Pacific Coast Torpedo Station, Keyport Industrial District, Both sides of ...

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

Pacific Coast Torpedo Station, Keyport Industrial District, Both sides of Second Street, between Dedrick Drive and Liberty Bay and one building west of Dedrick Drive and south of Second Street, Keyport, Kitsap County, WA

49 CFR 174.5 - Carrier's materials and supplies.

Code of Federal Regulations, 2014 CFR

2014-10-01

... requirements of this subchapter do not apply to railway torpedoes or fusees when carried in engines or rail cars. Railway torpedoes must be in closed metal boxes when not in use. [Amdt. 174-26B, 41 FR 57071, Dec...

49 CFR 174.5 - Carrier's materials and supplies.

Code of Federal Regulations, 2013 CFR

2013-10-01

... requirements of this subchapter do not apply to railway torpedoes or fusees when carried in engines or rail cars. Railway torpedoes must be in closed metal boxes when not in use. [Amdt. 174-26B, 41 FR 57071, Dec...

49 CFR 174.5 - Carrier's materials and supplies.

Code of Federal Regulations, 2010 CFR

2010-10-01

... requirements of this subchapter do not apply to railway torpedoes or fusees when carried in engines or rail cars. Railway torpedoes must be in closed metal boxes when not in use. [Amdt. 174-26B, 41 FR 57071, Dec...

49 CFR 174.5 - Carrier's materials and supplies.

Code of Federal Regulations, 2012 CFR

2012-10-01

... requirements of this subchapter do not apply to railway torpedoes or fusees when carried in engines or rail cars. Railway torpedoes must be in closed metal boxes when not in use. [Amdt. 174-26B, 41 FR 57071, Dec...

49 CFR 174.5 - Carrier's materials and supplies.

Code of Federal Regulations, 2011 CFR

2011-10-01

... requirements of this subchapter do not apply to railway torpedoes or fusees when carried in engines or rail cars. Railway torpedoes must be in closed metal boxes when not in use. [Amdt. 174-26B, 41 FR 57071, Dec...

An immunoglobulin M monoclonal antibody, recognizing a subset of acetylcholinesterase molecules from electric organs of Electrophorus and Torpedo, belongs to the HNK-1 anti-carbohydrate family.

PubMed

Bon, S; Méflah, K; Musset, F; Grassi, J; Massoulié, J

1987-12-01

An immunoglobulin M (IgM) monoclonal antibody (mAb Elec-39), obtained against asymmetric acetylcholinesterase (AChE) from Electrophorus electric organs, also reacts with a fraction of globular AChE (amphiphilic G2 form) from Torpedo electric organs. This antibody does not react with asymmetric AChE from Torpedo electric organs or with the enzyme from other tissues of Electrophorus or Torpedo. The corresponding epitope is removed by endoglycosidase F, showing that it is a carbohydrate. The subsets of Torpedo G2 that react or do not react with Elec-39 (Elec-39+ and Elec-39-) differ in their electrophoretic mobility under nondenaturing conditions; the Elec-39+ component also binds the lectins from Pisum sativum and Lens culinaris. Whereas the Elec-39- component is present at the earliest developmental stages examined, an Elec-39+ component becomes distinguishable only around the 70-mm stage. Its proportion increases progressively, but later than the rapid accumulation of the total G2 form. In immunoblots, mAb Elec-39 recognizes a number of proteins other than AChE from various tissues of several species. The specificity of Elec-39 resembles that of a family of anti-carbohydrate antibodies that includes HNK-1, L2, NC-1, NSP-4, as well as IgMs that occur in human neuropathies. Although some human neuropathy IgMs that recognize the myelin-associated glycoprotein did not react with Elec-39+ AChE, mAbs HNK-1, NC-1, and NSP-4 showed the same selectivity as Elec-39 for Torpedo G2 AChE, but differed in the formation of immune complexes.

27 CFR 447.21 - The U.S. Munitions Import List.

Code of Federal Regulations, 2010 CFR

2010-04-01

...—launch vehicles, guided missiles, ballistic missiles, rockets, torpedoes, bombs and mines (a) Rockets (including but not limited to meteorological and other sounding rockets), bombs, grenades, torpedoes, depth..., the following: Fuses and components for the items in this category, bomb racks and shackles, bomb...

Integration of the NRL Digital Library.

ERIC Educational Resources Information Center

King, James

2001-01-01

The Naval Research Laboratory (NRL) Library has identified six primary areas that need improvement: infrastructure, InfoWeb, TORPEDO Ultra, journal data management, classified data, and linking software. It is rebuilding InfoWeb and TORPEDO Ultra as database-driven Web applications, upgrading the STILAS library catalog, and creating other support…

Coupling the Torpedo microplate-receptor binding assay with mass spectrometry to detect cyclic imine neurotoxins.

PubMed

Aráoz, Rómulo; Ramos, Suzanne; Pelissier, Franck; Guérineau, Vincent; Benoit, Evelyne; Vilariño, Natalia; Botana, Luis M; Zakarian, Armen; Molgó, Jordi

2012-12-04

Cyclic imine neurotoxins constitute an emergent family of neurotoxins of dinoflagellate origin that are potent antagonists of nicotinic acetylcholine receptors. We developed a target-directed functional method based on the mechanism of action of competitive agonists/antagonists of nicotinic acetylcholine receptors for the detection of marine cyclic imine neurotoxins. The key step for method development was the immobilization of Torpedo electrocyte membranes rich in nicotinic acetylcholine receptors on the surface of microplate wells and the use of biotinylated-α-bungarotoxin as tracer. Cyclic imine neurotoxins competitively inhibit biotinylated-α-bungarotoxin binding to Torpedo-nicotinic acetylcholine receptors in a concentration-dependent manner. The microplate-receptor binding assay allowed rapid detection of nanomolar concentrations of cyclic imine neurotoxins directly in shellfish samples. Although highly sensitive and specific for the detection of neurotoxins targeting nicotinic acetylcholine receptors as a class, the receptor binding assay cannot identify a given analyte. To address the low selectivity of the microplate-receptor binding assay, the cyclic imine neurotoxins tightly bound to the coated Torpedo nicotinic receptor were eluted with methanol, and the chemical nature of the eluted ligands was identified by mass spectrometry. The immobilization of Torpedo electrocyte membranes on the surface of microplate wells proved to be a high-throughput format for the survey of neurotoxins targeting nicotinic acetylcholine receptors directly in shellfish matrixes with high sensitivity and reproducibility.

Coupling the Torpedo Microplate-Receptor Binding Assay with Mass Spectrometry to Detect Cyclic Imine Neurotoxins

PubMed Central

Aráoz, Rómulo; Ramos, Suzanne; Pelissier, Franck; Guérineau, Vincent; Benoit, Evelyne; Vilariño, Natalia; Botana, Luis M.; Zakarian, Armen; Molgó, Jordi

2014-01-01

Cyclic imine neurotoxins constitute an emergent family of neurotoxins of dinoflagellate origin that are potent antagonists of nicotinic acetylcholine receptors. We developed a target-directed functional method based on the mechanism of action of competitive agonists/antagonists of nicotinic acetylcholine receptors for the detection of marine cyclic imine neurotoxins. The key step for method development was the immobilization of Torpedo electrocyte membranes rich in nicotinic acetylcholine receptors on the surface of microplate wells and the use of biotinylated-α-bungarotoxin as tracer. Cyclic imine neurotoxins competitively inhibit biotinylated-α-bungarotoxin binding to Torpedo-nicotinic acetylcholine receptors in a concentration-dependent manner. The microplate-receptor binding assay allowed rapid detection of nanomolar concentrations of cyclic imine neurotoxins directly in shellfish samples. Although highly sensitive and specific for the detection of neurotoxins targeting nicotinic acetylcholine receptors as a class, the receptor binding assay cannot identify a given analyte. To address the low selectivity of the microplate-receptor binding assay, the cyclic imine neurotoxins tightly bound to the coated Torpedo nicotinic receptor were eluted with methanol, and the chemical nature of the eluted ligands was identified by mass spectrometry. The immobilization of Torpedo electrocyte membranes on the surface of microplate wells proved to be a high-throughput format for the survey of neurotoxins targeting nicotinic acetylcholine receptors directly in shellfish matrixes with high sensitivity and reproducibility. PMID:23131021

CAST FLOOR WITH VIEW OF TORPEDO LADLE (BENEATH CAST FLOOR) ...

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

CAST FLOOR WITH VIEW OF TORPEDO LADLE (BENEATH CAST FLOOR) AND KEEPERS OF THE CAST HOUSE FLOOR, S.L. KIMBROUGH AND DAVID HOLMES. - U.S. Steel, Fairfield Works, Blast Furnace No. 8, North of Valley Road, West of Ensley-Pleasant Grove Road, Fairfield, Jefferson County, AL

Investigation of Single-Stage Modified Turbine of Mark 25 Torpedo Power Plant

NASA Technical Reports Server (NTRS)

Hoyt, Jack W.

1947-01-01

Efficiency investigations have been made on a single-stage modification of the turbine of a Mark 25 aerial torpedo to determine the performance of the unit with five different turbine nozzles. The output of the turbine blades was computed by analyzing the windage and mechanical-friction losses of the unit. The turbine was faund to be most efficient with a cast nozzle having sharp-edged inlets to the nine nozzle ports. An analysis af the effectiveness af the first and second stages of the standard Mark 25 torpedo turbine indicates that the first- stage turbine contributes nearly all the brake power produced at blade-jet speed ratios above 0.26.

TORPEDO: Networked Access to Full-Text and Page-Image Representations of Physics Journals and Technical Reports.

ERIC Educational Resources Information Center

Atkinson, Roderick D.; Stackpole, Laurie E.

1995-01-01

The Naval Research Laboratory (NRL) Library and the American Physical Society (APS) are experimenting with electronically disseminating journals and reports in a project called TORPEDO (The Optical Retrieval Project: Electronic Documents Online). Scanned journals and reports are converted to ASCII, then attached to bibliographic information, and…

19. Interior first level view looking north within forward (north) ...

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

19. Interior first level view looking north within forward (north) section of firing pier. Objects pictured include torpedo cart (left), floor-mounted roller tray (extending to lower right), and (at center rear), deck-type firing tube. - Naval Torpedo Station, Firing Pier, North end of Gould Island in Narragansett Bay, Newport, Newport County, RI

22 CFR 121.5 - Apparatus and devices under Category IV(c).

Code of Federal Regulations, 2011 CFR

2011-04-01

... 22 Foreign Relations 1 2011-04-01 2011-04-01 false Apparatus and devices under Category IV(c). 121... UNITED STATES MUNITIONS LIST Enumeration of Articles § 121.5 Apparatus and devices under Category IV(c... units, bomb ejectors, torpedo tubes, torpedo and guided missile boosters, guidance systems equipment and...

Synapsin I is associated with cholinergic nerve terminals in the electric organs of Torpedo, Electrophorus, and Malapterurus and copurifies with Torpedo synaptic vesicles.

PubMed

Volknandt, W; Naito, S; Ueda, T; Zimmermann, H

1987-08-01

Using an affinity-purified monospecific polyclonal antibody against bovine brain synapsin I, the distribution of antigenically related proteins was investigated in the electric organs of the three strongly electric fish Torpedo marmorata, Electrophorus electricus, Malapterurus electricus and in the rat diaphragm. On application of indirect fluorescein isothiocyanate-immunofluorescence and using alpha-bungarotoxin for identification of synaptic sites, intense and very selective staining of nerve terminals was found in all of these tissues. Immunotransfer blots of tissue homogenates revealed specific bands whose molecular weights are similar to those of synapsin Ia and synapsin Ib. Moreover, synapsin I-like proteins are still attached to the synaptic vesicles that were isolated in isotonic glycine solution from Torpedo electric organ by density gradient centrifugation and chromatography on Sephacryl-1000. Our results suggest that synapsin I-like proteins are also associated with cholinergic synaptic vesicles of electric organs and that the electric organ may be an ideal source for studying further the functional and molecular properties of synapsin.

Antigenic role of single residues within the main immunogenic region of the nicotinic acetylcholine receptor.

PubMed Central

Papadouli, I; Potamianos, S; Hadjidakis, I; Bairaktari, E; Tsikaris, V; Sakarellos, C; Cung, M T; Marraud, M; Tzartos, S J

1990-01-01

The target of most of the autoantibodies against the acetylcholine receptor (AChR) in myasthenic sera is the main immunogenic region (MIR) on the extracellular side of the AChR alpha-subunit. Binding of anti-MIR monoclonal antibodies (mAbs) has been recently localized between residues alpha 67 and alpha 76 of Torpedo californica electric organ (WNPADYGGIK) and human muscle (WNPDDYGGVK) AChR. In order to evaluate the contribution of each residue to the antigenicity of the MIR, we synthesized peptides corresponding to residues alpha 67-76 from Torpedo and human AChRs, together with 13 peptide analogues. Nine of these analogues had one residue of the Torpedo decapeptide replaced by L-alanine, three had a structure which was intermediate between those of the Torpedo and human alpha 67-76 decapeptides, and one had D-alanine in position 73. Binding studies employing six anti-MIR mAbs and all 15 peptides revealed that some residues (Asn68 and Asp71) are indispensable for binding by all mAbs tested, whereas others are important only for binding by some mAbs. Antibody binding was mainly restricted to residues alpha 68-74, the most critical sequence being alpha 68-71. Fish electric organ and human MIR form two distinct groups of strongly overlapping epitopes. Some peptide analogues enhanced mAb binding compared with Torpedo and human peptides, suggesting that the construction of a very antigenic MIR is feasible. PMID:1695844

Torpedo maculopathy: Two case reports and a literature review.

PubMed

de Manuel-Triantafilo, S; Gili, P; Bañuelos Bañuelos, J

2016-08-01

The cases concern a 4 year-old boy and 25 year-old female with 20/20 visual acuity, who presented with a unilateral non-pigmented macular lesion, temporal to the fovea, a torpedo shaped defect in the retinal pigment epithelium (RPE). Optical coherence tomography showed attenuation of the RPE signal, and in the second patient there proved to be a neurosensory detachment, RPE atrophy, and thinning of the retinal layers. The lesion was hypoautofluorescent and hyperfluorescent on fluorescein angiography. Torpedo maculopathy is an asymptomatic characteristic lesion which should be considered in the differential diagnosis of macular lesions in children and young patients. Copyright © 2016 Sociedad Española de Oftalmología. Published by Elsevier España, S.L.U. All rights reserved.

Agelenopsis aperta venom and FTX, a purified toxin, inhibit acetylcholine release in Torpedo synaptosomes.

PubMed

Moulian, N; Gaudry-Talarmain, Y M

1993-06-01

The presence of P-type calcium channels in synaptosomes prepared from electric organ of Torpedo marmorata was investigated by using the venom of Agelenopsis aperta, a toxin purified from it, FTX, and its synthetic analog. We analysed the action of these agents on acetylcholine release which was continuously followed using a chemiluminescent assay. Agelenopsis aperta venom, FTX and synthetic FTX inhibit acetylcholine release from synaptosomes induced by a presynaptic membrane depolarization with 60 mM KCl. A stronger inhibition of acetylcholine release was observed with the venom than with FTX (70 and 50%, respectively). Another way of triggering acetylcholine release from Torpedo synaptosomes is to insert in the presynaptic membrane a calcium ionophore A23187 which allows the bypass of the natural calcium channels. The venom of Agelenopsis aperta inhibits A23187-evoked acetylcholine release. Purified and synthetic FTX does not possess this property, suggesting that this inhibition of acetylcholine release was due to other toxins of the venom. Another type of pharmacological sensitivity of Torpedo calcium channels was also demonstrated using omega-conotoxin GVIA. At a concentration of 20 microM, this toxin was able to inhibit about 35% of KCl-evoked acetylcholine release. When FTX + omega-conotoxin GVIA were applied together, the inhibitory effect on KCl-evoked acetylcholine release was not significantly increased in comparison with the one observed with FTX alone. In conclusion, we examined the effect of different agents on acetylcholine release from Torpedo marmorata electric organ synaptosomes; acetylcholine release was elicited with KCl depolarization and followed continuously with a chemiluminescent assay.(ABSTRACT TRUNCATED AT 250 WORDS)

Pascagoula Harbor, Mississippi, Feasibility Report on Improvement of the Federal Deep-Draft Navigation Channel. Volume 1. Main Report and Environmental Impact Statement.

DTIC Science & Technology

1985-03-01

cerifera) and stands of Cogongrass, locally known as ’Jap Grass’ ( Imperata cylindrica ) and torpedo grass (Panicum repens). The lower southeastern-most...dominated by wax myrtle and sea myrtle with stands of Cogongrass, locally known as ’Jap Grass’ ( Imperata cylindrica ) and torpedo grass (Panicum repens

Summary of Recent Hybrid Torpedo Powerplant Studies

DTIC Science & Technology

2007-12-01

engine (such as the one used in SCEPS), a generic open-cycle expander engine that operates on a mixture of combustion products, a Brayton cycle engine ...difficult to produce an efficient engine that operates at a high backpressure . This particular value was chosen because it was used in a study of various... Effect of Design High Speed .........................................................................13 Figure 4: Hybrid vs. Conventional Torpedo Range

Ciguatoxin extracted from poisonous moray eels Gymnothorax javanicus triggers acetylcholine release from Torpedo cholinergic synaptosomes via reversed Na(+)-Ca2+ exchange.

PubMed

Molgó, J; Gaudry-Talarmain, Y M; Legrand, A M; Moulian, N

1993-09-17

Ciguatoxin (CTX) (0.1 pM to 10 nM) added to a suspension of Torpedo synaptosomes incubated in Ca(2+)-free medium caused no detectable acetylcholine (ACh) release. However, subsequent addition of Ca2+ caused a large ACh release that depended on time of exposure, dose of CTX and on [Ca2+]. Tetrodotoxin completely prevented CTX-induced Ca(2+)-dependent ACh release. Simultaneous blockade of Ca2+ channel subtypes by FTX, a toxin extracted from the venom of the spider Agelenopsis aperta, omega-conotoxin and Gd3+ did not prevent ACh release caused by CTX, upon addition of Ca2+. These results suggest that CTX activates the reversed operation of the Na+/Ca2+ exchange system allowing the entry of Ca2+ in exchange for Na+. It is concluded that Torpedo synaptosomes are endowed with Na+ channels sensitive to pico- to nanomolar concentrations of CTX.

Mechanical characterisation of the TorPeDO: a low frequency gravitational force sensor

NASA Astrophysics Data System (ADS)

McManus, D. J.; Forsyth, P. W. F.; Yap, M. J.; Ward, R. L.; Shaddock, D. A.; McClelland, D. E.; Slagmolen, B. J. J.

2017-07-01

Newtonian noise is likely to be a future challenge at low frequencies for Advanced LIGO and other second generation gravitational wave detectors. We present the TorPeDO system: a dual torsion pendulum sensor designed to measure local gravitational forces to high precision. Gravitational forces induce a differential rotation between the two torsion beams, which is measured with an optical read-out. Both torsion pendulums have a common suspension point, tunable centre of mass, and resonant frequency. This produces a high level of mechanical common mode noise cancellation. We report on a controls prototype of the TorPeDO system, presenting the frequency response and tuning range of both pendulums. A noise budget and mechanical cross-coupling model for this system are also presented. We demonstrate frequency tuning of the two torsion pendulums to a difference of 4.3 μHz.

X-Ray Crystallographic Studies on Acetylcholinesterase and on Its Interaction with Anticholinesterase Agents.

DTIC Science & Technology

1994-11-24

complexes with reversible ligands, including edrophonium, d-tubocurarine and huperzine A , diffracting to similar resolution. The X26c Laue beam line...The EMBL-DESY synchrotron facility at Hamburg was employed to collect a complete 2.3 A data set for a crystal of native Torpedo AChE, as well as for...at the NSLS synchrotron facility at Brookhaven National Laboratory (BNL) was used to obtain a Laue diffraction pattern for a crystal of native Torpedo

Torpedoes and Their Impact on Naval Warfare

DTIC Science & Technology

2017-01-01

wind to get to their destinations. This meant ships were no Overview 11 longer at the mercy of nature since they were no longer dependent on wind and...ships had to slip their cables to avoid the exploding torpedoes. However, although 10 mines exploded, none of them came in contact with a French...ahead” just doesn’t have the same ring to it; this appears to be a case where it is better to be eloquent rather than technically accurate. The

An Illustrative Case Study for Twentieth Century Defense Planners: The Technology and Politics of United States Coastal Defense, 1880-1898.

DTIC Science & Technology

1980-04-24

plunging fire on the armored decks of attacking ships. Some inventors and technicians would propose increased use of submarine mines and torpedoes for...and mines , see "The Defense of Our Sea-Ports," Harper’s Weekly 71 (November 1885): 928-930 and the "Endicott Report," p. 97; for the Navy’s role, see...urgently re- quired, the character and kind of defenses best adapted for each, with reference to armament [and] the utilization of torpedoes, mines

Increasing the Kill Effectiveness of High Energy Laser (HEL) Combat System

DTIC Science & Technology

2015-03-01

mm Machine Gun These versatile craft are Chinese imports. Some vessels have been configured without missiles in order to carry the larger MLRS...Displacement: 28.16 tons Armament: (2) 533 mm Torpedo Tubes Length: 21.12 m (1) 12.7 machine gun Beam: 5.77 m Draft: 0.87 m Speed: 20.6 m/s...m (2) Nasr ASM Draft: 0.67 m (2) 12.7 mm machine gun Speed: 26.7 m/s The original, low-observable torpedo boat, IPS-16 was imported from

Comparative effects of aluminum and ouabain on synaptosomal choline uptake, acetylcholine release and (Na+/K+)ATPase.

PubMed

Silva, Virgília S; Nunes, M Alexandra; Cordeiro, J Miguel; Calejo, Ana I; Santos, Sofia; Neves, Paulo; Sykes, António; Morgado, Fernando; Dunant, Yves; Gonçalves, Paula P

2007-07-17

Closing the gap between adverse health effects of aluminum and its mechanisms of action still represents a huge challenge. Cholinergic dysfunction has been implicated in neuronal injury induced by aluminum. Previously reported data also indicate that in vivo and in vitro exposure to aluminum inhibits the mammalian (Na(+)/K(+))ATPase, an ubiquitous plasma membrane pump. This study was undertaken with the specific aim of determining whether in vitro exposure to AlCl(3) and ouabain, the foremost utilized selective inhibitor of (Na(+)/K(+))ATPase, induce similar functional modifications of cholinergic presynaptic nerve terminals, by comparing their effects on choline uptake, acetylcholine release and (Na(+)/K(+))ATPase activity, on subcellular fractions enriched in synaptic nerve endings isolated from rat brain, cuttlefish optic lobe and torpedo electric organ. Results obtained show that choline uptake by rat synaptosomes was inhibited by submillimolar AlCl(3), whereas the amount of choline taken up by synaptosomes isolated from cuttlefish and torpedo remained unchanged. Conversely, choline uptake was reduced by ouabain to a large extent in all synaptosomal preparations analyzed. In contrast to ouabain, which modified the K(+) depolarization evoked release of acetylcholine by rat, cuttlefish and torpedo synaptosomal fractions, AlCl(3) induced reduction of stimulated acetylcholine release was only observed when rat synaptosomes were challenged. Finally, it was observed that the aluminum effect on cuttlefish and torpedo synaptosomal (Na(+)/K(+))ATPase activity was slight when compared to its inhibitory action on mammalian (Na(+)/K(+))ATPase. In conclusion, inhibition of (Na(+)/K(+))ATPase by AlCl(3) and ouabain jeopardized the high-affinity (Na(+)-dependent, hemicholinium-3 sensitive) uptake of choline and the Ca(2+)-dependent, K(+) depolarization evoked release of acetylcholine by rat, cuttlefish and torpedo synaptosomal fractions. The effects of submillimolar AlCl(3) on choline uptake and acetylcholine release only resembled those of ouabain when rat synaptosomes were assayed. Therefore, important differences were found between the species regarding the cholinotoxic action of aluminum. The variability of (Na(+)/K(+))ATPase sensitivity to aluminum of cholinergic neurons might contribute to their differential susceptibility to this neurotoxic agent.

Contributions of Torpedo nicotinic acetylcholine receptor gamma Trp-55 and delta Trp-57 to agonist and competitive antagonist function.

PubMed

Xie, Y; Cohen, J B

2001-01-26

Results of affinity-labeling studies and mutational analyses provide evidence that the agonist binding sites of the nicotinic acetylcholine receptor (nAChR) are located at the alpha-gamma and alpha-delta subunit interfaces. For Torpedo nAChR, photoaffinity-labeling studies with the competitive antagonist d-[(3)H]tubocurarine (dTC) identified two tryptophans, gammaTrp-55 and deltaTrp-57, as the primary sites of photolabeling in the non-alpha subunits. To characterize the importance of gammaTrp-55 and deltaTrp-57 to the interactions of agonists and antagonists, Torpedo nAChRs were expressed in Xenopus oocytes, and equilibrium binding assays and electrophysiological recordings were used to examine the functional consequences when either or both tryptophans were mutated to leucine. Neither substitution altered the equilibrium binding of dTC. However, the deltaW57L and gammaW55L mutations decreased acetylcholine (ACh) binding affinity by 20- and 7,000-fold respectively. For the wild-type, gammaW55L, and deltaW57L nAChRs, the concentration dependence of channel activation was characterized by Hill coefficients of 1.8, 1.1, and 1.7. For the gammaW55L mutant, dTC binding at the alpha-gamma site acts not as a competitive antagonist but as a coactivator or partial agonist. These results establish that interactions with gamma Trp-55 of the Torpedo nAChR play a crucial role in agonist binding and in the agonist-induced conformational changes that lead to channel opening.

Detection of a Double Relic in the Torpedo Cluster: SPT-CL J0245-5302

NASA Astrophysics Data System (ADS)

Zheng, Q.; Johnston-Hollitt, M.; Duchesne, S. W.; Li, W. T.

2018-06-01

The Torpedo cluster, SPT-CL J0245-5302 (S0295) is a massive, merging cluster at a redshift of z = 0.300, which exhibits a strikingly similar morphology to the Bullet cluster 1E 0657-55.8 (z = 0.296), including a classic bow shock in the cluster's intra-cluster medium revealed by Chandra X-ray observations. We present Australia Telescope Compact Array data centred at 2.1 GHz and Murchison Widefield Array data at frequencies between 72 MHz and 231 MHz which we use to study the properties of the cluster. We characterise a number of discrete and diffuse radio sources in the cluster, including the detection of two previously unknown radio relics on the cluster periphery. The average spectral index of the diffuse emission between 70 MHz and 3.1 GHz is α =-1.63_{-0.10}^{+0.10} and a radio-derived Mach number for the shock in the west of the cluster is calculated as M = 2.04. The Torpedo cluster is thus a double relic system at moderate redshift.

Design, synthesis, and characterization of a 39 amino acid peptide mimic of the main immunogenic region of the Torpedo acetylcholine receptor.

PubMed

Trinh, Vu B; Foster, Alex J; Fairclough, Robert H

2014-05-01

We have designed a 39 amino acid peptide mimic of the conformation-dependent main immunogenic region (MIR) of the Torpedo acetylcholine receptor (TAChR) that joins three discontinuous segments of the Torpedo α-subunit, α(1-12), α(65-79), and α(110 - 115) with two GS linkers: This 39MIR-mimic was expressed in E. coli as a fusion protein with an intein-chitin-binding domain (IChBD) to permit affinity collection on chitin beads. Six MIR-directed monoclonal antibodies (mAbs) bind to this complex and five agonist/antagonist site directed mAbs do not. The complex of MIR-directed mAb-132A with 39MIR has a Kd of (2.11±0.11)×10(-10)M, which is smaller than (7.13±1.20)×10(-10)M for the complex of mAb-132A with α(1-161) and about the same as 3.4×10(-10)M for that of mAb-132A with TAChR. Additionally, the 39MIR-IChBD adsorbs all MIR-directed antibodies (Abs) from an experimental autoimmune myasthenia gravis (EAMG) rat serum. Hence, the 39MIR-mimic has the potential to inactivate or remove pathogenic Torpedo MIR-directed Abs from EAMG sera and to direct a magic bullet to the memory B-cells that produce those pathogenic Abs. The hope is to use this as a guide to produce a mimic of the human MIR on the way to an antigen specific therapeutic agent to treat MG. Copyright © 2014 Elsevier Ltd. All rights reserved.

Photoautotrophic Culture of Coffea arabusta Somatic Embryos: Photosynthetic Ability and Growth of Different Stage Embryos

PubMed Central

AFREEN, F.; ZOBAYED, S. M. A.; KOZAI, T.

2002-01-01

Coffea arabusta somatic embryos were cultured and development of stomata, rate of CO2 fixation or production, chlorophyll content and chlorophyll fluorescence were studied in embryos at different stages of development. Cotyledonary and germinated embryos have photosynthetic capacity, although pretreatment at a high photosynthetic photon flux (PPF) (100 µmol m–2 s–1) for 14 d increased photosynthetic ability. Except in a very small number of cases, stomata did not develop fully in precotyledonary stage embryos and were absent in torpedo stage embryos. Low chlorophyll content (90–130 µg g–1 fresh mass) was noted in torpedo and precotyledonary stage embryos compared with cotyledonary and germinated embryos (300–500 µg g–1 fresh mass). Due to the absence of stomata and low chlorophyll content in the torpedo and precotyledonary stage embryos, the photosynthetic rate was low and, in some cases, CO2 production was observed. These data suggest that the cotyledonary stage is the earliest stage that can be cultured photoautotrophically to ensure plantlet development. When grown photoautotrophically (in a sugar‐free medium with CO2 enrichment in the culture headspace and high photosynthetic photon flux), torpedo and precotyledonary stage embryos lost 20–25 % of their initial dry mass after 60 d of culture. However, in cotyledonary and germinated embryos, the dry mass of each embryo increased by 10 and 50 %, respectively. By using a porous supporting material, growth (especially root growth) was increased in cotyledonary stage embryos. In addition, photoautotrophic conditions, high PPF (100–150 µmol m–2 s–1) and increased CO2 concentration (1100 µmol mol–1) were found to be necessary for the development of plantlets from cotyledonary stage embryos. PMID:12125763

Analyses of battle casualties by weapon type aboard U.S. Navy warships.

PubMed

Blood, C G

1992-03-01

The number of casualties was determined for 513 incidents involving U.S. Navy warships sunk or damaged during World War II. Ship type and weapon were significant factors in determining the numbers of wounded and killed. Multiple weapon attacks and kamikazes yielded more wounded in action than other weapon types. Multiple weapons and torpedos resulted in a higher incidence of killed in action than other weapons. Penetrating wounds and burns were the most prominent injury types. Kamikaze attacks yielded significantly more burns than incidents involving bombs, gunfire, torpedos, mines, and multiple weapons. Mine explosions were responsible for more strains, sprains, and dislocations than the other weapon types.

Summary of Investigations of Mark 25 Aerial-Torpedo Turbine

NASA Technical Reports Server (NTRS)

Schum, Harold J.; Whitney, Warren J.; Buckner, Howard A., Jr.

1950-01-01

The power plant from a Mark 25 aerial torpedo was investigated both as a two-stage turbine and as a single-stage modified turbine to determine the effect on overall performance of nozzle size and shape, first-stage rotor-blade configuration, and axial nozzle-rotor running clearance. Performance was evaluated in terms of brake, rotor, and blade efficiencies. All the performance data were obtained for inlet total to outlet static pressure ratios of 8, 15 (design), and 20 with inlet conditions maintained constant at 95 pounds per square inch gage and 1000 F for rotor speeds from approximately 6000 to 18,000 rpm.

The sinking of the Lusitania: reviewing the evidence.

PubMed

Wood, M G; Smith, D I; Hayns, M R

2002-01-01

On the afternoon of 7 May 1915 the Cunard Liner Lusitania was torpedoed by a German U-boat whilst en route to Liverpool. Consequently in sank with the loss of 1,195 lives. A series of investigative and formal research exercises, undertaken in the light of eye-witness accounts of the events surrounding that tragedy, has given rise to a number of hypotheses concerning the loss of this vessel. In this paper all the available evidence concerning the attack, and the one or more explosions that occurred, is summarised. The conclusions regarding the torpedo effects and the most likely causes of the secondary events are reported.

Standardization of the experimental autoimmune myasthenia gravis (EAMG) model by immunization of rats with Torpedo californica acetylcholine receptors — Recommendations for methods and experimental designs

PubMed Central

Losen, Mario; Martinez-Martinez, Pilar; Molenaar, Peter C.; Lazaridis, Konstantinos; Tzartos, Socrates; Brenner, Talma; Duan, Rui-Sheng; Luo, Jie; Lindstrom, Jon; Kusner, Linda

2015-01-01

Myasthenia gravis (MG) with antibodies against the acetylcholine receptor (AChR) is characterized by a chronic, fatigable weakness of voluntary muscles. The production of autoantibodies involves the dysregulation of T cells which provide the environment for the development of autoreactive B cells. The symptoms are caused by destruction of the postsynaptic membrane and degradation of the AChR by IgG autoantibodies, predominantly of the G1 and G3 subclasses. Active immunization of animals with AChR from mammalian muscles, AChR from Torpedo or Electrophorus electric organs, and recombinant or synthetic AChR fragments generates a chronic model of MG, termed experimental autoimmune myasthenia gravis (EAMG). This model covers cellular mechanisms involved in the immune response against the AChR, e.g. antigen presentation, T cell-help and regulation, B cell selection and differentiation into plasma cells. Our aim is to define standard operation procedures and recommendations for the rat EAMG model using purified AChR from the Torpedo californica electric organ, in order to facilitate more rapid translation of preclinical proof of concept or efficacy studies into clinical trials and, ultimately, clinical practice. PMID:25796590

Inhibition of cation channel function at the nicotinic acethylcholine receptor from Torpedo: Agonist self-inhibition and anesthetic drugs

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

Forman, S.A.

1989-01-01

Modulation of the nicotinic acethylcholine receptor from Torpedo by cholinergic agonists, local anesthetics, and n-alkanols was studied using {sup 86}Rb{sup +} flux studies in sealed native Torpedo electroplaque membrane vesicles. Reliable concentration-response and kinetic data were obtained using manual ten sec filtration assays in vesicles partially blocked with alpha-bungarotoxin to remove spare receptors and quenched-flow assays to assess initial {sup 86}Rb{sup +} flux rates or the rate of drug-induced receptor inactivation. Concentration response relationships for the agonists acetylcholine, carbamylcholine, suberyldicholine, phenyltrimethylammonium, and (-)-nicotine are all bell-shape due to stimulation of cation channel opening at low concentrations and inhibition of channelsmore » at higher concentrations. The rate of agonist-induced fast desensitization (k{sub d}) increases with (acetylcholine) in parallel with channel activation, suggesting that desensitization proceeds from the open state and/or states in rapid equilibrium with it. At self-inhibitory acetylcholine concentrations, a new rapid inactivation (rate = k{sub f}) is observed before fast desensitization. The rate and extent of rapid inactivation is compatible with bimolecular association between acethylcholine and inhibitory site with K{sub B} = 40 mM.« less

Occurrence of the Leech, Pontobdella muricata Linnaeus, on Elasmobranch Species in the Northern and Central Adriatic Sea.

PubMed

Bolognini, Luca; Leoni, Simone; Polidori, Piero; Grati, Fabio; Scarcella, Giuseppe; Pellini, Giulio; Domenichetti, Filippo; Ferrà, Carmen; Fabi, Gianna

2016-12-01

This study provides a parasitological analysis of the elasmobranch species caught in the northern and central Adriatic Sea. Sixty-two marine leeches were recorded on 747 individuals of Raja clavata Linnaeus, 1758 (thornback ray), Myliobatis aquila Linnaeus, 1758 (common eagle ray), and Torpedo marmorata Risso, 1810 (marbled torpedo ray) caught in 56 hauls over a 5 yr period. All leeches were identified as Pontobdella muricata, which is a typical ectoparasite of benthic elasmobranchs. The prevalence of infection ranged from 7.11% on R. clavata to 12.00% on M. aquila. The intensity of infection, the preferential sites of attachment to the host, and the periodicity of infection were evaluated.

H and T subunits of acetylcholinesterase from Torpedo, expressed in COS cells, generate all types of globular forms

PubMed Central

1992-01-01

We analyzed the production of Torpedo marmorata acetylcholinesterase (AChE) in transfected COS cells. We report that the presence of an aspartic acid at position 397, homologous to that observed in other cholinesterases and related enzymes (Krejci, E., N. Duval, A. Chatonnet, P. Vincens, and J. Massoulie. 1991. Proc. Natl. Acad. Sci. USA. 88:6647-6651), is necessary for catalytic activity. The presence of an asparagine in the previously reported cDNA sequence (Sikorav, J.L., E. Krejci, and J. Massoulie. 1987. EMBO (Eur. Mol. Biol. Organ.) J. 6:1865-1873) was most likely due to a cloning error (codon AAC instead of GAC). We expressed the T and H subunits of Torpedo AChE, which differ in their COOH-terminal region and correspond respectively to the collagen-tailed asymmetric forms and to glycophosphatidylinositol-anchored dimers of Torpedo electric organs, as well as a truncated T subunit (T delta), lacking most of the COOH- terminal peptide. The transfected cells synthesized similar amounts of AChE immunoreactive protein at 37 degrees and 27 degrees C. However AChE activity was only produced at 27 degrees C and, even at this temperature, only a small proportion of the protein was active. We analyzed the molecular forms of active AChE produced at 27 degrees C. The H polypeptides generated glycophosphatidylinositol-anchored dimers, resembling the corresponding natural AChE form. The cells also released non-amphiphilic dimers G2na. The T polypeptides generated a series of active forms which are not produced in Torpedo electric organs: G1a, G2a, G4a, and G4na cellular forms and G2a and G4na secreted forms. The amphiphilic forms appeared to correspond to type II forms (Bon, S., J. P. Toutant, K. Meflah, and J. Massoulie. 1988. J. Neurochem. 51:776- 785; Bon, S., J. P. Toutant, K. Meflah, and J. Massoulie. 1988. J. Neurochem. 51:786-794), which are abundant in the nervous tissue and muscles of higher vertebrates (Bon, S., T. L. Rosenberry, and J. Massoulie. 1991. Cell. Mol. Neurobiol. 11:157-172). The H and T catalytic subunits are thus sufficient to account for all types of known AChE forms. The truncated T delta subunit yielded only non- amphiphilic monomers, demonstrating the importance of the T COOH- terminal peptide in the formation of oligomers, and in the hydrophobic character of type II forms. PMID:1639848

Biosynthesis of acetyl-coenzyme A in the electric organ of Torpedo marmorata in relation to acetylcholine metabolism.

PubMed Central

Diebler, M F; Morot-Gaudry, Y

1977-01-01

Formation of acetyl-CoA through acetyl-CoA synthetase (forward reaction) and through choline acyltransferase (backward reaction) was investigated in tissue extract from the electric organ of Torpedo marmorata. When the tissue extract was submitted to gel filtration on Sephadex G-25, the formation of acetyl-CoA by acetyl-CoA synthetase appeared fully dependent on ATP and CoA and partially dependent on acetate (an endogenous supply of acetate is discussed). Choline acetyltransferase was a potent source of acetyl-CoA, only requiring acetylcholine and CoA, and was much more efficient than acetyl-CoA synthetase for concentrations of acetylcholine likely to be present in nerve endings. PMID:23101

Structure of the glycosyl-phosphatidylinositol membrane anchor of acetylcholinesterase from the electric organ of the electric-fish, Torpedo californica.

PubMed Central

Mehlert, A; Varon, L; Silman, I; Homans, S W; Ferguson, M A

1993-01-01

The structure of the glycan moiety of the glycosyl-phosphatidylinositol (GPI) membrane anchor from Torpedo californica (electric fish) electric-organ acetylcholinesterase was solved using n.m.r., methylation analysis and chemical and enzymic micro-sequencing. Two structures were found to be present: Glc alpha 1-2Man alpha 1-2Man alpha 1-6Man alpha 1-4GlcN alpha 1-6myo-inositol and Glc alpha 1-2Man alpha 1-2Man alpha 1-6(GalNAc beta 1-4)Man alpha 1-4GlcN alpha 1-6myo-inositol. The presence of glucose in this GPI anchor structure is a novel feature. The anchor was also shown to contain 2.3 residues of ethanolamine per molecule. PMID:8257440

The adenosine-triphosphatase system responsible for cation transport in electric organ: exclusion of phospholipids as intermediates

PubMed Central

Glynn, I. M.; Slayman, Carolyn W.; Eichberg, J.; Dawson, R. M. C.

1965-01-01

1. Subcellular fractions were prepared from the electric organs of Electrophorus and Torpedo and assayed for adenosine-triphosphatase activity. 2. Treatment of the `low-speed' fraction from Torpedo with m-urea gave an adenosine-triphosphatase preparation that was almost completely (98%) inhibited by ouabain (0·1mg./ml.) and dependent on the simultaneous presence of Na+ and K+. 3. The adenosine-triphosphatase preparations were exposed to [γ-32P]ATP for 30sec. in the presence of (i) Na+, (ii) K+, (iii) Na++K+ and (iv) Na++K++ouabain. No significant labelling of phosphatidic acid, triphosphoinositide or any other phospholipid was observed. 4. The results suggest that phospholipids do not act as phosphorylated intermediates in the `transport adenosine-triphosphatase' system of electric organ. PMID:14340060

Early Rockets

NASA Image and Video Library

2004-04-15

All through the 13th to the 15th Centuries there were reports of many rocket experiments. For example, Joanes de Fontana of Italy designed a surface-rurning, rocket-powered torpedo for setting enemy ships on fire

Clip and Save.

ERIC Educational Resources Information Center

Hubbard, Guy

2003-01-01

Provides a reproduction of a painting called "Torpedo" by Roy Lichtenstein that was chosen because of facial expression. Includes learning activities for use with students as well as background information about the artist and the painting. (CMK)

Epidermal patterning genes are active during embryogenesis in Arabidopsis.

PubMed

Costa, Silvia; Dolan, Liam

2003-07-01

Epidermal cells in the root of Arabidopsis seedling differentiate either as hair or non-hair cells, while in the hypocotyl they become either stomatal or elongated cells. WEREWOLF (WER) and GLABRA2 (GL2) are positive regulators of non-hair and elongated cell development. CAPRICE (CPC) is a positive regulator of hair cell development in the root. We show that WER, GL2 and CPC are expressed and active during the stages of embryogenesis when the pattern of cells in the epidermis of the root-hypocotyl axis forms. GL2 is first expressed in the future epidermis in the heart stage embryo and its expression is progressively restricted to those cells that will acquire a non-hair identity in the transition between torpedo and mature stage. The expression of GL2 at the heart stage requires WER function. WER and CPC are transiently expressed throughout the root epidermal layer in the torpedo stage embryo when the cell-specific pattern of GL2 expression is being established in the epidermis. We also show that WER positively regulates CPC transcription and GL2 negatively regulates WER transcription in the mature embryo. We propose that the restriction of GL2 to the future non-hair cells in the root epidermis can be correlated with the activities of WER and CPC during torpedo stage. In the embryonic hypocotyl we show that WER controls GL2 expression. We also provide evidence indicating that CPC may also regulate GL2 expression in the hypocotyl.

Photoaffinity labeling of the Torpedo californica nicotinic acetylcholine receptor with an aryl azide derivative of phosphatidylserine

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

Blanton, M.P.; Wang, H.H.

1990-02-06

A photoactivatable analogue of phosphatidylserine, {sup 125}I-labeled 4-azidosalicylic acid-phosphatidylserine ({sup 125}I ASA-PS), was used to label both native acetylcholine receptor (AchR)-rich membranes from Torpedo californica and AchR membranes affinity purified from Torpedo reconstituted into asolectin vesicles. The radioiodinated arylazido group attaches directly to the phospholipid head group and thus probes for regions of the AchR structure in contact with the negatively charged head group of phosphatidylserine. All four subunits of the AchR incorporated the label, with the {alpha} subunit incorporating approximately twice as much as each of the other subunits on a per mole basis. The regions of the AchRmore » {alpha} subunit that incorporated {sup 125}I ASA-PS were mapped by Staphylococcus aureus V8 protease digestion. The majority of label incorporated into fragments representing a more complete digestion of the {alpha} subunit was localized to 11.7- and 10.1-kDa V8 cleavage fragments, both beginning at Asn-339 and of sufficient length to contain the hydrophobic region M4. An 18.7-kDa fragment beginning at Ser-173 and of sufficient length to contain the hydrophobic regions M1, M2, and M3 was also significantly labeled. In contrast, V8 cleavage fragments representing roughly a third of the amino-terminal portion of the {alpha} subunit incorporated little or no detectable amount of probe.« less

76 FR 25299 - Notice of Petitions by Firms for Determination of Eligibility To Apply for Trade Adjustment...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-05-04

... manufactures acoustic Inc. Braintree, MA 02184. countermeasures--electro-acoustic products used to decoy/confuse acoustic homing torpedoes, sonar transducers. Any party having a substantial interest in these...

Group Learning.

ERIC Educational Resources Information Center

Black, Susan

1992-01-01

Research suggests that cooperative learning works best when students are first taught group-processing skills, such as leadership, decision making, communication, trust building, and conflict management. Inadequate teacher training and boring assignments can torpedo cooperative learning efforts. Administrators should reassure teachers with…

There's a Green Glob in Your Classroom.

ERIC Educational Resources Information Center

Dugdale, Sharon

1983-01-01

Discusses computer games (called intrinsic models) focusing on mathematics rather than on unrelated motivations (flashing lights or sounds). Games include "Green Globs," (equations/linear functions), "Darts"/"Torpedo" (fractions), "Escape" (graphing), and "Make-a-Monster" (equivalent fractions and…

Somatic embryogenesis in wild relatives of cotton (Gossypium Spp.)

PubMed Central

Rao, Abdul Qayyum; Hussain, S. Sarfraz; Shahzad, M. Saqib; Bokhari, S. Yassir Abbas; Raza, M. Hashim; Rakha, Allah; Majeed, A.; Shahid, A. Ali; Saleem, Zafar; Husnain, Tayyab; Riazuddin, S.

2006-01-01

Wild cotton species can contribute a valuable gene pool for agronomically desirable cultivated tetraploid cultivars. In order to exploit diploid cotton a regeneration system is required to achieve transformation based goals. The present studies aimed at optimizing the conditions for regeneration of local varieties as well as wild species of cotton. Different callus induction media were tested with varying concentrations of hormones in which sucrose was used as nutritional source. Different explants (hypocotyls, cotyledon, root) were used to check the regeneration of both local cotton plants and wild relatives using T & G medium, BAP medium, CIM medium, EMMS medium, and cell suspension medium. Different stages of embryogenicity such as early torpedo stage, late torpedo stage, heart stage, globular stage and cotyledonary stage were observed in wild relatives of cotton. The results of this study pave the way for establishing future transformation methods. PMID:16532531

Pressure reversal of the action of octanol on postsynaptic membranes from Torpedo.

PubMed Central

Braswell, L. M.; Miller, K. W.; Sauter, J. F.

1984-01-01

Octanol increases the binding of [3H]-acetylcholine to the desensitized state of the nicotinic receptor in postsynaptic membranes prepared from Torpedo californica. This increase in binding results from an increase in the affinity of [3H]-acetylcholine for its receptor without any change in the number of sites or the shape of the acetylcholine binding curve. High pressures of helium (300 atm) decrease [3H]-acetylcholine binding by a mechanism that changes only the affinity of acetylcholine binding. Helium pressure reverses the effect of octanol on the affinity of [3H]-acetylcholine for its receptor. This pressure reversal of the action of octanol at a postsynaptic membrane is consistent either with pressure counteracting an octanol-induced membrane expansion or with independent mechanisms for the actions of octanol and pressure. The data do not conform with a mechanism in which pressure displaces octanol from a binding site on the receptor protein. PMID:6487895

Inhibition of cholinesterases by stereoisomers of Huperzine-A

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

Saxena, A.; Qian, N.; Kovach, I.M.

1993-05-13

Huperzine-A, a potential drug for the treatment of Alzheimer's disease and possible pretreament for nerve agent toxicity, has recently been characterized as a reversible inhibitor of cholinesterases (Ashani et al., BBRC, 184:719-726, 1992). Long-term incubation of purified cholinesterases with Huperzine-A did not show any chemical modification of Huperzine-A. The dissociation constant, K(I), for fetal bovine serum acetylcholinesterase (FBS AChE) was approximately 20 nM, for Torpedo AChE was 215 nM, and for horse serum butyrylcholinesterase (BChE) was 40 micrometers M. Inhibition studies with the two stereoisomers of Huperzine-A have shown that naturally occurring (-)-Huperzine-A inhibited FBS AChE 35-fold more potently thanmore » (+)-Huperzine-A, with K(I) values of 6.2 nM and 210 nM, respectively. These results are in agreement with those reported previously using crude preparations of rat cortical AChE (McKinney et al., Eur. J. Pharmacol., 203, 303-305, 1991). (-)-Huperzine-A, on the other hand, was 80-fold more potent than (+)-Huperzine-A in inhibiting Torpedo AChE, with K(I), values of 0.25 micrometers M and 22 micrometer M, respectively. No significant differences in K(I) were observed for the two stereoisomers of Huperzine-A with horse serum BChE, indicating the lack of stereoselectivity of this compound for BChE. Molecular modeling studies involving docking of each of the two stereoisomers of Huperzine-A into the active-site gorge of Torpedo AChE also revealed that (-)-Huperzine-A gave a better fit than (+)-Huperzine-A.« less

Integrated genomics and proteomics of the Torpedo californica electric organ: concordance with the mammalian neuromuscular junction

PubMed Central

2011-01-01

Background During development, the branchial mesoderm of Torpedo californica transdifferentiates into an electric organ capable of generating high voltage discharges to stun fish. The organ contains a high density of cholinergic synapses and has served as a biochemical model for the membrane specialization of myofibers, the neuromuscular junction (NMJ). We studied the genome and proteome of the electric organ to gain insight into its composition, to determine if there is concordance with skeletal muscle and the NMJ, and to identify novel synaptic proteins. Results Of 435 proteins identified, 300 mapped to Torpedo cDNA sequences with ≥2 peptides. We identified 14 uncharacterized proteins in the electric organ that are known to play a role in acetylcholine receptor clustering or signal transduction. In addition, two human open reading frames, C1orf123 and C6orf130, showed high sequence similarity to electric organ proteins. Our profile lists several proteins that are highly expressed in skeletal muscle or are muscle specific. Synaptic proteins such as acetylcholinesterase, acetylcholine receptor subunits, and rapsyn were present in the electric organ proteome but absent in the skeletal muscle proteome. Conclusions Our integrated genomic and proteomic analysis supports research describing a muscle-like profile of the organ. We show that it is a repository of NMJ proteins but we present limitations on its use as a comprehensive model of the NMJ. Finally, we identified several proteins that may become candidates for signaling proteins not previously characterized as components of the NMJ. PMID:21798097

33 CFR 334.1190 - Hood Canal and Dabob Bay, Wash.; naval non-explosive torpedo testing area.

Code of Federal Regulations, 2013 CFR

2013-07-01

... southwesterly to the point of beginning. (2) The regulations. (i) Propeller-driven or other noise-generating craft shall not work their screws or otherwise generate other than incidental noise in the area during...

33 CFR 334.1190 - Hood Canal and Dabob Bay, Wash.; naval non-explosive torpedo testing area.

Code of Federal Regulations, 2012 CFR

2012-07-01

... southwesterly to the point of beginning. (2) The regulations. (i) Propeller-driven or other noise-generating craft shall not work their screws or otherwise generate other than incidental noise in the area during...

33 CFR 334.1190 - Hood Canal and Dabob Bay, Wash.; naval non-explosive torpedo testing area.

Code of Federal Regulations, 2014 CFR

2014-07-01

... southwesterly to the point of beginning. (2) The regulations. (i) Propeller-driven or other noise-generating craft shall not work their screws or otherwise generate other than incidental noise in the area during...

1. Aerial view of northwest circular bastion showing ruins of ...

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

1. Aerial view of northwest circular bastion showing ruins of metal roof added in 20th century. Torpedo filling station in background and barracks to the right. - Fort Hamilton, Northwest Circular Bastion, Rose Island, Newport, Newport County, RI

49 CFR 173.54 - Forbidden explosives.

Code of Federal Regulations, 2013 CFR

2013-10-01

... subpart. (b) An explosive mixture or device containing a chlorate and also containing: (1) An ammonium... explosive. (d) Propellants that are unstable, condemned or deteriorated. (e) Nitroglycerin, diethylene... detonator. (h) Fireworks containing yellow or white phosphorus. (i) A toy torpedo, the maximum outside...

49 CFR 173.54 - Forbidden explosives.

Code of Federal Regulations, 2014 CFR

2014-10-01

... subpart. (b) An explosive mixture or device containing a chlorate and also containing: (1) An ammonium... explosive. (d) Propellants that are unstable, condemned or deteriorated. (e) Nitroglycerin, diethylene... detonator. (h) Fireworks containing yellow or white phosphorus. (i) A toy torpedo, the maximum outside...

