scholarly journals Fighting cancer with oncolytic viral therapy: identifying threshold parameters for success

2021 ◽  
Author(s):  
Sana Jahedi ◽  
Lin Wang ◽  
James Watmough
Keyword(s):  
Tumor Size ◽  
Initial Conditions ◽  
Horizontal Transmission ◽  
Infection Prevalence ◽  
Virus Dynamics ◽  
Two Dimensional ◽  
Free Virus ◽  
Oncolytic Viral Therapy ◽  
Viral Therapy ◽  
Optimum Threshold

We model interactions between cancer cells and free virus during oncolytic viral therapy. One of our main goals is to identify parameter regions which yield treatment failure or success. We show that the tumor size under therapy at a certain time is less than the tumor size without therapy. We determine the minimum tumor size by the therapy and parameter regions under which this minimum is attained. Our analysis shows there are two thresholds for the horizontal transmission rate: a "Control threshold", the threshold above which treatment is efficient, and an "optimum threshold'', the threshold beyond which infection prevalence reaches 100% and the tumor shrinks to its smallest size. Moreover, we explain how changes in the virulence level of the free virus alters the optimum threshold and the minimum tumor size. We identify a threshold for the virulence level of the virus and show how this threshold depends on timescale of virus dynamics. Our results suggests that when timescale of virus dynamics is fast, administration of a more virulent virus leads into more tumor reduction. When viral timescale is slow, a higher virulence will have drawbacks on the results, such as high amplitude oscillations. Furthermore, our numerical observation depicts fast and slow dynamics. Our numerical simulations indicate there exists a two-dimensional globally attracting surface that includes unstable manifold of the interior equilibrium. All solutions with positive initial conditions rapidly approach this two-dimensional attracting surface. In contrast, the trajectories on the attracting surface slowly tend to the periodic solution.

Waves and turbulence on a beta-plane

1975 ◽  
Vol 69 (3) ◽  
pp. 417-443 ◽  
Author(s):  
Peter B. Rhines
Keyword(s):  
Weak Interaction ◽  
Initial Conditions ◽  
Computer Experiments ◽  
Zonal Flow ◽  
Similarity Solutions ◽  
Large Reynolds Number ◽  
Two Dimensional ◽  
Homogeneous Fluid ◽  
Restoring Force ◽  
Model Equations

Two-dimensional eddies in a homogeneous fluid at large Reynolds number, if closely packed, are known to evolve towards larger scales. In the presence of a restoring force, the geophysical beta-effect, this cascade produces a field of waves without loss of energy, and the turbulent migration of the dominant scale nearly ceases at a wavenumber kβ = (β/2U)½ independent of the initial conditions other than U, the r.m.s. particle speed, and β, the northward gradient of the Coriolis frequency.The conversion of turbulence into waves yields, in addition, more narrowly peaked wavenumber spectra and less fine-structure in the spatial maps, while smoothly distributing the energy about physical space.The theory is discussed, using known integral constraints and similarity solutions, model equations, weak-interaction wave theory (which provides the terminus for the cascade) and other linearized instability theory. Computer experiments with both finite-difference and spectral codes are reported. The central quantity is the cascade rate, defined as \[ T = 2\int_0^{\infty} kF(k)dk/U^3\langle k\rangle , \] where F is the nonlinear transfer spectrum and 〈k〉 the mean wavenumber of the energy spectrum. (In unforced inviscid flow T is simply U−1d〈k〉−1/dt, or the rate at which the dominant scale expands in time t.) T is shown to have a mean value of 3·0 × 10−2 for pure two-dimensional turbulence, but this decreases by a factor of five at the transition to wave motion. We infer from weak-interaction theory even smaller values for k [Lt ] kβ.After passing through a state of propagating waves, the homogeneous cascade tends towards a flow of alternating zonal jets which, we suggest, are almost perfectly steady. When the energy is intermittent in space, however, model equations show that the cascade is halted simply by the spreading of energy about space, and then the end state of a zonal flow is probably not achieved.The geophysical application is that the cascade of pure turbulence to large scales is defeated by wave propagation, helping to explain why the energy-containing eddies in the ocean and atmosphere, though significantly nonlinear, fail to reach the size of their respective domains, and are much smaller. For typical ocean flows, $k_{\beta}^{-1} = 70\,{\rm km} $, while for the atmosphere, $k_{\beta}^{-1} = 1000\,{\rm km}$. In addition the cascade generates, by itself, zonal flow (or more generally, flow along geostrophic contours).

