Cancer therapeutic potential of combinatorial immuno- and vaso-modulatory interventions

Currently, most of the basic mechanisms governing tumor-immune system interactions, in combination with modulations of tumor-associated vasculature, are far from being completely understood. Here, we propose a mathematical model of vascularized tumor growth, where the main novelty is the modeling of the interplay between functional tumor vasculature and effector cell recruitment dynamics. Parameters are calibrated on the basis of different in vivo immunocompromised Rag1-/- and wild-type (WT) BALB/c murine tumor growth experiments. The model analysis supports that tumor vasculature normalization can be a plausible and effective strategy to treat cancer when combined with appropriate immuno-stimulations. We find that improved levels of functional tumor vasculature, potentially mediated by normalization or stress alleviation strategies, can provide beneficial outcomes in terms of tumor burden reduction and growth control. Normalization of tumor blood vessels opens a therapeutic window of opportunity to augment the antitumor immune responses, as well as to reduce the intratumoral immunosuppression and induced-hypoxia due to vascular abnormalities. The potential success of normalizing tumor-associated vasculature closely depends on the effector cell recruitment dynamics and tumor sizes. Furthermore, an arbitrary increase of initial effector cell concentration does not necessarily imply a better tumor control. We evidence the existence of an optimal concentration range of effector cells for tumor shrinkage. Based on these findings, we suggest a theory-driven therapeutic proposal that optimally combines immuno- and vaso-modulatory interventions

Resonating bipolarons

Electrons coupled to local lattice deformations end up in selftrapped localized molecular states involving their binding into bipolarons when the coupling is stronger than a certain critical value. Below that value they exist as essentially itinerant electrons. We propose that the abrupt crossover between the two regimes can be described by resonant pairing similar to the Feshbach resonance in binary atomic collision processes. Given the intrinsically local nature of the exchange of pairs of itinerant electrons and localized bipolarons, we demonstrate the occurrence of such a resonance on a finite-size cluster made out of metallic atoms surrounding a polaronic ligand center.Comment: 7 pages, 4 figures, to be published in Europhysics Letter

Water vapor emission from IRC+10216 and other carbon-rich stars: model predictions and prospects for multitransition observations

We have modeled the emission of H2O rotational lines from the extreme C-rich star IRC+10216. Our treatment of the excitation of H2O emissions takes into account the excitation of H2O both through collisions, and through the pumping of the nu2 and nu3 vibrational states by dust emission and subsequent decay to the ground state. Regardless of the spatial distribution of the water molecules, the H2O 1_{10}-1_{01} line at 557 GHz observed by the Submillimeter Wave Astronomy Satellite (SWAS) is found to be pumped primarily through the absorption of dust-emitted photons at 6 $\mu$m in the nu2 band. As noted by previous authors, the inclusion of radiative pumping lowers the ortho-H2O abundance required to account for the 557 GHz emission, which is found to be (0.5-1)x10^{-7} if the presence of H2O is a consequence of vaporization of orbiting comets or Fischer-Tropsch catalysis. Predictions for other submillimeter H2O lines that can be observed by the Herschel Space Observatory (HSO) are reported. Multitransition HSO observations promise to reveal the spatial distribution of the circumstellar water vapor, discriminating among the several hypotheses that have been proposed for the origin of the H2O vapor in the envelope of IRC+10216. We also show that, for observations with HSO, the H2O 1_{10}-1_{01} 557 GHz line affords the greatest sensitivity in searching for H2O in other C-rich AGB stars.Comment: 35 pages, 12 figures, to be published in The Astrophysical Journa

High-excitation OH and H_2O lines in Markarian 231: the molecular signatures of compact far-infrared continuum sources