Final Environmental Assessment: Hurlburt Field Skeet & Trap Club

DTIC Science & Technology

2008-07-01

Invasive Species). To date, 18 Category I and 8 Category II species have been documented on Eglin AFB. Chinese tallow, or popcorn tree ( Triadica ... sebifera ), cogon grass (Imperata cylindrical), Japanese climbing fern (Lygodium japonicum), Chinese privet/hedge (Ligustrum sinense), and torpedo grass

Discrete Element Method (DEM) Simulations using PFC3D

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

Matt Evans

Contains input scripts, background information, reduced data, and results associated with the discrete element method (DEM) simulations of interface shear tests, plate anchor pullout tests, and torpedo anchor installation and pullout tests, using the software PFC3D (v4.0).

33 CFR 334.1190 - Hood Canal and Dabob Bay, Wash.; naval non-explosive torpedo testing area.

Code of Federal Regulations, 2010 CFR

2010-07-01

... CORPS OF ENGINEERS, DEPARTMENT OF THE ARMY, DEPARTMENT OF DEFENSE DANGER ZONE AND RESTRICTED AREA... the area. (iii) No vessel shall anchor in the area except between the shore and the 10-fathom depth...

33 CFR 334.1190 - Hood Canal and Dabob Bay, Wash.; naval non-explosive torpedo testing area.

Code of Federal Regulations, 2011 CFR

2011-07-01

... CORPS OF ENGINEERS, DEPARTMENT OF THE ARMY, DEPARTMENT OF DEFENSE DANGER ZONE AND RESTRICTED AREA... the area. (iii) No vessel shall anchor in the area except between the shore and the 10-fathom depth...

Cerebellar pathology in childhood-onset vs. adult-onset essential tremor.

PubMed

Louis, Elan D; Kuo, Sheng-Han; Tate, William J; Kelly, Geoffrey C; Faust, Phyllis L

2017-10-17

Although the incidence of ET increases with advancing age, the disease may begin at any age, including childhood. The question arises as to whether childhood-onset ET cases manifest the same sets of pathological changes in the cerebellum as those whose onset is during adult life. We quantified a broad range of postmortem features (Purkinje cell [PC] counts, PC axonal torpedoes, a host of associated axonal changes [PC axonal recurrent collateral count, PC thickened axonal profile count, PC axonal branching count], heterotopic PCs, and basket cell rating) in 60 ET cases (11 childhood-onset and 49 adult-onset) and 30 controls. Compared to controls, childhood-onset ET cases had lower PC counts, higher torpedo counts, higher heterotopic PC counts, higher basket cell plexus rating, and marginally higher PC axonal recurrent collateral counts. The median PC thickened axonal profile count and median PC axonal branching count were two to five times higher in childhood-onset ET than controls, but the differences did not reach statistical significance. Childhood-onset and adult-onset ET had similar PC counts, torpedo counts, heterotopic PC counts, basket cell plexus rating, PC axonal recurrent collateral counts, PC thickened axonal profile count and PC axonal branching count. In conclusion, we found that childhood-onset and adult-onset ET shared similar pathological changes in the cerebellum. The data suggest that pathological changes we have observed in the cerebellum in ET are a part of the pathophysiological cascade of events in both forms of the disease and that both groups seem to reach the same pathological endpoints at a similar age of death. Copyright © 2017 Elsevier B.V. All rights reserved.

Computational Fluid Dynamics of the Boundary Layer Characteristics of a Pacific Bluefin Tuna

DTIC Science & Technology

2015-09-18

17  LIST OF ABBREVIATIONS AND ACRONYMS 2D Two Dimensional 3D Three Dimensional AUV Autonomous...Finally, this research has the potential to advance technology of various Navy systems, e.g., torpedo and autonomous underwater vehicle ( AUV ) drag

Treatment of experimental myasthenia gravis with total lymphoid irradiation

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

de Silva, S.; Blum, J.E.; McIntosh, K.R.

1988-07-01

Total lymphoid irradiation (TLI) has been reported to be effective in the immunosuppressive treatment of certain human and experimental autoimmune disorders. We have investigated the effects of TLI in Lewis rats with experimental autoimmune myasthenia gravis (EAMG) produced by immunization with purified torpedo acetylcholine receptor (AChR). The radiation is given in 17 divided fractions of 200 rad each, and nonlymphoid tissues are protected by lead shielding. This technique suppresses the immune system, while minimizing side effects, and permits the repopulation of the immune system by the patient's own bone marrow cells. Our results show that TLI treatment completely prevented themore » primary antibody response to immunization with torpedo AChR, it rapidly abolished the ongoing antibody response in established EAMG, and it suppressed the secondary (anamnestic) response to a boost of AChR. No EAMG animals died during TLI treatment, compared with six control animals that died of EAMG. TLI produces powerful and prompt immunosuppression and may eventually prove useful in the treatment of refractory human myasthenia gravis.« less

Air blast injuries killed the crew of the submarine H.L. Hunley.

PubMed

Lance, Rachel M; Stalcup, Lucas; Wojtylak, Brad; Bass, Cameron R

2017-01-01

The submarine H.L. Hunley was the first submarine to sink an enemy ship during combat; however, the cause of its sinking has been a mystery for over 150 years. The Hunley set off a 61.2 kg (135 lb) black powder torpedo at a distance less than 5 m (16 ft) off its bow. Scaled experiments were performed that measured black powder and shock tube explosions underwater and propagation of blasts through a model ship hull. This propagation data was used in combination with archival experimental data to evaluate the risk to the crew from their own torpedo. The blast produced likely caused flexion of the ship hull to transmit the blast wave; the secondary wave transmitted inside the crew compartment was of sufficient magnitude that the calculated chances of survival were less than 16% for each crew member. The submarine drifted to its resting place after the crew died of air blast trauma within the hull.

An electric generator using living Torpedo electric organs controlled by fluid pressure-based alternative nervous systems

PubMed Central

Tanaka, Yo; Funano, Shun-ichi; Nishizawa, Yohei; Kamamichi, Norihiro; Nishinaka, Masahiro; Kitamori, Takehiko

2016-01-01

Direct electric power generation using biological functions have become a research focus due to their low cost and cleanliness. Unlike major approaches using glucose fuels or microbial fuel cells (MFCs), we present a generation method with intrinsically high energy conversion efficiency and generation with arbitrary timing using living electric organs of Torpedo (electric rays) which are serially integrated electrocytes converting ATP into electric energy. We developed alternative nervous systems using fluid pressure to stimulate electrocytes by a neurotransmitter, acetylcholine (Ach), and demonstrated electric generation. Maximum voltage and current were 1.5 V and 0.64 mA, respectively, with a duration time of a few seconds. We also demonstrated energy accumulation in a capacitor. The current was far larger than that using general cells other than electrocytes (~pA level). The generation ability was confirmed against repetitive cycles and also after preservation for 1 day. This is the first step toward ATP-based energy harvesting devices. PMID:27241817

An electric generator using living Torpedo electric organs controlled by fluid pressure-based alternative nervous systems

NASA Astrophysics Data System (ADS)

Tanaka, Yo; Funano, Shun-Ichi; Nishizawa, Yohei; Kamamichi, Norihiro; Nishinaka, Masahiro; Kitamori, Takehiko

2016-05-01

Direct electric power generation using biological functions have become a research focus due to their low cost and cleanliness. Unlike major approaches using glucose fuels or microbial fuel cells (MFCs), we present a generation method with intrinsically high energy conversion efficiency and generation with arbitrary timing using living electric organs of Torpedo (electric rays) which are serially integrated electrocytes converting ATP into electric energy. We developed alternative nervous systems using fluid pressure to stimulate electrocytes by a neurotransmitter, acetylcholine (Ach), and demonstrated electric generation. Maximum voltage and current were 1.5 V and 0.64 mA, respectively, with a duration time of a few seconds. We also demonstrated energy accumulation in a capacitor. The current was far larger than that using general cells other than electrocytes (~pA level). The generation ability was confirmed against repetitive cycles and also after preservation for 1 day. This is the first step toward ATP-based energy harvesting devices.

Cryopreservation of embryogenic callus of Aesculus hippocastanum L. by vitrification or one-step freezing.

PubMed

Lambardi, Maurizio; De Carlo, Anna; Capuana, Maurizio

2005-01-01

An effective procedure for the cryopreservation of horse chestnut (Aesculus hippocastanum L.) embryogenic callus by vitrification/one-step freezing is described here. In particular, the study focused on the possibility of recovering the full proliferation potential of the embryogenic lines after storage in liquid nitrogen. The developmental stage of the embryogenic lines was shown to play an important role. Ninety-min incubation in PVS2 and preservation at -196 degrees C of callus samples, containing a prevalence of embryogenic masses at an advanced stage of somatic embryo maturation (i.e., the torpedo stage), gave optimum regrowth of healthy and proliferating embryogenic callus. Moreover, raising the thawing temperature to 45 degrees C yielded the maximum survival (94%) of torpedo-stage embryogenic samples, recovery of proliferation and, in more than 70% of cases, maturation to the cotyledonary stage. This study opens the way to the possibility of safe, long-term storage in liquid nitrogen of valuable embryogenic lines of horse chestnut, avoiding repeated subculturing.

From The Cover: Microtransplantation of functional receptors and channels from the Alzheimer's brain to frog oocytes

NASA Astrophysics Data System (ADS)

Miledi, R.; Dueñas, Z.; Martinez-Torres, A.; Kawas, C. H.; Eusebi, F.

2004-02-01

About a decade ago, cell membranes from the electric organ of Torpedo and from the rat brain were transplanted to frog oocytes, which thus acquired functional Torpedo and rat neurotransmitter receptors. Nevertheless, the great potential that this method has for studying human diseases has remained virtually untapped. Here, we show that cell membranes from the postmortem brains of humans that suffered Alzheimer's disease can be microtransplanted to the plasma membrane of Xenopus oocytes. We show also that these postmortem membranes carry neurotransmitter receptors and voltage-operated channels that are still functional, even after they have been kept frozen for many years. This method provides a new and powerful approach to study directly the functional characteristics and structure of receptors, channels, and other membrane proteins of the Alzheimer's brain. This knowledge may help in understanding the basis of Alzheimer's disease and also help in developing new treatments. -aminobutyric acid receptors | sodium channels | calcium channels | postmortem brain

Air blast injuries killed the crew of the submarine H.L. Hunley

PubMed Central

Stalcup, Lucas; Wojtylak, Brad; Bass, Cameron R.

2017-01-01

The submarine H.L. Hunley was the first submarine to sink an enemy ship during combat; however, the cause of its sinking has been a mystery for over 150 years. The Hunley set off a 61.2 kg (135 lb) black powder torpedo at a distance less than 5 m (16 ft) off its bow. Scaled experiments were performed that measured black powder and shock tube explosions underwater and propagation of blasts through a model ship hull. This propagation data was used in combination with archival experimental data to evaluate the risk to the crew from their own torpedo. The blast produced likely caused flexion of the ship hull to transmit the blast wave; the secondary wave transmitted inside the crew compartment was of sufficient magnitude that the calculated chances of survival were less than 16% for each crew member. The submarine drifted to its resting place after the crew died of air blast trauma within the hull. PMID:28832592

Purification of Torpedo californica post-synaptic membranes and fractionation of their constituent proteins.

PubMed Central

Elliott, J; Blanchard, S G; Wu, W; Miller, J; Strader, C D; Hartig, P; Moore, H P; Racs, J; Raftery, M A

1980-01-01

A rapid methof for preparation of membrane fractions highly enriched in nicotinic acetylcholine receptor from Torpedo californica electroplax is described. The major step in this purification involves sucrose-density-gradient centrifugation in a reorienting rotor. Further purification of these membranes can be achieved by selective extraction of proteins by use of alkaline pH or by treatment with solutions of lithium di-idosalicylate. The alkali-treated membranes retain functional characteristics of the untreated membranes and in addition contain essentially only the four polypeptides (mol.wts. 40000, 50000, 60000 and 65000) characteristic of the receptor purified by affinity chromatography. Dissolution of the purified membranes or of the alkali-treated purified membranes in sodium cholate solution followed by sucrose-density-gradient centrifugation in the same detergent solution yields solubilized receptor preparations comparable with the most highly purified protein obtained by affinity-chromatographic procedures. Images Fig. 1. Fig. 2. Fig. 3. Fig. 5. Fig. 7. PLATE 1 PMID:7387629

WASTE MINIZATION OPPORTUNITY ASSESSMENT: NAVAL UNDERSEA WARFARE ENGINEERING STATION - KEYPORT, WA

EPA Science Inventory

This report describes the application of EPA's waste minimization assessment procedures to a torpedo maintenance facility at the Naval Undersea Warfare Engineering Station, Keyport, WA. he assessment focused on the Mark 48 shop and the Mark 46 shop. hese shops service the Mark 48...

ELEVATION OF FACILITY 667 WITH GRADUATED SCALE IN 1' INCREMENTS. ...

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

ELEVATION OF FACILITY 667 WITH GRADUATED SCALE IN 1' INCREMENTS. NOTE: THE TORPEDO IN THE FOREGROUND IS A DISPLAY ASSOCIATED WITH FACILITY 683. VIEW FACING NORTHEAST - U.S. Naval Base, Pearl Harbor, Gymnasium Building, North Waterfront & Pierce Street near Berth S-13, Pearl City, Honolulu County, HI

Mini-Warriors: Microelectromechanical Systems: A Munitions Revolution

DTIC Science & Technology

2014-02-01

hand-held con- troller senses and transmits body movements to the video game—much like the Lycra suit with 85 MEMS, worn by ac- tors, which aided...for the anti-torpedo tor- pedo . Although it uses a macro-size fuze, significantly reduced in size by the Division, its experimental MEMS fuze informed

14. View south from first level roof of firing pier. ...

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

14. View south from first level roof of firing pier. Pitched corrugated metal roof marks location of the frame approach connecting the firing pier to the shop (shown in left distance). - Naval Torpedo Station, Firing Pier, North end of Gould Island in Narragansett Bay, Newport, Newport County, RI

36 CFR 7.97 - Golden Gate National Recreation Area.

Code of Federal Regulations, 2011 CFR

2011-07-01

... THE INTERIOR SPECIAL REGULATIONS, AREAS OF THE NATIONAL PARK SYSTEM § 7.97 Golden Gate National... Alcatraz Island. (b) Powerless flight. The use of devices designed to carry persons through the air in..., sidewalks and grass lawn of the former Coast Guard Station complex) that stretches east from the Torpedo...

45. 'Replace Starboard Elevator and Repairs, Gould Island, Building No. ...

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

45. 'Replace Starboard Elevator and Repairs, Gould Island, Building No. 35,' approved 26 July 1981, NUSC Drawing No. 80-67, NAV. FAC. Drawing No. 2,047,203. Scales as noted. - Naval Torpedo Station, Firing Pier, North end of Gould Island in Narragansett Bay, Newport, Newport County, RI

An Experiment in Voice Data Entry for Imagery Interpretation Reporting.

DTIC Science & Technology

1981-03-01

INTERCEPTORS 219 KOTLIN CLASS KOTLIN CLASS- 22e KOTLN SAM CL KOTLIN -SAM CLASS 221 SKORY CLASS SKORY CLASS_ 222 RIVA CLASS RIGA CLASS 223 GRISHA CLASS GRISHA...INTERCEPTORS ----------------------------------------- ---------------------- INSTALLATION 0362-V34273 *2 PROBABLE SKORY CLASS DESTROYERS *3 CONFIRMED KOTLIN ...CLASS TORPEDO BOATS! 4 CONFIRMED KOTLIN SAM-CLASS DETSTROYERS

Waste minimization opportunity assessment: Naval Undersea Warfare Engineering Station, Keyport, Washington. Project summary

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

NONE

The Environmental Protection Agency (EPA) has developed a systematic approach to identify, select and implement options to reduce or eliminate hazardous waste. The report describes the application of the waste minimization assessment procedures to a torpedo maintenance facility at the Naval Undersea Warfare Engineering Station in Keyport, WA (NUWES Keyport).

Developing Behavioral Metrics for Decision-Making in Marine Corps Small-Units

DTIC Science & Technology

2013-09-01

BACKGROUND A. HISTORY OF ASSESSMENTS The sinking of the British passenger liner RMS Lusitania by a German submarine in 1915 (Lauriat, 1915), and the...a narrative of the torpedoing and sinking of the RMS Lusitania by a German submarine off the Irish coast May 7, 1915. Boston, MA: Houghton Mifflin

Effect of Turbine Axial Nozzle-Wheel Clearance on Performance of Mark 25 Torpedo Power Plant

NASA Technical Reports Server (NTRS)

Hoyt, Jack W.; Kottas, Harry

1948-01-01

Investigations were made of the turbine from a Mark 25 torpedo to determine the performance of the unit with three different turbine nozzles at various axial nozzle-wheel clearances. Turbine efficiency with a reamed nondivergent nozzle that uses the axial clearance space for gas expansion was little affected by increasing the axial running clearance from 0.030 to 0.150 inch. Turbine efficiency with cast nozzles that expanded the gas inside the nozzle passage was found to be sensitive to increased axial nozzle-wheel clearance. A cast nozzle giving a turbine brake efficiency of 0.525 at an axial running clearance of 0.035 inch gave a brake efficiency of 0.475 when the clearance was increased to 0.095 inch for the same inlet-gas conditions and blade-jet speed ratio. If the basis for computing the isentropic power available to the turbine is the temperature inside the nozzle rather then the temperature in the inlet-gas pipe, an increase in turbine efficiency of about 0.01 is indicated.

Performance of Single-Stage Turbine of Mark 25 Torpedo Power Plant with Two Special Nozzles. II; Efficiency with 20 Degrees-Inlet-Angle Rotor Blades

NASA Technical Reports Server (NTRS)

Schum, Harold J.; Whitney, Warren J.

1949-01-01

A single-stage modification of the turbine from a Mark 25 torpedo power plant was investigated to determine the performance with two nozzle designs in combination with special rotor blades having a 20 inlet angle. The performance is presented in terms of blade, rotor, and brake efficiency as a function of blade-jet speed ratio for pressure ratios of 8, 15 (design), and 20. The blade efficiency with the nozzle having circular pas- sages (K) was equal to or higher than that with the nozzle having rectangular passages (J) for all pressure ratios and speeds investigated. The maximum blade efficiency of 0.571 was obtained with nozzle K at a pressure ratio of 8 and a blade-jet speed ratio of 0.296. The difference in blade efficiency was negligible at a pressure ratio of 8 at the low speeds; the maxim difference was 0.040 at a pressure ratio of 20 and a blade-jet speed ratio of 0.260.

The non-competitive acetylcholinesterase inhibitor APS12-2 is a potent antagonist of skeletal muscle nicotinic acetylcholine receptors

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

Grandič, Marjana; Aráoz, Romulo; Molgó, Jordi

APS12-2, a non-competitive acetylcholinesterase inhibitor, is one of the synthetic analogs of polymeric alkylpyridinium salts (poly-APS) isolated from the marine sponge Reniera sarai. In the present work the effects of APS12-2 were studied on isolated mouse phrenic nerve–hemidiaphragm muscle preparations, using twitch tension measurements and electrophysiological recordings. APS12-2 in a concentration-dependent manner blocked nerve-evoked isometric muscle contraction (IC{sub 50} = 0.74 μM), without affecting directly-elicited twitch tension up to 2.72 μM. The compound (0.007–3.40 μM) decreased the amplitude of miniature endplate potentials until a complete block by concentrations higher than 0.68 μM, without affecting their frequency. Full size endplate potentials,more » recorded after blocking voltage-gated muscle sodium channels, were inhibited by APS12-2 in a concentration-dependent manner (IC{sub 50} = 0.36 μM) without significant change in the resting membrane potential of the muscle fibers up to 3.40 μM. The compound also blocked acetylcholine-evoked inward currents in Xenopus oocytes in which Torpedo (α1{sub 2}β1γδ) muscle-type nicotinic acetylcholine receptors (nAChRs) have been incorporated (IC{sub 50} = 0.0005 μM), indicating a higher affinity of the compound for Torpedo (α1{sub 2}β1γδ) than for the mouse (α1{sub 2}β1γε) nAChR. Our data show for the first time that APS12-2 blocks neuromuscular transmission by a non-depolarizing mechanism through an action on postsynaptic nAChRs of the skeletal neuromuscular junction. -- Highlights: ► APS12-2 produces concentration-dependent inhibition of nerve-evoked muscle contraction in vitro. ► APS12-2 blocks MEPPs and EPPs at the neuromuscular junction. APS12-2 blocks ACh-activated current in Xenopus oocytes incorporated with Torpedo nAChRs.« less

The acetylcholinesterase inhibitor BW284c51 is a potent blocker of Torpedo nicotinic AchRs incorporated into the Xenopus oocyte membrane

PubMed Central

Olivera-Bravo, Silvia; Ivorra, Isabel; Morales, Andrés

2004-01-01

This work was aimed to determine if 1,5-bis(4-allyldimethylammoniumphenyl)pentan-3-one dibromide (BW284c51), the most selective acetylcholinesterase inhibitor (AchEI), affects the nicotinic acetylcholine (Ach) receptor (AchR) function. Purified Torpedo nicotinic AchRs were injected into Xenopus laevis oocytes and BW284c51 effects on Ach- and carbamylcholine (Cch)-elicited currents were assessed using the voltage-clamp technique. BW284c51 (up to 1 mM) did not evoke any change in the oocyte membrane conductance. When BW284c51 (10 pM–100 μM) and Ach were coapplied, Ach-evoked currents (IAch) were reversibly inhibited in a concentration-dependent manner (Hill coefficient, 1; IC50, 0.2–0.5 μM for 0.1–1000 μM Ach). Cch-elicited currents showed a similar inhibition by BW284c51. IAch blockade by BW284c51 showed a strong voltage dependence, being only apparent at hyperpolarising potentials. BW284c51 also enhanced IAch desensitisation. BW284c51 changed the Ach concentration-dependence curve of Torpedo AchR response from two-site to single-site kinetics, without noticeably affecting the EC50 value. The BW284c51 blocking effect was highly selective for nicotinic over muscarinic receptors. BW284c51 inhibition potency was stronger than that of tacrine, and similar to that of d-tubocurarine (d-TC). Coapplication of BW284c51 with either tacrine or d-TC revealed synergistic inhibitory effects. Our results indicate that BW284c51 antagonises nicotinic AchRs in a noncompetitive way by blocking the receptor channel, and possibly by other, yet unknown, mechanisms. Therefore, besides acting as a selective AchEI, BW284c51 constitutes a powerful and reversible blocker of nicotinic AchRs that might be used as a valuable tool for understanding their function. PMID:15644872

Desformylflustrabromine (dFBr) and [3H]dFBr-Labeled Binding Sites in a Nicotinic Acetylcholine Receptor

PubMed Central

Hamouda, Ayman K.; Wang, Ze-Jun; Stewart, Deirdre S.; Jain, Atul D.; Glennon, Richard A.

2015-01-01

Desformylflustrabromine (dFBr) is a positive allosteric modulator (PAM) of α4β2 and α2β2 nAChRs that, at concentrations >1 µM, also inhibits these receptors and α7 nAChRs. However, its interactions with muscle-type nAChRs have not been characterized, and the locations of its binding site(s) in any nAChR are not known. We report here that dFBr inhibits human muscle (αβεδ) and Torpedo (αβγδ) nAChR expressed in Xenopus oocytes with IC50 values of ∼1 μM. dFBr also inhibited the equilibrium binding of ion channel blockers to Torpedo nAChRs with higher affinity in the nAChR desensitized state ([3H]phencyclidine; IC50 = 4 μM) than in the resting state ([3H]tetracaine; IC50 = 60 μM), whereas it bound with only very low affinity to the ACh binding sites ([3H]ACh, IC50 = 1 mM). Upon irradiation at 312 nm, [3H]dFBr photoincorporated into amino acids within the Torpedo nAChR ion channel with the efficiency of photoincorporation enhanced in the presence of agonist and the agonist-enhanced photolabeling inhibitable by phencyclidine. In the presence of agonist, [3H]dFBr also photolabeled amino acids in the nAChR extracellular domain within binding pockets identified previously for the nonselective nAChR PAMs galantamine and physostigmine at the canonical α-γ interface containing the transmitter binding sites and at the noncanonical δ-β subunit interface. These results establish that dFBr inhibits muscle-type nAChR by binding in the ion channel and that [3H]dFBr is a photoaffinity probe with broad amino acid side chain reactivity. PMID:25870334

Components of Torpedo electric organ and muscle that cause aggregation of acetylcholine receptors on cultured muscle cells

PubMed Central

1984-01-01

The synaptic portion of a muscle fiber's basal lamina sheath has molecules tightly bound to it that cause aggregation of acetylcholine receptors (AChRs) on regenerating myofibers. Since basal lamina and other extracellular matrix constituents are insoluble in isotonic saline and detergent solutions, insoluble detergent-extracted fractions of tissues receiving cholinergic input may provide an enriched source of the AChR-aggregating molecules for detailed characterization. Here we demonstrate that such an insoluble fraction from Torpedo electric organ, a tissue with a high concentration of cholinergic synapses, causes AChRs on cultured chick muscle cells to aggregate. We have partially characterized the insoluble fraction, examined the response of muscle cells to it, and devised ways of extracting the active components with a view toward purifying them and learning whether they are similar to those in the basal lamina at the neuromuscular junction. The insoluble fraction from the electric organ was rich in extracellular matrix constituents; it contained structures resembling basal lamina sheaths and had a high density of collagen fibrils. It caused a 3- to 20-fold increase in the number of AChR clusters on cultured myotubes without significantly affecting the number or size of the myotubes. The increase was first seen 2-4 h after the fraction was added to cultures and it was maximal by 24 h. The AChR-aggregating effect was dose dependent and was due, at least in part, to lateral migration of AChRs present in the muscle cell plasma membrane at the time the fraction was applied. Activity was destroyed by heat and by trypsin. The active component(s) was extracted from the insoluble fraction with high ionic strength or pH 5.5 buffers. The extracts increased the number of AChR clusters on cultured myotubes without affecting the number or degradation rate of surface AChRs. Antiserum against the solubilized material blocked its effect on AChR distribution and bound to the active component. Insoluble fractions of Torpedo muscle and liver did not cause AChR aggregation on cultured myotubes. However a low level of activity was detected in pH 5.5 extracts from the muscle fraction. The active component(s) in the muscle extract was immunoprecipitated by the antiserum against the material extracted from the electric organ insoluble fraction. This antiserum also bound to extracellular matrix in frog muscles, including the myofiber basal lamina sheath. Thus the insoluble fraction of Torpedo electric organ is rich in AChR-aggregating molecules that are also found in muscle and has components antigenically similar to those in myofiber basal lamina. PMID:6746740

U.S. EPA, Pesticide Product Label, RED TORPEDO USE-AS-IS RAT KILLER, 12/14/1967

EPA Pesticide Factsheets

2011-04-21

... ".dh('t'p an \\,lill\\(,ITlllJ'tt'd ,1Ippl~ of 11:111 1'11' nl.; at It'.I;t II) Ii:l\\';, fll) mil" ;\\1 it-:l"\\ 1:) '1:1:,', If kli~ I)('crill\\l'-; >(ur. m()ld~' 't!' Ot!kr\\":l'-jlOI;Cd, it .. ...

78 FR 45017 - Amendment to the International Traffic in Arms Regulations: Revision of U.S. Munitions List...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-07-25

...)(i)(A) through (D), on the basis that commercial articles would otherwise be covered. The Department notes that the criteria in (A) through (D) are modified by the criteria of paragraph (a)(1)(i). However..., submarines, other undersea vehicles, torpedoes, or mines, having any of the following: (A) Multi-static...

41. 'Firing Pier, Second Floor Plan, Section No. 2,' submitted ...

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

41. 'Firing Pier, Second Floor Plan, Section No. 2,' submitted 29 December 1941 by John Brackett, Consulting Engineer, to Public Works Department, Bureau of Yards & Docks. PW Drawing 3867-46, Y&D Drawing 190841. Scale 1/4' = 1'. - Naval Torpedo Station, Firing Pier, North end of Gould Island in Narragansett Bay, Newport, Newport County, RI

42. 'Firing Pier, Second Floor Plan, Section No. 3,' submitted ...

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

42. 'Firing Pier, Second Floor Plan, Section No. 3,' submitted 29 December 1941 by John Brackett, Consulting Engineer, to Public Works Department, Bureau of Yards & Docks. PW Drawing 3868-46, Y&D Drawing 190842. Scale 1/4' = 1'. - Naval Torpedo Station, Firing Pier, North end of Gould Island in Narragansett Bay, Newport, Newport County, RI

36. 'Firing Pier, First Floor Plan, Section No. 1,' submitted ...

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

36. 'Firing Pier, First Floor Plan, Section No. 1,' submitted 29 December 1941 by John Brackett, Consulting Engineer, to Public Works Department, Bureau of Yards & Docks. PW Drawing 3862-46, Y&D Drawing 190836. Scale 1/4' = 1'. - Naval Torpedo Station, Firing Pier, North end of Gould Island in Narragansett Bay, Newport, Newport County, RI

43. 'Firing Pier, Third and Fourth Floors and Roof Plan,' ...

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

43. 'Firing Pier, Third and Fourth Floors and Roof Plan,' submitted 29 December 1941 by John Brackett, Consulting Engineer, to Public Works Department, Bureau of Yards & Docks. PW Drawing 3869-46, Y&D Drawing 190843. Scale 1/4' = 1'. - Naval Torpedo Station, Firing Pier, North end of Gould Island in Narragansett Bay, Newport, Newport County, RI

38. 'Firing Pier, First Floor Plan, Section No. 3,' submitted ...

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

38. 'Firing Pier, First Floor Plan, Section No. 3,' submitted 29 December 1941 by John Brackett, Consulting Engineer, to Public Works Department, Bureau of Yards & Docks. PW Drawing 3864-46, Y&D Drawing 190838. Scale 1/4' = 1'. - Naval Torpedo Station, Firing Pier, North end of Gould Island in Narragansett Bay, Newport, Newport County, RI

40. 'Firing Pier, Second Floor Plan, Section No. 1,' submitted ...

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

40. 'Firing Pier, Second Floor Plan, Section No. 1,' submitted 29 December 1941 by John Brackett, Consulting Engineer, to Public Works Department, Bureau of Yards & Docks. PW Drawing 3866-46, Y&D Drawing 190840. Scale 1/4' = 1'. - Naval Torpedo Station, Firing Pier, North end of Gould Island in Narragansett Bay, Newport, Newport County, RI

30. 'Gould Island Facilities, General Plan,' submitted 29 December 1941 ...

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

30. 'Gould Island Facilities, General Plan,' submitted 29 December 1941 by John Brackett, Consulting Engineer, to Public Works Department, Bureau of Yards & Docks. PW Drawing 3859-46, Y&D Drawing 190833. Scales 1' = 50' and 1' = 10'. - Naval Torpedo Station, Firing Pier, North end of Gould Island in Narragansett Bay, Newport, Newport County, RI

39. 'Firing Pier, First Floor Plan, Section No. 4,' submitted ...

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

39. 'Firing Pier, First Floor Plan, Section No. 4,' submitted 29 December 1941 by John Brackett, Consulting Engineer, to Public Works Department, Bureau of Yards & Docks. PW Drawing 3865-46, Y&D Drawing 190839. Scale 1/4' = 1'. - Naval Torpedo Station, Firing Pier, North end of Gould Island in Narragansett Bay, Newport, Newport County, RI

37. 'Firing Pier, First Floor Plan, Section No. 2,' submitted ...

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

37. 'Firing Pier, First Floor Plan, Section No. 2,' submitted 29 December 1941 by John Brackett, Consulting Engineer, to Public Works Department, Bureau of Yards & Docks. PW Drawing 3863-46, Y&D Drawing 190837. Scale 1/4' = 1. - Naval Torpedo Station, Firing Pier, North end of Gould Island in Narragansett Bay, Newport, Newport County, RI

Developing and Managing a Local Digital Archive for Integrated Access to Journals and Other Publications.

ERIC Educational Resources Information Center

Stackpole, Laurie

2001-01-01

The Naval Research Laboratory Library has made significant progress providing its distributed user community with a single point-of-access to information needed to support scientific research through TORPEDO "Ultra," a digital archive that in many respects functions as an electronic counterpart of a traditional library. It consists of…

Stacked Buoyant Payload Launcher

DTIC Science & Technology

2013-05-14

unit, the signal ejector , or through the escape hatch lockout trunk. Each of these deployment methods has disadvantages. [0005] Torpedo tubes are... ejector tube can accommodate payloads approximately three inches in diameter. Thus, payload size is extremely limited. The escape hatch lockout trunk...signal ejector tube. Additionally, the system 10 can launch multiple payloads during one launch sequence, or can provide multiple launches at

Counterrotating Propulsive System.

DTIC Science & Technology

1981-12-01

Propellers ," David Taylor Model Basin Report 1342, February 1960. 7. Miller, M.L., " Experimental Determination of Unsteady Forces on Counter- rotating...21. Miller, M.L., " Experimental Determination of Unsteady Forces on Contra- rotating Propellers for Application to Torpedoes," David W. Taylor Naval...pair of counterrotating propellers in a uniform in- flow is given by Reference [14] with the same results. On the

77 FR 841 - Taking and Importing Marine Mammals: Taking Marine Mammals Incidental to U.S. Navy Operations of...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-01-06

... threats is decreasing, and at the same time, improvements in torpedo design are extending the effective... relatively short period of time. It is likely that any marine mammal would be able to avoid the surveillance... duration of any continuous frequency sound transmission is no longer than 10 sec and the time between pings...

The Cuban Interventionary Forces: The Growing Strategic and Regional Threat to the United States and NATO.

DTIC Science & Technology

1986-12-01

enough fuel for a six-week voyage, fourteen torpedoes and deck guns, and * ..was capable of 17.5 knots surfaced and 7.5 submerged . This 127 P-’ -k. /O...firpd iri c- his top administrators, Politburo m~ mbr ,, -In 1 66 * B followers since the early days of the revolutionary struggle against Batista. Among

2011 Chemical, Biological, Radiological, and Nuclear Survivability Conference

DTIC Science & Technology

2011-05-18

Protection (barrier, sorptive and reactive material technologies) o Top surface antimicrobial treatments (kills spores, bacteria, fungi, viruses ) o...Warning System (TWS) CDD - Countermeasure Anti-Torpedo ( CAT ) CDD UNCLASSIFIED Joint Program Executive Office for Chemical and Biological Defense May...Creating viruses de novo Biological Threats UNCLASSIFIED JPEO-CBD Radiological/Nuclear (RN) Status and Path Forward • Issue: No identified DoD

Expression of functional neurotransmitter receptors in Xenopus oocytes after injection of human brain membranes

NASA Astrophysics Data System (ADS)

Miledi, Ricardo; Eusebi, Fabrizio; Martínez-Torres, Ataúlfo; Palma, Eleonora; Trettel, Flavia

2002-10-01

The Xenopus oocyte is a very powerful tool for studies of the structure and function of membrane proteins, e.g., messenger RNA extracted from the brain and injected into oocytes leads to the synthesis and membrane incorporation of many types of functional receptors and ion channels, and membrane vesicles from Torpedo electroplaques injected into oocytes fuse with the oocyte membrane and cause the appearance of functional Torpedo acetylcholine receptors and Cl channels. This approach was developed further to transplant already assembled neurotransmitter receptors from human brain cells to the plasma membrane of Xenopus oocytes. Membranes isolated from the temporal neocortex of a patient, operated for intractable epilepsy, were injected into oocytes and, within a few hours, the oocyte membrane acquired functional neurotransmitter receptors to -aminobutyric acid, -amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid, kainate, and glycine. These receptors were also expressed in the plasma membrane of oocytes injected with mRNA extracted from the temporal neocortex of the same patient. All of this makes the Xenopus oocyte a more useful model than it already is for studies of the structure and function of many human membrane proteins and opens the way to novel pathophysiological investigations of some human brain disorders.

Morphological and Genetic Evidence for Multiple Evolutionary Distinct Lineages in the Endangered and Commercially Exploited Red Lined Torpedo Barbs Endemic to the Western Ghats of India

PubMed Central

Dahanukar, Neelesh; Anvar Ali, Palakkaparambil Hamsa; Tharian, Josin; Raghavan, Rajeev; Antunes, Agostinho

2013-01-01

Red lined torpedo barbs (RLTBs) (Cyprinidae: Puntius) endemic to the Western Ghats Hotspot of India, are popular and highly priced freshwater aquarium fishes. Two decades of indiscriminate exploitation for the pet trade, restricted range, fragmented populations and continuing decline in quality of habitats has resulted in their ‘Endangered’ listing. Here, we tested whether the isolated RLTB populations demonstrated considerable variation qualifying to be considered as distinct conservation targets. Multivariate morphometric analysis using 24 size-adjusted characters delineated all allopatric populations. Similarly, the species-tree highlighted a phylogeny with 12 distinct RLTB lineages corresponding to each of the different riverine populations. However, coalescence-based methods using mitochondrial DNA markers identified only eight evolutionarily distinct lineages. Divergence time analysis points to recent separation of the populations, owing to the geographical isolation, more than 5 million years ago, after the lineages were split into two ancestral stocks in the Paleocene, on north and south of a major geographical gap in the Western Ghats. Our results revealing the existence of eight evolutionarily distinct RLTB lineages calls for the re-determination of conservation targets for these cryptic and endangered taxa. PMID:23894533

A higher risk of congenital anomalies in the offspring of personnel who served aboard a Norwegian missile torpedo boat

PubMed Central

Mageroy, N; Mollerlokken, O J; Riise, T; Koefoed, V; Moen, B E

2006-01-01

Background In the 1990s, congenital anomalies were reported among children whose fathers had served aboard a Norwegian missile torpedo boat (MTB). The Royal Norwegian Navy asked the University of Bergen to look into this problem as one part of a general health and work environment surveillance. Aims To estimate any increased risk of having children with congenital anomalies and having stillborn children among the offspring of workers that had served aboard the MTB and to investigate possible differences in exposure and other risk factors between these groups. Methods Data from a cross‐sectional study among all current employees of the Norwegian Navy (n = 2265, response rate 58%) were analysed. Results The prevalence ratio of having a child with congenital malformations associated with working on the ship was 4.0 (95% CI 1.9 to 8.6). The prevalence ratio of having a child who was stillborn or died within one week was 4.1 (95% CI 1.7 to 9.9). Conclusion Service aboard the MTB was associated with an increased risk of having children with congenital birth defects and having children that were stillborn. The causes of these findings are unknown. PMID:16421386

Experimental Determination of Unsteady Forces on Contrarotating Propellers for Application to Torpedoes

DTIC Science & Technology

1981-12-01

Experimental determination of Unsteady Forces on Contrarotating Propellers in Uniform Flow ," David Taylor Naval Ship R&D Center, Ship Performance...were planned to determine the unsteady forces on contrarotating propellers in a 4-cycle wake, there were also experiments made in uniform flow to check...Subtitle) S. TYPE OF REPORT G PERIOD COVERED Experimental Determination of Unsteady Forces on

25. Aerial photograph dated 20 June 1942, showing north end ...

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

25. Aerial photograph dated 20 June 1942, showing north end of Gould Island from the northeast (caption on photo is in error). Shop and power plant under construction at left, firing pier under construction at far right. Photo courtesy of Naval Undersea Warfare Center, Division Newport, Rhode Island. - Naval Torpedo Station, Firing Pier, North end of Gould Island in Narragansett Bay, Newport, Newport County, RI

Women in Combat: Issues for Congress

DTIC Science & Technology

2015-12-03

report suggested that these changes might have the benefit of expanding career opportunities for women, while increasing flexibility for field...Squad Assessment Tasks Day 1:  Hike 1 kilometer uphill with 28-pound assault pack and personal weapon.  Scramble over 8-foot shipping container...Allow engineers to move forward and fire two breaching shots with Bangalore torpedoes. Day 2:  Hike 7 kilometers with weapons and 59-pound

The Submarine, 1776-1918

DTIC Science & Technology

2004-01-01

destruction of many civilian lives in sunken passenger ships—notably the Cunard liner Lusitania , attacked in May 1915 with a loss of 1,200 lives, 128...former Ger- man passenger liners interned by their owners in American harbors in order to avoid capture by blockading British cruisers. Eventually there...submarines torpedoed merchant ships, including passenger liners , without warning. Then, because they had no way of rescuing those who had survived the

Naval Facilities Engineering Command Needs to Improve Controls Over Task Order Administration

DTIC Science & Technology

2015-07-02

consolidated joint use Submarine Learning Center and Submarine Squadron Headquarters facility that: • includes training space for submarine crews, and...allows frequent and timely interaction between Headquarters personnel, Submarine Learning Center instructors, and waterfront operations personnel...Introduction DODIG-2015-141 │ 3 Project P-528 provides a Torpedo Exercise Support facility that: • supports submarine crew training and certification to

Gene expression analysis of flax seed development

PubMed Central

2011-01-01

Background Flax, Linum usitatissimum L., is an important crop whose seed oil and stem fiber have multiple industrial applications. Flax seeds are also well-known for their nutritional attributes, viz., omega-3 fatty acids in the oil and lignans and mucilage from the seed coat. In spite of the importance of this crop, there are few molecular resources that can be utilized toward improving seed traits. Here, we describe flax embryo and seed development and generation of comprehensive genomic resources for the flax seed. Results We describe a large-scale generation and analysis of expressed sequences in various tissues. Collectively, the 13 libraries we have used provide a broad representation of genes active in developing embryos (globular, heart, torpedo, cotyledon and mature stages) seed coats (globular and torpedo stages) and endosperm (pooled globular to torpedo stages) and genes expressed in flowers, etiolated seedlings, leaves, and stem tissue. A total of 261,272 expressed sequence tags (EST) (GenBank accessions LIBEST_026995 to LIBEST_027011) were generated. These EST libraries included transcription factor genes that are typically expressed at low levels, indicating that the depth is adequate for in silico expression analysis. Assembly of the ESTs resulted in 30,640 unigenes and 82% of these could be identified on the basis of homology to known and hypothetical genes from other plants. When compared with fully sequenced plant genomes, the flax unigenes resembled poplar and castor bean more than grape, sorghum, rice or Arabidopsis. Nearly one-fifth of these (5,152) had no homologs in sequences reported for any organism, suggesting that this category represents genes that are likely unique to flax. Digital analyses revealed gene expression dynamics for the biosynthesis of a number of important seed constituents during seed development. Conclusions We have developed a foundational database of expressed sequences and collection of plasmid clones that comprise even low-expressed genes such as those encoding transcription factors. This has allowed us to delineate the spatio-temporal aspects of gene expression underlying the biosynthesis of a number of important seed constituents in flax. Flax belongs to a taxonomic group of diverse plants and the large sequence database will allow for evolutionary studies as well. PMID:21529361

Manpower and Personnel Requirements Determination Methodologies (MANPERS).

DTIC Science & Technology

1984-12-01

Landing Ship Dock ( LSD -4) propulsion system 3. Advanced Light Weight Torpedo 4. A new destroyer class (DDGX) 5. Undergraduate Jet Flight Training System...The pragmatic norm considers a theory acceptable to the extent it serves the scientific purpose for which it was designed. F -14 Shaw and Costanzo (1970...invalidated. * The usual procedure is revision either of procedures or theoretical * structure. Shaw and Costanzo (1970) further specified five desirable (but

Droning On: American Strategic Myopia Toward Unmanned Aerial Systems

DTIC Science & Technology

2013-12-01

torpedo, nicknamed the “Bug.”3 This system consisted of pre-set pneumatic and electrical controls that stabilized and guided it toward...race their homemade drones around Mount Damavand.88 These competitions and DIY efforts provide short-term innovation of unmanned technologies. This...an even greater threat to the homeland comes from homegrown or lone wolf actor’s possession of unmanned technology. DIY kits aid in building drones

A Summary of the Naval Postgraduate School Research Program.

DTIC Science & Technology

1982-05-01

and testing of PCM modu- lation formats, design and test of an underwater video line using a diver’s handheld camera and bi-directional interconnection...to design and develop advanced control schemes which successfully optimize the tor- pedo steering performance for Project Courageous. cummary: Work...investigating the feasibility and design of fiber optic communications in underwater torpedo ranges. Summary: An underwater fiber optic video uplink was

A Simulation Model for Setting Terms for Performance Based Contract Terms

DTIC Science & Technology

2010-05-01

torpedo self-noise and the use of ruggedized, embedded, digital micro - processors . The latter capability made it possible for digitally controlled...inventories are: System Reliability, Product Reliability, Operational Availability, Mean Time to Repair (MTTR), Mean Time to Failure ( MTTF ...Failure ( MTTF ) Mean Logistics Delay Time (MLDT) Mean Supply Response Time (MSRT) D ep en de nt M et ric s Mean Accumulated Down Time (MADT

Investigations and Tests in the Towing Basin at Guidonia

NASA Technical Reports Server (NTRS)

Cremona, C

1939-01-01

The experimental methods at the Guidonia towing basin are discussed including specifications. Some of the components examined are the bridge towing carriage, side towing carriage, catapult installation, and dynamometer systems. Tests were performed on hulls and floats, as well as motor boats and torpedo shaped bodies. Theoretical investigations were also performed to determine pressure distributions on geometrically simple bodies, propagation of small wave motions, and planing and submerged surfaces.

FBIS report. Science and technology: Japan, February 20, 1996

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

NONE

1996-02-20

;Partial Contents: Energy (Japan: MHI Discovers Maritime Photo Plankton that Produces Ethanol from CO2, Japan: Tokyo Electric Power Co.`s PAFC Development); Telecommunications (Japan: Report on 1st Asian Telecommunications Industry Exchange, Japan: MPT Reports Test Evaluation Results for PHS); Defense Industries (Japan: Expert on Shipbuilding, Welding Technology, Japan: Komatsu R&D Chief on Dream of Ground Robots; Japan: Defense Simulator Series, Part 7: Torpedo Simulator).

Improving the Parametric Method of Cost Estimating Relationships of Naval Ships

DTIC Science & Technology

2014-06-01

tool since the total cost of the ship is broken down into smaller parts as defined by the WBS. The Navy currently uses the Expanded Ship Work Breakdown...Includes boilers , reactors, turbines, gears, shafting, propellers, steam piping, lube oil piping, and radiation 300 Electric Plant Includes ship...spaces, ladders, storerooms, laundry, and workshops 700 Armament Includes guns, missile launchers, ammunition handling and stowage, torpedo tubes , depth

Tether Deployer And Brake

NASA Technical Reports Server (NTRS)

Carroll, Joseph A.; Alexander, Charles M.

1993-01-01

Design concept promises speed, control, and reliability. Scheme for deploying tether provides for fast, free, and snagless payout and fast, dependable braking. Developed for small, expendable tethers in outer space, scheme also useful in laying transoceanic cables, deploying guidance wires to torpedoes and missiles, paying out rescue lines from ship to ship via rockets, deploying antenna wires, releasing communication and power cables to sonobuoys and expendable bathythermographs, and in reeling out lines from fishing rods.

Highlights of the Department of the Navy FY 2013 Budget

DTIC Science & Technology

2012-02-01

ability to perform undersea warfare to include high altitude launched torpedo capability, surface warfare and ISR missions make it a critical force...60B and SH-60F helicopters, whose primary mission areas are undersea warfare and surface warfare. This platform will have numerous capability...sensors to detect, localize, classify and identify undersea threats at a safe distance from friendly ships. The Remote Multi-Mission Vehicle provides

Archaeological Testing of the Confederate Obstructions. 1Mb28, Mobile Harbor, Alabama.

DTIC Science & Technology

1985-07-01

Historical Society of America, Staten Island, New York. 58 - . . -. . Maury, Dabney H. - 1864 Statement Concerning Placement of Torpedoes Across...Minnesota Historical Society , St. Paul. Merrill, Col. W. E. 1866 Report on the Present Condition of the Harbor of Mobile. MSon file, National...194. Polk, James K. 1971 Pensacola Commerce and Industry: 1821-1860. MSon file, Pensacola Historical Society , Pensacola. Scruggs, J.H., Jr. 1953

Reexamining the role of choline transporter-like (Ctlp) proteins in choline transport.

PubMed

Zufferey, Rachel; Santiago, Teresa C; Brachet, Valerie; Ben Mamoun, Choukri

2004-02-01

In Saccharomyces cerevisiae, choline enters the cell via a single high-affinity transporter, Hnmlp. hnm1delta cells lacking HNM1 gene are viable. However, they are unable to transport choline suggesting that no additional active choline transporters are present in this organism. A complementation study of a choline auxotrophic mutant, ctrl-ise (hnm1-ise), using a cDNA library from Torpedo marmorata electric lobe identified a membrane protein named Torpedo marmorata choline transporter-like, tCtl1p. tCtllp was proposed to mediate a high-affinity choline transport (O'Regan et al., 1999, Proc. Natl. Acad. Sci.). Homologs of tCtl1p have been identified in other organisms, including yeast (Pns1p, YOR161c) and are postulated to function as choline transporters. Here we provide several lines of evidence indicating that Ctlp proteins are not involved in choline transport. Loss of PNS1 has no effect on choline transport and overexpression of either PNS1 or tCTL1 does not restore choline uptake activity of choline transport-defective mutants. The data presented here call into question the role of proteins of the CTL family in choline transport and suggest that the mechanism by which tCTL1 complements hnm1-ise mutant is independent of its ability to transport choline.

Stabilization of a metastable state of Torpedo californica acetylcholinesterase by chemical chaperones

PubMed Central

Millard, Charles B.; Shnyrov, Valery L.; Newstead, Simon; Shin, Irina; Roth, Esther; Silman, Israel; Weiner, Lev

2003-01-01

Chemical modification of Torpedo californica acetylcholinesterase by the natural thiosulfinate allicin produces an inactive enzyme through reaction with the buried cysteine Cys 231. Optical spectroscopy shows that the modified enzyme is “native-like,” and inactivation can be reversed by exposure to reduced glutathione. The allicin-modified enzyme is, however, metastable, and is converted spontaneously and irreversibly, at room temperature, with t1/2 ≃ 100 min, to a stable, partially unfolded state with the physicochemical characteristics of a molten globule. Osmolytes, including trimethylamine-N-oxide, glycerol, and sucrose, and the divalent cations, Ca2+, Mg2+, and Mn2+ can prevent this transition of the native-like state for >24 h at room temperature. Trimethylamine-N-oxide and Mg2+ can also stabilize the native enzyme, with only slight inactivation being observed over several hours at 39°C, whereas in their absence it is totally inactivated within 5 min. The stabilizing effects of the osmolytes can be explained by their differential interaction with the native and native-like states, resulting in a shift of equilibrium toward the native state. The stabilizing effects of the divalent cations can be ascribed to direct stabilization of the native state, as supported by differential scanning calorimetry. PMID:14500892

Copper-Based Torpedo Guidance Wire: Applications and Environmental Considerations

DTIC Science & Technology

2013-06-01

on day 91 had an additional toxicity evaluation using the developing larvae of the Mediterranean mussel, Mytilus galloprovincialis, concurrently...recent study conducted in 2008 did not. 4.3.1.3 Baird’s Beaked Whale (Berardius bairdii) Baird’s beaked whales have a diet consisting of benthic fish... Mediterranean are formed as Cuvier’s beaked whales chase down and feed upon benthic prey (Woodside, David, Frantzis, and Hooker, 2006). One of the easiest 38

Survey of P-3C Mission Profiles for Development of the T56-A-14 Duty Cycle.

DTIC Science & Technology

1982-01-01

Pilot Training (FAM) 3. Logistics (LOG) 4. Post Maintenance Check Flight ( PMCF ) 5. Minelaying and Torpedo Certification (MAT) MISSION FREQUENCY DATA...998 649 675 43 FAM 715 800 585 610 677 43 LOG 95 62 209 132 124 8 PMCF 35 48 46 18 37 2 MAT 89 36 1 75 33 58 4 3 4 N ADC-83026 -60 These data show an

Jointness or Jointless at Leyte

DTIC Science & Technology

1989-03-31

tol JOINTNESS OR JOINTLESS AT LEYTE BY LIEUTENANT COLONEL KENNY J. JEFFERSON DESTRIBUTION STATMMERT A: Approved IoT Publ.C rx f. df trf~iitien Is...and to -support the operation with naval, air force, and submarine weapon systems and Vrotect against Japanese invasion forces from the surrounding...as the "early warning system " for the fleet and independently engage targets with torpedoes. Admiral Nishimura’s Force C would be the first to enter

The Evolution of Joint Operations during the Civil War

DTIC Science & Technology

2009-06-12

requested a large quantity of anti-personnel mines to enhance the minefield in front of the land face.64 Lamb‘s requests did not elicit a significant... mines the Confederates had buried. Several of the men realized what they were (buried anti-personnel torpedoes) and systematically disabled them by...devices which today would include booby traps, land mines , naval mines and others. 118 Traverse--A fortified gun emplacement in a fortified position

Implementing the Seapower Strategy

DTIC Science & Technology

2008-01-01

between the two ends. Here is an example. When Britannia ruled the waves with a global navy to pro- tect the empire, Sir Julian Corbett specified three...because torpedo boats, submarines, and mines threatened cheap kills.7 Upon the rise of the German High Seas Fleet in the decades before World War I...face swarms of small combatants are being developed with accompanying search and attack systems. We have reawakened to the threats from mines and quiet

Photolabeling a Nicotinic Acetylcholine Receptor (nAChR) with an (α4)3(β2)2 nAChR-Selective Positive Allosteric Modulator

PubMed Central

Deba, Farah; Wang, Ze-Jun; Cohen, Jonathan B.

