Characteristic of Nitron for Use as a Chemical Sensor in Studies of the Upper Atmosphere

NASA Technical Reports Server (NTRS)

Meadows, Kapres; Wright, Cassandra K.; Sims, S. C.; Morris, V. R.

1997-01-01

We are investigating the use of nitron as a potential chemical sensor for nitric acid and other electron deficient nitrogen oxides. Solutions of nitron in 1-propanol, toluene, and chloroform have been tested for use on a piezoelectric quartz crystal microbalance. We are testing various solvents and metal cations which can maximize the lifetime and reaction specificity of nitron so that they may be used as chemical coatings for stratospheric measurement of trace gases. Results of the work to date will be shown, and future direction discussed.

LANN wing design

NASA Technical Reports Server (NTRS)

Firth, G. C.

1983-01-01

The LANN wing is the result of a joint effort between Lockheed, the Air Force, NASA, and the Netherlands to measure unsteady pressures at transonic speeds. It is a moderate-aspect-ratio transport wing configuration. The wing was machined from NITRONIC 40 and has 12 percent thick supercritical airfoil sections.

Condensation cyclization reactions of electron deficient aromatics. 4: Tricyclic nitropropene nitronates from the reaction of phloroglucinol and cycloalkanones with sym-trinitrobenzene

NASA Technical Reports Server (NTRS)

Strauss, M. J.; Taylor, S. P. B.; Shindo, H.

1972-01-01

Interesting similarities have been shown between the reactions of sym-trinitrobenzene with cycloalkanones, and with phloroglucinol. Previously unsuspected common intermediates have been shown to intervene. The structurally similar products in each case are tricyclic nitropropene nitronates. Protonation of these yields the corresponding nitronic acids in certain instances.

High temperature phase chemistries and solidification mode prediction in nitrogen-strengthened austenitic stainless steels

NASA Astrophysics Data System (ADS)

Ritter, Ann M.; Henry, Michael F.; Savage, Warren F.

1984-07-01

Nitronic 50 and Nitronic 50W, two nitrogen-strengthened stainless steels, were heat treated over a wide range of temperatures, and the compositions of the ferrite and austenite at each temperature were measured with analytical electron microscopy techniques. The compositional data were used to generate the (γ + δ phase field on a 58 pct Fe vertical section. Volume fractions of ferrite and austenite were calculated from phase chemistries and compared with volume fractions determined from optical micrographs. Weld solidification modes were predicted by reference to the Cr and Ni contents of each alloy, and the results were compared with predictions based on the ratios of calculated Cr and Ni equivalents for the alloys. Nitronic 50, which contained ferrite and austenite at the solidus temperature of 1370 °C, solidified through the eutectic triangle, and the weld microstructure was similar to that of austenitic-ferritic solidification. Nitronic 50W was totally ferritic at 1340 °C and solidified as primary delta ferrite. During heat treatments, Nitronic 50 and Nitronic 50W precipitated secondary phases, notably Z-phase (NbCrN), sigma phase, and stringered phases rich in Mn and Cr.

Manufacturing Methods and Techniques for Miniature High Voltage Hybrid Multiplier Modules

DTIC Science & Technology

1977-05-06

technologies and materials,, and to demonstrate the production line capability to fabricate at the rate of 125 acceptable units per 40 hour week. - iv...Miraloma Avenue Anaheim, CA 92803 Dr. Andrew Tlcki1 Nitron Cornoratlon 10420 Bubb Road Cunertino, CA 95014 S I Commander RAt)C * ATTN: RBRII/Mr. J. Brauer

Government-owned CubeSat Next Generation Bus Reference Architecture

DTIC Science & Technology

2014-08-02

satellites placed in orbit has been growing exponentially since 1999 as demonstrated by more than 40 CubeSats being launched in the last quarter of 2013...Emhart Helicoil #2(.086)-56 x 0.172 inch long, Nitronic 60 stainless steel. A trade-study was conducted regarding the choice of metric versus SAE

Evaluation of candidate Stirling engine heater tube alloys for 1000 hours at 760 C

NASA Technical Reports Server (NTRS)

Misencik, J. A.

1980-01-01

Six tubing alloys were endurance tested in a diesel fired, Stirling engine simulator materials test rig for 1000 hours of 760 C while pressurized at 17 to 21 MPa with either hydrogen or helium. The alloys tested were N 155, A 286, Incoloy 800, 19 9DL, Nitronic 40 and 316 stainless steel. The alloys were in the form of thin wall tubing. Hydrogen permeated rapidly through the tube walls of all six alloys when they were heated to 760 C. Helium was readily contained. Creep rupture failures occurred in four of the six alloys pressurized with hydrogen. Only two alloys survived the 1000 hour endurance test with no failures. Simultaneous exposure to either hydrogen or helium and the combustion environment did not seriously degrade the tensile strength of the six alloys in room temperature or 760 C tests after exposure. Decreases in room temperature ductility were observed and are attributed to aging rather than to hydrogen embrittlement in three of the alloys. However, there may be a hydrogen embrittlement effect in the N 155, 19 9DL, and Nitronic 40 alloys.

Characterization of the Chemical Constitution and Profile of Pharmacological Activity of PGB(x).

DTIC Science & Technology

1982-02-26

ischemia. Fed. Proc. 40 , 692 (1980). 3. Burkman, A. M. and Phornchirasilp, S., Prostaglandin Bx enhances the inotropic efficacy (Emax) of...nitroketone 10 was then converted to the sodium salt of the corresponding nitronic acid on treatment with an equimolar amount of sodium metabolite in...bromide in chloroform-ethyl acetate to give unsaturated aldehyde 12 in 40 ’ yield. The reaction of compound 9 with dimethyl (2-oxoheptvl) phosphonate in

NCEL (Naval Civil Engineering Laboratory) Quarterly Abstracts of Technical Documents, 1 April to 30 June 1987.

DTIC Science & Technology

1987-06-30

release; distribution unlimited. 87 8 3075 TABLE OF CONTENTS page TECHNICAL NOTES N-1764 Validation of Nitronic 33 in Reinforced and Prestressed...TECHNICAL WES K- 1764 Validation of Nitrovic 33 In Reeinforced and Prestressed Concrete, Apr 1987, James F. Jenkins (public release) Nitronic 33...prestressing strand are not acceptable. Before Nitronic 33 stainless steel prestressed concrete waterfront structures were constructed, it was necessary to

PASS-predicted design, synthesis and biological evaluation of cyclic nitrones as nootropics.

PubMed

Marwaha, Alka; Goel, R K; Mahajan, Mohinder P

2007-09-15

Out of 400 virtually designed imidazoline N-oxides, five cyclic nitrones were selected on the basis of PASS prediction as potent nootropics and were evaluated for their biological activities in albino mice. The selected N-alkyl and aryl-substituted nitrones were found to be excellent nootropics. A series of lead compounds acting as cognition enhancers have been provided, which can be further exploited in search of such New Chemical Entities (NCEs).

Effects of Ammonium Dinitramide in Human Liver Slices: An EPR/Spin Trapping Study.

DTIC Science & Technology

1995-09-01

environmentally safe than AP. EPR/spin trapping studies with the spin trap N-tert-butyl-a-phenyl nitrone (PBN lOmM) for 5 min in the presence of ADN yielded...N-tert-butyl-a-phenyl nitrone PBN 17. SECURITY CLASSIFICATION OF REPORT UNCLASSIFIED 18. SECURITY CLASSIFICATION OF THIS PAGE UNCLASSIFIED... nitrone s second SCN- thiocyanate SD standard deviation Vll INTRODUCTION This is a study of the reactions of free radicals formed when ammonium

Reactivities of Substituted α-Phenyl-N-tert-butyl Nitrones

PubMed Central

2015-01-01

In this work, a series of α-phenyl-N-tert-butyl nitrones bearing one, two, or three substituents on the tert-butyl group was synthesized. Cyclic voltammetry (CV) was used to investigate their electrochemical properties and showed a more pronounced substituent effect for oxidation than for reduction. Rate constants of superoxide radical (O2•–) reactions with nitrones were determined using a UV–vis stopped-flow method, and phenyl radical (Ph•) trapping rate constants were measured by EPR spectroscopy. The effect of N-tert-butyl substitution on the charge density and electron density localization of the nitronyl carbon as well as on the free energies of nitrone reactivity with O2•– and HO2• were computationally rationalized at the PCM/B3LYP/6-31+G**//B3LYP/6-31G* level of theory. Theoretical and experimental data showed that the rates of the reaction correlate with the nitronyl carbon charge density, suggesting a nucleophilic nature of O2•– and Ph• addition to the nitronyl carbon atom. Finally, the substituent effect was investigated in cell cultures exposed to hydrogen peroxide and a correlation between the cell viability and the oxidation potential of the nitrones was observed. Through a combination of computational methodologies and experimental methods, new insights into the reactivity of free radicals with nitrone derivatives have been proposed. PMID:24968285

Efficiency of PBN to Trap 3-CAR in B6C3F1 Mouse Liver Slices: An EPR Study.

DTIC Science & Technology

1995-09-01

be identified by electron paramagnetic resonance (EPR) using the spin trap N-tert-butyl-a phenyl nitrone (PBN). To quantitate the radicals detected...phenyl nitrone TCE trichloroethylene Vll INTRODUCTION Understanding free radical reactions is important to the military. The main objective of this...short lived radical with a spin trap’, usually a nitrone or nitroso compound yielding a longer lived nitroxide spin adduct which can be detected by

Activated Metal Oxide Surfaces as Highly Basic and Reducing Environments.

DTIC Science & Technology

1987-05-21

were formed, as illustrated by [Mg iO] and 93 12[Mg9AI301 2] . Unique reaction properties were described. 2. Spin Traps Organic nitroso and nitrone ...J. V. Ortiz, R. Basu and Y. Ohrn, Chem. Phys. Lett. 103, 29 (1983). 39. K. J. Klabunde and A. Whetten, J. Am. Chem. Soc., 108, 6529 (1986). 40 . G. H...editor, Elsevier, in press. 40 . F. Mousa and K. J. Klabunde, "Base Condensation of Carbonyl Compounds on Thermally Activated Magnesium Oxide

Water Quality Criteria for Nitrocellulose

DTIC Science & Technology

1986-06-01

38 . 6. REFERENCES. .................................................... 40 ’ 7. GLOSSARY...Flexible "collodion, FM--NIS, Guncotton, IX 3/5, Kodak Li 115, LR 115, Nitrocel- lulose E950, Nitrocotton, Nitron , Nixon N/C, NTs 62, Nrs 218, Nrs 222...0OCf 38.79 15.8 40 ,827h 24 mo 1 42.69 6.5 1,526 24 mo 3 NAI 6.7 NDJ 24 mo 10 38.35 13.8 36,031k Mouse 24 mo 0 37 6.2 0 (female) 24 ma 1of 34.2 12.8

Distributed Computing for Signal Processing: Modeling of Asynchronous Parallel Computation.

DTIC Science & Technology

1986-03-01

the proposed approaches 16, 16, 40 . 451. The conclusion most often reached is that the best scheme to use in a particular design depends highly upon...76. 40 . Siegel, H. J., McMillen. R. J., and Mueller. P. T.. Jr. A survey of interconnection methods for reconligurable parallel processing systems...addressing meehaanm distributed in the network area rimonication% tit reach gigabit./second speeds je g.. PoCoS83 .’ i.V--i the lirO! lk i nitronment is

VLSI (Very Large Scale Integrated Circuits) Device Reliability Models.

DTIC Science & Technology

1984-12-01

CIRCUIT COMPLEXITY FAILURE RATES FOR... A- 40 MOS SSI/MSI DEVICES IN FAILURE PER 106 HOURS TABLE 5.1.2.5-19: C1 AND C2 CIRCUIT COMPLEXITY FAILURE RATES FOR...A- 40 MOS SSI/MSI DEVICES IN FAILURE PER 106 HOURS TABLE 5.1.2.5-19: Cl AND C2 CIRCUIT COMPLEXITY FAILURE RATES FOR... A-41 LINEAR DEVICES IN...19 National Semiconductor 20 Nitron 21 Raytheon 22 Sprague 23 Synertek 24 Teledyne Crystalonics 25 TRW Semiconductor 26 Zilog The following companies

Development of a Nitride Dispersion Strengthened (NDS) Metallic Alloy for High-Temperature Recuperators

DTIC Science & Technology

1985-06-01

Alloy 2- 40 2-17 Summary of Tensile and Creep/Rupture Results on 0.010-in.-Thick NDS 200 Material 2-41 2-18 Brazing Alloy Screening Tests on NOS 300 2-44...Nitride Strengthening Process 100 - - 90 - __ __ __ __ - 80 __ AFTER NITRIDE AND DENITRIDE CYCLE S 60 - - -- C,50- _ - 40 . 0 200 400 600 800 1000 1200...commercially with development of the 200-series stainless steels and the Nitronic alloys (Armco Steel designation). Manganese also is known to

Pressure Oscillations in a Liquid Propellant Gun - Possible Dependence on Propellant Burning Rate

DTIC Science & Technology

1992-06-01

corresponding nitrone (Smith 1966), an undesirable side reaction. The dilute DEHAN solution thus obtained was concentrated to 93.64 weight-percent by water...0.3- 0.0- 0.1- 0- 0 20 40 60 80 100 120 140 160 180 200 TDER (=a) 460 :-- woM Figure 6. Gas Production From the Combustion of Propellants 4600 and

Microscopic Study of the Influence of Impurities on Interface Bonding.

DTIC Science & Technology

1985-01-25

with different impurities (P,S) levels were specially made by Armco, Inc. In addition to these four alloys, commercial alloys including Armco’s Nitronic ...25 30 40 50 60 70 Percent Intergranular, % IG Figu re A. 10 Variation of K and plane stress Keff with IGA for the Fe-P-W specimens. 20 AIO 40 Fe-P-Mo...iIS- Ke f f q !m=- 0.218 35 E 30 - 30- ~m=-0. 145 25 20 25 30 40 50 60 70 Percent Intergranular, % IG Figurej A.9 Vriation of K and plane stress Keff

/sup 13/C NMR spectra of cyclic nitrones. 2. 1- and 4-substituted 2,2,5,5-tetramethyl-3-imidazoline 3-oxides

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

Grigor'ev, I.A.; Shchukin, G.I.; Martin, V.V.

1985-08-01

The chemical shift of the carbon atom of the nitrone group in the /sup 13/C NMR spectra of 3-imidazoline 3-oxides lies in the region of 117-152 ppm and depends on the electronic effect of the substituents at positions 1, 4, and 5 of the heterocycle. Increase in the electron-withdrawing character of the substituent at these positions leads to an upfield shift of the signal for the nitrone carbon atom, and this corresponds to the increase in electron density on it.

Melatonin and Nitrones As Potential Therapeutic Agents for Stroke

PubMed Central

Romero, Alejandro; Ramos, Eva; Patiño, Paloma; Oset-Gasque, Maria J.; López-Muñoz, Francisco; Marco-Contelles, José; Ayuso, María I.; Alcázar, Alberto

2016-01-01

Stroke is a disease of aging affecting millions of people worldwide, and recombinant tissue-type plasminogen activator (r-tPA) is the only treatment approved. However, r-tPA has a low therapeutic window and secondary effects which limit its beneficial outcome, urging thus the search for new more efficient therapies. Among them, neuroprotection based on melatonin or nitrones, as free radical traps, have arisen as drug candidates due to their strong antioxidant power. In this Perspective article, an update on the specific results of the melatonin and several new nitrones are presented. PMID:27932976

Identifying the site of spin trapping in proteins by a combination of liquid chromatography, ELISA, and off-line tandem mass spectrometry.

PubMed

Lardinois, Olivier M; Detweiler, Charles D; Tomer, Kenneth B; Mason, Ronald P; Deterding, Leesa J

2008-03-01

An off-line mass spectrometry method that combines immuno-spin trapping and chromatographic procedures has been developed for selective detection of the nitrone spin trap 5,5-dimethyl-1-pyrroline-N-oxide (DMPO) covalently attached to proteins, an attachment which occurs only subsequent to DMPO trapping of free radicals. In this technique, the protein-DMPO nitrone adducts are digested to peptides with proteolytic agents, peptides from the enzymatic digest are separated by HPLC, and enzyme-linked immunosorbent assays (ELISA) using polyclonal anti-DMPO nitrone antiserum are used to detect the eluted HPLC fractions that contain DMPO nitrone adducts. The fractions showing positive ELISA signals are then concentrated and characterized by tandem mass spectrometry (MS/MS). This method, which constitutes the first liquid chromatography-ELISA-mass spectrometry (LC-ELISA-MS)-based strategy for selective identification of DMPO-trapped protein residues in complex peptide mixtures, facilitates location and preparative fractionation of DMPO nitrone adducts for further structural characterization. The strategy is demonstrated for human hemoglobin, horse heart myoglobin, and sperm whale myoglobin, three globin proteins known to form DMPO-trappable protein radicals on treatment with H(2)O(2). The results demonstrate the power of the new experimental strategy to select DMPO-labeled peptides and identify sites of DMPO covalent attachments.

Endotoxin-induced mortality in rats is reduced by nitrones

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

Hamburger, S.A.; McCay, P.B.

The goal of these investigations was to determine if nitrone spin-trapping agents can alter mortality associated with endotoxemia in the rat. Reactive free radicals attack nitrone spin-trapping agents forming relatively reactive, persistent free radical spin adducts. We administered 85 mM (10 ml/kg) of alpha-phenyl N-tert-butyl nitrone (PBN), alpha-4-pyridyl-N-oxide N-tert-butyl nitrone (4-POBN), 5,5-dimethyl-1-pyrroline-N-oxide (DMPO), or vehicle (saline i.p.) 30 min before endotoxin (25 mg/kg i.p.) or vehicle to Sprague-Dawley (SD) or Holtzman virus-free (HVF) rats (n = 10-17/group). All vehicle-treated rats receiving endotoxin were dead by 1 day. At 7 days, 83% of PBN-treated SD, 42% of PBN- or POBN-treated HVF,more » and 25% of DMPO-treated HVF rats were alive. The difference in survival of PBN-treated animals between strains may reflect the higher susceptibility of HVF rats to endotoxin. The observed reduction in mortality may be related to the well-established capacity of spin-trapping agents to capture reactive free radicals that may be generated in target tissues in response to endotoxin, and that would otherwise react with cell components and produce tissue injury.« less

Electrostatic Discharge Susceptibility Data. Volume 2

DTIC Science & Technology

1989-03-13

Electric Company (NEC) BEC Beckman Instruments NIT Nitron BEN Bendix NSC National Semi CCL Croven Crystal Ltd. NUC Nucleonic Prod CEN Centralab PLE...IR OF 500% AT VR= 35V. 39 CHANGE IN IS OF 500% AT VS= -IOv. 40 CHANGE IN RESISTANCF OF .1%. 41 CHANGE IN RESISTANCE OF 2%. 42 CHANGE IN VOL OF .050V...34 240K OHM MODEL. 35 250 OHM MODEL. 36 250K OHM MODEL. 37 27.2% OF TOTAL NUMBER OF PiNS FAILED. 38 270K OHM MODEL. 39 294K OHM MODEL. 40 297K OHM

Comparison of Performance and Oxidation of Nitronic-50 and Stainless Steel 316 in Subcritical and Supercritical Water Environments

NASA Astrophysics Data System (ADS)

Karmiol, Zachary; Chidambaram, Dev

2016-05-01

This work investigates two austenitic stainless steels, Nitronic-50 and stainless steel 316, for use in both subcritical and supercritical water (SCW) conditions. The mechanical characteristics of the materials were investigated using slow strain rate testing in a SCW test loop under the following conditions: nitrogen at ambient temperature and pressure, liquid water at 473 K (200 °C) and 8 MPa, liquid water at 573 K (300 °C) and 15 MPa, and SCW at 698 K (425 °C) and 27 MPa. The surfaces of the failed samples were characterized using Raman spectroscopy, and X-ray photoelectron spectroscopy. Nitronic-50 was found to have superior mechanical strength characteristics at all conditions compared to stainless steel 316. At all elevated temperature conditions, stainless steel 316 was found to have a surface film consisting of iron oxides, while the surface film of Nitronic-50 predominantly consisted of nickel-iron spinel.

Accessing 2-substituted piperidine iminosugars by organometallic addition/intramolecular reductive amination: aldehyde vs. nitrone route.

PubMed

Mirabella, S; Fibbi, G; Matassini, C; Faggi, C; Goti, A; Cardona, F

2017-11-07

A dual synthetic strategy to afford 2-substituted trihydroxypiperidines is disclosed. The procedure involved Grignard addition either to a carbohydrate-derived aldehyde or to a nitrone derived thereof, and took advantage of an efficient ring-closure reductive amination strategy in the final cyclization step. An opposite diastereofacial preference was demonstrated in the nucleophilic attack to the two electrophiles, which would finally produce the same piperidine diastereoisomer as the major product. However, use of a suitable Lewis acid in the Grignard addition to the nitrone allowed reversing the selectivity, giving access to 2-substituted piperidines with the opposite configuration at C-2.

[1,4]-sigmatropic rearrangement of chiral nitrones and their utilization in the synthesis of new iminosugars.

PubMed

Malinowski, Maciej; Rowicki, Tomasz; Guzik, Patrycja; Gryszel, Maciej; Łapczyński, Sebastian; Wielechowska, Monika; Czerwińska, Karolina; Madura, Izabela; Sas, Wojciech

2016-01-14

Reflection on the epimerization of the α-stereocenter of sugar nitrones leads to the conclusion that the process may occur through [1,4]-sigmatropic rearrangement. Participation of an ionic mechanism was excluded by a deuterium labeling experiment, and DFT calculations showed a reasonable energy barrier for the proposed [1,4]-shift. Products of the intramolecular 1,3-dipolar cycloaddition of the studied nitrones were utilized in the diversity-oriented synthesis of polyhydroxy derivatives of piperidine, indolizidine and quinolizidine. Minimal activity against the screened glucosidases and human melanoma cell lines was observed for some of the obtained compounds.

Meteoroid Bumper Experiment on Explorer 46

DTIC Science & Technology

1981-01-01

4 1 21-6-9, now known as Nitronic 40 : P..•gistered trademark of Armco Steel Corp. £ 4 t During launch, the panels were rolled up like window shades...41 74 058 05 23 58 25 .136 End --- 26 .137 End --- 27 .136 (*) (*) 28 .135 73 025 20 01 44 73 026 13 25 28 29 .134 73 317 02 40 50 73 318 12 57 26 30...h m s y d h m s 38 0.119 End --- 39 .118 End --- 40 .120 End -- 41 .123 73 288 19 42 42 73 289 11 21 38 42 .128 End --- 43 .131 End 44 .133 End -- 45

Kinetics studies of rapid strain-promoted [3 + 2]-cycloadditions of nitrones with biaryl-aza-cyclooctynone.

PubMed

McKay, Craig S; Chigrinova, Mariya; Blake, Jessie A; Pezacki, John Paul

2012-04-21

Strain-promoted cycloadditions of cyclic nitrones with biaryl-aza-cyclooctynone (BARAC) proceed with rate constants up to 47.3 M(-1) s(-1), this corresponds to a 47-fold rate enhancement relative to reaction of BARAC with benzyl azide and a 14-fold enhancement over previously reported strain promoted alkyne-nitrone cycloadditions (SPANC). Studies of the SPANC reaction using the linear free energy relationship defined by the Hammett equation demonstrated that the cycloaddition reaction has a rho value of 0.25 ± 0.04, indicating that reaction is not sensitive to substituents and thus should have broad applicability. This journal is © The Royal Society of Chemistry 2012

Nitrone Cycloadditions of 1,2-Cyclohexadiene

PubMed Central

Barber, Joyann S.; Styduhar, Evan D.; Pham, Hung V.; McMahon, Travis C.; Houk, K. N.; Garg, Neil K.

2016-01-01

We report the first 1,3-dipolar cycloadditions of 1,2-cyclohexadiene, a rarely exploited strained allene. 1,2-Cyclohexadiene is generated in situ under mild conditions and trapped with nitrones to give isoxazolidine products in synthetically useful yields. The reactions occur regioselectively and exhibit a notable endo preference, thus resulting in the controlled formation of two new bonds and two stereogenic centers. DFT calculations of stepwise and concerted reaction pathways are used to rationalize the observed selectivities. Moreover, the strategic manipulation of nitrone cycloadducts demonstrates the utility of this methodology for the assembly of compounds bearing multiple heterocyclic units. These studies showcase the exploitation of a traditionally avoided reactive intermediate in chemical synthesis. PMID:26854652

F-35 Pollution Prevention Activities

DTIC Science & Technology

2008-02-26

Cover Page Bushing Replacement Lab Testing • F-35 Evaluation of Alternative Materials – ToughMet, Nitronic 50 /60, 304/HBN, SBIR Developed, etc...Completed SCC and Salt Fog exposure – All F-35 Bushings ɚ.5”Ø Switched to Cold Worked Nitronic 60 – Phase 5 test plan Evaluating Installation Issues • ASC

Theoretical Investigations of Nitrocubane Decomposition.

DTIC Science & Technology

1988-02-29

this line are the ammonium nitronate salts, e.g., 5j rNH C(NO,) 3 The synthesis and characterization of nitrocubanes such as these is currently of...arceenit i th the experimental results is also very good except at the 0% 40 30 00 C-)0 ~10 00 10 -0.8 -0.4 0.0 0.4 0.8 1.2 s(aO) 1Fiunpre 2. Comparison...excellent (differences of 18- 40 %) but at higher temperatures the computed rates are f .actors of 2.2 to 2.7 lwer than the results of Hack et. al. The

Toxicokinetics Metabolism and Genotoxicity of Nitropropane in Rats and Mice

DTIC Science & Technology

1990-10-01

Daw’ey rats, 4-6 days old, were exposed togeth"er with their darns for 3 weeks (6 h/d, 5 d/w) to 2-NP vapours of 0, 24±1.3, 40 ±4,9, 50±2.7, 80_±5.6...significantly different from controls at all conc3ntrations in females, and at concentrations higher than 40 ppm in males. In the semilogarithmic plot linear dose...which have not yet been identified. Perhaps the shift of 2-NP to its nitronate anion which can occur under physiological condtions (Fiala et al. (1987

A metal-free general procedure for oxidation of secondary amines to nitrones.

PubMed

Gella, Carolina; Ferrer, Eric; Alibés, Ramon; Busqué, Félíx; de March, Pedro; Figueredo, Marta; Font, Josep

2009-08-21

An efficient and metal-free protocol for direct oxidation of secondary amines to nitrones has been developed, using Oxone in a biphasic basic medium as the sole oxidant. The method is general and tolerant with other functional groups or existing stereogenic centers, providing rapid access to enantiomerically pure compounds in good yields.

Evaluation of Extracellular Endosulfatase HSULF-2 in Breast Cancer Cell WNT Signaling and Its Inhibition by a Sulfate Ester Derivative of Synthetic Antioxidant

DTIC Science & Technology

2010-08-01

Breast Cancer, Balb/c nude mice, hydrogen peroxide, extracellular matrix, sulfatase, extracellular sulfatase, aryl sulfatase, PBN, nitrones , phenyl...previously made in studying the anti‐cancer activity of the PBN  nitrones  has helped us generate new novel and testable  ideas for future research in...cancer development appears to be still in question.    Anti‐cancer activity of the PBN‐ nitrones . PBN refers to α‐phenyl‐tert‐butylnitrone. Our

Cascade oxime formation, cyclization to a nitrone, and intermolecular dipolar cycloaddition.

PubMed

Furnival, Rachel C; Saruengkhanphasit, Rungroj; Holberry, Heather E; Shewring, Jonathan R; Guerrand, Hélène D S; Adams, Harry; Coldham, Iain

2016-11-22

Simple haloaldehydes, including enolisable aldehydes, were found to be suitable for the formation of cyclic products by cascade (domino) condensation, cyclisation, dipolar cycloaddition chemistry. This multi-component reaction approach to heterocyclic compounds was explored by using hydroxylamine, a selection of aldehydes, and a selection of activated dipolarophiles. Initial condensation gives intermediate oximes that undergo cyclisation with displacement of halide to give intermediate nitrones; these nitrones undergo in situ intermolecular dipolar cycloaddition reactions to give isoxazolidines. The cycloadducts from using dimethyl fumarate were treated with zinc/acetic acid to give lactam products and this provides an easy way to prepare pyrrolizinones, indolizinones, and pyrrolo[2,1-a]isoquinolinones. The chemistry is illustrated with a very short synthesis of the pyrrolizidine alkaloid macronecine and a formal synthesis of petasinecine.

Reactions of in situ generated N-Boc nitrones with aromatic and heteroaromatic grignard reagents: application to the synthesis of zileuton.

PubMed

Guinchard, Xavier; Denis, Jean-Noël

2008-03-07

A new class of alpha-aromatic-N-hydroxylamines has been prepared by reaction of tert-butyl (phenylsulfonyl)alkyl-N-hydroxycarbamates with aromatic and heteroaromatic Grignard reagents. Reactions proceed via a base-assisted elimination of the phenylsulfonyl group leading to N-Boc nitrones. This methodology has been applied to the synthesis of zileuton.

Chemistry and Technology of the Production of Fiber Nitron (Khimiya i Tekhnologiya Proizvodstva Volokna Nitron),

DTIC Science & Technology

1987-07-17

of some salts, mainly thiocyanate sodium. With wet spinning are used water/aqueous precipitation baths or organic coagulants (glycerin, hexanetriol ...comparatively small. During utilization of glycerine, isopropyl, butyl, hexanetriol baths into composition of bath for increasing elasticity of fiber...the number of C-atoms in the chain of their molecules. Therefore the glycerine bath is more than "rigid", than hexanetriol , whose effect/action is

Mechanical Properties and Seawater Behavior of Nitronic 50 (22Cr-13Ni- 5Mn) Plate

DTIC Science & Technology

1976-01-01

Bal - balance misc - miscellaneous cfh - cubic feet per hour mpy - mils per year c/m - cycles per minute my - millivolts CVN - Charpy V-notch No...High-Cycle Fatigue Specimens F_gure 6 - Drawings; Low-Cycle Fatigue Specimens Figure 7 - Curve; Charpy V-Notch Impact Toughness Versus Temperature...for Nitronic 50 Base Plate FiGure 8 - Curve; Charpy V-Notch Toughness Versus Tempera- ture for Nitrcnic 50 Weldments Figure 9 - Photographs; Fracture

Grignard reagent-mediated conversion of an acyl nitroso-anthracene cycloadduct to a nitrone.

PubMed

Chen, Weibin; Day, Cynthia S; King, S Bruce

2006-11-24

An intramolecular hetero-Diels-Alder cycloadduct of an acyl nitroso compound and a 9,10-dimethyl anthracene derivative was prepared as a potential nitroxyl (HNO) donor. This compound did not release HNO under any of the conditions tested. Treatment of this cycloadduct with excess MeMgCl resulted in the formation of a nitrone, whose structure was confirmed by X-ray crystallography. A mechanism where MeMgCl acts as a nucleophile, strong base, and Lewis acid possibly explains the formation of this product.

Grignard Reagent-Mediated Conversion of an Acyl Nitroso-Anthracene Cycloadduct to a Nitrone

PubMed Central

Chen, Weibin; Day, Cynthia S.

2012-01-01

An intramolecular hetero-Diels-Alder cycloadduct of an acyl nitroso compound and a 9, 10-dimethyl anthracene derivative was prepared as a potential nitroxyl (HNO) donor. This compound did not release HNO under any of the conditions tested. Treatment of this cycloadduct with excess MeMgCl resulted in the formation of a nitrone, whose structure was confirmed by X-ray crystallography. A mechanism where MeMgCl acts as a nucleophile, strong base and Lewis acid possibly explains the formation of this product. PMID:17109552

Phenyl-alpha-tert-butyl nitrone reverses mitochondrial decay in acute Chagas' disease.

PubMed

Wen, Jian-Jun; Bhatia, Vandanajay; Popov, Vsevolod L; Garg, Nisha Jain

2006-12-01

In this study, we investigated the mechanism(s) of mitochondrial functional decline in acute Chagas' disease. Our data show a substantial decline in respiratory complex activities (39 to 58%) and ATP (38%) content in Trypanosoma cruzi-infected murine hearts compared with normal controls. These metabolic alterations were associated with an approximately fivefold increase in mitochondrial reactive oxygen species production rate, substantial oxidative insult of mitochondrial membranes and respiratory complex subunits, and >60% inhibition of mtDNA-encoded transcripts for respiratory complex subunits in infected myocardium. The antioxidant phenyl-alpha-tert-butyl nitrone (PBN) arrested the oxidative damage-mediated loss in mitochondrial membrane integrity, preserved redox potential-coupled mitochondrial gene expression, and improved respiratory complex activities (47 to 95% increase) and cardiac ATP level (>or=40% increase) in infected myocardium. Importantly, PBN resulted twofold decline in mitochondrial reactive oxygen species production rate in infected myocardium. Taken together, our data demonstrate the pathological significance of oxidative stress in metabolic decay and energy homeostasis in acute chagasic myocarditis and further suggest that oxidative injuries affecting mitochondrial integrity-dependent expression and activity of the respiratory complexes initiate a feedback cycle of electron transport chain inefficiency, increased reactive oxygen species production, and energy homeostasis in acute chagasic hearts. PBN and other mitochondria-targeted antioxidants may be useful in altering mitochondrial decay and oxidative pathology in Chagas' disease.

OKN-007 decreases free radical levels in a preclinical F98 rat glioma model.

PubMed

Coutinho de Souza, Patricia; Smith, Nataliya; Atolagbe, Oluwatomisin; Ziegler, Jadith; Njoku, Charity; Lerner, Megan; Ehrenshaft, Marilyn; Mason, Ronald P; Meek, Bill; Plafker, Scott M; Saunders, Debra; Mamedova, Nadezda; Towner, Rheal A

2015-10-01

Free radicals are associated with glioma tumors. Here, we report on the ability of an anticancer nitrone compound, OKN-007 [Oklahoma Nitrone 007; a disulfonyl derivative of α-phenyl-tert-butyl nitrone (PBN)] to decrease free radical levels in F98 rat gliomas using combined molecular magnetic resonance imaging (mMRI) and immunospin-trapping (IST) methodologies. Free radicals are trapped with the spin-trapping agent, 5,5-dimethyl-1-pyrroline N-oxide (DMPO), to form DMPO macromolecule radical adducts, and then further tagged by immunospin trapping by an antibody against DMPO adducts. In this study, we combined mMRI with a biotin-Gd-DTPA-albumin-based contrast agent for signal detection with the specificity of an antibody for DMPO nitrone adducts (anti-DMPO probe), to detect in vivo free radicals in OKN-007-treated rat F98 gliomas. OKN-007 was found to significantly decrease (P < 0.05) free radical levels detected with an anti-DMPO probe in treated animals compared to untreated rats. Immunoelectron microscopy was used with gold-labeled antibiotin to detect the anti-DMPO probe within the plasma membrane of F98 tumor cells from rats administered anti-DMPO in vivo. OKN-007 was also found to decrease nuclear factor erythroid 2-related factor 2, inducible nitric oxide synthase, 3-nitrotyrosine, and malondialdehyde in ex vivo F98 glioma tissues via immunohistochemistry, as well as decrease 3-nitrotyrosine and malondialdehyde adducts in vitro in F98 cells via ELISA. The results indicate that OKN-007 effectively decreases free radicals associated with glioma tumor growth. Furthermore, this method can potentially be applied toward other types of cancers for the in vivo detection of macromolecular free radicals and the assessment of antioxidants. Copyright © 2015. Published by Elsevier Inc.

The carbanion of nitroethane is an inhibitor of, and not a substrate for, flavocytochrome b2 [L-(+)-lactate dehydrogenase

PubMed Central

Genet, R; Lederer, F

1990-01-01

Although nitroethane does not bind to the active site of flavocytochrome b2, its anion, ethane nitronate, behaves as a competitive inhibitor, with a Ki of 2.2 mM. No electron transfer can be detected between the nitronate and the enzyme, in contrast with the observations of other workers on D-amino acid oxidase. Propionate is a competitive inhibitor, with a Ki of 28 mM. The significance of these results with respect to the proposed carbanion mechanism and the putative existence of a covalent enzyme-substrate intermediate is discussed. PMID:2178603

/sup 13/C NMR spectra of cyclic nitrones. 1. 2-substituted 4-methyl- and 4-phenyl-1-hydroxy-5,5-dimethyl-3-imidazoline 3-oxides

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

Grigor'ev, I.A.; Martin, V.V.; Shchukin, G.I.

1985-08-01

The introduction of an N-oxide oxygen atom into azomethines leads to an upfield shift of the signals for the carbon atom of the C=N group in the /sup 13/C NMR spectra by 30-33 ppm. This is consistent with the increase in the electron density on this atom. The signal of the nitrone carbon atom is observed in the region of 140-147 ppm, depending on the nature of the substituent at the C/sub (2)/ atom of the 3-imidazoline 3-oxide ring.

A Unique (3+2) Annulation Reaction between Meldrum's Acid and Nitrones: Mechanistic Insight by ESI-IMS-MS and DFT Studies.

PubMed

Lespes, Nicolas; Pair, Etienne; Maganga, Clisy; Bretier, Marie; Tognetti, Vincent; Joubert, Laurent; Levacher, Vincent; Hubert-Roux, Marie; Afonso, Carlos; Loutelier-Bourhis, Corinne; Brière, Jean-François

2018-03-15

The fragile intermediates of the domino process leading to an isoxazolidin-5-one, triggered by unique reactivity between Meldrum's acid and an N-benzyl nitrone in the presence of a Brønsted base, were determined thanks to the softness and accuracy of electrospray ionization mass spectrometry coupled to ion mobility spectrometry (ESI-IMS-MS). The combined DFT study shed light on the overall organocatalytic sequence that starts with a stepwise (3+2) annulation reaction that is followed by a decarboxylative protonation sequence encompassing a stereoselective pathway issue. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Causation in a Cascade: The Origins of Selectivities in Intramolecular Nitrone Cycloadditions

PubMed Central

Krenske, Elizabeth H.; Agopcan, Sesil; Aviyente, Viktorya; Houk, K. N.; Johnson, Brian A.; Holmes, Andrew B.

2012-01-01

The factors controlling chemo-, regio-, and stereoselectivity in a cascade of reactions starting from a bis(cyanoalkenyl)oxime and proceeding via nitrone cycloadditions, have been unravelled through a series of density functional calculations with several different functionals. Both kinetic and thermodynamic control of the reaction cascade are important depending upon conditions. Kinetic control is analysed by the distortion/interaction model and is found to be dictated by differences in distortions of the cycloaddends in the transition states. A new mechanism competing with that originally proposed in the application of these reactions to the histrionicotoxin synthesis is discovered in these studies. PMID:22788115

Stereo-, Regio-, and Chemoselective [3 + 2]-Cycloaddition of (2E,4E)-Ethyl 5-(Phenylsulfonyl)penta-2,4-dienoate with Various Azomethine Ylides, Nitrones, and Nitrile Oxides: Synthesis of Pyrrolidine, Isoxazolidine, and Isoxazoline Derivatives and a Computational Study.

PubMed

Sankar, Ulaganathan; Surya Kumar, Ch Venkata; Subramanian, V; Balasubramanian, K K; Mahalakshimi, S

2016-03-18

One-pot chemo-, regio-, and stereoselective synthesis of series of heterocyclic and spiroheterocyclic compounds was accomplished through mono- and bis[3 + 2]-cycloaddition reactions of (2E,4E)-ethyl 5-(phenylsulfonyl)penta-2,4-dienoate as a dipolarophile with azomethine ylides, nitrones, and nitrile oxides in good yields. The structures of the products were established by spectroscopic techniques as well as by single-crystal XRD study, and DFT calculations were performed to further understand the mechanism of this [3 + 2]-cycloaddition reaction.

Old Yellow Enzyme: Stepwise reduction of nitro-olefins and catalysis of aci-nitro tautomerization

PubMed Central

Meah, Younus; Massey, Vincent

2000-01-01

The Old Yellow Enzyme has been shown to catalyze efficiently the NADPH-linked reduction of nitro-olefins. The reduction of the nitro-olefin proceeds in a stepwise fashion, with formation of a nitronate intermediate that is freely dissociable from the enzyme. The first step involves hydride transfer from the enzyme-reduced flavin to carbon 2 of the nitro-olefin. The protonation of the nitronate at carbon 1 to form the final nitroalkane product also is catalyzed by the enzyme and involves Tyr-196 as an active site acid/base. This residue also is involved in aci-nitro tautomerization of nitroalkanes, the first example of a nonredox reaction catalyzed by the enzyme. PMID:10995477

Effect of oxide films on hydrogen permeability of candidate Stirling engine heater head tube alloys

NASA Technical Reports Server (NTRS)

Schuon, S. R.; Misencik, J. A.

1981-01-01

The effect of oxide films developed in situ from CO/CO2 doped hydrogen on high pressure hydrogen permeability at 820 C was studied on N-155, A-286, IN 800, 19-9DL, Nitronic 40, HS-188, and IN 718 tubing in a Stirling materials simulator. The hydrogen permeability decreased with increasing dopant levels of CO or CO2 and corresponding decreases in oxide porosity. Minor reactive alloying elements strongly influenced permeability. At high levels of CO or CO2, a liquid oxide formed on alloys with greater than 50 percent Fe. This caused increased permeability. The oxides formed on the inside tube walls were analyzed and their effective permeabilities were calculated.

Experimental and theoretical studies on the structural, spectroscopic and hydrogen bonding on 4-nitro-n-(2,4-dinitrophenyl) benzenamine

NASA Astrophysics Data System (ADS)

Subhapriya, G.; Kalyanaraman, S.; Jeyachandran, M.; Ragavendran, V.; Krishnakumar, V.

2018-04-01

Synthesized 4-nitro-N-(2,4-dinitrophenyl) benzenamine (NDPBA) molecule was confirmed applying the tool of NMR. Theoretical prediction addressed the NMR chemical shifts and correlated well with the experimental data. The molecule subjected to theoretical DFT at 6-311++G** level unraveled the spectroscopic and structural properties of the NDPBA molecule. Moreover the structural features proved the occurrence of intramolecular Nsbnd H· · O hydrogen bonding in the molecule which was further confirmed with the help of Frontier molecular orbital analysis. Vibrational spectroscopic characterization through FT-IR and Raman experimentally and theoretically gave an account for the vibrational properties. An illustration of the topology of the molecule theoretically helped also in finding the hydrogen bonding energy.

Development of an Accelerated Methodology to Study Degradation of Materials in Supercritical Water for Application in High Temperature Power Plants

NASA Astrophysics Data System (ADS)

Rodriguez, David

The decreasing supply of fossil fuel sources, coupled with the increasing concentration of green house gases has placed enormous pressure to maximize the efficiency of power generation. Increasing the outlet temperature of these power plants will result in an increase in operating efficiency. By employing supercritical water as the coolant in thermal power plants (nuclear reactors and coal power plants), the plant efficiency can be increased to 50%, compared to traditional reactors which currently operate at 33%. The goal of this dissertation is to establish techniques to characterize the mechanical properties and corrosion behavior of materials exposed to supercritical water. Traditionally, these tests have been long term exposure tests spanning months. The specific goal of this dissertation is to develop a methodology for accelerated estimation of corrosion rates in supercritical water that can be sued as a screening tool to select materials for long term testing. In this study, traditional methods were used to understand the degradation of materials in supercritical water and establish a point of comparison to the first electrochemical studies performed in supercritical water. Materials studied included austenitic steels (stainless steel 304, stainless steel 316 and Nitronic 50) and nickel based alloys (Inconel 625 and 718). Surface chemistry of the oxide layer was characterized using scanning electron microscopy, X-ray diffraction, FT-IR, Raman and X-ray photoelectron spectroscopies. Stainless steel 304 was subjected to constant tensile load creep tests in water at a pressure of 27 MPa and at temperatures of 200 °C, 315 °C and supercritical water at 450 °C for 24 hours. It was determined that the creep rate for stainless steel 304 exposed to supercritical water would be unacceptable for use in service. It was observed that the formation of hematite was favored in subcritical temperatures, while magnetite was formed in the supercritical region. Corrosion of stainless steel 316, Nitronic 50, Inconel 625 and Inconel 718 was exposed to supercritical water at 530 °C and ultra-supercritical water at 600 °C and was studied as a function exposure time. When exposed to supercritical water, Nitronic 50 and stainless steel 316 were observed to have similar mass gains; however, stainless steel 316 was found to gain less mass than Nitronic 50 in exposure tests performed in ultra-supercritical water. Stainless steel 316 developed surface films primarily composed of iron oxides, while the surface of Nitronic 50 contained a mixture of iron, chromium and manganese oxides. Inconels 625 and 718 samples were exposed to these temperatures for 24, 96, and 200 hours. Inconel 718 exhibited greater mass gain than Inconel 625 for all temperatures and exposure times. For the first time, corrosion rates in supercritical water were determined using electrochemical techniques. The corrosion rates of stainless steel 316, Nitronic 50, Inconel 625 and Inconel 718 were estimated in supercritical and ultra-supercritical water using electrochemical impedance spectroscopy and electrochemical frequency modulation. For all conditions tested, the corrosion rates obtained from electrochemical testing followed similar trends to the long-term gravimetric results. As a screening tool, this protocol can potentially reduce the time required for corrosion rate studies from thousands of hours to 24 hours.

Novel pyrrolinones as N-methyl-D-aspartate receptor antagonists.

PubMed

Poschenrieder, Hermann; Stachel, Hans-Dietrich; Höfner, Georg; Mayer, Peter

2005-04-01

A series of oximes, deriving from 2-arylidene-pyrroline-3,4-diones (7, 8, 22, 23) has been prepared. The presence of tautomers in their solutions has been established by spectroscopic means. The compounds reacted with diazomethane chiefly by N-methylation forming nitrones (10, 11). The analogously prepared 2-arylidene-4-nitropyrrolin-3-ones (12, 13, 24, 25), formally derived from nitrotetramic acids, yielded nitronic acid esters (14, 15, 26) upon reaction with diazomethane. The structures were elucidated by spectral evidence and-in the case of compounds 10 and 20b-by X-ray diffraction analysis. The binding affinity of some of the new compounds toward the N-methyl-d-aspartate (NMDA) (glycine site) receptor has been measured thus providing the basis for further structure-activity relationship studies. Oxime 8b showed the highest binding potency (Ki= 9.2 microM).

Synthesis of densely functionalized enantiopure indolizidines by ring-closing metathesis (RCM) of hydroxylamines from carbohydrate-derived nitrones

PubMed Central

Bonanni, Marco; Marradi, Marco; Cardona, Francesca; Cicchi, Stefano; Goti, Andrea

2007-01-01

Background Indolizidine alkaloids widely occur in nature and display interesting biological activity. This is the reason for which their total synthesis as well as the synthesis of non-natural analogues still attracts the attention of many research groups. To establish new straightforward accesses to these molecules is therefore highly desirable. Results The ring closing metathesis (RCM) of enantiopure hydroxylamines bearing suitable unsaturated groups cleanly afforded piperidine derivatives in good yields. Further cyclization and deprotection of the hydroxy groups gave novel highly functionalized indolizidines. The synthesis of a pyrroloazepine analogue is also described. Conclusion We have developed a new straightforward methodology for the synthesis of densely functionalized indolizidines and pyrroloazepine analogues in 6 steps and 30–60% overall yields from enantiopure hydroxylamines obtained straightforwardly from carbohydrate-derived nitrones. PMID:18076753

Reactivity of superoxide radical anion and hydroperoxyl radical with alpha-phenyl-N-tert-butylnitrone (PBN) derivatives.

PubMed

Durand, Grégory; Choteau, Fanny; Pucci, Bernard; Villamena, Frederick A

2008-12-04

Nitrones have exhibited pharmacological activity against radical-mediated pathophysiological conditions and as analytical reagents for the identification of transient radical species by electron paramagnetic resonance (EPR) spectroscopy. In this work, competitive spin trapping, stopped-flow kinetics, and density functional theory (DFT) were employed to assess and predict the reactivity of O(2)(*-) and HO(2)(*) with various para-substituted alpha-phenyl-N-tert-butylnitrone (PBN) spin traps. Rate constants of O(2)(*-) trapping by nitrones were determined using competitive UV-vis stopped-flow method with phenol red (PR) as probe, while HO(2)(*) trapping rate constants were calculated using competition kinetics with 5,5-dimethylpyrroline N-oxide (DMPO) by employing EPR spectroscopy. The effects of the para substitution on the charge density of the nitronyl-carbon and on the free energies of nitrone reactivity with O(2)(*-) and HO(2)(*) were computationally rationalized at the PCM/B3LYP/6-31+G(d,p)//B3LYP/6-31G(d) level of theory. Theoretical and experimental data show that the rate of O(2)(*-) addition to PBN derivatives is not affected by the polar effect of the substituents. However, the reactivity of HO(2)(*) follows the Hammett equation and is increased as the substituent becomes more electron withdrawing. This supports the conclusion that the nature of HO(2)(*) addition to PBN derivatives is electrophilic, while the addition of O(2)(*-) to PBN-type compounds is only weakly electrophilic.

Welding of Vanadium, Tantalum, 304L and 21-6-9 Stainless Steels, and Titanium Alloys at Lawrence Livermore National Laboratory using a Fiber Delivered 2.2 kW Diode Pumped CW Nd:YAG Laser

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

Palmer, T; Elmer, J; Pong, R

This report summarizes the results of a series of laser welds made between 2003 and 2005 at Lawrence Livermore National Laboratory (LLNL). The results are a compilation of several, previously unpublished, internal LLNL reports covering the laser welding of vanadium, tantalum, 304L stainless steel, 21-6-9 (Nitronic 40) steel, and Ti-6Al-4V. All the welds were made using a Rofin Sinar DY-022 diode pumped continuous wave Nd:YAG laser. Welds are made at sharp focus on each material at various power levels and travel speeds in order to provide a baseline characterization of the performance of the laser welder. These power levels aremore » based on measurements of the output power of the laser system, as measured by a power meter placed at the end of the optics train. Based on these measurements, it appears that the system displays a loss of approximately 10% as the beam passes through the fiber optic cable and laser optics. Since the beam is delivered to the fixed laser optics through a fiber optic cable, the effects of fiber diameter are also briefly investigated. Because the system utilizes 1:1 focusing optics, the laser spot size at sharp focus generally corresponds to the diameter of the fiber with which the laser is delivered. Differences in the resulting weld penetration in the different materials system are prevalent, with the welds produced on the Nitronic 40 material displaying the highest depths (> 5 mm) and minimal porosity. A Primes focusing diagnostic has also been installed on this laser system and used to characterize the size and power density distribution of the beams as a function of both power and focus position. Further work is planned in which this focusing diagnostic will be used to better understand the effects of changes in beam properties on the resulting weld dimensions in these and other materials systems.« less

Comparison of Nitronic 50 and Stainless Steel 316 for use in Supercritical Water Environments

NASA Astrophysics Data System (ADS)

Karmiol, Zachary

Increased efficiency can greatly benefit any mode of power production. Many proposed coal, natural gas, and nuclear reactors attempt to realize this goal through the use of increased operating temperatures and pressures, and as such require materials capable of withstanding extreme conditions. One such design employs supercritical water, which in addition to high temperatures and pressures is also highly oxidizing. A critical understanding of both mechanical and oxidation characteristics of candidate materials are required to determine the viability of materials for these reactors. This work investigates two potential materials, austenitic stainless steels, namely, Nitronic-50 and stainless steel 316, for use in these conditions. The supercritical water loop at the University of Nevada, Reno allowed for the study of materials at both subcritical and supercritical conditions. The materials were investigated mechanically using slow strain rate tests under conditions ranging from an inert nitrogen atmosphere, to both subcritical and supercritical water, with the failed samples surface characterized by optical microscopy, scanning electron microscopy, and Raman spectroscopy. Electrochemical studies were performed via potentiodynamic polarization in subcritical water only, and characterized using Raman spectroscopy. The samples were also exposed to supercritical water, and characterized using Raman spectroscopy. Nitronic-50 was found to have superior mechanical characteristics to stainless steel 316. SS-316 was found to have a surface film consisting of iron oxides, while the surface film of N-50 consisted predominantly of nickel-iron spinel. The crack interior of the sample was different from the exterior, indicating that the time and temperature of the exposure might play a defining role in determining the chemistry of the film.

Sequential Diels–Alder/[3,3]-sigmatropic rearrangement reactions of β-nitrostyrene with 3-methyl-1,3-pentadiene

PubMed Central

Pipic, Alma; Zeller, Matthias; Tsetsakos, Panagiota

2013-01-01

Summary The tin(IV)-catalyzed reaction of β-nitrostyrene with (E)-3-methyl-1,3-pentadiene in toluene afforded two major nitronic ester cycloadducts in 27% and 29% yield that arise from the reaction at the less substituted diene double bond. Also present were four cycloadducts from the reaction at the higher substituted diene double bond, two of which were the formal cycloadducts of (Z)-3-methyl-1,3-pentadiene. A Friedel–Crafts alkylation product from the reaction of the diene, β-nitrostyrene, and toluene was also obtained in 10% yield. The tin(IV)-catalyzed reaction of β-nitrostyrene with (Z)-3-methyl-1,3-pentadiene in dichloromethane afforded four nitronic ester cycloadducts all derived from the reaction at the higher substituted double bond. One cycloadduct was isolated in 45% yield and two others are formal adducts of the E-isomer of the diene. The product formation in these reactions is consistent with a stepwise mechanism involving a zwitterionic intermediate. The initially isolated nitronic ester cycloadducts underwent tin(IV)-catalyzed interconversion, presumably via zwitterion intermediates. Cycloadducts derived from the reaction at the less substituted double bond of (E)-3-methyl-1,3-pentadiene underwent a [3,3]-sigmatropic rearrangement on heating to afford 4-nitrocyclohexenes. Cycloadducts derived from the reaction at the higher substituted diene double bond of either diene failed to undergo a thermal rearrangement. Rates and success of the rearrangement are consistent with a concerted mechanism possessing a dipolar transition state. An initial assessment of substituent effects on the rearrangement process is presented. PMID:24204426

Computational Investigation of the Photochemical Reaction Path of Some Synthesized and Experimentally Analyzed Small-Chain Conjugated Nitrones.

PubMed

Saini, Praveen; Banerjee, Mainak; Chattopadhyay, Anjan

2016-01-28

This combined theoretical and experimental study has revealed the photochemistry of two small open-chain conjugated N-methylnitrone systems with phenyl substitutions at the C-terminal positions. The UV spectra of these synthesized nitrones have shown intense peaks around 330 nm while the new bands formed near 260 nm after their photoirradiation are predicted to be arising from the photoproduct oxaziridine. Photoexcitation of α-styryl N-methylnitrone populates the first excited singlet state which relaxes by 8 kcal/mol from the vertically excited state and subsequently goes toward the lowest-energy conical intersection (CI) geometry (situated 27-30 kcal/mol below) with a terminal CNO-kink. Following the gradient difference vectors of this CI, we have located the oxaziridine structure with its characteristic geometry at roughly 14 kcal/mol above the ground state. This whole process is triggered by a transfer of electronic cloud from oxygen to the conjugated chain side. On the other hand, the photoexcitation of the nonplanar 3,3-diphenylethylene N-methylnitrone has two strong singlet-singlet absorptions with almost 5 D transition moment values. Here the initial S2-S1 relaxation is followed by oxaziridine formation through the terminally twisted CI. However, the initially photoexcited S1 state in this nitrone is found to head toward some other direction with transfer of huge amount of nonbonding electron cloud of oxygen to the π* orbital, creating a stable excited state geometry with an elongated N-O bond which gets involved in a sloped CI with the ground state.

Preliminary results on the development of vacuum brazed joints for cryogenic wind tunnel aerofoil models

NASA Technical Reports Server (NTRS)

Wigley, D. A.; Sandefur, P. G., Jr.; Lawing, P. L.

