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Gabriel F. Calvo

Publications and source records attributed to Gabriel F. Calvo.

15 recordsLinked to original sources

Modelling the role of flux density and coating on nanoparticle internalization by tumor cells under centrifugation

Nanoparticle (NP)-based applications are becoming increasingly important in the biomedical field. However, understanding the interactions of NPs with biofluids and cells is a major issue in order to develop novel approaches aimed at boosting their internalization and, therefore, their translation into the clinic. To this end, we put forward a transport mathematical model to describe the spatio-temporal dynamics of iron oxide NPs and their interaction with cells under moderate centrifugation. Our numerical simulations allowed us to quantify the relevance of the flux density as one of the unavoidable key features driving NPs interaction with the media as well as for cell internalization processes. These findings will help to increase the efficiency of cell labelling for biomedical applications.

q-bio.QM

Modelling the effect of vascular status on tumour evolution and outcome after thermal therapy

Microscale oxygenation plays a prominent role in tumour progression. Spatiotemporal variability of oxygen distribution in the tumour microenvironment contributes to cellular heterogeneity and to the emergence of normoxic and hypoxic populations. Local levels of oxygen strongly affect the response of tumours to the administration of different therapeutic modalities and, more generally, to the phenomenon of resistance to treatments. Several interventions have been proposed to improve tumour oxygenation, being the elevation of the local temperature (hyperthermia) an important one. While other factors such as the metabolic activity have to be considered, the proficiency of the tumour vascular system is a key factor both for the tissue oxygenation and for its temperature maps. Consequently, the interplay of these factors has attracted considerable attention from the mathematical modelling perspective. Here we put forward a transport-based system of partial differential equations aimed at describing the dynamics of healthy and tumour cell subpopulations at the microscale in a region placed between two blood vessels. By using this model with diverse flow conditions, we analyse the oxygen and temperature profiles that arise in different scenarios of vascular status, both during free progression and under thermal therapy. We find that low oxygen levels are associated to elevations of temperature in locations preferentially populated by hypoxic cells, and hyperthermia-induced cell death, being strongly dependent on blood flow, would only appear under highly disrupted conditions of the local vasculature. This results in a noticeable effect of heat on hypoxic cells. Additionally, when pronounced cell death occurs, it is followed by a significant increase in the oxygen levels.

q-bio.TO

Universal scaling laws rule explosive growth inhuman cancers

Most physical and other natural systems are complex entities composed of a large number of interacting individual elements. It is a surprising fact that they often obey the so-called scaling laws relating an observable quantity with a measure of the size of the system. Here we describe the discovery of universal superlinear metabolic scaling laws in human cancers. This dependence underpins increasing tumour aggressiveness, due to evolutionary dynamics, which leads to an explosive growth as the disease progresses. We validated this dynamic using longitudinal volumetric data of different histologies from large cohorts of cancer patients. To explain our observations we put forward increasingly complex biologically-inspired mathematical models that captured the key processes governing tumor growth. Our models predicted that the emergence of superlinear allometric scaling laws is an inherently three-dimensional phenomenon. Moreover, the scaling laws thereby identified allowed us to define a set of metabolic metrics with prognostic value, thus providing added clinical utility to the base findings.

q-bio.TO

CAR T cell therapy in B-cell acute lymphoblastic leukaemia: Insights from mathematical models

Immunotherapies use components of the patient immune system to selectively target cancer cells. The use of CAR T cells to treat B-cell malignancies --leukaemias and lymphomas-- is one of the most successful examples, with many patients experiencing long-lasting complete responses to this therapy. This treatment works by extracting the patient's T cells and adding them the CAR group, which enables them to recognize and target cells carrying the antigen CD19+, that is expressed in these haematological tumors. Here we put forward a mathematical model describing the time response of leukaemias to the injection of CAR T-cells. The model accounts for mature and progenitor B-cells, tumor cells, CAR T cells and side effects by incorporating the main biological processes involved. The model explains the early post-injection dynamics of the different compartments and the fact that the number of CAR T cells injected does not critically affect the treatment outcome. An explicit formula is found that provides the maximum CAR T cell expansion in-vivo and the severity of side effects. Our mathematical model captures other known features of the response to this immunotherapy. It also predicts that CD19+ tumor relapses could be the result of the competition between tumor and CAR T cells analogous to predator-prey dynamics. We discuss this fact on the light of available evidences and the possibility of controlling relapses by early re-challenging of the tumor with stored CAR T cells.