2016-01-01

Positive allosteric modulators (PAMs) of nicotinic acetylcholine (ACh) receptors (nAChRs) have potential clinical applications in the treatment of nicotine dependence and many neuropsychiatric conditions associated with decreased brain cholinergic activity, and 3-(2-chlorophenyl)-5-(5-methyl-1-(piperidin-4-yl)-1H-pyrrazol-4-yl)isoxazole (CMPI) has been identified as a PAM selective for neuronal nAChRs containing the α4 subunit. In this report, we compare CMPI interactions with low-sensitivity (α4)3(β2)2 and high-sensitivity (α4)2(β2)3 nAChRs, and with muscle-type nAChRs. In addition, we use the intrinsic reactivity of [3H]CMPI upon photolysis at 312 nm to identify its binding sites in Torpedo nAChRs. Recording from Xenopus oocytes, we found that CMPI potentiated maximally the responses of (α4)3(β2)2 nAChR to 10 μM ACh (EC10) by 400% and with an EC50 of ∼1 µM. CMPI produced a left shift of the ACh concentration-response curve without altering ACh efficacy. In contrast, CMPI inhibited (∼35% at 10 µM) ACh responses of (α4)2(β2)3 nAChRs and fully inhibited human muscle and Torpedo nAChRs with IC50 values of ∼0.5 µM. Upon irradiation at 312 nm, [3H]CMPI photoincorporated into each Torpedo [(α1)2β1γδ] nAChR subunit. Sequencing of peptide fragments isolated from [3H]CMPI-photolabeled nAChR subunits established photolabeling of amino acids contributing to the ACh binding sites (αTyr190, αTyr198, γTrp55, γTyr111, γTyr117, δTrp57) that was fully inhibitable by agonist and lower-efficiency, state-dependent [3H]CMPI photolabeling within the ion channel. Our results establish that CMPI is a potent potentiator of nAChRs containing an α4:α4 subunit interface, and that its intrinsic photoreactivy makes it of potential use to identify its binding sites in the (α4)3(β2)2 nAChR. PMID:26976945

Installation of the Douglas XSB2D-1 in the Test Section of the 40x80 Foot Wind Tunnel at Ames.

NASA Image and Video Library

1944-06-12

Test section of the Ames 40 x 80 foot wind tunnel with the overhead doors open. XSB2D-1 airplane being lowered onto the struts by the overhead crane. Mechanics and engineers on orchard ladders aligning the model with ball sockets on the struts. The Douglas BTD Destroyer was an American dive/ torpedo bomber developed for the United States Navy during World War II.

Real-Time Modeling of Cross-Body Flow for Torpedo Tube Recovery of the Phoenix Autonomous Underwater Vehicle (AUV)

DTIC Science & Technology

1998-03-01

34Numerical Recipes in C," second edition, Cambridge University Press, Cambridge England, 1992. Marco, David , "Autonomous Control of Underwater...in the viewer. -202- LIST OF REFERENCES Ames, Andrea L., Nadeau, David R., Moreland, John L., VRML 2.0 Sourcebook, Second edition, John Wiley...McGhee, Bob, "The Phoenix Autonomous Underwater Vehicle," AI-Based Mobile Robots, editors David Kortenkamp, Pete Bonasso and Robin Murphy, MJT/AAAI

29. Aerial photograph (1973) looking south across Gould Island. Firing ...

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

29. Aerial photograph (1973) looking south across Gould Island. Firing pier (still possessing third and fourth levels) in foreground. Pitched roof extending from south end of firing pier marks location of frame approach between pier and shop building (center rear) and power plant (to right of shop). Photo courtesy of Naval Undersea Warfare Center, Division Newport, Rhode Island. - Naval Torpedo Station, Firing Pier, North end of Gould Island in Narragansett Bay, Newport, Newport County, RI

Evaluation Of Model Based Systems Engineering Processes For Integration Into Rapid Acquisition Programs

DTIC Science & Technology

2016-09-01

Failure MTBCF Mean Time Between Critical Failure MIRV Multiple Independently-targetable Reentry Vehicle MK6LE MK6 Guidance System Life Extension...programs were the MK54 Lightweight Torpedo program, a Raytheon Radar program, and the Life Extension of the MK6 Guidance System (MK6LE) of the...activities throughout the later life -cycle phases. MBSE allowed the programs to manage the evolution of simulation capabilities, as well as to assess the

A Companion for Aspirant Air Warriors: A Handbook for Personal Professional Study

DTIC Science & Technology

2010-05-01

evacuation had been conceptualized to rescue political leader Leon Gambetta from the Prussian siege of Paris during the Franco-Prussian War. Carrier...69. Douhet, Giulio. The Command of the Air. Washington, DC: Office of Air Force History, 1983. (Reprint of 1942 edition. Originally published in 1921...of Brest when British torpedo planes caught up with her. One of them put a weapon into the ship’s steering gear, jamming it so that it could only

Specific stimulated uptake of acetylcholine by Torpedo electric organ synaptic vesicles.

PubMed Central

Parsons, S M; Koenigsberger, R

1980-01-01

The specificity of acetylcholine uptake by synaptic vesicles isolated from the electric organ of Torpedo californica was studied. In the absence of cofactors, [3H]acetylcholine was taken up identically to[14C]choline in the same solution (passive uptake), and the equilibrium concentration achieved inside the vesicles was equal to the concentration outside. In the presence of MgATP, [3H]acetylcholine and [14C]choline in the same solution were taken up identically, except only about half as much of each was taken up (suppressed uptake). [3H]Acetylcholine uptake was stimulated by MgATP and HCO3- about 4-fold relative to suppressed uptake, for a net concentrative uptake of about 2:1 (stimulated uptake). Uptake of [14C]choline in the same solution remained at the suppressed level. [3H]Acetylcholine taken up under stimulated conditions migrated with vesicles containing [14C]mannitol on analytical glycerol density gradients during centrifugation. Vesicle were treated with nine protein modification reagents under mild conditions. Two reagents had no effect on, dithiothreitol potentiated, and six reagents strongly inhibited subsequent stimulated uptake of [3H]acetylcholine. The results indicate that uptake of acetylcholine is conditionally specific for the transported substrate, is carried out by the synaptic vesicles rather than a contaminant of the preparation, and requires a functional protein system containing a critical sulfhydryl group. PMID:6934549

Mapping of a binding site for ATP within the extracellular region of the Torpedo nicotinic acetylcholine receptor beta-subunit.

PubMed

Schrattenholz, A; Roth, U; Godovac-Zimmermann, J; Maelicke, A

1997-10-28

Using 2,8,5'-[3H]ATP as a direct photoaffinity label for membrane-bound nicotinic acetylcholine receptor (nAChR) from Torpedo marmorata, we have identified a binding site for ATP in the extracellular region of the beta-subunit of the receptor. Photolabeling was completely inhibited in the presence of saturating concentrations of nonradioactive ATP, whereas neither the purinoreceptor antagonists suramin, theophyllin, and caffeine nor the nAChR antagonists alpha-bungarotoxin and d-tubocurarine affected the labeling reaction. Competitive and noncompetitive nicotinic agonists and Ca2+ increased the yield of the photoreaction by up to 50%, suggesting that the respective binding sites are allosterically linked with the ATP site. The dissociation constant KD of binding of ATP to the identified site on the nAChR was of the order of 10(-4) M. Sites of labeling were found in the sequence regions Leu11-Pro17 and Asp152-His163 of the nAChR beta-subunit. These regions may represent parts of a single binding site for ATP, which is discontinuously distributed within the primary structure of the N-terminal extracellular domain. The existence of an extracellular binding site for ATP confirms, on the molecular level, that this nucleotide can directly act on nicotinic receptors, as has been suggested from previous electrophysiological and biochemical studies.

Comment on Underwater Explosion (UWE) Analysis of the ROKS Cheonan Incident by S.G. Kim and Y. Kitterman

NASA Astrophysics Data System (ADS)

Kim, Kwang Sup

2013-03-01

The analysis of the seismic and infrasound data recorded at the time of the Cheonan incident led Kim and Gitterman (this journal, published on line August 2012) to conclude that a non-contact underwater explosion had sunk the ship. They also concluded that one of the mines deployed by the South Korean Navy many years ago in the area and then abandoned sank the ship. Their mine theory that is based on the explosive charge weights they calculated by means of two methods using the bubble period determined by their analysis, however, appears to be invalid. Although the incident had occurred in a shallow sea with a depth of less than 50m, the authors used the methods that are applicable only to free-field underwater explosions. The consideration of the influence on the bubble period of the nearby sea surface and bottom and the nearby ship's hull would double the calculated weights. In addition, the authors ignored several evidences that support the torpedo theory. One of them is aluminum-containing white powder found in large quantities at certain substrates in the retrieved Cheonan. However, the conclusion of the official investigation group that the torpedo was made in North Korea is based on a circumstantial evidence and is yet to be proven with other more direct evidences.

Isolation and characterization of full-length cDNA clones coding for cholinesterase from fetal human tissues

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

Prody, C.A.; Zevin-Sonkin, D.; Gnatt, A.

1987-06-01

To study the primary structure and regulation of human cholinesterases, oligodeoxynucleotide probes were prepared according to a consensus peptide sequence present in the active site of both human serum pseudocholinesterase and Torpedo electric organ true acetylcholinesterase. Using these probes, the authors isolated several cDNA clones from lambdagt10 libraries of fetal brain and liver origins. These include 2.4-kilobase cDNA clones that code for a polypeptide containing a putative signal peptide and the N-terminal, active site, and C-terminal peptides of human BtChoEase, suggesting that they code either for BtChoEase itself or for a very similar but distinct fetal form of cholinesterase. Inmore » RNA blots of poly(A)/sup +/ RNA from the cholinesterase-producing fetal brain and liver, these cDNAs hybridized with a single 2.5-kilobase band. Blot hybridization to human genomic DNA revealed that these fetal BtChoEase cDNA clones hybridize with DNA fragments of the total length of 17.5 kilobases, and signal intensities indicated that these sequences are not present in many copies. Both the cDNA-encoded protein and its nucleotide sequence display striking homology to parallel sequences published for Torpedo AcChoEase. These finding demonstrate extensive homologies between the fetal BtChoEase encoded by these clones and other cholinesterases of various forms and species.« less

Fuel Delivery System.

DTIC Science & Technology

1996-07-24

to fuel tank 27 aboard 23 test torpedo 26. Pressure switch 19B operates to close solenoid 24 valve 22A and concurrently open solenoid valve 22D...leading to a pump explosion. The boost pump 4 is driven by its 11 motor 14B and positive displacement pump 1 by its respective 12 motor 14A. Pressure ... switch 19A monitors the head pressure 13 created by the boost pump 4 and it will shut off the motor 14A of 14 the positive displacement pump 1 if

Analysis of the 35th Division’s Application of Operational Art During World War I

DTIC Science & Technology

2017-05-25

seizing the cargo and letting the crew escape. The German torpedo sinking of the British ocean liner Arabic, on August 19, 1915, took two more American...the United States established the 35th Division and designated members of the Kansas and Missouri National Guards to fill its ranks. On August 3, 1917...Kansas and Missouri National Guards into federal service on August 5, 1917 to serve as part of the American Expeditionary Force. On August 23, 1917, the

Cognitive Performance Degradation on Sonar Operator and Torpedo Data Control Unit Operator after One Night of Sleep Deprivation

DTIC Science & Technology

1985-09-01

8 II. SLEEP AND SOME CHARACTERISTICS . . . . . o . . 13 A. C"YCLE AND CYCLE EFFECT ... ......... 11 B. SLEEP DEPRIVATION...17 E. NAP: RESTORATIVE POWER AND SIDE EFFECTS OF THE NAP o . . o o o o e o o . o * o e o . 19 III. SLEEP LOSS AND...war periods. The effect of this situ- ation is a requirement for long hours of physically and mentally exhausting work without sleep. The silent war

The Shock and Vibration Bulletin. Part 1. Keynote Address, Invited Papers, Panel Sessions, Modal Test and Analysis.

DTIC Science & Technology

1978-09-01

SNAPSHOT PICTURE VIDEO TAPE 35-MM PHOTO TRANSPARENCY MICROFILM Figure 2 - Gross Area Information Density other across the organization. Then we developed...the finite element In the modeling of a tor- method. The torpedo hull is divided pedo for shock and vibration analysis, ,. into primary structural...length of the tor- 16. Figure 15 presents the magnitude pedo with several circumferential trac- and phase of motor motion, and Fig. 16 ings at

Naval Ocean Systems Center’s Catalog of Abstracts of Patents Available for Licensing by U.S. Businesses

DTIC Science & Technology

1990-09-01

Mk 46 Mod 5 APPARATUS torpedo. Inventor: John P. Bott APPLICATIONS: The apparatus has applications Patent Number 4,204,552; dated 27 May 1980 for any...Number 4,315,651; dated 16 February 1980 1982 ABSTRACT: A sea-water pressure regulator ABSTRACT: A coupling that is readily attach- valve is provided...CALIBRATION the area of acoustic calibration and qualityassurance. Inventor: George 0. Pickens assurance. Patent Number 4,205,394; dated 24 May 1980

A Novel Detector of Broadband Transient Signals

DTIC Science & Technology

2006-11-01

accroissement soudain de l’énergie spectrale observé pendant une courte période sur une vaste gamme de fréquences. Contrairement aux autres méthodes de...nombre d’applications différentes dans lesquelles les transitoires se manifestent sous forme d’un accroissement soudain de l’énergie spectrale observé...torpedo bearing error of 20 degrees (θ = θ1 + 20) was introduced (equation (16)). Al - though, in this case r2 was reduced, the two transients were

Military Review. Volume 82, Number 2, March-April 2002

DTIC Science & Technology

2002-04-01

Association (1997), 399-411. 6. A.M. Friedlander, S.L. Welkos, M.L.M. Pitt, J.W. Ezzell , P.L. Worsham, K.J. Rose, et al., �Postexposure Prophylaxis Against...forces. The helicopter drop should be from two to three miles behind the target, so that instead of going deeper into enemy territory for the attack...333 pages, $25.00. Two weeks before the end of World War II, a Japanese submarine in the Philippine Sea, about 350 miles East of Leyte, torpedoed

Stackable In-Line Surface Missile Launch System for a Modular Payload Bay

DTIC Science & Technology

2004-11-08

stacked modules 14 are connected 8 and sealed to form a single long continuous missile tube . 9 Flexible seals may be used at the base of each missile...vehicles, such as missiles, 22 both through vertical launch via specialized launch tubes on the 23 submarine, and horizontal launch via the submarine’s...torpedo 24 tubes . In some cases, the missiles are quite large, such as the 1 1 Tomahawk missile, which requires sufficient support for the 2 large

Assault on the USS LIBERTY: Deliberate Action or Tragic Accident?

DTIC Science & Technology

2007-03-30

fear of an Egyptian attack from the sea compounded with the explosion at al-‘Arish, set the events into motion.74 The torpedo boats miscalculated...differences with the USS Liberty. The Liberty is 200 feet longer, covered with antennas, and has a state-of-the-art parabolic satellite dish.85 Perhaps...collection position.] 14 Ibid, 13. 15 Ibid, 14. 16 William D. Gerhard and Henry W. Millington, Attack on a Sigint Collector , the U.S.S Liberty

Identification and Evaluation of Submerged Anomalies, Mobile Harbor, Alabama.

DTIC Science & Technology

1984-10-01

Bay Waters , 1864-1865 APPENDIX B: Description of Maps in National ill Archives Collection V LIST OF FIGURES Figure Page cover Torpedo Raft in Mobile Bay...Anomaly D-E 51 13 Magnetometer Chart, Anomaly F 53 14 Sketch of Steel Wreckage Found at Anomaly F 54 15 Approaches to Mobile City by Water (Merrill...Osage (1863-65) 84 30 CSS Albemarle, Prototype for the Huntsville 86 31 Magnolia, CSA-Utilized Vessel 109 32 Approaches to Mobile City by Water (1864

International Workshop on Structural and Functional Aspects of the Cholinergic Synapse Held in Jerusalem, Isreal on 30 August-4 September 1987

DTIC Science & Technology

1987-09-01

77) Large scale purification of the acetylcholine receptor protein In its membrane-bound and detergent extracted forms from Torpedo marmorata...maintenance of the postsynaptic apparatus in the adult. Our studies have alac led to the Identification of agrin, a protein that is extracted from the synapse...in extracts of muscle, and monoclonal antibodies directed against &grin recognize molecules highly concentrated in the synaptic basal lamina at the

Submarine Hydraulic Fluid Explosion Mitigation and Fire Threats to Ordnance

DTIC Science & Technology

2005-01-18

capable of absorbing large amounts of energy from a developing explosion if the mist can be delivered, in sufficient quantity, to the point of origin of...doors (H8, H13 , H14, D10, D11, SI and S2 in Figure 1) during the explosion tests. In addition, the frame bay ducts that connect 3 the torpedo room and...appreciable impact on the overpressure, explosion tests were run with and without the dummy ordnance. Two replicate tests of each configuration were conducted

Protective Coatings for Aluminum Torpedoes

DTIC Science & Technology

1983-06-01

Circeo it Cmader and Director of CERL, and Dr. L . R. Shaffer is Technical Director. 3 = -. =-e ° 𔄁 -i , i ..... rar DD FORM 1473 2 FOREWORD 3 LIST...Amerccat 9 Thinner 72 A12 Gas Chrouatogrm flughson VIS 3236-26 Wash Primer 73 L FIGURES (Cont’d) Number Page A13 .as Chroasatogram: Hughson TS 3236-23...intercoat adhesion problems providing the old surface is clean. A vinyl coating system manufactured by Ameron, 201 North Berry Street, Bret, CA 92621, was

Unmanned Three-Environment Vehicle (U3V)

DTIC Science & Technology

2014-08-01

calculations and complex geometries, the number of panels per partition will be greater than 400 . The only high-lift devices permitted in TORNADO are...from nose (Nm) Speed (kts) Take-off 12 20 = Weight 2,618 -36,130 63 Cruise 4 2 = Weight 2,104 -32,178 100 Underwater sprint -1.2 0 Negligible...illustrated in Figure 30. Figure 30 – Effective power against speed for a range of torpedo shaped UUVs 0 50 100 150 200 250 300 350 400 450 500 0.0

Pushing the Horizon. Seventy-Five Years of High Stakes Science and Technology at the Naval Research Laboratory

DTIC Science & Technology

2001-01-01

torpedo the British ocean liner Lusitania , which was carrying more than 1200 passengers. As the ship steamed by the south- east coast of Ireland on its...1,198 passengers who lost their lives, 128 were U.S. citizens.2 The sinking of the Lusitania was traumatic to the collective Ameri- can psyche. Large...arsenals at a time when American interests clearly were threatened.3 Within a week of the Lusitania tragedy, President Wilson began sending stern

Defeating the U-boat. Inventing Antisubmarine Warfare (Newport Papers Number 36)

DTIC Science & Technology

2010-08-01

did not explain how this number had been arrived at but claimed it could be achieved by no more than four cruisers and twelve armed liners in the...cover of darkness, ambush and destroy the largest unarmed liners afloat.33 Aube made clear that unlike in the past, ships, their crews, and cargoes...would not be captured but sunk without warning: “Having fol- lowed the liner from afar, come nightfall, the torpedo-boat will, perfectly silently and

Synthetic. cap alpha. subunit peptide 125-147 of human nicotinic acetylcholine receptor induces antibodies to native receptor

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

McCormick, D.J.; Griesmann, G.E.; Huang, Z.

1986-03-05

A synthetic peptide corresponding to residues 125-147 of the Torpedo acetylcholine receptor (AChR) ..cap alpha.. subunit proved to be a major antigenic region of the AChR. Rats inoculated with 50 ..mu..g of peptide (T ..cap alpha.. 125-147) developed T cell immunity and antibodies to native AChR and signs of experimental autoimmune myasthenia gravis. They report the synthesis and preliminary testing of a disulfide-looped peptide comprising residues 125-147 of the human AChR ..cap alpha.. subunit. Peptide H ..cap alpha.. 125-147 differs from T ..cap alpha.. 125-147 at residues 139 (Glu for Gln) and 143 (Ser for Thr). In immunoprecipitation assays, antibodiesmore » to Torpedo AChR bound /sup 125/I-labelled H..cap alpha.. 125-147 antibody bound H..cap alpha.. 125-147, but monoclonal antibodies to an immunodominant region of native AChR bound neither H..cap alpha.. 125-147 nor T ..cap alpha.. 125-147. Rats immunized with H ..cap alpha.. 125-147 produced anti-mammalian muscle AChR antibodies that induced modulation of AChRs from cultured human myotubes. Thus, region 125-147 of the human AChR ..cap alpha.. subunit is extracellular in muscle, and is both antigenic and immunogenic. It remains to be determined whether or not autoantibodies to this region may in part cause the weakness or myasthenia gravis in man.« less

Effects of Lipid-Analog Detergent Solubilization on the Functionality and Lipidic Cubic Phase Mobility of the Torpedo californica Nicotinic Acetylcholine Receptor

PubMed Central

Padilla-Morales, Luis F.; Morales-Pérez, Claudio L.; De La Cruz-Rivera, Pamela C.; Asmar-Rovira, Guillermo; Báez-Pagán, Carlos A.

2011-01-01

Over the past three decades, the Torpedo californica nicotinic acetylcholine receptor (nAChR) has been one of the most extensively studied membrane protein systems. However, the effects of detergent solubilization on nAChR stability and function are poorly understood. The use of lipid-analog detergents for nAChR solubilization has been shown to preserve receptor stability and functionality. The present study used lipid-analog detergents from phospholipid-analog and cholesterol-analog detergent families for solubilization and affinity purification of the receptor and probed nAChR ion channel function using planar lipid bilayers (PLBs) and stability using analytical size exclusion chromatography (A-SEC) in the detergent-solubilized state. We also examined receptor mobility on the lipidic cubic phase (LCP) by measuring the nAChR mobile fraction and diffusion coefficient through fluorescence recovery after photobleaching (FRAP) experiments using lipid-analog and non-lipid-analog detergents. Our results show that it is possible to isolate stable and functional nAChRs using lipid-analog detergents, with characteristic ion channel currents in PLBs and minimal aggregation as observed in A-SEC. Furthermore, fractional mobility and diffusion coefficient values observed in FRAP experiments were similar to the values observed for these parameters in the recently LCP-crystallized β2-adrenergic receptor. The overall results show that phospholipid-analog detergents with 16 carbon acyl-chains support nAChR stability, functionality and LCP mobility. PMID:21922299

High resolution labeling of cholinergic nerve terminals using a specific fully active biotinylated botulinum neurotoxin type A.

PubMed

Arribas, M; Blasi, J; Egea, G; Fariñas, I; Solsona, C; Marsal, J

1993-12-15

We report here on the synthesis and characterization of a fully active biotinylated derivative of the botulinum neurotoxin type A. Different ratios of biotin: botulinum toxin were tested to optimize derivatizing conditions and a ratio of 35:1 was selected for further experiments. The average number of biotin groups per toxin molecule was estimated to be 7.8, occurring at both heavy and light chains, and almost all externally located and easily accessible to recognition by streptavidin. The modified toxin retained its toxicity and its ability to interact with biological membranes. Apart from its suitability for detection in Western blots and in microtiter well plates, biotinylated botulinum toxin proved to be adequate for morphological labeling studies at both light and electron microscopy. Peroxidase histochemistry in cryostat sections of intoxicated rat hemidiaphragm muscles showed a distinct labeling of end-plates. Electron microscopy studies were performed on the electric organ of Torpedo marmorata using colloidal gold-conjugated streptavidin for detection. After intoxication of electric organ fragments with the modified toxin, gold labels were found associated with the presynaptic plasma membrane of nerve terminals and with the membrane of synaptic vesicles. Moreover, the distribution of biotinylated botulinum toxin binding sites over the membrane of synaptosomes isolated from the electric organ of Torpedo and their relationship with intramembrane particles were analyzed using the replica-staining label-fracture technique. It was found that the toxin is never associated with intramembrane particles.

Isolation and characterization of full-length cDNA clones coding for cholinesterase from fetal human tissues.

PubMed Central

Prody, C A; Zevin-Sonkin, D; Gnatt, A; Goldberg, O; Soreq, H

1987-01-01

To study the primary structure and regulation of human cholinesterases, oligodeoxynucleotide probes were prepared according to a consensus peptide sequence present in the active site of both human serum pseudocholinesterase (BtChoEase; EC 3.1.1.8) and Torpedo electric organ "true" acetylcholinesterase (AcChoEase; EC 3.1.1.7). Using these probes, we isolated several cDNA clones from lambda gt10 libraries of fetal brain and liver origins. These include 2.4-kilobase cDNA clones that code for a polypeptide containing a putative signal peptide and the N-terminal, active site, and C-terminal peptides of human BtChoEase, suggesting that they code either for BtChoEase itself or for a very similar but distinct fetal form of cholinesterase. In RNA blots of poly(A)+ RNA from the cholinesterase-producing fetal brain and liver, these cDNAs hybridized with a single 2.5-kilobase band. Blot hybridization to human genomic DNA revealed that these fetal BtChoEase cDNA clones hybridize with DNA fragments of the total length of 17.5 kilobases, and signal intensities indicated that these sequences are not present in many copies. Both the cDNA-encoded protein and its nucleotide sequence display striking homology to parallel sequences published for Torpedo AcChoEase. These findings demonstrate extensive homologies between the fetal BtChoEase encoded by these clones and other cholinesterases of various forms and species. Images PMID:3035536

Embling Production in Althaea officinalis L., Through Somatic Embryogenesis and Their Appraisal via Histological and Scanning Electron Microscopical Studies.

PubMed

Naz, Ruphi; Anis, Mohammad; Alatar, Abdulrahman A

2017-07-01

In vitro propagation of a medicinally important plant, Althaea officinalis, has been achieved through somatic embryogenesis. Somatic embryos (globular to torpedo-shaped embryos) were induced on Murashige and Skoog's (MS) medium augmented with various concentrations of 2,4-dichlorophenoxyacetic acid (2,4-D, 5.0, 10.0, 15.0, 20.0, and 25.0) alone or combined with N6-benzylaminopurine (BA, 0.1, 0.5, 1.0, 1.5, and 2.0 μM). These were directly formed from the cut ends and subsequently spread on the whole surface of internodal explants. For embryo maturation, torpedo embryos were transferred on a medium containing different levels of BA (0.1, 0.5, or 1.0 μM) and abscisic acid (ABA) (0.5, 1.0, or 1.5 μM) or α-naphthalene acetic acid (NAA) (0.1, 0.5 or 1.0 μM). Among the different concentrations tested, 0.5 μM BA along with 1.0 μM ABA was found most effective, on which a highest yield (58.0%) with an optimum number (35.0) of mature embryos (cotyledonary stage) was observed after 2 weeks of transfer. Germination of cotyledonary embryos into plantlets with 68% were observed on ½ MS medium. Histological and scanning electron microscopical (SEM) studies proved that the regenerated structures were somatic embryos and not shoot primordia. Plants grew vigorously when transferred to a greenhouse.

Interaction of 18-methoxycoronaridine with nicotinic acetylcholine receptors in different conformational states

PubMed Central

Arias, Hugo R.; Rosenberg, Avraham; Feuerbach, Dominik; Targowska-Duda, Katarzyna M.; Maciejewski, Ryszard; Jozwiak, Krzysztof; Moaddel, Ruin; Glick, Stanley D.; Wainer, Irving W.

2013-01-01

The interaction of 18-methoxycoronaridine (18-MC) with nicotinic acetylcholine receptors (AChRs) was compared with that for ibogaine and phencyclidine (PCP). The results established that 18-MC: (a) is more potent than ibogaine and PCP inhibiting (±)-epibatidine-induced AChR Ca2+ influx. The potency of 18-MC is increased after longer pre-incubation periods, which is in agreement with the enhancement of [3H]cytisine binding to resting but activatable Torpedo AChRs, (b) binds to a single site in the Torpedo AChR with high affinity and inhibits [3H]TCP binding to desensitized AChRs in a steric fashion, suggesting the existence of overlapping sites. This is supported by our docking results indicating that 18-MC interacts with a domain located between the serine (position 6′) and valine (position 13′) rings, and (c) inhibits [3H]TCP, [3H] ibogaine, and [3H]18-MC binding to desensitized AChRs with higher affinity compared to resting AChRs. This can be partially attributed to a slower dissociation rate from the desensitized AChR compared to that from the resting AChR. The enthalpic contribution is more important than the entropic contribution when 18-MC binds to the desensitized AChR compared to that for the resting AChR, and vice versa. Ibogaine analogs inhibit the AChR by interacting with a luminal domain that is shared with PCP, and by inducing desensitization. PMID:20303928

Defense Acquisition Programs: Status of Selected Systems

DTIC Science & Technology

1989-12-01

Separation Fyout Events I Chute Deployment a r Broach Events Torpedo Search/Attack Tp WtEr . Guidance Limits Torl Water Entry * Engine Start Floatup * Chute...100 general purpose AN/UK-4450 special purpose Power 138 kilowatts Tomahawk ____________________Weight 32 tons Cooling Water 150 gallons/minute Req I...operated outsid(’ V’s. waters . V - (’ lin , t" {I li’,X;I%. 1 il , 77,1 h’Iod 12 t~lwpc( w ’ %.% ith 119 tli d i a ’ .’]H I cf 41 ll i.( lff;il( I;k

Shipbuilding and the Wilson Administration: The Development of Policy, 1914-1917

DTIC Science & Technology

1989-01-01

Movement On 7 May 1915 the German submarine U-20 torpedoed the British passenger liner Lusitania off the Irish coast. Almost twelve hundred people...the Atlantic. Then, in 1844, a yard in Bristol turned out the Great Britain, a liner of 3,270 gross tons driven by a screw propeller. The success of...The first large vessel to be launched with a steel hull was the 1,777-ton liner 8R.otmahbn, built on the Clyde In 1877. The great advantage of steel was

Hardware-in-the-loop simulation for undersea vehicle applications

NASA Astrophysics Data System (ADS)

Kelf, Michael A.

2001-08-01

Torpedoes and other Unmanned Undersea Vehicles (UUV) are employed by submarines and surface combatants, as well as aircraft, for undersea warfare. These vehicles are autonomous devices whose guidance systems rival the complexity of the most sophisticated air combat missiles. The tactical environment for undersea warfare is a difficult one in terms of target detection,k classification, and pursuit because of the physics of underwater sounds. Both hardware-in-the-loop and all-digital simulations have become vital tools in developing and evaluating undersea weapon and vehicle guidance performance in the undersea environment.

Acetylcholine, ATP, and proteoglycan are common to synaptic vesicles isolated from the electric organs of electric eel and electric catfish as well as from rat diaphragm.

PubMed

Volknandt, W; Zimmermann, H

1986-11-01

Cholinergic synaptic vesicles were isolated from the electric organs of the electric eel (Electrophorus electricus) and the electric catfish (Malapterurus electricus) as well as from the diaphragm of the rat by density gradient centrifugation followed by column chromatography on Sephacryl-1000. This was verified by both biochemical and electron microscopic criteria. Differences in size between synaptic vesicles from the various tissue sources were reflected by their elution pattern from the Sephacryl column. Specific activities of acetylcholine (ACh; in nmol/mg of protein) of chromatography-purified vesicle fractions were 36 (electric eel), 2 (electric catfish), and 1 (rat diaphragm). Synaptic vesicles from all three sources contained ATP in addition to ACh (molar ratios of ACh/ATP, 9-12) as well as binding activity for an antibody raised against Torpedo cholinergic synaptic vesicle proteoglycan. Synaptic vesicles from rat diaphragm contained binding activity for the monoclonal antibody asv 48 raised against a rat brain 65-kilodalton synaptic vesicle protein. Antibody asv 48 binding was absent from electric eel and electric catfish synaptic vesicles. These antibody binding results, which were obtained by a dot blot assay on isolated vesicles, directly correspond to the immunocytochemical results demonstrating fluorescein isothiocyanate staining in the respective nerve terminals. Our results imply that ACh, ATP, and proteoglycan are common molecular constituents of motor nerve terminal-derived synaptic vesicles from Torpedo to rat. In addition to ACh, both ATP and proteoglycan may play a specific role in the process of cholinergic signal transmission.

Biosynthesis and secretion of catalytically active acetylcholinesterase in Xenopus oocytes microinjected with mRNA from rat brain and from Torpedo electric organ.

PubMed

Soreq, H; Parvari, R; Silman, I

1982-02-01

A novel technique was developed for monitoring the level of the mRNA species that direct the synthesis of acetylcholinesterase (AcChoEase; acetylcholine acetylhydrolase, EC 3.1.1.7), using microinjected Xenopus oocytes as a translation system. When injected with poly(A)-containing RNA from whole rat brain or rat cerebellum and from electric organ of Torpedo ocellata, Xenopus oocytes synthesize and secrete catalytically active cholinesterase. The newly synthesized enzyme, which is mostly secreted into the oocytes incubation medium, appears to be primarily AcChoEase because it is inhibited by the specific inhibitor BW 284C51. The new enzymatic activity can be detected after injection of as little as 12.5 ng of poly(A)-containing RNA per oocyte, and there is a linear dependence of the oocytes' ability to form AcChoEase on the amount of injected RNA. The AcChoEase mRNA displays a tau 1/2 of about 10 +/- 3 hr in injected oocytes. The abundance of AcChoEase mRNA in the total nonfractionated mRNA injected was calculated to be ca. 1 x 10(-5), a value similar to the level of AcChoEase protein determined in rat brain. The combination of the high turnover number of AcChoEase, the efficiency of the oocyte system, and the sensitivity of the assay used thus permit the accurate monitoring of the scarce mRNA species that direct the synthesis of this enzyme.

The Dinoflagellate Toxin 20-Methyl Spirolide-G Potently Blocks Skeletal Muscle and Neuronal Nicotinic Acetylcholine Receptors

PubMed Central

Couesnon, Aurélie; Aráoz, Rómulo; Iorga, Bogdan I.; Benoit, Evelyne; Reynaud, Morgane; Servent, Denis; Molgó, Jordi

2016-01-01

The cyclic imine toxin 20-methyl spirolide G (20-meSPX-G), produced by the toxigenic dinoflagellate Alexandrium ostenfeldii/Alexandrium peruvianum, has been previously reported to contaminate shellfish in various European coastal locations, as revealed by mouse toxicity bioassay. The aim of the present study was to determine its toxicological profile and its molecular target selectivity. 20-meSPX-G blocked nerve-evoked isometric contractions in isolated mouse neuromuscular preparations, while it had no action on contractions elicited by direct electrical stimulation, and reduced reversibly nerve-evoked compound muscle action potential amplitudes in anesthetized mice. Voltage-clamp recordings in Xenopus oocytes revealed that 20-meSPX-G potently inhibited currents evoked by ACh on Torpedo muscle-type and human α7 nicotinic acetylcholine receptors (nAChR), whereas lower potency was observed in human α4β2 nAChR. Competition-binding assays showed that 20-meSPX-G fully displaced [3H]epibatidine binding to HEK-293 cells expressing the human α3β2 (Ki = 0.040 nM), whereas a 90-fold lower affinity was detected in human α4β2 nAChR. The spirolide displaced [125I]α-bungarotoxin binding to Torpedo membranes (Ki = 0.028 nM) and in HEK-293 cells expressing chick chimeric α7-5HT3 nAChR (Ki = 0.11 nM). In conclusion, this is the first study to demonstrate that 20-meSPX-G is a potent antagonist of nAChRs, and its subtype selectivity is discussed on the basis of molecular docking models. PMID:27563924

Somatic embryogenesis and plant regeneration in tissue cultures of sweet potato (Ipomea batatas Poir.).

PubMed

Liu, J R; Cantliffe, D J

1984-06-01

Leaf, shoot-tip, stem, and root explants of sweet potato (Ipomea batatas Poir.) gave rise to two kinds of callus on nutrient agar medium containing 0.5 to 2.0 mg/l 2,4-D. One callus, bright- to pale-yellow, was compact and organized, while the other was dull-yellow and friable. The former callus gave rise to numerous globular and heart-shaped embryoids. When transferred onto hormone-free medium, the embryoids readily developed into a torpedo-shape before germination. The plantlets were transplanted to soil where they flowered and formed storage roots at maturity.

A salute to the nurses of World War II.

PubMed

Breakiron, M

1995-11-01

The nation recently celebrated the 50th anniversary of World War II (WWII) with a renewed interest in Pearl Harbor and D-Day (ie, the day the Allies invaded Europe.) One group of war heroes--all volunteers--received little attention, although they endured bombings, torpedoes, antiaircraft fire, prison, starvation, and death. They were the nurses of WWII. They served all over the world and left a legacy that today's perioperative nurses are committed to preserving. This article was written to honor the nurses of WWII. It relates only a few stories of thousands that could be told.

Functional analysis of Torpedo californica nicotinic acetylcholine receptors in multiple activation states by SSM-based electrophysiology.

PubMed

Niessen, K V; Muschik, S; Langguth, F; Rappenglück, S; Seeger, T; Thiermann, H; Worek, F

2016-04-15

Organophosphorus compounds (OPC), i.e. nerve agents or pesticides, are highly toxic due to their strong inhibition potency against acetylcholinesterase (AChE). Inhibited AChE results in accumulation of acetylcholine in the synaptic cleft and thus the desensitisation of the nicotinic acetylcholine receptor (nAChR) in the postsynaptic membrane is provoked. Direct targeting of nAChR to reduce receptor desensitisation might be an alternative therapeutic approach. For drug discovery, functional properties of potent therapeutic candidates need to be investigated in addition to affinity properties. Solid supported membrane (SSM)-based electrophysiology is useful for functional characterisation of ligand-gated ion channels like nAChRs, as charge translocations via capacitive coupling of the supporting membrane can be measured. By varying the agonist (carbamoylcholine) concentration, different functional states of the nAChR were initiated. Using plasma membrane preparations obtained from Torpedo californica electric organ, functional properties of selected nAChR ligands and non-oxime bispyridinium compounds were investigated. Depending on overall-size, the bispyridinium compounds enhanced or inhibited cholinergic signals induced by 100 μM carbamoylcholine. Applying excessive concentrations of the agonist carbamoylcholine provoked desensitisation of the nAChRs, whereas addition of bispyridinium compounds bearing short alkyl linkers exhibited functional recovery of previously desensitised nAChRs. The results suggest that these non-oxime bispyridinium compounds possibly interacted with nAChR subtypes in a manner of a positive allosteric modulator (PAM). The described newly developed functional assay is a valuable tool for the assessment of functional properties of potential compounds such as nAChR modulating ligands, which might be a promising approach in the therapeutically treatment of OPC-poisonings. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Diverse inhibitory actions of quaternary ammonium cholinesterase inhibitors on Torpedo nicotinic ACh receptors transplanted to Xenopus oocytes

PubMed Central

Olivera-Bravo, Silvia; Ivorra, Isabel; Morales, Andrés

2007-01-01

Background and purpose: This work was aimed at comparing and analysing the effects and mechanisms of action of the quaternary ammonium cholinesterase inhibitors (QChEIs) BW284c51, decamethonium and edrophonium, on nicotinic ACh receptor (nAChR) function. Experimental approach: nAChRs purified from Torpedo electroplax were transplanted to oocytes and currents elicited by ACh (IACh) either alone or in presence of these QChEIs were recorded. Key results: None of the QChEIs, by itself, elicited changes in membrane conductance; however, when co-applied with ACh, all of them decreased IACh in a concentration-dependent way. The mechanisms of nAChR inhibition were different for these QChEIs. BW284c51 blockade was non-competitive and voltage-dependent, although it also affected the nH of the dose-response curve. By contrast, decamethonium and edrophonium inhibition, at –60 mV, was apparently competitive and did not modify either desensitisation or nH. Decamethonium effects were voltage-independent and washed out slowly after its removal; by contrast, edrophonium blockade had strong voltage dependence and its effects disappeared quickly after its withdrawal. Analysis of the voltage-dependent blockade indicated that BW284c51 bound to a shallow site into the channel pore, whereas edrophonium bound to a deeper locus. Accordingly, additive inhibitory effects on IACh were found among any pairs of these QChEIs. Conclusions and implications: The tested QChEIs bound to the nAChR at several and different loci, which might account for their complex inhibitory behaviour, acting both as allosteric effectors and, in the case of BW284c51 and edrophonium, as open channel blockers. PMID:17572698

Assessment of Homology Templates and an Anesthetic Binding Site within the γ-Aminobutyric Acid Receptor

PubMed Central

Bertaccini, Edward J.; Yoluk, Ozge; Lindahl, Erik R.; Trudell, James R.

2013-01-01

Background Anesthetics mediate portions of their activity via modulation of the γ-aminobutyric acid receptor (GABAaR). While its molecular structure remains unknown, significant progress has been made towards understanding its interactions with anesthetics via molecular modeling. Methods The structure of the torpedo acetylcholine receptor (nAChRα), the structures of the α4 and β2 subunits of the human nAChR, the structures of the eukaryotic glutamate-gated chloride channel (GluCl), and the prokaryotic pH sensing channels, from Gloeobacter violaceus and Erwinia chrysanthemi, were aligned with the SAlign and 3DMA algorithms. A multiple sequence alignment from these structures and those of the GABAaR was performed with ClustalW. The Modeler and Rosetta algorithms independently created three-dimensional constructs of the GABAaR from the GluCl template. The CDocker algorithm docked a congeneric series of propofol derivatives into the binding pocket and scored calculated binding affinities for correlation with known GABAaR potentiation EC50’s. Results Multiple structure alignments of templates revealed a clear consensus of residue locations relevant to anesthetic effects except for torpedo nAChR. Within the GABAaR models generated from GluCl, the residues notable for modulating anesthetic action within transmembrane segments 1, 2, and 3 converged on the intersubunit interface between alpha and beta subunits. Docking scores of a propofol derivative series into this binding site showed strong linear correlation with GABAaR potentiation EC50. Conclusion Consensus structural alignment based on homologous templates revealed an intersubunit anesthetic binding cavity within the transmembrane domain of the GABAaR, which showed correlation of ligand docking scores with experimentally measured GABAaR potentiation. PMID:23770602

Assessment of homology templates and an anesthetic binding site within the γ-aminobutyric acid receptor.

PubMed

Bertaccini, Edward J; Yoluk, Ozge; Lindahl, Erik R; Trudell, James R

2013-11-01

Anesthetics mediate portions of their activity via modulation of the γ-aminobutyric acid receptor (GABAaR). Although its molecular structure remains unknown, significant progress has been made toward understanding its interactions with anesthetics via molecular modeling. The structure of the torpedo acetylcholine receptor (nAChRα), the structures of the α4 and β2 subunits of the human nAChR, the structures of the eukaryotic glutamate-gated chloride channel (GluCl), and the prokaryotic pH-sensing channels, from Gloeobacter violaceus and Erwinia chrysanthemi, were aligned with the SAlign and 3DMA algorithms. A multiple sequence alignment from these structures and those of the GABAaR was performed with ClustalW. The Modeler and Rosetta algorithms independently created three-dimensional constructs of the GABAaR from the GluCl template. The CDocker algorithm docked a congeneric series of propofol derivatives into the binding pocket and scored calculated binding affinities for correlation with known GABAaR potentiation EC50s. Multiple structure alignments of templates revealed a clear consensus of residue locations relevant to anesthetic effects except for torpedo nAChR. Within the GABAaR models generated from GluCl, the residues notable for modulating anesthetic action within transmembrane segments 1, 2, and 3 converged on the intersubunit interface between α and β subunits. Docking scores of a propofol derivative series into this binding site showed strong linear correlation with GABAaR potentiation EC50. Consensus structural alignment based on homologous templates revealed an intersubunit anesthetic binding cavity within the transmembrane domain of the GABAaR, which showed a correlation of ligand docking scores with experimentally measured GABAaR potentiation.

Topological dispositions of lysine. alpha. 380 and lysine. gamma. 486 in the acetylcholine receptor from Torpedo californica

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

Dwyer, B.P.

1991-04-23

The locations have been determined, with respect to the plasma membrane, of lysine {alpha}380 and lysine {gamma}486 in the {alpha} subunit and the {gamma} subunit, respectively, of the nicotinic acetylcholine receptor from Torpedo californica. Immunoadsorbents were constructed that recognize the carboxy terminus of the peptide GVKYIAE released by proteolytic digestion from positions 378-384 in the amino acid sequence of the {alpha} subunit of the acetylcholine receptor and the carboxy terminus of the peptide KYVP released by proteolytic digestion from positions 486-489 in the amino acid sequence of the {gamma} subunit. They were used to isolate these peptides from proteolytic digestsmore » of polypeptides from the acetylcholine receptor. Sealed vesicles containing the native acetylcholine receptor were labeled with pyridoxal phosphate and sodium ({sup 3}H)-borohydride. The effect of saponin on the incorporation of pyridoxamine phosphate into lysine {alpha}380 and lysine {gamma}486 from the acetylcholine receptor in these vesicles was assessed with the immunoadsorbents. The conclusions that follow from these results are that lysine {alpha}380 is on the inside surface of a vesicle and lysine {gamma}486 is on the outside surface. Because a majority (85%) of the total binding sites for {alpha}-bungarotoxin bind the toxin in the absence of saponin, the majority of the vesicles are right side out with the inside of the vesicle corresponding to the cytoplasmic surface and the outside of the vesicle corresponding to the extracytoplasmic, synaptic surface. Because lysine {alpha}380 and lysine {gamma}486 lie on opposite sides of the membrane, a membrane-spanning segment must be located between the two positions occupied by these two amino acids in the common sequence of a polypeptide of the acetylcholine receptor.« less

Complex alternative splicing of acetylcholinesterase transcripts in Torpedo electric organ; primary structure of the precursor of the glycolipid-anchored dimeric form.

PubMed Central

Sikorav, J L; Duval, N; Anselmet, A; Bon, S; Krejci, E; Legay, C; Osterlund, M; Reimund, B; Massoulié, J

1988-01-01

In this paper, we show the existence of alternative splicing in the 3' region of the coding sequence of Torpedo acetylcholinesterase (AChE). We describe two cDNA structures which both diverge from the previously described coding sequence of the catalytic subunit of asymmetric (A) forms (Schumacher et al., 1986; Sikorav et al., 1987). They both contain a coding sequence followed by a non-coding sequence and a poly(A) stretch. Both of these structures were shown to exist in poly(A)+ RNAs, by S1 mapping experiments. The divergent region encoded by the first sequence corresponds to the precursor of the globular dimeric form (G2a), since it contains the expected C-terminal amino acids, Ala-Cys. These amino acids are followed by a 29 amino acid extension which contains a hydrophobic segment and must be replaced by a glycolipid in the mature protein. Analyses of intact G2a AChE showed that the common domain of the protein contains intersubunit disulphide bonds. The divergent region of the second type of cDNA consists of an adjacent genomic sequence, which is removed as an intron in A and Ga mRNAs, but may encode a distinct, less abundant catalytic subunit. The structures of the cDNA clones indicate that they are derived from minor mRNAs, shorter than the three major transcripts which have been described previously (14.5, 10.5 and 5.5 kb). Oligonucleotide probes specific for the asymmetric and globular terminal regions hybridize with the three major transcripts, indicating that their size is determined by 3'-untranslated regions which are not related to the differential splicing leading to A and Ga forms. Images PMID:3181125

Improved methodology to obtain large quantities of correctly folded recombinant N-terminal extracellular domain of the human muscle acetylcholine receptor for inducing experimental autoimmune myasthenia gravis in rats

PubMed Central

Sun, Chenjing; Zhang, Hongliang; Xu, Jiang; Gao, Jie

2013-01-01

Introduction Human myasthenia gravis (MG) is an autoimmune disorder of the neuromuscular system. Experimental autoimmune myasthenia gravis (EAMG) is a well-established animal model for MG that can be induced by active immunization with the Torpedo californica-derived acetylcholine receptor (AChR). Due to the expensive cost of purifying AChR from Torpedo californica, the development of an easier and more economical way of inducing EAMG remains critically needed. Material and methods Full-length cDNA of the human skeletal muscle AChR α1 subunit was obtained from TE671 cells. The DNA fragment encoding the extracellular domain (ECD) was then amplified by polymerase chain reaction (PCR) and inserted into pET-16b. The reconstructed plasmid was transformed into the host strain BL21(DE3)pLysS, which was derived from Escherichia coli. Isopropyl-β-D-thiogalactopyranoside (IPTG) was used to induce the expression of the N-terminal ECD. The produced protein was purified with immobilized Ni2+ affinity chromatography and refolded by dialysis. Results The recombinant protein was efficiently refolded to soluble active protein, which was verified by ELISA. After immunization with the recombinant ECD, all rats acquired clinical signs of EAMG. The titer of AChR antibodies in the serum was significantly higher in the EAMG group than in the control group, indicating successful induction of EAMG. Conclusions We describe an improved procedure for refolding recombinant ECD of human muscle AChR. This improvement allows for the generation of large quantities of correctly folded recombinant ECD of human muscle AChR, which provides for an easier and more economical way of inducing the animal model of MG. PMID:24904677

Origins of Host-Specific Populations of the Blast Pathogen Magnaporthe oryzae in Crop Domestication With Subsequent Expansion of Pandemic Clones on Rice and Weeds of Rice

PubMed Central

Couch, Brett C.; Fudal, Isabelle; Lebrun, Marc-Henri; Tharreau, Didier; Valent, Barbara; van Kim, Pham; Nottéghem, Jean-Loup; Kohn, Linda M.

2005-01-01

Rice, as a widely and intensively cultivated crop, should be a target for parasite host shifts and a source for shifts to co-occurring weeds. Magnaporthe oryzae, of the M. grisea species complex, is the most important fungal pathogen of rice, with a high degree of host specificity. On the basis of 10 loci from six of its seven linkage groups, 37 multilocus haplotypes among 497 isolates of M. oryzae from rice and other grasses were identified. Phylogenetic relationships among isolates from rice (Oryza sativa), millet (Setaria spp.), cutgrass (Leersia hexandra), and torpedo grass (Panicum repens) were predominantly tree like, consistent with a lack of recombination, but from other hosts were reticulate, consistent with recombination. The single origin of rice-infecting M. oryzae followed a host shift from a Setaria millet and was closely followed by additional shifts to weeds of rice, cutgrass, and torpedo grass. Two independent estimators of divergence time indicate that these host shifts predate the Green Revolution and could be associated with rice domestication. The rice-infecting lineage is characterized by high copy number of the transposable element MGR586 (Pot3) and, except in two haplotypes, by a loss of AVR-Co39. Both mating types have been retained in ancestral, well-distributed rice-infecting haplotypes 10 (mainly temperate) and 14 (mainly tropical), but only one mating type was recovered from several derived, geographically restricted haplotypes. There is evidence of a common origin of both ACE1 virulence genotypes in haplotype 14. Host-haplotype association is evidenced by low pathogenicity on hosts associated with other haplotypes. PMID:15802503

Performance of Single-Stage Turbine of Mark 25 Torpedo Power Plant with Two Special Nozzles. III; Efficiency with Standard Rotor Blades

NASA Technical Reports Server (NTRS)

Schum, Harold J.; Whitney, Warren J.

1949-01-01

A Mark 25 torpedo power plant modified to operate as a single-stage turbine was investigated to determine the performance with two nozzle designs and a standard first-stage rotor having 0.40-inch blades with a 17O met-air angle. Both nozzles had smaller port cross-sectional areas than those nozzles of similar design, which were previously investigated. The performance of the two nozzles was compared on the basis of blade, rotor, and brake efficiencies as a function of blade-jet speed ratio for pressure ratios of 8, 15 (design), and 20. At pressure ratios of 15 and 20, the blade efficiency obtained with the nozzle having circular passages (K) was higher than that obtained with the nozzle having rectangular passages (J). At a pressure ratio of 8, the efficiencies obtained with the two nozzles were comparable for blade-jet speed ratios of less than 0.260. For blade-jet speed ratios exceeding this value, nozzle K yielded slightly higher efficiencies. The maximum blade efficiency of 0.569 was obtained with nozzle K at a pressure ratio of 8 and a blade-jet speed ratio of 0.295. At design speed and pressure ratio, nozzle K yielded a maximum blade efficiency of 0.534, an increase of 0.031 over that obtained with nozzle J. When the blade efficiencies of the two nozzles were compared with those of four other nozzles previously investigated, the maximum difference for the six nozzles with this rotor was 0.050. From, this comparison, no specific effect of nozzles size or shape on over-all performance was discernible.