1981-01-01

The results of initial experiments show that high-strength void-free bonds can be formed by vacuum brazing of stainless steels using copper and nickel-based filler metals. In Nitronic 40, brazed joints have been formed with strengths in excess of the yield strength of the parent metal, and even at liquid nitrogen temperatures the excellent mechanical properties of the parent metal are only slightly degraded. The poor toughness of 15-5 P.H. stainless steel at cryogenic temperatures is lowered even further by the presence of the brazed bonds investigated. It is highly unlikely that the technique would be used for any critical areas of aerofoil models intended for low-temperature service. Nevertheless, the potential advantages of this simplified method of construction still have attractions for use at ambient temperatures.

Evaluation of the mechanical properties of electroslag refined iron alloys

NASA Technical Reports Server (NTRS)

Bhat, G. K.

1976-01-01

Nitronic 40 (21Cr-6N-9Mn), HY-130, 9Ni-4Co, and D-6 alloys were prepared and evaluated in the form of 15.2 mm thick plates. Smooth bar tensile tests, double-edge sharp notch fracture toughness tests Charpy V-notch impact tests were conducted on appropriate heat treated specimens of the four steel plates at 22 C, -50 C, -100 C, -150 C, and -196 C. Similar material characterization, including metallographic evaluation studies on air melt and vacuum arc melt grades of same four alloy steels were conducted for comparative purposes. A cost analysis of manufacturing plates of air melt, electroslag remelt and vacuum arc remelt grades was performed. The results of both material characterization and cost analyses pointed out certain special benefits of electroslag processing iron base alloys.

Synthesis, Antimicrobial, and Antioxidant Activities of Chalcogen-Containing Nitrone Derivatives from (R)-citronellal

PubMed Central

Ferraz, Mariana C.; Mano, Renata A.; Oliveira, Daniela H.; Maia, Darla S. V.; Silva, Wladimir P.; Savegnago, Lucielli; Lenardão, Eder J.; Jacob, Raquel G.

2017-01-01

Background: The main constituents of Cymbopogonnardus (L) Rendle and C. citratus (DC) Stapfessential oils are (R)-citronellal and citral, respectively. Organochalcogen compounds can boost the biological activities of natural products. Methods: Several chalcogen-containing nitrones derived from (R)-citronellal and citral were prepared and evaluated for their antimicrobial and antioxidant activities. The antimicrobial activity was evaluated by the disc diffusion test and the antioxidant properties were evaluated in vitro by DPPH (1,1-diphenyl-2-picryl-hydrazyl), ABTS (2,2′-azino-bis(3-ethylbenzthiazoline-6-sulfonic acid), and FRAP (ferric ion reducing antioxidant power) assays. Results: In the antimicrobial assay, (E)-N,3,7-trimethyl-3-(phenylthio)oct-6-en-1-imine oxide 5c exhibited halos between 21.5 mm (Escherichia coli O157:H7) and 26.0 mm (Listeria monocytogenes), while (E)-N,3,7-trimethyloct-6-en-1-imine oxide 5d presented halos between 22.5 mm (E. coli O157:H7) and 31.0 mm (L. monocytogenes). (E)-N,3,7-Trimethyl-2-(phenylthio)oct-6-en-1-imine oxide 5a showed the lowest minimal inhibitory concentration (MIC) value against Bacillus cereus (0.48 mM), and 5c was the most potent bactericide, with a minimal bactericidal concentration (MBC) of 0.52 mM for E. coli O157:H7. In the antioxidant assays, 5c, 5d, and 10 ((E)-3,7-dimethyl-2-(phenylselanyl)oct-6-enal oxime) were the most actives in the DPPH, ABTS, and FRAP assays, respectively. Conclusions: The presence of a phenylthio group in the nitrone increases its antimicrobial activity against Gram-positive and Gram-negative foodborne pathogens in the disk diffusion test and the antioxidant activity in vitro. PMID:28930254

Use of spin traps to detect superoxide production in living cells by electron paramagnetic resonance (EPR) spectroscopy.

PubMed

Abbas, Kahina; Babić, Nikola; Peyrot, Fabienne

2016-10-15

Detection of superoxide produced by living cells has been an on-going challenge in biology for over forty years. Various methods have been proposed to address this issue, among which spin trapping with cyclic nitrones coupled to EPR spectroscopy, the gold standard for detection of radicals. This technique is based on the nucleophilic addition of superoxide to a diamagnetic cyclic nitrone, referred to as the spin trap, and the formation of a spin adduct, i.e. a persistent radical with a characteristic EPR spectrum. The first application of spin trapping to living cells dates back 1979. Since then, considerable improvements of the method have been achieved both in the structures of the spin traps, the EPR methodology, and the design of the experiments including appropriate controls. Here, we will concentrate on technical aspects of the spin trapping/EPR technique, delineating recent breakthroughs, inherent limitations, and potential artifacts. Copyright © 2016 Elsevier Inc. All rights reserved.

Drugs for stroke: action of nitrone (Z)-N-(2-bromo-5-hydroxy-4-methoxybenzylidene)-2-methylpropan-2-amine oxide on rat cortical neurons in culture subjected to oxygen-glucose-deprivation.

PubMed

Arce, Carmen; Diaz-Castroverde, Sabela; Canales, María J; Marco-Contelles, José; Samadi, Abdelouahid; Oset-Gasque, María J; González, María P

2012-09-01

The action of (Z)-N-(2-bromo-5-hydroxy-4-methoxybenzylidene)-2-methylpropan-2-amine oxide (RP6) on rat cortical neurons in culture, under oxygen-glucose-deprivation conditions, is reported. Cortical neurons in culture were treated during 1 h with OGD. After, they were placed under normal conditions during 24 h (reperfusion) in absence and presence of RP6. Different parameters were measured under each condition (control, 1 h OGD and 1 h OGD + reperfusion in absence and presence of RP6). RP6 protects neurons against ROS generation, lipid peroxidation levels, LDH release and mitochondrial membrane potential alteration, when administered during reperfusion after the OGD damage. Consequently, these results show that nitrone RP6 protects cells against ischemia injury produced during the reoxygenation, and could be a potential drug for the ictus therapy. Copyright © 2012. Published by Elsevier Masson SAS.

Spin forming development

NASA Astrophysics Data System (ADS)

Gates, W. G.

1982-05-01

Bendix product applications require the capability of fabricating heavy gage, high strength materials. Five commercial sources have been identified that have the capability of spin forming metal thicknesses greater than 9.5 mm and four equipment manufacturers produce machines with this capability. Twelve assemblies selected as candidates for spin forming applications require spin forming of titanium, 250 maraging steel, 17-4 pH stainless steel, Nitronic 40 steel, 304 L stainless steel, and 6061 aluminum. Twelve parts have been cold spin formed from a 250 maraging steel 8.1 mm wall thickness machine preform, and six have been hot spin formed directly from 31.8-mm-thick flat plate. Thirty-three Ti-6Al-4V titanium alloy parts and 26 17-4 pH stainless steel parts have been hot spin formed directly from 31.8-mm-thick plate. Hot spin forming directly from plate has demonstrated the feasibility and favorable economics of this fabrication technique for Bendix applications.

Measurement of S-nitrosylated Proteins in Tissues of Rats Fed Diets with Differing Levels of Nitrite

DTIC Science & Technology

2011-12-01

project could be substantial. Excluding immediate deaths, 50 % of all battlefield deaths (KIAs) occur within 5 minutes of injury, prior to the...exists for quantitation of DMPO thioethers. Furthermore, DMPO exhibits low cytotoxicity. In spin trapping experiments, cells tolerate this nitrone in

RAPID MEASUREMENT OF AQUEOUS HYDROXYL RADICAL CONCENTRATIONS IN STEADY-STATE HO· FLUX SYSTEMS

EPA Science Inventory

The spin-trap compound a-(4-pyridyl-1-oxide)-N-tert-butyl-nitrone (4-POBN) is utilized for the detection and quantitation of the hydroxyl radical (HO·) in aqueous solution. Capillary electrophoresis enables rapid analysis of the probe compound. The thermally unstable HO· radical ...

The Stress Corrosion Resistance and the Cryogenic Temperature Mechanical Behavior of 18-3 Mn (Nitronic 33) Stainless Steel Parent and Welded Material

NASA Technical Reports Server (NTRS)

Montano, J. W.

1976-01-01

The ambient and cryogenic temperature mechanical properties and the ambient temperature stress corrosion results of 18-3 Mn (Nitronic 33)stainless steel, longitudinal and transverse, as received and as welded (TIG) material specimens manufactured from 0.063 inch thick sheet material, were described. The tensile test results indicate an increase in ultimate tensile and yield strengths with decreasing temperature. The elongation remained fairly constant to -200 F, but below that temperature the elongation decreased to less than 6.0% at liquid hydrogen temperature. The notched tensile strength (NTS) for the parent metal increased with decreasing temperature to liquid nitrogen temperature. Below -320 F the NTS decreased rapidly. The notched/unnotched (N/U) tensile ratio of the parent material specimens remained above 0.9 from ambient to -200 F, and decreased to approximately 0.65 and 0.62, respectively, for the longitudinal and transverse directions at liquid hydrogen temperature. After 180 days of testing, only those specimens exposed to the salt spray indicated pitting and some degradation of mechanical properties.

Imaging free radicals in organelles, cells, tissue, and in vivo with immuno-spin trapping.

PubMed

Mason, Ronald Paul

2016-08-01

The accurate and sensitive detection of biological free radicals in a reliable manner is required to define the mechanistic roles of such species in biochemistry, medicine and toxicology. Most of the techniques currently available are either not appropriate to detect free radicals in cells and tissues due to sensitivity limitations (electron spin resonance, ESR) or subject to artifacts that make the validity of the results questionable (fluorescent probe-based analysis). The development of the immuno-spin trapping technique overcomes all these difficulties. This technique is based on the reaction of amino acid- and DNA base-derived radicals with the spin trap 5, 5-dimethyl-1-pyrroline N-oxide (DMPO) to form protein- and DNA-DMPO nitroxide radical adducts, respectively. These adducts have limited stability and decay to produce the very stable macromolecule-DMPO-nitrone product. This stable product can be detected by mass spectrometry, NMR or immunochemistry by the use of anti-DMPO nitrone antibodies. The formation of macromolecule-DMPO-nitrone adducts is based on the selective reaction of free radical addition to the spin trap and is thus not subject to artifacts frequently encountered with other methods for free radical detection. The selectivity of spin trapping for free radicals in biological systems has been proven by ESR. Immuno-spin trapping is proving to be a potent, sensitive (a million times higher sensitivity than ESR), and easy (not quantum mechanical) method to detect low levels of macromolecule-derived radicals produced in vitro and in vivo. Anti-DMPO antibodies have been used to determine the distribution of free radicals in cells and tissues and even in living animals. In summary, the invention of the immuno-spin trapping technique has had a major impact on the ability to accurately and sensitively detect biological free radicals and, subsequently, on our understanding of the role of free radicals in biochemistry, medicine and toxicology. Published by Elsevier B.V.

A Torquoselective Extrusion of Isoxazoline N-Oxides. Application to the Synthesis of Aryl Vinyl and Divinyl Ketones for Nazarov Cyclization

PubMed Central

Canterbury, Daniel P.; Herrick, Ildiko R.; Um, Joann; Houk, K. N.; Frontier, Alison J.

2009-01-01

A mild, convenient reaction sequence for the synthesis of Nazarov cyclization substrates is described. The [3+2] dipolar cycloaddition of a nitrone and an electron-deficient alkyne gives an isolable isoxazoline intermediate, which upon oxidation undergoes stereoselective extrusion of nitrosomethane to give aryl vinyl or divinyl ketones. PMID:20161228

N-tert-butylmethanimine N-oxide is an efficient spin-trapping probe for EPR analysis of glutathione thiyl radical

PubMed Central

Scott, Melanie J.; Billiar, Timothy R.; Stoyanovsky, Detcho A.

2016-01-01

The electron spin resonance (EPR) spin-trapping technique allows detection of radical species with nanosecond half-lives. This technique is based on the high rates of addition of radicals to nitrones or nitroso compounds (spin traps; STs). The paramagnetic nitroxides (spin-adducts) formed as a result of reactions between STs and radical species are relatively stable compounds whose EPR spectra represent “structural fingerprints” of the parent radical species. Herein we report a novel protocol for the synthesis of N-tert-butylmethanimine N-oxide (EBN), which is the simplest nitrone containing an α-H and a tertiary α′-C atom. We present EPR spin-trapping proof that: (i) EBN is an efficient probe for the analysis of glutathione thiyl radical (GS•); (ii) β-cyclodextrins increase the kinetic stability of the spin-adduct EBN/•SG; and (iii) in aqueous solutions, EBN does not react with superoxide anion radical (O2−•) to form EBN/•OOH to any significant extent. The data presented complement previous studies within the context of synthetic accessibility to EBN and efficient spin-trapping analysis of GS•. PMID:27941944

The stress corrosion resistance and the cryogenic temperature mechanical properties of annealed Nitronic 60 bar material

NASA Technical Reports Server (NTRS)

Montano, J. W. L.

1977-01-01

Ambient and cryogenic temperature mechanical properties and the ambient temperature stress corrosion properties of annealed, straightened, and centerless ground Nitronic 60 stainless steel alloy bar material are presented. The mechanical properties of longitudinal specimens were evaluated at test temperatures from ambient to liquid hydrogen. The tensile test data indicated increasing strength with decreasing temperature to -196 C. Below liquid nitrogen temperature the smooth tensile and notched tensile strengths decreased slightly while the elongation and reduction of area decreased drastically. The Charpy V-notched impact energy decreased steadily with decreasing test temperature. Stress corrosion tests were performed on longitudinal tensile specimens and transverse C-ring specimens exposed to: alternate immersion in a 3.5% NaCl bath; humidity cabinet; and a 5% salt spray atmosphere. The longitudinal tensile specimens experienced no corrosive attack. Approximately 3/4 of the transverse C-rings exposed to alternate immersion and to salt spray experienced a pitting attack on the top and bottom ends. Additional stress corrosion tests were performed on transverse tensile specimens. No failures occurred in the 90% stressed specimens exposed for 90 days in the alternate immersion and salt spray environments

Fluorogenic Strain-Promoted Alkyne-Diazo Cycloadditions

PubMed Central

Friscourt, Frédéric; Fahrni, Christoph J.; Boons, Geert-Jan

2016-01-01

Fluorogenic reactions in which non- or weakly-fluorescent reagents produce highly fluorescent products are attractive for detecting a broad range of compounds in the fields of bio-conjugation and material sciences. We report here that Fl-DIBO, a dibenzocyclooctyne derivative modified with a cyclopropenone moiety, can undergo fast strain-promoted cycloadditions under catalyst-free conditions with azides, nitrones, nitrile oxides as well as mono- and disubstituted diazo-derivatives. While the reaction with nitrile oxides, nitrones and disubstituted diazo compounds gave cycloadducts with low quantum yield, monosubstituted diazo reagents produced 1H-pyrazole derivatives that exhibited a ~160-fold fluorescence enhancement over Fl-DIBO combined with a greater than 10,000-fold increase in brightness. Concluding from quantum chemical calculations, fluorescence quenching of 3H-pyrazoles, which are formed by reaction with disubstituted diazo-derivatives, is likely due to the presence of energetically low-lying (n,π*) states. The fluorogenic probe Fl-DIBO was successfully employed for the labeling of diazo-tagged proteins without detectable background signal. Diazo-derivatives are emerging as attractive reporters for the labeling of biomolecules and the studies presented here demonstrate that Fl-DIBO can be employed for visualizing such biomolecules without the need for probe washout. PMID:26330090

Characterization of nitrogen effects in high energy density weldments of Nitronic 40 stainless steel

NASA Astrophysics Data System (ADS)

Pfeif, Erik Andrew

Variation in the welding environment for laser beam welding and electron beam welding can alter the resulting weld chemical composition, microstructure and therefore the mechanical properties. The room temperature mechanical properties of Nitronic 40 stainless steel weld metal from three different heats containing 0.24, 0.28, and 0.31 wt. pct. nitrogen were evaluated for continuous mode Ytterbium doped Fiber laser welds conducted with argon and nitrogen shielding gases, and for electron beam welds. The bulk nitrogen contents were monitored and the resulting properties were then related to microstructural features measured using Electron BackScatter Diffraction (EBSD). Traditional tensile testing of weld metal is conducted on composite tensile bars consisting of base metal and weld metal often leading to failure in the region adjacent to the weld due to strength mismatch at the weld interface. These tests provide composite strength but do not specifically determine the mechanical properties of the heterogeneous weld metal. In this research, microtensile testing was conducted to characterize the properties of the different regions of the weld. The microtensile testing procedures were developed using two geometries of tensile bars measuring the properties through the thickness of 3 mm full penetration welds. In all cases an increase in the strength of the weld metal was found to occur, though the electron beam welds exhibited a higher strength than the laser welds. Standard predictive equations were found to under-predict the strength of the laser welds, even when average grain size or intercept distances were measured. The contribution of nitrogen solid solution strengthening was consistent at approximately 513 MPa per wt. pct. nitrogen. Similar cooling rates and heat inputs allow for a comparison across high energy density welding techniques. Though microstructural differences through the depth of the weld metal were observed as nitrogen vaporization decreased and cooling rates increased. Vermicular ferrite, lacy ferrite and intercellular ferrite were identified as predicted in prior research done on high nitrogen austenitic stainless steels. The resulting laser weld metal microstructures were analyzed with EBSD for grain size and ferrite content measurements, while grain boundary character was determined for a Hansen model used for multi-scale mechanical property measurements. It was found that the low angle grain boundaries were the predominant microstructural feature responsible for strengthening within the weld metal and that this contribution must be accounted for when predicting yield strength of the weld metal.

76 FR 61643 - Airworthiness Directives; The Boeing Company Model 737-600, -700, -700C, -800, -900, and -900ER...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-10-05

... thumbnail fairing edge seals on both sides of the engines with Nitronic 60 stainless steel alloy seals. This proposed AD was prompted by reports of excessive in-service wear damage of the thumbnail fairing edge seal... failure of the fire seal, which could allow a fire in the fan compartment to spread beyond the firewall...

4'-alpha-C-Branched N,O-nucleosides: synthesis and biological properties.

PubMed

Chiacchio, Ugo; Genovese, Filippo; Iannazzo, Daniela; Piperno, Anna; Quadrelli, Paolo; Antonino, Corsaro; Romeo, Roberto; Valveri, Vincenza; Mastino, Antonio

2004-07-15

The synthesis of 4'-alpha-C-branched N,O-nucleosides has been described, based on the 1,3-dipolar cycloaddition of nitrones with vinyl acetate followed by coupling with silylated nucleobases, The obtained compounds have been evaluated for their activity against HSV-1, HSV-2, HTLV-1. Cytotoxicity and apoptotic activity have been also investigated: compound 10c shows moderate apoptotic activity in Molt-3 cells.

Tetramethylpyrazine nitrone, a multifunctional neuroprotective agent for ischemic stroke therapy

PubMed Central

Zhang, Zaijun; Zhang, Gaoxiao; Sun, Yewei; Szeto, Samuel S. W.; Law, Henry C. H.; Quan, Quan; Li, Guohui; Yu, Pei; Sho, Eiketsu; Siu, Michael K. W.; Lee, Simon M. Y.; Chu, Ivan K.; Wang, Yuqiang

2016-01-01

TBN, a novel tetramethylpyrazine derivative armed with a powerful free radical-scavenging nitrone moiety, has been reported to reduce cerebral infarction in rats through multi-functional mechanisms of action. Here we study the therapeutic effects of TBN on non-human primate model of stroke. Thirty male Cynomolgus macaques were subjected to stroke with 4 hours ischemia and then reperfusion. TBN were injected intravenously at 3 or 6 hours after the onset of ischemia. Cerebral infarction was examined by magnetic resonance imaging at 1 and 4 weeks post ischemia. Neurological severity scores were evaluated during 4 weeks observation. At the end of experiment, protein markers associated with the stroke injury and TBN treatment were screened by quantitative proteomics. We found that TBN readily penetrated the blood brain barrier and reached effective therapeutic concentration after intravenous administration. It significantly reduced brain infarction and modestly preserved the neurological function of stroke-affected arm. TBN suppressed over-expression of neuroinflammatory marker vimentin and decreased the numbers of GFAP-positive cells, while reversed down-regulation of myelination-associated protein 2′, 3′-cyclic-nucleotide 3′-phosphodiesterase and increased the numbers of NeuN-positive cells in the ipsilateral peri-infarct area. TBN may serve as a promising new clinical candidate for the treatment of ischemic stroke. PMID:27841332

Serendipitous findings while researching oxygen free radicals.

PubMed

Floyd, Robert A

2009-04-15

This review is based on the honor of receiving the Discovery Award from the Society of Free Radical Biology and Medicine. The review is reflective and presents our thinking that led to experiments that yielded novel observations. Critical questioning of our understanding of oxygen free radicals in biomedical problems led us to use and develop more direct and extremely sensitive methods. This included nitrone free radical spin trapping and HPLC-electrochemical detection. This technology led to the pioneering use of salicylate to trap hydroxyl free radicals and show increased flux in ischemia/reperfused brain regions and also to first sensitively detect 8-hydroxyl-2-deoxyguanosine in oxidatively damaged DNA and help assess its role in cancer development. We demonstrated that methylene blue (MB) photoinduces formation of 8-hydroxyguanine in DNA and RNA and discovered that MB sensitively photoinactivates RNA viruses, including HIV and the West Nile virus. Studies in experimental stroke led us serendipitously to discover that alpha-phenyl-tert-butylnitrone (PBN) was neuroprotective if given after the stroke. This led to extensive commercial development of NXY-059, a PBN derivative, for the treatment of stroke. More recently we discovered that PBN nitrones have potent anti-cancer activity and are active in preventing hearing loss caused by acute acoustical trauma.

Fluorogenic Strain-Promoted Alkyne-Diazo Cycloadditions.

PubMed

Friscourt, Frédéric; Fahrni, Christoph J; Boons, Geert-Jan

2015-09-28

Fluorogenic reactions, in which non- or weakly fluorescent reagents produce highly fluorescent products, are attractive for detecting a broad range of compounds in the fields of bioconjugation and material sciences. Herein, we report that a dibenzocyclooctyne derivative modified with a cyclopropenone moiety (Fl-DIBO) can undergo fast strain-promoted cycloaddition reactions under catalyst-free conditions with azides, nitrones, nitrile oxides, as well as mono- and disubstituted diazo-derivatives. Although the reaction with nitrile oxides, nitrones, and disubstituted diazo compounds gave cycloadducts with low quantum yield, monosubstituted diazo reagents produced 1H-pyrazole derivatives that exhibited an approximately 160-fold fluorescence enhancement over Fl-DIBO combined with a greater than 10,000-fold increase in brightness. Concluding from quantum chemical calculations, fluorescence quenching of 3H-pyrazoles, which are formed by reaction with disubstituted diazo-derivatives, is likely due to the presence of energetically low-lying (n,π*) states. The fluorogenic probe Fl-DIBO was successfully employed for the labeling of diazo-tagged proteins without detectable background signal. Diazo-derivatives are emerging as attractive reporters for the labeling of biomolecules, and the studies presented herein demonstrate that Fl-DIBO can be employed for visualizing such biomolecules without the need for probe washout. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Serendipitous Findings While Researching Oxygen Free Radicals

PubMed Central

Floyd, Robert A.

2009-01-01

This review is based on the honor of receiving the Discovery Award from the Society of Free Radical Biology and Medicine. The review is reflective and presents our thinking which led to experiments that yielded novel observations. Critical questioning of our understanding of oxygen free radicals in biomedical problems led us to use and develop more direct and extremely sensitive methods. This included nitrone free radical spin-trapping and HPLC-electrochemical detection. This technology led to the pioneering use of salicylate to trap hydroxyl free radicals and show increased flux in ischemia/reperfused brain regions and to also first sensitively detect 8-hydroxy-droxyguanosine (8-OHdG) in oxidative-damaged DNA and help assess its role in cancer development. We demonstrated that Methylene Blue (MB) photo-induced formation of 8-hydroxy-guanine in DNA and RNA and discovered that MB sensitively photo-inactivated RNA viruses including HIV and the West Nile Virus. Studies in experimental stroke led us to serendipitously discover that α-phenyl-tert-butylnitrone (PBN) was neuroprotective if given after the stroke. This led to extensive commercial development of NXY-059, a PBN derivative, for the treatment of stroke. More recently we discovered that PBN-nitrones have potent anti-cancer activity and are active in preventing hearing loss caused by acute acoustical trauma. PMID:19439210

Research in Energetic Compounds.

DTIC Science & Technology

1981-01-01

The ring is thus amenable to electrophilic opening. Efforts to polymerize 3, 3-dinitrooxetane will be continued. An intermediate In the preparation of...r- nitronate salts and formaldehyde.2 This reaction is ported to give a stable dialkoxide salt. In order to explore markedly inhibited by a fluorine ...a to nitro as a manifes- further the chemistry of 2-fluoro-2-nitro-I,3-propanediol, tation of the " fluorine effect" or the destabilization of a we

The Use of Nitrone Cycloadditions in the Synthesis of Beta-Amino Aldehydes and Unsaturated Amines.

DTIC Science & Technology

1986-01-01

with alkenes (dipolarophiles) to produce isoxazolidines (2) in a fashion similar to the (4+2] Diels - Alder reaction.’ The cycloaddition results in...structures to study enzyme inhibition, and they serve as useful intermediates in the synthesis of $-lactams. 3 3 Table IV summarizes attempts to oxidize p...84% yield (Table V, entry 3). Due to the mechanistic imperative, acid catalyzed elimination always yielded the allylic amine in which the alkene

Protective Mechanisms of Nitrone Antioxidants in Kanic Acid Induced Neurodegeneration

DTIC Science & Technology

2004-01-01

Hong, Dextromethorphan modulates the AP-1 DNA bind- Med. 14 (1993) 633-642. ing activity induced by kainic acid, Brain Res. 824 (1999) 125-132. [71 S.C...Hong, The effect of dextromethorphan on kainic acid-induced after kainic acid-induced seizures, Free Radical Biol. Med. 18 seizures in the rat...Bing, G., Bronstein, D., McMillian, M., Hong, J.-S. (1996) the effects of dextromethorphan on kainic acid-induced seizures in the rat. J. Neurotoxic

Facile and enantiospecific syntheses of (6S,7R)-6-chloro-7-benzyloxy-, (7S)-halo-, and (7S)-hydroxy-cocaine and natural (-)-cocaine from D-(-)-ribose.

PubMed

Shing, Tony K M; So, King H

2011-06-03

First syntheses of C6,7 and C7 enantiopure cocaine analogues were achieved from D-(-)-ribose via a trans-acetonide controlled endo-selective intramolecular nitrone-alkene cycloaddition (INAC) as the key step. This synthetic scheme allows practical preparation of cocaine analogues for bioevaluation as potential candidates for the treatment of cocaine addiction and as potential conjugates for immunotherapy.

From N-triisopropylsilylpyrrole to an optically active C-4 substituted pyroglutamic acid: total synthesis of penmacric acid.

PubMed

Berini, Christophe; Pelloux-Léon, Nadia; Minassian, Frédéric; Denis, Jean-Noël

2009-11-07

The stereoselective synthesis of penmacric acid, an optically active C-4 substituted pyroglutamic acid, has been efficiently achieved through an unusual 11-step sequence starting from simple N-triisopropylsilylpyrrole. The key-steps are the initial addition of the pyrrole nucleus onto a chiral nitrone and the obtention of the pyroglutamic acid moiety by reductive hydrogenation of the pyrrole followed by oxidation of the corresponding pyrrolidine into pyrrolidinone.

The stress corrosion resistance and the cryogenic temperature mechanical properties of hot rolled Nitronic 32 bar material

NASA Technical Reports Server (NTRS)

Montano, J. W. L.

1977-01-01

The ambient and cryogenic temperature mechanical properties and the ambient temperature stress corrosion properties of hot rolled and centerless ground Nitronic 32 stainless steel bar material are presented. The mechanical properties of longitudinal specimens were evaluated at test temperatures from ambient to liquid hydrogen. The tensile test data indicated increasing smooth tensile strength with decreasing temperature to liquid hydrogen temperature. However, below -200 F (-129.0 C) the notched tensile strength decreased slightly and below -320 F (-196.0 C) the decrease was significant. The elongation and reduction of area decreased drastically at temperatures below -200 F (-129.0 C). The Charpy V-notched impact energy decreased steadily with decreasing test temperature. Stress corrosion tests were performed on longitudinal tensile specimens stressed to 0, 75, and 90 percent of the 0.2 percent yield strength and on transverse 'C'-ring specimens stressed to 75 and 90 percent of the yield strength and exposed to: alternate immersion in a 3.5 percent NaCl bath, humidity cabinet environment, and a 5 percent salt spray atmosphere. The longitudinal tensile specimens experienced no corrosive attack; however, the 'C'-rings exposed to the alternate immersion and to the salt spray experienced some shallow etching and pitting, respectively. Small cracks appeared in two of the 'C'-rings after one month exposure to the salt spray.

Evaluation of dopants in hydrogen to reduce hydrogen permeation in candidate Stirling engine heater head tube alloys at 760 deg and 820 deg

NASA Technical Reports Server (NTRS)

Misencik, J. A.

1982-01-01

Alloy tubes filled with hydrogen doped with various amounts of carbon monoxide, carbon dioxide, ethane, ethylene, methane, ammonia, or water were heated in a diesel fuel-fired Stirling engine simulator materials test rig for 100 hours at 21 MPa and 760 or 820 C to determine the effectiveness of the dopants in reducing hydrogen permeation through the hot tube walls. Ultra high purity (UHP) hydrogen was used for comparison. The tube alloys were N-155, A-286, Incoloy 800, Nitronic 40, 19-9DL, 316 stainless steel, Inconel 718, and HS-188. Carbon dioxide and carbon monoxide in the concentration range 0.2 to 5 vol % were most effective in reducing hydrogen permeation through the hot tube walls for all alloys. Ethane, ethylene, methane, ammonia, and water at the concentrations investigated were not effective in reducing the permeation below that achieved with UHP hydrogen. One series of tests were conducted with UHP hydrogen in carburized tubes. Carburization of the tubes prior to exposure reduced permeation to values similar to those for carbon monoxide; however, carbon dioxide was the most effective dopant.

Technology for pressure-instrumented thin airfoil models, phase 1

NASA Technical Reports Server (NTRS)

Wigley, D. A.

1985-01-01

A network of channels was chemically milled into one surface of a pair of matched plates having bond planes which were neither planar or profiled to match the contour of the trailing edge of a supercritical airfoil for testing in cryogenic wind tunnels. Vacuum brazing bonded the plates together to create a network of pressure passages without blockages or cross leaks. The greatest success was achieved with the smaller samples and planar bonding surfaces. In larger samples, problems were encountered due to warpage created by the relief of residual stresses. Successful bonds were formed by brazing A286, Nitronic 40 and 300 series stainless steels at 1065 C using AMS 4777B brazing alloy, but excessive grain growth occurred in samples of 200 grade 18 nickel maraging steels. Good bonds were obtained with maraging steel using a 47 percent Nickel-47 percent Palladium-6 percent Silicon alloy and brazing at 927 C. Electro-Discharge-Machining was an effective method of cutting profiled bond planes and airfoil contours. Orifices of good definition were obtained when the EDM wire cut passed through predrilled holes. Possible configurations for joints between small segments and the larger main wing were also studied.

IMMUNO-SPIN TRAPPING FROM BIOCHEMISTRY TO MEDICINE: advances, challenges, and pitfalls

PubMed Central

Gomez-Mejiba, Sandra E.; Zili, Zhai; Della-Vedova, Maria C.; Muñoz, Marcos D.; Chatterjee, Saurabh; Towner, Rheal A.; Hensley, Kenneth; Floyd, Robert A.; Mason, Ronald P.; Ramirez, Dario C.

2013-01-01

BACKGROUND Immuno-spin trapping (IST) is based on the reaction of a spin trap with a free radical to form a stable nitrone adduct, followed by the use of antibodies, rather than traditional electron paramagnetic resonance spectroscopy, to detect the nitrone adduct. IST has been successfully applied to mechanistic in vitro studies, and recently, macromolecule-centered radicals have been detected in models of drug-induced agranulocytosis, hepatotoxicity, cardiotoxicity, and ischemia/reperfusion, as well as in models of neurological, metabolic and immunological diseases. SCOPE OF THE REVIEW To critically evaluate advances, challenges, and pitfalls as well as the scientific opportunities of IST as applied to the study of protein-centered free radicals generated in stressed organelles, cells, tissues and animal models of disease and exposure. MAJOR CONCLUSIONS Because the spin trap has to be present at high enough concentrations in the microenvironment where the radical is formed, the possible effects of the spin trap on gene expression, metabolism and cell physiology have to be considered in the use of IST and in the interpretation of results. These factors have not yet been thoroughly dealt with in the literature. GENERAL SIGNIFICANCE The identification of radicalized proteins during cell/tissue response to stressors will help define their role in the complex cellular response to stressors and pathogenesis; however, the fidelity of spin trapping/ immuno-detection and the effects of the spin trap on the biological system should be considered. PMID:23644035

Region-selective effects of neuroinflammation and antioxidant treatment on peripheral benzodiazepine receptors and NMDA receptors in the rat brain

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

Biegon, A.; Alvarado, M.; Budinger, T.F.

2001-12-10

Following induction of acute neuroinflammation by intracisternal injection of endotoxin (lipopolysaccharide) in rats, quantitative autoradiography was used to assess the regional level of microglial activation and glutamate (NMDA) receptor binding. The possible protective action of the antioxidant phenyl-tert-butyl nitrone in this model was tested by administering the drug in the drinking water for 6 days starting 24 hours after endotoxin injection. Animals were killed 7 days post-injection and consecutive cryostat brain sections labeled with [3H]PK11195 as a marker of activated microglia and [125I]iodoMK801 as a marker of the open-channel, activated state of NMDA receptors. Lipopolysaccharide increased [3H]PK11195 binding in themore » brain, with the largest increases (2-3 fold) in temporal and entorhinal cortex, hippocampus, and substantia innominata. A significant (>50 percent) decrease in [125I]iodoMK801 binding was found in the same brain regions. Phenyl-tert-butyl nitrone treatment resulted in a partial inhibition ({approx}25 percent decrease) of the lipopolysaccharide-induced increase in [3H]PK11195 binding but completely reversed the lipopolysaccharide-induced decrease in [125I]iodoMK80 binding in the entorhinal cortex, hippocampus, and substantia innominata. Loss of NMDA receptor function in cortical and hippocampal regions may contribute to the cognitive deficits observed in diseases with a neuroinflammatory component, such as meningitis or Alzheimer's disease.« less

Use of EPR Spin-Trapping Techniques to Detect Radicals from Rat Lung Lavage Fluid Following Sulfur Mustard Vapor Exposure

DTIC Science & Technology

1993-05-13

lung injury. Anesthetized rats were intratracheally intubated and exposed to 0.35 mg HD vapor over 50 min, Immediately, 1 hr or 24 hr after exposure...lungs were lavaged with the spin trap, alpha-phenyl-t-butyl nitrone (PBN; 0.35 mg/ml). Recovered lavage fluid was assayed by EPR spectroscopy for...in EtOH (100 Ml), or EtOH alone (control), was placed in a water Jacketed (37° C) vapor generator and the rats .ere exposed for 50 min. by which time

Novel spirobicyclic artemisinin analogues (artemalogues): Synthesis and antitumor activities.

PubMed

Liu, Gang; Song, Shanshan; Shu, Shiqi; Miao, Zehong; Zhang, Ao; Ding, Chunyong

2015-10-20

The sesquiterpene lactone framework of artemisinin was used as a drug repositioning prototype for the development of novel antitumor drugs. Several series of novel artemisinin analogues (artemalogues) were designed and synthesized through 1,3-dipolar cycloaddition of artemisitene with nitrile oxides or nitrones. The isoxazolidine-containing spirobicyclic artemalogue 11b turns out to be the most potent with low micromolar IC₅₀ values against all three tumor cells, which were at least 4- to 14-fold more potent than the parent artemisinin. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

Materials Selection for Superheater Tubes in Municipal Solid Waste Incineration Plants

NASA Astrophysics Data System (ADS)

Morales, M.; Chimenos, J. M.; Fernández, A. I.; Segarra, M.

2014-09-01

Corrosion reduces the lifetime of municipal solid waste incineration (MSWI) superheater tubes more than any other cause. It can be minimized by the careful selection of those materials that are most resistant to corrosion under operating conditions. Since thousands of different materials are already known and many more are developed every year, here the selection methodology developed by Prof. Ashby of the University of Cambridge was used to evaluate the performance of different materials to be used as MSWI superheater tubes. The proposed materials can operate at steam pressures and temperatures over 40 bars and 400 °C, respectively. Two case studies are presented: one makes a balanced selection between mechanical properties and cost per thermal unit; and the other focuses on increasing tube lifetime. The balanced selection showed that AISI 410 martensitic stainless steel (wrought, hard tempered) is the best candidate with a good combination of corrosion resistance, a relatively low price (0.83-0.92 €/kg) and a good thermal conductivity (23-27 W/m K). Meanwhile, Nitronic 50/XM-19 stainless steel is the most promising candidate for long-term selection, as it presents high corrosion resistance with a relatively low price (4.86-5.14 €/kg) compared to Ni-alloys.

Welded tie plate feasibility study for ITER central solenoid structure

NASA Astrophysics Data System (ADS)

Walsh, R.; McRae, D.; Dalder, E.; Litherland, S.; Goddard, R.; Han, K.; Trosen, M.; Kuhlmann, D. D.

2014-01-01

The result of a Nitronic 50 (N50) weld-screening program conducted in support of CS-Tie Plate Structure Design and Development is reported here. The goal of this program is to evaluate four different weld practices and to select the best weld practice for thick section welding of the N50 tie plate structure. The structure design specifies both the weld and base metals have the same minimum mechanical properties requirements. The criteria for selecting the best weld practice are based on the combination of the 295 K tensile properties and the 4 K-tensile, fatigue, and fracture-toughness properties.

Oxidation of spin-traps by chlorine dioxide (ClO2) radical in aqueous solutions: first ESR evidence of formation of new nitroxide radicals.

PubMed

Ozawa, T; Miura, Y; Ueda, J

1996-01-01

The reactivities of the chlorine dioxide (ClO2), which is a stable free radical towards some water-soluble spin-traps were investigated in aqueous solutions by an electron spin resonance (ESR) spectroscopy. The ClO2 radical was generated from the redox reaction of Ti3+ with potassium chlorate (KClO3) in aqueous solutions. When one of the spin-traps, 5,5-dimethyl-1-pyrroline N-oxide (DMPO), was included in the Ti3+-KClO3 reaction system, ESR spectrum due to the ClO2 radical completely disappeared and a new ESR spectrum [aN(1) = 0.72 mT, aH(2) = 0.41 mT], which is different from that of DMPO-ClO2 adduct, was observed. The ESR parameters of this new ESR signal was identical to those of 5,5-dimethylpyrrolidone-(2)-oxyl-(1) (DMPOX), suggesting the radical species giving the new ESR spectrum is assignable to DMPOX. The similar ESR spectrum consisting of a triplet [aN(1) = 0.69 mT] was observed when the derivative of DMPO, 3,3,5,5-tetramethyl-1-pyrroline N-oxide (M4PO) was included in the Ti3+-KClO3 reaction system. This radical species is attributed to the oxidation product of M4PO, 3,3,5,5-tetramethylpyrrolidone-(2)-oxyl-(1) (M4POX). When another nitrone spin-trap, alpha-(4-pyridyl-1-oxide)-N-t-butylnitrone (POBN) was used as a spin-trap, the ESR signal intensity due to the ClO2 radical decreased and a new ESR signal consisting of a triplet [aN(1) = 0.76 mT] was observed. The similar ESR spectrum was observed when N-t-butyl-alpha- nitrone (PBN) was used as a spin-trap. This ESR parameter [a(N)(1) = 0.85 mT] was identical to the oxidation product of PBN, PBNX. Thus, the new ESR signal observed from POBN may be assigned to the oxidation product of POBN, POBNX. These results suggest that the ClO2, radical does not form the stable spin adducts with nitrone spin-traps, but oxidizes these spin-traps to give the corresponding nitroxyl radicals. On the other hand, nitroso spin-traps, 5,5-dibromo-4-nitrosobenzenesulfonate (DBNBS), and 2-methyl-2-nitrosopropane (MNP) did not trap the ClO2 radical. This result indicates that an unpaired electron of the ClO2 radical is localized on oxygen atom, because nitroso spin-traps cannot form the stable spin adduct with oxygen-centered radical.

Effect of sliding velocity on the tribological behavior of copper and associated nanostructure development

NASA Astrophysics Data System (ADS)

Emge, Andrew

The unlubricated sliding of metals is important in many mechanical devices covering a wide range of sliding velocities. However, the effect of sliding velocity on the tribological behavior of unlubricated metals has not been widely studied. Similarly, the relationship between microstructures developed at high sliding velocities and tribological behavior has not been studied in depth. Microstructures produced at low sliding velocities have been studied extensively and commonly include nanocrystalline or fine grained material near the sliding surface with heavily deformed microstructures further from the surface. The current research relates two aspects of the sliding friction of ductile metals, the effect of sliding velocity and the production of nanocrystalline tribomaterial. The project focused on the effects of sliding velocity on the frictional behavior of oxygen free high conductivity (OFHC) copper sliding against 440C stainless steel, Nitronic 40 stainless steel, and copper. Low velocity tests were performed with a pin on disk tribometer. High velocity tests were performed with a rotating barrel gas gun (RBGG) which combined impact with sliding. The RBGG provides sliding velocities as high as 5.5 m/s and impact velocities as high as 12 m/s while maintaining sliding times on the order of tens of microseconds. Changes in the coefficient of friction, microstructure, and composition were studied. Surface and subsurface microstructures of the worn samples were characterized with a range of instruments including scanning electron microscopy (SEM) with energy dispersive X-ray spectroscopy (EDS), focused ion beam (FIB) milling and imaging, transmission electron microscopy (TEM) with EDS, orientation imaging microscopy (OIM), and nanoindentation. In the case of self-mated copper the sliding velocity had little effect on the coefficient of friction for both experimental apparatuses. For the case of copper sliding against 440C stainless steel on the pin on disk system the friction was found to increase with sliding velocity and was strongly influenced by material transfer from the copper to the steel pin. An increase in the coefficient of friction with sliding velocity was observed for the sliding of OFHC copper against Nitronic 40 steel in RBGG tests. The increase in the coefficient of friction was correlated to an increase in subsurface plastic deformation and grain refinement. The growth of the nanocrystalline tribolayer in copper after sliding against 440C stainless steel at varying times was studied at sliding velocities of 0.05 and 1.0 m/s. A sliding velocity of 0.05 m/s produced a consistent nanocrystalline layer in as little as 10 s. The thickness of the nanocrystalline layer grew to an average thickness of 3 microm after 10 ks of sliding, but large variations in thickness were observed. A sliding velocity of 1.0 m/s produced a continuous nanocrystalline layer after 10 s of sliding. Ledges developed on the wear tracks at longer sliding times which greatly influenced the tribolayer thickness making it difficult to quantify. Dynamic recrystallization of the tribolayer also led to difficulties in measuring its thickness.

An experimental and computational investigation of dynamic ductile fracture in stainless steel welds

NASA Astrophysics Data System (ADS)

Kothnur, Vasanth Srinivasa

The high strain rate viscoplastic flow and fracture behavior of NITRONIC-50 and AL6XN stainless steel weldments are studied under dynamic loading conditions. The study is primarily motivated by interest in modeling the micromechanics of dynamic ductile failure in heterogeneous weldments. The high strain rate response of specimens machined from the parent, weld and heat-affected zones of NITRONIC-50 and AL6XN weldments is reported here on the basis of experiments conducted in a compression Kolsky bar configuration. The failure response of specimens prepared from the various material zones is investigated under high rate loading conditions in a tension Kolsky bar set-up. The microstructure of voided fracture process zones in these weldments is studied using X-ray Computed Microtomography. To model the preferential evolution of damage near the heat-affected zone, a finite deformation elastic-viscoplastic constitutive model for porous materials is developed. The evolution of the macroscopic flow response and the porous microstructure have been analysed in two distinctive regimes: pre-coalescence and post-coalescence. The onset of void coalescence is analyzed on the basis of upper-bound models to obtain the limit-loads needed to sustain a localized mode of plastic flow in the inter-void ligament. A finite element framework for the integration of the porous material response under high rate loading conditions is implemented as a user-subroutine in ABAQUS/Explicit. To address the effect of mesh sensitivity of numerical simulations of ductile fracture, a microstructural length scale is used to discretize finite element models of test specimens. Results from a detailed finite element study of the deformation and damage evolution in AL6XN weldments are compared with experimental observations.

Integration of Fermentation and Organic Synthesis: Studies of Roquefortine C and Biosynthetic Derivatives

NASA Astrophysics Data System (ADS)

Gober, Claire Marie

Roquefortine C is one of the most ubiquitous indoline alkaloids of fungal origin. It has been isolated from over 30 different species of Penicillium fungi and has garnered attention in recent years for its role as a biosynthetic precursor to the triazaspirocyclic natural products glandicoline B, meleagrin, and oxaline. The triazaspirocyclic motif, which encompasses three nitrogen atoms attached to one quaternary carbon forming a spirocyclic scaffold, is a unique chemical moiety that has been shown to impart a wide array of biological activity, from anti-bacterial activity and antiproliferative activity against cancer cell lines to anti-biofouling against marine organisms. Despite the promise of these compounds in the pharmaceutical and materials industries, few syntheses of triazaspirocycles exist in the literature. The biosynthesis of roquefortine C-derived triazaspirocycles, however, provides inspiration for the synthesis of these compounds, namely through a nitrone-promoted transannular rearrangement. This type of internal rearrangement has never been carried out synthetically and would provide an efficient stereoselective synthesis of triazaspirocycles. This work encompasses efforts towards elucidating the biosynthetic pathway of roquefortine C-derived triazaspirocycles as well as synthetic efforts towards the construction of triazaspirocycles. Chapter 1 will discuss a large-scale fermentation procedure for the production of roquefortine C from Penicillium crustosum. Chapters 2 and 3 explore (through enzymatic and synthetic means, respectively) the formation of the key indoline nitrone moiety required for the proposed transannular rearrangement. Finally, chapter 4 will discuss synthetic efforts towards the synthesis of triazaspirocycles. This work has considerably enhanced our understanding of the roquefortine C biosynthetic pathway and the unique chemistry of this natural product, and our efforts towards the synthesis of triazaspirocycles will facilitate the use of these compounds in numerous applications.

Materials screening tests for the krypton-85 storage development program

NASA Astrophysics Data System (ADS)

Nagata, P. K.

1981-04-01

The results of a materials testing program for krypton-85 storage techniques are reported. Corrosion and stress corrosion tests were performed on a variety of materials including AISI 4130, Type 316 SS, Type 304 SS, Type 310 SS, Nitronic 50, and alloy A286. Test environments were high-purity liquid rubidium, liquid rubidium contaminated with oxygen, and rubidium hydroxide. Oxygen and water contaminations in liquid rubidium were found to greatly increase both general and localized corrosion of the materials tested. Alloy A286, Type 304 SS, and AISI 4130 were eliminated as candidate materials due to their susceptibility to general corrosion and stress corrosion cracking.

Kinugasa reactions in water: from green chemistry to bioorthogonal labelling.

PubMed

Chigrinova, Mariya; MacKenzie, Douglas A; Sherratt, Allison R; Cheung, Lawrence L W; Pezacki, John Paul; Pezacki, Paul

2015-04-16

The Kinugasa reaction has become an efficient method for the direct synthesis of β-lactams from substituted nitrones and copper(I) acetylides. In recent years, the reaction scope has been expanded to include the use of water as the solvent, and with micelle-promoted [3+2] cycloadditions followed by rearrangement furnishing high yields of β-lactams. The high yields of stable products under aqueous conditions render the modified Kinugasa reaction amenable to metabolic labelling and bioorthogonal applications. Herein, the development of methods for use of the Kinugasa reaction in aqueous media is reviewed, with emphasis on its potential use as a bioorthogonal coupling strategy.

6-Azido hyacinthacine A2 gives a straightforward access to the first multivalent pyrrolizidine architectures.

PubMed

D'Adamio, Giampiero; Parmeggiani, Camilla; Goti, Andrea; Moreno-Vargas, Antonio J; Moreno-Clavijo, Elena; Robina, Inmaculada; Cardona, Francesca

2014-08-28

The synthesis of the first multivalent pyrrolizidine iminosugars is reported. The key azido intermediates 4 and 31 were prepared after suitable synthetic elaboration of the cycloadduct obtained from 1,3-dipolar cycloaddition of D-arabinose derived nitrone to dimethylacrylamide. The key step of the strategy was the stereoselective installation of an azido moiety at C-6 of the pyrrolizidine skeleton. The click reaction with different monovalent and dendrimeric alkyne scaffolds allowed the preparation of a library of new mono- and multivalent pyrrolizidine compounds that were preliminarily assayed as glycosidase inhibitors towards a panel of commercially available glycosyl hydrolases.

5-Nitro-N 4,N 6-diphenyl­pyrimidine-4,6-diamine: polarized mol­ecules linked into π-stacked chains via three-centre C—H⋯(O)2 hydrogen bonds

PubMed Central

Rodríguez, Ricaurte; Nogueras, Manuel; Cobo, Justo; Glidewell, Christopher

2009-01-01

Mol­ecules of the title compound, C16H13N5O2, have no inter­nal symmetry despite the symmetric pattern of substitution in the pyrimidine ring. The intra­molecular distances indicate polarization of the electronic structure. There are two intra­molecular N—H⋯O hydrogen bonds and mol­ecules are linked into centrosymmetric dimers by pairs of three-centre C—H⋯(O)2 hydrogen bonds. These dimers are linked into chains by means of a π–π stacking inter­action. PMID:19726856

Highly sensitive free radical detection by nitrone-functionalized gold nanoparticles

NASA Astrophysics Data System (ADS)

Du, Libo; Huang, Saipeng; Zhuang, Qianfen; Jia, Hongying; Rockenbauer, Antal; Liu, Yangping; Liu, Ke Jian; Liu, Yang

2014-01-01

The detection of free radicals and related species has attracted significant attention in recent years because of their critical roles in physiological and pathological processes. Among the methods for the detection of free radicals, electron spin resonance (ESR) coupled with the use of the spin trapping technique has been an effective approach for characterization and quantification of these species due to its high specificity. However, its application in biological systems, especially in in vivo systems, has been greatly limited partially due to the low reaction rate between the currently available spin traps with biological radicals. To overcome this drawback, we herein report the first example of nitrone functionalized gold nanoparticles (Au@EMPO) as highly efficient spin traps in which the thiolated EMPO (2-(ethoxycarbonyl)-2-methyl-3,4-dihydro-2H-pyrrole 1-oxide) derivative was self-assembled on gold nanoparticles. Kinetic studies showed that Au@EMPO has a 137-fold higher reaction rate constant with &z.rad;OH than PBN (N-tert-butyl-α-phenylnitrone). Owing to the high rate of trapping &z.rad;OH by Au@EMPO as well as the high stability of the resulting spin adduct (t1/2 ~ 56 min), Au@EMPO affords 124-fold higher sensitivity for &z.rad;OH than EMPO. Thus, this new nanospin trap shows great potential in trapping the important radicals such as &z.rad;OH in various biological systems and provides a novel strategy to design spin traps with much improved properties.The detection of free radicals and related species has attracted significant attention in recent years because of their critical roles in physiological and pathological processes. Among the methods for the detection of free radicals, electron spin resonance (ESR) coupled with the use of the spin trapping technique has been an effective approach for characterization and quantification of these species due to its high specificity. However, its application in biological systems, especially in in vivo systems, has been greatly limited partially due to the low reaction rate between the currently available spin traps with biological radicals. To overcome this drawback, we herein report the first example of nitrone functionalized gold nanoparticles (Au@EMPO) as highly efficient spin traps in which the thiolated EMPO (2-(ethoxycarbonyl)-2-methyl-3,4-dihydro-2H-pyrrole 1-oxide) derivative was self-assembled on gold nanoparticles. Kinetic studies showed that Au@EMPO has a 137-fold higher reaction rate constant with &z.rad;OH than PBN (N-tert-butyl-α-phenylnitrone). Owing to the high rate of trapping &z.rad;OH by Au@EMPO as well as the high stability of the resulting spin adduct (t1/2 ~ 56 min), Au@EMPO affords 124-fold higher sensitivity for &z.rad;OH than EMPO. Thus, this new nanospin trap shows great potential in trapping the important radicals such as &z.rad;OH in various biological systems and provides a novel strategy to design spin traps with much improved properties. Electronic supplementary information (ESI) available. See DOI: 10.1039/c3nr04559e

Effect of oxide films on hydrogen permeability of candidate Stirling heater head tube alloys

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

Schuon, S R; Misencik, J A

1981-01-01

High pressure hydrogen has been selected as the working fluid for the developmental automotive Stirling engine. Containment of the working fluid during operation of the engine at high temperatures and at high hydrogen gas pressures is essential for the acceptance of the Stirling engine as an alternative to the internal combustion engine. Most commercial alloys are extremely permeable to pure hydrogen at high temperatures. A program was undertaken at NASA Lewis Research Center (LeRC) to reduce hydrogen permeability in the Stirling engine heater head tubes by doping the hydrogen working fluid with CO or CO/sub 2/. Small additions of thesemore » gases were shown to form an oxide on the inside tube wall and thus reduce hydrogen permeability. A study of the effects of dopant concentration, alloy composition, and effects of surface oxides on hydrogen permeability in candidate heater head tube alloys is summarized. Results showed that hydrogen permeability was similar for iron-base alloys (N-155, A286, IN800, 19-9DL, and Nitronic 40), cobalt-base alloys (HS-188) and nickel-base alloys (IN718). In general, the permeability of the alloys decreased with increasing concentration of CO or CO/sub 2/ dopant, with increasing oxide thickness, and decreasing oxide porosity. At high levels of dopants, highly permeable liquid oxides formed on those alloys with greater than 50% Fe content. Furthermore, highly reactive minor alloying elements (Ti, Al, Nb, and La) had a strong influence on reducing hydrogen permeability.« less

Design and Analysis of the Warm-To Suspension Links for Jefferson Lab's 11 Gev/c Super High Momentum Spectrometer

NASA Astrophysics Data System (ADS)

Sun, E.; Brindza, P.; Lassiter, S.; Fowler, M.

2010-04-01

This paper describes design and analysis performed for the warm-to-cold suspension links of the warm iron yoke superconducting quadrupole magnets, and superconducting dipole magnet. The results of investigation of titanium Ti-6Al-4V and Nitronic 50 stainless steel for the suspension links to support the cold mass, preloads, forces due to cryogenic temperature, and imbalanced magnetic forces from misalignments are presented. Allowable stresses at normal-case scenarios and worst-case scenarios, space constraints, and heat leak considerations are discussed. Principles of the ASME Pressure Vessel Code were used to determine allowable stresses. Optimal angles of the suspension links were obtained by calculation and finite element methods. The stress levels of suspension links at multiple scenarios are presented, discussed, and compared with the allowable stresses.

Fluorescent Dendritic Micro-Hydrogels: Synthesis, Analysis and Use in Single-Cell Detection.

PubMed

Christadore, Lisa; Grinstaff, Mark W; Schaus, Scott E

2018-04-18

Hydrogels are of keen interest for a wide range of medical and biotechnological applications including as 3D substrate structures for the detection of proteins, nucleic acids, and cells. Hydrogel parameters such as polymer wt % and crosslink density are typically altered for a specific application; now, fluorescence can be incorporated into such criteria by specific macromonomer selection. Intrinsic fluorescence was observed at λ max 445 nm from hydrogels polymerized from lysine and aldehyde- terminated poly(ethylene glycol) macromonomers upon excitation with visible light. The hydrogel’s photochemical properties are consistent with formation of a nitrone functionality. Printed hydrogels of 150 μm were used to detect individual cell adherence via a decreased in fluorescence. The use of such intrinsically fluorescent hydrogels as a platform for cell sorting and detection expands the current repertoire of tools available.

Exploring the Chemistry of Bicyclic Isoxazolidines for the Multicomponent Synthesis of Glycomimetic Building Blocks.

