Avalanches in the lung: A statistical mechanical model

We study a statistical mechanical model for the dynamics of lung inflation which incorporates recent experimental observations on the opening of individual airways by a cascade or avalanche mechanism. Using an exact mapping of the avalanche problem onto percolation on a Cayley tree, we analytically derive the exponents describing the size distribution of the first avalanches and test the analytical solution by numerical simulations. We find that the tree-like structure of the airways together with the simplest assumptions concerning opening threshold pressures of each airway, is sufficient to explain the existence of power-law distributions observed experimentally.Comment: 4 pages, Figures avaliable by mail from [email protected], REVTE

A Role of Myocardin Related Transcription Factor-A (MRTF-A) in Scleroderma Related Fibrosis.

In scleroderma (systemic sclerosis, SSc), persistent activation of myofibroblast leads to severe skin and organ fibrosis resistant to therapy. Increased mechanical stiffness in the involved fibrotic tissues is a hallmark clinical feature and a cause of disabling symptoms. Myocardin Related Transcription Factor-A (MRTF-A) is a transcriptional co-activator that is sequestered in the cytoplasm and translocates to the nucleus under mechanical stress or growth factor stimulation. Our objective was to determine if MRTF-A is activated in the disease microenvironment to produce more extracellular matrix in progressive SSc. Immunohistochemistry studies demonstrate that nuclear translocation of MRTF-A in scleroderma tissues occurs in keratinocytes, endothelial cells, infiltrating inflammatory cells, and dermal fibroblasts, consistent with enhanced signaling in multiple cell lineages exposed to the stiff extracellular matrix. Inhibition of MRTF-A nuclear translocation or knockdown of MRTF-A synthesis abolishes the SSc myofibroblast enhanced basal contractility and synthesis of type I collagen and inhibits the matricellular profibrotic protein, connective tissue growth factor (CCN2/CTGF). In MRTF-A null mice, basal skin and lung stiffness was abnormally reduced and associated with altered fibrillar collagen. MRTF-A has a role in SSc fibrosis acting as a central regulator linking mechanical cues to adverse remodeling of the extracellular matrix

On the behaviour of lung tissue under tension and compression

Lung injuries are common among those who suffer an impact or trauma. The relative severity of injuries up to physical tearing of tissue have been documented in clinical studies. However, the specific details of energy required to cause visible damage to the lung parenchyma are lacking. Furthermore, the limitations of lung tissue under simple mechanical loading are also not well documented. This study aimed to collect mechanical test data from freshly excised lung, obtained from both Sprague-Dawley rats and New Zealand White rabbits. Compression and tension tests were conducted at three different strain rates: 0.25, 2.5 and 25 min−1. This study aimed to characterise the quasi-static behaviour of the bulk tissue prior to extending to higher rates. A nonlinear viscoelastic analytical model was applied to the data to describe their behaviour. Results exhibited asymmetry in terms of differences between tension and compression. The rabbit tissue also appeared to exhibit stronger viscous behaviour than the rat tissue. As a narrow strain rate band is explored here, no conclusions are being drawn currently regarding the rate sensitivity of rat tissue. However, this study does highlight both the clear differences between the two tissue types and the important role that composition and microstructure can play in mechanical response

Interplay between geometry and flow distribution in an airway tree

Uniform fluid flow distribution in a symmetric volume can be realized through a symmetric branched tree. It is shown here, however, that the flow partitioning can be highly sensitive to deviations from exact symmetry if inertial effects are present. This is found by direct numerical simulation of the Navier-Stokes equations in a 3D tree geometry. The flow asymmetry is quantified and found to depend on the Reynolds number. Moreover, for a given Reynolds number, we show that the flow distribution depends on the aspect ratio of the branching elements as well as their angular arrangement. Our results indicate that physiological variability should be severely restricted in order to ensure uniform fluid distribution in a tree. This study suggests that any non-uniformity in the air flow distribution in human lungs should be influenced by the respiratory conditions, rest or hard exercise

Avalanches in Breakdown and Fracture Processes

We investigate the breakdown of disordered networks under the action of an increasing external---mechanical or electrical---force. We perform a mean-field analysis and estimate scaling exponents for the approach to the instability. By simulating two-dimensional models of electric breakdown and fracture we observe that the breakdown is preceded by avalanche events. The avalanches can be described by scaling laws, and the estimated values of the exponents are consistent with those found in mean-field theory. The breakdown point is characterized by a discontinuity in the macroscopic properties of the material, such as conductivity or elasticity, indicative of a first order transition. The scaling laws suggest an analogy with the behavior expected in spinodal nucleation.Comment: 15 pages, 12 figures, submitted to Phys. Rev. E, corrected typo in authors name, no changes to the pape

Fractional-order viscoelasticity applied to describe uniaxial stress relaxation of human arteries.

Viscoelastic models can be used to better understand arterial wall mechanics in physiological and pathological conditions. The arterial wall reveals very slow time-dependent decays in uniaxial stress-relaxation experiments, coherent with weak power-law functions. Quasi-linear viscoelastic (QLV) theory was successfully applied to modeling such responses, but an accurate estimation of the reduced relaxation function parameters can be very difficult. In this work, an alternative relaxation function based on fractional calculus theory is proposed to describe stress relaxation experiments in strips cut from healthy human aortas. Stress relaxation (1 h) was registered at three incremental stress levels. The novel relaxation function with three parameters was integrated into the QLV theory to fit experimental data. It was based in a modified Voigt model, including a fractional element of order α, called spring–pot. The stressrelaxation predictionwas accurate and fast. Sensitivity plots for each parameter presented a minimum near their optimal values. Least-squares errors remained below 2%. Values of order α = 0.1–0.3 confirmed a predominant elastic behavior. The other two parameters of the model can be associated to elastic and viscous constants that explain the time course of the observed relaxation function. The fractional-order model integrated into the QLV theory proved to capture the essential features of the arterial wall mechanical response

Mir-21-Sox2 Axis Delineates Glioblastoma Subtypes with Prognostic Impact.