Neurofilament protein levels: quantitative analysis in essential tremor cerebellar cortex.

PubMed

Louis, Elan D; Ma, Karen; Babij, Rachel; Cortés, Etty; Liem, Ronald K; Vonsattel, Jean-Paul G; Faust, Phyllis L

2012-06-14

Essential tremor (ET) is among the most prevalent neurological diseases. A substantial increase in the number of Purkinje cell axonal swellings (torpedoes) has been identified in ET brains. We recently demonstrated that torpedoes in ET contain an over-accumulation of disorganized neurofilament (NF) proteins. This now raises the question whether NF protein composition and/or phosphorylation state in cerebellar tissue might differ between ET cases and controls. We used a Western blot analysis to compare the levels and phosphorylation state of NF proteins and α-internexin in cerebellar tissue from 47 ET cases versus 26 controls (2:1 ratio). Cases and controls did not differ with respect to the cerebellar levels of NF-light (NF-L), NF-medium (NF-M), NF-heavy (NF-H), or α-internexin. However, SMI-31 levels (i.e., phosphorylated NF-H) and SMI-32 levels (i.e., non-phosphorylated NF-H) were significantly higher in ET cases than controls (1.28±0.47 vs. 1.06±0.32, p=0.02; and 1.38±0.75 vs. 1.00±0.42, p=0.006). Whether the abnormal phosphorylation state that we observed is a cause of defective axonal transport and/or function of NFs in ET is not known. NF abnormalities have been demonstrated in several neurodegenerative diseases. Regardless of whether these protein aggregates are the cause or consequence of these diseases, NF abnormalities have been shown to be an important factor in the cellular disruption observed in several neurodegenerative diseases. Therefore, further analyses of these NF abnormalities and their mechanisms are important to enhance our understanding of disease pathogenesis in ET. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Electricity in the treatment of nervous system disease.

PubMed

Fodstad, H; Hariz, M

2007-01-01

Electricity has been used in medicine for almost two millenniums beginning with electrical chocks from the torpedo fish and ending with the implantation of neuromodulators and neuroprostheses. These implantable stimulators aim to improve functional independence and quality of life in various groups of disabled people. New indications for neuromodulation are still evolving and the field is rapidly advancing. Thanks to modern science and computer technology, electrotherapy has reached a degree of sophistication where it can be applied relatively safely and effectively in a variety of nervous system diseases, including pain, movement disorders, epilepsy, Tourette syndrome, psychiatric disease, addiction, coma, urinary incontinence, impotence, infertility, respiratory paralysis, tinnitus and blindness.

Noise: My 62 years of it!

NASA Astrophysics Data System (ADS)

Miller, Laymon N.

2004-05-01

Imagine getting paid for having fun! Well, in retrospect, it was fun; but there were several tough challenges. Even those are worth remembering. From 1941 to 1982, there were acoustic torpedoes, HVAC acoustics, noise and vibration in auditoriums, aircraft and airport noise, OSHA and industrial noise control, power plants, community noise problems, vbration, railroad and subway vibration control, legal acoustics, noise manuals, and noise courses-and a few other things that don't fit into those neat categories. Some specific jobs could be named, but that would take away the suspense and the surprise. But 1941 to 1982 is only 41 years. How about the other 20-odd years?

[Universal stripper for varicose vein surgery].

PubMed

Fischer, R

1996-03-01

We report on new stripper guides that facilitate the introduction of the stripper from the proximal side. At the same time they allow for smaller skin incisions and fewer nerve lesions. The 60-cm-long cable instead of the conventional one (90 cm long) is adequate for partial stripping. Due to its shortness, it is less annoying in the operation field and it allows rotational control of the Tiemann guide. The "dolphin" and the "torpedo" help to remove segments of the saphenous vein that are left behind. All these instruments are available as a set in a small box, which is handy for the scrub nurse.

Electrical apparatus used in medicine before 1900.

PubMed Central

Cambridge, N A

1977-01-01

The Ancients had at their disposal torpedo fish, amber and magnets. It was not until the sixteenth century that ideas on the strange behaviour of amber and magnets were put forward. The eighteenth century saw the application of Newton's theories of matter and the introduction of the electrostatic machine, Galvanism and Volta's battery. In the nineteenth century there was extensive application of electricity in medical practice, with the development of electrocautery apparatus and illuminated cystoscopes, the pioneering of the electrocardiogram and the discovery of X-rays. Images Fig 1 Fig 2 Fig 3 Fig 4 Fig 5 Fig 6 Fig 7 Fig 8 Fig 9 Fig 10 Fig 11 Fig 12 PMID:335397

System for effecting underwater coupling of optical fiber cables characterized by a novel V-probe cable capture mechanism

NASA Astrophysics Data System (ADS)

Hillenbrand, Christopher F.; Barron, Thomas D.; Nugent, David M.

1995-03-01

A submarine trails one fiber optic cable and an undersea vehicle is controlled by this first cable. A missile/torpedo trails a second cable that is to be coupled to the first cable. The second cable has a segment suspended vertically underwater between a buoyant pod and a sea anchor type buoy. The undersea vehicle, or Autonomous Undersea Vehicle, (AUV) hunts for the pod by conventional homing means. A forked cable pickup device in the nose of the AUV captures the suspended cable segment directing it into a slot so a male socket in the underside of the pod mates with a female socket in the slot.

The nicotinic acetylcholine receptor: Binding of nitroxide analogs of a local anesthetic and a photoactivatable analog of phosphatidylserine

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

Blanton, M.P.

1989-01-01

Electron spin resonance was used to contrast the accessibility of tertiary and quaternary amine local anesthetics to their high affinity binding site in the desensitized Torpedo californica acetylcholine receptor (AchR). Preincubation of AchR-rich membranes with agonist resulted in a substantial reduction in the initial association of the quaternary amine local anesthetic C6SLMEI with the receptor. The time-dependent reduction in association follows a biphasic exponential function having rate constants of 0.19 min{sup {minus}1} and 0.03 min{sup {minus}1}. In contrast, agonist preincubation did not produce a comparable decrease in the association of C6SL, a tertiary amine analog, with the AchR. The resultsmore » are modeled in two ways: (1) A charge gate near the channel mouth in the desensitized receptor limits access of the permanently charged cationic local anesthetic (C6SLMEI), but not for the uncharged form of the tertiary amine anesthetic C6SL. (2) A hydrophobic pathway, possibly through a corridor in the annular lipid surrounding receptor subunits, allows the uncharged form of C6SL to reach the high affinity binding site in the AchR. A photoactivatable analog of phosphatidylserine {sup 125}I 4-azido salicylic acid-phosphatidylserine ({sup 125}I ASA-PS) was use to label both Torpedo californica acetylcholine receptor-rich membranes and reconstituted AchR membranes. All four subunits of the AchR were found to incorporate label, with the {alpha} subunit incorporating approximately twice as much as each of the other subunits on a per mole basis. The regions of the AchR {alpha} subunit that incorporate {sup 125}I ASA-PS were mapped by Staphylococcus aureus V8 protease digestion. Eighty-one per cent of the incorporated label was localized to 11.7 and 10.1 kdal V8 cleavage fragments.« less

Performance of Single-Stage Turbine of Mark 25 Torpedo Power Plant with Two Nozzles and Three Rotor-Blade Designs

NASA Technical Reports Server (NTRS)

Schum, Harold J.; Whitney, Warren J.

1949-01-01

A single-stage modification of the turbine from a Mark 25 torpedo power plant was investigated to determine the performance with two nozzles and three rotor-blade designs. The performance was evaluated in terms of brake, rotor, and blade efficiencies at pressure ratios of 8, 15 (design), and 20. The blade efficiencies with the two nozzles are compared with those obtained with four other nozzles previously investigated with the same three rotor-blade designs. Blade efficiency with the cast nozzle of rectangular cross section (J) was higher than that with the circular reamed nozzle (K) at all speeds and pressure ratios with a rotor having a 0.45-inch 17 degree-inlet-angle blades. The efficiencies for both these nozzles were generally low compared with those of the four other nozzles previously investigated in combination with this rotor. At pressure ratios of 15 and 20, the blade efficiencies with nozzle K and the two rotors with 0.40-inch blades having different inlet angles were higher than with the four other nozzles, but the efficiency with nozzle J was generally low. Increasing the blade inlet angle from 17 degrees to 20 degrees had little effect on turbine performance, whereas changing the blade length from 0.40 to 0.45 inch had a marked effect. Although a slight correlation of efficiency with nozzle size was noted for the rotor with 0.45-inch 17 degree-inlet-angle blades, no such effect was discernible ,for the two rotors with 0.40-inch blades.Losses in the supersonic air stream resulting from the complex flow path in the small air passages are probably a large percentage of the total losses, and apparently the effects of changing nozzle size and shape within the limits investigated are of secondary importance.

Fourier transform coupled tryptophan scanning mutagenesis identifies a bending point on the lipid-exposed δM3 transmembrane domain of the Torpedo californica nicotinic acetylcholine receptor

PubMed Central

Caballero-Rivera, Daniel; Cruz-Nieves, Omar A; Oyola-Cintrón, Jessica; Torres-Núñez, David A; Otero-Cruz, José D

2011-01-01

The nicotinic acetylcholine receptor (nAChR) is a member of a family of ligand-gated ion channels that mediate diverse physiological functions, including fast synaptic transmission along the peripheral and central nervous systems. Several studies have made significant advances toward determining the structure and dynamics of the lipid-exposed domains of the nAChR. However, a high-resolution atomic structure of the nAChR still remains elusive. In this study, we extended the Fourier transform coupled tryptophan scanning mutagenesis (FT-TrpScanM) approach to gain insight into the secondary structure of the δM3 transmembrane domain of the Torpedo californica nAChR, to monitor conformational changes experienced by this domain during channel gating, and to identify which lipid-exposed positions are linked to the regulation of ion channel kinetics. The perturbations produced by periodic tryptophan substitutions along the δM3 transmembrane domain were characterized by two-electrode voltage clamp and 125I-labeled α-bungarotoxin binding assays. The periodicity profiles and Fourier transform spectra of this domain revealed similar helical structures for the closed- and open-channel states. However, changes in the oscillation patterns observed between positions Val-299 and Val-304 during transition between the closed- and open-channel states can be explained by the structural effects caused by the presence of a bending point introduced by a Thr-Gly motif at positions 300–301. The changes in periodicity and localization of residues between the closed-and open-channel states could indicate a structural transition between helix types in this segment of the domain. Overall, the data further demonstrate a functional link between the lipid-exposed transmembrane domain and the nAChR gating machinery. PMID:21785268

A bursting potassium channel in isolated cholinergic synaptosomes of Torpedo electric organ.

PubMed Central

Edry-Schiller, J; Ginsburg, S; Rahamimoff, R

1991-01-01

1. Pinched-off cholinergic nerve terminals (synaptosomes) prepared from the electric organ of Torpedo ocelata were fused into large structures (greater than 20 microns) using dimethyl sulphoxide and polyethylene glycol 1500, as previously described for synaptic vesicles from the same organ. 2. The giant fused synaptosomes were easily amenable to the patch clamp technique and 293 seals with a resistance greater than 4 G omega were obtained in the 'cell-attached' configuration. In a large fraction of the experiments, an 'inside-out' patch configuration was achieved. 3. Several types of unitary ionic currents were observed. This study describes the most frequently observed single-channel activity which was found in 247 out of the 293 membrane patches (84.3%). 4. The single-channel current-voltage relation was linear between -60 and 20 mV and showed a slope conductance of 23.8 +/- 1.3 pS when the pipette contained 350-390 mM-Na+ and the bath facing the inside of the synaptosomal membrane contained 390 mM-K+. 5. From extrapolated reversal potential measurements, it was concluded that this channel has a large selectivity for K+ over Na+ (70.4 +/- 11.5, mean +/- S.E.M.). Chloride ions are not transported significantly through this potassium channel. 6. This potassium channel has a low probability of opening. The probability of being in the open state increases upon depolarization and reaches about 1% when the inside of the patch is 20 mV positive compared to the pipette side. 7. The mean channel open time increases with depolarization; thus the product current x time (= charge) also increases upon depolarization, showing properties of an outward rectifier. 8. The potassium channel in the giant synaptosome membrane has a bursting behaviour. Open-time distribution, closed-time distribution and a Poisson analysis indicate that the minimal kinetic scheme requires one open state and three closed states. PMID:1654418

Damped flexible seal

DOEpatents

DuBois, Neil J.; Amaral, Antonio M.

1992-10-27

A damped flexible seal assembly for a torpedo isolates the tailcone thereof rom vibrational energy present in the drive shaft assembly. A pair of outside flanges, each of which include an inwardly facing groove and an O-ring constrained therein, provide a watertight seal against the outer non-rotating surface of the drive shaft assembly. An inside flange includes an outwardly-facing groove and an O-ring constrained therein, and provides a watertight seal against the inner surface of the tail cone. Two cast-in-place elastomeric seals provide a watertight seal between the flanges and further provide a damping barrier between the outside flanges and the inside flanges for damping vibrational energy present in the drive shaft assembly before the energy can reach the tailcone through the seal assembly.

James Cameron discusses record dive and science concerns

NASA Astrophysics Data System (ADS)

Showstack, Randy; Balcerak, Ernie

2012-12-01

James Cameron, the explorer and filmmaker, led a 4 December panel at the AGU Fall Meeting in San Francisco to discuss his daring dive on 26 March to the bottom of the ocean in a one-person vertical "torpedo" submarine, the Deepsea Challenger, and to present some initial science findings from expedition samples and data. The dive touched the bottom of the Challenger Deep, a valley in the floor of the nearly 11-kilometer-deep Mariana Trench in the western Pacific Ocean. The vessel landed close to the same depth and at a location similar to where Don Walsh and Jacques Piccard descended in the Trieste bathyscaphe on 23 January 1960 at a then record-setting depth of 10,911 meters.

The role of The Gentleman's Magazine in the dissemination of knowledge about electric fish in the eighteenth century.

PubMed

Finger, Stanley; Ferguson, Ian

2009-10-01

Although torpedoes and Malopterurus, a Nile catfish, had been described and even used medically in antiquity, their discharges were poorly understood before the second half of the eighteenth century. It was then that their actions, along with those of certain South American "eels," became firmly associated with electricity. The realization that an animal could produce electricity marked a turning point in the history of neurophysiology, which had long described nerve actions with recourse to animal spirits. By examining The Gentleman's Magazine during the period when electric fish were becoming electrical, one can begin to appreciate how new discoveries about these unusual creatures captured the imagination of scientists and were filtered down to the literate public.

Unusual electron-dense dome associates with compound plasmodesmata in the embryo-suspensor of genus Sedum (Crassulaceae).

PubMed

Kozieradzka-Kiszkurno, Małgorzata; Bohdanowicz, Jerzy

2010-11-01

Plasmodesmata ensure the continuity of cytoplasm between plant cells and play an important part in the intercellular communication and signal transduction. During the development of the suspensor of both Sedum acre L. and Sedum hispanicum L., changes in the ultrastructure of plasmodesmata and adjoining cytoplasm are observed. Numerous simple plasmodesmata are present in the inner wall of the two-celled embryo separating the basal cell from the apical cell. From the early-globular to the torpedo stage of embryo development, the part of the wall separating the basal cell from the first layer of the chalazal suspensor cells is perforated by unusual, compound plasmodesmata. The role and the sort of transport through these plasmodesmata are discussed.

Forcing the Navy to sell cigarettes on ships: how the tobacco industry and politicians torpedoed Navy tobacco control.

PubMed

Offen, Naphtali; Arvey, Sarah R; Smith, Elizabeth A; Malone, Ruth E

2011-03-01

In 1986, the US Navy announced the goal of becoming smoke-free by 2000. However, efforts to restrict tobacco sales and use aboard the USS Roosevelt prompted tobacco industry lobbyists to persuade their allies in Congress to legislate that all naval ships must sell tobacco. Congress also removed control of ships' stores from the Navy. By 1993, the Navy abandoned its smoke-free goal entirely and promised smokers a place to smoke on all ships. Congressional complicity in promoting the agenda of the tobacco industry thwarted the Navy's efforts to achieve a healthy military workforce. Because of military lobbying constraints, civilian pressure on Congress may be necessary to establish effective tobacco control policies in the armed forces.

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

Nabavi, Sadeq; Nazar, Ross N., E-mail: rnnazar@uoguelph.ca

The maturation of many small nuclear RNAs is dependent on RNase III-like endonuclease mediated cleavage, which generates a loading site for the exosome complex that trims the precursor at its 3' end. Using a temperature sensitive Pac1 nuclease, here we show that the endonuclease cleavage is equally important in terminating the transcription of the U2 snRNA in Schizosaccharomyces pombe. Using a temperature sensitive Dhp1p 5' {yields} 3' exonuclease, we demonstrate that it also is an essential component of the termination pathway. Taken together the results support a 'reversed torpedoes' model for the termination and maturation of the U2 snRNA; themore » Pac1 endonuclease cleavage provides entry sites for the 3' and 5' exonuclease activities, leading to RNA maturation in one direction and transcript termination in the other.« less

Forcing the Navy to Sell Cigarettes on Ships: How the Tobacco Industry and Politicians Torpedoed Navy Tobacco Control

PubMed Central

Arvey, Sarah R.; Smith, Elizabeth A.; Malone, Ruth E.

2011-01-01

In 1986, the US Navy announced the goal of becoming smoke-free by 2000. However, efforts to restrict tobacco sales and use aboard the USS Roosevelt prompted tobacco industry lobbyists to persuade their allies in Congress to legislate that all naval ships must sell tobacco. Congress also removed control of ships’ stores from the Navy. By 1993, the Navy abandoned its smoke-free goal entirely and promised smokers a place to smoke on all ships. Congressional complicity in promoting the agenda of the tobacco industry thwarted the Navy's efforts to achieve a healthy military workforce. Because of military lobbying constraints, civilian pressure on Congress may be necessary to establish effective tobacco control policies in the armed forces. PMID:21233435

Reduced swimming performance repeatedly evolves upon loss of migration in landlocked populations of Alewife

USGS Publications Warehouse

Velotta, Jonathan P.; McCormick, Stephen; Jones, Andrew W.; Schultz, Eric T.

2018-01-01

Whole-organism performance tasks are accomplished by the integration of morphological traits and physiological functions. Understanding how evolutionary change in morphology and physiology influences whole-organism performance will yield insight into the factors that shape its own evolution. We demonstrate that nonmigratory populations of alewife (Alosa pseudoharengus) have evolved reduced swimming performance in parallel, compared with their migratory ancestor. In contrast to theoretically and empirically based predictions, poor swimming among nonmigratory populations is unrelated to the evolution of osmoregulation and occurs despite the fact that nonmigratory alewives have a more fusiform (torpedo-like) body shape than their ancestor. Our results suggest that elimination of long-distance migration from the life cycle has shaped performance more than changes in body shape and physiological regulatory capacity.

External combustion engine having a combustion expansion chamber

NASA Astrophysics Data System (ADS)

Duva, Anthony W.

1993-03-01

This patent application discloses an external combustion engine having a combustion expansion chamber. The engine includes a combustion chamber for generating a high-pressure, energized gas from a monopropellant fuel, and a cylinder for receiving the energized gas through a rotary valve to perform work on a cylinder disposed therein. A baffle plate is positioned between the combustion area and expansion area for reducing the pressure of the gas. The combustion area and expansion area are separated by a baffle plate having a flow area which is sufficiently large to eliminate the transmission of pressure pulsations from the combustion area to the expansion area while being small enough to provide for substantially complete combustion in the combustion area. The engine is particularly well suited for use in a torpedo.

A case of deep burns, while diving The Lusitania.

PubMed

Curran, John N; McGuigan, Kevin G; O'Broin, Eoin

2010-07-01

We present the first documented case of severe burns, sustained by a diver as a result of auto-ignition of air-activated heat packs at high partial pressure of oxygen and high ambient pressure. Our patient was diving the shipwreck of The Lusitania off the south coast of Ireland. This is a significant wreck, lying 90 metres down on the seabed. Torpedoed by a German U-boat in 1915, its loss prompted American involvement in WW1. Several unlikely events combined in this case to bring about serious and life threatening injuries. Herein we discuss the case and explore some of the physical and chemical processes that lead to these injuries. Copyright 2009 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.

Norwegian monitoring (1990-2015) of the marine environment around the sunken nuclear submarine Komsomolets.

PubMed

Gwynn, Justin P; Heldal, Hilde Elise; Flo, Janita K; Sværen, Ingrid; Gäfvert, Torbjörn; Haanes, Hallvard; Føyn, Lars; Rudjord, Anne Liv

2018-02-01

Norway has monitored the marine environment around the sunken Russian nuclear submarine Komsomolets since 1990. This study presents an overview of 25 years of Norwegian monitoring data (1990-2015). Komsomolets sank in 1989 at a depth of 1680 m in the Norwegian Sea while carrying two nuclear torpedoes in its armament. Subsequent Soviet and Russian expeditions to Komsomolets have shown that releases from the reactor have occurred and that the submarine has suffered considerable damage to its hulls. Norwegian monitoring detected 134 Cs in surface sediments around Komsomolets in 1993 and 1994 and elevated activity concentrations of 137 Cs in bottom seawater between 1991 and 1993. Since then and up to 2015, no increased activity concentrations of radionuclides above values typical for the Norwegian Sea have been observed in any environmental sample collected by Norwegian monitoring. In 2013 and 2015, Norwegian monitoring was carried out using an acoustic transponder on the sampling gear that allowed samples to be collected at precise locations, ∼20 m from the hull of Komsomolets. The observed 238 Pu/ 239,240 Pu activity ratios and 240 Pu/ 239 Pu atom ratios in surface sediments sampled close to Komsomolets in 2013 did not indicate any releases of Pu isotopes from reactor or the torpedo warheads. Rather, these values probably reflect the overprinting of global fallout ratios with fluxes of these Pu isotopes from long-range transport of authorised discharges from nuclear reprocessing facilities in Northern Europe. However, due to the depth at which Komsomolets lies, the collection of seawater and sediment samples in the immediate area around the submarine using traditional sampling techniques from surface vessels is not possible, even with the use of acoustic transponders. Further monitoring is required in order to have a clear understanding of the current status of Komsomolets as a potential source of radioactive contamination to the Norwegian marine environment. Such monitoring should involve the use of ROVs or submersibles in order to obtain samples next to and within the different compartments of the submarine. Copyright © 2017 Elsevier Ltd. All rights reserved.

Fail-safe transcription termination: Because one is never enough.

PubMed

Lemay, Jean-François; Bachand, François

2015-01-01

Termination of RNA polymerase II (RNAPII) transcription is a fundamental step of gene expression that involves the release of the nascent transcript and dissociation of RNAPII from the DNA template. As transcription termination is intimately linked to RNA 3' end processing, termination pathways have a key decisive influence on the fate of the transcribed RNA. Quite remarkably, when reaching the 3' end of genes, a substantial fraction of RNAPII fail to terminate transcription, requiring the contribution of alternative or "fail-safe" mechanisms of termination to release the polymerase. This point of view covers redundant mechanisms of transcription termination and how they relate to conventional termination models. In particular, we expand on recent findings that propose a reverse torpedo model of termination, in which the 3'5' exonucleolytic activity of the RNA exosome targets transcription events associated with paused and backtracked RNAPII.

Autonomous Underwater Navigation and Optical Mapping in Unknown Natural Environments.

PubMed

Hernández, Juan David; Istenič, Klemen; Gracias, Nuno; Palomeras, Narcís; Campos, Ricard; Vidal, Eduard; García, Rafael; Carreras, Marc

2016-07-26

We present an approach for navigating in unknown environments while, simultaneously, gathering information for inspecting underwater structures using an autonomous underwater vehicle (AUV). To accomplish this, we first use our pipeline for mapping and planning collision-free paths online, which endows an AUV with the capability to autonomously acquire optical data in close proximity. With that information, we then propose a reconstruction pipeline to create a photo-realistic textured 3D model of the inspected area. These 3D models are also of particular interest to other fields of study in marine sciences, since they can serve as base maps for environmental monitoring, thus allowing change detection of biological communities and their environment over time. Finally, we evaluate our approach using the Sparus II, a torpedo-shaped AUV, conducting inspection missions in a challenging, real-world and natural scenario.

Discovery of CLC transport proteins: cloning, structure, function and pathophysiology

PubMed Central

Jentsch, Thomas J

2015-01-01

Abstract After providing a personal description of the convoluted path leading 25 years ago to the molecular identification of the Torpedo Cl− channel ClC-0 and the discovery of the CLC gene family, I succinctly describe the general structural and functional features of these ion transporters before giving a short overview of mammalian CLCs. These can be categorized into plasma membrane Cl− channels and vesicular Cl−/H+-exchangers. They are involved in the regulation of membrane excitability, transepithelial transport, extracellular ion homeostasis, endocytosis and lysosomal function. Diseases caused by CLC dysfunction include myotonia, neurodegeneration, deafness, blindness, leukodystrophy, male infertility, renal salt loss, kidney stones and osteopetrosis, revealing a surprisingly broad spectrum of biological roles for chloride transport that was unsuspected when I set out to clone the first voltage-gated chloride channel. PMID:25590607

Transcatheter Arterial Embolization for Postpartum Hemorrhage: Indications, Technique, Results, and Complications

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

Soyer, Philippe, E-mail: philippe.soyer@lrb.aphp.fr; Dohan, Anthony, E-mail: anthony.dohan@lrb.aphp.fr; Dautry, Raphael, E-mail: raphael-dautry@yahoo.fr

Postpartum hemorrhage (PPH) is a potentially life-threatening condition, which needs multidisciplinary management. Uterine atony represents up to 80 % of all causes of PPH. Transcatheter arterial embolization (TAE) has now a well-established role in the management of severe PPH. TAE allows stopping the bleeding in 90 % of women with severe PHH, obviating surgery. Pledgets of gelatin sponge as torpedoes are commonly used for safe TAE, and coils, glue, and microspheres have been primarily used in specific situations such as arterial rupture, pseudoaneurysm, and arteriovenous fistula. TAE is a minimally invasive procedure with a low rate of complications, which preserves future fertility.more » Knowledge of causes of PPH, potential risks, and limitations of TAE is essential for a timely decision, optimizing TAE, preventing irreversible complications, avoiding hysterectomy, and ultimately preserving fertility.« less

Autonomous Underwater Navigation and Optical Mapping in Unknown Natural Environments

PubMed Central

Hernández, Juan David; Istenič, Klemen; Gracias, Nuno; Palomeras, Narcís; Campos, Ricard; Vidal, Eduard; García, Rafael; Carreras, Marc

2016-01-01

We present an approach for navigating in unknown environments while, simultaneously, gathering information for inspecting underwater structures using an autonomous underwater vehicle (AUV). To accomplish this, we first use our pipeline for mapping and planning collision-free paths online, which endows an AUV with the capability to autonomously acquire optical data in close proximity. With that information, we then propose a reconstruction pipeline to create a photo-realistic textured 3D model of the inspected area. These 3D models are also of particular interest to other fields of study in marine sciences, since they can serve as base maps for environmental monitoring, thus allowing change detection of biological communities and their environment over time. Finally, we evaluate our approach using the Sparus II, a torpedo-shaped AUV, conducting inspection missions in a challenging, real-world and natural scenario. PMID:27472337

Fail-safe transcription termination: Because one is never enough

PubMed Central

Lemay, Jean-François; Bachand, François

2015-01-01

Termination of RNA polymerase II (RNAPII) transcription is a fundamental step of gene expression that involves the release of the nascent transcript and dissociation of RNAPII from the DNA template. As transcription termination is intimately linked to RNA 3′ end processing, termination pathways have a key decisive influence on the fate of the transcribed RNA. Quite remarkably, when reaching the 3′ end of genes, a substantial fraction of RNAPII fail to terminate transcription, requiring the contribution of alternative or “fail-safe” mechanisms of termination to release the polymerase. This point of view covers redundant mechanisms of transcription termination and how they relate to conventional termination models. In particular, we expand on recent findings that propose a reverse torpedo model of termination, in which the 3′5′ exonucleolytic activity of the RNA exosome targets transcription events associated with paused and backtracked RNAPII. PMID:26273910

Some responses of the electric ray (Torpedo marmorata) to low ambient oxygen tensions.

PubMed

Hughes, G M; Johnston, I A

1978-04-01

I. Blood samples were taken during prolonged hypoxia experiments in which the inspired water oxygen tension was less than 10 mmHg. The oxygen tension of the post-branchial blood was about 5 mmHg and its pH shows a significant lowering from normoxic levels. 2. The decrease in blood pH is correlated with increases in levels of lactate and pyruvate. The lactate/pyruvate ratio increases during hypoxia. 3. An increase in blood succinate was also found, and strongly suggests the accumulation of multiple anaerobic end-products within the tissues. 4. Recovery of normoxic levels of succinate takes place almost immediately following the restart of ventilation whereas the decrease in lactate concentration is slower. 5. It is concluded that these adaptations may be related to the habitat of the fish at low tide in pools where the Po2 may fall very markedly.

A context-specific latent inhibition effect in a human conditioned suppression task.

PubMed

Byron Nelson, James; del Carmen Sanjuan, Maria

2006-06-01

Three studies used a computer video game preparation to demonstrate latent inhibition in adult humans. In all studies participants fired torpedoes at a target spaceship by clicking the mouse. Conditioned stimuli (CSs) were presented in the form of coloured "sensors" at the bottom of the screen. Conditioning was conducted by pairing a sensor with an attack from the target spaceship. Participants learned to suppress their rate of mouse clicking in preparation for an attack. In Experiment 1 a total of 10 preexposures to the sensor CS, prior to conditioning, retarded acquisition of suppression. In Experiment 2 the effect of preexposure was shown to be context specific. Experiment 3 showed little generalization of the preexposure effect from one sensor CS to another. Experiment 3 also showed that preexposure did not make the sensor CS inhibitory. Comparisons with conditioned suppression procedures with animals and negative-priming procedures are briefly discussed.

Synthesis and discovery of highly functionalized mono- and bis-spiro-pyrrolidines as potent cholinesterase enzyme inhibitors.

PubMed

Kia, Yalda; Osman, Hasnah; Suresh Kumar, Raju; Basiri, Alireza; Murugaiyah, Vikneswaran

2014-04-01

Novel mono and bis spiropyrrolidine derivatives were synthesized via an efficient ionic liquid mediated, 1,3-dipolar cycloaddition methodology and evaluated in vitro for their AChE and BChE inhibitory activities in search for potent cholinesterase enzyme inhibitors. Most of the synthesized compounds displayed remarkable AChE inhibitory activities with IC50 values ranging from 1.68 to 21.85 μM, wherein compounds 8d and 8j were found to be most active inhibitors against AChE and BChE with IC50 values of 1.68 and 2.75 μM, respectively. Molecular modeling simulation on Torpedo californica AChE and human BChE receptors, showed good correlation between IC50 values and binding interaction template of the most active inhibitors docked into the active site of their relevant enzymes. Copyright © 2014 Elsevier Ltd. All rights reserved.

All Prime Contract Awards by State or Country, Place, and Contractor, FY83, Part 5 (LaGrange, Indiana-Escanaba, Michigan).

DTIC Science & Technology

1983-01-01

N00104-83-CA014 B C A 1 2 2 1361 000 AS DEPTH CHARGE EXPLOSIVE COMPO 8 A 3 4 J 018 1 B J 1 J 174 2 E JA116 4000 N00104-83-CA014 B C A 1 2 2 1386 000 A6... EXPLOSIVE ORD DISPOSAL TOOL- 8 A 6 4 J 018 1 B J 1 E 84 2 A JA116 1398 N00104-63-CA026 B C A 1 3 2 1361 000 AS DEPTH CHARGE EXPLOSIVE COMPO 8 A 3 4 J...CA088 B C A 1 2 2 1356 000 AS TORPEDO EXPLOSIVE COMPONENTS 8 A 3 5 A 1001 5 B J 1 H 195 2 G PAIOt A700 N00140-83-CBA83 B C Z 1 2 2 R414 000 51 MOT

Amino acid sequence of human cholinesterase. Annual report, 30 September 1984-30 September 1985

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

Lockridge, O.

1985-10-01

The active-site serine residue is located 198 amino acids from the N-terminal. The active-site peptide was isolated from three different genetic types of human serum cholinesterase: from usual, atypical, and atypical-silent genotypes. It was found that the amino acid sequence of the active-site peptide was identical in all three genotypes. Comparison of the complete sequences of cholinesterase from human serum and acetylcholinesterase from the electric organ of Torpedo californica shows an identity of 53%. Cholinesterase is of interest to the Department of Defense because cholinesterase protects against organophosphate poisons of the type used in chemical warfare. The structural results presentedmore » here will serve as the basis for cloning the gene for cholinesterase. The potential uses of large amounts of cholinesterase would be for cleaning up spills of organophosphates and possibly for detoxifying exposed personnel.« less

The Scientific Papers of the Honourable Henry Cavendish, F. R. S. 2 Volume Set

NASA Astrophysics Data System (ADS)

Cavendish, Henry; Clerk Maxwell, James; Thorpe, Edward, , Sir; Larmor, Joseph, , Sir

2011-02-01

Volume 1: Preface Sir Joseph Larmor; Introduction; First published paper on electricity, 1771; Preliminary propositions; Appendix; Thoughts concerning electricity; Account of the experiments; Second published paper on electricity, 1776; Experiments in 1771; Experiments in 1772; Experiments in 1773; Measurers; Experiments with the artificial torpedo; Resistance to electricity; Results of comparisons of charges; Results on resistance; Notes by the editor, 1879 James Clerk Maxwell; Life of Cavendish Thomas Young; Index to Cavendish Manuscripts. Volume 2: Introduction; Reprint of papers communicated by Cavendish to the Royal Society and published in the Philosophical Transactions; Unpublished papers from the original manuscripts in the possession of the Duke of Devonshire, K. G., LL. D., F. R. S.; Cavendish's mathematical and dynamical manuscripts Sir Joseph Larmor; Cavendish as a geologist Sir Archibald Geikie; Cavendish's astronomical manuscripts Sir Frank W. Dyson; Cavendish's magnetic work Charles Chree; Index.

Dynamic Subcellular Localization of Iron during Embryo Development in Brassicaceae Seeds

PubMed Central

Ibeas, Miguel A.; Grant-Grant, Susana; Navarro, Nathalia; Perez, M. F.; Roschzttardtz, Hannetz

2017-01-01

Iron is an essential micronutrient for plants. Little is know about how iron is loaded in embryo during seed development. In this article we used Perls/DAB staining in order to reveal iron localization at the cellular and subcellular levels in different Brassicaceae seed species. In dry seeds of Brassica napus, Nasturtium officinale, Lepidium sativum, Camelina sativa, and Brassica oleracea iron localizes in vacuoles of cells surrounding provasculature in cotyledons and hypocotyl. Using B. napus and N. officinale as model plants we determined where iron localizes during seed development. Our results indicate that iron is not detectable by Perls/DAB staining in heart stage embryo cells. Interestingly, at torpedo development stage iron localizes in nuclei of different cells type, including integument, free cell endosperm and almost all embryo cells. Later, iron is detected in cytoplasmic structures in different embryo cell types. Our results indicate that iron accumulates in nuclei in specific stages of embryo maturation before to be localized in vacuoles of cells surrounding provasculature in mature seeds. PMID:29312417

Discovering the African freshwater "torpedo": legendary Ethiopia, religious controversies, and a catfish capable of reanimating dead fish.

PubMed

Piccolino, Marco; Finger, Stanley; Barbara, Jean-Gaël

2011-07-01

The electric catfishes of African rivers and lakes, once depicted on Egyptian tomb art, have been largely overlooked in histories and reviews of electric fish biology and animal electricity. This article examines how Westerners, especially Dominican and Jesuit missionaries, discovered them in Ethiopia and other parts of Africa at the beginning of the seventeenth century. What transpired took place against the backdrop of tales involving the Bible, Prester John's mythical empire, and imaginary animals with fabulous powers. In effect, how they were found is related to attempts to convert Ethiopian Christians to true Catholicism, hopes of discovering great riches, and opportunities to trade, and not with the efforts of skilled natural philosophers to document and conduct experiments on the wildlife of this continent. Nevertheless, the early descriptions by Europeans circulated, and during the next century these catfishes began to be used in experiments that helped to make animal electricity a reality.

[The history of electrostimulation in rehabilitation medicine].

PubMed

Dolhem, R

2008-07-01

In antiquity, the electrical properties of torpedo fishes were used for therapeutic purposes (in headache and gout). In the 18th century, some practitioners used Leyde jars (Musschenbroek, 1746) and electrostatic devices to treat (notably) neuralgia, contractures and paralysis. L. Galvani's (1737-1798) description of "animal electricity" and A. Volta's (1745-1827) discovery of bimetallic electricity and invention of the voltaic battery prompted renewed interest in the therapeutic effects of galvanism. In the mid-19th century, Duchenne de Boulogne (1806-1875) improved electrotherapy procedures with volta and magnetofaradaic apparatuses. During the first half of the 20th century, research in electrophysiology (chronaxia and rheobasis) progressed in parallel with the work of electroradiologists such as A. d'Arsonval (1851-1940) and his high-frequency currents. From the 1960s onwards, the combination of progress in electronics with data processing and the miniaturization of medical devices opened up the way to today's electrostimulation techniques and their implementations in physical medicine and rehabilitation.

Convergence in Underwater Swimming Between Nature and Engineering

NASA Astrophysics Data System (ADS)

Bandyopadhyay, Promode R.; Boller, Michael

2004-11-01

We are interested in comparing the hydrodynamic performance of underwater vehicles and swimming animals which are believed to have been optimized via evolution. Cruising and maneuvering are treated separately. Platforms like submarines are primarily cruising vehicles, while torpedoes are dexterous in both. In swimming animals, generally, red muscle is used for cruising while white muscle is used for maneuvering motions. Data from literature is examined comparing shaft/muscle power versus displacement. Experiments also have been carried out with captive mackerel and bluefish that are known to be open water fish and are proficient in both cruising and maneuvering. Their trajectories around obstacles have been recorded and analyzed. Similar figure of eight' maneuvering trajectory data of engineering underwater vehicles have also been analyzed. It is shown that there is convergence between nature and engineering in cruising that extend over eight decades of variation in power and displacement. However, swimming animals are still more proficient in maneuvering, although the gap has been closing of late.

CDK regulation of transcription by RNAP II: Not over 'til it's over?

PubMed

Fisher, Robert P

2017-03-15

Transcription by RNA polymerase (RNAP) II is regulated at multiple steps by phosphorylation, catalyzed mainly by members of the cyclin-dependent kinase (CDK) family. The CDKs involved in transcription have overlapping substrate specificities, but play largely non-redundant roles in coordinating gene expression. Novel functions and targets of CDKs have recently emerged at the end of the transcription cycle, when the primary transcript is cleaved, and in most cases polyadenylated, and transcription is terminated by the action of the "torpedo" exonuclease Xrn2, which is a CDK substrate. Collectively, various functions have been ascribed to CDKs or CDK-mediated phosphorylation: recruiting cleavage and polyadenylation factors, preventing premature termination within gene bodies while promoting efficient termination of full-length transcripts, and preventing extensive readthrough transcription into intergenic regions or neighboring genes. The assignment of precise functions to specific CDKs is still in progress, but recent advances suggest ways in which the CDK network and RNAP II machinery might cooperate to ensure timely exit from the transcription cycle.

Cloning and functional expression of a plant voltage-dependent chloride channel.

PubMed Central

Lurin, C; Geelen, D; Barbier-Brygoo, H; Guern, J; Maurel, C

1996-01-01

Plant cell membrane anion channels participate in basic physiological functions, such as cell volume regulation and signal transduction. However, nothing is known about their molecular structure. Using a polymerase chain reaction strategy, we have cloned a tobacco cDNA (CIC-Nt1) encoding a 780-amino acid protein with several putative transmembrane domains. CIC-Nt1 displays 24 to 32% amino acid identity with members of the animal voltage-dependent chloride channel (CIC) family, whose archetype is CIC-0 from the Torpedo marmorata electric organ. Injection of CIC-Nt1 complementary RNA into Xenopus oocytes elicited slowly activating inward currents upon membrane hyperpolarization more negative than -120 mV. These currents were carried mainly by anions, modulated by extracellular anions, and totally blocked by 10 mM extracellular calcium. The identification of CIC-Nt1 extends the CIC family to higher plants and provides a molecular probe for the study of voltage-dependent anion channels in plants. PMID:8624442

Computer simulation of the active site of human serum cholinesterase

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

Kefang Jiao; Song Li; Zhengzheng Lu

1996-12-31

The first 3D-structure of acetylchelinesterase from Torpedo California electric organ (T.AChE) was published by JL. Sussman in 1991. We have simulated 3D-structure of human serum cholinesterase (H.BuChE) and the active site of H.BuChE. It is discovered by experiment that the residue of H.BuChE is still active site after a part of H.BuChE is cut. For example, the part of 21KD + 20KD is active site of H.BuChE. The 20KD as it is. Studies on these peptides by Hemelogy indicate that two active peptides have same negative electrostatic potential maps diagram. These negative electrostatic areas attached by acetyl choline with positivemore » electrostatic potency. We predict that 147...236 peptide of AChE could be active site because it was as 20KD as with negative electrostatic potential maps. We look forward to proving from other ones.« less

Combined effects of a thymic peptide, thymopoietin and myasthenic patient sera in rat myotube culture.

PubMed

Eymard, B; Aimé, C; Cottin, C; Morel, E; Goldstein, G; Bach, J F; Berrih-Aknin, S

1992-10-01

We investigated in a rat myotube assay the combined effect of 26 myasthenic (MG) patient sera and a thymic peptide, thymopoietin (Tpo) which had previously been shown to bind Torpedo and human AChR and to compete with alpha-bungarotoxin (alpha-Bgt) binding. Cultures were first exposed to Tpo alone for 3 h (0.3, 7.5, 15 nM), then MG sera (5% final dilution) were added for an additional 18 h. Reduction in the amount of 125I-alpha-Bgt binding sites in the presence of various concentrations of Tpo were similar with control sera and in all the patients with low or undetectable anti-AChR Ab (11 cases). In cultures exposed to Tpo and sera with high anti-AChR Ab titre (15 cases), Tpo and anti-AChR Ab have an additive capacity to reduce the number of alpha-Bgt binding sites. The results are compatible with the hypothesis that anti-AChR Ab and Tpo could impair neuromuscular transmission by complementary mechanisms.

Desensitization of the nicotinic acetylcholine receptor by diisopropylfluorophosphate.

PubMed

Eldefrawi, M E; Schweizer, G; Bakry, N M; Valdes, J J

1988-01-01

The interaction of diisopropylfluorophosphate (DFP) with the nicotinic acetylcholine (ACh) receptor of Torpedo electric organ was studied, using [3H]-phencyclidine ([3H]-PCP) as a reporter probe. Phencyclidine binds with different kinetics to resting, activated, and desensitized receptor conformations. Although DFP did not inhibit binding of [3H]-ACh or 125I-alpha-bungarotoxin (BGT) to the receptor recognition sites and potentiated in a time-dependent manner [3H]-PCP binding to the receptor's high-affinity allosteric site, it inhibited the ACh- or carbamylcholine-stimulated [3H]-PCP binding. This suggested that DFP bound to a third kind of site on the receptor and affected receptor conformation. Preincubation of the membranes with DFP increased the receptor's affinity for carbamylcholine by eightfold and raised the pseudo-first-order rate of [3H]-PCP binding to that of an agonist-desensitized receptor. Accordingly, it is suggested that DFP induces receptor desensitization by binding to a site that is distinct from the recognition or high-affinity noncompetitive sites.

Mechanism of action of chromogranin A on catecholamine release: molecular modeling of the catestatin region reveals a β-strand/loop/β-strand structure secured by hydrophobic interactions and predictive of activity

PubMed Central

Tsigelny, Igor; Mahata, Sushil K.; Taupenot, Laurent; Preece, Nicholas E.; Mahata, Manjula; Khan, Imran; Parmer, Robert J.; O’Connor, Daniel T.

2009-01-01

A novel fragment of chromogranin A, known as ‘catestatin’ (bovine chromogranin A344–364), inhibits catecholamine release from chromaffin cells and noradrenergic neurons by acting as a non-competitive nicotinic cholinergic antagonist, and may therefore constitute an endogenous autocrine feedback regulator of sympathoadrenal activity. To characterize how this activity depends on the peptide’s structure, we searched for common 3-dimensional motifs for this primary structure or its homologs. Catestatin’s primary structure bore significant (29–35.5% identity, general alignment score 44–57) sequence homology to fragment sequences within three homologs of known 3-dimensional structures, based on solved X-ray crystals: 8FAB, 1PKM, and 2IG2. Each of these sequences exists in nature as a β-strand/loop/β-strand structure, stabilized by hydrophobic interactions between the β-strands. The catestatin structure was stable during molecular dynamics simulations. The catestatin loop contains three Arg residues, whose electropositive side chains form the terminus of the structure, and give rise to substantial uncompensated charge asymmetry in the molecule. A hydrophobic moment plot revealed that catestatin is the only segment of chromogranin A predicted to contain amphiphilic β-strand. Circular dichroism in the far ultraviolet showed substantial (63%) β-sheet structure, especially in a hydrophobic environment. Alanine-substitution mutants of catestatin established a crucial role for the three central arginine residues in the loop (Arg351, Arg353, and Arg358), though not for two arginine residues in the strand region toward the amino-terminus. [125I]Catestatin bound to Torpedo membranes at a site other than the nicotinic agonist binding site. When the catestatin structure was ‘docked’ with the extracellular domain of the Torpedo nicotinic cholinergic receptor, it interacted principally with the β and δ subunits, in a relatively hydrophobic region of the cation pore extracellular orifice, and the complex of ligand and receptor largely occluded the cation pore, providing a structural basis for the non-competitive nicotinic cholinergic antagonist properties of the peptide. We conclude that a homology model of catestatin correctly predicts actual features of the peptide, both physical and biological. The model suggests particular spatial and charge features of the peptide which may serve as starting points in the development of non-peptide mimetics of this endogenous nicotinic cholinergic antagonist. PMID:9809795

Structure-function relationship in the binding of snake neurotoxins to the torpedo membrane receptor.

PubMed

Chicheportiche, R; Vincent, J P; Kopeyan, C; Schweitz, H; Lazdunski, M

1975-05-20

The Cys30-Cus34 bridge present in all long neutotoxins (71-74 amino acids, 5 disulfide bridges), but not in short toxins (60-63 amino acids, 4 disulfide bridges), is exposed at the surface since it can be reduced rapidly and selectively by sodium borohydride. Reduction and alkylation of the Cys30-Cys34 bridge of Naja haje neurotoxin III hardly alter the conformational properties of this model long toxin. Although alkylation by iodoacetic acid of th -SH groups liberated by reduction abolishes the toxicity, alkylation by iodoacetamide or ethylenimine does not affect the curarizing efficacy of the toxin. The Cys30-Cys34 bridge is not very important for the toxic activity of long neurotoxins. Reduction of the Cys30-Cys34 bridge followed by alkylation with radioactive iodoacetamide gave a labeled and active toxin which is a convenient derivative for binding experiments to the toxin receptor in membranes of the Torpedo electric organ. The binding capacity of these membrane is 1200 pmol of toxin/mg of membrane protein. The dissociation constant of the modified toxin-receptor complex at pH 7.4, 20 degrees is 10 minus 8m. Reduction with carbroxamidomethylation of the Cys30-Cys34 bridge decreases the affinity of the native Naja haje toxin only by a factor of 15. Carboxymethylation after reduction prevents binding to the membrane receptor. The binding properties of the derivative obtained by reduction and aminoethylation of Cys30-Cys34 are very similar to those of native neurotoxin III; the affinity is decreased only by a factor of 5. Binding properties to Toredo membrane of long neurotoxins (Naja haje neurotoxin III) and short neurotoxins (Naje haje toxin I and Naja mossambica toxin I) have been compared. Dissociation constants of receptor-long neurotoxin and receptor-short neurotoxin complexes are very similar (5.7 minus 8.2 times 10(-10) M at pH 7.4, 20degrees. However, the kinetics of complex formation and complex dissociation are quite different. Short neurotoxins associate 6-7 times faster with the toxin receptor and dissociate about 5-9 times faster that long neurotoxins. Acetylation and dansylation of Lys53 and Lys 27 decrease the affinity of long and short toxins for their receptor by a factor of about 200 at pH 7.4, 20 degrees, mainly because of the slower rate of association with the receptor.

Rapid B-rep model preprocessing for immersogeometric analysis using analytic surfaces

PubMed Central

Wang, Chenglong; Xu, Fei; Hsu, Ming-Chen; Krishnamurthy, Adarsh

2017-01-01

Computational fluid dynamics (CFD) simulations of flow over complex objects have been performed traditionally using fluid-domain meshes that conform to the shape of the object. However, creating shape conforming meshes for complicated geometries like automobiles require extensive geometry preprocessing. This process is usually tedious and requires modifying the geometry, including specialized operations such as defeaturing and filling of small gaps. Hsu et al. (2016) developed a novel immersogeometric fluid-flow method that does not require the generation of a boundary-fitted mesh for the fluid domain. However, their method used the NURBS parameterization of the surfaces for generating the surface quadrature points to enforce the boundary conditions, which required the B-rep model to be converted completely to NURBS before analysis can be performed. This conversion usually leads to poorly parameterized NURBS surfaces and can lead to poorly trimmed or missing surface features. In addition, converting simple geometries such as cylinders to NURBS imposes a performance penalty since these geometries have to be dealt with as rational splines. As a result, the geometry has to be inspected again after conversion to ensure analysis compatibility and can increase the computational cost. In this work, we have extended the immersogeometric method to generate surface quadrature points directly using analytic surfaces. We have developed quadrature rules for all four kinds of analytic surfaces: planes, cones, spheres, and toroids. We have also developed methods for performing adaptive quadrature on trimmed analytic surfaces. Since analytic surfaces have frequently been used for constructing solid models, this method is also faster to generate quadrature points on real-world geometries than using only NURBS surfaces. To assess the accuracy of the proposed method, we perform simulations of a benchmark problem of flow over a torpedo shape made of analytic surfaces and compare those to immersogeometric simulations of the same model with NURBS surfaces. We also compare the results of our immersogeometric method with those obtained using boundary-fitted CFD of a tessellated torpedo shape, and quantities of interest such as drag coefficient are in good agreement. Finally, we demonstrate the effectiveness of our immersogeometric method for high-fidelity industrial scale simulations by performing an aerodynamic analysis of a truck that has a large percentage of analytic surfaces. Using analytic surfaces over NURBS avoids unnecessary surface type conversion and significantly reduces model-preprocessing time, while providing the same accuracy for the aerodynamic quantities of interest. PMID:29051678

The effects of external acoustic pressure fields on a free-running supercavitating projectile.

PubMed

Cameron, Peter J K; Rogers, Peter H; Doane, John W

2010-12-01

Proliferation of supercavitating torpedoes has motivated research on countermeasures against them as well as on the fluid phenomenon which makes them possible. The goal of this research was to investigate an envisaged countermeasure, an acoustic field capable of slowing or diverting the weapon by disrupting the cavitation envelope. The research focused on the interactions between high pressure amplitude sound waves and a supercavity produced by a small free-flying projectile. The flight dynamics and cavity geometry measurements were compared to control experiments and theoretical considerations were made for evaluating the effects. Corrugations on the cavity/water interface caused by the pressure signal have been observed and characterized. Results also show that the accuracy of a supercavitating projectile can be adversely affected by the sound signal. This research concludes with results that indicate that it is acoustic cavitation in the medium surrounding the supercavity, caused by the high pressure amplitude sound, that is responsible for the reduced accuracy. A hypothesis has been presented addressing the means by which the acoustic cavitation could cause this effect.

Free-Spinning Tunnel Tests of a 1/24-Scale Model of the Grumman XTB3F-1 Airplane, TED No. NACA DE304

NASA Technical Reports Server (NTRS)

Berman, Theodore

1947-01-01

In accordance with a request of the Bureau of Aeronautics, Navy Department, tests were performed in the Langley 20-foot free-spinning tunnel to determine the spin and recovery characteristics of a 1/24 scale model of the Grumman XTB3F-1 airplane. The airplane is a two-place, midwing torpedo bomber equipped with a tractor propeller and an auxiliary jet engine. The effect of control setting and movement on the erect and inverted spin and recovery characteristics of the model were determined for the normal loading. Brief tests with mass extended slightly along the fuselage were also made, however, in order to determine the effect of such a mass variation on elevator effectiveness. Tests were performed to determine the size of emergency spin-recovery tail and wing-tip parachutes required for satisfactory recovery by parachute action alone. The investigation also included emergency pilot-escape tests and tests to determine the rudder pedal and elevator stick forces necessary to move the rudder and elevator for recovery.