q-bio.TO

Combined therapies of antithrombotics and antioxidants delay in silico brain tumor progression

Glioblastoma multiforme, the most frequent type of primary brain tumor, is a rapidly evolving and spatially heterogeneous high-grade astrocytoma that presents areas of necrosis, hypercellularity and microvascular hyperplasia. The aberrant vasculature leads to hypoxic areas and results in an increase of the oxidative stress selecting for more invasive tumor cell phenotypes. In our study we assay in silico different therapeutic approaches which combine antithrombotics, antioxidants and standard radiotherapy. To do so, we have developed a biocomputational model of glioblastoma multiforme that incorporates the spatio-temporal interplay among two glioma cell phenotypes corresponding to oxygenated and hypoxic cells, a necrotic core and the local vasculature whose response evolves with tumor progression. Our numerical simulations predict that suitable combinations of antithrombotics and antioxidants may diminish, in a synergetic way, oxidative stress and the subsequent hypoxic response. This novel therapeutical strategy, with potentially low or no toxicity, might reduce tumor invasion and further sensitize glioblastoma multiforme to conventional radiotherapy or other cytotoxic agents, hopefully increasing median patient overall survival time.

q-bio.QM

Effective Particle Methods for Fisher-Kolmogorov Equations: Theory and Applications to Brain Tumor Dynamics

Extended systems governed by partial differential equations can, under suitable conditions, be approximated by means of sets of ordinary differential equations for global quantities capturing the essential features of the systems dynamics. Here we obtain a small number of effective equations describing the dynamics of single-front and localized solutions of Fisher-Kolmogorov type equations. These solutions are parametrized by means of a minimal set of time-dependent quantities for which ordinary differential equations ruling their dynamics are found. A comparison of the finite dimensional equations and the dynamics of the full partial differential equation is made showing a very good quantitative agreement with the dynamics of the partial differential equation. We also discuss some implications of our findings for the understanding of the growth progression of certain types of primary brain tumors and discuss possible extensions of our results to related equations arising in different modelling scenarios.

q-bio.QM

Hypoxic Cell Waves around Necrotic Cores in Glioblastoma: A Biomathematical Model and its Therapeutic Implications

Glioblastoma is a rapidly evolving high-grade astrocytoma that is distinguished pathologically from lower grade gliomas by the presence of necrosis and microvascular hiperplasia. Necrotic areas are typically surrounded by hypercellular regions known as "pseudopalisades" originated by local tumor vessel occlusions that induce collective cellular migration events. This leads to the formation of waves of tumor cells actively migrating away from central hypoxia. We present a mathematical model that incorporates the interplay among two tumor cell phenotypes, a necrotic core and the oxygen distribution. Our simulations reveal the formation of a traveling wave of tumor cells that reproduces the observed histologic patterns of pseudopalisades. Additional simulations of the model equations show that preventing the collapse of tumor microvessels leads to slower glioma invasion, a fact that might be exploited for therapeutic purposes.

q-bio.QM

A Quantum-mechanical Approach for Constrained Macromolecular Chains

Many approaches to three-dimensional constrained macromolecular chains at thermal equilibrium, at about room temperatures, are based upon constrained Classical Hamiltonian Dynamics (cCHDa). Quantum-mechanical approaches (QMa) have also been treated by different researchers for decades. QMa address a fundamental issue (constraints versus the uncertainty principle) and are versatile: they also yield classical descriptions (which may not coincide with those from cCHDa, although they may agree for certain relevant quantities). Open issues include whether QMa have enough practical consequences which differ from and/or improve those from cCHDa. We shall treat cCHDa briefly and deal with QMa, by outlining old approaches and focusing on recent ones.

