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J W Evans

Publications and source records attributed to J W Evans.

At least 19 recordsLinked to original sources
PubMed2006

Chemical diffusion of CO in mixed CO + O adlayers and reaction-front propagation in CO oxidation on Pd(100).

Within the framework of a realistic atomistic lattice-gas model, we present the theoretical formulation and simulation procedures for precise analysis of the chemical diffusion flux of highly mobile CO within a nonuniform interacting mixed CO + O adlayer on a Pd(100) surface. The approach applies in both regimes of relatively immobile unequilibrated and fairly mobile near-equilibrated O adlayer distributions. Spatiotemporal behavior in surface reactions is controlled by chemical diffusion in mixed adlayers. Thus, we naturally integrate the above analysis with a previously developed multiscale modeling strategy to describe mesoscale reaction front propagation in CO oxidation on Pd(100). This treatment avoids using a simplified prescription of chemical diffusion and reaction kinetics as in traditional mean-field reaction-diffusion equation approaches.

Journal Article↗
PubMed2006

Atomistic lattice-gas modeling of CO oxidation on Pd(100): temperature-programmed spectroscopy and steady-state behavior.

We have developed an atomistic lattice-gas model for the catalytic oxidation of CO on single-crystal Pd(100) surfaces under ultrahigh vacuum conditions. This model necessarily incorporates an detailed description of adlayer ordering and adsorption-desorption kinetics both for CO on Pd(100), and for oxygen on Pd(100). Relevant energetic parameters are determined by comparing model predictions with experiment, together with some guidance from density functional theory calculations. The latter also facilitates description of the interaction and reaction of adsorbed CO and oxygen. Kinetic Monte Carlo simulations of this reaction model are performed to predict temperature-programmed reaction spectra, as well as steady-state bifurcation behavior.

Journal Article↗
PubMed2005

Theoretical analysis of mound slope selection during unstable multilayer growth.

A "step dynamics" model is developed for mound formation during multilayer homoepitaxy. Downward funneling of atoms deposited at step edges is incorporated and controls mound slope selection. Behavior of the selected slope differs from that predicted by phenomenological continuum treatments where the lateral mass current vanishes identically. Instead, this current is shown to vary periodically and vanish only on average. An exact coarse-grained continuum formulation with appropriate boundary conditions is derived and recovers step dynamics results.

Journal Article↗
PubMed2003

Critical behavior in an atomistic model for a bistable surface reaction: CO oxidation with rapid CO diffusion.

We analyze critical behavior associated with the loss of bistability for an atomistic model for CO oxidation on surfaces in the limit of infinite diffusion of CO. The model includes infinite nearest-neighbor repulsions between adsorbed immobile O. We use a "hybrid" treatment incorporating a lattice-gas description of the O adlayer, but tracking just the number of adsorbed CO (which are randomly distributed on non-O sites). The critical exponents obtained from a finite-size-scaling analysis on LxL site surfaces with periodic boundary conditions show that the "hybrid" reaction model belongs to the mean-field universality class, despite strong spatial correlations in the O adlayer. We also quantify finite-size effects in the global bifurcation diagram, revealing a significant shift of the bistable region with decreasing system size. Our study elucidates fluctuation effects observed in experiments of CO oxidation on the nanoscale facets of metal-field emitter tips.

Journal Article↗
PubMed2002

Passive and active oxidation of Si(100) by atomic oxygen: a theoretical study of possible reaction mechanisms.

Reaction mechanisms for oxidation of the Si(100) surface by atomic oxygen were studied with high-level quantum mechanical methods in combination with a hybrid QM/MM (Quantum mechanics/Molecular Mechanics) method. Consistent with previous experimental and theoretical results, three structures, "back-bond", "on-dimer", and "dimer-bridge", are found to be the most stable initial surface products for O adsorption (and in the formation of SiO(2) films, i.e., passive oxidation). All of these structures have significant diradical character. In particular, the "dimer-bridge" is a singlet diradical. Although the ground state of the separated reactants, O+Si(100), is a triplet, once the O atom makes a chemical bond with the surface, the singlet potential energy surface is the ground state. With mild activation energy, these three surface products can be interconverted, illustrating the possibility of the thermal redistribution among the initial surface products. Two channels for SiO desorption (leading to etching, i.e., active oxidation) have been found, both of which start from the back-bond structure. These are referred to as the silicon-first (SF) and oxygen-first (OF) mechanisms. Both mechanisms require an 89.8 kcal/mol desorption barrier, in good agreement with the experimental estimates of 80-90 kcal/mol. "Secondary etching" channels occurring after initial etching may account for other lower experimental desorption barriers. The calculated 52.2 kcal/mol desorption barrier for one such secondary etching channel suggests that the great variation in reported experimental barriers for active oxidation may be due to these different active oxidation channels.