Molecular Dynamics of Mouse Acetylcholinesterase Complexed with Huperzine A

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

Tara, Sylvia; Helms, Volkhard H.; Straatsma, TP

1999-03-16

Two molecular dynamics simulations were performed for a modeled complex of mouse acetylcholinesterase liganded with huperzine A (HupA). Analysis of these simulations shows that HupA shifts in the active site toward Tyr 337 and Phe 338, and that several residues in the active site area reach out to make hydrogen bonds with the inhibitor. Rapid fluctuations of the gorge width are observed, ranging from widths that allow substrate access to the active site, to pinched structures that do not allow access of molecules as small as water. Additional openings or channels to the active site are found. One opening ismore » formed in the side wall of the active site gorge by residues Val 73, Asp 74, Thr 83, Glu 84, and Asn 87. Another opening is formed at the base of the gorge by residues Trp 86, Val 132, Glu 202, Gly 448, and Ile 451. Both of these openings have been observed separately in the Torpedo californica form of the enzyme. These channels could allow transport of waters and ions to and from the bulk solution.« less

Specific chemical and structural damage to proteins produced by synchrotron radiation.

PubMed

Weik, M; Ravelli, R B; Kryger, G; McSweeney, S; Raves, M L; Harel, M; Gros, P; Silman, I; Kroon, J; Sussman, J L

2000-01-18

Radiation damage is an inherent problem in x-ray crystallography. It usually is presumed to be nonspecific and manifested as a gradual decay in the overall quality of data obtained for a given crystal as data collection proceeds. Based on third-generation synchrotron x-ray data, collected at cryogenic temperatures, we show for the enzymes Torpedo californica acetylcholinesterase and hen egg white lysozyme that synchrotron radiation also can cause highly specific damage. Disulfide bridges break, and carboxyl groups of acidic residues lose their definition. Highly exposed carboxyls, and those in the active site of both enzymes, appear particularly susceptible. The catalytic triad residue, His-440, in acetylcholinesterase, also appears to be much more sensitive to radiation damage than other histidine residues. Our findings have direct practical implications for routine x-ray data collection at high-energy synchrotron sources. Furthermore, they provide a direct approach for studying the radiation chemistry of proteins and nucleic acids at a detailed, structural level and also may yield information concerning putative "weak links" in a given biological macromolecule, which may be of structural and functional significance.

Dimeric arrangement and structure of the membrane-bound acetylcholine receptor studied by electron microscopy.

PubMed Central

Zingsheim, H P; Neugebauer, D C; Frank, J; Hänicke, W; Barrantes, F J

1982-01-01

The acetylcholine receptor protein (AChR) from the electric organ of Torpedo marmorata is studied in its membrane-bound form by electron microscopy and single-particle image averaging. About half the molecule protrudes from the membrane surface by approximately 5 nm. The low-resolution 3-D structure of this hydrated portion, including its handedness, can be deduced from averaged axial and lateral projections and from freeze-etched membrane surfaces. In native membrane fragments, a dimeric form of the AChR is observed and the relative orientation of the AChR monomers within the dimer is established. The dimers disappear upon disulfide reduction of the membrane preparations, whereas the average axial projections of the AChR monomer remain unaffected. Since the existence of disulfide bonds linking AChR monomers between their respective delta-subunits is well documented, the approximate position of the delta-subunit within the low-resolution structure of the AChR molecule can be deduced from the structure of the dimers. Images Fig. 1. Fig. 2. Fig. 3. PMID:7188351

Modular nonvolatile solid state recorder (MONSSTR) update

NASA Astrophysics Data System (ADS)

Klang, Mark R.; Small, Martin B.; Beams, Tom

2001-12-01

Solid state recorders have begun replacing traditional tape recorders in fulfilling the requirement to record images on airborne platforms. With the advances in electro-optical, IR, SAR, Multi and Hyper-spectral sensors and video recording requirements, solid state recorders have become the recorder of choice. Solid state recorders provide the additional storage, higher sustained bandwidth, less power, less weight and smaller footprint to meet the current and future recording requirements. CALCULEX, Inc., manufactures a non-volatile flash memory solid state recorder called the MONSSTR (Modular Non-volatile Solid State Recorder). MONSSTR is being used to record images from many different digital sensors on high performance aircraft such as the RF- 4, F-16 and the Royal Air Force Tornado. MONSSTR, with its internal multiplexer, is also used to record instrumentation data. This includes multiple streams of PCM and multiple channels of 1553 data. Instrumentation data is being recorded by MONSSTR systems in a range of platforms including F-22, F-15, F-16, Comanche Helicopter and US Navy torpedos. MONSSTR can also be used as a cockpit video recorder. This paper will provide an update of the MONSSTR.

Morphology of ovary and spermathecae of the parasitoid Eibesfeldtphora tonhascai Brown (Diptera: Phoridae).

PubMed

Farder-Gomes, Cliver Fernandes; Santos, Helen Cristina Pinto; Oliveira, Marco Antonio; Zanuncio, José Cola; Serrão, José Eduardo

2018-06-16

Eibesfeldtphora tonhascai (Diptera: Phoridae) is a parasitoid of leaf-cutting ants and a potential biological control agent against these insect pests. This study describes the morphology of the ovary and spermatheca of E. tonhascai. The female reproductive tract of this parasitoid has a pair of meroistic polytrophic ovaries, two lateral oviducts that open into a common oviduct, an elongated accessory gland, and two spermathecae. Young oocytes are small and spherical, and their size increases as yolk is stored in the cytoplasm. This process is followed by chorion production by follicular cells. Mature oocytes are elliptical or torpedo-shaped. The reservoir wall of the spermatheca has type III glandular cells with cytoplasm rich in free ribosomes, rough endoplasmic reticulum, and secretory vesicles. The apical surface of these cells has microvilli associated with mitochondria. The reservoir lumen is lined by a cuticle and filled with spermatozoa. This is the first report of the ovary and spermatheca morphology of E. tonhascai and contributes to the comprehension of the reproductive biology of this parasitoid of leaf-cutting ants.

What are Head Cavities? - A History of Studies on Vertebrate Head Segmentation.

PubMed

Kuratani, Shigeru; Adachi, Noritaka

2016-06-01

Motivated by the discovery of segmental epithelial coeloms, or "head cavities," in elasmobranch embryos toward the end of the 19th century, the debate over the presence of mesodermal segments in the vertebrate head became a central problem in comparative embryology. The classical segmental view assumed only one type of metamerism in the vertebrate head, in which each metamere was thought to contain one head somite and one pharyngeal arch, innervated by a set of cranial nerves serially homologous to dorsal and ventral roots of spinal nerves. The non-segmental view, on the other hand, rejected the somite-like properties of head cavities. A series of small mesodermal cysts in early Torpedo embryos, which were thought to represent true somite homologs, provided a third possible view on the nature of the vertebrate head. Recent molecular developmental data have shed new light on the vertebrate head problem, explaining that head mesoderm evolved, not by the modification of rostral somites of an amphioxus-like ancestor, but through the polarization of unspecified paraxial mesoderm into head mesoderm anteriorly and trunk somites posteriorly.

Assessing the binding of cholinesterase inhibitors by docking and molecular dynamics studies.

PubMed

Ali, M Rejwan; Sadoqi, Mostafa; Møller, Simon G; Boutajangout, Allal; Mezei, Mihaly

2017-09-01

In this report we assessed by docking and molecular dynamics the binding mechanisms of three FDA-approved Alzheimer drugs, inhibitors of the enzyme acetylcholinesterase (AChE): donepezil, galantamine and rivastigmine. Dockings by the softwares Autodock-Vina, PatchDock and Plant reproduced the docked conformations of the inhibitor-enzyme complexes within 2Å of RMSD of the X-ray structure. Free-energy scores show strong affinity of the inhibitors for the enzyme binding pocket. Three independent Molecular Dynamics simulation runs indicated general stability of donepezil, galantamine and rivastigmine in their respective enzyme binding pocket (also referred to as gorge) as well as the tendency to form hydrogen bonds with the water molecules. The binding of rivastigmine in the Torpedo California AChE binding pocket is interesting as it eventually undergoes carbamylation and breaks apart according to the X-ray structure of the complex. Similarity search in the ZINC database and targeted docking on the gorge region of the AChE enzyme gave new putative inhibitor molecules with high predicted binding affinity, suitable for potential biophysical and biological assessments. Copyright © 2017 Elsevier Inc. All rights reserved.

System for effecting underwater coupling of optical fiber cables characterized by a novel lateral arm cable capture mechanism

NASA Astrophysics Data System (ADS)

Hillenbrand, Christopher F.

1995-03-01

A submarine trails one fiber optic cable and an undersea vehicle is controlled by this first cable. A missile/torpedo trails a second cable that is to be coupled to the first cable. The second cable has a segment suspended vertically underwater between a buoyant pod and a sea anchor type buoy. The undersea vehicle, or autonomous undersea vehicle, (AUV) hunts for the pod by conventional homing components, and cable capturing arms on the vehicle direct the cable's movement relative to the vehicle into a pod mating position that achieves optical coupling of the two cables. In one embodiment two arms are pivotably mounted to the vehicle's sides so one arm captures the suspended cable segment directing it into a slot so a male socket in the underside of the pod mates with a female socket in the slot. Another embodiment accomplishes the same result with a device in which the arms are formed as the off-shoots of a forked cable pickup device in the nose of the AUV.

Electrical stimulation in exercise training

NASA Technical Reports Server (NTRS)

Kroll, Walter

1994-01-01

Electrical stimulation has a long history of use in medicine dating back to 46 A.D. when the Roman physician Largus found the electrical discharge of torpedo fishes useful in the treatment of pain produced by headache and gout. A rival Greek physician, Dioscorides, discounted the value of the torpedo fish for headache relief but did recommend its use in the treatment of hemorrhoids. In 1745, the Leyden jar and various sized electrostatic generators were used to treat angina pectoris, epilepsy, hemiplegia, kidney stones, and sciatica. Benjamin Franklin used an electrical device to treat successfully a young woman suffering from convulsive fits. In the late 1800's battery powered hydroelectric baths were used to treat chronic inflammation of the uterus while electrified athletic supporters were advertised for the treatment of male problems. Fortunately, such an amusing early history of the simple beginnings of electrical stimulation did not prevent eventual development of a variety of useful therapeutic and rehabilitative applications of electrical stimulation. Over the centuries electrical stimulation has survived as a modality in the treatment of various medical disorders with its primary application being in the rehabilitation area. Recently, a surge of new interest in electrical stimulation has been kindled by the work of a Russian sport scientist who reported remarkable muscle strength and endurance improvements in elite athletes. Yakov Kots reported his research on electric stimulation and strength improvements in 1977 at a Canadian-Soviet Exchange Symposium held at Concordia University in Montreal. Since then an explosion of new studies has been seen in both sport science and in medicine. Based upon the reported works of Kots and the present surge of new investigations, one could be misled as to the origin of electrical stimulation as a technique to increase muscle strength. As a matter of fact, electric stimulation has been used as a technique to improve muscle strength for over a century. Bigelow reported in 1894, for example, the use of electrical stimulation on a young man for the purpose of increasing muscle strength. Employing a rapidly alternating sinusoidal induced current and a dynamometer for strength testing, Bigelow reported that the total lifting capacity of a patient increased from 4328 pounds to 4639 pounds after only 25 minutes of stimulation. In 1965, Massey et al. reported on the use of an Isotron electrical stimulator that emitted a high frequency current. Interestingly enough, the frequencies used by Massey et al. and the frequencies used by Bigelow in 1894 were in the same range of frequencies reported by Kots as being the most effective in strength development. It would seem the Russian secret of high frequency electrical stimulation for strength development, then, is not a modern development at all.

Novel Tacrine-Benzofuran Hybrids as Potent Multitarget-Directed Ligands for the Treatment of Alzheimer's Disease: Design, Synthesis, Biological Evaluation, and X-ray Crystallography.

PubMed

Zha, Xiaoming; Lamba, Doriano; Zhang, Lili; Lou, Yinghan; Xu, Changxu; Kang, Di; Chen, Li; Xu, Yungen; Zhang, Luyong; De Simone, Angela; Samez, Sarah; Pesaresi, Alessandro; Stojan, Jure; Lopez, Manuela G; Egea, Javier; Andrisano, Vincenza; Bartolini, Manuela

2016-01-14

Twenty-six new tacrine-benzofuran hybrids were designed, synthesized, and evaluated in vitro on key molecular targets for Alzheimer's disease. Most hybrids exhibited good inhibitory activities on cholinesterases and β-amyloid self-aggregation. Selected compounds displayed significant inhibition of human β-secretase-1 (hBACE-1). Among the 26 hybrids, 2e showed the most interesting profile as a subnanomolar selective inhibitor of human acetylcholinesterase (hAChE) (IC50 = 0.86 nM) and a good inhibitor of both β-amyloid aggregation (hAChE- and self-induced, 61.3% and 58.4%, respectively) and hBACE-1 activity (IC50 = 1.35 μM). Kinetic studies showed that 2e acted as a slow, tight-binding, mixed-type inhibitor, while X-ray crystallographic studies highlighted the ability of 2e to induce large-scale structural changes in the active-site gorge of Torpedo californica AChE (TcAChE), with significant implications for structure-based drug design. In vivo studies confirmed that 2e significantly ameliorates performances of scopolamine-treated ICR mice. Finally, 2e administration did not exhibit significant hepatotoxicity.

Action of tremorgenic mycotoxins on GABA/sub A/ receptor

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

Gant, D.B.; Cole, R.J.; Valdes, J.J.

1987-11-09

The effects of four tremorgenic and one nontremorgenic mycotoxins were studied on ..gamma..-aminobutyric acid (GABA/sub A/) receptor binding and function in rat brain and on binding of a voltage-operated Cl/sup -/ channel in Torpedo electric organ. None of the mycotoxins had significant effect on (/sup 3/H)muscimol or (/sup 3/H)flunitrazepam binding to the GAMA/sup A/ receptor. However, only the four tremorgenic mycotoxins inhibited GABA-induced /sup 36/Cl/sup -/ influx and (/sup 35/S)t-butylbicyclophosphorothionate ((/sup 35/S)TBPS) binding in rate brain membranes, while the nontremorgenic verruculotoxin had no effect. Inhibition of (/sup 35/S)TBPS binding by paspalinine was non-competitive. This suggests that tremorgenic mycotoxins inhibit GABA/submore » A/ receptor function by binding close to the receptor's Cl/sup -/ channel. On the voltage-operated Cl/sup -/ channel, only high concentrations of verruculogen and verruculotoxin caused significant inhibition of the channel's binding of (/sup 35/S)TBPS. The data suggest that the tremorgenic action of these mycotoxins may be due in part to their inhibition of GABA/sub A/ receptor function. 21 references, 4 figures, 2 tables.« less

Mapping of the acetylcholine binding site of the nicotinic acetylcholine receptor: ( sup 3 H)nicotine as an agonist photoaffinity label

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

Middleton, R.E.; Cohen, J.B.

1991-07-16

The agonist ({sup 3}H)nicotine was used as a photoaffinity label for the acetylcholine binding sties on the Torpedo nicotinic acetylcholine receptor (AChR). ({sup 3}H)Nicotine binds at equilibrium with K{sub eq} = 0.6 {mu}M to the agonist binding sites. Irradiation with 254-nm light of AChR-rich membranes equilibrated with ({sup 3}H)nicotine resulted in covalent incorporation into the {alpha}- and {gamma}-subunits, which was inhibited by agonists and competitive antagonists but not by noncompetitive antagonists. Inhibition of labeling by d-tubocurarine demonstrated that the {alpha}-subunit was labeled via both agonist sites but the {gamma}-subunit was labeled only via the site that binds d-tubocurarine with highmore » affinity. Chymotryptic digestion of the {alpha}-subunit confirmed that Try-198 was the principal amino acid labeled by ({sup 3}H)nicotine. This confirmation required a novel radiosequencing strategy employing o-phthalaldehyde ({sup 3}H)Nicotine, which is the first photoaffinity agonist used, labels primarily Tyr-198 in contrast to competitive antagonist affinity labels, which label primarily Tyr-190 and Cys-192/Cys-193.« less

Rectal suppository: commonsense and mode of insertion.

PubMed

Abd-el-Maeboud, K H; el-Naggar, T; el-Hawi, E M; Mahmoud, S A; Abd-el-Hay, S

1991-09-28

Rectal suppository is a well-known form of medication and its use is increasing. The commonest shape is one with an apex (pointed end) tapering to a base (blunt end). Because of a general lack of information about mode of insertion, we asked 360 lay subjects (Egyptians and non-Egyptians) and 260 medical personnel (physicians, pharmacists, and nurses) by questionnaire which end they inserted foremost. Apart from 2 individuals, all subjects suggested insertion with the apex foremost. Commonsense was the most frequent basis for this practice (86.9% of lay subjects and 84.6% of medical personnel) followed by information from a relative, a friend, or medical personnel, or from study at medical school. Suppository insertion with the base or apex foremost was compared in 100 subjects (60 adults, 40 infants and children). Retention with the former method was more easily achieved in 98% of the cases, with no need to introduce a finger in the anal canal (1% vs 83%), and lower expulsion rate (0% vs 3%). The designer of the "torpedo-shaped" suppository suggested its insertion with apex foremost. Our data suggest that a suppository is better inserted with the base foremost. Reversed vermicular contractions or pressure gradient of the anal canal might press it inwards.

Historical Examples of Lobbying: The Case of Strasbourg Astronomical Observatories

NASA Astrophysics Data System (ADS)

Heck, Andre

2012-08-01

Several astronomical observatories have been established in Strasbourg in very differing contexts. In the late 17th century, an observing post (scientifically sterile) was put on top of a tower, the Hospital Gate, essentially for the prestige of the city and the notoriety of the university. In the 19th century, the observatory built on the Académie hosting the French university was the first attempt to set up in the city a real observatory equipped with genuine instrumentation with the purpose of carrying out serious research, but the succession of political regimes in France and the continual bidding for moving the university to other locations, together with the faltering of later scholars, torpedoed any significant scientific usage of the place. After the 1870-1871 Franco-Prussian war, the German authorities set up a prestigious university campus with a whole range of institutes together with a modern observatory consisting of several buildings and hosting a flotilla of excellent instruments, including the then largest refractor of the country. This paper illustrates various types of lobbying used in the steps above while detailing, from archive documents largely unexploited so far, original research on the two first observatories.

Protective sheath for a continuous measurement thermocouple

DOEpatents

Phillippi, R.M.

1991-12-03

Disclosed is a protective thermocouple sheath of a magnesia graphite refractory material for use in continuous temperature measurements of molten metal in a metallurgical ladle and having a basic slag layer thereon. The sheath includes an elongated torpedo-shaped sheath body formed of a refractory composition and having an interior borehole extending axially therethrough and adapted to receive a thermocouple. The sheath body includes a lower end which is closed about the borehole and forms a narrow, tapered tip. The sheath body also includes a first body portion integral with the tapered tip and having a relatively constant cross section and providing a thin wall around the borehole. The sheath body also includes a second body portion having a relatively constant cross section larger than the cross section of the first body portion and providing a thicker wall around the borehole. The borehole terminates in an open end at the second body portion. The tapered tip is adapted to penetrate the slag layer and the thicker second body portion and its magnesia constituent material are adapted to withstand chemical attack thereon from the slag layer. The graphite constituent improves thermal conductivity of the refractory material and, thus, enhances the thermal responsiveness of the device. 4 figures.

Protective sheath for a continuous measurement thermocouple

DOEpatents

Phillippi, R. Michael

1991-01-01

Disclosed is a protective thermocouple sheath of a magnesia graphite refractory material for use in continuous temperature measurements of molten metal in a metallurgical ladle and having a basic slag layer thereon. The sheath includes an elongated torpedo-shaped sheath body formed of a refractory composition and having an interior borehole extending axially therethrough and adapted to receive a thermocouple. The sheath body includes a lower end which is closed about the borehole and forms a narrow, tapered tip. The sheath body also includes a first body portion integral with the tapered tip and having a relatively constant cross section and providing a thin wall around the borehole. The sheath body also includes a second body portion having a relatively constant cross section larger than the cross section of the first body portion and providing a thicker wall around the borehole. The borehole terminates in an open end at the second body portion. The tapered tip is adapted to penetrate the slag layer and the thicker second body portion and its magnesia constituent material are adapted to withstand chemical attack thereon from the slag layer. The graphite constituent improves thermal conductivity of the refractory material and, thus, enhances the thermal responsiveness of the device.

Association of the HNK-1 epitope with the detergent-soluble G4 isoform of acetylcholinesterase from human neuroblastoma cells.

PubMed

Johnson, G; Moore, S W

2001-07-01

The HNK-1 carbohydrate epitope is expressed in neural and natural killer cells and is a mediator of cell adhesion. It is well documented that acetylcholinesterase has a secondary function in cell adhesion and differentiation. The presence of HNK-1 on isoforms of Torpedo and Electrophorus acetylcholinesterase, as well as isoforms from the bovine central nervous system has been described. In this paper, we have investigated the association of the epitope with acetylcholinesterase from human neuroblastoma cells. Acetylcholinesterase was extracted, with or without detergent, purified on immunoaffinity columns and the isoforms separated by sucrose density gradient sedimentation. Secreted acetylcholinesterase, from spent serum-free culture medium, was similarly treated. The presence of the HNK-1 epitope was determined by ELISA using the anti-HNK-1 and Elec 39 monoclonal antibodies. The epitope was found to be associated with the detergent-soluble G4 isoform, but not with the hydrophilic G1 nor the secreted hydrophilic G4 isoforms. Likewise, no HNK-1 was observed associated with human erythrocyte acetylcholinesterase. These results indicate that acetylcholinesterase-G4, anchored in the extracellular membrane, is capable of mediating cell-substrate adhesion through HNK-1.

The monoclonal antibodies Elec-39, HNK-1 and NC-1 recognize common structures in the nervous system and muscles of vertebrates.

PubMed

Mailly, P; Younès-Chennouft, A B; Bon, S

1989-01-01

The IgM monoclonal antibodies, Elec-39, HNK-1 and NC-1, recognize the same subset of Torpedo electric organ acetylcholinesterase (AChE). We show that they react against a glycosphingolipid (SGPG) containing a sulfated glucuronic acid (SGA). The three antibodies appear essentially identical in their specificity but differ in their affinity for the antigens. We have examined their binding in the CNS, nerves and muscles of several vertebrate species, at the optical and in some cases at the electron microscope level. All three antibodies label the same structures: they show diffuse staining around neuromuscular endplates and label the plasma membrane of the Schwann cells, surrounding the outer layer of myelin sheaths. In the adult rat CNS, the antibodies label certain defined structures, notably extracellular material in the habenula and in the CA2 layer of the hippocampus. In the cortex and cerebellum, they label the surface of neural processes and terminals apposed to large multipolar neurons and Purkinje cells, as well as membranous material contained in inclusions dispersed in the cytoplasm of these neurons. These localizations are consistent with the suggestion that the SGA-antigens may be involved in cellular interactions.

Predicting the transmembrane secondary structure of ligand-gated ion channels.

PubMed

Bertaccini, E; Trudell, J R

2002-06-01

Recent mutational analyses of ligand-gated ion channels (LGICs) have demonstrated a plausible site of anesthetic action within their transmembrane domains. Although there is a consensus that the transmembrane domain is formed from four membrane-spanning segments, the secondary structure of these segments is not known. We utilized 10 state-of-the-art bioinformatics techniques to predict the transmembrane topology of the tetrameric regions within six members of the LGIC family that are relevant to anesthetic action. They are the human forms of the GABA alpha 1 receptor, the glycine alpha 1 receptor, the 5HT3 serotonin receptor, the nicotinic AChR alpha 4 and alpha 7 receptors and the Torpedo nAChR alpha 1 receptor. The algorithms utilized were HMMTOP, TMHMM, TMPred, PHDhtm, DAS, TMFinder, SOSUI, TMAP, MEMSAT and TOPPred2. The resulting predictions were superimposed on to a multiple sequence alignment of the six amino acid sequences created using the CLUSTAL W algorithm. There was a clear statistical consensus for the presence of four alpha helices in those regions experimentally thought to span the membrane. The consensus of 10 topology prediction techniques supports the hypothesis that the transmembrane subunits of the LGICs are tetrameric bundles of alpha helices.

Chemical and molecular aspects on interactions of galanthamine and its derivatives with cholinesterases.

PubMed

Gulcan, Hayrettin O; Orhan, Ilkay E; Sener, Bilge

2015-01-01

Dual action of galanthamine as potent cholinesterase inhibitor and nicotinic modulator has attracted a great attention to be used in the treatment of AD. Consequently, galanthamine, a natural alkaloid isolated from a Galanthus species (snowdrop, Amaryllidaceae), has become an attractive model compound for synthesis of its novel derivatives to discover new drug candidates. Numerous studies have been done to elucidate interactions between galanthamine and its different derivatives and the enzymes; acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) using in vitro and in silico experimental models. The in vitro studies revealed that galanthamine inhibits AChE in strong, competitive, long-acting, and reversible manner as well as BChE, although its selectivity towards AChE is much higher than BChE. The in silico studies carried out by employing molecular docking experiments as well as molecular dynamics simulations pointed out to existence of strong interactions of galanthamine with the active gorge of AChE, mostly of Torpedo californica (the Pasific electric ray) origin. In this review, we evaluate the mainstays of cholinesterase inhibitory action of galanthamine and its various derivatives from the point of view of chemical and molecular aspects.

Drug binding to the acetylcholine receptor: Nitroxide analogs of phencyclidine and a local anesthetic

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

Palma, A.L.

1988-01-01

The interaction of noncompetitive inhibitors (NCIs) with Torpedo californica native nicotinic acetylcholine receptor (nAChR) membranes was examined primarily by the technique of electron paramagnetic resonance (EPR) spectroscopy. The goal of this work being to define some of the physical characteristics for the site(s) of association between an NCI and the nAChR membrane. A nitroxide labeled analog of a quaternary amine local anesthetic, 2-(N,N-dimethyl-N-4-(2,2,6,6-tetramethylpiperidinoxyl)amino)-ethyl 4-hexyloxybenzoate iodide (C6SLMeI), displays a strongly immobilized EPR component when added to nAChR membranes in the presence of carbamylcholine (carb). To further this work, a nitroxide labeled analog of phencyclidine (PCP), a potent NCI, was synthesized. 4-phenyl-4-(1-piperidinyl)-2,2,6,6-tetramethylpiperidinoxylmore » (PPT) exhibited one-third the potency of PCP in inhibiting nAChR mediated ion flux, and from competition binding studies with ({sup 3}H)PCP displayed a K{sub D} of 0.21 {mu}M towards a carb desensitized nAChR and a K{sub 0.5} of 18 {mu}M for a resting {alpha}-bungarotoxin treated nAChR.« less

Everything's Relative: And Other Fables from Science and Technology

NASA Astrophysics Data System (ADS)

Rothman, Tony

2003-09-01

The surprising truth behind many of the most cherished "facts" in science history Morse invented the telegraph, Bell the telephone, Edison the light bulb, and Marconi the radio . . . right? Well . . . the truth is slightly more complicated. The history of science and technology is riddled with apocrypha, inaccuracies, and falsehoods, and physicist Tony Rothman has taken it upon himself to throw a monkey wrench into the works. Combining a storyteller's gifts with a scientist's focus and hardheaded devotion to the facts-such as they may be-Rothman breaks down many of the most famous "just-so" stories of physics, astronomy, chemistry, biology, and technology to give credit where credit is truly due. From Einstein's possible misunderstanding of his own theories to actress Hedy Lemarr's role in the invention of the radio-controlled torpedo, he dredges his way through the legends of science history in relating the fascinating stories behind some of the most important, and often unsung, breakthroughs in science. Tony Rothman, PhD (Bryn Mawr, PA), is a Research Associate at Bryn Mawr College. He is the author of seven other critically acclaimed science books and a frequent contributor to leading science publications, including Scientific American and Discover.

Taspine: bioactivity-guided isolation and molecular ligand-target insight of a potent acetylcholinesterase inhibitor from Magnolia x soulangiana.

PubMed

Rollinger, Judith M; Schuster, Daniela; Baier, Elisabeth; Ellmerer, Ernst P; Langer, Thierry; Stuppner, Hermann

2006-09-01

A bioactivity-guided approach was taken to identify the acetylcholinesterase (AChE, EC 3.1.1.7) inhibitory agent in a Magnolia x soulangiana extract using a microplate enzyme assay with Ellman's reagent. This permitted the isolation of the alkaloids taspine (1) and (-)-asimilobine (2), which were detected for the first time in this species. Compound 1 showed a significantly higher effect on AChE than the positive control galanthamine and selectively inhibited the enzyme in a long-lasting and concentration-dependent fashion with an IC(50) value of 0.33 +/- 0.07 muM. Extensive molecular docking studies were performed with human and Torpedo californica-AChE employing Gold software to rationalize the binding interaction. The results suggested ligand 1 to bind in an alternative binding orientation when compared to galanthamine. While this is located in close vicinity to the catalytic amino acid triad, the 1-AChE complex was found to be stabilized by (i) sandwich-like pi-stacking interactions between the planar aromatic ligand (1) and the Trp84 and Phe330 of the enzyme, (ii) an esteratic site anchoring with the amino side chain, and (iii) a hydrogen-bonding network.

Vertical transmission of Prunus necrotic ringspot virus: hitch-hiking from gametes to seedling.

PubMed

Amari, Khalid; Burgos, Lorenzo; Pallás, Vicente; Sánchez-Pina, Maria Amelia

2009-07-01

The aim of this work was to follow Prunus necrotic ringspot virus (PNRSV) infection in apricot reproductive tissues and transmission of the virus to the next generation. For this, an analysis of viral distribution in apricot reproductive organs was carried out at different developmental stages. PNRSV was detected in reproductive tissues during gametogenesis. The virus was always present in the nucellus and, in some cases, in the embryo sac. Studies within infected seeds at the embryo globular stage revealed that PNRSV infects all parts of the seed, including embryo, endosperm and testa. In the torpedo and bent cotyledon developmental stages, high concentrations of the virus were detected in the testa and endosperm. At seed maturity, PNRSV accumulated slightly more in the embryo than in the cotyledons. In situ hybridization showed the presence of PNRSV RNA in embryos obtained following hand-pollination of virus-free pistils with infected pollen. Interestingly, tissue-printing from fruits obtained from these pistils showed viral RNA in the periphery of the fruits, whereas crosses between infected pistils and infected pollen resulted in a total invasion of the fruits. Taken together, these results shed light on the vertical transmission of PNRSV from gametes to seedlings.

Micropropagation of bioencapsulation and ultrastructural features of sainfoin (Onobrychis viciifolia) grown in vivo and in vitro.

PubMed

Mohajer, Sadegh; Mat Taha, Rosna; Mohajer, Minoo; Khorasani Esmaeili, Arash

2014-01-01

To explore the potential of in vitro rapid regeneration, three varieties (Golpaygan-181, Orumieh-1763, and Gorgan-1601) of sainfoin (Onobrychis viciifolia Scop. syn. Onobrychis sativa L.) were evaluated. For the first time, an encapsulation protocol was established from somatic embryogenic callus in torpedo and cotyledonary stages to create artificial seeds. Callus derived from different concentrations of Kinetin (0-2.0 mg L(-1)) and Indole-3-acetic acid (0-2.0 mg L(-1)) was coated with sodium alginate and subsequently cultured either in Murashige and Skoog (MS) medium or in soil substrate. Adventitious shoots from synthetic beads developed into rooting in full and half strength MS medium supplemented with various concentrations of auxin and cytokinin. Prolonged water conservation of black and red soils (1:1) had the highest rate of survival plantlets in the acclimatization process. Diverse resistance techniques in Onobrychis viciifolia were evaluated when the plants were subjected to water deficiency. Higher frequency of epicuticular waxes was observed in in vivo leaves compared to in vitro leaves. Jagged trichomes nonsecreting glands covered by spines were only observed in the lower leaf side. Ultimately, stomata indices were 0.127 (abaxial), 0.188 (adaxial) in in vivo and 0.121 (abaxial), 0.201 (adaxial) in in vitro leaves.

Potent 3-Hydroxy-2-Pyridine Aldoxime Reactivators of Organophosphate-Inhibited Cholinesterases with Predicted Blood-Brain Barrier Penetration.

PubMed

Zorbaz, Tamara; Braïki, Anissa; Maraković, Nikola; Renou, Julien; de la Mora, Eugenio; Maček Hrvat, Nikolina; Katalinić, Maja; Silman, Israel; Sussman, Joel L; Mercey, Guillaume; Gomez, Catherine; Mougeot, Romain; Pérez, Belén; Baati, Rachid; Nachon, Florian; Weik, Martin; Jean, Ludovic; Kovarik, Zrinka; Renard, Pierre-Yves

2018-04-19

A new series of 3-hydroxy-2-pyridine aldoxime compounds have been designed, synthesised and tested in vitro, in silico, and ex vivo as reactivators of human acetylcholinesterase (hAChE) and butyrylcholinesterase (hBChE) inhibited by organophosphates (OPs), for example, VX, sarin, cyclosarin, tabun, and paraoxon. The reactivation rates of three oximes (16-18) were determined to be greater than that of 2-PAM and comparable to that of HI-6, two pyridinium aldoximes currently used by the armies of several countries. The interactions important for a productive orientation of the oxime group within the OP-inhibited enzyme have been clarified by molecular-modelling studies, and by the resolution of the crystal structure of the complex of oxime 17 with Torpedo californica AChE. Blood-brain barrier penetration was predicted for oximes 15-18 based on their physicochemical properties and an in vitro brain membrane permeation assay. Among the evaluated compounds, two morpholine-3-hydroxypyridine aldoxime conjugates proved to be promising reactivators of OP-inhibited cholinesterases. Moreover, efficient ex vivo reactivation of phosphylated native cholinesterases by selected oximes enabled significant hydrolysis of VX, sarin, paraoxon, and cyclosarin in whole human blood, which indicates that the oximes have scavenging potential. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Limiting factors to advancing thermal battery technology for naval applications

NASA Astrophysics Data System (ADS)

Davis, Patrick B.; Winchester, Clinton S.

1991-10-01

Thermal batteries are primary reserve electrochemical power sources using molten salt electrolyte which experience little effective aging while in storage or dormant deployment. Thermal batteries are primarily used in military applications, and are currently used in a wide variety of Navy devices such as missiles, torpedoes, decays, and training targets, usually as power supplies in guidance, propulsion, and Safe/Arm applications. Technology developments have increased the available energy and power density ratings by an order of magnitude in the last ten years. Present thermal batteries, using lithium anodes and metal sulfide cathodes, are capable of performing applications where only less rugged and more expensive silver oxide/zinc or silver/magnesium chloride seawater batteries could serve previously. Additionally, these batteries are capable of supplanting lithium/thionyl chloride reserve batteries in a variety of specifically optimized designs. Increases in thermal battery energy and power density capabilities are not projected to continue with the current available technology. Several battery designs are now at the edge of feasibility and safety. Since future naval systems are likely to require continued growth of battery energy and power densities, there must be significant advances in battery technology. Specifically, anode alloy composition and new cathode materials must be investigated to allow for safe development and deployment of these high power, higher energy density batteries.

Body shape transformation along a shared axis of anatomical evolution in labyrinth fishes (Anabantoidei).

PubMed

Collar, David C; Quintero, Michelle; Buttler, Bernardo; Ward, Andrea B; Mehta, Rita S

2016-03-01

Major morphological transformations, such as the evolution of elongate body shape in vertebrates, punctuate evolutionary history. A fundamental step in understanding the processes that give rise to such transformations is identification of the underlying anatomical changes. But as we demonstrate in this study, important insights can also be gained by comparing these changes to those that occur in ancestral and closely related lineages. In labyrinth fishes (Anabantoidei), rapid evolution of a highly derived torpedo-shaped body in the common ancestor of the pikehead (Luciocephalus aura and L. pulcher) occurred primarily through exceptional elongation of the head, with secondary contributions involving reduction in body depth and lengthening of the precaudal vertebral region. This combination of changes aligns closely with the primary axis of anatomical diversification in other anabantoids, revealing that pikehead evolution involved extraordinarily rapid change in structures that were ancestrally labile. Finer-scale examination of the anatomical components that determine head elongation also shows alignment between the pikehead evolutionary trajectory and the primary axis of cranial diversification in anabantoids, with much higher evolutionary rates leading to the pikehead. Altogether, our results show major morphological transformation stemming from extreme change along a shared morphological axis in labyrinth fishes. © 2016 The Author(s). Evolution © 2016 The Society for the Study of Evolution.

High-frequency plant regeneration through cyclic secondary somatic embryogenesis in black pepper (Piper nigrum L.).

PubMed

Nair, R Ramakrishnan; Dutta Gupta, S

2006-01-01

A high-frequency plantlet regeneration protocol was developed for black pepper (Piper nigrum L.) through cyclic secondary somatic embryogenesis. Secondary embryos formed from the radicular end of the primary somatic embryos which were originally derived from micropylar tissues of germinating seeds on growth regulator-free SH medium in the absence of light. The process of secondary embryogenesis continued in a cyclic manner from the root pole of newly formed embryos resulting in clumps of somatic embryos. Strength of the medium and sucrose concentration influenced the process of secondary embryogenesis and fresh weight of somatic embryo clumps. Full-strength SH medium supplemented with 1.5% sucrose produced significantly higher fresh weight and numbers of secondary somatic embryos while 3.0 and 4.5% sucrose in the medium favored further development of proliferated embryos into plantlets. Ontogeny of secondary embryos was established by histological analysis. Secondary embryogenic potential was influenced by the developmental stage of the explanted somatic embryo and stages up to "torpedo" were more suitable. A single-flask system was standardized for proliferation, maturation, germination and conversion of secondary somatic embryos in suspension cultures. The system of cyclic secondary somatic embryogenesis in black pepper described here represents a permanent source of embryogenic material that can be used for genetic manipulations of this crop species.

Naturally occurring disulfide-bound dimers of three-fingered toxins: a paradigm for biological activity diversification.

PubMed

Osipov, Alexey V; Kasheverov, Igor E; Makarova, Yana V; Starkov, Vladislav G; Vorontsova, Olga V; Ziganshin, Rustam Kh; Andreeva, Tatyana V; Serebryakova, Marina V; Benoit, Audrey; Hogg, Ronald C; Bertrand, Daniel; Tsetlin, Victor I; Utkin, Yuri N

2008-05-23

Disulfide-bound dimers of three-fingered toxins have been discovered in the Naja kaouthia cobra venom; that is, the homodimer of alpha-cobratoxin (a long-chain alpha-neurotoxin) and heterodimers formed by alpha-cobratoxin with different cytotoxins. According to circular dichroism measurements, toxins in dimers retain in general their three-fingered folding. The functionally important disulfide 26-30 in polypeptide loop II of alpha-cobratoxin moiety remains intact in both types of dimers. Biological activity studies showed that cytotoxins within dimers completely lose their cytotoxicity. However, the dimers retain most of the alpha-cobratoxin capacity to compete with alpha-bungarotoxin for binding to Torpedo and alpha7 nicotinic acetylcholine receptors (nAChRs) as well as to Lymnea stagnalis acetylcholine-binding protein. Electrophysiological experiments on neuronal nAChRs expressed in Xenopus oocytes have shown that alpha-cobratoxin dimer not only interacts with alpha7 nAChR but, in contrast to alpha-cobratoxin monomer, also blocks alpha3beta2 nAChR. In the latter activity it resembles kappa-bungarotoxin, a dimer with no disulfides between monomers. These results demonstrate that dimerization is essential for the interaction of three-fingered neurotoxins with heteromeric alpha3beta2 nAChRs.

Mammalian Nicotinic Acetylcholine Receptors: From Structure to Function

PubMed Central

Albuquerque, Edson X.; Pereira, Edna F. R.; Alkondon, Manickavasagom; Rogers, Scott W.

2009-01-01

The classical studies of nicotine by Langley at the turn of the 20th century introduced the concept of a “receptive substance,” from which the idea of a “receptor” came to light. Subsequent studies aided by the Torpedo electric organ, a rich source of muscle-type nicotinic receptors (nAChRs), and the discovery of α-bungarotoxin, a snake toxin that binds pseudo-irreversibly to the muscle nAChR, resulted in the muscle nAChR being the best characterized ligand-gated ion channel hitherto. With the advancement of functional and genetic studies in the late 1980s, the existence of nAChRs in the mammalian brain was confirmed and the realization that the numerous nAChR subtypes contribute to the psychoactive properties of nicotine and other drugs of abuse and to the neuropathology of various diseases, including Alzheimer’s, Parkinson’s, and schizophrenia, has since emerged. This review provides a comprehensive overview of these findings and the more recent revelations of the impact that the rich diversity in function and expression of this receptor family has on neuronal and nonneuronal cells throughout the body. Despite these numerous developments, our understanding of the contributions of specific neuronal nAChR subtypes to the many facets of physiology throughout the body remains in its infancy. PMID:19126755

The Role of Cholesterol in the Activation of Nicotinic Acetylcholine Receptors.

PubMed

Baenziger, John E; Domville, Jaimee A; Therien, J P Daniel

2017-01-01

Cholesterol is a potent modulator of the nicotinic acetylcholine receptor (nAChR) from Torpedo. Here, we review current understanding of the mechanisms underlying cholesterol-nAChR interactions in the context of increasingly available high-resolution structural and functional data. Cholesterol and other lipids influence function by conformational selection and kinetic mechanisms, stabilizing varying proportions of activatable vs nonactivatable conformations, as well as influencing the rates of transitions between conformational states. In the absence of cholesterol and anionic lipids, the nAChR adopts an uncoupled conformation that binds agonist but does not undergo agonist-induced conformational transitions-unless the nAChR is located in a relatively thick lipid bilayer, such as that found in cholesterol-rich lipid rafts. We highlight different sites of cholesterol action, including the lipid-exposed M4 transmembrane α-helix. Cholesterol and other lipids likely alter function by modulating interactions between M4 and the adjacent transmembrane α-helices, M1 and M3. These same interactions have been implicated in both the folding and trafficking of nAChRs to the cell surface. We evaluate the nature of cholesterol-nAChR interactions, considering the evidence supporting the roles of both direct binding to allosteric sites and cholesterol-induced changes in bulk membrane physical properties. © 2017 Elsevier Inc. All rights reserved.

Fertilization-independent seed development in Arabidopsis thaliana

PubMed Central

Chaudhury, Abdul M.; Ming, Luo; Miller, Celia; Craig, Stuart; Dennis, Elizabeth S.; Peacock, W. James

1997-01-01

We report mutants in Arabidopsis thaliana (fertilization-independent seed: fis) in which certain processes of seed development are uncoupled from the double fertilization event that occurs after pollination. These mutants were isolated as ethyl methanesulfonate-induced pseudo-revertants of the pistillata phenotype. Although the pistillata (pi) mutant has short siliques devoid of seed, the fis mutants in the pi background have long siliques containing developing seeds, even though the flowers remain free of pollen. The three fis mutations map to loci on three different chromosomes. In fis1 and fis2 seeds, the autonomous endosperm nuclei are diploid and the endosperm develops to the point of cellularization; the partially developed seeds then atrophy. In these two mutants, proembryos are formed in a low proportion of seeds and do not develop beyond the globular stage. When FIS/fis plants are pollinated by pollen from FIS/FIS plants, ≈50% of the resulting seeds contain fully developed embryos; these seeds germinate and form viable seedlings (FIS/FIS). The other 50% of seeds shrivel and do not germinate; they contain embryos arrested at the torpedo stage (FIS/fis). In normal sexual reproduction, the products of the FIS genes are likely to play important regulatory roles in the development of seed after fertilization. PMID:9108133

Fertilization-independent seed development in Arabidopsis thaliana.

PubMed

Chaudhury, A M; Ming, L; Miller, C; Craig, S; Dennis, E S; Peacock, W J

1997-04-15

We report mutants in Arabidopsis thaliana (fertilization-independent seed:fis) in which certain processes of seed development are uncoupled from the double fertilization event that occurs after pollination. These mutants were isolated as ethyl methanesulfonate-induced pseudo-revertants of the pistillata phenotype. Although the pistillata (pi) mutant has short siliques devoid of seed, the fis mutants in the pi background have long siliques containing developing seeds, even though the flowers remain free of pollen. The three fis mutations map to loci on three different chromosomes. In fis1 and fis2 seeds, the autonomous endosperm nuclei are diploid and the endosperm develops to the point of cellularization; the partially developed seeds then atrophy. In these two mutants, proembryos are formed in a low proportion of seeds and do not develop beyond the globular stage. When FIS/fis plants are pollinated by pollen from FIS/FIS plants, approximately 50% of the resulting seeds contain fully developed embryos; these seeds germinate and form viable seedlings (FIS/FIS). The other 50% of seeds shrivel and do not germinate; they contain embryos arrested at the torpedo stage (FIS/fis). In normal sexual reproduction, the products of the FIS genes are likely to play important regulatory roles in the development of seed after fertilization.

The Electrophysiology of Electric Organs of Marine Electric Fishes

PubMed Central

Bennett, M. V. L.; Wurzel, M.; Grundfest, H.

1961-01-01

Single electroplaques of Torpedo nobiliana have been studied with microelectrode recording. Direct evidence is presented that the only electrogenically reactive membrane of the cells is on the innervated surface and that this membrane is electrically inexcitable. Responses are not evoked by depolarizing currents applied to this membrane, but only by stimulating the innervating nerve fibers. The responses arise after a latency of 1 to 3 msec. This latency is not affected by large depolarizing or hyperpolarizing changes in membrane potential. Various properties that have been theoretically associated with electrically inexcitable responses have been also demonstrated to occur in the electroplaques. The neurally evoked response is not propagated actively in the membrane and may have different amplitudes and forms in closely adjacent regions. The maximal responses frequently are slightly larger than the recorded resting potential but the apparent small overshoot may be due to difficulty in recording the full resting potential. The responses are subject to electrochemical gradation and appear inverted in sign on applying strong outward currents across the innervated membrane. This membrane is cholinoceptive and shows marked desensitization. The membrane of the uninnervated surface has a very low resistance, a factor that aids maximum output of current during the discharge of the electric organ. PMID:19873534

Taspine: Bioactivity-Guided Isolation and Molecular Ligand–Target Insight of a Potent Acetylcholinesterase Inhibitor from Magnolia x soulangiana

PubMed Central

Rollinger, Judith M.; Schuster, Daniela; Baier, Elisabeth; Ellmerer, Ernst P.; Langer, Thierry; Stuppner, Hermann

2012-01-01

A bioactivity-guided approach was taken to identify the acetylcholinesterase (AChE, EC 3.1.1.7) inhibitory agent in a Magnolia x soulangiana extract using a microplate enzyme assay with Ellman’s reagent. This permitted the isolation of the alkaloids taspine (1) and (−)-asimilobine (2), which were detected for the first time in this species. Compound 1 showed a significantly higher effect on AChE than the positive control galanthamine and selectively inhibited the enzyme in a long-lasting and concentration-dependent fashion with an IC50 value of 0.33 ± 0.07 μM. Extensive molecular docking studies were performed with human and Torpedo californica-AChE employing Gold software to rationalize the binding interaction. The results suggested ligand 1 to bind in an alternative binding orientation when compared to galanthamine. While this is located in close vicinity to the catalytic amino acid triad, the 1–AChE complex was found to be stabilized by (i) sandwich-like π-stacking interactions between the planar aromatic ligand (1) and the Trp84 and Phe330 of the enzyme, (ii) an esteratic site anchoring with the amino side chain, and (iii) a hydrogen-bonding network. PMID:16989531

[On the first studies of electrophysiology].

PubMed

de Micheli, Alfredo

2011-01-01

A historical outline of the evolution of electrophysiology from the eighteenth century is shortly presented. Topics concerning the so called animal electricity starting from the observations on descharges of Torpedo fish until Bolognese Galvani's researches on the frogs are exposed. The points of view of their oppositionists also are examined. These ones, leaded by the physicist Alessandro Volta, professor in the University of Pavia, believed that electricity detected by galvanists was not inherent to animal but was due to the action of the metallic conductors present in the circuit: contact electricity. Only towards the middle of the nineteenth century the physicist Carlo Matteucci attained to demonstrate the existente of the real animal electricity in form of injury current. It was possible to determine that quantitatively thanks to the capillary electrometer built in 1872 by the French physicist Gabriel Lippmann. This instrument was used by the English physiologist Waller in order to obtain the primitive electrocardiographic tracings in humans (1887). At beginnings of the twentieth century, the Dutch professor Willem Einthoven, of the University of Leiden, introduced his string galvanometer which permitted to allow the modern electrocardiography. So it was possible to record the electrical potentials of myocardial cells, first in vitro, later in isolated and perfused heart, son after in dog's heart in situ and finally in human heart. Therefore now it is possible to effectuate endocardial and epicardial mappings, indispensable in order to diagnose and treat the cardiac arrhythmias.

Combining laser-assisted microdissection (LAM) and RNA-seq allows to perform a comprehensive transcriptomic analysis of epidermal cells of Arabidopsis embryo.

PubMed

Sakai, Kaori; Taconnat, Ludivine; Borrega, Nero; Yansouni, Jennifer; Brunaud, Véronique; Paysant-Le Roux, Christine; Delannoy, Etienne; Martin Magniette, Marie-Laure; Lepiniec, Loïc; Faure, Jean Denis; Balzergue, Sandrine; Dubreucq, Bertrand

2018-01-01

Genome-wide characterization of tissue- or cell-specific gene expression is a recurrent bottleneck in biology. We have developed a sensitive approach based on ultra-low RNA sequencing coupled to laser assisted microdissection for analyzing different tissues of the small Arabidopsis embryo. We first characterized the number of genes detected according to the quantity of tissue yield and total RNA extracted. Our results revealed that as low as 0.02 mm 2 of tissue and 50 pg of total RNA can be used without compromising the number of genes detected. The optimised protocol was used to compare the epidermal versus mesophyll cell transcriptomes of cotyledons at the torpedo-shaped stage of embryo development. The approach was validated by the recovery of well-known epidermal genes such AtML1 or AtPDF2 and genes involved in flavonoid and cuticular waxes pathways. Moreover, the interest and sensitivity of this approach were highlighted by the characterization of several transcription factors preferentially expressed in epidermal cells. This technical advance unlocks some current limitations of transcriptomic analyses and allows to investigate further and efficiently new biological questions for which only a very small amounts of cells need to be isolated. For instance, it paves the way to increasing the spatial accuracy of regulatory networks in developing small embryo of Arabidopsis or other plant tissues.

Glutathione and abscisic acid supplementation influences somatic embryo maturation and hormone endogenous levels during somatic embryogenesis in Podocarpus lambertii Klotzsch ex Endl.

PubMed

Fraga, Hugo Pacheco de Freitas; Vieira, Leila do Nascimento; Puttkammer, Catarina Corrêa; Dos Santos, Henrique Pessoa; Garighan, Julio de Andrade; Guerra, Miguel Pedro

2016-12-01

Here we propose a protocol for embryogenic cultures induction, proliferation and maturation for the Brazilian conifer Podocarpus lambertii, and investigated the effect of abscisic acid (ABA) and glutathione (GSH) supplementation on the maturation phase. ABA, zeatin (Z) and salicylic acid (SA) endogenous levels were quantified. Number of somatic embryos obtained in ABA-supplemented treatment was significant higher than in ABA-free treatment, showing the relevance of ABA supplementation during somatic embryos maturation. Histological analysis showed the stereotyped sequence of developmental stages in conifer somatic embryos, reaching the late torpedo-staged embryo. GSH supplementation in maturation culture medium improved the somatic embryos number and morphological features. GSH 0mM and GSH 0.1mM treatments correlated with a decreased ABA endogenous level during maturation, while GSH 0.5mM treatment showed constant levels. All treatments resulted in decreased Z endogenous levels, supporting the concept that cytokinins are important during the initial cell division but not for the later stages of embryo development. The lowest SA levels found in GSH 0.5mM treatment were coincident with early embryonic development, and this treatment resulted in the highest development of somatic embryos. Thus, a correlation between lower SA levels and improved somatic embryo formation can be hypothesized. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

The overlooked literary path to modern electrophysiology: philosophical dialogues, novels, and travel books.

PubMed

Finger, Stanley

2013-01-01

The early history of neurophysiology has two important roots. The earlier of the two involves various ideas about invisible animal spirits traversing the nerves. The other, which emerged during the eighteenth century, is based on the idea that the elusive spirits are electrical-that animal electricity really does exist. The latter idea stemmed in part from what was being discovered about three types of electric fishes and their shocks prior to Galvani's broader claim in 1791 for animal electricity. This contribution focuses on how the shocks of each of these fishes had been described by three writers outside the fields of physiology and medicine: Plato, the well-known Greek philosopher, who actually provided the first good description of the powers of torpedo rays; Aphra Behn, a leading English Restoration playwright and novelist, who introduced many English speakers to the creature that would become best known as the "electric eel"; and Michel Adanson, a French botanist, who seemed to be the first to compare albeit the electric catfish's shocks to those from a known source of electricity, a Leyden jar. All three authors were famous in their day, and all played important roles in the history of biological electricity by making others aware of one of Nature's wonders, fishes that could "torpify," even without direct contact. © 2013 Elsevier B.V. All rights reserved.

