Journal ArticlemBio · December 21, 2021
Calcineurin is a critical enzyme in fungal pathogenesis and antifungal drug tolerance and, therefore, an attractive antifungal target. Current clinically accessible calcineurin inhibitors, such as FK506, are immunosuppressive to humans, so exploiting calci ...
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Journal ArticleSci Immunol · October 29, 2021
Vaccine development to prevent Salmonella Typhi infections has accelerated over the past decade, resulting in licensure of new vaccines, which use the Vi polysaccharide (Vi PS) of the bacterium conjugated to an unrelated carrier protein as the active compo ...
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Journal ArticleBiochem Biophys Res Commun · May 21, 2020
The 12-kDa FK506-binding protein (FKBP12) is the target of the commonly used immunosuppressive drug FK506. The FKBP12-FK506 complex binds to calcineurin and inhibits its activity, leading to immunosuppression and preventing organ transplant rejection. Our ...
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Journal Article · 2020
Calcineurin is a critical enzyme in fungal pathogenesis and antifungal drug tolerance and, therefore, an attractive antifungal target. Current clinically-accessible calcineurin inhibitors, such as FK506, are immunosuppressive to humans, so exploiting calci ...
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Journal ArticleNat Commun · September 19, 2019
Calcineurin is important for fungal virulence and a potential antifungal target, but compounds targeting calcineurin, such as FK506, are immunosuppressive. Here we report the crystal structures of calcineurin catalytic (CnA) and regulatory (CnB) subunits c ...
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Journal ArticleBiomol NMR Assign · April 2019
Invasive fungal infections are a leading cause of death in immunocompromised patients and remain difficult to treat since fungal pathogens, like mammals, are eukaryotes and share many orthologous proteins. As a result, current antifungal drugs have limited ...
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Journal ArticlemBio · April 26, 2016
UNLABELLED: Invasive fungal infections remain difficult to treat and require novel targeting strategies. The 12-kDa FK506-binding protein (FKBP12) is a ubiquitously expressed peptidyl-prolyl isomerase with considerable homology between fungal pathogens and ...
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Journal ArticleProc Natl Acad Sci U S A · January 28, 2014
The membrane proximal external region (MPER) of HIV-1 glycoprotein (gp) 41 is involved in viral-host cell membrane fusion. It contains short amino acid sequences that are binding sites for the HIV-1 broadly neutralizing antibodies 2F5, 4E10, and 10E8, maki ...
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Journal ArticleJ Exp Med · February 11, 2013
Many human monoclonal antibodies that neutralize multiple clades of HIV-1 are polyreactive and bind avidly to mammalian autoantigens. Indeed, the generation of neutralizing antibodies to the 2F5 and 4E10 epitopes of HIV-1 gp41 in man may be proscribed by i ...
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Journal ArticleMethods Mol Biol · 2012
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A living cell is a complex system that contains many biological macromolecules and small molecules necessary for survival, in a relatively small volume. It is within this crowded and complex cellular environment that proteins function making in-cell studie ...
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Journal ArticleBMC Genomics · November 14, 2011
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BACKGROUND: Whole-genome sequencing of bacteria has proceeded at an exponential pace but annotation validation has lagged behind. For instance, the MetJ regulon, which controls methionine biosynthesis and transport, has been studied almost exclusively in E ...
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Journal ArticleNat Struct Mol Biol · December 2010
The monoclonal antibody 13H11 shares part of its epitope in the HIV-1 gp41 membrane-proximal external region (MPER) with the rare, broadly neutralizing human antibody 2F5. Although 13H11 partially cross-blocked 2F5 binding, 13H11 is non-neutralizing and do ...
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Journal ArticleBiochemistry · April 20, 2010
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We have used analytical ultracentrifugation to characterize the binding of the methionine repressor protein, MetJ, to synthetic oligonucleotides containing zero to five specific recognition sites, called metboxes. For all lengths of DNA studied, MetJ binds ...
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Journal ArticleProc Natl Acad Sci U S A · March 31, 2009
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Atomic level characterization of proteins and other macromolecules in the living cell is challenging. Recent advances in NMR instrumentation and methods, however, have enabled in-cell studies with prospects for multidimensional spectral characterization of ...
