright © 2010 Elsevier Inc. All rights reserved.

  3. Effects of low-level exposure to sarin and cyclosarin during the 1991 Gulf War on brain function and brain structure in US veterans

    PubMed Central

    Chao, Linda L.; Rothlind, Johannes C.; Cardenas, Valerie A.; Meyerhoff, Dieter J.; Weiner, Michael W.

    2010-01-01

    Background Potentially more than 100,000 US troops may have been exposed to the organophosphate chemical warfare agents sarin (GB) and cyclosarin (GF) when a munitions dump at Khamisiyah, Iraq was destroyed during the Gulf War (GW) in 1991. Although little is known about the long-term neurobehavioral or neurophysiological effects of low-dose exposure to GB/GF in humans, recent studies of GW veterans from the Devens Cohort suggest decrements in certain cognitive domains and atrophy in brain white matter occur individuals with higher estimated levels of presumed GB/GF exposure. The goal of the current study is to determine the generalizability of these findings in another cohort of GW veterans with suspected GB/GF exposure. Methods Neurobehavioral and imaging data collected in a study on Gulf War Illness between 2002–2007 were used in this study. We focused on the data of 40 GW-deployed veterans categorized as having been exposed to GB/GF at Khamisiyah, Iraq and 40 matched controls. Magnetic resonance images (MRI) of the brain were analyzed using automated and semi-automated image processing techniques that produced volumetric measurements of gray matter (GM), white matter (WM), cerebrospinal fluid (CSF) and hippocampus. Results GW veterans with suspected GB/GF exposure had reduced total GM and hippocampal volumes compared to their unexposed peers (p≤0.01). Although there were no group differences in measures of cognitive function or total WM volume, there were significant, positive correlations between total WM volume and measures of executive function and visuospatial abilities in veterans with suspected GB/GF exposure. Conclusions These findings suggest that low-level exposure to GB/GF can have deleterious effects on brain structure and brain function more than decade later. PMID:20580739

  4. Synergistic Effects of Bacillus amyloliquefaciens (GB03) and Water Retaining Agent on Drought Tolerance of Perennial Ryegrass

    PubMed Central

    Su, An-Yu; Niu, Shu-Qi; Liu, Yuan-Zheng; He, Ao-Lei; Zhao, Qi; Li, Meng-Fei; Han, Qing-Qing; Ali Khan, Sardar

    2017-01-01

    Water retaining agent (WRA) is widely used for soil erosion control and agricultural water saving. Here, we evaluated the effects of the combination of beneficial soil bacterium Bacillus amyloliquefaciens strain GB03 and WRA (the compound is super absorbent hydrogels) on drought tolerance of perennial ryegrass (Lolium perenne L.). Seedlings were subjected to natural drought for maximum 20 days by stopping watering and then rewatered for seven days. Plant survival rate, biomass, photosynthesis, water status and leaf cell membrane integrity were measured. The results showed that under severe drought stress (20-day natural drought), compared to control, GB03, WRA and GB03+WRA all significantly improved shoot fresh weight, dry weight, relative water content (RWC) and chlorophyll content and decreased leaf relative electric conductivity (REC) and leaf malondialdehyde (MDA) content; GB03+WRA significantly enhanced chlorophyll content compared to control and other two treatments. Seven days after rewatering, GB03, WRA and GB03+WRA all significantly enhanced plant survival rate, biomass, RWC and maintained chlorophyll content compared to control; GB03+WRA significantly enhanced plant survival rate, biomass and chlorophyll content compared to control and other two treatments. The results established that GB03 together with water retaining agent promotes ryegrass growth under drought conditions by improving survival rate and maintaining chlorophyll content. PMID:29232909

  5. In Vivo Microdialysis and Electroencephalographic Activity in Freely Moving Guinea Pigs Exposed to Organophosphorus Nerve Agents Sarin and VX: Analysis of Acetylcholine and Glutamate

    DTIC Science & Technology

    2011-01-01

    3. DATES COVERED (From - To) 4. TITLE AND SUBTITLE In vivo microdialysis and electroencephalographic activity in freely moving guinea pigs 5a...microdialysis and electroencephalographic activity in freely moving guinea pigs exposed to organophosphorus nerve agents sarin and VX: analysis of...brain seizure activity . This robust double multi- variate design provides greater fidelity when comparing data while also reducing the required number

  6. Neuroimmune Effects of Inhaling Low Dose Sarin

    DTIC Science & Technology

    2008-02-01

    system Because two of the Japanese sarin terrorism survivors succumbed to Legionella infection nearly two years after the sarin exposure (Kamimura...lung organism, Legionella . However, our results indicated that both adaptive (antibody and T cell receptor-mediated responses) as well inflammatory...H. Niino, K. Saitoh, and A. Saitoh. 1998. Legionella pneumonia caused by aspiration of hot spring water after sarin exposure. Nihon. Kokyuki. Gakkai

  7. GC-MS/MS Analyses of Biological Samples in Support of Developmental Toxic Effects on Subcutaneous Exposure of Rats to GB

    DTIC Science & Technology

    2015-11-01

    cholinergic symptoms after the release of GB in the Tokyo subway system (Ohbu et al., 1997). In fact, infants and small children may be at greater...Matsui, R.; Sakurai, K.; Hinohara, S. Sarin Poisoning on Tokyo Subway . South. Med. J. 1997, 90, 587–593. Russell, R.W.; Overstreet, D.H. Mechanisms

  8. Assessing Protection Against OP Pesticides and Nerve Agents Provided by Wild-Type HuPON1 Purified from Trichoplusia ni Larvae or Induced via Adenoviral Infection

    DTIC Science & Technology

    2013-01-01

    times the median lethal dose (LD50) of the OP nerve agents tabun (GA), sarin (GB), soman (GD), and cyclosarin (GF), or chlorpyrifos oxon, the toxic...metabolite of the OP pesticide chlorpyrifos . In the second model, mice were infected with an adenovirus that induced expression of HuPON1 and then...mice are dramati- cally more susceptible to the toxic metabolites of the OP pesticides diazinon and chlorpyrifos (diazoxon and chlorpyrifos oxon

  9. Effects of low-level sarin and cyclosarin exposure and Gulf War Illness on brain structure and function: a study at 4T.

    PubMed

    Chao, Linda L; Abadjian, Linda; Hlavin, Jennifer; Meyerhoff, Deiter J; Weiner, Michael W

    2011-12-01

    More than 100,000 US troops were potentially exposed to chemical warfare agents sarin (GB) and cyclosarin (GF) when an ammunition dump at Khamisiyah, Iraq was destroyed during the 1991 Persian Gulf War (GW). We previously found reduced total gray matter (GM) volume in 40 GW veterans with suspected GB/GF exposure relative to 40 matched, unexposed GW veterans on a 1.5T MR scanner. In this study, we reexamine the relationship between GB/GF exposure and volumetric measurements of gross neuroanatomical structures in a different cohort of GW veterans on a 4T MR scanner. Neuropsychological and magnetic resonance imaging (MRI) data from a cross sectional study on Gulf War Illness performed between 2005 and 2010 were used in this study. 4T MRI data were analyzed using automated image processing techniques that produced volumetric measurements of gray matter (GM), white matter (WM) and cerebrospinal fluid (CSF). Binary comparisons of 64 GB/GF exposed veterans and 64 'matched', unexposed veterans revealed reduced GM (p=0.03) and WM (p=0.03) volumes in the exposed veterans. Behaviorally, exposed veterans committed more errors of omission (p=0.02) and tended to have slower responses (p=0.05) than unexposed veterans on the Continuous Performance Test (CPT), a measure sustained and selective attention. Regression analyses confirmed that GB/GF exposure status predicted GM (β=-0.11, p=0.02) and WM (β=-0.14, p=0.03) volumes, and number of CPT omission errors (β=0.22, p=0.02) over and above potentially confounding demographic, clinical, and psychosocial variables. There was no dose-response relationship between estimated levels of GB/GF exposure and brain volume. However, we did find an effect of Gulf War Illness/Chronic Multisymptom Illness on both GM and WM volume in the GB/GF exposed veterans. These findings confirm previous reports by our group and others of central nervous system pathology in GW veterans with suspected exposure to low levels of GB/GF two decades after the

  10. Department of Defense Chemical and Biological Defense Program. Volume I: Annual Report to Congress

    DTIC Science & Technology

    2002-04-01

    The M21 RSCAAL is an automatic scanning, passive infrared sensor that detects nerve ( GA , GB, and GD) and blister (H and L) agent vapor clouds based on...Point Detection GA - tabun, a nerve agent System GAO - General Accounting Office IPE - Individual Protective Equipment GAS - Group A Streptococcus...IPR - In-Process Review GB - sarin , a nerve agent IPT - Integrated Product Team GC - gas chromatography IR&D - Independent Research & Development GD

  11. NEUROBEHAVIORAL TERATOGENICITY OF SARIN IN AN AVIAN MODEL

    PubMed Central

    Yanai, Joseph; Pinkas, Adi; Seidler, Frederic J.; Ryde, Ian T.; Van der Zee, Eddy A.; Slotkin, Theodore A.

    2009-01-01

    Nerve gas organophosphates like sarin are likely to be used in urban terrorism, leading to widespread exposures of pregnant women and young children. Here, we established a model for sarin neurobehavioral teratogenicity in the developing chick so as to explore the consequences of apparently subtoxic sarin exposure and the mechanisms underlying synaptic and behavioral deficits. Chicken eggs were injected with sarin (2, 6 and 12 μg/kg) on incubation days 2 and 6, treatments that did not decrease hatching and did not evoke dysmorphology. After hatching the chicks were tested for filial imprinting and neurochemical markers known to be critical for imprinting. Imprinting was reduced at 2 and 6 μg/kg but not at the highest dose. Acetylcholinesterase and choline acetyltransferase were unaffected but sarin reduced the concentration of the high-affinity choline transporter, the rate-limiting factor in acetylcholine utilization. The concentration of PKC isoforms was assessed in the imprinting-related intermediate part of the medial hyperstriatum ventrale, the region most closely associated with cholinergic function in imprinting behavior. Sarin reduced the concentration of all isoforms (α, β, γ) with a similar, biphasic dose-response curve to that seen for behavioral performance, a relationship noted in previous work with organophosphate pesticides. Our results indicate that otherwise subtoxic exposures to sarin produce neurodevelopmental deficits; since we utilized a chick model, which is devoid of maternal confounds that are present in mammalian development, the adverse effects of sarin are mediated directly in the developing organism. PMID:19660543

  12. Novel brain-penetrating oximes for reactivation of cholinesterase inhibited by sarin and VX surrogates.

    PubMed

    Chambers, Janice E; Meek, Edward C; Chambers, Howard W

    2016-06-01

    Current oxime reactivators for organophosphate-inhibited cholinesterase (ChE) do not effectively cross the blood-brain barrier and therefore cannot restore brain ChE activity in vivo. Our laboratories have studied highly relevant sarin and VX surrogates, which differ from their respective nerve agents only in the leaving group and thereby leave ChE phosphylated with the same chemical moiety as sarin and VX. Our laboratories have developed novel substituted phenoxyalkyl pyridinium oximes that lead to reduced ChE inhibition in the brains of rats challenged with a high sublethal dosage of the sarin surrogate, whereas 2-PAM did not, using a paradigm designed to demonstrate brain penetration. In addition, treatment of rats with these novel oximes is associated with attenuation of seizure-like behavior compared to rats treated with 2-PAM, providing additional evidence that the oximes penetrate the blood-brain barrier. Further, some of the oximes provided 24-h survival superior to 2-PAM, and shortened the duration of seizure-like behavior when rats were challenged with lethal dosages of the sarin and VX surrogates, providing additional support for the conclusion that these oximes penetrate the brain. © 2016 New York Academy of Sciences.

  13. Toxicity of the Organophosphate Chemical Warfare Agents GA, GB, and VX: Implications for Public Protection.

    PubMed Central

    Munro, N

    1994-01-01

    The nerve agents, GA, GB, and VX are organophosphorus esters that form a major portion of the total agent volume contained in the U.S. stockpile of unitary chemical munitions. Congress has mandated the destruction of these agents, which is currently slated for completion in 2004. The acute, chronic, and delayed toxicity of these agents is reviewed in this analysis. The largely negative results from studies of genotoxicity, carcinogenicity, developmental, and reproductive toxicity are also presented. Nerve agents show few or delayed effects. At supralethal doses, GB can cause delayed neuropathy in antidote-protected chickens, but there is no evidence that it causes this syndrome in humans at any dose. Agent VX shows no potential for inducing delayed neuropathy in any species. In view of their lack of genotoxcity, the nerve agents are not likely to be carcinogens. The overreaching concern with regard to nerve agent exposure is the extraordinarily high acute toxicity of these substances. Furthermore, acute effects of moderate exposure such as nausea, diarrhea, inability to perform simple mental tasks, and respiratory effects may render the public unable to respond adequately to emergency instructions in the unlikely event of agent releaase, making early warning and exposure avoidance important. Likewise, exposure or self-contamination of first responders and medical personnel must be avoided. Control limits for exposure via surface contact of drinking water are needed, as are detection methods for low levels in water or foodstuffs. Images Figure 2. PMID:9719666

  14. Quantitative proteomic analysis of the brainstem following lethal sarin exposure.

    PubMed

    Meade, Mitchell L; Hoffmann, Andrea; Makley, Meghan K; Snider, Thomas H; Schlager, John J; Gearhart, Jeffery M

    2015-06-22

    The brainstem represents a major tissue area affected by sarin organophosphate poisoning due to its function in respiratory and cardiovascular control. While the acute toxic effects of sarin on brainstem-related responses are relatively unknown, other brain areas e.g., cortex or cerebellum, have been studied more extensively. The study objective was to analyze the guinea pig brainstem toxicology response following sarin (2×LD50) exposure by proteome pathway analysis to gain insight into the complex regulatory mechanisms that lead to impairment of respiratory and cardiovascular control. Guinea pig exposure to sarin resulted in the typical acute behavior/physiology outcomes with death between 15 and 25min. In addition, brain and blood acetylcholinesterase activity was significantly reduced in the presence of sarin to 95%, and 89%, respectively, of control values. Isobaric-tagged (iTRAQ) liquid chromatography tandem mass spectrometry (LC-MS/MS) identified 198 total proteins of which 23% were upregulated, and 18% were downregulated following sarin exposure. Direct gene ontology (GO) analysis revealed a sarin-specific broad-spectrum proteomic profile including glutamate-mediated excitotoxicity, calcium overload, energy depletion responses, and compensatory carbohydrate metabolism, increases in ROS defense, DNA damage and chromatin remodeling, HSP response, targeted protein degradation (ubiquitination) and cell death response. With regards to the sarin-dependent effect on respiration, our study supports the potential interference of sarin with CO2/H(+) sensitive chemoreceptor neurons of the brainstem retrotrapezoid nucleus (RTN) that send excitatory glutamergic projections to the respiratory centers. In conclusion, this study gives insight into the brainstem broad-spectrum proteome following acute sarin exposure and the gained information will assist in the development of novel countermeasures. Published by Elsevier B.V.

  15. Novel brain-penetrating oximes for reactivation of cholinesterase inhibited by sarin and VX surrogates

    PubMed Central

    Chambers, Janice E.; Meek, Edward C.; Chambers, Howard W.

    2016-01-01

    Current oxime reactivators for organophosphate-inhibited cholinesterase (ChE) do not effectively cross the blood–brain barrier and therefore cannot restore brain ChE activity in vivo. Our laboratories have studied highly relevant sarin and VX surrogates, which differ from their respective nerve agents only in the leaving group and thereby leave ChE phosphylated with the same chemical moiety as sarin and VX. Our laboratories have invented novel substituted phenoxyalkyl pyridinium oximes (U.S. Patent 9,227,937 B2) that lead to reduced ChE inhibition in the brains of rats challenged with a high sublethal dosage of the sarin surrogate, whereas 2-PAM did not, using a paradigm designed to demonstrate brain penetration. In addition, these novel oximes also showed an attenuation of seizure-like behavior compared to rats treated with 2-PAM, giving additional evidence of the ability of these oximes to penetrate the blood–brain barrier. Further, some of these oximes provided 24-hour survival superior to 2-PAM and shortened the duration of seizure-like behavior when rats were challenged with lethal dosages of the sarin and VX surrogates, providing additional support for the concept of these life-saving oximes penetrating the brain. PMID:27153507

  16. Toxicity of the organophosphate chemical warfare agents GA, GB, and VX: Implications for public protection

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Munro, N.B.; Ambrose, K.R.; Watson, A.P.

    1994-01-01

    The nerve agents, GA, GB, and VX are organophosphorus esters that form a major portion of the total agent volume contained in the U.S. stockpile of unitary chemical munitions. Congress has mandated the destruction of these agents, which is currently slated for completion in 2004. The acute, chronic, and delayed toxicity of these agents is reviewed in this analysis. The largely negative results from studies of genotoxicity, carcinogenicity, developmental, and reproductive toxicity are also presented. Nerve agents show few or delayed effects. At supralethal doses, GB can cause delayed neuropathy in antidote-protected chickens, but there is not evidence that itmore » causes this syndrome in humans at any dose. Agent VX shows no potential for inducing delayed neuropathy in any species. In view of their lack of genotoxicity, the nerve agent exposure is the extraordinarily high acute toxicity of these substances. Futhermore, acute effects of moderate exposure such as nausea, diarrhea, inability to perform simple mental tasks, and respiratory effects may render the public unable to respond adequately to emergency instructions in the unlikely event of agent release, making early warning and exposure avoidance important. Likewise, exposure or self-contamination of first responders and medical personnel must be avoided. Control limits for exposure via surface contact of drinking water are needed, as are detection methods for low levels in water or foodstuffs. 187 refs., 3 figs., 7 tabs.« less

  17. Selective Surface Acoustic Wave-Based Organophosphorus Sensor Employing a Host-Guest Self-Assembly Monolayer of β-Cyclodextrin Derivative

    PubMed Central

    Pan, Yong; Mu, Ning; Shao, Shengyu; Yang, Liu; Wang, Wen; Xie, Xiao; He, Shitang

    2015-01-01

    Self-assembly and molecular imprinting technologies are very attractive technologies for the development of artificial recognition systems and provide chemical recognition based on need and not happenstance. In this paper, we employed a β-cyclodextrin derivative surface acoustic wave (SAW) chemical sensor for detecting the chemical warfare agents (CWAs) sarin (O-Isoprophyl methylphosphonofluoridate, GB). Using sarin acid (isoprophyl hydrogen methylphosphonate) as an imprinting template, mono[6-deoxy-6-[(mercaptodecamethylene)thio

  18. United States Army Biomedical Research and Development Laboratory Annual Progress Report FY90

    DTIC Science & Technology

    1991-01-01

    pesticide . Parallel and follow-on studies will include hydrolysis products of nerve agents , vesicants, and agents of...Division FO Fog oil FORSCOM U.S. Army Forces Command FY Fiscal year 249 GA The nerve agent tabun GB The nerve agent soman GD The nerve agent sarin GLP... Nerve Agents , Industrial Hygiene Sampling, Microbiology, Combustion Products, Liquid Gun Propellant, Organic Chemistry, Inorganic

  19. Screening of nerve agent degradation products by MALDI-TOFMS.

    PubMed

    Shu, You-Ren; Su, An-Kai; Liu, Ju-Tsung; Lin, Cheng-Huang

    2006-07-01

    A novel method for the rapid screening of degradation products derived from nerve agents by matrix-assisted laser desorption ionization time-of-flight mass spectrometry is described. Five standard products were selected as model compounds, including isopropyl methylphosphonic acid (IMPA), pinacolyl methylphosphonic acid (PMPA), ethyl methylphosphonic acid (EMPA), isobutyl methylphosphonic acid (i-BuMPA), and cyclohexyl methylphosphonic acid (CHMPA), which are degradation products of Sarin (GB), Soman (GD), VX, Russian VX (RVX), and GF, respectively. For comparison, CHCA (alpha-cyano-4-hydroxycinnamic acid) and DCCA (7-(diethylamino)coumarin-3-carboxylic acid) were used as the MALDI-matrix when the third harmonic generation (355 nm) of a Nd:YAG laser and a hydrogen Raman laser (multifrequency laser) were used, respectively. The method permitted the five nerve agent degradation products to be screened rapidly and successfully, suggesting that it has the potential for use as a routine monitoring tool.

  20. Treatment with endotracheal therapeutics after sarin microinstillation inhalation exposure increases blood cholinesterase levels in guinea pigs.

    PubMed

    Che, Magnus M; Song, Jian; Oguntayo, Samuel; Doctor, Bhupendra P; Rezk, Peter; Perkins, Michael W; Sciuto, Alfred M; Nambiar, Madhusoodana P

    2012-05-01

    Acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) activities were measured in the blood and tissues of animals that are treated with a number of endotracheally aerosolized therapeutics for protection against inhalation toxicity to sarin. Therapeutics included, aerosolized atropine methyl bromide (AMB), scopolamine or combination of AMB with salbutamol, sphingosine 1-phosphate, keratinocyte growth factor, adenosine A1 receptor antisense oligonucleotide (EPI2010), 2,3-diacetyloxybenzoic acid (2,3 DABA), oxycyte, and survanta. Guinea pigs exposed to 677.4 mg/m(3) or 846.5 mg/m(3) (1.2 LCt(50)) sarin for 4 min using a microinstillation inhalation exposure technique and treated 1 min later with the aerosolized therapeutics. Treatment with all therapeutics significantly increased the survival rate with no convulsions throughout the 24 h study period. Blood AChE activity determined using acetylthiocholine as substrate showed 20% activity remaining in sarin-exposed animals compare to controls. In aerosolized AMB and scopolamine-treated animals the remaining AChE activity was significantly higher (45-60%) compared to sarin-exposed animals (p < 0.05). Similarly, treatment with all the combination therapeutics resulted in significant increase in blood AChE activity in comparison to sarin-exposed animals although the increases varied between treatments (p < 0.05). BChE activity was increased after treatment with aerosolized therapeutics but was lesser in magnitude compared to AChE activity changes. Various tissues showed elevated AChE activity after therapeutic treatment of sarin-exposed animals. Increased AChE and BChE activities in animals treated with nasal therapeutics suggest that enhanced breathing and reduced respiratory toxicity/lung injury possibly contribute to rapid normalization of chemical warfare nerve agent inhibited cholinesterases.

  1. EPA Science Matters Newsletter: Chemical Warfare Agent Analytical Standards Facilitate Lab Testing (Published November 2013)

    EPA Pesticide Factsheets

    Learn about the EPA chemists' efforts to develop methods for detecting extremely low concentrations of nerve agents, such as sarin, VX, soman and cyclohexyl sarin, and the blister agent sulfur mustard.

  2. Development of Novel Decontamination Techniques for Chemical Agents (GB, VX, HD) Contaminated Facilities. Phase II. Laboratory Evaluation of Novel Agent Decontamination Concepts

    DTIC Science & Technology

    1985-06-21

    mild steel, unpainted mild steel, and porous (i.e., concrete and unglazed porcelain ) test coupons contaminated with agent to a hot-gas composition near...unpainted *’ mild steel, painted stainless steel, concrete, and unglazed porcelain * coupons contaminated with HD, GB, or VX. The detectable limit for the Sub...similar decontamination efficiency was observable in the concrete and unglazed porcelain tests for an initial dose level of 1.8 mg agent/g of material

  3. Molecular and dissociative adsorption of DMMP, Sarin and Soman on dry and wet TiO2(110) using density functional theory

    NASA Astrophysics Data System (ADS)

    Quintero, Yenny Cardona; Nagarajan, Ramanathan

    2018-09-01

    Titania, among the metal oxides, has shown promising characteristics for the adsorption and decontamination of chemical warfare nerve agents, due to its high stability and rapid decomposition rates. In this study, the adsorption energy and geometry of the nerve agents Sarin and Soman, and their simulant dimethyl methyl phosphonate (DMMP) on TiO2 rutile (110) surface were calculated using density functional theory. The molecular and dissociative adsorption of the agents and simulant on dry as well as wet metal oxide surfaces were considered. For the wet system, computations were done for the cases of both molecularly adsorbed water (hydrated conformation) and dissociatively adsorbed water (hydroxylated conformation). DFT calculations show that dissociative adsorption of the agents and simulant is preferred over molecular adsorption for both dry and wet TiO2. The dissociative adsorption on hydrated TiO2 shows higher stability among the different configurations considered. The dissociative structure of DMMP on hydrated TiO2 (the most stable one) was identified as the dissociation of a methyl group and its adsorption on the TiO2 surface. For the nerve agents Sarin and Soman on hydrated TiO2 the dissociative structure was by the dissociation of the F atom from the molecule and its interaction with a Ti atom from the surface, which could indicate a reduction in the toxicity of the products. This study shows the relevance of water adsorption on the metal oxide surface for the stability and dissociation of the simulant DMMP and the nerve agents Sarin and Soman on TiO2.

  4. Chiral separation of G-type chemical warfare nerve agents via analytical supercritical fluid chromatography.

    PubMed

    Kasten, Shane A; Zulli, Steven; Jones, Jonathan L; Dephillipo, Thomas; Cerasoli, Douglas M

    2014-12-01

    Chemical warfare nerve agents (CWNAs) are extremely toxic organophosphorus compounds that contain a chiral phosphorus center. Undirected synthesis of G-type CWNAs produces stereoisomers of tabun, sarin, soman, and cyclosarin (GA, GB, GD, and GF, respectively). Analytical-scale methods were developed using a supercritical fluid chromatography (SFC) system in tandem with a mass spectrometer for the separation, quantitation, and isolation of individual stereoisomers of GA, GB, GD, and GF. Screening various chiral stationary phases (CSPs) for the capacity to provide full baseline separation of the CWNAs revealed that a Regis WhelkO1 (SS) column was capable of separating the enantiomers of GA, GB, and GF, with elution of the P(+) enantiomer preceding elution of the corresponding P(-) enantiomer; two WhelkO1 (SS) columns had to be connected in series to achieve complete baseline resolution. The four diastereomers of GD were also resolved using two tandem WhelkO1 (SS) columns, with complete baseline separation of the two P(+) epimers. A single WhelkO1 (RR) column with inverse stereochemistry resulted in baseline separation of the GD P(-) epimers. The analytical methods described can be scaled to allow isolation of individual stereoisomers to assist in screening and development of countermeasures to organophosphorus nerve agents. © 2014 The Authors. Chirality published by John Wiley Periodicals, Inc.

  5. Chiral Separation of G-type Chemical Warfare Nerve Agents via Analytical Supercritical Fluid Chromatography

    PubMed Central

    Kasten, Shane A; Zulli, Steven; Jones, Jonathan L; Dephillipo, Thomas; Cerasoli, Douglas M

    2014-01-01

    Chemical warfare nerve agents (CWNAs) are extremely toxic organophosphorus compounds that contain a chiral phosphorus center. Undirected synthesis of G-type CWNAs produces stereoisomers of tabun, sarin, soman, and cyclosarin (GA, GB, GD, and GF, respectively). Analytical-scale methods were developed using a supercritical fluid chromatography (SFC) system in tandem with a mass spectrometer for the separation, quantitation, and isolation of individual stereoisomers of GA, GB, GD, and GF. Screening various chiral stationary phases (CSPs) for the capacity to provide full baseline separation of the CWNAs revealed that a Regis WhelkO1 (SS) column was capable of separating the enantiomers of GA, GB, and GF, with elution of the P(+) enantiomer preceding elution of the corresponding P(–) enantiomer; two WhelkO1 (SS) columns had to be connected in series to achieve complete baseline resolution. The four diastereomers of GD were also resolved using two tandem WhelkO1 (SS) columns, with complete baseline separation of the two P(+) epimers. A single WhelkO1 (RR) column with inverse stereochemistry resulted in baseline separation of the GD P(–) epimers. The analytical methods described can be scaled to allow isolation of individual stereoisomers to assist in screening and development of countermeasures to organophosphorus nerve agents. Chirality 26:817–824, 2014. © 2014 The Authors. Chirality published by John Wiley Periodicals, Inc. PMID:25298066

  6. Effects of low-level sarin and cyclosarin exposure on white matter integrity in Gulf War Veterans.

    PubMed

    Chao, Linda L; Zhang, Yu; Buckley, Shannon

    2015-05-01

    We previously found evidence of reduced gray and white matter volume in Gulf War (GW) veterans with predicted low-level exposure to sarin (GB) and cyclosarin (GF). Because loss of white matter tissue integrity has been linked to both gray and white matter atrophy, the current study sought to test the hypothesis that GW veterans with predicted GB/GF exposure have evidence of disrupted white matter microstructural integrity. Measures of fractional anisotropy and directional (i.e., axial and radial) diffusivity were assessed from the 4T diffusion tensor images (DTI) of 59 GW veterans with predicted GB/GF exposure and 59 "matched" unexposed GW veterans (mean age: 48 ± 7 years). The DTI data were analyzed using regions of interest (ROI) analyses that accounted for age, sex, total brain gray and white matter volume, trauma exposure, posttraumatic stress disorder, current major depression, and chronic multisymptom illness status. There were no significant group differences in fractional anisotropy or radial diffusivity. However, there was increased axial diffusivity in GW veterans with predicted GB/GF exposure compared to matched, unexposed veterans throughout the brain, including the temporal stem, corona radiata, superior and inferior (hippocampal) cingulum, inferior and superior fronto-occipital fasciculus, internal and external capsule, and superficial cortical white matter blades. Post hoc analysis revealed significant correlations between higher fractional anisotropy and lower radial diffusivity with better neurobehavioral performance in unexposed GW veterans. In contrast, only increased axial diffusivity in posterior limb of the internal capsule was associated with better psychomotor function in GW veterans with predicted GB/GF exposure. The finding that increased axial diffusivity in a region of the brain that contains descending corticospinal fibers was associated with better psychomotor function and the lack of significant neurobehavioral deficits in veterans

  7. Assay techniques for detection of exposure to sulfur mustard, cholinesterase inhibitors, sarin, soman, GF, and cyanide. Technical bulletin

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    NONE

    1996-05-01

    This technical bulletin provides analytical techniques to identify toxic chemical agents in urine or blood samples. It is intended to provide the clinician with laboratory tests to detect exposure to sulfur mustard, cholinesterase inhibitors, sarin, soman, GF, and cyanide.

  8. Broad-Spectrum Liquid- and Gas-Phase Decontamination of Chemical Warfare Agents by One-Dimensional Heteropolyniobates.

    PubMed

    Guo, Weiwei; Lv, Hongjin; Sullivan, Kevin P; Gordon, Wesley O; Balboa, Alex; Wagner, George W; Musaev, Djamaladdin G; Bacsa, John; Hill, Craig L

    2016-06-20

    A wide range of chemical warfare agents and their simulants are catalytically decontaminated by a new one-dimensional polymeric polyniobate (P-PONb), K12 [Ti2 O2 ][GeNb12 O40 ]⋅19 H2 O (KGeNb) under mild conditions and in the dark. Uniquely, KGeNb facilitates hydrolysis of nerve agents Sarin (GB) and Soman (GD) (and their less reactive simulants, dimethyl methylphosphonate (DMMP)) as well as mustard (HD) in both liquid and gas phases at ambient temperature and in the absence of neutralizing bases or illumination. Three lines of evidence establish that KGeNb removes DMMP, and thus likely GB/GD, by general base catalysis: a) the k(H2 O)/k(D2 O) solvent isotope effect is 1.4; b) the rate law (hydrolysis at the same pH depends on the amount of P-PONb present); and c) hydroxide is far less active against the above simulants at the same pH than the P-PONbs themselves, a critical control experiment. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  9. The by-products generated during sarin synthesis in the Tokyo sarin disaster induced inhibition of natural killer and cytotoxic T lymphocyte activity.

    PubMed

    Li, Q; Hirata, Y; Piao, S; Minami, M

    2000-05-05

    More than 5000 passengers on Tokyo subway trains were injured by the nerve gas, sarin and its by-products. Analysis of phosphor-carrying metabolites of sarin and its by-products in urine samples from the victims suggested that they were exposed not only to sarin, but also by-products generated during sarin synthesis, i.e. diisopropyl methylphosphonate (DIMP) and diethyl methylphosphonate (DEMP). We suspected genetic after-effects due to sarin by-products, thus, we checked the frequency of sister chromatid exchange (SCE) and found that SCE was significantly higher in the victims than in a control group, and that DIMP and DEMP significantly induced human lymphocyte SCE in vitro. In the present study, to explore whether DIMP and DEMP, which induced a high frequency of SCE of lymphocytes, also affected the lymphocyte functions, we examined the effect of DIMP and DEMP on splenic natural killer (NK) and splenic cytotoxic T lymphocyte (CTL) activity in mice, and NK activity of human lymphocytes in vitro. We found that DIMP and DEMP significantly inhibited NK and CTL activity in a dose-dependent manner. The inhibition induced by DIMP was stronger than that by DEMP. The effect of DIMP and DEMP on the splenic NK activity of mice was stronger than on the splenic CTL activity, and the human lymphocytes is more sensitive to DIMP and DEMP than the splenocytes of mice.

  10. Probing the reactivation process of sarin-inhibited acetylcholinesterase with α-nucleophiles: hydroxylamine anion is predicted to be a better antidote with DFT calculations.

    PubMed

    Khan, Md Abdul Shafeeuulla; Lo, Rabindranath; Bandyopadhyay, Tusar; Ganguly, Bishwajit

    2011-08-01

    Inactivation of acetylcholinesterase (AChE) due to inhibition by organophosphorus (OP) compounds is a major threat to human since AChE is a key enzyme in neurotransmission process. Oximes are used as potential reactivators of OP-inhibited AChE due to their α-effect nucleophilic reactivity. In search of more effective reactivating agents, model studies have shown that α-effect is not so important for dephosphylation reactions. We report the importance of α-effect of nucleophilic reactivity towards the reactivation of OP-inhibited AChE with hydroxylamine anion. We have demonstrated with DFT [B3LYP/6-311G(d,p)] calculations that the reactivation process of sarin-serine adduct 2 with hydroxylamine anion is more efficient than the other nucleophiles reported. The superiority of hydroxylamine anion to reactivate the sarin-inhibited AChE with sarin-serine adducts 3 and 4 compared to formoximate anion was observed in the presence and absence of hydrogen bonding interactions of Gly121 and Gly122. The calculated results show that the rates of reactivation process of adduct 4 with hydroxylamine anion are 261 and 223 times faster than the formoximate anion in the absence and presence of such hydrogen bonding interactions. The DFT calculated results shed light on the importance of the adjacent carbonyl group of Glu202 for the reactivation of sarin-serine adduct, in particular with formoximate anion. The reverse reactivation reaction between hydroxylamine anion and sarin-serine adduct was found to be higher in energy compared to the other nucleophiles, which suggests that this α-nucleophile can be a good antidote agent for the reactivation process. Copyright © 2011 Elsevier Inc. All rights reserved.

  11. Quantitation of five organophosphorus nerve agent metabolites in serum using hydrophilic interaction liquid chromatography and tandem mass spectrometry

    PubMed Central

    Hamelin, Elizabeth I.; Schulze, Nicholas D.; Shaner, Rebecca L.; Coleman, Rebecca M.; Lawrence, Richard J.; Crow, Brian S.; Jakubowski, E. M.; Johnson, Rudolph C.

    2015-01-01

    Although nerve agent use is prohibited, concerns remain for human exposure to nerve agents during decommissioning, research, and warfare. Exposure can be detected through the analysis of the hydrolysis products in urine as well as blood. An analytical method to detect exposure to five nerve agents, including VX, VR (Russian VX), GB (sarin), GD (soman) and GF (cyclosarin), through the analysis of the hydrolysis products, which are the primary metabolites, in serum has been developed and characterized. This method uses solid phase extraction coupled with high performance liquid chromatography for separation and isotopic dilution tandem mass spectrometry for detection. An uncommon buffer of ammonium fluoride was used to enhance ionization and improve sensitivity when coupled with hydrophilic interaction liquid chromatography resulting in detection limits from 0.3–0.5 ng/mL. The assessment of two quality control samples demonstrated high accuracy (101–105%) and high precision (5–8%) for the detection of these five nerve agent hydrolysis products in serum. PMID:24633507

  12. A Gas Chromotographic-Mass Spectrometric Approach to Examining Stereoselective Interaction of Human Plasma Proteins with Soman

    DTIC Science & Technology

    2008-02-01

    ABSTRACT See reprint. 15. SUBJECT TERMS Human plasma proteins, soman, nerve agent , bioscavenger, gas chromatography, mass spectrometry 16. SECURITY...usually referred to as nerve agents ) are tabun (ethyl dimethylamidocyanophosphate, or GA ), sarin (iso- propyl methylfluorophosphonate, or GB), soman...Pharmacology and toxicology of chemical warfare agents Ann. Acad. Med. Singapore 2&: 104-107 (1997). 11. C Macilwain. Study proves Iraq used nerve gas . Nature 3

  13. Effects of sarin on the nervous system in rescue team staff members and police officers 3 years after the Tokyo subway sarin attack.

    PubMed

    Nishiwaki, Y; Maekawa, K; Ogawa, Y; Asukai, N; Minami, M; Omae, K

    2001-11-01

    Although the clinical manifestations of acute sarin poisoning have been reported in detail, no comprehensive study of the chronic physical and psychiatric effects of acute sarin poisoning has been carried out. To clarify the chronic effects of sarin on the nervous system, a cross-sectional epidemiologic study was conducted 3 years after the Tokyo subway sarin attack. Subjects consisted of the rescue team staff members and police officers who had worked at the disaster site. Subjects consisted of 56 male exposed subjects and 52 referent subjects matched for age and occupation. A neurobehavioral test, stabilometry, and measurement of vibration perception thresholds were performed, as well as psychometric tests to assess traumatic stress symptoms. The exposed group performed less well in the backward digit span test than the referent group in a dose-effect manner. This result was the same after controlling for possible confounding factors and was independent of traumatic stress symptoms. In other tests of memory function, except for the Benton visual retention test (mean correct answers), effects related to exposure were also suggested, although they were not statistically significant. In contrast, the dose-effect relationships observed in the neurobehavioral tests (psychomotor function) were unclear. None of the stabilometry and vibration perception threshold parameters had any relation to exposure. Our findings suggest the chronic decline of memory function 2 years and 10 months to 3 years and 9 months after exposure to sarin in the Tokyo subway attack, and further study is needed.

  14. Effects of sarin on the nervous system in rescue team staff members and police officers 3 years after the Tokyo subway sarin attack.

    PubMed Central

    Nishiwaki, Y; Maekawa, K; Ogawa, Y; Asukai, N; Minami, M; Omae, K

    2001-01-01

    Although the clinical manifestations of acute sarin poisoning have been reported in detail, no comprehensive study of the chronic physical and psychiatric effects of acute sarin poisoning has been carried out. To clarify the chronic effects of sarin on the nervous system, a cross-sectional epidemiologic study was conducted 3 years after the Tokyo subway sarin attack. Subjects consisted of the rescue team staff members and police officers who had worked at the disaster site. Subjects consisted of 56 male exposed subjects and 52 referent subjects matched for age and occupation. A neurobehavioral test, stabilometry, and measurement of vibration perception thresholds were performed, as well as psychometric tests to assess traumatic stress symptoms. The exposed group performed less well in the backward digit span test than the referent group in a dose-effect manner. This result was the same after controlling for possible confounding factors and was independent of traumatic stress symptoms. In other tests of memory function, except for the Benton visual retention test (mean correct answers), effects related to exposure were also suggested, although they were not statistically significant. In contrast, the dose-effect relationships observed in the neurobehavioral tests (psychomotor function) were unclear. None of the stabilometry and vibration perception threshold parameters had any relation to exposure. Our findings suggest the chronic decline of memory function 2 years and 10 months to 3 years and 9 months after exposure to sarin in the Tokyo subway attack, and further study is needed. PMID:11713003

  15. Fluoride Ion Regeneration of Cyclosarin (Gf) from Minipig Tissue and Fluids Following Whole Body GF Vapor Exposure

    DTIC Science & Technology

    2006-11-01

    Quantitation of organophosphorus nerve agent metabolites in human urine using isotope dilution gas chromatography- tandem mass spectrometry. J. Anal...Recent developments to improve nerve agent biomarker techniques include methods for measuring fluoride regenerated Sarin (GB) in blood and tissue...Our efforts extend the fluoride ion regeneration method to be able to determine cyclosarin (GF) in red blood cells, plasma, and tissue of minipig

  16. Comparison of the efficacy of HI6 and 2-PAM against soman, tabun, sarin, and VX in the rabbit

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Koplovitz, I.; Stewart, J.R.

    1994-12-31

    This study compared the efficacy of H16 and 2-PAM against nerve agent (soman tabun sarin and VX) -induced lethality in the atropinesterase-free rabbits pretreated with vehicle (controls) or pyridostigmine. Treatment was administered at signs or 2 min after agent challenge and consisted ofoxime (l00umol/lkg) + atropine 13 mg(kg) (alone or together with diazepam). Twenty-four-h LD50 values were calculated for soman- and tabun-intoxicated animals, whereas 24-h survival was noted in animals given 10 LD50s of sarin or VX. In pyridostigmine and control rabbits intoxicated with soman and treated with oxime + atropine (alone or together with diazepam), HI6 was 35 timesmore » more effective than 2-PAM. In contrast 1116 was less effective than 2-PAM against tabun poisoning. In pyridostigmine-pretreated animals exposed to tabun, efficacy was increased more than 3-fold when compare to tabun-challenged animals treated with atropine + H16 alone. Both oximes were highly effective against satin and VX. These findings suggest that Hifi could replace 2-PAM as therapy for nerve agent poisoning because it is superior to 2-PAM against soman, and when used in pyridostigmine-pretreated animals it affords excellent protection against all four nerve agents when used in combination with atropine (alone or together with diazepam) therapy.« less

  17. Extending injury prevention methodology to chemical terrorism preparedness: the Haddon Matrix and sarin.

    PubMed

    Varney, Shawn; Hirshon, Jon Mark; Dischinger, Patricia; Mackenzie, Colin

    2006-01-01

    The Haddon Matrix offers a classic epidemiological model for studying injury prevention. This methodology places the public health concepts of agent, host, and environment within the three sequential phases of an injury-producing incident-pre-event, event, and postevent. This study uses this methodology to illustrate how it could be applied in systematically preparing for a mass casualty disaster such as an unconventional sarin attack in a major urban setting. Nineteen city, state, federal, and military agencies responded to the Haddon Matrix chemical terrorism preparedness exercise and offered feedback in the data review session. Four injury prevention strategies (education, engineering, enforcement, and economics) were applied to the individual factors and event phases of the Haddon Matrix. The majority of factors identified in all phases were modifiable, primarily through educational interventions focused on individual healthcare providers and first responders. The Haddon Matrix provides a viable means of studying an unconventional problem, allowing for the identification of modifiable factors to decrease the type and severity of injuries following a mass casualty disaster such as a sarin release. This strategy could be successfully incorporated into disaster planning for other weapons attacks that could potentially cause mass casualties.

  18. Central Acetylcholinesterase Reactivation by Oximes Improves Survival and Terminates Seizures Following Nerve Agent Intoxication

    DTIC Science & Technology

    2009-01-01

    activity ; GB = sarin; im = intramuscular; ip = intraperitoneal; LD50 = median lethal dose 50%; MINA = monoisonitrosoacetone; MMB-4 = methoxime; OP...inhibited acetylcholinesterase (AChE) activity . We have studied the capability of the tertiary oximes monoisonitrosoacetone (MINA) and diacetylmonoxime...of 20, 26, 35, 46 and 60 mg/kg, there were 0, 9, 17, 60, and 75%, respectively, of animals never exhibited EEG seizure activity with 43, 64, 75, 90

  19. Propagation of damage in the rat brain following sarin exposure: Differential progression of early processes

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Lazar, Shlomi; Egoz, Inbal; Brandeis, Rachel

    Sarin is an irreversible organophosphate cholinesterase inhibitor and a highly toxic warfare agent. Following the overt, dose-dependent signs (e.g. tremor, hyper secretion, seizures, respiratory depression and eventually death), brain damage is often reported. The goal of the present study was to characterize the early histopathological and biochemical events leading to this damage. Rats were exposed to 1LD50 of sarin (80 μg/kg, i.m.). Brains were removed at 1, 2, 6, 24 and 48 h and processed for analysis. Results showed that TSPO (translocator protein) mRNA increased at 6 h post exposure while TSPO receptor density increased only at 24 h. Inmore » all brain regions tested, bax mRNA decreased 1 h post exposure followed by an increase 24 h later, with only minor increase in bcl2 mRNA. At this time point a decrease was seen in both anti-apoptotic protein Bcl2 and pro-apoptotic Bax, followed by a time and region specific increase in Bax. An immediate elevation in ERK1/2 activity with no change in JNK may indicate an endogenous “first response” mechanism used to attenuate the forthcoming apoptosis. The time dependent increase in the severity of brain damage included an early bi-phasic activation of astrocytes, a sharp decrease in intact neuronal cells, a time dependent reduction in MAP2 and up to 15% of apoptosis. Thus, neuronal death is mostly due to necrosis and severe astrocytosis. The data suggests that timing of possible treatments should be determined by early events following exposure. For example, the biphasic changes in astrocytes activity indicate a possible beneficial effects of delayed anti-inflammatory intervention. - Highlights: • The severity of brain damage post 1LD50 sarin exposure is time dependent. • Sarin induce differential progression of early processes in the rat brain. • Potential treatments should be timed according to early events following exposure. • The biphasic astrocytes activity suggests a delay in anti

  20. Fragmentation of molecular ions in differential mobility spectrometry as a method for identification of chemical warfare agents.

    PubMed

    Maziejuk, M; Puton, J; Szyposzyńska, M; Witkiewicz, Z

    2015-11-01

    The subject of the work is the use of differential mobility spectrometry (DMS) for the detection of chemical warfare agents (CWA). Studies were performed for mustard gas, i.e., bis(2-chloroethyl)sulfide (HD), sarin, i.e., O-isopropyl methylphosphonofluoridate (GB) and methyl salicylate (MS) used as test compounds. Measurements were conducted with two ceramic DMS analyzers of different constructions allowing the generation of an electric field with an intensity of more than 120 Td. Detector signals were measured for positive and negative modes of operation in a temperature range from 0 to 80 °C. Fragmentations of ions containing analyte molecules were observed for all tested compounds. The effective temperatures of fragmentation estimated on the basis of dispersion plots were equal from about 148 °C for GB to 178 °C for MS. It was found that values of separation voltage (SV) and compensation voltage (CV) at which the fragmentation of sample ions is observed may be the parameters improving the certainty of detection for different analytes. The DMS analyzers enabling the observation of ion fragmentation can be successfully used for effective CWA detection. Copyright © 2015. Published by Elsevier B.V.

  1. Repeated low-dose exposures to sarin, soman, or VX affect acoustic startle in guinea pigs.

    PubMed

    Smith, C D; Lee, R B; Moran, A V; Sipos, M L

    2016-01-01

    Chemical warfare nerve agents (CWNAs) are known to cause behavioral abnormalities in cases of human exposures and in animal models. The behavioral consequences of single exposures to CWNAs that cause observable toxic signs are particularly well characterized in animals; however, less is known regarding repeated smaller exposures that may or may not cause observable toxic signs. In the current study, guinea pigs were exposed to fractions (0.1, 0.2, or 0.4) of a medial lethal dose (LD50) of sarin, soman, or VX for two weeks. On each exposure day, and for a post-exposure period, acoustic startle response (ASR) was measured in each animal. Although relatively few studies use guinea pigs to measure behavior, this species is ideal for CWNA-related experiments because their levels of carboxylesterases closely mimic those of humans, unlike rats or mice. Results showed that the 0.4 LD50 doses of soman and VX transiently increased peak startle amplitude by the second week of injections, with amplitude returning to baseline by the second week post-exposure. Sarin also increased peak startle amplitude independent of week. Latencies to peak startle and PPI were affected by agent exposure but not consistently among the three agents. Most of the changes in startle responses returned to baseline following the cessation of exposures. These data suggest that doses of CWNAs not known to produce observable toxic signs in guinea pigs can affect behavior in the ASR paradigm. Further, these deficits are transient and usually return to baseline shortly after the end of a two-week exposure period. Published by Elsevier Inc.

  2. Evaluation of risk assessment guideline levels for the chemical warfare agents mustard, GB, and VX.

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Hartmann, H.; Environmental Assessment

    2002-06-01

    The U.S. Army has estimated acute lethality guideline levels for inhalation of the chemical warfare agents mustard, GB, and VX. These levels are expressed as dosages measured in milligram-minutes per cubic meter (mg-min/m3). The National Advisory Council has also proposed acute emergency guideline levels (AEGLs) for the agents. The AEGLs are threshold exposure limits for the general public for mild effects, serious adverse effects, and lethality. They are expressed as air concentrations (in units of mg/m3) and are applicable to emergency exposure periods ranging from 10 min to 8 h. The report discusses strengths and deficiencies in the levels, importantmore » parameters (i.e., exposure time, breathing rate) that need to be explicitly addressed in deriving the guideline levels, and possible impacts that could result from using AEGLs instead of guideline dosages in future assessments.« less

  3. Analysis of Nerve Agent Metabolites from Hair for Long-Term Verification of Nerve Agent Exposure

    DTIC Science & Technology

    2016-05-09

    Analysis of Nerve Agent Metabolites from Hair for Long-Term Verification of Nerve Agent Exposure Amanda S. Appel,† John H. McDonough,‡ Joseph D...feasible. In this study, hair was evaluated as a long-term repository of nerve agent hydrolysis products. Pinacolyl methylphosphonic acid (PMPA...hydrolysis product of soman) and isopropyl methylphosphonic acid (IMPA; hydrolysis product of sarin) were extracted from hair samples with N,N

  4. Optical constants of neat liquid-chemical warfare agents and related materials measured by infrared spectroscopic ellipsometry

    NASA Astrophysics Data System (ADS)

    Yang, C. S.-C.; Williams, B. R.; Hulet, M. S.; Tiwald, T. E.; Miles, R. W., Jr.; Samuels, A. C.

    2011-05-01

    We studied various liquids using a vertical attenuated total reflection (ATR) liquid sampling assembly in conjunction with Infrared Variable Angle Spectroscopic Ellipsometry (IR-VASE), to determine the infrared optical constants of several bulk liquids related to chemical warfare. The index of refraction, n, and the extinction coefficient, k, of isopropyl methylphosphonofluoridate (Sarin or GB), isopropyl alcohol (IPA) (a precursor of GB), and dimethyl methylphosphonate (DMMP)-a commonly employed simulant for GB, measured by our vertical ATR IR-VASE setup are closely matched to those found in other studies. We also report the optical constants of cyclohexyl methylphosphonofluoridate (GF), 2-(diisopropylamino)ethyl methylphosphonothioate (VX), bis-(2-chloroethyl) sulfide (HD), and 2-chlorovinyl dichloroarsine (L, Lewisite). The ATR IR-VASE technique affords an accurate measurement of the optical constants of these hazardous compounds.

  5. Engineering Bacteria to Catabolize the Carbonaceous Component of Sarin: Teaching E. coli to Eat Isopropanol

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Brown, Margaret E.; Mukhopadhyay, Aindrila; Keasling, Jay D.

    In this paper, we report an engineered strain of Escherichia coli that catabolizes the carbonaceous component of the extremely toxic chemical warfare agent sarin. Enzymatic decomposition of sarin generates isopropanol waste that, with this engineered strain, is then transformed into acetyl-CoA by enzymatic conversion with a key reaction performed by the acetone carboxylase complex (ACX). We engineered the heterologous expression of the ACX complex from Xanthobacter autotrophicus PY2 to match the naturally occurring subunit stoichiometry and purified the recombinant complex from E. coli for biochemical analysis. Incorporating this ACX complex and enzymes from diverse organisms, we introduced an isopropanol degradationmore » pathway in E. coli, optimized induction conditions, and decoupled enzyme expression to probe pathway bottlenecks. Our engineered E. coli consumed 65% of isopropanol compared to no-cell controls and was able to grow on isopropanol as a sole carbon source. Finally, in the process, reconstitution of this large ACX complex (370 kDa) in a system naïve to its structural and mechanistic requirements allowed us to study this otherwise cryptic enzyme in more detail than would have been possible in the less genetically tractable native Xanthobacter system.« less

  6. The inhibition, reactivation and mechanism of VX-, sarin-, fluoro-VX and fluoro-sarin surrogates following their interaction with HuAChE and HuBuChE.

    PubMed

    Chao, Chih-Kai; Balasubramanian, Narayanaganesh; Gerdes, John M; Thompson, Charles M

    2018-06-16

    In this study, the mechanisms of HuAChE and HuBChE inhibition by Me-P(O) (OPNP) (OR) [PNP = p-nitrophenyl; R = CH 2 CH 3 , CH 2 CH 2 F, OCH(CH 3 ) 2 , OCH(CH 3 ) (CH 2 F)] representing surrogates and fluoro-surrogates of VX and sarin were studied by in vitro kinetics and mass spectrometry. The in vitro measures showed that the VX- and fluoro-VX surrogates were relatively strong inhibitors of HuAChE and HuBChE (k i  ∼ 10 5 -10 6  M -1 min -1 ) and underwent spontaneous and 2-PAM-mediated reactivation within 30 min. The sarin surrogates were weaker inhibitors of HuAChE and HuBChE (k i  ∼ 10 4 -10 5  M -1 min -1 ), and in general did not undergo spontaneous reactivation, although HuAChE adducts were partially reactivatable at 18 h using 2-PAM. The mechanism of HuAChE and HuBChE inhibition by the surrogates was determined by Q-TOF and MALDI-TOF mass spectral analyses. The surrogate-adducted proteins were trypsin digested and the active site-containing peptide bearing the OP-modified serine identified by Q-TOF as triply- and quadruply-charged ions representing the respective increase in mass of the attached OP moiety. Correspondingly, monoisotopic ions of the tryptic peptides representing the mass increase of the OP-adducted peptide was identified by MALDI-TOF. The mass spectrometry analyses validated the identity of the OP moiety attached to HuAChE or HuBChE as MeP(O) (OR)-O-serine peptides (loss of the PNP leaving group) via mechanisms consistent with those found with chemical warfare agents. MALDI-TOF MS analyses of the VX-modified peptides versus time showed a steady reduction in adduct versus parent peptide (reactivation), whereas the sarin-surrogate-modified peptides remained largely intact over the course of the experiment (24 h). Overall, the presence of a fluorine atom on the surrogate modestly altered the rate constants of inhibition and reactivation, however, the mechanism of inhibition (ejection of PNP group) did not change

  7. Impact of ambient gases on the mechanism of [Cs8Nb6O19]-promoted nerve-agent decomposition.

    PubMed

    Kaledin, Alexey L; Driscoll, Darren M; Troya, Diego; Collins-Wildman, Daniel L; Hill, Craig L; Morris, John R; Musaev, Djamaladdin G

    2018-02-28

    The impact of ambient gas molecules (X), NO 2 , CO 2 and SO 2 on the structure, stability and decontamination activity of Cs 8 Nb 6 O 19 polyoxometalate was studied computationally and experimentally. It was found that Cs 8 Nb 6 O 19 absorbs these molecules more strongly than it adsorbs water and Sarin (GB) and that these interactions hinder nerve agent decontamination. The impacts of diamagnetic CO 2 and SO 2 molecules on polyoxoniobate Cs 8 Nb 6 O 19 were fundamentally different from that of NO 2 radical. At ambient temperatures, weak coordination of the first NO 2 radical to Cs 8 Nb 6 O 19 conferred partial radical character on the polyoxoniobate and promoted stronger coordination of the second NO 2 adsorbent to form a stable diamagnetic Cs 8 Nb 6 O 19 /(NO 2 ) 2 species. Moreover, at low temperatures, NO 2 radicals formed stable dinitrogen tetraoxide (N 2 O 4 ) that weakly interacted with Cs 8 Nb 6 O 19 . It was found that both in the absence and presence of ambient gas molecules, GB decontamination by the Cs 8 Nb 6 O 19 species proceeds via general base hydrolysis involving: (a) the adsorption of water and the nerve agent on Cs 8 Nb 6 O 19 /(X), (b) concerted hydrolysis of a water molecule on a basic oxygen atom of the polyoxoniobate and nucleophilic addition of the nascent OH group to the phosphorus center of Sarin, and (c) rapid reorganization of the formed pentacoordinated-phosphorus intermediate, followed by dissociation of either HF or isopropanol and formation of POM-bound isopropyl methyl phosphonic acid (i-MPA) or methyl phosphonofluoridic acid (MPFA), respectively. The presence of the ambient gas molecules increases the energy of the intermediate stationary points relative to the asymptote of the reactants and slightly increases the hydrolysis barrier. These changes closely correlate with the Cs 8 Nb 6 O 19 -X complexation energy. The most energetically stable intermediates of the GB hydrolysis and decontamination reaction were found to be Cs 8 Nb 6 O

  8. Efficacy of liquid and foam decontamination technologies for chemical warfare agents on indoor surfaces.

    PubMed

    Love, Adam H; Bailey, Christopher G; Hanna, M Leslie; Hok, Saphon; Vu, Alex K; Reutter, Dennis J; Raber, Ellen

    2011-11-30

    Bench-scale testing was used to evaluate the efficacy of four decontamination formulations on typical indoor surfaces following exposure to the liquid chemical warfare agents sarin (GB), soman (GD), sulfur mustard (HD), and VX. Residual surface contamination on coupons was periodically measured for up to 24h after applying one of four selected decontamination technologies [0.5% bleach solution with trisodium phosphate, Allen Vanguard Surface Decontamination Foam (SDF™), U.S. military Decon Green™, and Modec Inc. and EnviroFoam Technologies Sandia Decontamination Foam (DF-200)]. All decontamination technologies tested, except for the bleach solution, performed well on nonporous and nonpermeable glass and stainless-steel surfaces. However, chemical agent residual contamination typically remained on porous and permeable surfaces, especially for the more persistent agents, HD and VX. Solvent-based Decon Green™ performed better than aqueous-based bleach or foams on polymeric surfaces, possibly because the solvent is able to penetrate the polymer matrix. Bleach and foams out-performed Decon Green for penetrating the highly polar concrete surface. Results suggest that the different characteristics needed for an ideal and universal decontamination technology may be incompatible in a single formulation and a strategy for decontaminating a complex facility will require a range of technologies. Copyright © 2011 Elsevier B.V. All rights reserved.

  9. Simultaneous Measurement of Tabun, Sarin, Soman, Cyclosarin, VR, VX, and VM Adducts to Tyrosine in Blood Products by Isotope Dilution UHPLC-MS/MS

    PubMed Central

    Crow, Brian S.; Pantazides, Brooke G.; Quiñones-González, Jennifer; Garton, Joshua W.; Carter, Melissa D.; Perez, Jonas W.; Watson, Caroline M.; Tomcik, Dennis J.; Crenshaw, Michael D.; Brewer, Bobby N.; Riches, James R.; Stubbs, Sarah J.; Read, Robert W.; Evans, Ronald A.; Thomas, Jerry D.; Blake, Thomas A.; Johnson, Rudolph C.

    2015-01-01

    This work describes a new specific, sensitive, and rapid stable isotope dilution method for the simultaneous detection of the organophosphorus nerve agents (OPNAs) tabun (GA), sarin (GB), soman (GD), cyclosarin (GF), VR, VX, and VM adducts to tyrosine (Tyr). Serum, plasma, and lysed whole blood samples (50 µL) were prepared by protein precipitation followed by digestion with Pronase. Specific Tyr adducts were isolated from the digest by a single solid phase extraction (SPE) step, and the analytes were separated by reversed-phase ultra high performance liquid chromatography (UHPLC) gradient elution in less than 2 min. Detection was performed on a triple quadrupole tandem mass spectrometer using time-triggered selected reaction monitoring (SRM) in positive electrospray ionization (ESI) mode. The calibration range was characterized from 0.100–50.0 ng/mL for GB– and VR– Tyr and 0.250–50.0 ng/mL for GA–, GD–, GF–, and VX/VM–Tyr (R2 ≥ 0.995). Inter- and intra-assay precision had coefficients of variation of ≤17 and ≤10%, respectively, and the measured concentration accuracies of spiked samples were within 15% of the targeted value for multiple spiking levels. The limit of detection was calculated to be 0.097, 0.027, 0.018, 0.074, 0.023, and 0.083 ng/mL for GA–, GB–, GD–, GF–, VR–, and VX/VM–Tyr, respectively. A convenience set of 96 serum samples with no known nerve agent exposure was screened and revealed no baseline values or potential interferences. This method provides a simple and highly specific diagnostic tool that may extend the time postevent that a confirmation of nerve agent exposure can be made with confidence. PMID:25286390

  10. Effective countermeasure against poisoning by organophosphorus insecticides and nerve agents.

    PubMed

    Albuquerque, Edson X; Pereira, Edna F R; Aracava, Yasco; Fawcett, William P; Oliveira, Maristela; Randall, William R; Hamilton, Tracey A; Kan, Robert K; Romano, James A; Adler, Michael

    2006-08-29

    The nerve agents soman, sarin, VX, and tabun are deadly organophosphorus (OP) compounds chemically related to OP insecticides. Most of their acute toxicity results from the irreversible inhibition of acetylcholinesterase (AChE), the enzyme that inactivates the neurotransmitter acetylcholine. The limitations of available therapies against OP poisoning are well recognized, and more effective antidotes are needed. Here, we demonstrate that galantamine, a reversible and centrally acting AChE inhibitor approved for treatment of mild to moderate Alzheimer's disease, protects guinea pigs from the acute toxicity of lethal doses of the nerve agents soman and sarin, and of paraoxon, the active metabolite of the insecticide parathion. In combination with atropine, a single dose of galantamine administered before or soon after acute exposure to lethal doses of soman, sarin, or paraoxon effectively and safely counteracted their toxicity. Doses of galantamine needed to protect guinea pigs fully against the lethality of OPs were well tolerated. In preventing the lethality of nerve agents, galantamine was far more effective than pyridostigmine, a peripherally acting AChE inhibitor, and it was less toxic than huperzine, a centrally acting AChE inhibitor. Thus, a galantamine-based therapy emerges as an effective and safe countermeasure against OP poisoning.

  11. Effective countermeasure against poisoning by organophosphorus insecticides and nerve agents

    PubMed Central

    Albuquerque, Edson X.; Pereira, Edna F. R.; Aracava, Yasco; Fawcett, William P.; Oliveira, Maristela; Randall, William R.; Hamilton, Tracey A.; Kan, Robert K.; Romano, James A.; Adler, Michael

    2006-01-01

    The nerve agents soman, sarin, VX, and tabun are deadly organophosphorus (OP) compounds chemically related to OP insecticides. Most of their acute toxicity results from the irreversible inhibition of acetylcholinesterase (AChE), the enzyme that inactivates the neurotransmitter acetylcholine. The limitations of available therapies against OP poisoning are well recognized, and more effective antidotes are needed. Here, we demonstrate that galantamine, a reversible and centrally acting AChE inhibitor approved for treatment of mild to moderate Alzheimer’s disease, protects guinea pigs from the acute toxicity of lethal doses of the nerve agents soman and sarin, and of paraoxon, the active metabolite of the insecticide parathion. In combination with atropine, a single dose of galantamine administered before or soon after acute exposure to lethal doses of soman, sarin, or paraoxon effectively and safely counteracted their toxicity. Doses of galantamine needed to protect guinea pigs fully against the lethality of OPs were well tolerated. In preventing the lethality of nerve agents, galantamine was far more effective than pyridostigmine, a peripherally acting AChE inhibitor, and it was less toxic than huperzine, a centrally acting AChE inhibitor. Thus, a galantamine-based therapy emerges as an effective and safe countermeasure against OP poisoning. PMID:16914529

  12. The Potential Neurotoxic Effects of Low-Dose Sarin Exposure in a Guinea Pig Model

    DTIC Science & Technology

    2002-01-01

    1 THE POTENTIAL NEUROTOXIC EFFECTS OF LOW-DOSE SARIN EXPOSURE IN A GUINEA PIG MODEL Melinda R. Roberson, PhD, Michelle B. Schmidt...Proving Ground, MD 21010 USA ABSTRACT This study is assessing the effects in guinea pigs of repeated low-dose exposure to the nerve...COVERED - 4. TITLE AND SUBTITLE The Potential Neurotoxic Effects Of Low-Dose Sarin Exposure In A Guinea Pig Model 5a. CONTRACT NUMBER 5b

  13. Impact of ambient gases on the mechanism of [Cs8Nb6O19]-promoted nerve-agent decomposition† †Dedicated to the memory of Prof. Keiji Morokuma. ‡ ‡Electronic supplementary information (ESI) available: (1) The calculated transition states, intermediates and products of the GB hydrolysis and their important geometry parameters (in Å) for X = SO2, (2) the calculated adsorption energies (in kcal mol–1) of NO2 radicals to Cs8Nb6O19, (3) Cartesian coordinates for all reported structures in xyz format. (structure.xyz). See DOI: 10.1039/c7sc04997h

    PubMed Central

    Kaledin, Alexey L.; Driscoll, Darren M.; Troya, Diego; Collins-Wildman, Daniel L.

    2018-01-01

    The impact of ambient gas molecules (X), NO2, CO2 and SO2 on the structure, stability and decontamination activity of Cs8Nb6O19 polyoxometalate was studied computationally and experimentally. It was found that Cs8Nb6O19 absorbs these molecules more strongly than it adsorbs water and Sarin (GB) and that these interactions hinder nerve agent decontamination. The impacts of diamagnetic CO2 and SO2 molecules on polyoxoniobate Cs8Nb6O19 were fundamentally different from that of NO2 radical. At ambient temperatures, weak coordination of the first NO2 radical to Cs8Nb6O19 conferred partial radical character on the polyoxoniobate and promoted stronger coordination of the second NO2 adsorbent to form a stable diamagnetic Cs8Nb6O19/(NO2)2 species. Moreover, at low temperatures, NO2 radicals formed stable dinitrogen tetraoxide (N2O4) that weakly interacted with Cs8Nb6O19. It was found that both in the absence and presence of ambient gas molecules, GB decontamination by the Cs8Nb6O19 species proceeds via general base hydrolysis involving: (a) the adsorption of water and the nerve agent on Cs8Nb6O19/(X), (b) concerted hydrolysis of a water molecule on a basic oxygen atom of the polyoxoniobate and nucleophilic addition of the nascent OH group to the phosphorus center of Sarin, and (c) rapid reorganization of the formed pentacoordinated-phosphorus intermediate, followed by dissociation of either HF or isopropanol and formation of POM-bound isopropyl methyl phosphonic acid (i-MPA) or methyl phosphonofluoridic acid (MPFA), respectively. The presence of the ambient gas molecules increases the energy of the intermediate stationary points relative to the asymptote of the reactants and slightly increases the hydrolysis barrier. These changes closely correlate with the Cs8Nb6O19–X complexation energy. The most energetically stable intermediates of the GB hydrolysis and decontamination reaction were found to be Cs8Nb6O19/X-MPFA-(i-POH) and Cs8Nb6O19/X-(i-MPA)-HF both in the absence and

  14. Fluorescent discrimination between traces of chemical warfare agents and their mimics.

    PubMed

    Díaz de Greñu, Borja; Moreno, Daniel; Torroba, Tomás; Berg, Alexander; Gunnars, Johan; Nilsson, Tobias; Nyman, Rasmus; Persson, Milton; Pettersson, Johannes; Eklind, Ida; Wästerby, Pär

    2014-03-19

    An array of fluorogenic probes is able to discriminate between nerve agents, sarin, soman, tabun, VX and their mimics, in water or organic solvent, by qualitative fluorescence patterns and quantitative multivariate analysis, thus making the system suitable for the in-the-field detection of traces of chemical warfare agents as well as to differentiate between the real nerve agents and other related compounds.

  15. Hormone-dependence of sarin lethality in rats: Sex differences and stage of the estrous cycle

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Smith, Carl D., E-mail: carl.d.smith179.mil@mail.mil; Wright, Linnzi K.M.; Garcia, Gregory E.

    Chemical warfare nerve agents (CWNAs) are highly toxic compounds that cause a cascade of symptoms and death, if exposed casualties are left untreated. Numerous rodent models have investigated the toxicity and mechanisms of toxicity of CWNAs, but most are limited to male subjects. Given the profound physiological effects of circulating gonadal hormones in female rodents, it is possible that the daily cyclical fluctuations of these hormones affect females' sensitivity to the lethal effects of CWNAs, and previous reports that included female subjects did not control for the stage of the hormonal cycle. The aim of the current study was tomore » determine the 24-hour median lethal dose (LD{sub 50}) of the CWNA sarin in male, ovariectomized (OVEX) female, and female rats during different stages of the estrous cycle (diestrus, proestrus, and estrus). Additionally, baseline activity levels of plasma acetylcholinesterase, butyrylcholinesterase, and carboxylesterase were measured to determine differences among the groups. Results indicated that females in proestrus had a significantly higher LD{sub 50} of sarin compared to OVEX and estrous females. Although some sex differences were observed in the activity levels of plasma esterases, they were not consistent and likely not large enough to significantly affect the LD{sub 50}s. These results suggest that hormonal cyclicity can influence the outcome of CWNA-related studies using female rodents, and that this variability can be minimized by controlling for the stage of the cycle. Additional research is necessary to determine the precise mechanism of the observed differences because it is unlikely to be solely explained by plasma esterase activity. - Highlights: • The LD{sub 50} of sarin was determined in female rats throughout the stages of the estrous cycle. • Females in proestrus had a significantly higher LD{sub 50} compared to estrous or ovariectomized females. • No sex differences were observed between male and

  16. Fate of chemical warfare agents and toxic industrial chemicals in landfills.

    PubMed

    Bartelt-Hunt, Shannon L; Barlaz, Morton A; Knappe, Detlef R U; Kjeldsen, Peter

    2006-07-01

    One component of preparedness for a chemical attack is planning for the disposal of contaminated debris. To assess the feasibility of contaminated debris disposal in municipal solid waste (MSW) landfills, the fate of selected chemical warfare agents (CWAs) and toxic industrial chemicals (TICs) in MSW landfills was predicted with a mathematical model. Five blister agents [sulfur mustard (HD), nitrogen mustard (HN-2), lewisite (L), ethyldichloroarsine (ED), and phosgene oxime (CX)], eight nerve agents [tabun (GA), sarin (GB), soman (GD), GE, GF, VX, VG, and VM], one riot-control agent [CS], and two TICs [furan and carbon disulfide] were studied. The effects of both infiltration (climate) and contaminant biodegradability on fate predictions were assessed. Model results showed that hydrolysis and gas-phase advection were the principal fate pathways for CWAs and TICs, respectively. Apart from CX and the TICs, none of the investigated compounds was predicted to persist in a landfill for more than 5 years. Climate had little impact on CWA/TIC fate, and biodegradability was only important for compounds with long hydrolysis half-lives. Monte Carlo simulations were performed to assess the influence of uncertainty in model input parameters on CWA/TIC fate predictions. Correlation analyses showed that uncertainty in hydrolysis rate constants was the primary contributor to variance of CWA fate predictions, while uncertainty in the Henry's Law constant and landfill gas-production rate accounted for most of the variance of TIC fate predictions. CWA hydrolysates were more persistent than the parent CWAs, but limited information is available on abiotic or biotic transformation rates for these chemicals.

  17. Stable-carbon isotope ratios for sourcing the nerve-agent precursor methylphosphonic dichloride and its products

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Moran, James J.; Fraga, Carlos G.; Nims, Megan K.

