Coupled Reversible and Irreversible Bistable Switches Underlying TGF-\beta-induced Epithelial to Mesenchymal Transition

Epithelial to mesenchymal transition (EMT) plays important roles in embryonic development, tissue regeneration and cancer metastasis. While several feedback loops have been shown to regulate EMT, it remains elusive how they coordinately modulate EMT response to TGF-\beta treatment. We construct a mathematical model for the core regulatory network controlling TGF-\beta-induced EMT. Through deterministic analyses and stochastic simulations, we show that EMT is a sequential two-step program that an epithelial cell first transits to partial EMT then to the mesenchymal state, depending on the strength and duration of TGF-\beta stimulation. Mechanistically the system is governed by coupled reversible and irreversible bistable switches. The SNAIL1/miR-34 double negative feedback loop is responsible for the reversible switch and regulates the initiation of EMT, while the ZEB/miR-200 feedback loop is accountable for the irreversible switch and controls the establishment of the mesenchymal state. Furthermore, an autocrine TGF-\beta/miR-200 feedback loop makes the second switch irreversible, modulating the maintenance of EMT. Such coupled bistable switches are robust to parameter variation and molecular noise. We provide a mechanistic explanation on multiple experimental observations. The model makes several explicit predictions on hysteretic dynamic behaviors, system response to pulsed stimulation and various perturbations, which can be straightforwardly tested.Comment: 32 pages, 8 figures, accepted by Biophysical Journa

Unusual Compression Behavior of Columbite TiO2 via First-Principles Calculations

The physical mechanisms behind the reduction of the bulk modulus of a high-pressure cubic TiO2 phase are confirmed by first-principles calculations. An unusual and abrupt change occurs in the dependence of energy on pressure at 43 GPa, indicating a pressure-induced phase transition from columbite TiO2 to a newly-identified modified fluorite TiO2 with a Pca21 symmetry. Oxygen atom displacement in Pca21 TiO2 unexpectedly reduces the bulk modulus by 34% relative to fluorite TiO2. This discovering provides a direct evidence for understanding the compressive properties of such groups of homologous materialsComment: [email protected] or [email protected]

Infinite critical boson non-Fermi liquid on heterostructure interfaces

We study the emergence of non-Fermi liquid on heterostructure interfaces where there exists an infinite number of critical boson modes accounting for the magnetic fluctuations in two spatial dimensions. The interfacial Dzyaloshinskii-Moriya interaction naturally arises in magnetic interactions due to the absence of inversion symmetry, resulting in a degenerate contour for the low-energy bosonic modes in the momentum space which simultaneously becomes critical near the magnetic phase transition. The itinerant electrons are scattered by the critical boson contour via the Yukawa coupling. When the boson contour is much smaller than the Fermi surface, it is shown that, there exists a regime with a dynamic critical exponent z=3 while the boson contour still controls the low-energy magnetic fluctuations. Using a self-consistent renormalization calculation for this regime, we uncover a prominent non-Fermi liquid behavior in the resistivity with a characteristic temperature scaling power. These findings open up new avenues for understanding boson-fermion interactions and the novel fermionic quantum criticality.Comment: 17 pages(with Appendix), 7 figure