cond-mat.soft

Spin and Orbital angular momentum propagation in anisotropic media: theory

This paper is devoted to study the propagation of light beams carrying orbital angular momentum in optically anisotropic media. We first review some properties of homogeneous anisotropic media, and describe how the paraxial formalism is modified in order to proceed with a new approach dealing with a general setting of paraxial propagation along uniaxial inhomogeneous media. This approach is suitable for describing the space-variant-optical-axis phase plates.

physics.optics

Bright Solitary Waves in Malignant Gliomas

We put forward a nonlinear wave model describing the fundamental physio-pathologic features of an aggressive type of brain tumors: glioblastomas. Our model accounts for the invasion of normal tissue by a proliferating and propagating rim of active glioma cancer cells in the tumor boundary and the subsequent formation of a necrotic core. By resorting to numerical simulations, phase space analysis and exact solutions, we prove that bright solitary tumor waves develop in such systems.

nlin.PS

Transferring orbital and spin angular momenta of light to atoms

Light beams carrying orbital angular momentum, such as Laguerre-Gaussian beams, give rise to the violation of the standard dipolar selection rules during the interaction with matter yielding, in general, an exchange of angular momentum larger than hbar per absorbed photon. By means of ab initio 3D numerical simulations, we investigate in detail the interaction of a hydrogen atom with intense Gaussian and Laguerre-Gaussian light pulses. We analyze the dependence of the angular momentum exchange with the polarization, the orbital angular momentum, and the carrier-envelope phase of light, as well as with the relative position between the atom and the light vortex. In addition, a quantum-trajectory approach based on the de Broglie-Bohm formulation of quantum mechanics is used to gain physical insight into the absorption of angular momentum by the hydrogen atom.

quant-ph

Measuring the Complete Transverse Spatial Mode Spectrum of a Wave Field

We put forward a method that allows the experimental determination of the entire spatial mode spectrum of any arbitrary monochromatic wave field in a plane normal to its propagation direction. For coherent optical fields, our spatial spectrum analyzer can be implemented with a small number of benchmark refractive elements embedded in a single Mach-Zehnder interferometer. We detail an efficient setup for measuring in the Hermite-Gaussian mode basis. Our scheme should also be feasible in the context of atom optics for analyzing the spatial profiles of macroscopic matter waves.

quant-ph

Exact Bright and Dark Spatial Soliton Solutions in Saturable Nonlinear Media

We present exact analytical bright and dark (black and grey) solitary wave solutions of a nonlinear Schrodinger-type equation describing the propagation of spatial beams in media exhibiting a saturable nonlinearity (such as centrosymmetric photorefractive materials). A qualitative study of the stationary equation is carried out together with a discussion of the stability of the solutions.

nlin.SI

Manipulation of single-photon states encoded in transverse spatial modes: possible and impossible tasks

Controlled generation and manipulation of photon states encoded in their spatial degrees of freedom is a crucial ingredient in many quantum information tasks exploiting higher-than-two dimensional encoding. Here, we prove the impossibility to arbitrarily modify $d$-level state superpositions (qu$d$its) for $d>2$, encoded in the transverse modes of light, with optical components associated to the group of symplectic transforms (Gaussian operations). Surprisingly, we also provide an explicit construction of how non-Gaussian operations acting on mode subspaces do enable to overcome the limit $d=2$. In addition, this set of operations realizes the full SU(3) algebra.

quant-ph

Spin-induced angular momentum switching

When light is transmitted through optically inhomogeneous and anisotropic media the spatial distribution of light can be modified according to its input polarization state. A complete analysis of this process, based on the paraxial approximation, is presented, and we show how it can be exploited to produce a spin-controlled-change in the orbital angular momentum of light beams propagating in patterned space-variant-optical-axis phase plates. We also unveil a new effect. The development of a strong modulation in the angular momentum change upon variation of the optical path through the phase plates.

quant-ph