UNLABELLED: Glioblastoma (GBM) is the most aggressive human brain tumor. Although several molecular subtypes of GBM are recognized, a robust molecular prognostic marker has yet to be identified. Here, we report that the stemness regulator Sox2 is a new, clinically important target of microRNA-21 (miR-21) in GBM, with implications for prognosis. Using the MiR-21-Sox2 regulatory axis, approximately half of all GBM tumors present in the Cancer Genome Atlas (TCGA) and in-house patient databases can be mathematically classified into high miR-21/low Sox2 (Class A) or low miR-21/high Sox2 (Class B) subtypes. This classification reflects phenotypically and molecularly distinct characteristics and is not captured by existing classifications. Supporting the distinct nature of the subtypes, gene set enrichment analysis of the TCGA dataset predicted that Class A and Class B tumors were significantly involved in immune/inflammatory response and in chromosome organization and nervous system development, respectively. Patients with Class B tumors had longer overall survival than those with Class A tumors. Analysis of both databases indicated that the Class A/Class B classification is a better predictor of patient survival than currently used parameters. Further, manipulation of MiR-21-Sox2 levels in orthotopic mouse models supported the longer survival of the Class B subtype. The MiR-21-Sox2 association was also found in mouse neural stem cells and in the mouse brain at different developmental stages, suggesting a role in normal development. Therefore, this mechanism-based classification suggests the presence of two distinct populations of GBM patients with distinguishable phenotypic characteristics and clinical outcomes. SIGNIFICANCE STATEMENT: Molecular profiling-based classification of glioblastoma (GBM) into four subtypes has substantially increased our understanding of the biology of the disease and has pointed to the heterogeneous nature of GBM. However, this classification is not mechanism based and its prognostic value is limited. Here, we identify a new mechanism in GBM (the miR-21-Sox2 axis) that can classify ∼50% of patients into two subtypes with distinct molecular, radiological, and pathological characteristics. Importantly, this classification can predict patient survival better than the currently used parameters. Further, analysis of the miR-21-Sox2 relationship in mouse neural stem cells and in the mouse brain at different developmental stages indicates that miR-21 and Sox2 are predominantly expressed in mutually exclusive patterns, suggesting a role in normal neural development

How self-organized criticality works: A unified mean-field picture

We present a unified mean-field theory, based on the single site approximation to the master-equation, for stochastic self-organized critical models. In particular, we analyze in detail the properties of sandpile and forest-fire (FF) models. In analogy with other non-equilibrium critical phenomena, we identify the order parameter with the density of ``active'' sites and the control parameters with the driving rates. Depending on the values of the control parameters, the system is shown to reach a subcritical (absorbing) or super-critical (active) stationary state. Criticality is analyzed in terms of the singularities of the zero-field susceptibility. In the limit of vanishing control parameters, the stationary state displays scaling characteristic of self-organized criticality (SOC). We show that this limit corresponds to the breakdown of space-time locality in the dynamical rules of the models. We define a complete set of critical exponents, describing the scaling of order parameter, response functions, susceptibility and correlation length in the subcritical and supercritical states. In the subcritical state, the response of the system to small perturbations takes place in avalanches. We analyze their scaling behavior in relation with branching processes. In sandpile models because of conservation laws, a critical exponents subset displays mean-field values ($\nu=1/2$ and $\gamma = 1$) in any dimensions. We treat bulk and boundary dissipation and introduce a new critical exponent relating dissipation and finite size effects. We present numerical simulations that confirm our results. In the case of the forest-fire model, our approach can distinguish between different regimes (SOC-FF and deterministic FF) studied in the literature and determine the full spectrum of critical exponents.Comment: 21 RevTex pages, 3 figures, submitted to Phys. Rev.

Entrepreneurial-intention constraint model: A comparative analysis among post-graduate management students in India, Singapore and Malaysia

YesAlthough literature on entrepreneurship has increasingly focused on intention-based models, not much emphasis has been laid on understanding the combined effect of contextual and situational factors along with support of university environment on the formation of entrepreneurial intention among students. In an effort to make up for this shortfall, by taking Theory of Planned Behavior as basic framework, the present study seeks to understand the influence of three of the most important factors, viz. (a) endogenous barriers, (b) exogenous environment, and (c) university environment and support on the entrepreneurial intention among management students. The study sample consisted of 1,097 students, wherein 526 students were from India, 252 from Singapore, and 319 were from Malaysia. The results indicates that along with positive attitude and perceived behavioral control that directly influences entrepreneurial intention, university environment and support and exogenous environment also have an indirect but significant impact on shaping of entrepreneurial intention among students. With this, it was found that exogenous environment was found to have a negative relationship with both attitude towards behavior and perceived behavioral control for all three countries.The full-text of this article will be released for public view at the end of the publisher embargo on 2 Jun 2018