222 research outputs found
Study of Strain and Temperature Dependence of Metal Epitaxy
Metallic films are important in catalysis, magneto-optic storage media, and
interconnects in microelectronics, and it is crucial to predict and control
their morphologies. The evolution of a growing crystal is determined by the
behavior of each individual atom, but technologically relevant structures have
to be described on a time scale of the order of (at least) tenths of a second
and on a length scale of nanometers. An adequate theory of growth should
describe the atomistic level on very short time scales (femtoseconds), the
formation of small islands (microseconds), as well as the evolution of
mesoscopic and macroscopic structures (tenths of seconds).
The development of efficient algorithms combined with the availability of
cheaper and faster computers has turned density functional theory (DFT) into a
reliable and feasible tool to study the microscopic aspects of growth phenomena
(and many other complex processes in materials science, condensed matter
physics, and chemistry). In this paper some DFT results for diffusion
properties on metallic surfaces are presented. Particularly, we will discuss
the current understanding of the influences of strain on the diffusion (energy
barrier and prefactor) of a single adatom on a substrate.
A DFT total energy calculation by its nature is primarily a static
calculation. An accurate way to describe the spatial and temporal development
of a growing crystal is given by kinetic Monte Carlo (KMC). We will describe
the method and its combination with microscopic parameters obtained from ab
initio calculations. It is shown that realistic ab initio kinetic Monte Carlo
simulations are able to predict an evolving mesoscopic structure on the basis
of microscopic details.Comment: 25 pages, 6 figures, In: ``Morphological Organisation during
Epitaxial Growth and Removal'', Eds. Z. Zhang, M. Lagally. World Scientific,
Singapore 1998. other related publications can be found at
http://www.rz-berlin.mpg.de/th/paper.htm
Density Functional Theory of Epitaxial Growth of Metals
This chapter starts with a summary of the atomistic processes that occur
during epitaxy. We then introduce density functional theory (DFT) and describe
its implementation into state-of-the-art computations of complex processes in
condensed matter physics and materials science. In particular we discuss how
DFT can be used to calculate parameters of microscopic processes such as
adsorption and surface diffusion, and how they can be used to study the
macroscopic time and length scales of realistic growth conditions. This meso-
and macroscopic regime is described by the ab initio kinetic Monte Carlo
approach. We discuss several specific theoretical studies that highlight the
importance of the different diffusion mechanisms at step edges, the role of
surfactants, and the influence of surface stress. The presented results are for
specific materials (namely silver and aluminum), but they are explained in
simple physical pictures suggesting that they also hold for other systems.Comment: 55 pages, 20 figures, to be published "Growth of Ultrathin Epitaxial
Layers", The Chemical Physics of Soild Surfaces, Vol. 8, Eds D. A. King and
D. P. Woodruff (Elsevier Science, Amsterdam, 1997
Molecular mechanism of MBX2319 inhibition of Escherichia coli AcrB multidrug efflux pump and comparison with other inhibitors
Efflux pumps of the resistance nodulation division (RND) superfamily, such as AcrB, make a major contribution to multidrug resistance in Gram-negative bacteria. The development of inhibitors of the RND pumps would improve the efficacy of current and next-generation antibiotics. To date, however, only one inhibitor has been cocrystallized with AcrB. Thus, in silico struc- ture-based analysis is essential for elucidating the interaction between other inhibitors and the efflux pumps. In this work, we used computer docking and molecular dynamics simulations to study the interaction between AcrB and the compound MBX2319, a novel pyranopyridine efflux pump inhibitor with potent activity against RND efflux pumps of Enterobacteriaceae species, as well as other known inhibitors (D13-9001, 1-[1-naphthylmethyl]-piperazine, and phenylalanylarginine-Ăź-naphthyl-amide) and the binding of doxorubicin to the efflux-defective F610A variant of AcrB. We also analyzed the binding of a sub- strate, minocycline, for comparison. Our results show that MBX2319 binds very tightly to the lower part of the distal pocket in the B protomer of AcrB, strongly interacting with the phenylalanines lining the hydrophobic trap, where the hydrophobic por- tion of D13-9001 was found to bind by X-ray crystallography. Additionally, MBX2319 binds to AcrB in a manner that is similar to the way in which doxorubicin binds to the F610A variant of AcrB. In contrast, 1-(1-naphthylmethyl)-piperazine and phenylalanylarginine-Ăź-naphthylamide appear to bind to somewhat different areas of the distal pocket in the B protomer of AcrB than does MBX2319. However, all inhibitors (except D13-9001) appear to distort the structure of the distal pocket, impairing the proper binding of substrates
The steady-state of heterogeneous catalysis, studied by first-principles statistical mechanics
The turn-over frequency of the catalytic oxidation of CO at RuO2(110) was
calculated as function of temperature and partial pressures using ab initio
statistical mechanics. The underlying energetics of the gas-phase molecules,
dissociation, adsorption, surface diffusion, surface chemical reactions, and
desorption were obtained by all-electron density-functional theory. The
resulting CO2 formation rate [in the full (T, p_CO, p_O2)-space], the movies
displaying the atomic motion and reactions over times scales from picoseconds
to seconds, and the statistical analyses provide insights into the concerted
actions ruling heterogeneous catalysis and open thermodynamic systems in
general.Comment: 4 pages including 3 figures, Related publications can be found at
http://www.fhi-berlin.mpg.de/th/paper.htm
Hematologic and biochemical reference intervals in Shetland Sheepdogs