The sodium channel in membranes of electroplax. Binding of batrachotoxinin-a [(3)H]benzoate to particulate preparations from electric eel (electrophorus).

PubMed

McNeal, E T; Daly, J W

1986-01-01

Batrachotoxinin-A [(3)H]benzoate ([(3)H]BTX-B) binds specifically and with high affinity (K(D) 48 nM) to sites (B(max) 2.1 pmol/mg protein) associated with voltage-dependent sodium channels in rodent brain vesicular preparations. High affinity binding requires the presence of scorpion (Leiurus) venom and a membrane potential. Local anesthetics antagonize the binding. Nonspecific binding is defined in the presence of veratridine. In particulate preparations from electroplax of the eel Electrophorus electricus, [(3)H]BTX-B binds with a K(D) of about 140 nM and a B(max) of 2.5 pmol/mg protein in the presence of scorpion venom. Higher concentrations of scorpion venom are required to enhance binding in Electrophorus preparations than in brain preparations. Local anesthetics antagonize binding in Electrophorus preparations with potencies similar to those in brain preparations. Veratridine and batrachotoxin are less potent in blocking binding in Electrophorus than in brain preparations. It appears likely that binding in Electrophorus preparations is primarily to membrane fragments rather than vesicular entities as in brain. Binding of [(3)H]BTX-B to particulate preparations from electroplax of the ray Torpedo californica and the catfish Malapterurus electricus is mainly nonspecific. Scorpion venom does not enhance total binding and local anesthetics are not effective in antagonizing binding.

Guidelines for standard preclinical experiments in the mouse model of myasthenia gravis induced by acetylcholine receptor immunization.

PubMed

Tuzun, Erdem; Berrih-Aknin, Sonia; Brenner, Talma; Kusner, Linda L; Le Panse, Rozen; Yang, Huan; Tzartos, Socrates; Christadoss, Premkumar

2015-08-01

Myasthenia gravis (MG) is an autoimmune disorder characterized by generalized muscle weakness due to neuromuscular junction (NMJ) dysfunction brought by acetylcholine receptor (AChR) antibodies in most cases. Although steroids and other immunosuppressants are effectively used for treatment of MG, these medications often cause severe side effects and a complete remission cannot be obtained in many cases. For pre-clinical evaluation of more effective and less toxic treatment methods for MG, the experimental autoimmune myasthenia gravis (EAMG) induced by Torpedo AChR immunization has become one of the standard animal models. Although numerous compounds have been recently proposed for MG mostly by using the active immunization EAMG model, only a few have been proven to be effective in MG patients. The variability in the experimental design, immunization methods and outcome measurements of pre-clinical EAMG studies make it difficult to interpret the published reports and assess the potential for application to MG patients. In an effort to standardize the active immunization EAMG model, we propose standard procedures for animal care conditions, sampling and randomization of mice, experimental design and outcome measures. Utilization of these standard procedures might improve the power of pre-clinical EAMG experiments and increase the chances for identifying promising novel treatment methods that can be effectively translated into clinical trials for MG. Copyright © 2015 Elsevier Inc. All rights reserved.

Ionic liquid mediated synthesis of mono- and bis-spirooxindole-hexahydropyrrolidines as cholinesterase inhibitors and their molecular docking studies.

PubMed

Kia, Yalda; Osman, Hasnah; Kumar, Raju Suresh; Basiri, Alireza; Murugaiyah, Vikneswaran

2014-02-15

One pot, three-component reaction of 1-acryloyl-3,5-bisarylmethylidenepiperidin-4-ones with isatin and sarcosine in molar ratios of 1:1:1 and 1:2:2 furnished to mono- and bis-spiropyrrolidine heterocyclic hybrids comprising functionalized piperidine, pyrrolidine and oxindole structural motifs. Both mono and bis-spiropyrrolidines displayed good inhibitory activity against acetylcholinesterase (AChE) with IC₅₀ values of 2.36-9.43 μM. For butyrylcholinesterase (BChE), mono-cycloadducts in series 8 with IC₅₀ values of lower than 10 μM displayed better inhibitory activities than their bis-cycloadduct analogs in series 9 with IC₅₀ values of 7.44-19.12 μM. The cycloadducts 9j and 8e were found to be the most potent AChE and BChE inhibitors with IC₅₀ values of 2.35 and 3.21 μM, respectively. Compound 9j was found to be competitive inhibitor of AChE while compound 8e was a mixed-mode inhibitor of BChE with calculated Ki values of 2.01 and 6.76 μM, respectively. Molecular docking on Torpedo californica AChE and human BChE showed good correlation between IC₅₀ values and free binding energy values of the synthesized compounds docked into the active site of the enzymes. Copyright © 2014 Elsevier Ltd. All rights reserved.

Proton conductivity in ampullae of Lorenzini jelly

PubMed Central

Josberger, Erik E.; Hassanzadeh, Pegah; Deng, Yingxin; Sohn, Joel; Rego, Michael J.; Amemiya, Chris T.; Rolandi, Marco

2016-01-01

In 1678, Stefano Lorenzini first described a network of organs of unknown function in the torpedo ray—the ampullae of Lorenzini (AoL). An individual ampulla consists of a pore on the skin that is open to the environment, a canal containing a jelly and leading to an alveolus with a series of electrosensing cells. The role of the AoL remained a mystery for almost 300 years until research demonstrated that skates, sharks, and rays detect very weak electric fields produced by a potential prey. The AoL jelly likely contributes to this electrosensing function, yet the exact details of this contribution remain unclear. We measure the proton conductivity of the AoL jelly extracted from skates and sharks. The room-temperature proton conductivity of the AoL jelly is very high at 2 ± 1 mS/cm. This conductivity is only 40-fold lower than the current state-of-the-art proton-conducting polymer Nafion, and it is the highest reported for a biological material so far. We suggest that keratan sulfate, identified previously in the AoL jelly and confirmed here, may contribute to the high proton conductivity of the AoL jelly with its sulfate groups—acid groups and proton donors. We hope that the observed high proton conductivity of the AoL jelly may contribute to future studies of the AoL function. PMID:27386543

Neuropathology of Cervical Dystonia

PubMed Central

Prudente, C.N.; Pardo, C.A.; Xiao, J.; Hanfelt, J.; Hess, E.J.; LeDoux, M.S.; Jinnah, H.A.

2012-01-01

The aim of this study was to search for neuropathological changes in postmortem brain tissue of individuals with cervical dystonia (CD). Multiple regions of formalin-preserved brains were collected from patients with CD and controls and examined with an extensive battery of histopathological stains in a two-stage study design. In stage one, 4 CD brains underwent a broad screening neuropathological examination. In stage two, these 4 CD brains were combined with 2 additional CD brains, and the subjective findings were quantified and compared to 16 age-matched controls. The initial subjective neuropathological assessment revealed only two regions with relatively consistent changes. The substantia nigra had frequent ubiquitin-positive intranuclear inclusions known as Marinesco bodies. Additionally, the cerebellum showed patchy loss of Purkinje cells, areas of focal gliosis and torpedo bodies. Other brain regions showed minor or inconsistent changes. In the second stage of the analysis, quantitative studies failed to reveal significant differences in the numbers of Marinesco bodies in CD versus controls, but confirmed a significantly lower Purkinje cell density in CD. Molecular investigations revealed 4 of the CD cases and 2 controls to harbor sequence variants in non-coding regions of THAP1, and these cases had lower Purkinje cell densities regardless of whether they had CD. The findings suggest that subtle neuropathological changes such as lower Purkinje cell density may be found in primary CD when relevant brain regions are investigated with appropriate methods. PMID:23195594

Colorimetric microtiter plate receptor-binding assay for the detection of freshwater and marine neurotoxins targeting the nicotinic acetylcholine receptors

USGS Publications Warehouse

Rubio, Fernando; Kamp, Lisa; Carpino, Justin; Faltin, Erin; Loftin, Keith A.; Molgó, Jordi; Aráoz, Rómulo

2014-01-01

Anatoxin-a and homoanatoxin-a, produced by cyanobacteria, are agonists of nicotinic acetylcholine receptors (nAChRs). Pinnatoxins, spirolides, and gymnodimines, produced by dinoflagellates, are antagonists of nAChRs. In this study we describe the development and validation of a competitive colorimetric, high throughput functional assay based on the mechanism of action of freshwater and marine toxins against nAChRs. Torpedo electrocyte membranes (rich in muscle-type nAChR) were immobilized and stabilized on the surface of 96-well microtiter plates. Biotinylated α-bungarotoxin (the tracer) and streptavidin-horseradish peroxidase (the detector) enabled the detection and quantitation of anatoxin-a in surface waters and cyclic imine toxins in shellfish extracts that were obtained from different locations across the US. The method compares favorably to LC/MS/MS and provides accurate results for anatoxin-a and cyclic imine toxins monitoring. Study of common constituents at the concentrations normally found in drinking and environmental waters, as well as the tolerance to pH, salt, solvents, organic and inorganic compounds did not significantly affect toxin detection. The assay allowed the simultaneous analysis of up to 25 samples within 3.5 h and it is well suited for on-site or laboratory monitoring of low levels of toxins in drinking, surface, and ground water as well as in shellfish extracts.

The specific interaction of the photosensitizer methylene blue with acetylcholinesterase provides a model system for studying the molecular consequences of photodynamic therapy.

PubMed

Silman, Israel; Roth, Esther; Paz, Aviv; Triquigneaux, Mathilde M; Ehrenshaft, Marilyn; Xu, Yechun; Shnyrov, Valery L; Sussman, Joel L; Deterding, Leesa J; Ashani, Yacov; Mason, Ronald P; Weiner, Lev

2013-03-25

The photosensitizer, methylene blue (MB), generates singlet oxygen ((1)O2) that irreversibly inhibits Torpedo californica acetylcholinesterase (TcAChE). In the dark MB inhibits reversibly, binding being accompanied by a bathochromic shift that can be used to show its displacement by other reversible inhibitors binding to the catalytic 'anionic' subsite (CAS), the peripheral 'anionic' subsite (PAS), or bridging them. Data concerning both reversible and irreversible inhibition are here reviewed. MB protects TcAChE from thermal denaturation, and differential scanning calorimetry reveals a ~8 °C increase in the denaturation temperature. The crystal structure of the MB/TcAChE complex reveals a single MB stacked against W279 in the PAS, pointing down the gorge towards the CAS. The intrinsic fluorescence of the irreversibly inhibited enzyme displays new emission bands that can be ascribed to N'-formylkynurenine (NFK); this was indeed confirmed using anti-NFK antibodies. Mass spectroscopy revealed that two Trp residues, Trp84 in the CAS, and Trp279 in the PAS, were the only Trp residues, out of a total of 14, significantly modified by photo-oxidation, both being converted to NFK. In the presence of competitive inhibitors that displace MB from the gorge, their modification is completely prevented. Thus, photo-oxidative damage caused by MB involves targeted release of (1)O2 by the bound photosensitizer within the aqueous milieu of the active-site gorge. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Designing Second Generation Anti-Alzheimer Compounds as Inhibitors of Human Acetylcholinesterase: Computational Screening of Synthetic Molecules and Dietary Phytochemicals

PubMed Central

Amat-ur-Rasool, Hafsa; Ahmed, Mehboob

2015-01-01

Alzheimer's disease (AD), a big cause of memory loss, is a progressive neurodegenerative disorder. The disease leads to irreversible loss of neurons that result in reduced level of acetylcholine neurotransmitter (ACh). The reduction of ACh level impairs brain functioning. One aspect of AD therapy is to maintain ACh level up to a safe limit, by blocking acetylcholinesterase (AChE), an enzyme that is naturally responsible for its degradation. This research presents an in-silico screening and designing of hAChE inhibitors as potential anti-Alzheimer drugs. Molecular docking results of the database retrieved (synthetic chemicals and dietary phytochemicals) and self-drawn ligands were compared with Food and Drug Administration (FDA) approved drugs against AD as controls. Furthermore, computational ADME studies were performed on the hits to assess their safety. Human AChE was found to be most approptiate target site as compared to commonly used Torpedo AChE. Among the tested dietry phytochemicals, berberastine, berberine, yohimbine, sanguinarine, elemol and naringenin are the worth mentioning phytochemicals as potential anti-Alzheimer drugs The synthetic leads were mostly dual binding site inhibitors with two binding subunits linked by a carbon chain i.e. second generation AD drugs. Fifteen new heterodimers were designed that were computationally more efficient inhibitors than previously reported compounds. Using computational methods, compounds present in online chemical databases can be screened to design more efficient and safer drugs against cognitive symptoms of AD. PMID:26325402

Designing Second Generation Anti-Alzheimer Compounds as Inhibitors of Human Acetylcholinesterase: Computational Screening of Synthetic Molecules and Dietary Phytochemicals.

PubMed

Amat-Ur-Rasool, Hafsa; Ahmed, Mehboob

2015-01-01

Alzheimer's disease (AD), a big cause of memory loss, is a progressive neurodegenerative disorder. The disease leads to irreversible loss of neurons that result in reduced level of acetylcholine neurotransmitter (ACh). The reduction of ACh level impairs brain functioning. One aspect of AD therapy is to maintain ACh level up to a safe limit, by blocking acetylcholinesterase (AChE), an enzyme that is naturally responsible for its degradation. This research presents an in-silico screening and designing of hAChE inhibitors as potential anti-Alzheimer drugs. Molecular docking results of the database retrieved (synthetic chemicals and dietary phytochemicals) and self-drawn ligands were compared with Food and Drug Administration (FDA) approved drugs against AD as controls. Furthermore, computational ADME studies were performed on the hits to assess their safety. Human AChE was found to be most approptiate target site as compared to commonly used Torpedo AChE. Among the tested dietry phytochemicals, berberastine, berberine, yohimbine, sanguinarine, elemol and naringenin are the worth mentioning phytochemicals as potential anti-Alzheimer drugs The synthetic leads were mostly dual binding site inhibitors with two binding subunits linked by a carbon chain i.e. second generation AD drugs. Fifteen new heterodimers were designed that were computationally more efficient inhibitors than previously reported compounds. Using computational methods, compounds present in online chemical databases can be screened to design more efficient and safer drugs against cognitive symptoms of AD.

Nonanesthetic alcohols dissolve in synaptic membranes without perturbing their lipids.

PubMed Central

Miller, K W; Firestone, L L; Alifimoff, J K; Streicher, P

1989-01-01

While many theories of general anesthesia postulate a lipid site of action, there has been no adequate explanation for the lack of anesthetic potency of the highly hydrophobic primary alkanols with more than 12 carbons (the cut-off). Some work suggests that these nonanesthetic alcohols do not dissolve in membranes. Other work contradicts this and suggests that an anesthetic site on a protein provides a better explanation. Here we show that both the anesthetic dodecanol and the nonanesthetic tetradecanol are taken up equally well into the tissues of animals and into isolated postsynaptic membranes. When a group of Rana pipiens tadpoles were treated with dodecanol, half were anesthetized by 4.7 microM (free aqueos concentration), and the corresponding concentration in the tissues was found to be 0.4 mmol per kg wet weight. Prolonged exposure (92 hr) to tetradecanol produced even higher tissue concentrations (0.7 mmol per kg wet weight), yet no anesthetic effects were observed. Furthermore, general anesthetics are thought to act on postsynaptic membranes but both alkanols partitioned into postsynaptic membranes from Torpedo electroplaques. The spin label, 12-doxyl stearate, was incorporated into these membranes. The lipid order parameter it reported was decreased by the anesthetic alcohols (octanol, decanol, and dodecanol), whereas the nonanesthetic alcohols either did not change it significantly (tetradecanol) or actually increased it (hexadecanol and octadecanol). Thus, although lipid solubility is unable to account for the pharmacology of the cut-off in potency of the long-chain alcohols, lipid perturbations provide an accurate description. PMID:2783782

Cytological analysis of ginseng carpel development.

PubMed

Silva, Jeniffer; Kim, Yu-Jin; Xiao, Dexin; Sukweenadhi, Johan; Hu, Tingting; Kwon, Woo-Saeng; Hu, Jianping; Yang, Deok-Chun; Zhang, Dabing

2017-09-01

Panax ginseng Meyer, commonly known as ginseng, is considered one of the most important herbs with pharmaceutical values due to the presence of ginsenosides and is cultivated for its highly valued root for medicinal purposes. Recently, it has been recognized that ginseng fruit contains high contents of triterpene such as ginsenoside Re as pharmaceutical compounds. However, it is unclear how carpel, the female reproductive tissue of flowers, is formed during the three-year-old growth before fruit is formed in ginseng plants. Here, we report P. ginseng carpel development at the cytological level, starting from the initial stage of ovule development to seed development. The carpel of P. ginseng is composed of two free stigmas, two free styles, and one epigynous bilocular ovary containing one ovule in each locule. Based on our cytological study, we propose that the female reproductive development in P. ginseng can be classified into seven stages: early phase of ovule development, megasporogenesis, megagametogenesis, pre-fertilization, fertilization, post-fertilization, and seed development. We also describe the correlation of the female and male gametophyte development and compare morphological differences in carpel development between ginseng and other higher plants. One unique feature for ginseng seed development is that it takes 40 days for the embryo to develop to the early torpedo stage and that the embryo is small relative to the seed size, which could be a feature of taxonomic importance. This study will provide an integral tool for the study of the reproductive development and breeding of P. ginseng.

Establishment of the regeneration system for Vicia faba L.

PubMed

Bahgat, Shimaa; Shabban, Omer A; El-Shihy, Osama; Lightfoot, David A; El-Shemy, Hany A

2009-01-01

A reliable regeneration system for faba bean has been difficult to establish and therefore, the genetic improvement of Vicia faba L. was delayed. The paper describes a method of somatic embryo induction in callus of V. faba. Two Egyptian faba bean cultivars 'Giza 2' and '24 Hyto' were used. Callus was induced from epicotyls and shoot tips cultured on MS or Gamborg medium supplemented with 3% sucrose and 0.025% (w/v) for each of ascorbic and citric acid, 0.8% agar and different concentrations of 10 mg/l BAP, 0.5 mg/l of each NAA and 2,4-dichlorophenoxyacetic acid (M1) and 1 mg/l BAP and 0.5 mg/l NAA (M2) . The media with BAP, NAA and 2,4-D were optimal for embryogenic callus induction. Somatic embryos developed after transfer of the callus to 1/2 B5 medium with no plant growth regulators. There were various stages of somatic embryo development present including globular, heart-shaped, torpedo, and cotyledonary stages. Embryos developed into plantlets and plants were regenerated. RAPD analyses were performed to investigate the genetic stability of the regenerated plants obtained from different treatments and different explants. The cultivar Giza 2 exhibited more genetic stability than cultivar 24 Hyto. In conclusion, a regeneration system was established suitable for both gene transformation and the isolation of somaclonal mutants. The regeneration system will be used in order to improve the nutritional value of faba bean.

Somatic embryogenesis, scanning electron microscopy, histology and biochemical analysis at different developing stages of embryogenesis in six date palm (Phoenix dactylifera L.) cultivars.

PubMed

Aslam, Junaid; Khan, Saeed Ahmad; Cheruth, Abdul Jaleel; Mujib, Abdul; Sharma, Maheshwar Pershad; Srivastava, Prem Shanker

2011-10-01

An efficient somatic embryogenesis system has been established in six date palm (Phoenix dactylifera L.) cultivars (Barhee, Zardai, Khalasah, Muzati, Shishi and Zart). Somatic embryogenesis (SE) was growth regulators and cultivars dependent. Friable embryogenic callus was induced from excised shoot tips on MS medium supplemented with various auxins particularly 2,4-dichlorophenoxyacetic acid (2,4-D, 1.5 mg 1(-l)). Suspension culture increased embryogenesis potentiality. Only a-naphthaleneacetic acid (NAA, 0.5 mg 1(-1)) produced somatic embryos in culture. Somatic embryos germinated and converted into plantlets in N(6)-benzyladenine (BAP, 0.75 mg 1(-l)) added medium following a treatment with thidiazuron (TDZ, 1.0 mg 1(-l)) for maturation. Scanning electron microscopy showed early stages of somatic embryo particularly, globular types, and was in masses. Different developing stages of embryogenesis (heart, torpedo and cotyledonary) were observed under histological preparation of embryogenic callus. Biochemical screening at various stages of somatic embryogenesis (embryogenic callus, somatic embryos, matured, germinated embryos and converted plantlets) of date palm cultivars has been conducted and discussed in detail. The result discussed in this paper indicates that somatic embryos were produced in numbers and converted plantlets can be used as a good source of alternative propagation. Genetic modification to the embryo precursor cell may improve the fruit quality and yield further.

INHIBITION OF HUMAN ACETYL- AND BUTYRYLCHOLINESTERASE BY NOVEL CARBAMATES OF (−)- AND (+)-TETRAHYDROFUROBENZOFURAN AND METHANOBENZODIOXEPINE

PubMed Central

Luo, Weiming; Yu, Qian-sheng; Kulkarni, Santosh S.; Parrish, Damon A.; Holloway, Harold W.; Tweedie, David; Shafferman, Avigdor; Lahiri, Debomoy K.; Brossi, Arnold; Greig, Nigel H.

2008-01-01

A new enantiomeric synthesis utilizing classical resolution provided two novel series of optically active inhibitors of cholinesterase: (−)- and (+)- O-carbamoyl phenols of tetrahydrofurobenzofuran and methanobenzodioxepine. An additional two series of (−)- and (+)-O-carbamoyl phenols of pyrroloindole and furoindole were obtained by known procedures, and their anticholinesterase actions were similarly quantified against freshly prepared human acetyl- (AChE) and butyrylcholinesterase (BChE). Both enantiomeric forms of each series demonstrated potent cholinesterase inhibitory activity (with IC50 values as low as 10 nM for AChE and 3 nM for BChE), with the exception of the (+)-O-carbamoyl phenols of pyrroloindole that lacked activity (IC50 values > 1 µM). Based on the biological data of these four series, a SAR analysis was provided by molecular volume calculations. In addition, a probable transition state model was established according to the known X-ray structure of a transition state complex of Torpedo californica AChE-m-(N,N,N,trimethylammonio)-2,2,2-trifluoroacetophenone (TcAChE-TMTFA). This model proved valuable in explaining the enantio-selectivity and enzyme subtype selectivity of each series. These carbamates are more or similarly potent to anticholinesterases in current clinical use; providing not only inhibitors of potential clinical relevance but also pharmacological tools to define drug-enzyme binding interactions within an enzyme crucial in the maintenance of cognition and numerous systemic physiological functions in health, aging and disease. PMID:16570913

Structure-function relationships of curaremimetic neurotoxin loop 2 and of a structurally similar segment of rabies virus glycoprotein in their interaction with the nicotinic acetylcholine receptor

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

Lentz, T.L.

1991-11-12

Peptides corresponding to portions of curaremimetic neurotoxin loop 2 and to a structurally similar segment of rabies virus glycoprotein were synthetically modified in order to gain information on structure-function relationships of neurotoxin loop 2 interactions with the acetylcholine receptor. Binding of synthetic peptides to the acetylcholine receptor of Torpedo electric organ membranes was assessed by measuring their ability to inhibit the binding of {sup 125}I-{alpha}-bungarotoxin to the receptor. The peptides showing the highest affinity for the receptor were a peptide corresponding to the sequence of loop 2 (residues 25-44) of Ophiophagus hannah (king cobra) toxin b and the structurally similarmore » segment of CVS rabies virus glycoprotein. These affinities were comparable to those of d-tubocurarine and suberyldicholine. These results demonstrate the importance of loop 2 in the neurotoxin interaction with the receptor. N- and C-terminal deletions of the loop 2 peptides and substitution of residues invariant or highly conserved among neurotoxins were performed in order to determine the role of individual residues in binding. Residues 25-40 are the most crucial in the interaction with the acetylcholine receptor. Since this region of the glycoprotein contains residues corresponding to all of the functionally invariant neurotoxin residues, it may interact with the acetylcholine receptor through a mechanism similar to that of the neurotoxins.« less

Vision and lack of vision in the ocean.

PubMed

Marshall, Justin

2017-06-05

As land-locked animals, when we visualise the ocean our mind's eye may see crashing waves or a vast blue expanse stretching to the horizon, a raft of torpedoing penguins, a glimpse of colourful coral reef fish from the shark-free safety of a sandy beach. Underwater, the crystal-clear, and in fact not at all silent, world of Jacques Cousteau, or more recently David Attenborough, is a wonderland that some cannot wait to witness first hand as divers, while others are content to see it on a screen. Spend a bit of time underwater, in the English Channel for example, and a few facts emerge. Most obviously, much of this underwater realm is visually very different to land and indeed to the cherry-picked clear waters of documentaries. It may be disappointingly murky and monochromatic. Perhaps surprisingly, therefore, on close inspection the diversity of eye designs and light sensing mechanisms that evolved in the ocean are more varied than on land, reflecting the greater range of light environments and lifestyles of the marine world. Particularly in the last ten years, the destructive influence we are having on the oceans has become visibly obvious, not just to fisheries biologists and ecologists, but to anyone returning to a favourite dive spot or reef resort. Climate change, as a result of burning fossil fuels, human greed and carelessness with plastic disposal, are rapidly degrading entire oceanic ecosystems. Copyright © 2017 Elsevier Ltd. All rights reserved.

Natural compounds interacting with nicotinic acetylcholine receptors: from low-molecular weight ones to peptides and proteins.

PubMed

Kudryavtsev, Denis; Shelukhina, Irina; Vulfius, Catherine; Makarieva, Tatyana; Stonik, Valentin; Zhmak, Maxim; Ivanov, Igor; Kasheverov, Igor; Utkin, Yuri; Tsetlin, Victor

2015-05-14

Nicotinic acetylcholine receptors (nAChRs) fulfill a variety of functions making identification and analysis of nAChR subtypes a challenging task. Traditional instruments for nAChR research are d-tubocurarine, snake venom protein α-bungarotoxin (α-Bgt), and α-conotoxins, neurotoxic peptides from Conus snails. Various new compounds of different structural classes also interacting with nAChRs have been recently identified. Among the low-molecular weight compounds are alkaloids pibocin, varacin and makaluvamines C and G. 6-Bromohypaphorine from the mollusk Hermissenda crassicornis does not bind to Torpedo nAChR but behaves as an agonist on human α7 nAChR. To get more selective α-conotoxins, computer modeling of their complexes with acetylcholine-binding proteins and distinct nAChRs was used. Several novel three-finger neurotoxins targeting nAChRs were described and α-Bgt inhibition of GABA-A receptors was discovered. Information on the mechanisms of nAChR interactions with the three-finger proteins of the Ly6 family was found. Snake venom phospholipases A2 were recently found to inhibit different nAChR subtypes. Blocking of nAChRs in Lymnaea stagnalis neurons was shown for venom C-type lectin-like proteins, appearing to be the largest molecules capable to interact with the receptor. A huge nAChR molecule sensible to conformational rearrangements accommodates diverse binding sites recognizable by structurally very different compounds.

Natural Compounds Interacting with Nicotinic Acetylcholine Receptors: From Low-Molecular Weight Ones to Peptides and Proteins

PubMed Central

Kudryavtsev, Denis; Shelukhina, Irina; Vulfius, Catherine; Makarieva, Tatyana; Stonik, Valentin; Zhmak, Maxim; Ivanov, Igor; Kasheverov, Igor; Utkin, Yuri; Tsetlin, Victor

2015-01-01

Nicotinic acetylcholine receptors (nAChRs) fulfill a variety of functions making identification and analysis of nAChR subtypes a challenging task. Traditional instruments for nAChR research are d-tubocurarine, snake venom protein α-bungarotoxin (α-Bgt), and α-conotoxins, neurotoxic peptides from Conus snails. Various new compounds of different structural classes also interacting with nAChRs have been recently identified. Among the low-molecular weight compounds are alkaloids pibocin, varacin and makaluvamines C and G. 6-Bromohypaphorine from the mollusk Hermissenda crassicornis does not bind to Torpedo nAChR but behaves as an agonist on human α7 nAChR. To get more selective α-conotoxins, computer modeling of their complexes with acetylcholine-binding proteins and distinct nAChRs was used. Several novel three-finger neurotoxins targeting nAChRs were described and α-Bgt inhibition of GABA-A receptors was discovered. Information on the mechanisms of nAChR interactions with the three-finger proteins of the Ly6 family was found. Snake venom phospholipases A2 were recently found to inhibit different nAChR subtypes. Blocking of nAChRs in Lymnaea stagnalis neurons was shown for venom C-type lectin-like proteins, appearing to be the largest molecules capable to interact with the receptor. A huge nAChR molecule sensible to conformational rearrangements accommodates diverse binding sites recognizable by structurally very different compounds. PMID:26008231

Somatic embryogenesis, scanning electron microscopy, histology and biochemical analysis at different developing stages of embryogenesis in six date palm (Phoenix dactylifera L.) cultivars

PubMed Central

Aslam, Junaid; Khan, Saeed Ahmad; Cheruth, Abdul Jaleel; Mujib, Abdul; Sharma, Maheshwar Pershad; Srivastava, Prem Shanker

2011-01-01

An efficient somatic embryogenesis system has been established in six date palm (Phoenix dactylifera L.) cultivars (Barhee, Zardai, Khalasah, Muzati, Shishi and Zart). Somatic embryogenesis (SE) was growth regulators and cultivars dependent. Friable embryogenic callus was induced from excised shoot tips on MS medium supplemented with various auxins particularly 2,4-dichlorophenoxyacetic acid (2,4-D, 1.5 mg 1−l). Suspension culture increased embryogenesis potentiality. Only a-naphthaleneacetic acid (NAA, 0.5 mg 1−1) produced somatic embryos in culture. Somatic embryos germinated and converted into plantlets in N6-benzyladenine (BAP, 0.75 mg 1−l) added medium following a treatment with thidiazuron (TDZ, 1.0 mg 1−l) for maturation. Scanning electron microscopy showed early stages of somatic embryo particularly, globular types, and was in masses. Different developing stages of embryogenesis (heart, torpedo and cotyledonary) were observed under histological preparation of embryogenic callus. Biochemical screening at various stages of somatic embryogenesis (embryogenic callus, somatic embryos, matured, germinated embryos and converted plantlets) of date palm cultivars has been conducted and discussed in detail. The result discussed in this paper indicates that somatic embryos were produced in numbers and converted plantlets can be used as a good source of alternative propagation. Genetic modification to the embryo precursor cell may improve the fruit quality and yield further. PMID:23961149

Simultaneous Silencing of Two Arginine Decarboxylase Genes Alters Development in Arabidopsis

PubMed Central

Sánchez-Rangel, Diana; Chávez-Martínez, Ana I.; Rodríguez-Hernández, Aída A.; Maruri-López, Israel; Urano, Kaoru; Shinozaki, Kazuo; Jiménez-Bremont, Juan F.

2016-01-01

Polyamines (PAs) are small aliphatic polycations that are found ubiquitously in all organisms. In plants, PAs are involved in diverse biological processes such as growth, development, and stress responses. In Arabidopsis thaliana, the arginine decarboxylase enzymes (ADC1 and 2) catalyze the first step of PA biosynthesis. For a better understanding of PA biological functions, mutants in PA biosynthesis have been generated; however, the double adc1/adc2 mutant is not viable in A. thaliana. In this study, we generated non-lethal A. thaliana lines through an artificial microRNA that simultaneously silenced the two ADC genes (amiR:ADC). The generated transgenic lines (amiR:ADC-L1 and -L2) showed reduced AtADC1 and AtADC2 transcript levels. For further analyses the amiR:ADC-L2 line was selected. We found that the amiR:ADC-L2 line showed a significant decrease of their PA levels. The co-silencing revealed a stunted growth in A. thaliana seedlings, plantlets and delay in its flowering rate; these phenotypes were reverted with PA treatment. In addition, amiR:ADC-L2 plants displayed two seed phenotypes, such as yellow and brownish seeds. The yellow mutant seeds were smaller than adc1, adc2 mutants and wild type seeds; however, the brownish were the smallest seeds with arrested embryos at the torpedo stage. These data reinforce the importance of PA homeostasis in the plant development processes. PMID:27014322

Fatigue and Muscle Atrophy in a Mouse Model of Myasthenia Gravis Is Paralleled by Loss of Sarcolemmal nNOS

PubMed Central

Meinen, Sarina; Lin, Shuo; Rüegg, Markus A.; Punga, Anna Rostedt

2012-01-01

Myasthenia Gravis (MG) patients suffer from chronic fatigue of skeletal muscles, even after initiation of proper immunosuppressive medication. Since the localization of neuronal nitric oxide synthase (nNOS) at the muscle membrane is important for sustained muscle contraction, we here study the localization of nNOS in muscles from mice with acetylcholine receptor antibody seropositive (AChR+) experimental autoimmune MG (EAMG). EAMG was induced in 8 week-old male mice by immunization with AChRs purified from torpedo californica. Sham-injected wild type mice and mdx mice, a model for Duchenne muscular dystrophy, were used for comparison. At EAMG disease grade 3 (severe myasthenic weakness), the triceps, sternomastoid and masseter muscles were collected for analysis. Unlike in mdx muscles, total nNOS expression as well as the presence of its binding partner syntrophin α-1, were not altered in EAMG. Immunohistological and biochemical analysis showed that nNOS was lost from the muscle membrane and accumulated in the cytosol, which is likely the consequence of blocked neuromuscular transmission. Atrophy of all examined EAMG muscles were supported by up-regulated transcript levels of the atrogenes atrogin-1 and MuRF1, as well as MuRF1 protein, in combination with reduced muscle fiber diameters. We propose that loss of sarcolemmal nNOS provides an additional mechanism for the chronic muscle fatigue and secondary muscle atrophy in EAMG and MG. PMID:22952904

Loss of Mitochondrial Malate Dehydrogenase Activity Alters Seed Metabolism Impairing Seed Maturation and Post-Germination Growth in Arabidopsis1[OPEN

PubMed Central

2016-01-01

Mitochondrial malate dehydrogenase (mMDH; EC 1.1.1.37) has multiple roles; the most commonly described is its catalysis of the interconversion of malate and oxaloacetate in the tricarboxylic acid cycle. The roles of mMDH in Arabidopsis (Arabidopsis thaliana) seed development and germination were investigated in mMDH1 and mMDH2 double knockout plants. A significant proportion of mmdh1mmdh2 seeds were nonviable and developed only to torpedo-shaped embryos, indicative of arrested seed embryo growth during embryogenesis. The viable mmdh1mmdh2 seeds had an impaired maturation process that led to slow germination rates as well as retarded post-germination growth, shorter root length, and decreased root biomass. During seed development, mmdh1mmdh2 showed a paler green phenotype than the wild type and exhibited deficiencies in reserve accumulation and reduced final seed biomass. The respiration rate of mmdh1mmdh2 seeds was significantly elevated throughout their maturation, consistent with the previously reported higher respiration rate in mmdh1mmdh2 leaves. Mutant seeds showed a consistently higher content of free amino acids (branched-chain amino acids, alanine, serine, glycine, proline, and threonine), differences in sugar and sugar phosphate levels, and lower content of 2-oxoglutarate. Seed-aging assays showed that quiescent mmdh1mmdh2 seeds lost viability more than 3 times faster than wild-type seeds. Together, these data show the important role of mMDH in the earliest phases of the life cycle of Arabidopsis. PMID:27208265

Tetronarce cowleyi, sp. nov., a new species of electric ray from southern Africa (Chondrichthyes: Torpediniformes: Torpedinidae).

PubMed

Ebert, David A; Haas, Diane L; De Carvalho, Marcelo R

2015-03-19

A new species of torpedo ray, Tetronarce cowleyi, sp. nov., is described from specimens collected from the southeastern Atlantic Ocean. The new species is placed in the genus Tetronarce based on a uniform dorsal coloration and absence of papillae around the spiracles. The new species is distinguished from its closest congeners, the North Atlantic Tetronarce nobiliana Bonnaparte, 1835, and southwestern Atlantic Tetronarce puelcha Lahille, 1926, by a combination of morphological characteristics including a shorter spiracular length, a proportionally greater head length as measured between snout margin and fifth gill openings, a proportionally greater preoral snout length, a uniform shiny black or dark gray dorsal surface, lacking any prominent markings, and a creamy white ventral color with dark edges in juveniles but fading with growth. Teteronarce cowleyi, sp. nov., is further distinguished from T. nobiliana by its more circular anterior disc shape (vs. relatively straight in T. nobiliana), fewer tooth rows (32/28 vs. 38-53/38-52 in T. nobiliana), greater mouth width (1.5-1.7 times as great as interorbital width vs. 0.5-0.6 times interorbital width in T. nobiliana), smaller distance between second dorsal and caudal fins (3.5-4.9% vs. 6.6-6.8% in T. nobiliana), and a clasper length extending nearly to lower caudal fin origin (claspers in T. nobiliana that extend only two-thirds distance between second dorsal and caudal fins). Teteronarce cowleyi, sp. nov., is known from Walvis Bay, Namibia to Algoa Bay, Eastern Cape, South Africa, at depths of 110 to 457 m.

Is the Fungus Magnaporthe Losing DNA Methylation?

PubMed Central

Ikeda, Ken-ichi; Van Vu, Ba; Kadotani, Naoki; Tanaka, Masaki; Murata, Toshiki; Shiina, Kohta; Chuma, Izumi; Tosa, Yukio; Nakayashiki, Hitoshi

2013-01-01

The long terminal repeat retrotransposon, Magnaporthe gypsy-like element (MAGGY), has been shown to be targeted for cytosine methylation in a subset of Magnaporthe oryzae field isolates. Analysis of the F1 progeny from a genetic cross between methylation-proficient (Br48) and methylation-deficient (GFSI1-7-2) isolates revealed that methylation of the MAGGY element was governed by a single dominant gene. Positional cloning followed by gene disruption and complementation experiments revealed that the responsible gene was the DNA methyltransferase, MoDMT1, an ortholog of Neurospora crassa Dim-2. A survey of MAGGY methylation in 60 Magnaporthe field isolates revealed that 42 isolates from rice, common millet, wheat, finger millet, and buffelgrass were methylation proficient while 18 isolates from foxtail millet, green bristlegrass, Japanese panicgrass, torpedo grass, Guinea grass, and crabgrass were methylation deficient. Phenotypic analyses showed that MoDMT1 plays no major role in development and pathogenicity of the fungus. Quantitative polymerase chain reaction analysis showed that the average copy number of genomic MAGGY elements was not significantly different between methylation-deficient and -proficient field isolates even though the levels of MAGGY transcript were generally higher in the former group. MoDMT1 gene sequences in the methylation-deficient isolates suggested that at least three independent mutations were responsible for the loss of MoDMT1 function. Overall, our data suggest that MoDMT1 is not essential for the natural life cycle of the fungus and raise the possibility that the genus Magnaporthe may be losing the mechanism of DNA methylation on the evolutionary time scale. PMID:23979580

Seismic Observation of the 26 March 2010 Sinking of the South Korean Naval Vessel Cheonanham

NASA Astrophysics Data System (ADS)

Rhee, S.; Hong, T.

2011-12-01

A South Korean naval vessel, Cheonanham, sank at ~2.5 km southwest from Bakryeong Island (37.929°N, 124.601°E) in 21:22 local time (12:22 UTC) on 26 March 2010. Only 58 people out of the 104 crew members were rescued from the incident, and the other 46 sailors were dead or missing in the incident. Three plausible causes of the sinking were raised: (1) striking by an explosive source (torpedo or mine), (2) shear breakage due to strain accumulation by fatigue, and (3) collision with a sunken rock. The incident was recorded as an M1.5 event at local seismic stations. We analyze local seismic records and investigate the source properties. The event location is determined not only by a usual location method, but also using low-frequency horizontal polarization analysis. The determined event location agrees with the reported sinking location. The S-wave amplitudes are found to be comparable to the P-wave amplitudes. Seismic waves coupled from shock waves are observed, which allows us to constrain the epicentral distance and explosion-source feature. The coupled shock waves have a dominant frequency of ~32 Hz. The shock waves and high P/S amplitude ratios suggest an underwater explosion that is responsible for the vessel sinking. The spectral contents of P waves allows us to constrain the source depth in the water. We infer the depth of the explosion in the sea by comparing the observed spectra with synthetic spectra. We compare the seismic features with those from nuclear explosions.

Novel immunotoxin: a fusion protein consisting of gelonin and an acetylcholine receptor fragment as a potential immunotherapeutic agent for the treatment of Myasthenia gravis.

PubMed

Hossann, Martin; Li, Zhuoyu; Shi, Yawei; Kreilinger, Ulrike; Büttner, Jörn; Vogel, Pia D; Yuan, Jingming; Wise, John G; Trommer, Wolfgang E

2006-03-01

In continuation of our attempts for antigen-specific suppression of the immune system [I.L. Urbatsch, R.K.M. Sterz, K. Peper, W.E. Trommer, Eur. J. Immunol. 23(1993) 776-779] a novel fusion protein composed of amino acids 4-181 of the extracellular domain of the alpha-subunit of the human muscle acetylcholine receptor and the plant toxin gelonin was expressed in Escherichia coli. The fusion protein formed inclusion bodies but could be solubilized in the presence of guanidinium hydrochloride. After a simple two step purification and refolding procedure, it exhibited a native structure at least in the main immunogenic region as shown by antibodies recognizing a conformational epitope. Half maximal inhibition of translation was achieved at 46 ng/ml as compared to 4.6 ng/ml for native and 2.4 for recombinant gelonin. Its use as therapeutic agent for the treatment of Myasthenia gravis was investigated in an animal model. Female Lewis rats were immunized with complete acetylcholine receptor from the electric ray Torpedo californica and developed thereafter experimental autoimmune M. gravis. Quantitative assessment of the disease was achieved by repetitive stimulation of the Nervus tibialis. Rats showed no symptoms of M. gravis, neither visually nor electrophysiologically after treatment with the fusion protein as determined one and seven weeks after the second application. This approach may also be useful for the therapy of further autoimmune diseases by substituting other autoantigens for the AchR fragment in the fusion protein.

NMR structure and action on nicotinic acetylcholine receptors of water-soluble domain of human LYNX1.

PubMed

Lyukmanova, Ekaterina N; Shenkarev, Zakhar O; Shulepko, Mikhail A; Mineev, Konstantin S; D'Hoedt, Dieter; Kasheverov, Igor E; Filkin, Sergey Yu; Krivolapova, Alexandra P; Janickova, Helena; Dolezal, Vladimir; Dolgikh, Dmitry A; Arseniev, Alexander S; Bertrand, Daniel; Tsetlin, Victor I; Kirpichnikov, Mikhail P

2011-03-25

Discovery of proteins expressed in the central nervous system sharing the three-finger structure with snake α-neurotoxins provoked much interest to their role in brain functions. Prototoxin LYNX1, having homology both to Ly6 proteins and three-finger neurotoxins, is the first identified member of this family membrane-tethered by a GPI anchor, which considerably complicates in vitro studies. We report for the first time the NMR spatial structure for the water-soluble domain of human LYNX1 lacking a GPI anchor (ws-LYNX1) and its concentration-dependent activity on nicotinic acetylcholine receptors (nAChRs). At 5-30 μM, ws-LYNX1 competed with (125)I-α-bungarotoxin for binding to the acetylcholine-binding proteins (AChBPs) and to Torpedo nAChR. Exposure of Xenopus oocytes expressing α7 nAChRs to 1 μM ws-LYNX1 enhanced the response to acetylcholine, but no effect was detected on α4β2 and α3β2 nAChRs. Increasing ws-LYNX1 concentration to 10 μM caused a modest inhibition of these three nAChR subtypes. A common feature for ws-LYNX1 and LYNX1 is a decrease of nAChR sensitivity to high concentrations of acetylcholine. NMR and functional analysis both demonstrate that ws-LYNX1 is an appropriate model to shed light on the mechanism of LYNX1 action. Computer modeling, based on ws-LYNX1 NMR structure and AChBP x-ray structure, revealed a possible mode of ws-LYNX1 binding.

Ceruleotoxin: identification in the venom of Bungarus fasciatus, molecular properties and importance of phospholipase A2 activity for neurotoxicity.

PubMed

Bon, C; Saliou, B

1983-01-01

Ceruleotoxin is a potent neurotoxin which was originally purified from a batch of venom labelled Bungarus caeruleus, from the Pasteur Institute. Since NOBLE et al. have shown that this batch differs in its protein composition from that of B. caeruleus provided by Miami Serpentarium, we decided to clarify this point by comparing the composition of venoms from various Bungarus species of several origins. Although individual variations exist between samples of the same species, the venom from B. multicinctus, B. caeruleus and B. fasciatus possess characteristic protein compositions which allowed us to identify the batch used to purify ceruleotoxin as a B. fasciatus venom. We identified and purified ceruleotoxin from each of the five samples of B. fasciatus venoms tested. We failed to find this neurotoxin in either B. multicinctus or B. caeruleus venoms. Purified ceruleotoxin is a slightly basic protein with an isoelectric point of 7.4 which possesses a significant phospholipase A2 activity (200 mumoles lecithin hydrolyzed per min per mg) and a high lethal potency (i.v. LD50 in mice 0.03-0.07 mg/kg). It is composed of two identical subunits of 13,000 mol. wt. which resemble pancreas and snake venom phospholipases in their amino acid composition. Like crotoxin, ceruleotoxin irreversibly blocks the postsynaptic response of Torpedo and Electrophorus electroplaques to cholinergic agonists without preventing the binding of acetylcholine to its receptor. By hydrolyzing critical lipids of the postsynaptic membrane, it stabilizes the acetylcholine receptor - ionophore assembly in a desensitized state.

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

Miller, J.V.; Lukas, R.J.; Bennett, E.L.

The agonist binding affinity of nicotinic acetylcholine receptor (nAChR) from Torpedo californica electroplax, as inferred from ability of agonist to inhibit specific curaremimetic neurotoxin binding to nAChR, is sensitive to the duration of exposure to agonist. The concentration of carbachol necessary to prevent one-half of toxin binding over a 30 min incubation with nAChR (K/sub 30/) is 10 ..mu..M when toxin and carbachol are simultaneously added to membrane-bound nAChR, and 3 ..mu..M when nAChR are pretreated with carbachol for 30 min prior to the addition of toxin. These alterations in agonist affinity may be mimicked by modification of nAChR thiolmore » groups. Affinity of nAChR for carbachol is decreased following treatment with dithiothreitol (DTT). Dithio-bis-nitrobenzoic acid treatment of DTT-reduced membranes yields K/sub 30/ values of 5 ..mu..M for carbachol, while N-ethylmaleimide treatment of DTT-reduced nAChR produces nAChR with reduced affinity for carbachol, reflected to K/sub 30/ values of about 400 ..mu..M. In the absence of Ca/sup + +/, K/sub 30/ values for carbachol binding to native and DTT-reduced nAChR are diminished 3 to 6 fold. These affinity alterations are not observed with d-tubocurarine (antagonist) binding to nAChR. Thus, Ca/sup + +/ and the oxidation state of nAChR thiols appear to affect the affinity of nAChR for agonists (but not antagonists), and may therefore be related to agonist-mediated events in receptor activation and/or desensitization.« less

T-cell antigenic sites involved in myasthenia gravis: correlations with antibody titre and disease severity.

PubMed

Berrih-Aknin, S; Cohen-Kaminsky, S; Lepage, V; Neumann, D; Bach, J F; Fuchs, S

1991-02-01

We have evaluated the ability of eight synthetic peptides corresponding to selected regions of the alpha-subunit from human (H) or Torpedo (T) acetylcholine receptor (AChR) to stimulate proliferative responses of peripheral blood lymphocytes (PBL) and thymic cells from patients with Myasthenia Gravis (MG) in comparison to healthy controls. Using PBL, two of the peptides were most reactive: in the 40 myasthenic patients tested, peptide 169-181 (H) induced significant proliferative responses in 10 patients and peptide 351-368 (H) in five, while there was no response in any of the 34 healthy controls tested. Interestingly, clear associations between proliferation to peptides and clinical data were observed. Indeed, among responding patients, all presented thymic hyperplasia and most showed a high anti-AChR Ab titre and/or a severe form of the disease. In addition, responses to AChR cytoplasmic sequences were observed only in severely affected patients. Correlation with HLA-DR haplotype, sought in a subgroup of patients, indicated that response to 169-181 (H) is associated with HLA-DR5 in the patients presenting a high anti-AChR antibody titre. Using thymic lymphocytes, few responses were obtained with the human peptides, suggesting that the frequency of autoreactive cells is lower than in the blood. Similar to PBL, responses to peptides were observed only with lymphocytes isolated from hyperplastic thymuses. The correlations observed between responses to peptides and clinical parameters underline the pathophysiological relevance of our data and indicate that pathogenic and nonpathogenic T-cell antigenic sites involved in the anti-AChR response could be identified by this approach.

Structure-activity relationship of ibogaine analogs interacting with nicotinic acetylcholine receptors in different conformational states.

PubMed

Arias, Hugo R; Feuerbach, Dominik; Targowska-Duda, Katarzyna M; Jozwiak, Krzysztof

2011-09-01

The interaction of ibogaine analogs with nicotinic acetylcholine receptors (AChRs) in different conformational states was studied by functional and structural approaches. The results established that ibogaine analogs: (a) inhibit (±)-epibatidine-induced Ca²⁺ influx in human embryonic muscle AChRs with the following potency sequence (IC(50) in μM): (±)-18-methylaminocoronaridine (5.9±0.3)∼(±)-18-methoxycoronaridine (18-MC) (6.8±0.8)>(-)-ibogaine (17±3)∼(+)-catharanthine (20±1)>(±)-albifloranine (46±13), (b) bind to the [³H]TCP binding site with higher affinity when the Torpedo AChR is in the desensitized state compared to that in the resting state. Similar results were obtained using [³H]18-MC. These and docking results suggest a steric interaction between TCP and ibogaine analogs for the same site, (c) enhance [³H]cytisine binding to resting but not to desensitized AChRs, with desensitizing potencies (apparent EC₅₀) that correlate very well with the pK(i) values in the desensitized state, and (d) there are good bilinear correlations between the ligand molecular volumes and their affinities in the desensitized and resting states, with an optimal volume of ∼345 ų for the ibogaine site. These results indicate that the size of the binding sites for ibogaine analogs, located between the serine and nonpolar rings and shared with TCP, is an important structural feature for binding and for inducing desensitization. Copyright © 2011 Elsevier Ltd. All rights reserved.

Homologous kappa-neurotoxins exhibit residue-specific interactions with the alpha 3 subunit of the nicotinic acetylcholine receptor: a comparison of the structural requirements for kappa-bungarotoxin and kappa-flavitoxin binding.

PubMed

McLane, K E; Weaver, W R; Lei, S; Chiappinelli, V A; Conti-Tronconi, B M

1993-07-13

kappa-Flavotoxin (kappa-FTX), a snake neurotoxin that is a selective antagonist of certain neuronal nicotinic acetylcholine receptors (AChRs), has recently been isolated and characterized [Grant, G. A., Frazier, M. W., & Chiappinelli, V. A. (1988) Biochemistry 27, 1532-1537]. Like the related snake toxin kappa-bungarotoxin (kappa-BTX), kappa-FTX binds with high affinity to alpha 3 subtypes of neuronal AChRs, even though there are distinct sequence differences between the two toxins. To further characterize the sequence regions of the neuronal AChR alpha 3 subunit involved in formation of the binding site for this family of kappa-neurotoxins, we investigated kappa-FTX binding to overlapping synthetic peptides screening the alpha 3 subunit sequence. A sequence region forming a "prototope" for kappa-FTX was identified within residues alpha 3 (51-70), confirming the suggestions of previous studies on the binding of kappa-BTX to the alpha 3 subunit [McLane, K. E., Tang, F., & Conti-Tronconi, B. M. (1990) J. Biol. Chem. 265, 1537-1544] and alpha-bungarotoxin to the Torpedo AChR alpha subunit [Conti-Tronconi, B. M., Tang, F., Diethelm, B. M., Spencer, S. R., Reinhardt-Maelicke, S., & Maelicke, A. (1990) Biochemistry 29, 6221-6230] that this sequence region is involved in formation of a cholinergic site. Single residue substituted analogues, where each residue of the sequence alpha 3 (51-70) was sequentially replaced by a glycine, were used to identify the amino acid side chains involved in the interaction of this prototope with kappa-FTX.(ABSTRACT TRUNCATED AT 250 WORDS)

Mechanism behind Resistance against the Organophosphate Azamethiphos in Salmon Lice (Lepeophtheirus salmonis)

PubMed Central

Kaur, Kiranpreet; Helgesen, Kari Olli; Bakke, Marit Jørgensen; Horsberg, Tor Einar

2015-01-01

Acetylcholinesterase (AChE) is the primary target for organophosphates (OP). Several mutations have been reported in AChE to be associated with the reduced sensitivity against OP in various arthropods. However, to the best of our knowledge, no such reports are available for Lepeophtheirus salmonis. Hence, in the present study, we aimed to determine the association of AChE(s) gene(s) with resistance against OP. We screened the AChE genes (L. salmonis ace1a and ace1b) in two salmon lice populations: one sensitive (n=5) and the other resistant (n=5) for azamethiphos, a commonly used OP in salmon farming. The screening led to the identification of a missense mutation Phe362Tyr in L. salmonis ace1a, (corresponding to Phe331 in Torpedo californica AChE) in all the samples of the resistant population. We confirmed the potential role of the mutation, with reduced sensitivity against azamethiphos in L. salmonis, by screening for Phe362Tyr in 2 sensitive and 5 resistant strains. The significantly higher frequency of the mutant allele (362Tyr) in the resistant strains clearly indicated the possible association of Phe362Tyr mutation in L. salmonis ace1a with resistance towards azamethiphos. The 3D modelling, short term survival experiments and enzymatic assays further supported the imperative role of Phe362Tyr in reduced sensitivity of L. salmonis for azamethiphos. Based on all these observations, the present study, for the first time, presents the mechanism of resistance in L. salmonis against azamethiphos. In addition, we developed a rapid diagnostic tool for the high throughput screening of Phe362Tyr mutation using High Resolution Melt analysis. PMID:25893248

Identification of amino acids in the nicotinic acetylcholine receptor agonist binding site and ion channel photolabeled by 4-[(3-trifluoromethyl)-3H-diazirin-3-yl]benzoylcholine, a novel photoaffinity antagonist.

