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Carmen Molina-Paris

Publications and source records attributed to Carmen Molina-Paris.

At least 19 recordsLinked to original sources

Mechanistic mathematical model of the in vitro infection dynamics of Bunyamwera and Batai viruses including MOI-dependent shortening of the eclipse phase

We develop a deterministic mathematical model to quantify the distinct in vitro infection dynamics of Bunyamwera virus (BUNV) and Batai virus (BATV) in A549 cells, incorporating cell division and natural death, continued entry of virions into already-infected cells, and shortening of the eclipse phase driven by re-infection. The model parameters were estimated making use of viral decay data, growth curves at two different inoculum concentrations, and extra-cellular genome copy measurements (for BUNV) via Markov chain Monte Carlo. Genome copy measurements were essential for constraining estimates of the number of cells that can become infected per unit of infectious virus for BUNV. We found that BUNV exhibited substantially longer eclipse and infectious periods than BATV, while BATV showed a higher per-cell virus production rate. Re-infection was predicted to shorten the eclipse phase for both viruses, but the effect was markedly stronger for BUNV. Together, these results provide a quantitative comparison of the in vitro viral kinetics of BUNV and BATV and reveal substantial differences in their replication dynamics.

q-bio.QM↗

Quantification of Ebola virus replication kinetics in vitro

Mathematical modelling has successfully been used to provide quantitative descriptions of many viral infections, but for the Ebola virus, which requires biosafety level 4 facilities for experimentation, modelling can play a crucial role. Ebola modelling efforts have primarily focused on in vivo virus kinetics, e.g., in animal models, to aid the development of antivirals and vaccines. But, thus far, these studies have not yielded a detailed specification of the infection cycle, which could provide a foundational description of the virus kinetics and thus a deeper understanding of their clinical manifestation. Here, we obtain a diverse experimental data set of the Ebola infection in vitro, and then make use of Bayesian inference methods to fully identify parameters in a mathematical model of the infection. Our results provide insights into the distribution of time an infected cell spends in the eclipse phase (the period between infection and the start of virus production), as well as the rate at which infectious virions lose infectivity. We suggest how these results can be used in future models to describe co-infection with defective interfering particles, which are an emerging alternative therapeutic.

q-bio.CB↗

Stochastic models of the binding kinetics of VEGF-A to VEGFR1 and VEGFR2 in endothelial cells

Vascular endothelial growth factor receptors (VEGFRs) are receptor tyrosine kinases (RTKs) that regulate proliferation, migration, angiogenesis and vascular permeability of endothelial cells. VEGFR1 and VEGFR2 bind vascular endothelial growth factors (VEGFs), inducing receptor dimerisation and activation, characterised by phosphorylation of tyrosine residues in their cytoplasmic domain. Although experimental evidence suggests that RTK signalling occurs both on the plasma membrane and intra-cellularly, and reveals the role of endocytosis in RTK signal transduction, we still lack knowledge of VEGFR phosphorylation-site use and of the spatiotemporal regulation of VEGFR signalling. In this paper, we introduce four stochastic mathematical models to study the binding kinetics of vascular endothelial growth factor VEGF-A to VEGFR1 and VEGFR2, and phosphorylation. The formation of phosphorylated dimers on the cell surface is a two-step process: diffusive transport and binding. The first two of our models only consider VEGFR2, which allows us to introduce new stochastic descriptors making use of a matrix-analytic approach. The two remaining models describe the competition of VEGFR1 and VEGFR2 for ligand availability, and are analysed making use of Gillespie simulations and the van Kampen approximation. Under the hypothesis that bound phosphorylated receptor dimers are the signalling units, we study the time to reach a threshold number of such complexes. Our results indicate that the presence of VEGFR1 does not only affect the timescale to reach a given signalling threshold, but it also affects the maximum attainable threshold. This result is consistent with the conjectured role of VEGFR1 as a decoy receptor, that prevents VEGF-A binding to VEGFR2, and thus, VEGFR2 attaining suitable phosphorylation levels. We identify an optimum range of ligand concentration for sustained dimer phosphorylation.

