300 research outputs found
Resonance bifurcations from robust homoclinic cycles
We present two calculations for a class of robust homoclinic cycles with
symmetry Z_n x Z_2^n, for which the sufficient conditions for asymptotic
stability given by Krupa and Melbourne are not optimal.
Firstly, we compute optimal conditions for asymptotic stability using
transition matrix techniques which make explicit use of the geometry of the
group action.
Secondly, through an explicit computation of the global parts of the Poincare
map near the cycle we show that, generically, the resonance bifurcations from
the cycles are supercritical: a unique branch of asymptotically stable period
orbits emerges from the resonance bifurcation and exists for coefficient values
where the cycle has lost stability. This calculation is the first to explicitly
compute the criticality of a resonance bifurcation, and answers a conjecture of
Field and Swift in a particular limiting case. Moreover, we are able to obtain
an asymptotically-correct analytic expression for the period of the bifurcating
orbit, with no adjustable parameters, which has not proved possible previously.
We show that the asymptotic analysis compares very favourably with numerical
results.Comment: 24 pages, 3 figures, submitted to Nonlinearit
Classification and stability of simple homoclinic cycles in R^5
The paper presents a complete study of simple homoclinic cycles in R^5. We
find all symmetry groups Gamma such that a Gamma-equivariant dynamical system
in R^5 can possess a simple homoclinic cycle. We introduce a classification of
simple homoclinic cycles in R^n based on the action of the system symmetry
group. For systems in R^5, we list all classes of simple homoclinic cycles. For
each class, we derive necessary and sufficient conditions for asymptotic
stability and fragmentary asymptotic stability in terms of eigenvalues of
linearisation near the steady state involved in the cycle. For any action of
the groups Gamma which can give rise to a simple homoclinic cycle, we list
classes to which the respective homoclinic cycles belong, thus determining
conditions for asymptotic stability of these cycles.Comment: 34 pp., 4 tables, 30 references. Submitted to Nonlinearit
Functional and phenotypical comparison of myofibroblasts derived from biopsies and bronchoalveolar lavage in mild asthma and scleroderma
BACKGROUND: Activated fibroblasts, which have previously been obtained from bronchoalveolar lavage fluid (BALF), are proposed to be important cells in the fibrotic processes of asthma and scleroderma (SSc). We have studied the motility for BALF derived fibroblasts in patients with SSc that may explain the presence of these cells in the airway lumen. Furthermore, we have compared phenotypic alterations in activated fibroblasts from BALF and bronchial biopsies from patients with mild asthma and SSc that may account for the distinct fibrotic responses. METHODS: Fibroblasts were cultured from BALF and bronchial biopsies from patients with mild asthma and SSc. The motility was studied using a cell migration assay. Western Blotting was used to study the expression of alpha-smooth muscle actin (α-SMA), ED-A fibronectin, and serine arginine splicing factor 20 (SRp20). The protein expression pattern was analyzed to reveal potential biomarkers using two-dimensional electrophoresis (2-DE) and sequencing dual matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF-TOF). The Mann-Whitney method was used to calculate statistical significance. RESULTS: Increased migration and levels of ED-A fibronectin were observed in BALF fibroblasts from both groups of patients, supported by increased expression of RhoA, Rac1, and the splicing factor SRp20. However, these observations were exclusively accompanied by increased expression of α-SMA in patients with mild asthma. Compared to BALF fibroblasts in mild asthma, fibroblasts in SSc displayed a differential protein expression pattern of cytoskeletal- and scavenger proteins. These identified proteins facilitate cell migration, oxidative stress, and the excessive deposition of extracellular matrix observed in patients with SSc. CONCLUSION: This study demonstrates a possible origin for fibroblasts in the airway lumen in patients with SSc and important differences between fibroblast phenotypes in mild asthma and SSc. The findings may explain the distinct fibrotic processes and highlight the motile BALF fibroblast as a potential target cell in these disorders
Requirement of Podocalyxin in TGF-Beta Induced Epithelial Mesenchymal Transition
