A kinetic Monte Carlo method for the atomic-scale simulation of chemical vapor deposition: Application to diamond

We present a method for simulating the chemical vapor deposition (CVD) of thin films. The model is based upon a three-dimensional representation of film growth on the atomic scale that incorporates the effects of surface atomic structure and morphology. Film growth is simulated on lattice. The temporal evolution of the film during growth is examined on the atomic scale by a Monte Carlo technique parameterized by the rates of the important surface chemical reactions. The approach is similar to the N-fold way in that one reaction occurs at each simulation step, and the time increment between reaction events is variable. As an example of the application of the simulation technique, the growth of {111}-oriented diamond films was simulated for fifteen substrate temperatures ranging from 800 to 1500 K. Film growth rates and incorporated vacancy and H atom concentrations were computed at each temperature. Under typical CVD conditions, the simulated growth rates vary from about 0.1 to 0.8 μm/hr between 800 and 1500 K and the activation energy for growth on the {111}: H surface between 800 and 1100 K is 11.3 kcal/mol. The simulations predict that the concentrations of incorporated point defects are low at substrate temperatures below 1300 K, but become significant above this temperature. If the ratio between growth rate and point defect concentration is used as a measure of growth efficiency, ideal substrate temperatures for the growth of {111}-oriented diamond films are in the vicinity of 1100 to 1200 K. © 1997 American Institute of Physics.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/70750/2/JAPIAU-82-12-6293-1.pd

Tracking marine mammals in 3D using electronic tag data

1. Information about at-depth behaviour of marine mammals is fundamental yet very hard to obtain from direct visual observation. Animal-borne multisensor electronic tags provide a unique window of observation into such behaviours. 2. Electronic tag sensors allow the estimation of the animal's 3-dimensional (3D) orientation, depth and speed. Using tag flow noise level to provide an estimate of animal speed, we extend existing approaches of 3D track reconstruction by allowing the direction of movement to differ from that of the animal's longitudinal axis. 3. Data are processed by a hierarchical Bayesian model that allows processing of multisource data, accounting for measurement errors and testing hypotheses about animal movement by comparing models. 4. We illustrate the approach by reconstructing the 3D track of a 52-min deep dive of a Blainville's beaked whale Mesoplodon densirostris adult male fit with a digital tag (DTAG) in the Bahamas. At depth, the whale alternated regular movements at large speed (>1·5 m s-1) and more complex movements at lower speed (<1·5 m s-1) with differences between movement and longitudinal axis directions of up to 28°. The reconstructed 3D track agrees closely with independent acoustic-based localizations. 5. The approach is potentially applicable to study the underwater behaviour (e.g. response to anthropogenic disturbances) of a wide variety of species of marine mammals fitted with triaxial magnetometer and accelerometer tags.PostprintPeer reviewe

Etching effects during the chemical vapor deposition of (100) diamond

Current theories of CVD growth on (100) diamond are unable to account for the numerous experimental observations of slow-growing, locally smooth (100)(2×1)(100)(2×1) films. In this paper we use quantum mechanical calculations of diamond surface thermochemistry and atomic-scale kinetic Monte Carlo simulations of deposition to investigate the efficacy of preferential etching as a mechanism that can help to reconcile this discrepancy. This etching mechanism allows for the removal of undercoordinated carbon atoms from the diamond surface. In the absence of etching, simulated growth on the (100)(2×1)(100)(2×1) surface is faster than growth on the (110) and (111) surfaces, and the (100) surface is atomically rough. When etching is included in the simulations, the (100) growth rates decrease to values near those observed experimentally, while the rates of growth on the other surfaces remain largely unaffected and similar to those observed experimentally. In addition, the etching mechanism promotes the growth of smooth (100) surface regions in agreement with numerous scanning probe studies. © 1999 American Institute of Physics.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/70606/2/JCPSA6-111-9-4291-1.pd

Crack tip microplasticity mediated by microstructure gradients

Traditional fracture theories infer damage at cracks (local field) by surveying loading conditions away from cracks (far field). This approach has been successful in predicting ductile fracture, but it normally assumes isotropic and homogeneous materials. However, myriads of manufacturing procedures induce heterogeneous microstructural gradients that can affect the accuracy of traditional fracture models. This work presents a microstructure-sensitive finite element approach to explore the shielding effects of grain size and crystallographic orientation gradients on crack tip microplasticity and blunting. A dislocation density-based crystal plasticity model conveys texture evolution, grain size effects, and directional hardening by computing the constraint from dislocation structures. The results demonstrate that the microstructure can act as a buffer between the local and far fields that affects the crack tip microplasticity variability. For nominal opening loading, grain size and texture affect the local ductility and induce a non-negligible multiaxial plastic deformation. Furthermore, driving forces based on measuring displacements away from the crack tip are less affected by the microstructure, which suggests that traditional experimental methods smear out important crack tip variability

Coupled Simulations of Mechanical Deformation and Microstructural Evolution Using Polycrystal Plasticity and Monte Carlo Potts Models

The microstructural evolution of heavily deformed polycrystalline Cu is simulated by coupling a constitutive model for polycrystal plasticity with the Monte Carlo Potts model for grain growth. The effects of deformation on boundary topology and grain growth kinetics are presented. Heavy deformation leads to dramatic strain-induced boundary migration and subsequent grain fragmentation. Grain growth is accelerated in heavily deformed microstructures. The implications of these results for the thermomechanical fatigue failure of eutectic solder joints are discussed

Structure-Guided Design and Optimization of Dipeptidyl Inhibitors of Norovirus 3CL Protease. Structure-Activity Relationships and Biochemical, X-ray Crystallographic, Cell-Based, and In Vivo Studies