PubMed

Chiara, David C; Trinidad, Jonathan C; Wang, Dong; Ziebell, Michael R; Sullivan, Deirdre; Cohen, Jonathan B

2003-01-21

[(3)H]4-[(3-trifluoromethyl)-3H-diazirin-3-yl]benzoylcholine (TDBzcholine) was synthesized and used as a photoaffinity probe to map the orientation of an aromatic choline ester within the agonist binding sites of the Torpedo nicotinic acetylcholine receptor (nAChR). TDBzcholine acts as a nAChR competitive antagonist that binds at equilibrium with equal affinity to both agonist sites (K(D) approximately 10 microM). Upon UV irradiation (350 nm), nAChR-rich membranes equilibrated with [(3)H]TDBzcholine incorporate (3)H into the alpha, gamma, and delta subunits in an agonist-inhibitable manner. The specific residues labeled by [(3)H]TDBzcholine were determined by N-terminal sequence analysis of subunit fragments produced by enzymatic cleavage and purified by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and/or reversed-phase high-performance liquid chromatography. For the alpha subunit, [(3)H]TDBzcholine photoincorporated into alphaCys-192, alphaCys-193, and alphaPro-194. For the gamma and delta subunits, [(3)H]TDBzcholine incorporated into homologous leucine residues, gammaLeu-109 and deltaLeu-111. The photolabeling of these amino acids suggests that when the antagonist TDBzcholine occupies the agonist binding sites, the Cys-192-193 disulfide and Pro-194 from the alpha subunit Segment C are oriented toward the agonist site and are in proximity to gammaLeu-109/deltaLeu-111 in Segment E, a conclusion consistent with the structure of the binding site in the molluscan acetylcholine binding protein, a soluble protein that is homologous to the nAChR extracellular domain.

Linking Essential Tremor to the Cerebellum: Neuropathological Evidence.

PubMed

Louis, Elan D

2016-06-01

A fundamental question about essential tremor (ET) is whether its associated pathological changes and disease mechanisms are linkable to a specific brain region. To that end, recent tissue-based studies have made significant strides in elucidating changes in the ET brain. Emerging from these studies is increasing neuropathological evidence linking ET to the cerebellum. These studies have systematically identified a broad range of structural, degenerative changes in the ET cerebellum, spanning across all Purkinje cell compartments. These include the dendritic compartment (where there is an increase in number of Purkinje cell dendritic swellings, a pruning of the dendritic arbor, and a reduction in spine density), the cell body (where, aside from reductions in Purkinje cell linear density in some studies, there is an increase in the number of heterotopic Purkinje cell soma), and the axonal compartment (where a plethora of changes in axonal morphology have been observed, including an increase in the number of thickened axonal profiles, torpedoes, axonal recurrent collaterals, axonal branching, and terminal axonal sprouting). Additional changes, possibly due to secondary remodeling, have been observed in neighboring neuronal populations. These include a hypertrophy of basket cell axonal processes and changes in the distribution of climbing fiber-Purkinje cell synapses. These changes all distinguish ET from normal control brains. Initial studies further indicate that the profile (i.e., constellation) of these changes may separate ET from other diseases of the cerebellum, thereby serving as a disease signature. With the discovery of these changes, a new model of ET has arisen, which posits that it may be a neurodegenerative disorder centered in the cerebellar cortex. These newly emerging neuropathological studies pave the way for anatomically focused, hypothesis-driven, molecular mechanistic studies of disease pathogenesis.

Cleanup/stimulation of a horizontal wellbore using propellants

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

Rougeot, J.E.; Lauterbach, K.A.

1993-01-01

This report documents the stimulation/cleanup of a horizontal well bore (Wilson 25) using propellants. The Wilson 25 is a Bartlesville Sand well located in the Flatrock Field, Osage County, Oklahoma. The Wilson 25 was drilled to determine if horizontal drilling could be used as a means to economically recover primary oil that had been left in place in a mostly abandoned oil field because of the adverse effects of water coning. Pump testing of the Wilson 25 horizontal well bore before cleanup or stimulation produced 6 barrels of oil and .84 barrels of water per day. The high percentage ofmore » daily oil production to total daily fluid production indicated that the horizontal well bore had accessed potentially economical oil reserves if the fluid production rate could be increased by performing a cleanup/stimulation treatment. Propellants were selected as an inexpensive means to stimulate and cleanup the near well bore area in a uniform manner. The ignition of a propellant creates a large volume of gas which penetrates the formation, creating numerous short cracks through which hydrocarbons can travel into the well bore. More conventional stimulation/cleanup techniques were either significantly more expensive, less likely to treat uniformly, or could not be confined to the near well bore area. Three different propellant torpedo designs were tested with a total of 304' of horizontal well bore being shot and producible. The initial test shot caused 400' of the horizontal well bore to become plugged off, and subsequently it could not be production tested. The second and third test shots were production tested, with the oil production being increased 458% and 349%, respectively, on a per foot basis. The Wilson 25 results indicate that a propellant shot treatment is an economically viable means to cleanup/stimulate a horizontal well bore.« less

Kinetics of Huperzine A Dissociation from Acetylcholinesterase via Multiple Unbinding Pathways.

PubMed

Rydzewski, J; Jakubowski, R; Nowak, W; Grubmüller, H

2018-06-12

The dissociation of huperzine A (hupA) from Torpedo californica acetylcholinesterase ( TcAChE) was investigated by 4 μs unbiased and biased all-atom molecular dynamics (MD) simulations in explicit solvent. We performed our study using memetic sampling (MS) for the determination of reaction pathways (RPs), metadynamics to calculate free energy, and maximum-likelihood estimation (MLE) to recover kinetic rates from unbiased MD simulations. Our simulations suggest that the dissociation of hupA occurs mainly via two RPs: a front door along the axis of the active-site gorge (pwf) and through a new transient side door (pws), i.e., formed by the Ω-loop (residues 67-94 of TcAChE). An analysis of the inhibitor unbinding along the RPs suggests that pws is opened transiently after hupA and the Ω-loop reach a low free-energy transition state characterized by the orientation of the pyridone group of the inhibitor directed toward the Ω-loop plane. Unlike pws, pwf does not require large structural changes in TcAChE to be accessible. The estimated free energies and rates agree well with available experimental data. The dissociation rates along the unbinding pathways are similar, suggesting that the dissociation of hupA along pws is likely to be relevant. This indicates that perturbations to hupA- TcAChE interactions could potentially induce pathway hopping. In summary, our results characterize the slow-onset inhibition of TcAChE by hupA, which may provide the structural and energetic bases for the rational design of the next-generation slow-onset inhibitors with optimized pharmacokinetic properties for the treatment of Alzheimer's disease.

Advanced Modular "All in One" Battery System with Intelligent Autonomous Cell Balancing Management

NASA Astrophysics Data System (ADS)

Petitdidier, X.; Pasquier, E.; Defer, M.; Koch, M.; Knorr, W.

2008-09-01

A new generation of energy storage systems based on Li-ion technology emerged at the end of the last century.To perform the first tests in safe conditions, Saft designed a simple electronic.Today, all Li-ion batteries for autonomous applications such as drones, launchers, missiles, torpedoes and "human" applications such as cellular, laptop, hybrid vehicle and nearly sub-marines need a Battery Management System.The minimum in terms of functions is the overcharge and over-discharge protections.For a battery made of 2 cells connected in series or more, a balancing system is added to maintain the available energy during all the life of the battery. For stringent/demanding applications, the state of charge and state of health are calculated by one or more computers.It is now time to take benefit of the past 10 years of Saft's experience in the domain to re-evaluate the constraints of Li-ion batteries and provide customers with improved products by optimizing the battery management.Benefits of electronic for satellite applications:• Full control over battery.• Confidence whatever the possible change of conditions in environment.• The battery system can resist long exposure to gradient conditions with mitigated and stabilized impact on performances.• The balancing function allow to use all the energy of all the cells: optimize of installed energy (compact design, mass saving). It started out with the basic fact that electrochemists are not intended to be space rated electronic experts and vice versa, even if Saft has a good heritage in the electronic battery management system. Consequently, considering heritage and expertise in their respective core businesses, Saft and ASP teamed up.It became necessary to provide an "all in one" modular energy storage system with intelligent autonomous cell balancing management.

Alexander von Humboldt: galvanism, animal electricity, and self-experimentation part 2: the electric eel, animal electricity, and later years.

PubMed

Finger, Stanley; Piccolino, Marco; Stahnisch, Frank W

2013-01-01

After extensive experimentation during the 1790s, Alexander von Humboldt remained skeptical about "animal electricity" (and metallic electricity), writing instead about an ill-defined galvanic force. With his worldview and wishing to learn more, he studied electric eels in South America just as the new century began, again using his body as a scientific instrument in many of his experiments. As had been the case in the past and for many of the same reasons, some of his findings with the electric eel (and soon after, Italian torpedoes) seemed to argue against biological electricity. But he no longer used galvanic terminology when describing his electric fish experiments. The fact that he now wrote about animal electricity rather than a different "galvanic" force owed much to Alessandro Volta, who had come forth with his "pile" (battery) for multipling the physical and perceptable effects of otherwise weak electricity in 1800, while Humboldt was deep in South America. Humboldt probably read about and saw voltaic batteries in the United States in 1804, but the time he spent with Volta in 1805 was probably more significant in his conversion from a galvanic to an electrical framework for understanding nerve and muscle physiology. Although he did not continue his animal electricity research program after this time, Humboldt retained his worldview of a unified nature and continued to believe in intrinsic animal electricity. He also served as a patron to some of the most important figures in the new field of electrophysiology (e.g., Hermann Helmholtz and Emil du Bois-Reymond), helping to take the research that he had participated in to the next level.

Nicotinic acetylcholine receptor probed with a photoactivatable agonist: improved labeling specificity by addition of CeIV/glutathione. Extension to laser flash photolabeling.

PubMed

Grutter, T; Goeldner, M; Kotzyba-Hibert, F

1999-06-08

The molecular structure of Torpedo marmorata acetylcholine binding sites has been investigated previously by photoaffinity labeling. However, besides the nicotine molecule [Middleton et al. (1991) Biochemistry 30, 6987-6997], all other photosensitive probes used for this purpose interacted only with closed receptor states. In the perspective of mapping the functional activated state, we synthesized and developed a new photoactivatable agonist of nAChR capable of alkylation of the acetylcholine (ACh) binding sites, as reported previously [Kotzyba-Hibert et al. (1997) Bioconjugate Chem. 8, 472-480]. Here, we describe the setup of experimental conditions that were made in order to optimize the photolabeling reaction and in particular its specificity. We found that subsequent addition of the oxidant ceric ion (CeIV) and reduced glutathione before the photolabeling step lowered considerably nonspecific labeling (over 90% protection with d-tubocurarine) without affecting the binding properties of the ACh binding sites. As a consequence, irradiation at 360 nm for 20 min in these new conditions gave satisfactory coupling yields (7.5%). A general mechanism was proposed to explain the successive reactions occurring and their drastic effect on the specificity of the labeling reaction. Last, these incubation conditions can be extended to nanosecond pulsed laser photolysis leading to the same specific photoincorporation as for usual irradiations (8.5% coupling yield of ACh binding sites, 77% protection with carbamylcholine). Laser flash photocoupling of a diazocyclohexadienoyl probe on nAChR was achieved for the first time. Taken together, these data indicate that future investigation of the molecular dynamics of allosteric transitions occurring at the activated ACh binding sites should be possible.

Navy Applications of High-Frequency Acoustics

NASA Astrophysics Data System (ADS)

Cox, Henry

2004-11-01

Although the emphasis in underwater acoustics for the last few decades has been in low-frequency acoustics, motivated by long range detection of submarines, there has been a continuing use of high-frequency acoustics in traditional specialized applications such as bottom mapping, mine hunting, torpedo homing and under ice navigation. The attractive characteristics of high-frequency sonar, high spatial resolution, wide bandwidth, small size and relatively low cost must be balanced against the severe range limitation imposed by attenuation that increases approximately as frequency-squared. Many commercial applications of acoustics are ideally served by high-frequency active systems. The small size and low cost, coupled with the revolution in small powerful signal processing hardware has led to the consideration of more sophisticated systems. Driven by commercial applications, there are currently available several commercial-off-the-shelf products including acoustic modems for underwater communication, multi-beam fathometers, side scan sonars for bottom mapping, and even synthetic aperture side scan sonar. Much of the work in high frequency sonar today continues to be focused on specialized applications in which the application is emphasized over the underlying acoustics. Today's vision for the Navy of the future involves Autonomous Undersea Vehicles (AUVs) and off-board ASW sensors. High-frequency acoustics will play a central role in the fulfillment of this vision as a means of communication and as a sensor. The acoustic communication problems for moving AUVs and deep sensors are discussed. Explicit relationships are derived between the communication theoretic description of channel parameters in terms of time and Doppler spreads and ocean acoustic parameters, group velocities, phase velocities and horizontal wavenumbers. Finally the application of synthetic aperture sonar to the mine hunting problems is described.

Bivalent ligands derived from Huperzine A as acetylcholinesterase inhibitors.

PubMed

Haviv, H; Wong, D M; Silman, I; Sussman, J L

2007-01-01

The naturally occurring alkaloid Huperzine A (HupA) is an acetylcholinesterase (AChE) inhibitor that has been used for centuries as a Chinese folk medicine in the context of its source plant Huperzia Serrata. The potency and relative safety of HupA rendered it a promising drug for the ameliorative treatment of Alzheimer's disease (AD) vis-à-vis the "cholinergic hypothesis" that attributes the cognitive decrements associated with AD to acetylcholine deficiency in the brain. However, recent evidence supports a neuroprotective role for HupA, suggesting that it could act as more than a mere palliative. Biochemical and crystallographic studies of AChE revealed two potential binding sites in the active-site gorge of AChE, one of which, the "peripheral anionic site" at the mouth of the gorge, was implicated in promoting aggregation of the beta amyloid (Abeta) peptide responsible for the neurodegenerative process in AD. This feature of AChE facilitated the development of dual-site binding HupA-based bivalent ligands, in hopes of concomitantly increasing AChE inhibition potency by utilizing the "chelate effect", and protecting neurons from Abeta toxicity. Crystal structures of AChE allowed detailed modeling and docking studies that were instrumental in enhancing the understanding of underlying principles of bivalent inhibitor-enzyme dynamics. This monograph reviews two categories of HupA-based bivalent ligands, in which HupA and HupA fragments serve as building blocks, with a focus on the recently solved crystallographic structures of Torpedo californica AChE in complex with such bifunctional agents. The advantages and drawbacks of such structured-based drug design, as well as species differences, are highlighted and discussed.

New insights into roles of cell wall invertase in early seed development revealed by comprehensive spatial and temporal expression patterns of GhCWIN1 in cotton.

PubMed

Wang, Lu; Ruan, Yong-Ling

2012-10-01

Despite substantial evidence on the essential roles of cell wall invertase (CWIN) in seed filling, it remains largely unknown how CWIN exerts its regulation early in seed development, a critical stage that sets yield potential. To fill this knowledge gap, we systematically examined the spatial and temporal expression patterns of a major CWIN gene, GhCWIN1, in cotton (Gossypium hirsutum) seeds from prefertilization to prestorage phase. GhCWIN1 messenger RNA was abundant at the innermost seed coat cell layer at 5 d after anthesis but became undetectable at 10 d after anthesis, at the onset of its differentiation into transfer cells characterized by wall ingrowths, suggesting that CWIN may negatively regulate transfer cell differentiation. Within the filial tissues, GhCWIN1 transcript was detected in endosperm cells undergoing nuclear division but not in those cells at the cellularization stage, with similar results observed in Arabidopsis (Arabidopsis thaliana) endosperm for CWIN, AtCWIN4. These findings indicate a function of CWIN in nuclear division but not cell wall biosynthesis in endosperm, contrasting to the role proposed for sucrose synthase (Sus). Further analyses revealed a preferential expression pattern of GhCWIN1 and AtCWIN4 in the provascular region of the torpedo embryos in cotton and Arabidopsis seed, respectively, indicating a role of CWIN in vascular initiation. Together, these novel findings provide insights into the roles of CWIN in regulating early seed development spatially and temporally. By comparing with previous studies on Sus expression and in conjunction with the expression of other related genes, we propose models of CWIN- and Sus-mediated regulation of early seed development.

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.

The Minimum M3-M4 Loop Length of Neurotransmitter-activated Pentameric Receptors Is Critical for the Structural Integrity of Cytoplasmic Portals*

PubMed Central

Baptista-Hon, Daniel T.; Deeb, Tarek Z.; Lambert, Jeremy J.; Peters, John A.; Hales, Tim G.

2013-01-01

The 5-HT3A receptor homology model, based on the partial structure of the nicotinic acetylcholine receptor from Torpedo marmorata, reveals an asymmetric ion channel with five portals framed by adjacent helical amphipathic (HA) stretches within the 114-residue loop between the M3 and M4 membrane-spanning domains. The positive charge of Arg-436, located within the HA stretch, is a rate-limiting determinant of single channel conductance (γ). Further analysis reveals that positive charge and volume of residue 436 are determinants of 5-HT3A receptor inward rectification, exposing an additional role for portals. A structurally unresolved stretch of 85 residues constitutes the bulk of the M3-M4 loop, leaving a >45-Å gap in the model between M3 and the HA stretch. There are no additional structural data for this loop, which is vestigial in bacterial pentameric ligand-gated ion channels and was largely removed for crystallization of the Caenorhabditis elegans glutamate-activated pentameric ligand-gated ion channels. We created 5-HT3A subunit loop truncation mutants, in which sequences framing the putative portals were retained, to determine the minimum number of residues required to maintain their functional integrity. Truncation to between 90 and 75 amino acids produced 5-HT3A receptors with unaltered rectification. Truncation to 70 residues abolished rectification and increased γ. These findings reveal a critical M3-M4 loop length required for functions attributable to cytoplasmic portals. Examination of all 44 subunits of the human neurotransmitter-activated Cys-loop receptors reveals that, despite considerable variability in their sequences and lengths, all M3-M4 loops exceed 70 residues, suggesting a fundamental requirement for portal integrity. PMID:23740249

Different glycosylation in acetylcholinesterases from mammalian brain and erythrocytes.

PubMed

Liao, J; Heider, H; Sun, M C; Brodbeck, U

1992-04-01

Acetylcholinesterases (EC 3.1.1.7, AChE) have varying amounts of carbohydrates attached to the core protein. Sequence analysis of the known primary structures gives evidence for several asparagine-linked carbohydrates. From the differences in molecular mass determined on sodium dodecyl sulfate-polyacrylamide gel before and after deglycosylation with N-glycosidase F (EC 3.2.2.18), it is seen that dimeric AChE from red cell membranes is more heavily glycosylated than the tetrameric brain enzyme. Furthermore, dimeric and tetrameric forms of bovine AChE are more heavily glycosylated than the corresponding human enzymes. Monoclonal antibodies 2E6, 1H11, and 2G8 raised against detergent-soluble AChE from electric organs of Torpedo nacline timilei as well as Elec-39 raised against AChE from Electrophorus electricus cross-reacted with AChE from bovine and human brain but not with AChE from erythrocytes. Treatment of the enzyme with N-glycosidase F abolished binding of monoclonal antibodies, suggesting that the epitope, or part of it, consists of N-linked carbohydrates. Analysis of N-acetylglucosamine sugars revealed the presence of N-acetylglucosamine in all forms of cholinesterases investigated, giving evidence for N-linked glycosylation. On the other hand, N-acetylgalactosamine was not found in AChE from human and bovine brain or in butyrylcholinesterase (EC 3.1.1.8) from human serum, indicating that these forms of cholinesterase did not contain O-linked carbohydrates. Despite the notion that within one species, the different forms of AChE arise from one gene by different splicing, our present results show that dimeric erythrocyte and tetrameric brain AChE must undergo different postsynthetic modifications leading to differences in their glycosylation patterns.

Metabolite profiling of somatic embryos of Cyclamen persicum in comparison to zygotic embryos, endosperm, and testa

PubMed Central

Winkelmann, Traud; Ratjens, Svenja; Bartsch, Melanie; Rode, Christina; Niehaus, Karsten; Bednarz, Hanna

2015-01-01

Somatic embryogenesis has been shown to be an efficient in vitro plant regeneration system for many crops such as the important ornamental plant Cyclamen persicum, for which this regeneration pathway of somatic embryogenesis is of interest for the vegetative propagation of parental lines as well as elite plants. However, somatic embryogenesis is not commercially used in many crops due to several unsolved problems, such as malformations, asynchronous development, deficiencies in maturation and germination of somatic embryos. In contrast, zygotic embryos in seeds develop and germinate without abnormalities in most cases. Instead of time-consuming and labor-intensive experiments involving tests of different in vitro culture conditions and plant growth regulator supplements, we follow a more directed approach. Zygotic embryos served as a reference and were compared to somatic embryos in metabolomic analyses allowing the future optimization of the in vitro system. The aims of this study were to detect differences in the metabolite profiles of torpedo stage somatic and zygotic embryos of C. persicum. Moreover, major metabolites in endosperm and testa were identified and quantified. Two sets of extracts of two to four biological replicates each were analyzed. In total 52 metabolites were identified and quantified in the different tissues. One of the most significant differences between somatic and zygotic embryos was that the proline concentration in the zygotic embryos was about 40 times higher than that found in somatic embryos. Epicatechin, a scavenger for reactive oxygen species, was found in highest abundance in the testa. Sucrose, the most abundant metabolite was detected in significantly higher concentrations in zygotic embryos. Also, a yet unknown trisaccharide, was significantly enriched in zygotic embryos. PMID:26300898

Global patterns and clines in the growth of common carp Cyprinus carpio.

PubMed

Vilizzi, L; Copp, G H

2017-07-01

This review provides a meta-analytical assessment of the global patterns and clines in the growth of Cyprinus carpio as measured by length-at-age (L t ) or von Bertalanffy growth function (VBGF) parameters, mass-length relationship (W-L t ) and condition factor, based on literature data. In total, 284 studies were retrieved spanning 91 years of research and carried out on 381 waterbodies-locations in 50 countries in all five continents. Although native C. carpio achieved larger (asymptotic) size relative to its non-native counterpart, the latter grew faster during the first 7 years of life. Lentic populations (especially in natural lakes) also achieved larger sizes relative to lotic ones and the same was true for populations in cold and temperate v. arid climates. Unlike previous studies (on much more restricted datasets), only weak latitudinal clines in instantaneous growth rate, L t at age 3 and mortality were observed globally and this was probably due to the presence of counter-gradient growth variation at all representative age classes (i.e. 1-10 years). Slightly negative allometry was revealed by the W-L t and the related form factor tended to distinguish the more elongated and torpedo-shaped body typical of the wild form from the deeper body of feral-domesticated C. carpio. Existing population dynamics models for C. carpio will benefit from the comprehensive range of waterbody type × climate class-specific VBGF parameters provided in the present study; whereas, more studies are needed on the species' growth in tropical regions and to unravel the possibility of confounding effects on age estimation due to both historical and methodological reasons. © 2017 The Fisheries Society of the British Isles.

NACA/NASA test pilot Stanley P. Butchart

NASA Technical Reports Server (NTRS)

1954-01-01

Stanley P. Butchart joined the National Advisory Committee for Aeronautics' High-Speed Flight Research Station on May 10, 1951. Stan was the fourth research pilot hired at the Station affording him the opportunity to fly the early research aircraft. Stan began a flying career while attending Junior College. He received primary and secondary civilian pilot training, enlisting in the U.S. Navy in July 1942. Stan took his Navy air training at Corpus Christi, Texas. Upon completion of training he was assigned to a torpedo-bomber Air Group, VT-51, flying Grumman-General Motors TBM Avenger, a torpedo-bomber, from the carrier San Jacinto in the South Pacific. When World War II ended, Stan was released from active duty as a Navy Lieutenant, with a Distinguished Flying Cross and a Presidential Unit Citation among his service medals. Butchart elected to stay in the Naval Reserve group and flew for an additional 5 years while he attended the University of Washington. By 1950, Stan had earned bachelor degrees in aeronautical engineering and mechanical engineering. After graduation he went to work for Boeing Aircraft as a junior design engineer and was assigned to the B-47 body group. In May 1951, he arrived at the NACA facility to start a career as a research pilot. Stan flew the Douglas D-558-I #3 (12 flights, first on October 19, 1951), the Douglas D-558-II #3 (2 pilot check-out flights, first on June 26, 1953), Northrop X-4 (4 flights, first on May 27, 1952), Bell X-5 (13 flights, first in early December 1952). Other aircraft flown on research projects were the Boeing KC-135 Stratotanker, Convair CV-990, Boeing B-52-003, Boeing B-747, North American F-100A, Convair F-102, Piper PA-30 Twin Comanche, General Dynamics F-111, Boeing B-720, Convair CV-880, and the Boeing B-47 Stratojet, his favorite. he also flew many other aircraft. Stan did nearly all of the big airplane work at the Center. The biggest work load was flying the Boeing B-29 Stratofortress (Navy designation: P2B). At this time the pilot of the aircraft was the one in charge. It was the pilot who called for the chase planes before drop time, then for the fire trucks to be in position, and he counted down for the launch of the experimental aircraft after making sure everything and everyone was `ready.' The P2B was used in the launching of the D-558s while the B-29 carried the X-1s to altitude for drops. Stan was pilot of the P2B for 1 drop of the D-558-II #1 (1951 - 1954), 63 drops of the D-558-II #2 (1951 - 1956), and 38 drops of the D-558-II #3 (1951 - 1956). As pilot of the B-29 Stan flew for 1 drop of the Bell X-1A (1955), 13 drops of the Bell X-1B (1956-1958) and 22 drops of the X-1E (1955 - 1958). During the lifting body tow tests Stan was pilot of the R4D that towed the M2-F1 to altitude for release. He made 14 tows in 1966. On June 13, 1966, Stanley P. Butchart became the Chief Pilot at the National Aeronautics and Space Administrations' Flight Research Center and a few weeks later was named Acting Director of Flight Operations. There were 6 pilots assigned to the flight office at this time. On December 10, 1966, Stan became Chief of Flight Operations a position he held until his retirement on February 27, 1976. Stan authored several reports and presented research papers. He is a charter member of the Society of Experimental Test Pilots that had a membership of 65 in 1955, when chartered. Stan was elected to be a Fellow and had the honor of being the President in 1980. Butchart was presented the NACA Exceptional Service Medal for his decisions and actions in the X-1A explosion while attached to the B-29 aircraft on August 8, 1955.

Cerebellar Expression of Copper Chaperone for Superoxide, Cytosolic Cu/Zn-Superoxide Dismutase, 4-Hydroxy-2-Nonenal, Acrolein and Heat Shock Protein 32 in Patients with Menkes Kinky Hair Disease: Immunohistochemical Study

PubMed Central

Yokoyama, Atsushi; Ohno, Kousaku; Hirano, Asao; Shintaku, Masayuki; Kato, Masako; Hayashi, Kazuhiko; Kato, Shinsuke

2014-01-01

Background To clarify the pathogenesis of cerebellar Purkinje cell death in patients with Menkes kinky hair disease (MD), a disorder of copper absorption, we investigated the morphological and functional abnormalities of residual Purkinje cells in MD patients and the mechanism of cell death. Methods Seven MD patients and 39 neurologically normal autopsy cases were studied. We performed histopathological and quantitative analyses of the Purkinje cells. In addition, we used immunohistochemistry to detect copper-dependent enzymes [cytosolic Cu/Zn-superoxide dismutase (SOD1) and copper chaperone for superoxide dismutase (CCS)], oxidative stress markers [4-hydroxy-2-nonenal (HNE) and acrolein] and heat shock protein 32 (hsp 32). Results The surviving MD Purkinje cells showed abnormal development, such as somatic sprouts and heterotopic location. Due to maldevelopment and degeneration, dendrites showed the cactus and weeping willow patterns. Axonal degeneration led to the formation of torpedoes. Quantitative analysis revealed loss of approximately 50% of the Purkinje cells in MD patients. Almost all of the normal Purkinje cells were positive for immunostaining by anti-CCS and anti-SOD1 antibodies, with staining of the cell bodies, dendrites and axons. Normal Purkinje cells were not stained by antibodies for HNE, acrolein or hsp 32. In MD patients, the majority of Purkinje cells were positive for CCS, but the positive rate for SOD1 was only about 23%. Approximately 56%, 42% and 40% of the Purkinje cells of MD patients were positive for HNE, acrolein and hsp 32, respectively. Conclusion In MD patients, about 50% of the Purkinje cells have been lost due to maldevelopment and degeneration. In the residual Purkinje cells, CCS expression seems to be nearly normal as a protective response to decreased SOD1 activity due to copper deficiency. Because oxidative stress is elevated secondary to decreased SOD1 activity, hsp 32 is induced as another protective mechanism. PMID:25067875

Cerebellar expression of copper chaperone for superoxide, cytosolic cu/zn-superoxide dismutase, 4-hydroxy-2-nonenal, acrolein and heat shock protein 32 in patients with menkes kinky hair disease: immunohistochemical study.

PubMed

Yokoyama, Atsushi; Ohno, Kousaku; Hirano, Asao; Shintaku, Masayuki; Kato, Masako; Hayashi, Kazuhiko; Kato, Shinsuke

2014-03-01

To clarify the pathogenesis of cerebellar Purkinje cell death in patients with Menkes kinky hair disease (MD), a disorder of copper absorption, we investigated the morphological and functional abnormalities of residual Purkinje cells in MD patients and the mechanism of cell death. Seven MD patients and 39 neurologically normal autopsy cases were studied. We performed histopathological and quantitative analyses of the Purkinje cells. In addition, we used immunohistochemistry to detect copper-dependent enzymes [cytosolic Cu/Zn-superoxide dismutase (SOD1) and copper chaperone for superoxide dismutase (CCS)], oxidative stress markers [4-hydroxy-2-nonenal (HNE) and acrolein] and heat shock protein 32 (hsp 32). The surviving MD Purkinje cells showed abnormal development, such as somatic sprouts and heterotopic location. Due to maldevelopment and degeneration, dendrites showed the cactus and weeping willow patterns. Axonal degeneration led to the formation of torpedoes. Quantitative analysis revealed loss of approximately 50% of the Purkinje cells in MD patients. Almost all of the normal Purkinje cells were positive for immunostaining by anti-CCS and anti-SOD1 antibodies, with staining of the cell bodies, dendrites and axons. Normal Purkinje cells were not stained by antibodies for HNE, acrolein or hsp 32. In MD patients, the majority of Purkinje cells were positive for CCS, but the positive rate for SOD1 was only about 23%. Approximately 56%, 42% and 40% of the Purkinje cells of MD patients were positive for HNE, acrolein and hsp 32, respectively. In MD patients, about 50% of the Purkinje cells have been lost due to maldevelopment and degeneration. In the residual Purkinje cells, CCS expression seems to be nearly normal as a protective response to decreased SOD1 activity due to copper deficiency. Because oxidative stress is elevated secondary to decreased SOD1 activity, hsp 32 is induced as another protective mechanism.

Electrochemical approaches for chemical and biological analysis on Mars

NASA Technical Reports Server (NTRS)

Kounaves, Samuel P.

2003-01-01

Obtaining in situ chemical data from planetary bodies such as Mars or Europa can present significant challenges. The one analytical technique that has many of the requisite characteristics to meet such a challenge is electroanalysis. Described here are three electroanalytical devices designed for in situ geochemical and biological analysis on Mars. The Mars Environmental Compatibility Assessment (MECA) was built and flight qualified for the now cancelled NASA Mars 2001 Lander. Part of MECA consisted of four "cells" containing arrays of electrochemical based sensors for measuring the ionic species in soil samples. A next-generation MECA, the Robotic Chemical Analysis Laboratory (RCAL), uses a carousel-type system to allow for greater customization of analytical procedures. A second instrument, proposed as part of the 2007 CryoScout mission, consists of a flow-through inorganic chemical analyzer (MICA). CryoScout is a torpedo-like device designed for subsurface investigation of the stratigraphic climate record embedded in Mars' north polar cap. As the CryoScout melts its way through the ice cap, MICA will collect and analyze the meltwater for a variety of inorganics and chemical parameters. By analyzing the chemistry locked in the layers of dust, salt, and ice, geologists will be able to determine the recent history of climate, water, and atmosphere on Mars and link it to the past. Finally, electroanalysis shows its abilities in the detection of possible microorganism on Mars or elsewhere in the solar system. To identify an unknown microorganism, one that may not even use Earth-type biochemistry, requires a detection scheme which makes minimal assumptions and looks for the most general features. Recent work has demonstrated that the use of an array of electrochemical sensors which monitors the changes in a solution via electrical conductivity, pH, and ion selective electrodes, can be used to detect minute chemical perturbations caused by the growth of bacteria and with the correct methodology provide unamibiguous detection of such life forms.

Immunization with Recombinantly Expressed LRP4 Induces Experimental Autoimmune Myasthenia Gravis in C57BL/6 Mice.

PubMed

Ulusoy, Canan; Çavuş, Filiz; Yılmaz, Vuslat; Tüzün, Erdem

2017-07-01

Myasthenia gravis (MG) is an autoimmune disease of the neuromuscular junction (NMJ), characterized with muscle weakness. While MG develops due to acetylcholine receptor (AChR) antibodies in most patients, antibodies to muscle-specific receptor tyrosine kinase (MuSK) or low-density lipoprotein receptor-related protein 4 (LRP4) may also be identified. Experimental autoimmune myasthenia gravis (EAMG) has been previously induced by both LRP4 immunization and passive transfer of LRP4 antibodies. Our aim was to confirm previous results and to test the pathogenic effects of LRP4 immunization in a commonly used mouse strain C57BL/6 (B6) using a recombinantly expressed human LRP4 protein. B6 mice were immunized with human LRP4 in CFA, Torpedo Californica AChR in CFA or only CFA. Clinical and pathogenic aspects of EAMG were compared among groups. LRP4- and AChR-immunized mice showed comparable EAMG clinical severity. LRP4-immunized mice displayed serum antibodies to LRP4 and NMJ IgG and complement factor C3 deposits. IgG2 was the dominant anti-LRP4 isotype. Cultured lymph node cells of LRP4- and AChR-immunized mice gave identical pro-inflammatory cytokine (IL-6, IFN-γ and IL-17) responses to LRP4 and AChR stimulation, respectively. Our results confirm the EAMG-inducing action of LRP4 immunization and identify B6 as a LRP4-EAMG-susceptible mouse strain. Demonstration of complement fixing anti-LRP4 antibodies in sera and complement/IgG deposits at the NMJ of LRP4-immunized mice indicates complement activation as a putative pathogenic mechanism. We have thus developed a practical LRP4-induced EAMG model using a non-conformational protein and a widely available mouse strain for future investigation of LRP4-related MG.

Eyes in the sea: Unlocking the mysteries of the ocean using industrial, remotely operated vehicles (ROVs).

PubMed

Macreadie, Peter I; McLean, Dianne L; Thomson, Paul G; Partridge, Julian C; Jones, Daniel O B; Gates, Andrew R; Benfield, Mark C; Collin, Shaun P; Booth, David J; Smith, Luke L; Techera, Erika; Skropeta, Danielle; Horton, Tammy; Pattiaratchi, Charitha; Bond, Todd; Fowler, Ashley M

2018-09-01

For thousands of years humankind has sought to explore our oceans. Evidence of this early intrigue dates back to 130,000BCE, but the advent of remotely operated vehicles (ROVs) in the 1950s introduced technology that has had significant impact on ocean exploration. Today, ROVs play a critical role in both military (e.g. retrieving torpedoes and mines) and salvage operations (e.g. locating historic shipwrecks such as the RMS Titanic), and are crucial for oil and gas (O&G) exploration and operations. Industrial ROVs collect millions of observations of our oceans each year, fueling scientific discoveries. Herein, we assembled a group of international ROV experts from both academia and industry to reflect on these discoveries and, more importantly, to identify key questions relating to our oceans that can be supported using industry ROVs. From a long list, we narrowed down to the 10 most important questions in ocean science that we feel can be supported (whole or in part) by increasing access to industry ROVs, and collaborations with the companies that use them. The questions covered opportunity (e.g. what is the resource value of the oceans?) to the impacts of global change (e.g. which marine ecosystems are most sensitive to anthropogenic impact?). Looking ahead, we provide recommendations for how data collected by ROVs can be maximised by higher levels of collaboration between academia and industry, resulting in win-win outcomes. What is clear from this work is that the potential of industrial ROV technology in unravelling the mysteries of our oceans is only just beginning to be realised. This is particularly important as the oceans are subject to increasing impacts from global change and industrial exploitation. The coming decades will represent an important time for scientists to partner with industry that use ROVs in order to make the most of these 'eyes in the sea'. Copyright © 2018. Published by Elsevier B.V.

High Resolution Observations of Dissolved Iron Distribution Along a Coastal Offshore Transect in the Eastern North Atlantic.

NASA Astrophysics Data System (ADS)

Blain, S.; Laes, A.; Laan, P.; Achterberg, E.; de Baar, H.

2002-12-01

In order to better understand and quantify the inputs of iron from below in the water column a detailed section from the coast to offshore has been studied in the eastern North Atlantic. The section, extended from 47°36 58 N, 4°14 51 W (depth 96 m) to 46°00 00 N, 8°00 00 W (depth 4912 m). The cruise took place in March 2002, on board R/V Pelagia, as part of the European Union project IRONAGES. Fifteen stations have been sampled for dissolved iron (DFe) and nutrients analysis. Go Flo bottles mounted on a kevlar cable were used for clean seawater sampling in the water column. A torpedo fish and trace metal clean bellows pump were used for surface sampling. Sample were filtered on-line through an 0.2 μm cartridge. The DFe concentrations were measured onboard using a FIA method with on line preconcentration (8-HQ resin) and chemiluminescence detection (mean blank = 28 pM, mean limit of detection= 39 pM). The coastal stations over the shelf showed the highest concentrations of DFe. In this part of the transect, the concentration decreased from the surface to the bottom. Maxima (1-2.4 nM) were associated with increase in turbidity demonstrating the DFe inputs associated with re-suspended sediments and/or pore waters. In the eastern part of the transect, water of the Loire river has been identified has a source of iron. Close to the shelf break the two dimensional iron distribution became more complex. A tidal front, internal waves and slope currents created a patchy distribution of DFe. Evertheless the input from below was always observable at depth between 500 and 1200 m. Finally, in the western part of the transect, off the plateau, the concentration of DFe was strongly correlated with the occurrence of different water masses (see abstract by A. Laës).

Modeling of Shoreline Changes of Tulamben Coast, Bali Indonesia

NASA Astrophysics Data System (ADS)

Yuanita, Nita; Pratama, Roka; Husrin, Semeidi

2015-04-01

Modeling of Shoreline Changes of Tulamben Coast, Bali Indonesia Tulamben coast is located in Lombok Strait on the northeastern coast of Bali island, Indonesia, as part of Karang Asem district. Severe erosion along the coastline has long been occurred in Karang Asem area and threatening houses, religious buildings (Hindu temples), and a national heritage site. As one of most popular diving site in Bali Island, Tulamben attracted many local and international tourist since 1980. The main attraction of Tulamben diving site is the USAT Liberty ship that was shipwrecked in Tulamben beach in 1942, after attacked by Japanese torpedo in Lombok Strait. Currently about 150 diver visit Tulamben per day. Due to physical changes of coastal environmental such as coastal erosion, sliding, and scouring, the shipwreck is vulnerable. It had been slipped off the beach several times and is predicted would be moved to deeper offshore floor if it is not protected. Coastal erosion in Karang Asem district is occurred probably due to interaction between cross-shore and long-shore wave-generated current and river sand supply decreasing after sand mining activities. In this study, the effect of cross-shore and longshore transport to coastal erosion in Tulamben is analyzed by doing numerical model. Numerical simulation of shoreline changes is performed by using Beach Processes Module of CEDAS (Coastal Engineering Design and Analysis System) consists of SBEACH and GENESIS. The model domain is covered Karang Asem coastline about 60 km length and wave data is calculated from hourly wind data (10 years). Simulated shoreline is calibrated using shoreline data from 1972 to 2013. Using calibrated model, then the simulation is performed from 2003 - 2013. From the simulation it is determined that longshore current and longshore sediment contribute to coastal erosion in Tulamben. Based on model results, several alternatives of general layout and configuration of coastal protection structures is proposed. The most optimum coastal protection system is determined by simulating proposed alternative using GENESIS.

Cleanup/stimulation of a horizontal wellbore using propellants. Final report

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

Rougeot, J.E.; Lauterbach, K.A.

1993-01-01

This report documents the stimulation/cleanup of a horizontal well bore (Wilson 25) using propellants. The Wilson 25 is a Bartlesville Sand well located in the Flatrock Field, Osage County, Oklahoma. The Wilson 25 was drilled to determine if horizontal drilling could be used as a means to economically recover primary oil that had been left in place in a mostly abandoned oil field because of the adverse effects of water coning. Pump testing of the Wilson 25 horizontal well bore before cleanup or stimulation produced 6 barrels of oil and .84 barrels of water per day. The high percentage ofmore » daily oil production to total daily fluid production indicated that the horizontal well bore had accessed potentially economical oil reserves if the fluid production rate could be increased by performing a cleanup/stimulation treatment. Propellants were selected as an inexpensive means to stimulate and cleanup the near well bore area in a uniform manner. The ignition of a propellant creates a large volume of gas which penetrates the formation, creating numerous short cracks through which hydrocarbons can travel into the well bore. More conventional stimulation/cleanup techniques were either significantly more expensive, less likely to treat uniformly, or could not be confined to the near well bore area. Three different propellant torpedo designs were tested with a total of 304` of horizontal well bore being shot and producible. The initial test shot caused 400` of the horizontal well bore to become plugged off, and subsequently it could not be production tested. The second and third test shots were production tested, with the oil production being increased 458% and 349%, respectively, on a per foot basis. The Wilson 25 results indicate that a propellant shot treatment is an economically viable means to cleanup/stimulate a horizontal well bore.« less

Induction of somatic embryogenesis in explants of shoot cultures established from adult Eucalyptus globulus and E. saligna × E. maidenii trees.

PubMed

Corredoira, E; Ballester, A; Ibarra, M; Vieitez, A M

2015-06-01

A reproducible procedure for induction of somatic embryogenesis (SE) from adult trees of Eucalyptus globulus Labill. and the hybrid E. saligna Smith × E. maidenii has been developed for the first time. Somatic embryos were obtained from both shoot apex and leaf explants of all three genotypes evaluated, although embryogenic frequencies were significantly influenced by the species/genotype, auxin and explant type. Picloram was more efficient for somatic embryo induction than naphthaleneacetic acid (NAA), with the highest frequency of induction being obtained in Murashige and Skoog medium containing 40 µM picloram and 40 mg l(-1) gum Arabic, in which 64% of the shoot apex explants and 68.8% of the leaf explants yielded somatic embryos. The embryogenic response of the hybrid was higher than that of the E. globulus, especially when NAA was used. The cultures initiated on picloram-containing medium consisted of nodular embryogenic structures surrounded by a mucilaginous coating layer that emerged from a watery callus developed from the initial explants. Cotyledonary somatic embryos were differentiated after subculture of these nodular embryogenic structures on a medium lacking plant growth regulators. Histological analysis confirmed the bipolar organization of the somatic embryos, with shoot and root meristems and closed procambial tissue that bifurcated into small cotyledons. The root pole was more differentiated than the shoot pole, which appeared to be formed by a few meristematic layers. Maintenance of the embryogenic lines by secondary SE was attained by subculturing individual cotyledonary embryos or small clusters of globular and torpedo embryos on medium with 16.11 µM NAA at 4- to 5-week intervals. Somatic embryos converted into plantlets after being transferred to liquid germination medium although plant regeneration remained poor. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

How does huperzine A enter and leave the binding gorge of acetylcholinesterase? Steered molecular dynamics simulations.

PubMed

Xu, Yechun; Shen, Jianhua; Luo, Xiaomin; Silman, Israel; Sussman, Joel L; Chen, Kaixian; Jiang, Hualiang

2003-09-17

The entering and leaving processes of Huperzine A (HupA) binding with the long active-site gorge of Torpedo californica acetylcholinesterase (TcAChE) have been investigated by using steered molecular dynamics simulations. The analysis of the force required along the pathway shows that it is easier for HupA to bind to the active site of AChE than to disassociate from it, which for the first time interprets at the atomic level the previous experimental result that unbinding process of HupA is much slower than its binding process to AChE. The direct hydrogen bonds, water bridges, and hydrophobic interactions were analyzed during two steered molecular dynamics (SMD) simulations. Break of the direct hydrogen bond needs a great pulling force. The steric hindrance of bottleneck might be the most important factor to produce the maximal rupture force for HupA to leave the binding site but it has a little effect on the binding process of HupA with AChE. Residue Asp72 forms a lot of water bridges with HupA leaving and entering the AChE binding gorge, acting as a clamp to take out HupA from or put HupA into the active site. The flip of the peptide bond between Gly117 and Gly118 has been detected during both the conventional MD and SMD simulations. The simulation results indicate that this flip phenomenon could be an intrinsic property of AChE and the Gly117-Gly118 peptide bond in both HupA bound and unbound AChE structures tends to adopt the native enzyme structure. At last, in a vacuum the rupture force is increased up to 1500 pN while in water solution the greatest rupture force is about 800 pN, which means water molecules in the binding gorge act as lubricant to facilitate HupA entering or leaving the binding gorge.

[Relationships between venomous function and innate immune function].

PubMed

Goyffon, Max; Saul, Frederick; Faure, Grazyna

2015-01-01

Venomous function is investigated in relation to innate immune function in two cases selected from scorpion venom and serpent venom. In the first case, structural analysis of scorpion toxins and defensins reveals a close interrelation between both functions (toxic and innate immune system function). In the second case, structural and functional studies of natural inhibitors of toxic snake venom phospholipases A2 reveal homology with components of the innate immune system, leading to a similar conclusion. Although there is a clear functional distinction between neurotoxins, which act by targeting membrane ion channels, and the circulating defensins which protect the organism from pathogens, the scorpion short toxins and defensins share a common protein folding scaffold with a conserved cysteine-stabilized alpha-beta motif of three disulfide bridges linking a short alpha helix and an antiparallel beta sheet. Genomic analysis suggests that these proteins share a common ancestor (long venom toxins were separated from an early gene family which gave rise to separate short toxin and defensin families). Furthermore, a scorpion toxin has been experimentally synthetized from an insect defensin, and an antibacterial scorpion peptide, androctonin (whose structure is similar to that of a cone snail venom toxin), was shown to have a similar high affinity for the postsynaptic acetylcholine receptor of Torpedo sp. Natural inhibitors of phospholipase A2 found in the blood of snakes are associated with the resistance of venomous snakes to their own highly neurotoxic venom proteins. Three classes of phospholipases A2 inhibitors (PLI-α, PLI-β, PLI-γ) have been identified. These inhibitors display diverse structural motifs related to innate immune proteins including carbohydrate recognition domains (CRD), leucine rich repeat domains (found in Toll-like receptors) and three finger domains, which clearly differentiate them from components of the adaptive immune system. Thus, in structure, function and phylogeny, venomous function in both vertebrates and invertebrates are clearly interrelated with innate immune function. © Société de Biologie, 2016.

Modulation of immune responses and suppression of experimental autoimmune myasthenia gravis by surgical denervation of the spleen

PubMed Central

Bakhiet, M; Yu, L-Y; Özenci, V; Khan, A; Shi, F-D

2006-01-01

Critical interactions between the nervous system and the immune system during experimental autoimmune myasthenia gravis (EAMG) were examined in an animal model for human MG after immunization of adult female Lewis rats with Torpedo acetylcholine receptor (AChR) and complete Freund's adjuvant. Immunized rats depicted marked clinical severity of the disease. Using enzyme-linked immunospot (ELISPOT) assay and in situ hybridization techniques, immune responses in these animals were examined and showed elevated numbers of anti-AChR IgG secreting B cells and AChR reactive interferon (IFN)-γ-secreting cells, enhanced mRNA expression of the proinflammatory cytokines IFN-γ and tumour necrosis factor (TNF)-α as Th1 subset and the anti-inflammatory cytokines interleukin (IL)-4 and IL-10 as a Th2 subset, and transforming growth factor (TGF)-β as a Th3 cytokine. Corticosterone and prostaglandin E2 (PGE2) levels were measured by radioimmunoassay and illustrated increased production after immunization. Surgical denervation of the spleen reduced significantly the clinical severity of the disease, suppressed the numbers of IgG and IFN-γ-secreting cells, down-regulated the mRNA expression for cytokines and reduced corticosterone and PGE2 production. As controls, sham-operated rats were used and showed results as the EAMG non-denervated control rats. The data present herein, and for the first time, substantial effects of the nervous system on immune responses that may influence the outcome of EAMG. These effects were not dependent on cytokine inhibitory mediators such as prostaglandins or stress hormones. IL-10 and TGF-β, the two potent immunosuppressive cytokines, were also suppressed, indicating a general suppression by splenic denervation. More investigations are initiated at our laboratories to understand the evident neural control over the immune system during challenges leading to the break of tolerance and development of autoimmunity, which may assist in innovative therapeutic approaches. PMID:16634803

Identification of Propofol Binding Sites in a Nicotinic Acetylcholine Receptor with a Photoreactive Propofol Analog*

PubMed Central

Jayakar, Selwyn S.; Dailey, William P.; Eckenhoff, Roderic G.; Cohen, Jonathan B.

2013-01-01

Propofol, a widely used intravenous general anesthetic, acts at anesthetic concentrations as a positive allosteric modulator of γ-aminobutyric acid type A receptors and at higher concentration as an inhibitor of nicotinic acetylcholine receptors (nAChRs). Here, we characterize propofol binding sites in a muscle-type nAChR by use of a photoreactive analog of propofol, 2-isopropyl-5-[3-(trifluoromethyl)-3H-diazirin-3-yl]phenol (AziPm). Based upon radioligand binding assays, AziPm stabilized the Torpedo nAChR in the resting state, whereas propofol stabilized the desensitized state. nAChR-rich membranes were photolabeled with [3H]AziPm, and labeled amino acids were identified by Edman degradation. [3H]AziPm binds at three sites within the nAChR transmembrane domain: (i) an intrasubunit site in the δ subunit helix bundle, photolabeling in the nAChR desensitized state (+agonist) δM2-18′ and two residues in δM1 (δPhe-232 and δCys-236); (ii) in the ion channel, photolabeling in the nAChR resting, closed channel state (−agonist) amino acids in the M2 helices (αM2-6′, βM2-6′ and -13′, and δM2-13′) that line the channel lumen (with photolabeling reduced by >90% in the desensitized state); and (iii) at the γ-α interface, photolabeling αM2-10′. Propofol enhanced [3H]AziPm photolabeling at αM2-10′. Propofol inhibited [3H]AziPm photolabeling within the δ subunit helix bundle at lower concentrations (IC50 = 40 μm) than it inhibited ion channel photolabeling (IC50 = 125 μm). These results identify for the first time a single intrasubunit propofol binding site in the nAChR transmembrane domain and suggest that this is the functionally relevant inhibitory binding site. PMID:23300078

Electrochemical approaches for chemical and biological analysis on Mars.

