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241
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Introduction
Ping Ao currently works at the Shanghai Center for Quantitative Life Sciences at Shanghai University and at the Shanghai Center for Systems Biomedicine, Shanghai Jiao Tong University. Ping does research in Systems Biology---Metabolic network dynamics, gensis and progression of cancer, evolution, and stochastic processes; Condensed Matter Physics and Quantum Physics. Their current main project is 'Endogenous molecular-cellular network theory for cancer'.
Publications
Publications (241)
A noisy stabilized Kuramoto-Sivashinsky equation is analyzed by stochastic decomposition. For values of the control parameter for which periodic stationary patterns exist, the dynamics can be decomposed into diffusive and transverse parts which act on a stochastic potential. The relative positions of stationary states in the stochastic global poten...
The Hall anomaly, as appears in the mixed-state Hall resistivity of type-II superconductors, has been the subject of numerous theories, but there is not yet a consensus on its origin. In this paper, we conduct a quantitative analysis of the magnetotransport measurements on Bi2.1Sr1.9CaCu2.0O8+δ (BSCCO) thin films by Zhao et al. [Phys. Rev. Lett. 12...
Stochastic gradient descent (SGD), a widely used algorithm in deep-learning neural networks has attracted continuing studies for the theoretical principles behind its success. A recent work uncovered a generic inverse variance-flatness (IVF) relation between the variance of neural weights and the landscape flatness of loss function near solutions u...
A noisy stabilized Kuramoto-Sivashinsky equation is analyzed by stochastic decomposition. For values of control parameter for which periodic stationary patterns exist, the dynamics can be decomposed into diffusive and transverse parts which act on a stochastic potential. The relative positions of stationary states in the stochastic global potential...
No one has proved that mathematically general stochastic dynamical systems have a special structure. Thus, we introduce a structure of a general stochastic dynamical system. According to scientific understanding, we assert that its deterministic part can be decomposed into three significant parts: the gradient of the potential function, friction ma...
Hall anomaly, as appears in the mixed-state Hall resistivity of type-II superconductors, has had numerous theories but yet a consensus on its origin. In this work, we conducted a quantitative analysis of the magnetotransport measurements on BSCCO thin films by Zhao et al. [Phys. Rev. Lett. 122, 247001 (2019)] and validate a previously proposed vaca...
The existence of a smooth Lyapunov function for any smooth planar dynamical system with one limit cycle is proved, which is based on a novel decomposition of the dynamical system from the perspective of mechanics and some definitions and known theorems. By considering the smooth simple closed curve in the complex plane corresponding to the limit cy...
Divergence is usually used to determine the dissipation of a dynamical system, but some researchers have noticed that it can lead to elusive contradictions. In this article, a criterion, dissipative power, beyond divergence for judging the dissipation of a system is presented, which is based on the knowledge of classical mechanics and a novel dynam...
Significance
Vortex or pattern formations are caused by nonlinear interactions within a complex system far from equilibrium. They cannot be well described by variational methods based on traditional potential functions. We aim to bridge the gap in this research. A previously developed stochastic decomposition on finite dimensions is extended to con...
DOI:https://doi.org/10.1103/PhysRevLett.124.249701
The classical development hierarchy of pancreatic cell fate commitments describes that multipotent progenitors (MPs) first bifurcate into tip cells and trunk cells, and then these cells give rise to acinar cells and endocrine/ductal cells separately. However, lineage tracings reveal that pancreatic progenitors are highly heterogeneous in tip and tr...
An amendment to this paper has been published and can be accessed via a link at the top of the paper.
We uncover a novel phenomenon from a recent artificial light-harvesting experiment [P.-Z. Chen et al., Angew. Chem., Int. Ed. Engl. 55, 2759 (2016)] on organic nanocrystals of self-assembled difluoroboron chromophores. A resonant confinement of a polariton under strong photon-exciton coupling is predicted to exist within the microcavity of the crys...
[This corrects the article DOI: 10.1098/rsos.190418.].
The production of secondary metabolites, while important for bioengineering purposes, presents a paradox in itself. Though widely existing in plants and bacteria, they have no definite physiological roles. Yet in both native habitats and laboratories, their production appears robust and follows apparent metabolic switches. We show in this work that...
Although the limit cycle have been studied for more than 100 years, the existence of its Lyapunov function is still poorly understood. By considering a common limit cycle system, a puzzle related to the existence of Lyapunov functions for Limit cycle system is proposed and studied in this paper: The divergence is not equal to zero, while the trajec...
The existence of Lyapunov function for the planar system with an arbitrary limit cycle is proved. Firstly, the generalized definition of Lyapunov function for fixed point and limit cycle are given, respectively. And they are logically consistent with the definition in dynamical systems textbooks. Secondly, combined with Schoenflies theorem, Riemann...
How tissue turnover occurs is a fundamental concern of treatment for various diseases. Here we focus on pancreatic beta-cell replacement, which is highly related with pathology and therapies of diabetes. Whether new pancreatic beta-cells arise via pre-existing beta-cells or differentiation of precursor cells has been a long debate. Recent experimen...
