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Selected solute atoms can strongly interact with and slow down the diffusion of point defects in alloy systems. While such additions can be beneficial, for instance to promote microstructural stability during thermal annealing or during irradiation by energetic particles, they create significant computational challenges when simulating these evolutions using atomistic techniques such as kinetic Monte Carlo (KMC) simulations. Point defect trapping in energy basins created by clusters of solute atoms leads to frequent re-visiting of states with short residence times, which dramatically reduces the efficiency of traditional KMC algorithms. We introduce here a hybrid algorithm that combines and expand on two prior KMC algorithms, the Chain KMC and the equilibrating basin KMC. This hybrid algorithm, referred to as the Equilibrating Chain algorithm, utilizes Chain KMC as previously reported, but leverages the data-handling framework to build an occupation distribution of the basin, allowing the equilibrating basin assumption to be statistically tested and applied. For a model A-B trapping alloy system on a face-centered cubic lattice, statistical comparisons of basin exit and cluster dissolution kinetics between traditional and accelerated KMC algorithms are presented to demonstrate the accuracy and the efficiency of the new algorithm. We also discuss our algorithm in the context of other accelerated KMC algorithms.

Cross correlation techniques applied to EBSD patterns have led to what has been termed “high-resolution EBSD” (HR-EBSD). The technique yields higher accuracy orientation and strain data which is obtained by comparing a given EBSD pattern with either a real or a simulated reference pattern. Real reference patterns are often taken from a “central” position in a given grain, where it is hoped that the material is “strain-free”, and they enable the determination of relative changes in orientation and strain from that present in the lattice at the reference position. Simulated patterns, on the other hand, enable comparison of the sample lattice with that of a perfect lattice, resulting in a measure of absolute strain and orientation. However, the simulated pattern method has several drawbacks, including the need to accurately specify microscope geometry, the lower fidelity/detail of simulated patterns compared with real patterns, and the potential for microscope-specific bias in the measured patterns (such as due to optical distortion). These drawbacks have led to much debate about the utility of the cross-correlation technique using simulated patterns. This paper is the first to assess the accuracy of the simulated pattern method relative to the real pattern approach in a setting where accuracy can be reasonably determined, thus providing a fair assessment of the potential of the simulated pattern technique. Based upon recent developments towards a standard material for assessing strain mapping techniques, this paper assesses the overall accuracy of the simulated pattern technique. Mismatch strains are calculated using both the real and simulated pattern techniques for a SiGe film deposited on a Si substrate. While the simulated pattern technique is not as accurate or precise as the real pattern technique for providing relative strains, it provides an estimate of absolute strain that is not available via the real pattern approach.

Transcriptional responses of microorganisms to environmental perturbations are broad and complex, and often involve regulatory cascades in which an interplay of regulatory factors trigger a specific expression program. Here, we describe how Pseudomonas responds to challenges from toxic chemicals, for which they use a dedicated program that subsequently confers resistance to these compounds. A mosaic of domains has been recruited to sense and metabolize these chemicals in order to obtain energy and carbon.

Two phenotypic missense mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) channel pore (L346P and R347P in transmembrane (TM) segment 6) involve gain of a proline residue, but only L346P represents a significant loss of segment hydropathy. We show here that, for synthetic peptides corresponding to sequences of CFTR TM6 segments, circular dichroism spectra of wild type and R347P TM6 in membrane mimetic environments are virtually identical, but L346P loses approximately 50% helicity, implying a membrane insertion defect in the latter mutant. A similar defect was observed in the corresponding double-spanning ("hairpin") TM5/6-L346P synthetic peptide. Examination of the biogenesis of CFTR revealed that the full-length protein harboring the L346P mutation is rapidly degraded at the endoplasmic reticulum (ER), whereas the wild type and the R347P protein process normally. Furthermore, a second site mutation (R347I) that restores in vitro membrane insertion and folding of the TM5/6-L346P peptide also rescues the folding and cell surface chloride channel function of full-length L346P CFTR. The correlated in vitro/in vivo results demonstrate that destabilizing local hydrophobic character represents a sufficient signal for marking CFTR as a non-native protein by the ER quality control, with accompanying deleterious consequences to global protein folding events.

Many of the genes (pags (phoP activated genes) and prgs (phoP repressed genes)) regulated by the PhoP and PhoQ proteins (PhoP/Q) are necessary for survival of Salmonella typhimurium in murine macrophages and pathogenesis in mice. Although a great deal is known about the S. typhimurium phoP/Q regulon, little has been done with the human specific pathogen S. typhi, prompting us to investigate S. typhi phoP/Q regulated genes. Isogenic phoP12 (null) and phoP24 (constitutive) strains were constructed in S. typhi Ty2 and S. typhimurium C5 strains. Comparison of whole cell proteins from these strains by SDS-PAGE showed differences in both the number and molecular mass of PhoP/Q regulated proteins. This suggested that S. typhi and S. typhimurium may have different PhoP/Q regulated proteins and/or that their regulation may be different. A genetic procedure was developed to isolate mutations in PhoP/Q regulated genes. This involved random MudJ transposon mutagenesis of a phoP12 mutant, creating lacZ-gene fusions, and screening for Lac+ or Lac- colonies. A mobilizable plasmid carrying the phoP24 mutant gene was conjugated into these insertion mutants. Those that changed from Lac- to Lac+ were inferred to be pag::MudJ insertions and those that changed from Lac+ to Lac- were inferred to be prg::MudJ insertions. Five mutants with PhoP/Q regulated MudJ fusions were found by this scheme. The mutations were termed pqa (PhoPQ activated) and pqr (PhoPQ repressed) to distinguish them from other PhoP/Q regulated genes. The pqa/pqr::MudJ mutations were transduced into S. typhi phoP+ and phoP24 strains by Vi-l phage transduction. Characterization of the mutants (Southern blot analysis, beta-galactosidase activity on indicator plates and in liquid cultures) strongly suggested that their MudJ insertion mutations were in five different genes. Further characterization involved determining cationic peptide sensitivity and mouse virulence. Two mutants were found to be sensitive to the antimicrobial peptide melittin.