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Journal ArticleJ Biol Chem · November 10, 2006
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The Met regulon in Escherichia coli encodes several proteins responsible for the biosynthesis of methionine. Regulation of the expression of most of these proteins is governed by the methionine repressor protein MetJ and its co-repressor, the methionine de ...
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Journal ArticleJ Am Chem Soc · August 10, 2005
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High-field, heteronuclear NMR spectroscopy of biological macromolecules in native cellular environments is limited by the low concentrations present and the long data acquisition times needed for the experiments. Successful 1D and 2D heteronuclear NMR data ...
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Journal ArticleNucleic Acids Res · June 15, 2001
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Recent NMR-based, chemical shift mapping experiments with the minimal DNA-binding domain of XPA (XPA-MBD: M98-F219) suggest that a basic cleft located in the loop-rich subdomain plays a role in DNA-binding. Here, XPA-DNA interactions are further characteri ...
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Journal ArticleMutat Res · June 5, 2001
XPA is a central protein component of nucleotide excision repair (NER), a ubiquitous, multi-component cellular pathway responsible for the removal and repair of many structurally distinct DNA lesions from the eukaryotic genome. The solution structure of th ...
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Journal ArticleBiochemistry · November 16, 1999
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Human XPA is an essential component in the multienzyme nucleotide excision repair (NER) pathway. The solution structure of the minimal DNA binding domain of XPA (XPA-MBD: M98-F219) was recently determined [Buchko et al. (1998) Nucleic Acids Res. 26, 2779-2 ...
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Journal ArticleJ Virol · January 1999
Immunogenic peptides containing epitopes of the gp120 C4 and V3 regions from human immunodeficiency virus strains MN and EV91 have been studied by nuclear magnetic resonance and molecular modeling and used as immunogens in rhesus monkeys. The results, comb ...
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Journal ArticleProtein and Peptide Letters · January 1, 1997
Solution NMR studies of τD1, an 18-residue microtubule binding peptide from domain 1 of human tau protein, are reported. Using 2D 1H NMR (TOCSY, NOESY and ROESY) at 5 and 37°C, we assigned the resonances of almost all protons of τD1 at pH 4.2,5. ...
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Journal ArticleJ Mol Biol · December 20, 1996
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Perdeuteration of all non-exchangeable proton sites can significantly increase the size of proteins and protein complexes for which NMR resonance assignments and structural studies are possible. Backbone 1H, 15N, 13CO, 13C alpha and 13C beta chemical shift ...
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Journal ArticleProtein Sci · December 1996
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Core-packing mutants of proteins often approach molten globule states, and hence may have attributes of folding intermediates. We have studied a core-packing mutant of thioredoxin, L78K, in which a leucine residue is substituted by lysine, using 15N hetero ...
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Journal ArticleBiochemistry · April 23, 1996
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A critical problem to overcome on HIV vaccine design is the variability among HIV strains. One strategy to solve this problem is the construction of multicomponent immunogens reflective of common HIV motifs. Currently, it is not known if these motifs shoul ...
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Journal ArticleJ Magn Reson B · July 1995
The advantageous use of sinc-shaped pulses in heteronuclear half filters is explored for studying biological macromolecules. The typical square, or hard, pulse used in half-filter pulse sequences for heteronuclear excitation results in suboptimal suppressi ...
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Journal ArticleJ Biomol NMR · June 1995
The protein human carbonic anhydrase II (HCA II) has been isotopically labeled with 2H, 13C and 15N for high-resolution NMR assignment studies and pulse sequence development. To increase the sensitivity of several key 1H/13C/15N triple-resonance correlatio ...
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Journal ArticleBiochemistry · March 14, 1995
The binding interactions of the methionine repressor protein, MetJ, from Escherichia coli with its cognate, metbox DNA sequence and corepressor S-adenosylmethionine were examined using calorimetric methods. A detailed thermodynamic characterization of this ...
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Journal ArticleTechniques in Protein Chemistry · January 1, 1995
Human carbonic anhydrase (HCA) is ubiquitous in living systems with seven different mammalian isozymes (CAI to CAVII), and HCAII is one of the largest monomeric proteins currently, being studied by NMR, making it a good system on which to demonstrate the a ...
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Journal ArticleBiochemistry · March 1, 1994
Solution conformations of a 40-residue hybrid peptide containing T-helper epitopes and B-cell determinants from envelope glycoprotein gp120 of human immunodeficiency virus (HIV) have been investigated with NMR. Peptides of this general design are highly im ...