We show that in the recent artificial light-harvesting experiment [Angewandte Chemie Intl. Ed. 55, 2759 (2016)] on organic nanocrystals self-assembled from difluoroboron chromophores, the spontaneous emission of an excited pigment should undergo a two-step process. It would first decay to an excitonic polariton confined by cavity resonance via stro...
Quantifying the escape rate from a meta-stable state is essential to understand a wide range of dynamical processes. Kramers’ classical rate formula is the product of an exponential function of the potential barrier height and a pre-factor related to the friction coefficient. Although many applications of the rate formula focused on the exponential...
In light of ever apparent limitation of the current dominant cancer mutation theory, a quantitative hypothesis for cancer genesis and progression, endogenous molecular-cellular network hypothesis has been proposed from the systems biology perspective, now for more than 10 years. It was intended to include both the genetic and epigenetic causes to u...
An innovative theoretical framework for stochastic dynamics based on the decomposition of a stochastic differential equation (SDE) into a dissipative component, a detailed-balance-breaking component, and a dual-role potential landscape has been developed, which has fruitful applications in physics, engineering, chemistry, and biology. It introduces...
Quantifying stochastic processes is essential to understand many natural phenomena, particularly in biology, including cell-fate decision in developmental processes as well as genesis and progression of cancers. While various attempts have been made to construct potential landscape in high dimensional systems and to estimate rare transitions, they...
Colorectal cancer (CRC) has complex pathological features that defy the linearadditive reasoning prevailing in current biomedicine studies. In pursuing a mechanistic understanding behind such complexity, we constructed a core molecular-cellular interaction network underlying CRC and investigated its nonlinear dynamical properties. The hypothesis an...
We obtain stochastic dynamics from a system-plus-bath mechanism as an extension of the Caldeira-Leggett (CL) model in the classical regime. An effective magnetic field and response functions with both longitudinal and transverse parts are exactly generated from the bath of harmonic oscillators. The effective magnetic field and transverse response a...
A decade ago mainstream molecular biologists regarded it impossible or biologically ill-motivated to understand the dynamics of complex biological phenomena, such as cancer genesis and progression, from a network perspective. Indeed, there are numerical difficulties even for those who were determined to explore along this direction. Undeterred, sev...
Cancer is a complex disease: its pathology cannot be properly understood in terms of independent players-genes, proteins, molecular pathways, or their simple combinations. This is similar to many-body physics of a condensed phase that many important properties are not determined by a single atom or molecule. The rapidly accumulating large 'omics' d...
Polycyclic tetramate macrolactams (PTMs) were identified as distinct secondary metabolites of the mangrove-derived Streptomyces xiamenensis 318. Together with three known compounds—ikarugamycin (1), capsimycin (2) and capsimycin B (3)—two new compounds, capsimycin C (4) with trans-diols and capsimycin D (5) with trans-configurations at C-13/C-14, h...
Connections between a “SDE decomposition” to other frameworks constructing landscape in non-equilibrium processes were discussed by Zhou and Li [J. Chem. Phys. 144, 094109 (2016)]. It was speculated that the SDE decomposition would not be generally unique. In this comment, we demonstrate both mathematically and physically that the speculation is in...
By integrating four lines of thoughts: symmetry breaking originally advanced by Anderson, bifurcation from nonlinear dynamical systems, Landau’s phenomenological theory of phase transition, and the mechanism of emergent rare events first studied by Kramers, we introduce a possible framework for understanding mesoscopic dynamics that links (i) fast...
While the biochemistry of metabolism in many organisms is well studied, details of the metabolic dynamics are not fully explored yet. Acquiring adequate in vivo kinetic parameters experimentally has always been an obstacle. Unless the parameters of a vast number of enzyme-catalyzed reactions happened to fall into very special ranges, a kinetic mode...
We consider the nonlinear stochastic dynamics of dissipative Hamiltonian systems with state-dependent friction and diffusion connected by the fluctuation-dissipation relation in high dimensions. The system under study has a close connection to Ao’s framework in constructing a dynamical potential for non-equilibrium processes without detailed balanc...
Acute promyelocytic leukemia (APL) remains the best example of a malignancy that can be cured clinically by differentiation therapy. We demonstrate that APL may emerge from a dynamical endogenous molecular-cellular network obtained from normal, non-cancerous molecular interactions such as signal transduction and translational regulation under physi...
An innovative theoretical framework for stochastic dynamics based on a decomposition of a stochastic differential equation (SDE) has been developed with an evident advantage in connecting deterministic and stochastic dynamics, as well as useful applications in physics, engineering, chemistry and biology. It introduces the A-type stochastic integrat...
Cancers have been typically characterized by genetic mutations. Patterns of such mutations have traditionally been analysed by posteriori statistical association approaches. One may ponder the possibility of a priori determination of any mutation regularity. Here by exploring biological processes implied in a mechanistic theory recently developed (...
To develop and evaluate the long-term prophylactic treatment for chronic diseases such as osteoporosis requires a clear view of mechanism at the molecular and systems level. While molecular signaling pathway studies for osteoporosis are extensive, a unifying mechanism is missing. In this work, we provide experimental and systems-biology evidences t...
