Exploiting the synergy between carboplatin and ABT-737 in the treatment of ovarian carcinomas

Platinum drug-resistance in ovarian cancers is a major factor contributing to chemotherapeutic resistance of recurrent disease. Members of the Bcl-2 family such as the anti-apoptotic protein Bcl-XL have been shown to play a role in this resistance. Consequently, concurrent inhibition of Bcl-XL in combination with standard chemotherapy may improve treatment outcomes for ovarian cancer patients. Here, we develop a mathematical model to investigate the potential of combination therapy with ABT-737, a small molecule inhibitor of Bcl-XL, and carboplatin, a platinum-based drug, on a simulated tumor xenograft. The model is calibrated against in vivo\ud experimental data, wherein tumor xenografts were established in mice and treated with ABT-737 and carboplatin on a fixed periodic schedule, alone or in combination, and tumor sizes recorded regularly. We show that the validated model can be used to predict the minimum drug load that will achieve a predetermined level of tumor growth inhibition, thereby maximizing the synergy between the two drugs. Our simulations suggest that the time of infusion of each carboplatin dose is a critical parameter, with an 8-hour infusion of carboplatin administered each week combined with a daily bolus dose of ABT-737 predicted to minimize residual disease. We also investigate the potential of ABT-737 co-therapy with carboplatin to prevent or delay the onset of carboplatin-resistance under two scenarios. When resistance is acquired as a result of aberrant DNA-damage repair in cells treated with carboplatin, the model is used to identify drug delivery schedules that induce tumor remission with even low doses of combination therapy. When resistance is intrinsic, due to a pre-existing cohort of resistant cells, tumor remission is no longer feasible, but our model can be used to identify dosing strategies that extend disease-free survival periods. These results underscore the potential of our model to accelerate the development of novel therapeutics such as ABT-737, by predicting optimal treatment strategies when these drugs are given in combination with currently approved cancer medications

Simultaneous Inference of User Representations and Trust

Inferring trust relations between social media users is critical for a number of applications wherein users seek credible information. The fact that available trust relations are scarce and skewed makes trust prediction a challenging task. To the best of our knowledge, this is the first work on exploring representation learning for trust prediction. We propose an approach that uses only a small amount of binary user-user trust relations to simultaneously learn user embeddings and a model to predict trust between user pairs. We empirically demonstrate that for trust prediction, our approach outperforms classifier-based approaches which use state-of-the-art representation learning methods like DeepWalk and LINE as features. We also conduct experiments which use embeddings pre-trained with DeepWalk and LINE each as an input to our model, resulting in further performance improvement. Experiments with a dataset of $\sim$356K user pairs show that the proposed method can obtain an high F-score of 92.65%.Comment: To appear in the proceedings of ASONAM'17. Please cite that versio

Electrochemical Energy Storage Subsystems Study, Volume 2

The effects on life cycle costs (LCC) of major design and performance technology parameters for multi kW LEO and GEO energy storage subsystems using NiCd and NiH2 batteries and fuel cell/electrolysis cell devices were examined. Design, performance and LCC dynamic models are developed based on mission and system/subsystem requirements and existing or derived physical and cost data relationships. The models are exercised to define baseline designs and costs. Then the major design and performance parameters are each varied to determine their influence on LCC around the baseline values

Electrochemical energy storage subsystems study, volume 1

The effects on life cycle costs (LCC) of major design and performance technology parameters for multi kW LEO and GEO energy storage subsystems using NiCd and NiH2 batteries and fuel cell/electrolysis cell devices were examined. Design, performance and LCC dynamic models are developed based on mission and system/subsystem requirements and existing or derived physical and cost data relationships. The models define baseline designs and costs. The major design and performance parameters are each varied to determine their influence on LCC around the baseline values

