A multi-scale modeling framework for individualized, spatiotemporal prediction of drug effects and toxicological risk

International audienceIn this study, we focus on a novel multi-scale modeling approach for spatiotemporal prediction of the distribution of substances and resulting hepatotoxicity by combining cellular models, a 2D liver model, and whole body model. As a case study, we focused on predicting human hepatotoxicity upon treatment with acetaminophen based on in vitro toxicity data and potential inter-individual variability in gene expression and enzyme activities. By aggregating mechanistic, genome-based in silico cells to a novel 2D liver model and eventually to a whole body model, we predicted pharmacokinetic properties, metabolism, and the onset of hepatotoxicity in an in silico patient. Depending on the concentration of acetaminophen in the liver and the accumulation of toxic metabolites, cell integrity in the liver as a function of space and time as well as changes in the elimination rate of substances were estimated. We show that the variations in elimination rates also influence the distribution of acetaminophen and its metabolites in the whole body. Our results are in agreement with experimental results. What is more, the integrated model also predicted variations in drug toxicity depending on alterations of metabolic enzyme activities. Variations in enzyme activity, in turn, reflect genetic characteristics or diseases of individuals. In conclusion, this framework presents an important basis for efficiently integrating inter-individual variability data into models, paving the way for personalized or stratified predictions of drug toxicity and efficacy

Can black holes be torn up by phantom dark energy in cyclic cosmology?

Infinitely cyclic cosmology is often frustrated by the black hole problem. It has been speculated that this obstacle in cyclic cosmology can be removed by taking into account a peculiar cyclic model derived from loop quantum cosmology or the braneworld scenario, in which phantom dark energy plays a crucial role. In this peculiar cyclic model, the mechanism of solving the black hole problem is through tearing up black holes by phantom. However, using the theory of fluid accretion onto black holes, we show in this paper that there exists another possibility: that black holes cannot be torn up by phantom in this cyclic model. We discussed this possibility and showed that the masses of black holes might first decrease and then increase, through phantom accretion onto black holes in the expanding stage of the cyclic universe.Comment: 6 pages, 2 figures; discussions adde

Horava-Lifshitz Dark Energy

We formulate Horava-Lifshitz cosmology with an additional scalar field that leads to an effective dark energy sector. We find that, due to the inherited features from the gravitational background, Horava-Lifshitz dark energy naturally presents very interesting behaviors, possessing a varying equation-of-state parameter, exhibiting phantom behavior and allowing for a realization of the phantom divide crossing. In addition, Horava-Lifshitz dark energy guarantees for a bounce at small scale factors and it may trigger the turnaround at large scale factors, leading naturally to cyclic cosmology.Comment: 17 pages, no figures, version published at EJP

Dissipative Future Universe without Big Rip

The present study deals with dissipative future universe without big rip in context of Eckart formalism. The generalized chaplygin gas, characterized by equation of state $p=-\frac{A}{\rho^\frac{1}{\alpha}}$, has been considered as a model for dark energy due to its dark-energy-like evolution at late time. It is demonstrated that, if the cosmic dark energy behaves like a fluid with equation of state $p=\omega\rho$; $\omega < -1$, as well as chaplygin gas simultaneously then the big rip problem does not arises and the scale factor is found to be regular for all time.Comment: 6 pages, 2 figures, To appear in Int. J. Theor. Phy

The Influence of Free Quintessence on Gravitational Frequency Shift and Deflection of Light with 4D momentum

Based on the 4D momentum, the influence of quintessence on the gravitational frequency shift and the deflection of light are examined in modified Schwarzschild space. We find that the frequency of photon depends on the state parameter of quintessence $w_q$: the frequency increases for $-1<w_q<-1/3$ and decreases for $-1/3<w_q<0$. Meanwhile, we adopt an integral power number $a$ ($a = 3\omega_q + 2$) to solve the orbital equation of photon. The photon's potentials become higher with the decrease of $\omega_q$. The behavior of bending light depends on the state parameter $\omega_q$ sensitively. In particular, for the case of $\omega_q = -1$, there is no influence on the deflection of light by quintessence. Else, according to the H-masers of GP-A redshift experiment and the long-baseline interferometry, the constraints on the quintessence field in Solar system are presented here.Comment: 12 pages, 2 figures, 4 tables. European Physical Journal C in pres