q-bio.BM↗

Breakdown of the semiclassical approximation during the early stages of preheating

The validity of the semiclassical approximation is investigated during the preheating phase in models of chaotic inflation using a modification of a criterion previously proposed for semiclassical gravity. If the modified criterion is violated then fluctuations of the two-point function for the quantum fields are large and the semiclassical approximation is not valid. Evidence is provided that the semiclassical approximation breaks down during the early stages of preheating, well before either scattering effects or backreaction effects are important.

gr-qc↗

Validity of the semiclassical approximation during the preheating phase of chaotic inflation

The semiclassical approximation has frequently been used to describe the initial stage of particle production, often called preheating, which occurs after the inflationary epoch in chaotic models of inflation. During this phase backreaction effects from the produced particles on the inflaton field are significant, and one might be concerned about the validity of the semiclassical approximation, even though large backreaction effects are allowed if the inflaton field is coupled to a large number of quantum fields. A criterion is presented for the validity of the semiclassical approximation in this case and the question of whether this criterion is satisfied during preheating is addressed.

gr-qc↗

Acoustic geometry for general relativistic barotropic irrotational fluid flow

"Acoustic spacetimes", in which techniques of differential geometry are used to investigate sound propagation in moving fluids, have attracted considerable attention over the last few decades. Most of the models currently considered in the literature are based on non-relativistic barotropic irrotational fluids, defined in a flat Newtonian background. The extension, first to special relativistic barotropic fluid flow, and then to general relativistic barotropic fluid flow in an arbitrary background, is less straightforward than it might at first appear. In this article we provide a pedagogical and simple derivation of the general relativistic "acoustic spacetime" in an arbitrary (d+1) dimensional curved-space background.

gr-qc↗

Cosmological Horizon Modes and Linear Response in de Sitter Spacetime

Linearized fluctuations of quantized matter fields and the spacetime geometry around de Sitter space are considered in the case that the matter fields are conformally invariant. Taking the unperturbed state of the matter to be the de Sitter invariant Bunch-Davies state, the linear variation of the stress tensor about its self-consistent mean value serves as a source for fluctuations in the geometry through the semi-classical Einstein equations. This linear response framework is used to investigate both the importance of quantum backreaction and the validity of the semi-classical approximation in cosmology. The full variation of the stress tensor, delta T^a_b contains two kinds of terms: (1) those that depend explicitly upon the linearized metric variation delta g_{cd} through the [T^a_b, T^{cd}] causal response function; and (2) state dependent variations, independent of delta g_{cd}. For perturbations of the first kind, the criterion for the validity of the semi-classical approximation in de Sitter space is satisfied for fluctuations on all scales well below the Planck scale. The perturbations of the second kind contain additional massless scalar degrees of freedom associated with changes of state of the fields on the cosmological horizon scale. These scalar degrees of freedom arise necessarily from the local auxiliary field form of the effective action associated with the trace anomaly, are potentially large on the horizon scale, and therefore can lead to substantial non-linear quantum backreaction effects in cosmology.

gr-qc↗

Study of the preheating phase of chaotic inflation

Particle production and its effects on the inflaton field are investigated during the preheating phase of chaotic inflation using a model consisting of a massive scalar inflaton field coupled to N massless quantum scalar fields. The effects of spacetime curvature and interactions between the quantum fields are ignored. A large N expansion is used to obtain a coupled set of equations including a backreaction equation for the classical inflaton field. Previous studies of preheating using these equations have been done. Here the first numerical solutions to the full set of equations are obtained for various values of the coupling constant and the initial amplitude of the inflaton field. States are chosen so that initially the backreaction effects on the inflaton field are small and the mode equations for the quantum fields take the form of Mathieu equations. Potential problems relating to the parametric amplification of certain modes of the quantum fields are identified and resolved. A detailed study of the damping of the inflaton field is undertaken. Some predictions of previous studies are verified and some new results are obtained.