    The ability to connect a chemical threat agent to a specific batch of a synthetic precursor can provide a fingerprint to contribute to effective forensic investigations. Stable isotope analysis can leverage intrinsic, natural isotopic variability within the molecules of a threat agent to unlock embedded chemical fingerprints in the material. Methylphosphonic dichloride (DC) is a chemical precursor to the nerve agent sarin. It is converted to methylphosphonic difluoride (DF) as part of the sarin synthesis process. We used a suite of commercially available DC stocks to both evaluate the potential for δ13C analysis to be used as a fingerprinting toolmore » in sarin-related investigations and to develop sample preparation techniques (using chemical hydrolysis) that can simplify isotopic analysis of DC and its synthetic products. We demonstrate that natural isotopic variability in DC results in at least three distinct, isotope-resolved clusters within the thirteen stocks we analyzed. Isotopic variability in the carbon feedstock (i.e., methanol) used for DC synthesis is likely inherited by the DC samples we measured. We demonstrate that the hydrolysis of DC and DF to methylphosphonic acid (MPA) can be used as a preparative step for isotopic analysis because the reaction does not impart a measureable isotopic fractionation. MPA is more chemically stable, less toxic, and easier to handle than DC or DF. Further, the hydrolysis method we demonstrated can be applied to a suite of other precursors or to sarin itself, thereby providing a potentially valuable forensic tool.« less

  18. Stable-Carbon Isotope Ratios for Sourcing the Nerve-Agent Precursor Methylphosphonic Dichloride and Its Products

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Moran, James J.; Fraga, Carlos G.; Nims, Megan K.

    The ability to connect a chemical threat agent to a specific batch of a synthetic precursor can provide a fingerprint to contribute to effective forensic investigations. Stable isotope analysis can leverage intrinsic, natural isotopic variability within the molecules of a threat agent to unlock embedded chemical fingerprints in the material. Methylphosphonic dichloride (DC) is a chemical precursor to the nerve agent sarin. DC is converted to methylphosphonic difluoride (DF) as part of the sarin synthesis process. We used a suite of commercially available DC stocks to both evaluate the potential for δ 13C analysis to be used as a fingerprintingmore » tool in sarin-related investigations and to develop sample preparation techniques (using chemical hydrolysis) that can simplify isotopic analysis of DC and its synthetic products. We demonstrate that natural isotopic variability in DC results in at least three distinct, isotope-resolved clusters within the thirteen stocks we analyzed. Isotopic variability in the carbon feedstock (i.e., methanol) used for DC synthesis is likely inherited by the DC samples we measured. Here, we demonstrate that the hydrolysis of DC and DF to methylphosphonic acid (MPA) can be used as a preparative step for isotopic analysis because the reaction does not impart a significant isotopic fractionation. MPA is more chemically stable, less toxic, and easier to handle than DC or DF. Further, the hydrolysis method we demonstrated can be applied to a suite of other precursors or to sarin itself, thereby providing a potentially valuable forensic tool.« less

  19. Stable-Carbon Isotope Ratios for Sourcing the Nerve-Agent Precursor Methylphosphonic Dichloride and Its Products

    DOE PAGES

    Moran, James J.; Fraga, Carlos G.; Nims, Megan K.

    2018-04-01

    The ability to connect a chemical threat agent to a specific batch of a synthetic precursor can provide a fingerprint to contribute to effective forensic investigations. Stable isotope analysis can leverage intrinsic, natural isotopic variability within the molecules of a threat agent to unlock embedded chemical fingerprints in the material. Methylphosphonic dichloride (DC) is a chemical precursor to the nerve agent sarin. DC is converted to methylphosphonic difluoride (DF) as part of the sarin synthesis process. We used a suite of commercially available DC stocks to both evaluate the potential for δ 13C analysis to be used as a fingerprintingmore » tool in sarin-related investigations and to develop sample preparation techniques (using chemical hydrolysis) that can simplify isotopic analysis of DC and its synthetic products. We demonstrate that natural isotopic variability in DC results in at least three distinct, isotope-resolved clusters within the thirteen stocks we analyzed. Isotopic variability in the carbon feedstock (i.e., methanol) used for DC synthesis is likely inherited by the DC samples we measured. Here, we demonstrate that the hydrolysis of DC and DF to methylphosphonic acid (MPA) can be used as a preparative step for isotopic analysis because the reaction does not impart a significant isotopic fractionation. MPA is more chemically stable, less toxic, and easier to handle than DC or DF. Further, the hydrolysis method we demonstrated can be applied to a suite of other precursors or to sarin itself, thereby providing a potentially valuable forensic tool.« less

  20. Stable-carbon isotope ratios for sourcing the nerve-agent precursor methylphosphonic dichloride and its products.

    PubMed

    Moran, James J; Fraga, Carlos G; Nims, Megan K

    2018-08-15

    The ability to connect a chemical threat agent to a specific batch of a synthetic precursor can provide a fingerprint to contribute to effective forensic investigations. Stable isotope analysis can leverage intrinsic, natural isotopic variability within the molecules of a threat agent to unlock embedded chemical fingerprints in the material. Methylphosphonic dichloride (DC) is a chemical precursor to the nerve agent sarin. DC is converted to methylphosphonic difluoride (DF) as part of the sarin synthesis process. We used a suite of commercially available DC stocks to both evaluate the potential for δ 13 C analysis to be used as a fingerprinting tool in sarin-related investigations and to develop sample preparation techniques (using chemical hydrolysis) that can simplify isotopic analysis of DC and its synthetic products. We demonstrate that natural isotopic variability in DC results in at least three distinct, isotope-resolved clusters within the thirteen stocks we analyzed. Isotopic variability in the carbon feedstock (i.e., methanol) used for DC synthesis is likely inherited by the DC samples we measured. We demonstrate that the hydrolysis of DC and DF to methylphosphonic acid (MPA) can be used as a preparative step for isotopic analysis because the reaction does not impart a significant isotopic fractionation. MPA is more chemically stable, less toxic, and easier to handle than DC or DF. Further, the hydrolysis method we demonstrated can be applied to a suite of other precursors or to sarin itself, thereby providing a potentially valuable forensic tool. Copyright © 2018. Published by Elsevier B.V.

  1. Cardiovascular effects of the adenosine A1 receptor agonist N6-cyclopentyladenosine (CPA) decisive for its therapeutic efficacy in sarin poisoning.

    PubMed

    Joosen, Marloes J A; Bueters, Tjerk J H; van Helden, Herman P M

    2004-01-01

    Mortality and occurrence of cholinergic symptoms upon sarin intoxication (144 micro g/kg s.c., approximately 2 x LD50) in rats is completely prevented by treatment with the adenosine A1 receptor agonist N6-cyclopentyladenosine (CPA, 2 mg/kg i.m.). Previously, we have shown that CPA treatment altered the distribution of sarin into the brain, presumably through its cardiovascular side effects. Therefore, the objective of the present study was to evaluate the contribution of the cardiodepressant effects of CPA to its therapeutic efficacy against sarin intoxication. Intramuscular treatment of rats with 0.5 and 2.0 mg/kg CPA 1 min after sarin poisoning attenuated most cholinergic symptoms and prevented mortality, which seemed to be directly associated with an immediate strong and long-lasting bradycardia and hypotension caused by CPA. Treatment with lower doses of CPA (0.1 and 0.05 mg/kg i.m.) caused similar levels of bradycardia and hypotension, albeit a few minutes later than at the higher doses of CPA. Upon sarin intoxication, this was correlated with increased incidence of cholinergic symptoms and decreased survival rates. Pretreatment with the peripheral adenosine A1 receptor antagonist 8- p-sulphophenyltheophylline (8-PST, 20 mg/kg i.p.) counteracted the cardiodepressant effects of 0.05 mg/kg CPA almost completely, thereby nearly abolishing its therapeutic efficacy against sarin poisoning. In conclusion, the present results strongly indicate that bradycardia and hypotension induced by the peripheral adenosine A1 receptor play a prominent role in the therapeutic efficacy of CPA in cases of sarin poisoning.

  2. Younger rats are more susceptible to the lethal effects of sarin than adult rats: 24 h LC50 for whole-body (10 and 60 min) exposures.

    PubMed

    Wright, Linnzi K M; Lumley, Lucille A; Lee, Robyn B; Taylor, James T; Miller, Dennis B; Muse, William T; Emm, Edward J; Whalley, Christopher E

    2017-04-01

    Chemical warfare nerve agents (CWNA) inhibit acetylcholinesterase and are among the most lethal chemicals known to man. Children are predicted to be vulnerable to CWNA exposure because of their smaller body masses, higher ventilation rates and immature central nervous systems. While a handful of studies on the effects of CWNA in younger animals have been published, exposure routes relevant to battlefield or terrorist situations (i.e. inhalation for sarin) were not used. Thus, we estimated the 24 h LC 50 for whole-body (10 and 60 min) exposure to sarin using a stagewise, adaptive dose design. Specifically, male and female Sprague-Dawley rats were exposed to a range of sarin concentrations (6.2-44.0 or 1.6-12.5 mg/m³) for either 10 or 60 min, respectively, at six different times during their development (postnatal day [PND] 7, 14, 21, 28, 42 and 70). For male and female rats, the lowest LC 50 values were observed for PND 14 and the highest LC 50 values for PND 28. Sex differences were observed only for PND 42 for the 10 min exposures and PND 21 and 70 for the 60 min exposures. Thus, younger rats (PND 14) were more susceptible than older rats (PND 70) to the lethal effects of whole-body exposure to sarin, while adolescent (PND 28) rats were the least susceptible and sex differences were minimal. These results underscore the importance of controlling for the age of the animal in research on the toxic effects associated with CWNA exposure.

  3. Crystal structures of human group-VIIA phospholipase A2 inhibited by organophosphorus nerve agents exhibit non-aged complexes

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Samanta, Uttamkumar; Kirby, Stephen D.; Srinivasan, Prabhavathi

    The enzyme group-VIIA phospholipase A2 (gVIIA-PLA2) is bound to lipoproteins in human blood and hydrolyzes the ester bond at the sn-2 position of phospholipid substrates with a short sn-2 chain. The enzyme belongs to a serine hydrolase superfamily of enzymes, which react with organophosphorus (OP) nerve agents. OPs ultimately exert their toxicity by inhibiting human acetycholinesterase at nerve synapses, but may additionally have detrimental effects through inhibition of other serine hydrolases. We have solved the crystal structures of gVIIA-PLA2 following inhibition with the OPs diisopropylfluorophosphate, sarin, soman and tabun. The sarin and soman complexes displayed a racemic mix of P{submore » R} and P{sub S} stereoisomers at the P-chiral center. The tabun complex displayed only the P{sub R} stereoisomer in the crystal. In all cases, the crystal structures contained intact OP adducts that had not aged. Aging refers to a secondary process OP complexes can go through, which dealkylates the nerve agent adduct and results in a form that is highly resistant to either spontaneous or oxime-mediated reactivation. Non-aged OP complexes of the enzyme were corroborated by trypsin digest and matrix-assisted laser desorption ionization mass spectrometry of OP-enzyme complexes. The lack of stereoselectivity of sarin reaction was confirmed by gas chromatography/mass spectrometry using a chiral column to separate and quantitate the unbound stereoisomers of sarin following incubation with enzyme. The structural details and characterization of nascent reactivity of several toxic nerve agents is discussed with a long-term goal of developing gVIIA-PLA2 as a catalytic bioscavenger of OP nerve agents.« less

  4. Crystal structures of human group-VIIA phospholipase A2 inhibited by organophosphorus nerve agents exhibit non-aged complexes.

    PubMed

    Samanta, Uttamkumar; Kirby, Stephen D; Srinivasan, Prabhavathi; Cerasoli, Douglas M; Bahnson, Brian J

    2009-08-15

    The enzyme group-VIIA phospholipase A2 (gVIIA-PLA2) is bound to lipoproteins in human blood and hydrolyzes the ester bond at the sn-2 position of phospholipid substrates with a short sn-2 chain. The enzyme belongs to a serine hydrolase superfamily of enzymes, which react with organophosphorus (OP) nerve agents. OPs ultimately exert their toxicity by inhibiting human acetycholinesterase at nerve synapses, but may additionally have detrimental effects through inhibition of other serine hydrolases. We have solved the crystal structures of gVIIA-PLA2 following inhibition with the OPs diisopropylfluorophosphate, sarin, soman and tabun. The sarin and soman complexes displayed a racemic mix of P(R) and P(S) stereoisomers at the P-chiral center. The tabun complex displayed only the P(R) stereoisomer in the crystal. In all cases, the crystal structures contained intact OP adducts that had not aged. Aging refers to a secondary process OP complexes can go through, which dealkylates the nerve agent adduct and results in a form that is highly resistant to either spontaneous or oxime-mediated reactivation. Non-aged OP complexes of the enzyme were corroborated by trypsin digest and matrix-assisted laser desorption ionization mass spectrometry of OP-enzyme complexes. The lack of stereoselectivity of sarin reaction was confirmed by gas chromatography/mass spectrometry using a chiral column to separate and quantitate the unbound stereoisomers of sarin following incubation with enzyme. The structural details and characterization of nascent reactivity of several toxic nerve agents is discussed with a long-term goal of developing gVIIA-PLA2 as a catalytic bioscavenger of OP nerve agents.

  5. Dual Role of Water in Heterogeneous Catalytic Hydrolysis of Sarin by Zirconium-Based Metal-Organic Frameworks.

    PubMed

    Momeni, Mohammad R; Cramer, Christopher J

    2018-05-22

    Recent experimental studies on Zr IV -based metal-organic frameworks (MOFs) have shown the extraordinary effectiveness of these porous materials for the detoxification of phosphorus-based chemical warfare agents (CWAs). However, pressing challenges remain with respect to characterizing these catalytic processes both at the molecular and crystalline levels. We here use theory to compare the reactivity of different zirconium-based MOFs for the catalytic hydrolysis of the CWA sarin, using both periodic and cluster modeling. We consider both hydrated and dehydrated secondary building units, as well as linker functionalized MOFs, to more fully understand and rationalize available experimental findings as well as to enable concrete predictions for achieving higher activities for the decomposition of CWAs.

  6. Metal-Organic Framework Modified Glass Substrate for Analysis of Highly Volatile Chemical Warfare Agents by Paper Spray Mass Spectrometry.

    PubMed

    Dhummakupt, Elizabeth S; Carmany, Daniel O; Mach, Phillip M; Tovar, Trenton M; Ploskonka, Ann M; Demond, Paul S; DeCoste, Jared B; Glaros, Trevor

    2018-03-07

    Paper spray mass spectrometry has been shown to successfully analyze chemical warfare agent (CWA) simulants. However, due to the volatility differences between the simulants and real G-series (i.e., sarin, soman) CWAs, analysis from an untreated paper substrate proved difficult. To extend the analytical lifetime of these G-agents, metal-organic frameworks (MOFs) were successfully integrated onto the paper spray substrates to increase adsorption and desorption. In this study, several MOFs and nanoparticles were tested to extend the analytical lifetimes of sarin, soman, and cyclosarin on paper spray substrates. It was found that the addition of either UiO-66 or HKUST-1 to the paper substrate increased the analytical lifetime of the G-agents from less than 5 min detectability to at least 50 min.

  7. A comparison of the reactivating and therapeutic efficacy of two novel bispyridinium oximes (K727, K733) with the oxime HI-6 and obidoxime in sarin-poisoned rats and mice.

    PubMed

    Kassa, Jiri; Sepsova, Vendula; Matouskova, Lenka; Horova, Anna; Musilek, Kamil

    2015-03-01

    The ability of two novel bispyridinium oximes K727 and K733 and currently available oximes (HI-6, obidoxime) to reactivate sarin-inhibited acetylcholinesterase and to reduce acute toxicity of sarin was evaluated. To investigate the reactivating efficacy of the oximes, the rats were administered intramuscularly with atropine and oximes in equitoxic doses corresponding to 5% of their LD50 values at 1 min after the intramuscular administration of sarin at a dose of 24 µg/kg (LD50). The activity of acetylcholinesterase was measured at 60 min after sarin poisoning. The LD50 value of sarin in non-treated and treated mice was assessed using probit-logarithmical analysis of death occurring within 24 h after intramuscular administration of sarin at five different doses. In vivo determined percentage of reactivation of sarin-inhibited rat blood, diaphragm and brain acetylcholinesterase showed that the potency of both novel oximes K727 and K733 to reactivate sarin-inhibited acetylcholinesterase roughly corresponds to the reactivating efficacy of obidoxime. On the other hand, the oxime HI-6 was found to be the most efficient reactivator of sarin-inhibited acetylcholinesterase. While the oxime HI-6 was able to reduce the acute toxicity of sarin >3 times, both novel oximes and obidoxime decreased the acute toxicity of sarin <2 times. Based on the results, we can conclude that the reactivating and therapeutic efficacy of both novel oximes K727 and K733 is significantly lower compared to the oxime HI-6 and, therefore, they are not suitable for the replacement of the oxime HI-6 for the antidotal treatment of acute sarin poisoning.

  8. Differences between male and female rhesus monkey erythrocyte acetylcholinesterase and plasma cholinesterase activity before and after exposure to sarin

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Woodard, C.L.; Calamaio, C.A.; Kaminskis, A.

    The female rhesus monkey has a menstrual cycle like the human. Additionally, several differences in enzyme levels between males and females and in the female during the menstrual cycle are present. Therefore we quantitated plasma cholinesterase (ChE/BuChE) and erythrocyte (RBC) acetylcholinesterase (AChE) activity before and after exposure to sarin (GB)(1 5 ug/kg, iv; a 0.75 LD50), in male and female rhesus (Macaca mulatta) monkeys. Twenty-eight-day preexposure baseline plasma ChE and RBC AChE values for six male and six female rhesus monkeys were compared for intra-animal, within sex and between sex differences. After these baseline values were obtained, the organophosphorus (OP)more » compound/Isopropyl methylphosphono-fluoridate (GB) was administered to atropinized monkeys to determine if there was a significant in vivo difference between the sexes in their response to this intoxication in regard to the rate of BuChE /AChE inhibition, pyridine-2-aldoxime methyl chloride (2-PAM) reactivation of the phosphonylated BuChE and the rate of aging of the phosphonylated:BuChE/AChE. In the pre-exposure portion of the protocol; the intra-animal and intra-group BuChE/AChE variations were found to be minimal; but there were significant differences between the male and female monkeys in both plasma BuChE and RBC AChE levels; although probably clinically insignificant in respect to an OP intoxication. No significant cyclic fluctuations were seen during the 28-day study in either sex.« less

  9. Computational Simulation of Vibrational Overtone Spectral Regions: Sarin

    DTIC Science & Technology

    2006-12-01

    level have been used to determine the vapour phase local mode parameters, [ and Dx, for each oscillator in the two spectrally significant conformers...approach to spectral simulation reported herein should be undertaken by acquiring the experimental spectral regions of several CWAs in the vapour and liquid...33 viii DRDC Suffield TR 2006-220 List of figures Figure 1: The vapour phase structures of the three lowest energy conformers of sarin, calculated

  10. Evaluation of CryoSat-2 SARIn vs. SAR Arctic Sea Ice Freeboard

    NASA Astrophysics Data System (ADS)

    Di Bella, A.; Skourup, H.; Forsberg, R.

    2017-12-01

    Earth climate is a complex system which behaviour is dictated by the interaction among many components. Sea ice, one of these fundamental components, interacts directly with the oceans and the atmosphere playing an important role in defining heat exchange processes and, thus, impacting weather patterns on a global scale. Sea ice thickness estimates have notably improved in the last couple of decades, however, the uncertainty of such estimates is still significant. For the past 7 years, the ESA CryoSat-2 (CS2) mission has provided a unique opportunity to observe polar regions due to its extended coverage up to 88° N/S. The SIRAL radar altimeter on board CS2 enables the sea ice community to estimate sea ice thickness by measuring the sea ice freeboard. Studies by Armitage and Davidson [2014] and Di Bella et al. [submitted] showed that the interferometric capabilities of SIRAL can be used to retrieve an increased number of valid sea surface heights in sea ice covered regions and thus reduce the random uncertainty of the estimated freeboards, especially in areas with a sparse lead distribution. This study focuses on the comparison between sea ice freeboard estimates obtained by processing L1B SARIn data inside the Wingham box - an area in the Arctic Ocean where SIRAL has acquired SARIn data for 4 years - and those obtained by processing L1B SAR data in the area surrounding the box. This comparison evaluates CS2 performance on Arctic sea ice from a statistical perspective by analysing the continuity of freeboard estimates in areas where SIRAL switches between SAR and SARIn acquisition modes. Data collected during the Operation IceBridge and CryoVEx field campaigns are included in the study as an additional validation. Besides investigating the possibility of including the phase information from SIRAL in currently available freeboard estimates, this results provide valuable information for a possible SARIn CryoSat follow-on mission.

  11. Generation and evaluation of Cryosat-2 SARIn L1b Interferometric elevation

    NASA Astrophysics Data System (ADS)

    DONG, Y.; Zhang, K.; Liu, Q.; MA, J.; WANG, J.

    2016-12-01

    CryoSat-2 radar altimeter data have successfully used in mapping surface elevations of ice caps and ice sheets, finding the change of surface height in polar area. The SARIn mode of Synthetic Aperture Interferometric Altimeter (SIRAL), which working similar with the traditional Interferometric Synthetic Aperture Radar (IFSAR) method, can improve the across- and along-track resolution by IFSAR processing algorithm. In this study, three L1b Baseline-C SARIn tracks over the Filchner ice shelf are used to generate the location and height of ground points in sloping glacial terrain. The elevation data is mapped and validated with IceBridge Airborne Topographic Mapper (ATM) data acquired at Nov. 2, 2012. The comparison with ATM data shows a mean difference of -1.91 m with a stand deviation of 4.04 m.

  12. Can 100Gb/s wavelengths be deployed using 10Gb/s engineering rules?

    NASA Astrophysics Data System (ADS)

    Saunders, Ross; Nicholl, Gary; Wollenweber, Kevin; Schmidt, Ted

    2007-09-01

    A key challenge set by carriers for 40Gb/s deployments was that the 40Gb/s wavelengths should be deployable over existing 10Gb/s DWDM systems, using 10Gb/s link engineering design rules. Typical 10Gb/s link engineering rules are: 1. Polarization Mode Dispersion (PMD) tolerance of 10ps (mean); 2. Chromatic Dispersion (CD) tolerance of +/-700ps/nm 3. Operation at 50GHz channel spacing, including transit through multiple cascaded [R]OADMs; 4. Optical reach up to 2,000km. By using a combination of advanced modulation formats and adaptive dispersion compensation (technologies rarely seen at 10Gb/s outside of the submarine systems space), vendors did respond to the challenge and broadly met this requirement. As we now start to explore feasible technologies for 100Gb/s optical transport, driven by 100GE port availability on core IP routers, the carrier challenge remains the same. 100Gb/s links should be deployable over existing 10Gb/s DWDM systems using 10Gb/s link engineering rules (as listed above). To meet this challenge, optical transport technology must evolve to yet another level of complexity/maturity in both modulation formats and adaptive compensation techniques. Many clues as to how this might be achieved can be gained by first studying sister telecommunications industries, e.g. satellite (QPSK, QAM, LDCP FEC codes), wireless (advanced DSP, MSK), HDTV (TCM), etc. The optical industry is not a pioneer of new ideas in modulation schemes and coding theory, we will always be followers. However, we do have the responsibility of developing the highest capacity "modems" on the planet to carry the core backbone traffic of the Internet. As such, the key to our success will be to analyze the pros and cons of advanced modulation/coding techniques and balance this with the practical limitations of high speed electronics processing speed and the challenges of real world optical layer impairments. This invited paper will present a view on what advanced technologies are likely

  13. Protection against soman and sarin exposure by transdermal physostigmine and scopolamine

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Meshulam, Y.; Davidovici, R.; Levy, A.

    1993-05-13

    The purpose of this study was to evaluate the prophylactic efficacy of physostigmine (physo), administered via sustained release (SR) methods, with and without scopolamine, against soman and sarin exposure in guinea-pigs. Transdermal physo pad (3 sq cm/kg; 60-80 ug/sq cm), containing a vehicle based on propionic acid, was applied onto the dorsal back of the animals, 24 hours before exposure to the cholinesterase (ChE) inhibitors. At the time of exposure, physo concentrations in brain and plasma were 3.6 ng/g and 4.1 ng/ml respectively. Brain and whole blood ChE activity were inhibited to 70% and 57% of their original activity. Transdermalmore » physo by itself protected up to 70% of the animals exposed to 1.5 LD(50) of soman or sarin (100% mortality was recorded in the control group). Combining transdermal physo with Scopoderm (by Ciba Geigy Inc.) provided full protection against 1.5 LD(50).« less

  14. Infrared signature of micro-hydration in the organophosphate sarin: An ab initio study

    DOE PAGES

    Alam, Todd M.; Pearce, Charles Joseph

    2015-06-28

    The infrared (IR) spectra of micro-hydrated Sarin•(H 2O) n clusters containing between one and four explicit waters have been studied using ab initio density functional theory (DFT) methods. The phosphate group P=O bond vibration region (~1270 to 1290 cm –1) revealed the largest frequency variation with hydration, with a frequency red shift reflecting the direct hydrogen bond formation between the P=O of Sarin and water. Small variations to the P-F stretch (~810 to 815 cm –1) and the C-O-P vibrational modes (~995 to 1004 cm –1) showed that the water interactions with these functional groups were minor, and that themore » structures of Sarin were not extensively perturbed in the hydrated complexes. Increasing the number of explicit hydration waters produced only small vibrational changes in the lowest free energy complexes. These minor changes were consistent with a single water-phosphate hydrogen bond being the dominant structure, though a second water-phosphate hydrogen bond was observed in some complexes and was identified by an additional red shift of the P=O bond vibration. As a result, the H 2O•H 2O vibrational modes (~3450 to 3660 cm –1) increased in complexity with higher hydration levels and reflect the extended hydrogen bonding networks formed between the explicit waters in the hydrated Sarin clusters.« less

  15. Stable adducts of nerve agents sarin, soman and cyclosarin with TRIS, TES and related buffer compounds--characterization by LC-ESI-MS/MS and NMR and implications for analytical chemistry.

    PubMed

    Gäb, Jürgen; John, Harald; Melzer, Marco; Blum, Marc-Michael

    2010-05-15

    Buffering compounds like TRIS are frequently used in chemical, biochemical and biomedical applications to control pH in solution. One of the prerequisites of a buffer compound, in addition to sufficient buffering capacity and pH stability over time, is its non-reactivity with other constituents of the solution. This is especially important in the field of analytical chemistry where analytes are to be determined quantitatively. Investigating the enzymatic hydrolysis of G-type nerve agents sarin, soman and cyclosarin in buffered solution we have identified stable buffer adducts of TRIS, TES and other buffer compounds with the nerve agents. We identified the molecular structure of these adducts as phosphonic diesters using 1D (1)H-(31)P HSQC NMR and LC-ESI-MS/MS techniques. Reaction rates with TRIS and TES are fast enough to compete with spontaneous hydrolysis in aqueous solution and to yield substantial amounts (up to 20-40%) of buffer adduct over the course of several hours. A reaction mechanism is proposed in which the amino function of the buffer serves as an intramolecular proton acceptor rendering the buffer hydroxyl groups nucleophilic enough for attack on the phosphorus atom of the agents. Results show that similar buffer adducts are formed with a range of hydroxyl and amino function containing buffers including TES, BES, TRIS, BIS-TRIS, BIS-TRIS propane, Tricine, Bicine, HEPES and triethanol amine. It is recommended to use alternative buffers like MOPS, MES and CHES when working with G-type nerve agents especially at higher concentrations and over prolonged times. Copyright (c) 2010 Elsevier B.V. All rights reserved.

  16. Investigating the Hydrolysis Reactions of a Chemical Warfare Agent Surrogate. A Systematic Study using 1H, 13C, 17O, 19F, 31P, and 35Cl NMR Spectroscopy

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Alam, Todd M.; Wilson, Brendan W.

    2015-07-24

    During the summer of 2015, I participated in the DHS HS-STEM fellowship at Sandia National Laboratories (SNL, NM) under the supervision of Dr. Todd M. Alam in his Nuclear Magnetic Resonance (NMR) Spectroscopy research group. While with the group, my main project involved pursing various hydrolysis reactions with Diethyl Chlorophosphate (DECP), a surrogate for the agent Sarin (GB). Specifically, I performed different hydrolysis reactions, monitored and tracked the different phosphorous containing species using phosphorous ( 31P) NMR spectroscopy. With the data collected, I performed kinetics studies mapping the rates of DECP hydrolysis. I also used the NMR of different nucleimore » such as 1H, 13C, 17O, and 35Cl to help understand the complexity of the reactions that take place. Finally, my last task at SNL was to work with Insensitive Nuclei Enhanced by Polarization Transfer (INEPT) NMR Spectroscopy optimizing conditions for 19F- 31P filtering NMR experiments.« less

  17. Unexpected nerve gas exposure in the city of Matsumoto: report of rescue activity in the first sarin gas terrorism.

    PubMed

    Okudera, H; Morita, H; Iwashita, T; Shibata, T; Otagiri, T; Kobayashi, S; Yanagisawa, N

    1997-09-01

    This report describes the rescue activities and the exposure of rescue and hospital personnel from the first unexpected nerve gas terrorist attack using sarin (isopropyl methylphophonofluoridate) in the city of Matsumoto at midnight on June 27, 1994. The details of the emergency activities in the disaster were studied based on the records from emergency departments of the affiliated hospitals and records from the firehouse. About 600 people, including residents and rescue staff, were exposed to sarin gas. Fifty-eight residents were admitted to hospitals, and 7 died. Among 95 rescuers and the duty doctor from the doctor car, 8 had mild symptoms of poisoning. All the rescue activity took place without gas masks or decontamination procedures. In this case of unexpected mass exposure to sarin gas, the emergency rescue system for a large disaster in Matsumoto city, which had been established for a conflagration or a local earthquake, was effective.

  18. CryoSat-2 SAR and SARin Inland Water Heights from the CRUCIAL project

    NASA Astrophysics Data System (ADS)

    Benveniste, J.; Restano, M.; Ambrózio, A.; Moore, P.; Birkinshaw, S.

    2017-12-01

    CRUCIAL was an ESA/STSE funded project investigating innovative land and inland water applications from CryoSat-2 with a forward-look component to the Sentinel-3 and Jason-CS/Sentinel-6 missions. The high along-track sampling of CryoSat-2 in its SAR and SARin modes offers the opportunity to recover high frequency signals over inland waters. A methodology was developed to process the FBR L1A Doppler beams to form a waveform product using ground cell gridding, beam steering and beam stacking. Inland water heights from CryoSat-2 are derived by using a set of empirical retrackers formulated for inland water applications. Results of the processing strategy include a comparison of waveforms and heights from the burst echoes (80 m along-track) and from multi-look waveforms (320 m along-track). SAR and SARin FBR data are available for the Amazon, Brahmaputra and Mekong for 2011-2015. FBR SAR results are compared against stage data from the nearest gauge. Heights from Tonlé Sap are also compared against Jason-2 data from the United States Department of Agriculture. A strategy to select the number of multi-looks over rivers was designed based on the rms of heights across Tonlé Sap. Comparisons include results from the empirical retrackers and from waveforms and heights obtained via ESA's Grid Processing on Demand (G-POD/SARvatore) using the SAMOSA2 retracker. Results of FBR SARin processing for the Amazon and Brahmaputra are presented including comparison of heights from the two antennae, extraction of slope of the ground surface and validation against ground data where appropriate.

  19. CryoSat Level1b SAR/SARin BaselineC: Product Format and Algorithm Improvements

    NASA Astrophysics Data System (ADS)

    Scagliola, Michele; Fornari, Marco; Di Giacinto, Andrea; Bouffard, Jerome; Féménias, Pierre; Parrinello, Tommaso

    2015-04-01

    CryoSat was launched on the 8th April 2010 and is the first European ice mission dedicated to the monitoring of precise changes in the thickness of polar ice sheets and floating sea ice. Cryosat carries an innovative radar altimeter called the Synthetic Aperture Interferometric Altimeter (SIRAL), that transmits pulses at a high pulse repetition frequency thus making the received echoes phase coherent and suitable for azimuth processing. This allows to reach a significantly improved along track resolution with respect to traditional pulse-width limited altimeters. CryoSat is the first altimetry mission operating in SAR mode and continuous improvements in the Level1 Instrument Processing Facility (IPF1) are being identified, tested and validated in order to improve the quality of the Level1b products. The current IPF, Baseline B, was released in operation in February 2012. A reprocessing campaign followed, in order to reprocess the data since July 2010. After more than 2 years of development, the release in operations of Baseline C is expected in the first half of 2015. BaselineC Level1b products will be distributed in an updated format, including for example the attitude information (roll, pitch and yaw) and, for SAR/SARIN, the waveform length doubled with respect to Baseline B. Moreveor, various algorithm improvements have been identified: • a datation bias of about -0.5195 ms will be corrected (SAR/SARIn) • a range bias of about 0.6730 m will be corrected (SAR/SARIn) • a roll bias of 0.1062 deg and a pitch bias of 0.0520 deg • Surface sample stack weighting to filter out the single look echoes acquired at highest look angle, that results in a sharpening of the 20Hz waveforms With the operational release of BaselineC, the second CryoSat reprocessing campaign will be initiated, taking benefit of the upgrade implemented in the IPF1 processing chain but also at IPF2 level. The reprocessing campaign will cover the full Cryosat mission starting on 16th July 2010

  20. Mass Spectrometry to Identify New Biomarkers of Nerve Agent Exposure

    DTIC Science & Technology

    2010-04-01

    target for oganophosphorus agent (OP) binding to enzymes is the active site serine in the consensus sequence GlyXSerXGly of acetylcholinesterase. By...human plasma. Task 6. Use a second method, for example enzyme activity assays or immunoprecipitation, to confirm the identity of soman-labeled proteins...spectrometry identifies covalent binding of soman, sarin, chlorpyrifos oxon, diisopropyl fluorophosphate, and FP-biotin to tyrosines on tubulin: a potential

  1. Kinetics of degradation of sulfur mustard and sarin simulants on HKUST-1 metal organic framework.

    PubMed

    Roy, Anuradha; Srivastava, Avanish K; Singh, Beer; Shah, Dilip; Mahato, Timir Haran; Srivastava, Anchal

    2012-10-28

    The applicability of HKUST-1 for the degradation of sulfur mustard and sarin simulants was studied with and without coadsorbed water. Degradation was found to be via hydrolysis and dependent on the nucleophilic substitution reaction, vapour pressure and molecular diameter of the toxicants.

  2. High-sensitivity, high-selectivity detection of chemical warfare agents

    NASA Astrophysics Data System (ADS)

    Pushkarsky, Michael B.; Webber, Michael E.; Macdonald, Tyson; Patel, C. Kumar N.

    2006-01-01

    We report high-sensitivity detection of chemical warfare agents (nerve gases) with very low probability of false positives (PFP). We demonstrate a detection threshold of 1.2ppb (7.7μg/m3 equivalent of Sarin) with a PFP of <1:106 in the presence of many interfering gases present in an urban environment through the detection of diisopropyl methylphosphonate, an accepted relatively harmless surrogate for the nerve agents. For the current measurement time of ˜60s, a PFP of 1:106 corresponds to one false alarm approximately every 23months. The demonstrated performance satisfies most current homeland and military security requirements.

  3. Efficacy of novel phenoxyalkyl pyridinium oximes as brain-penetrating reactivators of cholinesterase inhibited by surrogates of sarin and VX.

    PubMed

    Chambers, Janice E; Chambers, Howard W; Funck, Kristen E; Meek, Edward C; Pringle, Ronald B; Ross, Matthew K

    2016-11-25

    Pyridinium oximes are strong nucleophiles and many are effective reactivators of organophosphate-inhibited cholinesterase (ChE). However, the current oxime reactivators are ineffective at crossing the blood-brain barrier and reactivating brain ChE in the intact organism. Our laboratories have developed a series of substituted phenoxyalkyl pyridinium oximes (US patent 9,227,937 B2) with the goal of identifying reactivators effective in crossing the blood-brain barrier. The first 35 of the series were found to have similar in vitro efficacy as reactivators of ChE inhibited by a sarin surrogate (phthalimidyl isopropyl methylphosphonate, PIMP) or a VX surrogate (nitrophenyl ethyl methylphosphonate, NEMP) in bovine brain preparations as previously observed in rat brain preparations. A number of these novel oximes have shown the ability to decrease the level of ChE inhibition in the brains of rats treated with a high sublethal dosage of either a sarin surrogate (nitrophenyl isopropyl methylphosphonate, NIMP) or the VX surrogate NEMP. Levels of reactivation at 2 h after oxime administration were up to 35% while the currently approved therapeutic, 2-PAM, yielded no reduction in brain ChE inhibition. In addition, there was evidence of attenuation of seizure-like behavior with several of the more effective novel oximes, but not 2-PAM. Therefore these novel oximes have demonstrated an ability to reactivate inhibited ChE in brain preparations from two species and in vivo data support their ability to enter the brain and provide a therapeutic action. These novel oximes have the potential to be developed into improved antidotes for nerve agent therapy. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  4. Identification of chemical warfare agents from vapor samples using a field-portable capillary gas chromatography/membrane-interfaced electron ionization quadrupole mass spectrometry instrument with Tri-Bed concentrator.

    PubMed

    Nagashima, Hisayuki; Kondo, Tomohide; Nagoya, Tomoki; Ikeda, Toru; Kurimata, Naoko; Unoke, Shohei; Seto, Yasuo

    2015-08-07

    A field-portable gas chromatograph-mass spectrometer (Hapsite ER system) was evaluated for the detection of chemical warfare agents (CWAs) in the vapor phase. The system consisted of Tri-Bed concentrator gas sampler (trapping time: 3s(-1)min), a nonpolar low thermal-mass capillary gas chromatography column capable of raising temperatures up to 200°C, a hydrophobic membrane-interfaced electron ionization quadrupole mass spectrometer evacuated by a non-evaporative getter pump for data acquisition, and a personal computer for data analysis. Sample vapors containing as little as 22μg sarin (GB), 100μg soman (GD), 210μg tabun (GA), 55μg cyclohexylsarin (GF), 4.8μg sulfur mustard, 390μg nitrogen mustard 1, 140μg of nitrogen mustard 2, 130μg nitrogen mustard 3, 120μg of 2-chloroacetophenone and 990μg of chloropicrin per cubic meter could be confirmed after Tri-Bed micro-concentration (for 1min) and automated AMDIS search within 12min. Using manual deconvolution by background subtraction of neighboring regions on the extracted ion chromatograms, the above-mentioned CWAs could be confirmed at lower concentration levels. The memory effects were also examined and we found that blister agents showed significantly more carry-over than nerve agents. Gasoline vapor was found to interfere with the detection of GB and GD, raising the concentration limits for confirmation in the presence of gasoline by both AMDIS search and manual deconvolution; however, GA and GF were not subject to interference by gasoline. Lewisite 1, and o-chlorobenzylidene malononitrile could also be confirmed by gas chromatography, but it was hard to quantify them. Vapors of phosgene, chlorine, and cyanogen chloride could be confirmed by direct mass spectrometric detection at concentration levels higher than 2, 140, and 10mg/m(3) respectively, by bypassing the micro-concentration trap and gas chromatographic separation. Copyright © 2015 Elsevier B.V. All rights reserved.

  5. Lessons learned from the Syrian sarin attack: evaluation of a clinical syndrome through social media.

    PubMed

    Rosman, Yossi; Eisenkraft, Arik; Milk, Nadav; Shiyovich, Arthur; Ophir, Nimrod; Shrot, Shai; Kreiss, Yitshak; Kassirer, Michael

    2014-05-06

    On the night of 21 August 2013, sarin was dispersed in the eastern outskirts of Damascus, killing 1400 civilians and severely affecting thousands more. This article aims to delineate the clinical presentation and management of a mass casualty event caused by a nerve agent as shown in the social media. Authors searched YouTube for videos uploaded of this attack and identified 210 videos. Of these, 67 met inclusion criteria and were evaluated in the final analysis.These videos displayed 130 casualties; 119 (91.5%) of which were defined as moderately injured or worse. The most common clinical signs were dyspnea (53.0%), diaphoresis (48.5%), and loss of consciousness (40.7%). Important findings included a severe shortage of supporting measures and lack of antidotal autoinjectors. Decontamination, documented in 25% of the videos, was done in an inefficient manner. Protective gear was not noticed, except for sporadic use of latex gloves and surgical masks.This is believed to be the first time that social media was used to evaluate clinical data and management protocols to better prepare against future possible events.

  6. "Newer, bigger, older" with NASA GIBS

    NASA Astrophysics Data System (ADS)

    Schmaltz, J. E.; Alarcon, C.; Boller, R. A.; Cechini, M. F.; De Cesare, C.; De Luca, A. P.; Hall, J. R.; Huang, T.; King, J.; Plesea, L.; Pressley, N. N.; Roberts, J. T.; Rodriguez, J. D.; Thompson, C. K.

    2015-12-01

    The year 2015 witnessed a vast expansion of NASA's Global Imagery Browse Services (GIBS) in a number of dimensions. Near real time imagery was added from a slew of additional sensors including GPM, SMAP, AMSR2, VIIRS, CERES, MOPITT, SSMI, and Aquarius, many of these representing measurements that had not been available in GIBS previously. The SMAP layers are also pioneering a new capability for GIBS to display individual granules. Higher resolution imagery, up to 30m/pixel, is now available in GIBS for some sensors, including ASTER GDEM and L1T and Web-Enabled Landsat Data (WELD). The imagery record is being extended into the past with the entire record of data from MODIS and AMSR-E reprocessing campaigns.

  7. An Acetylcholinesterase-Based Chronoamperometric Biosensor for Fast and Reliable Assay of Nerve Agents

    PubMed Central

    Pohanka, Miroslav; Adam, Vojtech; Kizek, Rene

    2013-01-01

    The enzyme acetylcholinesterase (AChE) is an important part of cholinergic nervous system, where it stops neurotransmission by hydrolysis of the neurotransmitter acetylcholine. It is sensitive to inhibition by organophosphate and carbamate insecticides, some Alzheimer disease drugs, secondary metabolites such as aflatoxins and nerve agents used in chemical warfare. When immobilized on a sensor (physico-chemical transducer), it can be used for assay of these inhibitors. In the experiments described herein, an AChE- based electrochemical biosensor using screen printed electrode systems was prepared. The biosensor was used for assay of nerve agents such as sarin, soman, tabun and VX. The limits of detection achieved in a measuring protocol lasting ten minutes were 7.41 × 10−12 mol/L for sarin, 6.31 × 10−12 mol/L for soman, 6.17 × 10−11 mol/L for tabun, and 2.19 × 10−11 mol/L for VX, respectively. The assay was reliable, with minor interferences caused by the organic solvents ethanol, methanol, isopropanol and acetonitrile. Isopropanol was chosen as suitable medium for processing lipophilic samples. PMID:23999806

  8. Functional Fluorescent Protein Insertions in Herpes Simplex Virus gB Report on gB Conformation before and after Execution of Membrane Fusion

    PubMed Central

    Gallagher, John R.; Atanasiu, Doina; Saw, Wan Ting; Paradisgarten, Matthew J.; Whitbeck, J. Charles; Eisenberg, Roselyn J.; Cohen, Gary H.

    2014-01-01

    Entry of herpes simplex virus (HSV) into a target cell requires complex interactions and conformational changes by viral glycoproteins gD, gH/gL, and gB. During viral entry, gB transitions from a prefusion to a postfusion conformation, driving fusion of the viral envelope with the host cell membrane. While the structure of postfusion gB is known, the prefusion conformation of gB remains elusive. As the prefusion conformation of gB is a critical target for neutralizing antibodies, we set out to describe its structure by making genetic insertions of fluorescent proteins (FP) throughout the gB ectodomain. We created gB constructs with FP insertions in each of the three globular domains of gB. Among 21 FP insertion constructs, we found 8 that allowed gB to remain membrane fusion competent. Due to the size of an FP, regions in gB that tolerate FP insertion must be solvent exposed. Two FP insertion mutants were cell-surface expressed but non-functional, while FP insertions located in the crown were not surface expressed. This is the first report of placing a fluorescent protein insertion within a structural domain of a functional viral fusion protein, and our results are consistent with a model of prefusion HSV gB constructed from the prefusion VSV G crystal structure. Additionally, we found that functional FP insertions from two different structural domains could be combined to create a functional form of gB labeled with both CFP and YFP. FRET was measured with this construct, and we found that when co-expressed with gH/gL, the FRET signal from gB was significantly different from the construct containing CFP alone, as well as gB found in syncytia, indicating that this construct and others of similar design are likely to be powerful tools to monitor the conformation of gB in any model system accessible to light microscopy. PMID:25233449

  9. Mechanisms of Organophosphorus (OP) Injury: Sarin-Induced Hippocampal Gene Expression Changes and Pathway Perturbation

    DTIC Science & Technology

    2012-01-01

    components of the endomembrane system, including endoplasmic reticulum (ER) and Golgi apparatus were significantly down-regulated. As a result of...impairment in dopaminergic functions (Lucot JB, personal communication). Interestingly, data on sarin exposures have shown inhibition of new memory...quite unexpected that the endoplasmic reticulum (ER) and Golgi apparatus , the subcellular organelles essential for processing (e.g., folding, post

  10. Seasonal sea surface and sea ice signal in the fjords of Eastern Greenland from CryoSat-2 SARin altimetry

    NASA Astrophysics Data System (ADS)

    Abulaitijiang, Adili; Baltazar Andersen, Ole; Stenseng, Lars

    2014-05-01

    Cryosat-2 offers the first ever possibility to perform coastal altimetric studies using SAR-Interferometry. This enabled qualified measurements of sea surface height (SST) in the fjords in Greenland. Scoresbysund fjord on the east coast of Greenland is the largest fjord in the world which is also covered by CryoSat-2 SAR-In mask making it a good test region. Also, the tide gauge operated by DTU Space is sitting in Scoresbysund bay, which provides solid ground-based sea level variation records throughout the year. We perform an investigation into sea surface height variation since the start of the Cryosat-2 mission using SAR-In L1B data processed with baseline B processing. We have employed a new develop method for projecting all SAR-In observations in the Fjord onto a centerline up the Fjord. Hereby we can make solid estimates of the annual and (semi-) annual signal in sea level/sea ice freeboard within the Fjord. These seasonal height variations enable us to derive sea ice freeboard changes in the fjord from satellite altimetry. Derived sea level and sea-ice freeboard can be validated by comparison with the tide gauge observations for sea level and output from the Microwave Radiometer derived observations of sea ice freeboard developed at the Danish Meteorological Institute.

  11. An in vitro and in vivo evaluation of the efficacy of recombinant human liver prolidase as a catalytic bioscavenger of chemical warfare nerve agents.

    PubMed

    Rezk, Peter E; Zdenka, Pierre; Sabnekar, Praveena; Kajih, Takwen; Mata, David G; Wrobel, Chester; Cerasoli, Douglas M; Chilukuri, Nageswararao

    2015-01-01

    In this study, we determined the ability of recombinant human liver prolidase to hydrolyze nerve agents in vitro and its ability to afford protection in vivo in mice. Using adenovirus containing the human liver prolidase gene, the enzyme was over expressed by 200- to 300-fold in mouse liver and purified to homogeneity by affinity and gel filtration chromatography. The purified enzyme hydrolyzed sarin, cyclosarin and soman with varying rates of hydrolysis. The most efficient hydrolysis was with sarin, followed by soman and by cyclosarin {apparent kcat/Km [(1.9 ± 0.3), (1.7 ± 0.2), and (0.45 ± 0.04)] × 10(5 )M(-1 )min(-1), respectively}; VX and tabun were not hydrolyzed by the recombinant enzyme. The enzyme hydrolyzed P (+) isomers faster than the P (-) isomers. The ability of recombinant human liver prolidase to afford 24 hour survival against a cumulative dose of 2 × LD50 of each nerve agent was investigated in mice. Compared to mice injected with a control virus, mice injected with the prolidase expressing virus contained (29 ± 7)-fold higher levels of the enzyme in their blood on day 5. Challenging these mice with two consecutive 1 × LD50 doses of sarin, cyclosarin, and soman resulted in the death of all animals within 5 to 8 min from nerve agent toxicity. In contrast, mice injected with the adenovirus expressing mouse butyrylcholinesterase, an enzyme which is known to afford protection in vivo, survived multiple 1 × LD50 challenges of these nerve agents and displayed no signs of toxicity. These results suggest that, while prolidase can hydrolyze certain G-type nerve agents in vitro, the enzyme does not offer 24 hour protection against a cumulative dose of 2 × LD50 of G-agents in mice in vivo.

  12. Fine Ice Sheet margins topography from swath processing of CryoSat SARIn mode data

    NASA Astrophysics Data System (ADS)

    Gourmelen, N.; Escorihuela, M. J.; Shepherd, A.; Foresta, L.; Muir, A.; Briggs, K.; Hogg, A. E.; Roca, M.; Baker, S.; Drinkwater, M. R.

    2014-12-01

    Reference and repeat-observations of Glacier and Ice Sheet Margin (GISM) topography are critical to identify changes in ice thickness, provide estimates of mass gain or loss and thus quantify the contribution of the cryosphere to sea level change. The lack of such sustained observations was identified in the Integrated Global Observing Strategy (IGOS) Cryosphere Theme Report as a major shortcoming. Conventional altimetry measurements over GISMs exist, but coverage has been sparse and characterized by coarse ground resolution. Additionally, and more importantly, they proved ineffective in the presence of steep slopes, a typical feature of GISM areas. Since the majority of Antarctic and Greenland ice sheet mass loss is estimated to lie within 100 km from the coast, but only about 10% is surveyed, there is the need for more robust and dense observations of GISMs, in both time and space. The ESA Altimetry mission CryoSat aims at gaining better insight into the evolution of the Cryosphere. CryoSat's revolutionary design features a Synthetic Interferometric Radar Altimeter (SIRAL), with two antennas for interferometry. The corresponding SAR Interferometer (SARIn) mode of operation increases spatial resolution while resolving the angular origin of off-nadir echoes occurring over sloping terrain. The SARIn mode is activated over GISMs and the elevation for the Point Of Closest Approach (POCA) is a standard product of the CryoSat mission. Here we present an approach for more comprehensively exploiting the SARIn mode of CryoSat and produce an ice elevation product with enhanced spatial resolution compared to standard CryoSat-2 height products. In this so called L2-swath processing approach, the full CryoSat waveform is exploited under specific conditions of signal and surface characteristics. We will present the rationale, validation exercises and preliminary results from the Eurpean Space Agency's STSE CryoTop study over selected test regions of the margins of the Greenland

  13. Symptoms of Gulf War veterans possibly exposed to organophosphate chemical warfare agents at Khamisiyah, Iraq.

    PubMed

    McCauley, L A; Rischitelli, G; Lambert, W E; Lasarev, M; Sticker, D L; Spencer, P S

    2001-01-01

    During the 1991 Gulf War, some Allied troops were potentially exposed to sarin/cyclosarin as the result of the destruction of Iraqi munitions at Khamisiyah. To evaluate the prevalence of past and current symptoms known to be associated with exposure to these chemical warfare agents, the authors conducted a computer-assisted telephone survey of 2,918 U.S. Gulf War veterans. Veterans who had participated in or witnessed the demolition in 1991 were more likely to report historical or extant symptoms than were veterans from other military units. These results should be viewed cautiously because they are based on symptoms recalled nine years after the event without precise characterization of exposure. Nonetheless, the findings suggest that symptoms consistent with low-level sarin exposure may have initially occurred, and health effects may have persisted in the veterans who were nearest to the demolition activity. Further research is warranted.

  14. Synthesis and in vitro reactivation study of isonicotinamide derivatives of 2-(hydroxyimino)-N-(pyridin-3-yl)acetamide as reactivators of Sarin and VX inhibited human acetylcholinesterase (hAChE).

    PubMed

    Karade, Hitendra N; Raviraju, G; Acharya, B N; Valiveti, Aditya Kapil; Bhalerao, Uma; Acharya, Jyotiranjan

    2016-09-15

    Previously (Karade et al., 2014), we have reported the synthesis and in vitro evaluation of bis-pyridinium derivatives of pyridine-3-yl-(2-hydroxyimino acetamide), as reactivators of sarin and VX inhibited hAChE. Few of the molecules showed superior in vivo protection efficacy (mice model) (Kumar et al., 2014; Swami et al., 2016) in comparison to 2-PAM against DFP and sarin poisoning. Encouraged by these results, herein we report the synthesis and in vitro evaluation of isonicotinamide derivatives of pyridine-3-yl-(2-hydroxyimino acetamide) (4a-4d) against sarin and VX inhibited erythrocyte ghost hAChE. Reactivation kinetics of these compounds was studied and the determined kinetic parameters were compared with that of commercial reactivators viz. 2-PAM and obidoxime. In comparison to 2-PAM and obidoxime, oxime 4a and 4b exhibited enhanced reactivation efficacy toward sarin inhibited hAChE while oxime 4c showed far greater reactivation efficacy toward VX inhibited hAChE. The acid dissociation constant and IC50 values of these oximes were determined and correlated with the observed reactivation potential. Copyright © 2016 Elsevier Ltd. All rights reserved.

  15. Ice elevation change from Swath Processing of CryoSat SARIn Mode Data

    NASA Astrophysics Data System (ADS)

    Foresta, Luca; Gourmelen, Noel; Shepherd, Andrew; Muir, Alan; Nienow, Pete

    2015-04-01

    Reference and repeat-observations of Glacier and Ice Sheet Margin (GISM) topography are critical to identify changes in ice elevation, provide estimates of mass gain or loss and thus quantify the contribution of the cryosphere to sea level rise (e.g. McMillan et al., 2014). The Synthetic Interferometric Radar Altimeter (SIRAL) onboard the ESA radar altimetry CryoSat (CS) mission has collected ice elevation measurements since 2010. The corresponding SARIn mode of operation, activated over GISM areas, provides high spatial resolution in the along-track direction while resolving the angular origin of echoes (i.e. across-track). The current ESA SARIn processor calculates the elevation of the Point Of Closest Approach (POCA) within each waveform and maps of elevation change in Antarctica and Greenland have been produced using the regular CS height product (McMillan et al., 2014; Helm et al., 2014). Data from the CS-SARIn mode has also been used to produce measurements of ice elevation beyond the POCA, also known as swath elevation (Hawley et al. 2009; Gray et al., 2013; ESA-STSE CryoTop project). Here we use the swath processing approach to generate maps of ice elevation change from selected regions around the margins of the Greenland and Antarctic Ice Sheets. We discuss the impact of the swath processing on the spatial resolution and precision of the resulting ice elevation field and compare our results to current dh/dt estimates. References: ESA STSE CryoTop project - http://www.stse-cryotop.org/ Gray L., Burgess D., Copland L., Cullen R., Galin N., Hawley R. and Helm V. Interferometric swath processing of Cryosat data for glacial ice topography. The Cryosphere, 7(6):1857-1867, December 2013. Hawley R.L., Shepherd A., Cullen R., Helm V. and WIngham D.J. Ice-sheet elevations from across-track processing of airborne interferometric radar altimetry. Geophysical Research Letters, 36(22):L22501, November 2009. Helm V., Humbert A. and Miller H. Elevation and elevation

  16. Acute toxicity of some nerve agents and pesticides in rats.

    PubMed

    Misik, Jan; Pavlikova, Ruzena; Cabal, Jiri; Kuca, Kamil

    2015-01-01

    Highly toxic organophosphorus compounds (V- and G-nerve agents) were originally synthesized for warfare or as agricultural pesticides. Data on their acute toxicity are rare and patchy. Therefore, there is a need for integrated summary comparing acute toxicity of organophosphates using different administration routes in the same animal model with the same methodology. Based on original data, a summary of in vivo acute toxicity of selected V- and G-nerve agents (tabun, sarin, soman, VX, Russian VX) and organophosphates paraoxon (POX) and diisopropyl fluorophosphate (DFP) in rats has been investigated. Male Wistar rats were exposed to organophosphates in several administration routes (i.m., i.p., p.o, s.c., p.c.). The acute toxicity was evaluated by the assessment of median lethal dose (LD50, mg kg(-1)) 2, 4, and 24 hours post exposure. V-agents were the most toxic presented with LD50 ranged from 0.0082 mg kg(-1) (VX, i.m.) to 1.402 mg kg(-1) (Russian VX, p.o.), followed by G-agents (LD50 = 0.069 mg kg(-1)/soman, i.m./ - 117.9 mg kg(-1)/sarin, p.c./), organophosphate POX and DFP (LD50 = 0.321 mg kg(-1)/POX, i.m./ - 420 mg kg(-1)/DFP, p.c./). Generally, i.m. administration was the most toxic throughout all tested agents and ways of administration (LD50 = 0.0082 mg kg(-1)/VX/ - 1.399 mg kg(-1)/DFP/) whereas p.c. way was responsible for lowest acute toxicity (LD50 = 0.085 mg kg(-1)/VX/ - 420 mg kg(-1)/DFP/). The acute toxicity of selected organophosphorus compounds is summarized throughout this study. Although the data assessed in rats are rather illustrative prediction for human, it presents a valuable contribution, indicating the toxic potential and harmfulness of organophosphates.

  17. Multifunctional Ultra-high Vacuum Apparatus for Studies of the Interactions of Chemical Warfare Agents on Complex Surfaces

    DTIC Science & Technology

    2014-01-02

    of the formation of a hydrogen-bonded hydroxyl. Characteristic modes of the sarin molecule itself are also ob- served. These experimental results show...chemical warfare agent, surface science, uptake, decontamination, filtration , UHV, XPS, FTIR, TPD REPORT DOCUMENTATION PAGE 11. SPONSOR/MONITOR’S...challenges that accompany the research of these toxic, often very low vapor pressure, compounds. While results of vacuum-based surface science

  18. Vesicants and nerve agents in chemical warfare. Decontamination and treatment strategies for a changed world.

    PubMed

    Devereaux, Asha; Amundson, Dennis E; Parrish, J S; Lazarus, Angeline A

    2002-10-01

    Vesicants and nerve agents have been used in chemical warfare for ages. They remain a threat in today's altered political climate because they are relatively simple to produce, transport, and deploy. Vesicants, such as mustard and lewisite, can affect the skin, eyes, respiratory system, and gastrointestinal system. They leave affected persons at risk for long-term effects. Nerve agents, such as tabun, sarin, soman, and VX, hyperstimulate the muscarinic and nicotinic receptors of the nervous system. Physicians need to familiarize themselves with the clinical findings of such exposures and the decontamination and treatment strategies necessary to minimize injuries and deaths.

  19. The Different Sensitive Behaviors of a Hydrogen-Bond Acidic Polymer-Coated SAW Sensor for Chemical Warfare Agents and Their Simulants

    PubMed Central

    Long, Yin; Wang, Yang; Du, Xiaosong; Cheng, Luhua; Wu, Penglin; Jiang, Yadong

    2015-01-01

    A linear hydrogen-bond acidic (HBA) linear functionalized polymer (PLF), was deposited onto a bare surface acoustic wave (SAW) device to fabricate a chemical sensor. Real-time responses of the sensor to a series of compounds including sarin (GB), dimethyl methylphosphonate (DMMP), mustard gas (HD), chloroethyl ethyl sulphide (2-CEES), 1,5-dichloropentane (DCP) and some organic solvents were studied. The results show that the sensor is highly sensitive to GB and DMMP, and has low sensitivity to HD and DCP, as expected. However, the sensor possesses an unexpected high sensitivity toward 2-CEES. This good sensing performance can’t be solely or mainly attributed to the dipole-dipole interaction since the sensor is not sensitive to some high polarity solvents. We believe the lone pair electrons around the sulphur atom of 2-CEES provide an electron-rich site, which facilitates the formation of hydrogen bonding between PLF and 2-CEES. On the contrary, the electron cloud on the sulphur atom of the HD molecule is offset or depleted by its two neighbouring strong electron-withdrawing groups, hence, hydrogen bonding can hardly be formed. PMID:26225975

  20. Gastric Adenocarcinomas Express the Glycosphingolipid Gb3/CD77: Targeting of Gastric Cancer Cells with Shiga Toxin B-Subunit.

    PubMed

    Geyer, Philipp Emanuel; Maak, Matthias; Nitsche, Ulrich; Perl, Markus; Novotny, Alexander; Slotta-Huspenina, Julia; Dransart, Estelle; Holtorf, Anne; Johannes, Ludger; Janssen, Klaus-Peter

    2016-05-01

    The B-subunit of the bacterial Shiga toxin (STxB), which is nontoxic and has low immunogenicity, can be used for tumor targeting of breast, colon, and pancreatic cancer. Here, we tested whether human gastric cancers, which are among the most aggressive tumor entities, express the cellular receptor of Shiga toxin, the glycosphingolipid globotriaosylceramide (Gb3/CD77). The majority of cases showed an extensive staining for Gb3 (36/50 cases, 72%), as evidenced on tissue sections of surgically resected specimen. Gb3 expression was detected independent of type (diffuse/intestinal), and was negatively correlated to increasing tumor-node-metastasis stages (P = 0.0385), as well as with markers for senescence. Gb3 expression in nondiseased gastric mucosa was restricted to chief and parietal cells at the bottom of the gastric glands, and was not elevated in endoscopic samples of gastritis (n = 10). Gb3 expression in established cell lines of gastric carcinoma was heterogeneous, with 6 of 10 lines being positive, evidenced by flow cytometry. STxB was taken up rapidly by live Gb3-positive gastric cancer cells, following the intracellular retrograde transport route, avoiding lysosomes and rapidly reaching the Golgi apparatus and the endoplasmic reticulum. Treatment of the Gb3-expressing gastric carcinoma cell line St3051 with STxB coupled to SN38, the active metabolite of the topoisomerase type I inhibitor irinotecan, resulted in >100-fold increased cytotoxicity, as compared with irinotecan alone. No cytotoxicity was observed on gastric cancer cell lines lacking Gb3 expression, demonstrating receptor specificity of the STxB-SN38 compound. Thus, STxB is a highly specific transport vehicle for cytotoxic agents in gastric carcinoma. Mol Cancer Ther; 15(5); 1008-17. ©2016 AACR. ©2016 American Association for Cancer Research.

  1. Metabonomics of Pig Blood Plasma Following Whole Body Exposure to Low Levels of Gb Vapor

    DTIC Science & Technology

    2005-10-01

    METABONOMICS OF PIG BLOOD PLASMA FOLLOWING WHOLE BODY EXPOSURE TO LOW LEVELS OF GB VAPOR Vicky L. H. Bevilacqua▲, Terrence G...of chemometrics and NMR will yield metabonomics data useful for establishing biochemical markers for agent exposure. Ideally, such markers would...associated with environmental change, a field recently referred to as " metabonomics ." High field nuclear magnetic resonance (NMR) has emerged as a

  2. Biodegradation of Organophosphate Chemical Warfare Agents by Activated Sludge

    DTIC Science & Technology

    2012-03-01

    Holmstedt, B. (1963). Structure- activity relationships of the organophosphorus anticholinesterase agents. In: Koelle, G.B. (ed.), Handbuch...BIODEGRADATION OF ORGANOPHOSPHATE CHEMICAL WARFARE AGENTS BY ACTIVATED SLUDGE Steven J. Schuldt...AFIT/GES/ENV/12-M04 BIODEGRADATION OF ORGANOPHOSPHATE CHEMICAL WARFARE AGENTS BY ACTIVATED SLUDGE THESIS Presented to the

  3. Supralethal poisoning by any of the classical nerve agents is effectively counteracted by procyclidine regimens in rats.

    PubMed

    Myhrer, Trond; Mariussen, Espen; Enger, Siri; Aas, Pål

    2015-09-01

    A treatment regimen consisting of HI-6, levetiracetam, and procyclidine (termed the triple regimen) has previously been shown to work as a universal therapy against soman poisoning in rats, since it has capacities to function as both prophylactic and therapeutic measure. The purpose of the present study was to examine whether the triple regimen may have antidotal efficacy against intoxication by other classical nerve agents than soman. The treatment was given 1 and 5 min after exposure to a supralethal dose of nerve agents, and the results showed that the triple regimen successfully prevented or terminated seizures and preserved the lives of rats exposed to 5×LD50 of soman, sarin, cyclosarin, or VX, but solely 3×LD50 of tabun was managed by this regimen. To meet the particular antidotal requirements of tabun, the triple regimen was reinforced with obidoxime and was made to a quadruple regimen that effectively treated rats intoxicated by 5×LD50 of tabun. The rats recovered very well and the majority gained pre-exposure body weight within 7 days. Neuropathology was seen in all groups regardless of whether the rats seized or not. The most extensive damage was produced by sarin and cyclosarin. Differentiation between the nerve agents' potency to cause lesions was probably seen because the efficacious treatments ensured survival of supralethal poisoning. A combination of 2 oximes and 2 anticonvulsants may be a prerequisite to counteract effectively high levels of poisoning by any classical nerve agent. Copyright © 2015 Elsevier Inc. All rights reserved.

  4. Preliminary screening of alternative technologies to incineration for treatment of chemical-agent-contaminated soil, Rocky Mountain Arsenal

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Shem, L.M.; Rosenblatt, D.H.; Smits, M.P.

    1995-12-01

    In support of the U.S. Army`s efforts to determine the best technologies for remediation of soils, water, and structures contaminated with pesticides and chemical agents, Argonne National Laboratory has reviewed technologies for treating soils contaminated with mustard, lewisite, sarin, o-ethyl s-(2- (diisopropylamino)ethyl)methyl-phosphonothioate (VX), and their breakdown products. This report focuses on assessing alternatives to incineration for dealing with these contaminants. For each technology, a brief description is provided, its suitability and constraints on its use are identified, and its overall applicability for treating the agents of concern is summarized. Technologies that merit further investigation are identified.

  5. Daily Planet Imagery: GIBS MODIS Products on ArcGIS Online

    NASA Astrophysics Data System (ADS)

    Plesea, L.

    2015-12-01

    The NASA EOSDIS Global Imagery Browse Services (GIBS) is rapidly becoming an invaluable GIS resource for the science community and for the public at large. Reliable, fast access to historical as well as near real time, georeferenced images form a solid basis on which many innovative applications and projects can be built. Esri has recognized the value of this effort and is a GIBS user and collaborator. To enable the use of GIBS services within the ArcGIS ecosystem, Esri has built a GIBS reflector server at http://modis.arcgis.com, server which offers the facilities of a time enabled Mosaic Service on top of the GIBS provided images. Currently the MODIS reflectance products are supported by this mosaic service, possibilities of handling other GIBS products are being explored. This reflector service is deployed on the Amazon Elastic Compute Cloud platform, and is freely available to the end users. Due to the excellent response time from GIBS, image tiles do not have to be stored by the Esri mosaic server, all needed data being retrieved directly from GIBS when needed, continuously reflecting the state of GIBS, and greatly simplifying the maintenance of this service. Response latency is usually under one second, making it easy to interact with the data. The remote data access is achieved by using the Geospatial Data Abstraction Library (GDAL) Tiled Web Map Server (TWMS) driver. The response time of this server is excellent, usually under one second. The MODIS imagery has proven to be one of the most popular ones on the ArcGIS Online platform, where it is frequently use to provide temporal context to maps, or by itself, to tell a compelling story.

  6. CMOS plasmonics in WDM data transmission: 200 Gb/s (8 × 25Gb/s) transmission over aluminum plasmonic waveguides.

    PubMed

    Dabos, G; Manolis, A; Papaioannou, S; Tsiokos, D; Markey, L; Weeber, J-C; Dereux, A; Giesecke, A L; Porschatis, C; Chmielak, B; Pleros, N

    2018-05-14

    We demonstrate wavelength-division-multiplexed (WDM) 200 Gb/s (8 × 25 Gb/s) data transmission over 100 μm long aluminum (Al) surface-plasmon-polariton (SPP) waveguides on a Si 3 N 4 waveguide platform at telecom wavelengths. The Al SPP waveguide was evaluated in terms of signal integrity by performing bit-error-rate (BER) measurements that revealed error-free operation for all eight 25 Gb/s non-return-to-zero (NRZ) modulated data channels with power penalties not exceeding 0.2 dB at 10 -9 . To the best of our knowledge, this is the first demonstration of WDM enabled data transmission over complementary-metal-oxide-semiconductor (CMOS) SPP waveguides fueling future development of CMOS compatible plasmo-photonic devices for on-chip optical interconnections.

  7. Estimating Lethal and Severe Toxic Effects in Minipigs Following 10, 60, and 180 Minutes of Whole-Body GB Vapor Exposure

    DTIC Science & Technology

    2006-03-01

    povidone-iodine) followed either by an application of isopropyl alcohol or a sporicidal agent. The surgical area was then covered with sterile drapes ...for Ten Minutes. MLRR 1952, 150. 20. Bide, R.W.; Armour , S.J.; Yee, E. Estimation of Human Toxicity from Animal Toxicity Data: GB Toxicity Reassessed

  8. History and perspectives of bioanalytical methods for chemical warfare agent detection.

    PubMed

    Black, Robin M

    2010-05-15

    This paper provides a short historical overview of the development of bioanalytical methods for chemical warfare (CW) agents and their biological markers of exposure, with a more detailed overview of methods for organophosphorus nerve agents. Bioanalytical methods for unchanged CW agents are used primarily for toxicokinetic/toxicodynamic studies. An important aspect of nerve agent toxicokinetics is the different biological activity and detoxification pathways for enantiomers. CW agents have a relatively short lifetime in the human body, and are hydrolysed, metabolised, or adducted to nucleophilic sites on macromolecules such as proteins and DNA. These provide biological markers of exposure. In the past two decades, metabolites, protein adducts of nerve agents, vesicants and phosgene, and DNA adducts of sulfur and nitrogen mustards, have been identified and characterized. Sensitive analytical methods have been developed for their detection, based mainly on mass spectrometry combined with gas or liquid chromatography. Biological markers for sarin, VX and sulfur mustard have been validated in cases of accidental and deliberate human exposures. The concern for terrorist use of CW agents has stimulated the development of higher throughput analytical methods in support of homeland security. Copyright (c) 2010. Published by Elsevier B.V.

  9. The Fate of Chemical Warfare Agents in the Environment

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Talmage, Sylvia Smith; Munro, Nancy B; Watson, Annetta Paule

    2007-01-01

    Chemical Warfare Agents, Second Edition has been totally revised since the successful first edition and expanded to about three times the length, with many new chapters and much more in-depth consideration of all the topics. The chapters have been written by distinguished international experts in various aspects of chemical warfare agents and edited by an experienced team to produce a clear review of the field. The book now contains a wealth of material on the mechanisms of action of the major chemical warfare agents, including the nerve agent cyclosarin, formally considered to be of secondary importance, as well as ricinmore » and abrin. Chemical Warfare Agents, Second Edition discusses the physico-chemical properties of chemical warfare agents, their dispersion and fate in the environment, their toxicology and management of their effects on humans, decontamination and protective equipment. New chapters cover the experience gained after the use of sarin to attack travelers on the Tokyo subway and how to deal with the outcome of the deployment of riot control agents such as CS gas. This book provides a comprehensive review of chemical warfare agents, assessing all available evidence regarding the medical, technical and legal aspects of their use. It is an invaluable reference work for physicians, public health planners, regulators and any other professionals involved in this field.« less

  10. Evaluation of Chemical Warfare Agent Wipe Sampling ...

    EPA Pesticide Factsheets

    Report This investigation tested specific (CWAs), including sarin (GB), soman (GD), cyclosarin (GF), sulfur mustard (HD), and O-ethyl-S-(2-diisopropylaminoethyl) methylphosphonothioate (VX) on the non-ideal (e.g., porous and permeable) surfaces of drywall, vinyl tile, wood, laminate, and coated glass. Pesticides (diazinon and malathion) were used so that a comparison is possible with existing literature data (1). Experiments included testing with coupons having surface areas of 10 cm2 and 100 cm2. The 10-cm2 coupons were of a size that could easily be extracted in a 2 oz jar (to provide comparative data for CWA recoveries generated by direct extraction) and the 100-cm2 coupons better represented the area of a surface that might typically be sampled by wipe extraction. In addition, CWA, at a normalized surface concentration of 0.1 µg per cm2 surface area, were spiked on coupons of the tested surfaces. Wipes were wetted with either dichloromethane (DCM) or isopropanol (IPA) before sampling for CWA. Experimental parameters include multiple wipe types, porous/permeable surfaces, coupon surface area, solvent used to wet the wipe (i.e., wetting solvent), and the utility of VX-d14 as an extracted internal standard.

