Model of surface instabilities induced by stress

We propose a model based on a Ginzburg-Landau approach to study a strain relief mechanism at a free interface of a non-hydrostatically stressed solid, commonly observed in thin-film growth. The evolving instability, known as the Grinfeld instability, is studied numerically in two and three dimensions. Inherent in the description is the proper treatment of nonlinearities. We find these nonlinearities can lead to competitive coarsening of interfacial structures, corresponding to different wavenumbers, as strain is relieved. We suggest ways to experimentally measure this coarsening.Comment: 4 pages (3 figures included

Finite to infinite steady state solutions, bifurcations of an integro-differential equation

We consider a bistable integral equation which governs the stationary solutions of a convolution model of solid--solid phase transitions on a circle. We study the bifurcations of the set of the stationary solutions as the diffusion coefficient is varied to examine the transition from an infinite number of steady states to three for the continuum limit of the semi--discretised system. We show how the symmetry of the problem is responsible for the generation and stabilisation of equilibria and comment on the puzzling connection between continuity and stability that exists in this problem

Varicella-Zoster viruses associated with post-herpetic neuralgia induce sodium current density increases in the ND7-23 Nav-1.8 neuroblastoma cell line

Post-herpetic neuralgia (PHN) is the most significant complication of herpes zoster caused by reactivation of latent Varicella-Zoster virus (VZV). We undertook a heterologous infection in vitro study to determine whether PHN-associated VZV isolates induce changes in sodium ion channel currents known to be associated with neuropathic pain. Twenty VZV isolates were studied blind from 11 PHN and 9 non-PHN subjects. Viruses were propagated in the MeWo cell line from which cell-free virus was harvested and applied to the ND7/23-Nav1.8 rat DRG x mouse neuroblastoma hybrid cell line which showed constitutive expression of the exogenous Nav 1.8, and endogenous expression of Nav 1.6 and Nav 1.7 genes all encoding sodium ion channels the dysregulation of which is associated with a range of neuropathic pain syndromes. After 72 hrs all three classes of VZV gene transcripts were detected in the absence of infectious virus. Single cell sodium ion channel recording was performed after 72 hr by voltage-clamping. PHN-associated VZV significantly increased sodium current amplitude in the cell line when compared with non-PHN VZV, wild-type (Dumas) or vaccine VZV strains ((POka, Merck and GSK). These sodium current increases were unaffected by acyclovir pre-treatment but were abolished by exposure to Tetrodotoxin (TTX) which blocks the TTX-sensitive fast Nav 1.6 and Nav 1.7 channels but not the TTX-resistant slow Nav 1.8 channel. PHN-associated VZV sodium current increases were therefore mediated in part by the Nav 1.6 and Nav 1.7 sodium ion channels. An additional observation was a modest increase in message levels of both Nav1.6 and Nav1.7 mRNA but not Nav 1.8 in PHN virally infected cells

Trapped and excited w modes of stars with a phase transition and R>=5M

The trapped $w$-modes of stars with a first order phase transition (a density discontinuity) are computed and the excitation of some of the modes of these stars by a perturbing shell is investigated. Attention is restricted to odd parity (``axial'') $w$-modes. With $R$ the radius of the star, $M$ its mass, $R_{i}$ the radius of the inner core and $M_{i}$ the mass of such core, it is shown that stars with $R/M\geq 5$ can have several trapped $w$-modes, as long as $R_{i}/M_{i}<2.6$. Excitation of the least damped $w$-mode is confirmed for a few models. All of these stars can only exist however, for values of the ratio between the densities of the two phases, greater than $\sim 46$. We also show that stars with a phase transition and a given value of $R/M$ can have far more trapped modes than a homogeneous single density star with the same value of $R/M$, provided both $R/M$ and $R_{i}/M_{i}$ are smaller than 3. If the phase transition is very fast, most of the stars with trapped modes are unstable to radial oscillations. We compute the time of instability, and find it to be comparable to the damping of the $w$-mode excited in most cases where $w$-mode excitation is likely. If on the other hand the phase transition is slow, all the stars are stable to radial oscillations.Comment: To appear in Physical Review