PubMed

Hoogenboom, Jorin; Lutz, Martin; Zuilhof, Han; Wennekes, Tom

2016-10-07

Starting from a chiral furanone, the nitrone-olefin [3 + 2] cycloaddition can be used to obtain bicyclic isoxazolidines for which we report a set of reactions to selectively modify each functional position. These synthetically versatile bicyclic isoxazolidines allowed us to obtain complex glycomimetic building blocks, like iminosugars, via multicomponent chemistry. For example, a library of 20 pipecolic acid derivatives, a recurring motif in various prescription drugs, could be obtained via a one-pot Staudinger/aza-Wittig/Ugi three-component reaction of a bicyclic isoxazolidine-derived azido-hemiacetal. Notably, specific pipecolic acids in this library were obtained via hydrolysis of an unique tricyclic imidate side product of the Ugi reaction. The azido-hemiacetal was also converted into an aza-C-glycoside iminosugar via an unprecendented one-pot Staudinger/aza-Wittig/Mannich reaction.

alpha-(Phenylazo)-4-nitrobenzyl cyanide, a new acid-base indicator.

PubMed

Légrádi, L

1970-02-01

A new acid-base indicator, alpha-(phenylazo)-4-nitrobenzyl cyanide, is proposed. The indicator changes colour from yellow to violet in the presence of alkali owing to the formation of a nitronic acid structure. This indicator is applicable for the titration of weak acids in acetone and ethanol media or in a mixture of these organic solvents and water, with 0.1M aqueous sodium hydroxide as titrant. The absorption spectra have been recorded for the indicator in 25%, 50% and 75% aqueous ethanol and acetone. By means of the spectra the dissociation constants in these media have been determined. The pK value of alpha-(phenylazo)-4-nitrobenzyl cyanide is 12.10 in water, and is decreased considerably in acetone but only slightly in ethanol. This behaviour is similar to that of positively charged weak acids and irregular for a weak acid carrying no charge or a negative charge.

Fatigue and fracture properties of a super-austenitic stainless steel at 295 K and 4 K

NASA Astrophysics Data System (ADS)

McRae, D. M.; Walsh, R. P.; Dalder, E. N. C.; Litherland, S.; Trosen, M.; Kuhlmann, D. J.

2014-01-01

The tie plate structure for the ITER Central Solenoid (CS) is required to have high strength and good fatigue and fracture behavior at both room temperature and 4 K. A super-austenitic stainless steel - UNS 20910, commonly referred to by its trade name, Nitronic 50 (N50) - has been chosen for consideration to fulfill this task, due to its good room temperature and cryogenic yield strengths and weldability. Although N50 is often considered for cryogenic applications, little published data exists at 4 K. Here, a full series of tests have been conducted at 295 K and 4 K, and static tensile properties of four forgings of commercially-available N50 are reported along with fatigue life, fatigue crack growth rate (FCGR), and fracture toughness data. This study makes a significant contribution to the cryogenic mechanical properties database of high strength, paramagnetic alloys with potential for superconducting magnet applications.

Fatigue and fracture of three austenitic stainless steels at cryogenic temperatures

NASA Astrophysics Data System (ADS)

McRae, D. M.; Balachandran, S.; Walsh, R. P.

2017-12-01

For the past couple decades, 316LN stainless steel has remained the “go-to” alloy for structural components intended for cryogenic temperature service, partially because of its favorable mechanical properties, but also because of the data available in the literature for T = 4 K. In recent years, some interest has arisen to investigate and develop stronger and tougher alloys for cryogenic structural components, particularly for magnet systems like ITER. This study presents new 4 K fatigue crack growth rate (FCGR) and fracture toughness data for Nitronic® 50 and JK2LB stainless steels, compiles existing data for these alloys, and compares them with 316LN data found in literature. This study intends to further expand the existing cryogenic data set for these alloys, clarify key differences between them to better facilitate mechanical design, and potentially bolster further alloy development.

Cu-catalyzed aerobic oxidative cyclizations of 3-N-hydroxyamino-1,2-propadienes with alcohols, thiols, and amines to form α-O-, S-, and N-substituted 4-methylquinoline derivatives.

PubMed

Sharma, Pankaj; Liu, Rai-Shung

2015-03-16

A one-pot, two-step synthesis of α-O-, S-, and N-substituted 4-methylquinoline derivatives through Cu-catalyzed aerobic oxidations of N-hydroxyaminoallenes with alcohols, thiols, and amines is described. This reaction sequence involves an initial oxidation of N-hydroxyaminoallenes with NuH (Nu = OH, OR, NHR, and SR) to form 3-substituted 2-en-1-ones, followed by Brønsted acid catalyzed intramolecular cyclizations of the resulting products. Our mechanistic analysis suggests that the reactions proceed through a radical-type mechanism rather than a typical nitrone-intermediate route. The utility of this new Cu-catalyzed reaction is shown by its applicability to the synthesis of several 2-amino-4-methylquinoline derivatives, which are known to be key precursors to several bioactive molecules. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Dual catalysis for enantioselective convergent synthesis of enantiopure vicinal amino alcohols.

PubMed

Ye, Chen-Xi; Melcamu, Yared Yohannes; Li, Heng-Hui; Cheng, Jiang-Tao; Zhang, Tian-Tian; Ruan, Yuan-Ping; Zheng, Xiao; Lu, Xin; Huang, Pei-Qiang

2018-01-29

Enantiopure vicinal amino alcohols and derivatives are essential structural motifs in natural products and pharmaceutically active molecules, and serve as main chiral sources in asymmetric synthesis. Currently known asymmetric catalytic protocols for this class of compounds are still rare and often suffer from limited scope of substrates, relatively low regio- or stereoselectivities, thus prompting the development of more effective methodologies. Herein we report a dual catalytic strategy for the convergent enantioselective synthesis of vicinal amino alcohols. The method features a radical-type Zimmerman-Traxler transition state formed from a rare earth metal with a nitrone and an aromatic ketyl radical in the presence of chiral N,N'-dioxide ligands. In addition to high level of enantio- and diastereoselectivities, our synthetic protocol affords advantages of simple operation, mild conditions, high-yielding, and a broad scope of substrates. Furthermore, this protocol has been successfully applied to the concise synthesis of pharmaceutically valuable compounds (e.g., ephedrine and selegiline).

Mechanism of Oxidative Amidation of Nitroalkanes with Oxygen and Amine Nucleophiles by Using Electrophilic Iodine.

PubMed

Li, Jing; Lear, Martin J; Kwon, Eunsang; Hayashi, Yujiro

2016-04-11

Recently, we developed a direct method to oxidatively convert primary nitroalkanes into amides that entailed mixing an iodonium source with an amine, base, and oxygen. Herein, we systematically investigated the mechanism and likely intermediates of such methods. We conclude that an amine-iodonium complex first forms through N-halogen bonding. This complex reacts with aci-nitronates to give both α-iodo- and α,α-diiodonitroalkanes, which can act as alternative sources of electrophilic iodine and also generate an extra equimolar amount of I(+) under O2. In particular, evidence supports α,α-diiodonitroalkane intermediates reacting with molecular oxygen to form a peroxy adduct; alternatively, these tetrahedral intermediates rearrange anaerobically to form a cleavable nitrite ester. In either case, activated esters are proposed to form that eventually reacts with nucleophilic amines in a traditional fashion. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Evaluation of weldments in type 21-6-9 stainless steel for compact ignition tokamak structural applications, phase 1

NASA Astrophysics Data System (ADS)

Alexander, D. J.; Goodwin, G. M.; Bloom, E. E.

1991-06-01

Primary design considerations for the Compact Ignition Tokamak toroidal field-coil cases are yield strength and toughness in the temperature range from 77 to 300 K. Type 21-6-9 stainless steel, also still known by its original Armco Steel Company trade name Nitronic 40, is the proposed alloy for this application. It has high yield strength and usually adequate base metal toughness, but weldments in thick sections have not been adequately characterized in terms of mechanical properties or hot-cracking propensity. In this study, weldability of the alloy in heavy sections and the mechanical properties of the resultant welds were investigated including tensile yield strength and Charpy V-notch toughness at 77 K and room temperature. Weldments were made in four different base metals using seven different filler metals. None of the weldments showed any indication of hot-cracking problems. All base metals, including weldment heat-affected zones, were found to have adequate strength and impact toughness at both test temperatures. Weld metals, on the other hand, except ERNiCr-3 and ENiCrFe-3, had impact toughnesses of less than 67 J at 77 K. Inconel 82 had an average weld metal impact toughness of over 135 J at 77 K, and although its strength at 77 K is less than that of type 21-6-9 base metal, at this point it is considered to be the first-choice filler metal. Phase 2 of this program will concentrate on composition refinement and process/procedure optimization for the generic ERNiCr-3 composition and will generate a design data base for base and weld metal, including tensile, fracture toughness, and crack growth rate data.

Kinetic and thermodynamic acidities of substituted 1-benzyl-1-methoxy-2-nitroethylenes. Strong reduction of the transition state imbalance compared to other nitroalkanes.

PubMed

Bernasconi, Claude F; Ali, Mahammad; Gunter, Janette C

2003-01-08

Acidity constants of six substituted 1-benzyl-1-methoxy-2-nitroethylenes (2-Z with Z = m-NO(2), m-CF(3), m-Cl, H, p-Me, p-MeO) and their respective nitronic acids were determined in 50% DMSO-50% water (v/v) at 20 degrees C. Kinetic data were obtained on the reversible deprotonation of all six 2-Z by OH(-) and piperidine and on the reversible deprotonation of 2-NO(2)() by piperazine, 1-(2-hydroxyethyl)piperazine, and morpholine in the same solvent. These data allowed a determination of the Brønsted coefficients alpha (dependence on acidity of 2-Z) and beta (dependence on amine basicity). The fact that alpha > beta indicates the presence of a transition state imbalance which, however, is much smaller than that for the deprotonation of arylnitromethanes. The reasons for this reduction in the imbalance and their relevance to a recent study of the deprotonation of Fischer carbene complexes are discussed.

alpha-Phenyl-N-tert-butyl nitrone attenuates methamphetamine-induced depletion of striatal dopamine without altering hyperthermia.

PubMed

Cappon, G D; Broening, H W; Pu, C; Morford, L; Vorhees, C V

1996-10-01

Methamphetamine (MA) administration to adult rats (4 x 10 mg/kg s.c.) induces neurotoxicity predominately characterized by a persistent reduction of neostriatal dopamine (DA) content. Hyperthermia following MA administration potentiates the resulting DA depletion. DA-derived free radicals are postulated to be a mechanism through which MA-induced neurotoxicity is produced. The spin trapping agent PBN reacts with free radicals to form nitroxyl adducts, thereby preventing damaging free radical reactions with cellular substrates. MA with saline pretreatment (Sal-MA) reduced neostriatal DA by 55% (P < 0.01 vs. Sal-Sal). MA with PBN pretreatment (PBN-MA) at 36 or 60 mg/kg reduced neostriatal DA by 36 and 22%, respectively (P < 0.05 and P < 0.01 vs Sal-MA) indicating partial protection. PBN pretreatment did not alter MA-induced hyperthermia. Thus, PBN does not attenuate MA-induced neurotoxicity by reducing MA-induced hyperthermia. These results support a role for free radicals in the generation of MA-induced dopaminergic neurotoxicity.

Mn cycling in marine biofilms: effect on the rate of localized corrosion.

PubMed

Dexter, S C; Xu, K; Luther, G L

2003-04-01

Microelectrodes of the Au-Hg amalgam type have been used together with square wave voltammetry to measure profiles of oxygen, peroxide, Fe, Mn and sulfur chemical species through the thickness of natural assemblage marine biofilms grown on stainless steel alloy Nitronic 50 (UNS S20910). The data show Mn+2 and peroxide together at locations where the dissolved oxygen concentration was low. Oxidized species of Fe were also found at some locations. Sulfur species (predominantly S-2) was often found at locations where the dissolved oxygen concentration was below the detectable limit. Confocal scanning laser microscopy was used to image the microbial assemblage at the locations of the chemical profile data. Organisms with a filamentous morphology were found in consortia with rod and coccoidal shaped microbes at locations where dissolved Mn and peroxide were measured. The filamentous forms were usually absent at locations where Mn was not detected. It is suggested that the filamentous organisms may be Mn metabolizers, and that peroxidatic Mn re-oxidation may be taking place within the biofilm.

Unexpected complexes from meta-phenylene bis(tert-butyl nitroxides) and gadolinium(III) 1,1,1,5,5,5-hexafluoropentane-2,4-dionate

NASA Astrophysics Data System (ADS)

Sekine, Hiroyasu; Ishida, Takayuki

2018-01-01

Coordination reaction of the stable ground triplet biradical biphenyl-3,5-diyl bis(tert-butyl nitroxide) and [Gd(hfac)3(H2O)2] unexpectedly gave complexes containing a dimerized diamagnetic ligand via a [3+3] cycloaddition of the benzene rings (hfac = 1,1,1,5,5,5-hexafluoropentane-2,4-dionate). To avoid such dimerization, we introduced a bulkier substituent into the ligand; namely, a new ground triplet biradical 5-mesityl-1,3-phenylene bis(tert-butyl nitroxide) was applied to this complexation scheme. However, an unexpected complex was again obtained in a different way, and the magnetic study revealed that the novel ligand involved was diamagnetic. The crystallographic analysis of the product clarified isomerization from the paramagnetic ligand to a diamagnetic N-tert-butylaminoquinone imine N-oxide ligand as a result of disproportionation from two open-shell nitroxide groups to closed-shell groups, an amine and a nitrone. The present paper reports the first structural evidence for a diamagnetic isomer of m-phenylene-bridged bisnitroxde compounds.

Evaluation of corrosion inhibitor simulating conditions of operation

NASA Astrophysics Data System (ADS)

Gómez, O.; Aponte, H.; Vera, E.; Pineda, Y.

2017-12-01

Operating conditions at the head of oil wells are critical, in addition to injecting water to increase the pressure while maintaining production cause deterioration in the metallic structures that transport fluids. One way to maintain integrity is the injection of inhibitors which plays an important role in protecting the pipes. In this study a molecule N-PHENYL NITRONE was obtained, which was evaluated by electrochemical tests (LPR) and Tafel Polarization Curves in a reactor controlling environments containing different dosages, pressure values, temperatures and flow velocity using working electrodes tubing API N 80, the reactor was connected to a potentiostat to determine corrosion rates, allowing the analysis of the influence of each variable on the protective behaviour of the inhibitor, and its efficiency against the decrease of the deterioration of the pipes. Corrosion products are analysed by X-Ray Diffraction (XRD). Photographic records of the surface verify the formation of iron carbonate (FeCO3). In addition, a mathematical analysis of the independent variables is performed to evaluate the effect that it has on the efficiency of corrosion inhibition.

Quantitative electron spin resonance (ESR) analysis of antioxidative properties using the acetaldehyde/xanthine oxidase system

NASA Astrophysics Data System (ADS)

Souchard, J.-P.; Nepveu, F.

1998-05-01

We present a method for the quantitative ESR analysis of the antioxidant properties of drugs using the acetaldhehyde/xanthine oxidase (AC/XOD) superoxide generating system and 5,5-dimethyl-l-pyrroline-N-oxide (DMPO) as spin trap. In stoichiometric conditions (AC/XOD, 60 mM/0.018 U), the resulting paramagnetic DMPO adduct disappeared with superoxide dismutase and remained when catalase or DMSO were used. That adduct was dependent only on superoxide and resulted from the trapping of a carboxyl radical by DMPO (aN = 15.2 G, aH = 18.9 G). Similar results were obtained using 4-pyridyl-l-oxide-N-t-butyl nitrone (POBN) as spin trap. The ESR signal of the DMPO-CO2- adduct was very stable and allowed quantitative analysis of the antioxidative activity of redox molecules from an IC{50} value representing the concentration causing 50% inhibition of its intensity. Among the tested compounds, manganese(II), complexes were the most effective, 25 times as active as ascorbic acid or (+)catechin and 500-fold more antioxidative than Trolox^R. Nous présentons une méthode d'analyse quantitative de l'activité antioxydante de composés d'intérêt pharmaceutique basée sur le système acétaldéhyde/xanthine oxydase (AC/XOD), l'utilisation de la RPE et du piégeage de spin avec le 5,5-diméthyl-l-pyrroline-N-oxyde (DMPO). Dans les conditions stoechiométriques {AC/XOD, 60 mM/0,018 U/ml}, l'adduit radicalaire résultant de ce système disparaît en présence de superoxyde dismutase et persiste en présence de catalase ou de DMSO. Cet adduit ne dépend que de la présence de l'anion superoxyde et provient du piégeage d'un radical carboxyle CO2- sur le DMPO (aN = 15.2 G, aH = 18.9 G). Des résultats similaires ont été obtenus avec le piégeur de spin 4-pyridyl-l-oxyde-N-t-butyl nitrone (POBN). Le signal RPE de l'adduit DMPO-CO2- est très stable et permet la quantification de l'activité antioxydante de pharmacophores redox par la détermination de la CI{50}, concentration qui diminue de 50 % son intensité. Parmi les composés testés, les complexes du manganèse sont les plus antioxydants, 25 fois plus actifs que la vitamine C ou la catéchine(+), 500 fois plus antioxydants que le Trolox^R.

Preliminary evaluation of cavitation resistance of type 316LN stainless steel in mercury using a vibratory horn

NASA Astrophysics Data System (ADS)

Pawel, S. J.; Manneschmidt, E. T.

2003-05-01

Type 316LN stainless steel in a variety of conditions (annealed, cold-worked, surface-modified) was exposed to cavitation conditions in stagnant mercury using a vibratory horn. The test conditions included peak-to-peak displacement of the specimen surface of 25 μm at a frequency of 20 kHz and a mercury temperature in the range -5 to 80 °C. Following a brief incubation period in which little or no damage was observed, specimens of annealed 316LN exhibited increasing weight loss and surface roughening with increasing exposure times. Examination of test surfaces with the scanning electron microscope revealed primarily general/uniform wastage in all cases but, for long exposure times, a few randomly oriented 'pits' were also observed. Type 316LN that was 50% cold-worked was considerably more resistant to cavitation erosion damage than annealed material, but the surface modifications (CrN coating, metallic glass coating, laser treatment to form a diamond-like surface) provided little or no protection for the substrate. In addition, the cavitation erosion resistance of other materials - Inconel 718, Nitronic 60, and Stellite 3 - was also compared with that of 316LN for identical screening test conditions.

Demonstration of free radical generation in the "stunned" myocardium in the conscious dog and identification of major differences between conscious and open-chest dogs.

PubMed Central

Li, X Y; McCay, P B; Zughaib, M; Jeroudi, M O; Triana, J F; Bolli, R

1993-01-01

Conscious dogs undergoing a 15-min coronary occlusion were given alpha-phenyl N-tert-butyl nitrone (PBN) and the local coronary venous plasma was analyzed by electron paramagnetic resonance spectroscopy. A prolonged myocardial release of PBN radical adducts was observed, which exhibited a burst in the initial minutes of reflow (peaking at 3 min) and then abated but continued for 1-3 h after reperfusion. Computer simulation revealed the presence of at least two PBN adducts (aN = 15.2 G and a beta H = 6.0 G; aN = 14.6 G and a beta H = 3.0 G), both consistent with the trapping of secondary carbon-centered radicals. No appreciable PBN adduct production was observed when collateral flow exceeded 30-40% of nonischemic flow, indicating that a flow reduction of at least 60% is necessary to trigger free radical reactions. There was a direct relationship between the magnitude of PBN adduct production and the severity of contractile dysfunction (r = 0.77), suggesting that the radicals generated upon reperfusion play a causal role in the subsequent stunning. The total release of PBN adducts after 3 h of reperfusion following a 15-min coronary occlusion was found to be approximately five times greater in open-chest compared with conscious dogs; at the same time, the recovery of wall thickening was markedly less in open-chest dogs. This study represents the first application of spin trapping to a conscious animal model of myocardial ischemia. The results demonstrate (a) that free radicals are generated in the stunned myocardium in the absence of the artificial or abnormal conditions associated with previously used models (isolated hearts, open-chest preparations), and (b) that both the severity of postischemic dysfunction and the magnitude of the attendant free radical production are greatly exaggerated in the open-chest dog, implying that previous conclusions derived from this model may not be applicable to conscious animals or to humans. This investigation also provides a method to measure free radicals in awake animals. PMID:8394382

[Curcumin inhibited rat colorectal carcinogenesis by activating PPAR-γ: an experimental study].

PubMed

Liu, Liu-bin; Duan, Chang-nong; Ma, Zeng-yi; Xu, Gang

2015-04-01

To explore the chemopreventive effect of curcumin on DMH induced colorectal carcinogenesis and the underlining mechanism. Totally 40 Wistar rats were divided into the model group and the curcumin group by random digit table, 20 in each group. Meanwhile, a normal control group was set up (n =10). A colorectal cancer model was induced by subcutaneously injecting 20 mg/kg DMH. The tumor incidence and the inhibition rate were calculated. The effect of curcumin on the expression of peroxisome proliferator-activated receptor gamma (PPARγ) in rat colon mucosal tissues was observed using immunohistochemistry and Western blot. HT 29 cell line were cultured and divided into a control group, the curcumin + GW9662 (2-chloro-5-nitro-N-4-phenylbenzamide) intervention group, and the curcumin group. The inhibition of different concentrations curcumin on HT29 cell line was detected using MTT. The expression of curcumin on PPARy was also detected using Western blot. The tumor incidence was 80. 00% (12/15 cases) in the model group, obviously higher than that of the curcumin group (58. 82%, 10/17 cases, P <0. 05). The inhibition rate of curcumin on DMH induced colorected carcinoma reached 26. 46%. Compared with the normal control group, the expression of PPARγ protein was significantly increased in the curcumin group and the model group (P <0. 01). Compared with the model group at the same time point, the expression of PPARy protein was significantly enhanced in the curcumin group (P <0. 05). MTT analysis showed that curcumin could inhibit the proliferation of in vitro HT 29 cells in dose and time dependent manners. The expression of PPARy protein was significantly increased in the GW9662 group and the curcumin group, showing statistical difference when compared with the normal control group (P <0. 01). Compared with the GW9662 group, the expression of PPARγ protein was significantly increased in the curcumin group (P <0. 01). Curcumin could inhibit DMH-induced rat colorectal carcinogenesis and the growth of in vitro cultured HT 29 cell line, which might be achieved by activating PPARy signal transduction pathway.

Mechanical Properties of Steel Encapsulated Metal Matrix Composites

NASA Astrophysics Data System (ADS)

Fudger, Sean; Klier, Eric; Karandikar, Prashant; McWilliams, Brandon; Ni, Chaoying

This research evaluates a coefficient of thermal expansion (CTE) mismatch induced residual compressive stress approach as a means of improving the ductility of metal matrix composites (MMCs). MMCs are frequently incorporated into advanced material systems due to their tailorable material properties. However, they often have insufficient strength and ductility for many structural applications. By combining MMCs with high strength steels in a hybridized, macro composite materials system that exploits the CTE mismatch, materials systems with improved strength, damage tolerance, and structural efficiency can be obtained. Macro hybridized systems consisting of steel encapsulated light metal MMCs were produced with the goal of creating a system which takes advantage of the high strength, modulus, and damage tolerance of steels and high specific stiffness and low density of MMCs while mitigating the high density of steels and the poor ductility of MMCs. Aluminum and magnesium based particulate reinforced MMCs combine many of the desirable characteristic of metals and ceramics, particularly the unique ability to tailor their CTE. This work aims to compare the performance of macro hybridized material systems consisting of aluminum or magnesium MMCs reinforced with Al2O3, SiC, or B4C particles and encapsulated by A36 steel, 304 stainless steel, or cold worked Nitronic® 50 stainless steels.

Site-specific radical formation in DNA induced by Cu(II)-H2O2 oxidizing system, using ESR, Immuno-spin trapping, LC/MS and MS/MS

PubMed Central

Bhattacharjee, Suchandra; Deterding, Leesa J.; Chatterjee, Saurabh; Jiang, JinJie; Ehrenshaft, Marilyn; Lardinois, Olivier; Ramirez, Dario C.; Tomer, Kenneth B.; Mason, Ronald P.

2011-01-01

Oxidative stress-related damage to the DNA macromolecule produces a multitude of lesions that are implicated in mutagenesis, carcinogenesis, reproductive cell death and aging. Many of these lesions have been studied and characterized by various techniques. Of the techniques that are available, the comet assay, HPLC-EC, GC-MS, HPLC-MS and especially HPLC-MS/MS remain the most widely used and have provided invaluable information on these lesions. However, accurate measurement of DNA damage has been a matter of debate. In particular, there have been reports of artifactual oxidation leading to erroneously high damage estimates. Further, most of these techniques measure the end product of a sequence of events and thus provide only limited information on the initial radical mechanism. We report here a qualitative measurement of DNA damage induced by a Cu(II)-H2O2 oxidizing system using immuno spin-trapping (IST) with EPR, MS and MS/MS. The radical generated is trapped by DMPO immediately upon formation. The DMPO adduct formed is initially EPR active but subsequently is oxidized to the stable nitrone, which can then be detected by IST and further characterized by MS and MS/MS. PMID:21382477

Oxidation of primary amines to oximes with molecular oxygen using 1,1-diphenyl-2-picrylhydrazyl and WO3/Al2O3 as catalysts.

PubMed

Suzuki, Ken; Watanabe, Tomonari; Murahashi, Shun-Ichi

2013-03-15

The oxidative transformation of primary amines to their corresponding oximes proceeds with high efficiency under molecular oxygen diluted with molecular nitrogen (O2/N2 = 7/93 v/v, 5 MPa) in the presence of the catalysts 1,1-diphenyl-2-picrylhydrazyl (DPPH) and tungusten oxide/alumina (WO3/Al2O3). The method is environmentally benign, because the reaction requires only molecular oxygen as the terminal oxidant and gives water as a side product. Various alicyclic amines and aliphatic amines can be converted to their corresponding oximes in excellent yields. It is noteworthy that the oxidative transformation of primary amines proceeds chemoselectively in the presence of other functional groups. The key step of the present oxidation is a fast electron transfer from the primary amine to DPPH followed by proton transfer to give the α-aminoalkyl radical intermediate, which undergoes reaction with molecular oxygen and hydrogen abstraction to give α-aminoalkyl hydroperoxide. Subsequent reaction of the peroxide with WO3/Al2O3 gives oximes. The aerobic oxidation of secondary amines gives the corresponding nitrones. Aerobic oxidative transformation of cyclohexylamines to cyclohexanone oximes is important as a method for industrial production of ε-caprolactam, a raw material for Nylon 6.

Antarctic polar stratospheric aerosols: The roles of nitrates, chlorides and sulfates

NASA Technical Reports Server (NTRS)

Pueschel, R. F.; Snetsinger, K. G.; Goodman, J. K.; Ferry, G. V.; Oberbeck, V. R.; Verma, S.; Fong, W.

1988-01-01

Nitric and hydrochloric acids have been postulated to condense in the winter polar stratosphere to become an important component of polar stratospheric clouds. One implication is that the removal of NO(y) from the gas phase by this mechanism allows high Cl(x) concentrations to react with O3, because the formation of ClNO3 is inhibited. Contributions of NO3 and Cl to the stratospheric aerosol were determined during the 1987 Airborne Antarctic Ozone Experiment by testing for the presence of nitrates and chlorides in the condensed phase. Aerosol particles were collected on four 500 micron diameter gold wires, each pretreated differently to give results that were specific to certain physical and chemical aerosol properties. One wire was carbon-coated for concentration and size analyses by scanning electron microscopy; X-ray energy dispersive analyses permitted the detection of S and Cl in individual particles. Three more wires were coated with Nitron, barium chloride and silver nitrate, respectively, to detect nitrate, sulfate and chloride in aerosol particles. All three ions, viz., sulfates, nitrates and chlorides were detected in the Antarctic stratospheric aerosol. In terms of number concentrations, the aerosol was dominated by sulfates, followed by chlorides and nitrates. An inverse linear regression can be established between nitrate concentrations and ozone mixing ratio, and between temperature and nitrates.

Preliminary studies on the activities of spin traps as scavengers of free radicals

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

Ogunbiyi, P.O.; Washington, I.

1991-03-15

The spin trapping agents, N-t-Butyl-a-phenyl-nitrone (PBN) and 5,5-Dimethyl-1-pyroline-N-oxide (DMPO) have been used to investigate the primary free radicals involved in various tissue injuries. Also, PBN and DMPO can provide some protection against free radical-induced lung injuries. However, their therapeutic potentials as free radical scavengers remained unexamined. In this study, the effects of PBN and DMPO on guinea pig lung microsomal lipid peroxidation were investigated using thiobarbituric acid-reactive substance assay. Superoxide anions (O{sup 2}{minus}) were generated in an enzymatic and a non-enzymatic system. PBN and DMPO each, significantly inhibited NADPH-stimulated lipid peroxidation irrespective of the presence of Fe{sup 3+}. Cytochrome cmore » reduction by the enzymatic and nitro blue tetrazolium reduction by the non-enzymatic O{sup 2}{minus} generating systems were both inhibited by PBN and DMPO as well as superoxide dismutase and dimethyl sulfoxide when compared with the controls. The spin traps exhibited lower potencies in these systems than the reference compounds, SOD and DMSO, which are well established as O{sup 2}{minus} and hydroxyl radical scavengers respectively. Results demonstrate the free radical scavenging properties of PBN and DMPO. This is an indication of their possible usefulness as antioxidants.« less

Biosynthetic studies on clavulanic acid: its biopathway and stereochemical course

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

Mao, S.S.

A degradative analysis allowed determination of the stereochemistry at C-9 of clavulanic acid produced by Streptomyces clavuigerus. An over-all inversion of configuration from the C/sub 5/-unit precursor ornithine was observed. The diastereomeric (1R,2R)- and (1S,2R)-(1-/sup 3/H)-glycerols were separately synthesized and administered. Complementary results demonstrated an overall retention of configuration paralleling cysteine incorporation in the biosynthesis of penicillin. 3-Hydroxyornithine, a potential precursor to clavulanic acid, was prepared by a 1,3-dipolar addition of a nitrone and vinylglycine. However, 3-hydroxyornithine was not taken up by the organism and this possible intermediate could not be shown to be a specific precursor to clavulanic acid.more » (2-/sup 3/H)-L-Ornithine displays a preferential incorporation relative to D-ornithine. An epimerization by a one-base mechanism is suggested by the retention of half the tritium activity. ..beta..-Alanine, a potential precursor of the ..beta..-lactam segment was examined and shown not to play a direct role in the biosynthesis. Further, 3-hydroxypropionyl-ornithine, a parallel amide to the tripeptide intermediate in penicillin biosynthesis, was not incorporated into clavulanic acid. The role of 3-hydroxypropionate and glycerol were examined in both starch and triglyceride fermentation media.« less

Synthesis of bis-Phosphate Iminoaltritol Enantiomers and Structural Characterization with Adenine Phosphoribosyltransferase.

PubMed

Harris, Lawrence D; Harijan, Rajesh K; Ducati, Rodrigo G; Evans, Gary B; Hirsch, Brett M; Schramm, Vern L

2018-01-19

Phosphoribosyl transferases (PRTs) are essential in nucleotide synthesis and salvage, amino acid, and vitamin synthesis. Transition state analysis of several PRTs has demonstrated ribocation-like transition states with a partial positive charge residing on the pentose ring. Core chemistry for synthesis of transition state analogues related to the 5-phospho-α-d-ribosyl 1-pyrophosphate (PRPP) reactant of these enzymes could be developed by stereospecific placement of bis-phosphate groups on an iminoaltritol ring. Cationic character is provided by the imino group and the bis-phosphates anchor both the 1- and 5-phosphate binding sites. We provide a facile synthetic path to these molecules. Cyclic-nitrone redox methodology was applied to the stereocontrolled synthesis of three stereoisomers of a selectively monoprotected diol relevant to the synthesis of transition-state analogue inhibitors. These polyhydroxylated pyrrolidine natural product analogues were bis-phosphorylated to generate analogues of the ribocationic form of 5-phosphoribosyl 1-phosphate. A safe, high yielding synthesis of the key intermediate represents a new route to these transition state mimics. An enantiomeric pair of iminoaltritol bis-phosphates (L-DIAB and D-DIAB) was prepared and shown to display inhibition of Plasmodium falciparum orotate phosphoribosyltransferase and Saccharomyces cerevisiae adenine phosphoribosyltransferase (ScAPRT). Crystallographic inhibitor binding analysis of L- and D-DIAB bound to the catalytic sites of ScAPRT demonstrates accommodation of both enantiomers by altered ring geometry and bis-phosphate catalytic site contacts.

Reactions of nitroxide radicals in aqueous solutions exposed to non-thermal plasma: limitations of spin trapping of the plasma induced species

NASA Astrophysics Data System (ADS)

Gorbanev, Yury; Stehling, Nicola; O'Connell, Deborah; Chechik, Victor

2016-10-01

Low temperature (‘cold’) atmospheric pressure plasmas have gained much attention in recent years due to their biomedical effects achieved through the interactions of plasma-induced species with the biological substrate. Monitoring of the radical species in an aqueous biological milieu is usually performed via electron paramagnetic resonance (EPR) spectroscopy using various nitrone spin traps, which form persistent radical adducts with the short-lived radicals. However, the stability of these nitroxide radical adducts in the plasma-specific environment is not well known. In this work, chemical transformations of nitroxide radicals in aqueous solutions using a model nitroxide 4-oxo-TEMPO were studied using EPR and LC-MS. The kinetics of the nitroxide decay when the solution was exposed to plasma were assessed, and the reactive pathways proposed. The use of different scavengers enabled identification of the types of reactive species which cause the decay, indicating the predominant nitroxide group reduction in oxygen-free plasmas. The 2H adduct of the PBN spin trap (PBN-D) was shown to decay similarly to the model molecule 4-oxo-TEMPO. The decay of the spin adducts in plasma-treated solutions must be considered to avoid rendering the spin trapping results unreliable. In particular, the selectivity of the decay indicated the limitations of the PTIO/PTI nitroxide system in the detection of nitric oxide.

Mutagenic and Cytotoxicity LQB 123 Profile: Safety and Tripanocidal Effect of a Phenyl-t-Butylnitrone Derivative

PubMed Central

Cupello, Mauricio Peixoto; Saraiva, Francis Monique; Ippolito, Pedro; Fernandes, Andréia da Silva; Costa, Debora de Sousa dos Santos; Paula, Jessica Isis Oliveira; Costa, Paulo Roberto Ribeiro; Dias, Ayres Guimarães

2017-01-01

The therapeutic options for Chagas disease are limited and its treatment presents a number of drawbacks including toxicity, drug resistance, and insufficient effectiveness against the chronic stage of the disease. Therefore, new therapeutical options are mandatory. In the present work, we evaluated the effect of a phenyl-tert-butylnitrone (PBN) derivate, LQB 123, against Trypanosoma cruzi forms. LQB 123 presented a trypanocidal effect against bloodstream trypomastigotes (IC50 = 259.4 ± 6.1 μM) and intracellular amastigotes infecting peritoneal macrophages (IC50 = 188.2 ± 47.5 μM), with no harmful effects upon the mammalian cells (CC50 values greater than 4 mM), resulting in a high selectivity index (CC50/IC50 > 20). Additionally, metacyclic trypomastigotes submitted to LQB 123 presented an IC50 of about 191.8 ± 10.5 μM and epimastigotes forms incubated with different concentrations of LQB 123 presented an inhibition of parasite growth with an IC50 of 255.1 ± 3.6 μM. Finally, we investigated the mutagenic potential of the nitrone by the Salmonella/microsome assay and observed no induction of mutagenicity even in concentrations as high as 33000 μM. Taken together, these results present a nonmutagenic compound, with trypanocidal activity against all relevant forms of T. cruzi, offering new insights into CD treatment suggesting additional in vivo tests. PMID:28316976

Mutagenic and Cytotoxicity LQB 123 Profile: Safety and Tripanocidal Effect of a Phenyl-t-Butylnitrone Derivative.

PubMed

Cupello, Mauricio Peixoto; Saraiva, Francis Monique; Ippolito, Pedro; Fernandes, Andréia da Silva; Menna-Barreto, Rubem Figueiredo Sadoko; Costa, Debora de Sousa Dos Santos; Paula, Jessica Isis Oliveira; Costa, Paulo Roberto Ribeiro; Nogueira, Natália Pereira; Felzenswalb, Israel; Dias, Ayres Guimarães; Paes, Marcia Cristina

2017-01-01

The therapeutic options for Chagas disease are limited and its treatment presents a number of drawbacks including toxicity, drug resistance, and insufficient effectiveness against the chronic stage of the disease. Therefore, new therapeutical options are mandatory. In the present work, we evaluated the effect of a phenyl- tert -butylnitrone (PBN) derivate, LQB 123, against Trypanosoma cruzi forms. LQB 123 presented a trypanocidal effect against bloodstream trypomastigotes (IC 50 = 259.4 ± 6.1  μ M) and intracellular amastigotes infecting peritoneal macrophages (IC 50 = 188.2 ± 47.5  μ M), with no harmful effects upon the mammalian cells (CC 50 values greater than 4 mM), resulting in a high selectivity index (CC 50 /IC 50 > 20). Additionally, metacyclic trypomastigotes submitted to LQB 123 presented an IC 50 of about 191.8 ± 10.5  μ M and epimastigotes forms incubated with different concentrations of LQB 123 presented an inhibition of parasite growth with an IC 50 of 255.1 ± 3.6  μ M. Finally, we investigated the mutagenic potential of the nitrone by the Salmonella /microsome assay and observed no induction of mutagenicity even in concentrations as high as 33000  μ M. Taken together, these results present a nonmutagenic compound, with trypanocidal activity against all relevant forms of T. cruzi , offering new insights into CD treatment suggesting additional in vivo tests.

A rapid, convenient, solventless green approach for the synthesis of oximes using grindstone chemistry.

PubMed

Saikia, Lakhinath; Baruah, Jejiron Maheswari; Thakur, Ashim Jyoti

2011-10-04

Synthesis of oximes is an important reaction in organic chemistry, because these versatile oximes are used for protection, purification, and characterization of carbonyl compounds. Nitriles, amides via Beckmann rearrangement, nitro compounds, nitrones, amines, and azaheterocycles can be synthesised from oximes. They also find applications for selective α-activation. In inorganic chemistry, oximes act as a versatile ligand.Several procedures for the preparation of oximes exist, but, most of them have not addressed the green chemistry issue. They are associated with generation of pollutants, requirement of high reaction temperature, low yields, lack of a generalized procedure, etc. Hence, there is a demand for developing an efficient, convenient, and non-polluting or less polluting alternative method for the preparation of oximes. In this context, bismuth compounds are very useful as they are cheap in general, commercially available, air stable crystalline solids, safe, and non-toxic, hence easy to handle. Carbonyl compounds (aliphatic, heterocyclic, and aromatic) were converted into the corresponding oximes in excellent yields by simply grinding the reactants at room temperature without using any solvent in the presence of Bi2O3. Most importantly, this method minimizes waste disposal problems, provides a simple yet efficient example of unconventional methodology and requires short time. We have developed a novel, quick, environmentally safe, and clean synthesis of aldoximes and ketoximes under solvent-free grinding condition.

Fabrication of refractive index distributions in polymer using a photochemical reaction

NASA Astrophysics Data System (ADS)

Kada, Takeshi; Obara, Atsushi; Watanabe, Toshiyuki; Miyata, Seizo; Liang, Chuan Xin; Machida, Hideaki; Kiso, Koichi

2000-01-01

We demonstrate that a photochemical reaction can create various distributions of refractive index in polymer. When the polymer containing a photochemically active material is irradiated by UV light, the photochemical reaction which breaks the π-conjugated system in the material and decreases its linear polarizability can reduce refractive index of the polymer. We prepared a PMMA film added DMAPN ((4-N,N-dimethylaminophenyl)-N'-phenylnitrone) with a rate of 23 wt % by use of spin coating. Electronic structural change of DMAPN and refractive indices of the film before and after UV irradiation were evaluated by UV absorption spectra and m-line method, respectively. The UV irradiation decreased λmax at 380 nm in the absorption spectra, which is attributed to nitrone, and the refractive indices exponentially with irradiation time. The change of refractive indices reached 0.028. The refractive index profile upon depth of the film was investigated by measuring refractive indices of stacked DMAPN/PMMA films. When UV with a power of 10.7 mW/cm2 irradiated upon three stacked DMAPN/PMMA films for 35 s, variation of the refractive index change showed a quadratic profile. The refractive index profile with various irradiation time can be accounted with the combination of the chemical kinetics with the steady state approximation and Lambert-Beer's law. Thus, the photochemical reaction can be used to control the refractive index distribution in polymer.

A Comprehensive Set of Impact Data for Common Aerospace Metals

DOE PAGES

Brake, Matthew; Reu, Phil L.; Aragon, Dannelle S.

2017-05-16

Our results for the two sets of impact experiments are reported here. In order to assist with model development using the impact data reported, the materials are mechanically characterized using a series of standard experiments. The first set of impact data comes from a series of coefficient of restitution experiments, in which a 2 meter long pendulum is used to study "in context" measurements of the coefficient of restitution for eight different materials (6061-T6 Aluminum, Phosphor Bronze alloy 510, Hiperco, Nitronic 60A, Stainless Steel 304, Titanium, Copper, and Annealed Copper). The coefficient of restitution is measured via two different techniques:more » digital image correlation and laser Doppler vibrometry. Due to the strong agreement of the two different methods, only results from the digital image correlation are reported. The coefficient of restitution experiments are "in context" as the scales of the geometry and impact velocities are representative of common features in the motivating application for this research. Finally, a series of compliance measurements are detailed for the same set of materials. Furthermore, the compliance measurements are conducted using both nano-indentation and micro-indentation machines, providing sub-nm displacement resolution and uN force resolution. Good agreement is seen for load levels spanned by both machines. As the transition from elastic to plastic behavior occurs at contact displacements on the order of 30 nm, this data set provides a unique insight into the transitionary region.« less

A Comprehensive Set of Impact Data for Common Aerospace Metals

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

Brake, Matthew; Reu, Phil L.; Aragon, Dannelle S.

Our results for the two sets of impact experiments are reported here. In order to assist with model development using the impact data reported, the materials are mechanically characterized using a series of standard experiments. The first set of impact data comes from a series of coefficient of restitution experiments, in which a 2 meter long pendulum is used to study "in context" measurements of the coefficient of restitution for eight different materials (6061-T6 Aluminum, Phosphor Bronze alloy 510, Hiperco, Nitronic 60A, Stainless Steel 304, Titanium, Copper, and Annealed Copper). The coefficient of restitution is measured via two different techniques:more » digital image correlation and laser Doppler vibrometry. Due to the strong agreement of the two different methods, only results from the digital image correlation are reported. The coefficient of restitution experiments are "in context" as the scales of the geometry and impact velocities are representative of common features in the motivating application for this research. Finally, a series of compliance measurements are detailed for the same set of materials. Furthermore, the compliance measurements are conducted using both nano-indentation and micro-indentation machines, providing sub-nm displacement resolution and uN force resolution. Good agreement is seen for load levels spanned by both machines. As the transition from elastic to plastic behavior occurs at contact displacements on the order of 30 nm, this data set provides a unique insight into the transitionary region.« less

Free radical generation in the brain precedes hyperbaric oxygen-induced convulsions.

PubMed

Torbati, D; Church, D F; Keller, J M; Pryor, W A

1992-01-01

We tested the hypothesis that hyperbaric oxygenation (HBO) generates free radicals in the brain before the onset of neurological manifestations of central nervous system (CNS) oxygen poisoning. Chronically cannulated, conscious rats were individually placed in a transparent pressure chamber and exposed to (1) 5 atmospheres absolute (ATA) oxygen for 15 min (n = 4); (2) 5 ATA oxygen for 30 min (n = 5), during which no visible convulsions occurred; (3) 5 ATA oxygen for 30 min with recurrent convulsions (n = 6); (4) 5 ATA oxygen until the appearance of the first visible convulsions (n = 5); (5) 4 ATA oxygen for 60 min during which no convulsions occurred (n = 5); and (6) 5 ATA air for 30 min (n = 5, controls). Immediately before compression, 1 mL of 0.1 M of alpha-phenyl-N-tert-butyl nitrone (PBN) was administered intravenously (iv) for spin trapping. At the termination of each experiment, rats were euthanized by pentobarbital iv and decompressed within 1 min. Brains were rapidly removed for preparation of lipid extracts (Folch). The presence of PBN spin adducts in the lipid extracts was examined by electron spin resonance (ESR) spectroscopy. ESR spectra from unconvulsed rats exposed to 5 ATA oxygen for 30 min revealed both oxygen-centered and carbon-centered PBN spin adducts in three of the five brains. One of the five rats in this group showed an ascorbyl signal in the ESR spectrum.(ABSTRACT TRUNCATED AT 250 WORDS)

Simple Biological Systems for Assessing the Activity of Superoxide Dismutase Mimics

PubMed Central

Tovmasyan, Artak; Reboucas, Julio S.

2014-01-01

Abstract Significance: Half a century of research provided unambiguous proof that superoxide and species derived from it—reactive oxygen species (ROS)—play a central role in many diseases and degenerative processes. This stimulated the search for pharmaceutical agents that are capable of preventing oxidative damage, and methods of assessing their therapeutic potential. Recent Advances: The limitations of superoxide dismutase (SOD) as a therapeutic tool directed attention to small molecules, SOD mimics, that are capable of catalytically scavenging superoxide. Several groups of compounds, based on either metal complexes, including metalloporphyrins, metallocorroles, Mn(II) cyclic polyamines, and Mn(III) salen derivatives, or non-metal based compounds, such as fullerenes, nitrones, and nitroxides, have been developed and studied in vitro and in vivo. Very few entered clinical trials. Critical Issues and Future Directions: Development of SOD mimics requires in-depth understanding of their mechanisms of biological action. Elucidation of both molecular features, essential for efficient ROS-scavenging in vivo, and factors limiting the potential side effects requires biologically relevant and, at the same time, relatively simple testing systems. This review discuses the advantages and limitations of genetically engineered SOD-deficient unicellular organisms, Escherichia coli and Saccharomyces cerevisiae as tools for investigating the efficacy and mechanisms of biological actions of SOD mimics. These simple systems allow the scrutiny of the minimal requirements for a functional SOD mimic: the association of a high catalytic activity for superoxide dismutation, low toxicity, and an efficient cellular uptake/biodistribution. Antioxid. Redox Signal. 20, 2416–2436. PMID:23964890

Characterization of Free Radicals Formed from COX-Catalyzed DGLA Peroxidation

PubMed Central

Xiao, Ying; Gu, Yan; Purwaha, Preeti; Ni, Kunyi; Law, Benedict; Mallik, Sanku; Qian, Steven Y.

2011-01-01

Like arachidonic acid (AA), dihomo-γ-linolenic acid (DGLA) is a 20-carbon ω-6 polyunsaturated fatty acid and a substrate of cyclooxygenase (COX). Through free radical reactions, COX metabolizes DGLA and AA to form well-known bioactive metabolites, namely, the 1- and 2-series of prostaglandins (PGs1 and PGs2), respectively. Unlike PGs2, which are viewed as pro-inflammatory, PGs1 possess anti-inflammatory and anticancer activities. However, the mechanisms linking the PGs to their bioactivities are still unclear, and radicals generated in COX-DGLA have not been detected. In order to better understand PGs biology and determine whether different reactions occur in COX-DGLA than in COX-AA, we have used LC/ESR/MS with a spin trap, α-[4-pyridyl-1-oxide]-N-tert-butyl nitrone (POBN), to characterize the carbon-centered radicals formed from COX-DGLA in vitro, including cellular peroxidation. A total of five types of DGLA-derived radicals were characterized as POBN adducts: m/z 266, m/z 296 and m/z 550 (same as and/or similar to COX-AA), and m/z 324 and m/z 354 (exclusively from COX-DGLA). Our results suggested that C-15 oxygenation to form PGGs occurs in both COX-DGLA and COX-AA; however, C-8 oxygenation occurs exclusively in COX-DGLA. This new finding will be further investigated for its association with different bioactivities of PGs, with potential implications for inflammatory diseases. PMID:21310230

Inhibitory effect of naturally occurring flavonoids on the formation of advanced glycation endproducts.

PubMed

Wu, Chi-Hao; Yen, Gow-Chin

2005-04-20

The objective of this study was to investigate the inhibitory effect of naturally occurring flavonoids on individual stage of protein glycation in vitro using the model systems of delta-Gluconolactone assay (early stage), BSA-methylglyoxal assay (middle stage), BSA-glucose assay, and G.K. peptide-ribose assay (last stage). In the early stage of protein glycation, luteolin, qucertin, and rutin exhibited significant inhibitory activity on HbA1C formation (p < 0.01), which were more effective than that of aminoguanidine (AG, 10 mM), a well-known inhibitor for advanced glycation endproducts (AGEs). For the middle stage, luteolin and rutin developed more significant inhibitory effect on methylglyoxal-medicated protein modification, and the IC50's were 66.1 and 71.8 microM, respectively. In the last stage of glycation, luteolin was found to be potent inhibitors of both the AGEs formation and the subsequent cross-linking of proteins. In addition, phenyl-tert-butyl-nitron served as a spin-trapping agent, and electron spin resonance (ESR) was used to explore the possible mechanism of the inhibitory effect of flavonoids on glycation. The results indicated that protein glycation was accompanied by oxidative reactions, as the ESR spectra showed a clear-cut radical signal. Statistical analysis showed that inhibitory capability of flavonoids against protein glycation was remarkably related to the scavenging free radicals derived from glycoxidation process (r = 0.79, p < 0.01). Consequently, the inhibitory mechanism of flavonoids against glycation was, at least partly, due to their antioxidant properties.

ESR study of a biological assay on whole blood: antioxidant efficiency of various vitamins.

PubMed

Stocker, Pierre; Lesgards, Jean-François; Vidal, Nicolas; Chalier, Florence; Prost, Michel

2003-04-07

This study deals with the activity of various vitamins against the radical-mediated oxidative damage in human whole blood. We have used a biological method that allows both the evaluation of plasma and that of red blood cell resistance against the free radicals induced by 2,2'-azobis (2-amidinopropane) hydrochloride (AAPH). Spin trapping measures using mainly 5-(diethoxyphosphoryl)-5-methyl-1-pyrolline N-oxide nitrone (DEPMPO) were carried out under several conditions to identify the free radicals implicated in this test. Only the oxygenated-centred radical generated from AAPH was found highly reactive to initiate red blood cell lysis. With DEPMPO only alkoxyl radicals were observed and no evidence was found for alkylperoxyl radicals. The antioxidant activity of several lipid- and water-soluble vitamins has been assessed by the biological assay and through two chemical methods. We have noticed high antioxidant activities for tocopherols (in the order delta>gamma>alpha) in the biological test but not through chemical methods. At 1 microM, the delta-tocopherol efficiency in inhibiting radical-induced red blood cell hemolysis was three times as high as the alpha-tocopherol efficiency. For beta-carotene no significant activity even in whole blood was shown. Highly surprising antioxidant activities were observed for acid folic and pyridoxine, compared to ascorbic acid. At 10 microM, the effectiveness of folic acid was almost three times as high as vitamin C. The biological test seems clinically more relevant than most other common assays because it can detect several classes of antioxidants.

ESR evidence for radical production from the reaction of ozone with unsaturated lipids

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

Church, D.F.; McAdams, M.L..; Pryor, W.A.

1991-03-15

The authors report electron spin resonance (ESR) spin trapping evidence for radical production by the reaction of ozone with unsaturated compounds. Soy and egg phosphatidylcholine liposomes, fatty acid emulsions, and homogeneous aqueous solutions of 3-hexenoic acid were treated with ozone in the presence of the spin trap {alpha}-phenyl-N-tert-butyl nitrone (PBN). Under these conditions, they observe spin adducts resulting from the trapping of both organic carbon- and oxygen-centered radicals. When the lipid-soluble antioxidant alpha-tocopherol is included in the liposomal systems, the formation of spin adducts is completely inhibited. The authors suggest that radicals giving rise to these spin adducts arise formmore » the rapid decomposition of the 1,2,3-trioxolane intermediate that is initially formed when ozone reacts with the carbon-carbon double bonds of the substrates. These free radicals are not formed by the decomposition of the Criegee ozonide, since little of the ozonide is formed in the presence of water. Although hydrogen peroxide is the predominate peroxidic product of the ozone/alkene reaction, its decomposition is not responsible for the observed radical production since neither catalase nor iron chelators significantly affect the spin adduct yield. The radical yield is approximately 1%. Since a polyunsaturated fatty acid (PUFA) such as linoleic acid produces much higher concentrations of spin trappable radicals than does the monounsaturated fatty oleic acid, the results also suggest that sites in the lung containing higher levels of PUFA may be an important target for radical formation.« less

HPN-07, a free radical spin trapping agent, protects against functional, cellular and electrophysiological changes in the cochlea induced by acute acoustic trauma

PubMed Central

Hu, Ning; Du, Xiaoping; Li, Wei; West, Matthew B.; Choi, Chul-Hee; Floyd, Robert; Kopke, Richard D.

2017-01-01

Oxidative stress is considered a major cause of the structural and functional changes associated with auditory pathologies induced by exposure to acute acoustic trauma AAT). In the present study, we examined the otoprotective effects of 2,4-disulfophenyl-N-tert-butylnitrone (HPN-07), a nitrone-based free radical trap, on the physiological and cellular changes in the auditory system of chinchilla following a six-hour exposure to 4 kHz octave band noise at 105 dB SPL. HPN-07 has been shown to suppress oxidative stress in biological models of a variety of disorders. Our results show that administration of HPN-07 beginning four hours after acoustic trauma accelerated and enhanced auditory/cochlear functional recovery, as measured by auditory brainstem responses (ABR), distortion product otoacoustic emissions (DPOAE), compound action potentials (CAP), and cochlear microphonics (CM). The normally tight correlation between the endocochlear potential (EP) and evoked potentials of CAP and CM were persistently disrupted after noise trauma in untreated animals but returned to homeostatic conditions in HPN-07 treated animals. Histological analyses revealed several therapeutic advantages associated with HPN-07 treatment following AAT, including reductions in inner and outer hair cell loss; reductions in AAT-induced loss of calretinin-positive afferent nerve fibers in the spiral lamina; and reductions in fibrocyte loss within the spiral ligament. These findings support the conclusion that early intervention with HPN-07 following an AAT efficiently blocks the propagative ototoxic effects of oxidative stress, thereby preserving the homeostatic and functional integrity of the cochlea. PMID:28832600

Mitochondrial reactive oxygen species production and respiratory complex activity in rats with pressure overload-induced heart failure

PubMed Central

Schwarzer, Michael; Osterholt, Moritz; Lunkenbein, Anne; Schrepper, Andrea; Amorim, Paulo; Doenst, Torsten

2014-01-01

We investigated the impact of cardiac reactive oxygen species (ROS) during the development of pressure overload-induced heart failure. We used our previously described rat model where transverse aortic constriction (TAC) induces compensated hypertrophy after 2 weeks, heart failure with preserved ejection fraction at 6 and 10 weeks, and heart failure with systolic dysfunction after 20 weeks. We measured mitochondrial ROS production rates, ROS damage and assessed the therapeutic potential of in vivo antioxidant therapies. In compensated hypertrophy (2 weeks of TAC) ROS production rates were normal at both mitochondrial ROS production sites (complexes I and III). Complex I ROS production rates increased with the appearance of diastolic dysfunction (6 weeks of TAC) and remained high thereafter. Surprisingly, maximal ROS production at complex III peaked at 6 weeks of pressure overload. Mitochondrial respiratory capacity (state 3 respiration) was elevated 2 and 6 weeks after TAC, decreased after this point and was significantly impaired at 20 weeks, when contractile function was also impaired and ROS damage was found with increased hydroxynonenal. Treatment with the ROS scavenger α-phenyl-N-tert-butyl nitrone or the uncoupling agent dinitrophenol significantly reduced ROS production rates at 6 weeks. Despite the decline in ROS production capacity, no differences in contractile function between treated and untreated animals were observed. Increased ROS production occurs early in the development of heart failure with a peak at the onset of diastolic dysfunction. However, ROS production may not be related to the onset of contractile dysfunction. PMID:24951621

Phase transformations during aging of a nitrogen-strengthened austenitic stainless steel

NASA Astrophysics Data System (ADS)

Ritter, Ann M.; Henry, Michael F.