hep-ph↗

Short distance and initial state effects in inflation: stress tensor and decoherence

We present a consistent low energy effective field theory framework for parameterizing the effects of novel short distance physics in inflation, and their possible observational signatures in the Cosmic Microwave Background. We consider the class of general homogeneous, isotropic initial states for quantum scalar fields in Robertson-Walker (RW) spacetimes, subject to the requirement that their ultraviolet behavior be consistent with renormalizability of the covariantly conserved stress tensor which couples to gravity. In the functional Schrödinger picture such states are coherent, squeezed, mixed states characterized by a Gaussian density matrix. This Gaussian has parameters which approach those of the adiabatic vacuum at large wave number, and evolve in time according to an effective classical Hamiltonian. The one complex parameter family of $α$ squeezed states in de Sitter spacetime does not fall into this UV allowed class, except for the special value of the parameter corresponding to the Bunch-Davies state. We determine the finite contributions to the inflationary power spectrum and stress tensor expectation value of general UV allowed adiabatic states, and obtain quantitative limits on the observability and backreaction effects of some recently proposed models of short distance modifications of the initial state of inflation. For all UV allowed states, the second order adiabatic basis provides a good description of particles created in the expanding RW universe. Due to the absence of particle creation for the massless, minimally coupled scalar field in de Sitter space, there is no phase decoherence in the simplest free field inflationary models. We apply adiabatic regularization to the renormalization of the decoherence functional in cosmology to corroborate this result.

hep-th↗

Tumor growth instability and the onset of invasion

Motivated by experimental observations, we develop a mathematical model of chemotactically directed tumor growth. We present an analytical study of the model as well as a numerical one. The mathematical analysis shows that: (i) tumor cell proliferation by itself cannot generate the invasive branching behaviour observed experimentally, (ii) heterotype chemotaxis provides an instability mechanism that leads to the onset of tumor invasion and (iii) homotype chemotaxis does not provide such an instability mechanism but enhances the mean speed of the tumor surface. The numerical results not only support the assumptions needed to perform the mathematical analysis but they also provide evidence of (i), (ii) and (iii). Finally, both the analytical study and the numerical work agree with the experimental phenomena.

physics.bio-ph↗

Characterizing Inflationary Perturbations: The Uniform Approximation

The spectrum of primordial fluctuations from inflation can be obtained using a mathematically controlled, and systematically extendable, uniform approximation. Closed-form expressions for power spectra and spectral indices may be found without making explicit slow-roll assumptions. Here we provide details of our previous calculations, extend the results beyond leading order in the approximation, and derive general error bounds for power spectra and spectral indices. Already at next-to-leading order, the errors in calculating the power spectrum are less than a per cent. This meets the accuracy requirement for interpreting next-generation CMB observations.

astro-ph↗

Large Scale Features of Rotating Forced Turbulence

Large scale features of a randomly isotropically forced incompressible and unbounded rotating fluid are examined in perturbation theory. At first order in both the random force amplitude and the angular velocity we find two types of modifications to the fluid equation of motion. The first correction transforms the molecular shear viscosity into a (rotation independent) effective viscosity. The second perturbative correction leads to a new large scale non-dissipative force proportional to the fluid angular velocity in the slow rotation regime. This effective force does no net work and alters the dispersion relation of inertial waves propagating in the fluid. Both dynamically generated corrections can be identified with certain components of the most general axisymmetric ``viscosity tensor'' for a Newtonian fluid.

physics.flu-dyn↗

Linear Response, Validity of Semi-Classical Gravity, and the Stability of Flat Space