Norovirus infection constitutes the primary cause of acute viral gastroenteritis. There are currently no vaccines or norovirus-specific antiviral therapeutics available for the management of norovirus infection. Norovirus 3C-like protease is essential for viral replication, consequently, inhibition of this enzyme is a fruitful avenue of investigation that may lead to the emergence of anti-norovirus therapeutics. We describe herein the optimization of dipeptidyl inhibitors of norovirus 3C-like protease using iterative SAR, X-ray crystallographic, and enzyme and cell-based studies. We also demonstrate herein in vivo efficacy of an inhibitor using the murine model of norovirus infection

Broad-Spectrum Antivirals against 3C or 3C-Like Proteases of Picornaviruses, Noroviruses, and Coronaviruses

This is the published version. Copyright American Society for MicrobiologyPhylogenetic analysis has demonstrated that some positive-sense RNA viruses can be classified into the picornavirus-like supercluster, which includes picornaviruses, caliciviruses, and coronaviruses. These viruses possess 3C or 3C-like proteases (3Cpro or 3CLpro, respectively), which contain a typical chymotrypsin-like fold and a catalytic triad (or dyad) with a Cys residue as a nucleophile. The conserved key sites of 3Cpro or 3CLpro may serve as attractive targets for the design of broad-spectrum antivirals for multiple viruses in the supercluster. We previously reported the structure-based design and synthesis of potent protease inhibitors of Norwalk virus (NV), a member of the Caliciviridae family. We report herein the broad-spectrum antiviral activities of three compounds possessing a common dipeptidyl residue with different warheads, i.e., an aldehyde (GC373), a bisulfite adduct (GC376), and an α-ketoamide (GC375), against viruses that belong to the supercluster. All compounds were highly effective against the majority of tested viruses, with half-maximal inhibitory concentrations in the high nanomolar or low micromolar range in enzyme- and/or cell-based assays and with high therapeutic indices. We also report the high-resolution X-ray cocrystal structures of NV 3CLpro-, poliovirus 3Cpro-, and transmissible gastroenteritis virus 3CLpro- GC376 inhibitor complexes, which show the compound covalently bound to a nucleophilic Cys residue in the catalytic site of the corresponding protease. We conclude that these compounds have the potential to be developed as antiviral therapeutics aimed at a single virus or multiple viruses in the picornavirus-like supercluster by targeting 3Cpro or 3CLpro

Making the Connection Between Microstructure and Mechanics

The purpose of microstructural control is to optimize materials properties. To that end, they have developed sophisticated and successful computational models of both microstructural evolution and mechanical response. However, coupling these models to quantitatively predict the properties of a given microstructure poses a challenge. This problem arises because most continuum response models, such as finite element, finite volume, or material point methods, do not incorporate a real length scale. Thus, two self-similar polycrystals have identical mechanical properties regardless of grain size, in conflict with theory and observations. In this project, they took a tiered risk approach to incorporate microstructure and its resultant length scales in mechanical response simulations. Techniques considered include low-risk, low-benefit methods, as well as higher-payoff, higher-risk methods. Methods studied include a constitutive response model with a local length-scale parameter, a power-law hardening rate gradient near grain boundaries, a local Voce hardening law, and strain-gradient polycrystal plasticity. These techniques were validated on a variety of systems for which theoretical analyses and/or experimental data exist. The results may be used to generate improved constitutive models that explicitly depend upon microstructure and to provide insight into microstructural deformation and failure processes. Furthermore, because mechanical state drives microstructural evolution, a strain-enhanced grain growth model was coupled with the mechanical response simulations. The coupled model predicts both properties as a function of microstructure and microstructural development as a function of processing conditions

Oxadiazole-Based Cell Permeable Macrocyclic Transition State Inhibitors of Norovirus 2CL Protease

Human noroviruses are the primary causative agents of acute gastroenteritis and a pressing public health burden worldwide. There are currently no vaccines or small molecule therapeutics available for the treatment or prophylaxis of norovirus infections. Norovirus 3CL protease plays a vital role in viral replication by generating structural and nonstructural proteins via the cleavage of the viral polyprotein. Thus, molecules that inhibit the viral protease may have potential therapeutic value. We describe herein the structure-based design, synthesis, and in vitro and cell-based evaluation of the first class of oxadiazole-based, permeable macrocyclic inhibitors of norovirus 3CL protease

Blocking airway mucous cell metaplasia by inhibiting EGFR antiapoptosis and IL-13 transdifferentiation signals

Epithelial hyperplasia and metaplasia are common features of inflammatory and neoplastic disease, but the basis for the altered epithelial phenotype is often uncertain. Here we show that long-term ciliated cell hyperplasia coincides with mucous (goblet) cell metaplasia after respiratory viral clearance in mouse airways. This chronic switch in epithelial behavior exhibits genetic susceptibility and depends on persistent activation of EGFR signaling to PI3K that prevents apoptosis of ciliated cells and on IL-13 signaling that promotes transdifferentiation of ciliated to goblet cells. Thus, EGFR blockade (using an irreversible EGFR kinase inhibitor designated EKB-569) prevents virus-induced increases in ciliated and goblet cells whereas IL-13 blockade (using s-IL-13Rα2-Fc) exacerbates ciliated cell hyperplasia but still inhibits goblet cell metaplasia. The distinct effects of EGFR and IL-13 inhibitors after viral reprogramming suggest that these combined therapeutic strategies may also correct epithelial architecture in the setting of airway inflammatory disorders characterized by a similar pattern of chronic EGFR activation, IL-13 expression, and ciliated-to-goblet cell metaplasia