Journal Article↗
PubMed2001

Catalytic CO oxidation on nanoscale Pt facets: effect of interfacet CO diffusion on bifurcation and fluctuation behavior.

We present lattice-gas modeling of the steady-state behavior in CO oxidation on the facets of nanoscale metal clusters, with coupling via interfacet CO diffusion. The model incorporates the key aspects of the reaction process, such as rapid CO mobility within each facet and strong nearest-neighbor repulsion between adsorbed O. The former justifies our use of a "hybrid" simulation approach treating the CO coverage as a mean-field parameter. For an isolated facet, there is one bistable region where the system can exist in either a reactive state (with high oxygen coverage) or a (nearly CO-poisoned) inactive state. Diffusion between two facets is shown to induce complex multistability in the steady states of the system. The bifurcation diagram exhibits two regions with bistabilities due to the difference between adsorption properties of the facets. We explore the role of enhanced fluctuations in the proximity of a cusp bifurcation point associated with one facet in producing transitions between stable states on that facet, as well as their influence on fluctuations on the other facet. The results are expected to shed more light on the reaction kinetics for supported catalysts.

Journal Article↗
PubMed2001

Metabolism of tirapazamine by multiple reductases in the nucleus.

Tirapazamine (TPZ, 3-amino-1,2,4-benzotriazine 1,4-di-N-oxide, SR4233, Tirazone), a bioreductive drug currently in clinical trials, is selectively toxic to hypoxic cells commonly found in solid tumors. The toxicity results from the intracellular metabolism of TPZ to a highly toxic radical. When oxygen levels are low, the TPZ radical reacts with cellular molecules, producing DNA damage and cell death. The much lower toxicity towards aerobic cells results from the back-oxidation of the TPZ radical by oxygen. A major unresolved aspect of the mechanism of TPZ is the identity of the reductase(s) in the cell responsible for activating the drug to its toxic form. We have studied both the metabolism of the drug using HPLC and the formation of the TPZ radical with a fluorescence assay using dihydrorhodamine 123. We also measured DNA double- and single-strand breaks produced by TPZ, using the comet assay. We demonstrated that multiple reductases in the nucleus metabolize TPZ under hypoxia. Using the cofactor dependence of the reductases for metabolizing TPZ and of the DNA damage caused by TPZ, we show that DNA single-strand breaks after TPZ metabolism are probably caused by the most abundant source of reductase in the nucleus. DNA double-strand breaks, on the other hand, are formed by TPZ metabolism by an unknown nuclear reductase that requires only NADPH for its activity. This study is the first to characterize multiple nuclear reductases capable of activating TPZ.

Antineoplastic Agents↗
PubMed2001

Evolution of two-dimensional wormlike nanoclusters on metal surfaces.

A pinch-off phenomenon is discovered in the evolution of 2D wormlike nanoclusters formed in homoepitaxial adlayers. This feature is shown to distinguish mass transport via periphery diffusion from other mechanisms. Continuum modeling of such evolution accurately describes experimental observations, particularly if one incorporates the anisotropy in step-edge line tension.

Journal Article↗
PubMed2001

Mitochondrial dysfunction after aerobic exposure to the hypoxic cytotoxin tirapazamine.

Tirapazamine (TPZ) is a bioreductive drug that exhibits a high degree of selective toxicity toward hypoxic cells, and at doses that are used clinically, little or no cell killing is observed in aerobic cells. Nonetheless, the effects of TPZ on aerobic tissues are still responsible for the dose limitations on the clinical administration of this drug. Clinical side effects include fatigue, muscle cramping, and reversible ototoxicity. We have investigated TPZ-induced changes in the mitochondria in aerobically exposed cells as a potential mediator of these side effects. Our data show that aerobic administration of TPZ at clinically relevant doses results in a profound loss in the mitochondrial membrane potential (MMP). We show that loss in the MMP occurs in a variety of cell lines in vitro and also occurs in muscle tissues in vivo. The loss in MMP is temporary because recovery occurs within 2 h. TPZ is directly metabolized within mitochondria to a DNA-damaging form, and this metabolism leads to both the cell-killing effects of TPZ on aerobic cells at high doses and to the loss in MMP at clinically relevant doses. Using cell lines derived from genetically modified mice with a targeted deletion in manganese superoxide dismutase, we have further distinguished the phenotypic effects of TPZ in mitochondria at high toxic doses versus those at clinically relevant doses. We have investigated several potential mechanisms for this TPZ-induced loss in MMP. Our results indicate no change in the rate of cellular respiration in TPZ-treated cells. This implies that the loss in MMP results from an inability of the inner mitochondrial membrane to sustain a potential across the membrane after TPZ treatment. Incubation of cells with an inhibitor of the mitochondrial permeability transition suggests that the loss of MMP may result from the regulated opening of a large mitochondria channel.