1985-10-01

An analytical electron microscopy study was undertaken in order to characterize intergranular and matrix precipitation accompanying intermediate temperature aging in NITRONIC 50, a nitrogen-strengthened austenitic stainless steel. Extensive precipitation on most grain boundaries had occurred after aging for 24 hours at 675 °C. The primary intergranular phase at that time was Cr-rich M23C6, and energy dispersive spectra taken on grain boundary segments between these carbides indicated Cr-depletion and Fe- and Ni-enhancement relative to the matrix. After aging for 336 and 1008 hours at 675 °C, M6C (eta-carbide) precipitates were also present on grain boundaries. These precipitates were distinguished from M23C6 on the basis of their lattice parameters and chemistries, with M6C containing less Cr and Fe, and more Ni, Mo, and Si than M23C6. The differences in chemistry were clarified by a statistical treatment of the spectra. The statistical analysis also showed that precipitates with a range of chemistries between M23C6 and M6C coexisted with these phases on the grain boundaries. Associated with this shift in precipitate stoichiometry was an increase in the average concentration of Cr and a decrease in the average concentration of Ni at the grain boundaries. Intergranular sigma phase was also observed after times 24 hours at 675 °C, with sigma precipitating on grain boundaries containing carbides. Intragranular precipitates observed to be stable up to 1008 hours at 675 °C included Z-phase, a complex nitride which had formed during solution annealing; M7C3 carbides, which nucleated at Z-phase/austenite interfaces; M23C6 carbides, which precipitated on incoherent twin boundaries; and Cr-rich MN precipitates, which nucleated on dislocations.

In vivo detection of free radicals using molecular MRI and immuno-spin trapping in a mouse model for amyotrophic lateral sclerosis.

PubMed

Towner, Rheal A; Smith, Nataliya; Saunders, Debra; Lupu, Florea; Silasi-Mansat, Robert; West, Melinda; Ramirez, Dario C; Gomez-Mejiba, Sandra E; Bonini, Marcelo G; Mason, Ronald P; Ehrenshaft, Marilyn; Hensley, Kenneth

2013-10-01

Free radicals associated with oxidative stress play a major role in amyotrophic lateral sclerosis (ALS). By combining immuno-spin trapping and molecular magnetic resonance imaging, in vivo trapped radical adducts were detected in the spinal cords of SOD1(G93A)-transgenic (Tg) mice, a model for ALS. For this study, the nitrone spin trap DMPO (5,5-dimethyl-1-pyrroline N-oxide) was administered (ip) over 5 days before administration (iv) of an anti-DMPO probe (anti-DMPO antibody covalently bound to an albumin-gadolinium-diethylenetriamine pentaacetic acid-biotin MRI contrast agent) to trap free radicals. MRI was used to detect the presence of the anti-DMPO radical adducts by a significant sustained increase in MR signal intensities (p < 0.05) or anti-DMPO probe concentrations measured from T₁ relaxations (p < 0.01). The biotin moiety of the anti-DMPO probe was targeted with fluorescence-labeled streptavidin to locate the probe in excised tissues. Negative controls included either Tg ALS mice initially administered saline rather than DMPO followed by the anti-DMPO probe or non-Tg mice initially administered DMPO and then the anti-DMPO probe. The anti-DMPO probe was found to bind to neurons via colocalization fluorescence microscopy. DMPO adducts were also confirmed in diseased/nondiseased tissues from animals administered DMPO. Apparent diffusion coefficients from diffusion-weighted images of spinal cords from Tg mice were significantly elevated (p < 0.001) compared to wild-type controls. This is the first report regarding the detection of in vivo trapped radical adducts in an ALS model. This novel, noninvasive, in vivo diagnostic method can be applied to investigate the involvement of free radical mechanisms in ALS rodent models. Copyright © 2013 Elsevier Inc. All rights reserved.

In vivo targeted molecular magnetic resonance imaging of free radicals in diabetic cardiomyopathy within mice.

PubMed

Towner, R A; Smith, N; Saunders, D; Carrizales, J; Lupu, F; Silasi-Mansat, R; Ehrenshaft, M; Mason, R P

2015-01-01

Free radicals contribute to the pathogenesis of diabetic cardiomyopathy. We present a method for in vivo observation of free radical events within murine diabetic cardiomyopathy. This study reports on in vivo imaging of protein/lipid radicals using molecular MRI (mMRI) and immuno-spin trapping (IST) in diabetic cardiac muscle. To detect free radicals in diabetic cardiomyopathy, streptozotocin (STZ)-exposed mice were given 5,5-dimethyl-pyrroline-N-oxide (DMPO) and administered an anti-DMPO probe (biotin-anti-DMPO antibody-albumin-Gd-DTPA). For controls, non-diabetic mice were given DMPO (non-disease control), and administered an anti-DMPO probe; or diabetic mice were given DMPO but administered a non-specific IgG contrast agent instead of the anti-DMPO probe. DMPO administration started at 7 weeks following STZ treatment for 5 days, and the anti-DMPO probe was administered at 8 weeks for MRI detection. MRI was used to detect a significant increase (p < 0.001) in MRI signal intensity (SI) from anti-DMPO nitrone adducts in diabetic murine left-ventricular (LV) cardiac tissue, compared to controls. Regional increases in MR SI in the LV were found in the apical and upper-left areas (p < 0.01 for both), compared to controls. The biotin moiety of the anti-DMPO probe was targeted with fluorescently-labeled streptavidin to locate the anti-DMPO probe in excised cardiac tissues, which indicated elevated fluorescence only in cardiac muscle of mice administered the anti-DMPO probe. Oxidized lipids and proteins were also found to be significantly elevated (p < 0.05 for both) in diabetic cardiac muscle compared to controls. It can be concluded that diabetic mice have more heterogeneously distributed radicals in cardiac tissue than non-diabetic mice.

Evaluation of oxidative stress and antioxidant status: Correlation with the severity of sepsis.

PubMed

Kumar, S; Gupta, E; Kaushik, S; Kumar Srivastava, V; Mehta, S K; Jyoti, A

2018-04-01

Sepsis is a condition caused by infection followed by unregulated inflammatory response which may lead to the organ dysfunction. During such condition, over-production of oxidants is one of the factors which contribute cellular toxicity and ultimately organ failure and mortality. Antioxidants having free radicals scavenging activity exert protective role in various diseases. This study has been designed to evaluate the levels of oxidative and antioxidative activity in sepsis patients and their correlation with the severity of the sepsis. A total of 100 sepsis patients and 50 healthy controls subjects were enrolled in this study from the period October 2016 to June 2017. The investigation included measurements of oxidative enzyme, myeloperoxidase (MPO), antioxidant enzymes including superoxide dismutase activity (SOD) and catalase activity (CAT) and cytokines (TNF-α, IL-8 and IFN-γ). Furthermore, the level of these activities was correlated with severity of sepsis. Augmented levels of oxidants were found in sepsis as demonstrated by DMPO nitrone adduct formation and plasma MPO level activity (1.37 ± 0.51 in sepsis vs 0.405 ± 0.16 in control subjects). Cytokines were also found to be increased in sepsis patients. However, plasma SOD and CAT activities were significantly attenuated (P < .001) in the sepsis patients compared with controls subjects. Moreover, inverse relation between antioxidant enzymes (SOD and CAT) and organ failure assessment (SOFA), physiological score (APACHE II), organ toxicity specific markers have been observed as demonstrated by Pearson's correlation coefficient. This study suggests that imbalance between oxidant and antioxidant plays key role in the severity of sepsis. © 2018 The Foundation for the Scandinavian Journal of Immunology.

Toxic indole alkaloids avrainvillamide and stephacidin B produced by a biocide tolerant indoor mold Aspergillus westerdijkiae.

PubMed

Mikkola, Raimo; Andersson, Maria A; Hautaniemi, Maria; Salkinoja-Salonen, Mirja S

2015-06-01

Toxic Aspergillus westerdijkiae were present in house dust and indoor air fall-out from a residence and a kindergarten where the occupants suffered from building related ill health. The A. westerdijkiae isolates produced indole alkaloids avrainvillamide (445 Da) and its dimer stephacidin B (890 Da). It grew and sporulated in presence of high concentrations of boron or polyguanidine (PHMB, PHMG) based antimicrobial biocides used to remediate mold infested buildings. The boar sperm cells were used as sensor cells to purify toxins from HPLC fractions of the fungal biomass. Submicromolar concentrations (EC50 0.3-0.4 μM) blocked boar spermatozoan motility and killed porcine kidney tubular epithelial cells (PK-15). Plate grown hyphal mass of the A. westerdijkiae isolates contained 300-750 ng of avrainvillamide and 30-300 ng of stephacidin B per mg (wet weight). The toxins induced rapid (30 min) loss of boar sperm motility, followed (24 h) by loss of mitochondrial membrane potential (ΔΨm). Apoptotic cell death was observed in PK-15 cell monolayers, prior to cessation of glucose uptake or loss of ΔΨm. Avrainvillamide and stephacidin B were 100-fold more potent towards the porcine cells than the mycotoxins stephacidin A, ochratoxin A, sterigmatocystin and citrinin. The high toxicity of stephacidin B indicates a role of nitrone group in the mechanism of toxicity. Avrainvillamide and stephacidin B represent a new class of toxins with possible a threat to human health in buildings. Furthermore, the use of biocides highly enhanced the growth of toxigenic A. westerdijkiae. Copyright © 2015 Elsevier Ltd. All rights reserved.

Effects of cyclooxygenase inhibitor pretreatment on nitric oxide production, nNOS and iNOS expression in rat cerebellum.

PubMed

Di Girolamo, G; Farina, M; Riberio, M L; Ogando, D; Aisemberg, J; de los Santos, A R; Martí, M L; Franchi, A M

2003-07-01

1. The therapeutic effect of nonsteroidal anti-inflammatory drugs (NSAIDs) is thought to be due mainly to its inhibition of cyclooxygenase (COX) enzymes, but there is a growing body of research that now demonstrates a variety of NSAIDs effects on cellular signal transduction pathways other than those involving prostaglandins. 2. Nitric oxide (NO) as a free radical and an agent that gives rise to highly toxic oxidants (peroxynitrile, nitric dioxide, nitron ion), becomes a cause of neuronal damage and death in some brain lesions such as Parkinson and Alzheimer disease, and Huntington's chorea. 3. In the present study, the in vivo effect of three NSAIDs (lysine clonixinate (LC), indomethacine (INDO) and meloxicam (MELO)) on NO production and nitric oxide synthase expression in rat cerebellar slices was analysed. Rats were treated with (a) saline, (b) lipopolysaccharide (LPS) (5 mg kg(-1), i.p.), (c) saline in combination with different doses of NSAIDs and (d) LPS in combination with different doses of NSAIDs and then killed 6 h after treatment. 4. NO synthesis, evaluated by Bred and Snyder technique, was increased by LPS. This augmentation was inhibited by coadministration of the three NSAIDs assayed. None of the NSAIDs tested was able to modify control NO synthesis. 5. Expression of iNOS and neural NOS (nNOS) was detected by Western blotting in control and LPS-treated rats. LC and INDO, but not MELO, were able to inhibit the expression of these enzymes. 6. Therefore, reduction of iNOS and nNOS levels in cerebellum may explain, in part, the anti-inflammatory effect of these NSAIDs and may also have importance in the prevention of NO-mediated neuronal injury.

Effects of cyclooxygenase inhibitor pretreatment on nitric oxide production, nNOS and iNOS expression in rat cerebellum

PubMed Central

DiGirolamo, G; Farina, M; Riberio, M L; Ogando, D; Aisemberg, J; de los Santos, A R; Martí, M L; Franchi, A M

2003-01-01

The therapeutic effect of nonsteroidal anti-inflammatory drugs (NSAIDs) is thought to be due mainly to its inhibition of cyclooxygenase (COX) enzymes, but there is a growing body of research that now demonstrates a variety of NSAIDs effects on cellular signal transduction pathways other than those involving prostaglandins. Nitric oxide (NO) as a free radical and an agent that gives rise to highly toxic oxidants (peroxynitrile, nitric dioxide, nitron ion), becomes a cause of neuronal damage and death in some brain lesions such as Parkinson and Alzheimer disease, and Huntington's chorea. In the present study, the in vivo effect of three NSAIDs (lysine clonixinate (LC), indomethacine (INDO) and meloxicam (MELO)) on NO production and nitric oxide synthase expression in rat cerebellar slices was analysed. Rats were treated with (a) saline, (b) lipopolysaccharide (LPS) (5 mg kg−1, i.p.), (c) saline in combination with different doses of NSAIDs and (d) LPS in combination with different doses of NSAIDs and then killed 6 h after treatment. NO synthesis, evaluated by Bred and Snyder technique, was increased by LPS. This augmentation was inhibited by coadministration of the three NSAIDs assayed. None of the NSAIDs tested was able to modify control NO synthesis. Expression of iNOS and neural NOS (nNOS) was detected by Western blotting in control and LPS-treated rats. LC and INDO, but not MELO, were able to inhibit the expression of these enzymes. Therefore, reduction of iNOS and nNOS levels in cerebellum may explain, in part, the anti-inflammatory effect of these NSAIDs and may also have importance in the prevention of NO-mediated neuronal injury. PMID:12871835

Immunolocalization of hypochlorite-induced, catalase-bound free radical formation in mouse hepatocytes

PubMed Central

Bonini, Marcelo G.; Siraki, Arno G.; Atanassov, Boyko S.; Mason., Ronald P.

2007-01-01

The establishment of oxidants as mediators of signal transduction has renewed the interest of investigators in oxidant production and metabolism. In particular, H2O2 has been demonstrated to play pivotal roles in mediating cell differentiation, proliferation and death. Intracellular concentrations of H2O2 are modulated by its rate of production and its rate of decomposition by catalase and peroxidases. In inflammation and infection some of the H2O2 is converted to hypochlorous acid, a key mediator of the host immune response against pathogens. In vivo HOCl production is mediated by myeloperoxidase, which uses excess H2O2 to oxidize Cl−. Mashino and Fridovich (1988) observed that a high excess of HOCl over catalase inactivated the enzyme by mechanisms that remain unclear. The potential relevance of this as an alternative mechanism for catalase activity control and its potential impact on H2O2-mediated signaling and HOCl-production compelled us to explore in depth the HOCl-mediated catalase inactivation pathways. Here, we demonstrate that HOCl induces formation of catalase protein radicals and carbonyls, which are temporally correlated with catalase aggregation. Hypochlorite-induced catalase aggregation and free radical formation that paralleled the enzyme loss of function in vitro were also detected in mouse hepatocytes treated with the oxidant. Interestingly, the novel immunospin-trapping technique was applied to image radical production in the cells. Indeed, in HOCl-treated hepatocytes, catalase and protein-DMPO nitrone adducts were colocalized in the cells’ peroxisomes. In contrast, when hepatocytes from catalase-knockout mice were treated with hypochlorous acid, there was extensive production of free radicals in the plasma membrane. Because free radicals are short-lived species with fundamental roles in biology, the possibility of their detection and localization to cell compartments is expected to open new and stimulating research venues in the interface of chemistry, biology and medicine. PMID:17275685

Combined molecular MRI and immuno-spin-trapping for in vivo detection of free radicals in orthotopic mouse GL261 gliomas.

PubMed

Towner, Rheal A; Smith, Nataliya; Saunders, Debra; De Souza, Patricia Coutinho; Henry, Leah; Lupu, Florea; Silasi-Mansat, Robert; Ehrenshaft, Marilyn; Mason, Ronald P; Gomez-Mejiba, Sandra E; Ramirez, Dario C

2013-12-01

Free radicals play a major role in gliomas. By combining immuno-spin-trapping (IST) and molecular magnetic resonance imaging (mMRI), in vivo levels of free radicals were detected within mice bearing orthotopic GL261 gliomas. The nitrone spin trap DMPO (5,5-dimethyl pyrroline N-oxide) was administered prior to injection of an anti-DMPO probe (anti-DMPO antibody covalently bound to a bovine serum albumin (BSA)-Gd (gadolinium)-DTPA (diethylene triamine penta acetic acid)-biotin MRI contrast agent) to trap tumor-associated free radicals. mMRI detected the presence of anti-DMPO adducts by either a significant sustained increase (p<0.001) in MR signal intensity or a significant decrease (p<0.001) in T1 relaxation, measured as %T1 change. In vitro assessment of the anti-DMPO probe indicated a significant decrease (p<0.0001) in T1 relaxation in GL261 cells that were oxidatively stressed with hydrogen peroxide, compared to controls. The biotin moiety of the anti-DMPO probe was targeted with fluorescently-labeled streptavidin to locate the anti-DMPO probe in excised brain tissues. As a negative control a non-specific IgG antibody covalently bound to the albumin-Gd-DTPA-biotin construct was used. DMPO adducts were also confirmed in tumor tissue from animals administered DMPO, compared to non-tumor brain tissue. GL261 gliomas were found to have significantly increased malondialdehyde (MDA) protein adducts (p<0.001) and 3-nitrotyrosine (3-NT) (p<0.05) compared to normal mouse brain tissue, indicating increased oxidized lipids and proteins, respectively. Co-localization of the anti-DMPO probe with either 3-NT or 4-hydroxynonenal was also observed. This is the first report regarding the detection of in vivo levels of free radicals from a glioma model. © 2013.

Tissue plasminogen activator (tPA) and matrix metalloproteinases in the pathogenesis of stroke: therapeutic strategies.

PubMed

Adibhatla, Rao Muralikrishna; Hatcher, James F

2008-06-01

Today there exists only one FDA-approved treatment for ischemic stroke; i.e., the serine protease tissue-type plasminogen activator (tPA). In the aftermath of the failed stroke clinical trials with the nitrone spin trap/radical scavenger, NXY-059, a number of articles raised the question: are we doing the right thing? Is the animal research truly translational in identifying new agents for stroke treatment? This review summarizes the current state of affairs with plasminogen activators in thrombolytic therapy. In addition to therapeutic value, potential side effects of tPA also exist that aggravate stroke injury and offset the benefits provided by reperfusion of the occluded artery. Thus, combinational options (ultrasound alone or with microspheres/nanobubbles, mechanical dissociation of clot, activated protein C (APC), plasminogen activator inhibitor-1 (PAI-1), neuroserpin and CDP-choline) that could offset tPA toxic side effects and improve efficacy are also discussed here. Desmoteplase, a plasminogen activator derived from the saliva of Desmodus rotundus vampire bat, antagonizes vascular tPA-induced neurotoxicity by competitively binding to low-density lipoprotein related-receptors (LPR) at the blood-brain barrier (BBB) interface, minimizing the tPA uptake into brain parenchyma. tPA can also activate matrix metalloproteinases (MMPs), a family of endopeptidases comprised of 24 mammalian enzymes that primarily catalyze the turnover and degradation of the extracellular matrix (ECM). MMPs have been implicated in BBB breakdown and neuronal injury in the early times after stroke, but also contribute to vascular remodeling, angiogenesis, neurogenesis and axonal regeneration during the later repair phase after stroke. tPA, directly or by activation of MMP-9, could have beneficial effects on recovery after stroke by promoting neurovascular repair through vascular endothelial growth factor (VEGF). However, any treatment regimen directed at MMPs must consider their pleiotropic nature and the likelihood of either beneficial or detrimental effects that might depend on the timing of the treatment in relation to the stage of brain injury.

The Microstructural Evolution of Fatigue Cracks in FCC Metals

NASA Astrophysics Data System (ADS)

Gross, David William

The microstructural evolution during fatigue crack propagation was investigated in a variety of planar and wavy slip FCC metals. The planar materials included Haynes 230, Nitronic 40, and 316 stainless steel, and the wavy materials included pure nickel and pure copper. Three different sets of experiments were performed to fully characterize the microstructural evolution. The first, performed on Haynes 230, mapped the strain field ahead a crack tip using digital image correlation and electron backscatter diffraction techniques. Focused ion beam (FIB) lift-out techniques were then utilized to extract transmission electron microscopy (TEM) samples at specific distances from the crack tip. TEM investigations compared the measured strain to the microstructure. Overall, the strain measured via DIC and EBSD was only weakly correlated to the density of planar slip bands in the microstructure. The second set of experiments concerned the dislocation structure around crack tips. This set of experiments was performed on all the materials. The microstructure at arrested fatigue cracks on the free surface was compared to the microstructure found beneath striations on the fracture surfaces by utilizing FIB micromachining to create site-specific TEM samples. The evolved microstructure depended on the slip type. Strong agreement was found between the crack tip microstructure at the free surface and the fracture surface. In the planar materials, the microstructure in the plastic zone consisted of bands of dislocations or deformation twins, before transitioning to a refined sub-grain microstructure near the crack flank. The sub-grain structure extended 300-500 nm away from the crack flank in all the planar slip materials studied. In contrast, the bulk structure in the wavy slip material consisted of dislocation cells and did not transition to a different microstructure as the crack tip was approached. The strain in wavy slip was highest near the crack tip, as the misorientations between the dislocation cells increased and the cell size decreased as the crack flank was approached. The final set of experiments involved reloading the arrested crack tips in monotonic tension. This was performed on both the Haynes 230 and 316 stainless steel. This technique exposed the fracture surface and location of the arrested crack tip away from the free surface, allowing for a sample to be extracted via FIB micromachining and TEM evaluation of the microstructure. This permitted the crack tip microstructure to be investigated without exposing the microstructure to crack closure or free surface effects. These experiments confirmed what was inferred from the earlier experiments, namely that the banded structure was a product of the crack tip plastic zone and the refined structure was a product of the strain associated with crack advance. Overall the microstructural complexity presented in this work was much higher than would be predicted by current models of fatigue crack propagation. It is recommended that future models attempt to simulate interactions between the dislocations emitted during fatigue crack growth and the pre-existing microstructure to more accurately simulate the processes occurring at the crack tip during crack growth.

Superior Ballistic Impact Resistance Achieved by the Co-Base Alloy Haynes 25

NASA Technical Reports Server (NTRS)

Hebsur, Mohan G.; Noebe, Ronald D.; Revilock, Duane M.

2003-01-01

The fan case in a jet engine is required to contain a fan blade in the rare event of a blade loss during operation. Because of its function, the fan case is the largest structural component in high-bypass-ratio turbofan engines used in commercial aircraft. Therefore, the use of lighter and stronger materials would be advantageous in most engines and is practically a necessity in the latest generation of high-bypass engines. Small panels, 7 in. wide by 7 in. long, of a number of metallic alloys were impact tested at room temperature with a 0.50-caliber blunt-nose titanium alloy projectile at the NASA Glenn Research Center (ref. 1). These metallic systems included several high-strength aluminum (Al) alloys, Al-based laminates, aluminum metal matrix composites (Al-MMCs), nickel-base superalloys (Inconel 718 and 625), several titanium (Ti) alloys in different heat treated conditions, 304L stainless steel, a stainless-steel-based laminate, and a high strength steel (Nitronic 60). It was determined that a simple Co-base alloy (Haynes 25) had the best impact resistance on an areal weight basis. Haynes 25 was at least 10 percent better than IMI 550, the best titanium alloy tested to date, and it was far superior to other metals, especially at higher impact velocities (greater than 1100 ft/sec). Because this material could be ideal for fan containment applications in supersonic aircraft as a replacement for titanium, impact tests were also conducted at 371 oC and compared with results from alloys tested at elevated temperature under previous programs (i.e., Inconel 718, Ti-6242, M-152, Timetal 21S, and Aeromet 100). Although cobalt-base alloys are used in some high-temperature engine applications, to our knowledge they are not used in any containment systems. Advantages of cobalt over titanium include lower cost, easier processing, better high-temperature strength, and no fire hazard if tip rub occurs. Future plans include testing of lightweight sandwich panels with Haynes 25 as a core material in the form of a foam or lattice block structure and scaling up the current tests by using blade-simulating projectiles impacting large plates and half rings.

Novel miniaturized sensors for potentiometric batch and flow-injection analysis (FIA) of perchlorate in fireworks and propellants.

PubMed

Almeer, Saeed H M A; Zogby, Ibrahim A; Hassan, Saad S M

2014-11-01

Three planar miniaturized perchlorate membrane sensors (3×5 mm(2)) are prepared using a flexible Kaptan substrate coated with nitron-perchlorate (NT-ClO4) [sensor 1], methylene blue-perchlorate (MB-ClO4) [sensor II] and indium-porphyrin (In-Por) [sensor III] as electroactive materials in PVC membranes plasticized with 2-NPPE. Sensors I, II and III display near-Nernstian response for 1.0×10(-5)-1.0×10(-2), 3.1×10(-5)-1.0×10(-2) and 3.1×10(-6)-1.0×10(-2) mol L(-1) ClO4(-) with lower detection limits of 6.1×10(-6), 6.9×10(-6) and 1.2×10(-6) mol L(-1), and anionic calibration slopes of 50.9±0.4, 48.4±0.4 and 57.7±0.3 mV decade(-1), respectively. Methods for determining perchlorate using these sensors offer many attractive advantages including simplicity, flexibility, cost effectiveness, wide linear dynamic response range (0.1-1000 ppm), low detection limit (<1.2×10(-6) mol L(-1)≡0.1 ppm), small sample test volume (100 μL), safety, short response time (<20 s), long life span (~8 weeks), and extended wide working pH range (4.5-8.0). The sensors show high selectivity in the presence of some inorganic ions (e.g., PO4(3-), SO4(2-), S2O3(2-), NO2(-), NO3(-), N3(-), CN(-), Cl(-), Br(-), I(-)) and automation feasibility. Indium-porphyrin based membrane sensor (sensor III) is used as a detector in a wall-jet flow injection set-up to enable accurate flow injection analysis (FIA) of perchlorate in some fireworks without interferences from the associated reducing agents (sulfur and charcoal), binders (dextrin, lactose), coloring agents (calcium, strontium, copper, iron, sodium), color brighten (linseed oil) and regulators (aluminum flakes) which are commonly used in the formulations. The sensor is also used for perchlorate assessment in some propellant powders. The results fairly agree with data obtained by ion-chromatography. Copyright © 2014 Elsevier B.V. All rights reserved.

Tempol, an intracellular antioxidant, inhibits tissue factor expression, attenuates dendritic cell function, and is partially protective in a murine model of cerebral malaria.

PubMed

Francischetti, Ivo M B; Gordon, Emile; Bizzarro, Bruna; Gera, Nidhi; Andrade, Bruno B; Oliveira, Fabiano; Ma, Dongying; Assumpção, Teresa C F; Ribeiro, José M C; Pena, Mirna; Qi, Chen-Feng; Diouf, Ababacar; Moretz, Samuel E; Long, Carole A; Ackerman, Hans C; Pierce, Susan K; Sá-Nunes, Anderson; Waisberg, Michael

2014-01-01

The role of intracellular radical oxygen species (ROS) in pathogenesis of cerebral malaria (CM) remains incompletely understood. We undertook testing Tempol--a superoxide dismutase (SOD) mimetic and pleiotropic intracellular antioxidant--in cells relevant to malaria pathogenesis in the context of coagulation and inflammation. Tempol was also tested in a murine model of CM induced by Plasmodium berghei Anka infection. Tempol was found to prevent transcription and functional expression of procoagulant tissue factor in endothelial cells (ECs) stimulated by lipopolysaccharide (LPS). This effect was accompanied by inhibition of IL-6, IL-8, and monocyte chemoattractant protein (MCP-1) production. Tempol also attenuated platelet aggregation and human promyelocytic leukemia HL60 cells oxidative burst. In dendritic cells, Tempol inhibited LPS-induced production of TNF-α, IL-6, and IL-12p70, downregulated expression of co-stimulatory molecules, and prevented antigen-dependent lymphocyte proliferation. Notably, Tempol (20 mg/kg) partially increased the survival of mice with CM. Mechanistically, treated mice had lowered plasma levels of MCP-1, suggesting that Tempol downmodulates EC function and vascular inflammation. Tempol also diminished blood brain barrier permeability associated with CM when started at day 4 post infection but not at day 1, suggesting that ROS production is tightly regulated. Other antioxidants-such as α-phenyl N-tertiary-butyl nitrone (PBN; a spin trap), MnTe-2-PyP and MnTBAP (Mn-phorphyrin), Mitoquinone (MitoQ) and Mitotempo (mitochondrial antioxidants), M30 (an iron chelator), and epigallocatechin gallate (EGCG; polyphenol from green tea) did not improve survival. By contrast, these compounds (except PBN) inhibited Plasmodium falciparum growth in culture with different IC50s. Knockout mice for SOD1 or phagocyte nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (gp91(phox-/-)) or mice treated with inhibitors of SOD (diethyldithiocarbamate) or NADPH oxidase (diphenyleneiodonium) did not show protection or exacerbation for CM. Results with Tempol suggest that intracellular ROS contribute, in part, to CM pathogenesis. Therapeutic targeting of intracellular ROS in CM is discussed.

Analytical and Experimental Nanomechanical Approaches to Understanding the Ductile-to-Brittle Transition

NASA Astrophysics Data System (ADS)

Hintsala, Eric Daniel

This dissertation presents progress towards understanding the ductile-to-brittle transition (DBT) using a mixture of nanomechanical experiments and an analytical model. The key concept is dislocation shielding of crack tips, which is occurs due to a dislocation back stress. In order to properly evaluate the role of these interactions, in-situ experiments are ideal by reducing the number of interacting dislocations and allowing direct observation of cracking behavior and the dislocations themselves. First, in-situ transmission electron microscope (TEM) compression experiments of plasma-synthesized silicon nanocubes (NCs) are presented which shows plastic strains greater than 50% in a semi-brittle material. The mechanical properties are discussed and plasticity mechanisms are identified using post-mortem imaging with a combination of dark field and high-resolution imaging. This observations help to develop a back stress model which is used to fit the hardening regime. This represents the first study of its kind where back stresses are used in a discrete manner to match hardening rates. However, the important measurable quantities for evaluating the DBT include fracture toughness values and energetic activation parameters for cracking and plasticity. In order to do this, a new method for doing in-situ fracture experiments is explored. This method is pre-notched three point bending experiments, which were fabricated by focused ion beam (FIB) milling. Two different materials are evaluated: a model ductile material, Nitronic 50, an austenitic steel alloy, and a model brittle material, silicon. These experiments are performed in-situ scanning electron microscope (SEM) and TEM and explore different aspects including electron backscatter diffraction (EBSD) to track deformation in SEM scale experiments, pre-notching using a converged TEM beam to produce sharper notches better replicating natural cracks, etching procedures to reduce residual FIB damage and elevated temperature experiments. Lastly, an analytical method to predict DBTs is presented which can account for effects of strain rate, temperature and impurity presence. The model is tested by pre-existing data on macroscopic compact tension specimens of single crystal Fe-3%Si. Next, application of the model to nano/micro scale fracture toughness experiments is explored and the large number of confounding variables is discussed in detail. A first attempt at fitting is also presented.

PBN (Phenyl-N-Tert-Butylnitrone)-Derivatives Are Effective in Slowing the Visual Cycle and Rhodopsin Regeneration and in Protecting the Retina from Light-Induced Damage

PubMed Central

Stiles, Megan; Moiseyev, Gennadiy P.; Budda, Madeline L.; Linens, Annette; Brush, Richard S.; Qi, Hui; White, Gary L.; Wolf, Roman F.; Ma, Jian-xing; Floyd, Robert; Anderson, Robert E.; Mandal, Nawajes A.

2015-01-01

A2E and related toxic molecules are part of lipofuscin found in the retinal pigment epithelial (RPE) cells in eyes affected by Stargardt’s disease, age-related macular degeneration (AMD), and other retinal degenerations. A novel therapeutic approach for treating such degenerations involves slowing down the visual cycle, which could reduce the amount of A2E in the RPE. This can be accomplished by inhibiting RPE65, which produces 11-cis-retinol from all-trans-retinyl esters. We recently showed that phenyl-N-tert-butylnitrone (PBN) inhibits RPE65 enzyme activity in RPE cells. In this study we show that like PBN, certain PBN-derivatives (PBNDs) such as 4-F-PBN, 4-CF3-PBN, 3,4-di-F-PBN, and 4-CH3-PBN can inhibit RPE65 and synthesis of 11-cis-retinol in in vitro assays using bovine RPE microsomes. We further demonstrate that systemic (intraperitoneal, IP) administration of these PBNDs protect the rat retina from light damage. Electroretinography (ERG) and histological analysis showed that rats treated with PBNDs retained ~90% of their photoreceptor cells compared to a complete loss of function and 90% loss of photoreceptors in the central retina in rats treated with vehicle/control injections. Topically applied PBN and PBNDs also significantly slowed the rate of the visual cycle in mouse and baboon eyes. One hour dark adaptation resulted in 75–80% recovery of bleachable rhodopsin in control/vehicle treated mice. Eye drops of 5% 4-CH3-PBN were most effective, inhibiting the regeneration of bleachable rhodopsin significantly (60% compared to vehicle control). In addition, a 10% concentration of PBN and 5% concentration of 4-CH3-PBN in baboon eyes inhibited the visual cycle by 60% and by 30%, respectively. We have identified a group of PBN related nitrones that can reach the target tissue (RPE) by systemic and topical application and slow the rate of rhodopsin regeneration and therefore the visual cycle in mouse and baboon eyes. PBNDs can also protect the rat retina from light damage. There is potential in developing these compounds as preventative therapeutics for the treatment of human retinal degenerations in which the accumulation of lipofuscin may be pathogenic. PMID:26694648

PBN (Phenyl-N-Tert-Butylnitrone)-Derivatives Are Effective in Slowing the Visual Cycle and Rhodopsin Regeneration and in Protecting the Retina from Light-Induced Damage.

PubMed

Stiles, Megan; Moiseyev, Gennadiy P; Budda, Madeline L; Linens, Annette; Brush, Richard S; Qi, Hui; White, Gary L; Wolf, Roman F; Ma, Jian-Xing; Floyd, Robert; Anderson, Robert E; Mandal, Nawajes A

2015-01-01

A2E and related toxic molecules are part of lipofuscin found in the retinal pigment epithelial (RPE) cells in eyes affected by Stargardt's disease, age-related macular degeneration (AMD), and other retinal degenerations. A novel therapeutic approach for treating such degenerations involves slowing down the visual cycle, which could reduce the amount of A2E in the RPE. This can be accomplished by inhibiting RPE65, which produces 11-cis-retinol from all-trans-retinyl esters. We recently showed that phenyl-N-tert-butylnitrone (PBN) inhibits RPE65 enzyme activity in RPE cells. In this study we show that like PBN, certain PBN-derivatives (PBNDs) such as 4-F-PBN, 4-CF3-PBN, 3,4-di-F-PBN, and 4-CH3-PBN can inhibit RPE65 and synthesis of 11-cis-retinol in in vitro assays using bovine RPE microsomes. We further demonstrate that systemic (intraperitoneal, IP) administration of these PBNDs protect the rat retina from light damage. Electroretinography (ERG) and histological analysis showed that rats treated with PBNDs retained ~90% of their photoreceptor cells compared to a complete loss of function and 90% loss of photoreceptors in the central retina in rats treated with vehicle/control injections. Topically applied PBN and PBNDs also significantly slowed the rate of the visual cycle in mouse and baboon eyes. One hour dark adaptation resulted in 75-80% recovery of bleachable rhodopsin in control/vehicle treated mice. Eye drops of 5% 4-CH3-PBN were most effective, inhibiting the regeneration of bleachable rhodopsin significantly (60% compared to vehicle control). In addition, a 10% concentration of PBN and 5% concentration of 4-CH3-PBN in baboon eyes inhibited the visual cycle by 60% and by 30%, respectively. We have identified a group of PBN related nitrones that can reach the target tissue (RPE) by systemic and topical application and slow the rate of rhodopsin regeneration and therefore the visual cycle in mouse and baboon eyes. PBNDs can also protect the rat retina from light damage. There is potential in developing these compounds as preventative therapeutics for the treatment of human retinal degenerations in which the accumulation of lipofuscin may be pathogenic.

Mechanisms of perinatal cerebral injury in fetus and newborn.

PubMed

Delivoria-Papadopoulos, M; Mishra, O P

2000-01-01

Cerebral hypoxia in the fetus and newborn results in neonatal morbidity and mortality as well as long-term sequelae such as mental retardation, seizure disorders, and cerebral palsy. In the developing brain, determinants of susceptibility to hypoxia should include the lipid composition of the brain cell membrane, the rate of lipid peroxidation, the presence of antioxidant defenses, and the development and modulation of excitatory amino acid neurotransmitter receptors such as the N-methyl-D-aspartate (NMDA) receptor, the intracellular Ca2+, and the intranuclear Ca(2+)-dependent mechanisms. In addition to the developmental status of these cellular components, the response of these potential mechanisms to hypoxia determines the fate of the hypoxic brain cell in the developing brain. Using electron spin resonance spectroscopy of alpha-phenyl-N-tert-butyl-nitrone spin adducts, studies from our laboratory demonstrated that tissue hypoxia results in increased free radical generation in the cortex of fetal guinea pigs and newborn piglets. Pretreatment with MgSO4 significantly decreased the hypoxia-induced increase in free radical generation in the term fetal brain. We also showed that brain tissue hypoxia modifies the NMDA receptor ion-channel recognition and modulatory sites. Furthermore, a higher increase in NMDA receptor agonist-dependent Ca2+ in synaptosomes was demonstrated. The increase in intracellular Ca2+ may activate several enzymatic pathways such as phospholipase A2 and metabolism of archidonic acid by cyclooxygenase and lipoxygenase, conversion of xanthine dehydrogenase to xanthine oxidase by proteases, and activation of nitric oxide synthase. Using inhibitors of each of these enzymes such as cyclooxygenase (indomethacin), lipoxygenase (nordihydroguaiaretic acid), xanthine oxidase (allopurinol), and nitric oxide synthase (N-nitro-L-arginine), studies have shown that these enzyme reactions result in oxygen free radical generation, membrane peroxidation, and cell membrane dysfunction in the hypoxic brain. Specifically, generation of nitric oxide free radicals during hypoxia may lead to nitration and nitrosylation of specific membrane proteins and receptors, resulting in dysfunction of receptors and enzymes. We conclude that hypoxia-induced modification of the NMDA receptor leading to increased intracellular Ca2+ results in free radical generation and cell injury. We suggest that during hypoxia the increased intracellular Ca2+ may lead to increased intranuclear Ca2+ concentration and alter nuclear events including transcription of specific apoptotic genes and activation of endonucleases, resulting in programmed cell death.

Residual Stress Induced Mechanical Property Enhancement in Steel Encapsulated Light Metal Matrix Composites

NASA Astrophysics Data System (ADS)

Fudger, Sean James

Macro hybridized systems consisting of steel encapsulated light metal matrix composites (MMCs) were produced with the goal of creating a low cost/light weight composite system with enhanced mechanical properties. MMCs are frequently incorporated into advanced material systems due to their tailorable material properties. However, they often have insufficient ductility for many structural applications. The macro hybridized systems take advantage of the high strength, modulus, and damage tolerance of steels and high specific stiffness and low density of MMCs while mitigating the high density of steels and the poor ductility of MMCs. Furthermore, a coefficient of thermal expansion (CTE) mismatch induced residual compressive stress method is utilized as a means of improving the ductility of the MMCs and overall efficiency of the macro hybridized systems. Systems consisting of an A36, 304 stainless steel, or NitronicRTM 50 stainless steel shell filled with an Al-SiC, Al-Al2O3, or Mg-B4C MMC are evaluated in this work. Upon cooling from processing temperatures, residual strains are generated due to a CTE mismatch between each of the phases. The resulting systems offer higher specific properties and a more structurally efficient system can be attained. Mechanical testing was performed and improvements in yield stress, ultimate tensile stress, and ductility were observed. However, the combination of these dissimilar materials often results in the formation of intermetallic compounds. In certain loading situations, these typically brittle intermetallic layers can result in degraded performance. X-ray Diffraction (XRD), X-ray Energy Dispersive Spectroscopy (EDS), and Electron Backscatter Diffraction (EBSD) are utilized to characterize the intermetallic layer formation at the interface between the steel and MMC. As the residual stress condition in each phase has a large impact on the mechanical property improvement, accurate quantification of these strains/stresses is paramount. X-ray Diffraction Residual Stress Analysis (XRD-RSA) or Neutron diffraction was performed on numerous systems in multiple steel shell thickness variations. The analysis shows variation in the measured strain and stress results due to outer steel thickness, difference in CTE between materials, and relative position within the composite. Improvements in mechanical properties, namely ductility and yield stress, are a direct result of these measured strains.

microRNA-34a-Mediated Down-Regulation of the Microglial-Enriched Triggering Receptor and Phagocytosis-Sensor TREM2 in Age-Related Macular Degeneration.

PubMed

Bhattacharjee, Surjyadipta; Zhao, Yuhai; Dua, Prerna; Rogaev, Evgeny I; Lukiw, Walter J

2016-01-01

The aggregation of Aβ42-peptides and the formation of drusen in age-related macular degeneration (AMD) are due in part to the inability of homeostatic phagocytic mechanisms to clear self-aggregating Aβ42-peptides from the extracellular space. The triggering receptor expressed in myeloid/microglial cells-2 (TREM2), a trans-membrane-spanning, sensor-receptor of the immune-globulin/lectin-like gene superfamily is a critical component of Aβ42-peptide clearance. Here we report a significant deficit in TREM2 in AMD retina and in cytokine- or oxidatively-stressed microglial (MG) cells. RT-PCR, miRNA-array, LED-Northern and Western blot studies indicated up-regulation of a microglial-enriched NF-кB-sensitive miRNA-34a coupled to a down-regulation of TREM2 in the same samples. Bioinformatics/transfection-luciferase reporter assays indicated that miRNA-34a targets the 299 nucleotide TREM2-mRNA-3'UTR, resulting in TREM2 down-regulation. C8B4-microglial cells challenged with Aβ42 were able to phagocytose these peptides, while miRNA-34a down-regulated both TREM2 and the ability of microglial-cells to phagocytose. Treatment of TNFα-stressed MG cells with phenyl-butyl nitrone (PBN), caffeic-acid phenethyl ester (CAPE), the NF-kB - [corrected] inhibitor/resveratrol analog CAY10512 or curcumin abrogated these responses. Incubation of anti-miRNA-34a (AM-34a) normalized miRNA-34a abundance and restored TREM2 back to homeostatic levels. These data support five novel observations: (i) that a ROS- and NF-kB - [corrected] sensitive, miRNA-34a-mediated modulation of TREM2 may in part regulate the phagocytic response; (ii) that gene products encoded on two different chromosomes (miRNA-34a at chr1q36.22 and TREM2 at chr6p21.1) orchestrate a phagocytic-Aβ42-peptide clearance-system; (iii) that this NF-kB-mediated-miRNA-34a-TREM2 mechanism is inducible from outside of the cell; (iv) that when operating normally, this pathway can clear Aβ42 peptide monomers from the extracellular medium; and (v) that anti-NF-kB and/or anti-miRNA (AM)-based therapeutic strategies may be useful against deficits in TREM-2 receptor-based-sensing and -phagocytic signaling that promote pathogenic amyloidogenesis.

microRNA-34a-Mediated Down-Regulation of the Microglial-Enriched Triggering Receptor and Phagocytosis-Sensor TREM2 in Age-Related Macular Degeneration

PubMed Central

Dua, Prerna; Rogaev, Evgeny I.; Lukiw, Walter J.

2016-01-01

The aggregation of Aβ42-peptides and the formation of drusen in age-related macular degeneration (AMD) are due in part to the inability of homeostatic phagocytic mechanisms to clear self-aggregating Aβ42-peptides from the extracellular space. The triggering receptor expressed in myeloid/microglial cells-2 (TREM2), a trans-membrane-spanning, sensor-receptor of the immune-globulin/lectin-like gene superfamily is a critical component of Aβ42-peptide clearance. Here we report a significant deficit in TREM2 in AMD retina and in cytokine- or oxidatively-stressed microglial (MG) cells. RT-PCR, miRNA-array, LED-Northern and Western blot studies indicated up-regulation of a microglial-enriched NF-кB-sensitive miRNA-34a coupled to a down-regulation of TREM2 in the same samples. Bioinformatics/transfection-luciferase reporter assays indicated that miRNA-34a targets the 299 nucleotide TREM2-mRNA-3’UTR, resulting in TREM2 down-regulation. C8B4-microglial cells challenged with Aβ42 were able to phagocytose these peptides, while miRNA-34a down-regulated both TREM2 and the ability of microglial-cells to phagocytose. Treatment of TNFα-stressed MG cells with phenyl-butyl nitrone (PBN), caffeic-acid phenethyl ester (CAPE), the NF-B-inhibitor/resveratrol analog CAY10512 or curcumin abrogated these responses. Incubation of anti-miRNA-34a (AM-34a) normalized miRNA-34a abundance and restored TREM2 back to homeostatic levels. These data support five novel observations: (i) that a ROS- and NF-B-sensitive, miRNA-34a-mediated modulation of TREM2 may in part regulate the phagocytic response; (ii) that gene products encoded on two different chromosomes (miRNA-34a at chr1q36.22 and TREM2 at chr6p21.1) orchestrate a phagocytic-Aβ42-peptide clearance-system; (iii) that this NF-kB-mediated-miRNA-34a-TREM2 mechanism is inducible from outside of the cell; (iv) that when operating normally, this pathway can clear Aβ42 peptide monomers from the extracellular medium; and (v) that anti-NF-kB and/or anti-miRNA (AM)-based therapeutic strategies may be useful against deficits in TREM-2 receptor-based-sensing and -phagocytic signaling that promote pathogenic amyloidogenesis. PMID:26949937

Role of oxidative metabolites of cocaine in toxicity and addiction: oxidative stress and electron transfer.

PubMed

Kovacic, Peter

2005-01-01

Cocaine is one of the principal drugs of abuse. Although impressive advances have been made, unanswered questions remain concerning mechanism of toxicity and addiction. Discussion of action mode usually centers on receptor binding and enzyme inhibition, with limited attention to events at the molecular level. This review provides extensive evidence in support of the hypothesis that oxidative metabolites play important roles comprising oxidative stress (OS), reactive oxygen species (ROS), and electron transfer (ET). The metabolites include norcocaine and norcocaine derivatives: nitroxide radical, N-hydroxy, nitrosonium, plus cocaine iminium and formaldehyde. Observed formation of ROS is rationalized by redox cycling involving several possible ET agents. Three potential ones are present in the form of oxidative metabolites, namely, nitroxide, nitrosonium, and iminium. Most attention has been devoted to the nitroxide-hydroxylamine couple which has been designated by various investigators as the principal source of ROS. The proximate ester substituent is deemed important for intramolecular stabilization of reactive intermediates. Reduction potential of nitroxide is in accord with plausibility of ET in the biological milieu. Toxicity by cocaine, with evidence for participation of OS, is demonstrated for many body components, including liver, central nervous system, cardiovascular system, reproductive system, kidney, mitochondria, urine, and immune system. Other adverse effects associated with ROS comprise teratogenesis and apoptosis. Examples of ROS generated are lipid peroxides and hydroxyl radical. Often observed were depletion of antioxidant defenses, and protection by added antioxidants, such as, thiol, salicylate, and deferoxamine. Considerable evidence supports the contention that oxidative ET metabolites of cocaine are responsible for much of the observed OS. Quite significantly, the pro-oxidant, toxic effects, including generation of superoxide and lipid peroxyl radicals, plus depletion of glutathione, elicited by nitroxide or the hydroxylamine derivative, were greater than for the parent drug. The formaldehyde metabolite also appears to play a role. Mechanistic similarity to the action of neurotoxin 3,3'-iminodipropionitrile is pointed out. A number of literature strategies for treatment of addiction are addressed. However, no effective interventions are currently available. An hypothesis for addiction is offered based on ET and ROS at low concentrations. Radicals may aid in cell signaling entailing redox processes which influence ion transport, neuromodulation, and transcription. Ideas are suggested for future work dealing with health promotion. These include use of AOs, both dietary and supplemental, trapping of the norcocaine metabolite by non-toxic complexing agents, and use of nitrones for capturing harmful radical species.

Elucidation of Mechanisms and Selectivities of Metal-Catalyzed Reactions using Quantum Chemical Methodology.

PubMed

Santoro, Stefano; Kalek, Marcin; Huang, Genping; Himo, Fahmi

2016-05-17

Quantum chemical techniques today are indispensable for the detailed mechanistic understanding of catalytic reactions. The development of modern density functional theory approaches combined with the enormous growth in computer power have made it possible to treat quite large systems at a reasonable level of accuracy. Accordingly, quantum chemistry has been applied extensively to a wide variety of catalytic systems. A huge number of problems have been solved successfully, and vast amounts of chemical insights have been gained. In this Account, we summarize some of our recent work in this field. A number of examples concerned with transition metal-catalyzed reactions are selected, with emphasis on reactions with various kinds of selectivities. The discussed cases are (1) copper-catalyzed C-H bond amidation of indoles, (2) iridium-catalyzed C(sp(3))-H borylation of chlorosilanes, (3) vanadium-catalyzed Meyer-Schuster rearrangement and its combination with aldol- and Mannich-type additions, (4) palladium-catalyzed propargylic substitution with phosphorus nucleophiles, (5) rhodium-catalyzed 1:2 coupling of aldehydes and allenes, and finally (6) copper-catalyzed coupling of nitrones and alkynes to produce β-lactams (Kinugasa reaction). First, the methodology adopted in these studies is presented briefly. The electronic structure method in the great majority of these kinds of mechanistic investigations has for the last two decades been based on density functional theory. In the cases discussed here, mainly the B3LYP functional has been employed in conjunction with Grimme's empirical dispersion correction, which has been shown to improve the calculated energies significantly. The effect of the surrounding solvent is described by implicit solvation techniques, and the thermochemical corrections are included using the rigid-rotor harmonic oscillator approximation. The reviewed examples are chosen to illustrate the usefulness and versatility of the adopted methodology in solving complex problems and proposing new detailed reaction mechanisms that rationalize the experimental findings. For each of the considered reactions, a consistent mechanism is presented, the experimentally observed selectivities are reproduced, and their sources are identified. Reproducing selectivities requires high accuracy in computing relative transition state energies. As demonstrated by the results summarized in this Account, this accuracy is possible with the use of the presented methodology, benefiting of course from a large extent of cancellation of systematic errors. It is argued that as the employed models become larger, the number of rotamers and isomers that have to be considered for every stationary point increases and a careful assessment of their energies is therefore necessary in order to ensure that the lowest energy conformation is located. This issue constitutes a bottleneck of the investigation in some cases and is particularly important when analyzing selectivities, since small energy differences need to be reproduced.

RNA-Seq transcriptome analysis of Amaranthus palmeri with differential tolerance to glufosinate herbicide

PubMed Central

Salas-Perez, Reiofeli A.; Saski, Christopher A.; Noorai, Rooksana E.; Srivastava, Subodh K.; Lawton-Rauh, Amy L.; Nichols, Robert L.

2018-01-01

Amaranthus palmeri (Amaranthaceae) is a noxious weed in several agroecosystems and in some cases seriously threatens the sustainability of crop production in North America. Glyphosate-resistant Amaranthus species are widespread, prompting the use of alternatives to glyphosate such as glufosinate, in conjunction with glufosinate-resistant crop cultivars, to help control glyphosate-resistant weeds. An experiment was conducted to analyze the transcriptome of A. palmeri plants that survived exposure to 0.55 kg ha-1 glufosinate. Since there was no record of glufosinate use at the collection site, survival of plants within the population are likely due to genetic expression that pre-dates selection; in the formal parlance of weed science this is described as natural tolerance. Leaf tissues from glufosinate-treated and non-treated seedlings were harvested 24 h after treatment (HAT) for RNA-Seq analysis. Global gene expression was measured using Illumina DNA sequence reads from non-treated and treated surviving (presumably tolerant, T) and susceptible (S) plants. The same plants were used to determine the mechanisms conferring differential tolerance to glufosinate. The S plants accumulated twice as much ammonia as did the T plants, 24 HAT. The relative copy number of the glufosinate target gene GS2 did not differ between T and S plants, with 1 to 3 GS2 copies in both biotypes. A reference cDNA transcriptome consisting of 72,780 contigs was assembled, with 65,282 sequences putatively annotated. Sequences of GS2 from the transcriptome assembly did not have polymorphisms unique to the tolerant plants. Five hundred sixty-seven genes were differentially expressed between treated T and S plants. Of the upregulated genes in treated T plants, 210 were more highly induced than were the upregulated genes in the treated S plants. Glufosinate-tolerant plants had greater induction of ABC transporter, glutathione S-transferase (GST), NAC transcription factor, nitronate monooxygenase (NMO), chitin elicitor receptor kinase (CERK1), heat shock protein 83, ethylene transcription factor, heat stress transcription factor, NADH-ubiquinone oxidoreductase, ABA 8’-hydroxylase, and cytochrome P450 genes (CYP72A, CYP94A1). Seven candidate genes were selected for validation using quantitative real time-PCR. While GST was upregulated in treated tolerant plants in at least one population, CYP72A219 was consistently highly expressed in all treated tolerant biotypes. These genes are candidates for contributing tolerance to glufosinate. Taken together, these results show that differential induction of stress-protection genes in a population can enable some individuals to survive herbicide application. Elevated expression of detoxification-related genes can get fixed in a population with sustained selection pressure, leading to evolution of resistance. Alternatively, sustained selection pressure could select for mutation(s) in the GS2 gene with the same consequence. PMID:29672568

22 CFR 40.54-40.59 - [Reserved

Code of Federal Regulations, 2010 CFR

2010-04-01

... 22 Foreign Relations 1 2010-04-01 2010-04-01 false [Reserved] 40.54-40.59 Section 40.54-40.59 Foreign Relations DEPARTMENT OF STATE VISAS REGULATIONS PERTAINING TO BOTH NONIMMIGRANTS AND IMMIGRANTS... Immigrants §§ 40.54-40.59 [Reserved] ...

Levels of human platelet-derived soluble CD40 ligand depend on haplotypes of CD40LG-CD40-ITGA2

PubMed Central

Aloui, Chaker; Prigent, Antoine; Tariket, Sofiane; Sut, Caroline; Fagan, Jocelyne; Cognasse, Fabrice; Chakroun, Tahar; Garraud, Olivier; Laradi, Sandrine

2016-01-01

Increased circulating soluble CD40 ligand (sCD40L) is commonly associated with inflammatory disorders. We aimed to investigate whether gene polymorphisms in CD40LG, CD40 and ITGA2 are associated with a propensity to secrete sCD40L; thus, we examined this issue at the level of human platelets, the principal source of sCD40L. We performed single polymorphism and haplotype analyses to test for the effect of twelve polymorphisms across the CD40LG, CD40 and ITGA2 genes in blood donors. ITGA2 presented a positive association with rs1126643, with a significant modification in sCD40L secretion (carriers of C allele, P = 0.02), unlike the investigated CD40LG and CD40 polymorphisms. One CD40LG haplotype (TGGC) showing rs975379 (C/T), rs3092952 (A/G), rs3092933 (A/G) and rs3092929 (A/C) was associated with increased sCD40L levels (1.906 μg/L (95% CI: 1.060 to 2.751); P = 0.000009). The sCD40L level was associated with the inter-chromosomal CD40LG/CD40/ITGA2 haplotype (ATC), displaying rs3092952 (A/G), rs1883832 (C/T) and rs1126643 (C/T), with increased sCD40L levels (P = 0.0135). Our results help to decipher the genetic role of CD40LG, CD40 and ITGA2 with regard to sCD40L levels found in platelet components. Given the crucial role of sCD40L, this haplotype study in a transfusion model may be helpful to further determine the role of haplotypes in inflammatory clinical settings. PMID:27094978

Enhancement of CD4(+) T cell response and survival via coexpressed OX40/OX40L in Graves' disease.