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Conference · January 1, 1994
This chapter discusses nuclear magnetic resonance (NMR) methods used to derive solution conformations in peptides. Two-dimensional proton NMR spectroscopy provides an important tool for identifying preferred conformers in otherwise unstructured peptides. T ...
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Journal ArticleBiochemistry · August 31, 1993
The heme protein subunit of sulfite reductase (SiR-HP; M(r) 64,000) from Escherichia coli as isolated contains the isobacteriochlorin siroheme exchange-coupled to a [4Fe-4S] cluster in the 2+ oxidation state. SiR-HP in the presence of a suitable electron d ...
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Journal ArticleBiochemistry · March 23, 1993
The isolated hemeprotein subunit of sulfite reductase (SiR-HP) from Escherichia coli consists of a high spin ferric isobacteriochlorin (siroheme) coupled to a diamagnetic [4Fe-4S]2+ cluster. When supplied with an artificial electron donor, such as methyl v ...
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Journal ArticleAm J Obstet Gynecol · January 1993
OBJECTIVE: Initial phosphorus magnetic resonance spectroscopy observations on the oxygen metabolism of placental villi from normal term pregnancies are described. STUDY DESIGN: Villi were suspended in medium and perifused within a custom-designed 30 mm nuc ...
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Journal ArticleSynthetic Communications · September 1, 1992
The catalytic reduction of a variety of α. β-unsaturated compounds into saturated analogs in the presence of other reducible moieties is described using ammonium formate as a hydrogen source. The rate dependence on the concentration of Pd-C catalyst as wel ...
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Journal ArticleSynthetic Communications · September 1, 1992
Temperature control and solvent specification are used to reduce aromatic aldehydes and ketones to intermediate alcohols rather than methylene derivatives using HCO2NH4as a catalytic hydrogen transfer agent. A mechanism for the cataly ...
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Journal ArticleAm J Obstet Gynecol · August 1992
OBJECTIVE: Phosphorus 31 magnetic resonance spectroscopy studies were carried out on placentas from normal vaginal and elective cesarean deliveries without antenatal complications and from pregnancies complicated by intrauterine growth retardation of unkno ...
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Journal ArticleJ Biomol NMR · March 1992
A 3D optimized, refocused HNCA experiment is described. It is demonstrated to yield a dramatic increase in sensitivity when applied to [13C, 15N]-labeled human carbonic anhydrase II, a 29-kDa protein. The reasons for the gain in sensitivity are discussed, ...
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Journal ArticleNMR Biomed · October 1991
A MR spectroscopy method is described for the simultaneous discrimination and observation of sodium from the three compartments created by an intact cell monolayer. Results are reported for Madin Darby Canine Kidney (MDCK) cells, an epithelial-like continu ...
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Journal ArticleBiochemistry · May 7, 1991
Uniform double labeling of proteins for NMR studies can be prohibitively expensive, even with an efficient expression and purification scheme, due largely to the high cost of [13C6, 99%]glucose. We demonstrate here that uniformly (greater than 95%) 13C and ...
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Journal ArticleAm J Obstet Gynecol · January 1991
Phosphorus 31 magnetic resonance spectroscopic studies of fresh placental tissue are reported that indicate resonances for adenosine triphosphate, inorganic phosphate, sugar phosphates-phosphomonoesters, and phosphodiesters. Perchloric acid extract methods ...
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Journal ArticleMagn Reson Med · March 1990
Analysis of biological fluids by proton magnetic resonance spectroscopy is often complicated by dynamic range problems created from the large water resonance. Gel filtration chromatography is found to be a simple and nondestructive method for exchanging D2 ...
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Journal ArticleInt J Rad Appl Instrum A · 1989
A new synthesis is described for the production of the positron emitting radiopharmaceutical R-(+)-7-chloro-8-hydroxy-2,3,4,5-tetrahydro-3-N-[11C]methyl-1-phenyl-1H- 3-benzazepine (SCH 23390, 2a). This novel method involves reductive carboxylation, in whic ...
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Journal ArticleInt J Rad Appl Instrum A · 1989
Radiolabeled chlorpromazine was prepared by carboxylation of the N-trimethylsilyl derivative of norchlorpromazine with [11C]carbon dioxide, followed by in situ lithium aluminum hydride reduction. Radiochemical yields of 22-24% and radiochemical purities in ...