Stress-driven instability in growing multilayer films

We investigate the stress-driven morphological instability of epitaxially growing multilayer films, which are coherent and dislocation-free. We construct a direct elastic analysis, from which we determine the elastic state of the system recursively in terms of that of the old states of the buried layers. In turn, we use the result for the elastic state to derive the morphological evolution equation of surface profile to first order of perturbations, with the solution explicitly expressed by the growth conditions and material parameters of all the deposited layers. We apply these results to two kinds of multilayer structures. One is the alternating tensile/compressive multilayer structure, for which we determine the effective stability properties, including the effect of varying surface mobility in different layers, its interplay with the global misfit of the multilayer film, and the influence of asymmetric structure of compressive and tensile layers on the system stability. The nature of the asymmetry properties found in stability diagrams is in agreement with experimental observations. The other multilayer structure that we study is one composed of stacked strained/spacer layers. We also calculate the kinetic critical thickness for the onset of morphological instability and obtain its reduction and saturation as number of deposited layers increases, which is consistent with recent experimental results. Compared to the single-layer film growth, the behavior of kinetic critical thickness shows deviations for upper strained layers.Comment: 27 pages, 11 figures; Phys. Rev. B, in pres

Mutant calreticulin knockin mice develop thrombocytosis and myelofibrosis without a stem cell self-renewal advantage.

Somatic mutations in the endoplasmic reticulum chaperone calreticulin (CALR) are detected in approximately 40% of patients with essential thrombocythemia (ET) and primary myelofibrosis (PMF). Multiple different mutations have been reported, but all result in a +1-bp frameshift and generate a novel protein C terminus. In this study, we generated a conditional mouse knockin model of the most common CALR mutation, a 52-bp deletion. The mutant novel human C-terminal sequence is integrated into the otherwise intact mouse CALR gene and results in mutant CALR expression under the control of the endogenous mouse locus. CALRdel/+ mice develop a transplantable ET-like disease with marked thrombocytosis, which is associated with increased and morphologically abnormal megakaryocytes and increased numbers of phenotypically defined hematopoietic stem cells (HSCs). Homozygous CALRdel/del mice developed extreme thrombocytosis accompanied by features of MF, including leukocytosis, reduced hematocrit, splenomegaly, and increased bone marrow reticulin. CALRdel/+ HSCs were more proliferative in vitro, but neither CALRdel/+ nor CALRdel/del displayed a competitive transplantation advantage in primary or secondary recipient mice. These results demonstrate the consequences of heterozygous and homozygous CALR mutations and provide a powerful model for dissecting the pathogenesis of CALR-mutant ET and PMF

Shape Transition in the Epitaxial Growth of Gold Silicide in Au Thin Films on Si(111)

Growth of epitaxial gold silicide islands on bromine-passivated Si(111) substrates has been studied by optical and electron microscopy, electron probe micro analysis and helium ion backscattering. The islands grow in the shape of equilateral triangles up to a critical size beyond which the symmetry of the structure is broken, resulting in a shape transition from triangle to trapezoid. The island edges are aligned along $Si[110]$ directions. We have observed elongated islands with aspect ratios as large as 8:1. These islands, instead of growing along three equivalent [110] directions on the Si(111) substrate, grow only along one preferential direction. This has been attributed to the vicinality of the substrate surface.Comment: revtex version 3.0, 11 pages 4 figures available on request from [email protected] - IP/BBSR/93-6

Epitaxial growth in dislocation-free strained alloy films: Morphological and compositional instabilities

