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

The likely Fermi Detection of the Supernova Remnant RCW 103

We report on the results from our $\gamma$-ray analysis of the supernova remnant (SNR) RCW 103 region. The data were taken with the Large Area Telescope on board the Fermi Gamma-ray Space Telescope. An extended source is found at a position consistent with that of RCW 103, and its emission was only detected above 1 GeV (10$\sigma$ significance), having a power-law spectrum with a photon index of 2.0$\pm$0.1. We obtain its 1--300 GeV spectrum, and the total flux gives a luminosity of 8.3$\times 10^{33}$ erg s$^{-1}$ at a source distance of 3.3 kpc. Given the positional coincidence and property similarities of this source with other SNRs, we identify it as the likely Fermi $\gamma$-ray counterpart to RCW 103. Including radio measurements of RCW 103, the spectral energy distribution (SED) is modeled by considering emission mechanisms based on both hadronic and leptonic scenarios. We find that models in the two scenarios can reproduce the observed SED, while in the hadronic scenario the existence of SNR--molecular-cloud interaction is suggested as a high density of the target protons is required.Comment: 6 pages, 3 figures, accepted for publication in Ap

Topological crystalline protection in a photonic system

Topological crystalline insulators are a class of materials with a bulk energy gap and edge or surface modes, which are protected by crystalline symmetry, at their boundaries. They have been realized in electronic systems: in particular, in SnTe. In this work, we propose a mechanism to realize photonic boundary states topologically protected by crystalline symmetry. We map this one-dimensional system to a two-dimensional lattice model with opposite magnetic fields, as well as opposite Chern numbers in its even and odd mirror parity subspaces, thus corresponding to a topological mirror insulator. Furthermore, we test how sensitive and robust edge modes depend on their mirror parity by performing time dependent evolution simulation of edge modes in a photonic setting with realistic experimental parameters.Comment: 10 pages, 7 figure

GeV {\gamma}-ray Emission Detected by Fermi-LAT Probably Associated with the Thermal Composite Supernova Remnant Kesteven 41 in a Molecular Environment

Hadron emission from supernova remnant (SNR)-molecular cloud (MC) association systems has been widely regarded as a probe of the shock-accelerated cosmic-ray protons. Here, we report on the detection of a {\gamma}-ray emission source, with a significance of 24{\sigma} in 0.2-300 GeV, projected to lie to the northwest of the thermal composite SNR Kesteven 41, using 5.6 years of Fermi-Large Area Telescope (LAT) observation data. No significant long-term variability in the energy range 0.2--300 GeV is detected around this source. The 3{\sigma} error circle, 0.09 degree; in radius, covers the 1720MHz OH maser and is essentially consistent with the location of the V_{LSR} ~-50 km/s MC with which the SNR interacts. The source emission has an exponential cutoff power-law spectrum with a photon index of 1.9+/-0.1 and a cutoff energy of 4.0+/-0.9 GeV, and the corresponding 0.2-300 GeV luminosity is ~1.3*10^36 erg/s at a distance of 12 kpc. There is no radio pulsar in the 3{\sigma} circle responsible for the high {\gamma}-ray luminosity. While the inverse Compton scattering scenario would lead to a difficulty in the electron energy budget, the source emission can naturally be explained by the hadronic interaction between the relativistic protons accelerated by the shock of SNR Kesteven 41 and the adjacent northwestern MC. In this paper, we present a list of Galactic thermal composite SNRs detected at GeV {\gamma}-ray energies by Fermi-LAT is presented