  11. How well does urinary lyso-Gb3 function as a biomarker in Fabry disease?

    PubMed

    Auray-Blais, Christiane; Ntwari, Aimé; Clarke, Joe T R; Warnock, David G; Oliveira, João Paulo; Young, Sarah P; Millington, David S; Bichet, Daniel G; Sirrs, Sandra; West, Michael L; Casey, Robin; Hwu, Wuh-Liang; Keutzer, Joan M; Zhang, X Kate; Gagnon, René

    2010-12-14

    Fabry disease is characterized by accumulation of glycosphingolipids, such as globotriaosylceramide (Gb(3)), in many tissues and body fluids. A novel plasma biomarker, globotriaosylsphingosine (lyso-Gb(3)), is increased in patients with the disease. Until now, lyso-Gb(3) was not detectable in urine, possibly because of the presence of interfering compounds. We undertook to: 1) characterize lyso-Gb(3) in urine; 2) develop a method to quantitate urinary lyso-Gb(3) by mass spectrometry; 3) evaluate urinary lyso-Gb(3) as a potential biomarker for Fabry disease; and 4) determine whether lyso-Gb(3) is an inhibitor of α-galactosidase A activity. We analyzed urinary lyso-Gb(3) from 83 Fabry patients and 77 healthy age-matched controls. The intraday and interday bias and precision of the method were <15%. Increases in lyso-Gb(3)/creatinine correlated with the concentrations of Gb(3) (r(2)=0.43), type of mutations (p=0.0006), gender (p<0.0001) and enzyme replacement therapy status (p=0.0012). Urine from healthy controls contained no detectable lyso-Gb(3). Lyso-Gb(3) did not inhibit GLA activity in dried blood spots. Increased urinary excretion of lyso-Gb(3) of Fabry patients correlated well with a number of indicators of disease severity. Lyso-Gb(3) is a reliable independent biomarker for clinically important characteristics of Fabry disease. Copyright © 2010 Elsevier B.V. All rights reserved.

  12. μ-PADs for detection of chemical warfare agents.

    PubMed

    Pardasani, Deepak; Tak, Vijay; Purohit, Ajay K; Dubey, D K

    2012-12-07

    Conventional methods of detection of chemical warfare agents (CWAs) based on chromogenic reactions are time and solvent intensive. The development of cost, time and solvent effective microfluidic paper based analytical devices (μ-PADs) for the detection of nerve and vesicant agents is described. The detection of analytes was based upon their reactions with rhodamine hydroxamate and para-nitrobenzyl pyridine, producing red and blue colours respectively. Reactions were optimized on the μ-PADs to produce the limits of detection (LODs) as low as 100 μM for sulfur mustard in aqueous samples. Results were quantified with the help of a simple desktop scanner and Photoshop software. Sarin achieved a linear response in the two concentration ranges of 20-100 mM and 100-500 mM, whereas the response of sulfur mustard was found to be linear in the concentration range of 10-75 mM. Results were precise enough to establish the μ-PADs as a valuable tool for security personnel fighting against chemical terrorism.

  13. Metal-organic frameworks for the removal of toxic industrial chemicals and chemical warfare agents.

    PubMed

    Bobbitt, N Scott; Mendonca, Matthew L; Howarth, Ashlee J; Islamoglu, Timur; Hupp, Joseph T; Farha, Omar K; Snurr, Randall Q

    2017-06-06

    Owing to the vast diversity of linkers, nodes, and topologies, metal-organic frameworks can be tailored for specific tasks, such as chemical separations or catalysis. Accordingly, these materials have attracted significant interest for capture and/or detoxification of toxic industrial chemicals and chemical warfare agents. In this paper, we review recent experimental and computational work pertaining to the capture of several industrially-relevant toxic chemicals, including NH 3 , SO 2 , NO 2 , H 2 S, and some volatile organic compounds, with particular emphasis on the challenging issue of designing materials that selectively adsorb these chemicals in the presence of water. We also examine recent research on the capture and catalytic degradation of chemical warfare agents such as sarin and sulfur mustard using metal-organic frameworks.

  14. Herpesvirus gB: A Finely Tuned Fusion Machine

    PubMed Central

    Cooper, Rebecca S.; Heldwein, Ekaterina E.

    2015-01-01

    Enveloped viruses employ a class of proteins known as fusogens to orchestrate the merger of their surrounding envelope and a target cell membrane. Most fusogens accomplish this task alone, by binding cellular receptors and subsequently catalyzing the membrane fusion process. Surprisingly, in herpesviruses, these functions are distributed among multiple proteins: the conserved fusogen gB, the conserved gH/gL heterodimer of poorly defined function, and various non-conserved receptor-binding proteins. We summarize what is currently known about gB from two closely related herpesviruses, HSV-1 and HSV-2, with emphasis on the structure of the largely uncharted membrane interacting regions of this fusogen. We propose that the unusual mechanism of herpesvirus fusion could be linked to the unique architecture of gB. PMID:26690469

  15. Low-cost and miniaturized 100-Gb/s (2 × 50 Gb/s) PAM-4 TO-packaged ROSA for data center networks.

    PubMed

    Kang, Sae-Kyoung; Huh, Joon Young; Lee, Jie Hyun; Lee, Joon Ki

    2018-03-05

    We design and implement a cost-effective and compact 100-Gb/s (2 × 50 Gb/s) PAM-4 receiver optical sub-assembly (ROSA) by using a TO-can package instead of an expensive box-type package. It consists of an optical demultiplexer, two PIN-PDs and a 2-channel linear transimpedance amplifier. The components are passively aligned and assembled using alignment marks engraved on each part. With a real-time PAM-4 DSP chip, we measured the back-to-back receiver sensitivities of the 100-Gb/s ROSA based on TO-56 to be less than -13.2 dBm for both channels at a bit error rate of 2.4e-4. The crosstalk penalty due to the adjacent channel interference was observed around 0.1 dB.

  16. Decontamination of adsorbed chemical warfare agents on activated carbon using hydrogen peroxide solutions.

    PubMed

    Osovsky, Ruth; Kaplan, Doron; Nir, Ido; Rotter, Hadar; Elisha, Shmuel; Columbus, Ishay

    2014-09-16

    Mild treatment with hydrogen peroxide solutions (3-30%) efficiently decomposes adsorbed chemical warfare agents (CWAs) on microporous activated carbons used in protective garments and air filters. Better than 95% decomposition of adsorbed sulfur mustard (HD), sarin, and VX was achieved at ambient temperatures within 1-24 h, depending on the H2O2 concentration. HD was oxidized to the nontoxic HD-sulfoxide. The nerve agents were perhydrolyzed to the respective nontoxic methylphosphonic acids. The relative rapidity of the oxidation and perhydrolysis under these conditions is attributed to the microenvironment of the micropores. Apparently, the reactions are favored due to basic sites on the carbon surface. Our findings suggest a potential environmentally friendly route for decontamination of adsorbed CWAs, using H2O2 without the need of cosolvents or activators.

  17. Synthesis and in-vitro reactivation screening of imidazolium aldoximes as reactivators of sarin and VX-inhibited human acetylcholinesterase (hAChE).

    PubMed

    Sharma, Rahul; Gupta, Bhanushree; Sahu, Arvind Kumar; Acharya, Jyotiranjan; Satnami, Manmohan L; Ghosh, Kallol K

    2016-11-25

    Post-treatment of organophosphate (OP) poisoning involves the application of oxime reactivator as an antidote. Structurally different oximes are widely studied to examine their kinetic and mechanistic behavior against OP-inhibited cholinesterase enzyme. A series of structurally related 1,3-disubstituted-2-[(hydroxyiminomethyl)alkyl]imidazolium halides (5a-5e, 9a-9c) were synthesized and further evaluated for their in-vitro reactivation ability to reactivate sarin- and VX-inhibited human acetylcholinesterase (hAChE). The observed results were compared with the reactivation efficacy of standard reactivators; 2-PAM, obidoxime and HI-6. Amongst the synthesized oximes, 5a, 9a and 9b were found to be most potent reactivators against sarin-inhibited hAChE while in case of VX only 9a exhibited comparable reactivity with 2-PAM. Incorporation of pyridinium ring to the imidazole ring resulted in substantial increase in the reactivation strength of prepared reactivator. Physicochemical properties of synthesized reactivators have also been evaluated. Copyright © 2016. Published by Elsevier Ireland Ltd.

  18. Manganese (Mn) Oxidation Increases Intracellular Mn in Pseudomonas putida GB-1

    PubMed Central

    Banh, Andy; Chavez, Valarie; Doi, Julia; Nguyen, Allison; Hernandez, Sophia; Ha, Vu; Jimenez, Peter; Espinoza, Fernanda; Johnson, Hope A.

    2013-01-01

    Bacterial manganese (Mn) oxidation plays an important role in the global biogeochemical cycling of Mn and other compounds, and the diversity and prevalence of Mn oxidizers have been well established. Despite many hypotheses of why these bacteria may oxidize Mn, the physiological reasons remain elusive. Intracellular Mn levels were determined for Pseudomonas putida GB-1 grown in the presence or absence of Mn by inductively coupled plasma mass spectrometry (ICP-MS). Mn oxidizing wild type P. putida GB-1 had higher intracellular Mn than non Mn oxidizing mutants grown under the same conditions. P. putida GB-1 had a 5 fold increase in intracellular Mn compared to the non Mn oxidizing mutant P. putida GB-1-007 and a 59 fold increase in intracellular Mn compared to P. putida GB-1 ∆2665 ∆2447. The intracellular Mn is primarily associated with the less than 3 kDa fraction, suggesting it is not bound to protein. Protein oxidation levels in Mn oxidizing and non oxidizing cultures were relatively similar, yet Mn oxidation did increase survival of P. putida GB-1 when oxidatively stressed. This study is the first to link Mn oxidation to Mn homeostasis and oxidative stress protection. PMID:24147089

  19. Quantum-Chemical Study of the Adsorption of DMMP and Sarin on gamma-Al2O3

    DTIC Science & Technology

    2007-02-01

    In this and in the following section, ∆Eads is not corrected for zero-point vibrational energy ( ZPE ); however, a counterpoise correction for basis set...Ångstroms and the bond angle is in degrees. Values in parentheses are BSSE-corrected (∆Eads C ) results. ∆Eads has not been corrected for ZPE . b 6-31G...sets. The ∆ Eads C values are given in parentheses. No ZPE corrections have been applied. e The basis sets used were 6-311G(df) for Sarin and for the Al

  20. The ASCI Network for SC 2000: Gigabyte Per Second Networking

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    PRATT, THOMAS J.; NAEGLE, JOHN H.; MARTINEZ JR., LUIS G.

    2001-11-01

    This document highlights the Discom's Distance computing and communication team activities at the 2000 Supercomputing conference in Dallas Texas. This conference is sponsored by the IEEE and ACM. Sandia's participation in the conference has now spanned a decade, for the last five years Sandia National Laboratories, Los Alamos National Lab and Lawrence Livermore National Lab have come together at the conference under the DOE's ASCI, Accelerated Strategic Computing Initiatives, Program rubric to demonstrate ASCI's emerging capabilities in computational science and our combined expertise in high performance computer science and communication networking developments within the program. At SC 2000, DISCOM demonstratedmore » an infrastructure. DISCOM2 uses this forum to demonstrate and focus communication and pre-standard implementation of 10 Gigabit Ethernet, the first gigabyte per second data IP network transfer application, and VPN technology that enabled a remote Distributed Resource Management tools demonstration. Additionally a national OC48 POS network was constructed to support applications running between the show floor and home facilities. This network created the opportunity to test PSE's Parallel File Transfer Protocol (PFTP) across a network that had similar speed and distances as the then proposed DISCOM WAN. The SCINET SC2000 showcased wireless networking and the networking team had the opportunity to explore this emerging technology while on the booth. This paper documents those accomplishments, discusses the details of their convention exhibit floor. We also supported the production networking needs of the implementation, and describes how these demonstrations supports DISCOM overall strategies in high performance computing networking.« less

  1. Measurement of breakthrough volumes of volatile chemical warfare agents on a poly(2,6-diphenylphenylene oxide)-based adsorbent and application to thermal desorption-gas chromatography/mass spectrometric analysis.

    PubMed

    Kanamori-Kataoka, Mieko; Seto, Yasuo

    2015-09-04

    To establish adequate on-site solvent trapping of volatile chemical warfare agents (CWAs) from air samples, we measured the breakthrough volumes of CWAs on three adsorbent resins by an elution technique using direct electron ionization mass spectrometry. The trapping characteristics of Tenax(®) TA were better than those of Tenax(®) GR and Carboxen(®) 1016. The latter two adsorbents showed non-reproducible breakthrough behavior and low VX recovery. The specific breakthrough values were more than 44 (sarin) L/g Tenax(®) TA resin at 20°C. Logarithmic values of specific breakthrough volume for four nerve agents (sarin, soman, tabun, and VX) showed a nearly linear correlation with the reciprocals of their boiling points, but the data point of sulfur mustard deviated from this linear curve. Next, we developed a method to determine volatile CWAs in ambient air by thermal desorption-gas chromatography (TD-GC/MS). CWA solutions that were spiked into the Tenax TA(®) adsorbent tubes were analyzed by a two-stage TD-GC/MS using a Tenax(®) TA-packed cold trap tube. Linear calibration curves for CWAs retained in the resin tubes were obtained in the range between 0.2pL and 100pL for sarin, soman, tabun, cyclohexylsarin, and sulfur mustard; and between 2pL and 100pL for VX and Russian VX. We also examined the stability of CWAs in Tenax(®) TA tubes purged with either dry or 50% relative humidity air under storage conditions at room temperature or 4°C. More than 80% sarin, soman, tabun, cyclohexylsarin, and sulfur mustard were recovered from the tubes within 2 weeks. In contrast, the recoveries of VX and Russian VX drastically reduced with storage time at room temperature, resulting in a drop to 10-30% after 2 weeks. Moreover, we examined the trapping efficiency of Tenax TA(®) adsorbent tubes for vaporized CWA samples (100mL) prepared in a 500mL gas sampling cylinder. In the concentration range of 0.2-2.5mg/m(3), >50% of sarin, soman, tabun, cyclohexylsarin, and HD were

  2. Setting up a mobile Lidar (DIAL) system for detecting chemical warfare agents

    NASA Astrophysics Data System (ADS)

    Kavosh Tehrani, M.; Mohammad, M. Malek; Jaafari, E.; Mobashery, A.

    2015-03-01

    The mobile light detection and ranging DIAL system of Malek Ashtar University of Technology has been developed for the detection of chemical warfare agents whose absorption wavelengths are in the range of 9.2-10.8 μm tunable CO2 lasers of the system. In this paper, this system is first described and then ammonia detection is analyzed experimentally. Also, experimental results of detecting a sarin agent simulant, dimethyl-methyl phosphonate (DMMP), are presented. The power levels received from different ranges to detect specific concentrations of NH3 and DMMP have been measured and debated. The primary test results with a 150 ns clipped pulse width by passive pinhole plasma shutter indicate that the system is capable of monitoring several species of pollutants in the range of about 1 km, with a 20 m spatial and 2 min temporal resolution.

  3. 120. NORTH PLANT GB BULK STORAGE BUILDING AND AMMUNITION DEMOLITION ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    120. NORTH PLANT GB BULK STORAGE BUILDING AND AMMUNITION DEMOLITION FACILITY AT CENTER AND CASE FILLING PLANT/CLUSTER ASSEMBLY BUILDING (BUILDING 1601/1606) IN BACKGROUND, FROM GB MANUFACTURING PLANT. VIEW TO WEST. - Rocky Mountain Arsenal, Bounded by Ninety-sixth Avenue & Fifty-sixth Avenue, Buckley Road, Quebec Street & Colorado Highway 2, Commerce City, Adams County, CO

  4. Genome Information Broker (GIB): data retrieval and comparative analysis system for completed microbial genomes and more

    PubMed Central

    Fumoto, Masaki; Miyazaki, Satoru; Sugawara, Hideaki

    2002-01-01

    Genome Information Broker (GIB) is a powerful tool for the study of comparative genomics. GIB allows users to retrieve and display partial and/or whole genome sequences together with the relevant biological annotation. GIB has accumulated all the completed microbial genome and has recently been expanded to include Arabidopsis thaliana genome data from DDBJ/EMBL/GenBank. In the near future, hundreds of genome sequences will be determined. In order to handle such huge data, we have enhanced the GIB architecture by using XML, CORBA and distributed RDBs. We introduce the new GIB here. GIB is freely accessible at http://gib.genes.nig.ac.jp/. PMID:11752256

  5. Reversed enantioselectivity of diisopropyl fluorophosphatase against organophosphorus nerve agents by rational design.

    PubMed

    Melzer, Marco; Chen, Julian C-H; Heidenreich, Anne; Gäb, Jürgen; Koller, Marianne; Kehe, Kai; Blum, Marc-Michael

    2009-12-02

    Diisopropyl fluorophosphatase (DFPase) from Loligo vulgaris is an efficient and robust biocatalyst for the hydrolysis of a range of highly toxic organophosphorus compounds including the nerve agents sarin, soman, and cyclosarin. In contrast to the substrate diisopropyl fluorophosphate (DFP) the nerve agents possess an asymmetric phosphorus atom, which leads to pairs of enantiomers that display markedly different toxicities. Wild-type DFPase prefers the less toxic stereoisomers of the substrates which leads to slower detoxification despite rapid hydrolysis. Enzyme engineering efforts based on rational design yielded two quadruple enzyme mutants with reversed enantioselectivity and overall enhanced activity against tested nerve agents. The reversed stereochemical preference is explained through modeling studies and the crystal structures of the two mutants. Using the engineered mutants in combination with wild-type DFPase leads to significantly enhanced activity and detoxification, which is especially important for personal decontamination. Our findings may also be of relevance for the structurally related enzyme human paraoxonase (PON), which is of considerable interest as a potential catalytic in vivo scavenger in case of organophosphorus poisoning.

  6. Neuroinflammatory Pathobiology in Gulf War Illness: Characterization with an Animal Model

    DTIC Science & Technology

    2013-08-01

    GFAP,IL6,CCL2, TNF, L118, Lif, IL10 Hip, Ctx Ctx Ctx CORT=corticosterone;(200mg/L) for days 7-14 P8= pyridostigmine bromide ;P8(2.5 mg/kg/day, s.c...reversible acetylcholinesterase (AChE) inhibitor pyridostigmine bromide (PB), the insect repellent DEET and, potentially, the nerve agent, sarin. These...acetylcholinesterase (AChE) inhibitor, pyridostigmine bromide (PB), the insect repellent, DEET, and, potentially, acutely to the nerve agent sarin. Previously, we

  7. [Analysis on the accuracy of simple selection method of Fengshi (GB 31)].

    PubMed

    Li, Zhixing; Zhang, Haihua; Li, Suhe

    2015-12-01

    To explore the accuracy of simple selection method of Fengshi (GB 31). Through the study of the ancient and modern data,the analysis and integration of the acupuncture books,the comparison of the locations of Fengshi (GB 31) by doctors from all dynasties and the integration of modern anatomia, the modern simple selection method of Fengshi (GB 31) is definite, which is the same as the traditional way. It is believed that the simple selec tion method is in accord with the human-oriented thought of TCM. Treatment by acupoints should be based on the emerging nature and the individual difference of patients. Also, it is proposed that Fengshi (GB 31) should be located through the integration between the simple method and body surface anatomical mark.

  8. Development of an automated on-line pepsin digestion-liquid chromatography-tandem mass spectrometry configuration for the rapid analysis of protein adducts of chemical warfare agents.

    PubMed

    Carol-Visser, Jeroen; van der Schans, Marcel; Fidder, Alex; Hulst, Albert G; van Baar, Ben L M; Irth, Hubertus; Noort, Daan

    2008-07-01

    Rapid monitoring and retrospective verification are key issues in protection against and non-proliferation of chemical warfare agents (CWA). Such monitoring and verification are adequately accomplished by the analysis of persistent protein adducts of these agents. Liquid chromatography-mass spectrometry (LC-MS) is the tool of choice in the analysis of such protein adducts, but the overall experimental procedure is quite elaborate. Therefore, an automated on-line pepsin digestion-LC-MS configuration has been developed for the rapid determination of CWA protein adducts. The utility of this configuration is demonstrated by the analysis of specific adducts of sarin and sulfur mustard to human butyryl cholinesterase and human serum albumin, respectively.

  9. Effects of the mosquito larvicide GB-1111 on bird eggs

    USGS Publications Warehouse

    Hoffman, D.J.; Albers, P.H.; Melancon, M.J.; Miles, A.K.

    2004-01-01

    Golden Bear Oil (GB-1111; legal trade name for GB-1313) is a petroleum distillate used in the United States and other countries as a mosquito larvicide. As part of an evaluation of the potential effects of GB-1111 on birds, fertile eggs of mallards (Anas platyrhynchos) and bobwhite (Colinus virginianus) were incubated in the laboratory, and treated on day 4 of incubation with external applications equivalent to either 0, 1/3, 1, 3 or 10 times the maximum rate (X) of 47 l/ha (5 gal/A) of field application of GB-1111. Hatching success was significantly reduced in mallards treated at 3 and 10 times the maximum field application, with a calculated approximate LD50 of 1.9 times the maximum field application. Most mortality occurred within a week of treatment. Hepatic P450-associated monooxygenase activity (ethoxyresorufin-O-dealkylase; EROD) was negatively related to dose. In the 3X group there was a significant increase in the concentration of hepatic reduced glutathione (GSH) but a decrease in proteinbound thiols (PBSH). Hatching success of bobwhite was marginally reduced at the highest level of treatment (10X). Other effects at this level in bobwhite included a significant increase in incidence of abnormal embryos or hatchlings, lower body and liver weights, and a twofold increase in hepatic microsomal EROD activity in hatchlings. The recommended maximum rate of field application of GB-1111 is unlikely to impair the survival or development of bobwhite embryos but is potentially toxic to mallard embryos under conditions of larvicide drift or spray overlap.

  10. Crystal structure of Gib2, a signal-transducing protein scaffold associated with ribosomes in Cryptococcus neoformans

    NASA Astrophysics Data System (ADS)

    Ero, Rya; Dimitrova, Valya Tenusheva; Chen, Yun; Bu, Wenting; Feng, Shu; Liu, Tongbao; Wang, Ping; Xue, Chaoyang; Tan, Suet Mien; Gao, Yong-Gui

    2015-03-01

    The atypical Gβ-like/RACK1 Gib2 protein promotes cAMP signalling that plays a central role in regulating the virulence of Cryptococcus neoformans. Gib2 contains a seven-bladed β transducin structure and is emerging as a scaffold protein interconnecting signalling pathways through interactions with various protein partners. Here, we present the crystal structure of Gib2 at a 2.2-Å resolution. The structure allows us to analyse the association between Gib2 and the ribosome, as well as to identify the Gib2 amino acid residues involved in ribosome binding. Our studies not only suggest that Gib2 has a role in protein translation but also present Gib2 as a physical link at the crossroads of various regulatory pathways important for the growth and virulence of C. neoformans.

  11. 10 Gb/s operation of photonic crystal silicon optical modulators.

    PubMed

    Nguyen, Hong C; Sakai, Yuya; Shinkawa, Mizuki; Ishikura, Norihiro; Baba, Toshihiko

    2011-07-04

    We report the first experimental demonstration of 10 Gb/s modulation in a photonic crystal silicon optical modulator. The device consists of a 200 μm-long SiO2-clad photonic crystal waveguide, with an embedded p-n junction, incorporated into an asymmetric Mach-Zehnder interferometer. The device is integrated on a SOI chip and fabricated by CMOS-compatible processes. With the bias voltage set at 0 V, we measure a V(π)L < 0.056 V∙cm. Optical modulation is demonstrated by electrically driving the device with a 2(31) - 1 bit non-return-to-zero pseudo-random bit sequence signal. An open eye pattern is observed at bitrates of 10 Gb/s and 2 Gb/s, with and without pre-emphasis of the drive signal, respectively.

  12. Vapor Pressure of GB

    DTIC Science & Technology

    2009-04-01

    equation. The Podoll and Parish low temperature measured vapor pressure data (-35 and -25 °C) were included in our analysis . Penski summarized the...existing literature data for GB in his 1994 data review and analysis .6 He did not include the 0 °C Podoll and Parish measured vapor pressure data point...35.9 Pa) in his analysis because the error associated with this point was Ŗ to 10 times greater than the other values". He did not include the -10 °C

  13. Biocatalytic nerve agent detoxification in fire fighting foams.

    PubMed

    LeJeune, K E; Russell, A J

    1999-03-20

    Current events across the globe necessitate rapid technological advances to combat the epidemic of nerve agent chemical weapons. Biocatalysis has emerged as a viable tool in the detoxification of organophosphorus neurotoxins, such as the chemical weapons VX and sarin. Efficient detoxification of contaminated equipment, machinery, and soils are of principal concern. This study describes the incorporation of a biocatalyst (organophosphorus hydrolase, E.C. 3.1.8.1) into conventional formulations of fire fighting foam. The capacity of fire fighting foams to decrease volatilization of contained contaminants, increase surface wettability, and control the rate of enzyme delivery to large areas makes them useful vehicles for enzyme application at surfaces. The performance of enzyme containing foams has been shown to be not only reproducible but also predictable. An empirical model provides reasonable estimations for the amounts of achievable surface decontamination as a function of the important parameters of the system. Theoretical modeling illustrates that the enzyme-containing foam is capable of extracting agent from the surface and is catalytically active at the foam-surface interface and throughout the foam itself. Biocatalytic foam has proven to be an effective, "environmentally friendly" means of surface and soil decontamination.

  14. Indirect-blocking ELISA for detecting antibodies against glycoprotein B (gB) of porcine cytomegalovirus (PCMV).

    PubMed

    Liu, Xiao; Zhu, Ling; Shi, Xiaohong; Xu, Zhiwen; Mei, Miao; Xu, Weiwei; Zhou, Yuancheng; Guo, Wanzhu; Wang, Xiaoyu

    2012-12-01

    The major epitope region of the glycoprotein B (gB) gene of the porcine cytomegalovirus (PCMV), with a length of 270 bp, was cloned and expressed in Escherichia coli Rosetta (DE3). The major gB epitope was detected using an agar gel precipitation and Western blot analysis with the polyclonal antibodies specific for the major epitope. An indirect-blocking enzyme-linked immunosorbent assay (ELISA) was developed using the expressed major gB epitope as a coating antigen for the detection of PCMV antibodies. The results of the tests show that the indirect-blocking ELISA has 98% specificity and 97.8% sensitivity. No cross-reactions were observed between the major gB epitope and the antibodies against other virus, which indicates that the gB epitope is specific for PCMV antibodies. The indirect-blocking ELISA is a highly specific, sensitive method for detecting anti-PCMV gB antibodies. Copyright © 2012 Elsevier B.V. All rights reserved.

  15. Study of efficacy of reactivator HI 6 in reactivation of immobilized acetylcholinesterase, inhibited by organophosphorus chemical warfare agents of the "G" series.

    PubMed

    Hoskovcová, Monika; Halámek, Emil; Kobliha, Zbynĕk

    2009-01-01

    Reactivation with bis quaternary aldoxime HI-6, chemical formula 1-(2-hydroxyamino-methylpyridinium)-3-(4-carbamoylpyridinium)-2-oxapropane dichloride of immobilized enzyme acetylcholinesterase inhibited by nerve agent type "G" was studied. This aldoxime is effective in reactivation of sarin-inhibited acetylcholinesterase. Substantially lower reactivation potency was observed with cyclosarin-inhibited enzyme and almost no effect was found for that acetylcholinesterase is the enzyme complex. HI 6 is completely ineffective towards the soman-inhibited enzyme: After a 2-minute inhibition of the enzyme with soman no ability to define reactivator the inhibited enzymes and complexes.

  16. Operation of the Chemical Agent Munitions Disposal System (CAMDS) at Tooele Army Depot, Utah.

    DTIC Science & Technology

    1978-09-01

    parts furnace where the container is opened to expose the agent; the agent is boiled out and burned ; and the residual container is heat treated for...fuze booster to expose the booster pellet so it will burn instead of detonate in the Deactivation Furnace. A portion of the solution in the coolant...demilitarization equipment exposed to agent GB will be chemically decontaminated to prepare for operations with burstered mustard projectiles. The

  17. Hand-held analyser based on microchip electrophoresis with contactless conductivity detection for measurement of chemical warfare agent degradation products

    NASA Astrophysics Data System (ADS)

    Duran, Karolina-Petkovic; Zhu, Yonggang; Chen, Chuanpin; Swallow, Anthony; Stewart, Robert; Hoobin, Pam; Leech, Patrick; Ovenden, Simon

    2008-12-01

    This paper reports on the development of a hand-held device for on-site detection of organophosphonate nerve agent degradation products. This field-deployable analyzer relies on efficient microchip electrophoresis separation of alkyl methylphosphonic acids and their sensitive contactless conductivity detection. Miniaturized, low-powered design is coupled with promising analytical performance for separating the breakdown products of chemical warfare agents such as Soman, Sarin and VX . The detector has a detection limit of about 10 μg/mL and has a good linear response in the range 10-300 μg/mL concentration range. Applicability to environmental samples is demonstrated .The new hand-held analyzer offers great promise for converting conventional ion chromatography or capillary electrophoresis sophisticated systems into a portable forensic laboratory for faster, simpler and more reliable on-site screening.

  18. Effects of the mosquito larvicide GB-1111 on red-winged blackbird embryos

    USGS Publications Warehouse

    Albers, P.H.; Hoffman, D.J.; Buscemi, D.M.; Melancon, M.J.

    2003-01-01

    Golden Bear Oil (GB-111 I; legal trade name for GB-1313) is a petroleum distillate that is used in the United States and other countries as a larvicide for mosquito suppression. As part of a multi-species evaluation of the potential effects of GB-1111 on birds, red-winged blackbird eggs were collected, artificially incubated, and treated with one of five amounts of GB-1111 varying from 0 to 10 times the expected exposure from a spray application of the maximum recommended amount (X=47 l/ha, 5 gal/ac). The application of 10 X caused a significant reduction in hatching success. A dose-related reduction of hepatic microsomal mono-oxygenase activity (EROD) was detected. Among body weights, skeletal measurements, and age at death, only crownrump length was different among experimental groups. Overall, the potential hazard to embryos of a representative wetland passerine appears minimal until the application rate exceeds 3 X.

  19. Analysis of chemical weapons decontamination waste from old ton containers from Johnston Atoll using multiple analytical methods

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Creasy, W.R.; Brickhouse, M.D.; Morrisse, K.M.

    1999-07-01

    Decontamination waste from chemical weapons (CW) agents has been stored in ton containers on Johnston Atoll since 1971. The waste was recently sampled and analyzed to determine its chemical composition in preparation for future cleanups. Due to the range of products and analytical requirements, multiple chromatographic and spectroscopic methods were necessary, including gas chromatography/mass spectrometry (GC/MS), gas chromatography/atomic emission detection (GC/AED), liquid chromatography/mass spectrometry (LC/MS), capillary electrophoresis (CE), and nuclear magnetic resonance spectroscopy (NMR). The samples were screened for residual agents. No residual sarin (GB) or VX was found to detection limits of 20 ng/mL, but 3% of the samplesmore » contained residual sulfur mustard (HD) at < 140 ng/mL. Decontamination products of agents were identified. The majority (74%) of the ton containers were documented correctly, in that the observed decontamination products were in agreement with the labeled agent type, but for a number of the containers, the contents were not in agreement with the labels. In addition, arsenic compounds that are decontamination products of the agent lewisite (L) were observed in a few ton containers, suggesting that lewisite was originally present but not documented. This study was a prototype to demonstrate the level of effort required to characterize old bulk CW-related waste.« less

  20. 40 CFR 180.1111 - Bacillus subtilis GB03; exemption from the requirement of a tolerance.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 23 2010-07-01 2010-07-01 false Bacillus subtilis GB03; exemption from... FOOD Exemptions From Tolerances § 180.1111 Bacillus subtilis GB03; exemption from the requirement of a tolerance. The biofungicide Bacillus subtilis GB03 is exempted from the requirement of a tolerance in or on...

  1. The role of the oximes HI-6 and HS-6 inside human acetylcholinesterase inhibited with nerve agents: a computational study.

    PubMed

    Cuya, Teobaldo; Gonçalves, Arlan da Silva; da Silva, Jorge Alberto Valle; Ramalho, Teodorico C; Kuca, Kamil; C C França, Tanos

    2017-10-27

    The oximes 4-carbamoyl-1-[({2-[(E)-(hydroxyimino) methyl] pyridinium-1-yl} methoxy) methyl] pyridinium (known as HI-6) and 3-carbamoyl-1-[({2-[(E)-(hydroxyimino) methyl] pyridinium-1-yl} methoxy) methyl] pyridinium (known as HS-6) are isomers differing from each other only by the position of the carbamoyl group on the pyridine ring. However, this slight difference was verified to be responsible for big differences in the percentual of reactivation of acetylcholinesterase (AChE) inhibited by the nerve agents tabun, sarin, cyclosarin, and VX. In order to try to find out the reason for this, a computational study involving molecular docking, molecular dynamics, and binding energies calculations, was performed on the binding modes of HI-6 and HS-6 on human AChE (HssAChE) inhibited by those nerve agents.

  2. Ginkgo biloba Extract (GbE) Stimulates the Hypothalamic Serotonergic System and Attenuates Obesity in Ovariectomized Rats

    PubMed Central

    Banin, Renata M.; de Andrade, Iracema S.; Cerutti, Suzete M.; Oyama, Lila M.; Telles, Mônica M.; Ribeiro, Eliane B.

    2017-01-01

    Menopause is associated with increased risk to develop obesity but the mechanisms involved are not fully understood. We have shown that Ginkgo biloba extract (GbE) improved diet-induced obesity. Since GbE might be effective in the treatment of obesity related to menopause, avoiding the side effects of hormone replacement therapy, we investigated the effect of GbE on hypothalamic systems controlling energy homeostasis. Wistar rats were either ovariectomized (OVX) or Sham-operated. After 2 months, either 500 mg.kg-1 of GbE or vehicle were administered daily by gavage for 14 days. A subset of animals received an intracerebroventricular (i.c.v.) injection of serotonin (300 μg) or vehicle and food intake was measured after 12 and 24 h. Another subset was submitted to in vivo microdialysis and 5-HT levels of the medial hypothalamus were measured by high performance liquid chromatography, before and up to 2 h after the administration of 500 mg.kg-1 of GbE. Additional animals were used for quantification of 5-HT1A, 5-HT1B, 5-HT2C, 5-HTT, and pro-opiomelanocortin hypothalamic protein levels by Western blotting. OVX increased food intake and body weight and adiposity while GbE attenuated these alterations. i.c.v. serotonin significantly reduced food intake in Sham, Sham + GbE, and OVX + GbE groups while it failed to do so in the OVX group. In the OVX rats, GbE stimulated 5-HT microdialysate levels while it reduced hypothalamic 5-HTT protein levels. The results indicate that GbE improved the ovariectomy-induced resistance to serotonin hypophagia, at least in part through stimulation of the hypothalamic serotonergic activity. Since body weight gain is one of the most important consequences of menopause, the stimulation of the serotonergic transmission by GbE may represent a potential alternative therapy for menopause-related obesity. PMID:28928661

  3. Blaptica dubia as sentinels for exposure to chemical warfare agents - a pilot study.

    PubMed

    Worek, Franz; Seeger, Thomas; Neumaier, Katharina; Wille, Timo; Thiermann, Horst

    2016-11-16

    The increased interest of terrorist groups in toxic chemicals and chemical warfare agents presents a continuing threat to our societies. Early warning and detection is a key component for effective countermeasures against such deadly agents. Presently available and near term solutions have a number of major drawbacks, e.g. lack of automated, remote warning and detection of primarily low volatile chemical warfare agents. An alternative approach is the use of animals as sentinels for exposure to toxic chemicals. To overcome disadvantages of vertebrates the present pilot study was initiated to investigate the suitability of South American cockroaches (Blaptica dubia) as warning system for exposure to chemical warfare nerve and blister agents. Initial in vitro experiments with nerve agents showed an increasing inhibitory potency in the order tabun - cyclosarin - sarin - soman - VX of cockroach cholinesterase. Exposure of cockroaches to chemical warfare agents resulted in clearly visible and reproducible reactions, the onset being dependent on the agent and dose. With nerve agents the onset was related to the volatility of the agents. The blister agent lewisite induced signs largely comparable to those of nerve agents while sulfur mustard exposed animals exhibited a different sequence of events. In conclusion, this first pilot study indicates that Blaptica dubia could serve as a warning system to exposure of chemical warfare agents. A cockroach-based system will not detect or identify a particular chemical warfare agent but could trigger further actions, e.g. specific detection and increased protective status. By designing appropriate boxes with (IR) motion sensors and remote control (IR) camera automated off-site warning systems could be realized. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  4. NETGEAR ProSAFE M4300 Series 10-GbE Switch Tutorial

    DTIC Science & Technology

    2016-11-01

    ARL-TN-0803 ● NOV 2016 US Army Research Laboratory NETGEAR ProSAFE M4300 Series 10-GbE Switch Tutorial by Benjamin Kenawell...Disclaimers The findings in this report are not to be construed as an official Department of the Army position unless so designated by other...NETGEAR ProSAFE M4300 Series 10-GbE Switch Tutorial by Benjamin Kenawell Science and Engineering Apprentice Program (SEAP), Adelphi, MD Brian

  5. Determination of trace amounts of chemical warfare agent degradation products in decontamination solutions with NMR spectroscopy.

    PubMed

    Koskela, Harri; Rapinoja, Marja-Leena; Kuitunen, Marja-Leena; Vanninen, Paula

    2007-12-01

    Decontamination solutions are used for an efficient detoxification of chemical warfare agents (CWAs). As these solutions can be composed of strong alkaline chemicals with hydrolyzing and oxidizing properties, the analysis of CWA degradation products in trace levels from these solutions imposes a challenge for any analytical technique. Here, we present results of application of nuclear magnetic resonance spectroscopy for analysis of trace amounts of CWA degradation products in several untreated decontamination solutions. Degradation products of the nerve agents sarin, soman, and VX were selectively monitored with substantially reduced interference of background signals by 1D 1H-31P heteronuclear single quantum coherence (HSQC) spectrometry. The detection limit of the chemicals was at the low part-per-million level (2-10 microg/mL) in all studied solutions. In addition, the concentration of the degradation products was obtained with sufficient confidence with external standards.

  6. Demonstration of an 8*10-Gb/s OTDM system

    NASA Astrophysics Data System (ADS)

    Huo, Li; Yang, Yanfu; Lou, Caiyun; Gao, Yizhi

    2005-03-01

    An 8*10 Gb/s optical time-division-multiplexing (OTDM) system was demonstrated with an electroabsorption modulator (EAM) based short pulse generator followed by a two-stage nonlinear compression scheme which generated stable 10-GHz, 2-ps full-width at half-maximum (FWHM) pulse train, an opto-electronic oscillator (OEO) that extracted 10-GHz clock with a timing jitter of 300 fs from 80-Gb/s OTDM signal and a self cascaded EAM which produced a switching window of about 10 ps. A back-to-back error free demultiplexing experiment with a power penalty of 3.25 dB was carried out to verify the system performance.

  7. Effects of low-level sarin and cyclosarin exposure on hippocampal microstructure in Gulf War Veterans.

    PubMed

    Chao, Linda L; Zhang, Yu

    2018-05-04

    In early March 1991, shortly after the end of the Gulf War (GW), a munitions dump was destroyed at Khamisiyah, Iraq. Later, in 1996, the dump was found to have contained the organophosphorus (OP) nerve agents sarin and cyclosarin. We previously reported evidence of smaller hippocampal volumes in GW veterans with predicted exposure to the Khamisiyah plume compared to unexposed GW veterans. To investigate whether these macroscopic hippocampal volume changes are accompanied by microstructural alterations in the hippocampus, the current study acquired diffusion-tensor imaging (DTI), T1-, and T2-weighted images from 170 GW veterans (mean age: 53 ± 7 years), 81 of whom had predicted exposure to the Khamisiyah plume according to Department of Defense (DOD) plume modeling. We examined fractional anisotropy (FA), mean diffusivity (MD), and grey matter (GM) density from a hippocampal region of interest (ROI). Results indicate that, even after accounting for total hippocampal GM density (or hippocampal volume), age, sex, apolipoprotein ε4 genotype, and potential confounding OP pesticide exposures, hippocampal MD significantly predicted Khamisiyah exposure status (model p = 0.005, R 2  = 0.215, standardized coefficient β = 0.26, t = 2.85). Hippocampal MD was also inversely correlated with verbal memory learning performance in the entire study sample (p = 0.001). There were no differences in hippocampal FA or GM density; however, veterans with predicted Khamisiyah exposure had smaller hippocampal volumes compared to unexposed veterans. Because MD is sensitive to general microstructural disruptions that lead to increased extracellular spaces due to neuronal death, inflammation and gliosis, and/or to axonal loss or demyelination, these findings suggest that low-level exposure to the Khamisiyah plume has a detrimental, lasting effects on both macro- and micro-structure of the hippocampus. Copyright © 2018. Published by Elsevier Inc.

  8. Miniaturized low-cost ion mobility spectrometer for fast detection of chemical warfare agents.

    PubMed

    Zimmermann, Stefan; Barth, Sebastian; Baether, Wolfgang K M; Ringer, Joachim

    2008-09-01

    Ion mobility spectrometry (IMS) is a well-known method for detecting hazardous compounds in air. Typical applications are the detection of chemical warfare agents, highly toxic industrial compounds, explosives, and drugs of abuse. Detection limits in the low part per billion range, fast response times, and simple instrumentation make this technique more and more popular. In particular, there is an increasing demand for miniaturized low-cost IMS for hand-held devices and air monitoring of public areas by sensor networks. In this paper, we present a miniaturized aspiration condenser type ion mobility spectrometer for fast detection of chemical warfare agents. The device is easy to manufacture and allows single substance identification down to low part per billion-level concentrations within seconds. The improved separation power results from ion focusing by means of geometric constraints and fluid dynamics. A simple pattern recognition algorithm is used for the identification of trained substances in air. The device was tested at the German Armed Forces Scientific Institute for Protection Technologies-NBC-Protection. Different chemical warfare agents, such as sarin, tabun, soman, US-VX, sulfur mustard, nitrogen mustard, and lewisite were tested. The results are presented here.

  9. Circadian Rhythms of Heart Rate and Locomotion After Treatment With Low-Dose Acetylcholinesterase Inhibitors

    DTIC Science & Technology

    2006-01-01

    with pyridostigmine bromide (PB), a carbamate AChE by air conditioned vans and air-freight to the Laboratory inhibitor that does not cross the blood ...15. SUBJECT TERMS Nerve agents, sarin, pyridostigmine bromide, cerebral glucose utilization, cerebrovascular circulation, low dose cholinesterase ...March 2006" Accepted 12 May 2006 ABSTRACT: This study tested the hypothesis that repeated exposure to low levels of sarin, pyridostigmine bromide (PB

  10. Loktanella spp. Gb03 as an algicidal bacterium, isolated from the culture of Dinoflagellate Gambierdiscus belizeanus.

    PubMed

    Bloh, Anmar Hameed; Usup, Gires; Ahmad, Asmat

    2016-02-01

    Bacteria associated with harmful algal blooms can play a crucial role in regulating algal blooms in the environment. This study aimed at isolating and identifying algicidal bacteria in Dinoflagellate culture and to determine the optimum growth requirement of the algicidal bacteria, Loktanella sp. Gb-03. The Dinoflagellate culture used in this study was supplied by Professor Gires Usup's Laboratory, School of Environmental and Natural Resources Sciences, Faculty of Science and Technology, University Kebangsaan Malaysia, Malaysia. The culture was used for the isolation of Loktanella sp., using biochemical tests, API 20 ONE kits. The fatty acid content of the isolates and the algicidal activity were further evaluated, and the phenotype was determined through the phylogenetic tree. Gram-negative, non-motile, non-spore-forming, short rod-shaped, aerobic bacteria (Gb01, Gb02, Gb03, Gb04, Gb05, and Gb06) were isolated from the Dinoflagellate culture. The colonies were pink in color, convex with a smooth surface and entire edge. The optimum growth temperature for the Loktanella sp. Gb03 isolate was determined to be 30°C, in 1% of NaCl and pH7. Phylogenetic analysis based on 16S rRNA gene sequences showed that the bacterium belonged to the genus Loktanella of the class Alphaproteobacteria and formed a tight cluster with the type strain of Loktanella pyoseonensis (97.0% sequence similarity). On the basis of phenotypic, phylogenetic data and genetic distinctiveness, strain Gb-03, were placed in the genus Loktanella as the type strain of species. Moreover, it has algicidal activity against seven toxic Dinoflagellate. The algicidal property of the isolated Loktanella is vital, especially where biological control is needed to mitigate algal bloom or targeted Dinoflagellates.

  11. Loktanella spp. Gb03 as an algicidal bacterium, isolated from the culture of Dinoflagellate Gambierdiscus belizeanus

    PubMed Central

    Bloh, Anmar Hameed; Usup, Gires; Ahmad, Asmat

    2016-01-01

    Aim: Bacteria associated with harmful algal blooms can play a crucial role in regulating algal blooms in the environment. This study aimed at isolating and identifying algicidal bacteria in Dinoflagellate culture and to determine the optimum growth requirement of the algicidal bacteria, Loktanella sp. Gb-03. Materials and Methods: The Dinoflagellate culture used in this study was supplied by Professor Gires Usup's Laboratory, School of Environmental and Natural Resources Sciences, Faculty of Science and Technology, University Kebangsaan Malaysia, Malaysia. The culture was used for the isolation of Loktanella sp., using biochemical tests, API 20 ONE kits. The fatty acid content of the isolates and the algicidal activity were further evaluated, and the phenotype was determined through the phylogenetic tree. Results: Gram-negative, non-motile, non-spore-forming, short rod-shaped, aerobic bacteria (Gb01, Gb02, Gb03, Gb04, Gb05, and Gb06) were isolated from the Dinoflagellate culture. The colonies were pink in color, convex with a smooth surface and entire edge. The optimum growth temperature for the Loktanella sp. Gb03 isolate was determined to be 30°C, in 1% of NaCl and pH7. Phylogenetic analysis based on 16S rRNA gene sequences showed that the bacterium belonged to the genus Loktanella of the class Alphaproteobacteria and formed a tight cluster with the type strain of Loktanella pyoseonensis (97.0% sequence similarity). Conclusion: On the basis of phenotypic, phylogenetic data and genetic distinctiveness, strain Gb-03, were placed in the genus Loktanella as the type strain of species. Moreover, it has algicidal activity against seven toxic Dinoflagellate. The algicidal property of the isolated Loktanella is vital, especially where biological control is needed to mitigate algal bloom or targeted Dinoflagellates. PMID:27051199

  12. Epstein-Barr Virus Glycoprotein gB and gHgL Can Mediate Fusion and Entry in trans, and Heat Can Act as a Partial Surrogate for gHgL and Trigger a Conformational Change in gB

    PubMed Central

    Chesnokova, Liudmila S.; Ahuja, Munish K.

    2014-01-01

    ABSTRACT Epstein-Barr virus (EBV) fusion with an epithelial cell requires virus glycoproteins gHgL and gB and is triggered by an interaction between gHgL and integrin αvβ5, αvβ6, or αvβ8. Fusion with a B cell requires gHgL, gp42, and gB and is triggered by an interaction between gp42 and human leukocyte antigen class II. We report here that, like alpha- and betaherpesviruses, EBV, a gammaherpesvirus, can mediate cell fusion if gB and gHgL are expressed in trans. Entry of a gH-null virus into an epithelial cell is possible if the epithelial cell expresses gHgL, and entry of the same virus, which phenotypically lacks gHgL and gp42, into a B cell expressing gHgL is possible in the presence of a soluble integrin. Heat is capable of inducing the fusion of cells expressing only gB, and the proteolytic digestion pattern of gB in virions changes in the same way following the exposure of virus to heat or to soluble integrins. It is suggested that the Gibbs free energy released as a result of the high-affinity interaction of gHgL with an integrin contributes to the activation energy required to cause the refolding of gB from a prefusion to a postfusion conformation. IMPORTANCE The core fusion machinery of herpesviruses consists of glycoproteins gB and gHgL. We demonstrate that as in alpha- and betaherpesvirus, gB and gHgL of the gammaherpesvirus EBV can mediate fusion and entry when expressed in trans in opposing membranes, implicating interactions between the ectodomains of the proteins in the activation of fusion. We further show that heat and exposure to a soluble integrin, both of which activate fusion, result in the same changes in the proteolytic digestion pattern of gB, possibly representing the refolding of gB from its prefusion to its postfusion conformation. PMID:25142593

  13. Mapping regions of Epstein-Barr virus (EBV) glycoprotein B (gB) important for fusion function with gH/gL

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Plate, Aileen E.; Reimer, Jessica J.; Jardetzky, Theodore S.

    Glycoproteins gB and gH/gL are required for entry of Epstein-Barr virus (EBV) into cells, but the role of each glycoprotein and how they function together to mediate fusion is unclear. Analysis of the functional homology of gB from the closely related primate gammaherpesvirus, rhesus lymphocryptovirus (Rh-LCV), showed that EBV gB could not complement Rh gB due to a species-specific dependence between gB and gL. To map domains of gB required for this interaction, we constructed a panel of EBV/Rh gB chimeric proteins. Analysis showed that insertion of Rh gB from residues 456 to 807 restored fusion function of EBV gBmore » with Rh gH/gL, suggesting this region of gB is important for interaction with gH/gL. Split YFP bimolecular complementation (BiFC) provided evidence of an interaction between EBV gB and gH/gL. Together, our results suggest the importance of a gB-gH/gL interaction in EBV-mediated fusion with B cells requiring the region of EBV gB from 456 to 807.« less

  14. Structural characterization of chemical warfare agent degradation products in decontamination solutions with proton band-selective (1)H-(31)P NMR spectroscopy.

    PubMed

    Koskela, Harri; Hakala, Ullastiina; Vanninen, Paula

    2010-06-15

    Decontamination solutions, which are usually composed of strong alkaline chemicals, are used for efficient detoxification of chemical warfare agents (CWAs). The analysis of CWA degradation products directly in decontamination solutions is challenging due to the nature of the matrix. Furthermore, occasionally an unforeseen degradation pathway can result in degradation products which could be eluded to in standard analyses. Here, we present the results of the application of proton band-selective (1)H-(31)P NMR spectroscopy, i.e., band-selective 1D (1)H-(31)P heteronuclear single quantum coherence (HSQC) and band-selective 2D (1)H-(31)P HSQC-total correlation spectroscopy (TOCSY), for ester side chain characterization of organophosphorus nerve agent degradation products in decontamination solutions. The viability of the approach is demonstrated with a test mixture of typical degradation products of nerve agents sarin, soman, and VX. The proton band-selective (1)H-(31)P NMR spectroscopy is also applied in characterization of unusual degradation products of VX in GDS 2000 solution.

  15. Effects of the mosquito larvicide GB-1111 on mallard and bobwhite embryos

    USGS Publications Warehouse

    Stickel, W.H.

    2000-01-01

    Golden Bear Oil or GB-1111 is a petroleum distillate that is used throughout the United States as a larvicide for mosquito pupae. The oil forms a barrier at the air-water interface, which suffocates air-breathing insects. There are few published studies on non-target effects of GB-1111 but the product label warns that ?GB-1111 is toxic to fish and other aquatic organisms.? Fertile eggs of mallards (Anas platyrhynchos) and bobwhite (Colinus virginianus) were incubated in the laboratory, and treated on days 4 or 11 of incubation with external applications equivalent to either 0, 1/3, 1, 3, or 10 times the maximum rate (5 gal/A) of field application of GB-1111. Hatching success was significantly reduced in mallards treated on day 4 or day 11 at 3 and 10 times the maximum field application, with a calculated approximate LD50 of 1.9 times the maximum field application. Most mortality occurred within a week of treatment. Hatching success of bobwhite was only reduced at the highest level of treatment. Other effects at this level in bobwhite included a significant increase in incidence of abnormal embryos/ hatchlings, lower body and liver weights of hatchlings and a two-fold increase in hepatic microsomal P450-associated monooxygenase activity (EROD) in hatchlings. Recommended rates of field application of GB-1111 are potentially toxic to mallard embryos, especially under conditions of larvicide drift or spray overlap, but unlikely to impair the survival or development of bobwhite embryos.

  16. The evolution of interaction between grain boundary and irradiation-induced point defects: Symmetric tilt GB in tungsten

    NASA Astrophysics Data System (ADS)

    Li, Hong; Qin, Yuan; Yang, Yingying; Yao, Man; Wang, Xudong; Xu, Haixuan; Phillpot, Simon R.

    2018-03-01

    Molecular dynamics method is used and scheme of calculational tests is designed. The atomic evolution view of the interaction between grain boundary (GB) and irradiation-induced point defects is given in six symmetric tilt GB structures of bcc tungsten with the energy of the primary knock-on atom (PKA) EPKA of 3 and 5 keV and the simulated temperature of 300 K. During the collision cascade with GB structure there are synergistic mechanisms to reduce the number of point defects: one is vacancies recombine with interstitials, and another is interstitials diffuse towards the GB with vacancies almost not move. The larger the ratio of the peak defect zone of the cascades overlaps with the GB region, the statistically relative smaller the number of surviving point defects in the grain interior (GI); and when the two almost do not overlap, vacancy-intensive area generally exists nearby GBs, and has a tendency to move toward GB with the increase of EPKA. In contrast, the distribution of interstitials is relatively uniform nearby GBs and is affected by the EPKA far less than the vacancy. The GB has a bias-absorption effect on the interstitials compared with vacancies. It shows that the number of surviving vacancies statistically has increasing trend with the increase of the distance between PKA and GB. While the number of surviving interstitials does not change much, and is less than the number of interstitials in the single crystal at the same conditions. The number of surviving vacancies in the GI is always larger than that of interstitials. The GB local extension after irradiation is observed for which the interstitials absorbed by the GB may be responsible. The designed scheme of calculational tests in the paper is completely applicable to the investigation of the interaction between other types of GBs and irradiation-induced point defects.

  17. Investigating the effect of mutation on the thermo stability of GB1 protein

    NASA Astrophysics Data System (ADS)

    Sawitri, K. N.; Sumaryada, T.; Ambarsari, L.; Wahyudi, S. T.

    2018-04-01

    The thermo stability of wild-type and mutants of the B1 domain of Protein G (GB1 protein) have been studied using molecular dynamics simulation and free energy perturbation simulation. This research is aimed to examine what residue or what interaction that has a major role in the thermo stability of GB1 protein thermo stability by using the point mutation method. Based on the analysis, the unfolding of wild-type protein occurred in 500 K simulation at 704 ps. The mutations were chosen based on the changes in some analysis parameters and the calculated net solvation free energy change. It was found that a simple replacement of a positively charged residue in the β-sheet (K4S) decreases the stability of GB1 protein (unfolding at 452 ps), while the replacement of a negatively charged residue in the α-helix (E27G) increases the stability (unfolding at 846 ps). It was also found that the K4A mutation will break the α-helix and all β-sheet into the coil and turn. All those results suggest that the non-bonded interaction has the major role in the thermo stability of GB1 protein with the β-sheets were identified as the most important structure in the thermo stability of GB1 protein..

  18. Metal Inhibition of Growth and Manganese Oxidation in Pseudomonas putida GB-1

    NASA Astrophysics Data System (ADS)

    Pena, J.; Sposito, G.

    2009-12-01

    Biogenic manganese oxides (MnO2) are ubiquitous nanoparticulate minerals that contribute to the adsorption of nutrient and toxicant metals, the oxidative degradation of various organic compounds, and the respiration of metal-reducing bacteria in aquatic and terrestrial environments. The formation of these minerals is catalyzed by a diverse and widely-distributed group of bacteria and fungi, often through the enzymatic oxidation of aqueous Mn(II) to Mn(IV). In metal-impacted ecosystems, toxicant metals may alter the viability and metabolic activity of Mn-oxidizing organisms, thereby limiting the conditions under which biogenic MnO2 can form and diminishing their potential as adsorbent materials. Pseudomonas putida GB-1 (P. putida GB-1) is a model Mn-oxidizing laboratory culture representative of freshwater and soil biofilm-forming bacteria. Manganese oxidation in P. putida GB-1 occurs via two single-electron-transfer reactions, involving a multicopper oxidase enzyme found on the bacterial outer membrane surface. Near the onset of the stationary phase of growth, dark brown MnO2 particles are deposited in a matrix of bacterial cells and extracellular polymeric substances, thus forming heterogeneous biomineral assemblages. In this study, we assessed the influence of various transition metals on microbial growth and manganese oxidation capacity in a P. putida GB-1 culture propagated in a nutrient-rich growth medium. The concentration-response behavior of actively growing P. putida GB-1 cells was investigated for Fe, Co, Ni, Cu and Zn at pH ≈ 6 in the presence and absence of 1 mM Mn. Toxicity parameters such as EC0, EC50 and Hillslope, and EC100 were obtained from the sigmoidal concentration-response curves. The extent of MnO2 formation in the presence of the various metal cations was documented 24, 50, 74 and 104 h after the metal-amended medium was inoculated. Toxicity values were compared to twelve physicochemical properties of the metals tested. Significant

  19. 113Gb/s (10 x 11.3Gb/s) ultra-low power EAM driver array.

    PubMed

    Vaernewyck, Renato; Bauwelinck, Johan; Yin, Xin; Pierco, Ramses; Verbrugghe, Jochen; Torfs, Guy; Li, Zhisheng; Qiu, Xing-Zhi; Vandewege, Jan; Cronin, Richard; Borghesani, Anna; Moodie, David

    2013-01-14

    This paper presents an ultra-low power SiGe BiCMOS IC for driving a 10 channel electro-absorption modulator (EAM) array at 113Gb/s for wavelength division multiplexing passive optical network (WDM-PON) applications. With an output swing of 2.5V(pp), the EAM driver array consumes only 2.2W or 220mW per channel, 50% below the state of the art. Both the output swing and bias are configurable between 1.5 and 3.0V(pp) and 0.75-2.15V respectively.

  20. Epstein-Barr virus glycoprotein gB and gHgL can mediate fusion and entry in trans, and heat can act as a partial surrogate for gHgL and trigger a conformational change in gB.

    PubMed

    Chesnokova, Liudmila S; Ahuja, Munish K; Hutt-Fletcher, Lindsey M

    2014-11-01

    Epstein-Barr virus (EBV) fusion with an epithelial cell requires virus glycoproteins gHgL and gB and is triggered by an interaction between gHgL and integrin αvβ5, αvβ6, or αvβ8. Fusion with a B cell requires gHgL, gp42, and gB and is triggered by an interaction between gp42 and human leukocyte antigen class II. We report here that, like alpha- and betaherpesviruses, EBV, a gammaherpesvirus, can mediate cell fusion if gB and gHgL are expressed in trans. Entry of a gH-null virus into an epithelial cell is possible if the epithelial cell expresses gHgL, and entry of the same virus, which phenotypically lacks gHgL and gp42, into a B cell expressing gHgL is possible in the presence of a soluble integrin. Heat is capable of inducing the fusion of cells expressing only gB, and the proteolytic digestion pattern of gB in virions changes in the same way following the exposure of virus to heat or to soluble integrins. It is suggested that the Gibbs free energy released as a result of the high-affinity interaction of gHgL with an integrin contributes to the activation energy required to cause the refolding of gB from a prefusion to a postfusion conformation. The core fusion machinery of herpesviruses consists of glycoproteins gB and gHgL. We demonstrate that as in alpha- and betaherpesvirus, gB and gHgL of the gammaherpesvirus EBV can mediate fusion and entry when expressed in trans in opposing membranes, implicating interactions between the ectodomains of the proteins in the activation of fusion. We further show that heat and exposure to a soluble integrin, both of which activate fusion, result in the same changes in the proteolytic digestion pattern of gB, possibly representing the refolding of gB from its prefusion to its postfusion conformation. Copyright © 2014, American Society for Microbiology. All Rights Reserved.

  1. A Comprehensive Evaluation of the Efficacy of Leading Oxime Therapies in Guinea Pigs Exposed to Organophosphorus Chemical Warfare Agents or Pesticides

    PubMed Central

    Wilhelm, Christina M.; Snider, Thomas H.; Babin, Michael C.; Jett, David A.; Platoff, Gennady E.; Yeung, David T.

    2014-01-01

    The currently fielded pre-hospital therapeutic regimen for the treatment of organophosphorus (OP) poisoning in the United States (U.S.) is the administration of atropine in combination with an oxime antidote (2-PAM Cl) to reactivate inhibited acetylcholinesterase (AChE). Depending on clinical symptoms, an anticonvulsant, e.g., diazepam, may also be administered. Unfortunately, 2-PAM Cl does not offer sufficient protection across the range of OP threat agents, and there is some question as to whether it is the most effective oxime compound available. The objective of the present study is to identify an oxime antidote, under standardized and comparable conditions, that offers protection at the FDA approved human equivalent dose (HED) of 2-PAM Cl against tabun (GA), sarin (GB), soman (GD), cyclosarin (GF), and VX, and the pesticides paraoxon, chlorpyrifos oxon, and phorate oxon. Male Hartley guinea pigs were subcutaneously challenged with a lethal level of OP and treated at approximately 1 min post challenge with atropine followed by equimolar oxime therapy (2-PAM Cl, HI-6 DMS, obidoxime Cl2, TMB-4, MMB4-DMS, HLö-7 DMS, MINA, and RS194B) or therapeutic-index (TI) level therapy (HI-6 DMS, MMB4-DMS, MINA, and RS194B). Clinical signs of toxicity were observed for 24 hours post challenge and blood cholinesterase [AChE and butyrylcholinesterase (BChE)] activity was analyzed utilizing a modified Ellman’s method. When the oxime is standardized against the HED of 2-PAM Cl for guinea pigs, the evidence from clinical observations, lethality, quality of life (QOL) scores, and cholinesterase reactivation rates across all OPs indicated that MMB4 DMS and HLö-7 DMS were the two most consistently efficacious oximes. PMID:25448441

  2. Comparative genome analysis of Lactobacillus plantarum GB-LP3 provides candidates of survival-related genetic factors.

    PubMed

    Jeon, Soomin; Jung, Jaehoon; Kim, Kwondo; Yoo, DongAhn; Lee, Chanho; Kang, Jungsun; Cho, Kyungjin; Kang, Dae-Kyung; Kwak, Woori; Yoon, Sook Hee; Kim, Heebal; Cho, Seoae

    2017-09-01

    Lactobacillus plantarum is found in various environmental niches such as in the gastrointestinal tract of an animal host or a fermented food. This species isolated from a certain environment is known to possess a variety of properties according to inhabited environment's adaptation. However, a causal relationship of a genetic factor and phenotype affected by a specific environment has not been systematically comprehended. L. plantarum GB-LP3 strain was isolated from Korean traditional fermented vegetable and the whole genome of GB-LP3 was sequenced. Comparative genome analysis of GB-LP3, with other 14 L. plantarum strains, was conducted. In addition, genomic island regions were investigated. The assembled whole GB-LP3 genome contained a single circular chromosome of 3,206,111bp with the GC content of 44.7%. In the phylogenetic tree analysis, GB-LP3 was in the closest distance from ZJ316. The genomes of GB-LP3 and ZJ316 have the high level of synteny. Functional genes that are related to prophage, bacteriocin, and quorum sensing were found through comparative genomic analysis with ZJ316 and investigation of genomic islands. dN/dS analysis identified that the gene coding for phosphonate ABC transporter ATP-binding protein is evolutionarily accelerated in GB-LP3. Our study found that potential candidate genes that are affected by environmental adaptation in Korea traditional fermented vegetable. Copyright © 2017. Published by Elsevier B.V.

  3. The fusion loops and membrane proximal region of Epstein-Barr virus glycoprotein B (gB) can function in the context of herpes simplex virus 1 gB when substituted individually but not in combination.

    PubMed

    Zago, Anna; Connolly, Sarah A; Spear, Patricia G; Longnecker, Richard

    2013-01-01

    Among the herpesvirus glycoprotein B (gB) fusion proteins, the hydrophobic content of fusion loops and membrane proximal regions (MPRs) are inversely correlated with each other. We examined the functional importance of the hydrophobicity of these regions by replacing them in herpes simplex virus type 1 gB with corresponding regions from Epstein-Barr virus gB. We show that fusion activity is dependent on the structural context in which the specific loops and MPR sequences exist, rather than a simple hydrophobic relationship. Copyright © 2012 Elsevier B.V. All rights reserved.

  4. Concise and Efficient Fluorescent Probe via an Intromolecular Charge Transfer for the Chemical Warfare Agent Mimic Diethylchlorophosphate Vapor Detection.

    PubMed

    Yao, Junjun; Fu, Yanyan; Xu, Wei; Fan, Tianchi; Gao, Yixun; He, Qingguo; Zhu, Defeng; Cao, Huimin; Cheng, Jiangong

    2016-02-16

    Sarin, used as chemical warfare agents (CWAs) for terrorist attacks, can induce a number of virulent effects. Therefore, countermeasures which could realize robust and convenient detection of sarin are in exigent need. A concise charge-transfer colorimetric and fluorescent probe (4-(6-(tert-butyl)pyridine-2-yl)-N,N-diphenylaniline, TBPY-TPA) that could be capable of real-time and on-site monitoring of DCP vapor was reported in this contribution. Upon contact with DCP, the emission band red-shifted from 410 to 522 nm upon exposure to DCP vapor. And the quenching rate of TBPY-TPA reached up to 98% within 25 s. Chemical substances such as acetic acid (HAc), dimethyl methylphosphonate (DMMP), pinacolyl methylphosphonate (PAMP), and triethyl phosphate (TEP) do not interfere with the detection. A detection limit for DCP down to 2.6 ppb level is remarkably achieved which is below the Immediately Dangerous to Life or Health concentration. NMR data suggested that a transformation of the pyridine group into pyridinium salt via a cascade reaction is responsible for the sensing process which induced the dramatic fluorescent red shift. All of these data suggest TBPY-TPA is a promising fluorescent sensor for a rapid, simple, and low-cost method for DCP detection, which could be easy to prepare as a portable chemosensor kit for its practical application in real-time and on-site monitoring.

  5. STIMULUS: End-System Network Interface Controller for 100 Gb/s Wide Area Networks

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Zarkesh-Ha, Payman

    2014-09-12

    The main goal of this research grant is to develop a system-level solution leveraging novel technologies that enable network communications at 100 Gb/s or beyond. University of New Mexico in collaboration with Acadia Optronics LLC has been working on this project to develop the 100 Gb/s Network Interface Controller (NIC) under this Department of Energy (DOE) grant.

  6. Comparison of High Performance Network Options: EDR InfiniBand vs.100Gb RDMA Capable Ethernet

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Kachelmeier, Luke Anthony; Van Wig, Faith Virginia; Erickson, Kari Natania

    These are the slides for a presentation at the HPC Mini Showcase. This is a comparison of two different high performance network options: EDR InfiniBand and 100Gb RDMA capable ethernet. The conclusion of this comparison is the following: there is good potential, as shown with the direct results; 100Gb technology is too new and not standardized, thus deployment effort is complex for both options; different companies are not necessarily compatible; if you want 100Gb/s, you must get it all from one place.

  7. Catch the A-Train from the NASA GIBS/Worldview Platform

    NASA Astrophysics Data System (ADS)

    Schmaltz, J. E.; Alarcon, C.; Baynes, K.; Boller, R. A.; Cechini, M. F.; De Cesare, C.; De Luca, A. P.; Gunnoe, T.; King, B. A.; King, J.; Pressley, N. N.; Roberts, J. T.; Rodriguez, J.; Thompson, C. K.; Wong, M. M.

    2016-12-01

    The satellites and instruments of the Afternoon Train are providing an unprecedented combination of nearly simultaneous measurements. One of the challenges for researchers and applications users is to sift through these combinations to find particular sets of data that correspond to their interests. Using visualization of the data is one way to explore these combinations. NASA's Worldview tool is designed to do just that - to interactively browse full-resolution satellite imagery. Worldview (https://worldview.earthdata.nasa.gov/) is web-based and developed using open libraries and standards (OpenLayers, JavaScript, CSS, HTML) for cross-platform compatibility. It addresses growing user demands for access to full-resolution imagery by providing a responsive, interactive interface with global coverage and no artificial boundaries. In addition to science data imagery, Worldview provides ancillary datasets such as coastlines and borders, socio-economic layers, and satellite orbit tracks. Worldview interacts with the Earthdata Search Client to provide download of the data files associated with the imagery being viewed. The imagery used by Worldview is provided NASA's Global Imagery Browse Services (GIBS - https://earthdata.nasa.gov/gibs) which provide highly responsive, highly scalable imagery services. Requests are made via the OGC Web Map Tile Service (WMTS) standard. In addition to Worldview, other clients can be developed using a variety of web-based libraries, desktop and mobile app libraries, and GDAL script-based access. GIBS currently includes more than 106 science data sets from seven instruments aboard three of the A-Train satellites and new data sets are being added as part of the President's Big Earth Data Initiative (BEDI). Efforts are underway to include new imagery types, such as vectors and curtains, into Worldview/GIBS which will be used to visualize additional A-Train science parameters.

  8. NASA GIBS & Worldview - Lesson Ready Visualizations

    NASA Astrophysics Data System (ADS)

    Cechini, M. F.; Boller, R. A.; Baynes, K.; Gunnoe, T.; Wong, M. M.; Schmaltz, J. E.; De Luca, A. P.; King, J.; Roberts, J. T.; Rodriguez, J.; Thompson, C. K.; Alarcon, C.; De Cesare, C.; Pressley, N. N.

    2016-12-01

    For more than 20 years, the NASA Earth Observing System (EOS) has operated dozens of remote sensing satellites collecting 14 Petabytes of data that span thousands of science parameters. Within these observations are keys the Earth Scientists have used to unlock many things that we understand about our planet. Also contained within these observations are a myriad of opportunities for learning and education. The trick is making them accessible to educators and students in convenient and simple ways so that effort can be spent on lesson enrichment and not overcoming technical hurdles. The NASA Global Imagery Browse Services (GIBS) system and NASA Worldview website provide a unique view into EOS data through daily full resolution visualizations of hundreds of earth science parameters. For many of these parameters, visualizations are available within hours of acquisition from the satellite. For others, visualizations are available for the entire mission of the satellite. Accompanying the visualizations are visual aids such as color legends, place names, and orbit tracks. By using these visualizations, educators and students can observe natural phenomena that enrich a scientific education. This presentation will provide an overview of the visualizations available in NASA GIBS and Worldview and how they are accessed. We will also provide real-world examples of how the visualizations have been used in educational settings including planetariums, visitor centers, hack-a-thons, and public organizations.

  9. Compact and high-sensitivity 100-Gb/s (4 × 25 Gb/s) APD-ROSA with a LAN-WDM PLC demultiplexer.

    PubMed

    Yoshimatsu, Toshihide; Nada, Masahiro; Oguma, Manabu; Yokoyama, Haruki; Ohno, Tetsuichiro; Doi, Yoshiyuki; Ogawa, Ikuo; Takahashi, Hiroshi; Yoshida, Eiji

    2012-12-10

    We demonstrate an integrated 100 GbE receiver optical sub-assembly (ROSA) that incorporates a monolithic four-channel avalanche photodiode (APD) array and a planer lightwave circuit (PLC) based LAN-WDM demultiplexer. A record minimum receiver sensitivity of -20 dBm and 50-km error-free SMF transmission without an optical amplifier have been achieved.