Streptomyces xiamenensis 318, a moderate halophile isolated from a mangrove sediment, produces the anti-fibrotic compound xiamenmycin. The whole genome sequence of strain 318 was obtained through long-read single-molecule real-time (SMRT) sequencing, high-throughput Illumina HiSeq and 454 pyrosequencing technologies. The assembled genome comprises...
We report that nontrivial topology of a driven Brownian particle restricted on a ring leads to anomalous behaviors on free energy change. Starting from steady states with identical distribution and current on the ring, free energy changes are distinct and nonperiodic after the system is driven by the same periodic force protocol. We demonstrate our...
Xiamenmycins, a series of prenylated benzopyran compounds with anti-fibrotic bioactivities, were isolated from a mangrove-derived Streptomyces xiamenensis. To fulfil the requirements of pharmaceutical investigations, a high production of xiamenmycin is needed. In this study,, the authors present a kinetic metabolic model to evaluate fluxes in an en...
Genetically identical cells exposed to homogeneous environment can show remarkable phenotypic difference. To predict how phenotype is shaped, understanding of how each factor contributes is required. During gene expression processes, noise could arise either intrinsically in biochemical processes of gene expression or extrinsically from other cellu...
Intratumor heterogeneity is a common phenomenon and impedes cancer therapy and research. Gastric cancer (GC) cells have generally been classified into two heterogeneous cellular phenotypes, the gastric and intestinal types, yet the mechanisms of maintaining two phenotypes and controlling phenotypic transition are largely unknown. A qualitative syst...
We explored endogenous molecular-cellular network hypothesis for prostate cancer by constructing relevant endogenous interaction network model and analyzing its dynamical properties. Molecular regulations involved in cell proliferation, apoptosis, differentiation and metabolism are included in a hierarchical mathematical modeling scheme. This dynam...
The inhomogeneity of multiplicative white noise leads to various coupling modes between deterministic and stochastic forces. We investigate the phase transition induced by the variation of the coupling mode through manipulating its characteristic parameter continuously. Even when the noise strength is fixed, an increase of this parameter can enhanc...
Adaptive landscape, proposed by Sewall Wright, has been used to find optimized solutions of a system. The optimized solution of an evolutionary system is when evolution maximizes or minimizes the value of some function of the trait under consideration, thus providing an absolute measure of fixation for a biological process in a probabilistic sense....
Bridging equilibrium and nonequilibrium statistical physics attracts
sustained interest. A hallmark of nonequilibrium system is a breakdown of
detailed balance. In addition, a priori potential function corresponding to the
Boltzmann-Gibbs distribution is typically absent. By decomposing the dynamics
into a dissipative part and a non-detailed balanc...
Alzheimer's disease (AD) is a severe neurodegenerative disorder without curative treatment. Extensive data on pathological molecular processes have been accumulated over the last years. These data combined allows a systems biology approach to identify key regulatory elements of AD and to establish a model descriptive of the disease process which ca...
Motivated by progress in theoretical biology a recent proposal on a general and quantitative dynamical framework for nonequilibrium processes and dynamics of complex systems is briefly reviewed. It is nothing but the evolutionary process discovered by Charles Darwin and Alfred Wallace. Such general and structured dynamics may be tentatively named “...
A quantitative hypothesis for cancer genesis and progression-the endogenous molecular-cellular network hypothesis, intended to include both genetic and epigenetic causes of cancer-has been proposed recently. Using this hypothesis, here we address the molecular basis for maintaining normal liver and hepatocellular carcinoma (HCC), and the potential...
Age-related bone loss and osteoporosis are associated with bone remodeling changes that are featured with decreased trabecular and periosteal bone formation relative to bone resorption. Current anticatabolic therapies focusing on the inhibition of bone resorption may not be sufficient in the prevention or reversal of age-related bone deterioration...
The presence of multiplicative noise can alter measurements of forces acting
on nanoscopic objects. Taking into account of multiplicative noise, we derive a
series of non-equilibrium thermodynamical equalities as generalization of the
Jarzynski equality, the Hatano-Sasa's relation and the detailed fluctuation
theorem. Our result demonstrates that t...
In a phage λ genetic switch model, bistable dynamical behavior can be destroyed due to the bifurcation caused by inappropriately chosen model parameters. Since the values of many parameters with biological
significance often cannot be accurately acquired, it is thus of fundamental importance to analyze how and to
which extent the system dynamics is...
Under the effect of strong genetic drift, it is highly probable to observe gene fixation or gene loss in a population, shown by singular peaks on a potential landscape. The genetic drift-induced noise gives rise to two-time-scale diffusion dynamics on the bipeaked landscape. We find that the logarithmically divergent (singular) peaks do not necessa...
We demonstrate that the conventional path integral formulations generate
inconsistent results exemplified by the geometric Brownian motion under the
general stochastic interpretation. We thus develop a novel path integral
formulation for the overdamped Langevin equation with the multiplicative noise.
The present path integral leads to the correspon...