Epithelial mesenchymal transition (EMT) is characterized by the development of mesenchymal properties such as a fibroblast-like morphology with altered cytoskeletal organization and enhanced migratory potential. We report that the expression of podocalyxin (PODXL), a member of the CD34 family, is markedly increased during TGF-β induced EMT. PODXL is enriched on the leading edges of migrating A549 cells. Silencing of podocalyxin expression reduced cell ruffle formation, spreading, migration and affected the expression patterns of several proteins that normally change during EMT (e.g., vimentin, E-cadherin). Cytoskeletion assembly in EMT was also found to be dependent on the production of podocalyin. Compositional analysis of podocalyxin containing immunoprecipitates revealed that collagen type 1 was consistently associated with these isolates. Collagen type 1 was also found to co-localize with podocalyxin on the leading edges of migrating cells. The interactions with collagen may be a critical aspect of podocalyxin function. Podocalyxin is an important regulator of the EMT like process as it regulates the loss of epithelial features and the acquisition of a motile phenotype
Nrf2 protects against pulmonary fibrosis by regulating the lung oxidant level and Th1/Th2 balance
<p>Abstract</p> <p>Background</p> <p>Pulmonary fibrosis is a progressive and lethal disorder. Although the precise mechanisms of pulmonary fibrosis are not fully understood, oxidant/antioxidant and Th1/Th2 balances may play an important role in many of the processes of inflammation and fibrosis. The transcription factor Nrf2 acts as a critical regulator for various inflammatory and immune responses by controlling oxidative stress. We therefore investigated the protective role of Nrf2 against the development of pulmonary fibrosis.</p> <p>Methods</p> <p>To generate pulmonary fibrosis, both wild-type C57BL/6 mice and Nrf2-deficient mice of the same background were administered bleomycin intratracheally.</p> <p>Results</p> <p>The survival of Nrf2-deficient mice after bleomycin administration was significantly lower than that of wild-type mice. The degree of bleomycin-induced initial pulmonary inflammation and pulmonary fibrosis was much more severe in Nrf2-deficient mice than in wild-type mice. The expression of antioxidant enzymes and phase II detoxifying enzymes was significantly reduced in the lungs of Nrf2-deficient mice, concomitant with an elevation of lung 8-isoprostane level, compared with wild-type mice. The expression of Th2 cytokines, such as interleukin-4 and interleukin-13, was significantly elevated in the lungs of Nrf2-deficient mice with an increase in the number of Th2 cells that express GATA-binding protein 3.</p> <p>Conclusions</p> <p>The results indicated that Nrf2 protects against the development of pulmonary fibrosis by regulating the cellular redox level and lung Th1/Th2 balance. Thus, Nrf2 might be an important genetic factor in the determination of susceptibility to pulmonary fibrosis.</p
Recommended from our members
An explicit state-space approach to the one-block super-optimal distance problem
An explicit state-space approach is presented for solving the super-optimal Nehari-extension problem. The approach is based on the all-pass dilation technique developed in (Jaimoukha and Limebeer in SIAM J Control Optim 31(5):1115–1134, 1993) which offers considerable advantages compared to traditional methods relying on a diagonalisation procedure via a Schmidt pair of the Hankel operator associated with the problem. As a result, all derivations presented in this work rely only on simple linear-algebraic arguments. Further, when the simple structure of the one-block problem is taken into account, this approach leads to a detailed and complete state-space analysis which clearly illustrates the structure of the optimal solution and allows for the removal of all technical assumptions (minimality, multiplicity of largest Hankel singular value, positive-definiteness of the solutions of certain Riccati equations) made in previous work (Halikias et al. in SIAM J Control Optim 31(4):960–982, 1993; Limebeer et al. in Int J Control 50(6):2431–2466, 1989). The advantages of the approach are illustrated with a numerical example. Finally, the paper presents a short survey of super-optimization, the various techniques developed for its solution and some of its applications in the area of modern robust control
Latency Associated Peptide Has In Vitro and In Vivo Immune Effects Independent of TGF-β1
Latency Associated Peptide (LAP) binds TGF-β1, forming a latent complex.
Currently, LAP is presumed to function only as a sequestering agent for active
TGF-β1. Previous work shows that LAP can induce epithelial cell
migration, but effects on leukocytes have not been reported. Because of the
multiplicity of immunologic processes in which TGF-β1 plays a role, we
hypothesized that LAP could function independently to modulate immune responses.
In separate experiments we found that LAP promoted chemotaxis of human monocytes
and blocked inflammation in vivo in a murine model of the
delayed-type hypersensitivity response (DTHR). These effects did not involve
TGF-β1 activity. Further studies revealed that disruption of specific
LAP-thrombospondin-1 (TSP-1) interactions prevented LAP-induced responses. The
effect of LAP on DTH inhibition depended on IL-10. These data support a novel
role for LAP in regulating monocyte trafficking and immune modulation
- …