The role of pinning and instability in a class of non-equilibrium growth models

We study the dynamics of a growing crystalline facet where the growth mechanism is controlled by the geometry of the local curvature. A continuum model, in (2+1) dimensions, is developed in analogy with the Kardar-Parisi-Zhang (KPZ) model is considered for the purpose. Following standard coarse graining procedures, it is shown that in the large time, long distance limit, the continuum model predicts a curvature independent KPZ phase, thereby suppressing all explicit effects of curvature and local pinning in the system, in the "perturbative" limit. A direct numerical integration of this growth equation, in 1+1 dimensions, supports this observation below a critical parametric range, above which generic instabilities, in the form of isolated pillared structures lead to deviations from standard scaling behavior. Possibilities of controlling this instability by introducing statistically "irrelevant" (in the sense of renormalization groups) higher ordered nonlinearities have also been discussed.Comment: 10 pages, 4 figures, references updated and minor changes in the text, to appear in Euro. Phys. J.

Genome-wide transcription analysis of interaction between the human macrophage and Mycobacterium tuberculosis during concurrent drug administration by conventional and novel methods

Targeted drug delivery to alveolar macrophages harboring Mycobacterium tuberculosis (Mtb) holds promise of high efficacy against pulmonary tuberculosis (TB). It was investigated whether inhalable microparticles (MP) can rescue macrophages from ‘alternative’ activation induced by pathogenic Mtb in addition to achieving targeted drug delivery. A genome-wide transcription analysis (Affymetrix HG-U133 Plus 2.0 DNA microarray) of THP-1 cell line derived macrophages was undertaken after exposing them to infection with 10 MOI of MTB H37Rv at 0, 12 and 24 hours post infection. The Molecular markers of macrophage bactericidal activity were assayed in THP-1- and primary human peripheral blood mononuclear cell (PBMC)-derived macrophages, in the presence or absence of soluble anti-tuberculosis drugs, drug-containing MP and blank MP. About 1,500 genes were differentially upregulated and about 500 genes differentially downregulated in response to various modes of treatment. Variations were also observed in the kinetics of gene expression. Cluster analysis indicated activation of several pathways related to innate immune response (cytokines, chemokines, receptors and ligands), apoptosis, cytoskeleton and membrane remodeling, general metabolism and general housekeeping. Some of these results were validated at the functional level, by studying caspase activities, concentrations and time-courses of effector molecules , rates/extents of apoptosis and nitrite oxide induction. Production of cytokines and NO, apoptosis, and bacterial survival were studied as pharmacodynamic outcomes. Cytokine responses of THP-1 derived macrophages were estimated. MP reversed suppression of tumor necrosis factor (TNF) induced by infection, and transiently upregulated γ-interferon (IFN-γ). Drug-free MP surprisingly induced IFN-γ, but not TNF. Primary cells responded to MP, regardless of drug content, by upregulation of NO; but THP-1-derived cells did not respond to blank MP. About 19% of infected cells exposed to MP underwent apoptosis as compared to ~11% cells treated with soluble drugs or blank MP. Cell death induced by blank MP was caspase-independent. Only drug-containing MP induced apoptosis through caspase-8 and caspase-9. Bacterial survival after different treatments varied between individuals. In the best case, while untreated infection resulted in survival of 900±141 colony forming units (CFU), treatment with soluble drugs, drug-containing MP and blank MP respectively, reduced CFU counts to 8.5± 0.7, 3±1.4 and 102±138.6. The results suggest a role of the drug delivery system in macrophage activation as a component of therapeutic strategy against TB