PubMed

Wang, Qin; Shi, Bi-Min; Xie, Fang; Fu, Zhao-Yang; Chen, Yong-Jing; An, Jing-Nan; Ma, Yu; Liu, Cui-Ping; Zhang, Xue-Kun; Zhang, Xue-Guang

2016-07-15

OX40/OX40L pathway plays a very important role in the antigen priming T cells and effector T cells. In the present study, we aimed to examine the involvement of OX40/OX40L pathway in the activation of autoreactive T cells in patients with Grave's disease (GD). We found that OX40 and OX40L were constitutively coexpressed on peripheral CD4(+) T cells from GD patients using flow cytometry analysis. The levels of OX40 and OX40L coexpression on CD4(+) T cells were shown to be correlated with TRAbs. Cell proliferation assay showed that blocking OX40/OX40L signal inhibited T cell proliferation and survival, which suggested that OX40/OX40L could enhance CD4(+) T cell proliferation and maintain their long-term survival in GD by self-enhancing loop of T cell activation independent of APCs. Confocal microscopy and coimmunoprecipitation analysis further revealed that OX40 and OX40L formed a functional complex, which may facilitate signal transduction from OX40L to OX40 and contribute to the pathogenesis of GD. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

22 CFR 40.12-40.19 - [Reserved

Code of Federal Regulations, 2010 CFR

2010-04-01

... 22 Foreign Relations 1 2010-04-01 2010-04-01 false [Reserved] 40.12-40.19 Section 40.12-40.19 Foreign Relations DEPARTMENT OF STATE VISAS REGULATIONS PERTAINING TO BOTH NONIMMIGRANTS AND IMMIGRANTS UNDER THE IMMIGRATION AND NATIONALITY ACT, AS AMENDED Medical Grounds of Ineligibility §§ 40.12-40.19...

22 CFR 40.42-40.49 - [Reserved

Code of Federal Regulations, 2010 CFR

2010-04-01

... 22 Foreign Relations 1 2010-04-01 2010-04-01 false [Reserved] 40.42-40.49 Section 40.42-40.49 Foreign Relations DEPARTMENT OF STATE VISAS REGULATIONS PERTAINING TO BOTH NONIMMIGRANTS AND IMMIGRANTS UNDER THE IMMIGRATION AND NATIONALITY ACT, AS AMENDED Public Charge §§ 40.42-40.49 [Reserved] ...

22 CFR 40.7-40.8 - [Reserved

Code of Federal Regulations, 2010 CFR

2010-04-01

... 22 Foreign Relations 1 2010-04-01 2010-04-01 false [Reserved] 40.7-40.8 Section 40.7-40.8 Foreign Relations DEPARTMENT OF STATE VISAS REGULATIONS PERTAINING TO BOTH NONIMMIGRANTS AND IMMIGRANTS UNDER THE IMMIGRATION AND NATIONALITY ACT, AS AMENDED General Provisions §§ 40.7-40.8 [Reserved] ...

22 CFR 40.36-40.39 - [Reserved

Code of Federal Regulations, 2010 CFR

2010-04-01

... 22 Foreign Relations 1 2010-04-01 2010-04-01 false [Reserved] 40.36-40.39 Section 40.36-40.39 Foreign Relations DEPARTMENT OF STATE VISAS REGULATIONS PERTAINING TO BOTH NONIMMIGRANTS AND IMMIGRANTS UNDER THE IMMIGRATION AND NATIONALITY ACT, AS AMENDED Security and Related Grounds §§ 40.36-40.39...

46 CFR 167.40-40 - Radar.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 46 Shipping 7 2010-10-01 2010-10-01 false Radar. 167.40-40 Section 167.40-40 Shipping COAST GUARD... Requirements § 167.40-40 Radar. All mechanically propelled vessels of 1,600 gross tons and over in ocean or coastwise service must be fitted with a marine radar system for surface navigation. Facilities for plotting...

46 CFR 167.40-40 - Radar.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 46 Shipping 7 2011-10-01 2011-10-01 false Radar. 167.40-40 Section 167.40-40 Shipping COAST GUARD... Requirements § 167.40-40 Radar. All mechanically propelled vessels of 1,600 gross tons and over in ocean or coastwise service must be fitted with a marine radar system for surface navigation. Facilities for plotting...

46 CFR 167.40-40 - Radar.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 46 Shipping 7 2012-10-01 2012-10-01 false Radar. 167.40-40 Section 167.40-40 Shipping COAST GUARD... Requirements § 167.40-40 Radar. All mechanically propelled vessels of 1,600 gross tons and over in ocean or coastwise service must be fitted with a marine radar system for surface navigation. Facilities for plotting...

46 CFR 167.40-40 - Radar.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 46 Shipping 7 2013-10-01 2013-10-01 false Radar. 167.40-40 Section 167.40-40 Shipping COAST GUARD... Requirements § 167.40-40 Radar. All mechanically propelled vessels of 1,600 gross tons and over in ocean or coastwise service must be fitted with a marine radar system for surface navigation. Facilities for plotting...

46 CFR 167.40-40 - Radar.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 46 Shipping 7 2014-10-01 2014-10-01 false Radar. 167.40-40 Section 167.40-40 Shipping COAST GUARD... Requirements § 167.40-40 Radar. All mechanically propelled vessels of 1,600 gross tons and over in ocean or coastwise service must be fitted with a marine radar system for surface navigation. Facilities for plotting...

The Role of Soluble CD40L Ligand in Human Carcinogenesis.

PubMed

Angelou, Anastasios; Antoniou, Efstathios; Garmpis, Nikolaos; Damaskos, Christos; Theocharis, Stamatios; Margonis, Georgios-Antonios

2018-05-01

The role of CD40/CD40L in carcinogenesis is widely examined. The mechanisms linking the CD40/CD40L system and the soluble form of CD40 ligand (sCD40L) with neoplasia are nowadays a topic of intensive research. CD40L and sCD40L belong to the TNF superfamily and are molecules with a proinflammatory role. A variety of cells express CD40L such as the immune system cells, the endothelial cells and activated platelets. Although many medications such as statins have been shown to reduce sCD40L, it is still debated whether specific treatments targeting the CD40/CD40L system will prove to be effective against carcinogenesis in the near future. A comprehensive search of the Pubmed Database was conducted for English-language studies using a list of key words. At diagnosis, serum samples of patients with neoplasia contained higher levels of sCD40L than healthy controls, suggesting that sCD40L may play a predictive role in human carcinogenesis. Patients with neoplasia had higher circulating sCD40L levels and it is likely that sCD40L may have a predictive role. It is still unclear whether sCD40L can be used as a therapeutic target. Copyright© 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

46 CFR 32.40-40 - Other spaces-T/ALL.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 46 Shipping 1 2014-10-01 2014-10-01 false Other spaces-T/ALL. 32.40-40 Section 32.40-40 Shipping... REQUIREMENTS Accommodations for Officers and Crew § 32.40-40 Other spaces—T/ALL. Each vessel must have— (a... with hot and cold fresh water; (b) Recreation spaces; and (c) A space or spaces of adequate size...

46 CFR 32.40-40 - Other spaces-T/ALL.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 46 Shipping 1 2011-10-01 2011-10-01 false Other spaces-T/ALL. 32.40-40 Section 32.40-40 Shipping... REQUIREMENTS Accommodations for Officers and Crew § 32.40-40 Other spaces—T/ALL. Each vessel must have— (a... with hot and cold fresh water; (b) Recreation spaces; and (c) A space or spaces of adequate size...

46 CFR 32.40-40 - Other spaces-T/ALL.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 46 Shipping 1 2010-10-01 2010-10-01 false Other spaces-T/ALL. 32.40-40 Section 32.40-40 Shipping... REQUIREMENTS Accommodations for Officers and Crew § 32.40-40 Other spaces—T/ALL. Each vessel must have— (a... with hot and cold fresh water; (b) Recreation spaces; and (c) A space or spaces of adequate size...

46 CFR 32.40-40 - Other spaces-T/ALL.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 46 Shipping 1 2012-10-01 2012-10-01 false Other spaces-T/ALL. 32.40-40 Section 32.40-40 Shipping... REQUIREMENTS Accommodations for Officers and Crew § 32.40-40 Other spaces—T/ALL. Each vessel must have— (a... with hot and cold fresh water; (b) Recreation spaces; and (c) A space or spaces of adequate size...

46 CFR 32.40-40 - Other spaces-T/ALL.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 46 Shipping 1 2013-10-01 2013-10-01 false Other spaces-T/ALL. 32.40-40 Section 32.40-40 Shipping... REQUIREMENTS Accommodations for Officers and Crew § 32.40-40 Other spaces—T/ALL. Each vessel must have— (a... with hot and cold fresh water; (b) Recreation spaces; and (c) A space or spaces of adequate size...

75 FR 52292 - Airworthiness Directives; Diamond Aircraft Industries GmbH Models DA 40 and DA 40F Airplanes

Federal Register 2010, 2011, 2012, 2013, 2014

2010-08-25

... Industries GmbH Models DA 40 and DA 40F Airplanes AGENCY: Federal Aviation Administration (FAA), Department... new airworthiness directive (AD) for all Diamond Aircraft Industries GmbH Models DA 40 and DA 40F... received information from Diamond Aircraft Industries GmbH that the Models DA 40 and DA 40F airplanes have...

47 CFR 15.231 - Periodic operation in the band 40.66-40.70 MHz and above 70 MHz.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 47 Telecommunication 1 2012-10-01 2012-10-01 false Periodic operation in the band 40.66-40.70 MHz... Periodic operation in the band 40.66-40.70 MHz and above 70 MHz. (a) The provisions of this section are restricted to periodic operation within the band 40.66-40.70 MHz and above 70 MHz. Except as shown in...

47 CFR 15.231 - Periodic operation in the band 40.66-40.70 MHz and above 70 MHz.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 47 Telecommunication 1 2014-10-01 2014-10-01 false Periodic operation in the band 40.66-40.70 MHz... Periodic operation in the band 40.66-40.70 MHz and above 70 MHz. (a) The provisions of this section are restricted to periodic operation within the band 40.66-40.70 MHz and above 70 MHz. Except as shown in...

47 CFR 15.231 - Periodic operation in the band 40.66-40.70 MHz and above 70 MHz.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 47 Telecommunication 1 2013-10-01 2013-10-01 false Periodic operation in the band 40.66-40.70 MHz... Periodic operation in the band 40.66-40.70 MHz and above 70 MHz. (a) The provisions of this section are restricted to periodic operation within the band 40.66-40.70 MHz and above 70 MHz. Except as shown in...

47 CFR 15.231 - Periodic operation in the band 40.66-40.70 MHz and above 70 MHz.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 47 Telecommunication 1 2011-10-01 2011-10-01 false Periodic operation in the band 40.66-40.70 MHz... Periodic operation in the band 40.66-40.70 MHz and above 70 MHz. (a) The provisions of this section are restricted to periodic operation within the band 40.66-40.70 MHz and above 70 MHz. Except as shown in...

From Goal to Reality 40-40-20: A Report on Strategies to Meet Oregon's 40-40-20 Education Goals

ERIC Educational Resources Information Center

Oregon University System, 2012

2012-01-01

Oregon's Legislature in 2011 affirmed a clear and ambitious goal for the State, known as the "40-40-20" goal, which states that by 2025 all adult Oregonians will hold a high school diploma or equivalent, 40% of them will have an associate's degree or a meaningful postsecondary certificate, and 40% will hold a bachelor's degree or…

40 CFR 40.160 - Reports.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 40 Protection of Environment 1 2012-07-01 2012-07-01 false Reports. 40.160 Section 40.160 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY GRANTS AND OTHER FEDERAL ASSISTANCE RESEARCH AND DEMONSTRATION GRANTS § 40.160 Reports. ...

40 CFR 40.160 - Reports.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 40 Protection of Environment 1 2014-07-01 2014-07-01 false Reports. 40.160 Section 40.160 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY GRANTS AND OTHER FEDERAL ASSISTANCE RESEARCH AND DEMONSTRATION GRANTS § 40.160 Reports. ...

40 CFR 273.40 - Exports.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 40 Protection of Environment 26 2010-07-01 2010-07-01 false Exports. 273.40 Section 273.40... UNIVERSAL WASTE MANAGEMENT Standards for Large Quantity Handlers of Universal Waste § 273.40 Exports. A... exporter in 40 CFR 262.53, 262.56(a)(1) through (4), (6), and (b) and 262.57; (b) Export such universal...

Involvement of nuclear factor {kappa}B in platelet CD40 signaling

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

Hachem, Ahmed; Yacoub, Daniel; Centre Hospitalier Universite de Montreal, 264 boul. Rene-Levesque est, Montreal, Quebec, Canada H2X 1P1

Highlights: Black-Right-Pointing-Pointer sCD40L induces TRAF2 association to CD40 and NF-{kappa}B activation in platelets. Black-Right-Pointing-Pointer I{kappa}B{alpha} phosphorylation downstream of CD40L/CD40 signaling is independent of p38 MAPK phosphorylation. Black-Right-Pointing-Pointer I{kappa}B{alpha} is required for sCD40L-induced platelet activation and potentiation of aggregation. -- Abstract: CD40 ligand (CD40L) is a thrombo-inflammatory molecule that predicts cardiovascular events. Platelets constitute the major source of soluble CD40L (sCD40L), which has been shown to potentiate platelet activation and aggregation, in a CD40-dependent manner, via p38 mitogen activated protein kinase (MAPK) and Rac1 signaling. In many cells, the CD40L/CD40 dyad also induces activation of nuclear factor kappa B (NF-{kappa}B). Givenmore » that platelets contain NF-{kappa}B, we hypothesized that it may be involved in platelet CD40 signaling and function. In human platelets, sCD40L induces association of CD40 with its adaptor protein the tumor necrosis factor receptor associated factor 2 and triggers phosphorylation of I{kappa}B{alpha}, which are abolished by CD40L blockade. Inhibition of I{kappa}B{alpha} phosphorylation reverses sCD40L-induced I{kappa}B{alpha} phosphorylation without affecting p38 MAPK phosphorylation. On the other hand, inhibition of p38 MAPK phosphorylation has no effect on I{kappa}B{alpha} phosphorylation, indicating a divergence in the signaling pathway originating from CD40 upon its ligation. In functional studies, inhibition of I{kappa}B{alpha} phosphorylation reverses sCD40L-induced platelet activation and potentiation of platelet aggregation in response to a sub-threshold concentration of collagen. This study demonstrates that the sCD40L/CD40 axis triggers NF-{kappa}B activation in platelets. This signaling pathway plays a critical role in platelet activation and aggregation upon sCD40L stimulation and may represent an important target against thrombo-inflammatory disorders.« less

Enhanced levels of soluble CD40 ligand exacerbate platelet aggregation and thrombus formation through a CD40-dependent tumor necrosis factor receptor-associated factor-2/Rac1/p38 mitogen-activated protein kinase signaling pathway.

PubMed

Yacoub, Daniel; Hachem, Ahmed; Théorêt, Jean-François; Gillis, Marc-Antoine; Mourad, Walid; Merhi, Yahye

2010-12-01

CD40 ligand is a thromboinflammatory molecule that predicts cardiovascular events. Platelets constitute the major source of soluble CD40 ligand (sCD40L), which has been shown to influence platelet activation, although its exact functional impact on platelets and the underlying mechanisms remain undefined. We aimed to determine the impact and the signaling mechanisms of sCD40L on platelets. sCD40L strongly enhances platelet activation and aggregation. Human platelets treated with a mutated form of sCD40L that does not bind CD40, and CD40(-/-) mouse platelets failed to elicit such responses. Furthermore, sCD40L stimulation induces the association of the tumor necrosis factor receptor-associated factor-2 with platelet CD40. Notably, sCD40L primes platelets through activation of the small GTPase Rac1 and its downstream target p38 mitogen-activated protein kinase, which leads to platelet shape change and actin polymerization. Moreover, sCD40L exacerbates thrombus formation and leukocyte infiltration in wild-type mice but not in CD40(-/-) mice. sCD40L enhances agonist-induced platelet activation and aggregation through a CD40-dependent tumor necrosis factor receptor-associated factor-2/Rac1/p38 mitogen-activated protein kinase signaling pathway. Thus, sCD40L is an important platelet primer predisposing platelets to enhanced thrombus formation in response to vascular injury. This may explain the link between circulating levels of sCD40L and cardiovascular diseases.

Influence of corn silage hybrid type on lactation performance by Holstein dairy cows.

PubMed

Akins, M S; Shaver, R D

2014-12-01

The primary objective of this study was to determine lactation performance by dairy cows fed nutridense (ND), dual-purpose (DP), or brown midrib (BM) corn silage hybrids at the same concentration in the diets. A secondary objective was to determine lactation performance by dairy cows fed NutriDense corn silage at a higher concentration in the diet. One hundred twenty-eight Holstein and Holstein × Jersey cows (105 ± 38 d in milk) were stratified by breed and parity and randomly assigned to 16 pens of 8 cows each. Pens were then randomly assigned to 1 of 4 treatments. Three treatment total mixed rations (TMR; DP40, BM40, and ND40) contained 40% of dry matter (DM) from the respective corn silage hybrid and 20% of DM from alfalfa silage. The fourth treatment TMR had ND corn silage as the sole forage at 65% of DM (ND65). A 2-wk covariate adjustment period preceded the treatment period, with all pens receiving a TMR with equal proportions of DP40, BM40, and ND40. Following the covariate period, cows were fed their assigned treatment diets for 11 wk. nutridense corn silage had greater starch and lower neutral detergent fiber (NDF) content than DP or BM, resulting in ND40 having greater energy content (73.2% of total digestible nutrients, TDN) than DP40 or BM40 (71.9 and 71.4% TDN, respectively). Cows fed BM40 had greater milk yield than DP40, whereas ND40 tended to have greater milk yield and had greater protein and lactose yields compared with DP40. No differences in intake, component-corrected milk yields, or feed efficiency were detected between DP40, BM40, and ND40. Milk yield differences may be due to increased starch intake for ND40 and increased digestible NDF intake for BM40 compared with DP40. Intake and milk yield and composition were similar for ND40 compared with BM40, possibly due to counteracting effects of higher starch intake for ND40 and higher digestible NDF intake for BM40. Feeding ND65 reduced intake, and thus milk and component yields, compared with ND40 due to either increased ruminal starch digestibility or increased rumen fill for ND65. Nutridense corn silage was a viable alternative to both DP and BM at 40% of diet DM; however, lactation performance was reduced when nutridense corn silage was fed at 65% of DM. Copyright © 2014 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Prevalence and stability of human serum antibodies to simian virus 40 VP1 virus-like particles.

PubMed

Lundstig, Annika; Eliasson, Linda; Lehtinen, Matti; Sasnauskas, Kestutis; Koskela, Pentti; Dillner, Joakim

2005-06-01

Possible human infection with simian virus 40 (SV40) has been of great concern ever since SV40 was discovered in polio vaccines. Human populations are SV40-seropositive, but because of serological cross-reactivity between SV40 and the human polyomaviruses BK virus (BKV) and JC virus (JCV), it is debatable whether these antibodies are specific. An SV40-specific serological assay was established, based on purified virus-like particles (VLPs), where the SV40 VLPs were blocked with hyperimmune sera to BKV and JCV. Competition with SV40 hyperimmune sera was used as a confirmatory test. Among 288 Swedish children of between 1 and 13 years of age, 7.6 % had SV40-specific antibodies. SV40 seroprevalence reached a peak of 14 % at 7-9 years of age. Among 100 control patients with benign tumours, 9 % were SV40-seropositive. However, SV40 DNA was not detectable in corresponding buffy-coat samples. In serial samples taken up to 5 years apart from 141 Finnish women participating in the population-based serological screening for congenital infections, only two of 141 women were SV40-seropositive in both samples. Six women seroconverted and eight women had a loss of antibodies over time. None of the SV40-seropositive samples contained detectable SV40 DNA. In conclusion, there is a low prevalence of SV40-specific antibodies in the Nordic population. The SV40 antibodies appear to have a low stability over time and their origin is not clear.

Immunization of mice with baculovirus-derived recombinant SV40 large tumour antigen induces protective tumour immunity to a lethal challenge with SV40-transformed cells.

PubMed Central

Shearer, M H; Bright, R K; Lanford, R E; Kennedy, R C

1993-01-01

In this study, we examined the humoral immune responses and in vivo tumour immunity induced by baculovirus recombinant simian virus 40 (SV40) large tumour antigen (rSV40 T-ag). BALB/c mice immunized with rSV40 T-ag produced antibody responses that recognized SV40 large tumour antigen (T-ag) by ELISA. Analysis of these anti-SV40 T-ag responses indicated that the antibodies recognized epitopes associated with both the carboxy and amino terminus of SV40 T-ag. This pattern of SV40 T-ag epitope recognition was similar to that observed in anti-SV40 T-ag responses induced by inoculation with irradiated SV40-transformed cells. Mice immunized with either rSV40 T-ag or with the inactivated transformed cells were protected from a subsequent in vivo lethal tumour challenge with live SV40-transformed cells. These studies suggest that humoral immune responses induced by rSV40 T-ag are similar in epitope specificity to that induced by inactivated SV40-transformed cells. In addition, recombinant tumour-specific antigens from papovaviruses, such as SV40, can be used to induce tumour immunity which protects from a subsequent lethal tumour challenge. This study may provide insight into the use of recombinant tumour antigens as putative tumour vaccines and in the development of active immunotherapeutic strategies for treating virus-induced cancers. PMID:7679059

Limited Surface Observations Climatic Summary (LISOCS) Bad Kreuznach AAF Germany.

DTIC Science & Technology

1988-02-01

GE GE GE GE GE GE FEET I IsO 90 80 61 48 𔃾 32 24 2G 16 12 10 8 5 4 0 NO CEIL 1 33.9 35.1 37.4 40.1 40.1 4n.1 40.4 40.4 40.4 40.4 40.4 40.4 40.4 40.4...93.3 93.3 93.3 93.3 93.3 93.3 93.3 GE 27001 68.6 75.1 88.1 94.9 96.1 96.6 97.2 97.2 97.4 97.4 97.4 97.4 97.4 97.4 97.4 GE Iei 1 68.6 75.1 88.1 94.9

OX40 ligand-transduced tumor cell vaccine synergizes with GM-CSF and requires CD40-Apc signaling to boost the host T cell antitumor response.

PubMed

Gri, Giorgia; Gallo, Elena; Di Carlo, Emma; Musiani, Piero; Colombo, Mario P

2003-01-01

Efficient T cell priming by GM-CSF and CD40 ligand double-transduced C26 murine colon carcinoma is not sufficient to cure metastases in a therapeutic setting. To determine whether a cellular vaccine that interacts directly with both APC and T cells in vivo might be superior, we generated C26 carcinoma cells transduced with the T cell costimulatory molecule OX40 ligand (OX40L) either alone (C26/OX40L) or together with GM-CSF (C26/GM/OX40L), which is known to activate APC. Mice injected with C26/OX40L cells displayed only a delay in tumor growth, while the C26/GM/OX40L tumor regressed in 85% of mice. Tumor rejection required granulocytes, CD4+, CD8+ T cells, and APC-mediated CD40-CD40 ligand cosignaling, but not IFN-gamma or IL-12 as shown using subset-depleted and knockout (KO) mice. CD40KO mice primed with C26/GM/OX40L cells failed to mount a CTL response, and T cells infiltrating the C26/GM/OX40L tumor were OX40 negative, suggesting an impairment in APC-T cell cross-talk in CD40KO mice. Indeed, CD4+ T cell-depleted mice failed to mount any CTL activity against the C26 tumor, while treatment with agonistic mAb to CD40, which acts on APC, bypassed the requirement for CD4+ T cells and restored CTL activation. C26/GM/OX40L cells cured 83% of mice bearing lung metastases, whereas C26/OX40L or C26/GM vaccination cured only 28 and 16% of mice, respectively. These results indicate the synergistic activity of OX40L and GM-CSF in a therapeutic setting.

40 CFR 161.40 - Consultation with the Agency.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 40 Protection of Environment 23 2010-07-01 2010-07-01 false Consultation with the Agency. 161.40 Section 161.40 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) PESTICIDE PROGRAMS DATA REQUIREMENTS FOR REGISTRATION OF ANTIMICROBIAL PESTICIDES General Provisions § 161.40 Consultation...

40 CFR 256.40 - Requirements.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 40 Protection of Environment 25 2014-07-01 2014-07-01 false Requirements. 256.40 Section 256.40 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) SOLID WASTES GUIDELINES FOR DEVELOPMENT AND IMPLEMENTATION OF STATE SOLID WASTE MANAGEMENT PLANS Facility Planning and Implementation § 256.40...

40 CFR 256.40 - Requirements.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 40 Protection of Environment 25 2011-07-01 2011-07-01 false Requirements. 256.40 Section 256.40 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) SOLID WASTES GUIDELINES FOR DEVELOPMENT AND IMPLEMENTATION OF STATE SOLID WASTE MANAGEMENT PLANS Facility Planning and Implementation § 256.40...

40 CFR 256.40 - Requirements.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 40 Protection of Environment 24 2010-07-01 2010-07-01 false Requirements. 256.40 Section 256.40 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) SOLID WASTES GUIDELINES FOR DEVELOPMENT AND IMPLEMENTATION OF STATE SOLID WASTE MANAGEMENT PLANS Facility Planning and Implementation § 256.40...

40 CFR 256.40 - Requirements.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 40 Protection of Environment 26 2013-07-01 2013-07-01 false Requirements. 256.40 Section 256.40 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) SOLID WASTES GUIDELINES FOR DEVELOPMENT AND IMPLEMENTATION OF STATE SOLID WASTE MANAGEMENT PLANS Facility Planning and Implementation § 256.40...

40 CFR 256.40 - Requirements.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 40 Protection of Environment 26 2012-07-01 2011-07-01 true Requirements. 256.40 Section 256.40 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) SOLID WASTES GUIDELINES FOR DEVELOPMENT AND IMPLEMENTATION OF STATE SOLID WASTE MANAGEMENT PLANS Facility Planning and Implementation § 256.40...

40 CFR 610.40 - General.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 40 Protection of Environment 30 2014-07-01 2014-07-01 false General. 610.40 Section 610.40 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) ENERGY POLICY FUEL ECONOMY RETROFIT DEVICES Test Procedures and Evaluation Criteria General Vehicle Test Procedures § 610.40 General. Two...

40 CFR 610.40 - General.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 40 Protection of Environment 30 2011-07-01 2011-07-01 false General. 610.40 Section 610.40 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) ENERGY POLICY FUEL ECONOMY RETROFIT DEVICES Test Procedures and Evaluation Criteria General Vehicle Test Procedures § 610.40 General. Two...

40 CFR 610.40 - General.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 40 Protection of Environment 31 2013-07-01 2013-07-01 false General. 610.40 Section 610.40 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) ENERGY POLICY FUEL ECONOMY RETROFIT DEVICES Test Procedures and Evaluation Criteria General Vehicle Test Procedures § 610.40 General. Two...

40 CFR 610.40 - General.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 40 Protection of Environment 31 2012-07-01 2012-07-01 false General. 610.40 Section 610.40 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) ENERGY POLICY FUEL ECONOMY RETROFIT DEVICES Test Procedures and Evaluation Criteria General Vehicle Test Procedures § 610.40 General. Two...

40 CFR 610.40 - General.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 40 Protection of Environment 29 2010-07-01 2010-07-01 false General. 610.40 Section 610.40 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) ENERGY POLICY FUEL ECONOMY RETROFIT DEVICES Test Procedures and Evaluation Criteria General Vehicle Test Procedures § 610.40 General. Two...

40 CFR 279.40 - Applicability.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 40 Protection of Environment 26 2010-07-01 2010-07-01 false Applicability. 279.40 Section 279.40 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) SOLID WASTES (CONTINUED) STANDARDS FOR THE MANAGEMENT OF USED OIL Standards for Used Oil Transporter and Transfer Facilities § 279.40...

40 CFR 279.40 - Applicability.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 40 Protection of Environment 28 2012-07-01 2012-07-01 false Applicability. 279.40 Section 279.40 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) SOLID WASTES (CONTINUED) STANDARDS FOR THE MANAGEMENT OF USED OIL Standards for Used Oil Transporter and Transfer Facilities § 279.40...

40 CFR 279.40 - Applicability.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 40 Protection of Environment 28 2013-07-01 2013-07-01 false Applicability. 279.40 Section 279.40 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) SOLID WASTES (CONTINUED) STANDARDS FOR THE MANAGEMENT OF USED OIL Standards for Used Oil Transporter and Transfer Facilities § 279.40...

40 CFR 279.40 - Applicability.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 40 Protection of Environment 27 2014-07-01 2014-07-01 false Applicability. 279.40 Section 279.40 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) SOLID WASTES (CONTINUED) STANDARDS FOR THE MANAGEMENT OF USED OIL Standards for Used Oil Transporter and Transfer Facilities § 279.40...

40 CFR 279.40 - Applicability.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 40 Protection of Environment 27 2011-07-01 2011-07-01 false Applicability. 279.40 Section 279.40 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) SOLID WASTES (CONTINUED) STANDARDS FOR THE MANAGEMENT OF USED OIL Standards for Used Oil Transporter and Transfer Facilities § 279.40...

Cysteine-rich Domain 1 of CD40 Mediates Receptor Self-assembly*

PubMed Central

Smulski, Cristian R.; Beyrath, Julien; Decossas, Marion; Chekkat, Neila; Wolff, Philippe; Estieu-Gionnet, Karine; Guichard, Gilles; Speiser, Daniel; Schneider, Pascal; Fournel, Sylvie

2013-01-01

The activation of CD40 on B cells, macrophages, and dendritic cells by its ligand CD154 (CD40L) is essential for the development of humoral and cellular immune responses. CD40L and other TNF superfamily ligands are noncovalent homotrimers, but the form under which CD40 exists in the absence of ligand remains to be elucidated. Here, we show that both cell surface-expressed and soluble CD40 self-assemble, most probably as noncovalent dimers. The cysteine-rich domain 1 (CRD1) of CD40 participated to dimerization and was also required for efficient receptor expression. Modelization of a CD40 dimer allowed the identification of lysine 29 in CRD1, whose mutation decreased CD40 self-interaction without affecting expression or response to ligand. When expressed alone, recombinant CD40-CRD1 bound CD40 with a KD of 0.6 μm. This molecule triggered expression of maturation markers on human dendritic cells and potentiated CD40L activity. These results suggest that CD40 self-assembly modulates signaling, possibly by maintaining the receptor in a quiescent state. PMID:23463508

Involvement of nuclear factor κB in platelet CD40 signaling.

PubMed

Hachem, Ahmed; Yacoub, Daniel; Zaid, Younes; Mourad, Walid; Merhi, Yahye

2012-08-17

CD40 ligand (CD40L) is a thrombo-inflammatory molecule that predicts cardiovascular events. Platelets constitute the major source of soluble CD40L (sCD40L), which has been shown to potentiate platelet activation and aggregation, in a CD40-dependent manner, via p38 mitogen activated protein kinase (MAPK) and Rac1 signaling. In many cells, the CD40L/CD40 dyad also induces activation of nuclear factor kappa B (NF-κB). Given that platelets contain NF-κB, we hypothesized that it may be involved in platelet CD40 signaling and function. In human platelets, sCD40L induces association of CD40 with its adaptor protein the tumor necrosis factor receptor associated factor 2 and triggers phosphorylation of IκBα, which are abolished by CD40L blockade. Inhibition of IκBα phosphorylation reverses sCD40L-induced IκBα phosphorylation without affecting p38 MAPK phosphorylation. On the other hand, inhibition of p38 MAPK phosphorylation has no effect on IκBα phosphorylation, indicating a divergence in the signaling pathway originating from CD40 upon its ligation. In functional studies, inhibition of IκBα phosphorylation reverses sCD40L-induced platelet activation and potentiation of platelet aggregation in response to a sub-threshold concentration of collagen. This study demonstrates that the sCD40L/CD40 axis triggers NF-κB activation in platelets. This signaling pathway plays a critical role in platelet activation and aggregation upon sCD40L stimulation and may represent an important target against thrombo-inflammatory disorders. Copyright © 2012 Elsevier Inc. All rights reserved.

Plasma membrane association facilitates conformational changes in the Marburg virus protein VP40 dimer.

PubMed

Bhattarai, Nisha; Gc, Jeevan B; Gerstman, Bernard S; Stahelin, Robert V; Chapagain, Prem P

2017-04-26

Filovirus infections cause hemorrhagic fever in humans and non-human primates that often results in high fatality rates. The Marburg virus is a lipid-enveloped virus from the Filoviridae family and is closely related to the Ebola virus. The viral matrix layer underneath the lipid envelope is formed by the matrix protein VP40 (VP40), which is also involved in other functions during the viral life-cycle. As in the Ebola virus VP40 (eVP40), the recently determined X-ray crystal structure of the Marburg virus VP40 (mVP40) features loops containing cationic residues that form a lipid binding basic patch. However, the mVP40 basic patch is significantly flatter with a more extended surface than in eVP40, suggesting the possibility of differences in the plasma membrane interactions and phospholipid specificity between the VP40 dimers. In this paper, we report on molecular dynamics simulations that investigate the roles of various residues and lipid types in PM association as well as the conformational changes of the mVP40 dimer facilitated by membrane association. We compared the structural changes of the mVP40 dimer with the mVP40 dimer in both lipid free and membrane associated conditions. Despite the significant structural differences in the crystal structure, the Marburg VP40 dimer is found to adopt a configuration very similar to the Ebola VP40 dimer after associating with the membrane. This conformational rearrangement upon lipid binding allows Marburg VP40 to localize and stabilize at the membrane surface in a manner similar to the Ebola VP40 dimer. Consideration of the structural information in its lipid-interacting condition may be important in targeting mVP40 for novel drugs to inhibit viral budding from the plasma membrane.

A critical role for both CD40 and VLA5 in angiotensin II-mediated thrombosis and inflammation.

PubMed

Senchenkova, Elena Y; Russell, Janice; Vital, Shantel A; Yildirim, Alper; Orr, A Wayne; Granger, D Neil; Gavins, Felicity N E

2018-06-01

Angiotensin II (Ang-II)-induced hypertension is associated with accelerated thrombus formation in arterioles and leukocyte recruitment in venules. The mechanisms that underlie the prothrombotic and proinflammatory responses to chronic Ang-II administration remain poorly understood. We evaluated the role of CD40/CD40 ligand (CD40L) signaling in Ang-II-mediated microvascular responses and assessed whether and how soluble CD40L (sCD40L) contributes to this response. Intravital video microscopy was performed to analyze leukocyte recruitment and dihydrorhodamine-123 oxidation in postcapillary venules. Thrombus formation in cremaster muscle arterioles was induced by using the light/dye endothelial cell injury model. Wild-type (WT), CD40 -/- , and CD40L -/- mice received Ang-II for 14 d via osmotic minipumps. Some mice were treated with either recombinant sCD40L or the VLA5 (very late antigen 5; α5β1) antagonist, ATN-161. Our results demonstrate that CD40 -/- , CD40L -/- , and WT mice that were treated with ATN-161 were protected against the thrombotic and inflammatory effects of Ang-II infusion. Infusion of sCD40L into CD40 -/- or CD40L -/- mice restored the prothrombotic effect of Ang-II infusion. Mice that were treated with ATN-161 and infused with sCD40L were protected against accelerated thrombosis. Collectively, these novel findings suggest that the mechanisms that underlie Ang-II-dependent thrombotic and inflammatory responses link to the signaling of CD40L via both CD40 and VLA5.-Senchenkova, E. Y., Russell, J., Vital, S. A., Yildirim, A., Orr, A. W., Granger, D. N., Gavins, F. N. E. A critical role for both CD40 and VLA5 in angiotensin II-mediated thrombosis and inflammation.

Evidence of SV40 infections in hospitalized children

NASA Technical Reports Server (NTRS)

Butel, J. S.; Jafar, S.; Wong, C.; Arrington, A. S.; Opekun, A. R.; Finegold, M. J.; Adam, E.

1999-01-01

Simian virus 40 (SV40) is known to have contaminated poliovirus vaccines used between 1955 and 1963. Accumulating reports have described the presence of SV40 DNA in human tumors and normal tissues, although the significance of human infections by SV40 is unknown. We investigated whether unselected hospitalized children had evidence of SV40 infections and whether any clinical correlations were apparent. Serum samples were examined for SV40 neutralizing antibody using a specific plaque reduction test; of 337 samples tested, 20 (5.9%) had antibody to SV40. Seropositivity increased with age and was significantly associated with kidney transplants (6 of 15 [40%] positive, P < .001). Many of the antibody-positive patients had impaired immune systems. Molecular assays (polymerase chain reaction and DNA sequence analysis) on archival tissue specimens confirmed the presence of SV40 DNA in 4 of the antibody-positive patients. This study, using 2 independent assays, shows the presence of SV40 infections in children born after 1980. We conclude that SV40 causes natural infections in humans.

40 CFR 230.40 - Sanctuaries and refuges.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 40 Protection of Environment 25 2011-07-01 2011-07-01 false Sanctuaries and refuges. 230.40 Section 230.40 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) OCEAN DUMPING SECTION... Impacts on Special Aquatic Sites § 230.40 Sanctuaries and refuges. (a) Sanctuaries and refuges consist of...

40 CFR 435.40 - Applicability; description of the coastal subcategory.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 40 Protection of Environment 31 2012-07-01 2012-07-01 false Applicability; description of the coastal subcategory. 435.40 Section 435.40 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY... Coastal Subcategory § 435.40 Applicability; description of the coastal subcategory. The provisions of this...

40 CFR 435.40 - Applicability; description of the coastal subcategory.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 40 Protection of Environment 31 2013-07-01 2013-07-01 false Applicability; description of the coastal subcategory. 435.40 Section 435.40 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY... Coastal Subcategory § 435.40 Applicability; description of the coastal subcategory. The provisions of this...

40 CFR 435.40 - Applicability; description of the coastal subcategory.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 40 Protection of Environment 30 2014-07-01 2014-07-01 false Applicability; description of the coastal subcategory. 435.40 Section 435.40 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY... Coastal Subcategory § 435.40 Applicability; description of the coastal subcategory. The provisions of this...

Rock bream (Oplegnathus fasciatus) IL-12p40: identification, expression, and effect on bacterial infection.

PubMed

Zhang, Lu; Zhang, Bao-Cun; Hu, Yong-Hua

2014-08-01

IL-12p40, also called IL-12β, is a subunit of the proinflammatory cytokines interleukin (IL)-12 and IL-23. In teleost, IL-12p40 homologues have been identified in several species, however, the biological function of fish IL-12p40 is essentially unknown. In this work, we reported the identification and analysis of an IL-12p40, OfIL-12p40, from rock bream (Oplegnathus fasciatus). OfIL-12p40 is composed of 361 amino acids and possesses a conserved IL-12p40 domain and a WSxWS signature motif characteristic of known IL-12p40. Constitutive expression of OfIL-12p40 occurred in multiple tissues and was highest in kidney. Experimental infection with bacterial pathogen upregulated the expression of OfIL-12p40 in kidney and spleen in a time-dependent manner. Purified recombinant OfIL-12p40 (rOfIL-12p40) stimulated the respiratory burst activity of peripheral blood leukocytes in a dose-dependent manner. rOfIL-12p40 also enhanced the resistance of rock bream against bacterial infection and upregulated the expression of innate immune genes in kidney. Taken together, these results indicate that OfIL-12p40 possesses cytokine-like property and plays a role in immune defense against bacterial infection. Copyright © 2014 Elsevier Ltd. All rights reserved.

40 CFR 716.40 - EPA requests for submission of further information.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 40 Protection of Environment 32 2013-07-01 2013-07-01 false EPA requests for submission of further information. 716.40 Section 716.40 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) TOXIC SUBSTANCES CONTROL ACT HEALTH AND SAFETY DATA REPORTING General Provisions § 716.40 EPA requests for...

40 CFR 716.40 - EPA requests for submission of further information.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 40 Protection of Environment 30 2010-07-01 2010-07-01 false EPA requests for submission of further information. 716.40 Section 716.40 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) TOXIC SUBSTANCES CONTROL ACT HEALTH AND SAFETY DATA REPORTING General Provisions § 716.40 EPA requests for...

40 CFR 716.40 - EPA requests for submission of further information.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 40 Protection of Environment 31 2011-07-01 2011-07-01 false EPA requests for submission of further information. 716.40 Section 716.40 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) TOXIC SUBSTANCES CONTROL ACT HEALTH AND SAFETY DATA REPORTING General Provisions § 716.40 EPA requests for...

40 CFR 716.40 - EPA requests for submission of further information.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 40 Protection of Environment 32 2012-07-01 2012-07-01 false EPA requests for submission of further information. 716.40 Section 716.40 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) TOXIC SUBSTANCES CONTROL ACT HEALTH AND SAFETY DATA REPORTING General Provisions § 716.40 EPA requests for...

40 CFR 716.40 - EPA requests for submission of further information.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 40 Protection of Environment 31 2014-07-01 2014-07-01 false EPA requests for submission of further information. 716.40 Section 716.40 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) TOXIC SUBSTANCES CONTROL ACT HEALTH AND SAFETY DATA REPORTING General Provisions § 716.40 EPA requests for...

40 CFR 40.115-5 - Person.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 40 Protection of Environment 1 2011-07-01 2011-07-01 false Person. 40.115-5 Section 40.115-5 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY GRANTS AND OTHER FEDERAL ASSISTANCE RESEARCH AND DEMONSTRATION GRANTS § 40.115-5 Person. (a) Under the Federal Water Pollution Control Act, an individual...

40 CFR 40.115-5 - Person.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 40 Protection of Environment 1 2010-07-01 2010-07-01 false Person. 40.115-5 Section 40.115-5 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY GRANTS AND OTHER FEDERAL ASSISTANCE RESEARCH AND DEMONSTRATION GRANTS § 40.115-5 Person. (a) Under the Federal Water Pollution Control Act, an individual...

40 CFR 40.115-6 - State.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 40 Protection of Environment 1 2011-07-01 2011-07-01 false State. 40.115-6 Section 40.115-6 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY GRANTS AND OTHER FEDERAL ASSISTANCE RESEARCH AND DEMONSTRATION GRANTS § 40.115-6 State. (a) Under the Federal Water Pollution Control Act, a State, the District...

41 CFR 109-40.113 - Insurance against transportation hazards.

Code of Federal Regulations, 2012 CFR

2012-01-01

... transportation hazards. 109-40.113 Section 109-40.113 Public Contracts and Property Management Federal Property..., TRANSPORTATION, AND MOTOR VEHICLES 40-TRANSPORTATION AND TRAFFIC MANAGEMENT 40.1-General Provision § 109-40.113 Insurance against transportation hazards. The policy of the Government with respect to insurance of its...

41 CFR 109-40.113 - Insurance against transportation hazards.

Code of Federal Regulations, 2013 CFR

2013-07-01

... transportation hazards. 109-40.113 Section 109-40.113 Public Contracts and Property Management Federal Property..., TRANSPORTATION, AND MOTOR VEHICLES 40-TRANSPORTATION AND TRAFFIC MANAGEMENT 40.1-General Provision § 109-40.113 Insurance against transportation hazards. The policy of the Government with respect to insurance of its...

41 CFR 109-40.103-2 - Disqualification and suspension of carriers.

Code of Federal Regulations, 2010 CFR

2010-07-01

... suspension of carriers. 109-40.103-2 Section 109-40.103-2 Public Contracts and Property Management Federal... AVIATION, TRANSPORTATION, AND MOTOR VEHICLES 40-TRANSPORTATION AND TRAFFIC MANAGEMENT 40.1-General Provision § 109-40.103-2 Disqualification and suspension of carriers. Disqualification and suspension are...

40 CFR 40.160-2 - Financial status report.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 40 Protection of Environment 1 2010-07-01 2010-07-01 false Financial status report. 40.160-2 Section 40.160-2 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY GRANTS AND OTHER FEDERAL ASSISTANCE RESEARCH AND DEMONSTRATION GRANTS § 40.160-2 Financial status report. A financial status report...

40 CFR 40.125-1 - Limitations on duration.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 40 Protection of Environment 1 2010-07-01 2010-07-01 false Limitations on duration. 40.125-1 Section 40.125-1 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY GRANTS AND OTHER FEDERAL ASSISTANCE RESEARCH AND DEMONSTRATION GRANTS § 40.125-1 Limitations on duration. (a) [Reserved] (b) No...

50 CFR 697.23 - Restricted gear areas.

Code of Federal Regulations, 2012 CFR

2012-10-01

.... 130 40°04.2′ N. 69°01.75′ W. 131 40°06.15′ N. 69°01.95′ W. 132 40°07.25′ N. 69°02.0′ W. 133 40°08.5′ N...: Inshore Boundary Point to Latitude Longitude 120 40°06.4′ N. 68°35.8′ W. 69 40°07.9′ N. 68°36.0′ W. 70 40°07.2′ N. 68°38.4′ W. 71 40°06.9′ N. 68°46.5′ W. 72 40°08.7′ N. 68°49.6′ W. 73 40°08.1′ N. 68°51.0′ W...

50 CFR 697.23 - Restricted gear areas.

Code of Federal Regulations, 2014 CFR

2014-10-01

.... 130 40°04.2′ N. 69°01.75′ W. 131 40°06.15′ N. 69°01.95′ W. 132 40°07.25′ N. 69°02.0′ W. 133 40°08.5′ N...: Inshore Boundary Point to Latitude Longitude 120 40°06.4′ N. 68°35.8′ W. 69 40°07.9′ N. 68°36.0′ W. 70 40°07.2′ N. 68°38.4′ W. 71 40°06.9′ N. 68°46.5′ W. 72 40°08.7′ N. 68°49.6′ W. 73 40°08.1′ N. 68°51.0′ W...

50 CFR 697.23 - Restricted gear areas.

Code of Federal Regulations, 2013 CFR

2013-10-01

.... 130 40°04.2′ N. 69°01.75′ W. 131 40°06.15′ N. 69°01.95′ W. 132 40°07.25′ N. 69°02.0′ W. 133 40°08.5′ N...: Inshore Boundary Point to Latitude Longitude 120 40°06.4′ N. 68°35.8′ W. 69 40°07.9′ N. 68°36.0′ W. 70 40°07.2′ N. 68°38.4′ W. 71 40°06.9′ N. 68°46.5′ W. 72 40°08.7′ N. 68°49.6′ W. 73 40°08.1′ N. 68°51.0′ W...

Functional characterization of Mia40p, the central component of the disulfide relay system of the mitochondrial intermembrane space.

PubMed

Grumbt, Barbara; Stroobant, Vincent; Terziyska, Nadia; Israel, Lars; Hell, Kai

2007-12-28

Mia40p and Erv1p are components of a translocation pathway for the import of cysteine-rich proteins into the intermembrane space of mitochondria. We have characterized the redox behavior of Mia40p and reconstituted the disulfide transfer system of Mia40p by using recombinant functional C-terminal fragment of Mia40p, Mia40C, and Erv1p. Oxidized Mia40p contains three intramolecular disulfide bonds. One disulfide bond connects the first two cysteine residues in the CPC motif. The second and the third bonds belong to the twin CX(9)C motif and bridge the cysteine residues of two CX(9)C segments. In contrast to the stabilizing disulfide bonds of the twin CX(9)C motif, the first disulfide bond was easily accessible to reducing agents. Partially reduced Mia40C generated by opening of this bond as well as fully reduced Mia40C were oxidized by Erv1p in vitro. In the course of this reaction, mixed disulfides of Mia40C and Erv1p were formed. Reoxidation of fully reduced Mia40C required the presence of the first two cysteine residues in Mia40C. However, efficient reoxidation of a Mia40C variant containing only the cysteine residues of the twin CX(9)C motif was observed when in addition to Erv1p low amounts of wild type Mia40C were present. In the reconstituted system the thiol oxidase Erv1p was sufficient to transfer disulfide bonds to Mia40C, which then could oxidize the variant of Mia40C. In summary, we reconstituted a disulfide relay system consisting of Mia40C and Erv1p.

Human Mars Mission: Weights and Mass Properties. Pt. 1

NASA Technical Reports Server (NTRS)

Brothers, Bobby

1999-01-01

This paper presents a final report on The Human Mars Mission Weights and Measures. The topics included in this report are: 1) Trans-Earth Injection Storage Human Mars Mission (HMM) Chemical Design Reference Mission (DRM) v4.0a Weight Breakout; 2) Ascent Stage HMM Chemical DRM v4.0a Weight Breakout; 3) Descent Stages HMM Chemical DRM v4.0a Weight Breakout; 4) Trans-Mars Injection Stages HMM Chemical DRM v4.0a Weight Breakout; 5) Trans-Earth Injection Stage HMM Solar Electric Propulsion (SEP) DRM v4.0a Weight Breakout; 6) Ascent Stage HMM SEP DRM v4.0a Weight Breakout; 7) Descent Stages HMM SEP DRM v4.0a Weight Breakout; 8) Trans-Mars Injection Stages HMM SEP DRM v4.0a Weight Breakout; 9) Crew Taxi Stage HMM SEP DRM v4.0 Weight Breakout; 10)Trans-Earth Injection Stage HMM Nuclear DRM v4.0a Weight Breakout; 11) Ascent Stage HMM Nuclear DRM v4.0a Weight Breakout; 12) Descent Stages HMM Nuclear DRM v4.0a Weight Breakout; 13) Trans-Mars Injection Stages HMM Nuclear DRM v4.0a Weight Breakout; and 14) HMM Mass Properties Coordinate System.

No detection of simian virus 40 in malignant mesothelioma in Korea.

PubMed

Eom, Minseob; Abdul-Ghafar, Jamshid; Park, Sun-Mi; Han, Joung Ho; Hong, Soon Won; Kwon, Kun Young; Ko, Eun Suk; Kim, Lucia; Kim, Wan Seop; Ha, Seung Yeon; Lee, Kyo Young; Lee, Chang Hun; Yoon, Hye Kyoung; Choi, Yoo Duk; Chung, Myoung Ja; Jung, Soon-Hee

2013-04-01

Simian virus 40 (SV40), a polyomavirus, was discovered as a contaminant of a human polio vaccine in the 1960s. It is known that malignant mesothelioma (MM) is associated with SV40, and that the virus works as a cofactor to the carcinogenetic effects of asbestos. However, the reports about the correlation between SV40 and MM have not been consistent. The purpose of this study is to identify SV40 in MM tissue in Korea through detection of SV40 protein and DNA. We analyzed 62 cases of available paraffin-blocks enrolled through the Korean Malignant Mesothelioma Surveillance System and performed immunohistochemistry for SV40 protein and real-time polymerase chain reaction (PCR) for SV40 DNA. Of 62 total cases, 40 had disease involving the pleura (64.5%), and 29 (46.8%) were found to be of the epithelioid subtype. Immunostaining demonstrated that all examined tissues were negative for SV40 protein. Sufficient DNA was extracted for real-time PCR analysis from 36 cases. Quantitative PCR of these samples showed no increase in SV40 transcript compared to the negative controls. SV40 is not associated with the development of MM in Korea.

Simian virus 40 (SV40)-like DNA sequences not detectable in finnish mesothelioma patients not exposed to SV40-contaminated polio vaccines.

PubMed

Hirvonen, A; Mattson, K; Karjalainen, A; Ollikainen, T; Tammilehto, L; Hovi, T; Vainio, H; Pass, H I; Di Resta, I; Carbone, M; Linnainmaa, K

1999-10-01

Occupational asbestos exposure can be demonstrated in 80% of mesothelioma cases. A possible role of simian virus 40 (SV40) in the etiology of mesothelioma was raised because several studies reported the presence and expression of SV40-like DNA sequences in human mesotheliomas. It is also known that expression of SV40 large T antigen inhibits cellular Rb and p53. This suggests that SV40 might render infected cells more susceptible to asbestos carcinogenicity. The SV40-like sequences are suggested to have arisen from contaminated polio vaccines. Millions of people in the United States and most European countries were inoculated with SV40-contaminated polio vaccine in 1955-1963. However, in Finland, where polio vaccination started in 1957, no SV40-contaminated vaccine was used. We used a polymerase chain reaction-based method to test for the presence of SV40-like sequences in DNA extracted from the frozen tumor tissues of 49 Finnish mesothelioma patients, most of whom had been occupationally exposed to asbestos. All of the Finnish tumor tissues tested negative for SV40-like sequences. The results suggest that the SV40-like sequences detected in mesothelioma tissue in some previous studies may indeed originate from SV40-contaminated polio vaccines. It is a matter of speculation whether the absence of SV40 infection has contributed to the relatively low incidence of mesothelioma in Finland (1/10(5) in 1990-1995). Copyright 1999 Wiley-Liss, Inc.

10 CFR 40.2 - Scope.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 10 Energy 1 2010-01-01 2010-01-01 false Scope. 40.2 Section 40.2 Energy NUCLEAR REGULATORY COMMISSION DOMESTIC LICENSING OF SOURCE MATERIAL General Provisions § 40.2 Scope. Except as provided in §§ 40.11 to 40.14, inclusive, the regulations in this part apply to all persons in the United States. This...

40 CFR 40.115-6 - State.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 40 Protection of Environment 1 2010-07-01 2010-07-01 false State. 40.115-6 Section 40.115-6... DEMONSTRATION GRANTS § 40.115-6 State. (a) Under the Federal Water Pollution Control Act, a State, the District... Territory of the Pacific Islands. (b) Under the Resource Conservation and Recovery Act, a State, the...

40 CFR 464.40 - Applicability; description of the zinc casting subcategory.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 40 Protection of Environment 31 2012-07-01 2012-07-01 false Applicability; description of the zinc casting subcategory. 464.40 Section 464.40 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) EFFLUENT GUIDELINES AND STANDARDS (CONTINUED) METAL MOLDING AND CASTING POINT SOURCE CATEGORY Zinc Casting Subcategory § 464.40...

40 CFR 464.40 - Applicability; description of the zinc casting subcategory.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 40 Protection of Environment 31 2013-07-01 2013-07-01 false Applicability; description of the zinc casting subcategory. 464.40 Section 464.40 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) EFFLUENT GUIDELINES AND STANDARDS (CONTINUED) METAL MOLDING AND CASTING POINT SOURCE CATEGORY Zinc Casting Subcategory § 464.40...

40 CFR 464.40 - Applicability; description of the zinc casting subcategory.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 40 Protection of Environment 30 2014-07-01 2014-07-01 false Applicability; description of the zinc casting subcategory. 464.40 Section 464.40 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) EFFLUENT GUIDELINES AND STANDARDS (CONTINUED) METAL MOLDING AND CASTING POINT SOURCE CATEGORY Zinc Casting Subcategory § 464.40...

40 CFR 430.40 - Applicability; description of the dissolving sulfite subcategory.

Code of Federal Regulations, 2011 CFR

2011-07-01

... dissolving sulfite subcategory. 430.40 Section 430.40 Protection of Environment ENVIRONMENTAL PROTECTION... CATEGORY Dissolving Sulfite Subcategory § 430.40 Applicability; description of the dissolving sulfite... at dissolving sulfite mills. ...

40 CFR 430.40 - Applicability; description of the dissolving sulfite subcategory.

Code of Federal Regulations, 2010 CFR

2010-07-01

... dissolving sulfite subcategory. 430.40 Section 430.40 Protection of Environment ENVIRONMENTAL PROTECTION... CATEGORY Dissolving Sulfite Subcategory § 430.40 Applicability; description of the dissolving sulfite... at dissolving sulfite mills. ...

Low Volatile Organic Compound (VOC) Chemical Agent Resistant Coating (CARC)

DTIC Science & Technology

2000-04-01

hv1p 30 0 4 7 120 40 B15 +++--·····-+ 46168 36521 28 75 5 hv1p 30 0 2 3 75 80 Bl6 ++++++++++++ 46168 36521 28 120 30 conv 240 I 4 7 120 80 Low...Conventional· Bl2 28 HVLP Bl3 7 Conventional 1.4 1.2 2 Bl4 7 HVLP 1.1 2.3 4 BlS 28 HVLP B16 28 Conventional Notes: I. Only panel sets coated with...p p Bl4 572 574 3.0 4.0 4.0 3.5 p p BIS 274 243 4.0 4.0 4.0 4.5 p p Bl6 360 334 4.0 4.0 4.0 4.0 p p Experimental Set WR 7 days /lSO"C Oil

Modulation of FcεRI-dependent mast cell response by OX40L via Fyn, PI3K, and RhoA.