  10. Nano-LC-MS/MS for Quantification of Lyso-Gb3 and Its Analogues Reveals a Useful Biomarker for Fabry Disease

    PubMed Central

    Sueoka, Hideaki; Ichihara, Junji; Tsukimura, Takahiro; Togawa, Tadayasu; Sakuraba, Hitoshi

    2015-01-01

    Biomarkers useful for diagnosis and evaluation of treatment for patients with Fabry disease are urgently needed. Recently, plasma globotriaosylsphingosine (lyso-Gb3) and lyso-Gb3-related analogues have attracted attention as promising biomarkers of Fabry disease. However, the plasma concentrations of lyso-Gb3 and its analogues are extremely low or below the detection limits in some Fabry patients as well as in healthy subjects. In this paper, we introduce the novel application of a nano-liquid chromatography-tandem mass spectrometry (nano-LC-MS/MS) system to the measurement of lyso-Gb3 and its analogues in plasma. Nano-LC-MS/MS requires smaller amounts of samples and is more sensitive than conventional techniques. Using this method, we measured the plasma concentrations of lyso-Gb3 and its analogues in 40 healthy subjects, 5 functional variants (males with E66Q), and various Fabry patients (9 classic Fabry males/9 mutations; 7 later-onset Fabry males/5 mutations; and 10 Fabry females/9 mutations). The results revealed that the mean lyso-Gb3 and lyso-Gb3(-2) concentrations in all the Fabry patient subgroups were statistically higher, especially in the classic Fabry males, than those in the functional variants and healthy subjects. The plasma concentrations of lyso-Gb3 and its analogues in healthy subjects, functional variants, and some Fabry patients with specific mutations (R112H and M296I) that cannot be established by conventional techniques were successfully determined by means of nano-LC-MS/MS. The lyso-Gb3 and lyso-Gb3(-2) concentrations in male patients with these mutations were lower than those in most Fabry patients having other mutations, but higher than those in the functional variants and healthy subjects. This new method is expected to be useful for sensitive determination of the plasma concentrations of lyso-Gb3 and its analogues. This study also revealed that not only lyso-Gb3 but also lyso-Gb3(-2) in plasma is a useful biomarker for the diagnosis of

  11. Development of Novel Decontamination Techniques for Chemical Agents (GB, VX, HD) Contaminated Facilities. Phase I. Identification and Evaluation of Novel Decontamination Concepts. Volume 1

    DTIC Science & Technology

    1983-02-01

    ACTIVITY . . . . . . 4 3.0 PHASE I RESULTS . . . . . . . . . . . . . . . . . . . . . . 5 3.1 RESOURCE REVIEW . . . . . . . . . . . . . 5 ŗ.1.1 Surveys...commonly known as mustard, is a vesicant while VX and GB are organophosphorus compounds which act as anticholinesterases . HD Cl-( CH)-S-(CH- );cI 0...order to satisfy the task objective, work during this phase . consisted of three principal interrelated activities . The goal of the first activity was

  12. Robustness of 40 Gb/s ASK modulation formats in the practical system infrastructure

    NASA Astrophysics Data System (ADS)

    Pincemin, Erwan; Tan, Antoine; Bezard, Aude; Tonello, Alessandro; Wabnitz, Stefano; Ania-Castañòn, Juan-Diego; Turitsyn, Sergei

    2006-12-01

    In this work, we theoretically and experimentally analyzed the resilience of 40 Gb/s amplitude shift keying modulation formats to transmission impairments in standard single-mode fiber lines as well as to optical filtering introduced by the optical add/drop multiplexer cascade. Our study is a pre-requisite to assess the implementation of cost-effective 40 Gb/s modulation technology in next generation high bit-rate robust optical transport networks.

  13. Translation of Toxicity Data into CW Agent Toxicity Estimates

    DTIC Science & Technology

    2003-07-01

    UNLIMITED UNCLASSIFIED/UNLIMITEDPrepared by Douglas R. Sommerville, PE US Army ECBC, APG, MD Dependence of Toxic Effect on Exposure Time Inhalation (IH...to longer exposure durations. Toxicity estimates for exposure durations ranging from 2 to 360 minutes have been derived for six agents (GA, GB, GD...individuals having effects greater in severity than the defining effect of the ECTYY Cn T = k Toxic load equation 5 6 Edgewood Chemical Biological Center

  14. Demonstration of 20Gb/s polarization-insensitive wavelength switching system for high-speed free-space optical network

    NASA Astrophysics Data System (ADS)

    Qian, Feng-chen; Ye, Ya-lin; Wen, Yu; Duan, Tao; Feng, Huan

    2015-10-01

    A 20Gb/s polarization-insensitive all-optical wavelength switching system for high-speed free-space optical communication (FSO) network is experimentally demonstrated All-optical wavelength conversion (AOWC) is implemented using four-wave mixing (FWM) by highly-nonlinear fiber (HNLF). In the experimental setup, a simple actively mode-locked fiber ring laser (AML-FRL) with repetition frequency from 1 to 15 GHz is used to generate eight 2.5Gb/s tributary signals, which are multiplexed into one 20Gb/s optical data stream. At the receiver, the 20 Gb/s OTDM data stream is demultiplexed down to 2.5 Gb/s via a polarization-insensitive FWM scheme. The whole space communication distance is over 10 meters in building hallway. The experimental results show that this system can stably run over 24 hours at 10-9 BER level, thus the proposed architecture can work at higher rate with wavelength-division multiplexing (WDM) and high order modulation schemes.

  15. Improved Growth and Metabolite Accumulation in Codonopsis pilosula (Franch.) Nannf. by Inoculation of Bacillus amyloliquefaciens GB03.

    PubMed

    Zhao, Qi; Wu, Yong-Na; Fan, Qin; Han, Qing-Qing; Paré, Paul W; Xu, Rui; Wang, Yin-Quan; Wang, Suo-Min; Zhang, Jin-Lin

    2016-11-02

    Codonopsis pilosula (Franch.) Nannf. is a traditional Chinese herbal medicinal plant and a low-cost succedaneum for Panax ginseng and contains various bioactivity components. In this work, we first evaluated the effects of the inoculation of the plant growth-promoting rhizobacteria Bacillus amyloliquefaciens strain GB03 on growth and metabolite accumulation of C. pilosula. The results demonstrated that application of B. amyloliquefaciens GB03 significantly improved the growth of C. pilosula compared to DH5α, Luria broth medium, and water treatment, respectively. On the other hand, we observed that the content of lobetyolin, one of the most important secondary metabolites in C. pilosula, was obviously improved by inoculation of GB03 and almost reached twice that compared to the other three treatments. In addition, some amino acids of roots were elevated by GB03, although not significantly. In conclusion, B. amyloliquefaciens GB03 could induce positive effects on the growth and further stimulate accumulation of secondary metabolites in C. pilosula.

  16. Development and Structural Modifications of Cholinesterase Reactivators against Chemical Warfare Agents in Last Decade: A Review.

    PubMed

    Sharma, Rahul; Gupta, Bhanushree; Singh, Namrata; Acharya, J R; Musilek, Kamil; Kuca, Kamil; Ghosh, Kallol Kumar

    2015-01-01

    Organophosphate (OP) pesticides and nerve agents are responsible for suicidal and accidental poisonings. The acute toxicity of nerve agents leads to progressive inhibition of the enzyme acetylcholinesterase (AChE) by phosphylation of serine residue at the active site of gorge. The recent massive destruction of Syrian civilians by nerve gas sarin, has again renewed the research attention of global science fraternity towards nerve agents, their mode of action and most prominently their therapeutic treatment. This review is principally focused on nerve agent intoxication. The common approach to deal with OP-intoxication is, application of antimuscarinic drug (atropine), anticonvulsant drug (diazepam) and clinically used oximes (pralidoxime, trimedoxime, obidoxime and asoxime). However, the existing therapeutic approach is arguable and has several failings to cure all kinds of nerve agent poisonings. Considering this issue, numerous oximes have been synthesized and screened through various in-vitro and in-vivo studies in last decade to overcome the downsides. At present, only a few oximes (bis pyridinum-oximes) exhibit sound efficacy against selective OPs. In spite of extensive efforts, till date no oxime is available as a universal antidote against all the classes of OPs. This review is centered on the recent developments and structural modification of AChE reactivators against nerve agent toxicity. In particular, a deeper look has been taken into chemical modifications of the reactivators by incorporation of different structural moieties targeted towards the increased reactivation affinity and improved blood brain barrier (BBB) penetration.

  17. [The VR, the Russian version of the nerve agent VX].

    PubMed

    Cuquel, A-C; Dorandeu, F; Ceppa, F; Renard, C; Burnat, P

    2015-05-01

    A product of the arms race during the Cold War, the Russian VX, or VR, is an organophosphorus compound that is a structural isomer of the western VX compound (or A4), with which it shares a very high toxicity. It is much less studied and known than VX because the knowledge of its existence is relatively recent. A very low volatility and high resistance in the environment make it a persistent agent. Poisoning occurs mainly following penetration through skin and mucosa but vapour inhalation is a credible risk in some circumstances. The clinical presentation may be differed by several hours and despite the absence of signs and symptoms, the casualty should not be considered as contamination or intoxication-free. This agent has a long residence time in blood, a characteristics that clearly differentiates it from other compounds such as sarin. The protocols for antidote administration may thus have to be changed accordingly. The fact that VR poisoned individuals will less respond to the current oxime therapy used in France, the 2-PAM and that VR represents a higher threat than VX, being probably possessed by some proliferating states, justify the interest for this toxic product. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

  18. Analysis of canine herpesvirus gB, gC and gD expressed by a recombinant vaccinia virus.

    PubMed

    Xuan, X; Kojima, A; Murata, T; Mikami, T; Otsuka, H

    1997-01-01

    The genes encoding the canine herpesvirus (CHV) glycoprotein B (gB), gC and gD homologues have been reported already. However, products of these genes have not been identified yet. Previously, we have identified three CHV glycoproteins, gp 145/112, gp80 and gp47 using a panel of monoclonal antibodies (MAbs). To determine which CHV glycoprotein corresponds to gB, gC or gD, the putative genes of gB, gC, and gD of CHV were inserted into the thymidine kinase gene of vaccinia virus LC16mO strain under the control of the early-late promoter for the vaccinia virus 7.5-kilodalton polypeptide. We demonstrated here that gp145/112, gp80 and gp47 were the translation products of the CHV gB, gC and gD genes, respectively. The antigenic authenticity of recombinant gB, gC and gD were confirmed by a panel of MAbs specific for each glycoprotein produced in CHV-infected cells. Immunization of mice with these recombinants produced high titers of neutralizing antibodies against CHV. These results suggest that recombinant vaccinia viruses expressing CHV gB, gC and gD may be useful to develop a vaccine to control CHV infection.

  19. 10-Gb/s direct modulation of polymer-based tunable external cavity lasers.

    PubMed

    Choi, Byung-Seok; Oh, Su Hwan; Kim, Ki Soo; Yoon, Ki-Hong; Kim, Hyun Soo; Park, Mi-Ran; Jeong, Jong Sool; Kwon, O-Kyun; Seo, Jun-Kyu; Lee, Hak-Kyu; Chung, Yun C

    2012-08-27

    We demonstrate a directly-modulated 10-Gb/s tunable external cavity laser (ECL) fabricated by using a polymer Bragg reflector and a high-speed superluminescent diode (SLD). The tuning range and output power of this ECL are measured to be >11 nm and 2.6 mW (@ 100 mA), respectively. We directly modulate this laser at 10 Gb/s and transmit the modulated signal over 20 km of standard single-mode fiber. The power penalty is measured to be <2.8 dB at the bit-error rate (BER) of 10(-10).

  20. Research on Coordinate Transformation Method of Gb-Sar Image Supported by 3d Laser Scanning Technology

    NASA Astrophysics Data System (ADS)

    Wang, P.; Xing, C.

    2018-04-01

    In the image plane of GB-SAR, identification of deformation distribution is usually carried out by artificial interpretation. This method requires analysts to have adequate experience of radar imaging and target recognition, otherwise it can easily cause false recognition of deformation target or region. Therefore, it is very meaningful to connect two-dimensional (2D) plane coordinate system with the common three-dimensional (3D) terrain coordinate system. To improve the global accuracy and reliability of the transformation from 2D coordinates of GB-SAR images to local 3D coordinates, and overcome the limitation of traditional similarity transformation parameter estimation method, 3D laser scanning data is used to assist the transformation of GB-SAR image coordinates. A straight line fitting method for calculating horizontal angle was proposed in this paper. After projection into a consistent imaging plane, we can calculate horizontal rotation angle by using the linear characteristics of the structure in radar image and the 3D coordinate system. Aided by external elevation information by 3D laser scanning technology, we completed the matching of point clouds and pixels on the projection plane according to the geometric projection principle of GB-SAR imaging realizing the transformation calculation of GB-SAR image coordinates to local 3D coordinates. Finally, the effectiveness of the method is verified by the GB-SAR deformation monitoring experiment on the high slope of Geheyan dam.

  1. Identification of a Third Mn(II) Oxidase Enzyme in Pseudomonas putida GB-1

    PubMed Central

    Smesrud, Logan; Tebo, Bradley M.

    2016-01-01

    ABSTRACT The oxidation of soluble Mn(II) to insoluble Mn(IV) is a widespread bacterial activity found in a diverse array of microbes. In the Mn(II)-oxidizing bacterium Pseudomonas putida GB-1, two Mn(II) oxidase genes, named mnxG and mcoA, were previously identified; each encodes a multicopper oxidase (MCO)-type enzyme. Expression of these two genes is positively regulated by the response regulator MnxR. Preliminary investigation into putative additional regulatory pathways suggested that the flagellar regulators FleN and FleQ also regulate Mn(II) oxidase activity; however, it also revealed the presence of a third, previously uncharacterized Mn(II) oxidase activity in P. putida GB-1. A strain from which both of the Mn(II) oxidase genes and fleQ were deleted exhibited low levels of Mn(II) oxidase activity. The enzyme responsible was genetically and biochemically identified as an animal heme peroxidase (AHP) with domain and sequence similarity to the previously identified Mn(II) oxidase MopA. In the ΔfleQ strain, P. putida GB-1 MopA is overexpressed and secreted from the cell, where it actively oxidizes Mn. Thus, deletion of fleQ unmasked a third Mn(II) oxidase activity in this strain. These results provide an example of an Mn(II)-oxidizing bacterium utilizing both MCO and AHP enzymes. IMPORTANCE The identity of the Mn(II) oxidase enzyme in Pseudomonas putida GB-1 has been a long-standing question in the field of bacterial Mn(II) oxidation. In the current work, we demonstrate that P. putida GB-1 employs both the multicopper oxidase- and animal heme peroxidase-mediated pathways for the oxidation of Mn(II), rendering this model organism relevant to the study of both types of Mn(II) oxidase enzymes. The presence of three oxidase enzymes in P. putida GB-1 deepens the mystery of why microorganisms oxidize Mn(II) while providing the field with the tools necessary to address this question. The initial identification of MopA as a Mn(II) oxidase in this strain required the

  2. High-speed 850-nm VCSELs for 40-Gb/s transmission

    NASA Astrophysics Data System (ADS)

    Gustavsson, Johan; Westbergh, Petter; Szczerba, Krzysztof; Haglund, Åsa; Larsson, Anders; Karlsson, Magnus; Andrekson, Peter; Hopfer, Friedhelm; Fiol, Gerrit; Bimberg, Dieter; Olsson, Bengt-Erik; Kristiansson, A.; Healy, Sorcha; O'Reilly, Eoin; Joel, Andrew

    2010-04-01

    We have explored the possibility to extend the data transmission rate for standard 850-nm GaAs-based VCSELs beyond the 10 Gbit/s limit of today's commercially available directly-modulated devices. By sophisticated tailoring of the design for high-speed performance we demonstrate that 10 Gb/s is far from the upper limit. For example, the thermal conductivity of the bottom mirror is improved by the use of binary compounds, and the electrical parasitics are kept at a minimum by incorporating a large diameter double layered oxide aperture in the design. We also show that the intrinsic high speed performance is significantly improved by replacing the traditional GaAs QWs with strained InGaAs QWs in the active region. The best overall performance is achieved for a device with a 9 μm diameter oxide aperture, having in a threshold current of 0.6 mA, a maximum output power of 9 mW, a thermal resistance of 1.9 °C/mW, and a differential resistance of 80 Ω. The measured 3dB bandwidth exceeds 20 GHz, and we experimentally demonstrate that the device is capable of error-free transmission (BER<10-12) under direct modulation at a record-high bit-rate of 32 Gb/s over 50 m of OM3 fiber at room temperature, and at 25 Gb/s over 100 m of OM3 fiber at 85 °C. We also demonstrate transmission at 40 Gb/s over 200 m of OM3+ fiber at room temperature using a subcarrier multiplexing scheme with a spectrally efficient 16 QAM modulation format. All transmission results were obtained with the VCSEL biased at current densities between 11-14 kA/cm2, which is close to the 10 kA/cm2 industry benchmark for reliability. Finally, we show that by a further reduction of the oxide capacitance and by reducing the photon lifetime using a shallow surface etch, a record bandwidth of 23 GHz for 850 nm VCSELs can be reached.

  3. A receptor-like kinase gene (GbRLK) from Gossypium barbadense enhances salinity and drought-stress tolerance in Arabidopsis

    PubMed Central

    2013-01-01

    Background Cotton (Gossypium spp.) is widely cultivated due to the important economic value of its fiber. However, extreme environmental degradation impedes cotton growth and production. Receptor-like kinase (RLK) proteins play important roles in signal transduction and participate in a diverse range of processes in response to plant hormones and environmental cues. Here, we introduced an RLK gene (GbRLK) from cotton into Arabidopsis and investigated its role in imparting abiotic stress tolerance. Results GbRLK transcription was induced by exogenously supplied abscisic acid (ABA), salicylic acid, methyl jasmonate, mock drought conditions and high salinity. We cloned the promoter sequence of this gene via self-formed adaptor PCR. Sequence analysis revealed that the promoter region contains many cis-acting stress-responsive elements such as ABRE, W-Box, MYB-core, W-Box core, TCA-element and others. We constructed a vector containing a 1,890-bp sequence in the 5′ region upstream of the initiation codon of this promoter and transformed it into Arabidopsis thaliana. GUS histochemical staining analysis showed that GbRLK was expressed mainly in leaf veins, petioles and roots of transgenic Arabidopsis, but not in the cotyledons or root hairs. GbRLK promoter activity was induced by ABA, PEG, NaCl and Verticillium dahliae. Transgenic Arabidopsis with constitutive overexpression of GbRLK exhibited a reduced rate of water loss in leaves in vitro, along with improved salinity and drought tolerance and increased sensitivity to ABA compared with non-transgenic Col-0 Arabidopsis. Expression analysis of stress-responsive genes in GbRLK Arabidopsis revealed that there was increased expression of genes involved in the ABA-dependent signaling pathway (AtRD20, AtRD22 and AtRD26) and antioxidant genes (AtCAT1, AtCCS, AtCSD2 and AtCSD1) but not ion transporter genes (AtNHX1, AtSOS1). Conclusions GbRLK is involved in the drought and high salinity stresses pathway by activating or

  4. A receptor-like kinase gene (GbRLK) from Gossypium barbadense enhances salinity and drought-stress tolerance in Arabidopsis.

    PubMed

    Zhao, Jun; Gao, Yulong; Zhang, Zhiyuan; Chen, Tianzi; Guo, Wangzhen; Zhang, Tianzhen

    2013-08-06

    Cotton (Gossypium spp.) is widely cultivated due to the important economic value of its fiber. However, extreme environmental degradation impedes cotton growth and production. Receptor-like kinase (RLK) proteins play important roles in signal transduction and participate in a diverse range of processes in response to plant hormones and environmental cues. Here, we introduced an RLK gene (GbRLK) from cotton into Arabidopsis and investigated its role in imparting abiotic stress tolerance. GbRLK transcription was induced by exogenously supplied abscisic acid (ABA), salicylic acid, methyl jasmonate, mock drought conditions and high salinity. We cloned the promoter sequence of this gene via self-formed adaptor PCR. Sequence analysis revealed that the promoter region contains many cis-acting stress-responsive elements such as ABRE, W-Box, MYB-core, W-Box core, TCA-element and others. We constructed a vector containing a 1,890-bp sequence in the 5' region upstream of the initiation codon of this promoter and transformed it into Arabidopsis thaliana. GUS histochemical staining analysis showed that GbRLK was expressed mainly in leaf veins, petioles and roots of transgenic Arabidopsis, but not in the cotyledons or root hairs. GbRLK promoter activity was induced by ABA, PEG, NaCl and Verticillium dahliae. Transgenic Arabidopsis with constitutive overexpression of GbRLK exhibited a reduced rate of water loss in leaves in vitro, along with improved salinity and drought tolerance and increased sensitivity to ABA compared with non-transgenic Col-0 Arabidopsis. Expression analysis of stress-responsive genes in GbRLK Arabidopsis revealed that there was increased expression of genes involved in the ABA-dependent signaling pathway (AtRD20, AtRD22 and AtRD26) and antioxidant genes (AtCAT1, AtCCS, AtCSD2 and AtCSD1) but not ion transporter genes (AtNHX1, AtSOS1). GbRLK is involved in the drought and high salinity stresses pathway by activating or participating in the ABA signaling

  5. A highly stable minimally processed plant-derived recombinant acetylcholinesterase for nerve agent detection in adverse conditions

    PubMed Central

    Rosenberg, Yvonne J.; Walker, Jeremy; Jiang, Xiaoming; Donahue, Scott; Robosky, Jason; Sack, Markus; Lees, Jonathan; Urban, Lori

    2015-01-01

    Although recent innovations in transient plant systems have enabled gram quantities of proteins in 1–2 weeks, very few have been translated into applications due to technical challenges and high downstream processing costs. Here we report high-level production, using a Nicotiana benthamiana/p19 system, of an engineered recombinant human acetylcholinesterase (rAChE) that is highly stable in a minimally processed leaf extract. Lyophylized clarified extracts withstand prolonged storage at 70 °C and, upon reconstitution, can be used in several devices to detect organophosphate (OP) nerve agents and pesticides on surfaces ranging from 0 °C to 50 °C. The recent use of sarin in Syria highlights the urgent need for nerve agent detection and countermeasures necessary for preparedness and emergency responses. Bypassing cumbersome and expensive downstream processes has enabled us to fully exploit the speed, low cost and scalability of transient production systems resulting in the first successful implementation of plant-produced rAChE into a commercial biotechnology product. PMID:26268538

  6. A highly stable minimally processed plant-derived recombinant acetylcholinesterase for nerve agent detection in adverse conditions.

    PubMed

    Rosenberg, Yvonne J; Walker, Jeremy; Jiang, Xiaoming; Donahue, Scott; Robosky, Jason; Sack, Markus; Lees, Jonathan; Urban, Lori

    2015-08-13

    Although recent innovations in transient plant systems have enabled gram quantities of proteins in 1-2 weeks, very few have been translated into applications due to technical challenges and high downstream processing costs. Here we report high-level production, using a Nicotiana benthamiana/p19 system, of an engineered recombinant human acetylcholinesterase (rAChE) that is highly stable in a minimally processed leaf extract. Lyophylized clarified extracts withstand prolonged storage at 70 °C and, upon reconstitution, can be used in several devices to detect organophosphate (OP) nerve agents and pesticides on surfaces ranging from 0 °C to 50 °C. The recent use of sarin in Syria highlights the urgent need for nerve agent detection and countermeasures necessary for preparedness and emergency responses. Bypassing cumbersome and expensive downstream processes has enabled us to fully exploit the speed, low cost and scalability of transient production systems resulting in the first successful implementation of plant-produced rAChE into a commercial biotechnology product.

  7. 133. NORTH PLANT SCRUBBER SYSTEM FOR GB MANUFACTURING PLANT. VIEW ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    133. NORTH PLANT SCRUBBER SYSTEM FOR GB MANUFACTURING PLANT. VIEW TO WEST. - Rocky Mountain Arsenal, Bounded by Ninety-sixth Avenue & Fifty-sixth Avenue, Buckley Road, Quebec Street & Colorado Highway 2, Commerce City, Adams County, CO

  8. Global Imagery Browse Services (GIBS) - Rapidly Serving NASA Imagery for Applications and Science Users

    NASA Astrophysics Data System (ADS)

    Schmaltz, J. E.; Ilavajhala, S.; Plesea, L.; Hall, J. R.; Boller, R. A.; Chang, G.; Sadaqathullah, S.; Kim, R.; Murphy, K. J.; Thompson, C. K.

    2012-12-01

    Expedited processing of imagery from NASA satellites for near-real time use by non-science applications users has a long history, especially since the beginning of the Terra and Aqua missions. Several years ago, the Land Atmosphere Near-real-time Capability for EOS (LANCE) was created to greatly expand the range of near-real time data products from a variety of Earth Observing System (EOS) instruments. NASA's Earth Observing System Data and Information System (EOSDIS) began exploring methods to distribute these data as imagery in an intuitive, geo-referenced format, which would be available within three hours of acquisition. Toward this end, EOSDIS has developed the Global Imagery Browse Services (GIBS, http://earthdata.nasa.gov/gibs) to provide highly responsive, scalable, and expandable imagery services. The baseline technology chosen for GIBS was a Tiled Web Mapping Service (TWMS) developed at the Jet Propulsion Laboratory. Using this, global images and mosaics are divided into tiles with fixed bounding boxes for a pyramid of fixed resolutions. Initially, the satellite imagery is created at the existing data systems for each sensor, ensuring the oversight of those most knowledgeable about the science. There, the satellite data is geolocated and converted to an image format such as JPEG, TIFF, or PNG. The GIBS ingest server retrieves imagery from the various data systems and converts them into image tiles, which are stored in a highly-optimized raster format named Meta Raster Format (MRF). The image tiles are then served to users via HTTP by means of an Apache module. Services are available for the entire globe (lat-long projection) and for both polar regions (polar stereographic projection). Requests to the services can be made with the non-standard, but widely known, TWMS format or via the well-known OGC Web Map Tile Service (WMTS) standard format. Standard OGC Web Map Service (WMS) access to the GIBS server is also available. In addition, users may request a

  9. Crystal Structures of Human Carboxylesterase 1 in Covalent Complexes with the Chemical Warfare Agents Soman and Tabun†,‡

    PubMed Central

    Fleming, Christopher D.; Edwards, Carol C.; Kirby, Stephen D.; Maxwell, Donald M.; Potter, Philip M.; Cerasoli, Douglas M.; Redinbo, Matthew R.

    2008-01-01

    The organophosphorus nerve agents sarin, soman, tabun, and VX exert their toxic effects by inhibiting the action of human acetylcholinesterase, a member of the serine hydrolase superfamily of enzymes. The current treatments for nerve agent exposure must be administered quickly to be effective and they often do not eliminate long-term toxic side effects associated with organophosphate poisoning. Thus, there is significant need for effective prophylactic methods to protect at-risk personnel from nerve agent exposure, and protein-based approaches have emerged as promising candidates. We present the 2.7 Å resolution crystal structures of the serine hydrolase human carboxylesterase 1 (hCE1), a broad-spectrum drug metabolism enzyme, in covalent acyl-enzyme intermediate complexes with the chemical weapons soman and tabun. The structures reveal that hCE1 binds stereoselectively to these nerve agents; for example, hCE1 appears to react preferentially with the 104-fold more lethal PS stereoisomer of soman relative to the PR form. In addition, structural features of the hCE1 active site indicate that the enzyme may be resistant to dead-end organophosphate aging reactions that permanently inactivate other serine hydrolases. Taken together, these data provide important structural details toward the goal of engineering hCE1 into an organophosphate hydrolase and protein-based therapeutic for nerve agent exposure. PMID:17407327

  10. Globotriaosylsphingosine (Lyso-Gb3) as a biomarker for cardiac variant (N215S) Fabry disease.

    PubMed

    Alharbi, Fahad J; Baig, Shanat; Auray-Blais, Christiane; Boutin, Michel; Ward, Douglas G; Wheeldon, Nigel; Steed, Rick; Dawson, Charlotte; Hughes, Derralynn; Geberhiwot, Tarekegn

    2018-03-01

    Fabry disease (FD) is a multi-systemic X-linked lysosomal disorder caused by the deficient activity of α-galactosidase-A enzyme, which leads to accumulation of glycosphingolipids in various body tissues. The N215S mutation is a known variant of FD, with a late onset cardiac phenotype. Consensus guidelines acknowledged the use of globotriaosylsphingosine (Lyso-Gb 3 ) as a diagnostic marker for classical FD but its utility for cardiac variant FD is not clear. We aim to characterize the clinical features and evaluate the diagnostic accuracy of plasma and urinary Lyso-Gb 3 levels in N215S cardiac variant FD patients. Thirty-four FD patients with the late-onset N215S cardiac variant mutation were enrolled along with 62 classical FD patients and 109 healthy controls. Plasma and urinary Lyso-Gb 3 and its analogues were analyzed by LC-MS/MS. Both FD males and females with N215S mutation showed Lyso-Gb 3 levels of (mean ± SEM) 9.7 ± 1.0 and 5.4 ± 0.8 nM, respectively. These levels were significantly higher than healthy control and lower than classical FD patients (p < 0.0001). Plasma Lyso-Gb 3 levels equal to or higher than 2.7 nM yielded a diagnostic sensitivity and specificity of 100% (AUC = 1, p < 0.0001). Cardiac involvement was frequent with 16/34 (47%) developing left ventricular hypertrophy. Three patients who underwent renal biopsy had the characteristic sphingolipid deposition in the podocytes while 6/19 (32%) had evidence of white matter changes or infarct on brain MRI. Taken together, cardiac variant N215S mutation is rather an attenuated form of classical FD. Plasma Lyso-Gb 3 is a diagnostic hallmark to differentiate N215S variant phenotype from subjects with no FD.

  11. Evaluation of the efficacy of a portable LIBS system for detection of CWA on surfaces.

    PubMed

    L'Hermite, D; Vors, E; Vercouter, T; Moutiers, G

    2016-05-01

    Laser-induced breakdown spectroscopy (LIBS) is a laser-based optical technique particularly suited for in situ surface analysis. A portable LIBS instrument was tested to detect surface chemical contamination by chemical warfare agents (CWAs). Test of detection of surface contamination was carried out in a toxlab facility with four CWAs, sarin (GB), lewisite (L1), mustard gas (HD), and VX, which were deposited on different substrates, wood, concrete, military green paint, gloves, and ceramic. The CWAs were detected by means of the detection of atomic markers (As, P, F, Cl, and S). The LIBS instrument can give a direct response in terms of detection thanks to an integrated interface for non-expert users or so called end-users. We have evaluated the capability of automatic detection of the selected CWAs. The sensitivity of our portable LIBS instrument was confirmed for the detection of a CWA at surface concentrations above 15 μg/cm(2). The simultaneous detection of two markers may lead to a decrease of the number of false positive.

  12. Monitoring of Diisopropyl Fluorophosphate Hydrolysis by Fluoride-Selective Polymeric Films Using Absorbance Spectroscopy

    PubMed Central

    Ramanathan, Madhumati; Wang, Lin; Wild, James R.; Meyeroff, Mark E.; Simonian, Aleksandr L.

    2012-01-01

    In this study, a novel system for the detection and quantification of organofluorophosphonates (OFP) has been developed by using an optical sensing polymeric membrane to detect the fluoride ions produced upon OFP hydrolysis. Diisopropyl fluorophosphate (DFP), a structural analogue of Type G Chemical Warfare Agents such as Sarin (GB) and Soman (GD), is used as the surrogate target analyte. An optical sensing fluoride-ion-selective polymeric film was formulated from plasticized PVC containing aluminum(III) octaethylporphyrin and ETH 7075 chromoionophore (Al[OEP]-ETH 7075). Selected formulations were used to detect the fluoride ions produced by the catalytic hydrolysis of DFP by the enzyme organophosphate hydrolase (OPH, EC 3.1.8.1). The changes in absorbance that corresponded to the deprotonated state of chromoionophore within the film results from simultaneous co-extraction of fluoride and protons as DFP hydrolysis takes place in the solution phase in contact with the film. The developed sensing system demonstrates excellent sensitivity for concentrations as low as 0.1 µM DFP. PMID:20441875

  13. 25 Gbps 850 nm photodiode for emerging 100 Gb ethernet applications

    NASA Astrophysics Data System (ADS)

    Joshi, Abhay; Rue, Jim; Becker, Don; Datta, Shubhashish; McFaul, Will

    2011-06-01

    The IEEE Std 802.3ba-2010 for 40 Gb and 100 Gb Ethernet was released in July, 2010. This standard will continue to evolve over the next several years. Two of the challenging transmit/receive architectures contained in this standard are the 100GBASE-LR4 (<10 km range) and 100GBASE-ER4 (<40 km range). Although presently envisioned for 1310 nm optical wavelengths, both of these 4 lane, 25.78 GBaud formats may be adopted for the impending 850 nm short reach optical backplane market, whose range is below 150 m. Driven by major computer server companies, such as IBM, HP and Oracle, the 850 nm Active Optical Cable (AOC) market is presently undergoing an increase of serial rates up to 25 Gbaud to enhance backplane interconnectivity. With AOCs up to 16 channels, the potential for up to 400 Gbps backhaul composite data rates will soon be possible. We report a 25 Gbps photodiode with quantum efficiency ~ 0.6 at 850 nm. This InGaAs/InP device was optimized for high quantum efficiency at 850 nm. When pigtailed with multimode fiber and integrated with an application-specific RF amplifier, the resultant photoreceiver will provide multiple functionalities for these 100 Gb Ethernet markets.

  14. 119. NORTH PLANT GB WAREHOUSE (BUILDING 1607), WITH DISCHARGED TON ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    119. NORTH PLANT GB WAREHOUSE (BUILDING 1607), WITH DISCHARGED TON CONTAINERS IN FOREGROUND. VIEW TO SOUTHEAST. - Rocky Mountain Arsenal, Bounded by Ninety-sixth Avenue & Fifty-sixth Avenue, Buckley Road, Quebec Street & Colorado Highway 2, Commerce City, Adams County, CO

  15. 10-m 9.51-Gb/s RGB laser diodes-based WDM underwater wireless optical communication.

    PubMed

    Kong, Meiwei; Lv, Weichao; Ali, Tariq; Sarwar, Rohail; Yu, Chuying; Qiu, Yang; Qu, Fengzhong; Xu, Zhiwei; Han, Jun; Xu, Jing

    2017-08-21

    The availability of the underwater wireless optical communication (UWOC) based on red (R), green (G) and blue (B) lights makes the realization of the RGB wavelength division multiplexing (WDM) UWOC system possible. By properly mixing RGB lights to form white light, the WDM UWOC system has prominent potentiality for simultaneous underwater illumination and high-speed communication. In this work, for the first time, we experimentally demonstrate a 9.51-Gb/s WDM UWOC system using a red-emitting laser diode (LD), a single-mode pigtailed green-emitting LD and a multi-mode pigtailed blue-emitting LD. By employing 32-quadrature amplitude modulation (QAM) orthogonal frequency division multiplexing (OFDM) modulation in the demonstration, the red-light, the green-light and the blue-light LDs successfully transmit signals with the data rates of 4.17 Gb/s, 4.17 Gb/s and 1.17 Gb/s, respectively, over a 10-m underwater channel. The corresponding bit error rates (BERs) are 2.2 × 10 -3 , 2.0 × 10 -3 and 2.3 × 10 -3 , respectively, which are below the forward error correction (FEC) threshold of 3.8 × 10 -3 .

  16. Hepatoprotective effect of manual acupuncture at acupoint GB34 against CCl4-induced chronic liver damage in rats

    PubMed Central

    Yim, Yun-Kyoung; Lee, Hyun; Hong, Kwon-Eui; Kim, Young-Il; Lee, Byung-Ryul; Kim, Tae-Han; Yi, Ji-Young

    2006-01-01

    AIM: To investigate the hepatoprotective effect of manual acupuncture at Yanglingquan (GB34) on CCl4-induced chronic liver damage in rats. METHODS: Rats were injected intraperitoneally with CCl4 (1 mL/kg) and treated with manual acupuncture using reinforcing manipulation techniques at left GB34 (Yanglingquan) 3 times a week for 10 wk. A non-acupoint in left gluteal area was selected as a sham point. To estimate the hepatoprotective effect of manual acupuncture at GB34, measurement of liver index, biochemical assays including serum ALT, AST, ALP and total cholesterol, histological analysis and blood cell counts were conducted. RESULTS: Manual acupuncture at GB34 reduced the liver index, serum ALT, AST, ALP and total cholesterol levels as compared with the control group and the sham acupuncture group. It also increased and normalized the populations of WBC and lymphocytes. CONCLUSION: Manual acupuncture with reinforcing manipulation techniques at left GB34 reduces liver toxicity, protects liver function and liver tissue, and normalizes immune activity in CCl4-intoxicated rats. PMID:16610030

  17. Experimental demonstration of free-space based 120 Gb/s reconfigurable card-to-card optical interconnects.

    PubMed

    Wang, Ke; Nirmalathas, Ampalavanapillai; Lim, Christina; Skafidas, Efstratios; Alameh, Kamal

    2014-10-01

    In this Letter, we propose and experimentally demonstrate a free-space based reconfigurable card-to-card optical interconnect architecture with 16-carrierless-amplitude-phase modulation. Experimental results show that up to 120 Gb/s (3×40  Gb/s) flexible interconnection can be achieved for up to 30 cm distance with a worst-case receiver sensitivity of -9.70  dBm.

  18. Acute toxicity of organophosphorus compounds in guinea pigs is sex- and age-dependent and cannot be solely accounted for by acetylcholinesterase inhibition.

    PubMed

    Fawcett, William P; Aracava, Yasco; Adler, Michael; Pereira, Edna F R; Albuquerque, Edson X

    2009-02-01

    This study was designed to test the hypothesis that the acute toxicity of the nerve agents S-[2-(diisopropylamino)ethyl]-O-ethyl methylphosphonothioate (VX), O-pinacolyl methylphosphonofluoridate (soman), and O-isopropyl methylphosphonofluoridate (sarin) in guinea pigs is age- and sex-dependent and cannot be fully accounted for by the irreversible inhibition of acetylcholinesterase (AChE). The subcutaneous doses of nerve agents needed to decrease 24-h survival of guinea pigs by 50% (LD(50) values) were estimated by probit analysis. In all animal groups, the rank order of LD(50) values was sarin > soman > VX. The LD(50) value of soman was not influenced by sex or age of the animals. In contrast, the LD(50) values of VX and sarin were lower in adult male than in age-matched female or younger guinea pigs. A colorimetric assay was used to determine the concentrations of nerve agents that inhibit in vitro 50% of AChE activity (IC(50) values) in guinea pig brain extracts, plasma, red blood cells, and whole blood. A positive correlation between LD(50) values and IC(50) values for AChE inhibition would support the hypothesis that AChE inhibition is a major determinant of the acute toxicity of the nerve agents. However, such a positive correlation was found only between LD(50) values and IC(50) values for AChE inhibition in brain extracts from neonatal and prepubertal guinea pigs. These results demonstrate for the first time that the lethal potencies of some nerve agents in guinea pigs are age- and sex-dependent. They also support the contention that mechanisms other than AChE inhibition contribute to the lethality of nerve agents.

  19. GbTCP, a cotton TCP transcription factor, confers fibre elongation and root hair development by a complex regulating system.

    PubMed

    Hao, Juan; Tu, Lili; Hu, Haiyan; Tan, Jiafu; Deng, Fenglin; Tang, Wenxin; Nie, Yichun; Zhang, Xianlong

    2012-10-01

    As the most important natural raw material for textile industry, cotton fibres are an excellent model for studying single-cell development. Although expression profiling and functional genomics have provided some data, the mechanism of fibre development is still not well known. A class I TCP transcription factor (designated GbTCP), encoding 344 amino acids, was isolated from the normalized cDNA library of sea-island cotton fibre (from -2 to 25 days post anthesis). GbTCP was preferentially expressed in the elongating cotton fibre from 5 to 15 days post anthesis. Some expression was also observed in stems, apical buds, and petals. RNAi silencing of GbTCP produced shorter fibre, a reduced lint percentage, and a lower fibre quality than the wild-type plants. Overexpression of GbTCP enhanced root hair initiation and elongation in Arabidopsis and regulated branching. Solexa sequencing and Affymetrix GeneChip analysis indicated that GbTCP positively regulates the level of jasmonic acid (JA) and, as a result, activates downstream genes (reactive oxygen species, calcium signalling, ethylene biosynthesis and response, and several NAC and WRKY transcription factors) necessary for elongation of fibres and root hairs. JA content analysis in cotton also confirmed that GbTCP has a profound effect on JA biosynthesis. In vitro ovule culture showed that an appropriate concentration of JA promoted fibre elongation. The results suggest that GbTCP is an important transcription factor for fibre and root hair development by regulating JA biosynthesis and response and other pathways, including reactive oxygen species, calcium channel and ethylene signalling.

  20. GbTCP, a cotton TCP transcription factor, confers fibre elongation and root hair development by a complex regulating system

    PubMed Central

    Zhang, Xianlong

    2012-01-01

    As the most important natural raw material for textile industry, cotton fibres are an excellent model for studying single-cell development. Although expression profiling and functional genomics have provided some data, the mechanism of fibre development is still not well known. A class I TCP transcription factor (designated GbTCP), encoding 344 amino acids, was isolated from the normalized cDNA library of sea-island cotton fibre (from –2 to 25 days post anthesis). GbTCP was preferentially expressed in the elongating cotton fibre from 5 to 15 days post anthesis. Some expression was also observed in stems, apical buds, and petals. RNAi silencing of GbTCP produced shorter fibre, a reduced lint percentage, and a lower fibre quality than the wild-type plants. Overexpression of GbTCP enhanced root hair initiation and elongation in Arabidopsis and regulated branching. Solexa sequencing and Affymetrix GeneChip analysis indicated that GbTCP positively regulates the level of jasmonic acid (JA) and, as a result, activates downstream genes (reactive oxygen species, calcium signalling, ethylene biosynthesis and response, and several NAC and WRKY transcription factors) necessary for elongation of fibres and root hairs. JA content analysis in cotton also confirmed that GbTCP has a profound effect on JA biosynthesis. In vitro ovule culture showed that an appropriate concentration of JA promoted fibre elongation. The results suggest that GbTCP is an important transcription factor for fibre and root hair development by regulating JA biosynthesis and response and other pathways, including reactive oxygen species, calcium channel and ethylene signalling. PMID:23105133

  1. 8 x 120 Gb/s unrepeatered transmission over 444 km (76.6 dB) using distributed Raman amplification and ROPA without discrete amplification.

    PubMed

    Chang, Do Il; Pelouch, Wayne; Patki, Pallavi; McLaughlin, John

    2011-12-12

    Unrepeatered transmission of 8 x 120 Gb/s over 444.2 km (76.6 dB) and multi-rate transmission of 8 x 120 Gb/s and 9 x 10.7 Gb/s over a 75.4 dB span have been demonstrated with off-line digital processing for the coherent 120 Gb/s channels. Transmission of 2 x 120 Gb/s with 7 x 12.5 Gb/s over 78 dB is also demonstrated with a real-time ASIC processor. All transmission results have been achieved using standard effective-area pure-silica-core fiber using forward and backward distributed Raman amplification and remotely-pumped erbium fiber. ASIC real-time processed results match well with off-line processing. © 2011 Optical Society of America

  2. Comparison of the lethal effects of chemical warfare nerve agents across multiple ages.

    PubMed

    Wright, Linnzi K M; Lee, Robyn B; Vincelli, Nicole M; Whalley, Christopher E; Lumley, Lucille A

    2016-01-22

    Children may be inherently more vulnerable than adults to the lethal effects associated with chemical warfare nerve agent (CWNA) exposure because of their closer proximity to the ground, smaller body mass, higher respiratory rate, increased skin permeability and immature metabolic systems. Unfortunately, there have only been a handful of studies on the effects of CWNA in pediatric animal models, and more research is needed to confirm this hypothesis. Using a stagewise, adaptive dose design, we estimated the 24h median lethal dose for subcutaneous exposure to seven CWNA in both male and female Sprague-Dawley rats at six different developmental times. Perinatal (postnatal day [PND] 7, 14 and 21) and adult (PND 70) rats were more susceptible than pubertal (PND 28 and 42) rats to the lethal effects associated with exposure to tabun, sarin, soman and cyclosarin. Age-related differences in susceptibility were not observed in rats exposed to VM, Russian VX or VX. Published by Elsevier Ireland Ltd.

  3. Low-voltage high-performance silicon photonic devices and photonic integrated circuits operating up to 30 Gb/s.

    PubMed

    Kim, Gyungock; Park, Jeong Woo; Kim, In Gyoo; Kim, Sanghoon; Kim, Sanggi; Lee, Jong Moo; Park, Gun Sik; Joo, Jiho; Jang, Ki-Seok; Oh, Jin Hyuk; Kim, Sun Ae; Kim, Jong Hoon; Lee, Jun Young; Park, Jong Moon; Kim, Do-Won; Jeong, Deog-Kyoon; Hwang, Moon-Sang; Kim, Jeong-Kyoum; Park, Kyu-Sang; Chi, Han-Kyu; Kim, Hyun-Chang; Kim, Dong-Wook; Cho, Mu Hee

    2011-12-19

    We present high performance silicon photonic circuits (PICs) defined for off-chip or on-chip photonic interconnects, where PN depletion Mach-Zehnder modulators and evanescent-coupled waveguide Ge-on-Si photodetectors were monolithically integrated on an SOI wafer with CMOS-compatible process. The fabricated silicon PIC(off-chip) for off-chip optical interconnects showed operation up to 30 Gb/s. Under differential drive of low-voltage 1.2 V(pp), the integrated 1 mm-phase-shifter modulator in the PIC(off-chip) demonstrated an extinction ratio (ER) of 10.5dB for 12.5 Gb/s, an ER of 9.1dB for 20 Gb/s, and an ER of 7.2 dB for 30 Gb/s operation, without adoption of travelling-wave electrodes. The device showed the modulation efficiency of V(π)L(π) ~1.59 Vcm, and the phase-shifter loss of 3.2 dB/mm for maximum optical transmission. The Ge photodetector, which allows simpler integration process based on reduced pressure chemical vapor deposition exhibited operation over 30 Gb/s with a low dark current of 700 nA at -1V. The fabricated silicon PIC(intra-chip) for on-chip (intra-chip) photonic interconnects, where the monolithically integrated modulator and Ge photodetector were connected by a silicon waveguide on the same chip, showed on-chip data transmissions up to 20 Gb/s, indicating potential application in future silicon on-chip optical network. We also report the performance of the hybrid silicon electronic-photonic IC (EPIC), where a PIC(intra-chip) chip and 0.13μm CMOS interface IC chips were hybrid-integrated.

  4. Fusion between perinuclear virions and the outer nuclear membrane requires the fusogenic activity of herpes simplex virus gB.

    PubMed

    Wright, Catherine C; Wisner, Todd W; Hannah, Brian P; Eisenberg, Roselyn J; Cohen, Gary H; Johnson, David C

    2009-11-01

    Herpesviruses cross nuclear membranes (NMs) in two steps, as follows: (i) capsids assemble and bud through the inner NM into the perinuclear space, producing enveloped virus particles, and (ii) the envelopes of these virus particles fuse with the outer NM. Two herpes simplex virus (HSV) glycoproteins, gB and gH (the latter, likely complexed as a heterodimer with gL), are necessary for the second step of this process. Mutants lacking both gB and gH accumulate in the perinuclear space or in herniations (membrane vesicles derived from the inner NM). Both gB and gH/gL are also known to act directly in fusing the virion envelope with host cell membranes during HSV entry into cells, i.e., both glycoproteins appear to function directly in different aspects of the membrane fusion process. We hypothesized that HSV gB and gH/gL also act directly in the membrane fusion that occurs during virus egress from the nucleus. Previous studies of the role of gB and gH/gL in nuclear egress involved HSV gB and gH null mutants that could potentially also possess gross defects in the virion envelope. Here, we produced recombinant HSV-expressing mutant forms of gB with single amino acid substitutions in the hydrophobic "fusion loops." These fusion loops are thought to play a direct role in membrane fusion by insertion into cellular membranes. HSV recombinants expressing gB with any one of four fusion loop mutations (W174R, W174Y, Y179K, and A261D) were unable to enter cells. Moreover, two of the mutants, W174Y and Y179K, displayed reduced abilities to mediate HSV cell-to-cell spread, and W174R and A261D exhibited no spread. All mutant viruses exhibited defects in nuclear egress, enveloped virions accumulated in herniations and in the perinuclear space, and fewer enveloped virions were detected on cell surfaces. These results support the hypothesis that gB functions directly to mediate the fusion between perinuclear virus particles and the outer NM.

  5. [Observation on therapeutic effect of acupuncture at Yanglingquan (GB 34) on sprain of external ankle joint].

    PubMed

    He, Xin-fang; Xu, Hai-bin

    2006-08-01

    To observe the increasing effect of Yanglingquan (GB 34) on sprain of external ankle joint. Seventy-nine cases of sprain of external ankle joint were semi-randomly divided into a treatment group (n = 46) and a control group (n = 33). The treatment group were treated with acupuncture at Yanglingquan (GB 34) and electro-magnetic therapy at local acupoints, and the control group with electro-magnetic therapy. The cured rate and the total effective rate were 67.4% and 91.3% in the treatment group, and 36.4% and 69.7% in the control group, respectively, with a significant difference between the two groups (P<0.01, P<0.05). Acupuncture at Yanglingquan (GB 34) has a better therapeutic effect on sprain of the external ankle joint.

  6. In Search of an Effective in vivo Reactivator for Organophosphorus Nerve Agent-Inhibited Acetylcholinesterase in the Central Nervous System

    DTIC Science & Technology

    2012-01-01

    monoisonitrosoacetone (MINA) crossed BBB, provided some degree of CNS AChE reactivation, enhanced survival, and mitigated the seizure activity following nerve agent...tissues (brain regions, diaphragm, heart, skeletal muscle) were collected. AChE activity was measured using the Ellman assay. In GB exposure, pro...therapy. Protecting and/or restoring AChE activity in the brain is a major goal in the treatment of nerve agent intoxication. Our long-term goal is to

  7. A comprehensive evaluation of the efficacy of leading oxime therapies in guinea pigs exposed to organophosphorus chemical warfare agents or pesticides

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Wilhelm, Christina M., E-mail: wilhelmc@battelle.org; Snider, Thomas H., E-mail: snidert@battelle.org; Babin, Michael C., E-mail: babinm@battelle.org

    The currently fielded pre-hospital therapeutic regimen for the treatment of organophosphorus (OP) poisoning in the United States (U.S.) is the administration of atropine in combination with an oxime antidote (2-PAM Cl) to reactivate inhibited acetylcholinesterase (AChE). Depending on clinical symptoms, an anticonvulsant, e.g., diazepam, may also be administered. Unfortunately, 2-PAM Cl does not offer sufficient protection across the range of OP threat agents, and there is some question as to whether it is the most effective oxime compound available. The objective of the present study is to identify an oxime antidote, under standardized and comparable conditions, that offers protection atmore » the FDA approved human equivalent dose (HED) of 2-PAM Cl against tabun (GA), sarin (GB), soman (GD), cyclosarin (GF), and VX, and the pesticides paraoxon, chlorpyrifos oxon, and phorate oxon. Male Hartley guinea pigs were subcutaneously challenged with a lethal level of OP and treated at approximately 1 min post challenge with atropine followed by equimolar oxime therapy (2-PAM Cl, HI-6 DMS, obidoxime Cl{sub 2}, TMB-4, MMB4-DMS, HLö-7 DMS, MINA, and RS194B) or therapeutic-index (TI) level therapy (HI-6 DMS, MMB4-DMS, MINA, and RS194B). Clinical signs of toxicity were observed for 24 h post challenge and blood cholinesterase [AChE and butyrylcholinesterase (BChE)] activity was analyzed utilizing a modified Ellman's method. When the oxime is standardized against the HED of 2-PAM Cl for guinea pigs, the evidence from clinical observations, lethality, quality of life (QOL) scores, and cholinesterase reactivation rates across all OPs indicated that MMB4 DMS and HLö-7 DMS were the two most consistently efficacious oximes. - Highlights: • First comprehensive evaluation of leading AChE oxime reactivators • All oximes are compared against current U.S. therapy 2-PAM Cl. • Relative therapeutic oxime efficacies against OP CWNA and pesticides • Contribution to more effective

  8. GB-InSAR monitoring and observational method for landslide emergency management: the Montaguto earthflow (AV, Italy)

    NASA Astrophysics Data System (ADS)

    Ferrigno, Federica; Gigli, Giovanni; Fanti, Riccardo; Intrieri, Emanuele; Casagli, Nicola

    2017-06-01

    On 10 March 2010, because of the heavy rainfall in the preceding days, the Montaguto landslide (Southern Italy) reactivated, affecting both state road 90 Delle Puglie and the Rome-Bari railway. A similar event occurred on May 2005 and on September 2009. As a result, the National Civil Protection Department (DPC) started an accurate monitoring and analysis program. A monitoring project using the GB-InSAR (ground-based interferometric synthetic aperture radar) system was emplaced to investigate the landslide kinematics, plan urgent safety measures for risk mitigation and design long-term stabilization work.Here, we present the GB-InSAR monitoring system results and its applications in the observational method (OM) approach. GB-InSAR is an established instrument for long-term campaigns aimed at early warning and monitoring during construction works. Our paper further develops these aspects in that it highlights how the OM based on the GB-InSAR technique can produce savings in terms of cost and time in engineering projects without compromising safety. This study focuses on the key role played by the monitoring activities during the design and planning activities, with special reference to the emergency phase.

  9. The Earth Observatory Natural Event Tracker (EONET): An API for Matching Natural Events to GIBS Imagery

    NASA Astrophysics Data System (ADS)

    Ward, K.

    2015-12-01

    Hidden within the terabytes of imagery in NASA's Global Imagery Browse Services (GIBS) collection are hundreds of daily natural events. Some events are newsworthy, devastating, and visibly obvious at a global scale, others are merely regional curiosities. Regardless of the scope and significance of any one event, it is likely that multiple GIBS layers can be viewed to provide a multispectral, dataset-based view of the event. To facilitate linking between the discrete event and the representative dataset imagery, NASA's Earth Observatory Group has developed a prototype application programming interface (API): the Earth Observatory Natural Event Tracker (EONET). EONET supports an API model that allows users to retrieve event-specific metadata--date/time, location, and type (wildfire, storm, etc.)--and web service layer-specific metadata which can be used to link to event-relevant dataset imagery in GIBS. GIBS' ability to ingest many near real time datasets, combined with its growing archive of past imagery, means that API users will be able to develop client applications that not only show ongoing events but can also look at imagery from before and after. In our poster, we will present the API and show examples of its use.

  10. Analysis of globotriaosylceramide (Gb3) isoforms/analogs in unfractionated leukocytes, B lymphocytes and monocytes from Fabry patients using ultra-high performance liquid chromatography/tandem mass spectrometry.

    PubMed

    Toupin, Amanda; Lavoie, Pamela; Arthus, Marie-Françoise; Abaoui, Mona; Boutin, Michel; Fortier, Carole; Ménard, Claudia; Bichet, Daniel G; Auray-Blais, Christiane

    2018-07-26

    Fabry disease is an X-linked lysosomal storage disorder with marked variability in the phenotype and genotype. Glycosphingolipids such as globotriaosylceramide (Gb 3 ) isoforms/analogs, globotriaosylsphingosine (lyso-Gb 3 ) and analogs, and galabiosylceramide (Ga 2 ) isoforms/analogs may accumulate in biological fluids and different organs. The aims of this study were to: 1) develop/validate a novel UHPLC-MS/MS method for relative quantitation of Gb 3 in leukocytes (unfractionated white blood cells), B lymphocytes and monocytes; 2) evaluate these biomarkers in a cohort of Fabry patients and healthy controls; and 3) assess correlations between these biomarkers, treatment and genotype. Whole blood, plasma and urine samples from 21 Fabry patients and 20 healthy controls were analyzed. Samples were purified by liquid-liquid extraction and analyzed by UHPLC-MS/MS in positive electrospray ionization. Methylated Gb 3 isoforms were detected, showing that a methylation process occurs at the cellular level. Our results show that there were no significant differences in the distribution of the different Gb 3 isoforms/analogs in blood cells between Fabry patients and healthy controls. In leukocyte, Gb 3 [(d18:1)(C14:0)], Gb 3 [(d18:1)(C16:0)], Gb 3 [(d18:1)(C16:0)]Me, Gb 3 [(d18:1)(C16:1)], Gb 3 [(d18:1)(C18:0)], Gb 3 [(d18:1)(C18:1)], Gb 3 [(d18:1)(C20:1)], Gb 3 [(d18:1)(C24:2)], Gb 3 [(d18:1)(C26:1)] and total Gb 3 allowed good discrimination between male Fabry patients and male controls, patients having higher biomarker levels than controls. Regarding B lymphocytes and monocytes, the same tendency was observed without reaching statistical significance. A positive concordance between mutation types and biomarker levels in white blood cells was established. Our results might provide a deeper mechanistic comprehension of the underlying biochemical processes of Gb 3 biomarkers in white blood cells of Fabry patients. Copyright © 2018 Elsevier B.V. All rights reserved.

  11. 100-Gb/s InP DP-IQ modulator for small-form-factor pluggable coherent transceivers

    NASA Astrophysics Data System (ADS)

    Kikuchi, Nobuhiro; Ogiso, Yoshihiro; Yamada, Eiichi

    2016-02-01

    We developed a compact InP-based DP-IQ modulator for small-form-factor pluggable coherent transceivers. The modulator achieves 112-Gb/s DP-QPSK modulation with a driving voltage of 6 Vppd. In addition, it provides 86-Gb/s DP-16 QAM signal generation and 240-km transmission with negligible degradation of BER performance. The halfwavelength voltage of our recent device is 1.9 V, and a high median extinction ratio of over 32 dB was achieved for more than 1,400 child MZ modulators. We have also proposed an athermal InP-based twin IQ modulator that enables us to use a modulator in a TEC-free operation. It contributes to lowering the power consumption of transceivers. Under a constant driving condition, there is little change in 56-Gb/s x 2 QPSK modulation characteristics in the range of 20 to 80°C.

  12. Targeting glucosylceramide synthase induction of cell surface globotriaosylceramide (Gb3) in acquired cisplatin-resistance of lung cancer and malignant pleural mesothelioma cells

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Tyler, Andreas, E-mail: andreas.tyler@medbio.umu.se; Johansson, Anders; Karlsson, Terese

    Background: Acquired resistance to cisplatin treatment is a caveat when treating patients with non-small cell lung cancer (NSCLC) and malignant pleural mesothelioma (MPM). Ceramide increases in response to chemotherapy, leading to proliferation arrest and apoptosis. However, a tumour stress activation of glucosylceramide synthase (GCS) follows to eliminate ceramide by formation of glycosphingolipids (GSLs) such as globotriaosylceramide (Gb3), the functional receptor of verotoxin-1. Ceramide elimination enhances cell proliferation and apoptosis blockade, thus stimulating tumor progression. GSLs transactivate multidrug resistance 1/P-glycoprotein (MDR1) and multidrug resistance-associated protein 1 (MRP1) expression which further prevents ceramide accumulation and stimulates drug efflux. We investigated the expressionmore » of Gb3, MDR1 and MRP1 in NSCLC and MPM cells with acquired cisplatin resistance, and if GCS activity or MDR1 pump inhibitors would reduce their expression and reverse cisplatin-resistance. Methods: Cell surface expression of Gb3, MDR1 and MRP1 and intracellular expression of MDR1 and MRP1 was analyzed by flow cytometry and confocal microscopy on P31 MPM and H1299 NSCLC cells and subline cells with acquired cisplatin resistance. The effect of GCS inhibitor PPMP and MDR1 pump inhibitor cyclosporin A for 72 h on expression and cisplatin cytotoxicity was tested. Results: The cisplatin-resistant cells expressed increased cell surface Gb3. Cell surface Gb3 expression of resistant cells was annihilated by PPMP whereas cyclosporin A decreased Gb3 and MDR1 expression in H1299 cells. No decrease of MDR1 by PPMP was noted in using flow cytometry, whereas a decrease of MDR1 in H1299 and H1299res was indicated with confocal microscopy. No certain co-localization of Gb3 and MDR1 was noted. PPMP, but not cyclosporin A, potentiated cisplatin cytotoxicity in all cells. Conclusions: Cell surface Gb3 expression is a likely tumour biomarker for acquired cisplatin

  13. NASA GIBS Use in Live Planetarium Shows

    NASA Astrophysics Data System (ADS)

    Emmart, C. B.

    2015-12-01

    The American Museum of Natural History's Hayden Planetarium was rebuilt in year 2000 as an immersive theater for scientific data visualization to show the universe in context to our planet. Specific astrophysical movie productions provide the main daily programming, but interactive control software, developed at AMNH allows immersive presentation within a data aggregation of astronomical catalogs called the Digital Universe 3D Atlas. Since 2006, WMS globe browsing capabilities have been built into a software development collaboration with Sweden's Linkoping University (LiU). The resulting Uniview software, now a product of the company SCISS, is operated by about fifty planetariums around that world with ability to network amongst the sites for global presentations. Public presentation of NASA GIBS has allowed authoritative narratives to be presented within the range of data available in context to other sources such as Science on a Sphere, NASA Earth Observatory and Google Earth KML resources. Specifically, the NOAA supported World Views Network conducted a series of presentations across the US that focused on local ecological issues that could then be expanded in the course of presentation to national and global scales of examination. NASA support of for GIBS resources in an easy access multi scale streaming format like WMS has tremendously enabled particularly facile presentations of global monitoring like never before. Global networking of theaters for distributed presentations broadens out the potential for impact of this medium. Archiving and refinement of these presentations has already begun to inform new types of documentary productions that examine pertinent, global interdependency topics.

  14. Limitations and challenges in treatment of acute chemical warfare agent poisoning.

    PubMed

    Thiermann, Horst; Worek, Franz; Kehe, Kai

    2013-12-05

    Recent news from Syria on a possible use of chemical warfare agents made the headlines. Furthermore, the motivation of terrorists to cause maximal harm shifts these agents into the public focus. For incidents with mass casualties appropriate medical countermeasures must be available. At present, the most important threats arise from nerve agents and sulfur mustard. At first, self-protection and protection of medical units from contamination is of utmost importance. Volatile nerve agent exposure, e.g. sarin, results in fast development of cholinergic crisis. Immediate clinical diagnosis can be confirmed on-site by assessment of acetylcholinesterase activity. Treatment with autoinjectors that are filled with 2mg atropine and an oxime (at present obidoxime, pralidoxime, TMB-4 or HI-6) are not effective against all nerve agents. A more aggressive atropinisation has to be considered and more effective oximes (if possible with a broad spectrum or a combination of different oximes) as well as alternative strategies to cope with high acetylcholine levels at synaptic sites should be developed. A further gap exists for the treatment of patients with sustained cholinergic crisis that has to be expected after exposure to persistent nerve agents, e.g. VX. The requirement for long-lasting artificial ventilation can be reduced with an oxime therapy that is optimized by using the cholinesterase status for guidance or by measures (e.g. scavengers) that are able to reduce the poison load substantially in the patients. For sulfur mustard poisoning no specific antidote is available until now. Symptomatic measures as used for treatment of burns are recommended together with surgical or laser debridement. Thus, huge amounts of resources are expected to be consumed as wound healing is impaired. Possible depots of sulfur mustard in tissues may aggravate the situation. More basic knowledge is necessary to improve substantially therapeutic options. The use of stem cells may provide a new

  15. Using Metal Complex Ion-Molecule Reactions in a Miniature Rectilinear Ion Trap Mass Spectrometer to Detect Chemical Warfare Agents

    NASA Astrophysics Data System (ADS)

    Graichen, Adam M.; Vachet, Richard W.

    2013-06-01

    The gas-phase reactions of a series of coordinatively unsaturated [Ni(L)n]y+ complexes, where L is a nitrogen-containing ligand, with chemical warfare agent (CWA) simulants in a miniature rectilinear ion trap mass spectrometer were investigated as part of a new approach to detect CWAs. Results show that upon entering the vacuum system via a poly(dimethylsiloxane) (PDMS) membrane introduction, low concentrations of several CWA simulants, including dipropyl sulfide (simulant for mustard gas), acetonitrile (simulant for the nerve agent tabun), and diethyl phosphite (simulant for nerve agents sarin, soman, tabun, and VX), can react with metal complex ions generated by electrospray ionization (ESI), thereby providing a sensitive means of detecting these compounds. The [Ni(L)n]2+ complexes are found to be particularly reactive with the simulants of mustard gas and tabun, allowing their detection at low parts-per-billion (ppb) levels. These detection limits are well below reported exposure limits for these CWAs, which indicates the applicability of this new approach, and are about two orders of magnitude lower than electron ionization detection limits on the same mass spectrometer. The use of coordinatively unsaturated metal complexes as reagent ions offers the possibility of further tuning the ion-molecule chemistry so that desired compounds can be detected selectively or at even lower concentrations.

  16. Catalytic degradation of the nerve agent VX by water-swelled polystyrene-supported ammonium fluorides.

    PubMed

    Marciano, Daniele; Goldvaser, Michael; Columbus, Ishay; Zafrani, Yossi

    2011-10-21

    The catalytic degradation of the nerve agent VX (O-ethyl S-2-(diisopropylamino)ethyl methylphosphonothioate) by water-swelled polymer-supported ammonium fluorides is described. VX (0.06-0.53 mol/mol F(-)) is rapidly degraded (t(1/2) ∼ 10-30 min) to form the "G-analogue" (O-ethyl methylphosphonofluoridate), which hydrolyzes (t(1/2) ∼ 1-1.5 h) to the nontoxic EMPA (ethyl methylphosphonic acid). The toxic desethyl-VX is not formed. The catalytic effect of fluoride is maintained even when 6 equiv of VX are loaded. GB (O-isopropyl methylphosphonofluoridate) and desethyl-VX agents are also degraded under these conditions.

  17. Improved slow-light performance of 10 Gb/s NRZ, PSBT and DPSK signals in fiber broadband SBS.

    PubMed

    Yi, Lilin; Jaouen, Yves; Hu, Weisheng; Su, Yikai; Bigo, Sébastien

    2007-12-10

    We have demonstrated error-free operations of slow-light via stimulated Brillouin scattering (SBS) in optical fiber for 10-Gb/s signals with different modulation formats, including non-return-to-zero (NRZ), phase-shaped binary transmission (PSBT) and differential phase-shiftkeying (DPSK). The SBS gain bandwidth is broadened by using current noise modulation of the pump laser diode. The gain shape is simply controlled by the noise density function. Super-Gaussian noise modulation of the Brillouin pump allows a flat-top and sharp-edge SBS gain spectrum, which can reduce slow-light induced distortion in case of 10-Gb/s NRZ signal. The corresponding maximal delay-time with error-free operation is 35 ps. Then we propose the PSBT format to minimize distortions resulting from SBS filtering effect and dispersion accompanied with slow light because of its high spectral efficiency and strong dispersion tolerance. The sensitivity of the 10-Gb/s PSBT signal is 5.2 dB better than the NRZ case with a same 35-ps delay. The maximal delay of 51 ps with error-free operation has been achieved. Futhermore, the DPSK format is directly demodulated through a Gaussian-shaped SBS gain, which is achieved using Gaussian-noise modulation of the Brillouin pump. The maximal error-free time delay after demodulation of a 10-Gb/s DPSK signal is as high as 81.5 ps, which is the best demonstrated result for 10-Gb/s slow-light.

  18. Tertiary Oximes on Brain Acetylcholinesterase and Central Excitatory Effects of Nerve Agents

    DTIC Science & Technology

    2012-01-01

    5 test doses of the oxime. Animals were euthanized 45 min after oxime treatment when blood and target tissues were collected. AChE activity was...the ability of MINA and DHAP to block or terminate nerve agent-induced electroencephalographic (EEG) seizure activity was evaluated. Animals...instrumented to record brain EEG activity were challenged with a seizure-inducing dose (2.0 x LD50) of GB, GF, or VX, and oxime was administered one min

  19. Reactivation of Brain Acetylcholinesterase by Monoisonitrosoacetone Increases the Therapeutic Efficacy Against Nerve Agents in Guinea Pigs

    DTIC Science & Technology

    2010-01-01

    hese findings support previous reports that protection of ChE nzyme activity in the brain as well as in peripheral tissues with entrally acting... activity . Animals were injected s.c. with either saline (0.5ml/kg) or a 1.0× LD50 dose of GB (42.0g/kg), GF (57.0g/kg), or VX (8.0g/kg). The severity...of toxic signs of each animal was scored at 13min after nerve agent. Fifteen minutes after nerve agent injection, when the inhibition of ChE activity

  20. Changes in Extracellular Striatal Acetylcholine and Brain Seizure Activity Following Acute Exposure to Nerve Against in Freely Moving Guinea Pigs

    DTIC Science & Technology

    2010-01-01

    Literature 3. DATES COVERED (From - To) 4. TITLE AND SUBTITLE Changes in extracellular striatal acetylcholine and brain seizure activity following...Acetylcholine, acetylcholinesterase, choline, guinea pig, in vivo microdialysis, nerve agents, organophosphorus compounds, sarin, seizure activity ...RESEARCH ARTICLE Changes in extracellular striatal acetylcholine and brain seizure activity following acute exposure to nerve agents in freely

  1. A structure-activity analysis of the variation in oxime efficacy against nerve agents

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Maxwell, Donald M.; Koplovitz, Irwin; Worek, Franz

    2008-09-01

    A structure-activity analysis was used to evaluate the variation in oxime efficacy of 2-PAM, obidoxime, HI-6 and ICD585 against nerve agents. In vivo oxime protection and in vitro oxime reactivation were used as indicators of oxime efficacy against VX, sarin, VR and cyclosarin. Analysis of in vivo oxime protection was conducted with oxime protective ratios (PR) from guinea pigs receiving oxime and atropine therapy after sc administration of nerve agent. Analysis of in vitro reactivation was conducted with second-order rate contants (k{sub r2}) for oxime reactivation of agent-inhibited acetylcholinesterase (AChE) from guinea pig erythrocytes. In vivo oxime PR and inmore » vitro k{sub r2} decreased as the volume of the alkylmethylphosphonate moiety of nerve agents increased from VX to cyclosarin. This effect was greater with 2-PAM and obidoxime (> 14-fold decrease in PR) than with HI-6 and ICD585 (< 3.7-fold decrease in PR). The decrease in oxime PR and k{sub r2} as the volume of the agent moiety conjugated to AChE increased was consistent with a steric hindrance mechanism. Linear regression of log (PR-1) against log (k{sub r2} {center_dot} [oxime dose]) produced two offset parallel regression lines that delineated a significant difference between the coupling of oxime reactivation and oxime protection for HI-6 and ICD585 compared to 2-PAM and obidoxime. HI-6 and ICD585 appeared to be 6.8-fold more effective than 2-PAM and obidoxime at coupling oxime reactivation to oxime protection, which suggested that the isonicotinamide group that is common to both of these oximes, but absent from 2-PAM and obidoxime, is important for oxime efficacy.« less

  2. Reactive chromophores for sensitive and selective detection of chemical warfare agents and toxic industrial chemicals

    NASA Astrophysics Data System (ADS)

    Frye-Mason, Greg; Leuschen, Martin; Wald, Lara; Paul, Kateri; Hancock, Lawrence F.

    2005-05-01

    A reactive chromophore developed at MIT exhibits sensitive and selective detection of surrogates for G-class nerve agents. This reporter acts by reacting with the agent to form an intermediate that goes through an internal cyclization reaction. The reaction locks the molecule into a form that provides a strong fluorescent signal. Using a fluorescent sensor platform, Nomadics has demonstrated rapid and sensitive detection of reactive simulants such as diethyl chloro-phosphate (simulant for sarin, soman, and related agents) and diethyl cyanophosphate (simulant for tabun). Since the unreacted chromophore does not fluoresce at the excitation wavelength used for the cyclized reporter, the onset of fluo-rescence can be easily detected. This fluorescence-based detection method provides very high sensitivity and could enable rapid detection at permissible exposure levels. Tests with potential interferents show that the reporter is very selective, with responses from only a few highly toxic, electrophilic chemicals such as phosgene, thionyl chloride, and strong acids such as HF, HCl, and nitric acid. Dimethyl methyl phosphonate (DMMP), a common and inactive simu-lant for other CW detectors, is not reactive enough to generate a signal. The unique selectivity to chemical reactivity means that a highly toxic and hazardous chemical is present when the reporter responds and illustrates that this sensor can provide very low false alarm rates. Current efforts focus on demonstrating the sensitivity and range of agents and toxic industrial chemicals detected with this reporter as well as developing additional fluorescent reporters for a range of chemical reactivity classes. The goal is to produce a hand-held sensor that can sensitively detect a broad range of chemical warfare agent and toxic industrial chemical threats.