Gravitational Coupling and Dynamical Reduction of The Cosmological Constant

We introduce a dynamical model to reduce a large cosmological constant to a sufficiently small value. The basic ingredient in this model is a distinction which has been made between the two unit systems used in cosmology and particle physics. We have used a conformal invariant gravitational model to define a particular conformal frame in terms of large scale properties of the universe. It is then argued that the contributions of mass scales in particle physics to the vacuum energy density should be considered in a different conformal frame. In this manner, a decaying mechanism is presented in which the conformal factor appears as a dynamical field and plays a key role to relax a large effective cosmological constant. Moreover, we argue that this model also provides a possible explanation for the coincidence problem.Comment: To appear in GR

Unifying phantom inflation with late-time acceleration: scalar phantom-non-phantom transition model and generalized holographic dark energy

The unifying approach to early-time and late-time universe based on phantom cosmology is proposed. We consider gravity-scalar system which contains usual potential and scalar coupling function in front of kinetic term. As a result, the possibility of phantom-non-phantom transition appears in such a way that universe could have effectively phantom equation of state at early time as well as at late time. In fact, the oscillating universe may have several phantom and non-phantom phases. As a second model we suggest generalized holographic dark energy where infrared cutoff is identified with combination of FRW parameters: Hubble constant, particle and future horizons, cosmological constant and universe life-time (if finite). Depending on the specific choice of the model the number of interesting effects occur: the possibility to solve the coincidence problem, crossing of phantom divide and unification of early-time inflationary and late-time accelerating phantom universe. The bound for holographic entropy which decreases in phantom era is also discussed.Comment: 13 pages, clarifications/refs added, to match with published versio

Interacting Generalised Cosmic Chaplygin gas in Loop quantum cosmology: A singularity free universe

In this work we investigate the background dynamics when dark energy is coupled to dark matter with a suitable interaction in the universe described by Loop quantum cosmology. Dark energy in the form of Generalised Cosmic Chaplygin gas is considered. A suitable interaction between dark energy and dark matter is taken into account in order to at least alleviate (if not solve) the cosmic coincidence problem. The dynamical system of equations is solved numerically and a stable scaling solution is obtained. A significant attempt towards the solution of the cosmic coincidence problem is taken. The statefinder parameters are also calculated to classify the dark energy model. Graphs and phase diagrams are drawn to study the variations of these parameters. It is seen that the background dynamics of Generalised Cosmic Chaplygin gas is completely consistent with the notion of an accelerated expansion in the late universe. From the graphs, generalised cosmic Chaplygin gas is identified as a dark fluid with a lesser negative pressure compared to Modified Chaplygin gas, thus supporting a 'No Big Rip' cosmology. It has also been shown that in this model the universe follows the power law form of expansion around the critical point, which is consistent with the known results. Future singularities that may be formed in this model as an ultimate fate of the universe has been studied in detail. It was found that the model is completely free from any types of future singularities.Comment: 10 pages, 10 figures. arXiv admin note: text overlap with arXiv:1109.1481, arXiv:1102.275

On Isotropic Turbulence in the Dark Fluid Universe

As first part of this work, experimental information about the decay of isotropic turbulence in ordinary hydrodynamics, u^2(t) proportional to t^{-6/5}, is used as input in FRW equations in order to investigate how an initial fraction f of turbulent kinetic energy in the cosmic fluid influences the cosmological development in the late, quintessence/phantom, universe. First order perturbative theory to the first order in f is employed. It turns out that both in the Hubble factor, and in the energy density, the influence from the turbulence fades away at late times. The divergences in these quantities near the Big Rip behave essentially as in a non-turbulent fluid. However, for the scale factor, the turbulence modification turns out to diverge logarithmically. As second part of our work, we consider the full FRW equation in which the turbulent part of the dark energy is accounted for by a separate term. It is demonstrated that turbulence occurrence may change the future universe evolution due to dissipation of dark energy. For instance, phantom-dominated universe becomes asymptotically a de Sitter one in the future, thus avoiding the Big Rip singularity.Comment: 10 pages, no figures, significant revision. Matches published versio

Holographic Dark Energy Model and Scalar-Tensor Theories

We study the holographic dark energy model in a generalized scalar tensor theory. In a universe filled with cold dark matter and dark energy, the effect of potential of the scalar field is investigated in the equation of state parameter. We show that for a various types of potentials, the equation of state parameter is negative and transition from deceleration to acceleration expansion of the universe is possible.Comment: 11 pages, no figure. To appear in General Relativity and Gravitatio