Motion and homogenization of vortices in anisotropic Type II superconductors

The motion of vortices in an anisotropic superconductor is considered. For a system of well-separated vortices, each vortex is found to obey a law of motion analogous to the local induction approximation, in which velocity of the vortex depends upon the local curvature and orientation. A system of closely packed vortices is then considered, and a mean field model is formulated in which the individual vortex lines are replaced by a vortex density

Theory of pattern-formation of metallic microparticles in poorly conducting liquid

We develop continuum theory of self-assembly and pattern formation in metallic microparticles immersed in a poorly conducting liquid in DC electric field. The theory is formulated in terms of two conservation laws for the densities of immobile particles (precipitate) and bouncing particles (gas) coupled to the Navier-Stokes equation for the liquid. This theory successfully reproduces correct topology of the phase diagram and primary patterns observed in the experiment [Sapozhnikov et al, Phys. Rev. Lett. v. 90, 114301 (2003)]: static crystals and honeycombs and dynamic pulsating rings and rotating multi-petal vortices.Comment: 4 pages, 5 figures, submitted to Phys. Rev. Let

Reaction Diffusion and Ballistic Annihilation Near an Impenetrable Boundary

The behavior of the single-species reaction process $A+A\to O$ is examined near an impenetrable boundary, representing the flask containing the reactants. Two types of dynamics are considered for the reactants: diffusive and ballistic propagation. It is shown that the effect of the boundary is quite different in both cases: diffusion-reaction leads to a density excess, whereas ballistic annihilation exhibits a density deficit, and in both cases the effect is not localized at the boundary but penetrates into the system. The field-theoretic renormalization group is used to obtain the universal properties of the density excess in two dimensions and below for the reaction-diffusion system. In one dimension the excess decays with the same exponent as the bulk and is found by an exact solution. In two dimensions the excess is marginally less relevant than the bulk decay and the density profile is again found exactly for late times from the RG-improved field theory. The results obtained for the diffusive case are relevant for Mg$^{2+}$ or Cd$^{2+}$ doping in the TMMC crystal's exciton coalescence process and also imply a surprising result for the dynamic magnetization in the critical one-dimensional Ising model with a fixed spin. For the case of ballistic reactants, a model is introduced and solved exactly in one dimension. The density-deficit profile is obtained, as is the density of left and right moving reactants near the impenetrable boundary.Comment: to appear in J. Phys.

Some combinatorial identities related to commuting varieties and Hilbert schemes

In this article we explore some of the combinatorial consequences of recent results relating the isospectral commuting variety and the Hilbert scheme of points in the plane

Exact Resummations in the Theory of Hydrodynamic Turbulence: I The Ball of Locality and Normal Scaling

This paper is the first in a series of three papers that aim at understanding the scaling behaviour of hydrodynamic turbulence. We present in this paper a perturbative theory for the structure functions and the response functions of the hydrodynamic velocity field in real space and time. Starting from the Navier-Stokes equations (at high Reynolds number Re) we show that the standard perturbative expansions that suffer from infra-red divergences can be exactly resummed using the Belinicher-L'vov transformation. After this exact (partial) resummation it is proven that the resulting perturbation theory is free of divergences, both in large and in small spatial separations. The hydrodynamic response and the correlations have contributions that arise from mediated interactions which take place at some space- time coordinates. It is shown that the main contribution arises when these coordinates lie within a shell of a "ball of locality" that is defined and discussed. We argue that the real space-time formalism developed here offers a clear and intuitive understanding of every diagram in the theory, and of every element in the diagrams. One major consequence of this theory is that none of the familiar perturbative mechanisms may ruin the classical Kolmogorov (K41) scaling solution for the structure functions. Accordingly, corrections to the K41 solutions should be sought in nonperturbative effects. These effects are the subjects of papers II and III in this series, that will propose a mechanism for anomalous scaling in turbulence, which in particular allows multiscaling of the structure functions.Comment: PRE in press, 18 pages + 6 figures, REVTeX. The Eps files of figures will be FTPed by request to [email protected]