  3. Demonstration of an 8 × 25-Gb/s optical time-division multiplexing system

    NASA Astrophysics Data System (ADS)

    Wang, Dong; Huo, Li; Li, Yunbo; Wang, Lei; Li, Han; Jiang, Xiangyu; Chen, Xin; Lou, Caiyun

    2017-11-01

    An 8 × 25-Gb/s optical time-division multiplexing (OTDM) system is demonstrated experimentally. The optical pulse source is based on optical frequency comb (OFC) generation and pulse shaping, which can generate nearly chirp-free 25-GHz 1.6-ps optical Gaussian pulse. The eightfold optical time-division demultiplexer consists of a single-driven dual-parallel Mach-Zehnder modulator (DPMZM) and a Mamyshev reshaper. Error-free demultiplexing of 8 × 25-Gb/s back-to-back (B2B) signal with a power penalty of 4.1 dB to 4.4 dB at a bit error rate (BER) of 10-9 is achieved to confirm the performance of the proposed system.

  4. Signal Characteristics of Super-Resolution Near-Field Structure Disks with 100 GB Capacity

    NASA Astrophysics Data System (ADS)

    Kim, Jooho; Hwang, Inoh; Kim, Hyunki; Park, Insik; Tominaga, Junji

    2005-05-01

    We report the basic characteristics of super resolution near-field structure (Super-RENS) media at a blue laser optical system (laser wavelength 405 nm, numerical aperture 0.85). Using a novel write once read many (WORM) structure for a blue laser system, we obtained a carrier-to-noise ratio (CNR) above 33 dB from the signal of the 37.5 nm mark length, which is equivalent to a 100 GB capacity with a 0.32 micrometer track pitch, and an eye pattern for 50 GB (2T: 75 nm) capacity using a patterned signal. Using a novel super-resolution material (tellurium, Te) with low super-resolution readout power, we also improved the read stability.

  5. Receiver Architecture for 12.5 Gb/s 16-ary Pulse Position Modulation (PPM) Signaling

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Mendez, A J; Gagliardi, R M; Hernandez, V J

    2008-07-11

    PPM is a signaling scheme that enables the transmission of multiple bits per symbol [1]. It has found favor in the regime of free space optical communications ('FSO' or 'Lasercom'); however, PPM has yet to be widely applied to fiber optic-based communications. Its limitation in fiber results from the exceedingly high bandwidth requirements needed to electronically process a directly detected pulse, especially as the symbol rate increases and the pulse width correspondingly decreases. As a solution, we introduced the concept of a virtual quadrant receiver for receiving 1.25 Gb/s 4-ary PPM, where photonic processing reduced the number of required electronicmore » components [2]. In this paper, we extend these photonic process techniques to a 16-ary, 12.5 Gb/s (10 Gb/s plus 8B/10B line coding) PPM communications system for fiber optic avionics, wherein much of the receiver processing is enabled by techniques based on planar lightwave circuits (PLCs). The architecture is applicable to higher input data rates and M-ary PPM. In the following, we present the PPM encoding and decoding architectures and numerically simulated results.« less

  6. Comparative Analysis of Glycoprotein B (gB) of Equine Herpesvirus Type 1 and Type 4 (EHV-1 and EHV-4) in Cellular Tropism and Cell-to-Cell Transmission

    PubMed Central

    Spiesschaert, Bart; Osterrieder, Nikolaus; Azab, Walid

    2015-01-01

    Glycoprotein B (gB) plays an important role in alphaherpesvirus cellular entry and acts in concert with gD and the gH/gL complex. To evaluate whether functional differences exist between gB1 and gB4, the corresponding genes were exchanged between the two viruses. The gB4-containing-EHV-1 (EHV-1_gB4) recombinant virus was analyzed for growth in culture, cell tropism, and cell entry rivaling no significant differences when compared to parental virus. We also disrupted a potential integrin-binding motif, which did not affect the function of gB in culture. In contrast, a significant reduction of plaque sizes and growth kinetics of gB1-containing-EHV-4 (EHV-4_gB1) was evident when compared to parental EHV-4 and revertant viruses. The reduction in virus growth may be attributable to the loss of functional interaction between gB and the other envelope proteins involved in virus entry, including gD and gH/gL. Alternatively, gB4 might have an additional function, required for EHV-4 replication, which is not fulfilled by gB1. In conclusion, our results show that the exchange of gB between EHV-1 and EHV-4 is possible, but results in a significant attenuation of virus growth in the case of EHV-4_gB1. The generation of stable recombinant viruses is a valuable tool to address viral entry in a comparative fashion and investigate this aspect of virus replication further. PMID:25654240

  7. A Liquid Chromatography-Quadrupole-Time-of-Flight Mass Spectrometric Assay for the Quantification of Fabry Disease Biomarker Globotriaosylceramide (GB3) in Fabry Model Mouse.

    PubMed

    Shin, Seok-Ho; Park, Min-Ho; Byeon, Jin-Ju; Lee, Byeong Ill; Park, Yuri; Ko, Ah-Ra; Seong, Mi-Ran; Lee, Soyeon; Kim, Mi Ra; Seo, Jinwook; Jung, Myung Eun; Jin, Dong-Kyu; Shin, Young G

    2018-06-07

    Fabry disease is a rare lysosomal storage disorder resulting from the lack of α-Gal A gene activity. Globotriaosylceramide (GB3, ceramide trihexoside) is a novel endogenous biomarker which predicts the incidence of Fabry disease. At the early stage efficacy/biomarker study, a rapid method to determine this biomarker in plasma and in all relevant tissues related to this disease simultaneously is required. However, the limited sample volume, as well as the various levels of GB3 in different matrices makes the GB3 quantitation very challenging. Hereby we developed a rapid method to identify GB3 in mouse plasma and various tissues. Preliminary stability tests were also performed in three different conditions: short-term, freeze-thaw, long-term. The calibration curve was well fitted over the concentration range of 0.042⁻10 μg/mL for GB3 in plasma and 0.082⁻20 μg/g for GB3 in various tissues. This method was successfully applied for the comparison of GB3 levels in Fabry model mice (B6;129-Gla tm1Kul /J), which has not been performed previously to the best of our knowledge.

  8. Health effects in Army Gulf War veterans possibly exposed to chemical munitions destruction at Khamisiyah, Iraq: Part I. Morbidity associated with potential exposure.

    PubMed

    Mahan, Clare M; Page, William F; Bullman, Tim A; Kang, Han K

    2005-11-01

    In March 1991, U.S. troops detonated the Khamisiyah, Iraq, ammunition depot, possibly releasing two chemical warfare agents, sarin and cyclosarin. The long-term health effects associated with possible exposure to these chemical warfare agents are unknown. This study was undertaken to investigate whether possible exposure was associated with morbidity among Army Gulf War veterans using morbidity data for 5,555 Army veterans who were deployed to the Gulf region. Responses to 86 self-assessed health measures, as reported in the 1995 Department of Veterans Affairs National Health Survey of Gulf War Era Veterans, were evaluated. We found little association between potential exposure and health, after adjustment for demographic variables, and conclude that potential exposure to sarin or cyclosarin at Khamisiyah does not seem to have adversely affected self-perceived health status, as evidenced by a wide range of health measures.

  9. Field trial of a quantum secured 10 Gb/s DWDM transmission system over a single installed fiber.

    PubMed

    Choi, Iris; Zhou, Yu Rong; Dynes, James F; Yuan, Zhiliang; Klar, Andreas; Sharpe, Andrew; Plews, Alan; Lucamarini, Marco; Radig, Christian; Neubert, Jörg; Griesser, Helmut; Eiselt, Michael; Chunnilall, Christopher; Lepert, Guillaume; Sinclair, Alastair; Elbers, Jörg-Peter; Lord, Andrew; Shields, Andrew

    2014-09-22

    We present results from the first field-trial of a quantum-secured DWDM transmission system, in which quantum key distribution (QKD) is combined with 4 × 10 Gb/s encrypted data and transmitted simultaneously over 26 km of field installed fiber. QKD is used to frequently refresh the key for AES-256 encryption of the 10 Gb/s data traffic. Scalability to over 40 DWDM channels is analyzed.

  10. Characterization, Function, and Transcriptional Profiling Analysis of 3-Hydroxy-3-methylglutaryl-CoA Synthase Gene (GbHMGS1) towards Stresses and Exogenous Hormone Treatments in Ginkgo biloba.

    PubMed

    Meng, Xiangxiang; Song, Qiling; Ye, Jiabao; Wang, Lanlan; Xu, Feng

    2017-10-12

    3-Hydroxy-3-methylglutaryl-CoA synthase (HMGS) is one of the rate-limiting enzymes in the mevalonate pathway as it catalyzes the condensation of acetoacetyl-CoA to form 3-hydroxy-3-methylglutaryl-CoA. In this study, A HMGS gene (designated as GbHMGS1 ) was cloned from Ginkgo biloba for the first time. GbHMGS1 contained a 1422-bp open-reading frame encoding 474 amino acids. Comparative and bioinformatics analysis revealed that GbHMGS1 was extensively homologous to HMGSs from other plant species. Phylogenetic analysis indicated that the GbHMGS1 belonged to the plant HMGS superfamily, sharing a common evolutionary ancestor with other HMGSs, and had a further relationship with other gymnosperm species. The yeast complement assay of GbHMGS1 in HMGS -deficient Saccharomyces cerevisiae strain YSC6274 demonstrated that GbHMGS1 gene encodes a functional HMGS enzyme. The recombinant protein of GbHMGS1 was successfully expressed in E. coli . The in vitro enzyme activity assay showed that the k cat and K m values of GbHMGS1 were 195.4 min -1 and 689 μM, respectively. GbHMGS1 was constitutively expressed in all tested tissues, including the roots, stems, leaves, female flowers, male flowers and fruits. The transcript accumulation for GbHMGS1 was highest in the leaves. Expression profiling analyses revealed that GbHMGS1 expression was induced by abiotic stresses (ultraviolet B and cold) and hormone treatments (salicylic acid, methyl jasmonate, and ethephon) in G. biloba , indicating that GbHMGS1 gene was involved in the response to environmental stresses and plant hormones.

  11. Selective chromo-fluorogenic detection of DFP (a Sarin and Soman mimic) and DCNP (a Tabun mimic) with a unique probe based on a boron dipyrromethene (BODIPY) dye.

    PubMed

    Barba-Bon, Andrea; Costero, Ana M; Gil, Salvador; Martínez-Máñez, Ramón; Sancenón, Félix

    2014-11-21

    A novel colorimetric probe (P4) for the selective differential detection of DFP (a Sarin and Soman mimic) and DCNP (a Tabun mimic) was prepared. Probe P4 contains three reactive sites; i.e. (i) a nucleophilic phenol group able to undergo phosphorylation with nerve gases, (ii) a carbonyl group as a reactive site for cyanide; and (iii) a triisopropylsilyl (TIPS) protecting group that is known to react with fluoride. The reaction of P4 with DCNP in acetonitrile resulted in both the phosphorylation of the phenoxy group and the release of cyanide, which was able to react with the carbonyl group of P4 to produce a colour modulation from pink to orange. In contrast, phosphorylation of P4 with DFP in acetonitrile released fluoride that hydrolysed the TIPS group in P4 to yield a colour change from pink to blue. Probe P4 was able to discriminate between DFP and DCNP with remarkable sensitivity; limits of detection of 0.36 and 0.40 ppm for DCNP and DFP, respectively, were calculated. Besides, no interference from other organophosphorous derivatives or with presence of acid was observed. The sensing behaviour of P4 was also retained when incorporated into silica gel plates or onto polyethylene oxide membranes, which allowed the development of simple test strips for the colorimetric detection of DCNP and DFP in the vapour phase. P4 is the first probe capable of colorimetrically differentiating between a Tabun mimic (DCNP) and a Sarin and Soman mimic (DFP).

  12. Spectroscopic and Computational Investigation of Room-Temperature Decomposition of a Chemical Warfare Agent Simulant on Polycrystalline Cupric Oxide

    DOE PAGES

    Trotochaud, Lena; Tsyshevsky, Roman; Holdren, Scott; ...

    2017-08-21

    Certain organophosphorus molecules are infamous due to their use as highly toxic nerve agents. The filtration materials currently in common use for protection against chemical warfare agents were designed before organophosphorus compounds were used as chemical weapons. A better understanding of the surface chemistry between simulant molecules and the individual filtration-material components is a critical precursor to the development of more effective materials for filtration, destruction, decontamination, and/or sensing of nerve agents. Here, we report on the surface adsorption and reactions of a sarin simulant molecule, dimethyl methylphosphonate (DMMP), with cupric oxide surfaces. In situ ambient pressure X-ray photoelectron andmore » infrared spectroscopies are coupled with density functional calculations to propose mechanisms for DMMP decomposition on CuO. We find extensive room temperature decomposition of DMMP on CuO, with the majority of decomposition fragments bound to the CuO surface. We observe breaking of PO-CH3, P-OCH3, and P-CH3bonds at room temperature. On the basis of these results, we identify specific DMMP decomposition mechanisms not seen on other metal oxides. Participation of lattice oxygen in the decomposition mechanism leads to significant changes in chemical and electronic surface environment, which are manifest in the spectroscopic and computational data. This study establishes a computational baseline for the study of highly toxic organophosphorous compounds on metal oxide surfaces.« less

  13. Spectroscopic and Computational Investigation of Room-Temperature Decomposition of a Chemical Warfare Agent Simulant on Polycrystalline Cupric Oxide

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Trotochaud, Lena; Tsyshevsky, Roman; Holdren, Scott

    Certain organophosphorus molecules are infamous due to their use as highly toxic nerve agents. The filtration materials currently in common use for protection against chemical warfare agents were designed before organophosphorus compounds were used as chemical weapons. A better understanding of the surface chemistry between simulant molecules and the individual filtration-material components is a critical precursor to the development of more effective materials for filtration, destruction, decontamination, and/or sensing of nerve agents. Here, we report on the surface adsorption and reactions of a sarin simulant molecule, dimethyl methylphosphonate (DMMP), with cupric oxide surfaces. In situ ambient pressure X-ray photoelectron andmore » infrared spectroscopies are coupled with density functional calculations to propose mechanisms for DMMP decomposition on CuO. We find extensive room temperature decomposition of DMMP on CuO, with the majority of decomposition fragments bound to the CuO surface. We observe breaking of PO-CH3, P-OCH3, and P-CH3bonds at room temperature. On the basis of these results, we identify specific DMMP decomposition mechanisms not seen on other metal oxides. Participation of lattice oxygen in the decomposition mechanism leads to significant changes in chemical and electronic surface environment, which are manifest in the spectroscopic and computational data. This study establishes a computational baseline for the study of highly toxic organophosphorous compounds on metal oxide surfaces.« less

  14. Quantification of [11C]GB67 binding to cardiac alpha1-adrenoceptors with positron emission tomography: validation in pigs.

    PubMed

    Park-Holohan, So-Jin; Asselin, Marie-Claude; Turton, David R; Williams, Sharron L; Hume, Susan P; Camici, Paolo G; Rimoldi, Ornella E

    2008-09-01

    An increase in human cardiac alpha(1)-adrenoceptor (alpha(1)-AR) density is associated with various diseases such as myocardial ischemia, congestive heart failure, hypertrophic cardiomyopathy and hypertension. Positron emission tomography (PET) with an appropriate radioligand offers the possibility of imaging receptor function in the normal and diseased heart. [(11)C]GB67, an analogue of prazosin, has been shown in rats to have potential as a PET ligand with high selectivity to alpha(1)-AR. However, alpha(1)-AR density is up to ten times higher in rat heart compared to that in man. The aim of the present preclinical study was to extend the previous evaluation to a large mammal heart, where the alpha(1)-AR density is comparable to man, and to validate a method for quantification before PET studies in man. Seven [(11)C]GB67 PET studies, with weight-adjusted target dose of either 5.29 MBq kg(-1) (pilot, test-retest and baseline-predose studies) or 8.22 MBq kg(-1) (baseline-displacement studies), were performed in four anaesthetised pigs (39.5 +/- 3.9 kg). Total myocardial volume of distribution (V (T)) was estimated under different pharmacological conditions using compartmental analysis with a radiolabelled metabolite-corrected arterial plasma input function. A maximum possible blocking dose of 0.12 mumol kg(-1) of unlabeled GB67 was given 20 min before [(11)C]GB67 administration in the predose study and 45 min after administration of [(11)C]GB67 in the displacement study. In addition, [(15)O]CO (3,000 MBq) and [(15)O]H(2)O, with weight adjusted target dose of 10.57 MBq kg(-1), were also administered for estimation of blood volume recovery (RC) of the left ventricular cavity and myocardial perfusion (MBF), respectively. [(11)C]GB67 V (T) values (in ml cm(-3)) were estimated to be 24.2 +/- 5.5 (range, 17.3-31.3), 10.1 (predose) and 11.6 (displacement). MBF did not differ within each pig, including between baseline and predose conditions. Predose and displacement

  15. Neuroinflammatory Pathobiology in Gulf War Illness: Characterization with an Animal Model

    DTIC Science & Technology

    2011-08-01

    evaluated alone and in combination (i.e. pyridostigmine bromide (PB), diethyl-m-toluamide (DEET), 5 lipopolysaccharide (LPS), corticosterone (CORT) and...acetylcholinesterase (AChE) inhibitor pyridostigmine bromide (PB), the insect repellent DEET and, potentially, the nerve agent, sarin. These combined

  16. Long term real-time GB_InSAR monitoring of a large rock slide

    NASA Astrophysics Data System (ADS)

    Crosta, G. B.; Agliardi, F.; Sosio, R.; Rivolta, C.; Mannucci, G.

    2011-12-01

    We analyze a long term monitoring dataset collected for a deep-seated rockslide (Ruinon, Lombardy, Italy). The rockslide has been actively monitored since 1997 by means of an in situ monitoring network (topographic benchmarks, GPS, wire extensometers) and since 2006 by a ground based radar. Monitoring data have been used to set-up and update the geological model, to identify rockslide extent and geometry, to analyse the sensitivity to seasonal changes and their impact on the reliability and early warning potential of monitoring data. GB-InSAR data allowed us to identify sectors characterized by different behaviours and associated to outcropping bedrock, thick debris cover, major structures. GB-Insar data have been used to set-up a "virtual monitoring network" by a posteriori selection of critical locations. Displacement time series extracted from GB-InSAR data provide a large amount of information even in debris-covered areas, when ground-based instrumentation fails. Such spatially-distributed, improved information, validated by selected ground-based measurements, allowed to establish new velocity and displacement thresholds for early warning purposes. The data are analysed to verify the dependency of the observed displacements on the line of sight orientation as well as on that of the framed resolution cell. Relationships with rainfall and morphological slope characteristics have been analysed to verify the sensitivity to rain intensity and amount and to distinguish among the different possible mechanisms.

  17. Draft Genome Sequence of Bacillus licheniformis Strain GB2, a Hydrocarbon-Degrading and Plant Growth-Promoting Soil Bacterium.

    PubMed

    Gkorezis, Panagiotis; Van Hamme, Jonathan; Bottos, Eric; Thijs, Sofie; Balseiro-Romero, Maria; Monterroso, Carmela; Kidd, Petra Suzan; Rineau, Francois; Weyens, Nele; Sillen, Wouter; Vangronsveld, Jaco

    2016-06-23

    We report the 4.39 Mb draft genome of Bacillus licheniformis GB2, a hydrocarbonoclastic Gram-positive bacterium of the family Bacillaceae, isolated from diesel-contaminated soil at the Ford Motor Company site in Genk, Belgium. Strain GB2 is an effective plant-growth promoter useful for diesel fuel remediation applications based on plant-bacterium associations. Copyright © 2016 Gkorezis et al.

  18. Forty Gb/s hybrid silicon Mach-Zehnder modulator with low chirp.

    PubMed

    Chen, Hui-Wen; Peters, Jonathan D; Bowers, John E

    2011-01-17

    We demonstrate a hybrid silicon modulator operating up to 40 Gb/s with 11.4 dB extinction ratio. The modulator has voltage-length product of 2.4 V-mm and chirp of -0.75 over the entire bias range. As a switch, it has a switching time less than 20 ps.

  19. A 3.125-Gb/s inductorless transimpedance amplifier for optical communication in 0.35 μm CMOS

    NASA Astrophysics Data System (ADS)

    Hui, Xu; Jun, Feng; Quan, Liu; Wei, Li

    2011-10-01

    A 3.125-Gb/s transimpedance amplifier (TIA) for an optical communication system is realized in 0.35 μm CMOS technology. The proposed TIA employs a regulated cascode configuration as the input stage, and adopts DC-cancellation techniques to stabilize the DC operating point. In addition, noise optimization is processed. The on-wafer measurement results show the transimpedance gain of 54.2 dBΩ and -3 dB bandwidth of 2.31 GHz. The measured average input referred noise current spectral density is about . The measured eye diagram is clear and symmetrical for 2.5-Gb/s and 3.125-Gb/s PRBS. Under a single 3.3-V supply voltage, the TIA consumes only 58.08 mW, including 20 mW from the output buffer. The whole die area is 465 × 435 μm2.

  20. Accessing Earth Science Data Visualizations through NASA GIBS & Worldview

    NASA Astrophysics Data System (ADS)

    Cechini, M. F.; Boller, R. A.; Baynes, K.; Wong, M. M.; King, B. A.; Schmaltz, J. E.; De Luca, A. P.; King, J.; Roberts, J. T.; Rodriguez, J.; Thompson, C. K.; Pressley, N. N.

    2017-12-01

    For more than 20 years, the NASA Earth Observing System (EOS) has operated dozens of remote sensing satellites collecting nearly 15 Petabytes of data that span thousands of science parameters. Within these observations are keys the Earth Scientists have used to unlock many things that we understand about our planet. Also contained within these observations are a myriad of opportunities for learning and education. The trick is making them accessible to educators and students in convenient and simple ways so that effort can be spent on lesson enrichment and not overcoming technical hurdles. The NASA Global Imagery Browse Services (GIBS) system and NASA Worldview website provide a unique view into EOS data through daily full resolution visualizations of hundreds of earth science parameters. For many of these parameters, visualizations are available within hours of acquisition from the satellite. For others, visualizations are available for the entire mission of the satellite. Accompanying the visualizations are visual aids such as color legends, place names, and orbit tracks. By using these visualizations, educators and students can observe natural phenomena that enrich a scientific education. This poster will provide an overview of the visualizations available in NASA GIBS and Worldview and how they are accessed. We invite discussion on how the visualizations can be used or improved for educational purposes.

  1. All-optical 10Gb/s ternary-CAM cell for routing look-up table applications.

    PubMed

    Mourgias-Alexandris, George; Vagionas, Christos; Tsakyridis, Apostolos; Maniotis, Pavlos; Pleros, Nikos

    2018-03-19

    We experimentally demonstrate the first all-optical Ternary-Content Addressable Memory (T-CAM) cell that operates at 10Gb/s and comprises two monolithically integrated InP Flip-Flops (FF) and a SOA-MZI optical XOR gate. The two FFs are responsible for storing the data bit and the ternary state 'X', respectively, with the XOR gate used for comparing the stored FF-data and the search bit. The experimental results reveal error-free operation at 10Gb/s for both Write and Ternary Content Addressing of the T-CAM cell, indicating that the proposed optical T-CAM cell could in principle lead to all-optical T-CAM-based Address Look-up memory architectures for high-end routing applications.

  2. VizieR Online Data Catalog: GB6 catalog of radio sources (Gregory+ 1996)

    NASA Astrophysics Data System (ADS)

    Gregory, P. C.; Scott, W. K.; Douglas, K.; Condon, J. J.

    1997-01-01

    The final set of sky maps from the Green Bank 4.85 GHz survey (Condon J.J., Broderick J.J., Seielstad G.A., Douglas K., & Gregory P.C. in 1994AJ....107.1829C) was used to construct the GB6 Catalog of sources stronger than S ~ 18 mJy in the declination range 0deg < Dec. < +75deg (Gregory P.C., Scott W.K., Douglas K., & Condon J.J. in 1996ApJS..103..427G). There are two machine-readable versions of the GB6 catalog, with coordinates precessed to B1950 (file b1950.dat) and J2000 (file j2000.dat). Each catalog file contains one line per source (75,162 lines each), and the sources are sorted by increasing B1950 or J2000 right ascension. (3 data files).

  3. Alanine substitution of conserved residues in the cytoplasmic tail of herpes simplex virus gB can enhance or abolish cell fusion activity and viral entry

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Ruel, Nancy; Zago, Anna; Spear, Patricia G.

    2006-03-01

    Herpes simplex virus (HSV) glycoprotein B (gB) is one of the four viral glycoproteins required for viral entry and cell fusion and is highly conserved among herpesviruses. Mutants of HSV type 2 gB were generated by substituting conserved residues in the cytoplasmic tail with alanine or by deleting 41 amino acids from the C-terminus. Some of the mutations abolished cell fusion activity and also prevented transport of gB to the cell surface, identifying residues in the gB cytoplasmic tail that are critical for intracellular transport of this glycoprotein. These mutations also prevented production of infectious virus, possibly because the mutantmore » forms of gB were not transported to the site of envelopment. Other mutations, particularly the deletion, significantly enhanced cell fusion activity. These mutations, as well as others described previously, identify regions of the gB cytoplasmic domain that modulate cell fusion activity.« less

  4. Effects of exogenous pyoverdines on Fe availability and their impacts on Mn(II) oxidation by Pseudomonas putida GB-1

    PubMed Central

    Lee, Sung-Woo; Parker, Dorothy L.; Geszvain, Kati; Tebo, Bradley M.

    2014-01-01

    Pseudomonas putida GB-1 is a Mn(II)-oxidizing bacterium that produces pyoverdine-type siderophores (PVDs), which facilitate the uptake of Fe(III) but also influence MnO2 formation. Recently, a non-ribosomal peptide synthetase mutant that does not synthesize PVD was described. Here we identified a gene encoding the PVDGB-1 (PVD produced by strain GB-1) uptake receptor (PputGB1_4082) of strain GB-1 and confirmed its function by in-frame mutagenesis. Growth and other physiological responses of these two mutants and of wild type were compared during cultivation in the presence of three chemically distinct sets of PVDs (siderotypes n°1, n°2, and n°4) derived from various pseudomonads. Under iron-limiting conditions, Fe(III) complexes of various siderotype n°1 PVDs (including PVDGB-1) allowed growth of wild type and the synthetase mutant, but not the receptor mutant, confirming that iron uptake with any tested siderotype n°1 PVD depended on PputGB1_4082. Fe(III) complexes of a siderotype n°2 PVD were not utilized by any strain and strongly induced PVD synthesis. In contrast, Fe(III) complexes of siderotype n°4 PVDs promoted the growth of all three strains and did not induce PVD synthesis by the wild type, implying these complexes were utilized for iron uptake independent of PputGB1_4082. These differing properties of the three PVD types provided a way to differentiate between effects on MnO2 formation that resulted from iron limitation and others that required participation of the PVDGB-1 receptor. Specifically, MnO2 production was inhibited by siderotype n°1 but not n°4 PVDs indicating PVD synthesis or PputGB1_4082 involvement rather than iron-limitation caused the inhibition. In contrast, iron limitation was sufficient to explain the inhibition of Mn(II) oxidation by siderotype n°2 PVDs. Collectively, our results provide insight into how competition for iron via siderophores influences growth, iron nutrition and MnO2 formation in more complex environmental

  5. Air Remedial Investigation. Version 3.1. Volume 1

    DTIC Science & Technology

    1988-08-01

    1987. Construction of facilities for the production of Sarin (CB) nerve agent began in 1950 and was completed in 1953. Manufacture of CB was continued...and chemical warfare agents . Although production has ceased at the South Plants’ facilities, contaminants have been observed in ground water near the... agents , were introduced to Basin A since 1943. Inorganic metals as well as inorganic non-metals are also present. The near-surface soil contamination is

  6. Aquatic Toxicity Screening of an ACWA Secondary Waste, GB-Hydrolysate

    DTIC Science & Technology

    2009-01-01

    Toxicity Comparison for GB-hydrolysates, Acetone, and Malathion Using O’Bryan and Ross Chemical Scoring System for Hazard and Exposure Identification ...hydrolysates, Acetone, and Malathion Using O’Bryan and Ross Chemical Scoring System for Hazard and Exposure Identification (5) and the U.S. Fish and...WWTF) or a TSDF. The toxicity results were ranked using the Chemical Scoring System for Hazard and Exposure Identification (5). This system is

  7. Scaling single-wavelength optical interconnects to 180 Gb/s with PAM-M and pulse shaping

    NASA Astrophysics Data System (ADS)

    Dris, Stefanos; Bakopoulos, Paraskevas; Argyris, Nikolaos; Spatharakis, Christos; Avramopoulos, Hercules

    2016-03-01

    Faced with surging datacenter traffic demand, system designers are turning to multi-level optical modulation with direct detection as the means of reaching 100 Gb/s in a single optical lane; a further upgrade to 400 Gb/s is envisaged through wavelength-multiplexing of multiple 100 Gb/s strands. In terms of modulation formats, PAM-4 and PAM-8 are considered the front-runners, striking a good balance between bandwidth-efficiency and implementation complexity. In addition, the emergence of energy-efficient, high-speed CMOS digital-to-analog converters (DACs) opens up new possibilities: Spectral shaping through digital filtering will allow squeezing even more data through low-cost, low-bandwidth electro-optic components. In this work we demonstrate an optical interconnect based on an EAM that is driven directly with sub-volt electrical swing by a 65 GSa/s arbitrary waveform generator (AWG). Low-voltage drive is particularly attractive since it allows direct interfacing with the switch/server ASIC, eliminating the need for dedicated, power-hungry and expensive electrical drivers. Single-wavelength throughputs of 180 and 120 Gb/s are experimentally demonstrated with 60 Gbaud optical PAM-8 and PAM-4 respectively. Successful transmission over 1250 m SMF is achieved with direct-detection, using linear equalization via offline digital signal processing in order to overcome the strong bandwidth limitation of the overall link (~20 GHz). The suitability of Nyquist pulse shaping for optical interconnects is also investigated experimentally with PAM-4 and PAM-8, at a lower symbol rate of 40 Gbaud (limited by the sampling rate of the AWG). To the best of our knowledge, the rates achieved are the highest ever using optical PAM-M formats.

  8. 300 Gb/s IM/DD based SDM-WDM-PON with laserless ONUs.

    PubMed

    Bao, Fangdi; Morioka, Toshio; Oxenløwe, Leif K; Hu, Hao

    2018-04-02

    A low-cost, high-speed SDM-WDM-PON architecture is proposed by using a multi-core fiber (MCF) and intensity modulation/directly detection (IM/DD). One of the MCF cores is used for sending laser sources from optical line terminal (OLT) to optical network unit (ONU), thus facilitating laserless and colorless ONUs, and providing ease of network management and maintenance. In addition, the wavelengths of the ONUs are controlled on the OLT side, which also enables flexible optical networks. Thanks to the low inter-core crosstalk of a MCF, downstream (DS) and upstream (US) signals are transmitted independently in different cores of the MCF, not only increasing the aggregated capacity but also avoiding the Rayleigh backscattering noise. Finally, a proof-of-principle experiment is performed by using a 7-core fiber, achieving 300 /120 Gb/s aggregated capacity for DS and US (3 × cores, 4 × wavelengths, 25/10 Gb/s per wavelength), respectively.

  9. Comparative Genomic Analysis of Lactobacillus plantarum GB-LP1 Isolated from Traditional Korean Fermented Food.

    PubMed

    Yu, Jihyun; Ahn, Sojin; Kim, Kwondo; Caetano-Anolles, Kelsey; Lee, Chanho; Kang, Jungsun; Cho, Kyungjin; Yoon, Sook Hee; Kang, Dae-Kyung; Kim, Heebal

    2017-08-28

    As probiotics play an important role in maintaining a healthy gut flora environment through antitoxin activity and inhibition of pathogen colonization, they have been of interest to the medical research community for quite some time now. Probiotic bacteria such as Lactobacillus plantarum , which can be found in fermented food, are of particular interest given their easy accessibility. We performed whole-genome sequencing and genomic analysis on a GB-LP1 strain of L. plantarum isolated from Korean traditional fermented food; this strain is well known for its functions in immune response, suppression of pathogen growth, and antitoxin effects. The complete genome sequence of GB-LP1 is a single chromosome of 3,040,388 bp with 2,899 predicted open reading frames. Genomic analysis of GB-LP1 revealed two CRISPR regions and genes showing accelerated evolution, which may have antibiotic and antitoxin functions. The aim of the present study was to predict strain specific-genomic characteristics and assess the potential of this new strain as lactic acid bacteria at the genomic level using in silico analysis. These results provide insight into the L. plantarum species as well as confirm the possibility of its utility as a candidate probiotic.

  10. On the reduced-complexity of LDPC decoders for beyond 400 Gb/s serial optical transmission

    NASA Astrophysics Data System (ADS)

    Djordjevic, Ivan B.; Xu, Lei; Wang, Ting

    2010-12-01

    Two reduced-complexity (RC) LDPC decoders are proposed, which can be used in combination with large-girth LDPC codes to enable beyond 400 Gb/s serial optical transmission. We show that optimally attenuated RC min-sum sum algorithm performs only 0.45 dB worse than conventional sum-product algorithm, while having lower storage memory requirements and much lower latency. We further evaluate the proposed algorithms for use in beyond 400 Gb/s serial optical transmission in combination with PolMUX 32-IPQ-based signal constellation and show that low BERs can be achieved for medium optical SNRs, while achieving the net coding gain above 11.4 dB.

  11. 40-Gb/s PDM-QPSK signal transmission over 160-m wireless distance at W-band.

    PubMed

    Xiao, Jiangnan; Yu, Jianjun; Li, Xinying; Xu, Yuming; Zhang, Ziran; Chen, Long

    2015-03-15

    We experimentally demonstrate a W-band optical-wireless transmission system over 160-m wireless distance with a bit rate up to 40 Gb/s. The optical-wireless transmission system adopts optical polarization-division-multiplexing (PDM), multiple-input multiple-output (MIMO) reception and antenna polarization diversity. Using this system, we experimentally demonstrate the 2×2 MIMO wireless delivery of 20- and 40-Gb/s PDM quadrature-phase-shift-keying (PDM-QPSK) signals over 640- and 160-m wireless links, respectively. The bit-error ratios (BERs) of these transmission systems are both less than the forward-error-correction (FEC) threshold of 3.8×10-3.

  12. A 30 Gb/s full-duplex bi-directional transmission optical wireless-over fiber integration system at W-band.

    PubMed

    Tang, Chanjuan; Yu, Jianjun; Li, Xinying; Chi, Nan; Xiao, Jiangnan; Tian, Yumin; Zhang, Junwen

    2014-01-13

    We propose and experimentally demonstrate a full-duplex bi-directional transmission optical wireless-over fiber integration system at W-band (75-100 GHz) with the speed up to 15 Gb/s for both 95.4 GHz link and 88.6 GHz link for the first time. The generation of millimeter-wave (mm-wave) wireless signal is based on the photonic technique by heterodyne mixing of an optical quadrature-phase-shift-keying (QPSK) signal with a free-running light at different wavelength. After 20 km fiber transmission, up to 30 Gb/s mm-wave signal is delivered over 2 m wireless link, and then converted to the optical signal for another 20 km fiber transmission. At the wireless receiver, coherent detection and advanced digital signal processing (DSP) are introduced to improve receiver sensitivity and system performance. With the OSNR of 15 dB, the bit error ratios (BERs) for 10 Gb/s signal transmission at 95.4 GHz and 88.6 GHz are below the forward-error-correction (FEC) threshold of 3.8 × 10(-3) whether post filter is used or not, while the BER for 15 Gb/s QPSK signal employing post filter in the link of 95.4 GHz is 2.9 × 10(-3).

  13. A 100-Gb/s noncoherent silicon receiver for PDM-DBPSK/DQPSK signals.

    PubMed

    Klamkin, Jonathan; Gambini, Fabrizio; Faralli, Stefano; Malacarne, Antonio; Meloni, Gianluca; Berrettini, Gianluca; Contestabile, Giampiero; Potì, Luca

    2014-01-27

    An integrated noncoherent silicon receiver for demodulation of 100-Gb/s polarization-division multiplexed differential quadrature phase-shift keying and polarization-division multiplexed differential binary phase-shift keying signals is demonstrated. The receiver consists of a 2D surface grating coupler, four Mach-Zehnder delay interferometers and four germanium balanced photodetectors.

  14. 50 Gb/s hybrid silicon traveling-wave electroabsorption modulator.

    PubMed

    Tang, Yongbo; Chen, Hui-Wen; Jain, Siddharth; Peters, Jonathan D; Westergren, Urban; Bowers, John E

    2011-03-28

    We have demonstrated a traveling-wave electroabsorption modulator based on the hybrid silicon platform. For a device with a 100 μm active segment, the small-signal electro/optical response renders a 3 dB bandwidth of around 42 GHz and its modulation efficiency reaches 23 GHz/V. A dynamic extinction ratio of 9.8 dB with a driving voltage swing of only 2 V was demonstrated at a transmission rate of 50 Gb/s. This represents a significant improvement for modulators compatible with integration of silicon-based photonic integrated circuits.

  15. [The development of neurotoxic agents as chemical weapons during the National Socialist period in Germany].

    PubMed

    López-Muñoz, F; Alamo, C; Guerra, J A; García-García, P

    The discovery and development of the so-called 'nerve agents' (neurotoxic substances to be used as weapons) took place in the Third Reich, largely thanks to the vast amount of progress being made in pharmacology in Germany at that time, both in academic and industrial terms. Furthermore, successive National Socialist governments set up a collaborative network made up of the academia, the chemical industry and military chiefs that also favoured this line of research. The first neurotoxic substance to be incorporated into the category of 'chemical warfare agent' did so almost wholly by chance. As part of the work being carried out on organophosphate-type pesticides and insecticides, Gerald Schrader, a chemist at the I.G. Farben company, synthesised tabun (ethyl N,N-dimethylphosphoramidocyanidate) and an incident involving accidental contamination of laboratory staff with this substance highlighted its potential toxicity. The same group of researchers later synthesised another substance with the same properties, sarin (isopropyl methylphosphonofluoridate). Both agents were studied for use as chemical weapons by Wolfgang Wirth. At the same time, a group led by Richard Kuhn, who won the Nobel Prize in Chemistry in 1938, synthesised pinacolyl methylphosphonofluoridate, otherwise known as soman. Pharmacological studies confirmed that the neurotoxic mechanism of action of these substances was the irreversible inhibition of the enzyme acetylcholinesterase, which is responsible for metabolising acetylcholine. Results also showed that an excess of this neurotransmitter led to a continuous over-stimulation of the cholinergic (nicotinic and muscarinic) receptors, which is what triggers the appearance of the wide range of symptoms of poisoning and their swift fatal effect.

  16. [Study of the relationship between the acupoints of Zhongzhu (TE 3), Yanglingquan (GB 34) and their corresponding cortical areas with the functional MRI].

    PubMed

    Tian, Li-Fang; Zhou, Cheng; Chen, Min; Zou, Ming-Zhu; Yang, Zheng-Han

    2009-07-01

    Using the functional magnetic resonance imaging (fMRI) to observe the distributed characteristic of excited cerebral cortical areas that induced by acupuncture-stimulating the Zhongzhu (TE 3) of the meridian of Hand-Shaoyang and Yanglingquan (GB 34) of the meridian of Foot-Shaoyang, and investigate the central neural mechanism on the effect of meridians and acupoints. Forty-two right handed healthy volunteers were randomly divided into Zhongzhu (TE 3) group and Yanglingquan (GB 34) group. The functional cortical changes during acupuncture-stimulating the Zhongzhu (TE 3) and Yanglingquan (GB 34) were successively scanned with fMRI, and the effected areas were determined through analysing the obtained data with SPM2 software. The main excited areas were bilateral frontal lobes, temporal lobes, cerebellum and occipital lobes successively in Zhongzhu (TE 3) group, and bilateral occipital lobes, cerebellum, frontal lobes and temporal lobes in Yanglingquan (GB 34) group in contrast. Acupuncture-stimulating both Zhongzhu (TE 3) and Yanglingquan (GB 34) can excite bilateral acoustic, visual and somatomotor cortices, which might be the central neural basis for clinical treatment on related diseases.

  17. Noncanonical Gβ Gib2 is a scaffolding protein promoting cAMP signaling through functions of Ras1 and Cac1 proteins in Cryptococcus neoformans.

    PubMed

    Wang, Yanli; Shen, Gui; Gong, Jinjun; Shen, Danyu; Whittington, Amy; Qing, Jiang; Treloar, Joshua; Boisvert, Scott; Zhang, Zhengguang; Yang, Cai; Wang, Ping

    2014-05-02

    Gβ-like/RACK1 functions as a key mediator of various pathways and contributes to numerous cellular functions in eukaryotic organisms. In the pathogenic fungus Cryptococcus neoformans, noncanonical Gβ Gib2 promotes cAMP signaling in cells lacking normal Gpa1 function while displaying versatility in interactions with Gα Gpa1, protein kinase Pkc1, and endocytic intersectin Cin1. To elucidate the Gib2 functional mechanism(s), we demonstrate that Gib2 is required for normal growth and virulence. We show that Gib2 directly binds to Gpa1 and Gγ Gpg1/Gpg2 and that it interacts with phosphodiesterase Pde2 and monomeric GTPase Ras1. Pde2 remains functionally dispensable, but Ras1 is found to associate with adenylyl cyclase Cac1 through the conserved Ras association domain. In addition, the ras1 mutant exhibits normal capsule formation, whereas the ras1 gpa1 mutant displays enhanced capsule formation, and the ras1 gpa1 cac1 mutant is acapsular. Collectively, these findings suggest that Gib2 promotes cAMP levels by relieving an inhibitory function of Ras1 on Cac1 in the absence of Gpa1. In addition, using GST affinity purification combined with mass spectrometry, we identified 47 additional proteins that interact with Gib2. These proteins have putative functions ranging from signal transduction, energy generation, metabolism, and stress response to ribosomal function. After establishing and validating a protein-protein interactive network, we believe Gib2 to be a key adaptor/scaffolding protein that drives the formation of various protein complexes required for growth and virulence. Our study reveals Gib2 as an essential component in deciphering the complexity of regulatory networks that control growth and virulence in C. neoformans.

  18. Identification of lysosomal and extralysosomal globotriaosylceramide (Gb3) accumulations before the occurrence of typical pathological changes in the endomyocardial biopsies of Fabry disease patients.

    PubMed

    Hsu, Ming-Jia; Chang, Fu-Pang; Lu, Yung-Hsiu; Hung, Sheng-Che; Wang, Yu-Chen; Yang, An-Hang; Lee, Han-Jui; Sung, Shih-Hsien; Wang, Yen-Feng; Yu, Wen-Chung; Hsu, Ting-Rong; Huang, Po-Hsun; Chang, Sheng-Kai; Dzhagalov, Ivan; Hsu, Chia-Lin; Niu, Dau-Ming

    2018-06-06

    Evaluation standards and treatment initiation timing have been debated for a long time, particularly for late-onset Fabry disease (FD), because of its slow progression. However, early initiation of enzyme replacement therapy (ERT) for FD could be effective in stabilizing the disease progression and potentially preventing irreversible organ damage. We aimed to examine globotriaosylceramide (Gb3) deposits in patients' endomyocardial biopsies to understand the early pathogenesis of FD cardiomyopathy. Immunofluorescent (IF) staining of Gb3 and lysosomal-associated membrane protein 1 (LAMP-1) was performed on endomyocardial biopsies of patients suspected of Fabry cardiomyopathy who had negative or only slight Gb3 accumulation determined by toluidine blue staining and electron microscopic examination. The IF staining results revealed that all patients examined had abundant Gb3 accumulation in their cardiomyocytes, including the ones who are negative for inclusion bodies. Furthermore, we found that early Gb3 deposits were mostly confined within lysosomes, while they appeared extralysosomally at a later stage. A significant amount of lysosomal Gb3 deposits could be detected by IF staining in cardiac tissue before the formation of inclusion bodies, suggesting the cardiomyocytes might have been experiencing cellular stress and damage early on, before the appearance of typical pathological changes of FD during the disease progression.

  19. Respiratory Complications of Organophosphorus Nerve Agent and Insecticide Poisoning. Implications for Respiratory and Critical Care

    PubMed Central

    Hulse, Elspeth J.; Davies, James O. J.; Simpson, A. John; Sciuto, Alfred M.

    2014-01-01

    Organophosphorus (OP) compound poisoning is a major global public health problem. Acute OP insecticide self-poisoning kills over 200,000 people every year, the majority from self-harm in rural Asia. Highly toxic OP nerve agents (e.g., sarin) are a significant current terrorist threat, as shown by attacks in Damascus during 2013. These anticholinesterase compounds are classically considered to cause an acute cholinergic syndrome with decreased consciousness, respiratory failure, and, in the case of insecticides, a delayed intermediate syndrome that requires prolonged ventilation. Acute respiratory failure, by central and peripheral mechanisms, is the primary cause of death in most cases. However, preclinical and clinical research over the last two decades has indicated a more complex picture of respiratory complications after OP insecticide poisoning, including onset of delayed neuromuscular junction dysfunction during the cholinergic syndrome, aspiration causing pneumonia and acute respiratory distress syndrome, and the involvement of solvents in OP toxicity. The treatment of OP poisoning has not changed over the last 50 years. However, a better understanding of the multiple respiratory complications of OP poisoning offers additional therapeutic opportunities. PMID:25419614

  20. High-quality permanent draft genome sequence of Rhizobium leguminosarum bv. viciae strain GB30; an effective microsymbiont of Pisum sativum growing in Poland

    DOE PAGES

    Mazur, Andrzej; De Meyer, Sofie E.; Tian, Rui; ...

    2015-07-16

    We report that Rhizobium leguminosarum bv. viciae GB30 is an aerobic, motile, Gram-negative, non-spore-forming rod that can exist as a soil saprophyte or as a legume microsymbiont of Pisum sativum. GB30 was isolated in Poland from a nodule recovered from the roots of Pisum sativum growing at Janow. GB30 is also an effective microsymbiont of the annual forage legumes vetch and pea. Here we describe the features of R. leguminosarum bv. viciae strain GB30, together with sequence and annotation. The 7,468,464 bp high-quality permanent draft genome is arranged in 78 scaffolds of 78 contigs containing 7,227 protein-coding genes and 75more » RNA-only encoding genes, and is part of the GEBA-RNB project proposal.« less

  1. High-quality permanent draft genome sequence of Rhizobium leguminosarum bv. viciae strain GB30; an effective microsymbiont of Pisum sativum growing in Poland

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Mazur, Andrzej; De Meyer, Sofie E.; Tian, Rui

    We report that Rhizobium leguminosarum bv. viciae GB30 is an aerobic, motile, Gram-negative, non-spore-forming rod that can exist as a soil saprophyte or as a legume microsymbiont of Pisum sativum. GB30 was isolated in Poland from a nodule recovered from the roots of Pisum sativum growing at Janow. GB30 is also an effective microsymbiont of the annual forage legumes vetch and pea. Here we describe the features of R. leguminosarum bv. viciae strain GB30, together with sequence and annotation. The 7,468,464 bp high-quality permanent draft genome is arranged in 78 scaffolds of 78 contigs containing 7,227 protein-coding genes and 75more » RNA-only encoding genes, and is part of the GEBA-RNB project proposal.« less

  2. Biodegradation of an Organophosphate Chemical Warfare Agent Simulant by Activated Sludge with Varying Solid Retention Times

    DTIC Science & Technology

    2013-03-21

    cause a response in the membrane (Robert, 1992). The transmitter must then be quickly removed to prevent abnormal excitation of the membranes (Robert...Health, 95(8), 1382-1388. Chapman, S., Kadar, T., & Gilat, E. (2006). Seizure duration following sarin exposure affects neuro -inflammatory markers

  3. 112 Gb/s transmission with a directly-modulated laser using FFT-based synthesis of orthogonal PAM and DMT signals.

    PubMed

    Ling, William A; Matsui, Yasuhiro; Daghighian, Henry M; Lyubomirsky, Ilya

    2015-07-27

    We report the experimental measurement of 112 Gb/s transmission back-to-back and through 12 km of S-SMF with a single directly-modulated laser (DML) using the novel modulation format Orthogonal PAM-DMT. This work demonstrates a record DML-based 112 Gb/s receiver sensitivity of -7.1 dBm at a BER of 10(-3), outperforming conventional PAM and DMT by approximately 2.5 dB.

  4. Nonlinear BCJR equalizer for suppression of intrachannel nonlinearities in 40 Gb/s optical communications systems.

    PubMed

    Djordjevic, Ivan B; Vasic, Bane

    2006-05-29

    A maximum a posteriori probability (MAP) symbol decoding supplemented with iterative decoding is proposed as an effective mean for suppression of intrachannel nonlinearities. The MAP detector, based on Bahl-Cocke-Jelinek-Raviv algorithm, operates on the channel trellis, a dynamical model of intersymbol interference, and provides soft-decision outputs processed further in an iterative decoder. A dramatic performance improvement is demonstrated. The main reason is that the conventional maximum-likelihood sequence detector based on Viterbi algorithm provides hard-decision outputs only, hence preventing the soft iterative decoding. The proposed scheme operates very well in the presence of strong intrachannel intersymbol interference, when other advanced forward error correction schemes fail, and it is also suitable for 40 Gb/s upgrade over existing 10 Gb/s infrastructure.

  5. 100 Gb/s optical discrete multi-tone transceivers for intra- and inter-datacenter networks

    NASA Astrophysics Data System (ADS)

    Okabe, Ryo; Tanaka, Toshiki; Nishihara, Masato; Kai, Yutaka; Takahara, Tomoo; Liu, Bo; Li, Lei; Tao, Zhenning; Rasmussen, Jens C.

    2016-03-01

    Discrete multi-tone (DMT) technology is an attractive modulation technology for short-reach application due to its high spectral efficiency and simple configuration. In this paper, we first explain the features of DMT technology then discuss the impact of fiber dispersion and chirp on the frequency responses of the DMT signal and the importance in the relationship between chirp and the optical transmission band. Next, we explain our experiments of 100-Gb/s DMT transmission of 10 km in the O-band using directly modulated lasers for low-cost application. In an inter-datacenter network of more than several tens of kilometers, fiber dispersion mainly limits system performance. We also discuss our experiment of 100-Gb/s DMT transmission up to 100 km in the C-band without a dispersion compensator by using vestigial sideband spectrum shaping and nonlinear compensation.

  6. 40 CFR 180.1111 - Bacillus subtilis GB03; exemption from the requirement of a tolerance.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... FOOD Exemptions From Tolerances § 180.1111 Bacillus subtilis GB03; exemption from the requirement of a... all raw agricultural commodities when used in accordance with good agricultural practices. [73 FR...

  7. Comparative Kinetics and Distribution to Target Tissues of Organophosphates Using Physiologically - Based Pharmacokinetic Modeling

    DTIC Science & Technology

    2008-03-01

    throughout history where nerve agents have been used on human populations, such as the subway bombing in Tokyo and Matsumoto, Japan. Data can be...kidney, fat, diaphragm, arterial blood, venous blood, bronchial passages, and the skin. The remaining tissues will be lumped together as either slowly...were then further developed as a weapon, whose primary effect is on the central nervous system. These agents are tabun, sarin, soman, and VX. They

  8. Modified hybrid subcarrier/amplitude/ phase/polarization LDPC-coded modulation for 400 Gb/s optical transmission and beyond.

    PubMed

    Batshon, Hussam G; Djordjevic, Ivan; Xu, Lei; Wang, Ting

    2010-06-21

    In this paper, we present a modified coded hybrid subcarrier/ amplitude/phase/polarization (H-SAPP) modulation scheme as a technique capable of achieving beyond 400 Gb/s single-channel transmission over optical channels. The modified H-SAPP scheme profits from the available resources in addition to geometry to increase the bandwidth efficiency of the transmission system, and so increases the aggregate rate of the system. In this report we present the modified H-SAPP scheme and focus on an example that allows 11 bits/Symbol that can achieve 440 Gb/s transmission using components of 50 Giga Symbol/s (GS/s).

  9. Bioreactor Performance Parameters for an Industrially-Promising Methanotroph Methylomicrobium buryatense 5GB1

    DOE PAGES

    Gilman, Alexey; Laurens, Lieve M.; Puri, Aaron W.; ...

    2015-11-16

    Methane is a feedstock of interest for the future, both from natural gas and from renewable biogas sources. Methanotrophic bacteria have the potential to enable commercial methane bioconversion to value-added products such as fuels and chemicals. A strain of interest for such applications is Methylomicrobium buryatense 5GB1, due to its robust growth characteristics. But, to take advantage of the potential of this methanotroph, it is important to generate comprehensive bioreactor-based datasets for different growth conditions to compare bioprocess parameters. The datasets of growth parameters, gas utilization rates, and products (total biomass, extracted fatty acids, glycogen, excreted acids) were obtained formore » cultures of M. buryatense 5GB1 grown in continuous culture under methane limitation and O2 limitation conditions. Additionally, experiments were performed involving unrestricted batch growth conditions with both methane and methanol as substrate. All four growth conditions show significant differences. The most notable changes are the high glycogen content and high formate excretion for cells grown on methanol (batch), and high O2:CH4 utilization ratio for cells grown under methane limitation. The results presented here represent the most comprehensive published bioreactor datasets for a gamma-proteobacterial methanotroph. This information shows that metabolism by M. buryatense 5GB1 differs significantly for each of the four conditions tested. O2 limitation resulted in the lowest relative O2 demand and fed-batch growth on methane the highest. Future studies are needed to understand the metabolic basis of these differences. However, these results suggest that both batch and continuous culture conditions have specific advantages, depending on the product of interest.« less

  10. Integration of GB-InSAR, laser scanning and in situ monitoring on the rockslope instability of Mannen/Børa (western Norway)

    NASA Astrophysics Data System (ADS)

    Rouyet, Line; Kristensen, Lene; Derron, Marc-Henri; Michoud, Clément; Harald, Blikra Lars; Michel, Jaboyedoff

    2013-04-01

    This work is part of a master thesis about the use of Ground-Based InSAR for the monitoring of rock instabilities (University of Lausanne in cooperation with the Åknes/Tafjord Early Warning Centre in Norway). Main goals are (1) the evaluation of the GB-InSAR potential to investigate different kinds of instabilities, (2) the combination of data from GB-InSAR, conventional in situ devices and laser scanning to get information about instability behavior and geometry. The rockslope instability of Mannen/Børa is located in Møre of Romsdal County (western Norway). Mannen is a complex rockslide of 15-25 mill. m3 of volume, affecting the left side of the Romsdalen valley. Børa is a large plateau directly located on its south-eastern side and showing signs of activity. In this case, the analysis included GB-InSAR data of 2011 and 2012 campaigns in Børa compared with results of a permanent GB-InSAR in Mannen. The results of continuous monitoring in Mannen (GPS, extensometers, laser-reflectors and tiltmeters) since end of 2009, as well as periodical GPS campaigns on Børa plateau were integrated. The analysis showed a quite regular inter-annual velocity with seasonal effects in Mannen site and a slower movement in Børa. Moreover, it allowed highlighting an area in mid-slope, affected by high variations and periodical inversions of movement in the overlap sector between the two GB-InSAR. The first interpretation of this pattern involves networks of water flow across the slope. A novel point of this site is to have two GB-InSAR systems (one permanent and one temporary) imaging the rockslope with an overlap of views. GB-InSAR results were compared to other types of monitoring data, in terms of spatial coverage (punctual vs. large area), temporal scale (continuous monitoring vs. periodical campaigns) or recorded information (eg. 3D vs. 1D along the LOS). Moreover, a structural geology analysis based on terrestrial and airborne laser scanning data provided information about

  11. Graphene oxide as sensitive layer in Love-wave surface acoustic wave sensors for the detection of chemical warfare agent simulants.

    PubMed

    Sayago, Isabel; Matatagui, Daniel; Fernández, María Jesús; Fontecha, José Luis; Jurewicz, Izabela; Garriga, Rosa; Muñoz, Edgar

    2016-02-01

    A Love-wave device with graphene oxide (GO) as sensitive layer has been developed for the detection of chemical warfare agent (CWA) simulants. Sensitive films were fabricated by airbrushing GO dispersions onto Love-wave devices. The resulting Love-wave sensors detected very low CWA simulant concentrations in synthetic air at room temperature (as low as 0.2 ppm for dimethyl-methylphosphonate, DMMP, a simulant of sarin nerve gas, and 0.75 ppm for dipropylene glycol monomethyl ether, DPGME, a simulant of nitrogen mustard). High responses to DMMP and DPGME were obtained with sensitivities of 3087 and 760 Hz/ppm respectively. Very low limit of detection (LOD) values (9 and 40 ppb for DMMP and DPGME, respectively) were calculated from the achieved experimental data. The sensor exhibited outstanding sensitivity, good linearity and repeatability to all simulants tested. The detection mechanism is here explained in terms of hydrogen bonding formation between the tested CWA simulants and GO. Copyright © 2015 Elsevier B.V. All rights reserved.

  12. Mutations in the conserved carboxy-terminal hydrophobic region of glycoprotein gB affect infectivity of herpes simplex virus.

    PubMed

    Wanas, E; Efler, S; Ghosh, K; Ghosh, H P

    1999-12-01

    Glycoprotein gB is the most highly conserved glycoprotein in the herpesvirus family and plays a critical role in virus entry and fusion. Glycoprotein gB of herpes simplex virus type 1 contains a hydrophobic stretch of 69 aa near the carboxy terminus that is essential for its biological activity. To determine the role(s) of specific amino acids in the carboxy-terminal hydrophobic region, a number of amino acids were mutagenized that are highly conserved in this region within the gB homologues of the family HERPESVIRIDAE: Three conserved residues in the membrane anchor domain, namely A786, A790 and A791, as well as amino acids G743, G746, G766, G770 and P774, that are non-variant in Herpesviridae, were mutagenized. The ability of the mutant proteins to rescue the infectivity of the gB-null virus, K082, in trans was measured by a complementation assay. All of the mutant proteins formed dimers and were incorporated in virion particles produced in the complementation assay. Mutants G746N, G766N, F770S and P774L showed negligible complementation of K082, whereas mutant G743R showed a reduced activity. Virion particles containing these four mutant glycoproteins also showed a markedly reduced rate of entry compared to the wild-type. The results suggest that non-variant residues in the carboxy-terminal hydrophobic region of the gB protein may be important in virus infectivity.

  13. 428-Gb/s single-channel coherent optical OFDM transmission over 960-km SSMF with constellation expansion and LDPC coding.

    PubMed

    Yang, Qi; Al Amin, Abdullah; Chen, Xi; Ma, Yiran; Chen, Simin; Shieh, William

    2010-08-02

    High-order modulation formats and advanced error correcting codes (ECC) are two promising techniques for improving the performance of ultrahigh-speed optical transport networks. In this paper, we present record receiver sensitivity for 107 Gb/s CO-OFDM transmission via constellation expansion to 16-QAM and rate-1/2 LDPC coding. We also show the single-channel transmission of a 428-Gb/s CO-OFDM signal over 960-km standard-single-mode-fiber (SSMF) without Raman amplification.

  14. Chimpanzee GB virus C and GB virus A E2 envelope glycoproteins contain a peptide motif that inhibits human immunodeficiency virus type 1 replication in human CD4+ T-cells

    PubMed Central

    McLinden, James H.; Stapleton, Jack T.; Klinzman, Donna; Murthy, Krishna K.; Chang, Qing; Kaufman, Thomas M.; Bhattarai, Nirjal

    2013-01-01

    GB virus type C (GBV-C) is a lymphotropic virus that can cause persistent infection in humans. GBV-C is not associated with any disease, but is associated with reduced mortality in human immunodeficiency virus type 1 (HIV-1)-infected individuals. Related viruses have been isolated from chimpanzees (GBV-Ccpz) and from New World primates (GB virus type A, GBV-A). These viruses are also capable of establishing persistent infection. We determined the nucleotide sequence encoding the envelope glycoprotein (E2) of two GBV-Ccpz isolates obtained from the sera of captive chimpanzees. The deduced GBV-Ccpz E2 protein differed from human GBV-C by 31 % at the amino acid level. Similar to human GBV-C E2, expression of GBV-Ccpz E2 in a tet-off human CD4+ Jurkat T-cell line significantly inhibited the replication of diverse HIV-1 isolates. This anti-HIV-replication effect of GBV-Ccpz E2 protein was reversed by maintaining cells in doxycycline to reduce E2 expression. Previously, we found a 17 aa region within human GBV-C E2 that was sufficient to inhibit HIV-1. Although GBV-Ccpz E2 differed by 3 aa differences in this region, the chimpanzee GBV-C 17mer E2 peptide inhibited HIV-1 replication. Similarly, the GBV-A peptide that aligns with this GBV-C E2 region inhibited HIV-1 replication despite sharing only 5 aa with the human GBV-C E2 sequence. Thus, despite amino acid differences, the peptide region on both the GBV-Ccpz and the GBV-A E2 protein inhibit HIV-1 replication similar to human GBV-C. Consequently, GBV-Ccpz or GBV-A infection of non-human primates may provide an animal model to study GB virus–HIV interactions. PMID:23288422

  15. A 10 Gb/s laser driver in 130 nm CMOS technology for high energy physics applications

    DOE PAGES

    Zhang, T.; Tavernier, F.; Moreira, P.; ...

    2015-02-19

    The GigaBit Laser Driver (GBLD) is a key on-detector component of the GigaBit Transceiver (GBT) system at the transmitter side. We have developed a 10 Gb/s GBLD (GBLD10) in a 130 nm CMOS technology, as part of the design efforts towards the upgrade of the electrical components of the LHC experiments. The GBLD10 is based on the distributed-amplifier (DA) architecture and achieves data rates up to 10 Gb/s. It is capable of driving VCSELs with modulation currents up to 12 mA. Furthermore, a pre-emphasis function has been included in the proposed laser driver in order to compensate for the capacitivemore » load and channel losses.« less

  16. 50Gb/s PAM-4 oxide VCSEL development progress at Broadcom

    NASA Astrophysics Data System (ADS)

    Wang, Jingyi; Murty, M. V. Ramana; Wang, Charlie; Hui, David; Lehman Harren, Ann; Chang, Hsu-Hao; Feng, Zheng-Wen; Fanning, Thomas R.; Sridhara, Aaditya; Taslim, Sumitro-Joyo; Cai, Xinle; Chu, Jason; Giovane, Laura M.

    2017-02-01

    This paper will review the device design and performance of Broadcom's 50Gb/s PAM-4 VCSEL to enable the next generation of transceivers using a PAM-4 advanced modulation scheme at 25-28 GBd. The VCSEL has been optimized to minimize noise and improve dynamic performance for cleaner eyes. Preliminary wear out lifetime studies indicate that the time to 1% failure exceeds 10 years, making the VCSELs suitable for data communication applications.

  17. Development and validation of KASP markers for the greenbug resistance gene Gb7 and the Hessian fly resistance gene H32 in wheat

    USDA-ARS?s Scientific Manuscript database

    Greenbug (GB, Schizaphis graminum Rondani) and Hessian fly [HF, Mayetiola destructor (Say)] are two major destructive insect pests of wheat (Triticum aestivum L) throughout wheat production regions of the United States and worldwide. GB and HF infestation can significantly reduce grain yield and qu...

  18. Fine genetic mapping of greenbug aphid resistance gene Gb3 in Aegilops tauschii

    USDA-ARS?s Scientific Manuscript database

    The greenbug is a serious aphid pest of wheat and sorghum in the southern High Plains of the US. The greenbug resistant gene Gb3 originated from the goatgrass has shown consistent and durable resistance against prevailing greenbug biotypes in wheat fields for moer than 30 years. Our goal is to clone...

  19. Ion mobility spectrometric analysis of vaporous chemical warfare agents by the instrument with corona discharge ionization ammonia dopant ambient temperature operation.

    PubMed

    Satoh, Takafumi; Kishi, Shintaro; Nagashima, Hisayuki; Tachikawa, Masumi; Kanamori-Kataoka, Mieko; Nakagawa, Takao; Kitagawa, Nobuyoshi; Tokita, Kenichi; Yamamoto, Soichiro; Seto, Yasuo

    2015-03-20

    The ion mobility behavior of nineteen chemical warfare agents (7 nerve gases, 5 blister agents, 2 lachrymators, 2 blood agents, 3 choking agents) and related compounds including simulants (8 agents) and organic solvents (39) was comparably investigated by the ion mobility spectrometry instrument utilizing weak electric field linear drift tube with corona discharge ionization, ammonia doping, purified inner air drift flow circulation operated at ambient temperature and pressure. Three alkyl methylphosphonofluoridates, tabun, and four organophosphorus simulants gave the intense characteristic positive monomer-derived ion peaks and small dimer-derived ion peaks, and the later ion peaks were increased with the vapor concentrations. VX, RVX and tabun gave both characteristic positive monomer-derived ions and degradation product ions. Nitrogen mustards gave the intense characteristic positive ion peaks, and in addition distinctive negative ion peak appeared from HN3. Mustard gas, lewisite 1, o-chlorobenzylidenemalononitrile and 2-mercaptoethanol gave the characteristic negative ion peaks. Methylphosphonyl difluoride, 2-chloroacetophenone and 1,4-thioxane gave the characteristic ion peaks both in the positive and negative ion mode. 2-Chloroethylethylsulfide and allylisothiocyanate gave weak ion peaks. The marker ion peaks derived from two blood agents and three choking agents were very close to the reactant ion peak in negative ion mode and the respective reduced ion mobility was fluctuated. The reduced ion mobility of the CWA monomer-derived peaks were positively correlated with molecular masses among structurally similar agents such as G-type nerve gases and organophosphorus simulants; V-type nerve gases and nitrogen mustards. The slope values of the calibration plots of the peak heights of the characteristic marker ions versus the vapor concentrations are related to the detection sensitivity, and within chemical warfare agents examined the slope values for sarin, soman

  20. Patient-Specific Neutralizing Antibody Responses to Herpes Simplex Virus Are Attributed to Epitopes on gD, gB, or Both and Can Be Type Specific

    PubMed Central

    Huang, Zhen-Yu; Gallagher, John R.; Lin, Yixin; Lou, Huan; Whitbeck, J. Charles; Wald, Anna; Cohen, Gary H.; Eisenberg, Roselyn J.

    2015-01-01

    ABSTRACT Herpes simplex virus 1 (HSV-1) and HSV-2 infect many humans and establish a latent infection in sensory ganglia. Although some infected people suffer periodic recurrences, others do not. Infected people mount both cell-mediated and humoral responses, including the production of virus-neutralizing antibodies (Abs) directed at viral entry glycoproteins. Previously, we examined IgGs from 10 HSV-seropositive individuals; all neutralized virus and were directed primarily against gD or gD+gB. Here, we expand our studies and examine 32 additional sera from HSV-infected individuals, 23 of whom had no recurrent disease. Using an Octet RED96 system, we screened all 32 serum samples directly for both glycoprotein binding and competition with known neutralizing anti-gD and -gB monoclonal Abs (MAbs). On average, the recurrent cohort exhibited higher binding to gD and gB and had higher neutralization titers. There were similar trends in the blocking of MAbs to critical gD and gB epitopes. When we depleted six sera of Abs to specific glycoproteins, we found different types of responses, but always directed primarily at gD and/or gB. Interestingly, in one dual-infected person, the neutralizing response to HSV-2 was due to gD2 and gB2, whereas HSV-1 neutralization was due to gD1 and gB1. In another case, virus neutralization was HSV-1 specific, with the Ab response directed entirely at gB1, despite this serum blocking type-common anti-gD and -gB neutralizing MAbs. These data are pertinent in the design of future HSV vaccines since they demonstrate the importance of both serotypes of gD and gB as immunogens. IMPORTANCE We previously showed that people infected with HSV produce neutralizing Abs directed against gD or a combination of gD+gB (and in one case, gD+gB+gC, which was HSV-1 specific). In this more extensive study, we again found that gD or gD+gB can account for the virus neutralizing response and critical epitopes of one or both of these proteins are represented in

  1. Patient-Specific Neutralizing Antibody Responses to Herpes Simplex Virus Are Attributed to Epitopes on gD, gB, or Both and Can Be Type Specific.

    PubMed

    Cairns, Tina M; Huang, Zhen-Yu; Gallagher, John R; Lin, Yixin; Lou, Huan; Whitbeck, J Charles; Wald, Anna; Cohen, Gary H; Eisenberg, Roselyn J

    2015-09-01

    Herpes simplex virus 1 (HSV-1) and HSV-2 infect many humans and establish a latent infection in sensory ganglia. Although some infected people suffer periodic recurrences, others do not. Infected people mount both cell-mediated and humoral responses, including the production of virus-neutralizing antibodies (Abs) directed at viral entry glycoproteins. Previously, we examined IgGs from 10 HSV-seropositive individuals; all neutralized virus and were directed primarily against gD or gD+gB. Here, we expand our studies and examine 32 additional sera from HSV-infected individuals, 23 of whom had no recurrent disease. Using an Octet RED96 system, we screened all 32 serum samples directly for both glycoprotein binding and competition with known neutralizing anti-gD and -gB monoclonal Abs (MAbs). On average, the recurrent cohort exhibited higher binding to gD and gB and had higher neutralization titers. There were similar trends in the blocking of MAbs to critical gD and gB epitopes. When we depleted six sera of Abs to specific glycoproteins, we found different types of responses, but always directed primarily at gD and/or gB. Interestingly, in one dual-infected person, the neutralizing response to HSV-2 was due to gD2 and gB2, whereas HSV-1 neutralization was due to gD1 and gB1. In another case, virus neutralization was HSV-1 specific, with the Ab response directed entirely at gB1, despite this serum blocking type-common anti-gD and -gB neutralizing MAbs. These data are pertinent in the design of future HSV vaccines since they demonstrate the importance of both serotypes of gD and gB as immunogens. We previously showed that people infected with HSV produce neutralizing Abs directed against gD or a combination of gD+gB (and in one case, gD+gB+gC, which was HSV-1 specific). In this more extensive study, we again found that gD or gD+gB can account for the virus neutralizing response and critical epitopes of one or both of these proteins are represented in sera of naturally

  2. Herpes simplex virus glycoproteins gB and gH function in fusion between the virion envelope and the outer nuclear membrane.

    PubMed

    Farnsworth, Aaron; Wisner, Todd W; Webb, Michael; Roller, Richard; Cohen, Gary; Eisenberg, Roselyn; Johnson, David C

    2007-06-12

    Herpesviruses must traverse the nuclear envelope to gain access to the cytoplasm and, ultimately, to exit cells. It is believed that herpesvirus nucleocapsids enter the perinuclear space by budding through the inner nuclear membrane (NM). To reach the cytoplasm these enveloped particles must fuse with the outer NM and the unenveloped capsids then acquire a second envelope in the trans-Golgi network. Little is known about the process by which herpesviruses virions fuse with the outer NM. Here we show that a herpes simplex virus (HSV) mutant lacking both the two putative fusion glycoproteins gB and gH failed to cross the nuclear envelope. Enveloped virions accumulated in the perinuclear space or in membrane vesicles that bulged into the nucleoplasm (herniations). By contrast, mutants lacking just gB or gH showed only minor or no defects in nuclear egress. We concluded that either HSV gB or gH can promote fusion between the virion envelope and the outer NM. It is noteworthy that fusion associated with HSV entry requires the cooperative action of both gB and gH, suggesting that the two types of fusion (egress versus entry) are dissimilar processes.

  3. Investigation of fiber dispersion impairment in 400GbE discrete multi-tone system for reach enhancement up to 40 km

    NASA Astrophysics Data System (ADS)

    Okabe, Ryo; Tanaka, Toshiki; Nishihara, Masato; Kai, Yutaka; Takahara, Tomoo; Chen, Hao; Yan, Weizhen; Tao, Zhenning; Rasmussen, Jens C.