PubMed

Sibilano, Riccardo; Frossi, Barbara; Suzuki, Ryo; D'Incà, Federica; Gri, Giorgia; Piconese, Silvia; Colombo, Mario P; Rivera, Juan; Pucillo, Carlo E

2012-09-01

The interaction of mast cells (MCs) with regulatory T cells through the OX40 ligand (OX40L):OX40 axis downregulates FcεRI-dependent immediate hypersensitivity responses both in vitro and in vivo. Little is known on OX40L-mediated intracellular signaling or on the mechanism by which OX40L engagement suppresses MC degranulation. We explored the role of OX40L engagement on IgE/antigen-triggered MCs both in vitro and in vivo. The soluble form of OX40 molecule was used to selectively trigger OX40L on MCs in vitro and was used to dissect OX40L contribution in an in vivo model of systemic anaphylaxis. OX40L:OX40 interaction led to the recruitment of C-terminal src kinase into lipid rafts, causing a preferential suppression of Fyn kinase activity and subsequent reduction in the phosphorylation of Gab2, the phosphatidylinositol 3-OH kinase regulatory subunit p85, and Akt, without affecting the Lyn pathway. Dampening of Fyn kinase activity also inhibited RhoA activation and microtubule nucleation, key regulators of MC degranulation. The in vivo administration of a blocking antibody to OX40L in wild-type mice caused enhanced immediate hypersensitivity, whereas the administration of soluble OX40 to regulatory T-cell-depleted or OX40-deficient mice reduced MC degranulation. The engagement of OX40L selectively suppresses Fyn-initiated signals required for MC degranulation and serves to limit immediate hypersensitivity. Our data suggest that soluble OX40 can restore the aberrant or absent regulatory T-cell activity, revealing a previously unappreciated homeostatic role for OX40L in setting the basal threshold of MC response. Copyright © 2012 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.

[Correlation between load of polyomavirus and hemorrhagic cystitis].

PubMed

Tong, Chun-Rong; Teng, Zhi-Ping; Liu, Hong-Xing; Cai, Peng; Ma, Si-Kun; Zhen, Cheng-Liang; Zeng, Yi; Lu, Dao-Pei

2007-09-01

To study the correlation between polyoma virus load and hemorrhagic cystitis after allogeneic stem cells transplantation for prevention of hemorrhagic cystitis. Blood and urine specimens were collected from 40 healthy persons, 40 patient with stem cells transplantation and 20 cases complicated with hemorrhagic cystitis for determination of VP1 gene of polyomaviruses BK virus (BKV)/Jamestown Canyon virus (JCV) and simian virus 40 (SV40) by polymerase chain reaction (PCR) and EvaGreen stain fluorescence quantitative assay. In the peripheral blood, all genes of BKV/JCV and SV40 were negative, while BKV gene in urine and blood from healthy persons and patient with stem cells transplantation was 15% (6/40) and 100% (40/40), respectively. The gene of JCV was positive in 10% (4/40) and 12% (5/40), the gene of SV40 was negative. Genes of BKV and JCV was detectable in urine specimens of healthy persons and there was a correlation between the load of polyomavirus and incidence of hemorrhagic cystitis.

Health screenings for women ages 40 to 64

MedlinePlus

Health maintenance visit - women - ages 40 to 64; Physical exam - women - ages 40 to 64; Yearly exam - ... 64; Checkup - women - ages 40 to 64; Women's health - ages 40 to 64; Preventive care - women - ages ...

77 FR 51695 - Airworthiness Directives; Honeywell International Inc. Turbofan Engines

Federal Register 2010, 2011, 2012, 2013, 2014

2012-08-27

... Airworthiness Directives; Honeywell International Inc. Turbofan Engines AGENCY: Federal Aviation Administration... Honeywell International Inc. TFE731-20R, -20AR, -20BR, -40, -40AR, - 40R, -50R, and -60 turbofan engines... Inc. TFE731-20R, -20AR, -20BR, -40, -40AR, -40R, -50R, and -60 turbofan engines: (i) With an engine...

17 CFR 40.7 - Delegations.

Code of Federal Regulations, 2013 CFR

2013-04-01

... ENTITIES § 40.7 Delegations. (a) Procedural matters. (1) The Commission hereby delegates, until it orders..., pursuant to § 40.3(c)(2) or § 40.5(c)(1)(ii) of this part, that the registered entity requesting approval...) To notify the registered entity, pursuant to § 40.3(e) or § 40.5(e) of this part, that the Commission...

17 CFR 40.7 - Delegations.

Code of Federal Regulations, 2014 CFR

2014-04-01

... ENTITIES § 40.7 Delegations. (a) Procedural matters. (1) The Commission hereby delegates, until it orders... § 40.3(c)(2) or § 40.5(c)(1)(ii) of this part, that the registered entity requesting approval amend the... the registered entity, pursuant to § 40.3(e) or § 40.5(e) of this part, that the Commission is not...

17 CFR 40.7 - Delegations.

Code of Federal Regulations, 2012 CFR

2012-04-01

... ENTITIES § 40.7 Delegations. (a) Procedural matters. (1) The Commission hereby delegates, until it orders..., pursuant to § 40.3(c)(2) or § 40.5(c)(1)(ii) of this part, that the registered entity requesting approval...) To notify the registered entity, pursuant to § 40.3(e) or § 40.5(e) of this part, that the Commission...

41 CFR 109-40.103-3 - International transportation.

Code of Federal Regulations, 2014 CFR

2014-01-01

... transportation. 109-40.103-3 Section 109-40.103-3 Public Contracts and Property Management Federal Property..., TRANSPORTATION, AND MOTOR VEHICLES 40-TRANSPORTATION AND TRAFFIC MANAGEMENT 40.1-General Provision § 109-40.103-3 International transportation. See 4 CFR 52.2 for a certificate required in nonuse of U.S. flag vessels or U.S...

40 CFR 40.140-3 - Federal Water Pollution Control Act.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 40 Protection of Environment 1 2013-07-01 2013-07-01 false Federal Water Pollution Control Act. 40.140-3 Section 40.140-3 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY GRANTS AND OTHER FEDERAL ASSISTANCE RESEARCH AND DEMONSTRATION GRANTS § 40.140-3 Federal Water Pollution Control Act. (a) All applications for grants under section 105...

40 CFR 260.40 - Additional regulation of certain hazardous waste recycling activities on a case-by-case basis.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 40 Protection of Environment 26 2011-07-01 2011-07-01 false Additional regulation of certain hazardous waste recycling activities on a case-by-case basis. 260.40 Section 260.40 Protection of... SYSTEM: GENERAL Rulemaking Petitions § 260.40 Additional regulation of certain hazardous waste recycling...

40 CFR 260.40 - Additional regulation of certain hazardous waste recycling activities on a case-by-case basis.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 40 Protection of Environment 25 2010-07-01 2010-07-01 false Additional regulation of certain hazardous waste recycling activities on a case-by-case basis. 260.40 Section 260.40 Protection of... SYSTEM: GENERAL Rulemaking Petitions § 260.40 Additional regulation of certain hazardous waste recycling...

40 CFR 260.40 - Additional regulation of certain hazardous waste recycling activities on a case-by-case basis.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 40 Protection of Environment 27 2013-07-01 2013-07-01 false Additional regulation of certain hazardous waste recycling activities on a case-by-case basis. 260.40 Section 260.40 Protection of... SYSTEM: GENERAL Rulemaking Petitions § 260.40 Additional regulation of certain hazardous waste recycling...

40 CFR 260.40 - Additional regulation of certain hazardous waste recycling activities on a case-by-case basis.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 40 Protection of Environment 26 2014-07-01 2014-07-01 false Additional regulation of certain hazardous waste recycling activities on a case-by-case basis. 260.40 Section 260.40 Protection of... SYSTEM: GENERAL Rulemaking Petitions § 260.40 Additional regulation of certain hazardous waste recycling...

40 CFR 260.40 - Additional regulation of certain hazardous waste recycling activities on a case-by-case basis.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 40 Protection of Environment 27 2012-07-01 2012-07-01 false Additional regulation of certain hazardous waste recycling activities on a case-by-case basis. 260.40 Section 260.40 Protection of... SYSTEM: GENERAL Rulemaking Petitions § 260.40 Additional regulation of certain hazardous waste recycling...

40 CFR Table 40 to Subpart Uuu of... - Requirements for Installation, Operation, and Maintenance of Continuous Opacity Monitoring...

Code of Federal Regulations, 2013 CFR

2013-07-01

... Systems 40 Table 40 to Subpart UUU of Part 63 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY...: Catalytic Cracking Units, Catalytic Reforming Units, and Sulfur Recovery Units Pt. 63, Subpt. UUU, Table 40 Table 40 to Subpart UUU of Part 63—Requirements for Installation, Operation, and Maintenance of...

40 CFR Table 40 to Subpart Uuu of... - Requirements for Installation, Operation, and Maintenance of Continuous Opacity Monitoring...

Code of Federal Regulations, 2011 CFR

2011-07-01

... Systems 40 Table 40 to Subpart UUU of Part 63 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY... Cracking Units, Catalytic Reforming Units, and Sulfur Recovery Units Pt. 63, Subpt. UUU, Table 40 Table 40 to Subpart UUU of Part 63—Requirements for Installation, Operation, and Maintenance of Continuous...

40 CFR Table 40 to Subpart Uuu of... - Requirements for Installation, Operation, and Maintenance of Continuous Opacity Monitoring...

Code of Federal Regulations, 2014 CFR

2014-07-01

... Systems 40 Table 40 to Subpart UUU of Part 63 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY...: Catalytic Cracking Units, Catalytic Reforming Units, and Sulfur Recovery Units Pt. 63, Subpt. UUU, Table 40 Table 40 to Subpart UUU of Part 63—Requirements for Installation, Operation, and Maintenance of...

40 CFR Table 40 to Subpart Uuu of... - Requirements for Installation, Operation, and Maintenance of Continuous Opacity Monitoring...

Code of Federal Regulations, 2012 CFR

2012-07-01

... Systems 40 Table 40 to Subpart UUU of Part 63 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY...: Catalytic Cracking Units, Catalytic Reforming Units, and Sulfur Recovery Units Pt. 63, Subpt. UUU, Table 40 Table 40 to Subpart UUU of Part 63—Requirements for Installation, Operation, and Maintenance of...

40 CFR Table 40 to Subpart Uuu of... - Requirements for Installation, Operation, and Maintenance of Continuous Opacity Monitoring...

Code of Federal Regulations, 2010 CFR

2010-07-01

... Systems 40 Table 40 to Subpart UUU of Part 63 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY... Cracking Units, Catalytic Reforming Units, and Sulfur Recovery Units Pt. 63, Subpt. UUU, Table 40 Table 40 to Subpart UUU of Part 63—Requirements for Installation, Operation, and Maintenance of Continuous...

Nuclear Data Sheets for A=40

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

Chen, Jun

The experimental nuclear structure data and decay data are evaluated for the known nuclides of mass 40 (Mg, Al, Si, P, S, Cl, Ar, K, Ca, Sc, Ti). Detailed evaluated nuclear structure information is presented with the best values recommended for level energies, half-lives, γ-ray energies and intensities, decay properties (energies, intensities and placement of radiations), and other spectroscopic data. The {sup 40}Ca and {sup 40}K nuclides remain as the most extensively studied from many different reactions and decays; no excited states are known in {sup 40}Mg, {sup 40}Al, {sup 40}P and {sup 40}Ti. This work supersedes the earlier fullmore » evaluation of A=40 by J. Cameron and B. Singh (2004Ca38).« less

Molecular evidence of simian virus 40 infections in children

NASA Technical Reports Server (NTRS)

Butel, J. S.; Arrington, A. S.; Wong, C.; Lednicky, J. A.; Finegold, M. J.

1999-01-01

Recent studies have detected simian virus 40 (SV40) DNA in certain human tumors and normal tissues. The significance of human infections by SV40, which was first discovered as a contaminant of poliovirus vaccines used between 1955 and 1963, remains unknown. The occurrence of SV40 infections in unselected hospitalized children was evaluated. Polymerase chain reaction and DNA sequence analyses were done on archival tissue specimens from patients positive for SV40 neutralizing antibody. SV40 DNA was identified in samples from 4 of 20 children (1 Wilms' tumor, 3 transplanted kidney samples). Sequence variation among SV40 regulatory regions ruled out laboratory contamination of specimens. This study shows the presence of SV40 infections in pediatric patients born after 1982.

Human CD40 ligand deficiency dysregulates the macrophage transcriptome causing functional defects that are improved by exogenous IFN-γ.

PubMed

Cabral-Marques, Otavio; Ramos, Rodrigo Nalio; Schimke, Lena F; Khan, Taj Ali; Amaral, Eduardo Pinheiro; Barbosa Bomfim, Caio César; Junior, Osvaldo Reis; França, Tabata Takahashi; Arslanian, Christina; Carola Correia Lima, Joanna Darck; Weber, Cristina Worm; Ferreira, Janaíra Fernandes; Tavares, Fabiola Scancetti; Sun, Jing; D'Imperio Lima, Maria Regina; Seelaender, Marília; Garcia Calich, Vera Lucia; Marzagão Barbuto, José Alexandre; Costa-Carvalho, Beatriz Tavares; Riemekasten, Gabriela; Seminario, Gisela; Bezrodnik, Liliana; Notarangelo, Luigi; Torgerson, Troy R; Ochs, Hans D; Condino-Neto, Antonio

2017-03-01

CD40 ligand (CD40L) deficiency predisposes to opportunistic infections, including those caused by fungi and intracellular bacteria. Studies of CD40L-deficient patients reveal the critical role of CD40L-CD40 interaction for the function of T, B, and dendritic cells. However, the consequences of CD40L deficiency on macrophage function remain to be investigated. We sought to determine the effect of CD40L absence on monocyte-derived macrophage responses. After observing the improvement of refractory disseminated mycobacterial infection in a CD40L-deficient patient by recombinant human IFN-γ (rhIFN-γ) adjuvant therapy, we investigated macrophage functions from CD40L-deficient patients. We analyzed the killing activity, oxidative burst, cytokine production, and in vitro effects of rhIFN-γ and soluble CD40 ligand (sCD40L) treatment on macrophages. In addition, the effect of CD40L absence on the macrophage transcriptome before and after rhIFN-γ treatment was studied. Macrophages from CD40L-deficient patients exhibited defective fungicidal activity and reduced oxidative burst, both of which improved in the presence of rhIFN-γ but not sCD40L. In contrast, rhIFN-γ and sCD40L ameliorate impaired production of inflammatory cytokines. Furthermore, rhIFN-γ reversed defective control of Mycobacterium tuberculosis proliferation by patients' macrophages. The absence of CD40L dysregulated the macrophage transcriptome, which was improved by rhIFN-γ. Additionally, rhIFN-γ increased expression levels of pattern recognition receptors, such as Toll-like receptors 1 and 2, dectin 1, and dendritic cell-specific intercellular adhesion molecule 3-grabbing nonintegrin in macrophages from both control subjects and patients. Absence of CD40L impairs macrophage development and function. In addition, the improvement of macrophage immune responses by IFN-γ suggests this cytokine as a potential therapeutic option for patients with CD40L deficiency. Copyright © 2016 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

Dendritic and tumor cell fusions transduced with adenovirus encoding CD40L eradicate B-cell lymphoma and induce a Th17-type response.

PubMed

Alvarez, E; Moga, E; Barquinero, J; Sierra, J; Briones, J

2010-04-01

Fusion of dendritic cells and tumor cells (FCs) constitutes a promising tool for generating an antitumor response because of their capacity to present tumor antigens and provide appropriate costimulatory signals. CD40-CD40L interaction has an important role in the maturation and survival of dendritic cells and provides critical help for T-cell priming. In this study, we sought to improve the effectiveness of FC vaccines in a murine model of B-cell lymphoma by engineering FCs to express CD40L by means of an adenovirus encoding CD40L (Adv-CD40L). Before transduction with Adv-CD40L, no CD40L expression was detected in FCs, DCs or tumor cells. The surface expression of CD40L in FC transduced with Adv-CD40L (FC-CD40L) ranged between 50 and 60%. FC-CD40L showed an enhanced expression of CD80, CD86, CD54 and MHC class II molecules and elicited a strong in vitro immune response in a syngeneic mixed lymphocyte reaction. Furthermore, FC-CD40L showed enhanced migration to secondary lymphoid organs. Splenocytes from mice treated with FC-CD40L had a dramatic increase in the production of IL-17, IL-6 and IFN-gamma, compared with controls. Treatment with the FC-CD40L vaccine induced regression of established tumors and increased survival. Our data demonstrate that FC transduced with Adv-CD40L enhances the antitumor effect of FC vaccines in a murine lymphoma model and this is associated with an increased Th17-type immune response.

Somatodendritic and excitatory postsynaptic distribution of neuron-type dystrophin isoform, Dp40, in hippocampal neurons

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

Fujimoto, Takahiro; Itoh, Kyoko, E-mail: kxi14@koto.kpu-m.ac.jp; Yaoi, Takeshi

2014-09-12

Highlights: • Identification of dystrophin (Dp) shortest isoform, Dp40, is a neuron-type Dp. • Dp40 expression is temporally and differentially regulated in comparison to Dp71. • Somatodendritic and nuclear localization of Dp40. • Dp40 is localized to excitatory postsynapses. • Dp40 might play roles in dendritic and synaptic functions. - Abstract: The Duchenne muscular dystrophy (DMD) gene produces multiple dystrophin (Dp) products due to the presence of several promoters. We previously reported the existence of a novel short isoform of Dp, Dp40, in adult mouse brain. However, the exact biochemical expression profile and cytological distribution of the Dp40 protein remainmore » unknown. In this study, we generated a polyclonal antibody against the NH{sub 2}-terminal region of the Dp40 and identified the expression profile of Dp40 in the mouse brain. Through an analysis using embryonic and postnatal mouse cerebrums, we found that Dp40 emerged from the early neonatal stages until adulthood, whereas Dp71, an another Dp short isoform, was highly detected in both prenatal and postnatal cerebrums. Intriguingly, relative expressions of Dp40 and Dp71 were prominent in cultured dissociated neurons and non-neuronal cells derived from mouse hippocampus, respectively. Furthermore, the immunocytological distribution of Dp40 was analyzed in dissociated cultured neurons, revealing that Dp40 is detected in the soma and its dendrites, but not in the axon. It is worthy to note that Dp40 is localized along the subplasmalemmal region of the dendritic shafts, as well as at excitatory postsynaptic sites. Thus, Dp40 was identified as a neuron-type Dp possibly involving dendritic and synaptic functions.« less

Heterogeneous expression and regulation of CD40 in human hepatocellular carcinoma.

PubMed

Holub, Margareta; Zakeri, Schaker M; Lichtenberger, Cornelia; Pammer, Johannes; Paolini, Pierre; Leifeld, Ludger; Rockenschaub, Susanne; Wolschek, Markus F; Steger, Günther; Willheim, Martin; Gangl, Alfred; Reinisch, Walter

2003-02-01

CD40, a member of the tumour necrosis factor receptor family, plays a major role in adaptive immune responses and contributes to cancer surveillance. Conflicting results have been reported recently on the expression and function of CD40 in carcinomas. The aim of the present study was to investigate the role of CD40 in human hepatoma. CD40 expression was examined in hepatomas and derived cell lines by immunohistochemistry, flow cytometry and reverse transcriptase polymerase chain reaction. We investigated in hepatoma cell lines the regulation of CD40 by pro-inflammatory cytokines and the effects of its ligation with soluble CD40L on the expression of co-stimulatory and pro-apoptotic cell-surface molecules and survival. CD40 was detected with a similar frequency of about 40% in hepatoma specimens and derived cell lines but not in normal hepatocytes. Tumour necrosis factor alpha and its combination with interferon gamma upregulated CD40 only in intrinsically positive cell lines. CD40 ligation had no effect on cell viability or surface expression of CD54, CD80, CD86 or CD95. CD40 is expressed variably in human hepatoma and enhanced by distinct pro-inflammatory cytokines. The lack of detectable effects of CD40 ligation does not support a major role of this molecule in hepatocellular carcinoma biology.

40 CFR 430.40 - Applicability; description of the dissolving sulfite subcategory.

Code of Federal Regulations, 2014 CFR

2014-07-01

... dissolving sulfite subcategory. 430.40 Section 430.40 Protection of Environment ENVIRONMENTAL PROTECTION... SOURCE CATEGORY Dissolving Sulfite Subcategory § 430.40 Applicability; description of the dissolving... production of pulp at dissolving sulfite mills. ...

40 CFR 430.40 - Applicability; description of the dissolving sulfite subcategory.

Code of Federal Regulations, 2012 CFR

2012-07-01

... dissolving sulfite subcategory. 430.40 Section 430.40 Protection of Environment ENVIRONMENTAL PROTECTION... SOURCE CATEGORY Dissolving Sulfite Subcategory § 430.40 Applicability; description of the dissolving... production of pulp at dissolving sulfite mills. ...

40 CFR 430.40 - Applicability; description of the dissolving sulfite subcategory.

Code of Federal Regulations, 2013 CFR

2013-07-01

... dissolving sulfite subcategory. 430.40 Section 430.40 Protection of Environment ENVIRONMENTAL PROTECTION... SOURCE CATEGORY Dissolving Sulfite Subcategory § 430.40 Applicability; description of the dissolving... production of pulp at dissolving sulfite mills. ...

40 CFR 180.613 - Flonicamid; tolerances for residues.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 12 0.60 Hop, dried cones 7.0 Okra 0.40 Potato, granules/flakes 0.40 Radish, tops 16 Spinach 9.0..., fruiting, group 8 0.40 Vegetable, leafy, except brassica, group 4, except spinach 4.0 Vegetable, root...

40 CFR 180.620 - Etofenprox; tolerances for residues.

Code of Federal Regulations, 2014 CFR

2014-07-01

... the commodity. Commodity Parts permillion Cattle, fat 10.0 Cattle, meat 0.40 Cattle, meat byproducts... subsection 5.0 Goat, fat 10.0 Goat, meat 0.40 Goat, meat byproducts 10.0 Hog, fat 4.0 Hog, meat 0.20 Hog, meat byproducts 4.0 Horse, fat 10.0 Horse, meat 0.40 Horse, meat byproducts 10.0 Milk 0.60 Poultry, fat...

40 CFR 40.145-2 - Federal Water Pollution Control Act.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 40 Protection of Environment 1 2013-07-01 2013-07-01 false Federal Water Pollution Control Act. 40.145-2 Section 40.145-2 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY GRANTS AND OTHER FEDERAL ASSISTANCE RESEARCH AND DEMONSTRATION GRANTS § 40.145-2 Federal Water Pollution Control Act. (a) No person in the United States shall on the...

Immune regulation by CD40-CD40-l interactions - 2; Y2K update.

PubMed

van Kooten, C

2000-11-01

CD40 is a cell surface receptor, which belongs to the TNF-R family, and which was first identified and functionally characterized on B lymphocytes. However, in recent years it has become clear that CD40 is expressed much broader, including expression on monocytes, dendritic cells, endothelial cells and epithelial cells. Therefore it is now thought that CD40 plays a more general role in immune regulation. The present paper reviews recent developments in this field of research, with main emphasis on CD40 signal transduction and on in vivo functions of CD40/CD40-L interactions.

Technical advance: soluble OX40 molecule mimics regulatory T cell modulatory activity on FcεRI-dependent mast cell degranulation.

PubMed

Sibilano, Riccardo; Gri, Giorgia; Frossi, Barbara; Tripodo, Claudio; Suzuki, Ryo; Rivera, Juan; MacDonald, Andrew S; Pucillo, Carlo E

2011-10-01

Tregs play a central role in modulating FcεRI-dependent MC effector functions in the course of the allergic response. Cellular interaction depends on the constitutive expression of OX40 on Tregs and the OX40L counterpart on MCs. Study of OX40L signaling on MCs is hampered by the need of a highly purified molecule, which triggers OX40L specifically. We now report that sOX40 mimics the physiological activity of Treg interaction by binding to activated MCs. When treated with sOX40, activated MCs showed decreased degranulation and Ca(++) influx, whereas PLC-γ2 phosphorylation remained unaffected. Once injected into experimental animals, sOX40 not only located within the endothelium but also in parenchyma, where it could be found in close proximity and apparently bound to MCs. This soluble molecule triggers MC-OX40L without the requirement of Tregs, thus allowing study of OX40L signaling pathways in MCs and in other OX40L-expressing cell populations. Importantly, as sOX40 inhibits MC degranulation, it may provide an in vivo therapeutic tool in allergic disease.

Nucleoprotein Complexes Containing Replicating Simian Virus 40 DNA: Comparison with Polyoma Nucleoprotein Complexes

PubMed Central

Hall, Mark R.; Meinke, William; Goldstein, David A.

1973-01-01

Procedures for isolating nucleoprotein complexes containing replicating polyoma DNA from infected mouse cells were used to prepare short-lived nucleoprotein complexes (r-SV40 complexes) containing replicating simian virus 40 (SV40) DNA from infected monkey cells. Like the polyoma complexes, r-SV40 complexes were only partially released from nuclei by cell lysis but could be extracted from nuclei by prolonged treatment with solutions containing Triton X-100. r-SV40 complexes sedimented faster than complexes containing SV40 supercoiled DNA (SV40 complex) in sucrose gradients, and both types of SV40 nucleoprotein complexes sedimented ahead of polyoma complexes containing supercoiled polyoma DNA (py complex). The sedimentation rates of py complex and SV40 complex were 56 and 61S, respectively, based on the sedimentation rate of the mouse large ribosomal subunit as a marker. r-SV40 complexes sedimented as multiple peaks between 56 and 75S. Sedimentation and buoyant density measurements indicated that protein is bound to all forms of SV40 DNA at about the same ratio of protein to DNA (1-2/1) as was reported for polyoma nucleoproteins. PMID:4359958

Technical Advance: Soluble OX40 molecule mimics regulatory T cell modulatory activity on FcεRI-dependent mast cell degranulation

PubMed Central

Sibilano, Riccardo; Gri, Giorgia; Frossi, Barbara; Tripodo, Claudio; Suzuki, Ryo; Rivera, Juan; MacDonald, Andrew S.; Pucillo, Carlo E.

2011-01-01

Tregs play a central role in modulating FcεRI-dependent MC effector functions in the course of the allergic response. Cellular interaction depends on the constitutive expression of OX40 on Tregs and the OX40L counterpart on MCs. Study of OX40L signaling on MCs is hampered by the need of a highly purified molecule, which triggers OX40L specifically. We now report that sOX40 mimics the physiological activity of Treg interaction by binding to activated MCs. When treated with sOX40, activated MCs showed decreased degranulation and Ca++ influx, whereas PLC-γ2 phosphorylation remained unaffected. Once injected into experimental animals, sOX40 not only located within the endothelium but also in parenchyma, where it could be found in close proximity and apparently bound to MCs. This soluble molecule triggers MC-OX40L without the requirement of Tregs, thus allowing study of OX40L signaling pathways in MCs and in other OX40L-expressing cell populations. Importantly, as sOX40 inhibits MC degranulation, it may provide an in vivo therapeutic tool in allergic disease. PMID:21653238

Soluble CD40 ligand directly alters glomerular permeability and may act as a circulating permeability factor in FSGS

PubMed Central

Doublier, Sophie; Zennaro, Cristina; Musante, Luca; Spatola, Tiziana; Candiano, Giovanni; Bruschi, Maurizio; Besso, Luca; Cedrino, Massimo; Carraro, Michele; Ghiggeri, Gian Marco; Camussi, Giovanni

2017-01-01

CD40/CD40 ligand (CD40L) dyad, a co-stimulatory bi-molecular complex involved in the adaptive immune response, has also potent pro-inflammatory actions in haematopoietic and non-haematopoietic cells. We describe here a novel role for soluble CD40L (sCD40L) as modifier of glomerular permselectivity directly acting on glomerular epithelial cells (GECs). We found that stimulation of CD40, constitutively expressed on GEC cell membrane, by the sCD40L rapidly induced redistribution and loss of nephrin in GECs, and increased albumin permeability in isolated rat glomeruli. Pre-treatment with inhibitors of CD40-CD40L interaction completely prevented these effects. Furthermore, in vivo injection of sCD40L induced a significant reduction of nephrin and podocin expression in mouse glomeruli, although no significant increase of urine protein/creatinine ratio was observed after in vivo injection. The same effects were induced by plasma factors partially purified from post-transplant plasma exchange eluates of patients with focal segmental glomerulosclerosis (FSGS), and were blocked by CD40-CD40L inhibitors. Moreover, 17 and 34 kDa sCD40L isoforms were detected in the same plasmapheresis eluates by Western blotting. Finally, the levels of sCD40Lwere significantly increased in serum of children both with steroid-sensitive and steroid-resistant nephrotic syndrome (NS), and in adult patients with biopsy-proven FSGS, compared to healthy subjects, but neither in children with congenital NS nor in patients with membranous nephropathy. Our results demonstrate that sCD40L directly modifies nephrin and podocin distribution in GECs. Moreover, they suggest that sCD40L contained in plasmapheresis eluates from FSGS patients with post-transplant recurrence may contribute, presumably cooperating with other mediators, to FSGS pathogenesis by modulating glomerular permeability. PMID:29155846

Soluble CD40 ligand directly alters glomerular permeability and may act as a circulating permeability factor in FSGS.

PubMed

Doublier, Sophie; Zennaro, Cristina; Musante, Luca; Spatola, Tiziana; Candiano, Giovanni; Bruschi, Maurizio; Besso, Luca; Cedrino, Massimo; Carraro, Michele; Ghiggeri, Gian Marco; Camussi, Giovanni; Lupia, Enrico

2017-01-01

CD40/CD40 ligand (CD40L) dyad, a co-stimulatory bi-molecular complex involved in the adaptive immune response, has also potent pro-inflammatory actions in haematopoietic and non-haematopoietic cells. We describe here a novel role for soluble CD40L (sCD40L) as modifier of glomerular permselectivity directly acting on glomerular epithelial cells (GECs). We found that stimulation of CD40, constitutively expressed on GEC cell membrane, by the sCD40L rapidly induced redistribution and loss of nephrin in GECs, and increased albumin permeability in isolated rat glomeruli. Pre-treatment with inhibitors of CD40-CD40L interaction completely prevented these effects. Furthermore, in vivo injection of sCD40L induced a significant reduction of nephrin and podocin expression in mouse glomeruli, although no significant increase of urine protein/creatinine ratio was observed after in vivo injection. The same effects were induced by plasma factors partially purified from post-transplant plasma exchange eluates of patients with focal segmental glomerulosclerosis (FSGS), and were blocked by CD40-CD40L inhibitors. Moreover, 17 and 34 kDa sCD40L isoforms were detected in the same plasmapheresis eluates by Western blotting. Finally, the levels of sCD40Lwere significantly increased in serum of children both with steroid-sensitive and steroid-resistant nephrotic syndrome (NS), and in adult patients with biopsy-proven FSGS, compared to healthy subjects, but neither in children with congenital NS nor in patients with membranous nephropathy. Our results demonstrate that sCD40L directly modifies nephrin and podocin distribution in GECs. Moreover, they suggest that sCD40L contained in plasmapheresis eluates from FSGS patients with post-transplant recurrence may contribute, presumably cooperating with other mediators, to FSGS pathogenesis by modulating glomerular permeability.

A Mouse Model of Transplacental Cocaine Exposure: Clinical Implications for Exposed Infants and Childrena.

PubMed

Kosofsky, Barry E; Wilkins, Aaron S

1998-06-01

To characterize the effects of cocaine on developing brain we have developed a mouse model of gestational cocaine exposure. We studied pregnant dams injected twice daily with cocaine HCl at 40, 20, or 10 mg/kg/day sc from embryonic days (E)8 to E17 (COC 40, COC20, and COC10, respectively), vehicle-injected dams allowed access to food ad libitum (SAL) or pair-fed with the COC 40 dams (SPF 40), animals pretreated with the short-acting α-adrenergic antagonist phentolamine prior to each cocaine injection (P COC 40), and animals administered phentolamine prior to saline (PHENT). COC 40, P COC 40, and SPF 40 dams demonstrated the lowest percentage weight gain during gestation. The surrogate-fostered offspring of COC 40, P COC 40, and SPF 40 dams demonstrated transient brain and body growth retardation on postnatal days (P)1 and P9 when compared to pups born to SAL dams. We conducted behavioral tests which allowed us to dissociate the indirect effect of cocaine-induced malnutrition from a direct effect of prenatal cocaine administration in altering postnatal behavior. Pups from all groups were tested for first-order Pavlovian conditioning on P9 or P12 or for the ability to ignore redundant information in a blocking paradigm on P50. Unlike the SPF 40, PHENT, and SAL controls, COC 40 and P COC 40 mice were unable to acquire an aversion to an odor previously paired with shock on P9, a learning deficit that resolved by P12. However, on P50, COC 40 mice and, to a lesser extent, P COC 40 and SPF 40 mice demonstrated a persistent behavioral deficit in our blocking paradigm, which may reflect alterations in selective attention. We discuss how these findings in our rodent model have developmental implications for human infants exposed to cocaine in utero.

A mouse model of transplacental cocaine exposure. Clinical implications for exposed infants and children.

PubMed

Kosofsky, B E; Wilkins, A S

1998-06-21

To characterize the effects of cocaine on developing brain we have developed a mouse model of gestational cocaine exposure. We studied pregnant dams injected twice daily with cocaine HCl at 40, 20, or 10 mg/kg/day sc from embryonic days (E)8 to E17 (COC 40, COC20, and COC10, respectively), vehicle-injected dams allowed access to food ad libitum (SAL) or pair-fed with the COC 40 dams (SPF 40), animals pretreated with the short-acting alpha-adrenergic antagonist phentolamine prior to each cocaine injection (P COC 40), and animals administered phentolamine prior to saline (PHENT). COC 40, P COC 40, and SPF 40 dams demonstrated the lowest percentage weight gain during gestation. The surrogate-fostered offspring of COC 40, P COC 40, and SPF 40 dams demonstrated transient brain and body growth retardation on postnatal days (P)1 and P9 when compared to pups born to SAL dams. We conducted behavioral tests which allowed us to dissociate the indirect effect of cocaine-induced malnutrition from a direct effect of prenatal cocaine administration in altering postnatal behavior. Pups from all groups were tested for first-order Pavlovian conditioning on P9 or P12 or for the ability to ignore redundant information in a blocking paradigm on P50. Unlike the SPF 40, PHENT, and SAL controls, COC 40 and P COC 40 mice were unable to acquire an aversion to an odor previously paired with shock on P9, a learning deficit that resolved by P12. However, on P50, COC 40 mice and, to a lesser extent, P COC 40 and SPF 40 mice demonstrated a persistent behavioral deficit in our blocking paradigm, which may reflect alterations in selective attention. We discuss how these findings in our rodent model have developmental implications for human infants exposed to cocaine in utero.

Cyclosporine-resistant, Rab27a-independent Mobilization of Intracellular Preformed CD40L Mediates Antigen-specific T Cell Help In Vitro

PubMed Central

Koguchi, Yoshinobu; Gardell, Jennifer L.; Thauland, Timothy J.; Parker, David C.

2011-01-01

CD40L is critically important for the initiation and maintenance of adaptive immune responses. It is generally thought that CD40L expression in CD4+ T cells is regulated transcriptionally and made from new mRNA following antigen recognition. However, recent studies with two-photon microscopy revealed that the majority of cognate interactions between effector CD4+ T cells and APCs are too short for de novo synthesis of CD40L. Given that effector and memory CD4+ T cells store preformed CD40L (pCD40L) in lysosomal compartments and that pCD40L comes to the cell surface within minutes of antigenic stimulation, we and others have proposed that pCD40L might mediate T cell-dependent activation of cognate APCs during brief encounters in vivo. However, it has not been shown that this relatively small amount of pCD40L is sufficient to activate APCs, owing to the difficulty of separating the effects of pCD40L from those of de novo CD40L and other cytokines in vitro. Here we show that pCD40L surface mobilization is resistant to cyclosporine or FK506 treatment, while de novo CD40L and cytokine expression are completely inhibited. These drugs thus provide a tool to dissect the role of pCD40L in APC activation. We find that pCD40L mediates selective activation of cognate but not bystander APCs in vitro and that mobilization of pCD40L does not depend on Rab27a, which is required for mobilization of lytic granules. Therefore, effector CD4+ T cells deliver pCD40L specifically to APCs on the same time scale as the lethal hit of CTLs but with distinct molecular machinery. PMID:21677130

40 CFR 427.40 - Applicability; description of the asbestos paper (elastomeric binder) subcategory.

Code of Federal Regulations, 2014 CFR

2014-07-01

... asbestos paper (elastomeric binder) subcategory. 427.40 Section 427.40 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) EFFLUENT GUIDELINES AND STANDARDS (CONTINUED) ASBESTOS MANUFACTURING POINT SOURCE CATEGORY Asbestos Paper (Elastomeric Binder) Subcategory § 427.40 Applicability...

40 CFR 427.40 - Applicability; description of the asbestos paper (elastomeric binder) subcategory.

Code of Federal Regulations, 2012 CFR

2012-07-01

... asbestos paper (elastomeric binder) subcategory. 427.40 Section 427.40 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) EFFLUENT GUIDELINES AND STANDARDS (CONTINUED) ASBESTOS MANUFACTURING POINT SOURCE CATEGORY Asbestos Paper (Elastomeric Binder) Subcategory § 427.40 Applicability...

40 CFR 427.40 - Applicability; description of the asbestos paper (elastomeric binder) subcategory.

Code of Federal Regulations, 2013 CFR

2013-07-01

... asbestos paper (elastomeric binder) subcategory. 427.40 Section 427.40 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) EFFLUENT GUIDELINES AND STANDARDS (CONTINUED) ASBESTOS MANUFACTURING POINT SOURCE CATEGORY Asbestos Paper (Elastomeric Binder) Subcategory § 427.40 Applicability...

40 CFR 180.546 - Mefenoxam; tolerances for residues.

Code of Federal Regulations, 2010 CFR

2010-07-01

... commodities: Commodity Parts per million Artichoke, globe 0.05 Atemoya 0.20 Canistel 0.40 Custard apple 0.20... Sapote, black 0.40 Sapote, mamey 0.40 Star apple 0.40 Starfruit 0.20 Sugar apple 0.20 (b) Section 18...

Analysis of the association between CD40 and CD40 ligand polymorphisms and systemic sclerosis.

PubMed

Teruel, María; Simeon, Carmen P; Broen, Jasper; Vonk, Madelon C; Carreira, Patricia; Camps, Maria Teresa; García-Portales, Rosa; Delgado-Frías, Esmeralda; Gallego, Maria; Espinosa, Gerard; Beretta, Lorenzo; Airó, Paolo; Lunardi, Claudio; Riemekasten, Gabriela; Witte, Torsten; Krieg, Thomas; Kreuter, Alexander; Distler, Jörg H W; Hunzelmann, Nicolas; Koeleman, Bobby P; Voskuyl, Alexandre E; Schuerwegh, Annemie J; González-Gay, Miguel Angel; Radstake, Timothy R D J; Martin, Javier

2012-06-25

The aim of the present study was to investigate the possible role of CD40 and CD40 ligand (CD40LG) genes in the susceptibility and phenotype expression of systemic sclerosis (SSc). In total, 2,670 SSc patients and 3,245 healthy individuals from four European populations (Spain, Germany, The Netherlands, and Italy) were included in the study. Five single-nucleotide polymorphisms (SNPs) of CD40 (rs1883832, rs4810485, rs1535045) and CD40LG (rs3092952, rs3092920) were genotyped by using a predesigned TaqMan allele-discrimination assay technology. Meta-analysis was assessed to determine whether an association exists between the genetic variants and SSc or its main clinical subtypes. No evidence of association between CD40 and CD40LG genes variants and susceptibility to SSc was observed. Similarly, no significant statistical differences were observed when SSc patients were stratified by the clinical subtypes, the serologic features, and pulmonary fibrosis. Our results do not suggest an important role of CD40 and CD40LG gene polymorphisms in the susceptibility to or clinical expression of SSc.

The influence of SV40 immortalization of human fibroblasts on p53-dependent radiation responses

NASA Technical Reports Server (NTRS)

Kohli, M.; Jorgensen, T. J.

1999-01-01

The simian virus 40 large tumor antigen (SV40 Tag) has been ascribed many functions critical to viral propagation, including binding to the mammalian tumor suppressor p53. Recent studies have demonstrated that SV40-transformed murine cells have functional p53. The status of p53 in SV40-immortalized human cells, however, has not been characterized. We have found that in response to ionizing radiation, p53-dependent p21 transactivation activity is present, albeit reduced, in SV40-immortalized cells and that this activity can be further reduced with either dominant negative p53 expression or higher SV40 Tag expression. Furthermore, overexpression of p53 in SV40-immortalized ataxia-telangiectasia (A-T) cells restores p53-dependent p21 induction to typical A-T levels. All SV40-immortalized cell lines exhibited an absence of G1 arrest. Moreover, all SV40-immortalized cell lines exhibited increased apoptosis relative to primary cells in response to ionizing radiation, suggesting that SV40 immortalization results in a unique phenotype with regard to DNA damage responses. Copyright 1999 Academic Press.

10 CFR 40.35 - Conditions of specific licenses issued pursuant to § 40.34.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 10 Energy 1 2010-01-01 2010-01-01 false Conditions of specific licenses issued pursuant to § 40.34. 40.35 Section 40.35 Energy NUCLEAR REGULATORY COMMISSION DOMESTIC LICENSING OF SOURCE MATERIAL... § 40.25 and a copy of Form NRC 244 to each person to whom he transfers source material in a product or...

Simian virus 40 T-antigen-related cell surface antigen: serological demonstration on simian virus 40-transformed monolayer cells in situ.

PubMed Central

Deppert, W; Hanke, K; Henning, R

1980-01-01

Simian virus 40 (SV40)-transformed monolayer cells were analyzed in situ by indirect immunofluorescence microscopy for the postulated cell surface location of SV40 T-antigen-related molecules. With antisera prepared against purified, sodium dodecyl sulfate-denatured SV40 T-antigen, positive surface staining was obtained when the cells had been treated with formaldehyde before immunofluorescence analysis. In contrast, living SV40-transformed cells analyzed in monolayer were surface fluorescence negative. The fixation procedure developed in this study combined with a double staining immunofluorescence technique allowed the simultaneous analysis of the same cells for the expression of both SV40 T-antigen-related surface antigen and nuclear T-antigen. The localization of SV40 T-antigen-related surface antigen on the outer surface of the plasma membrane of formaldehyde-fixed SV40-transformed cells was demonstrated directly by the protein A-mediated binding of Staphylococcus aureus bacteria on formaldehyde-fixed SV40-transformed cells precoated with antiserum against sodium dodecyl sulfate-denatured T-antigen. Both cell surface staining and S. aureus binding were found to be highly specific for SV40 T-antigen-related binding sites. These results indicate that T-antigen-related molecules in a cryptic form are located on the surface of SV40-transformed monolayer cells and can be detected in situ after modification of the cell surface architecture. Images PMID:6255189

Vitamin D regulation of OX40 ligand in immune responses to Aspergillus fumigatus.

PubMed

Nguyen, Nikki Lynn Hue; Chen, Kong; McAleer, Jeremy; Kolls, Jay K

2013-05-01

OX40 ligand (OX40L) is a costimulatory molecule involved in Th2 allergic responses. It has been shown that vitamin D deficiency is associated with increased OX40L expression in peripheral CD11c(+) cells and controls Th2 responses to Aspergillus fumigatus in vitro in cystic fibrosis (CF) patients with allergic bronchopulmonary aspergillosis (ABPA). To investigate if vitamin D deficiency regulated OX40L and Th2 responses in vivo, we examined the effect of nutritional vitamin D deficiency on costimulatory molecules in CD11c(+) cells and A. fumigatus-induced Th2 responses. Vitamin D-deficient mice showed increased expression of OX40L on lung CD11c(+) cells, and OX40L was critical for enhanced Th2 responses to A. fumigatus in vivo. In in vitro assays, vitamin D treatment led to vitamin D receptor (VDR) binding in the promoter region of OX40L and significantly decreased the promoter activity of the OX40L promoter. In addition, vitamin D altered NF-κB p50 binding in the OX40L promoter that may be responsible for repression of OX40L expression. These data show that vitamin D can act directly on OX40L, which impacts Th2 responses and supports the therapeutic use of vitamin D in diseases regulated by OX40L.

40 CFR 413.40 - Applicability: Description of the anodizing subcategory.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 40 Protection of Environment 28 2010-07-01 2010-07-01 true Applicability: Description of the anodizing subcategory. 413.40 Section 413.40 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) EFFLUENT GUIDELINES AND STANDARDS ELECTROPLATING POINT SOURCE CATEGORY Anodizing Subcategory...

40 CFR 427.40 - Applicability; description of the asbestos paper (elastomeric binder) subcategory.

Code of Federal Regulations, 2011 CFR

2011-07-01

... asbestos paper (elastomeric binder) subcategory. 427.40 Section 427.40 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) EFFLUENT GUIDELINES AND STANDARDS ASBESTOS MANUFACTURING POINT SOURCE CATEGORY Asbestos Paper (Elastomeric Binder) Subcategory § 427.40 Applicability; description of...

40 CFR 427.40 - Applicability; description of the asbestos paper (elastomeric binder) subcategory.

Code of Federal Regulations, 2010 CFR

2010-07-01

... asbestos paper (elastomeric binder) subcategory. 427.40 Section 427.40 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) EFFLUENT GUIDELINES AND STANDARDS ASBESTOS MANUFACTURING POINT SOURCE CATEGORY Asbestos Paper (Elastomeric Binder) Subcategory § 427.40 Applicability; description of...

40 CFR 180.546 - Mefenoxam; tolerances for residues.

Code of Federal Regulations, 2012 CFR

2012-07-01

... Canistel 0.40 Custard apple 0.20 Herbs, dried 55 Herbs, fresh 8.0 Kiwifruit 0.10 Mango 0.40 Onion, bulb..., mamey 0.40 Spinach 10 Star apple 0.40 Starfruit 0.20 Sugar apple 0.20 (b) Section 18 emergency...

40 CFR 180.546 - Mefenoxam; tolerances for residues.

Code of Federal Regulations, 2014 CFR

2014-07-01

... Canistel 0.40 Custard apple 0.20 Herbs, dried 55 Herbs, fresh 8.0 Kiwifruit 0.10 Mango 0.40 Onion, bulb..., mamey 0.40 Spinach 10 Star apple 0.40 Starfruit 0.20 Sugar apple 0.20 (b) Section 18 emergency...

40 CFR 180.546 - Mefenoxam; tolerances for residues.

Code of Federal Regulations, 2013 CFR

2013-07-01

... Canistel 0.40 Custard apple 0.20 Herbs, dried 55 Herbs, fresh 8.0 Kiwifruit 0.10 Mango 0.40 Onion, bulb..., mamey 0.40 Spinach 10 Star apple 0.40 Starfruit 0.20 Sugar apple 0.20 (b) Section 18 emergency...

40 CFR 180.546 - Mefenoxam; tolerances for residues.

Code of Federal Regulations, 2011 CFR

2011-07-01

... Canistel 0.40 Custard apple 0.20 Herbs, dried 55 Herbs, fresh 8.0 Kiwifruit 0.10 Mango 0.40 Onion, bulb..., mamey 0.40 Spinach 10 Star apple 0.40 Starfruit 0.20 Sugar apple 0.20 (b) Section 18 emergency...

40 CFR 31.40 - Monitoring and reporting program performance.

Code of Federal Regulations, 2010 CFR

2010-07-01

... performance. 31.40 Section 31.40 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY GRANTS AND OTHER FEDERAL ASSISTANCE UNIFORM ADMINISTRATIVE REQUIREMENTS FOR GRANTS AND COOPERATIVE AGREEMENTS TO STATE AND LOCAL GOVERNMENTS Post-Award Requirements Reports, Records, Retention, and Enforcement § 31.40...

40 CFR 415.40 - Applicability; description of the calcium chloride production subcategory.

Code of Federal Regulations, 2011 CFR

2011-07-01

... calcium chloride production subcategory. 415.40 Section 415.40 Protection of Environment ENVIRONMENTAL... SOURCE CATEGORY Calcium Chloride Production Subcategory § 415.40 Applicability; description of the calcium chloride production subcategory. The provisions of this subpart are applicable to discharges...

40 CFR 426.40 - Applicability; description of the plate glass manufacturing subcategory.

Code of Federal Regulations, 2010 CFR

2010-07-01

... plate glass manufacturing subcategory. 426.40 Section 426.40 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) EFFLUENT GUIDELINES AND STANDARDS GLASS MANUFACTURING POINT SOURCE CATEGORY Plate Glass Manufacturing Subcategory § 426.40 Applicability; description of the plate glass...

40 CFR 426.40 - Applicability; description of the plate glass manufacturing subcategory.

Code of Federal Regulations, 2011 CFR

2011-07-01

... plate glass manufacturing subcategory. 426.40 Section 426.40 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) EFFLUENT GUIDELINES AND STANDARDS GLASS MANUFACTURING POINT SOURCE CATEGORY Plate Glass Manufacturing Subcategory § 426.40 Applicability; description of the plate glass...

40 CFR 466.40 - Applicability; description of the copper basis material subcategory.

Code of Federal Regulations, 2010 CFR

2010-07-01

... copper basis material subcategory. 466.40 Section 466.40 Protection of Environment ENVIRONMENTAL... Copper Basis Material Subcategory § 466.40 Applicability; description of the copper basis material... into publicly owned treatment works from porcelain enameling of copper basis materials. ...

40 CFR 466.40 - Applicability; description of the copper basis material subcategory.

Code of Federal Regulations, 2011 CFR

2011-07-01

... copper basis material subcategory. 466.40 Section 466.40 Protection of Environment ENVIRONMENTAL... Copper Basis Material Subcategory § 466.40 Applicability; description of the copper basis material... into publicly owned treatment works from porcelain enameling of copper basis materials. ...

40 CFR 458.40 - Applicability; description of the carbon black lamp process subcategory.

Code of Federal Regulations, 2011 CFR

2011-07-01

... carbon black lamp process subcategory. 458.40 Section 458.40 Protection of Environment ENVIRONMENTAL... CATEGORY Carbon Black Lamp Process Subcategory § 458.40 Applicability; description of the carbon black lamp... production of carbon black by the lamp process. ...

40 CFR 410.40 - Applicability; description of the woven fabric finishing subcategory.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 40 Protection of Environment 28 2010-07-01 2010-07-01 true Applicability; description of the woven fabric finishing subcategory. 410.40 Section 410.40 Protection of Environment ENVIRONMENTAL PROTECTION... proofing, soil repellency application and a special finish application. ...

40 CFR 415.40 - Applicability; description of the calcium chloride production subcategory.

Code of Federal Regulations, 2010 CFR

2010-07-01

... calcium chloride production subcategory. 415.40 Section 415.40 Protection of Environment ENVIRONMENTAL... SOURCE CATEGORY Calcium Chloride Production Subcategory § 415.40 Applicability; description of the calcium chloride production subcategory. The provisions of this subpart are applicable to discharges...

40 CFR 40.115-1 - Construction.

Code of Federal Regulations, 2011 CFR

2011-07-01

... investigations and studies, surveys, designs, plans, working drawings, specifications, procedures, and other... 40 Protection of Environment 1 2011-07-01 2011-07-01 false Construction. 40.115-1 Section 40.115-1 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY GRANTS AND OTHER FEDERAL ASSISTANCE RESEARCH AND...

40 CFR 40.115-1 - Construction.

Code of Federal Regulations, 2010 CFR

2010-07-01

... investigations and studies, surveys, designs, plans, working drawings, specifications, procedures, and other... 40 Protection of Environment 1 2010-07-01 2010-07-01 false Construction. 40.115-1 Section 40.115-1 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY GRANTS AND OTHER FEDERAL ASSISTANCE RESEARCH AND...

40 CFR 40.115-1 - Construction.

Code of Federal Regulations, 2013 CFR

2013-07-01

... investigations and studies, surveys, designs, plans, working drawings, specifications, procedures, and other... 40 Protection of Environment 1 2013-07-01 2013-07-01 false Construction. 40.115-1 Section 40.115-1 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY GRANTS AND OTHER FEDERAL ASSISTANCE RESEARCH AND...

40 CFR 40.115-1 - Construction.

Code of Federal Regulations, 2014 CFR

2014-07-01

... investigations and studies, surveys, designs, plans, working drawings, specifications, procedures, and other... 40 Protection of Environment 1 2014-07-01 2014-07-01 false Construction. 40.115-1 Section 40.115-1 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY GRANTS AND OTHER FEDERAL ASSISTANCE RESEARCH AND...

40 CFR 40.115-1 - Construction.

Code of Federal Regulations, 2012 CFR

2012-07-01

... investigations and studies, surveys, designs, plans, working drawings, specifications, procedures, and other... 40 Protection of Environment 1 2012-07-01 2012-07-01 false Construction. 40.115-1 Section 40.115-1 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY GRANTS AND OTHER FEDERAL ASSISTANCE RESEARCH AND...

40 CFR 467.40 - Applicability; description of the forging subcategory.

Code of Federal Regulations, 2010 CFR

2010-07-01

... forging subcategory. 467.40 Section 467.40 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) EFFLUENT GUIDELINES AND STANDARDS ALUMINUM FORMING POINT SOURCE CATEGORY Forging Subcategory § 467.40 Applicability; description of the forging subcategory. This subpart applies to discharges of...

40 CFR 415.40 - Applicability; description of the calcium chloride production subcategory.

Code of Federal Regulations, 2012 CFR

2012-07-01

... calcium chloride production subcategory. 415.40 Section 415.40 Protection of Environment ENVIRONMENTAL... SOURCE CATEGORY Calcium Chloride Production Subcategory § 415.40 Applicability; description of the calcium chloride production subcategory. The provisions of this subpart are applicable to discharges...

40 CFR 415.40 - Applicability; description of the calcium chloride production subcategory.

Code of Federal Regulations, 2013 CFR

2013-07-01

... calcium chloride production subcategory. 415.40 Section 415.40 Protection of Environment ENVIRONMENTAL... SOURCE CATEGORY Calcium Chloride Production Subcategory § 415.40 Applicability; description of the calcium chloride production subcategory. The provisions of this subpart are applicable to discharges...

40 CFR 415.40 - Applicability; description of the calcium chloride production subcategory.

Code of Federal Regulations, 2014 CFR

2014-07-01

... calcium chloride production subcategory. 415.40 Section 415.40 Protection of Environment ENVIRONMENTAL... SOURCE CATEGORY Calcium Chloride Production Subcategory § 415.40 Applicability; description of the calcium chloride production subcategory. The provisions of this subpart are applicable to discharges...

40 CFR 405.40 - Applicability; description of the butter subcategory.

Code of Federal Regulations, 2014 CFR

2014-07-01

... butter subcategory. 405.40 Section 405.40 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) EFFLUENT GUIDELINES AND STANDARDS DAIRY PRODUCTS PROCESSING POINT SOURCE CATEGORY Butter Subcategory § 405.40 Applicability; description of the butter subcategory. The provisions of this subpart are...

40 CFR 405.40 - Applicability; description of the butter subcategory.

Code of Federal Regulations, 2013 CFR

2013-07-01

... butter subcategory. 405.40 Section 405.40 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) EFFLUENT GUIDELINES AND STANDARDS DAIRY PRODUCTS PROCESSING POINT SOURCE CATEGORY Butter Subcategory § 405.40 Applicability; description of the butter subcategory. The provisions of this subpart are...

40 CFR 405.40 - Applicability; description of the butter subcategory.

Code of Federal Regulations, 2010 CFR

2010-07-01

... butter subcategory. 405.40 Section 405.40 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) EFFLUENT GUIDELINES AND STANDARDS DAIRY PRODUCTS PROCESSING POINT SOURCE CATEGORY Butter Subcategory § 405.40 Applicability; description of the butter subcategory. The provisions of this subpart are...

40 CFR 405.40 - Applicability; description of the butter subcategory.

Code of Federal Regulations, 2012 CFR

2012-07-01

... butter subcategory. 405.40 Section 405.40 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) EFFLUENT GUIDELINES AND STANDARDS DAIRY PRODUCTS PROCESSING POINT SOURCE CATEGORY Butter Subcategory § 405.40 Applicability; description of the butter subcategory. The provisions of this subpart are...