Aerobiosis↗
PubMed1999

Cisplatin anti-tumour potentiation by tirapazamine results from a hypoxia-dependent cellular sensitization to cisplatin.

Tirapazamine (TPZ) is a new anticancer drug that is activated specifically at the low oxygen level typically found in solid tumours. It exhibits preferential cytotoxicity towards hypoxic cells and has been shown in preclinical studies with transplanted tumours and in phase II and III clinical trials to potentiate the anti-tumour efficacy of cisplatin without increasing its systemic toxicity. At present, the mechanism for this potentiation is unknown. Here we show that there is a schedule-dependent enhancement of cisplatin cytotoxicity by TPZ for cells in vitro that is similar to that seen with transplanted murine tumours. This cisplatin potentiation depends on the TPZ exposure being at oxygen concentrations below 1%, which are typical of many cells in tumours but not in normal tissues. Also, the interaction between TPZ and cisplatin does not occur in cells mutant in ERCC4, a protein essential for repair of DNA interstrand cross-links. Incubation of the cells with TPZ under hypoxia prior to cisplatin treatment increases cisplatin-induced DNA interstrand cross-links with kinetics suggesting that TPZ inhibits or delays repair of the DNA cross-links. In conclusion, we show that the tumour-specific potentiation of cisplatin cytotoxicity is likely the result of an interaction between TPZ and cisplatin at the cellular level that requires the low oxygen levels typical of those in solid tumours. The mechanism of the interaction appears to be through a potentiation of cisplatin-induced DNA interstrand cross-links, possibly as a result of a diminished or delayed repair of these lesions

3T3 Cells↗
PubMed1999

Deathbed scene narratives: a construct and linguistic analysis.

The present study explored temporal and self/other dimensions of death attitudes among young adults. One hundred seventy-two undergraduate students were randomly assigned to 1 of 4 conditions: writing about one's death (age unspecified), one's death as a young adult, or the death of another (age unspecified), or the death of other as a young adult. Results indicated that the death of another, but not of oneself, was associated with more realistic considerations of death (e.g., pain, negative emotions). In addition, participants who wrote about death at an early age were less likely to describe their own deaths with negative emotion or to discuss physiological aspects of death and were less likely to express romanticized notions of death. Implications of these results for death anxiety research are discussed.

Adolescent↗
PubMed1998

Tirapazamine is metabolized to its DNA-damaging radical by intranuclear enzymes.

Tirapazamine (TPZ), a new anticancer drug that is currently in Phase II and III clinical trials, has a unique mechanism of action. Its cytotoxicity is selective for hypoxic cells in solid tumors and results from DNA damage produced by a free radical, which is generated by enzymatic reduction of the parent molecule. However, there is no agreement as to which enzyme(s) are involved. Here, we have measured both DNA damage and TPZ metabolism in A549 human lung cancer cells and in isolated nuclei derived from the cells. We show that, although the nuclei metabolize TPZ at a rate that is only 20% of that of whole cells, they have levels of DNA damage that are similar to those of the cells. We also show that TPZ radicals that are formed outside nuclei do not contribute to intranuclear DNA damage. Thus, essentially all of the DNA damage from TPZ results from radicals generated within the nucleus, and the 80% of the drug metabolism that occurs in the cytoplasm is probably irrelevant for the activity of this drug in killing hypoxic cells.

Antineoplastic Agents↗
PubMed1997

Adaptation of human tumor cells to tirapazamine under aerobic conditions: implications of increased antioxidant enzyme activity to mechanism of aerobic cytotoxicity.