The ISO/LWS far-infrared spectrum of the ultraluminous galaxy Mkn 231 shows OH and H_2O lines in absorption from energy levels up to 300 K above the ground state, and emission in the [O I] 63 micron and [C II] 158 micron lines. Our analysis shows that OH and H_2O are radiatively pumped by the far-infrared continuum emission of the galaxy. The absorptions in the high-excitation lines require high far-infrared radiation densities, allowing us to constrain the properties of the underlying continuum source. The bulk of the far-infrared continuum arises from a warm (T_dust=70-100 K), optically thick (tau_100micron=1-2) medium of effective diameter 200-400 pc. In our best-fit model of total luminosity L_IR, the observed OH and H2O high-lying lines arise from a luminous (L/L_IR~0.56) region with radius ~100 pc. The high surface brightness of this component suggests that its infrared emission is dominated by the AGN. The derived column densities N(OH)>~10^{17} cm^{-2} and N(H_2O)>~6x10^{16} cm^{-2} may indicate XDR chemistry, although significant starburst chemistry cannot be ruled out. The lower-lying OH, [C II] 158 micron, and [O I] 63 micron lines arise from a more extended (~350 pc) starburst region. We show that the [C II] deficit in Mkn 231 is compatible with a high average abundance of C+ because of an extreme overall luminosity to gas mass ratio. Therefore, a [C II] deficit may indicate a significant contribution to the luminosity by an AGN, and/or by extremely efficient star formation.Comment: 16 pages, 6 figures, accepted for publication in The Astrophysical Journa

Microscopic mechanism for mechanical polishing of diamond (110) surfaces

Mechanically induced degradation of diamond, as occurs during polishing, is studied using total--energy pseudopotential calculations. The strong asymmetry in the rate of polishing between different directions on the diamond (110) surface is explained in terms of an atomistic mechanism for nano--groove formation. The post--polishing surface morphology and the nature of the polishing residue predicted by this mechanism are consistent with experimental evidence.Comment: 4 pages, 5 figure

The dynamics and mixing of small spherical particles in a plane, free shear layer

The equation of motion of small rigid spheres settling under gravity in a two-dimensional inviscid flow given by the Stuart solution of the Euler equations is analyzed as a fourdimensional dynamical system. It is shown that depending on the values of the Stokes, Grashof, and a scaled Reynolds number, particles may either sediment or remain permanently suspended in the flow. When suspension occurs, the particle trajectories are shown to be attracted by a single period, quasiperiodic, or chaotic orbits. A consequence of the existence of a strange attractor (chaotic orbit) is that heavy particles can reach a stage ofjhdization by which they remain indefinitely suspended in a layer of finite height located above the center of the Stuart vortices.Secretaria de Estado de Universidades e Investigación de España FPU-2868794

Hurst Coefficient in long time series of population size: Model for two plant populations with different reproductive strategies

Can the fractal dimension of fluctuations in population size be used to estimate extinction risk? The problem with estimating this fractal dimension is that the lengths of the time series are usually too short for conclusive results. This study answered this question with long time series data obtained from an iterative competition model. This model produces competitive extinction at different perturbation intensities for two different germination strategies: germination of all seeds vs. dormancy in half the seeds. This provided long time series of 900 years and different extinction risks. The results support the hypothesis for the effectiveness of the Hurst coefficient for estimating extinction risk

Comparative Study of Embedding Methods

Embedding experimental data is a common first step in many forms of dynamical analysis. The choice of appropriate embedding parameters (dimension and lag) is crucial to the success of the subsequent analysis. We argue here that the optimal embedding of a time series cannot be determined by criteria based solely on the time series itself. Therefore we base our analysis on an examination of systems that have explicit analytic representations. A comparison of analytically obtained results with those obtained by an examination of the corresponding time series provides a means of assessing the comparative success of different embedding criteria. The assessment also includes measures of robustness to noise. The limitations of this study are explicitly delineated. While bearing these limitations in mind, we conclude that for the examples considered here, the best identification of the embedding dimension was achieved with a global false nearest neighbors argument, and the best value of lag was identified by the mutual information function