40 CFR 405.40 - Applicability; description of the butter subcategory.

Code of Federal Regulations, 2011 CFR

2011-07-01

... butter subcategory. 405.40 Section 405.40 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) EFFLUENT GUIDELINES AND STANDARDS DAIRY PRODUCTS PROCESSING POINT SOURCE CATEGORY Butter Subcategory § 405.40 Applicability; description of the butter subcategory. The provisions of this subpart are...

Outcomes of labor epidural analgesia among women aged over 40: A single-institution retrospective study.

PubMed

Okazaki, Atsuko; Fukushima, Risa; Nagashima, Sayuri; Mazda, Yusuke; Tamura, Kazumi; Terui, Katsuo; Tanaka, Motoshi

2016-12-01

The purpose of this study was to investigate the effects of labor epidural analgesia (LEA) on maternal and neonatal outcomes among parturients aged 40 years or older. We retrospectively reviewed medical records of all laboring, singleton and cephalic deliveries at ≥36 weeks' gestation at the Saitama Medical Center from April 2003 to September 2012. Women aged ≥40 years who received LEA (≥40 with LEA group) were compared with women aged ≥40 years who delivered without LEA (≥40 without LEA group) and women <40 years who received LEA (<40 with LEA group). Extracted outcomes included mode of delivery, oxytocin augmentation, duration of labor, amount of estimated blood loss, umbilical artery pH, Apgar scores, and neonatal intensive care unit admission. This study included 4441 women. There were 74 women in the ≥40 with LEA group, 369 in the ≥40 without LEA group, and 601 in the <40 with LEA group. The maternal outcomes of emergency cesarean delivery rate (9.5%, 12.5%, 9.0%), instrumental delivery rate (33.8%, 10.3%, 28.3%), duration of labor (521 min, 321 min, 565 min), and estimated blood loss (524 g, 351 g, 412 g) were reported for the ≥40 with LEA, ≥40 without LEA, and <40 with LEA groups, respectively. Neonatal outcomes were not different between these groups. LEA use was not associated with emergency cesarean delivery in the multivariable analysis. Our study showed that parturients aged ≥40 with LEA can expect similar LEA-associated labor outcomes to younger parturients with LEA. © 2016 Japan Society of Obstetrics and Gynecology.

A cationic, C-terminal patch and structural rearrangements in Ebola virus matrix VP40 protein control its interactions with phosphatidylserine.

PubMed

Del Vecchio, Kathryn; Frick, Cary T; Gc, Jeevan B; Oda, Shun-Ichiro; Gerstman, Bernard S; Saphire, Erica Ollmann; Chapagain, Prem P; Stahelin, Robert V

2018-03-02

Ebola virus (EBOV) is a filamentous lipid-enveloped virus that causes hemorrhagic fever with a high fatality rate. Viral protein 40 (VP40) is the major EBOV matrix protein and regulates viral budding from the plasma membrane. VP40 is a transformer/morpheein that can structurally rearrange its native homodimer into either a hexameric filament that facilitates viral budding or an RNA-binding octameric ring that regulates viral transcription. VP40 associates with plasma-membrane lipids such as phosphatidylserine (PS), and this association is critical to budding from the host cell. However, it is poorly understood how different VP40 structures interact with PS, what essential residues are involved in this association, and whether VP40 has true selectivity for PS among different glycerophospholipid headgroups. In this study, we used lipid-binding assays, MD simulations, and cellular imaging to investigate the molecular basis of VP40-PS interactions and to determine whether different VP40 structures ( i.e. monomer, dimer, and octamer) can interact with PS-containing membranes. Results from quantitative analysis indicated that VP40 associates with PS vesicles via a cationic patch in the C-terminal domain (Lys 224, 225 and Lys 274, 275 ). Substitutions of these residues with alanine reduced PS-vesicle binding by >40-fold and abrogated VP40 localization to the plasma membrane. Dimeric VP40 had 2-fold greater affinity for PS-containing membranes than the monomer, whereas binding of the VP40 octameric ring was reduced by nearly 10-fold. Taken together, these results suggest the different VP40 structures known to form in the viral life cycle harbor different affinities for PS-containing membranes. © 2018 by The American Society for Biochemistry and Molecular Biology, Inc.

Human mesothelial cells are unusually susceptible to simian virus 40-mediated transformation and asbestos cocarcinogenicity

PubMed Central

Bocchetta, Maurizio; Di Resta, Ilaria; Powers, Amy; Fresco, Raoul; Tosolini, Alessandra; Testa, Joseph R.; Pass, Harvey I.; Rizzo, Paola; Carbone, Michele

2000-01-01

Mesothelioma, a malignancy associated with asbestos, has been recently linked to simian virus 40 (SV40). We found that infection of human mesothelial cells by SV40 is very different from the semipermissive infection thought to be characteristic of human cells. Mesothelial cells are uniformly infected but not lysed by SV40, a mechanism related to p53, and undergo cell transformation at an extremely high rate. Exposure of mesothelial cells to asbestos complemented SV40 mutants in transformation. Our data provide a mechanistic explanation for the ability of SV40 to transform mesothelial cells preferentially and indicate that asbestos and SV40 may be cocarcinogens. PMID:10954737

Simian virus 40 large T antigen associates with cyclin A and p33cdk2.

PubMed

Adamczewski, J P; Gannon, J V; Hunt, T

1993-11-01

In this paper we provide evidence that a fraction of large T antigen of simian virus 40 (SV40) interacts with cyclin A and p33cdk2 in both virus-infected and stably transformed cells. Immunoprecipitates of SV40 large T antigen from SV40-infected or SV40 large-T-antigen-transformed cells contain cyclin A, p33cdk2, and histone H1 kinase activity. Conversely, immunoprecipitates of cyclin A from these cells contain SV40 large T antigen. In this respect, SV40 large T antigen has properties similar to those of the E1A oncogene of adenoviruses and the E7 oncogene of human papillomaviruses.

40 CFR 255.40 - Notification of status.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 40 Protection of Environment 24 2010-07-01 2010-07-01 false Notification of status. 255.40 Section 255.40 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) SOLID WASTES... identification of regions and agencies as consensus is reached. (b) The appropriate level of detail and the...

40 CFR 471.40 - Applicability; description of the precious metals forming subcategory.

Code of Federal Regulations, 2010 CFR

2010-07-01

... precious metals forming subcategory. 471.40 Section 471.40 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) EFFLUENT GUIDELINES AND STANDARDS NONFERROUS METALS FORMING AND METAL POWDERS POINT SOURCE CATEGORY Precious Metals Forming Subcategory § 471.40 Applicability; description of the...

40 CFR 407.40 - Applicability; description of the frozen potato products subcategory.

Code of Federal Regulations, 2010 CFR

2010-07-01

... frozen potato products subcategory. 407.40 Section 407.40 Protection of Environment ENVIRONMENTAL... PROCESSING POINT SOURCE CATEGORY Frozen Potato Products Subcategory § 407.40 Applicability; description of the frozen potato products subcategory. The provisions of this subpart are applicable to discharges...

40 CFR 435.40 - Applicability; description of the coastal subcategory.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 40 Protection of Environment 29 2010-07-01 2010-07-01 false Applicability; description of the coastal subcategory. 435.40 Section 435.40 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) EFFLUENT GUIDELINES AND STANDARDS OIL AND GAS EXTRACTION POINT SOURCE CATEGORY Coastal...

40 CFR 435.40 - Applicability; description of the coastal subcategory.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 40 Protection of Environment 30 2011-07-01 2011-07-01 false Applicability; description of the coastal subcategory. 435.40 Section 435.40 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) EFFLUENT GUIDELINES AND STANDARDS OIL AND GAS EXTRACTION POINT SOURCE CATEGORY Coastal...

40 CFR 420.40 - Applicability; description of the steelmaking subcategory.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 40 Protection of Environment 28 2010-07-01 2010-07-01 true Applicability; description of the steelmaking subcategory. 420.40 Section 420.40 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) EFFLUENT GUIDELINES AND STANDARDS IRON AND STEEL MANUFACTURING POINT SOURCE CATEGORY Steelmaking...

40 CFR 414.40 - Applicability; description of the thermoplastic resins subcategory.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 40 Protection of Environment 29 2014-07-01 2012-07-01 true Applicability; description of the thermoplastic resins subcategory. 414.40 Section 414.40 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) EFFLUENT GUIDELINES AND STANDARDS ORGANIC CHEMICALS, PLASTICS, AND SYNTHETIC FIBERS...

40 CFR 414.40 - Applicability; description of the thermoplastic resins subcategory.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 40 Protection of Environment 29 2011-07-01 2009-07-01 true Applicability; description of the thermoplastic resins subcategory. 414.40 Section 414.40 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) EFFLUENT GUIDELINES AND STANDARDS ORGANIC CHEMICALS, PLASTICS, AND SYNTHETIC FIBERS...

40 CFR 414.40 - Applicability; description of the thermoplastic resins subcategory.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 40 Protection of Environment 30 2013-07-01 2012-07-01 true Applicability; description of the thermoplastic resins subcategory. 414.40 Section 414.40 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) EFFLUENT GUIDELINES AND STANDARDS ORGANIC CHEMICALS, PLASTICS, AND SYNTHETIC FIBERS...

40 CFR 414.40 - Applicability; description of the thermoplastic resins subcategory.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 40 Protection of Environment 30 2012-07-01 2012-07-01 false Applicability; description of the thermoplastic resins subcategory. 414.40 Section 414.40 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) EFFLUENT GUIDELINES AND STANDARDS ORGANIC CHEMICALS, PLASTICS, AND SYNTHETIC FIBERS...

40 CFR 417.40 - Applicability; description of the glycerine concentration subcategory.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 40 Protection of Environment 28 2010-07-01 2010-07-01 true Applicability; description of the glycerine concentration subcategory. 417.40 Section 417.40 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) EFFLUENT GUIDELINES AND STANDARDS SOAP AND DETERGENT MANUFACTURING POINT SOURCE...

40 CFR 417.40 - Applicability; description of the glycerine concentration subcategory.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 40 Protection of Environment 29 2011-07-01 2009-07-01 true Applicability; description of the glycerine concentration subcategory. 417.40 Section 417.40 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) EFFLUENT GUIDELINES AND STANDARDS SOAP AND DETERGENT MANUFACTURING POINT SOURCE...

40 CFR 417.40 - Applicability; description of the glycerine concentration subcategory.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 40 Protection of Environment 30 2013-07-01 2012-07-01 true Applicability; description of the glycerine concentration subcategory. 417.40 Section 417.40 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) EFFLUENT GUIDELINES AND STANDARDS SOAP AND DETERGENT MANUFACTURING POINT SOURCE...

40 CFR 417.40 - Applicability; description of the glycerine concentration subcategory.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 40 Protection of Environment 29 2014-07-01 2012-07-01 true Applicability; description of the glycerine concentration subcategory. 417.40 Section 417.40 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) EFFLUENT GUIDELINES AND STANDARDS SOAP AND DETERGENT MANUFACTURING POINT SOURCE...

40 CFR 417.40 - Applicability; description of the glycerine concentration subcategory.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 40 Protection of Environment 30 2012-07-01 2012-07-01 false Applicability; description of the glycerine concentration subcategory. 417.40 Section 417.40 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) EFFLUENT GUIDELINES AND STANDARDS SOAP AND DETERGENT MANUFACTURING POINT SOURCE...

40 CFR 440.40 - Applicability; description of the mercury ore subcategory.

Code of Federal Regulations, 2014 CFR

2014-07-01

... mercury ore subcategory. 440.40 Section 440.40 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) EFFLUENT GUIDELINES AND STANDARDS (CONTINUED) ORE MINING AND DRESSING POINT SOURCE CATEGORY Mercury Ore Subcategory § 440.40 Applicability; description of the mercury ore subcategory. The provisions...

40 CFR 440.40 - Applicability; description of the mercury ore subcategory.

Code of Federal Regulations, 2013 CFR

2013-07-01

... mercury ore subcategory. 440.40 Section 440.40 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) EFFLUENT GUIDELINES AND STANDARDS (CONTINUED) ORE MINING AND DRESSING POINT SOURCE CATEGORY Mercury Ore Subcategory § 440.40 Applicability; description of the mercury ore subcategory. The provisions...

40 CFR 440.40 - Applicability; description of the mercury ore subcategory.

Code of Federal Regulations, 2012 CFR

2012-07-01

... mercury ore subcategory. 440.40 Section 440.40 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) EFFLUENT GUIDELINES AND STANDARDS (CONTINUED) ORE MINING AND DRESSING POINT SOURCE CATEGORY Mercury Ore Subcategory § 440.40 Applicability; description of the mercury ore subcategory. The provisions...

40 CFR 418.40 - Applicability; description of the ammonium nitrate subcategory.

Code of Federal Regulations, 2012 CFR

2012-07-01

... ammonium nitrate subcategory. 418.40 Section 418.40 Protection of Environment ENVIRONMENTAL PROTECTION... Ammonium Nitrate Subcategory § 418.40 Applicability; description of the ammonium nitrate subcategory. The provisions of this subpart are applicable to discharges resulting from the manufacture of ammonium nitrate...

40 CFR 418.40 - Applicability; description of the ammonium nitrate subcategory.

Code of Federal Regulations, 2011 CFR

2011-07-01

... ammonium nitrate subcategory. 418.40 Section 418.40 Protection of Environment ENVIRONMENTAL PROTECTION... Ammonium Nitrate Subcategory § 418.40 Applicability; description of the ammonium nitrate subcategory. The provisions of this subpart are applicable to discharges resulting from the manufacture of ammonium nitrate...

40 CFR 418.40 - Applicability; description of the ammonium nitrate subcategory.

Code of Federal Regulations, 2013 CFR

2013-07-01

... ammonium nitrate subcategory. 418.40 Section 418.40 Protection of Environment ENVIRONMENTAL PROTECTION... Ammonium Nitrate Subcategory § 418.40 Applicability; description of the ammonium nitrate subcategory. The provisions of this subpart are applicable to discharges resulting from the manufacture of ammonium nitrate...

40 CFR 418.40 - Applicability; description of the ammonium nitrate subcategory.

Code of Federal Regulations, 2014 CFR

2014-07-01

... ammonium nitrate subcategory. 418.40 Section 418.40 Protection of Environment ENVIRONMENTAL PROTECTION... Ammonium Nitrate Subcategory § 418.40 Applicability; description of the ammonium nitrate subcategory. The provisions of this subpart are applicable to discharges resulting from the manufacture of ammonium nitrate...

40 CFR 82.40 - Technician training and certification.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 40 Protection of Environment 18 2013-07-01 2013-07-01 false Technician training and certification. 82.40 Section 82.40 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR..., videos or a hands-on demonstration. (2) Test subject material. The certification tests must adequately...

40 CFR 82.40 - Technician training and certification.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 40 Protection of Environment 18 2014-07-01 2014-07-01 false Technician training and certification. 82.40 Section 82.40 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR..., videos or a hands-on demonstration. (2) Test subject material. The certification tests must adequately...

40 CFR 82.40 - Technician training and certification.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 40 Protection of Environment 18 2012-07-01 2012-07-01 false Technician training and certification. 82.40 Section 82.40 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR..., videos or a hands-on demonstration. (2) Test subject material. The certification tests must adequately...

40 CFR 407.40 - Applicability; description of the frozen potato products subcategory.

Code of Federal Regulations, 2013 CFR

2013-07-01

... frozen potato products subcategory. 407.40 Section 407.40 Protection of Environment ENVIRONMENTAL... PROCESSING POINT SOURCE CATEGORY Frozen Potato Products Subcategory § 407.40 Applicability; description of the frozen potato products subcategory. The provisions of this subpart are applicable to discharges...

40 CFR 407.40 - Applicability; description of the frozen potato products subcategory.

Code of Federal Regulations, 2014 CFR

2014-07-01

... frozen potato products subcategory. 407.40 Section 407.40 Protection of Environment ENVIRONMENTAL... PROCESSING POINT SOURCE CATEGORY Frozen Potato Products Subcategory § 407.40 Applicability; description of the frozen potato products subcategory. The provisions of this subpart are applicable to discharges...

40 CFR 407.40 - Applicability; description of the frozen potato products subcategory.

Code of Federal Regulations, 2012 CFR

2012-07-01

... frozen potato products subcategory. 407.40 Section 407.40 Protection of Environment ENVIRONMENTAL... PROCESSING POINT SOURCE CATEGORY Frozen Potato Products Subcategory § 407.40 Applicability; description of the frozen potato products subcategory. The provisions of this subpart are applicable to discharges...

40 CFR 407.40 - Applicability; description of the frozen potato products subcategory.

Code of Federal Regulations, 2011 CFR

2011-07-01

... frozen potato products subcategory. 407.40 Section 407.40 Protection of Environment ENVIRONMENTAL... PROCESSING POINT SOURCE CATEGORY Frozen Potato Products Subcategory § 407.40 Applicability; description of the frozen potato products subcategory. The provisions of this subpart are applicable to discharges...

Ubiquitin Ligase WWP1 Interacts with Ebola Virus VP40 To Regulate Egress.

PubMed

Han, Ziying; Sagum, Cari A; Takizawa, Fumio; Ruthel, Gordon; Berry, Corbett T; Kong, Jing; Sunyer, J Oriol; Freedman, Bruce D; Bedford, Mark T; Sidhu, Sachdev S; Sudol, Marius; Harty, Ronald N

2017-10-15

Ebola virus (EBOV) is a member of the Filoviridae family and the cause of hemorrhagic fever outbreaks. The EBOV VP40 (eVP40) matrix protein is the main driving force for virion assembly and budding. Indeed, expression of eVP40 alone in mammalian cells results in the formation and budding of virus-like particles (VLPs) which mimic the budding process and morphology of authentic, infectious EBOV. To complete the budding process, eVP40 utilizes its PPXY L-domain motif to recruit a specific subset of host proteins containing one or more modular WW domains that then function to facilitate efficient production and release of eVP40 VLPs. In this report, we identified additional host WW-domain interactors by screening for potential interactions between mammalian proteins possessing one or more WW domains and WT or PPXY mutant peptides of eVP40. We identified the HECT family E3 ubiquitin ligase WWP1 and all four of its WW domains as strong interactors with the PPXY motif of eVP40. The eVP40-WWP1 interaction was confirmed by both peptide pulldown and coimmunoprecipitation assays, which also demonstrated that modular WW domain 1 of WWP1 was most critical for binding to eVP40. Importantly, the eVP40-WWP1 interaction was found to be biologically relevant for VLP budding since (i) small interfering RNA (siRNA) knockdown of endogenous WWP1 resulted in inhibition of eVP40 VLP egress, (ii) coexpression of WWP1 and eVP40 resulted in ubiquitination of eVP40 and a subsequent increase in eVP40 VLP egress, and (iii) an enzymatically inactive mutant of WWP1 (C890A) did not ubiquitinate eVP40 or enhance eVP40 VLP egress. Last, our data show that ubiquitination of eVP40 by WWP1 enhances egress of VLPs and concomitantly decreases cellular levels of higher-molecular-weight oligomers of eVP40. In sum, these findings contribute to our fundamental understanding of the functional interplay between host E3 ligases, ubiquitination, and regulation of EBOV VP40-mediated egress. IMPORTANCE Ebola virus (EBOV) is a high-priority, emerging human pathogen that can cause severe outbreaks of hemorrhagic fever with high mortality rates. As there are currently no approved vaccines or treatments for EBOV, a better understanding of the biology and functions of EBOV-host interactions that promote or inhibit viral budding is warranted. Here, we describe a physical and functional interaction between EBOV VP40 (eVP40) and WWP1, a host E3 ubiquitin ligase that ubiquitinates VP40 and regulates VLP egress. This viral PPXY-host WW domain-mediated interaction represents a potential new target for host-oriented inhibitors of EBOV egress. Copyright © 2017 American Society for Microbiology.

Clinical disease upregulates expression of CD40 and CD40 ligand on peripheral blood mononuclear cells from cattle naturally infected with Mycobacterium avium subsp. paratuberculosis

USDA-ARS?s Scientific Manuscript database

CD40 and CD40L interactions have costimulatory effects that are part of a complex series of events in host cellular and humoral immune responses and inflammation. The purpose of this study was to examine the changes in expression of CD40 and CD40L on peripheral blood mononuclear cells (PBMCs) isolat...

Autocrine stimulation of IL-10 is critical to the enrichment of IL-10-producing CD40(hi)CD5(+) regulatory B cells in vitro and in vivo.

PubMed

Kim, Hyuk Soon; Lee, Jun Ho; Han, Hee Dong; Kim, A-Ram; Nam, Seung Taek; Kim, Hyun Woo; Park, Young Hwan; Lee, Dajeong; Lee, Min Bum; Park, Yeong Min; Kim, Hyung Sik; Kim, Young Mi; You, Ji Chang; Choi, Wahn Soo

2015-01-01

IL-10-producing B (Breg) cells regulate various immune responses. However, their phenotype remains unclear. CD40 expression was significantly increased in B cells by LPS, and the Breg cells were also enriched in CD40(hi)CD5(+) B cells. Furthermore, CD40 expression on Breg cells was increased by IL-10, CD40 ligand, and B cell-activating factor, suggesting that CD40(hi) is a common phenotype of Breg cells. LPS-induced CD40 expression was largely suppressed by an anti-IL-10 receptor antibody and in IL-10(-/-)CD5(+)CD19(+) B cells. The autocrine effect of IL-10 on the CD40 expression was largely suppressed by an inhibitor of JAK/STAT3. In vivo, the LPS treatment increased the population of CD40(hi)CD5(+) Breg cells in mice. However, the population of CD40(hi)CD5(+) B cells was minimal in IL-10(-/-) mice by LPS. Altogether, our findings show that Breg cells are largely enriched in CD40(hi)CD5(+) B cells and the autocrine effect of IL-10 is critical to the formation of CD40(hi)CD5(+) Breg cells.

In situ 40K-40Ca ‘double-plus’ SIMS dating resolves Klokken feldspar 40K-40Ar paradox

NASA Astrophysics Data System (ADS)

Harrison, T. Mark; Heizler, Matthew T.; McKeegan, Kevin D.; Schmitt, Axel K.

2010-11-01

The 40K- 40Ca decay system has not been widely utilized as a geochronometer because quantification of radiogenic daughter is difficult except in old, extremely high K/Ca domains. Even these environments have not heretofore been exploited by ion microprobe analysis due to the very high mass resolving power (MRP) of 25,000 required to separate 40K + from 40Ca +. We introduce a method that utilizes doubly-charged K and Ca species which permits isotopic measurements to be made at relatively low MRP (~ 5000). We used this K-Ca 'double-plus' approach to address an enduring controversy in 40Ar/ 39Ar thermochronology revolving around exsolved alkali feldspars from the 1166 Ma Klokken syenite (southern Greenland). Ion microprobe 40K- 40Ca analysis of Klokken samples reveal both isochron and pseudoisochron behaviors that reflect episodic isotopic and chemical exchange of coarsely exsolved perthites and a near end-member K-feldspar until ≤ 719 Ma, and perhaps as late at ~ 400 Ma. Feldspar microtextures in the Klokken syenite evolved over a protracted interval by non-thermal processes (fluid-assisted recrystallization) and thus this sample makes a poor model from which to address the general validity of 40Ar/ 39Ar thermochronological methodologies.

CD40-CD40 Ligand Pathway is a Major Component of Acute Neuroinflammation and Contributes to Long-term Cognitive Dysfunction after Sepsis.

PubMed

Michels, Monique; Danieslki, Lucinéia Gainski; Vieira, Andriele; Florentino, Drielly; Dall'Igna, Dhébora; Galant, Letícia; Sonai, Beatriz; Vuolo, Francieli; Mina, Franciele; Pescador, Bruna; Dominguini, Diogo; Barichello, Tatiana; Quevedo, João; Dal-Pizzol, Felipe; Petronilho, Fabrícia

2015-03-26

Sepsis-associated encephalopathy (SAE) is associated with an increased rate of morbidity and mortality. It is not understood what the exact mechanism is for the brain dysfunction that occurs in septic patients, but brain inflammation and oxidative stress are a possible theory. Such events can occur through the alteration of molecules that perpetuate the inflammatory response. Thus, it is possible to postulate that CD40 may be involved in this process. The aim of this work is to evaluate the role of CD40-CD40L pathway activation in brain dysfunction associated with sepsis in an animal model. Microglia activation induces the upregulation of CD40-CD40L, both in vitro and in vivo. The inhibition of microglia activation decreases levels of CD40-CD40L in the brain and decreases brain inflammation, oxidative damage and blood brain barrier dysfunction. Despite this, anti-CD40 treatment does not improve mortality in this model. However, it is able to improve long-term cognitive impairment in sepsis survivors. In conclusion, there is a major involvement of the CD40-CD40L signaling pathway in long-term brain dysfunction in an animal model of sepsis.

CD40–CD40 Ligand Pathway Is a Major Component of Acute Neuroinflammation and Contributes to Long-term Cognitive Dysfunction after Sepsis

PubMed Central

Michels, Monique; Danieslki, Lucinéia Gainski; Vieira, Andriele; Florentino, Drielly; Dall’Igna, Dhébora; Galant, Letícia; Sonai, Beatriz; Vuolo, Francieli; Mina, Franciele; Pescador, Bruna; Dominguini, Diogo; Barichello, Tatiana; Quevedo, João; Dal-Pizzol, Felipe; Petronilho, Fabrícia

2015-01-01

Sepsis-associated encephalopathy (SAE) is associated with an increased rate of morbidity and mortality. It is not understood what the exact mechanism is for the brain dysfunction that occurs in septic patients, but brain inflammation and oxidative stress are a possible theory. Such events can occur through the alteration of molecules that perpetuate the inflammatory response. Thus, it is possible to postulate that CD40 may be involved in this process. The aim of this work is to evaluate the role of CD40–CD40L pathway activation in brain dysfunction associated with sepsis in an animal model. Microglia activation induces the upregulation of CD40–CD40L, both in vitro and in vivo. The inhibition of microglia activation decreases levels of CD40–CD40L in the brain and decreases brain inflammation, oxidative damage and blood brain barrier dysfunction. Despite this, anti-CD40 treatment does not improve mortality in this model. However, it is able to improve long-term cognitive impairment in sepsis survivors. In conclusion, there is a major involvement of the CD40–CD40L signaling pathway in long-term brain dysfunction in an animal model of sepsis. PMID:25822797

YKL-40 is differentially expressed in human embryonic stem cells and in cell progeny of the three germ layers.

PubMed

Brøchner, Christian B; Johansen, Julia S; Larsen, Lars A; Bak, Mads; Mikkelsen, Hanne B; Byskov, Anne Grete; Andersen, Claus Yding; Møllgård, Kjeld

2012-03-01

The secreted glycoprotein YKL-40 participates in cell differentiation, inflammation, and cancer progression. High YKL-40 expression is reported during early human development, but its functions are unknown. Six human embryonic stem cell (hESC) lines were cultured in an atmosphere of low or high oxygen tension, in culture medium with or without basic fibroblast growth factor, and on feeder layers comprising mouse embryonic fibroblasts or human foreskin fibroblasts to evaluate whether hESCs and their progeny produced YKL-40 and to characterize YKL-40 expression during differentiation. Secreted YKL-40 protein and YKL-40 mRNA expression were measured by enzyme-linked immunosorbent assay (ELISA) and quantitative RT-PCR. Serial-sectioned colonies were stained for YKL-40 protein and for pluripotent hESC (OCT4, NANOG) and germ layer (HNF-3β, PDX1, CD34, p63, nestin, PAX6) markers. Double-labeling showed YKL-40 expression in OCT4-positive hESCs, PAX6-positive neuroectodermal cells, and HNF-3β-positive endodermal cells. The differentiating progeny showed strong YKL-40 expression. Abrupt transition between YKL-40 and OCT4-positive hESCs and YKL-40-positive ecto- and neuroectodermal lineages was observed within the same epithelial-like layer. YKL-40-positive cells within deeper layers lacked contact with OCT4-positive cells. YKL-40 may be important in initial cell differentiation from hESCs toward ectoderm and neuroectoderm, with retained epithelial morphology, whereas later differentiation into endoderm and mesoderm involves a transition into the deeper layers of the colony.

Chimeric SV40 virus-like particles induce specific cytotoxicity and protective immunity against influenza A virus without the need of adjuvants

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

Kawano, Masaaki; Morikawa, Katsuma; Suda, Tatsuya

Virus-like particles (VLPs) are a promising vaccine platform due to the safety and efficiency. However, it is still unclear whether polyomavirus-based VLPs are useful for this purpose. Here, we attempted to evaluate the potential of polyomavirus VLPs for the antiviral vaccine using simian virus 40 (SV40). We constructed chimeric SV40-VLPs carrying an HLA-A{sup ⁎}02:01-restricted, cytotoxic T lymphocyte (CTL) epitope derived from influenza A virus. HLA-A{sup ⁎}02:01-transgenic mice were then immunized with the chimeric SV40-VLPs. The chimeric SV40-VLPs effectively induced influenza-specific CTLs and heterosubtypic protection against influenza A viruses without the need of adjuvants. Because DNase I treatment of the chimericmore » SV40-VLPs did not disrupt CTL induction, the intrinsic adjuvant property may not result from DNA contaminants in the VLP preparation. In addition, immunization with the chimeric SV40-VLPs generated long-lasting memory CTLs. We here propose that the chimeric SV40-VLPs harboring an epitope may be a promising CTL-based vaccine platform with self-adjuvant properties. - Highlights: • We constructed chimeric SV40-VLPs carrying an influenza virus-derived CTL epitope. • Chimeric SV40-VLPs induce influenza-specific CTLs in mice without adjuvants. • Chimeric SV40-VLPs induce heterosubtypic protection against influenza A viruses. • Chimeric SV40-VLPs induce long-lasting memory CTLs. • Chimeric SV40-VLPs is a promising vaccine platform with self-adjuvant properties.« less

Neofunctionalization of Duplicated Tic40 Genes Caused a Gain-of-Function Variation Related to Male Fertility in Brassica oleracea Lineages1[W][OPEN

PubMed Central

Dun, Xiaoling; Shen, Wenhao; Hu, Kaining; Zhou, Zhengfu; Xia, Shengqian; Wen, Jing; Yi, Bin; Shen, Jinxiong; Ma, Chaozhi; Tu, Jinxing; Fu, Tingdong; Lagercrantz, Ulf

2014-01-01

Gene duplication followed by functional divergence in the event of polyploidization is a major contributor to evolutionary novelties. The Brassica genus evolved from a common ancestor after whole-genome triplication. Here, we studied the evolutionary and functional features of Brassica spp. homologs to Tic40 (for translocon at the inner membrane of chloroplasts with 40 kDa). Four Tic40 loci were identified in allotetraploid Brassica napus and two loci in each of three basic diploid Brassica spp. Although these Tic40 homologs share high sequence identities and similar expression patterns, they exhibit altered functional features. Complementation assays conducted on Arabidopsis thaliana tic40 and the B. napus male-sterile line 7365A suggested that all Brassica spp. Tic40 homologs retain an ancestral function similar to that of AtTic40, whereas BolC9.Tic40 in Brassica oleracea and its ortholog in B. napus, BnaC9.Tic40, in addition, evolved a novel function that can rescue the fertility of 7365A. A homologous chromosomal rearrangement placed bnac9.tic40 originating from the A genome (BraA10.Tic40) as an allele of BnaC9.Tic40 in the C genome, resulting in phenotypic variation for male sterility in the B. napus near-isogenic two-type line 7365AB. Assessment of the complementation activity of chimeric B. napus Tic40 domain-swapping constructs in 7365A suggested that amino acid replacements in the carboxyl terminus of BnaC9.Tic40 cause this functional divergence. The distribution of these amino acid replacements in 59 diverse Brassica spp. accessions demonstrated that the neofunctionalization of Tic40 is restricted to B. oleracea and its derivatives and thus occurred after the divergence of the Brassica spp. A, B, and C genomes. PMID:25185122

Interaction of Macrophage Antigen 1 and CD40 Ligand Leads to IL-12 Production and Resistance in CD40-Deficient Mice Infected with Leishmania major.

PubMed

Okwor, Ifeoma; Jia, Ping; Uzonna, Jude E

2015-10-01

Although some studies indicate that the interaction of CD40 and CD40L is critical for IL-12 production and resistance to cutaneous leishmaniasis, others suggest that this pathway may be dispensable. In this article, we compared the outcome of Leishmania major infection in both CD40- and CD40L-deficient mice after treatment with rIL-12. We show that although CD40 and CD40L knockout (KO) mice are highly susceptible to L. major, treatment with rIL-12 during the first 2 wk of infection causes resolution of cutaneous lesions and control of parasite replication. Interestingly, although treated CD40 KO mice remained healed, developed long-term immunity, and were resistant to secondary L. major challenge, treated CD40L KO reactivated their lesion after cessation of rIL-12 treatment. Disease reactivation in CD40L KO mice was associated with impaired IL-12 and IFN-γ production and a concomitant increase in IL-4 production by cells from lymph nodes draining the infection site. We show that IL-12 production by dendritic cells and macrophages via CD40L-macrophage Ag 1 (Mac-1) interaction is responsible for the sustained resistance in CD40 KO mice after cessation of rIL-12 treatment. Blockade of CD40L-Mac-1 interaction with anti-Mac-1 mAb led to spontaneous disease reactivation in healed CD40 KO mice, which was associated with impaired IFN-γ response and loss of infection-induced immunity after secondary L. major challenge. Collectively, our data reveal a novel role of CD40L-Mac-1 interaction in IL-12 production, development, and maintenance of optimal Th1 immunity in mice infected with L. major. Copyright © 2015 by The American Association of Immunologists, Inc.

Neofunctionalization of duplicated Tic40 genes caused a gain-of-function variation related to male fertility in Brassica oleracea lineages.

PubMed

Dun, Xiaoling; Shen, Wenhao; Hu, Kaining; Zhou, Zhengfu; Xia, Shengqian; Wen, Jing; Yi, Bin; Shen, Jinxiong; Ma, Chaozhi; Tu, Jinxing; Fu, Tingdong; Lagercrantz, Ulf

2014-11-01

Gene duplication followed by functional divergence in the event of polyploidization is a major contributor to evolutionary novelties. The Brassica genus evolved from a common ancestor after whole-genome triplication. Here, we studied the evolutionary and functional features of Brassica spp. homologs to Tic40 (for translocon at the inner membrane of chloroplasts with 40 kDa). Four Tic40 loci were identified in allotetraploid Brassica napus and two loci in each of three basic diploid Brassica spp. Although these Tic40 homologs share high sequence identities and similar expression patterns, they exhibit altered functional features. Complementation assays conducted on Arabidopsis thaliana tic40 and the B. napus male-sterile line 7365A suggested that all Brassica spp. Tic40 homologs retain an ancestral function similar to that of AtTic40, whereas BolC9.Tic40 in Brassica oleracea and its ortholog in B. napus, BnaC9.Tic40, in addition, evolved a novel function that can rescue the fertility of 7365A. A homologous chromosomal rearrangement placed bnac9.tic40 originating from the A genome (BraA10.Tic40) as an allele of BnaC9.Tic40 in the C genome, resulting in phenotypic variation for male sterility in the B. napus near-isogenic two-type line 7365AB. Assessment of the complementation activity of chimeric B. napus Tic40 domain-swapping constructs in 7365A suggested that amino acid replacements in the carboxyl terminus of BnaC9.Tic40 cause this functional divergence. The distribution of these amino acid replacements in 59 diverse Brassica spp. accessions demonstrated that the neofunctionalization of Tic40 is restricted to B. oleracea and its derivatives and thus occurred after the divergence of the Brassica spp. A, B, and C genomes. © 2014 American Society of Plant Biologists. All Rights Reserved.

Activated platelets are the source of elevated levels of soluble CD40 ligand in the circulation of inflammatory bowel disease patients.

PubMed

Danese, S; Katz, J A; Saibeni, S; Papa, A; Gasbarrini, A; Vecchi, M; Fiocchi, C

2003-10-01

The CD40/CD40L system, a key regulator and amplifier of immune reactivity, is activated in inflammatory bowel disease (IBD) mucosa. To determine whether plasma levels of sCD40L are elevated in Crohn's disease (CD) and ulcerative colitis (UC) patients compared with normal controls, to investigate the cellular source of sCD40L, and to explore CD40L induction mechanisms. CD, UC, and normal control subjects were studied. The concentration of sCD40L in plasma and supernatants of freshly isolated platelets and autologous peripheral blood T cells (PBT) was measured by ELISA. Surface CD40L expression level was measured by flow cytometry in resting and thrombin activated platelets, and unstimulated and CD3/CD28 stimulated PBT before and after coculture with human intestinal microvascular endothelial cells (HIMEC). Compared with normal controls, plasma sCD40L levels were significantly higher in both CD and UC patients and proportional to the extent of mucosal inflammation. Platelets from IBD patients displayed a significantly higher surface CD40L expression than those from control subjects, and released greater amounts of sCD40L than autologous PBT. Contact with IL-1beta activated HIMEC induced significant upregulation of CD40L surface expression and release by platelets. Elevated levels of sCD40L in the circulation of IBD patients reflect enhanced surface expression and release of CD40L by platelets. This phenomenon translates to an increased platelet activation state apparently induced by passage through an inflamed mucosal microvascular bed, a conclusion supported by the positive correlation of plasma sCD40L levels with the extent of anatomical involvement by IBD. These results suggest that platelet-endothelial interactions critically contribute to activation of the CD40 pathway in IBD.

Binding of CD40L to Mac-1’s I-domain involves the EQLKKSKTL motif and mediates leukocyte recruitment and atherosclerosis – but does not affect immunity and thrombosis in mice

PubMed Central

Wolf, Dennis; Hohmann, Jan-David; Wiedemann, Ansgar; Bledzka, Kamila; Blankenbach, Hermann; Marchini, Timoteo; Gutte, Katharina; Zeschky, Katharina; Bassler, Nicole; Hoppe, Natalie; Rodriguez, Alexandra Ortiz; Herr, Nadine; Hilgendorf, Ingo; Stachon, Peter; Willecke, Florian; Dürschmied, Daniel; von zur Mühlen, Constantin; Soloviev, Dmitry A.; Zhang, Li; Bode, Christoph; Plow, Edward F.; Libby, Peter; Peter, Karlheinz; Zirlik, Andreas

2012-01-01

Rationale CD40L figures prominently in chronic inflammatory diseases such as atherosclerosis. However, since CD40L potently regulates immune function and haemostasis by interaction with CD40 receptor and the platelet integrin GPIIb/IIIa, its global inhibition compromises host defense and generated thromboembolic complications in clinical trials. We recently reported that CD40L mediates atherogenesis independently of CD40 and proposed Mac-1 as an alternate receptor. Objective Here, we molecularly characterized the CD40L-Mac-1 interaction and tested whether its selective inhibition by a small peptide modulates inflammation and atherogenesis in vivo. Methods and Results CD40L concentration-dependently bound to Mac-1 I-domain in solid phase binding assays, and a high affinity interaction was revealed by surface-plasmon-resonance analysis. We identified the motif EQLKKSKTL, an exposed loop between the α1 helix and the β-sheet B, on Mac-1 as binding site for CD40L. A linear peptide mimicking this sequence, M7, specifically inhibited the interaction of CD40L and Mac-1. cM7, a cyclisized version optimized for in vivo use, decreased peritoneal inflammation and inflammatory cell recruitment in vivo. Finally, LDLr-/- mice treated with intraperitoneal injections of cM7 developed smaller, less inflamed atherosclerotic lesions featuring characteristics of stability. However, cM7 did not interfere with CD40L-CD40 binding in vitro and CD40L-GPIIb/IIIa-mediated thrombus formation in vivo. Conclusions We present the novel finding that CD40L binds to the EQLKKSKTL motif on Mac-1 mediating leukocyte recruitment and atherogenesis. Specific inhibition of CD40L-Mac-1 binding may represent an attractive anti-inflammatory treatment strategy for atherosclerosis and other inflammatory conditions, potentially avoiding the unwanted immunologic and thrombotic effects of global inhibition of CD40L. PMID:21998326

Engaging the CD40-CD40L pathway augments T-helper cell responses and improves control of Mycobacterium tuberculosis infection

PubMed Central

Bizzell, Erica; Madan-Lala, Ranjna

2017-01-01

Mycobacterium tuberculosis (Mtb) impairs dendritic cell (DC) functions and induces suboptimal antigen-specific CD4 T cell immune responses that are poorly protective. Mucosal T-helper cells producing IFN-γ (Th1) and IL-17 (Th17) are important for protecting against tuberculosis (TB), but the mechanisms by which DCs generate antigen-specific T-helper responses during Mtb infection are not well defined. We previously reported that Mtb impairs CD40 expression on DCs and restricts Th1 and Th17 responses. We now demonstrate that CD40-dependent costimulation is required to generate IL-17 responses to Mtb. CD40-deficient DCs were unable to induce antigen-specific IL-17 responses after Mtb infection despite the production of Th17-polarizing innate cytokines. Disrupting the interaction between CD40 on DCs and its ligand CD40L on antigen-specific CD4 T cells, genetically or via antibody blockade, significantly reduced antigen-specific IL-17 responses. Importantly, engaging CD40 on DCs with a multimeric CD40 agonist (CD40LT) enhanced antigen-specific IL-17 generation in ex vivo DC-T cell co-culture assays. Further, intratracheal instillation of Mtb-infected DCs treated with CD40LT significantly augmented antigen-specific Th17 responses in vivo in the lungs and lung-draining lymph nodes of mice. Finally, we show that boosting CD40-CD40L interactions promoted balanced Th1/Th17 responses in a setting of mucosal DC transfer, and conferred enhanced control of lung bacterial burdens following aerosol challenge with Mtb. Our results demonstrate that CD40 costimulation by DCs plays an important role in generating antigen-specific Th17 cells and targeting the CD40-CD40L pathway represents a novel strategy to improve adaptive immunity to TB. PMID:28767735

40 CFR 422.40 - Applicability; description of the defluorinated phosphate rock subcategory.

Code of Federal Regulations, 2012 CFR

2012-07-01

... defluorinated phosphate rock subcategory. 422.40 Section 422.40 Protection of Environment ENVIRONMENTAL... Defluorinated Phosphate Rock Subcategory § 422.40 Applicability; description of the defluorinated phosphate rock... phosphate rock by application of high temperature treatment along with wet process phosphoric acid, silica...

40 CFR 422.40 - Applicability; description of the defluorinated phosphate rock subcategory.

Code of Federal Regulations, 2013 CFR

2013-07-01

... defluorinated phosphate rock subcategory. 422.40 Section 422.40 Protection of Environment ENVIRONMENTAL... Defluorinated Phosphate Rock Subcategory § 422.40 Applicability; description of the defluorinated phosphate rock... phosphate rock by application of high temperature treatment along with wet process phosphoric acid, silica...

40 CFR 422.40 - Applicability; description of the defluorinated phosphate rock subcategory.

Code of Federal Regulations, 2010 CFR

2010-07-01

... defluorinated phosphate rock subcategory. 422.40 Section 422.40 Protection of Environment ENVIRONMENTAL... Defluorinated Phosphate Rock Subcategory § 422.40 Applicability; description of the defluorinated phosphate rock... phosphate rock by application of high temperature treatment along with wet process phosphoric acid, silica...

40 CFR 422.40 - Applicability; description of the defluorinated phosphate rock subcategory.

Code of Federal Regulations, 2014 CFR

2014-07-01

... defluorinated phosphate rock subcategory. 422.40 Section 422.40 Protection of Environment ENVIRONMENTAL... Defluorinated Phosphate Rock Subcategory § 422.40 Applicability; description of the defluorinated phosphate rock... phosphate rock by application of high temperature treatment along with wet process phosphoric acid, silica...

40 CFR 422.40 - Applicability; description of the defluorinated phosphate rock subcategory.

Code of Federal Regulations, 2011 CFR

2011-07-01

... defluorinated phosphate rock subcategory. 422.40 Section 422.40 Protection of Environment ENVIRONMENTAL... Defluorinated Phosphate Rock Subcategory § 422.40 Applicability; description of the defluorinated phosphate rock... phosphate rock by application of high temperature treatment along with wet process phosphoric acid, silica...

40 CFR 434.40 - Applicability; description of the alkaline mine drainage subcategory.

Code of Federal Regulations, 2012 CFR

2012-07-01

... alkaline mine drainage subcategory. 434.40 Section 434.40 Protection of Environment ENVIRONMENTAL... BPT, BAT, BCT LIMITATIONS AND NEW SOURCE PERFORMANCE STANDARDS Alkaline Mine Drainage § 434.40 Applicability; description of the alkaline mine drainage subcategory. The provisions of this subpart are...

40 CFR 434.40 - Applicability; description of the alkaline mine drainage subcategory.

Code of Federal Regulations, 2013 CFR

2013-07-01

... alkaline mine drainage subcategory. 434.40 Section 434.40 Protection of Environment ENVIRONMENTAL... BPT, BAT, BCT LIMITATIONS AND NEW SOURCE PERFORMANCE STANDARDS Alkaline Mine Drainage § 434.40 Applicability; description of the alkaline mine drainage subcategory. The provisions of this subpart are...

40 CFR 434.40 - Applicability; description of the alkaline mine drainage subcategory.

Code of Federal Regulations, 2014 CFR

2014-07-01

... alkaline mine drainage subcategory. 434.40 Section 434.40 Protection of Environment ENVIRONMENTAL... BPT, BAT, BCT LIMITATIONS AND NEW SOURCE PERFORMANCE STANDARDS Alkaline Mine Drainage § 434.40 Applicability; description of the alkaline mine drainage subcategory. The provisions of this subpart are...

40 CFR 434.40 - Applicability; description of the alkaline mine drainage subcategory.

Code of Federal Regulations, 2010 CFR

2010-07-01

... alkaline mine drainage subcategory. 434.40 Section 434.40 Protection of Environment ENVIRONMENTAL..., BCT LIMITATIONS AND NEW SOURCE PERFORMANCE STANDARDS Alkaline Mine Drainage § 434.40 Applicability; description of the alkaline mine drainage subcategory. The provisions of this subpart are applicable to...

40 CFR 434.40 - Applicability; description of the alkaline mine drainage subcategory.

Code of Federal Regulations, 2011 CFR

2011-07-01

... alkaline mine drainage subcategory. 434.40 Section 434.40 Protection of Environment ENVIRONMENTAL..., BCT LIMITATIONS AND NEW SOURCE PERFORMANCE STANDARDS Alkaline Mine Drainage § 434.40 Applicability; description of the alkaline mine drainage subcategory. The provisions of this subpart are applicable to...

40 CFR 409.40 - Applicability; description of the Louisiana raw cane sugar processing subcategory.

Code of Federal Regulations, 2013 CFR

2013-07-01

... Louisiana raw cane sugar processing subcategory. 409.40 Section 409.40 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) EFFLUENT GUIDELINES AND STANDARDS SUGAR PROCESSING POINT SOURCE CATEGORY Louisiana Raw Cane Sugar Processing Subcategory § 409.40 Applicability; description of the...

40 CFR 409.40 - Applicability; description of the Louisiana raw cane sugar processing subcategory.

Code of Federal Regulations, 2012 CFR

2012-07-01

... Louisiana raw cane sugar processing subcategory. 409.40 Section 409.40 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) EFFLUENT GUIDELINES AND STANDARDS SUGAR PROCESSING POINT SOURCE CATEGORY Louisiana Raw Cane Sugar Processing Subcategory § 409.40 Applicability; description of the...

40 CFR 409.40 - Applicability; description of the Louisiana raw cane sugar processing subcategory.

Code of Federal Regulations, 2014 CFR

2014-07-01

... Louisiana raw cane sugar processing subcategory. 409.40 Section 409.40 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) EFFLUENT GUIDELINES AND STANDARDS SUGAR PROCESSING POINT SOURCE CATEGORY Louisiana Raw Cane Sugar Processing Subcategory § 409.40 Applicability; description of the...

41 CFR 109-40.5101 - Policy.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 41 Public Contracts and Property Management 3 2010-07-01 2010-07-01 false Policy. 109-40.5101... MOTOR VEHICLES 40-TRANSPORTATION AND TRAFFIC MANAGEMENT 40.51-Price-Anderson Coverage Certifications for Nuclear Shipments § 109-40.5101 Policy. Upon request of a carrier, an appropriate certification will be...

40 CFR 440.40 - Applicability; description of the mercury ore subcategory.

Code of Federal Regulations, 2011 CFR

2011-07-01

... mercury ore subcategory. 440.40 Section 440.40 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) EFFLUENT GUIDELINES AND STANDARDS ORE MINING AND DRESSING POINT SOURCE CATEGORY Mercury Ore Subcategory § 440.40 Applicability; description of the mercury ore subcategory. The provisions of subpart D...

An Evaluation of μ-Opioid Receptor (OPRM1) as a Predictor of Naltrexone Response in the Treatment of Alcohol Dependence

PubMed Central

Anton, Raymond F.; Oroszi, Gabor; O'Malley, Stephanie; Couper, David; Swift, Robert; Pettinati, Helen; Goldman, David

2008-01-01

Context: Naltrexone hydrochloride treatment for alcohol dependence works for some individuals but not for everyone. Asn40Asp, a functional polymorphism of the μ-opioid receptor gene (OPRM1), might predict naltrexone response. Objective: To evaluate whether individuals with alcoholism who are heterozygous (Asp40/Asn40) or homozygous (Asp40/Asp40) for the OPRM1 Asp40 allele respond better to naltrexone. Design: Pharmacogenetic analysis conducted between January 1, 2001, and January 31, 2004. Setting: Eleven academic sites in the COMBINE Study. Participants: Recently abstinent volunteers who met all 3 of the following conditions: (1) DSM-IV criteria for primary alcohol dependence; (2) participation in the COMBINE Study; and (3) availability of DNA. Interventions: Alcoholic subjects were treated for 16 weeks with 100 mg of naltrexone hydrochloride (234 Asn40 homozygotes and 67 with at least 1 copy of the Asp40 allele) or placebo (235 Asn40 homozygotes and 68 with at least 1 copy of the Asp40 allele). All participants received medical management (MM) alone or with combined behavioral intervention (CBI). Main Outcome Measures: Time trends in percentage of days abstinent, percentage of heavy drinking days, and rates of good clinical outcome. Results: Alcoholic subjects with an Asp40 allele receiving MM alone (no CBI) had an increased percentage of days abstinent (P=.07) and a decreased percentage of heavy drinking days (P=.04) if treated with naltrexone vs placebo, while those with the Asn40/Asn40 genotype showed no medication differences. If treated with MM alone and naltrexone, 87.1% of Asp40 carriers had a good clinical outcome, compared with only 54.8% of individuals with the Asn40/Asn40 genotype (odds ratio, 5.75; confidence interval, 1.88-17.54), while, if treated with placebo, 48.6% of Asp40 carriers and 54.0% of individuals with the Asn40/Asn40 genotype had a good clinical outcome (interaction between medication and genotype, P=.005). No gene×medication interactions were observed in those treated with both MM and CBI. Conclusions: These results confirm and extend the observation that the functionally significant OPRM1 Asp40 allele predicts naltrexone treatment response in alcoholic individuals. This relationship might be obscured, however, by other efficacious treatments. OPRM1 geno-typing in alcoholic individuals might be useful to assist in selecting treatment options. PMID:18250251

40 CFR 406.40 - Applicability; description of the bulgur wheat flour milling subcategory.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 40 Protection of Environment 28 2010-07-01 2010-07-01 true Applicability; description of the bulgur wheat flour milling subcategory. 406.40 Section 406.40 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) EFFLUENT GUIDELINES AND STANDARDS GRAIN MILLS POINT SOURCE CATEGORY Bulgur...

40 CFR 74.40 - Establishment of opt-in source allowance accounts.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 40 Protection of Environment 16 2011-07-01 2011-07-01 false Establishment of opt-in source allowance accounts. 74.40 Section 74.40 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED) SULFUR DIOXIDE OPT-INS Allowance Tracking and Transfer and End of Year...

40 CFR 409.40 - Applicability; description of the Louisiana raw cane sugar processing subcategory.

Code of Federal Regulations, 2011 CFR

2011-07-01

... Louisiana raw cane sugar processing subcategory. 409.40 Section 409.40 Protection of Environment... CATEGORY Louisiana Raw Cane Sugar Processing Subcategory § 409.40 Applicability; description of the Louisiana raw cane sugar processing subcategory. The provisions of this subpart are applicable to discharges...

40 CFR 409.40 - Applicability; description of the Louisiana raw cane sugar processing subcategory.

Code of Federal Regulations, 2010 CFR

2010-07-01

... Louisiana raw cane sugar processing subcategory. 409.40 Section 409.40 Protection of Environment... CATEGORY Louisiana Raw Cane Sugar Processing Subcategory § 409.40 Applicability; description of the Louisiana raw cane sugar processing subcategory. The provisions of this subpart are applicable to discharges...

40 CFR 96.40 - State trading program budget.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 40 Protection of Environment 21 2011-07-01 2011-07-01 false State trading program budget. 96.40... (CONTINUED) NOX BUDGET TRADING PROGRAM AND CAIR NOX AND SO2 TRADING PROGRAMS FOR STATE IMPLEMENTATION PLANS NOX Allowance Allocations § 96.40 State trading program budget. The State trading program budget...

41 CFR 109-40.5000 - Scope of subpart.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 41 Public Contracts and Property Management 3 2012-01-01 2012-01-01 false Scope of subpart. 109-40... Regulations System (Continued) DEPARTMENT OF ENERGY PROPERTY MANAGEMENT REGULATIONS AVIATION, TRANSPORTATION, AND MOTOR VEHICLES 40-TRANSPORTATION AND TRAFFIC MANAGEMENT 40.50-Bills of Lading § 109-40.5000 Scope...

41 CFR 109-40.5000 - Scope of subpart.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 41 Public Contracts and Property Management 3 2011-01-01 2011-01-01 false Scope of subpart. 109-40... Regulations System (Continued) DEPARTMENT OF ENERGY PROPERTY MANAGEMENT REGULATIONS AVIATION, TRANSPORTATION, AND MOTOR VEHICLES 40-TRANSPORTATION AND TRAFFIC MANAGEMENT 40.50-Bills of Lading § 109-40.5000 Scope...

41 CFR 109-40.5000 - Scope of subpart.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 41 Public Contracts and Property Management 3 2013-07-01 2013-07-01 false Scope of subpart. 109-40... Regulations System (Continued) DEPARTMENT OF ENERGY PROPERTY MANAGEMENT REGULATIONS AVIATION, TRANSPORTATION, AND MOTOR VEHICLES 40-TRANSPORTATION AND TRAFFIC MANAGEMENT 40.50-Bills of Lading § 109-40.5000 Scope...

41 CFR 109-40.5000 - Scope of subpart.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 41 Public Contracts and Property Management 3 2014-01-01 2014-01-01 false Scope of subpart. 109-40... Regulations System (Continued) DEPARTMENT OF ENERGY PROPERTY MANAGEMENT REGULATIONS AVIATION, TRANSPORTATION, AND MOTOR VEHICLES 40-TRANSPORTATION AND TRAFFIC MANAGEMENT 40.50-Bills of Lading § 109-40.5000 Scope...

41 CFR 109-40.5000 - Scope of subpart.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 41 Public Contracts and Property Management 3 2010-07-01 2010-07-01 false Scope of subpart. 109-40... Regulations System (Continued) DEPARTMENT OF ENERGY PROPERTY MANAGEMENT REGULATIONS AVIATION, TRANSPORTATION, AND MOTOR VEHICLES 40-TRANSPORTATION AND TRAFFIC MANAGEMENT 40.50-Bills of Lading § 109-40.5000 Scope...

26 CFR 40.0-1 - Introduction.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 26 Internal Revenue 16 2010-04-01 2010-04-01 true Introduction. 40.0-1 Section 40.0-1 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY (CONTINUED) MISCELLANEOUS EXCISE TAXES EXCISE TAX PROCEDURAL REGULATIONS § 40.0-1 Introduction. (a) In general. The regulations in this part 40 are...