    2015-01-01

    Discrete multi-tone (DMT) technology is an attractive modulation technique for short reach optical transmission system. One of the main factors that limit system performance is fiber dispersion, which is strongly influenced by the chirp characteristics of transmitters. We investigated the fiber dispersion impairment in a 400GbE (4 × 116.1-Gb/s) DMT system on LAN-WDM grid for reach enhancement up to 40 km through experiments and numerical simulations.

  4. Interaction of organophosphorus compounds with carboxylesterases in the rat.

    PubMed

    Jokanović, M; Kosanović, M; Maksimović, M

    1996-01-01

    Carboxylesterases (CarbE) are involved in detoxication of organophosphorus compounds (OPC) through two mechanisms: hydrolysis of ester bonds in OPC which contain them and binding of OPC at the active site of CarbE which reduces the amount of OPC available for acetylcholinesterase inhibition. This study of the interaction of rat plasma and liver CarbE with dichlorvos, soman and sarin in vitro and in vivo was undertaken in order to contribute to better understanding of the role of CarbE in detoxication of OPC. The results obtained have shown that inhibitory potency (I50) of dichlorvos, sarin and soman towards rat liver CarbE was 0.2 microM, 0.5 microM and 4.5 microM, respectively, for 20-min incubation at 25 degrees C. Second-order rate constants (k(a)) for liver CarbE inhibition were 2.3 x 10(5) M-1 min-1, 6.9 x 10(4) M-1 min-1 and 1.1 x 10(4) M-1 min-1 for dichlorvos, sarin and soman, respectively. The corresponding values for plasma CarbE could not be calculated because of dominant spontaneous reactivation of inhibited CarbE. CarbE inhibited with these OPC in vitro spontaneously reactivate with half-times of 18, 143 and 497 min for sarin, dichlorvos and soman in plasma and 111, 163 and 297 min for sarin, soman and dichlorvos in liver, respectively. These results were also confirmed in experiments in vivo in which rats were subcutaneously treated with 0.5 LD50 of these agents. The half-times of spontaneous reactivation of rat plasma CarbE in vivo were 1.2, 2.0 and 2.7 h for dichlorvos, sarin and soman, respectively. These findings have changed current understanding of the mechanism of interaction of CarbE with OPC and involvement of the enzymes in detoxication of OPC, suggesting an active and important role of the enzymes in metabolic conversions of OPC to their less toxic metabolites.

  5. A novel approach to multihazard modeling and simulation.

    PubMed

    Smith, Silas W; Portelli, Ian; Narzisi, Giuseppe; Nelson, Lewis S; Menges, Fabian; Rekow, E Dianne; Mincer, Joshua S; Mishra, Bhubaneswar; Goldfrank, Lewis R

    2009-06-01

    To develop and apply a novel modeling approach to support medical and public health disaster planning and response using a sarin release scenario in a metropolitan environment. An agent-based disaster simulation model was developed incorporating the principles of dose response, surge response, and psychosocial characteristics superimposed on topographically accurate geographic information system architecture. The modeling scenarios involved passive and active releases of sarin in multiple transportation hubs in a metropolitan city. Parameters evaluated included emergency medical services, hospital surge capacity (including implementation of disaster plan), and behavioral and psychosocial characteristics of the victims. In passive sarin release scenarios of 5 to 15 L, mortality increased nonlinearly from 0.13% to 8.69%, reaching 55.4% with active dispersion, reflecting higher initial doses. Cumulative mortality rates from releases in 1 to 3 major transportation hubs similarly increased nonlinearly as a function of dose and systemic stress. The increase in mortality rate was most pronounced in the 80% to 100% emergency department occupancy range, analogous to the previously observed queuing phenomenon. Effective implementation of hospital disaster plans decreased mortality and injury severity. Decreasing ambulance response time and increasing available responding units reduced mortality among potentially salvageable patients. Adverse psychosocial characteristics (excess worry and low compliance) increased demands on health care resources. Transfer to alternative urban sites was possible. An agent-based modeling approach provides a mechanism to assess complex individual and systemwide effects in rare events.

  6. X-Ray Crystallographic Studies on Acetylcholinesterase and Related Enzymes.

    DTIC Science & Technology

    1999-10-01

    nerve gas intoxication, as well as of insecticide poisoning. Such structures can yield direct information concerning the functional groups and steric...Glyll7His mutant (48). Recent solution of the 3D structures of conjugates of the nerve agents , sarin, soman, DFP and VX with 7cAChE (49, 50) has revealed... pesticides and chemical warfare agents is a topic of considerable environmental and toxicological importance. Hence, a substantial research effort is being

  7. A water balance approach to enhance national (GB) Daily Landslide Hazard Assessments

    NASA Astrophysics Data System (ADS)

    Dijkstra, Tom; Reeves, Helen; Freeborough, Katy; Dashwood, Claire; Pennington, Catherine; Jordan, Hannah; Hobbs, Peter; Richardson, Jennifer; Banks, Vanessa; Cole, Steven; Wells, Steven; Moore, Robert

    2017-04-01

    The British Geological Survey (BGS) is a member of the Natural Hazards Partnership (NHP) and delivers a national (GB) daily landslide hazard assessment (DLHA). The DLHA is based largely on 'expert' driven evaluations of the likelihood of landslides in response to antecedent ground conditions, adverse weather and reported landslide events. It concentrates on shallow translational slides and debris flows - events that most frequently have societal consequences by disrupting transport infrastructure and affecting buildings. Considerable experience with the issuing of DLHAs has been gained since 2012. However, it remains very difficult to appropriately assess changing ground conditions throughout GB even when good quality precipitation forecasts are available. Soil moisture sensors are available, but the network is sparse and not yet capable of covering GB to the detail required to underpin the forecasts. Therefore, we developed an approach where temporal and spatial variations in soil moisture can be obtained from a water balance model, representing processes in the near-surface and configured on a relatively coarse grid of 1 km2. Model outputs are not intended to be relevant to the slope scale. The assumption is that the likelihood of landslides being triggered by rainfall is dependent upon the soil moisture conditions of the near-surface, in combination with how much rain is forecast to occur for the following day. These variables form the basis for establishing thresholds to guide the issuing of DLHA and early warnings. The main aim is to obtain an insight into regional patterns of change and threshold exceedance. The BGS water balance model is still in its infancy and it requires substantial work to fine-tune and validate it. To test the performance of the BGS model we focused on an analysis of Scottish landslides (2004-2015) comprising translational slides and debris flows where the BGS model is conditionally evaluated against the Grid-to-Grid (G2G) Model. G2G is

  8. 5-Gb/s 0.18-μm CMOS 2:1 multiplexer with integrated clock extraction

    NASA Astrophysics Data System (ADS)

    Changchun, Zhang; Zhigong, Wang; Si, Shi; Peng, Miao; Ling, Tian

    2009-09-01

    A 5-Gb/s 2:1 MUX (multiplexer) with an on-chip integrated clock extraction circuit which possesses the function of automatic phase alignment (APA), has been designed and fabricated in SMIC's 0.18 μm CMOS technology. The chip area is 670 × 780 μm2. At a single supply voltage of 1.8 V, the total power consumption is 112 mW with an input sensitivity of less than 50 mV and an output single-ended swing of above 300 mV. The measurement results show that the IC can work reliably at any input data rate between 1.8 and 2.6 Gb/s with no need for external components, reference clock, or phase alignment between data and clock. It can be used in a parallel optic-fiber data interconnecting system.

  9. Annual Report 2013-2014: Theoretical Studies of Nerve Agents Adsorbed on Surfaces

    DTIC Science & Technology

    2014-07-08

    of the solvation of sarin by water are underway. The results should clarify how water affects desorption properties and the extent of solvation of...platinum activated nanocrystalline ZnO thick films. Sensors and Actuators B-Chemical 2012, 161, 372- 380. 5. Bermudez, V. M., Computational Study of...Rauk, A.; Shishkov, I. F.; Vilkov, L. V.; Koehler, K. F.; Kostyanovsky, R. G., DETERMINATION OF THE STRUCTURE AND CHIROPTICAL PROPERTIES OF THE

  10. VCSEL transmission at 10 Gb/s for 20 km single mode fiber WDM-PON without dispersion compensation or injection locking

    NASA Astrophysics Data System (ADS)

    Gibbon, T. B.; Prince, K.; Pham, T. T.; Tatarczak, A.; Neumeyr, C.; Rönneberg, E.; Ortsiefer, M.; Monroy, I. Tafur

    2011-01-01

    Vertical Cavity Surface Emitting Lasers (VCSELs) are extremely cost effective, energy efficient optical sources ideal for passive optical access networks. However, wavelength chirp and chromatic dispersion severely limit VCSEL performance at bit rates of 10 Gb/s and above. We experimentally show how off-center wavelength filtering of the VCSEL spectrum at an array waveguide grating can be used to mitigate the effect of chirp and the dispersion penalty. Transmission at 10 Gb/s VCSEL over 23.6 km of single mode fiber is experimentally demonstrated, with a dispersion penalty of only 2.9 dB. Simulated results are also presented which show that off-center wavelength filtering can extend the 10 Gb/s network reach from 11.7 km to 25.8 km for a 4 dB dispersion penalty. This allows for cheap and simple dispersion mitigation in next generation VCSEL-based optical access networks.

  11. Iron oxide functionalized graphene nano-composite for dispersive solid phase extraction of chemical warfare agents from aqueous samples.

    PubMed

    Chinthakindi, Sridhar; Purohit, Ajay; Singh, Varoon; Tak, Vijay; Goud, D Raghavender; Dubey, D K; Pardasani, Deepak

    2015-05-15

    Present study deals with the preparation and evaluation of graphene based magnetic nano-composite for dispersive solid phase extraction of Chemical Weapons Convention (CWC) relevant chemicals from aqueous samples. Nano-composite, Fe3O4@SiO2-G was synthesized by covalently bonding silica coated Fe3O4 onto the graphene sheets. Nerve agents (NA), Sulfur mustard (SM) and their non-toxic environmental markers were the target analytes. Extraction parameters like amount of sorbent, extraction time and desorption conditions were optimized. Dispersion of 20 milligram of sorbent in 200mL of water sample for 20min. followed by methanol/chloroform extraction produced average to good recoveries (27-94%) of targeted analytes. Recoveries of real agents exhibited great dependency upon sample pH and ionic strength. Sarin produced maximum recovery under mild acidic conditions (56% at pH 5) while VX demanded alkaline media (83% at pH 9). Salts presence in the aqueous samples was found to be advantageous, raising the recoveries to as high as 94% for SM. Excellent limits of detection (LOD) for sulphur mustard and VX (0.11ngmL(-1) and 0.19ngmL(-1) respectively) proved the utility of the developed method for the off-site analysis of CWC relevant chemicals. Copyright © 2015 Elsevier B.V. All rights reserved.

  12. Effectiveness of plasma lyso-Gb3 as a biomarker for selecting high-risk patients with Fabry disease from multispecialty clinics for genetic analysis.

    PubMed

    Maruyama, Hiroki; Miyata, Kaori; Mikame, Mariko; Taguchi, Atsumi; Guili, Chu; Shimura, Masaru; Murayama, Kei; Inoue, Takeshi; Yamamoto, Saori; Sugimura, Koichiro; Tamita, Koichi; Kawasaki, Toshihiro; Kajihara, Jun; Onishi, Akifumi; Sugiyama, Hitoshi; Sakai, Teiko; Murata, Ichijiro; Oda, Takamasa; Toyoda, Shigeru; Hanawa, Kenichiro; Fujimura, Takeo; Ura, Shigehisa; Matsumura, Mimiko; Takano, Hideki; Yamashita, Satoshi; Matsukura, Gaku; Tazawa, Ryushi; Shiga, Tsuyoshi; Ebato, Mio; Satoh, Hiroshi; Ishii, Satoshi

    2018-03-15

    PurposePlasma globotriaosylsphingosine (lyso-Gb3) is a promising secondary screening biomarker for Fabry disease. Here, we examined its applicability as a primary screening biomarker for classic and late-onset Fabry disease in males and females.MethodsBetween 1 July 2014 and 31 December 2015, we screened 2,360 patients (1,324 males) referred from 169 Japanese specialty clinics (cardiology, nephrology, neurology, and pediatrics), based on clinical symptoms suggestive of Fabry disease. We used the plasma lyso-Gb3 concentration, α-galactosidase A (α-Gal A) activity, and analysis of the α-Gal A gene (GLA) for primary and secondary screens, respectively.ResultsOf 8 males with elevated lyso-Gb3 levels (≥2.0 ng ml -1 ) and low α-Gal A activity (≤4.0 nmol h -1  ml -1 ), 7 presented a GLA mutation (2 classic and 5 late-onset). Of 15 females with elevated lyso-Gb3, 7 displayed low α-Gal A activity (5 with GLA mutations; 4 classic and 1 late-onset) and 8 exhibited normal α-Gal A activity (1 with a classic GLA mutation and 3 with genetic variants of uncertain significance).ConclusionPlasma lyso-Gb3 is a potential primary screening biomarker for classic and late-onset Fabry disease probands.Genet Med advance online publication, 15 March 2018; doi:10.1038/gim.2018.31.

  13. The potential of transferrin-pendant-type polyethyleneglycol liposomes encapsulating decahydrodecaborate-{sup 1}B (GB-10) as {sup 1}B-carriers for boron neutron capture therapy

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Masunaga, Shin-ichiro; Kasaoka, Satoshi; Maruyama, Kazuo

    2006-12-01

    Purpose: To evaluate GB-10-encapsulating transferrin (TF)-pendant-type polyethyleneglycol (PEG) liposomes as tumor-targeting {sup 1}B-carriers for boron neutron capture therapy. Methods and Materials: A free mercaptoundecahydrododecaborate-{sup 1}B (BSH) or decahydrodecaborate-{sup 1}B (GB-10) solution, bare liposomes, PEG liposomes, or TF-PEG liposomes were injected into SCC VII tumor-bearing mice, and {sup 1}B concentrations in the tumors and normal tissues were measured by {gamma}-ray spectrometry. Meanwhile, tumor-bearing mice were continuously given 5-bromo-2'-deoxyuridine (BrdU) to label all intratumor proliferating cells, then injected with these {sup 1}B-carriers containing BSH or GB-10 in the same manner. Right after thermal neutron irradiation, the response of quiescent (Q) cells wasmore » assessed in terms of the micronucleus frequency using immunofluorescence staining for BrdU. The frequency in the total tumor cells was determined from the BrdU nontreated tumors. Results: Transferrin-PEG liposomes showed a prolonged retention in blood circulation, low uptake by reticuloendothelial system, and the most enhanced accumulation of {sup 1}B in solid tumors. In general, the enhancing effects were significantly greater in total cells than Q cells. In both cells, the enhancing effects of GB-10-containing {sup 1}B-carriers were significantly greater than BSH-containing {sup 1}B-carriers, whether loaded in free solution or liposomes. In both cells, whether BSH or GB-10 was employed, the greatest enhancing effect was observed with TF-PEG liposomes followed in decreasing order by PEG liposomes, bare liposomes, and free BSH or GB-10 solution. In Q cells, the decrease was remarkable between PEG and bare liposomes. Conclusions: In terms of biodistribution characteristics and tumor cell-killing effect as a whole, including Q cells, GB-10 TF-PEG liposomes were regarded as promising {sup 1}B-carriers.« less

  14. Dynamics of the GB3 loop regions from MD simulation: how much of it is real?

    PubMed

    Li, Tong; Jing, Qingqing; Yao, Lishan

    2011-04-07

    A total of 1.1 μs of molecular dynamics (MD) simulations were performed to study the structure and dynamics of protein GB3. The simulation motional amplitude of the loop regions is generally overestimated in comparison with the experimental backbone N-H order parameters S(2). Two-state behavior is observed for several residues in these regions, with the minor state population in the range of 3-13%. Further inspection suggests that the (φ, ψ) dihedral angles of the minor states deviate from the GB3 experimental values, implying the existence of nonnative states. After fitting the MD trajectories of these residues to the NMR RDCs, the minor state populations are significantly reduced by at least 80%, suggesting that MD simulations are strongly biased toward the minor states, thus overestimating the dynamics of the loop regions. The optimized trajectories produce intra, sequential H(N)-H(α) RDCs and intra (3)J(HNHα) that are not included in the trajectories fitting for these residues that are closer to the experimental data. Unlike GB3, 0.55 μs MD simulations of protein ubiquitin do not show distinctive minor states, and the derived NMR order parameters are better converged. Our findings indicate that the artifacts of the simulations depend on the specific system studied and that one should be cautious interpreting the enhanced dihedral dynamics from long MD simulations.

  15. Distribution of human fecal marker GB-124 bacteriophages in urban sewage and reclaimed water of São Paulo city, Brazil.

    PubMed

    Prado, Tatiana; Bruni, Antônio de Castro; Barbosa, Mikaela Renata Funada; Bonanno, Vilma Marques Santos; Garcia, Suzi Cristina; Sato, Maria Inês Zanoli

    2018-04-01

    Bacteriophages infecting Bacteroides fragilis GB-124 have been described as potential markers of human fecal contamination in water sources. The aim of this study was to evaluate the occurrence of GB-124 phages in raw sewage, secondary effluents and reclaimed water of the São Paulo city using a low-cost microbial source tracking method. Samples were collected monthly from April 2015 to March 2016 in four municipal wastewater treatment plants that operate with activated sludge processes followed by different tertiary treatments (sand-anthracite filtration, membrane bioreactor/reverse osmosis) and final chlorination. GB-124 phages were detected in 100% of the raw sewage samples, with viral loads varying from 7.5 × 10 3 to 1.32 × 10 6 PFU/L. Virus removal efficiency in activated sludge processes ranged from 1.89 to 2.31 log 10 . Frequencies of phage detection were lower in reclaimed water samples (0-22.2%). The results indicated that GB-124 phage could be a complementary low-cost viral marker for the detection of human fecal pollution in waters impacted with urban sewage in this region. However, the datasets of tertiary effluents resulted in several samples with concentrations below the detection limit (DL ≤1 PFU/mL) suggesting the need to obtain analytical methods with lower DL for greater accuracy of negative results.

  16. Effect of different solvents extracts and mode of action of Loktanella spp. Gb03 on toxic dinoflagellate

    NASA Astrophysics Data System (ADS)

    Hameed, Anmar; Usup, Gires; Ahmad, Asmat

    2016-11-01

    This study was aimed to evaluate the algicidal activity of Loktanella sp. Gb-03 bacterial extracts against toxic dinoflagellate, using various polar and non-polar solvents. For this purpose, six different solvent extracts were prepared (i.e. methanol, ethyl acetate, hexane, chloroform, acetonitrile and water). Ratio of 1:100 (v:v) (extract to dinoflagellate culture) of each extract was used for preliminary algicidal activity screening against toxic dinoflagellate Coolia malaynesis. Dinoflagellate cells at the stationary phase (1.0 × 103 cells/ mL) were treated with 1% (v/v) of each extract by using 24-well microplate. The plates were then incubated for 24 hours at dinoflagellate culture condition (under a light intensity of 140 µmol m-2s-1 and 12:12 hours light:dark photoperiod). The result of algicidal activity screening showed that all 6 extracts from Loktanella sp. Gb-03 had different ranges of algicidal activity against the toxic dinoflagellates. Ethyl acetate extract showed the highest activity against C. malaynesis and also other harmful dinoflagellate (Alexandrium sp. Alexandrium leei, Alexandrium affine, Alexandrium tamiyavanichi, Alexandrium tamarense, Gambierdiscus belizeanus, and Ostreopsis). This study was the first to explore the algicidal activity of Loktanella sp. Gb-03 extracts against toxic dinoflagellate with ethyl acetate as the best solvent to extract algicidal active compounds.

  17. 45 Gb/s low complexity optical front-end for soft-decision LDPC decoders.

    PubMed

    Sakib, Meer Nazmus; Moayedi, Monireh; Gross, Warren J; Liboiron-Ladouceur, Odile

    2012-07-30

    In this paper a low complexity and energy efficient 45 Gb/s soft-decision optical front-end to be used with soft-decision low-density parity-check (LDPC) decoders is demonstrated. The results show that the optical front-end exhibits a net coding gain of 7.06 and 9.62 dB for post forward error correction bit error rate of 10(-7) and 10(-12) for long block length LDPC(32768,26803) code. The performance over a hard decision front-end is 1.9 dB for this code. It is shown that the soft-decision circuit can also be used as a 2-bit flash type analog-to-digital converter (ADC), in conjunction with equalization schemes. At bit rate of 15 Gb/s using RS(255,239), LDPC(672,336), (672, 504), (672, 588), and (1440, 1344) used with a 6-tap finite impulse response (FIR) equalizer will result in optical power savings of 3, 5, 7, 9.5 and 10.5 dB, respectively. The 2-bit flash ADC consumes only 2.71 W at 32 GSamples/s. At 45 GSamples/s the power consumption is estimated to be 4.95 W.

  18. Proceedings of the Symposium on Nuclear, Biological and Chemical Contamination Survivability (NBCCS). Developing Contamination-Survivable Defense Systems

    DTIC Science & Technology

    1994-10-01

    34 78.8Sam GA (Tabun) GB (Sarin) True TrAjectory Angle , .Detsetor Window 45.0 d eu l -F None Defined D ( Mustard ) E roun .~uf ac Tg~ 1 S ($I".) Froud...Q0.25 ,10 VX.13--P.C.03 0,2siDS2 rl*40 awwhnm~madth.ii w I 0376 1 101 ɘ.25 1£e10 VN1 PCW po:tS ypd ~ihnja.og.lwum 1[T 03V]60l1-1.51 60.4 VX-14 P.C.0 1ot...The MICAD N8008 Program WWUIat ---- ACALSPAN j C N FUNCTIONAL PERFORMANCE TEST RESULTS block gas 02 aIOLcK3ICAL III VX TOD UASELIPIK POT PS UJIO pir O

  19. A Review of the Literature on the Applications of CW Agents with Recommendations of Further Research on Thickened GD

    DTIC Science & Technology

    1975-12-01

    be effective not only in GD but also in VX, although as much as 30% is needed to form a gel. Wills cites the polymethacrylates : the methyl and ethyl...percutaneous toxicity of additives. Horton et al showed that a 50/50 mixture of GB with hexafluoroglutaric acid , phosgene oxime, or xylene is signifi- cantly...amounts of certain products of the decomposition of the agent, viz pinacolyl hydrogen methylphosphonate and methylphosphonic acid , as much as 40 weeks

  20. Emergency management of chemical weapons injuries.

    PubMed

    Anderson, Peter D

    2012-02-01

    The potential for chemical weapons to be used in terrorism is a real possibility. Classes of chemical weapons include nerve agents, vesicants (blister agents), choking agents, incapacitating agents, riot control agents, blood agents, and toxic industrial chemicals. The nerve agents work by blocking the actions of acetylcholinesterase leading to a cholinergic syndrome. Nerve agents include sarin, tabun, VX, cyclosarin, and soman. The vesicants include sulfur mustard and lewisite. The vesicants produce blisters and also damage the upper airways. Choking agents include phosgene and chlorine gas. Choking agents cause pulmonary edema. Incapacitating agents include fentanyl and its derivatives and adamsite. Riot control agents include Mace and pepper spray. Blood agents include cyanide. The mechanism of toxicity for cyanide is blocking oxidative phosphorylation. Toxic industrial chemicals include agents such as formaldehyde, hydrofluoric acid, and ammonia.

  1. 160-Gb/s all-optical phase-transparent wavelength conversion through cascaded SFG-DFG in a broadband linear-chirped PPLN waveguide.

    PubMed

    Lu, Guo-Wei; Shinada, Satoshi; Furukawa, Hideaki; Wada, Naoya; Miyazaki, Tetsuya; Ito, Hiromasa

    2010-03-15

    We experimentally demonstrated ultra-fast phase-transparent wavelength conversion using cascaded sum- and difference-frequency generation (cSFG-DFG) in linear-chirped periodically poled lithium niobate (PPLN). Error-free wavelength conversion of a 160-Gb/s return-to-zero differential phase-shift keying (RZ-DPSK) signal was successfully achieved. Thanks to the enhanced conversion bandwidth in the PPLN with linear-chirped periods, no optical equalizer was required to compensate the spectrum distortion after conversion, unlike a previous demonstration of 160-Gb/s RZ on-off keying (OOK) using fixed-period PPLN.

  2. Study of multiple unfolding trajectories and unfolded states of the protein GB1 under the physical property space.

    PubMed

    Wang, Jihua; Zhao, Liling; Dou, Xianghua; Zhang, Zhiyong

    2008-06-01

    Forty nine molecular dynamics simulations of unfolding trajectories of the segment B1 of streptococcal protein G (GB1) provide a direct demonstration of the diversity of unfolding pathway and give a statistically utmost unfolding pathway under the physical property space. Twelve physical properties of the protein were chosen to construct a 12-dimensional property space. Then the 12-dimensional property space was reduced to a 3-dimensional principle component property space. Under the property space, the multiple unfolding trajectories look like "trees", which have some common characters. The "root of the tree" corresponds to the native state, the "bole" homologizes the partially unfolded conformations, and the "crown" is in correspondence to the unfolded state. These unfolding trajectories can be divided into three types. The first one has the characters of straight "bole" and "crown" corresponding to a fast two-state unfolding pathway of GB1. The second one has the character of "the standstill in the middle tree bole", which may correspond to a three-state unfolding pathway. The third one has the character of "the circuitous bole" corresponding to a slow two-state unfolding pathway. The fast two-state unfolding pathway is a statistically utmost unfolding pathway or preferred pathway of GB1, which occupies 53% of 49 unfolding trajectories. In the property space all the unfolding trajectories construct a thermal unfolding pathway ensemble of GB1. The unfolding pathway ensemble resembles a funnel that is gradually emanative from the native state ensemble to the unfolded state ensemble. In the property space, the thermal unfolded state distribution looks like electronic cloud in quantum mechanics. The unfolded states of the independent unfolding simulation trajectories have substantial overlaps, indicating that the thermal unfolded states are confined by the physical property values, and the number of protein unfolded state are much less than that was believed before.

  3. Dual Ligand Insertion in gB and gD of Oncolytic Herpes Simplex Viruses for Retargeting to a Producer Vero Cell Line and to Cancer Cells.

    PubMed

    Petrovic, Biljana; Leoni, Valerio; Gatta, Valentina; Zaghini, Anna; Vannini, Andrea; Campadelli-Fiume, Gabriella

    2018-03-15

    Oncolytic viruses gain cancer specificity in several ways. Like the majority of viruses, they grow better in cancer cells that are defective in mounting the host response to viruses. Often, they are attenuated by deletion or mutation of virulence genes that counteract the host response or are naturally occurring oncolytic mutants. In contrast, retargeted viruses are not attenuated or deleted; their cancer specificity rests on a modified, specific tropism for cancer receptors. For herpes simplex virus (HSV)-based oncolytics, the detargeting-retargeting strategies employed so far were based on genetic modifications of gD. Recently, we showed that even gH or gB can serve as retargeting tools. To enable the growth of retargeted HSVs in cells that can be used for clinical-grade virus production, a double-retargeting strategy has been developed. Here we show that several sites in the N terminus of gB are suitable to harbor the 20-amino-acid (aa)-long GCN4 peptide, which readdresses HSV tropism to Vero cells expressing the artificial GCN4 receptor and thus enables virus cultivation in the producer noncancer Vero-GCN4R cell line. The gB modifications can be combined with a minimal detargeting modification in gD, consisting in the deletion of two residues, aa 30 and 38, and replacement of aa 38 with the scFv to human epidermal growth factor receptor 2 (HER2), for retargeting to the cancer receptor. The panel of recombinants was analyzed comparatively in terms of virus growth, cell-to-cell spread, cytotoxicity, and in vivo antitumor efficacy to define the best double-retargeting strategy. IMPORTANCE There is increasing interest in oncolytic viruses, following FDA and the European Medicines Agency (EMA) approval of HSV Oncovex GM-CSF , and, mainly, because they greatly boost the immune response to the tumor and can be combined with immunotherapeutic agents, particularly checkpoint inhibitors. A strategy to gain cancer specificity and avoid virus attenuation is to retarget the

  4. Computational Investigations of Potential Energy Function Development for Metal--Organic Framework Simulations, Metal Carbenes, and Chemical Warfare Agents

    NASA Astrophysics Data System (ADS)

    Cioce, Christian R.

    sigma donates, and subsequent back-bonding occurs into a pi* antibonding orbital. This is a different type of interaction not seen in the three existing classes of metal-carbene complexes, namely Fischer, Schrock, and Grubbs. Finally, the virtual engineering of enhanced chemical warfare agent (CWA) detection systems is discussed. As part of a U.S. Department of Defense supported research project, in silico chemical modifications to a previously synthesized zinc-porphyrin, ZnCS1, were made to attempt to achieve preferential binding of the nerve agent sarin versus its simulant, DIMP (diisopropyl methylphosphonate). Upon modification, a combination of steric effects and induced hydrogen bonding allowed for the selective binding of sarin. The success of this work demonstrates the role that high performance computing can play in national security research, without the associated costs and high security required for experimentation.

  5. 10 Gb/s optical carrier distributed network with W-band (0.1 THz) short-reach wireless communication system

    NASA Astrophysics Data System (ADS)

    Chow, C. W.; Yang, L. G.; Yeh, C. H.; Huang, C. B.; Shi, J. W.; Pan, C. L.

    2012-10-01

    Millimeter-wave (mm-wave) operated in W-band (75 GHz-0.11 THz) is of particular interests, since this frequency band can carry signals at much higher data rates. We demonstrate a 10 Gb/s optical carrier-distributed network with the wireless communication system. The mm-wave signal at carrier frequency of 0.1 THz is generated by a high speed near-ballistic uni-traveling carrier photodiode (NBUTC-PD) based transmitter (Tx), which is optically excited by optical short pulses. The optical pulse source is produced from a self-developed photonic mm-wave waveform generator (PMWG), which allows spectral line-by-line pulse shaping. Hence these optical pulses have high tolerance to fiber chromatic dispersion. The W-band 10 Gb/s wireless data is transmitted and received via a pair of horn antennas. The received 10 Gb/s data is envelope-detected and then used to drive an optical modulator at the remote antenna unit (RAU) to produce the upstream signal sending back to the central office (CO). 20 km single mode fiber (SMF) error free transmission is achieved. Analysis about the optimum repetition rate of the optical pulse source and the transmission performance of the upstream signal are also performed and discussed.

  6. Sports Injury and Illness Epidemiology: Great Britain Olympic Team (TeamGB) surveillance during the Sochi 2014 Winter Olympic Games

    PubMed Central

    Palmer-Green, Debbie; Elliott, Niall

    2015-01-01

    Background Sports injury and illness surveillance is the first step in injury and illness prevention, and is important for the protection of both athlete health and performance in major competitions. Aim To identify the prevalence, severity nature and causes of athlete injuries and illnesses in the Great Britain Olympic Team (TeamGB) during the Sochi 2014 Winter Olympic Games. Methods The observational prospective cohort study followed the Great Britain Injury/Illness Performance Project surveillance methodology and obtained information on injuries and illnesses that occurred during the Games between 30 January and 23 February 2014 in TeamGB athletes (n=56). Results Among the 56 TeamGB athletes, there were 27 injuries and 11 illnesses during the Olympic Games period. This equated to 39% sustaining at least one injury and 18% at least one illness, with an incidence of 48.2 injuries and 19.6 illnesses per 100 athletes, respectively. Of all injuries and illnesses, 9% and 7%, respectively, resulted in time loss. The risk of sustaining an injury was highest for freestyle skiing, skeleton and snowboarding; and lowest for curling, biathlon and Alpine skiing (with no reported injuries); with the lower limb being the most commonly injured location. Respiratory system illnesses were most frequently reported overall, and older female athletes were the ones most affected by illness. Conclusions The risk of injury was double the risk of illness for TeamGB athletes. Overall, the rate of time-loss issues was low. Methodological considerations are important when interpreting data, and prevention strategies should focus on those issues causing the greatest risk, in terms of prevalence and severity, to athlete health and performance. PMID:25425714

  7. A fully-integrated 12.5-Gb/s 850-nm CMOS optical receiver based on a spatially-modulated avalanche photodetector.

    PubMed

    Lee, Myung-Jae; Youn, Jin-Sung; Park, Kang-Yeob; Choi, Woo-Young

    2014-02-10

    We present a fully integrated 12.5-Gb/s optical receiver fabricated with standard 0.13-µm complementary metal-oxide-semiconductor (CMOS) technology for 850-nm optical interconnect applications. Our integrated optical receiver includes a newly proposed CMOS-compatible spatially-modulated avalanche photodetector, which provides larger photodetection bandwidth than previously reported CMOS-compatible photodetectors. The receiver also has high-speed CMOS circuits including transimpedance amplifier, DC-balanced buffer, equalizer, and limiting amplifier. With the fabricated optical receiver, detection of 12.5-Gb/s optical data is successfully achieved at 5.8 pJ/bit. Our receiver achieves the highest data rate ever reported for 850-nm integrated CMOS optical receivers.

  8. Sinkhole monitoring and early warning: An experimental and successful GB-InSAR application

    NASA Astrophysics Data System (ADS)

    Intrieri, Emanuele; Gigli, Giovanni; Nocentini, Massimiliano; Lombardi, Luca; Mugnai, Francesco; Fidolini, Francesco; Casagli, Nicola

    2015-07-01

    Sinkholes represent a natural risk that may hit catastrophically without clearly detectible precursors. However, they are often overlooked by people and administrators. Therefore sinkhole monitoring and associated early warnings constitute important research topics but, currently, only a few papers about sinkhole prediction can be found. In this paper an experience of sinkhole monitoring and early warning with GB-InSAR is described. The latter is a highly precise instrument that is able to produce displacement maps with metric spatial resolution. The described activities were carried out on Elba Island (central Italy), where karstified limestone set off the occurrence of nine sinkholes since 2008, all within less than 3000 m2, causing major damage to an important road and many indirect losses. In 1 year of monitoring two deforming areas were detected, and the point where a sinkhole was about to propagate to the street level was predicted, thus permitting the preventive closure of the road. The deformation area was larger than the hole generated by the sinkhole, thus showing a subsidence that continued for a prolonged time even after the cavity was filled up. The occurrence of a 1.5-m-wide sinkhole, undetected by the GB-InSAR, also showed the lower detection limit of the instrument.

  9. Transmission of 2 × 56 Gb/s PAM-4 signal over 100 km SSMF using 18 GHz DMLs.

    PubMed

    Zhou, Shiwei; Li, Xiang; Yi, Lilin; Yang, Qi; Fu, Songnian

    2016-04-15

    We experimentally demonstrate C-band 2 × 56 Gb/s pulse-amplitude modulation (PAM)-4 signal transmission over 100 km standard single-mode fiber (SSMF) using 18 GHz direct-modulated lasers (DMLs) and direct detection, without inline optical amplifier. A delay interferometer (DI) at the transmitter side is used to extend the transmission reach from 40 to 100 km. A digital Volterra filter at the receiver side is used to mitigate the nonlinear distortions. We obtain an average bit error ratio (BER) of 1.5 × 10(-3) for 2 × 56 Gb/s PAM-4 signal after 100 km SSMF transmission at the optimal input power, which is below the 7% forward error correction (FEC) threshold (3.8 × 10(-3)).

  10. Department of Transportation Inhalation Test of Neutralized GB Hydrolysate in Sprague-Dawley Rats

    DTIC Science & Technology

    2009-05-01

    a product solution resulting from chemically neutralizing GB with aqueous sodium hydroxide ( pH 12.8) as an acceptably treated waste that can be...transported offsite for secondary treatment. An acute inhalation toxicity test was conducted on a ph adjusted hydrolysate solution ( pH 7.8) to assess...day post-exposure period, an endpoint of the DOT study. The product solution from the neutralized ( pH 7.8) hydrolysate does not appear to pose an

  11. Efficacy of antidotes (midazolam, atropine and HI-6) on nerve agent induced molecular and neuropathological changes

    PubMed Central

    2014-01-01

    Background Recent alleged attacks with nerve agent sarin on civilians in Syria indicate their potential threat to both civilian and military population. Acute nerve agent exposure can cause rapid death or leads to multiple and long term neurological effects. The biochemical changes that occur following nerve agent exposure needs to be elucidated to understand the mechanisms behind their long term neurological effects and to design better therapeutic drugs to block their multiple neurotoxic effects. In the present study, we intend to study the efficacy of antidotes comprising of HI-6 (1-[[[4-(aminocarbonyl)-pyridinio]-methoxy]-methyl]-2-[(hydroxyimino) methyl] pyridinium dichloride), atropine and midazolam on soman induced neurodegeneration and the expression of c-Fos, Calpain, and Bax levels in discrete rat brain areas. Results Therapeutic regime consisting of HI-6 (50 mg/kg, i.m), atropine (10 mg/kg, i.m) and midazolam (5 mg/kg, i.m) protected animals against soman (2 × LD50, s.c) lethality completely at 2 h and 80% at 24 h. HI-6 treatment reactivated soman inhibited plasma and RBC cholinesterase up to 40%. Fluoro-Jade B (FJ-B) staining of neurodegenerative neurons showed that soman induced significant necrotic neuronal cell death, which was reduced by this antidotal treatment. Soman increased the expression of neuronal proteins including c-Fos, Bax and Calpain levels in the hippocampus, cerebral cortex and cerebellum regions of the brain. This therapeutic regime also reduced the soman induced Bax, Calpain expression levels to near control levels in the different brain regions studied, except a mild induction of c-Fos expression in the hippocampus. Conclusion Rats that received antidotal treatment after soman exposure were protected from mortality and showed reduction in the soman induced expression of c-Fos, Bax and Calpain and necrosis. Results highlight the need for timely administration of better antidotes than standard therapy in order to prevent the

  12. Efficacy of antidotes (midazolam, atropine and HI-6) on nerve agent induced molecular and neuropathological changes.

    PubMed

    RamaRao, Golime; Afley, Prachiti; Acharya, Jyothiranjan; Bhattacharya, Bijoy Krishna

    2014-04-04

    Recent alleged attacks with nerve agent sarin on civilians in Syria indicate their potential threat to both civilian and military population. Acute nerve agent exposure can cause rapid death or leads to multiple and long term neurological effects. The biochemical changes that occur following nerve agent exposure needs to be elucidated to understand the mechanisms behind their long term neurological effects and to design better therapeutic drugs to block their multiple neurotoxic effects. In the present study, we intend to study the efficacy of antidotes comprising of HI-6 (1-[[[4-(aminocarbonyl)-pyridinio]-methoxy]-methyl]-2-[(hydroxyimino) methyl] pyridinium dichloride), atropine and midazolam on soman induced neurodegeneration and the expression of c-Fos, Calpain, and Bax levels in discrete rat brain areas. Therapeutic regime consisting of HI-6 (50 mg/kg, i.m), atropine (10 mg/kg, i.m) and midazolam (5 mg/kg, i.m) protected animals against soman (2×LD50, s.c) lethality completely at 2 h and 80% at 24 h. HI-6 treatment reactivated soman inhibited plasma and RBC cholinesterase up to 40%. Fluoro-Jade B (FJ-B) staining of neurodegenerative neurons showed that soman induced significant necrotic neuronal cell death, which was reduced by this antidotal treatment. Soman increased the expression of neuronal proteins including c-Fos, Bax and Calpain levels in the hippocampus, cerebral cortex and cerebellum regions of the brain. This therapeutic regime also reduced the soman induced Bax, Calpain expression levels to near control levels in the different brain regions studied, except a mild induction of c-Fos expression in the hippocampus. Rats that received antidotal treatment after soman exposure were protected from mortality and showed reduction in the soman induced expression of c-Fos, Bax and Calpain and necrosis. Results highlight the need for timely administration of better antidotes than standard therapy in order to prevent the molecular and biochemical changes and

  13. Sports injury and illness epidemiology: Great Britain Olympic Team (TeamGB) surveillance during the Sochi 2014 Winter Olympic Games.

    PubMed

    Palmer-Green, Debbie; Elliott, Niall

    2015-01-01

    Sports injury and illness surveillance is the first step in injury and illness prevention, and is important for the protection of both athlete health and performance in major competitions. To identify the prevalence, severity nature and causes of athlete injuries and illnesses in the Great Britain Olympic Team (TeamGB) during the Sochi 2014 Winter Olympic Games. The observational prospective cohort study followed the Great Britain Injury/Illness Performance Project surveillance methodology and obtained information on injuries and illnesses that occurred during the Games between 30 January and 23 February 2014 in TeamGB athletes (n=56). Among the 56 TeamGB athletes, there were 27 injuries and 11 illnesses during the Olympic Games period. This equated to 39% sustaining at least one injury and 18% at least one illness, with an incidence of 48.2 injuries and 19.6 illnesses per 100 athletes, respectively. Of all injuries and illnesses, 9% and 7%, respectively, resulted in time loss. The risk of sustaining an injury was highest for freestyle skiing, skeleton and snowboarding; and lowest for curling, biathlon and Alpine skiing (with no reported injuries); with the lower limb being the most commonly injured location. Respiratory system illnesses were most frequently reported overall, and older female athletes were the ones most affected by illness. The risk of injury was double the risk of illness for TeamGB athletes. Overall, the rate of time-loss issues was low. Methodological considerations are important when interpreting data, and prevention strategies should focus on those issues causing the greatest risk, in terms of prevalence and severity, to athlete health and performance. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

  14. CryoSat SAR/SARin Level1b products: assessment of BaselineC and improvements towards BaselineD

    NASA Astrophysics Data System (ADS)

    Scagliola, Michele; Fornari, Marco; Bouffard, Jerome; Parrinello, Tommaso

    2017-04-01

    CryoSat was launched on the 8th April 2010 and is the first European ice mission dedicated to the monitoring of precise changes in the thickness of polar ice sheets and floating sea ice. Cryosat carries an innovative radar altimeter called the Synthetic Aperture Interferometric Altimeter (SIRAL), that transmits pulses at a high pulse repetition frequency thus making the received echoes phase coherent and suitable for azimuth processing. This allows to reach a significantly improved along track resolution with respect to traditional pulse-width limited altimeters. CryoSat is the first altimetry mission operating in SAR mode and continuous improvements in the Level1 Instrument Processing Facility (IPF1) are being identified, tested and validated in order to improve the quality of the Level1b products. The current IPF, Baseline C, was released in operation in April 2015 and the second CryoSat reprocessing campaign was jointly initiated, taking benefit of the upgrade implemented in the IPF1 processing chain but also of some specific configurations for the calibration corrections. In particular, the CryoSat Level1b BaselineC products generated in the framework of the second reprocessing campaign include refined information for what concerns the mispointing angles and the calibration corrections. This poster will thus detail thus the evolutions that are currently planned for the CryoSat BaselineD SAR/SARin Level1b products and the corresponding quality improvements that are expected.

  15. VCSEL-based optical transceiver module operating at 25 Gb/s and using a single CMOS IC

    NASA Astrophysics Data System (ADS)

    Afriat, Gil; Horwitz, Lior; Lazar, Dror; Issachar, Assaf; Pogrebinsky, Alexander; Ran, Adee; Shoor, Ehud; Bar, Roi; Saba, Rushdy

    2012-01-01

    We present here a low cost, small form factor, optical transceiver module composed of a CMOS IC transceiver, 850 nm emission wavelength VCSEL modulated at 25 Gb/s, and an InGaAs/InP PIN Photo Diode (PD). The transceiver IC is fabricated in a standard 28 nm CMOS process and integrates the analog circuits interfacing the VCSEL and PD, namely the VCSEL driver and Transimpedance Amplifier (TIA), as well as all other required transmitter and receiver circuits like Phase Locked Loop (PLL), Post Amplifier and Clock & Data Recovery (CDR). The transceiver module couples into a 62.5/125 um multi-mode (OM1) TX/RX fiber pair via a low cost plastic cover realizing the transmitter and receiver lens systems and demonstrates BER < 10-12 at the 25 Gb/s data rate over a distance of 3 meters. Using a 50/125 um laser optimized multi-mode fiber (OM3), the same performance was achieved over a distance of 30 meters.

  16. Safety and efficacy of a cytomegalovirus glycoprotein B (gB) vaccine in adolescent girls: A randomized clinical trial.

    PubMed

    Bernstein, David I; Munoz, Flor M; Callahan, S Todd; Rupp, Richard; Wootton, Susan H; Edwards, Kathryn M; Turley, Christine B; Stanberry, Lawrence R; Patel, Shital M; Mcneal, Monica M; Pichon, Sylvie; Amegashie, Cyrille; Bellamy, Abbie R

    2016-01-12

    Cytomegalovirus (CMV) is a leading cause of congenital infection and an important target for vaccine development. CMV seronegative girls between 12 and 17 years of age received CMV glycoprotein B (gB) vaccine with MF59 or saline placebo at 0, 1 and 6 months. Blood and urine were collected throughout the study for evidence of CMV infection based on PCR and/or seroconversion to non-vaccine CMV antigens. 402 CMV seronegative subjects were vaccinated (195 vaccine, 207 placebo). The vaccine was generally well tolerated, although local and systemic adverse events were significantly more common in the vaccine group. The vaccine induced gB antibody in all vaccine recipients with a gB geometric mean titer of 13,400 EU; 95%CI 11,436, 15,700, after 3 doses. Overall, 48 CMV infections were detected (21 vaccine, 27 placebo). In the per protocol population (124 vaccine, 125 placebo) vaccine efficacy was 43%; 95%CI: -36; 76, p=0.20. The most significant difference was after 2 doses, administered as per protocol; vaccine efficacy 45%, 95%CI: -9; 72, p=0.08. The vaccine was safe and immunogenic. Although the efficacy did not reach conventional levels of significance, the results are consistent with a previous study in adult women (Pass et al. N Engl J Med 2009;360:1191) using the same formulation. Copyright © 2015 Elsevier Ltd. All rights reserved.

  17. Enhanced 40 and 80 Gb/s wavelength conversion using a rectangular shaped optical filter for both red and blue spectral slicing.

    PubMed

    Raz, O; Herrera, J; Dorren, H J S

    2009-02-02

    By using a tunable filter with tunability of both bandwidth and wavelength and a very sharp filter roll-off, considerable improvement of all optical Wavelength Conversion, based on Cross Gain and Phase Modulation effects in a Semiconductor Optical Amplifier and spectral slicing, is shown. At 40 Gb/s slicing of blue spectral components is shown to result in a small penalty of 0.7 dB, with a minimal eye broadening, and at 80 Gb/s the low demonstrated 0.5 dB penalty is a dramatic improvement over previously reported wavelength converters using the same principal. Additionally, we give for the first time quantitative results for the case of red spectral slicing at 40 Gb/s which we found to have only 0.5 dB penalty and a narrower time response, as anticipated by previously published theoretical papers. Numerical simulations for the dependence of the eye opening on the filter characteristics highlight the importance of the combination of a sharp filter roll-off and a broad passband.

  18. Evaluation of Bacteroides fragilis GB-124 bacteriophages as novel human-associated faecal indicators in the United States

    EPA Science Inventory

    Phages infecting human-associated Bacteroides fragilis (GB-124 phages) have been employed in the European Union (EU) to identify human fecal pollution, but their utility for U.S. was unclear. Primary sewage effluent samples were collected seasonally from seven wastewater treatme...

  19. [Construction and eukaryotic expression of PVAX1-hPV58mE6E7fcGB composite gene vaccine].

    PubMed

    Wang, He; Yu, Jiyun; Li, Li

    2013-10-01

    To construct and express a composite gene vaccine for human papillomavirus 58(HPV58)-associated cervical cancer, we inserted HPV58mE6E7 fusion gene into pCI-Fc-GPI eukaryotic expression vector, constructing a recombinant plasmid named pCI-sig-HPV58mE6E7-Fc-GPI. Then we further inserted fragment of sig-HPV58mE6E7Fc-GPI into the novel vaccine vector PVAX1-IRES-GM/B7, constructing PVAX1-HPV58mE6E7FcGB composite gene vaccine. PVAX1-HPV58mE6E7FcGB vaccine was successfully constructed and identified by restriction endonuclease and sequencing analysis. Eukaryotic expression of fusion antigen sig-HPV58mE6E7-Fc-GPI and molecular ad-juvant GM-CSF and B7. 1 were proved to be realized at the same time by flow cytometry and immunofluorescence. So PVAX1-HPV58mE6E7FcGB can be taken as a candidate of therapeutic vaccine for HPV58-associated tumors and their precancerous transformations.

  20. Draft Genome Sequence of Pantoea ananatis GB1, a Plant-Growth-Promoting Hydrocarbonoclastic Root Endophyte, Isolated at a Diesel Fuel Phytoremediation Site Planted with Populus.

    PubMed

    Gkorezis, Panagiotis; Van Hamme, Jonathan D; Bottos, Eric M; Thijs, Sofie; Balseiro-Romero, Maria; Monterroso, Carmela; Kidd, Petra Suzan; Rineau, Francois; Weyens, Nele; Vangronsveld, Jaco

    2016-02-25

    We report the 4.76-Mb draft genome of Pantoea ananatis GB1, a Gram-negative bacterium of the family Enterobacteriaceae, isolated from the roots of poplars planted for phytoremediation of a diesel-contaminated plume at the Ford Motor Company site in Genk, Belgium. Strain GB1 promotes plant growth in various hosts and metabolizes hydrocarbons. Copyright © 2016 Gkorezis et al.

  1. 1.25-3.125 Gb/s per user PON with RSOA as phase modulator for statistical wavelength ONU

    NASA Astrophysics Data System (ADS)

    Chu, Guang Yong; Polo, Victor; Lerín, Adolfo; Tabares, Jeison; Cano, Iván N.; Prat, Josep

    2015-12-01

    We report a new scheme to support, cost efficiently, ultra-dense wavelength division multiplexing (UDWDM) for optical access networks. As validating experiment, we apply phase modulation of a reflective semiconductor optical amplifier (RSOA) at the ONU with a single DFB, and simplified coherent receiver at OLT for upstream. We extend the limited 3-dB modulation bandwidth of available uncooled To-can packaged RSOA (~400 MHz) and operate it at 3.125 Gb/s with the optimal performance for phase modulation using small and large signal measurement characteristics. The optimal condition is selected at input power of 0 dBm, with 70 mA bias condition. The sensitivities at 3.125 Gb/s (at BER=10-3) for heterodyne and intradyne detection reach -34.3 dBm and -38.8 dBm, respectively.

  2. A Toolkit For CryoSat Investigations By The ESRIN EOP-SER Altimetry Team

    NASA Astrophysics Data System (ADS)

    Dinardo, Salvatore; Bruno, Lucas; Benveniste, Jerome

    2013-12-01

    The scope of this work is to feature the new tool for the exploitation of the CryoSat data, designed and developed entirely by the Altimetry Team at ESRIN EOP-SER (Earth Observation - Exploitation, Research and Development). The tool framework is composed of two separate components: the first one handles the data collection and management, the second one is the processing toolkit. The CryoSat FBR (Full Bit Rate) data is downlinked uncompressed from the satellite, containing un-averaged individual echoes. This data is made available in the Kiruna CalVal server in a 10 day rolling archive. Daily at ESRIN all the CryoSat FBR data, in SAR and SARin Mode, are downloaded (around 30 Gigabytes) catalogued and archived in local ESRIN EOP-SER workstations. As of March 2013, the total amount of FBR data is over 9 Terabytes, with CryoSat acquisition dates spanning January 2011 to February 2013 (with some gaps). This archive was built by merging partial datasets available at ESTEC and NOAA, that have been kindly made available for EOP-SER team. The on-demand access to this low level data is restricted to expert users with validated ESA P.I. credentials. Currently the main users of the archiving functionality are the team members of the Project CP4O (STSE- CryoSat Plus for Ocean), CNES and NOAA. The second component of the service is the processing toolkit. On the EOP-SER workstations there is internally and independently developed software that is able to process the FBR data in SAR/SARin mode to generate multi-looked echoes (Level 1B) and subsequently able to re-track them in SAR and SARin mode (Level 2) over open ocean, exploiting the SAMOSA model and other internally developed models. The processing segment is used for research & development scopes, supporting the development contracts awarded confronting the deliverables to ESA, on site demonstrations/training to selected users, cross- comparison against third part products (CLS/CNES CPP Products for instance), preparation

  3. Atomistic simulation of the coupled adsorption and unfolding of protein GB1 on the polystyrenes nanoparticle surface

    NASA Astrophysics Data System (ADS)

    Xiao, HuiFang; Huang, Bin; Yao, Ge; Kang, WenBin; Gong, Sheng; Pan, Hai; Cao, Yi; Wang, Jun; Zhang, Jian; Wang, Wei

    2018-03-01

    Understanding the processes of protein adsorption/desorption on nanoparticles' surfaces is important for the development of new nanotechnology involving biomaterials; however, an atomistic resolution picture for these processes and for the simultaneous protein conformational change is missing. Here, we report the adsorption of protein GB1 on a polystyrene nanoparticle surface using atomistic molecular dynamic simulations. Enabled by metadynamics, we explored the relevant phase space and identified three protein states, each involving both the adsorbed and desorbed modes. We also studied the change of the secondary and tertiary structures of GB1 during adsorption and the dominant interactions between the protein and surface in different adsorption stages. The results we obtained from simulation were found to be more adequate and complete than the previous one. We believe the model presented in this paper, in comparison with the previous ones, is a better theoretical model to understand and explain the experimental results.

  4. GBLD10+: a compact low-power 10 Gb/s VCSEL driver

    DOE PAGES

    Zhang, T.; Kulis, S.; Gui, P.; ...

    2016-01-13

    We report the design and implementation of the GBLD10+, a low-power 10 Gb/s VCSEL driver for High Energy Physics (HEP) applications. With new circuit techniques, the driver consumes only 31 mW and occupies a small area of 400 μm × 1750 μm including the IO PADs and sealrings. These characteristics allow for multiple GBLD10+ ICs to be assembled side by side in a compact module, with each one directly wire bonded to one VCSEL diode. Finally, this makes the GBLD10+ a suitable candidate for the Versatile Link PLUS (VL +) project, offering flexibility in configuring multiple transmitters and receivers.

  5. Dual Split Protein-Based Fusion Assay Reveals that Mutations to Herpes Simplex Virus (HSV) Glycoprotein gB Alter the Kinetics of Cell-Cell Fusion Induced by HSV Entry Glycoproteins

    PubMed Central

    Atanasiu, Doina; Saw, Wan Ting; Gallagher, John R.; Hannah, Brian P.; Matsuda, Zene; Whitbeck, J. Charles; Cohen, Gary H.

    2013-01-01

    Herpes simplex virus (HSV) entry and cell-cell fusion require glycoproteins gD, gH/gL, and gB. We propose that receptor-activated changes to gD cause it to activate gH/gL, which then triggers gB into an active form. We employed a dual split-protein (DSP) assay to monitor the kinetics of HSV glycoprotein-induced cell-cell fusion. This assay measures content mixing between two cells, i.e., fusion, within the same cell population in real time (minutes to hours). Titration experiments suggest that both gD and gH/gL act in a catalytic fashion to trigger gB. In fact, fusion rates are governed by the amount of gB on the cell surface. We then used the DSP assay to focus on mutants in two functional regions (FRs) of gB, FR1 and FR3. FR1 contains the fusion loops (FL1 and FL2), and FR3 encompasses the crown at the trimer top. All FL mutants initiated fusion very slowly, if at all. However, the fusion rates caused by some FL2 mutants increased over time, so that total fusion by 8 h looked much like that of the WT. Two distinct kinetic patterns, “slow and fast,” emerged for mutants in the crown of gB (FR3), again showing differences in initiation and ongoing fusion. Of note are the fusion kinetics of the gB syn mutant (LL871/872AA). Although this mutant was originally included as an ongoing high-rate-of-fusion control, its initiation of fusion is so rapid that it appears to be on a “hair trigger.” Thus, the DSP assay affords a unique way to examine the dynamics of HSV glycoprotein-induced cell fusion. PMID:23946457

  6. Assessment and self-assessment of the pharmacists' competencies using the global competency framework (GbCF) in Serbia.

    PubMed

    Stojkov, Svetlana; Tadić, Ivana; Crnjanski, Tatjana; Krajnović, Dušanka

    2016-09-01

    Pharmacists' competence represents a dynamic framework of knowledge, skills and abilities to carry out tasks, and it reflects on improving the quality of life and on patients’ health. One of the documents for the Evaluation and Competency Development of Pharmacists is the Global Competency Framework (GbCF). The aim of this study was to implement the GBCF document into Serbian pharmacies, to perform assessment and self assessment of the competencies. The assessment and self-assessment of pharmacists’ competencies were performed during the period 2012−13 year in eight community pharmacy chains, in seven cities in Serbia. For assessment and self-assessment of pharmacists competencies the GbCF model was applied, which was adjusted to pharmaceutical practice and legislation in Serbia. External assessment was conducted by teams of pharmacists using the structured observation of the work of pharmacists during regular working hours. Evaluated pharmacists filled out the questionnaire about demographic indicators about the pharmacist and the pharmacy where they work. A total of 123 pharmacists were evaluated. Pharmacists’ Professional Competency Cluster (KK1) had the lowest score (average value 2.98), while the cluster Management and Organizational Competency (KK2) had the highest score (average value 3.15). The competence Recognition of the Diagnosis and Patient Counseling (K8), which belonged to the cluster KK1, had the lowest score (average value for assessment and self-assessment were 2.09, and 2.34, respectively) among the all evaluated competencies. GbCF might be considered as an instrument for the competencies' evaluation/selfevaluation and their improvement, accordingly.

  7. Cascaded all-optical operations in a hybrid integrated 80-Gb/s logic circuit.

    PubMed

    LeGrange, J D; Dinu, M; Sochor, T; Bollond, P; Kasper, A; Cabot, S; Johnson, G S; Kang, I; Grant, A; Kay, J; Jaques, J

    2014-06-02

    We demonstrate logic functionalities in a high-speed all-optical logic circuit based on differential Mach-Zehnder interferometers with semiconductor optical amplifiers as the nonlinear optical elements. The circuit, implemented by hybrid integration of the semiconductor optical amplifiers on a planar lightwave circuit platform fabricated in silica glass, can be flexibly configured to realize a variety of Boolean logic gates. We present both simulations and experimental demonstrations of cascaded all-optical operations for 80-Gb/s on-off keyed data.

  8. Sensitive detection of chemical agents and toxic industrial chemicals using active open-path FTIRs

    NASA Astrophysics Data System (ADS)

    Walter, William T.

    2004-03-01

    Active open-path FTIR sensors provide more sensitive detection of chemical agents than passive FTIRs, such as the M21 RSCAAL and JSLSCAD, and at the same time identify and quantify toxic industrial chemicals (TIC). Passive FTIRs are bistatic sensors relying on infrared sources of opportunity. Utilization of earth-based sources of opportunity limits the source temperatures available for passive chemical-agent FTIR sensors to 300° K. Active FTIR chemical-agent sensors utilize silicon carbide sources, which can be operated at 1500° K. The higher source temperature provides more than an 80-times increase in the infrared radiant flux emitted per unit area in the 7 to 14 micron spectral fingerprint region. Minimum detection limits are better than 5 μgm/m3 for GA, GB, GD, GF and VX. Active FTIR sensors can (1) assist first responders and emergency response teams in their assessment of and reaction to a terrorist threat, (2) provide information on the identification of the TIC present and their concentrations and (3) contribute to the understanding and prevention of debilitating disorders analogous to the Gulf War Syndrome for military and civilian personnel.

  9. International Aid and Development: Hearing Multilingualism, Learning from Intercultural Encounters in the History of OxfamGB

    ERIC Educational Resources Information Center

    Footitt, Hilary

    2017-01-01

    This article explores the context of intercultural relations in the field of international aid and development. Examining the activities of a large UK-based transnational NGO (OxfamGB) through a detailed reading of its own 60-year-long archived story, the article seeks to reimagine the "contact zones" of aid and development as…

  10. Proposed scheme for parallel 10Gb/s VSR system and its verilog HDL realization

    NASA Astrophysics Data System (ADS)

    Zhou, Yi; Chen, Hongda; Zuo, Chao; Jia, Jiuchun; Shen, Rongxuan; Chen, Xiongbin

    2005-02-01

    This paper proposes a novel and innovative scheme for 10Gb/s parallel Very Short Reach (VSR) optical communication system. The optimized scheme properly manages the SDH/SONET redundant bytes and adjusts the position of error detecting bytes and error correction bytes. Compared with the OIF-VSR4-01.0 proposal, the scheme has a coding process module. The SDH/SONET frames in transmission direction are disposed as follows: (1) The Framer-Serdes Interface (FSI) gets 16×622.08Mb/s STM-64 frame. (2) The STM-64 frame is byte-wise stripped across 12 channels, all channels are data channels. During this process, the parity bytes and CRC bytes are generated in the similar way as OIF-VSR4-01.0 and stored in the code process module. (3) The code process module will regularly convey the additional parity bytes and CRC bytes to all 12 data channels. (4) After the 8B/10B coding, the 12 channels is transmitted to the parallel VCSEL array. The receive process approximately in reverse order of transmission process. By applying this scheme to 10Gb/s VSR system, the frame size in VSR system is reduced from 15552×12 bytes to 14040×12 bytes, the system redundancy is reduced obviously.

  11. A cost-effective 25-Gb/s EML TOSA using all-in-one FPCB wiring and metal optical bench.

    PubMed

    Han, Young-Tak; Kwon, Oh-Kee; Lee, Dong-Hun; Lee, Chul-Wook; Leem, Young-Ahn; Shin, Jang-Uk; Park, Sang-Ho; Baek, Yongsoon

    2013-11-04

    We present a cost-effective 25-Gb/s electro-absorption modulator integrated laser (EML) transmitter optical sub-assembly (TOSA) using all-in-one flexible printed circuit board (FPCB) wiring and a metal optical bench (MOB). For a low cost and high bandwidth TOSA, internal and external wirings and feed-through of the TOSA to transmit radio-frequency (RF) signal are configured all-in-one using the FPCB. The FPCB is extended from an exterior of the TOSA package up to an EML chip inside the package through the slit formed on a rear sidewall of the package and die-bonded on the MOB. The EML TOSA shows a modulated output power of more than 3.5 dBm and a clear eye pattern with a dynamic extinction ratio of ~8.4 dB at a data rate of 25.78 Gb/s.

  12. Transmission of 51.56-Gb/s OOK signal using 1.55-μm directly modulated laser and duobinary electrical equalizer.

    PubMed

    Bae, S H; Kim, Hoon; Chung, Y C

    2016-10-03

    We demonstrate the transmission of 51.56-Gb/s on-off keying (OOK) signals generated by using a 1.55-μm directly modulated laser (DML) over 15-km long standard single-mode fiber. In this experiment, a duobinary electrical equalizer based on a finite-impulse-response filter is used at the receiver to increase the dispersion-limited transmission distance. We evaluate the performances of the 51.56-Gb/s OOK signals with respect to the transmission distance by using the frequency response analysis of the proposed system. This result is used to explain why it is effective to utilize the duobinary equalization (instead of binary equalization) for increasing the transmission distance.

  13. Investigation of the persistence of nerve agent degradation analytes on surfaces through wipe sampling and detection with ultrahigh performance liquid chromatography-tandem mass spectrometry.

    PubMed

    Willison, Stuart A

    2015-01-20

    The persistence of chemical warfare nerve agent degradation analytes on surfaces is important, from indicating the presence of nerve agent on a surface to guiding environmental restoration of a site after a release. Persistence was investigated for several chemical warfare nerve agent degradation analytes on indoor surfaces and presents an approach for wipe sampling of surfaces, followed by wipe extraction and liquid chromatography-tandem mass spectrometry detection. Commercially available wipe materials were investigated to determine optimal wipe recoveries. Tested surfaces included porous/permeable (vinyl tile, painted drywall, and wood) and largely nonporous/impermeable (laminate, galvanized steel, and glass) surfaces. Wipe extracts were analyzed by ultrahigh performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). UPLC provides a separation of targeted degradation analytes in addition to being nearly four times faster than high-performance liquid chromatography, allowing for greater throughput after a large-scale contamination incident and subsequent remediation events. Percent recoveries from nonporous/impermeable surfaces were 60-103% for isopropyl methylphosphonate (IMPA), GB degradate; 61-91% for ethyl methylphosphonate (EMPA), VX degradate; and 60-98% for pinacolyl methylphosphonate (PMPA), GD degradate. Recovery efficiencies for methyl phosphonate (MPA), nerve agent degradate, and ethylhydrogen dimethylphosphonate (EHDMAP), GA degradate, were lower, perhaps due to matrix effects. Diisopropyl methylphosphonate, GB impurity, was not recovered from surfaces. The resulting detection limits for wipe extracts were 0.065 ng/cm(2) for IMPA, 0.079 ng/cm(2) for MPA, 0.040 ng/cm(2) for EMPA, 0.078 ng/cm(2) for EHDMAP, and 0.013 ng/cm(2) for PMPA. The data indicate that laboratories may hold wipe samples for up to 30 days prior to analysis. Target analytes were observed to persist on surfaces for at least 6 weeks.

  14. Reliable Wide-Area Wavelength Division Multiplexing Passive Optical Network Accommodating Gigabit Ethernet and 10-Gb Ethernet Services

    NASA Astrophysics Data System (ADS)

    Nakamura, Hirotaka; Suzuki, Hiro; Kani, Jun-Ichi; Iwatsuki, Katsumi

    2006-05-01

    This paper proposes and demonstrates a reliable wide-area wavelength-division-multiplexing passive optical network (WDM-PON) with a wavelength-shifted protection scheme. This protection scheme utilizes the cyclic property of 2 × N athermal arrayed-waveguide grating and two kinds of wavelength allocations, each of which is assigned for working and protection, respectively. Compared with conventional protection schemes, this scheme does not need a 3-dB optical coupler, thus leading to ensure the large loss budget that is suited for wide-area WDM-PONs. It also features a passive access node and does not have a protection function in the optical network unit (ONU). The feasibility of the proposed scheme is experimentally confirmed by the carrier-distributed WDM-PON with gigabit Ethernet interface (GbE-IF) and 10-GbE-IF, in which the ONU does not employ a light source, and all wavelengths for upstream signals are centralized and distributed from the central office.

  15. A verotoxin 1 B subunit-lambda CRO chimeric protein specifically binds both DNA and globotriaosylceramide (Gb(3)) to effect nuclear targeting of exogenous DNA in Gb(3) positive cells.

    PubMed

    Facchini, L M; Lingwood, C A

    2001-09-10

    Inefficient nuclear incorporation of foreign DNA remains a critical roadblock in the development of effective nonviral gene delivery systems. DNA delivered by traditional protocols remains within endosomal/lysosomal vesicles, or is rapidly degraded in the cytoplasm. Verotoxin I (VT), an AB(5) subunit toxin produced by enterohaemorrhagic Escherichia coli, binds to the cell surface glycolipid, globotriaosylceramide (Gb(3)) and is internalized into preendosomes. VT is then retrograde transported to the Golgi, endoplasmic reticulum (ER), and nucleus of highly VT-sensitive cells. We have utilized this nuclear targeting of VT to design a unique delivery system which transports exogenous DNA via vesicular traffic to the nucleus. The nontoxic VT binding subunit (VTB) was fused to the lambda Cro DNA-binding repressor, generating a 14-kDa VTB-Cro chimera. VTB-Cro binds specifically via the Cro domain to a 25-bp DNA fragment containing the consensus Cro operator. VTB-Cro demonstrates simultaneous specific binding to Gb(3). Treatment of Vero cells with fluorescent-labeled Cro operator DNA in the presence of VTB-Cro, results in DNA internalization to the Golgi, ER, and nucleus, whereas fluorescent DNA alone is incorporated poorly and randomly within the cytoplasm. VTB-Cro mediated nuclear DNA transport is prevented by brefeldin A, consistent with Golgi/ER intracellular routing. Pretreatment with filipin had no effect, indicating that caveoli are not involved. This novel VTB-Cro shuttle protein may find practical applications in the fields of intracellular targeting, gene delivery, and gene therapy. Copyright 2001 Academic Press.

  16. Monolithically integrated quantum dot optical gain modulator with semiconductor optical amplifier for 10-Gb/s photonic transmission

    NASA Astrophysics Data System (ADS)

    Yamamoto, Naokatsu; Akahane, Kouichi; Umezawa, Toshimasa; Kawanishi, Tetsuya

    2015-03-01

    Short-range interconnection and/or data center networks require high capacity and a large number of channels in order to support numerous connections. Solutions employed to meet these requirements involve the use of alternative wavebands to increase the usable optical frequency range. We recently proposed the use of the T- and O-bands (Thousand band: 1000-1260 nm, Original band: 1260-1360 nm) as alternative wavebands because large optical frequency resources (>60 THz) can be easily employed. In addition, a simple and compact Gb/s-order high-speed optical modulator is a critical photonic device for short-range communications. Therefore, to develop an optical modulator that acts as a highfunctional photonic device, we focused on the use of self-assembled quantum dots (QDs) as a three-dimensional (3D) confined structure because QD structures are highly suitable for realizing broadband optical gain media in the T+O bands. In this study, we use the high-quality broadband QD optical gain to develop a monolithically integrated QD optical gain modulator (QD-OGM) device that has a semiconductor optical amplifier (QD-SOA) for Gb/s-order highspeed optical data generation in the 1.3-μm waveband. The insertion loss of the device can be compensated through the SOA, and we obtained an optical gain change of up to ~7 dB in the OGM section. Further, we successfully demonstrate a 10-Gb/s clear eye opening using the QD-OGM/SOA device with a clock-data recovery sequence at the receiver end. These results suggest that the monolithic QD-EOM/SOA is suitable for increasing the number of wavelength channels for smart short-range communications.

  17. A Direct Comparison of the MM-GB/SA Scoring Procedure and Free-Energy Perturbation Calculations Using Carbonic Anhydrase as a Test Case: Strengths and Pitfalls of Each Approach.

    PubMed

    Guimarães, Cristiano R W

    2011-07-12

    MM-GB/SA scoring and free energy perturbation (FEP) calculations have emerged as reliable methodologies to understand structural and energetic relationships to binding. In spite of successful applications to elucidate the structure-activity relationships for few pairs of ligands, the reality is that the performance of FEP calculations has rarely been tested for more than a handful of compounds. In this work, a series of 13 benzene sulfonamide inhibitors of carbonic anhydrase with binding free energies determined by isothermal titration calorimetry was selected as a test case. R(2) values of 0.70, 0.71, and 0.49 with the experiment were obtained with MM-GB/SA and FEP simulations run with MCPRO+ and Desmond, respectively. All methods work well, but the results obtained with Desmond are inferior to MM-GB/SA and MCPRO+. The main contrast between the methods is the level of sampling, ranging from full to restricted flexibility to single conformation for the complexes in Desmond, MCPRO+, and MM-GB/SA, respectively. The current and historical results obtained with MM-GB/SA qualify this approach as a more attractive alternative for rank-ordering; it can achieve equivalent or superior predictive accuracy and handle more structurally dissimilar ligands at a fraction of the computational cost of the rigorous free-energy methods. As for the large theoretical dynamic range for the binding energies, that seems to be a direct result of the degree of sampling in the simulations since MCPRO+ as well as MM-GB/SA are plagued by this. Van't Hoff analysis for selected pairs of ligands suggests that the wider scoring spread is not only affected by missing entropic contributions due to restricted sampling but also exaggerated enthalpic separation between the weak and potent compounds caused by diminished shielding of electrostatic interactions, thermal effects, and protein relaxation/strain.

