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

An SMDP-based Resource Management Scheme for Distributed Cloud Systems

In this paper, the resource management problem in geographically distributed cloud systems is considered. The Follow Me Cloud concept which enables service migration across federated data centers (DCs) is adopted. Therefore, there are two types of service requests to the DC, i.e., new requests (NRs) initiated in the local service area and migration requests (MRs) generated when mobile users move across service areas. A novel resource management scheme is proposed to help the resource manager decide whether to accept the service requests (NRs or MRs) or not and determine how much resources should be allocated to each service (if accepted). The optimization objective is to maximize the average system reward and keep the rejection probability of service requests under a certain threshold. Numerical results indicate that the proposed scheme can significantly improve the overall system utility as well as the user experience compared with other resource management schemes.Comment: 5 pages, 5 figures, conferenc

Photoactive Graphene — From Functionalization to Applications

Photoactive graphene fabricated by chemical functionalization of pristine graphene with different light-harvesting molecules has become one of the most exciting topics of graphene research in the last few years, which remarkably sustains and expands the graphene boom due to its great potentials in various applications. This chapter presents some important issues of photoactive graphene, covering material synthesis, electron/energy- transfer interaction, organic photovoltaic and photocatalystic applications. Of particular interest is the utilization of graphene as a two- dimensional platform to anchor organic conjugated aromatic molecules and their applications in photo-energy conversion and photocatalysis. Challenges currently faced by researchers and future perspectives in this field are also discussed

On the uniqueness of the non-minimal matter coupling in massive gravity and bigravity

In de Rham-Gabadadze-Tolley (dRGT) massive gravity and bigravity, a non-minimal matter coupling involving both metrics generically re-introduces the Boulware--Deser (BD) ghost. A non-minimal matter coupling via a simple, yet specific composite metric has been proposed, which eliminates the BD ghost below the strong coupling scale. Working explicitly in the metric formulation and for arbitrary spacetime dimensions, we show that this composite metric is the unique consistent non-minimal matter coupling below the strong coupling scale, which emerges out of two diagnostics, namely, absence of Ostrogradski ghosts in the decoupling limit and absence of the BD ghost from matter quantum loop corrections.Comment: v2: references added, matches accepted version in Physics Letters B v1: 6 pages, two-colum