PubMed

Kounaves, Samuel P

2003-02-17

Obtaining in situ chemical data from planetary bodies such as Mars or Europa can present significant challenges. The one analytical technique that has many of the requisite characteristics to meet such a challenge is electroanalysis. Described here are three electroanalytical devices designed for in situ geochemical and biological analysis on Mars. The Mars Environmental Compatibility Assessment (MECA) was built and flight qualified for the now cancelled NASA Mars 2001 Lander. Part of MECA consisted of four "cells" containing arrays of electrochemical based sensors for measuring the ionic species in soil samples. A next-generation MECA, the Robotic Chemical Analysis Laboratory (RCAL), uses a carousel-type system to allow for greater customization of analytical procedures. A second instrument, proposed as part of the 2007 CryoScout mission, consists of a flow-through inorganic chemical analyzer (MICA). CryoScout is a torpedo-like device designed for subsurface investigation of the stratigraphic climate record embedded in Mars' north polar cap. As the CryoScout melts its way through the ice cap, MICA will collect and analyze the meltwater for a variety of inorganics and chemical parameters. By analyzing the chemistry locked in the layers of dust, salt, and ice, geologists will be able to determine the recent history of climate, water, and atmosphere on Mars and link it to the past. Finally, electroanalysis shows its abilities in the detection of possible microorganism on Mars or elsewhere in the solar system. To identify an unknown microorganism, one that may not even use Earth-type biochemistry, requires a detection scheme which makes minimal assumptions and looks for the most general features. Recent work has demonstrated that the use of an array of electrochemical sensors which monitors the changes in a solution via electrical conductivity, pH, and ion selective electrodes, can be used to detect minute chemical perturbations caused by the growth of bacteria and with the correct methodology provide unamibiguous detection of such life forms.

Decreased bone mineral density in experimental myasthenia gravis in C57BL/6 mice.

PubMed

Oshima, Minako; Iida-Klein, Akiko; Maruta, Takahiro; Deitiker, Philip R; Atassi, M Zouhair

2017-09-01

Experimental autoimmune myasthenia gravis (EAMG), an animal model of myasthenia gravis (MG), can be induced in C57BL/6 (B6, H-2  b ) mice by 2-3 injections with Torpedo californica AChR (tAChR) in complete Freund's adjuvant. Some EAMG mice exhibit weight loss with muscle weakness. The loss in body weight, which is closely associated with bone structure, is particularly evident in EAMG mice with severe muscle weakness. However, the relationship between muscle weakness and bone loss in EAMG has not been studied before. Recent investigations on bone have shed light on association of bone health and immunological states. It is possible that muscle weakness in EAMG developed by anti-tAChR immune responses might accompany bone loss. We determined whether reduced muscle strength associates with decreased bone mineral density (BMD) in EAMG mice. EAMG was induced by two injections at 4-week interval of tAChR and adjuvants in two different age groups. The first tAChR injection was either at age 8 weeks or at 15 weeks. We measured BMD at three skeletal sites, including femur, tibia, and lumbar vertebrae, using dual energy X-ray absorptiometry. Among these bone areas, femur of EAMG mice in both age groups showed a significant decrease in BMD compared to control adjuvant-injected and to non-immunized mice. Reduction in BMD in induced EAMG at a later-age appears to parallel the severity of the disease. The results indicate that anti-tAChR autoimmune response alone can reduce bone density in EAMG mice. BMD reduction was also observed in adjuvant-injected mice in comparison to normal un-injected mice, suggesting that BMD decrease can occur even when muscle activity is normal. Decreased BMD observed in both tAChR-injected and adjuvant-injected mice groups were discussed in relation to innate immunity and bone-related immunology involving activated T cells and tumour necrosis factor-related cytokines that trigger osteoclastogenesis and bone loss.

The Potential of Aluminium Metal Powder as a Fuel for Space Propulsion Systems

NASA Astrophysics Data System (ADS)

Ismail, A. M.; Osborne, B.; Welch, C. S.

Metal powder propulsion systems have been addressed intermittently since the Second World War, initially in the field of underwater propulsion where research in the application of propelling torpedoes continues until this day. During the post war era, researchers attempted to utilise metal powders as a fuel for ram jet applications in missiles. The 1960's and 1970's saw additional interest in the use of `pure powder' propellants, i.e. fluidised metal fuel and oxidiser, both in solid particulate form. Again the application was for employment in space-constrained missiles where the idea was to maximise the performance of high energy density powder propellants in order to enhance the missile's flight duration. Metal powder as possible fuel was investigated for in-situ resource utilisation propulsion systems post-1980's where the emphasis was on the use of gaseous oxygen or liquid oxygen combined with aluminium metal powder for use as a ``lunar soil propellant'' or carbon dioxide and magnesium metal powder as a ``Martian propellant''.Albeit aluminium metal powder propellants are lower in performance than cryogenic and Earth storable propellants, the former does have an advantage inasmuch that the propulsion system is generic, i.e. it can be powered with chemicals mined and processed on Earth, the Moon and Mars. Thus, due to the potential refuelling capability, the lower performing aluminium metal powder propellant would effectively possess a much higher change in velocity (V) for multiple missions than the cryogenic or Earth storable propellant which is only suitable for one planet or one mission scenario, respectively.One of the principal limitations of long duration human spaceflight beyond cis-lunar orbit is the lack of refuelling capabilities on distant planets resulting in the reliance on con- ventional non-cryogenic, propellants produced on Earth. If one could develop a reliable propulsion system operating on pro- pellants derived entirely of ingredients found on nearby plan- etary bodies, then not only could mission duration be extended, larger amounts of payload could be ferried to and from the destination and eventually the cost of transporting propellant ingredients from Earth could be reduced, if not eliminated.

Fish consumption pattern among adults of different ethnics in Peninsular Malaysia

PubMed Central

Ahmad, Nurul Izzah; Wan Mahiyuddin, Wan Rozita; Tengku Mohamad, Tengku Rozaina; Ling, Cheong Yoon; Daud, Siti Fatimah; Hussein, Nasriyah Che; Abdullah, Nor Aini; Shaharudin, Rafiza; Sulaiman, Lokman Hakim

2016-01-01

Background Understanding different patterns of fish consumption is an important component for risk assessment of contaminants in fish. A few studies on food consumption had been conducted in Malaysia, but none of them focused specifically on fish consumption. The objectives of this study were to document the meal pattern among three major ethnics in Malaysia with respect to fish/seafood consumption, identify most frequently consumed fish and cooking method, and examine the influence of demographic factors on pattern of fish consumption among study subjects. Methods A cross-sectional survey was conducted between February 2008 and May 2009 to investigate patterns of fish consumption among Malaysian adults in Peninsular Malaysia. Adults aged 18 years and above were randomly selected and fish consumption data were collected using a 3-day prospective food diary. Results A total of 2,675 subjects, comprising male (44.2%) and female (55.7%) participants from major ethnics (Malays, 76.9%; Chinese, 14.7%; Indians, 8.3%) with a mean age of 43.4±16.2 years, were involved in this study. The results revealed 10 most frequently consumed marine fish in descending order: Indian mackerel, anchovy, yellowtail and yellow-stripe scads, tuna, sardines, torpedo scad, Indian and short-fin scads, pomfret, red snapper, and king mackerel. Prawn and squid were also among the most preferred seafood by study subjects. The most frequently consumed freshwater fish were freshwater catfish and snakehead. The most preferred cooking style by Malaysians was deep-fried fish, followed by fish cooked in thick and/or thin chili gravy, fish curry, and fish cooked with coconut milk mixed with other spices and flavorings. Overall, Malaysians consumed 168 g/day fish, with Malay ethnics’ (175±143 g/day) consumption of fish significantly (p<0.001) higher compared with the other two ethnic groups (Chinese=152±133 g/day, Indians=136±141 g/day). Conclusion Fish consumption was significantly associated with ethnicity, age, marital status, residential area, and years of education of adults in Peninsular Malaysia, and the data collected are beneficial for the purpose of health risk assessment on the intake of contaminants through fish/seafood consumption. PMID:27534846

Fish consumption pattern among adults of different ethnics in Peninsular Malaysia.

PubMed

Ahmad, Nurul Izzah; Wan Mahiyuddin, Wan Rozita; Tengku Mohamad, Tengku Rozaina; Ling, Cheong Yoon; Daud, Siti Fatimah; Hussein, Nasriyah Che; Abdullah, Nor Aini; Shaharudin, Rafiza; Sulaiman, Lokman Hakim

2016-01-01

Understanding different patterns of fish consumption is an important component for risk assessment of contaminants in fish. A few studies on food consumption had been conducted in Malaysia, but none of them focused specifically on fish consumption. The objectives of this study were to document the meal pattern among three major ethnics in Malaysia with respect to fish/seafood consumption, identify most frequently consumed fish and cooking method, and examine the influence of demographic factors on pattern of fish consumption among study subjects. A cross-sectional survey was conducted between February 2008 and May 2009 to investigate patterns of fish consumption among Malaysian adults in Peninsular Malaysia. Adults aged 18 years and above were randomly selected and fish consumption data were collected using a 3-day prospective food diary. A total of 2,675 subjects, comprising male (44.2%) and female (55.7%) participants from major ethnics (Malays, 76.9%; Chinese, 14.7%; Indians, 8.3%) with a mean age of 43.4±16.2 years, were involved in this study. The results revealed 10 most frequently consumed marine fish in descending order: Indian mackerel, anchovy, yellowtail and yellow-stripe scads, tuna, sardines, torpedo scad, Indian and short-fin scads, pomfret, red snapper, and king mackerel. Prawn and squid were also among the most preferred seafood by study subjects. The most frequently consumed freshwater fish were freshwater catfish and snakehead. The most preferred cooking style by Malaysians was deep-fried fish, followed by fish cooked in thick and/or thin chili gravy, fish curry, and fish cooked with coconut milk mixed with other spices and flavorings. Overall, Malaysians consumed 168 g/day fish, with Malay ethnics' (175±143 g/day) consumption of fish significantly (p<0.001) higher compared with the other two ethnic groups (Chinese=152±133 g/day, Indians=136±141 g/day). Fish consumption was significantly associated with ethnicity, age, marital status, residential area, and years of education of adults in Peninsular Malaysia, and the data collected are beneficial for the purpose of health risk assessment on the intake of contaminants through fish/seafood consumption.

Pancreatic and snake venom presynaptically active phospholipases A2 inhibit nicotinic acetylcholine receptors.

PubMed

Vulfius, Catherine A; Kasheverov, Igor E; Kryukova, Elena V; Spirova, Ekaterina N; Shelukhina, Irina V; Starkov, Vladislav G; Andreeva, Tatyana V; Faure, Grazyna; Zouridakis, Marios; Tsetlin, Victor I; Utkin, Yuri N

2017-01-01

Phospholipases A2 (PLA2s) are enzymes found throughout the animal kingdom. They hydrolyze phospholipids in the sn-2 position producing lysophospholipids and unsaturated fatty acids, agents that can damage membranes. PLA2s from snake venoms have numerous toxic effects, not all of which can be explained by phospholipid hydrolysis, and each enzyme has a specific effect. We have earlier demonstrated the capability of several snake venom PLA2s with different enzymatic, cytotoxic, anticoagulant and antiproliferative properties, to decrease acetylcholine-induced currents in Lymnaea stagnalis neurons, and to compete with α-bungarotoxin for binding to nicotinic acetylcholine receptors (nAChRs) and acetylcholine binding protein. Since nAChRs are implicated in postsynaptic and presynaptic activities, in this work we probe those PLA2s known to have strong presynaptic effects, namely β-bungarotoxin from Bungarus multicinctus and crotoxin from Crotalus durissus terrificus. We also wished to explore whether mammalian PLA2s interact with nAChRs, and have examined non-toxic PLA2 from porcine pancreas. It was found that porcine pancreatic PLA2 and presynaptic β-bungarotoxin blocked currents mediated by nAChRs in Lymnaea neurons with IC50s of 2.5 and 4.8 μM, respectively. Crotoxin competed with radioactive α-bungarotoxin for binding to Torpedo and human α7 nAChRs and to the acetylcholine binding protein. Pancreatic PLA2 interacted similarly with these targets; moreover, it inhibited radioactive α-bungarotoxin binding to the water-soluble extracellular domain of human α9 nAChR, and blocked acetylcholine induced currents in human α9α10 nAChRs heterologously expressed in Xenopus oocytes. These and our earlier results show that all snake PLA2s, including presynaptically active crotoxin and β-bungarotoxin, as well as mammalian pancreatic PLA2, interact with nAChRs. The data obtained suggest that this interaction may be a general property of all PLA2s, which should be proved by further experiments.

How electricity was discovered and how it is related to cardiology.

PubMed

de Micheli-Serra, Alfredo; Iturralde-Torres, Pedro; Izaguirre-Ávila, Raúl

2012-01-01

We relate the fundamental stages of the long road leading to the discovery of electricity and its uses in cardiology. The first observations on the electromagnetic phenomena were registered in ancient texts; many Greek and Roman writers referred to them, although they provided no explanations. The first extant treatise dates back to the XIII century and was written by Pierre de Maricourt during the siege of Lucera, Italy, by the army of Charles of Anjou, French king of Naples. There were no significant advances in the field of magnetism between the appearance of this treatise and the publication of the study De magnete magneticisque corporibus (1600) by the English physician William Gilbert. Scientists became increasingly interested in electromagnetic phenomena occurring in certain fish, i.e., the so-called electric ray that lived in the South American seas and the Torpedo fish that roamed the Mediterranean Sea. This interest increased in the 18th century, when condenser devices such as the Leyden jar were explored. It was subsequently demonstrated that the discharges produced by "electric fish" were of the same nature as those produced in this device. The famous "controversy" relating to animal electricity or electricity inherent to an animal's body also arose in the second half of the 18th century. The school of thought of the physicist Volta sustained the principle of a single electrical action generated by metallic contact. This led Volta to invent his electric pile, considered as the first wet cell battery. Toward the middle of the XIX century, the disciples of the physiologist Galvani were able to demonstrate the existence of animal electricity through experiments exploring the so-called current of injury. On the path of Volta's approach, many characteristics of electricity were detailed, which ultimately led to their usage in the industrial field. The route followed by Galvani-Nobili-Matteucci led to the successes of Waller, Einthoven, etcetera, enabling the modern conquests of electro-vectorcardiography. Copyright © 2012 Instituto Nacional de Cardiología Ignacio Chávez. Published by Masson Doyma México S.A. All rights reserved.

The Treatment of cardiovascular Risk in Primary care using Electronic Decision supOrt (TORPEDO) study-intervention development and protocol for a cluster randomised, controlled trial of an electronic decision support and quality improvement intervention in Australian primary healthcare.

PubMed

Peiris, David; Usherwood, Tim; Panaretto, Katie; Harris, Mark; Hunt, Jenny; Patel, Bindu; Zwar, Nicholas; Redfern, Julie; Macmahon, Stephen; Colagiuri, Stephen; Hayman, Noel; Patel, Anushka

2012-01-01

Large gaps exist in the implementation of guideline recommendations for cardiovascular disease (CVD) risk management. Electronic decision support (EDS) systems are promising interventions to close these gaps but few have undergone clinical trial evaluation in Australia. We have developed HealthTracker, a multifaceted EDS and quality improvement intervention to improve the management of CVD risk. It is hypothesised that the use of HealthTracker over a 12-month period will result in: (1) an increased proportion of patients receiving guideline-indicated measurements of CVD risk factors and (2) an increased proportion of patients at high risk will receive guideline-indicated prescriptions for lowering their CVD risk. Sixty health services (40 general practices and 20 Aboriginal Community Controlled Health Services (ACCHSs) will be randomised in a 1:1 allocation to receive either the intervention package or continue with usual care, stratified by service type, size and participation in existing quality improvement initiatives. The intervention consists of point-of-care decision support; a risk communication interface; a clinical audit tool to assess performance on CVD-related indicators; a quality improvement component comprising peer-ranked data feedback and support to develop strategies to improve performance. The control arm will continue with usual care without access to these intervention components. Quantitative data will be derived from cross-sectional samples at baseline and end of study via automated data extraction. Detailed process and economic evaluations will also be conducted. The general practice component of the study is approved by the University of Sydney Human Research Ethics Committee (HREC) and the ACCHS component is approved by the Aboriginal Health and Medical Research Council HREC. Formal agreements with each of the participating sites have been signed. In addition to the usual scientific forums, results will be disseminated via newsletters, study websites, face-to-face feedback forums and workshops. The trial is registered with the Australian Clinical Trials Registry ACTRN 12611000478910.

Effectiveness of Biomass Harvesting from Stormwater Detention Areas in Reducing Phosphorus Discharges

NASA Astrophysics Data System (ADS)

Shukla, A.; Shukla, S.

2014-12-01

Stormwater Detention Areas (SDAs) in agricultural landscapes are considered to be the most important Best Management Practice by state agencies in Florida. Two main processes responsible for Phosphorus (P) retention in SDAs are soil adsorption and plant uptake. Long term pumping of agricultural drainage may saturate the SDA's soil with P which can put these systems at the risk of becoming a source of P. Given that these systems already occupy part of the farmland and are costly to build, interventions are needed to sustain SDAs as a sink of P. Soil and vegetation P content at two SDAs (SDA1 and 2) in south Florida was quantified in addition to inflow and outflow P loads. Analyses showed that soil was saturated with limited to no P adsorption capacity remaining. Negative Soil Phosphorus Storage Capacity (SPSC) indicated that soil was at a risk of P release. Given these conditions, the only avenue to remove P from SDAs without any potentially undesirable ecological impacts, was biomass harvesting. At SDA1, results showed that harvesting the aboveground biomass would result in 19% extra P retention if the current vegetation (Para grass, Brachiaria mutica) is harvested. Given that aboveground tissue P content of Para grass is very low, replacing it with another native grass (Maidencane, Panicum hemitomon) and harvesting it annually could retain most of the incoming P load. A similar analysis showed that at SDA2, almost 40% additional P could be retained by harvesting aboveground biomass of the dominant vegetation (Torpedo Grass, Panicum repens and Smartweed, Polygonum hydropiperoides). A spatial analysis in conjunction with SPSC values and aboveground plant P indicated that biomass harvesting can transform both the SDAs from a source to sink in 2 to 3 years. A fifty year net present value analysis showed that overall it is an economically feasible strategy with an average annual benefit of 3,223 and 34,825 for SDA1 and 2, respectively. Harvesting aboveground biomass has the potential to become a part of "payment for environmental services" program and is one of the less intensive methods to sustain SDAs as a net sink of P in the long-term without causing detrimental effects to the downstream ecology.

Auv Multibeam Bathymetry and Sidescan Survey of the SS Montebello wreck Offshore Cambria CA

NASA Astrophysics Data System (ADS)

Caress, D. W.; Thomas, H.; Conlin, D.; Thompson, D.; Paull, C. K.

2010-12-01

An MBARI Mapping AUV survey of the SS Montebello wreck offshore Cambria, CA collected high-resolution multibeam bathymetry and sidescan imagery of the vessel and the surrounding seafloor. The Montebello was an oil tanker that was torpedoed and sunk about 11 km offshore in 275 m water depth by a Japanese submarine on December 23, 1941. The Montebello was loaded with 3,000,000 gallons of crude oil, and there is no evidence that significant leakage of that cargo occurred at the time of the sinking or in the 69 years since. The California Department of Fish and Game’s Office of Spill Prevention and Response (OSPR) commissioned the AUV survey as part of a multi-agency Montebello Task Force effort to assess the potential pollution threat. The survey data will be used to determine the extent and general character of the wreckage for a pending Task Force report and to guide any future ROV dive or assessment activity . The AUV surveyed the wreck site from altitudes of 75 and 25 m; the low-altitude high-resolution survey consists of a grid with a 50 m line spacing both parallel and orthogonal to the ship. The 200 kHz multibeam bathymetry images the wreck from both above and from the sides with an 0.5 m lateral resolution. The combination of soundings from all of the survey lines results in a three-dimensional distribution of soundings that delineates the external morphology and some of the internal structure of the wreck. 410 kHz chirp sidescan sonar data also image the site from both directions. The bathymetry data indicate that the Montebello was pitched forward down when it impacted the bottom, crushing and breaking off the bow section. Both forward and aft deckhouses are largely intact, and in fact the multibeam images the individual decks within those structures. About half of the forward mast remains, both amidships masts and the smokestack are missing. A good deal of the deck piping and equipment appears intact, and aside from the bow, the ship’s sides appear intact. The rudder is intact but leaning to port. The multibeam also imaged a considerable fish population above and around the wreck site.

Testing of SIR (a transformable robotic submarine) in Lake Tahoe for future deployment at West Antarctic Ice Sheet grounding lines of Siple Coast

NASA Astrophysics Data System (ADS)

Powell, R. D.; Scherer, R. P.; Griffiths, I.; Taylor, L.; Winans, J.; Mankoff, K. D.

2011-12-01

A remotely operated vehicle (ROV) has been custom-designed and built by DOER Marine to meet scientific requirements for exploring subglacial water cavities. This sub-ice rover (SIR) will explore and quantitatively document the grounding zone areas of the Ross Ice Shelf cavity using a 3km-long umbilical tether by deployment through an 800m-long ice borehole in a torpedo shape, which is also its default mode if operational failure occurs. Once in the ocean cavity it transforms via a diamond-shaped geometry into a rectangular form when all of its instruments come alive in its flight mode. Instrumentation includes 4 cameras (one forward-looking HD), a vertical scanning sonar (long-range imaging for spatial orientation and navigation), Doppler current meter (determine water current velocities), multi-beam sonar (image and swath map bottom topography), sub-bottom profiler (profile sub-sea-floor sediment for geological history), CTD (determine salinity, temperature and depth), DO meter (determine dissolved oxygen content in water), transmissometer (determine suspended particulate concentrations in water), laser particle-size analyzer (determine sizes of particles in water), triple laser-beams (determine size and volume of objects), thermistor probe (measure in situ temperatures of ice and sediment), shear vane probe (determine in situ strength of sediment), manipulator arm (deploy instrumentation packages, collect samples), shallow ice corer (collect ice samples and glacial debris), water sampler (determine sea water/freshwater composition, calibrate real-time sensors, sample microbes), shallow sediment corer (sample sea floor, in-ice and subglacial sediment for stratigraphy, facies, particle size, composition, structure, fabric, microbes). A sophisticated array of data handling, storing and displaying will allow real-time observations and environmental assessments to be made. This robotic submarine and other instruments will be tested in Lake Tahoe in September, 2011 and results will be presented on its trials and geological and biological findings down to the deepest depths of the lake. Other instruments include a 5m-ling percussion corer for sampling deeper sediments, an ice-tethered profiler with CTD and ACDP, and in situ oceanographic mooring designed to fit down a narrow (30cm-diameter) ice borehole that include interchangeable packages of ACDPs, CTDs, transmissometers, laser particle-size analyzer, DO meter, automated multi-port water sampler, water column nutrient analyzer, sediment porewater chemistry analyzer, down-looking color camera (see figure), and altimeter.

Peptides from puff adder Bitis arietans venom, novel inhibitors of nicotinic acetylcholine receptors.

PubMed

Vulfius, Catherine A; Spirova, Ekaterina N; Serebryakova, Marina V; Shelukhina, Irina V; Kudryavtsev, Denis S; Kryukova, Elena V; Starkov, Vladislav G; Kopylova, Nina V; Zhmak, Maxim N; Ivanov, Igor A; Kudryashova, Ksenia S; Andreeva, Tatyana V; Tsetlin, Victor I; Utkin, Yuri N

2016-10-01

Phospholipase A 2 (named bitanarin) possessing capability to block nicotinic acetylcholine receptors (nAChRs) was isolated earlier (Vulfius et al., 2011) from puff adder Bitis arietans venom. Further studies indicated that low molecular weight fractions of puff adder venom inhibit nAChRs as well. In this paper, we report on isolation from this venom and characterization of three novel peptides called baptides 1, 2 and 3 that reversibly block nAChRs. To isolate the peptides, the venom of B. arietans was fractionated by gel-filtration and reversed phase chromatography. The amino acid sequences of peptides were established by de novo sequencing using MALDI mass spectrometry. Baptide 1 comprised 7, baptides 2 and 3-10 amino acid residues, the latter being acetylated at the N-terminus. This is the first indication for the presence of such post-translational modification in snake venom proteins. None of the peptides contain cysteine residues. For biological activity studies the peptides were prepared by solid phase peptide synthesis. Baptide 3 and 2 blocked acetylcholine-elicited currents in isolated Lymnaea stagnalis neurons with IC 50 of about 50 μM and 250 μM, respectively. In addition baptide 2 blocked acetylcholine-induced currents in muscle nAChR heterologously expressed in Xenopus oocytes with IC 50 of about 3 μM. The peptides did not compete with radioactive α-bungarotoxin for binding to Torpedo and α7 nAChRs at concentration up to 200 μM that suggests non-competitive mode of inhibition. Calcium imaging studies on α7 and muscle nAChRs heterologously expressed in mouse neuroblastoma Neuro2a cells showed that on α7 receptor baptide 2 inhibited acetylcholine-induced increasing intracellular calcium concentration with IC 50 of 20.6 ± 3.93 μM. On both α7 and muscle nAChRs the suppression of maximal response to acetylcholine by about 50% was observed at baptide 2 concentration of 25 μM, the value being close to IC 50 on α7 nAChR. These data are in accord with non-competitive inhibition as follows from α-bungarotoxin binding experiments. The described peptides are the shortest peptides without disulfide bridges isolated from animal venom and capable to inhibit nAChR by non-competitive way. Copyright © 2016. Published by Elsevier Ltd.

[What is the link between the sister of the "Titanic" and the history of medicine in Palestine?].

PubMed

Greenberg, Zalman

2006-06-01

On 21st November 1916, the Royal Navy Hospital ship 'Britannic' (the sister ship of the 'Titanic') was torpedoed near the island of Kea in the Aegean Sea. Captain Dr. John Cropper, aged 52, was one of 30 people who drowned of the 1100 on board. Dr. Cropper was born in 1864, at Guisborough, England. He obtained his medical degree from Cambridge University in 1891. After his marriage to Anne Ellen Walker in 1895, the Church Missionary Society sent him on a medical mission to Palestine. Dr. Cropper stayed in Palestine for about 10 years working in Acre, Nablus, Ramallah and Jerusalem. He published his experiences in 35 articles and letters in English medical periodicals, more than anyone else did in Palestine at that time. In those publications, he described various operations that he carried out and observations on infectious diseases, most of which were the first descriptions from that remote and unhealthy country. His prominent research was in the field of malaria - the most common and important disease in Palestine during that period. It was less than two years after Grassi's discovery of the role of Anopheles mosquitoes as the vector of human malaria that Dr. Cropper carried out surveys of larval and adult mosquitoes in correlation with malarial distribution in Palestine. Dr. Cropper was the first who routinely examined slides microscopically in Palestine and correctly diagnosed the type of malaria. Dr. Cropper was also the first in Palestine to suggest antimalarial measures aimed directly at the mosquito vector and paid attention to ecological aspects such as breeding places and the daily behavior of adult mosquitoes. Dr. Cropper noted the common antimalarial measurements of that time, such as covering of wells, planting of Eucalyptus trees to drain swamps and the routine use of quinine as a preventive medicine, but he wrote that those measures were not effective under the local conditions. He suggested that the only effective measures must be aimed against the larval mosquitoes and he recommended the use of a sulphur compound in order to destroy the larvae. Only many years later were those observations recognized as being correct. In our local public scientific memory, we remember early researchers such as Dr. Hillel Jaffe, Prof. Peter Muehlens, Prof. Israel Kligler, Prof. Gideon Mer, Dr. Zvi Saliternik and many others. Dr. Cropper preceded all of them. The comprehensive contributions of this English doctor to the medical research in Palestine should not be forgotten.

Hysteria after Charcot: back to the future.

PubMed

Bogousslavsky, Julien

2011-01-01

The studies on hysteria and hypnotism probably constitute the most important long-term work of Jean-Martin Charcot and his school, starting around 1870 until Charcot's death in 1893. Désiré Bourneville, Charcot's sixth interne at La Salpêtrière, was probably instrumental in stimulating his mentor's interest in hysteria, while Charles Richet's 1875 article on somnambulism was the trigger for Charcot to introduce hypnotism into the management of hysterics. Albert Pitres, Paul Richer, Georges Gilles de la Tourette, Paul Sollier, Joseph Babinski, Sigmund Freud and Pierre Janet became the most famous of Charcot's collaborators on hysteria, either as 'guardians of the temple' (Richer, Gilles de la Tourette, who defended their mentor's concepts against Hippolyte Bernheim and the Nancy school in the dispute during the 1880-1890s), or in renewing the field in psychology (Janet and Freud, in the 1890s) or clinical neurology (Babinski in the 1900s). In 1908, a 'quarrel of hysteria' led several of Charcot's pupils into opposition with each other, from which Babinski was considered victorious against Charcot's successor Fulgence Raymond, despite the weaknesses of his theory on 'pithiatism'. During World War I, there was a new surge of interest in hysteria associated with war psycho-neuroses, and several students of Charcot became actively involved in medical military care (Sollier, Babinski, Gilbert Ballet, Achille Souques). Babinski's pupil Clovis Vincent developed a treatment called torpillage (torpedoing) against war hysteria, associating painful galvanic current discharges with 'persuasion', but this was dismissed after the soldiers, considering it as torture, rebelled. After World War I, the neurological and psychiatric interest in hysteria again faded away, and this condition largely went back to the no-man's land, where it had been before Charcot initiated his studies. A comprehensive look at the evolution of ideas on hysteria in the followers of Charcot shows that contrary to a common and artificially maintained view over the years, the modernity of several of his concepts remains remarkable, including: (1) his traumatic theory, which encompassed sexual factors nearly 20 years before Freud; (2) his evolution towards psychological and emotional issues, which opened the way for Janet and Freud, but unfortunately was largely ignored by Babinski; (3) his strong claim against Bernheim of the similarity of mental states in hypnotism and hysteria, which has recently been confirmed by functional magnetic resonance imaging; (4) his 'dynamic lesion' hypothesis, which now correlates well with neurophysiological mechanisms also demonstrated by functional imaging. Copyright © 2011 S. Karger AG, Basel.

Draft de novo transcriptome assembly and proteome characterization of the electric lobe of Tetronarce californica: a molecular tool for the study of cholinergic neurotransmission in the electric organ.

PubMed

Stavrianakou, Maria; Perez, Ricardo; Wu, Cheng; Sachs, Matthew S; Aramayo, Rodolfo; Harlow, Mark

2017-08-14

The electric organ of Tetronarce californica (an electric ray formerly known as Torpedo californica) is a classic preparation for biochemical studies of cholinergic neurotransmission. To broaden the usefulness of this preparation, we have performed a transcriptome assembly of the presynaptic component of the electric organ (the electric lobe). We combined our assembled transcriptome with a previous transcriptome of the postsynaptic electric organ, to define a MetaProteome containing pre- and post-synaptic components of the electric organ. Sequencing yielded 102 million paired-end 100 bp reads. De novo Trinity assembly was performed at Kmer 25 (default) and Kmers 27, 29, and 31. Trinity, generated around 103,000 transcripts, and 78,000 genes per assembly. Assemblies were evaluated based on the number of bases/transcripts assembled, RSEM-EVAL scores and informational content and completeness. We found that different assemblies scored differently according to the evaluation criteria used, and that while each individual assembly contained unique information, much of the assembly information was shared by all assemblies. To generate the presynaptic transcriptome (electric lobe), while capturing all information, assemblies were first clustered and then combined with postsynaptic transcripts (electric organ) downloaded from NCBI. The completness of the resulting clustered predicted MetaProteome was rigorously evaluated by comparing its information against the predicted proteomes from Homo sapiens, Callorhinchus milli, and the Transporter Classification Database (TCDB). In summary, we obtained a MetaProteome containing 92%, 88.5%, and 66% of the expected set of ultra-conserved sequences (i.e., BUSCOs), expected to be found for Eukaryotes, Metazoa, and Vertebrata, respectively. We cross-annotated the conserved set of proteins shared between the T. californica MetaProteome and the proteomes of H. sapiens and C. milli, using the H. sapiens genome as a reference. This information was used to predict the position in human pathways of the conserved members of the T. californica MetaProteome. We found proteins not detected before in T. californica, corresponding to processes involved in synaptic vesicle biology. Finally, we identified 42 transporter proteins in TCDB that were detected by the T. californica MetaProteome (electric fish) and not selected by a control proteome consisting of the combined proteomes of 12 widely diverse non-electric fishes by Reverse-Blast-Hit Blast. Combined, the information provided here is not only a unique tool for the study of cholinergic neurotransmission, but it is also a starting point for understanding the evolution of early vertebrates.

Acetylcholinesterases from Elapidae snake venoms: biochemical, immunological and enzymatic characterization.

PubMed

Frobert, Y; Créminon, C; Cousin, X; Rémy, M H; Chatel, J M; Bon, S; Bon, C; Grassi, J

1997-05-23

We analyzed 45 batches of venom from 20 different species belonging to 11 genera from the 3 main families of venomous snakes (Elapidae, Viperidae and Crotalidae). We found high acetylcholinesterase (AChE) activity in all venoms from Elapidae, except in those from the Dendroaspis genus. AChE was particularly abundant in Bungarus venoms which contain up to 8 mg of enzyme per gram of dried venom. We could not detect acetylcholinesterase activity in any batch of venom from Viperidae or Crotalidae. Titration of active sites with an organophosphorous agent (MPT) revealed that the AChE of all venoms have similar turnovers (6000 to 8000 s(-1)) which are clearly higher than those of Torpedo and mammalian enzymes but lower than that of Electrophorus. AChEs from the venom of elapid snakes of the Bungarus, Naja, Ophiophagus and Haemacatus genera were purified by affinity chromatography. SDS-PAGE analysis and sucrose gradient centrifugation demonstrated that AChE is exclusively present as a nonamphiphilic monomer. These enzymes are true AChEs, hydrolyzing acetylthiocholine faster than propionylthiocholine and butyrylthiocholine and exhibiting excess substrate inhibition. Twenty-seven different monoclonal antibodies directed against AChE from Bungarus fasciatus venom were raised in mice. Half of them recognized exclusively the Bungarus enzyme while the others cross-reacted with AChEs from other venoms. Polyspecific mAbs were used to demonstrate that venoms from Dendroaspis, which contain the AChE inhibitor fasciculin but lack AChE activity, were also devoid of immunoreactive AChE protein. AChE inhibitors acting at the active site (edrophonium, tacrine) and at the peripheral site (propidium, fasciculin), as well as bis-quaternary ligands (BW284C51, decamethonium), were tested against the venom AChEs from 11 different species. All enzymes had a very similar pattern of reactivity with regard to the different inhibitors, with the exception of fasciculin. AChEs from Naja and Haemacatus venoms were relatively insensitive to fasciculin inhibition (IC50 > 10(-6) M), while Bungarus (IC50 approximately 10(-8) M) and especially Ophiophagus (IC50 < 10(-10) M) AChEs were inhibited very efficiently. Ophiophagus and Bungarus AChEs were also efficiently inhibited by a monoclonal antibody (Elec-410) previously described as a specific ligand for the Electrophorus electricus peripheral site. Taken together, these results show that the venoms of most Elapidae snakes contain large amounts of a highly active non-amphiphilic monomeric AChE. All snake venom AChEs show strong immunological similarities and possess very similar enzymatic properties. However, they present quite different sensitivity to peripheral site inhibitors, fasciculin and the monoclonal antibody Elec-410.

The Moon and the U-47 in Scapa Flow

NASA Astrophysics Data System (ADS)

Schaefer, B. E.

2005-12-01

The skies above affect historical events here on Earth more than is generally realized. Events during wars are often tied to the Moon through operational requirements for illumination (or dark), high tides (or low), and even links to events in lunar calendars. World War II has many famous battles, commando operations, and naval sorties dictated in date by the Moon. Famous examples are D-Day (needing low tides and Full Moon illumination), the amphibious landing on Tarawa (needing but not getting high tides), El Alamein (requiring Full Moon light for the mine-clearers), the Great Escape from Stalag Luft III (chosen for the stealth possible with a New Moon), Mussolini's invasion of Albania (on Good Friday), and even Rudolf Hess' flight to Scotland (timed by a six-planet conjunction and aided in navigation by the Full Moon). This paper will concentrate on one event for which the Moon provided the primary trick for a major Nazi naval victory, while an aurora saved the British from an even worse disaster. The story is set in Scapa Flow, the huge anchorage in the Orkney Islands that was used as a primary base for the British Navy in blockading the North Sea. During World War I, German submarines had twice tried to slip into Scapa Flow but were sunk both times, and the anchorage later became the last resting place of the scuttled German High Seas Fleet. At the outbreak of World War II, then Commodore Karl Doenitz suggested that his ace U-boat captain consider sneaking into Scapa Flow to loose salvos of torpedoes at all the anchored ships. Captain Gunther Prien of the U-47 took up the challenge after realizing that the British had not completely blocked a narrow inlet. His plan was to surface the submarine and go in over the sunken block ships at the highest of spring tides. Spring tides require a syzygy (New or Full Moon), during which the high tides occur near noon or midnight. To be unobserved by onshore guards, the Moon should not be in the sky illuminating the waters. The requirement for darkness forced the choice of going in around midnight on a New Moon date. But this by itself would not have allowed the U-47 to ride high in the water, so Prien chose a New Moon night where the Moon was closest to Earth in its orbit (at perigee) and the spring tide would be at its extreme high. So, on 13 October 1939, the U-47 surfaced just outside Kirk Sound, scraped through the blocked passage, found the battleship HMS Royal Oak at anchor, and fired two salvos which quickly sank the ship killing 833 sailors. Prien could have continued hunting in the anchorage for more ships, but one of the brightest aurora of the year (which was near a sunspot maximum) started illuminating the waters. Prien wisely withdrew as the U-47 would rapidly have been trapped if spotted under the aurora-light. This disaster was a major propaganda victory for the Nazis and was a heavy blow when the British navy and prestige were soon all that separated England from powerful armies.

Treatment of neovascular age-related macular degeneration with a variable ranibizumab dosing regimen and one-time reduced-fluence photodynamic therapy: the TORPEDO trial at 2 years.

PubMed

Spielberg, Leigh; Leys, Anita

2010-07-01

The combination of verteporfin photodynamic therapy (PDT) and anti-angiogenics has been shown to be safe and efficacious in the treatment of choroidal neovascularization (CNV) secondary to age-related macular degeneration (AMD). The purpose of this study is to demonstrate long-term prevention of vision loss and improvement in best-corrected visual acuity (BCVA) after treatment with one-time reduced-fluence-rate PDT followed by administration of ranibizumab on a variable dosing regimen over 24 months in patients with neovascular AMD. Secondary outcome measures included the change in central macular thickness (CMT), reinjection frequency, and safety. This prospective, nonrandomized, open-label, single-center study enrolled 27 consecutive patients (27 eyes) presenting at the Leuven University Eye Hospital with previously untreated, active neovascular AMD between September 2006 and January 2007. All patients were treated with one-time, reduced-fluence-rate verteporfin PDT, followed by intravitreal ranibizumab 0.5 mg on the same day. A second and third ranibizumab injection were given at weeks 4 and 8, respectively, after which patients were followed up monthly for 24 months. Additional treatment with ranibizumab was administered to eyes with active neovascularization as indicated clinically and on imaging studies. Retreatment was based on the following criteria: (1) presence of subretinal fluid (SRF), intraretinal edema or sub-retinal pigment epithelial fluid, as seen on OCT; (2) increase of CMT by >100 mm on OCT; (3) signs of active CNV leakage on fluorescein angiography; (4) new sub- or intraretinal hemorrhage; and (5) BCVA decreased of > or =5 letters on the Early Treatment of Diabetic Retinopathy Study (ETDRS) chart. If any single criterion for reinjection was fulfilled, retreatment with ranibizumab was administered. Twenty-five patients completed the 2-year study. Occult CNV was present in 64% and retinal angiomatous proliferative (RAP) lesions were present in 24% of the study eyes. The remaining three eyes had lesions classified as classic (one eye) or predominantly classic (two eyes) CNV. Month 24 data are available for 25 eyes (25 patients; age 55-86 years; mean 77; standard deviation (SD) = 7.2). Mean baseline VA was 58.6 letters (range: 35-70; SD = 8.4); 24-month VA was 66.2 letters (35-82; 12.7), not including one warfarin-treated patient who suffered vitreous hemorrhage. The mean visual acuity improved by 7.2 letters (p < 0.05) and the mean CMT decreased by 146 mum. VA improved >3 lines (15 letters) in 16%; improved 1-3 lines in 20%; remained within one line of baseline in 32%, decreased 1-3 lines in 16%, and decreased >3 lines in 16%. Losses of >3 lines were due to vitreous hemorrhage, geographic atrophy, fibrosis, and growth of an initially small CNV lesion. An average of 5.1 injections (range: 3-9) were administered during the first 12 months, and 7.1 injections (3-13) over 24 months. A total of 178 injections were performed; no systemic side-effects, uveitis, or choroidal collateral vascular damage were observed. Two patients were lost to follow-up. Combined PDT and ranibizumab injection the same day was well tolerated in all patients. Eighty-four percent of patients had stable or improved vision at month 24.

CubeSub

NASA Technical Reports Server (NTRS)

Slettebo, Christian; Jonsson, Lars Jonas

2016-01-01

This presentation introduces and discusses the development of the CubeSub submersible concept, an Autonomous Underwater Vehicle (AUV) designed around the CubeSat satellite form factor. The presented work is part of the author's MSc thesis in Aerospace Engineering at the Royal Institute of Technology, Stockholm, Sweden, and was performed during an internship at the Mission Design Division of the NASA Ames Research Center, Moffett Field, CA. Still in the early stages of its development, the CubeSub is to become a submersible test-bed for technology qualified for underwater and space environments. With the long-term goal of exploring the underwater environments in outer space, such as the alleged subsurface ocean of Jupiter's moon Europa, a number of technology and operational procedures must be developed and matured. To assist in this, the CubeSub platform is introduced as a tool to allow engineers and scientists to easily test qualified technology underwater. A CubeSat is a class of miniaturized satellite built to a standardized size. The base size is 1U (U for unit), corresponding to a 100 x 100 x 113.5 cu mm cube. A 1U CubeSat can in other words easily be held in one hand. Stacking units give larger satellite sizes such as the also commonly used 1.5U, 2U and 3U. The CubeSat standard is in itself already well established and hundreds of CubeSats have to date been launched into space. Compatible technology is readily available and the know-how exists in the space industry, all of which makes it a firm ground to stand on for the CubeSub. The rationale behind using the CubeSat form factor is to make use of this pre-existing foundation, making the CubeSub easy to develop, modular and readily available. It will thereby aid in the process of maturing the concept of a fully space qualified submersible headed for outer space. As a further clarification, the CubeSub is itself not meant for outer space, but to facilitate development of such a vessel. Along with its uses as a testbed, the CubeSub also holds the potential to become a useful tool for exploration and experimentation here on Earth. A highly standardized system utilizing well-known hardware can reduce the cost and required work load for researchers wishing to perform experiments and exploration. Users could design sensors and experiments to comply with the already well established CubeSat standard, which are then carried by the CubeSub to the region of interest. This in turn means that the end users can focus more on formulating the experiment itself and less about how to get it where they want it. The CubeSub is designed to be built up by modules, which can be assembled in different configurations to fulfill different needs. Each module will be powered individually and intermodular communication will be wireless, removing the need for wiring. The inside of the cylindrical hull will be flooded with ambient water to enhance the interaction between payloads and surrounding environment. The overall torpedo-like shape is similar to that of a conventional AUV, slender and smooth. This is to make for a low drag, reduce the risk of snagging on surrounding objects and make it possible to deploy through an ice sheet via a narrow borehole or navigate in tight areas. To keep costs low and further accelerate development, rapid prototyping is utilized wherever possible. Full-scale prototypes are being constructed through 3D-printing and using COTS (Commercial Off-The-Shelf) components. 3D-printing is used both for the largest hull components and the relatively small and delicate propellers. Arduino boards are used for control and internal communication

Real-time visual mosaicking and navigation on the seafloor

NASA Astrophysics Data System (ADS)

Richmond, Kristof

Remote robotic exploration holds vast potential for gaining knowledge about extreme environments accessible to humans only with great difficulty. Robotic explorers have been sent to other solar system bodies, and on this planet into inaccessible areas such as caves and volcanoes. In fact, the largest unexplored land area on earth lies hidden in the airless cold and intense pressure of the ocean depths. Exploration in the oceans is further hindered by water's high absorption of electromagnetic radiation, which both inhibits remote sensing from the surface, and limits communications with the bottom. The Earth's oceans thus provide an attractive target for developing remote exploration capabilities. As a result, numerous robotic vehicles now routinely survey this environment, from remotely operated vehicles piloted over tethers from the surface to torpedo-shaped autonomous underwater vehicles surveying the mid-waters. However, these vehicles are limited in their ability to navigate relative to their environment. This limits their ability to return to sites with precision without the use of external navigation aids, and to maneuver near and interact with objects autonomously in the water and on the sea floor. The enabling of environment-relative positioning on fully autonomous underwater vehicles will greatly extend their power and utility for remote exploration in the furthest reaches of the Earth's waters---even under ice and under ground---and eventually in extraterrestrial liquid environments such as Europa's oceans. This thesis presents an operational, fielded system for visual navigation of underwater robotic vehicles in unexplored areas of the seafloor. The system does not depend on external sensing systems, using only instruments on board the vehicle. As an area is explored, a camera is used to capture images and a composite view, or visual mosaic, of the ocean bottom is created in real time. Side-to-side visual registration of images is combined with dead-reckoned navigation information in a framework allowing the creation and updating of large, locally consistent mosaics. These mosaics are used as maps in which the vehicle can navigate and localize itself with respect to points in the environment. The system achieves real-time performance in several ways. First, wherever possible, direct sensing of motion parameters is used in place of extracting them from visual data. Second, trajectories are chosen to enable a hierarchical search for side-to-side links which limits the amount of searching performed without sacrificing robustness. Finally, the map estimation is formulated as a sparse, linear information filter allowing rapid updating of large maps. The visual navigation enabled by the work in this thesis represents a new capability for remotely operated vehicles, and an enabling capability for a new generation of autonomous vehicles which explore and interact with remote, unknown and unstructured underwater environments. The real-time mosaic can be used on current tethered vehicles to create pilot aids and provide a vehicle user with situational awareness of the local environment and the position of the vehicle within it. For autonomous vehicles, the visual navigation system enables precise environment-relative positioning and mapping, without requiring external navigation systems, opening the way for ever-expanding autonomous exploration capabilities. The utility of this system was demonstrated in the field at sites of scientific interest using the ROVs Ventana and Tiburon operated by the Monterey Bay Aquarium Research Institute. A number of sites in and around Monterey Bay, California were mosaicked using the system, culminating in a complete imaging of the wreck site of the USS Macon , where real-time visual mosaics containing thousands of images were generated while navigating using only sensor systems on board the vehicle.

Obituary: Ralph Asher Alpher, 1921-2007

NASA Astrophysics Data System (ADS)

Koopman, Rebecca A.

2007-12-01

Ralph Asher Alpher, noted cosmologist, physicist, and educator, died on August 12, 2007, in Austin, Texas. Alpher developed the first model for primordial nucleosynthesis in the hot early Universe and, with Robert Herman, first predicted the cosmic microwave background radiation. During his long and productive career, he published over one-hundred papers, a book translation, chapters in a number of books (primarily in cosmology), and The Genesis of the Big Bang, a book about his life in cosmology, co-authored with Robert Herman. Ralph's work has been cited by the American Physical Society News as one of the Top Ten Astronomical Triumphs of the Millennium. Born in Washington, D.C., on February 3, 1921, Ralph was the youngest of four children of building contractor Samuel and Rose Maleson Alpher, immigrants from Russia and Latvia. He attended Roosevelt High School in Washington, graduating at the age of sixteen. A scholarship was offered by the Massachusetts Institute of Technology, but then suddenly withdrawn after a meeting with an alumnus. (Ralph would wonder all his life whether the withdrawal was due to his Jewish background.) Instead, he attended evening classes at George Washington University while working full time, earning his B.S. in 1943, his M.S. in 1945, and his Ph.D. in 1948. Ralph's master's thesis on the sources of energy in stars was completed with mentor George Gamow. Gamow then accepted him to work on a Ph.D. dissertation on the formation of galaxies, studying the growth of condensations in a relativistic homogeneous and isotropic expanding medium. Ralph found that such condensations would not grow, but before he finished writing, E. M. Lifshitz independently published similar results in 1946. Ralph started anew, this time modeling the buildup of elements by neutron capture in the hot, early phase of the Universe. Despite the approximations necessary in the pre-computer age, he found consistency with observed abundances of hydrogen and helium. The results were published in the famous Alpher-Bethe-Gamow paper in the Physical Review of April 1, 1948. Gamow, known for his sense of humor, added Bethe's name to the paper, resulting in the abbreviation αβγ. The physics-based approach to a non-static cosmological model of the Universe was viewed with excitement and over three-hundred people attended Ralph's dissertation defense. The story was picked up by the press, with the Washington Post headlining that the "World Began in 5 Minutes, New Theory" based on Ralph's answer to a question about how long primordial nucleosynthesis would have taken. At the same time that he was working on his revolutionary cosmological results, Ralph was hard at work during the day at the Department of Terrestrial Magnetism (1938-1940), the Naval Ordnance Laboratory (1940-1944), and the Johns Hopkins Applied Physics Laboratory (1944-1955). As a physicist contracted to the Navy, he made significant contributions to the development of technology to protect ships against magnetic mines and to magnetically detect submarines from the air. At the Applied Physics Laboratory, he developed a magnetic gradiometer proximity exploder for air-launched torpedoes and worked in programs to develop ground-launched antiaircraft guided missiles. After the war, he worked on supersonic gas dynamics and later cosmic radiation in a group headed by James A. Van Allen. In 1945, Ralph received the Naval Ordnance Development Award in recognition of his work. It was at the Applied Physics Laboratory in 1944 that Alpher met his longtime collaborator and friend Robert Herman, a specialist in molecular spectroscopy, with whom he would collaborate until Herman's death in 1997. Together Alpher and Herman reevaluated the nucleosynthesis calculations and further probed the physics of an early, hot Universe, publishing numerous papers between 1948-1955. The final paper, published in 1953 with James Follin, Jr., established the methodology used for dealing with physical conditions in the early Universe prior to nucleosynthesis. Early on, Alpher and Herman realized that if the expanding Universe began in a hot phase, relic radiation from the era when radiation and matter decoupled should fill the Universe. They published this result in Nature in 1948, predicting that the current temperature should be 5K. In talk after talk, and in a series of papers, they publicized their work and urged observers to start looking for this radiation, but without result. At the time, the model of the hot, expanding Universe, scornfully christened "Big Bang" by Fred Hoyle in 1950, was far from accepted by the cosmology community, especially since the measured value of the Hubble constant produced a very small evolutionary age. Even if the Big Bang model was correct, the consensus was that the relic radiation would be much too faint to detect. Dismayed by the lack of interest in their results, both Alpher and Herman decided in 1955 to give up academia, turning down positions offered at the University of Iowa with James van Allen, and instead accepting jobs at General Electric (GE) and General Motors. Both had families by that time. Ralph had met his wife, Louise Ellen Simons, in 1940. They married January 28, 1942, and had two children, Harriet and Victor. Ralph worked for 32 years at GE Research and Development Center in Niskayuna, New York, on a variety of projects including high-speed aerodynamics, theoretical problems involving the physics of television projection systems, magnetohydrodynamic methods, and, eventually, strategic planning and technology forecasting. The papers about the relic radiation languished in the literature, but Alpher and Herman kept up with developments in cosmology. One can imagine their excitement and gratification when they learned of the serendipitous detection of the cosmic microwave background by Arno Penzias and Robert Wilson in 1965 and found that their model temperature (with updated values of cosmological parameters) was in agreement with the 3K measurement. Their excitement soon turned to dismay as a flurry of resulting publications, most notably those of Robert Dicke, P. James Peebles, and collaborators at Princeton, reproduced their results but neglected to mention Alpher & Herman (1948). For much of the rest of their lives they waited for proper recognition of their prediction. The Nobel Prize of 1978 went to Penzias and Wilson, but Penzias cited Alpher and Herman in his acceptance speech. Gradually recognition came, although Gamow was often credited equally with Alpher and Herman, even though Gamow had not participated in the original calculations and had published independent calculations later shown to be incorrect. Ralph retired from GE in 1987. He taught from 1986 to 2004 at Union College as distinguished research professor, retiring in 2004. Students and faculty remember him fondly for his contributions to Union and his kind nature. Ralph was a member of the board of directors of Dudley Observatory and was its Administrator from 1987 to 2000. He was generous in donating his time to the community, serving on the board of the local public television station WMHT-- including a two-year term as its president--and as mentor to the Boy Scouts. (He was an Eagle Scout himself at age twelve). Among the awards Ralph earned are the Magellanic Premium of the American Philosophical Society, the George Vanderlinden Prize of the Belgium Royal Academy of Sciences Letters and Fine Arts, the George Wetherill Medal of the Franklin Institute, and the Mathematics Prize of the New York Academy of Sciences. In 1993, Alpher and Herman were awarded the Henry Draper Medal of the National Academy of Sciences for their early work on the Big Bang model, nucleosynthesis, and the prediction of the cosmic microwave background radiation. Steven Weinberg wrote in his 1993 book, The First Three Minutes, that Alpher carried out "the first thoroughly modern analysis of the early history of the Universe." Most recently, Ralph was awarded the 2005 National Medal of Science "for his unprecedented work in the areas of nucleosynthesis, for the prediction that universe expansion leaves behind background radiation, and for providing the model for the Big Bang theory."