  18. Optimization of Quantitative Proteomics Using 2-Dimensional Difference Gel Electrophoresis to Characterize Molecular Mechanisms of Chemical Warfare Nerve Agent Exposure in the Rat Brain

    DTIC Science & Technology

    2010-11-01

    minced finely with scissors, and transferred to a pre-cooled hand-held glass dounce homogenizer. The pestle was passed through the dounce until the...Nakajima, Sarin experiences in Japan : acute toxicity and long-term effects. Journal of the Neurological Sciences, 2006. 249(1): p. 76-85. 9. Shih, T.-M

  19. Upgrade of an optical network unit in a 40 Gb/s time and wavelength-division multiplexed passive optical network using an upstream tunable colorless laser

    NASA Astrophysics Data System (ADS)

    Bindhaiq, Salem; Supa'at, Abu Sahmah M.; Zulkifli, Nadiatulhuda; Shaddad, Redhwan Q.; Mataria, Abdallah

    2014-07-01

    A high data transmission rate is the main requirement for next-generation telecommunication networks. A design for a 40 Gb/s time and wavelength-division multiplexed passive optical network (TWDM-PON) for next-generation passive optical network stage 2 is presented. The use of a modulated grating Y-branch (MG-Y) laser is proposed as an upstream tunable colorless laser source to upgrade the optical network unit. The electronically tuned MG-Y externally modulated laser with a 10 Gb/s modulation rate is applied to a TWDM-PON and presented across a 3.2-nm tuning range. The performance of the proposed laser is analyzed in terms of bit error rate, eye diagram, and optical signal-to-noise ratio. The proposed TWDM-PON achieved an aggregated data rate of 40 Gb/s along 40 km of bidirectional fiber at a 1:128 splitting ratio without amplification and dispersion compensation.

  20. Engineered bi-histidine metal chelation sites map the structure of the mechanical unfolding transition state of an elastomeric protein domain GB1.

    PubMed

    Shen, Tao; Cao, Yi; Zhuang, Shulin; Li, Hongbin

    2012-08-22

    Determining the structure of the transition state is critical for elucidating the mechanism behind how proteins fold and unfold. Due to its high free energy, however, the transition state generally cannot be trapped and studied directly using traditional structural biology methods. Thus, characterizing the structure of the transition state that occurs as proteins fold and unfold remains a major challenge. Here, we report a novel (to our knowledge) method that uses engineered bi-histidine (bi-His) metal-binding sites to directly map the structure of the mechanical unfolding transition state of proteins. This method is adapted from the traditional ψ-value analysis, which uses engineered bi-His metal chelation sites to probe chemical (un)folding transition-state structure. The φ(M2+)(U)-value is defined as ΔΔG(‡-N)/ΔΔG(U-N), which is the energetic effects of metal chelation by the bi-His site on the unfolding energy barrier (ΔG(‡-N)) relative to its thermodynamic stability (ΔG(U-N)) and can be used to obtain information about the transition state in the mutational site. As a proof of principle, we used the small protein GB1 as a model system and set out to map its mechanical unfolding transition-state structure. Using single-molecule atomic force microscopy and spectrofluorimetry, we directly quantified the effect of divalent metal ion binding on the mechanical unfolding free energy and thermodynamic stability of GB1, which allowed us to quantify φ(M2+)(U)-values for different sites in GB1. Our results enabled us to map the structure of the mechanical unfolding transition state of GB1. Within GB1's mechanical unfolding transition state, the interface between force-bearing β-strands 1 and 4 is largely disrupted, and the first β-hairpin is partially disordered while the second β-hairpin and the α-helix remain structured. Our results demonstrate the unique application of ψ-value analysis in elucidating the structure of the transition state that occurs

  1. 12.5 Gb/s multi-channel broadcasting transmission for free-space optical communication based on the optical frequency comb module.

    PubMed

    Tan, Jun; Zhao, Zeping; Wang, Yuehui; Zhang, Zhike; Liu, Jianguo; Zhu, Ninghua

    2018-01-22

    A wide-spectrum, ultra-stable optical frequency comb (OFC) module with 100 GHz frequency intervals based on a quantum dot mode locked (QDML) laser is fabricated by our lab, and a scheme with 12.5 Gb/s multi-channel broadcasting transmission for free-space optical (FSO) communication is proposed based on the OFC module. The output power of the OFC is very stable, with the specially designed circuit and the flatness of the frequency comb over the span of 6 nm, which can be limited to 1.5 dB. Four channel wavelengths are chosen to demonstrate one-to-many channels for FSO communication, like optical wireless broadcast. The outdoor experiment is established to test the bit error rate (BER) and eye diagrams with 12.5 Gb/s on-off keying (OOK). The indoor experiment is used to test the highest traffic rate, which is up to 21 Gb/s for one-hop FSO communication. To the best of our knowledge, this scheme is the first to propose the realization of one-to-many broadcasting transmission for FSO communication based on the OFC module. The advantages of integration, miniaturization, channelization, low power consumption, and unlimited bandwidth of one-to-many broadcasting communication scheme, shows promising results on constructing the future space-air-ground-ocean (SAGO) FSO communication networks.

  2. Mitigation of Rayleigh crosstalk using noise suppression technique in 10-Gb/s REAM-SOA.

    PubMed

    Jeong, Jong Sool; Kim, Hyun-Soo; Choi, Byung-Seok; Kim, Dong Churl; Kim, Ki-Soo; Park, Mi-Ran; Kwon, O-Kyun

    2012-11-19

    We demonstrate a mitigation of Rayleigh back-scattering (RBS) impact in 10-Gb/s reflective electroabsorption modulator monolithically integrated with semiconductor optical amplifier (REAM-SOA). The technique is based on the intensity-noise suppression of the centralized incoherent seed-light, which enables smooth evolution of deployed DWDM applications. We exhibit the power penalty of less than 1 dB at the large RBS crosstalk value of about 8 dB when the optical power of seed-light is lowered about -10 dBm.

  3. Reference quality assembly of the 3.5 Gb genome of Capsicum annuum form a single linked-read library

    USDA-ARS?s Scientific Manuscript database

    Linked-Read sequencing technology has recently been employed successfully for de novo assembly of multiple human genomes, however the utility of this technology for complex plant genomes is unproven. We evaluated the technology for this purpose by sequencing the 3.5 gigabase (Gb) diploid pepper (Cap...

  4. Simultaneous DPSK demodulation and chirp management using delay interferometer in symmetric 40-Gb/s capability TWDM-PON system.

    PubMed

    Bi, Meihua; Xiao, Shilin; He, Hao; Yi, Lilin; Li, Zhengxuan; Li, Jun; Yang, Xuelin; Hu, Weisheng

    2013-07-15

    We propose a symmetric 40-Gb/s aggregate rate time and wavelength division multiplexed passive optical network (TWDM-PON) system with the capability of simultaneous downstream differential phase shift keying (DPSK) signal demodulation and upstream signal chirp management based on delay interferometer (DI). With the bi-pass characteristic of DI, we experimentally demonstrate the bidirectional transmission of signals at 10-Gb/s per wavelength, and achieve negligible power penalties after 50-km single mode fiber (SMF). For the uplink transmission with DI, a ~11-dB optical power budget improvement at a bit error ratio of 1e-3 is obtained and the extinction ratio (ER) of signal is also improved from 3.4 dB to 13.75 dB. Owing to this high ER, the upstream burst-mode transmitting is successfully presented in term of time-division multiplexing. Moreover, in our experiment, a ~38-dB power budget is obtained to support 256 users with 50-km SMF transmission.

  5. Experimental study of PAM-4, CAP-16, and DMT for 100 Gb/s short reach optical transmission systems.

    PubMed

    Zhong, Kangping; Zhou, Xian; Gui, Tao; Tao, Li; Gao, Yuliang; Chen, Wei; Man, Jiangwei; Zeng, Li; Lau, Alan Pak Tao; Lu, Chao

    2015-01-26

    Advanced modulation formats combined with digital signal processing and direct detection is a promising way to realize high capacity, low cost and power efficient short reach optical transmission system. In this paper, we present a detailed investigation on the performance of three advanced modulation formats for 100 Gb/s short reach transmission system. They are PAM-4, CAP-16 and DMT. The detailed digital signal processing required for each modulation format is presented. Comprehensive simulations are carried out to evaluate the performance of each modulation format in terms of received optical power, transmitter bandwidth, relative intensity noise and thermal noise. The performance of each modulation format is also experimentally studied. To the best of our knowledge, we report the first demonstration of a 112 Gb/s transmission over 10km of SSMF employing single band CAP-16 with EML. Finally, a comparison of computational complexity of DSP for the three formats is presented.

  6. Designing a Successful Acupuncture Treatment Program for Gulf War Illness

    DTIC Science & Technology

    2017-10-01

    altered white matter microstructural integrity in organophosphate (OP) pesticide, sarin nerve agent and pyridogstigmine bromide (PB) anti-nerve gas... Integration for chronic low back pain" PI: Jacobson (3/4/ 2011-6/21/2013) N = 46. Study Site: Spaulding Rehabilitation Hospital (SRH). In this cohort... integration (SI) plus outpatient rehabili- tation (OR) versus OR alone. The details of the study are described in a recent publication (Jacobson et al

  7. Replication-defective lymphocytic choriomeningitis virus vectors expressing guinea pig cytomegalovirus gB and pp65 homologs are protective against congenital guinea pig cytomegalovirus infection.

    PubMed

    Cardin, Rhonda D; Bravo, Fernando J; Pullum, Derek A; Orlinger, Klaus; Watson, Elizabeth M; Aspoeck, Andreas; Fuhrmann, Gerhard; Guirakhoo, Farshad; Monath, Thomas; Bernstein, David I

    2016-04-12

    Congenital cytomegalovirus infection can be life-threatening and often results in significant developmental deficits and/or hearing loss. Thus, there is a critical need for an effective anti-CMV vaccine. To determine the efficacy of replication-defective lymphocytic choriomeningitis virus (rLCMV) vectors expressing the guinea pig CMV (GPCMV) antigens, gB and pp65, in the guinea pig model of congenital CMV infection. Female Hartley strain guinea pigs were divided into three groups: Buffer control group (n = 9), rLCMV-gB group (n = 11), and rLCMV-pp65 (n = 11). The vaccines were administered three times IM at 1.54 × 10(6)FFU per dose at 21-day intervals. At two weeks after vaccination, the female guinea pigs underwent breeding. Pregnant guinea pigs were challenged SQ at ∼ 45-55 days of gestation with 1 × 10(5)PFU of GPCMV. Viremia in the dams, pup survival, weights of pups at delivery, and viral load in both dam and pup tissues were determined. Pup survival was significantly increased in the LCMV-gB vaccine group. There was 23% pup mortality in the gB vaccine group (p = 0.044) and 26% pup mortality in the pp65 vaccine group (p = 0.054) compared to 49% control pup mortality. The gB vaccine induced high levels of gB binding and detectable neutralizing antibodies, reduced dam viremia, and significantly reduced viral load in dam tissues compared to control dams (p < 0.03). Reduced viral load and transmission in pups born to gB-vaccinated dams was observed compared to pups from pp65-vaccinated or control dams. The rLCMV-gB vaccine significantly improved pup survival and also increased pup weights and gestation time. The gB vaccine was also more effective at decreasing viral load in dams and pups and limiting congenital transmission. Thus, rLCMV vectors that express CMV antigens may be an effective vaccine strategy for congenital CMV infection. Copyright © 2016 Elsevier Ltd. All rights reserved.

  8. Emergency management of the 2010 Mt. Rotolon landslide by means of a local scale GB-InSAR monitoring system

    NASA Astrophysics Data System (ADS)

    Frodella, William; Pazzi, Veronica; Morelli, Stefano; Salvatici, Teresa; Fanti, Riccardo

    2017-04-01

    Between October 31st and November 2nd 2010 the whole Veneto region (north-eastern Italy) was hit by heavy and persistent rainfall, which diffusely triggered floods and slope failures. In this framework on November 4th 2010 a detrital mass, approximately 225.000 m3 in volume, detached from the lowermost sector of the Mt. Rotolon landslide cover (located in the Vicentine Pre-Alps, upper Agno River Valley), channelizing within the Rotolon Creek riverbed and evolving into a highly mobile debris flow. The latter phenomena, characterized by a 3 km travel distance, damaged many hydraulic works, putting at high risk bridges and local roads located along the creek banks, together with the population of both the town of Recoaro Terme and the villages of Maltaure, Turcati and Parlati. Starting from the beginning of the emergency phase, the Civil Protection system was activated, involving the National Civil Protection Department, Veneto Region and local administrations personnel and technicians, as well as research centers. On December 8th 2010 a local scale monitoring system, based on a ground based interferometric radar (GB-InSAR), was implemented in order to evaluate the slope deformation pattern evolution in correspondence of the debris flow detachment sector, with the final aim of assessing the landslide residual risk and manage the emergency phase. Accurate geomorphological field surveys were also carried out, in order to study the landslide morphological features as to improve the radar data interpretation. The radar system acquired in continuous GB-InSAR data, such as displacement maps and time series of 10 selected monitoring points, which were uploaded via LAN network on a dedicated Web-based interface, shared with the technical stakeholders and decision makers involved in the emergency management and allowing for a near real time data routine visualization. This paper describes the outcomes of a 2 years GB-InSAR monitoring campaign (December 2010-November 2012

  9. Simple Laser Communications Terminal for Downlink from Earth Orbit at Rates Exceeding 10 Gb/s

    NASA Technical Reports Server (NTRS)

    Kovalik, Joseph M.; Hemmati, Hamid; Biswas, Abhijit; Roberts, William T.

    2013-01-01

    A compact, low-cost laser communications transceiver was prototyped for downlinking data at 10 Gb/s from Earth-orbiting spacecraft. The design can be implemented using flight-grade parts. With emphasis on simplicity, compactness, and light weight of the flight transceiver, the reduced-complexity design and development approach involves: 1. A high-bandwidth coarse wavelength division multiplexed (CWDM) (4 2.5 or 10-Gb/s data-rate) downlink transmitter. To simplify the system, emphasis is on the downlink. Optical uplink data rate is modest (due to existing and adequate RF uplink capability). 2. Highly simplified and compact 5-cm diameter clear aperture optics assembly is configured to single transmit and receive aperture laser signals. About 2 W of 4-channel multiplexed (1,540 to 1,555 nm) optically amplified laser power is coupled to the optical assembly through a fiber optic cable. It contains a highly compact, precision-pointing capability two-axis gimbal assembly to coarse point the optics assembly. A fast steering mirror, built into the optical path of the optical assembly, is used to remove residual pointing disturbances from the gimbal. Acquisition, pointing, and tracking are assisted by a beacon laser transmitted from the ground and received by the optical assembly, which will allow transmission of a laser beam. 3. Shifting the link burden to the ground by relying on direct detection optical receivers retrofitted to 1-m-diameter ground telescopes. 4. Favored mass and volume reduction over power-consumption reduction. The two major variables that are available include laser transmit power at either end of the link, and telescope aperture diameter at each end of the link. Increased laser power is traded for smaller-aperture diameters. 5. Use of commercially available spacequalified or qualifiable components with traceability to flight qualification (i.e., a flight-qualified version is commercially available). An example is use of Telecordia-qualified fiber

  10. Analysis of Chemical Warfare Agents: General Overview, LC-MS Review, In-House LC-ESI-MS Methods and Open Literature Bibliography

    DTIC Science & Technology

    2006-03-01

    Kurdish village. Most recently, sarin was released by the Aum Shinrikyo cult in the Tokyo underground transit system resulting in thousands seeking...a) Nerve (reacts irreversibly with cholinesterase which results in acetylcholine accumulation, continual stimulation of the body’s nervous system ...18]. The specificity of product scanning with moderate sector resolution, as well as the specificity of ammonia CI, were demonstrated with a hybrid

  11. Neurosciences and research on chemical weapons of mass destruction in Nazi Germany.

    PubMed

    Schmaltz, Florian

    2006-09-01

    As a side-product of industrial research, new chemical nerve agents (Tabun, Sarin, Soman) superior to those available to the Allied Forces were discovered in Nazi Germany. These agents were never used by Germany, even though they were produced at a large scale. This article explores the toxicological and physiological research into the mechanisms of action of these novel nerve agents, and the emergence of military research objectives in neurophysiological and neurotoxicological research. Recently declassified Allied military intelligence files document secret nerve agent research, leading to intensified research on anticholinesterase agents in the peripheral and the central nervous system. The article discusses the involvement of IG Farben scientists, educational, medical and military institutions, and of Nobel Prize laureate Richard Kuhn, director of the Kaiser Wilhelm Institute for Medical Research.

  12. Evaluation of methylated soy oil and water-based formulations of Bacillus thuringiensis var. Israelensis and Golden Bear Oil (GB-1111) against anopheles quadrimaculatus larvae in small rice plots.

    PubMed

    Dennett, J A; Lampman, R L; Novak, R J; Meisch, M V

    2000-12-01

    The efficacy of formulations containing methylated soybean oil (MSO) alone and with technical-grade Bacillus thuringiensis var. israelensis (Bti) were compared to Golden Bear Oil (GB-1111) and a water-based Bti formulation against 3rd- to 4th-stage Anopheles quadrimaculatus larvae confined to sentinel cages in small rice plots. Three replicates each of MSO with 2% Pyroter added as a surfactant (MSO + PYR), MSO with 2% Pyroter and 4 g of Bti technical powder (MSO + PYR + Bti), GB-1111, a water-based formulation with 4 g of Bti technical powder (Bti + water), and untreated controls were performed. Mosquito larvae were introduced on the 1st day of treatment and at 4 days posttreatment. Mortality was recorded at 24 and 48 h posttreatment for the 1st installation and at 5 days posttreatment for the 2nd installation. The Bti + water formulation provided 71% control and the MSO + PYR + Bti formulation achieved 64% control, whereas MSO + PYR and GB-1111 produced 16 and 18% control, respectively, at 24 h posttreatment. With the exception of MSO + PYR + Bti, which decreased by 2%, the mean percent control increased slightly at 48h posttreatment across remaining treatments, with Bti + water obtaining 72% control. This was significantly higher than GB-1111, which achieved 23% control at 48 h posttreatment. The MSO + PYR and MSO + PYR + Bti formulations yielded 56 and 62% control, respectively, during the same interval and were not significantly different from one another. Formulations containing MSO + PYR exhibited delayed activity similar to GB-1111, with all formulations except MSO + PYR + Bti providing greatest control at 48 h posttreatment. Both MSO formulations (MSO + PYR + Bti and MSO + PYR) were statistically comparable to Bti + water and GB-1111, respectively, at 24 and 48 h posttreatment. None of the formulations exhibited a residual activity adequate enough to control An. quadrimaculatus larvae for up to 5 days.

  13. The effects of battlefield contaminants on PEMFC performance

    NASA Astrophysics Data System (ADS)

    Moore, Jon M.; Adcock, Paul L.; Lakeman, J. Barry; Mepsted, Gary O.

    The effects of contaminants on the performance of an air breathing proton exchange membrane fuel cell (PEMFC) were investigated, by introduction into oxidant air fed to the fuel cell. The impact of the common pollutants sulphur dioxide, nitrogen dioxide, carbon monoxide, propane and benzene and the chemical warfare agents, sarin, sulphur mustard, cyanogen chloride (CNCl) and hydrogen cyanide (HCN) were assessed. At the concentrations studied, the common contaminants had either no effect on performance or caused a reversible depression. The chemical warfare agents all seriously compromised the performance of the fuel cells in an irreversible manner.

  14. Long-term health experience of jet engine manufacturing workers: VI: incidence of malignant central nervous system neoplasms in relation to estimated workplace exposures.

    PubMed

    Marsh, Gary M; Youk, Ada O; Buchanich, Jeanine M; Xu, Hui; Downing, Sarah; Kennedy, Kathleen J; Esmen, Nurtan A; Hancock, Roger P; Lacey, Steven E; Fleissner, Mary Lou

    2013-06-01

    To determine whether glioblastoma (GB) incidence rates among jet engine manufacturing workers were associated with specific chemical or physical exposures. Subjects were 210,784 workers employed from 1952 to 2001. We conducted a cohort incidence study and two nested case-control studies with focus on the North Haven facility where we previously observed a not statistically significant overall elevation in GB rates. We estimated individual-level exposure metrics for 11 agents. In the total cohort, none of the agent metrics considered was associated with increased GB risk. The GB incidence rates in North Haven were also not related to workplace exposures, including the "blue haze" exposure unique to North Haven. If not due to chance alone, GB rates in North Haven may reflect external occupational factors, nonoccupational factors, or workplace factors unique to North Haven unmeasured in the current evaluation.

  15. Dual-polarization multi-band optical OFDM transmission and transceiver limitations for up to 500 Gb/s uncompensated long-haul links.

    PubMed

    Giacoumidis, E; Jarajreh, M A; Sygletos, S; Le, S T; Farjady, F; Tsokanos, A; Hamié, A; Pincemin, E; Jaouën, Y; Ellis, A D; Doran, N J

    2014-05-05

    A number of critical issues for dual-polarization single- and multi-band optical orthogonal-frequency division multiplexing (DP-SB/MB-OFDM) signals are analyzed in dispersion compensation fiber (DCF)-free long-haul links. For the first time, different DP crosstalk removal techniques are compared, the maximum transmission-reach is investigated, and the impact of subcarrier number and high-level modulation formats are explored thoroughly. It is shown, for a bit-error-rate (BER) of 10(-3), 2000 km of quaternary phase-shift keying (QPSK) DP-MB-OFDM transmission is feasible. At high launched optical powers (LOP), maximum-likelihood decoding can extend the LOP of 40 Gb/s QPSK DP-SB-OFDM at 2000 km by 1.5 dB compared to zero-forcing. For a 100 Gb/s DP-MB-OFDM system, a high number of subcarriers contribute to improved BER but at the cost of digital signal processing computational complexity, whilst by adapting the cyclic prefix length the BER can be improved for a low number of subcarriers. In addition, when 16-quadrature amplitude modulation (16QAM) is employed the digital-to-analogue/analogue-to-digital converter (DAC/ADC) bandwidth is relaxed with a degraded BER; while the 'circular' 8QAM is slightly superior to its 'rectangular' form. Finally, the transmission of wavelength-division multiplexing DP-MB-OFDM and single-carrier DP-QPSK is experimentally compared for up to 500 Gb/s showing great potential and similar performance at 1000 km DCF-free G.652 line.

  16. The rapid moving Capriglio earth flow (Parma Province, North Italy): multi-temporal mapping and GB-InSAR monitoring

    NASA Astrophysics Data System (ADS)

    Bardi, Federica; Raspini, Federico; Frodella, William; Lombardi, Luca; Nocentini, Massimiliano; Gigli, Giovanni; Morelli, Stefano; Corsini, Alessandro; Casagli, Nicola

    2017-04-01

    This research presents the main findings of the multi-temporal mapping and of the long-term, real-time monitoring of the Capriglio landslide in the Emilian Apennines (Northern Italy). The landslide, triggered by prolonged rainfall and rapid snowmelt, activated of April 6th 2013. It is constituted by two main adjacent enlarging bodies with a roto-translational kinematics. They activated in sequence and subsequently joined into a large fast moving earth flow, channelizing downstream the Bardea Creek, for a total length of about 3600 meters. The landslide completely destroyed a 450 m sector of the provincial roadway S.P. 101, and its retrogression tendency put at high risk the Capriglio and Pianestolla villages, located in the upper watershed area of the Bardea River. Furthermore, the advancing toe seriously threatened the Antria bridge, representing the "Massese" provincial roadway S.P. 665R transect over the Bardea Creek, the only strategic roadway left able to connect the above-mentioned villages. With the final aim of supporting local authorities in the hazard assessment and risk management during the emergency phase, on May 5th 2013 aerial optical surveys were conducted to accurately map the landslide extension and evolution. Moreover, a GB-InSAR monitoring campaign was started in order to assess displacements of the whole landslide area. The versatility and flexibility of the GB-InSAR sensors allowed acquiring data with two different configurations, designed and set up to continuously retrieve information on the landslide movements rates (both in its upper slow-moving sectors and in its fast-moving toe). The first acquisition mode revealed that the Capriglio and Pianestolla villages were affected by minor displacements (order of magnitude of few millimetres per month). The second acquisition mode allowed to acquire data every 28'', reaching very high temporal resolution values by applying GB-InSAR technique (Monserrat et al., 2014; Caduff et al., 2015).

  17. 112 Gb/s sub-cycle 16-QAM Nyquist-SCM for intra-datacenter connectivity

    NASA Astrophysics Data System (ADS)

    Bakopoulos, Paraskevas; Dris, Stefanos; Argyris, Nikolaos; Spatharakis, Christos; Avramopoulos, Hercules

    2016-03-01

    Datacenter traffic is exploding. Ongoing advancements in network infrastructure that ride on Moore's law are unable to keep up, necessitating the introduction of multiplexing and advanced modulation formats for optical interconnects in order to overcome bandwidth limitations, and scale lane speeds with energy- and cost-efficiency to 100 Gb/s and beyond. While the jury is still out as to how this will be achieved, schemes relying on intensity modulation with direct detection (IM/DD) are regarded as particularly attractive, due to their inherent implementation simplicity. Moreover, the scaling-out of datacenters calls for longer transmission reach exceeding 300 m, requiring single-mode solutions. In this work we advocate using 16-QAM sub-cycle Nyquist-SCM as a simpler alternative to discrete multitone (DMT), but which is still more bandwidth-efficient than PAM-4. The proposed optical interconnect is demonstrated at 112 Gb/s, which, to the best of our knowledge, is the highest rate achieved in a single-polarization implementation of SCM. Off-the-shelf components are used: A DFB laser, a 24.3 GHz electro-absorption modulator (EAM) and a limiting photoreceiver, combined with equalization through digital signal processing (DSP) at the receiver. The EAM is driven by a low-swing (<1 V) arbitrary waveform generator (AWG), which produces a 28 Gbaud 16-QAM electrical signal with carrier frequency at ~15 GHz. Tight spectral shaping is leveraged as a means of maintaining signal fidelity when using low-bandwidth electro-optic components; matched root-raised-cosine transmit and receive filters with 0.1 excess bandwidth are thus employed. Performance is assessed through transmission experiments over 1250 m and 2000 m of SMF.

  18. FInal Technical Repot of the Project: Design and Implementation of Low-Power 10Gb/s/channel Laser/Silicon Photonics Modulator Drivers with SEU Tolerance for HL-LHC

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Gui, Ping

    During the funding period of this award from May 1, 2014 through March 30, 2016, we have accomplished the design, implementation and measurement results of two laser driver chips: LpGBLD10+ which is a low-power single-channel 10Gb/s laser driver IC, and LDQ10P, which is a 4x10Gb/s driver array chip for High Energy Physics (HEP) applications. With new circuit techniques, the driver consumes a record-low power consumption, 31 mW @10Gb/s/channel and occupies a small area of 400 µm × 1750 µm for the single-channel driver IC and 1900umx1700um for the LDQ10P chip. These characteristics allow for both the LpGBLD10+ ICs and LDQ10P suitable candidatemore » for the Versatile Link PLUS (VL+) project, offering flexibility in configuring multiple Transmitters and receivers.« less

  19. 107 Gb/s coherent optical OFDM transmission over 1000-km SSMF fiber using orthogonal band multiplexing.

    PubMed

    Shieh, W; Yang, Q; Ma, Y

    2008-04-28

    Coherent optical OFDM (CO-OFDM) has emerged as an attractive modulation format for the forthcoming 100 Gb/s Ethernet. However, even the spectral-efficient implementation of CO-OFDM requires digital-to-analog converters (DAC) and analog-to-digital converters (ADC) to operate at the bandwidth which may not be available today or may not be cost-effective. In order to resolve the electronic bandwidth bottleneck associated with DAC/ADC devices, we propose and elucidate the principle of orthogonal-band-multiplexed OFDM (OBM-OFDM) to subdivide the entire OFDM spectrum into multiple orthogonal bands. With this scheme, the DAC/ADCs do not need to operate at extremely high sampling rate. The corresponding mapping to the mixed-signal integrated circuit (IC) design is also revealed. Additionally, we show the proof-of-concept transmission experiment through optical realization of OBM-OFDM. To the best of our knowledge, we present the first experimental demonstration of 107 Gb/s QPSK-encoded CO-OFDM signal transmission over 1000 km standard-single- mode-fiber (SSMF) without optical dispersion compensation and without Raman amplification. The demonstrated system employs 2x2 MIMO-OFDM signal processing and achieves high electrical spectral efficiency with direct-conversion at both transmitter and receiver.

  20. A 5 Gb/s CMOS adaptive equalizer for serial link

    NASA Astrophysics Data System (ADS)

    Wu, Hongbing; Wang, Jingyu; Liu, Hongxia

    2018-04-01

    A 5 Gb/s adaptive equalizer with a new adaptation scheme is presented here by using 0.13 μm CMOS process. The circuit consists of the combination of equalizer amplifier, limiter amplifier and adaptation loop. The adaptive algorithm exploits both the low frequency gain loop and the equalizer loop to minimize the inter-symbol interference (ISI) for a variety of cable characteristics. In addition, an offset cancellation loop is used to alleviate the offset influence of the signal path. The adaptive equalizer core occupies an area of 0.3567 mm2 and consumes a power consumption of 81.7 mW with 1.8 V power supply. Experiment results demonstrate that the equalizer could compensate for a designed cable loss with 0.23 UI peak-to-peak jitter. Project supported by the National Natural Science Foundation of China (No. 61376099), the Foundation for Fundamental Research of China (No. JSZL2016110B003), and the Major Fundamental Research Program of Shaanxi (No. 2017ZDJC-26).

  1. Identification of QTL regions and SSR markers associated with resistance to reniform nematode in Gossypium barbadense L. accession GB713.

    PubMed

    Gutiérrez, Osman A; Robinson, Arin F; Jenkins, Johnie N; McCarty, Jack C; Wubben, Martin J; Callahan, Franklin E; Nichols, Robert L

    2011-02-01

    The identification of molecular markers that are closely linked to gene(s) in Gossypium barbadense L. accession GB713 that confer a high level of resistance to reniform nematode (RN), Rotylenchulus reniformis Linford & Oliveira, would be very useful in cotton breeding programs. Our objectives were to determine the inheritance of RN resistance in the accession GB713, to identify SSR markers linked with RN resistance QTLs, and to map these linked markers to specific chromosomes. We grew and scored plants for RN reproduction in the P(1), P(2), F(1), F(2), BC(1)P(1), and BC(1)P(2) generations from the cross of GB713 × Acala Nem-X. The generation means analysis using the six generations indicated that one or more genes were involved in the RN resistance of GB713. The interspecific F(2) population of 300 plants was genotyped with SSR molecular markers that covered most of the chromosomes of Upland cotton (G. hirsutum L.). Results showed two QTLs on chromosome 21 and one QTL on chromosome 18. One QTL on chromosome 21 was at map position 168.6 (LOD 28.0) flanked by SSR markers, BNL 1551_162 and GH 132_199 at positions 154.2 and 177.3, respectively. A second QTL on chromosome 21 was at map position 182.7 (LOD 24.6) flanked by SSR markers BNL 4011_155 and BNL 3279_106 at positions 180.6 and 184.5, respectively. Our chromosome 21 map had 61 SSR markers covering 219 cM. One QTL with smaller genetic effects was localized to chromosome 18 at map position 39.6 (LOD 4.0) and flanked by SSR markers BNL 1721_178 and BNL 569_131 at positions 27.6 and 42.9, respectively. The two QTLs on chromosome 21 had significant additive and dominance effects, which were about equal for each QTL. The QTL on chromosome 18 showed larger additive than dominance effects. Following the precedent set by the naming of the G. longicalyx Hutchinson & Lee and G. aridum [(Rose & Standley) Skovsted] sources of resistance, we suggest the usage of Ren (barb1) and Ren (barb2) to designate these QTLs on

  2. DOE Office of Scientific and Technical Information (OSTI.GOV)

    Che, Magnus M.; Conti, Michele; Chanda, Soma

    We evaluated the protective efficacy of nasal atropine methyl bromide (AMB) which does not cross the blood-brain barrier against sarin inhalation exposure. Age and weight matched male guinea pigs were exposed to 846.5 mg/m{sup 3} sarin using a microinstillation inhalation exposure technique for 4 min. The survival rate at this dose was 20%. Post-exposure treatment with nasal AMB (2.5 mg/kg, 1 min) completely protected against sarin induced toxicity (100% survival). Development of muscular tremors was decreased in animals treated with nasal AMB. Post-exposure treatment with nasal AMB also normalized acute decrease in blood oxygen saturation and heart rate following sarinmore » exposure. Inhibition of blood AChE and BChE activities following sarin exposure was reduced in animals treated with nasal AMB, indicating that survival increases the metabolism of sarin or expression of AChE. The body weight loss of animals exposed to sarin and treated with nasal AMB was similar to saline controls. No differences were observed in lung accessory lobe or tracheal edema following exposure to sarin and subsequent treatment with nasal AMB. Total bronchoalveolar lavage fluid (BALF) protein, a biomarker of lung injury, showed trends similar to saline controls. Surfactant levels post-exposure treatment with nasal AMB returned to normal, similar to saline controls. Alkaline phosphatase levels post-exposure treatment with nasal AMB were decreased. Taken together, these data suggest that nasal AMB blocks the copious airway secretion and peripheral cholinergic effects and protects against lethal inhalation exposure to sarin thus increasing survival.« less

  3. Low-Level Sarin (GB) Vapor Exposure in the Gottingen Minipig: Effect of Exposure Concentration and Duration on Pupil Size

    DTIC Science & Technology

    2006-09-01

    Macary, G. Comparative Study of the Opthalmological Observations in the Yucatan Micropig and the Gottingen Minipig. Scand. J Lab. Anim. Sci. 1998, 25...2002, 28(8), pp 1433-1438. 25. Yoss, R.E.; Moyer, N.J.; Hollenhorst, R.W. Hippus and Other Spontaneous Rhythmic Pupillary Waves. American J. Opthalmology

  4. Optical flare observed in the flaring gamma-ray blazar CGRaBS J0809+5341 (87GB 080551.6+535010)

    NASA Astrophysics Data System (ADS)

    Pursimo, Tapio; Galindo-Guil, F. J.; Serrano, Pere Blay; Ojha, Roopesh

    2017-11-01

    We report optical photometry of the blazar CGRaBS J0809+5341 (87GB 080551.6+535010), obtained with the 2.56m Nordic Optical Telescope in La Palma, to look for any enhanced optical activity associated with a recent flare in the daily averaged gamma-ray flux (ATel#10905).

  5. The Amino Terminus of Herpes Simplex Virus 1 Glycoprotein K (gK) Is Required for gB Binding to Akt, Release of Intracellular Calcium, and Fusion of the Viral Envelope with Plasma Membranes.

    PubMed

    Musarrat, Farhana; Jambunathan, Nithya; Rider, Paul J F; Chouljenko, V N; Kousoulas, K G

    2018-03-15

    Previously, we have shown that the amino terminus of glycoprotein K (gK) binds to the amino terminus of gB and that deletion of the amino-terminal 38 amino acids of gK prevents herpes simplex virus 1 (HSV-1) infection of mouse trigeminal ganglia after ocular infection and virus entry into neuronal axons. Recently, it has been shown that gB binds to Akt during virus entry and induces Akt phosphorylation and intracellular calcium release. Proximity ligation and two-way immunoprecipitation assays using monoclonal antibodies against gB and Akt-1 phosphorylated at S473 [Akt-1(S473)] confirmed that HSV-1(McKrae) gB interacted with Akt-1(S473) during virus entry into human neuroblastoma (SK-N-SH) cells and induced the release of intracellular calcium. In contrast, the gB specified by HSV-1(McKrae) gKΔ31-68, lacking the amino-terminal 38 amino acids of gK, failed to interact with Akt-1(S473) and induce intracellular calcium release. The Akt inhibitor miltefosine inhibited the entry of McKrae but not the gKΔ31-68 mutant into SK-N-SH cells. Importantly, the entry of the gKΔ31-68 mutant but not McKrae into SK-N-SH cells treated with the endocytosis inhibitors pitstop-2 and dynasore hydrate was significantly inhibited, indicating that McKrae gKΔ31-68 entered via endocytosis. These results suggest that the amino terminus of gK functions to regulate the fusion of the viral envelope with cellular plasma membranes. IMPORTANCE HSV-1 glycoprotein B (gB) functions in the fusion of the viral envelope with cellular membranes during virus entry. Herein, we show that a deletion in the amino terminus of glycoprotein K (gK) inhibits gB binding to Akt-1(S473), the release of intracellular calcium, and virus entry via fusion of the viral envelope with cellular plasma membranes. Copyright © 2018 American Society for Microbiology.

  6. Derivatization of organophosphorus nerve agent degradation products for gas chromatography with ICPMS and TOF-MS detection.

    PubMed

    Richardson, Douglas D; Caruso, Joseph A

    2007-06-01

    Separation and detection of seven V-type (venomous) and G-type (German) organophosphorus nerve agent degradation products by gas chromatography with inductively coupled plasma mass spectrometry (GC-ICPMS) is described. The nonvolatile alkyl phosphonic acid degradation products of interest included ethyl methylphosphonic acid (EMPA, VX acid), isopropyl methylphosphonic acid (IMPA, GB acid), ethyl hydrogen dimethylamidophosphate sodium salt (EDPA, GA acid), isobutyl hydrogen methylphosphonate (IBMPA, RVX acid), as well as pinacolyl methylphosphonic acid (PMPA), methylphosphonic acid (MPA), and cyclohexyl methylphosphonic acid (CMPA, GF acid). N-(tert-Butyldimethylsilyl)-N-methyltrifluroacetamide with 1% TBDMSCl was utilized to form the volatile TBDMS derivatives of the nerve agent degradation products for separation by GC. Exact mass confirmation of the formation of six of the TBDMS derivatives was obtained by GC-time of flight mass spectrometry (TOF-MS). The method developed here allowed for the separation and detection of all seven TBDMS derivatives as well as phosphate in less than ten minutes. Detection limits for the developed method were less than 5 pg with retention times and peak area precisions of less than 0.01 and 6%, respectively. This method was successfully applied to river water and soil matrices. To date this is the first work describing the analysis of chemical warfare agent (CWA) degradation products by GC-ICPMS.

  7. All-optical clock recovery for 100 Gb/s RZ-OOK signal after 25km transmission using a dual-mode beating DBR laser

    NASA Astrophysics Data System (ADS)

    Yu, Liqiang; Pan, Biwei; Lu, Dan; Zhao, Lingjuan

    2014-11-01

    All-optical clock recovery (AOCR) for 100 Gb/s RZ-OOK signal is demonstrated by using a dualmode beating DBR laser. Based on the injection-locking of the DBR (distributed Bragg reflector) laser, a 100-GHz optical clock is recovered. Timing jitter (<1 ps) derived from both phase noise and power fluctuation is measured by an optical sampling oscilloscope (OSO). Furthermore, clock recovery is also realized for the 100 Gb/s signal after 25 km transmission. After the 25-km SMF (5- dB loss) transmission, the signal-to-noise ratio (SNR) of the signal drops from 18 dB to 5.2 dB. The dependence of the timing jitter on the input power is investigated. The lowest timing jitter of 665 fs is realized when the input power is 3 dBm.

  8. [Chemical weapons and chemical terrorism].

    PubMed

    Nakamura, Katsumi

    2005-10-01

    Chemical Weapons are kind of Weapons of Mass Destruction (WMD). They were used large quantities in WWI. Historically, large quantities usage like WWI was not recorded, but small usage has appeared now and then. Chemical weapons are so called "Nuclear weapon for poor countrys" because it's very easy to produce/possession being possible. They are categorized (1) Nerve Agents, (2) Blister Agents, (3) Cyanide (blood) Agents, (4) Pulmonary Agents, (5) Incapacitating Agents (6) Tear Agents from the viewpoint of human body interaction. In 1997 the Chemical Weapons Convention has taken effect. It prohibits chemical weapons development/production, and Organization for the Prohibition of Chemical Weapons (OPCW) verification regime contributes to the chemical weapons disposal. But possibility of possession/use of weapons of mass destruction by terrorist group represented in one by Matsumoto and Tokyo Subway Sarin Attack, So new chemical terrorism countermeasures are necessary.

  9. Development of an advanced uncooled 10-Gb DFB laser for volume manufacture

    NASA Astrophysics Data System (ADS)

    Burns, Gordon; Charles, Paul M.

    2003-03-01

    Optical communication systems operating at 10Gbit/s such as 10Gigabit Ethernet are becoming more and more important in Local Area Networks (LAN) and Metropolitan Area Networks (MAN). This market requires optical transceivers of low cost, size and power consumption. This drives a need for uncooled DFB lasers directly modulated at 10Gbit/s. This paper describes the development of a state of the art uncooled high speed DFB laser which is capable of being manufactured in high volume at the low cost demanded by the GbE market. A DFB laser was designed by developing technological building blocks within the 'conventional" InGaAsP materials system, using existing well proven manufacturing processes modules wherever possible, limiting the design risk to a few key areas where innovation was required. The temperature and speed performance of the InGaAsP SMQW active layer system was carefully optimized and then coupled with a low parasitic lateral confinement system. Using concurrent engineering, new processes were demonstrated to have acceptable process capability within a manufacturing fabrication environment, proving their ability to support high volume manufacturing requirements. The DFB laser fabricated was shown to operate at 100C chip temperature with an open eye at 10Gbit/s operation (with an extinction ratio >5dB). Up to 90C operation this DFB shows threshold current as low as 29mA, optical power as high as 13mW and it meets the 10Gb scaled Ethernet mask with extinction ratio >6dB. It was found that the high temperature dynamic behavior of these lasers could not be fully predicted from static test data. A production test strategy was therefore followed where equipment was designed to fully test devices/subassemblies at 100C and up to 20Gbit/s at key points in the product build. This facilitated the rapid optimisation of product yields upon manufacturing ramp up and minimization of product costs. This state of the art laser is now transferred into volume manufacture.

  10. Enhanced 10 Gb/s operations of directly modulated reflective semiconductor optical amplifiers without electronic equalization.

    PubMed

    Presi, M; Chiuchiarelli, A; Corsini, R; Choudury, P; Bottoni, F; Giorgi, L; Ciaramella, E

    2012-12-10

    We report enhanced 10 Gb/s operation of directly modulated bandwidth-limited reflective semiconductor optical amplifiers. By using a single suitable arrayed waveguide grating we achieve simultaneously WDM demultiplexing and optical equalization. Compared to previous approaches, the proposed system results significantly more tolerant to seeding wavelength drifts. This removes the need for wavelength lockers, additional electronic equalization or complex digital signal processing. Uniform C-band operations are obtained experimentally with < 2 dB power penalty within a wavelength drift of 10 GHz (which doubles the ITU-T standard recommendations).

  11. 15 Gb/s OFDM-based VLC using direct modulation of 450 GaN laser diode

    NASA Astrophysics Data System (ADS)

    Viola, Shaun; Islim, Mohamed Sufyan; Watson, Scott; Videv, Stefan; Haas, Harald; Kelly, Anthony E.

    2017-10-01

    A record data rate for visible light communications (VLC) using a transistor outline (TO) packaged Gallium Nitride (GaN) laser diode is reported. Using a system 3 dB bandwidth of 1.4 GHz data transmission at 15 Gb/s is reported. This is achieved due to the use of orthogonal frequency division multiplexing (OFDM) in combination with a high system signal to noise ratio (SNR) and adaptive bit loading extending the effective bandwidth to 2.5 GHz. To the best of authors knowledge this is the highest reported data rate for single channel VLC.

  12. Engineered Bi-Histidine Metal Chelation Sites Map the Structure of the Mechanical Unfolding Transition State of an Elastomeric Protein Domain GB1

    PubMed Central

    Shen, Tao; Cao, Yi; Zhuang, Shulin; Li, Hongbin

    2012-01-01

    Determining the structure of the transition state is critical for elucidating the mechanism behind how proteins fold and unfold. Due to its high free energy, however, the transition state generally cannot be trapped and studied directly using traditional structural biology methods. Thus, characterizing the structure of the transition state that occurs as proteins fold and unfold remains a major challenge. Here, we report a novel (to our knowledge) method that uses engineered bi-histidine (bi-His) metal-binding sites to directly map the structure of the mechanical unfolding transition state of proteins. This method is adapted from the traditional ψ-value analysis, which uses engineered bi-His metal chelation sites to probe chemical (un)folding transition-state structure. The ϕM2+U-value is defined as ΔΔG‡-N/ΔΔGU-N, which is the energetic effects of metal chelation by the bi-His site on the unfolding energy barrier (ΔG‡-N) relative to its thermodynamic stability (ΔGU-N) and can be used to obtain information about the transition state in the mutational site. As a proof of principle, we used the small protein GB1 as a model system and set out to map its mechanical unfolding transition-state structure. Using single-molecule atomic force microscopy and spectrofluorimetry, we directly quantified the effect of divalent metal ion binding on the mechanical unfolding free energy and thermodynamic stability of GB1, which allowed us to quantify ϕM2+U-values for different sites in GB1. Our results enabled us to map the structure of the mechanical unfolding transition state of GB1. Within GB1’s mechanical unfolding transition state, the interface between force-bearing β-strands 1 and 4 is largely disrupted, and the first β-hairpin is partially disordered while the second β-hairpin and the α-helix remain structured. Our results demonstrate the unique application of ψ-value analysis in elucidating the structure of the transition state that occurs during the

  13. 4 channel × 10 Gb/s bidirectional optical subassembly using silicon optical bench with precise passive optical alignment.

    PubMed

    Kang, Eun Kyu; Lee, Yong Woo; Ravindran, Sooraj; Lee, Jun Ki; Choi, Hee Ju; Ju, Gun Wu; Min, Jung Wook; Song, Young Min; Sohn, Ik-Bu; Lee, Yong Tak

    2016-05-16

    We demonstrate an advanced structure for optical interconnect consisting of 4 channel × 10 Gb/s bidirectional optical subassembly (BOSA) formed using silicon optical bench (SiOB) with tapered fiber guiding holes (TFGHs) for precise and passive optical alignment of vertical-cavity surface-emitting laser (VCSEL)-to-multi mode fiber (MMF) and MMF-to-photodiode (PD). The co-planar waveguide (CPW) transmission line (Tline) was formed on the backside of silicon substrate to reduce the insertion loss of electrical data signal. The 4 channel VCSEL and PD array are attached at the end of CPW Tline using a flip-chip bonder and solder pad. The 12-channel ribbon fiber is simply inserted into the TFGHs of SiOB and is passively aligned to the VCSEL and PD in which no additional coupling optics are required. The fabricated BOSA shows high coupling efficiency and good performance with the clearly open eye patterns and a very low bit error rate of less than 10-12 order at a data rate of 10 Gb/s with a PRBS pattern of 231-1.

  14. The effects of high concentrations of ionic liquid on GB1 protein structure and dynamics probed by high-resolution magic-angle-spinning NMR spectroscopy

    DOE PAGES

    Warner, Lisa; Gjersing, Erica; Follett, Shelby E.; ...

    2016-08-11

    Ionic liquids have great potential in biological applications and biocatalysis, as some ionic liquids can stabilize proteins and enhance enzyme activity, while others have the opposite effect. However, on the molecular level, probing ionic liquid interactions with proteins, especially in solutions containing high concentrations of ionic liquids, has been challenging. In the present work the 13C, 15N-enriched GB1 model protein was used to demonstrate applicability of high-resolution magic-angle-spinning (HR-MAS) NMR spectroscopy to investigate ionic liquid-protein interactions. Effect of an ionic liquid (1-butyl-3-methylimidazolium bromide, [C 4-mim]Br) on GB1was studied over a wide range of the ionic liquid concentrations (0.6-3.5 M, whichmore » corresponds to 10-60% v/v). Interactions between GB1 and [C 4-mim]Br were observed from changes in the chemical shifts of the protein backbone as well as the changes in 15N ps-ns dynamics and rotational correlation times. Site-specific interactions between the protein and [C 4-mim]Br were assigned using 3D methods under HR-MAS conditions. Furthermore, HR-MAS NMR is a viable tool that could aid in elucidation of molecular mechanisms of ionic liquid-protein interactions.« less

  15. The effects of high concentrations of ionic liquid on GB1 protein structure and dynamics probed by high-resolution magic-angle-spinning NMR spectroscopy

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Warner, Lisa; Gjersing, Erica; Follett, Shelby E.

    Ionic liquids have great potential in biological applications and biocatalysis, as some ionic liquids can stabilize proteins and enhance enzyme activity, while others have the opposite effect. However, on the molecular level, probing ionic liquid interactions with proteins, especially in solutions containing high concentrations of ionic liquids, has been challenging. In the present work the 13C, 15N-enriched GB1 model protein was used to demonstrate applicability of high-resolution magic-angle-spinning (HR-MAS) NMR spectroscopy to investigate ionic liquid-protein interactions. Effect of an ionic liquid (1-butyl-3-methylimidazolium bromide, [C 4-mim]Br) on GB1was studied over a wide range of the ionic liquid concentrations (0.6-3.5 M, whichmore » corresponds to 10-60% v/v). Interactions between GB1 and [C 4-mim]Br were observed from changes in the chemical shifts of the protein backbone as well as the changes in 15N ps-ns dynamics and rotational correlation times. Site-specific interactions between the protein and [C 4-mim]Br were assigned using 3D methods under HR-MAS conditions. Furthermore, HR-MAS NMR is a viable tool that could aid in elucidation of molecular mechanisms of ionic liquid-protein interactions.« less

  16. The effects of high concentrations of ionic liquid on GB1 protein structure and dynamics probed by high-resolution magic-angle-spinning NMR spectroscopy.

    PubMed

    Warner, Lisa; Gjersing, Erica; Follett, Shelby E; Elliott, K Wade; Dzyuba, Sergei V; Varga, Krisztina

    2016-12-01

    Ionic liquids have great potential in biological applications and biocatalysis, as some ionic liquids can stabilize proteins and enhance enzyme activity, while others have the opposite effect. However, on the molecular level, probing ionic liquid interactions with proteins, especially in solutions containing high concentration of ionic liquids, has been challenging. In the present work the 13 C, 15 N-enriched GB1 model protein was used to demonstrate applicability of high-resolution magic-angle-spinning (HR-MAS) NMR spectroscopy to investigate ionic liquid - protein interactions. Effect of an ionic liquid (1-butyl-3-methylimidazolium bromide, [C 4 -mim]Br) on GB1was studied over a wide range of the ionic liquid concentrations (0.6 to 3.5 M, which corresponds to 10%-60% v/v). Interactions between GB1 and [C 4 -mim]Br were observed from changes in the chemical shifts of the protein backbone as well as the changes in 15 N ps-ns dynamics and rotational correlation times. Site-specific interactions between the protein and [C 4 -mim]Br were assigned using 3D methods under HR-MAS conditions. Thus, HR-MAS NMR is a viable tool that could aid in elucidation of the molecular mechanism of ionic liquid - protein interactions.

  17. Stack Characterization in CryoSat Level1b SAR/SARin Baseline C

    NASA Astrophysics Data System (ADS)

    Scagliola, Michele; Fornari, Marco; Di Giacinto, Andrea; Bouffard, Jerome; Féménias, Pierre; Parrinello, Tommaso

    2015-04-01

    CryoSat was launched on the 8th April 2010 and is the first European ice mission dedicated to the monitoring of precise changes in the thickness of polar ice sheets and floating sea ice. CryoSat is the first altimetry mission operating in SAR mode and it carries an innovative radar altimeter called the Synthetic Aperture Interferometric Altimeter (SIRAL), that transmits pulses at a high pulse repetition frequency thus making the received echoes phase coherent and suitable for azimuth processing. The current CryoSat IPF (Instrument Processing Facility), Baseline B, was released in operation in February 2012. After more than 2 years of development, the release in operations of the Baseline C is expected in the first half of 2015. It is worth recalling here that the CryoSat SAR/SARin IPF1 generates 20Hz waveforms in correspondence of an approximately equally spaced set of ground locations on the Earth surface, i.e. surface samples, and that a surface sample gathers a collection of single-look echoes coming from the processed bursts during the time of visibility. Thus, for a given surface sample, the stack can be defined as the collection of all the single-look echoes pointing to the current surface sample, after applying all the necessary range corrections. The L1B product contains the power average of all the single-look echoes in the stack: the multi-looked L1B waveform. This reduces the data volume, while removing some information contained in the single looks, useful for characterizing the surface and modelling the L1B waveform. To recover such information, a set of parameters has been added to the L1B product: the stack characterization or beam behaviour parameters. The stack characterization, already included in previous Baselines, has been reviewed and expanded in Baseline C. This poster describes all the stack characterization parameters, detailing what they represent and how they have been computed. In details, such parameters can be summarized in: - Stack

  18. Zero-bias 32 Gb/s evanescently coupled InGaAs/InP UTC-PDs

    NASA Astrophysics Data System (ADS)

    Sun, Siwei; Liang, Song; Xie, Xiao; Xu, Junjie; Guo, Lu; Zhu, Hongliang; Wang, Wei

    2018-05-01

    We report the design and fabrication of high speed evanescently coupled InGaAs/InP uni-traveling-carrier-photodiodes (UTC-PDs). A self-aligned passive waveguide is integrated with the PDs by a simple fabrication procedure. Open eye diagrams at 32 Gb/s under zero bias are demonstrated for the first time, to the best of our knowledge, from evanescently or edge coupled InP based PDs, which are easier to be integrated with other optical components than surface illuminated PDs. When used for photonic integrated circuits (PICs) applications, our PDs help to lower the electrical cross talk and power consumption of PICs chips.

  19. 25Gb/s 1V-driving CMOS ring modulator with integrated thermal tuning.

    PubMed

    Li, Guoliang; Zheng, Xuezhe; Yao, Jin; Thacker, Hiren; Shubin, Ivan; Luo, Ying; Raj, Kannan; Cunningham, John E; Krishnamoorthy, Ashok V

    2011-10-10

    We report a high-speed ring modulator that fits many of the ideal qualities for optical interconnect in future exascale supercomputers. The device was fabricated in a 130 nm SOI CMOS process, with 7.5 μm ring radius. Its high-speed section, employing PN junction that works at carrier-depletion mode, enables 25 Gb/s modulation and an extinction ratio >5 dB with only 1V peak-to-peak driving. Its thermal tuning section allows the device to work in broad wavelength range, with a tuning efficiency of 0.19 nm/mW. Based on microwave characterization and circuit modeling, the modulation energy is estimated ~7 fJ/bit. The whole device fits in a compact 400 μm2 footprint.

  20. Glioblastoma and chemoresistance to alkylating agents: Involvement of apoptosis, autophagy, and unfolded protein response.

    PubMed

    Hombach-Klonisch, Sabine; Mehrpour, Maryam; Shojaei, Shahla; Harlos, Craig; Pitz, Marshall; Hamai, Ahmed; Siemianowicz, Krzysztof; Likus, Wirginia; Wiechec, Emilia; Toyota, Brian D; Hoshyar, Reyhane; Seyfoori, Amir; Sepehri, Zahra; Ande, Sudharsana R; Khadem, Forough; Akbari, Mohsen; Gorman, Adrienne M; Samali, Afshin; Klonisch, Thomas; Ghavami, Saeid

    2018-04-01

    Despite advances in neurosurgical techniques and radio-/chemotherapy, the treatment of brain tumors remains a challenge. This is particularly true for the most frequent and fatal adult brain tumor, glioblastoma (GB). Upon diagnosis, the average survival time of GB patients remains only approximately 15months. The alkylating drug temozolomide (TMZ) is routinely used in brain tumor patients and induces apoptosis, autophagy and unfolded protein response (UPR). Here, we review these cellular mechanisms and their contributions to TMZ chemoresistance in brain tumors, with a particular emphasis on TMZ chemoresistance in glioma stem cells and GB. Copyright © 2017 Elsevier Inc. All rights reserved.

  1. Confirming the gamma-ray blazar nature of the low energy counterpart QSO GB6 J1604+5714 of 2FGL J1604.6+5710 with WISE

    NASA Astrophysics Data System (ADS)

    Massaro, F.; D'Abrusco, R.; Paggi, A.

    2012-06-01

    Following the rapid optical variability detected in the QSO GB6 J1604+5714 (=BZQJ1604+5714) (ATEL #4184), associated to the gamma-ray source 2FGL J1604.6+5710 (=1FGL J1604.3+5710) in Nolan et al. (2012 ApJS, 199, 31), we searched in the Wide-field Infrared Survey Explorer (WISE; Wright et al. 2010 AJ, 140, 1868) catalog at the VLBI position of the QSO GB6 J1604+5714 (R.A.(J2000): 16h04m37.3546s, Dec.(J2000): +57d14m36.660s) reported in Beasley et al......

  2. The transmission of symmetric 40 Gb/s TWDM-based NG-PON2 utilizing delay interferometer (DI) for RSOA bandwidth enhancement

    NASA Astrophysics Data System (ADS)

    Bindhaiq, Salem; Zulkifli, Nadiatulhuda; Supa'at, AbuSahmah M.

    2016-07-01

    Time and wavelength-division multiplexed passive optical network (TWDM-PON) has been finally selected as the pragmatic solution for the next-generation passive optical network stage 2 (NG-PON2). In this paper, we propose a symmetric 40 Gb/s TWDM-PON system with low cost reflective semiconductor optical amplifier (RSOA) for both downstream and upstream directions. A single bi-pass delay interferometer (DI), deployed in the optical line terminal (OLT), is used to enhance the poor performance of the RSOA with respect to the low bandwidth induced by laser chirp. With the help of the 40 GHz free spectrum range (FSR) DI, we show a successful transmission of the proposed work through simulation study where an aggregate capacity of 40 Gb/s is transported over 40 km transmission distance with 32 splits. The TWDM-PON system at BER of 10-6 has shown a minimum receiver sensitivity of -22.78 dBm and -22.71 dBm for both downstream and upstream, respectively with maximum power penalty of 2 dB for downstream channel and 2.39 dB for upstream channel.

  3. Sarin

    MedlinePlus

    ... Cyanogen chloride (CK) Digitalis Case Definition: Digitalis Poisoning Ethylene glycol Fentanyls and other opioids Case Definition: Opioids ( ... Thallium Toxic alcohols Case Definition: Toxic Alcohol Poisoning Ethylene glycol Trichothecene Case Definition: Trichothecene Mycotoxin Poisoning Unidentified ...

  4. Virtual Genome Walking across the 32 Gb Ambystoma mexicanum genome; assembling gene models and intronic sequence.

    PubMed

    Evans, Teri; Johnson, Andrew D; Loose, Matthew

    2018-01-12

    Large repeat rich genomes present challenges for assembly using short read technologies. The 32 Gb axolotl genome is estimated to contain ~19 Gb of repetitive DNA making an assembly from short reads alone effectively impossible. Indeed, this model species has been sequenced to 20× coverage but the reads could not be conventionally assembled. Using an alternative strategy, we have assembled subsets of these reads into scaffolds describing over 19,000 gene models. We call this method Virtual Genome Walking as it locally assembles whole genome reads based on a reference transcriptome, identifying exons and iteratively extending them into surrounding genomic sequence. These assemblies are then linked and refined to generate gene models including upstream and downstream genomic, and intronic, sequence. Our assemblies are validated by comparison with previously published axolotl bacterial artificial chromosome (BAC) sequences. Our analyses of axolotl intron length, intron-exon structure, repeat content and synteny provide novel insights into the genic structure of this model species. This resource will enable new experimental approaches in axolotl, such as ChIP-Seq and CRISPR and aid in future whole genome sequencing efforts. The assembled sequences and annotations presented here are freely available for download from https://tinyurl.com/y8gydc6n . The software pipeline is available from https://github.com/LooseLab/iterassemble .

  5. Biocontrol agents promote growth of potato pathogens, depending on environmental conditions.

    PubMed

    Cray, Jonathan A; Connor, Mairéad C; Stevenson, Andrew; Houghton, Jonathan D R; Rangel, Drauzio E N; Cooke, Louise R; Hallsworth, John E

    2016-05-01

    There is a pressing need to understand and optimize biological control so as to avoid over-reliance on the synthetic chemical pesticides that can damage environmental and human health. This study focused on interactions between a novel biocontrol-strain, Bacillus sp. JC12GB43, and potato-pathogenic Phytophthora and Fusarium species. In assays carried out in vitro and on the potato tuber, the bacterium was capable of near-complete inhibition of pathogens. This Bacillus was sufficiently xerotolerant (water activity limit for growth = 0.928) to out-perform Phytophthora infestans (~0.960) and challenge Fusarium coeruleum (~0.847) and Fusarium sambucinum (~0.860) towards the lower limits of their growth windows. Under some conditions, however, strain JC12GB43 stimulated proliferation of the pathogens: for instance, Fusarium coeruleum growth-rate was increased under chaotropic conditions in vitro (132 mM urea) by >100% and on tubers (2-M glycerol) by up to 570%. Culture-based assays involving macromolecule-stabilizing (kosmotropic) compatible solutes provided proof-of-principle that the Bacillus may provide kosmotropic metabolites to the plant pathogen under conditions that destabilize macromolecular systems of the fungal cell. Whilst unprecedented, this finding is consistent with earlier reports that fungi can utilize metabolites derived from bacterial cells. Unless the antimicrobial activities of candidate biocontrol strains are assayed over a full range of field-relevant parameters, biocontrol agents may promote plant pathogen infections and thereby reduce crop yields. These findings indicate that biocontrol activity, therefore, ought to be regarded as a mode-of-behaviour (dependent on prevailing conditions) rather than an inherent property of a bacterial strain. © 2016 The Authors. Microbial Biotechnology published by John Wiley & Sons Ltd and Society for Applied Microbiology.

  6. High-Density Near-Field Readout over 50 GB Capacity Using Solid Immersion Lens with High Refractive Index

    NASA Astrophysics Data System (ADS)

    Shinoda, Masataka; Saito, Kimihiro; Kondo, Takao; Ishimoto, Tsutomu; Nakaoki, Ariyoshi

    2003-02-01

    We have investigated high-density near-field readout using a solid immersion lens with a high refractive index. By using a glass material with a high refractive index of 2.08, we developed an optical pick-up with the effective numerical aperture of 1.8. We could observe a clear eye pattern for a 50 GB capacity disc in 120 mm diameter. We confirmed that the near-field readout system is promising method of realizing a high-density optical disc system.

  7. Total Ionizing Dose Influence on the Single Event Effect Sensitivity in Samsung 8Gb NAND Flash Memories

    NASA Astrophysics Data System (ADS)

    Edmonds, Larry D.; Irom, Farokh; Allen, Gregory R.

    2017-08-01

    A recent model provides risk estimates for the deprogramming of initially programmed floating gates via prompt charge loss produced by an ionizing radiation environment. The environment can be a mixture of electrons, protons, and heavy ions. The model requires several input parameters. This paper extends the model to include TID effects in the control circuitry by including one additional parameter. Parameters intended to produce conservative risk estimates for the Samsung 8 Gb SLC NAND flash memory are given, subject to some qualifications.

  8. Neuroprotective Mechanisms Activated in Non-seizing Rats Exposed to Sarin

    DTIC Science & Technology

    2015-06-04

    after kainic acid-induced seizures. Brain Res. 1424, 1–8. Johnson, E.A., Kan, R.K., 2010. The acute phase response and soman-induced status epilepticus ...2011. Comparison of status epilepticus models induced by pilocarpine and nerve agents – a systematic review of the underlying aetiology and adopted...2007) Nqo2 Loss of Nqo1 and Nqo2 leads to altered intracellular redox status , decreased expression and activation of NF-κB, and altered

  9. Laser photoacoustic spectroscopy helps fight terrorism: High sensitivity detection of chemical Warfare Agent and explosives

    NASA Astrophysics Data System (ADS)

    Patel, C. K. N.

    2008-01-01

    Tunable laser photoacoustic spectroscopy is maturing rapidly in its applications to real world problems. One of the burning problems of the current turbulent times is the threat of terrorist acts against civilian population. This threat appears in two distinct forms. The first is the potential release of chemical warfare agents (CWA), such as the nerve agents, in a crowded environment. An example of this is the release of Sarin by Aum Shinrikyo sect in a crowded Tokyo subway in 1995. An example of the second terrorist threat is the ever-present possible suicide bomber in crowded environment such as airports, markets and large buildings. Minimizing the impact of both of these threats requires early detection of the presence of the CWAs and explosives. Photoacoustic spectroscopy is an exquisitely sensitive technique for the detection of trace gaseous species, a property that Pranalytica has extensively exploited in its CO2 laser based commercial instrumentation for the sub-ppb level detection of a number of industrially important gases including ammonia, ethylene, acrolein, sulfur hexafluoride, phosphine, arsine, boron trichloride and boron trifluoride. In this presentation, I will focus, however, on our recent use of broadly tunable single frequency high power room temperature quantum cascade lasers (QCL) for the detection of the CWAs and explosives. Using external grating cavity geometry, we have developed room temperature QCLs that produce continuously tunable single frequency CW power output in excess of 300 mW at wavelengths covering 5 μm to 12 μm. I will present data that show a CWA detection capability at ppb levels with false alarm rates below 1:108. I will also show the capability of detecting a variety of explosives at a ppb level, again with very low false alarm rates. Among the explosives, we have demonstrated the capability of detecting homemade explosives such as triacetone triperoxide and its liquid precursor, acetone which is a common household

  10. The application of single particle aerosol mass spectrometry for the detection and identification of high explosives and chemical warfare agents

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Martin, Audrey Noreen

    2006-01-01

    Single Particle Aerosol Mass Spectrometry (SPAMS) was evaluated as a real-time detection technique for single particles of high explosives. Dual-polarity time-of-flight mass spectra were obtained for samples of 2,4,6-trinitrotoluene (TNT), 1,3,5-trinitro-1,3,5-triazinane (RDX), and pentaerythritol tetranitrate (PETN); peaks indicative of each compound were identified. Composite explosives, Comp B, Semtex 1A, and Semtex 1H were also analyzed, and peaks due to the explosive components of each sample were present in each spectrum. Mass spectral variability with laser fluence is discussed. The ability of the SPAMS system to identify explosive components in a single complex explosive particle (~1 pg) without the need formore » consumables is demonstrated. SPAMS was also applied to the detection of Chemical Warfare Agent (CWA) simulants in the liquid and vapor phases. Liquid simulants for sarin, cyclosarin, tabun, and VX were analyzed; peaks indicative of each simulant were identified. Vapor phase CWA simulants were adsorbed onto alumina, silica, Zeolite, activated carbon, and metal powders which were directly analyzed using SPAMS. The use of metal powders as adsorbent materials was especially useful in the analysis of triethyl phosphate (TEP), a VX stimulant, which was undetectable using SPAMS in the liquid phase. The capability of SPAMS to detect high explosives and CWA simulants using one set of operational conditions is established.« less

  11. Tyrosines of Human and Mouse Transferrin Covalently Labeled by Organophosphorus Agents: A New Motif for Binding to Proteins that Have No Active Site Serine

    PubMed Central

    Li, Bin; Schopfer, Lawrence M.; Grigoryan, Hasmik; Thompson, Charles M.; Hinrichs, Steven H.; Masson, Patrick; Lockridge, Oksana

    2009-01-01

    The expectation from the literature is that organophosphorus (OP) agents bind to proteins that have an active site serine. However, transferrin, a protein with no active site serine, was covalently modified in vitro by 0.5mM 10-fluoroethoxyphosphinyl-N-biotinamido pentyldecanamide, chlorpyrifos oxon, diisopropylfluorophosphate, dichlorvos, sarin, and soman. The site of covalent attachment was identified by analyzing tryptic peptides in the mass spectrometer. Tyr 238 and Tyr 574 in human transferrin and Tyr 238, Tyr 319, Tyr 429, Tyr 491, and Tyr 518 in mouse transferrin were labeled by OP. Tyrosine in the small synthetic peptide ArgTyrThrArg made a covalent bond with diisopropylfluorophosphate, chlorpyrifos oxon, and dichlorvos at pH 8.3. These results, together with our previous demonstration that albumin and tubulin bind OP on tyrosine, lead to the conclusion that OP bind covalently to tyrosine, and that OP binding to tyrosine is a new OP-binding residue. The OP-reactive tyrosines are activated by interaction with Arg or Lys. It is suggested that many proteins in addition to those already identified may be modified by OP on tyrosine. The extent to which tyrosine modification by OP can occur in vivo and the toxicological implications of such modifications require further investigation. PMID:18930948

  12. Electronic Equalization of Multikilometer 10-Gb/s Multimode Fiber Links: Mode-Coupling Effects

    NASA Astrophysics Data System (ADS)

    Balemarthy, Kasyapa; Polley, Arup; Ralph, Stephen E.

    2006-12-01

    This paper investigates the ability of electronic equalization to compensate for modal dispersion in the presence of mode coupling in multimode fibers (MMFs) at 10 Gb/s. Using a new time-domain experimental method, mode coupling is quantified in MMF. These results, together with a comprehensive link model, allow to determine the impact of mode coupling on the performance of MMF. The equalizer performance on links from 300 m to 8 km is quantified with and without modal coupling. It is shown that the mode-coupling effects are influenced by the specific index profile and increase the equalizer penalty by as much as 1 dBo for 1-km links and 2.3 dBo for 2-km links when using a standard model of fiber profiles at 1310 nm.

  13. A CWDM photoreceiver module for 10 Gb/s x 4ch interconnection based on a vertical-illumination-type Ge-on-Si photodetectors and a silica-based AWG

    NASA Astrophysics Data System (ADS)

    Jang, Ki-Seok; Joo, Jiho; Kim, Taeyong; Kim, Sanghoon; Oh, Jin Hyuk; Kim, In Gyoo; Kim, Sun Ae; Kim, Gyungock

    2015-03-01

    We report a 40 Gb/s photoreceiver based on vertical-illumination type Ge-on-Si photodetectors and a silica-based AWG demultiplexer by employing 4-channel CWDM. The 60um-diameter Ge-on-Si photodetector arrays, grown on a bulk silicon wafer by RPCVD and fabricated with CMOS-compatible process, have ~0.9 A/W responsivity with 13 GHz bandwidth at λ ~ 1330nm. Ge-on-Si photodetector arrays are hybrid-integrated with TIA/LAs and directly-coupled to the AWG. The low-cost FPCB-package based photoreceiver module shows 10.3 Gb/s × 4-channel interconnection with -11 ~ -12.2 dBm sensitivity at a BER = 10-12.

  14. GB-InSAR monitoring of slope deformations in a mountainous area affected by debris flow events

    NASA Astrophysics Data System (ADS)

    Frodella, William; Salvatici, Teresa; Pazzi, Veronica; Morelli, Stefano; Fanti, Riccardo

    2017-10-01

    Diffuse and severe slope instabilities affected the whole Veneto region (north-eastern Italy) between 31 October and 2 November 2010, following a period of heavy and persistent rainfall. In this context, on 4 November 2010 a large detrital mass detached from the cover of the Mt. Rotolon deep-seated gravitational slope deformation (DSGSD), located in the upper Agno River valley, channelizing within the Rotolon Creek riverbed and evolving into a highly mobile debris flow. The latter phenomena damaged many hydraulic works, also threatening bridges, local roads, and the residents of the Maltaure, Turcati, and Parlati villages located along the creek banks and the town of Recoaro Terme. From the beginning of the emergency phase, the civil protection system was activated, involving the National Civil Protection Department, Veneto Region, and local administrations' personnel and technicians, as well as scientific institutions. On 8 December 2010 a local-scale monitoring system, based on a ground-based interferometric synthetic aperture radar (GB-InSAR), was implemented in order to evaluate the slope deformation pattern evolution in correspondence of the debris flow detachment sector, with the final aim of assessing the landslide residual risk and managing the emergency phase. This paper describes the results of a 2-year GB-InSAR monitoring campaign (December 2010-December 2012) and its application for monitoring, mapping, and emergency management activities in order to provide a rapid and easy communication of the results to the involved technicians and civil protection personnel, for a better understanding of the landslide phenomena and the decision-making process in a critical landslide scenario.

  15. Cloning and function validation of a nb-arc-lrr-type candidate gene for the greenbug aphid resistance locus, Gb3, in wheat

    USDA-ARS?s Scientific Manuscript database

    The greenbug, Schizaphis graminum, is one of the most important aphid pests of small grain crops in many parts of the world. A single dominant gene, Gb3 originated from Aegilops tauschii has shown consistent and durable resistance against prevailing greenbug biotypes in wheat fields. A fine genetic ...

  16. Identification of V-type nerve agents in vapor samples using a field-portable capillary gas chromatography/membrane-interfaced electron ionization quadrupole mass spectrometry instrument with Tri-Bed concentrator and fluoridating conversion tube.