A quantitative test for the validity of the semi-classical approximation in gravity is given. The criterion proposed is that solutions to the semi-classical Einstein equations should be stable to linearized perturbations, in the sense that no gauge invariant perturbation should become unbounded in time. A self-consistent linear response analysis of these perturbations, based upon an invariant effective action principle, necessarily involves metric fluctuations about the mean semi-classical geometry, and brings in the two-point correlation function of the quantum energy-momentum tensor in a natural way. This linear response equation contains no state dependent divergences and requires no new renormalization counterterms beyond those required in the leading order semi-classical approximation. The general linear response criterion is applied to the specific example of a scalar field with arbitrary mass and curvature coupling in the vacuum state of Minkowski spacetime. The spectral representation of the vacuum polarization function is computed in n dimensional Minkowski spacetime, and used to show that the flat space solution to the semi-classical Einstein equations for n=4 is stable to all perturbations on distance scales much larger than the Planck length.

gr-qc↗

The Inflationary Perturbation Spectrum

Motivated by the prospect of testing inflation from precision cosmic microwave background observations, we present analytic results for scalar and tensor perturbations in single-field inflation models based on the application of uniform approximations. This technique is systematically improvable, possesses controlled error bounds, and does not rely on assuming the slow-roll parameters to be constant. We provide closed-form expressions for the power spectra and the corresponding scalar and tensor spectral indices.

astro-ph↗

Linear Response and the Validity of the Semi-Classical Approximation in Gravity

We propose a quantitative test for the validity of the semi-classical approximation in gravity, namely that the solutions to the semi-classical equations should be stable to linearized perturbations, in the sense that no gauge invariant perturbation should become unbounded in time. We show that a self-consistent linear response analysis of these perturbations based upon an invariant effective action principle involves metric fluctuations about the mean semi-classical geometry and brings in the two-point correlation function of the quantum energy-momentum tensor in a natural way. The properties of this correlation function are discussed and it is shown on general grounds that it contains no state-dependent divergences and requires no new renormalization counterterms beyond those required in the leading order semi-classical approximation.

gr-qc↗

Effective potential for classical field theories subject to stochastic noise

Classical field theories coupled to stochastic noise provide an extremely powerful tool for modeling phenomena as diverse as turbulence, pattern-formation, and the structural development of the universe itself. In this Letter we sketch a general formalism that maps such systems into a field theory language, and demonstrate how to extract the one-loop physics for an arbitrary classical field theory coupled to Gaussian noise. The amplitude of the noise two-point function serves as the loop-counting parameter and is the analog of Planck's constant hbar in quantum field theory. We define the effective action and the effective potential, and derive a general formula for the one-loop effective potential of a classical field theory coupled to translation-invariant Gaussian noise.

cond-mat.stat-mech↗

Small-scale properties of the KPZ equation and dynamical symmetry breaking

A functional integral technique is used to study the ultraviolet or short distance properties of the Kardar-Parisi-Zhang (KPZ) equation with white Gaussian noise. We apply this technique to calculate the one-loop effective potential for the KPZ equation. The effective potential is (at least) one-loop ultraviolet renormalizable in 1, 2, and 3 space dimensions, but non-renormalizable in 4 or higher space dimensions. This potential is intimately related to the probability distribution function (PDF) for the spacetime averaged field. For the restricted class of field configurations considered here, the KPZ equation exhibits dynamical symmetry breaking (DSB) via an analog of the Coleman-Weinberg mechanism in 1 and 2 space dimensions, but not in 3 space dimensions.

cond-mat.stat-mech↗

One-loop graviton corrections to Maxwell's equations

We compute the graviton induced corrections to Maxwell's equations in the one-loop and weak field approximations. The corrected equations are analogous to the classical equations in anisotropic and inhomogeneous media. We analyze in particular the corrections to the dispersion relations. When the wavelength of the electromagnetic field is much smaller than a typical length scale of the graviton two-point function, the speed of light depends on the direction of propagation and on the polarisation of the radiation. In the opposite case, the speed of light may also depend on the energy of the electromagnetic radiation. We study in detail wave propagation in two special backgrounds, flat Robertson-Walker and static, spherically symmetric spacetimes. In the case of a flat Robertson-Walker gravitational background we find that the corrected electromagnetic field equations correspond to an isotropic medium with a time-dependent effective refractive index. For a static, spherically symmetric background the graviton fluctuations induce a vacuum structure which causes birefringence in the propagation of light.

hep-th↗