The mechanisms of stability or instability in the strained alloy film growth are of intense current interest to both theorists and experimentalists. We consider dislocation-free, coherent, growing alloy films which could exhibit a morphological instability without nucleation. We investigate such strained films by developing a nonequilibrium, continuum model and by performing a linear stability analysis. The couplings of film-substrate misfit strain, compositional stress, deposition rate, and growth temperature determine the stability of film morphology as well as the surface spinodal decomposition. We consider some realistic factors of epitaxial growth, in particular the composition dependence of elastic moduli and the coupling between top surface and underlying bulk of the film. The interplay of these factors leads to new stability results. In addition to the stability diagrams both above and below the coherent spinodal temperature, we also calculate the kinetic critical thickness for the onset of instability as well as its scaling behavior with respect to misfit strain and deposition rate. We apply our results to some real growth systems and discuss the implications related to some recent experimental observations.Comment: 26 pages, 13 eps figure

Lipoprotein‐Associated Phospholipase A2 Activity Is a Marker of Risk But Not a Useful Target for Treatment in Patients With Stable Coronary Heart Disease

Background: We evaluated lipoprotein‐associated phospholipase A2 (Lp‐PLA2) activity in patients with stable coronary heart disease before and during treatment with darapladib, a selective Lp‐PLA2 inhibitor, in relation to outcomes and the effects of darapladib in the STABILITY trial. Methods and Results: Plasma Lp‐PLA2 activity was determined at baseline (n=14 500); at 1 month (n=13 709); serially (n=100) at 3, 6, and 18 months; and at the end of treatment. Adjusted Cox regression models evaluated associations between Lp‐PLA2 activity levels and outcomes. At baseline, the median Lp‐PLA2 level was 172.4 μmol/min per liter (interquartile range 143.1–204.2 μmol/min per liter). Comparing the highest and lowest Lp‐PLA2 quartile groups, the hazard ratios were 1.50 (95% CI 1.23–1.82) for the primary composite end point (cardiovascular death, myocardial infarction, or stroke), 1.95 (95% CI 1.29–2.93) for hospitalization for heart failure, 1.42 (1.07–1.89) for cardiovascular death, and 1.37 (1.03–1.81) for myocardial infarction after adjustment for baseline characteristics, standard laboratory variables, and other prognostic biomarkers. Treatment with darapladib led to a ≈65% persistent reduction in median Lp‐PLA2 activity. There were no associations between on‐treatment Lp‐PLA2 activity or changes of Lp‐PLA2 activity and outcomes, and there were no significant interactions between baseline and on‐treatment Lp‐PLA2 activity or changes in Lp‐PLA2 activity levels and the effects of darapladib on outcomes. Conclusions: Although high Lp‐PLA2 activity was associated with increased risk of cardiovascular events, pharmacological lowering of Lp‐PLA2 activity by ≈65% did not significantly reduce cardiovascular events in patients with stable coronary heart disease, regardless of the baseline level or the magnitude of change of Lp‐PLA2 activity

Improved functionalization of oleic acid-coated iron oxide nanoparticles for biomedical applications

Superparamagnetic iron oxide nanoparticles can providemultiple benefits for biomedical applications in aqueous environments such asmagnetic separation or magnetic resonance imaging. To increase the colloidal stability and allow subsequent reactions, the introduction of hydrophilic functional groups onto the particles’ surface is essential. During this process, the original coating is exchanged by preferably covalently bonded ligands such as trialkoxysilanes. The duration of the silane exchange reaction, which commonly takes more than 24 h, is an important drawback for this approach. In this paper, we present a novel method, which introduces ultrasonication as an energy source to dramatically accelerate this process, resulting in high-quality waterdispersible nanoparticles around 10 nmin size. To prove the generic character, different functional groups were introduced on the surface including polyethylene glycol chains, carboxylic acid, amine, and thiol groups. Their colloidal stability in various aqueous buffer solutions as well as human plasma and serum was investigated to allow implementation in biomedical and sensing applications.status: publishe