Background: Several breeds have physiological peculiarities that induce variations in reference intervals (RIs) compared with the general canine population. Shetland sheepdogs (SSs) are reported to be more predisposed to different diseases (eg, hyperlipidemia, gallbladder mucocele, and hypothyroidism). Consequently, a breed-specific approach is more often required. Objectives: The aim of this study was to determine whether the RIs of the general canine population could be applied to that of SSs, and to generate breed-specific RIs, where appropriate. Methods: Sixty\ua0clinically healthy and fasted SSs (36% of the population registered at the Italian Breed association) were examined. Routine hematology and biochemistry analyses were performed. The transference method was used to compare the results of SSs with the RIs of the general canine population. When these RIs were not validated, new RIs were generated according to the guidelines of the American Society of Veterinary Clinical Pathology. Differences associated with sex, age, coat color, and whether used as a pet, a herding dog, or an agility dog were also investigated. Results: The transference method validated for 30/38 SS RIs. For 6 of the remaining 8 variables, the difference with the claimed RIs could depend on preanalytical or analytical artifacts, whereas for glucose and total cholesterol, these differences could depend on breed peculiarities. However, in all SSs, the concentration of cholesterol was <12.95\ua0mmol/L. Relevant differences associated with sex, age, coat color, and use were not found. Conclusions: This study suggests that breed-specific RIs should be used for glucose and cholesterol in SSs
CO oxidation on Pd(100) at technologically relevant pressure conditions: A first-principles kinetic Monte Carlo study
The possible importance of oxide formation for the catalytic activity of
transition metals in heterogenous oxidation catalysis has evoked a lively
discussion over the recent years. On the more noble transition metals (like Pd,
Pt or Ag) the low stability of the common bulk oxides suggests primarily
sub-nanometer thin oxide films, so-called surface oxides, as potential
candidates that may be stabilized under gas phase conditions representative of
technological oxidation catalysis. We address this issue for the Pd(100) model
catalyst surface with first-principles kinetic Monte Carlo (kMC) simulations
that assess the stability of the well-characterized (sqrt{5} x sqrt{5})R27
surface oxide during steady-state CO oxidation. Our results show that at
ambient pressure conditions the surface oxide is stabilized at the surface up
to CO:O2 partial pressure ratios just around the catalytically most relevant
stoichiometric feeds (p(CO):p(O2) = 2:1). The precise value depends sensitively
on temperature, so that both local pressure and temperature fluctuations may
induce a continuous formation and decomposition of oxidic phases during
steady-state operation under ambient stoichiometric conditions.Comment: 13 pages including 5 figures; related publications can be found at
http://www.fhi-berlin.mpg.de/th/th.htm
The hydrolysis mechanism of the anticancer ruthenium drugs NAMI-A and ICR investigated by DFT-PCM calculations
(ImH)[trans-RuCl4(DMSO-S)(Im)], (Im = imidazole, DMSO-S = S-bonded dimethylsulfoxide), NAMI-A, is the first anticancer ruthenium compound that successfully completed Phase I clinical trials. NAMI-A shows a remarkable activity against lung metastases of solid tumors, but is not effective in the reduction of primary cancer. The structurally similar (ImH)[trans-RuCl4(Im)(2)], ICR (or KP418), and its indazole analog (KP1019) are promising candidate drugs in the treatment of colorectal cancers, but have no antimetastatic activity. Despite the pharmacological relevance of these compounds, no rationale has been furnished to explain their markedly different activity. While the nature of the chemical species responsible for their antimetastatic/anticancer activity has not been determined, it has been suggested that the difference between reduction potentials of NAMI-A and ICR may be the key to the different biological responses they induce. In this work, Density Functional Theory calculations were performed to investigate the hydrolysis of NAMI-A and ICR in both Ru-III and Ru-II oxidation states, up to the third aquation. In line with experimental findings, our calculations provide a picture of the hydrolysis of NAMI-A and ICR mainly as a stepwise loss of chloride ligands. While dissociation of Im is unlikely under neutral conditions, that of DMSO becomes competitive with the loss of chloride ions as the hydrolysis proceeds. Redox properties of NAMI-A and ICR and of their most relevant hydrolytic intermediates were also studied in order to monitor the effects of biological reductants on the mechanism of action. Our findings may contribute to the identification of the active compounds that interact with biological targets, and to explain the different biological activity of NAMI-A and ICR
Molecular interactions of carbapenem antibiotics with the multidrug efflux transporter acrb of escherichia coli
The drug/proton antiporter AcrB, engine of the major efflux pump AcrAB(Z)-TolC of Escherichia coli and other bacteria, is characterized by its impressive ability to transport chemically diverse compounds, conferring a multi-drug resistance (MDR) phenotype. Although hundreds of small molecules are known to be AcrB substrates, only a few co-crystal structures are available to date. Computational methods have been therefore intensively employed to provide structural and dynamical fingerprints related to transport and inhibition of AcrB. In this work, we performed a systematic computational investigation to study the interaction between representative carbapenem antibiotics and AcrB. We focused on the interaction of carbapenems with the so-called distal pocket, a region known for its importance in binding inhibitors and substrates of AcrB. Our findings reveal how the different physico-chemical nature of these antibiotics is reflected on their binding preference for AcrB. The molecular-level information provided here could help design new antibiotics less susceptible to the efflux mechanism
Modelling eNvironment for Isoforms (MoNvIso): A general platform to predict structural determinants of protein isoforms in genetic diseases
The seamless integration of human disease-related mutation data into protein structures is an essential component of any attempt to correctly assess the impact of the mutation. The key step preliminary to any structural modelling is the identification of the isoforms onto which mutations should be mapped due to there being several functionally different protein isoforms from the same gene. To handle large sets of data coming from omics techniques, this challenging task needs to be automatized. Here we present the MoNvIso (Modelling eNvironment for Isoforms) code, which identifies the most useful isoform for computational modelling, balancing the coverage of mutations of interest and the availability of templates to build a structural model of both the wild-type isoform and the related variants
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