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Journal ArticleJournal of Labelled Compounds and Radiopharmaceuticals · January 1, 1989
A one‐pot synthesis of [11C] labeled tamoxifen has been developed via reductive carboxylation. In this approach, [11C]CO2 is reacted with the N‐trimethylsilyl derivative of desmethyltamoxifen, followed by in situ sodium bis ...
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Journal ArticleMagn Reson Imaging · 1987
Magnetic forces exerted on surgical clips and the magnetic resonance imaging distortion they create in phantoms and rabbits at magnetic field strengths of 1.5 Tesla were investigated. Results are reported for both ligation and aneurysm clips manufactured f ...
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Journal ArticleMagn Reson Med · April 1986
Spin relaxation and chemical shifts by lanthanide chelate complexes are used to distinguish 23Na signals in a simulated two-compartment model. Both effects are significant in EDTA, DTPA, and TPP complexes of Gd and in the TPP complex of Dy. The simultaneou ...
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Journal ArticleComput Radiol · 1986
Surgical clips in postoperative patients create streak artifact on computed tomographic (CT) studies which often significantly degrade image quality. We have evaluated three types of surgical clips: tantalum, stainless steel, and titanium in a phantom and ...
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Journal ArticleJournal of Physical Chemistry · 1985
Chemisorption of NO on Rh/Al2O3 surfaces has been examined by FT-IR. The spectra are assigned to two forms of Rh(NO) as well as the Rh(NO)2 species. Apparent interconversion of the linear nitrosyl and dinitrosyl complexes is readily observed at room temper ...
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Journal ArticleJournal of Physical Chemistry · January 1, 1985
Chemisorption of NO on Rh/Al2O3 surfaces has been examined by FT-IR. The spectra are assigned to two forms of Rh(NO) as well as the Rh(NO)2 species. Apparent interconversion of the linear nitrosyl and dinitrosyl complexes i ...
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Journal ArticleInorganic Chemistry · January 1, 1982
The new reaction between sulfur dioxide and hexamethyldisilazane, which forms ((CH3)3Si)2O, (CH3)3SiNSO, and NH4(CH3)3SiOSO2, is characterized. In this react ...
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Journal ArticleJournal of the American Chemical Society · January 1, 1981
The reaction between ((CH3)3Si)2NH and S02 results in the formation of an ionic solid with empirical formula NH4(CH3)3SiOSO2 which readily “sublimes” at ambient temperature. Although (trimethylsilyl)ammonium bisulfite is a logical choice for a molecular fo ...
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Journal ArticleInorganic Chemistry · January 1, 1980
The direct, facilq reaction between sulfur dioxide and the common silylating agent hexamethyldisilazane (HMDS) resulting in the formation of 1, 1, 1-trimethyl-N-sulfinylsilanamine, (CH3)3 Si—N=S=0 (1), has not previously been reported ...
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Journal ArticleJournal of Physical Chemistry · January 1, 1979
Interpretation of vibrational energy transfer following kinetically controlled chemical activation is refined by incorporating multistep deactivation processes into the RRKM treatment of the excited molecule. The functional form of the initial primary prod ...
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Journal ArticleJournal of the Chemical Society Faraday Transactions 2 Molecular and Chemical Physics · December 1, 1978
The average energy of reaction for recoil hot species in a well scavenged system is defined explicitly and calculated for recoil tritium for hydrogen replacement reactions with cyclohexane and n-butane as a function of noble gas moderation. In general this ...
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Journal ArticleJournal of Physical Chemistry · January 1, 1978
Solid benzene at -196 °C was irradiated with 14CH+ and 14CH3+ ions at 10-eV kinetic energy. Yields were determined for the labeled hydrocarbon products: benzene, toluene, cycloheptatriene, diphenylmeth ...
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Journal ArticleJournal of Chemical Physics · January 1, 1978
A model for the kinetically controlled, nuclear recoil, chemical activation process is further developed to characterize the generation of excited cyclobutane and its subsequent unimolecular behavior. This approach specifically accounts for the overall eff ...
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Journal ArticleJournal of Physical Chemistry · 1978
Solid benzene at -196 °C was irradiated with 14CH+ and 14CH3+ ions at 10-eV kinetic energy. Yields were determined for the labeled hydrocarbon products: benzene, toluene, cycloheptatriene, diphenylmethane, biphenyl, and phenylcycloheptatriene. The radioact ...