40 CFR 425.40 - Applicability; description of the retan-wet finish-sides subcategory.

Code of Federal Regulations, 2013 CFR

2013-07-01

... retan-wet finish-sides subcategory. 425.40 Section 425.40 Protection of Environment ENVIRONMENTAL... POINT SOURCE CATEGORY Retan-Wet Finish-Sides Subcategory § 425.40 Applicability; description of the retan-wet finish-sides subcategory. The provisions of this subpart are applicable to process wastewater...

40 CFR 425.40 - Applicability; description of the retan-wet finish-sides subcategory.

Code of Federal Regulations, 2011 CFR

2011-07-01

... retan-wet finish-sides subcategory. 425.40 Section 425.40 Protection of Environment ENVIRONMENTAL... CATEGORY Retan-Wet Finish-Sides Subcategory § 425.40 Applicability; description of the retan-wet finish-sides subcategory. The provisions of this subpart are applicable to process wastewater discharges...

40 CFR 425.40 - Applicability; description of the retan-wet finish-sides subcategory.

Code of Federal Regulations, 2012 CFR

2012-07-01

... retan-wet finish-sides subcategory. 425.40 Section 425.40 Protection of Environment ENVIRONMENTAL... POINT SOURCE CATEGORY Retan-Wet Finish-Sides Subcategory § 425.40 Applicability; description of the retan-wet finish-sides subcategory. The provisions of this subpart are applicable to process wastewater...

40 CFR 425.40 - Applicability; description of the retan-wet finish-sides subcategory.

Code of Federal Regulations, 2014 CFR

2014-07-01

... retan-wet finish-sides subcategory. 425.40 Section 425.40 Protection of Environment ENVIRONMENTAL... POINT SOURCE CATEGORY Retan-Wet Finish-Sides Subcategory § 425.40 Applicability; description of the retan-wet finish-sides subcategory. The provisions of this subpart are applicable to process wastewater...

40 CFR 443.40 - Applicability; description of the linoleum and printed asphalt felt subcategory.

Code of Federal Regulations, 2010 CFR

2010-07-01

... linoleum and printed asphalt felt subcategory. 443.40 Section 443.40 Protection of Environment... PAVING AND ROOFING MATERIALS (TARS AND ASPHALT) POINT SOURCE CATEGORY Linoleum and Printed Asphalt Felt Subcategory § 443.40 Applicability; description of the linoleum and printed asphalt felt subcategory. The...

40 CFR 443.40 - Applicability; description of the linoleum and printed asphalt felt subcategory.

Code of Federal Regulations, 2012 CFR

2012-07-01

... linoleum and printed asphalt felt subcategory. 443.40 Section 443.40 Protection of Environment... THE PAVING AND ROOFING MATERIALS (TARS AND ASPHALT) POINT SOURCE CATEGORY Linoleum and Printed Asphalt Felt Subcategory § 443.40 Applicability; description of the linoleum and printed asphalt felt...

40 CFR 443.40 - Applicability; description of the linoleum and printed asphalt felt subcategory.

Code of Federal Regulations, 2013 CFR

2013-07-01

... linoleum and printed asphalt felt subcategory. 443.40 Section 443.40 Protection of Environment... THE PAVING AND ROOFING MATERIALS (TARS AND ASPHALT) POINT SOURCE CATEGORY Linoleum and Printed Asphalt Felt Subcategory § 443.40 Applicability; description of the linoleum and printed asphalt felt...

40 CFR 443.40 - Applicability; description of the linoleum and printed asphalt felt subcategory.

Code of Federal Regulations, 2011 CFR

2011-07-01

... linoleum and printed asphalt felt subcategory. 443.40 Section 443.40 Protection of Environment... PAVING AND ROOFING MATERIALS (TARS AND ASPHALT) POINT SOURCE CATEGORY Linoleum and Printed Asphalt Felt Subcategory § 443.40 Applicability; description of the linoleum and printed asphalt felt subcategory. The...

40 CFR 443.40 - Applicability; description of the linoleum and printed asphalt felt subcategory.

Code of Federal Regulations, 2014 CFR

2014-07-01

... linoleum and printed asphalt felt subcategory. 443.40 Section 443.40 Protection of Environment... THE PAVING AND ROOFING MATERIALS (TARS AND ASPHALT) POINT SOURCE CATEGORY Linoleum and Printed Asphalt Felt Subcategory § 443.40 Applicability; description of the linoleum and printed asphalt felt...

40 CFR 750.40 - Cross-examination.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 40 Protection of Environment 30 2010-07-01 2010-07-01 false Cross-examination. 750.40 Section 750... Processing and Distribution in Commerce Exemptions § 750.40 Cross-examination. (a) After the close of the... cross-examination. The request must be received by EPA within one week after a full transcript of the...

40 CFR 458.40 - Applicability; description of the carbon black lamp process subcategory.

Code of Federal Regulations, 2012 CFR

2012-07-01

... carbon black lamp process subcategory. 458.40 Section 458.40 Protection of Environment ENVIRONMENTAL... SOURCE CATEGORY Carbon Black Lamp Process Subcategory § 458.40 Applicability; description of the carbon black lamp process subcategory. The provisions of this subpart are applicable to discharges resulting...

40 CFR 96.40 - State trading program budget.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 40 Protection of Environment 20 2010-07-01 2010-07-01 false State trading program budget. 96.40... (CONTINUED) NOX BUDGET TRADING PROGRAM AND CAIR NOX AND SO2 TRADING PROGRAMS FOR STATE IMPLEMENTATION PLANS NOX Allowance Allocations § 96.40 State trading program budget. The State trading program budget...

40 CFR 74.40 - Establishment of opt-in source allowance accounts.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 40 Protection of Environment 16 2010-07-01 2010-07-01 false Establishment of opt-in source allowance accounts. 74.40 Section 74.40 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED) SULFUR DIOXIDE OPT-INS Allowance Tracking and Transfer and End of Year...

40 CFR 40.140-3 - Federal Water Pollution Control Act.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 40 Protection of Environment 1 2011-07-01 2011-07-01 false Federal Water Pollution Control Act. 40... FEDERAL ASSISTANCE RESEARCH AND DEMONSTRATION GRANTS § 40.140-3 Federal Water Pollution Control Act. (a... otherwise preventing pollution by industry, which method shall have industrywide application; (b) All...

40 CFR 40.140-3 - Federal Water Pollution Control Act.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 40 Protection of Environment 1 2010-07-01 2010-07-01 false Federal Water Pollution Control Act. 40... FEDERAL ASSISTANCE RESEARCH AND DEMONSTRATION GRANTS § 40.140-3 Federal Water Pollution Control Act. (a... otherwise preventing pollution by industry, which method shall have industrywide application; (b) All...

40 CFR 96.40 - State trading program budget.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 40 Protection of Environment 22 2013-07-01 2013-07-01 false State trading program budget. 96.40... (CONTINUED) NOX BUDGET TRADING PROGRAM AND CAIR NOX AND SO 2 TRADING PROGRAMS FOR STATE IMPLEMENTATION PLANS NOX Allowance Allocations § 96.40 State trading program budget. The State trading program budget...

40 CFR 96.40 - State trading program budget.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 40 Protection of Environment 22 2012-07-01 2012-07-01 false State trading program budget. 96.40... (CONTINUED) NOX BUDGET TRADING PROGRAM AND CAIR NOX AND SO2 TRADING PROGRAMS FOR STATE IMPLEMENTATION PLANS NOX Allowance Allocations § 96.40 State trading program budget. The State trading program budget...

40 CFR 96.40 - State trading program budget.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 40 Protection of Environment 21 2014-07-01 2014-07-01 false State trading program budget. 96.40... (CONTINUED) NOX BUDGET TRADING PROGRAM AND CAIR NOX AND SO2 TRADING PROGRAMS FOR STATE IMPLEMENTATION PLANS NOX Allowance Allocations § 96.40 State trading program budget. The State trading program budget...

40 CFR 40.140-3 - Federal Water Pollution Control Act.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 40 Protection of Environment 1 2014-07-01 2014-07-01 false Federal Water Pollution Control Act. 40... FEDERAL ASSISTANCE RESEARCH AND DEMONSTRATION GRANTS § 40.140-3 Federal Water Pollution Control Act. (a... otherwise preventing pollution by industry, which method shall have industrywide application; (b) All...

40 CFR 40.140-3 - Federal Water Pollution Control Act.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 40 Protection of Environment 1 2012-07-01 2012-07-01 false Federal Water Pollution Control Act. 40... FEDERAL ASSISTANCE RESEARCH AND DEMONSTRATION GRANTS § 40.140-3 Federal Water Pollution Control Act. (a... otherwise preventing pollution by industry, which method shall have industrywide application; (b) All...

40 CFR 458.40 - Applicability; description of the carbon black lamp process subcategory.

Code of Federal Regulations, 2010 CFR

2010-07-01

... carbon black lamp process subcategory. 458.40 Section 458.40 Protection of Environment ENVIRONMENTAL... CATEGORY Carbon Black Lamp Process Subcategory § 458.40 Applicability; description of the carbon black lamp process subcategory. The provisions of this subpart are applicable to discharges resulting from the...

Rotor-Bearing Dynamics Technology Design Guide. Part 1. Flexible Rotor Dynamics

DTIC Science & Technology

1980-06-01

DIMENSION TABLX(6O,122) (1254) CONMON/ BMAT /XLX(60,12O),YLX(60,120),ZLX(6O. 120), (1255) IXHALF(20,40),YHALF(20,40),ZNALF(20,40),QNALF(20,40) (1256) COMNON...ISO-1 (2969) 105 RETURN (2970) END IVK 317 - ~ --- = - 7: - (2971) SUBROUTINE IGNRL(HBEHD1 INDEXISO,DETER,IVARH) (2972) CONNON/ BMAT /XLX(60.120),YLX...8217,.SLANT’v, PHASE’lfM?;10 (3865) DIMENSION !RLAB(40),ICLAB(40) (3966) COMMON/ BMAT /XLX(60V120),YLX(60,120),ZLX(6OA 1201, (3867) +XHALF(20,40),YHALF(2O

Simian virus 40 large T antigen associates with cyclin A and p33cdk2.

PubMed Central

Adamczewski, J P; Gannon, J V; Hunt, T

1993-01-01

In this paper we provide evidence that a fraction of large T antigen of simian virus 40 (SV40) interacts with cyclin A and p33cdk2 in both virus-infected and stably transformed cells. Immunoprecipitates of SV40 large T antigen from SV40-infected or SV40 large-T-antigen-transformed cells contain cyclin A, p33cdk2, and histone H1 kinase activity. Conversely, immunoprecipitates of cyclin A from these cells contain SV40 large T antigen. In this respect, SV40 large T antigen has properties similar to those of the E1A oncogene of adenoviruses and the E7 oncogene of human papillomaviruses. Images PMID:8411358

Giant Spin Hall Effect and Switching Induced by Spin-Transfer Torque in a W /Co40Fe40B20/MgO Structure with Perpendicular Magnetic Anisotropy

NASA Astrophysics Data System (ADS)

Hao, Qiang; Xiao, Gang

2015-03-01

We obtain robust perpendicular magnetic anisotropy in a β -W /Co40Fe40B20/MgO structure without the need of any insertion layer between W and Co40Fe40B20 . This is achieved within a broad range of W thicknesses (3.0-9.0 nm), using a simple fabrication technique. We determine the spin Hall angle (0.40) and spin-diffusion length for the bulk β form of tungsten with a large spin-orbit coupling. As a result of the giant spin Hall effect in β -W and careful magnetic annealing, we significantly reduce the critical current density for the spin-transfer-torque-induced magnetic switching in Co40Fe40B20 . The elemental β -W is a superior candidate for magnetic memory and spin-logic applications.

Fat-free mass and excess post-exercise oxygen consumption in the 40 minutes after short-duration exhaustive exercise in young male Japanese athletes.

PubMed

Tahara, Yasuaki; Moji, Kazuhiko; Honda, Sumihisa; Nakao, Rieko; Tsunawake, Noriaki; Fukuda, Rika; Aoyagi, Kiyoshi; Mascie-Taylor, Nicholas

2008-05-01

The relationship between fat-free mass (FFM) and excess post-exercise oxygen consumption (EPOC) has not been well researched because of the relatively small number of subjects studied. This study investigated the effects of FFM on EPOC and EPOC/maximum oxygen consumption. 250 Japanese male athletes between 16 and 21 years old from Nagasaki prefecture had their EPOC measured up to 40 minutes after short-duration exhaustive exercise. The value was named as EPOC40 min. The proportions of EPOC up to 1, 3, 6, 10, and 25 minutes to EPOC40 min were calculated and named as P1, P3, P6, P10, and P25, respectively. Body size and composition, VO2max and resting metabolic rate (RMR) were also measured. Mean EPOC40 min was 9.04 L or 158 ml/kg FFM. EPOC40 min was related to FFM (r=0.55, p<0.001) and VO2max (r=0.37, p<0.001). The ratio of EPOC40 min to VO2max was related to FFM (r=0.28, p<0.001). P1, P3, P6, P10, and P25 were negatively related to EPOC40 min/FFM, EPOC40 min/VO2max, and FFM. Athletes who had larger FFM had larger EPOC40 40 min and EPOC40 40 min/VO2max, and smaller P1, P3, P10, and P25.

Regulation of expression of the ligand for CD40 on T helper lymphocytes.

PubMed

Castle, B E; Kishimoto, K; Stearns, C; Brown, M L; Kehry, M R

1993-08-15

Activated Th cells deliver contact-dependent signals to resting B lymphocytes that initiate and drive B cell proliferation. Recently, a ligand for the B lymphocyte membrane protein, CD40, has been identified that delivers contact-dependent Th cell signals to B cells. A dimeric soluble form of CD40 was produced and used to further characterize the regulation of expression of the CD40 ligand. Expression of the CD40 ligand was rapidly induced after Th lymphocyte activation, and its stability depended upon whether Th cells were activated with soluble or plastic-bound stimuli. Th cells activated with soluble stimuli rapidly turned over cell-surface CD40 ligand whereas Th cells activated with plastic-bound stimuli exhibited more stable CD40 ligand expression for up to 48 h. Removal of activated Th cells from the plastic-bound stimulus resulted in a rapid turnover of CD40 ligand, suggesting that continuous stimulation could maintain CD40 ligand expression. Ligation by soluble CD40 could also stabilize expression of CD40 ligand on the Th cell surface. Both CD40 ligand and IL-2 were transiently synthesized from 1 to 12 h after Th cell activation and had similar kinetics of synthesis. In Con A-activated Th cells newly synthesized CD40 ligand exhibited an initial high turnover (1.5 h t1/2) and after 5 h of Th cell activation became more stable (10-h t1/2). In Th cells activated with plastic-bound anti-CD3, CD40 ligand exhibited a similar biphasic turnover except that the rapid turnover phase began significantly later. This delay could allow more time for newly synthesized CD40 ligand to assemble or associate with other molecules and thus become stabilized on the cell surface. Newly synthesized CD40 ligand in Con A-activated Th cells appeared to not be efficient in delivering Th cell-dependent contact signals to resting B cells, implying the need for assembly or accessory proteins. Regulation of CD40 ligand expression was consistent with all the characteristics of Th cell-delivered contact signals to B cells and may contribute to the high degree of specificity in B cell responses.

Evidence against a 40 degrees C core temperature threshold for fatigue in humans.

PubMed

Ely, Brett R; Ely, Matthew R; Cheuvront, Samuel N; Kenefick, Robert W; Degroot, David W; Montain, Scott J

2009-11-01

Evidence suggests that core temperatures of approximately 40 degrees C can induce fatigue, although this may be confounded by coincident elevations in skin temperatures and maximal cardiovascular strain. In an observational field study to examine core temperature threshold for fatigue, we investigated whether running performance is impaired when rectal temperature (T(re)) is >40 degrees C and skin temperature remains modest. Seventeen competitive runners (7/10 women/men: 8 km best 1,759 +/- 78/1,531 +/- 60 s) completed 8-km track time trials in cool (WBGT approximately 13 degrees C; n = 6), warm (WBGT approximately 27 degrees C; n = 4), or both (n = 7) conditions. T(re), chest skin temperature, and heart rate were logged continuously; elapsed time was recorded every 200 m. Running velocity for T(re) >40 degrees C was compared with that for T(re) <40 degrees C for each runner. Changes in running velocity over the last 600 m were compared between runners with T(re) >40 degrees C and <40 degrees C. Twelve runners achieved T(re) >40.0 degrees C with >or=600 m remaining (range 600-3,400 m). Average running velocity for T(re) <40 degrees C (282 +/- 27 m/min) was not different from that for T(re) >40 degrees C (279 +/- 28 m/min; P = 0.82). There were no differences in running velocity during the final 600 m between runners with final T(re) >40 degrees C or <40 degrees C (P = 0.16). Chest skin temperature ranged from 30 to 34 degrees C, and heart rate was >95% of age-predicted maximum. Our observation that runners were able to sustain running velocity despite T(re) >40 degrees C is evidence against 40 degrees C representing a "critical" core temperature limit to performance.

p40 (ΔNp63) expression in breast disease and its correlation with p63 immunohistochemistry

PubMed Central

Kim, Sang Kyum; Jung, Woo Hee; Koo, Ja Seung

2014-01-01

p63 protein is widely used to identify myoepithelial cells in breast disease. There have been no comparative studies of the p63 antibodies which detect different isoforms. In this study, we examine the expression profiles of p63 protein in benign proliferative diseases and malignant tumors of the breast using pan-p63 and p40 antibodies, and analyze their diagnostic utility and clinical implications. We selected 32 adenoses, 34 intraductal papillomas, 31 ductal carcinoma in situ (DCIS), 257 invasive ductal carcinoma (IDC), and 36 metaplastic carcinomas, and created tissue microarray blocks from them. Immunohistochemical assays for p63 protein were performed on these samples. We investigated the expression patterns of the pan-p63 (TP63, 4A4, Dako, 1:700), p40 antibody [5-17, CalBiochem/EMD Biosciences, 1:2000, p40 (CB)], and p40 antibody [polyclonal, Diagnostic BioSystems, 1:100, p40 (DB)] in various forms of breast disease. We determined that p63 and p40 (DB) expression in myoepithelial cells was broadly similar and showed cognate clinicopathologic features, unlike p40 (CB). p40 (CB) was more sensitive (99.0%) but less specific (85.8%), and p63 was less sensitive (93.8%) in adenosis, IP, and DCIS. In IDCs, p63 and p40 (DB) had similar expression in cancer cells; p40 (CB) expression, however, was statistically different. In metaplastic carcinomas, both p63 and p40 (DB) had distinct expression profiles, according to their histologic subtypes. We conclude that p40 antibodies as well as pan-p63 antibody are specific and sensitive myoepithelial cell markers. Interpretation of p40 positivity in cancer cells, however, should be considered carefully, due to their relatively lower specificity. PMID:24696720

30 CFR 925.15 - Approval of Missouri regulatory program amendments.

Code of Federal Regulations, 2010 CFR

2010-07-01

..., 1980, March 12, 1981 July 23, 1982 10 CSR 40-2.080; 40-3.050; 40-3.100(4)(B); 40-6.010(6), .070, .090(3... January 17, 1983 10 CSR 40-8.030(6)(B)1, (C), (7)(A), (D), (8)(A)1, (E), (9)(A)2, (B), (10)(A), (13)(B), .050(8), .060. April 13, 1983 May 8, 1984 RSMo 444: .805, .830, .950, .955, .960, .965, .970; 10 CSR 40...

Preclinical Evaluation of Novel Dendritic Cell-Based Prostate Cancer Vaccines

DTIC Science & Technology

2008-01-01

relative to other activation modalities(1). Hence the chimeric CD40 was named inducible CD40 (iCD40). The high utility of iCD40-activated DCs (iCD40...recent published (1) studies have suggested a new method to promote DC function in vivo, manipulation of a chimeric inducible CD40. While we have...number of HLA alleles using peptide candidate approach. This precluded the development of immunoassays for direct measurements of PSMA-specific Th

Serum YKL-40 as a marker of liver fibrosis in patients with non-alcoholic fatty liver disease.

PubMed

Kumagai, Erina; Mano, Yohei; Yoshio, Sachiyo; Shoji, Hirotaka; Sugiyama, Masaya; Korenaga, Masaaki; Ishida, Tsuyoshi; Arai, Taeang; Itokawa, Norio; Atsukawa, Masanori; Hyogo, Hideyuki; Chayama, Kazuaki; Ohashi, Tomohiko; Ito, Kiyoaki; Yoneda, Masashi; Kawaguchi, Takumi; Torimura, Takuji; Nozaki, Yuichi; Watanabe, Sumio; Mizokami, Masashi; Kanto, Tatsuya

2016-10-14

Non-alcoholic fatty liver disease (NAFLD) is a common cause of chronic non-viral liver disease. YKL-40, chitinase-like protein expressed in multiple tissues including liver, is involved in cell proliferation, inflammation and remodeling of the extracellular matrix. The aim of this study was to assess whether serum YKL-40 levels are associated with liver fibrosis in NAFLD patients. Serum YKL-40 levels were quantified in 111 NAFLD patients and 23 HCC patients with NAFLD. To identify the source of YKL-40, immunofluorescence staining of liver specimens from NAFLD patients was performed. Serum YKL-40 levels in NAFLD patients increased in accordance with the progression of liver fibrosis. Multivariate analysis revealed that YKL-40 was one of the independent factors significantly associated with severe fibrosis (F3-4). We established a new predictive model for fibrosis of NAFLD, using logistic regression analysis: YKL-40 based fibrosis score = -0.0545 + type IV collagen 7s * 0.3456 + YKL-40 * 0.0024. Serum YKL-40 levels of HCC patients with non-cirrhotic NAFLD were significantly higher than those without HCC. Immunofluorescence staining showed that YKL-40 was expressed by macrophages in liver tissue of NAFLD patients. In conclusion, macrophage-derived YKL-40 is a feasible biomarker of liver fibrosis in NAFLD patients.

Transcutaneous immunization with an outer membrane protein of Porphyromonas gingivalis without adjuvant elicits marked antibody responses.

PubMed

Koizumi, Y; Kurita-Ochiai, T; Yamamoto, M

2008-04-01

We have previously reported that specific immunoglobulin G (IgG) antibodies induced by transcutaneous immunization (TCI) with a 40-kDa outer membrane protein (40k-OMP) of Porphyromonas gingivalis, with cholera toxin (CT) as adjuvant, inhibited coaggregation by P. gingivalis. In this study, we further pursue the potential of the 40k-OMP as a transcutaneous vaccine. TCI of rats administered 40k-OMP elicited significant 40k-OMP-specific serum IgG and IgA, as well as salivary IgG antibody titers. Importantly, these antibody responses were induced without adjuvant. Thus, both serum and saliva antibody titers induced by TCI with the 40k-OMP alone were identical to those of 40k-OMP plus cholera toxin as adjuvant. The serum antibody responses induced by 40k-OMP persisted for more than 140 days. On the other hand, salivary IgG anti-40k-OMP antibodies were gradually decreased. Analysis of antibody-forming cells (AFCs) confirmed the antibody titers by detecting high numbers of 40k-OMP-specific IgG AFCs in spleen and cervical lymph node. Since 40k-OMP-specific IgG inhibited the coaggregation of P. gingivalis with Streptococcus gordonii, and the hemagglutinin activity of P. gingivalis, TCI with the 40k-OMP may be important as an adjuvant-free immunogen for the prevention of chronic periodontitis.

40 CFR 90.1 - Applicability.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 1051.145(a)(3) for provisions related to this allowance. (c) In certain cases, the regulations in this... manufacturer uses the provisions of 40 CFR 1051.145(a)(3) to exempt them from the requirements of 40 CFR part...) Engines used in highway motorcycles. See 40 CFR part 86, subpart E. (3) Propulsion marine engines. See 40...

40 CFR 454.40 - Applicability; description of manufacture of tall oil rosin, pitch and fatty acids subcategory.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 40 Protection of Environment 31 2012-07-01 2012-07-01 false Applicability; description of manufacture of tall oil rosin, pitch and fatty acids subcategory. 454.40 Section 454.40 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) EFFLUENT GUIDELINES AND STANDARDS (CONTINUED) GUM AND...

40 CFR 454.40 - Applicability; description of manufacture of tall oil rosin, pitch and fatty acids subcategory.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 40 Protection of Environment 30 2014-07-01 2014-07-01 false Applicability; description of manufacture of tall oil rosin, pitch and fatty acids subcategory. 454.40 Section 454.40 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) EFFLUENT GUIDELINES AND STANDARDS (CONTINUED) GUM AND...

40 CFR 454.40 - Applicability; description of manufacture of tall oil rosin, pitch and fatty acids subcategory.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 40 Protection of Environment 31 2013-07-01 2013-07-01 false Applicability; description of manufacture of tall oil rosin, pitch and fatty acids subcategory. 454.40 Section 454.40 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) EFFLUENT GUIDELINES AND STANDARDS (CONTINUED) GUM AND...

40 CFR 40.160-3 - Reporting of inventions.

Code of Federal Regulations, 2010 CFR

2010-07-01

... application. (b) A final invention report is required within 90 days after completion of the project period... 40 Protection of Environment 1 2010-07-01 2010-07-01 false Reporting of inventions. 40.160-3... ASSISTANCE RESEARCH AND DEMONSTRATION GRANTS § 40.160-3 Reporting of inventions. As provided in appendix B of...

40 CFR 458.40 - Applicability; description of the carbon black lamp process subcategory.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 40 Protection of Environment 31 2013-07-01 2013-07-01 false Applicability; description of the carbon black lamp process subcategory. 458.40 Section 458.40 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) EFFLUENT GUIDELINES AND STANDARDS (CONTINUED) CARBON BLACK MANUFACTURING POINT SOURCE CATEGORY Carbon Black Lamp Process...

40 CFR 458.40 - Applicability; description of the carbon black lamp process subcategory.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 40 Protection of Environment 30 2014-07-01 2014-07-01 false Applicability; description of the carbon black lamp process subcategory. 458.40 Section 458.40 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) EFFLUENT GUIDELINES AND STANDARDS (CONTINUED) CARBON BLACK MANUFACTURING POINT SOURCE CATEGORY Carbon Black Lamp Process...

40 CFR 408.40 - Applicability; description of the non-remote Alaskan crab meat processing subcategory.

Code of Federal Regulations, 2010 CFR

2010-07-01

...-remote Alaskan crab meat processing subcategory. 408.40 Section 408.40 Protection of Environment... PROCESSING POINT SOURCE CATEGORY Non-Remote Alaskan Crab Meat Processing Subcategory § 408.40 Applicability; description of the non-remote Alaskan crab meat processing subcategory. The provisions of this subpart are...

40 CFR 40.145-2 - Federal Water Pollution Control Act.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 40 Protection of Environment 1 2010-07-01 2010-07-01 false Federal Water Pollution Control Act. 40... FEDERAL ASSISTANCE RESEARCH AND DEMONSTRATION GRANTS § 40.145-2 Federal Water Pollution Control Act. (a... or control of acid or other mine water pollution; and (2) That the State shall provide legal and...

40 CFR 40.145-2 - Federal Water Pollution Control Act.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 40 Protection of Environment 1 2011-07-01 2011-07-01 false Federal Water Pollution Control Act. 40... FEDERAL ASSISTANCE RESEARCH AND DEMONSTRATION GRANTS § 40.145-2 Federal Water Pollution Control Act. (a... or control of acid or other mine water pollution; and (2) That the State shall provide legal and...

40 CFR 40.145-2 - Federal Water Pollution Control Act.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 40 Protection of Environment 1 2014-07-01 2014-07-01 false Federal Water Pollution Control Act. 40... FEDERAL ASSISTANCE RESEARCH AND DEMONSTRATION GRANTS § 40.145-2 Federal Water Pollution Control Act. (a... or control of acid or other mine water pollution; and (2) That the State shall provide legal and...

40 CFR 40.145-2 - Federal Water Pollution Control Act.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 40 Protection of Environment 1 2012-07-01 2012-07-01 false Federal Water Pollution Control Act. 40... FEDERAL ASSISTANCE RESEARCH AND DEMONSTRATION GRANTS § 40.145-2 Federal Water Pollution Control Act. (a... or control of acid or other mine water pollution; and (2) That the State shall provide legal and...

47 CFR 15.229 - Operation within the band 40.66-40.70 MHz.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 47 Telecommunication 1 2010-10-01 2010-10-01 false Operation within the band 40.66-40.70 MHz. 15.229 Section 15.229 Telecommunication FEDERAL COMMUNICATIONS COMMISSION GENERAL RADIO FREQUENCY DEVICES Intentional Radiators Radiated Emission Limits, Additional Provisions § 15.229 Operation within the band 40.66...

40 CFR 408.40 - Applicability; description of the non-remote Alaskan crab meat processing subcategory.

Code of Federal Regulations, 2011 CFR

2011-07-01

...-remote Alaskan crab meat processing subcategory. 408.40 Section 408.40 Protection of Environment... PROCESSING POINT SOURCE CATEGORY Non-Remote Alaskan Crab Meat Processing Subcategory § 408.40 Applicability; description of the non-remote Alaskan crab meat processing subcategory. The provisions of this subpart are...

Prime Contract Awards Alphabetically by Contractor, by State or Country, and Place. Part 1. (102 Construction, Inc.-American National Management)

DTIC Science & Technology

1989-01-01

KTN M4 I- M MN 0 .1-4 4 r-ON- a N r-r- 00 ’- 400 N- cma 0C00 N PN- (0 *mm" 44)- I nI 40 4 , , , 1 -4 w - 1-4 m N -4 N~ Moo0 U, 0)IIO0 I ( -4 N C1) -40...0 -4 If 40M( II, 0. 0t 4 M 00m 0.-40-4 a- 0 C-4"ONNN00 - 400 4T Nl oil I 05( 1 C, 0 -. 1i 0D -4C >C -40 -4-4--4 -4 -4- 40 -40C>-J! 0-1 0 0>~I 51 I...0 40 If 0 10 M I I 0> InaO< < 4n 444U U’)nU"UU oU 40 CON ( D0a C>Q 0- r0 ?- NUn 11 < CO-4 II CI >0 0 - - 400 - "-4 - 4-0 4 0 >-0) O)N t I 41110 -4 If

Early Solar System Alkali Fractionation Events Recorded by K-Ca Isotopes in the Yamato-74442 LL-Chondritic Breccia

NASA Technical Reports Server (NTRS)

Tatsunori, T.; Misawa, K.; Okano, O.; Shih, C.-Y.; Nyquist, L. E.; Simon, J. I.; Tappa, M. J.; Yoneda, S.

2015-01-01

Radiogenic ingrowth of Ca-40 due to decay of K-40 occurred early in the solar system history causing the Ca-40 abundance to vary within different early-former reservoirs. Marshall and DePaolo ] demonstrated that the K-40/Ca-40 decay system could be a useful radiogenic tracer for studies of terrestrial rocks. Shih et al. [3,4] determined 40K/40Ca ages of lunar granitic rock fragments and discussed the chemical characteristics of their source materials. Recently, Yokoyama et al. [5] showed the application of the K-40/Ca-40 chronometer for high K/Ca materials in ordinary chondrites (OCs). High-precision calcium isotopic data are needed to constrain mixing processes among early solar system materials and the time of planetesimal formation. To better constrain the solar system calcium isotopic compositions among astromaterials, we have determined the calcium isotopic compositions of OCs and an angrite. We further estimated a source K/Ca ratio for alkali-rich fragments in a chondritic breccia using the estimated solar system initial Ca-40/Ca-44.

Decreased serum levels of sCD40L and IL-31 correlate in treated patients with Relapsing-Remitting Multiple Sclerosis.

PubMed

de J Guerrero-García, José; Rojas-Mayorquín, Argelia E; Valle, Yeminia; Padilla-Gutiérrez, Jorge R; Castañeda-Moreno, Víctor A; Mireles-Ramírez, Mario A; Muñoz-Valle, José F; Ortuño-Sahagún, Daniel

2018-01-01

The CD40/CD40L system is a binding key for co-stimulation of immune cells. Soluble form of CD40L has been widely studied as marker of inflammatory and autoimmune diseases. Here we analyze serum concentrations of sCD40L, as well as 14 cytokines, in patients with Multiple Sclerosis (MS) treated with Glatiramer acetate or Interferon beta. In the healthy control group, we found in serum a highly positive correlation between sCD40L and Interleukin (IL)-31, an anti-inflammatory Th2 cytokine. Additionally, an important reduction in IL-31 and sCD40L serum levels, as well as a significant reduction in CD40 mRNA expression and complete depletion of CD40L mRNA, detected from peripheral blood cells, was found in treated patients with MS. Therefore, sCD40L and IL-31 must be taken into account as possible prognostic markers when analyzing the disease progress of MS in order to provide more personalized treatment. Copyright © 2017 Elsevier GmbH. All rights reserved.

Host CD40 Is Essential for DCG Treatment Against Metastatic Lung Cancer.

PubMed

Yamashita, Kimihiro; Hasegawa, Hiroshi; Fujita, Mitsugu; Nishi, Masayasu; Tanaka, Tomoko; Arimoto, Akira; Suzuki, Satoshi; Kamigaki, Takashi; Kakeji, Yoshihiro

2016-07-01

For the application of invariant natural killer T (iNKT) cells in cancer therapy, the CD40-CD40L interaction is indispensable in administering alpha-galactosylceramide (αGalCer). We hypothesized that CD40 plays an important role in dendritic cells (DC) pulsed with αGalCer (DCGs) in the treatment of lung metastases. Wild-type (WT) and CD40(-/-) mice were treated with DCGs isolated from WT or CD40(-/-) mice in a B16F10 lung metastases model and NK and NKT cell activity in lungs and the spleen were examined. DCG treatment improved WT mice survival but CD40(-/-) hosts received no survival benefit. Conversely, attenuation of a therapeutic effect in mice treated with CD40(-/-) DCGs was not observed. The functional activities of NK and NKT cells in DCG-treated CD40(-/-) mice were partially suppressed. Host CD40 is essential for DCG treatment to have a therapeutic effect on B16F10 lung metastases. Copyright© 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

The role of CD40 and CD40L in bone mineral density and in osteoporosis risk: A genetic and functional study.

PubMed

Panach, Layla; Pineda, Begoña; Mifsut, Damián; Tarín, Juan J; Cano, Antonio; García-Pérez, Miguel Ángel

2016-02-01

Compelling data are revealing that the CD40/CD40L system is involved in bone metabolism. Furthermore, we have previously demonstrated that polymorphisms in both genes are associated with bone phenotypes. The aim of this study is to further characterize this association and to identify the causal functional mechanism. We conducted an association study of BMD with 15 SNPs in CD40/CD40L genes in a population of 779 women. In addition, we assessed the functionality of this association through the study of the allele-dependent expression of CD40 and CD40L in peripheral blood leukocytes (PBLs) and in human osteoblasts (OBs) obtained from bone explants by qPCR and by sequencing. When an allelic imbalance (AI) was detected, studies on allele-dependent in vitro transcription rate and on CpG methylation in the gene promoter were also performed. Our results confirm the genetic association between SNP rs116535 (T>C) of CD40L gene with LS-BMD. Regarding CD40 gene, two SNPs showed nominal P-values<0.05 for FN- and LS-BMD (Z-scores), although the association was not significant after correcting for multiple testing. Homozygous TT women for SNP rs1883832 (C>T) of CD40 gene showed a trend to have lower levels of OPG (Q-value=0.059), especially when women of BMD-quartile ends were selected (P<0.05). Regarding functionality, we detected an AI for rs1883832 with the C allele the most expressed in OBs and in PBLs. Since the rs116535 of CD40L gene did not show AI, it was not further analyzed. Finally, we described a differential methylation of CpGs in the CD40 promoter among women of high in comparison to low BMD. Our results suggest that the CD40/CD40L system plays a role in regulating BMD. Effectively, our data suggest that a decreased production of OPG could be the cause of the lower BMD observed in TT women for rs1883832 of the CD40 gene and that the degree of methylation of CpGs in the CD40 promoter could contribute to the acquisition of BMD. One possibility that deserves further study is whether the degree of methylation of the CD40 gene affects the level of CD40 expression and, consequently, the level of OPG. Copyright © 2015 Elsevier Inc. All rights reserved.

Association between serum soluble CD40 ligand levels and mortality in patients with severe sepsis.

PubMed

Lorente, Leonardo; Martín, María M; Varo, Nerea; Borreguero-León, Juan María; Solé-Violán, Jordi; Blanquer, José; Labarta, Lorenzo; Díaz, César; Jiménez, Alejandro; Pastor, Eduardo; Belmonte, Felipe; Orbe, Josune; Rodríguez, José A; Gómez-Melini, Eduardo; Ferrer-Agüero, José M; Ferreres, José; Llimiñana, María C; Páramo, José A

2011-03-15

CD40 Ligand (CD40L) and its soluble counterpart (sCD40L) are proteins that exhibit prothrombotic and proinflammatory properties on binding to their cell surface receptor CD40. The results of small clinical studies suggest that sCD40L levels could play a role in sepsis; however, there are no data on the association between sCD40L levels and mortality of septic patients. Thus, the aim of this study was to determine whether circulating sCD40L levels could be a marker of adverse outcome in a large cohort of patients with severe sepsis. This was a multicenter, observational and prospective study carried out in six Spanish intensive care units. Serum levels of sCD40L, tumour necrosis factor-alpha and interleukin-10, and plasma levels of tissue factor were measured in 186 patients with severe sepsis at the time of diagnosis. Serum sCD40L was also measured in 50 age- and sex-matched controls. Survival at 30 days was used as the endpoint. Circulating sCD40L levels were significantly higher in septic patients than in controls (P = 0.01), and in non-survivors (n = 62) compared to survivors (n = 124) (P = 0.04). However, the levels of CD40L were not different regarding sepsis severity. Logistic regression analysis showed that sCD40L levels >3.5 ng/mL were associated with higher mortality at 30 days (odds ratio = 2.89; 95% confidence interval = 1.37 to 6.07; P = 0.005). The area under the curve of sCD40L levels >3.5 ng/mL as predictor of mortality at 30 days was 0.58 (95% CI = 0.51 to 0.65; P = 0.03). In conclusion, circulating sCD40L levels are increased in septic patients and are independently associated with mortality in these patients; thus, its modulation could represent an attractive therapeutic target.

IL-12p40-dependent agonistic effects on the development of protective innate and adaptive immunity against Salmonella enteritidis.

PubMed

Lehmann, J; Bellmann, S; Werner, C; Schröder, R; Schütze, N; Alber, G

2001-11-01

To study a potential IL-12p40-dependent but IL-12p75-independent agonistic activity regulating the immune response against Salmonella Enteritidis, the course of infection in IL-12p35-deficient mice (IL-12p35(-/-), capable of producing IL-12p40) was compared with that of IL-12p40(-/-) mice. Mice lacking IL-12p40 revealed a higher mortality rate and higher bacterial organ burden than mice capable of producing IL-12p40. This phenotype was found in both genetically susceptible (BALB/c, Ity(s)) and resistant mice (129Sv/Ev, Ity(r)) indicating Ity-independent mechanisms. The more effective control of bacteria in the IL-12p35(-/-) mice was associated with elevated serum IFN-gamma and TNF-alpha levels. In contrast, IL-12p40(-/-) mice showed reduced IFN-gamma production, which was associated with significantly elevated serum IgE levels. Early during infection (days 3 and 4 postinfection), as well as late (day 20 postinfection), the number of infected phagocytes was strongly increased in the absence of IL-12p40 indicating impaired bactericidal activity when IL-12p40 was missing. Liver histopathology revealed a decreased number of mononuclear granulomas in IL-12p40(-/-) mice. Depletion of CD4(+) or CD8(+) T lymphocytes in vivo suggested that both T cell subpopulations contribute to the IL-12p40-dependent protective functions. Analysis of IL-12p40 vs IL-23p19 mRNA expression revealed an up-regulation of only IL-12p40 mRNA during Salmonella infection. Together these data indicate that IL-12p40 can induce protective mechanisms during both the innate and the adaptive type 1 immune response in Salmonella infection. This novel activity of IL-12p40 complements the well described dominant and essential role of IL-12p75 in protective immunity to Salmonella infection.

50 CFR 648.23 - Gear restrictions.

Code of Federal Regulations, 2011 CFR

2011-10-01

...′ 66°38.0′ M12 40°45.5′ 68°00.0′ M13 40°37.0′ 68°00.0′ M14 40°30.0′ 69°00.0′ M15 40°22.7′ 69°00.0′ M16...′ 67°10.0′ M10 41°18.6′ 66°24.8′ M11 40°55.5′ 66°38.0′ M12 40°45.5′ 68°00.0′ M13 40°37.0′ 68°00.0′ M14...

A Single Amino Acid Change in the Marburg Virus Matrix Protein VP40 Provides a Replicative Advantage in a Species-Specific Manner

PubMed Central

Koehler, Alexander; Kolesnikova, Larissa; Welzel, Ulla; Schudt, Gordian; Herwig, Astrid

2015-01-01

ABSTRACT Marburg virus (MARV) induces severe hemorrhagic fever in humans and nonhuman primates but only transient nonlethal disease in rodents. However, sequential passages of MARV in rodents boosts infection leading to lethal disease. Guinea pig-adapted MARV contains one mutation in the viral matrix protein VP40 at position 184 (VP40D184N). The contribution of the D184N mutation to the efficacy of replication in a new host is unknown. In the present study, we demonstrated that recombinant MARV containing the D184N mutation in VP40 [rMARVVP40(D184N)] grew to higher titers than wild-type recombinant MARV (rMARVWT) in guinea pig cells. Moreover, rMARVVP40(D184N) displayed higher infectivity in guinea pig cells. Comparative analysis of VP40 functions indicated that neither the interferon (IFN)-antagonistic function nor the membrane binding capabilities of VP40 were affected by the D184N mutation. However, the production of VP40-induced virus-like particles (VLPs) and the recruitment of other viral proteins to the budding site was improved by the D184N mutation in guinea pig cells, which resulted in the higher infectivity of VP40D184N-induced infectious VLPs (iVLPs) compared to that of VP40-induced iVLPs. In addition, the function of VP40 in suppressing viral RNA synthesis was influenced by the D184N mutation specifically in guinea pig cells, thus allowing greater rates of transcription and replication. Our results showed that the improved viral fitness of rMARVVP40(D184N) in guinea pig cells was due to the better viral assembly function of VP40D184N and its lower inhibitory effect on viral transcription and replication rather than modulation of the VP40-mediated suppression of IFN signaling. IMPORTANCE The increased virulence achieved by virus passaging in a new host was accompanied by mutations in the viral genome. Analyzing how these mutations affect the functions of viral proteins and the ability of the virus to grow within new host cells helps in the understanding of the molecular mechanisms increasing virulence. Using a reverse genetics approach, we demonstrated that a single mutation in MARV VP40 detected in a guinea pig-adapted MARV provided a replicative advantage of rMARVVP40(D184N) in guinea pig cells. Our studies show that this replicative advantage of rMARV VP40D184N was based on the improved functions of VP40 in iVLP assembly and in the regulation of transcription and replication rather than on the ability of VP40 to combat the host innate immunity. PMID:26581998

Heritability of peripheral refraction in Chinese children and adolescents: the Guangzhou Twin Eye study.

PubMed

Ding, Xiaohu; Lin, Zhi; Huang, Qunxiao; Zheng, Yingfeng; Congdon, Nathan; He, Mingguang

2012-01-10

To estimate the heritability of peripheral refraction in Chinese children and adolescents. The authors examined 72 monozygotic (MZ) twins and 48 dizygotic (DZ) twins aged 8 to 20 years from a population-based twin registry. Temporal and nasal peripheral refraction, each 40° from the visual axis, and axial refraction were measured using an autorefractor. Relative peripheral refractive error (RPRE) was defined as the peripheral refraction minus the axial refraction. Heritability was assessed by structural equation modeling after adjustment for age and sex. The mean and SD of temporal refraction (T(40)), nasal refraction (N(40)), RPRE-T(40), RPRE-N(40), and T(40)-N(40) asymmetry were -0.27 ± 2.0 D, 0.36 ± 2.19 D, 1.18 ± 1.39 D, 1.80 ± 1.69 D, and -0.62 ± 1.58 D, respectively. The intraclass correlations for T(40) refraction, N(40) refraction, RPRE-T(40), RPRE-N(40), and T(40)-N(40) asymmetry were 0.87, 0.83, 0.65, 0.74, and 0.58 for MZ pairs and 0.49, 0.42, 0.30, 0.41, and 0.32 for DZ pairs, respectively. A model with additive genetic and unique environmental effects was the most parsimonious, with heritability values estimated as 0.84, 0.76, 0.63, 0.70, and 0.55, respectively, for the peripheral refractive parameters. Additive genetic effects appear to explain most of the variance in peripheral refraction and relative peripheral refraction when adjusting for the effects of axial refraction.

The HTLV-I tax protein transcriptionally modulates OX40 antigen expression.

PubMed

Pankow, R; Dürkop, H; Latza, U; Krause, H; Kunzendorf, U; Pohl, T; Bulfone-Paus, S

2000-07-01

OX40 is a member of the TNF receptor family, expressed on activated T cells. It is the only costimulatory T cell molecule known to be specifically up-regulated in human T cell leukemia virus type-I (HTLV-I)-producing cells. In a T cell line, OX40 surface expression was shown to be induced by HTLV-I Tax alone. To understand molecular mechanisms of OX40 gene regulation and modulation by HTLV-I Tax, we have cloned the human OX40 gene and analyzed its 5'-flanking region. By reporter gene analysis with progressive 5' deletions from nucleotides -1259 to -64, we have defined a 157-bp DNA fragment as a minimal promoter for constitutive expression. In addition, we show that in the OX40+ cell line, Co, Tax is able to further increase OX40 surface expression. Up-regulation of OX40 promoter activity by Tax requires two upstream NF-kappaB sites, which are not active in the constitutive OX40 expression. Their deletion abrogates Tax responsiveness in reporter gene analysis. The site-directed mutagenesis of each NF-kappaB site demonstrates that cooperative NF-kappaB binding is a prerequisite for Tax-directed activity as neither site alone is sufficient for a full Tax responsiveness of the OX40 promoter. Upon Tax expression, both sites bind p65 and c-Rel. These data provide new insight into the direct regulation of OX40 by Tax and add to our understanding of the possible role of the OX40/OX40 ligand system in the proliferation of HTLV-I+ T cells.

South Atlantic Islands. Section 23. Weather and Climate

DTIC Science & Technology

1960-05-01

NOT RELEPASABLE TO FOREIGN NATIONALS PAav 23-13 NIS 64 AIR FORCE -MAY 1960 to 0000 Ist I00 W 0000 151O IS 200 LSI so no so 8 40 40 #0 40 40 40 40...IAV JV’Nit .1 11(1 SI (-ri NO o IKv A N N ViHS IWOi Asceiilon Island ...... Niux 85 87 88 88 87 85 84 83 82 83 83 84 88 20) MmN11 73 74 75 75 74 73 72

Cancer immunotherapy: activating innate and adaptive immunity through CD40 agonists

PubMed Central

Beatty, Gregory L.; Li, Yan; Long, Kristen B.

2017-01-01

INTRODUCTION CD40 is a promising therapeutic target for cancer immunotherapy. In patients with advanced solid malignancies, CD40 agonists have demonstrated some anti-tumor activity and a manageable toxicity profile. A 2nd generation of CD40 agonists has now been designed with optimized Fc receptor (FcR) binding based on preclinical evidence suggesting a critical role for FcR engagement in defining the potency of CD40 agonists in vivo. AREAS COVERED We provide a comprehensive review using PubMed and Google Patent databases on the current clinical status of CD40 agonists, strategies for applying CD40 agonists in cancer therapy, and the preclinical data that supports and is guiding the future development of CD40 agonists. EXPERT COMMENTARY There is a wealth of preclinical data that provide rationale on several distinct approaches for using CD40 agonists in cancer immunotherapy. This data illustrates the need to strategically combine CD40 agonists with other clinically active treatment regimens in order to realize the full potential of activating CD40 in vivo. Thus, critical to the success of this class of immune-oncology drugs, which have the potential to restore both innate and adaptive immunosurveillance, will be the identification of biomarkers for monitoring and predicting responses as well as informing mechanisms of treatment resistance. PMID:27927088

A novel blocking monoclonal antibody recognizing a distinct epitope of human CD40 molecule.

PubMed

Zhuang, Y; Huang, J; Zhou, Z; Ge, Y; Fan, Y; Qi, C; Zhen, L; Monchatre, E; Edelman, L; Zhang, X

2005-01-01

CD40, a member of the tumor necrosis factor receptor superfamily, is an important costimulatory molecule during the immune response. Here, we report a blocking mouse antihuman CD40 monoclonal antibody, mAb 3G3, of which the specificity was verified by flow cytometry and Western blot. It was shown by competition test that 3G3 bound to a different site (epitope) of CD40 from the reported CD40 mAbs, including clone mAb89, 3B2, and 5C11. It was also found that mAb 3G3 could inhibit homotypic aggregation of Daudi cells induced by the agonistic anti-CD40 mAb 5C11. Furthermore, mAb 3G3 effectively inhibited the proliferation of peripheral blood mononuclear cells in mixed lymphocyte reaction assay. Finally, a sensitive and specific soluble CD40 (sCD40) ELISA kit was established by matching mAb 3G3 with 5C11, and it was found that the levels of sCD40 in sera from patients with immune disorders such as hyperthyroidism, chronic nephritis, and rheumatoid arthritis were obviously higher than those from normal individuals. Thus, this blocking anti-CD40 mAb provides a novel tool for the study of CD40.

CD40 activation induces apoptosis in cultured human hepatocytes via induction of cell surface fas ligand expression and amplifies fas-mediated hepatocyte death during allograft rejection.

PubMed

Afford, S C; Randhawa, S; Eliopoulos, A G; Hubscher, S G; Young, L S; Adams, D H

1999-01-18

We propose that a novel mechanism of hepatocyte apoptosis, involving a cooperative interaction between CD40 and Fas, is involved in the hepatocyte loss of chronic liver allograft rejection. We detected increased hepatocyte expression of Fas, Fas ligand (FasL), and CD40 associated with dropout of centrilobular (acinar zone 3) hepatocytes in chronic allograft rejection. Expression of CD40 ligand (CD40L) was also increased but was largely restricted to CD68(+) macrophages. A functional role for CD40 and Fas in hepatocyte apoptosis was demonstrated in vitro using primary human hepatocytes and the HepG2 cell line in both of which apoptosis was induced, not only by cross-linking Fas directly but also via CD40 activation. Our data suggest that CD40 activation induces apoptosis via Fas because (a) ligation of CD40 upregulated hepatocyte FasL expression, and (b) apoptosis induced via activation of CD40 was prevented by a neutralizing monoclonal antibody to FasL. Thus, CD40 engagement triggers apoptosis of human hepatocytes and might amplify Fas-dependent hepatocyte apoptosis in chronic rejection and other inflammatory liver diseases in which Fas-mediated apoptosis is involved.

10 CFR 1.40 - [Reserved

Code of Federal Regulations, 2010 CFR

2010-01-01

... 10 Energy 1 2010-01-01 2010-01-01 false [Reserved] 1.40 Section 1.40 Energy NUCLEAR REGULATORY COMMISSION STATEMENT OF ORGANIZATION AND GENERAL INFORMATION Headquarters Staff Offices § 1.40 [Reserved] ...

Biodistribution of the GATA-3-specific DNAzyme hgd40 after inhalative exposure in mice, rats and dogs

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

Turowska, Agnieszka; Librizzi, Damiano; Baumgartl, Nadja

The DNAzyme hgd40 was shown to effectively reduce expression of the transcription factor GATA-3 RNA which plays an important role in the regulation of Th2-mediated immune mechanisms such as in allergic bronchial asthma. However, uptake, biodistribution and pharmacokinetics of hgd40 have not been investigated yet. We examined local and systemic distribution of hgd40 in naive mice and mice suffering from experimental asthma. Furthermore, we evaluated the pharmacokinetics as a function of dose following single and repeated administration in rats and dogs. Using intranasal administration of fluorescently labeled hgd40 we demonstrated that the DNAzyme was evenly distributed in inflamed asthmatic mousemore » lungs within minutes after single dose application. Systemic distribution was investigated in mice using radioactive labeled hgd40. After intratracheal application, highest amounts of hgd40 were detected in the lungs. High amounts were also detected in the bladder indicating urinary excretion as a major elimination pathway. In serum, low systemic hgd40 levels were detected already at 5 min post application (p.a.), subsequently decreasing over time to non-detectable levels at 2 h p.a. As revealed by Single Photon Emission Computed Tomography, trace amounts of hgd40 were detectable in lungs up to 7 days p.a. Also in the toxicologically relevant rats and dogs, hgd40 was detectable in blood only shortly after inhalative application. The plasma pharmacokinetic profile was dose and time dependent. Repeated administration did not lead to drug accumulation in plasma of dogs and rats. These pharmacokinetic of hgd40 provide guidance for clinical development, and support an infrequent and convenient dose administration regimen. - Highlights: • Local and systemic distribution of GATA-3-specific DNAzyme hgd40 was investigated. • Pharmacokinetics of hgd40 was tested in rats and dogs. • hgd40 dissolved in PBS was easily taken up into the lungs after local application. • No accumulation of hgd40 was observed after multiple treatments. • Pharmacokinetic properties of hgd40 support convenient dose administration regimen.« less

10 CFR 40.43 - Renewal of licenses.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 10 Energy 1 2010-01-01 2010-01-01 false Renewal of licenses. 40.43 Section 40.43 Energy NUCLEAR REGULATORY COMMISSION DOMESTIC LICENSING OF SOURCE MATERIAL Licenses § 40.43 Renewal of licenses. (a) Application for renewal of a specific license must be filed on NRC Form 313 and in accordance with § 40.31. (b...

40 CFR 97.40 - Trading program budget.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 40 Protection of Environment 21 2011-07-01 2011-07-01 false Trading program budget. 97.40 Section...) FEDERAL NOX BUDGET TRADING PROGRAM AND CAIR NOX AND SO2 TRADING PROGRAMS NOX Allowance Allocations § 97.40 Trading program budget. In accordance with §§ 97.41 and 97.42, the Administrator will allocate to the NOX...

40 CFR 454.40 - Applicability; description of manufacture of tall oil rosin, pitch and fatty acids subcategory.

Code of Federal Regulations, 2010 CFR

2010-07-01

... manufacture of tall oil rosin, pitch and fatty acids subcategory. 454.40 Section 454.40 Protection of... CHEMICALS MANUFACTURING POINT SOURCE CATEGORY Tall Oil Rosin, Pitch and Fatty Acids Subcategory § 454.40 Applicability; description of manufacture of tall oil rosin, pitch and fatty acids subcategory. The provisions...

40 CFR 454.40 - Applicability; description of manufacture of tall oil rosin, pitch and fatty acids subcategory.

Code of Federal Regulations, 2011 CFR

2011-07-01

... manufacture of tall oil rosin, pitch and fatty acids subcategory. 454.40 Section 454.40 Protection of... CHEMICALS MANUFACTURING POINT SOURCE CATEGORY Tall Oil Rosin, Pitch and Fatty Acids Subcategory § 454.40 Applicability; description of manufacture of tall oil rosin, pitch and fatty acids subcategory. The provisions...

40 CFR 97.40 - Trading program budget.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 40 Protection of Environment 20 2010-07-01 2010-07-01 false Trading program budget. 97.40 Section...) FEDERAL NOX BUDGET TRADING PROGRAM AND CAIR NOX AND SO2 TRADING PROGRAMS NOX Allowance Allocations § 97.40 Trading program budget. In accordance with §§ 97.41 and 97.42, the Administrator will allocate to the NOX...

40 CFR 261.40 - Conditional Exclusion for Used, Intact Cathode Ray Tubes (CRTs) Exported for Recycling.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 40 Protection of Environment 26 2014-07-01 2014-07-01 false Conditional Exclusion for Used, Intact Cathode Ray Tubes (CRTs) Exported for Recycling. 261.40 Section 261.40 Protection of Environment...) Exported for Recycling. Used, intact CRTs exported for recycling are not solid wastes if they meet the...