    PubMed

    Ohrui, Y; Nagoya, T; Kurimata, N; Sodeyama, M; Seto, Y

    2017-07-01

    A field-portable gas chromatography-mass spectrometry (GC-MS) system (Hapsite ER) was evaluated for the detection of nonvolatile V-type nerve agents (VX and Russian VX (RVX)) in the vapor phase. The Hapsite ER system consists of a Tri-Bed concentrator gas sampler, a nonpolar low thermal-mass capillary GC column and a hydrophobic membrane-interfaced electron ionization quadrupole mass spectrometer evacuated by a non-evaporative getter pump. The GC-MS system was attached to a VX-G fluoridating conversion tube containing silver nitrate and potassium fluoride. Sample vapors of VX and RVX were converted into O-ethyl methylphosphonofluoridate (EtGB) and O-isobutyl methylphosphonofluoridate (iBuGB), respectively. These fluoridated derivatives were detected within 10 min. No compounds were detected when the VX and RVX samples were analyzed without the conversion tube. A vapor sample of tabun (GA) was analyzed, in which GA and O-ethyl N,N-dimethylphosphoramidofluoridate were detected. The molar recovery percentages of EtGB and iBuGB from VX and RVX vapors varied from 0.3 to 17%, which was attributed to variations in the vaporization efficiency of the glass vapor container. The conversion efficiencies of the VX-G conversion tube for VX and RVX to their phosphonate derivatives were estimated to be 40%. VX and RVX vapors were detected at concentrations as low as 0.3 mg m -3 . Gasoline vapor was found to interfere with the analyses of VX and RVX. In the presence of 160 mg m -3 gasoline, the detection limits of VX and RVX vapor were increased to 20 mg m -3 . Copyright © 2017 John Wiley & Sons, Ltd. Copyright © 2017 John Wiley & Sons, Ltd.

  17. Neurosteroids for the potential protection of humans against organophosphate toxicity.

    PubMed

    Reddy, Doodipala Samba

    2016-08-01

    This article describes the therapeutic potential of neurosteroids as anticonvulsant antidotes for chemical intoxication caused by organophosphate pesticides and nerve agents or gases like sarin and soman. Toxic manifestations following nerve agent exposure, as evident in chemical attacks in Japan and Syria, include hypersecretion, respiratory distress, tremors, convulsions leading to status epilepticus (SE), and death. Benzodiazepines, such as diazepam, are the current anticonvulsants of choice for controlling nerve agent-induced life-threatening seizures, SE, and brain injury. Benzodiazepines can control acute seizures when given early, but they are less effective for delayed treatment of SE, which is characterized by rapid desensitization of synaptic GABA A receptors, benzodiazepine resistance, and brain injury. Neurosteroid-sensitive extrasynaptic GABA A receptors, however, remain unaffected by such events. Thus, anticonvulsant neurosteroids may produce more effective protection than benzodiazepines against a broad spectrum of chemical agents, even when given late after nerve agent exposure. © 2016 New York Academy of Sciences.

  18. Structured FBG filters for 10-Gb/s DPSK signal demodulation in single ended applications

    NASA Astrophysics Data System (ADS)

    Marazzi, L.; Boffi, P.; Parolari, P.; Martinelli, M.; Gatti, D.; Coluccelli, N.; Longhi, S.

    2011-05-01

    Differential phase-shift keying (DPSK) demodulations operated by a structured fiber Bragg grating (FBG) filter and by a Mach-Zehnder delay interferometer (MZDI) in a single-ended configuration are compared. Experimental measurements at 10 Gb/s demonstrate that a specially designed FBG outperforms an integrated-optic MZDI of ˜4 dB and ˜3.5 dB in back-to-back and after 25-km propagation, respectively. Both demodulators show low polarization sensitivity and signal frequency detuning dependence, but only MZDI operating point requires a thermal control. FBG filter proves an interesting solution for DPSK demodulation in low-cost applications and, moreover, can be designed to match colorless requirements of wave division multiplexed passive optical network (WDM-PON) applications.

  19. Elektronische Informationsdienste im Bildungswesen (Electronic Information Services in Education) Gesellschaft Information Bildung Conference (GIB) (2nd, Berlin, Germany, November 17-18, 1994).

    ERIC Educational Resources Information Center

    Diepold, Peter, Ed.; Rusch-Feja, Diann, Ed.

    These papers on educational technology were presented in three workshops at the second annual conference of the Society of Information Education (GIB). Discussion includes electronic networks, CD-ROMs, and online databases in education, the quality of educational software, database services and instructional methods, and the use of the Internet in…

  20. 40-Gb/s directly-modulated photonic crystal lasers under optical injection-locking

    NASA Astrophysics Data System (ADS)

    Chen, Chin-Hui; Takeda, Koji; Shinya, Akihiko; Nozaki, Kengo; Sato, Tomonari; Kawaguchi, Yoshihiro; Notomi, Masaya; Matsuo, Shinji

    2011-08-01

    CMOS integrated circuits (IC) usually requires high data bandwidth for off-chip input/output (I/O) data transport with sufficiently low power consumption in order to overcome pin-count limitation. In order to meet future requirements of photonic network interconnect, we propose an optical output device based on an optical injection-locked photonic crystal (PhC) laser to realize low-power and high-speed off-chip interconnects. This device enables ultralow-power operation and is suitable for highly integrated photonic circuits because of its strong light-matter interaction in the PhC nanocavity and ultra-compact size. High-speed operation is achieved by using the optical injection-locking (OIL) technique, which has been shown as an effective means to enhance modulation bandwidth beyond the relaxation resonance frequency limit. In this paper, we report experimental results of the OIL-PhC laser under various injection conditions and also demonstrate 40-Gb/s large-signal direct modulation with an ultralow energy consumption of 6.6 fJ/bit.

  1. Development of Novel Decontamination Techniques for Chemical Agents (GB, VX, HD) Contaminated Facilities. Phase 1. Identification and Evaluation of Novel Decontamination Concepts. Volume 2

    DTIC Science & Technology

    1983-02-01

    Phosphoric, citric or other acids may be used as coupling agent/solvents in the cleaning tank. Decontamination solutions may also be used. Ultrasonics may be...111-54 "THERMAL DECOMPOSITION USING CO2 LASER . . . . . . . . . . . . . . 111-63 >’HYDROBLASTING. III-70 (-7, ACID ETCH/ NUTRALIZATION...111-192 NITRIC ACID . . .*. . . . .\\. . . . . . . . . . . . . . . TII-197 AMMONIA • • . . . • . . . . • . . . . . .... . ...... . 111-202 DANC .1

  2. GB3.0: a platform for plant bio-design that connects functional DNA elements with associated biological data

    PubMed Central

    Vazquez-Vilar, Marta; Quijano-Rubio, Alfredo; Fernandez-del-Carmen, Asun; Sarrion-Perdigones, Alejandro; Ochoa-Fernandez, Rocio; Ziarsolo, Peio

    2017-01-01

    Abstract Modular DNA assembly simplifies multigene engineering in Plant Synthetic Biology. Furthermore, the recent adoption of a common syntax to facilitate the exchange of plant DNA parts (phytobricks) is a promising strategy to speed up genetic engineering. Following this lead, here, we present a platform for plant biodesign that incorporates functional descriptions of phytobricks obtained under pre-defined experimental conditions, and systematically registers the resulting information as metadata for documentation. To facilitate the handling of functional descriptions, we developed a new version (v3.0) of the GoldenBraid (GB) webtool that integrates the experimental data and displays it in the form of datasheets. We report the use of the Luciferase/Renilla (Luc/Ren) transient agroinfiltration assay in Nicotiana benthamiana as a standard to estimate relative transcriptional activities conferred by regulatory phytobricks, and show the consistency and reproducibility of this method in the characterization of a synthetic phytobrick based on the CaMV35S promoter. Furthermore, we illustrate the potential for combinatorial optimization and incremental innovation of the GB3.0 platform in two separate examples, (i) the development of a collection of orthogonal transcriptional regulators based on phiC31 integrase and (ii) the design of a small genetic circuit that connects a glucocorticoid switch to a MYB/bHLH transcriptional activation module. PMID:28053117

  3. [Premature return of the drivers' license--temporal limits according to section 69 a Abs. 7 StGB].

    PubMed

    Zabel, G E; Zabel, U

    1992-01-01

    1) Text of law and kind of crime (driving under the influence of alcohol) don't allow a reduction of the minimal period of revocation. 2) A new definition of section 69 a Abs. 7 StGB and a reduction respectively a renunciation of minimal period of revocation should give possibility to courts and reprieval authorities to ensure the inclusion of a large number of persons suitable for additional training and in cases of total abstinence traffic authority should regard the aptitude for participation in traffic as regranted.

  4. Phosphotriesterase variants with high methylphosphonatase activity and strong negative trade-off against phosphotriesters.

    PubMed

    Briseño-Roa, Luis; Timperley, Christopher M; Griffiths, Andrew D; Fersht, Alan R

    2011-01-01

    The most lethal organophosphorus nerve agents (NA), like sarin, soman, agent-VX and Russian-VX, share a methylphosphonate moiety. Pseudomonas diminuta phosphotriesterase (PTE) catalyses the hydrolysis of methylphosphonate NA analogues with a catalytic efficiency orders of magnitude lower than that towards the pesticide paraoxon. With a view to obtaining PTE variants that more readily accept methylphosphonate NA, ~75,000 PTE variants of the substrate-binding residues Gly-60, Ile-106, Leu-303 and Ser-308 were screened with fluorogenic analogues of the NA Russian-VX and cyclosarin. Seven new PTE variants were isolated, purified and their k(cat)/K(M) determined against five phosphotriesters and five methylphosphonate analogues of sarin, cyclosarin, soman, agent-VX and Russian-VX. The novel PTE variants exhibited as much as a 10-fold increase in activity towards the methylphosphonate compounds--many reaching a k(cat)/K(M) of 10⁶ M⁻¹ s⁻¹--and as much as a 29,000-fold decrease in their phosphotriesterase activity. The mutations found in two of the variants, SS0.5 (G60V/I106L/S308G) and SS4.5 (G60V/I106A/S308G), were modelled into a high-resolution structure of PTE-wild type and docked with analogues of cyclosarin and Russian-VX using Autodock 4.2. The kinetic data and docking simulations suggest that the increase in activity towards the methylphosphonates and the loss of function against the phosphotriesters were due to an alteration of the shape and hydrophobicity of the binding pocket that hinders the productive binding of non-chiral racemic phosphotriesters, yet allows the binding of the highly asymmetric methylphosphonates.

  5. Delayed Majority Game with Heterogeneous Learning Speeds for Financial Markets

    NASA Astrophysics Data System (ADS)

    Yoshimura, Yushi; Yamada, Kenta

    There are two famous statistical laws, so-called stylized facts, in financial markets. One is fat tail where the tail of price returns obeys a power law. The other is volatility clustering in which the autocorrelation function of absolute price returns decays with a power law. In order to understand relationships between the stylized facts and dealers' behaviors, we constructed a new agent-based model based on the grand canonical minority game (GCMG) and the Giardina-Bouchaud (GB) model. The recovery of stylized facts by GCMG and GB lacks of robustness. Therefore, based on the GCMG and GB model, we develop a new model that can reproduce stylized facts robustly. Furthermore, we find that heterogeneity of learning speeds of agents is important to reproduce the stylized facts.

  6. Comparison of monovalent glycoprotein B with bivalent gB/pp65 (GP83) vaccine for congenital cytomegalovirus infection in a guinea pig model: Inclusion of GP83 reduces gB antibody response but both vaccine approaches provide equivalent protection against pup mortality.

    PubMed

    Swanson, Elizabeth C; Gillis, Pete; Hernandez-Alvarado, Nelmary; Fernández-Alarcón, Claudia; Schmit, Megan; Zabeli, Jason C; Wussow, Felix; Diamond, Don J; Schleiss, Mark R

    2015-07-31

    Cytomegalovirus (CMV) subunit vaccine candidates include glycoprotein B (gB), and phosphoprotein ppUL83 (pp65). Using a guinea pig cytomegalovirus (GPCMV) model, this study compared immunogenicity, pregnancy outcome, and congenital viral infection following pre-pregnancy immunization with a three-dose series of modified vaccinia virus Ankara (MVA)-vectored vaccines consisting either of gB administered alone, or simultaneously with a pp65 homolog (GP83)-expressing vaccine. Vaccinated and control dams were challenged at midgestation with salivary gland-adapted GPCMV. Comparisons included ELISA and neutralizing antibody responses, maternal viral load, pup mortality, and congenital infection rates. Strikingly, ELISA and neutralization titers were significantly lower in the gB/GP83 combined vaccine group than in the gB group. However, both vaccines protected against pup mortality (63.2% in controls vs. 11.4% and 13.9% in gB and gB/GP83 combination groups, respectively; p<0.0001). Reductions in pup viral load were noted for both vaccine groups compared to control, but preconception vaccination resulted in a significant reduction in GPCMV transmission only in the monovalent gB group (26/44, 59% v. 27/34, 79% in controls; p<0.05). We conclude that, using the MVA platform, the addition of GP83 to a gB subunit vaccine interferes with antibody responses and diminishes protection against congenital GPCMV infection, but does not decrease protection against pup mortality. Copyright © 2015 Elsevier Ltd. All rights reserved.

  7. A multi-port 10GbE PCIe NIC featuring UDP offload and GPUDirect capabilities.

    NASA Astrophysics Data System (ADS)

    Ammendola, Roberto; Biagioni, Andrea; Frezza, Ottorino; Lamanna, Gianluca; Lo Cicero, Francesca; Lonardo, Alessandro; Martinelli, Michele; Stanislao Paolucci, Pier; Pastorelli, Elena; Pontisso, Luca; Rossetti, Davide; Simula, Francesco; Sozzi, Marco; Tosoratto, Laura; Vicini, Piero

    2015-12-01

    NaNet-10 is a four-ports 10GbE PCIe Network Interface Card designed for low-latency real-time operations with GPU systems. To this purpose the design includes an UDP offload module, for fast and clock-cycle deterministic handling of the transport layer protocol, plus a GPUDirect P2P/RDMA engine for low-latency communication with NVIDIA Tesla GPU devices. A dedicated module (Multi-Stream) can optionally process input UDP streams before data is delivered through PCIe DMA to their destination devices, re-organizing data from different streams guaranteeing computational optimization. NaNet-10 is going to be integrated in the NA62 CERN experiment in order to assess the suitability of GPGPU systems as real-time triggers; results and lessons learned while performing this activity will be reported herein.

  8. Effects of optical layer impairments on 2.5 Gb/s optical CDMA transmission.

    PubMed

    Feng, H; Mendez, A; Heritage, J; Lennon, W

    2000-07-03

    We conducted a computer simulation study to assess the effects of optical layer impairments on optical CDMA (O-CDMA) transmission of 8 asynchronous users at 2.5 Gb/s each user over a 214-km link. It was found that with group velocity dispersion compensation, two other residual effects, namely, the nonzero chromatic dispersion slope of the single mode fiber (which causes skew) and the non-uniform EDFA gain (which causes interference power level to exceed signal power level of some codes) degrade the signal to multi-access interference (MAI) ratio. In contrast, four wave mixing and modulation due to the Kerr and Raman contributions to the fiber nonlinear refractive index are less important. Current wavelength-division multiplexing (WDM) technologies, including dispersion management, EDFA gain flattening, and 3 rd order dispersion compensation, are sufficient to overcome the impairments to the O-CDMA transmission system that we considered.

  9. Epidemiological and Clinical Evidence for Residual Organophoshate Neurotoxicity

    DTIC Science & Technology

    2000-10-01

    agents have yet to be resolved, but if effects are observable, they would likely be manifest as persistent neurophysiologic or neuropsychologic effects...correlates with electrophysiological and neuropsychological evidence consistent with the reported sequelae of symptomatic exposure to sarin. The results of...26.5 13.6 2.3 (1.4,3.6) Abdominal cramping 16.1 14.9 1.1 (0.7,1.7) 24.7 11.6 2.4 (1.5,3.8) Increased hunger 13.5 12.5 1.1 (0.7,1.7) 17.9 12.1 1.6

  10. The characterization of the distant blazar GB6 J1239+0443 from flaring and low activity periods

    DOE PAGES

    Pacciani, L.; Donnarumma, I.; Denney, K. D.; ...

    2012-08-27

    In 2008, AGILE and Fermi detected gamma-ray flaring activity from the unidentified EGRET source 3EG J1236+0457, recently associated with a flat spectrum radio quasar (GB6 J1239+0443) at z = 1.762. The optical counterpart of the gamma-ray source underwent a flux enhancement of a factor of 15–30 in six years, and of ~10 in six months. Here, we interpret this flare-up in terms of a transition from an accretion-disc-dominated emission to a synchrotron-jet-dominated one. We analysed a Sloan Digital Sky Survey (SDSS) archival optical spectrum taken during a period of low radio and optical activity of the source. We estimated themore » mass of the central black hole using the width of the C iv emission line. In our work, we have also investigated SDSS archival optical photometric data and ultraviolet GALEX observations to estimate the thermal disc emission contribution of GB6 J1239+0443. This analysis of the gamma-ray data taken during the flaring episodes indicates a flat gamma-ray spectrum, with an extension of up to 15 GeV, with no statistically relevant sign of absorption from the broad-line region, suggesting that the blazar zone is located beyond the broad-line region. Our result is confirmed by the modelling of the broad-band spectral energy distribution (well constrained by the available multiwavelength data) of the flaring activity periods and by the accretion disc luminosity and black hole mass estimated by us using archival data.« less

  11. 128 Gb/s TWDM PON system using dispersion-supported transmission method

    NASA Astrophysics Data System (ADS)

    Bindhaiq, Salem; Zulkifli, Nadiatulhuda; Supa'at, Abusahmah M.; Idrus, Sevia M.; Salleh, M. S.

    2017-11-01

    Time and wavelength division multiplexed passive optical network (TWDM-PON) trend is considered as the most extraordinary trend of the next generation solution to accommodate exponential traffic growth for converged new services. In this paper, we briefly review recent progress on TWDM-PON system through the use of low cost directly modulated lasers (DMLs) transmission for various line rate transmissions to date. Furthermore, through simulation, we propose and evaluate a cost effective way to upgrade TWDM-PON up to a symmetric capacity of 128 Gb/s using fiber Bragg gratings (FBGs) in optical line terminal (OLT) as a paramount dispersion manager in high speed light-wave systems in both upstream and downstream directions. A low cost and potential chirpless directed modulated grating laser (DMGL) is employed for downstream link and DML with a single delay-interferometer (DI) is employed for upstream link. After illustrating the demonstrated system architecture and configuration, we present the results and analysis to prove the system feasibility. The results show that a successful transmission is achieved over 40 km single mode fiber with a power budget of 33.7 dB, which could support 1:256 splitting ratio.

  12. Experimental demonstration of record high 19.125 Gb/s real-time end-to-end dual-band optical OFDM transmission over 25 km SMF in a simple EML-based IMDD system.

    PubMed

    Giddings, R P; Hugues-Salas, E; Tang, J M

    2012-08-27

    Record high 19.125 Gb/s real-time end-to-end dual-band optical OFDM (OOFDM) transmission is experimentally demonstrated, for the first time, in a simple electro-absorption modulated laser (EML)-based 25 km standard SMF system using intensity modulation and direct detection (IMDD). Adaptively modulated baseband (0-2GHz) and passband (6.125 ± 2GHz) OFDM RF sub-bands, supporting line rates of 10 Gb/s and 9.125 Gb/s respectively, are independently generated and detected with FPGA-based DSP clocked at only 100 MHz and DACs/ADCs operating at sampling speeds as low as 4GS/s. The two OFDM sub-bands are electrically frequency-division-multiplexed (FDM) for intensity modulation of a single optical carrier by an EML. To maximize and balance the signal transmission performance of each sub-band, on-line adaptive features and on-line performance monitoring is fully exploited to optimize key OOFDM transceiver and system parameters, which includes subcarrier characteristics within each individual OFDM sub-band, total and relative sub-band power as well as EML operating conditions. The achieved 19.125 Gb/s over 25 km SMF OOFDM transmission system has an optical power budget of 13.5 dB, and shows almost identical bit error rate (BER) performances for both the baseband and passband signals. In addition, experimental investigations also indicate that the maximum achievable transmission capacity of the present system is mainly determined by the EML frequency chirp-enhanced chromatic dispersion effect, and the passband BER performance is not affected by the two sub-band-induced intermixing effect, which, however, gives a 1.2dB optical power penalty to the baseband signal transmission.

  13. Entropy Drives the Formation of Salt Bridges in the Protein GB3.

    PubMed

    Zhang, Ning; Wang, Yefei; An, Liaoyuan; Song, Xiangfei; Huang, Qingshan; Liu, Zhijun; Yao, Lishan

    2017-06-19

    Salt bridges are very common in proteins. But what drives the formation of protein salt bridges is not clear. In this work, we determined the strength of four salt bridges in the protein GB3 by measuring the ΔpK a values of the basic residues that constitute the salt bridges with a highly accurate NMR titration method at different temperatures. The results show that the ΔpK a values increase with temperature, thus indicating that the salt bridges are stronger at higher temperatures. Fitting of ΔpK a values to the van't Hoff equation yields positive ΔH and ΔS values, thus indicating that entropy drives salt-bridge formation. Molecular dynamics simulations show that the protein and solvent make opposite contributions to ΔH and ΔS. Specifically, the enthalpic gain contributed from the protein is more than offset by the enthalpic loss contributed from the solvent, whereas the entropic gain originates from the desolvation effect. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  14. Synergistic behavior of glycine betaine-urea mixture: A molecular dynamics study

    NASA Astrophysics Data System (ADS)

    Kumar, Narendra; Kishore, Nand

    2013-09-01

    Glycine betaine (GB) is one of the most important osmolyte which is known to stabilize proteins as well as counteract the denaturing effect of urea. There have been many studies indicating protein stabilization and counteraction of the effect of urea by GB. However, the exact mechanism of counteraction is still debated and is of important research interest. In this study, distribution functions, hydrogen bonds, and energetics were analysed to understand different interactions between GB and urea, and their solvation properties in presence of each other. The results show that in the GB-urea mixture, GB acted as a stronger osmolyte and urea became a weaker denaturing agent than its individual counterparts. The increase in the solvation of urea and GB in GB-urea mixture and their mutual interactions through hydrogen bonding and coulombic energy resulted in more involvement of GB and urea with solvent as well as with themselves. This might result in the increase of the exclusion of GB from protein surface and decrease in the protein-urea interactions in the mixture. This synergistic behavior might be the prime reason for the counteraction of denaturing effect of urea by GB.

  15. Geotechnical Containment Alternatives for Industrial Waste Basin F, Rocky Mountain Arsenal, Denver, Colorado. A quantitative Evaluation

    DTIC Science & Technology

    1979-09-01

    RMA have included the production of GB nerve gas, lewisite, mustard gas, arsenic chloride, anticrop agents , and chlorine - gas, as well as the...fabrication if munitions containing white phosphorus and chemical warfare agents . The demilitarization of GB munitions and mustard-filled munitions and the...i , i iSndy S BLUE of .4 I i i lly G BLOE -GRE ii 0 ir i Grntl C - -- - I WHITE Sh__ O ickeft dit SL ML B~d~ 0 20 40 60 80 too Ovd’ted o LL IOU,O

  16. Expression of Membrane-Bound Human AminopeptidaseP as a Soluble Enzyme and an Investigation into Its Efficacy Towards Offering Protection Against the Toxicity of Chemical Warfare Nerve Agents

    DTIC Science & Technology

    2016-09-01

    survival rate of guinea pigs from GF toxicity [31]. The overall catalytic efficiency of II-G1 reported by Worek against GF was 8.4 × 107 M-1 min-1 and...al., Protection against soman or VX poisoning by human butyrylcholinesterase in guinea pigs and cynomolgus monkeys. Chem Biol Interact, 2005. 157...97-102. 30. Valiyaveettil, M., et al., Protective efficacy of catalytic bioscavenger, paraoxonase 1 against sarin and soman exposure in guinea pigs

  17. Optical interconnects for in-plane high-speed signal distribution at 10 Gb/s: Analysis and demonstration

    NASA Astrophysics Data System (ADS)

    Chang, Yin-Jung

    With decreasing transistor size, increasing chip speed, and larger numbers of processors in a system, the performance of a module/system is being limited by the off-chip and off-module bandwidth-distance products. Optical links have moved from fiber-based long distance communications to the cabinet level of 1m--100m, and recently to the backplane-level (10cm--1m). Board-level inter-chip parallel optical interconnects have been demonstrated recently by researchers from Intel, IBM, Fujitsu, NTT and a few research groups in universities. However, the board-level signal/clock distribution function using optical interconnects, the lightwave circuits, the system design, a practically convenient integration scheme committed to the implementation of a system prototype have not been explored or carefully investigated. In this dissertation, the development of a board-level 1 x 4 optical-to-electrical signal distribution at 10Gb/s is presented. In contrast to other prototypes demonstrating board-level parallel optical interconnects that have been drawing much attention for the past decade, the optical link design for the high-speed signal broadcasting is even more complicated and the pitch between receivers could be varying as opposed to fixed-pitch design that has been widely-used in the parallel optical interconnects. New challenges for the board-level high-speed signal broadcasting include, but are not limited to, a new optical link design, a lightwave circuit as a distribution network, and a novel integration scheme that can be a complete radical departure from the traditional assembly method. One of the key building blocks in the lightwave circuit is the distribution network in which a 1 x 4 multimode interference (MMI) splitter is employed. MMI devices operating at high data rates are important in board-level optical interconnects and need to be characterized in the application of board-level signal broadcasting. To determine the speed limitations of MMI devices, the

  18. DOE Office of Scientific and Technical Information (OSTI.GOV)

    Gilat, E.; Kadar, T.; Levy, A.

    Centrally mediated seizures and convulsions are common consequences of exposure to organophosphates (OPs). These seizures rapidly progress to status epilepticus (SE) and contribute to profound brain injury. Effective management of these seizures is critical for minimization of brain damage. Nasal application of midazolam (1.5 mg/kg) after 5 min of sarin-induced electrographic seizure activity (EGSA) ameliorated EGSA and convulsive behavior (238 {+-} 90 s). Identical treatment after 30 min was not sufficient to ameliorate ECoG paradoxical activity and convulsive behavior. Nasal midazolam (1.5 mg/kg), together with scopolamine (1 mg/kg, im) after 5 min of EGSA, exerted a powerful and rapid anticonvulsantmore » effect (53 {+-} 10 s). Delaying the same treatment to 30 min of EGSA leads to attenuation of paroxysmal ECoG activity in all cases but total cessation of paroxysmal activity was not observed in most animals tested. Cognitive tests utilizing the Morris Water Maze demonstrated that nasal midazolam alone or together with scopolamine (im), administered after 5 min of convulsions, abolished the effect of sarin on learning. Both these treatments, when given after 30 min of convulsions, only decreased the sarin-induced learning impairments. Whereas rats which were not subject to the anticonvulsant agents did not show any memory for the platform location, both treatments (at 5 min as well as at 30 min) completely abolished the memory deficits. Both treatments equally blocked the impairment of reversal learning when given at 5 min. However, when administered after 30 min, midazolam alone reversed the impairments in reversal learning, while midazolam with scopolamine did not. Rats exposed to sarin and treated with the therapeutic regimen with the exclusion of midazolam exhibited severe brain lesions that encountered the hippocampus, pyriform cortex, and thalamus. Nasal midazolam at 5 min prevented brain damage, while delaying the midazolam treatment to 30 min of EGSA

  19. 40 Gb/s W-band (75-110 GHz) 16-QAM radio-over-fiber signal generation and its wireless transmission.

    PubMed

    Kanno, Atsushi; Inagaki, Keizo; Morohashi, Isao; Sakamoto, Takahide; Kuri, Toshiaki; Hosako, Iwao; Kawanishi, Tetsuya; Yoshida, Yuki; Kitayama, Ken-ichi

    2011-12-12

    The generation of a 40-Gb/s 16-QAM radio-over-fiber (RoF) signal and its demodulation of the wireless signal transmitted over free space of 30 mm in W-band (75-110 GHz) is demonstrated. The 16-QAM signal is generated by a coherent polarization synthesis method using a dual-polarization QPSK modulator. A combination of the simple RoF generation and the versatile digital receiver technique is suitable for the proposed coherent optical/wireless seamless network. © 2011 Optical Society of America

  20. Biological monitoring of exposure to nerve agents.

    PubMed Central

    Bajgar, J

    1992-01-01

    Changes in acetylcholinesterase activity in blood and some organs of rats after intoxication with sarin, soman, VX, and 2-dimethylaminoethyl-(dimethylamido)-phosphonofluoridate (GV), in doses of roughly 2 x LD50 given intramuscularly, were obtained from published data and by experiment. The time course of inhibition of acetylcholinesterase in blood, regions of brain, and diaphragm and the occurrence of signs and symptoms of poisoning (none, salivation, disturbed ventilation and fasciculations, convulsions, or death) were summarised and compared. When blood enzyme activities were 70-100% normal, no obvious signs were seen; at 60-70%, salivation occurred; at less than 30-55%, disturbed ventilation and fasciculations were seen, and at 15-30%, convulsions occurred. Less than 10% was fatal. In experiments with narcotised dogs, the blood acetylcholinesterase activity and the ability to reactivate it with trimedoxime were determined after intoxication by intramuscular administration of the four compounds. It is concluded that acetylcholinesterase activity in the blood corresponds to that in the target organs and can be considered as an appropriate parameter for biological monitoring of exposure to nerve gases. Moreover, determination of reactivation of blood acetylcholinesterase gives more information than simple determination of enzyme activity. PMID:1390271

  1. Globotriaosylsphingosine (lyso-Gb3) might not be a reliable marker for monitoring the long-term therapeutic outcomes of enzyme replacement therapy for late-onset Fabry patients with the Chinese hotspot mutation (IVS4+919G>A)

    PubMed Central

    2014-01-01

    Background In Taiwan, DNA-based newborn screening showed a surprisingly high incidence (1/875 in males and 1/399 in females) of a cardiac Fabry mutation (IVS4 + 919G > A). However, the natural course, long-term treatment outcomes and suitable biomarkers for monitoring the therapeutic outcomes of these patients are largely unknown. Methods Fabry disease (FD) patients who had received enzyme replacement therapy (ERT) for more than 1 year were enrolled in this study from December 2008 to April 2013. Periodic echocardiography and serum globotriaosylsphingosine (lyso-Gb3) analysis were carried out. Before and after ERT, left ventricular mass index (LVMI) and serum lyso-Gb3 level were compared and the correlation between the change of LVMI and the change of serum lyso-Gb3 were also analyzed. Results Thirty-six patients, in four patient groups, were enrolled: (1) 16 males with IVS4 + 919G > A mutation; (2) 7 females with IVS4 + 919G > A mutation; (3) 2 males with classical mutations; and (4) 11 females with classical mutations. The follow-up period was 13–46 months. There were significant LVMI reductions after ERT in all four groups after excluding confounding factors. However, interestingly, serum lyso-Gb3 decreased significantly in the early period after ERT in all groups, but increased gradually after an average of 11.1 months after ERT in late-onset male and female Fabry groups, even when their LVMI still decreased or remained stable. Furthermore, there was no correlation between the change of serum lyso-Gb3 and the change of LVMI in both classical and IVS4 + 919G > A FD patients. Conclusion Although lyso-Gb3 has a high diagnostic sensitivity in late-onset Fabry patients and has a good response to ERT during the early stages, it might not be a reliable marker for monitoring the long-term therapeutic outcomes of ERT for late-onset Fabry patients with the Chinese hotspot mutation (IVS4 + 919G > A). PMID:25047006

  2. Enhanced noise tolerance for 10 Gb/s Bi-directional cross-wavelength reuse colorless WDM-PON by using spectrally shaped OFDM signals

    NASA Astrophysics Data System (ADS)

    Choudhury, Pallab K.

    2018-05-01

    Spectrally shaped orthogonal frequency division multiplexing (OFDM) signal for symmetric 10 Gb/s cross-wavelength reuse reflective semiconductor optical amplifier (RSOA) based colorless wavelength division multiplexed passive optical network (WDM-PON) is proposed and further analyzed to support broadband services of next generation high speed optical access networks. The generated OFDM signal has subcarriers in separate frequency ranges for downstream and upstream, such that the re-modulation noise can be effectively minimized in upstream data receiver. Moreover, the cross wavelength reuse approach improves the tolerance against Rayleigh backscattering noise due to the propagation of different wavelengths in the same feeder fiber. The proposed WDM-PON is successfully demonstrated for 25 km fiber with 16-QAM (quadrature amplitude modulation) OFDM signal having bandwidth of 2.5 GHz for 10 Gb/s operation and subcarrier frequencies in 3-5.5 GHz and DC-2.5 GHz for downstream (DS) and upstream (US) transmission respectively. The result shows that the proposed scheme maintains a good bit error rate (BER) performance below the forward error correction (FEC) limit of 3.8 × 10-3 at acceptable receiver sensitivity and provides a high resilience against re-modulation and Rayleigh backscattering noises as well as chromatic dispersion.

  3. SU-F-T-461: Dosimetric Evaluation of Indigenous Farmer Type Chamber FAR65- GB for Reference Dosimetry of FFF MV Photon Beam

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Patwe, P; Mhatre, V; Dandekar, P

    Purpose: Indigenous Farmer type chamber FAR 65 GB is a reference class 0.6 cc ion chamber. It can be used for dosimetric evaluation of photon and high energy electron beams. We studied dosimetric characteristics of the chamber for 6MV and 10MV Flattening filter free FFF photon beams available on trueBEAM STx Linac. Methods: The study was carried out on trueBEAM STx Linac having 6 and 10 MV FFF photon beam with maximum dose rate 1400 and 2400 MU per min respectively. The dosimetric device to be evaluated is Rosalina Instruments FAR 65-GB Ion Chamber with active volume 0.65 cc, totalmore » active length 23.1cm, inner diameter of cylinder 6.2mm, wall thickness 0.4mm, inner electrode diameter 1mm. Inner and outer electrodes are made from Aluminium 2.7 gm per cc and graphite 1.82 gm per cc respectively. The ion chamber was placed along central axis of beam at 10cm depth and irradiated for 10cm × 10cm field size at SAD of 100 cm in plastic phantom. We studied Precision, Dose Linearity, Dose Rate dependence, directional dependence, Recombination effect. Recombination effect was determined using standard two-voltage method. Results: 1. Measurements were reproducible std deviation of 0.0105 and type A uncertainty 0.003265 under same set of reference conditions 2. Chamber exhibit dose linearity over a wider dose range. 3. Chamber shows dose rate independence for all available dose rate range. 4. Response of chamber with the angle of incidence of radiation is constant. 5. Recombination correction factors were 1.01848 and 1.02537 for dose rate 1400 and 2400 MU per min resp. Conclusion: Our study reveals that the chamber is prone to saturation effect at dose rate of 2400 MU per min. FAR 65-GB can be used for reference dosimetry of FFF MV photon beam with proper calculation of recombination effect.« less

  4. 40-Gb/s PAM4 with low-complexity equalizers for next-generation PON systems

    NASA Astrophysics Data System (ADS)

    Tang, Xizi; Zhou, Ji; Guo, Mengqi; Qi, Jia; Hu, Fan; Qiao, Yaojun; Lu, Yueming

    2018-01-01

    In this paper, we demonstrate 40-Gb/s four-level pulse amplitude modulation (PAM4) transmission with 10 GHz devices and low-complexity equalizers for next-generation passive optical network (PON) systems. Simple feed-forward equalizer (FFE) and decision feedback equalizer (DFE) enable 20 km fiber transmission while high-complexity Volterra algorithm in combination with FFE and DFE can extend the transmission distance to 40 km. A simplified Volterra algorithm is proposed for reducing computational complexity. Simulation results show that the simplified Volterra algorithm reduces up to ∼75% computational complexity at a relatively low cost of only 0.4 dB power budget. At a forward error correction (FEC) threshold of 10-3 , we achieve 31.2 dB and 30.8 dB power budget over 40 km fiber transmission using traditional FFE-DFE-Volterra and our simplified FFE-DFE-Volterra, respectively.

  5. A Model of Medical Countermeasures for Organophosphates

    DTIC Science & Technology

    2015-10-01

    Animal Data ................................................................. 51 6.2.1. Verifying AChE Activity ...17 Figure 4-3. Model Output for AChE Activity and Free/Stimulated Receptor Fraction with No OP Exposure...Figure 6-1. Sarin Model Output Compared to Individual AChE Activity in Acute Phase Following Tokyo Sarin Attack

  6. Chemical Warfare Agent Surface Adsorption: Hydrogen Bonding of Sarin and Soman to Amorphous Silica

    DTIC Science & Technology

    2014-03-17

    Prior to experiments, the gas manifold and dosing lines were heated, under vacuum, to 100 °C to minimize water contamination. A stainless steel ...23 L UHV chamber constructed out of 316L stainless steel with all ports equipped with con-flat flanges (Kurt J. Lesker Company). The chamber is...dosed as a neat vapor using a multivalved stainless steel high-vacuum manifold. The entire path of the manifold was evacuated and heated to 100 °C

  7. Pest resistance and agronomic performance of Upland cotton lines following eight generations of introgression of the BNL3279_105 DNA marker from Gossypium barbadense GB713

    USDA-ARS?s Scientific Manuscript database

    The BNL3279 primers give unique DNA markers that are closely linked with resistance to reniform nematodes in Gossypium longicalx, Gossypium barbadense GB713, and Gossypium aridum. Plants that had been selected and advanced based on reniform nematode bioassays for each of five or six generations of ...

  8. 500  Gb/s free-space optical transmission over strong atmospheric turbulence channels.

    PubMed

    Qu, Zhen; Djordjevic, Ivan B

    2016-07-15

    We experimentally demonstrate a high-spectral-efficiency, large-capacity, featured free-space-optical (FSO) transmission system by using low-density, parity-check (LDPC) coded quadrature phase shift keying (QPSK) combined with orbital angular momentum (OAM) multiplexing. The strong atmospheric turbulence channel is emulated by two spatial light modulators on which four randomly generated azimuthal phase patterns yielding the Andrews spectrum are recorded. The validity of such an approach is verified by reproducing the intensity distribution and irradiance correlation function (ICF) from the full-scale simulator. Excellent agreement of experimental, numerical, and analytical results is found. To reduce the phase distortion induced by the turbulence emulator, the inexpensive wavefront sensorless adaptive optics (AO) is used. To deal with remaining channel impairments, a large-girth LDPC code is used. To further improve the aggregate data rate, the OAM multiplexing is combined with WDM, and 500 Gb/s optical transmission over the strong atmospheric turbulence channels is demonstrated.

  9. Forest Service special agents, assistant special agents in charge, senior special agents, and supervisory special agents report: nationwide study

    Treesearch

    Deborah J. Chavez; Joanne F. Tynon

    2007-01-01

    This is the fourth in a series of studies to evaluate perceptions of U.S. Department of Agriculture Forest Service law enforcement personnel of the roles, responsibilities, and issues related to their jobs. An e-mail survey was administered to the 89 Forest Service special agents, assistant special agents in charge, senior special agents, and supervisory special agents...

  10. [Physician Assisted Suicide - Survey on § 217 StGB in Germany].

    PubMed

    Zenz, Julia; Rissing-van Saan, Ruth; Zenz, Michael

    2017-03-01

    Background  In late 2015, Germany passed a law (§ 217 StGB) prohibiting persons from aiding others in committing suicide on a regular, repetitive basis. Despite intensive societal debate and surveys about assisted dying, the present study was the first to examine attitudes towards the new legal regulation among professionals. Methods  In early 2016, all participants of a congress on palliative care received a one-page anonymous questionnaire to complete until the end of the conference. The questionnaire consisted of questions regarding assisted suicide and the new law. The participants were asked to express their agreement or disagreement on a 4 to 5-point Likert scale. Results  457 questionnaires (48 %) were completed, 138 from physicians, 318 from nurses, 1 non specified. More than 80 % knew about the new law. Only half of the respondents supported it. 54 % felt that the law did not sufficiently differentiate between an illegal form of assisted suicide and a form exempt from prosecution. For more than 40 % the new law made no sense. Conclusion  Professionals engaged in terminal care were reluctant to support a criminal liability of "business-like" physician-assisted suicide and suspected greater uncertainty among professionals in end of life care. © Georg Thieme Verlag KG Stuttgart · New York.

  11. Therapeutic efficacy of the adenosine A1 receptor agonist N6-cyclopentyladenosine (CPA) against organophosphate intoxication.

    PubMed

    Bueters, Tjerk J H; Groen, Bas; Danhof, Meindert; IJzerman, Ad P; Van Helden, Herman P M

    2002-11-01

    The objective of the present study was to investigate whether reduction of central acetylcholine (ACh) accumulation by adenosine receptor agonists could serve as a generic treatment against organophosphate (OP) poisoning. The OPs studied were tabun ( O-ethyl- N-dimethylphosphoramidocyanidate), sarin (isopropylmethylphosphonofluoridate), VX ( O-ethyl- S-2-diisopropylaminoethylmethylphosphonothiolate) and parathion ( O, O-diethyl- O-(4-nitrophenyl)phosphorothioate). The efficacy of the adenosine A(1) receptor agonist N(6)-cyclopentyladenosine (CPA) against an OP intoxication was examined on the basis of the occurrence of clinical symptoms that are directly associated with such intoxication. CPA (1-2 mg/kg) effectively attenuated the cholinergic symptoms and prevented mortality in lethally tabun- or sarin-intoxicated rats. In contrast, CPA (2 mg/kg) proved to be ineffective against VX or parathion intoxication. Intracerebral microdialysis studies revealed that survival of sarin-poisoned and CPA-treated animals coincided with a minor elevation of extracellular ACh concentrations in the brain relative to the baseline value, whereas an 11-fold increase in transmitter levels was observed in animals not treated with CPA. In VX-intoxicated rats, however, the ACh amounts increased 18-fold, irrespective of treatment with CPA. The striatal acetylcholinesterase (AChE) activity following a lethal sarin intoxication was completely abolished in the vehicle-treated animals, whereas 10% and 60% AChE activity remained in animals treated with 2 mg/kg CPA 1 min after or 2 min prior to the poisoning, respectively. In VX-intoxicated animals the AChE activity in the brain was strongly reduced (striatum 10%, hippocampus 1%) regardless of the CPA treatment. These results demonstrate that CPA is highly effective against tabun or sarin poisoning, but fails to protect against VX or parathion. Survival and attenuation of clinical signs in tabun- or sarin-poisoned animals are associated with a

  12. Doctor pharmaceutical utilization behaviour changed by the global budget programme strategies on hypertensive outpatient prescription.

    PubMed

    Wei, Ching-Kuo; Wang, Shun-Mu; Yeh, Ming-Kung

    2012-04-01

    This study was to examine changes in doctor pharmaceutical utilization behaviour in response to Taiwan's newly implemented National Health Insurance individual hospital global budget (GB) programme and the changes in health care costs and prescription trends for hypertensive (HT) patients. We analysed hospital outpatient prescription utilization with a pre-post individual hospital GB group and comparison group (the hospitals who did not join the programme) to evaluate the impact of GB strategies on hypertensive expenditure. Descriptive analyses were performed based on the average daily medication expenditure for each prescription, and average number of items per prescription. This study reviewed 16,770,057 outpatient records and prescription records of 213,568 hypertensive patients. The average total medication expense (+17.6%), HT medication expense (+8.8%), daily medication expense (+16.3%), and daily HT medication expense (+6.3%) significantly increased after the action. After the individual hospital GB action, hospital doctors participating in action switched their patients' prescription drugs to other less expensive drugs such as rennin-angiotensin-aldosterone system inhibitors (-1.1%). The increase in volume of medications prescribed for control group were significantly larger for both alfa- and beta-adrenergic blocking agents (1.5%), and calcium channel blocking agents (3.9%). The individual hospital GB programme slowed down the trend of prescription drug cost increasing rate and reduced the prescription drug volume in hospitals. © 2010 Blackwell Publishing Ltd.

  13. On-Site Detection as a Countermeasure to Chemical Warfare/Terrorism.

    PubMed

    Seto, Y

    2014-01-01

    On-site monitoring and detection are necessary in the crisis and consequence management of wars and terrorism involving chemical warfare agents (CWAs) such as sarin. The analytical performance required for on-site detection is mainly determined by the fatal vapor concentration and volatility of the CWAs involved. The analytical performance for presently available on-site technologies and commercially available on-site equipment for detecting CWAs interpreted and compared in this review include: classical manual methods, photometric methods, ion mobile spectrometry, vibrational spectrometry, gas chromatography, mass spectrometry, sensors, and other methods. Some of the data evaluated were obtained from our experiments using authentic CWAs. We concluded that (a) no technologies perfectly fulfill all of the on-site detection requirements and (b) adequate on-site detection requires (i) a combination of the monitoring-tape method and ion-mobility spectrometry for point detection and (ii) a combination of the monitoring-tape method, atmospheric pressure chemical ionization mass spectrometry with counterflow introduction, and gas chromatography with a trap and special detectors for continuous monitoring. The basic properties of CWAs, the concept of on-site detection, and the sarin gas attacks in Japan as well as the forensic investigations thereof, are also explicated in this article. Copyright © 2014 Central Police University.

  14. Some recollections of Porton in World War 1. Commentary.

    PubMed

    Garner, J P

    2003-06-01

    Chemical weapons now regularly feature in news reports and the threat from them has become widely recognised by the public at large. Terrorist actions such as the Tokyo subway incident in 1995, coupled with the persistent use of agents such as sulphur mustard and Sarin by the Iraqi regime over the last 20 years in the Iran/Iraq war and against the Kurds of Northern Iraq, make it easy to think that chemical weapons are a new phenomenon. This paper reminds us that many chemical agents were developed during WWI; indeed the first use of a chemical agent was the release of chlorine gas--a choking agent--by the Germans over the battlefields of Ypres in 1915. Porton Down remains at the very heart of chemicals and biological weapons research, albeit in a purely defensive capacity; few of the old buildings remain and the idyllic lifestyle in the Officer's Mess at Idmiston Manor has long since disappeared. These recollections provide a fascinating insight into scientific research at the time of World War I.

  15. Effects of Deep Electroacupuncture Stimulation at “Huantiao” (GB 30) on Expression of Apoptosis-Related Factors in Rats with Acute Sciatic Nerve Injury

    PubMed Central

    Dai, Lili; Ma, Tieming; Liu, Yuli; Ren, Lu; Bai, Zenghua; Li, Ye

    2015-01-01

    SD rats were randomly divided into normal control, model, deep EA, and shallow EA groups. The model was established by mechanical clamping of the sciatic nerve stem. For deep and shallow EA, the needles were inserted into “Huantiao” (GB 30) by about 16 mm and 7 mm, respectively, once daily for 14 days. The results showed that, compared with the normal control group, the nerve-muscle excitability of rat's hip muscle decreased and the nerve conduction velocity of sciatic nerve slowed down in the model group; meanwhile, the number of apoptotic cells and the expression level of Bax protein in the injured nerve increased significantly, and the expression level of Bcl-2 protein and the ratio of Bcl-2/Bax decreased considerably. Compared with the model group, the indices mentioned above were reversed in the two treatment groups, and the changes in the deep EA group were more significant than those in the shallow EA group. These results indicate that EA stimulation at GB 30 can improve the function of injured sciatic nerve, which is closely associated with its effects in upregulating the expression of apoptosis inhibitive factor Bcl-2 and downregulating apoptosis promotive factor Bax. Deep EA is relatively better. PMID:26167187

  16. Wide range operation of regenerative optical parametric wavelength converter using ASE-degraded 43-Gb/s RZ-DPSK signals.

    PubMed

    Gao, Mingyi; Kurumida, Junya; Namiki, Shu

    2011-11-07

    For sustainable growth of the Internet, wavelength-tunable optical regeneration is the key to scaling up high energy-efficiency dynamic optical path networks while keeping the flexibility of the network. Wavelength-tunable optical parametric regenerator (T-OPR) based on the gain saturation effect of parametric amplification in a highly nonlinear fiber is promising for noise reduction in phase-shift keying signals. In this paper, we experimentally evaluated the T-OPR performance for ASE-degraded 43-Gb/s RZ-DPSK signals over a 20-nm input wavelength range between 1527 nm and 1547 nm. As a result, we achieved improved power penalty performance for the regenerated idler with a proper pump power range.

  17. Preparing Change Agents for Change Agent Roles.

    ERIC Educational Resources Information Center

    Sedlacek, James R.

    Seventy-seven Spanish- and Portuguese-speaking agricultural change agents from developing Central and South American countries responded to a questionnaire which sought perceptions of the roles in which the change agents felt they were involved and the roles for which they felt they were being trained. The agents were participating in training…

  18. Role of water in aging of human butyrylcholinesterase inhibited by echothiophate: the crystal structure suggests two alternative mechanisms of aging.

    PubMed

    Nachon, Florian; Asojo, Oluwatoyin A; Borgstahl, Gloria E O; Masson, Patrick; Lockridge, Oksana

    2005-02-01

    Organophosphorus poisons (OP) bind covalently to the active-site serine of cholinesterases. The inhibited enzyme can usually be reactivated with powerful nucleophiles such as oximes. However, the covalently bound OP can undergo a suicide reaction (termed aging) yielding nonreactivatable enzyme. In human butyrylcholinesterase (hBChE), aging involves the residues His438 and Glu197 that are proximal to the active-site serine (Ser198). The mechanism of aging is known in detail for the nerve gases soman, sarin, and tabun as well as the pesticide metabolite isomalathion. Aging of soman- and sarin-inhibited acetylcholinesterase occurs by C-O bond cleavage, whereas that of tabun- and isomalathion-inhibited acetylcholinesterase occurs by P-N and P-S bond cleavage, respectively. In this work, the crystal structures of hBChE inhibited by the ophthalmic reagents echothiophate (nonaged and aged) and diisopropylfluorophosphate (aged) were solved and refined to 2.1, 2.25, and 2.2 A resolution, respectively. No appreciable shift in the position of the catalytic triad histidine was observed between the aged and nonaged conjugates of hBChE. This absence of shift contrasts with the aged and nonaged crystal structures of Torpedo californica acetylcholinesterase inhibited by the nerve agent VX. The nonaged hBChE structure shows one water molecule interacting with Glu197 and the catalytic triad histidine (His438). Interestingly, this water molecule is ideally positioned to promote aging by two mechanisms: breaking either a C-O bond or a P-O bond. Pesticides and certain stereoisomers of nerve agents are expected to undergo aging by breaking the P-O bond.

  19. [Alkylating agents].

    PubMed

    Pourquier, Philippe

    2011-11-01

    With the approval of mechlorethamine by the FDA in 1949 for the treatment of hematologic malignancies, alkylating agents are the oldest class of anticancer agents. Even though their clinical use is far beyond the use of new targeted therapies, they still occupy a major place in specific indications and sometimes represent the unique option for the treatment of refractory diseases. Here, we are reviewing the major classes of alkylating agents and their mechanism of action, with a particular emphasis for the new generations of alkylating agents. As for most of the chemotherapeutic agents used in the clinic, these compounds are derived from natural sources. With a complex but original mechanism of action, they represent new interesting alternatives for the clinicians, especially for tumors that are resistant to conventional DNA damaging agents. We also briefly describe the different strategies that have been or are currently developed to potentiate the use of classical alkylating agents, especially the inhibition of pathways that are involved in the repair of DNA lesions induced by these agents. In this line, the development of PARP inhibitors is a striking example of the recent regain of interest towards the "old" alkylating agents.

  20. Fiber-wireless transmission system of 108  Gb/sdata over 80 km fiber and 2×2multiple-input multiple-output wireless links at 100 GHz W-band frequency.

    PubMed

    Li, Xinying; Dong, Ze; Yu, Jianjun; Chi, Nan; Shao, Yufeng; Chang, G K

    2012-12-15

    We experimentally demonstrate a seamlessly integrated fiber-wireless system that delivers a 108  Gb/s signal through 80 km fiber and 1 m wireless transport over free space at 100 GHz adopting polarization-division-multiplexing quadrature-phase-shift-keying (PDM-QPSK) modulation and heterodyning coherent detection. The X- and Y-polarization components of the optical PDM-QPSK baseband signal are simultaneously upconverted to 100 GHz wireless carrier by optical polarization-diversity heterodyne beating, and then independently transmitted and received by two pairs of transmitter and receiver antennas, which form a 2×2 multiple-input multiple-output wireless link. At the wireless receiver, two-stage downconversion is performed firstly in the analog domain based on balanced mixer and sinusoidal radio frequency signal, and then in the digital domain based on digital signal processing (DSP). Polarization demultiplexing is realized by the constant modulus algorithm in the DSP part at the receiver. The bit-error ratio for the 108  Gb/s PDM-QPSK signal is less than the pre-forward-error-correction threshold of 3.8×10(-3) after both 1 m wireless delivery at 100 GHz and 80 km single-mode fiber-28 transmission. To our knowledge, this is the first demonstration to realize 100  Gb/s signal delivery through both fiber and wireless links at 100 GHz.

  1. Comparison of the oxime-induced reactivation of rhesus monkey, swine and guinea pig erythrocyte acetylcholinesterase following inhibition by sarin or paraoxon, using a perfusion model for the real-time determination of membrane-bound acetylcholinesterase activity.

    PubMed

    Herkert, Nadja M; Lallement, Guy; Clarençon, Didier; Thiermann, Horst; Worek, Franz

    2009-04-28

    Recently, a dynamically working in vitro model with real-time determination of membrane-bound human acetylcholinesterase (AChE) activity was shown to be a versatile model to investigate oxime-induced reactivation kinetics of organophosphate- (OP) inhibited enzyme. In this assay, AChE was immobilized on particle filters which were perfused with acetylthiocholine, Ellman's reagent and phosphate buffer. Subsequently, AChE activity was continuously analyzed in a flow-through detector. Now, it was an intriguing question whether this model could be used with erythrocyte AChE from other species in order to investigate kinetic interactions in the absence of annoying side reactions. Rhesus monkey, swine and guinea pig erythrocytes were a stable and highly reproducible enzyme source. Then, the model was applied to the reactivation of sarin- and paraoxon-inhibited AChE by obidoxime or HI 6 and it could be shown that the derived reactivation rate constants were in good agreement to previous results obtained from experiments with a static model. Hence, this dynamic model offers the possibility to investigate highly reproducible interactions between AChE, OP and oximes with human and animal AChE.

  2. Biophotonic ring resonator for ultrasensitive detection of DMMP as a simulant for organophosphorus agents.

    PubMed

    Bonnot, Karine; Cuesta-Soto, Francisco; Rodrigo, Manuel; Varriale, Antonio; Sanchez, Nuria; D'Auria, Sabato; Spitzer, Denis; Lopez-Royo, Francisco

    2014-05-20

    Combining photonic integrated circuits with a biologically based sensing approach has the ability to provide a new generation of portable and low-cost sensor devices with a high specificity and sensitivity for a number of applications in environmental monitoring, defense, and homeland security. We report herein on the specific biosensing under continuous air flow of DMMP, which is commonly used as a simulant and a precursor for the synthesis of Sarin. The proposed technology is based on the selective recognition of the targeted DMMP molecule by specifically modified proteins immobilized on photonic structures. The response of the biophotonic structures shows a high stability and accuracy over 3 months, allowing for the detection in diluted air of DMMP at concentration as low as 35 μg/m(3) (6.8 ppb) in less than 15 min. The performance of the developed technology satisfies most current homeland and military security requirements.

  3. Challenges and Ideas to Achieve Wireless 100 Gb/s Transmission: An Overview of Challenges and Solutions within the German Research Foundation (DFG) Special Priority Program SPP1655

    NASA Astrophysics Data System (ADS)

    Kraemer, Rolf

    2017-09-01

    Wireless communications is one of the fastest growing technology fields, driving numerous other innovations in electronics. One challenging research area within the wireless field is to achieve much higher transmission rates. First products with up to 3 Gb/s are in the market. In the coming years we predict this speed growing quickly up to and beyond 100 Gb/s. Today it is an open question how we can realize a wireless system at this speed. If we intend to use such systems in a mobile environment, we can only afford to spend approximately 1-10 pW/b for the end-to-end communication. This includes RF-transmission and all processing and protocol steps. The SPP1655 of the DFG was set up to investigate new paradigms for achieving the 100 Gb/s wireless transmission goal. Within 11 coordinated projects researchers from all over Germany are addressing several relevant issues ranging from the antennas and RF-Frontend, baseband-processing and error correction to protocol processing. A number of limitations of current approaches have to be investigated and new algorithms must be found in order to achieve the intended goal. One of the big challenges is finding the correct balance between analog and digital signal processing to achieve an extremely high performance at very low energy consumption. Another challenge is to find a good balance between bandwidth and bandwidth efficiency to achieve the 100 Gbps goal. Finally, protocol processing will need new approaches to decouple the central processor of a computer from the high-end input/output operations. Within this editorial we will address the main challenges and briefly outline the approaches of the running projects. The rest of this special issue will be devoted to more detailed descriptions and achievements of the individual projects of SPP1655.

  4. Full-duplex bidirectional transmission of 10-Gb/s millimeter-wave QPSK signal in E-band optical wireless link.

    PubMed

    Fang, Yuan; Yu, Jianjun; Chi, Nan; Xiao, Jiangnan

    2014-01-27

    We experimentally demonstrated full-duplex bidirectional transmission of 10-Gb/s millimeter-wave (mm-wave) quadrature phase shift keying (QPSK) signal in E-band (71-76 GHz and 81-86 GHz) optical wireless link. Single-mode fibers (SMF) are connected at both sides of the antenna for uplink and downlink which realize 40-km SMF and 2-m wireless link for bidirectional transmission simultaneously. We utilized multi-level modulation format and coherent detection in such E-band optical wireless link for the first time. Mm-wave QPSK signal is generated by photonic technique to increase spectrum efficiency and received signal is coherently detected to improve receiver sensitivity. After the coherent detection, digital signal processing is utilized to compensate impairments of devices and transmission link.

  5. Incorporating BDI Agents into Human-Agent Decision Making Research

    NASA Astrophysics Data System (ADS)

    Kamphorst, Bart; van Wissen, Arlette; Dignum, Virginia

    Artificial agents, people, institutes and societies all have the ability to make decisions. Decision making as a research area therefore involves a broad spectrum of sciences, ranging from Artificial Intelligence to economics to psychology. The Colored Trails (CT) framework is designed to aid researchers in all fields in examining decision making processes. It is developed both to study interaction between multiple actors (humans or software agents) in a dynamic environment, and to study and model the decision making of these actors. However, agents in the current implementation of CT lack the explanatory power to help understand the reasoning processes involved in decision making. The BDI paradigm that has been proposed in the agent research area to describe rational agents, enables the specification of agents that reason in abstract concepts such as beliefs, goals, plans and events. In this paper, we present CTAPL: an extension to CT that allows BDI software agents that are written in the practical agent programming language 2APL to reason about and interact with a CT environment.

  6. Chemical warfare agents.

    PubMed

    Kuca, Kamil; Pohanka, Miroslav

    2010-01-01

    Chemical warfare agents are compounds of different chemical structures. Simple molecules such as chlorine as well as complex structures such as ricin belong to this group. Nerve agents, vesicants, incapacitating agents, blood agents, lung-damaging agents, riot-control agents and several toxins are among chemical warfare agents. Although the use of these compounds is strictly prohibited, the possible misuse by terrorist groups is a reality nowadays. Owing to this fact, knowledge of the basic properties of these substances is of a high importance. This chapter briefly introduces the separate groups of chemical warfare agents together with their members and the potential therapy that should be applied in case someone is intoxicated by these agents.

  7. Biological Agents

    MedlinePlus

    ... E-Tools Safety and Health Topics / Biological Agents Biological Agents This page requires that javascript be enabled ... 202) 693-2300 if additional assistance is required. Biological Agents Menu Overview In Focus: Ebola Frederick A. ...

  8. Designing Agent Utilities for Coordinated, Scalable and Robust Multi-Agent Systems

    NASA Technical Reports Server (NTRS)

    Tumer, Kagan

    2005-01-01

    Coordinating the behavior of a large number of agents to achieve a system level goal poses unique design challenges. In particular, problems of scaling (number of agents in the thousands to tens of thousands), observability (agents have limited sensing capabilities), and robustness (the agents are unreliable) make it impossible to simply apply methods developed for small multi-agent systems composed of reliable agents. To address these problems, we present an approach based on deriving agent goals that are aligned with the overall system goal, and can be computed using information readily available to the agents. Then, each agent uses a simple reinforcement learning algorithm to pursue its own goals. Because of the way in which those goals are derived, there is no need to use difficult to scale external mechanisms to force collaboration or coordination among the agents, or to ensure that agents actively attempt to appropriate the tasks of agents that suffered failures. To present these results in a concrete setting, we focus on the problem of finding the sub-set of a set of imperfect devices that results in the best aggregate device. This is a large distributed agent coordination problem where each agent (e.g., device) needs to determine whether to be part of the aggregate device. Our results show that the approach proposed in this work provides improvements of over an order of magnitude over both traditional search methods and traditional multi-agent methods. Furthermore, the results show that even in extreme cases of agent failures (i.e., half the agents failed midway through the simulation) the system's performance degrades gracefully and still outperforms a failure-free and centralized search algorithm. The results also show that the gains increase as the size of the system (e.g., number of agents) increases. This latter result is particularly encouraging and suggests that this method is ideally suited for domains where the number of agents is currently in the

  9. 42.8 Gb/s ASK homodyne receiver using standard DFB lasers

    NASA Astrophysics Data System (ADS)

    Becker, D.; Mohr, D.; Datta, S.; Wree, C.; Bhandare, S.; Joshi, A.

    2009-05-01

    Optical synchronous coherent detection is attracting greater attention within the defense and security community because it allows linear recovery both of the amplitude and phase of optical signals. Fiber-based transmission impairments such as chromatic dispersion and polarization mode dispersion can be compensated in the electrical domain. Additionally, synchronous detection offers the potential of improved receiver sensitivity and extended reach versus direct or interferometric detection schemes. 28 Gbaud/112 Gb/s and 42.8 Gbaud transmissions are now being considered in fiber networks worldwide. Due to the lack of broadband high frequency components centered at IF values of 56 GHz and 86 GHz, respectively, the coherent heterodyne approach is not viable for these baud rates. The homodyne approach remains one of the choices available to fully exploit the advantages of synchronous coherent detection at these transmission data rates. In order to implement the homodyne receiver, optical phase locking between the signal and local oscillator laser (LO) is required. Digital approaches for this task rely upon very complex, fast, and high power-consumption chips. A homodyne receiver using an analog approach for phase locking would allow for increased system simplicity at a lower cost. Use of commercial-off-the-shelf (COTS) DFB lasers embedded within the receiver would also increase system feasibility for defense applications. We demonstrate synchronous demodulation of a 42.8 Gbaud signal using an analog optical phase-locked loop. The homodyne system was optimized to use COTS DFB lasers having an aggregate linewidth of ~2 MHz. We also analyze the impact of uncompensated phase noise on receiver performance.

  10. 49.6 Gb/s direct detection DMT transmission over 40 km single mode fibre using an electrically packaged silicon photonic modulator.

    PubMed

    Lacava, C; Cardea, I; Demirtzioglou, I; Khoja, A E; Ke, Li; Thomson, D J; Ruan, X; Zhang, F; Reed, G T; Richardson, D J; Petropoulos, P

    2017-11-27

    We present the characterization of a silicon Mach-Zehnder modulator with electrical packaging and show that it exhibits a large third-order intermodulation spurious-free dynamic range (> 100 dB Hz 2/3 ). This characteristic renders the modulator particularly suitable for the generation of high spectral efficiency discrete multi-tone signals and we experimentally demonstrate a single-channel, direct detection transmission system operating at 49.6 Gb/s, exhibiting a baseband spectral efficiency of 5 b/s/Hz. Successful transmission is demonstrated over various lengths of single mode fibre up to 40 km, without the need of any amplification or dispersion compensation.

  11. An upstream burst-mode equalization scheme for 40 Gb/s TWDM PON based on optimized SOA cascade

    NASA Astrophysics Data System (ADS)

    Sun, Xiao; Chang, Qingjiang; Gao, Zhensen; Ye, Chenhui; Xiao, Simiao; Huang, Xiaoan; Hu, Xiaofeng; Zhang, Kaibin

    2016-02-01

    We present a novel upstream burst-mode equalization scheme based on optimized SOA cascade for 40 Gb/s TWDMPON. The power equalizer is placed at the OLT which consists of two SOAs, two circulators, an optical NOT gate, and a variable optical attenuator. The first SOA operates in the linear region which acts as a pre-amplifier to let the second SOA operate in the saturation region. The upstream burst signals are equalized through the second SOA via nonlinear amplification. From theoretical analysis, this scheme gives sufficient dynamic range suppression up to 16.7 dB without any dynamic control or signal degradation. In addition, a total power budget extension of 9.3 dB for loud packets and 26 dB for soft packets has been achieved to allow longer transmission distance and increased splitting ratio.

  12. Bandwidth efficient bidirectional 5 Gb/s overlapped-SCM WDM PON with electronic equalization and forward-error correction.

    PubMed

    Buset, Jonathan M; El-Sahn, Ziad A; Plant, David V

    2012-06-18

    We demonstrate an improved overlapped-subcarrier multiplexed (O-SCM) WDM PON architecture transmitting over a single feeder using cost sensitive intensity modulation/direct detection transceivers, data re-modulation and simple electronics. Incorporating electronic equalization and Reed-Solomon forward-error correction codes helps to overcome the bandwidth limitation of a remotely seeded reflective semiconductor optical amplifier (RSOA)-based ONU transmitter. The O-SCM architecture yields greater spectral efficiency and higher bit rates than many other SCM techniques while maintaining resilience to upstream impairments. We demonstrate full-duplex 5 Gb/s transmission over 20 km and analyze BER performance as a function of transmitted and received power. The architecture provides flexibility to network operators by relaxing common design constraints and enabling full-duplex operation at BER ∼ 10(-10) over a wide range of OLT launch powers from 3.5 to 8 dBm.

  13. The oxidative TCA cycle operates during methanotrophic growth of the Type I methanotroph Methylomicrobium buryatense 5GB1.

    PubMed

    Fu, Yanfen; Li, Yi; Lidstrom, Mary

    2017-07-01

    Methanotrophs are a group of bacteria that use methane as sole carbon and energy source. Type I methanotrophs are gamma-proteobacterial methanotrophs using the ribulose monophosphate cycle (RuMP) cycle for methane assimilation. In order to facilitate metabolic engineering in the industrially promising Type I methanotroph Methylomicrobium buryatense 5GB1, flux analysis of cellular metabolism is needed and 13 C tracer analysis is a foundational tool for such work. This biological system has a single-carbon input and a special network topology that together pose challenges to the current well-established methodology for 13 C tracer analysis using a multi-carbon input such as glucose, and to date, no 13 C tracer analysis of flux in a Type I methanotroph has been reported. In this study, we showed that by monitoring labeling patterns of several key intermediate metabolites in core metabolism, it is possible to quantitate the relative flux ratios for important branch points, such as the malate node. In addition, it is possible to assess the operation of the TCA cycle, which has been thought to be incomplete in Type I methanotrophs. Surprisingly, our analysis provides direct evidence of a complete, oxidative TCA cycle operating in M. buryatense 5GB1 using methane as sole carbon and energy substrate, contributing about 45% of the total flux for de novo malate production. Combined with mutant analysis, this method was able to identify fumA (METBUDRAFT_1453/MBURv2__60244) as the primary fumarase involved in the oxidative TCA cycle, among 2 predicted fumarases, supported by 13 C tracer analysis on both fumA and fumC single knockouts. Interrupting the oxidative TCA cycle leads to a severe growth defect, suggesting that the oxidative TCA cycle functions to not only provide precursors for de novo biomass synthesis, but also to provide reducing power to the system. This information provides new opportunities for metabolic engineering of M. buryatense for the production of

  14. LDQ10: a compact ultra low-power radiation-hard 4 × 10 Gb/s driver array

    DOE PAGES

    Zeng, Z.; Zhang, T.; Wang, G.; ...

    2017-02-28

    Here, a High-speed and low-power VCSEL driver is an important component of the Versatile Link for the high-luminosity LHC (HL-LHC) experiments. A compact low-power radiation-hard 4 × 10 Gb/s VCSEL driver array (LDQ10) has been developed in 65 nm CMOS technology. Each channel in LDQ10 can provide a modulation current up to 8 mA and bias current up to 12 mA. Edge pre-emphasis is employed to compensate for the bandwidth limitations due to parasitic and the turn-on delay of VCSEL devices. LDQ10 occupies a chip area of 1900 μm × 1700 μm and consumes 130 mW power for typical currentmore » settings. The modulation amplitude degrades less than 5% after 300 Mrad total ionizing dose. LDQ10 can be directly wire-bonded to the VCSEL array and it is a suitable candidate for the Versatile Link.« less

  15. 22 CFR 51.22 - Passport agents and passport acceptance agents.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 22 Foreign Relations 1 2012-04-01 2012-04-01 false Passport agents and passport acceptance agents. 51.22 Section 51.22 Foreign Relations DEPARTMENT OF STATE NATIONALITY AND PASSPORTS PASSPORTS Application § 51.22 Passport agents and passport acceptance agents. (a) U.S. citizen employees of the...

  16. 22 CFR 51.22 - Passport agents and passport acceptance agents.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 22 Foreign Relations 1 2014-04-01 2014-04-01 false Passport agents and passport acceptance agents. 51.22 Section 51.22 Foreign Relations DEPARTMENT OF STATE NATIONALITY AND PASSPORTS PASSPORTS Application § 51.22 Passport agents and passport acceptance agents. (a) U.S. citizen employees of the...

  17. 22 CFR 51.22 - Passport agents and passport acceptance agents.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 22 Foreign Relations 1 2013-04-01 2013-04-01 false Passport agents and passport acceptance agents. 51.22 Section 51.22 Foreign Relations DEPARTMENT OF STATE NATIONALITY AND PASSPORTS PASSPORTS Application § 51.22 Passport agents and passport acceptance agents. (a) U.S. citizen employees of the...

  18. 22 CFR 51.22 - Passport agents and passport acceptance agents.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 22 Foreign Relations 1 2010-04-01 2010-04-01 false Passport agents and passport acceptance agents. 51.22 Section 51.22 Foreign Relations DEPARTMENT OF STATE NATIONALITY AND PASSPORTS PASSPORTS Application § 51.22 Passport agents and passport acceptance agents. (a) U.S. citizen employees of the...

  19. 22 CFR 51.22 - Passport agents and passport acceptance agents.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 22 Foreign Relations 1 2011-04-01 2011-04-01 false Passport agents and passport acceptance agents. 51.22 Section 51.22 Foreign Relations DEPARTMENT OF STATE NATIONALITY AND PASSPORTS PASSPORTS Application § 51.22 Passport agents and passport acceptance agents. (a) U.S. citizen employees of the...

  20. Seamless integration of 57.2-Gb/s signal wireline transmission and 100-GHz wireless delivery.

    PubMed

    Li, Xinying; Yu, Jianjun; Dong, Ze; Cao, Zizheng; Chi, Nan; Zhang, Junwen; Shao, Yufeng; Tao, Li

    2012-10-22

    We experimentally demonstrated the seamless integration of 57.2-Gb/s signal wireline transmission and 100-GHz wireless delivery adopting polarization-division-multiplexing quadrature-phase-shift-keying (PDM-QPSK) modulation with 400-km single-mode fiber-28 (SMF-28) transmission and 1-m wireless delivery. The X- and Y-polarization components of optical PDM-QPSK baseband signal are simultaneously up-converted to 100 GHz by optical polarization-diversity heterodyne beating, and then independently transmitted and received by two pairs of transmitter and receiver antennas, which make up a 2x2 multiple-input multiple-output (MIMO) wireless link based on microwave polarization multiplexing. At the wireless receiver, a two-stage down conversion is firstly done in analog domain based on balanced mixer and sinusoidal radio frequency (RF) signal, and then in digital domain based on digital signal processing (DSP). Polarization de-multiplexing is realized by constant modulus algorithm (CMA) based on DSP in heterodyne coherent detection. Our experimental results show that more taps are required for CMA when the X- and Y-polarization antennas have different wireless distance.