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Journal ArticleJournal of the American Chemical Society · January 1, 1978
Gas-phase reactions of nuclear recoil generated chlorine-38 atoms with 2,3-dichlorohexafluoro-2-butene (2,3-DCHF2B) result predominantly in chlorine for chlorine substitution. The reaction proceeds with geometrical isomerization, and the resulting cis-tran ...
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Journal ArticleJournal of Physical Chemistry · January 1, 1978
The reaction of nuclear recoil generated chlorine atoms with hydrogen to produce hydrogen chloride was studied in the presence of ethylene and iodine scavengers. The yield behavior is presented for this reaction over a relative average translational energy ...
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Journal ArticleJournal of Chemical Physics · January 1, 1977
A method is demonstrated for the determination of intermolecular energy transfer efficiencies in systems chemically activated by nuclear recoil reaction. Relative vibrational energy transfer efficiencies are determined for highly excited cyclobutane-t form ...
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Journal ArticleJournal of Physical Chemistry · January 1, 1977
A technique is developed for determining solvation numbers and hydration constants for metal ions. Stability constants are obtained that are essentially independent of the solution composition for a wide range of solvents. It is shown that two ROH molecule ...
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Journal ArticleJournal of Physical Chemistry · January 1, 1977
Addition and abstraction are the major reactions observed between nuclear recoil generated chlorine atoms and ethylene. The addition reaction is characterized, and its relative efficiency is determined for low energy chlorine in systems containing H2< ...
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Journal ArticleRadiochimica Acta · January 1, 1976
The energetics and mechanism of recoil hot tritium atom replacement reactions with cyclobutane are explored. Kinetic analysis of the pressure dependence for the total yields of hot replacement products is used to distinguish reactive processes. Results sho ...
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Journal ArticleChemical Physics Letters · July 1, 1975
Relative vibrational energy transfer efficiencies are determined for cyclobutane-t chemically activated to an average energy of 5 eV by recoil tritium replacement reaction. The pressure and composition dependence of the stabilization-decomposition ratio in ...
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Journal ArticleChemical Physics Letters · February 1, 1973
Characteristics of the collisional distribution function for reactive hot atoms in nuclear recoil systems are examined and illustrated for the T + H2 system both unmoderated and moderated with argon. Reaction induced extrema are evident in the c ...
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Journal ArticleJournal of the American Chemical Society · January 1, 1973
The origin of the isotope effect in the reaction of recoil chlorine atoms with methane and perdeuteriomethane was determined by diluting the systems with inert moderator to establish a unique steady-state collision distribution. The ratio of product yields ...
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Journal ArticleJournal of Chemical Physics · January 1, 1973
The collisional distribution function for recoil hot atom systems is examined to determine the influence of specific inelastic processes on the collision density over the reactive energy range. The inelastic processes considered result from collisional dis ...
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Journal ArticleRadiochimica Acta · January 1, 1972
The absolute yields of single replacement products CH318F and CD318F were determined in highly moderated systems for the reaction of 18F with CH4 and CD4 respectively. Carbon tetrafluoride moderator was used in dilutions of up to 98%. The ratio of yields i ...
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Journal ArticleJournal of Physical Chemistry · January 1, 1970
Relative energy transfer collision cross sections for several complex hydrocarbon and substituted hydrocarbon molecules have been determined in the methyl isocyanide thermal isomerization system. Particular interest was placed in the incremental cross sect ...
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Journal ArticleJournal of Physical Chemistry · January 1, 1970
The low-pressure thermal isomerization of methyl isocyanide has been studied at 280.5° in the presence of 109 different inert bath gases. Relative collisional activation-deactivation efficiencies β were measured. The attractive nature of the interaction is ...
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Journal ArticleJournal of Physical Chemistry · January 1, 1970
The inert gas effect on the thermal isomerization of methyl isocyanide at 280.5° by the members of the homologous series of n-perfluoroalkanes and n-nitriles has been studied up to C6 in both cases. Relative collision diameters of these molecule ...
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Journal ArticleJournal of Chemical Physics · January 1, 1969
The reactions with methane and ethane of hot chlorine atoms recoiling from the 40Ar (γ, p)39Cl nuclear reaction have been studied. Displacement reactions, analogous to those of hot hydrogen with alkanes, were found. In the case of met ...
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