Tirapazamine (TPZ, 3-amino-1,2,4-benzotriazine 1,4-di-N-oxide, SR 4233, WIN 59075) is a bioreductive antitumor agent with a high selective toxicity for hypoxic cells. The selective hypoxic toxicity of TPZ results from the rapid reoxidation of the one-electron reduction product, the TPZ radical, in the presence of molecular oxygen with the concomitant production of superoxide radical. Under hypoxia the TPZ radical kills cells by causing DNA double-strand breaks and chromosome aberrations. However, the mechanism of aerobic cytotoxicity is still a matter of debate. In this study, we investigated the mechanism of aerobic cytotoxicity by adapting human lung adenocarcinoma A549 cells to aerobic TPZ exposure and characterizing the changes associated with drug resistance. The adapted cells were resistant to aerobic TPZ exposures (with dose-modifying factors of up to 9.2), although hypoxic sensitivity was largely unchanged. Relative to the parental A549 cell line, adaptation to continuous aerobic TPZ exposure resulted in increased levels of manganese superoxide dismutase (up to 9.4-fold), moderate increases in glutathione reductase (up to 2.1-fold), and loss of both quinone oxidoreductase (DT-diaphorase) activity and NADPH cytochrome P450 reductase activity. There was essentially no change in the activity of the cytoplasmic form of superoxide dismutase (CuZnSOD), catalase, or glutathione peroxidase. The increased activity of antioxidant enzymes in the resistant cell lines (in particular MnSOD) strongly suggests that reactive oxygen species are, in large part, responsible for the toxicity of TPZ under aerobic conditions, and is consistent with aerobic and hypoxic drug cytotoxicity resulting from different mechanisms.

Adaptation, Biological↗
PubMed1997

Stable translocations detected by fluorescence in situ hybridization: a rapid surrogate end point to evaluate the efficacy of a potentiator of tumor response to radiotherapy.

Testing potential modifiers of the response of tumors to radiation therapy requires large, expensive, and time-consuming clinical trials. It would, therefore, be of value to have a rapid surrogate end point of tumor response that could be used to evaluate such modifiers. We here propose that radiation-induced stable chromosome translocations measured by fluorescence in situ hybridization (FISH) could fulfill this purpose. The assay requires that the ratio of nonlethal stable translocations to lethal dicentric aberrations be unity and not change with radiation dose and that radiation-induced stable translocations remain in the tumor cell population essentially indefinitely after irradiation. We have tested these assumptions with four human tumor cell lines in vitro at doses of 1-5 Gy and found them to be valid. We also modified the response to fractionated irradiation of a human tumor xenograft in three different ways and quantitated the tumor response using clonogenic cell survival and using the FISH stable translocation assay. Both assays gave similar values for the extent of radiation modification. These data suggest that this assay could allow clinical evaluation of potential radiation sensitizers with fewer patients and in shorter times than is the case with conventional clinical trials.

Animals↗
PubMed1996

Induction and repair of chromosome aberrations in scid cells measured by premature chromosome condensation.

Severe combined immunodeficient (scid) murine cells, which are defective in both repair of DNA double-strand breaks and V(D)J recombination, are deficient in DNA-dependent protein kinase (DNA-PK), a protein which forms an activated complex with the DNA end-binding Ku proteins (p80 and p70) upon association with damaged DNA. Xrs 5 cells are deficient in the Ku p80 protein and also fail to form an active DNA-PK repair complex. Since both scid and xrs cells are defective in the same protein complex, we compared the kinetics of chromosome repair in scid cells to results published previously for xrs 5 cells. C.B-17 cells, scid cells and scid cells complemented with a single human chromosome 8 were irradiated with 6 Gy and allowed to repair from 0-24 h before fusion to HeLa cells for chromosome condensation. Breaks and dicentrics were visualized by fluorescence in situ hybridization. All cells had the same initial amount of chromosome damage, but scid cells had a slower rate of rejoining, more unrejoined breaks and more dicentrics than C.B-17 and scid cells with human chromosome 8. The scid cells appear to respond differently than xrs 5 cells, despite both cells lacking an essential component of the same DNA repair complex.

Algorithms↗
PubMed1995

DNA-dependent kinase (p350) as a candidate gene for the murine SCID defect.

Severe combined immunodeficient (SCID) mice are deficient in a recombination process utilized in both DNA double-strand break repair and in V(D)J recombination. The phenotype of these mice involves both cellular hypersensitivity to ionizing radiation and a lack of B and T cell immunity. The catalytic subunit of DNA-dependent protein kinase, p350, was identified as a strong candidate for the murine gene SCID. Both p350 and a gene complementing the SCID defect colocalize to human chromosome 8q11. Chromosomal fragments expressing p350 complement the SCID phenotype, and p350 protein levels are greatly reduced in cells derived from SCID mice compared to cells from wild-type mice.

Animals↗