scholarly journals R-Process Nucleosynthesis in MHD Jet Explosions of Core-Collapse Supernovae

2013 ◽  
Vol 2013 ◽  
pp. 1-13
Author(s):  
Motoaki Saruwatari ◽  
Masa-aki Hashimoto ◽  
Ryohei Fukuda ◽  
Shin-ichiro Fujimoto
Keyword(s):  
Magnetic Field ◽  
Heavy Element ◽  
Initial Conditions ◽  
Core Collapse ◽  
Combined Effects ◽  
Two Dimensional ◽  
The Third ◽  
R Process ◽  
Helium Star ◽  
Hydrodynamic Code

We investigate the r-process nucleosynthesis during the magnetohydrodynamical (MHD) explosion of a supernova in a helium star of 3.3 M⊙, where effects of neutrinos are taken into account using the leakage scheme in the two-dimensional (2D) hydrodynamic code. Jet-like explosion due to the combined effects of differential rotation and magnetic field is able to erode the lower electron fraction matter from the inner layers. We find that the ejected material of low electron fraction responsible for the r-process comes out from just outside the neutrino sphere deep inside the Fe-core. It is found that heavy element nucleosynthesis depends on the initial conditions of rotational and magnetic fields. In particular, the third peak of the distribution is significantly overproduced relative to the solar system abundances, which would indicate a possible r-process site owing to MHD jets in supernovae.

scholarly journals An Agent-Based Model of Combination Oncolytic Viral Therapy and Anti-PD-1 Immunotherapy Reveals the Importance of Spatial Location When Treating Glioblastoma

Cancers ◽  
2021 ◽  
Vol 13 (21) ◽  
pp. 5314
Author(s):  
Kathleen M. Storey ◽  
Trachette L. Jackson
Keyword(s):  
Three Dimensional ◽  
Spatial Location ◽  
Adaptive Strategy ◽  
Treatment Modalities ◽  
Agent Based Model ◽  
Agent Based ◽  
Oncolytic Viral Therapy ◽  
Landscape Characteristics ◽  
Adaptive Immune ◽  
Viral Therapy

Oncolytic viral therapies and immunotherapies are of growing clinical interest due to their selectivity for tumor cells over healthy cells and their immunostimulatory properties. These treatment modalities provide promising alternatives to the standard of care, particularly for cancers with poor prognoses, such as the lethal brain tumor glioblastoma (GBM). However, uncertainty remains regarding optimal dosing strategies, including how the spatial location of viral doses impacts therapeutic efficacy and tumor landscape characteristics that are most conducive to producing an effective immune response. We develop a three-dimensional agent-based model (ABM) of GBM undergoing treatment with a combination of an oncolytic Herpes Simplex Virus and an anti-PD-1 immunotherapy. We use a mechanistic approach to model the interactions between distinct populations of immune cells, incorporating both innate and adaptive immune responses to oncolytic viral therapy and including a mechanism of adaptive immune suppression via the PD-1/PD-L1 checkpoint pathway. We utilize the spatially explicit nature of the ABM to determine optimal viral dosing in both the temporal and spatial contexts. After proposing an adaptive viral dosing strategy that chooses to dose sites at the location of highest tumor cell density, we find that, in most cases, this adaptive strategy produces a more effective treatment outcome than repeatedly dosing in the center of the tumor.

scholarly journals Phase Transition in Dynamical Systems: Defining Classes of Universality for Two-Dimensional Hamiltonian Mappings via Critical Exponents

2009 ◽  
Vol 2009 ◽  
pp. 1-22 ◽  
Author(s):  
Edson D. Leonel
Keyword(s):  
Phase Transition ◽  
Critical Exponents ◽  
Scaling Laws ◽  
Scaling Function ◽  
Initial Conditions ◽  
Invariant Tori ◽  
Dynamical Variable ◽  
Two Dimensional ◽  
Control Parameters ◽  
Average Value

A phase transition from integrability to nonintegrability in two-dimensional Hamiltonian mappings is described and characterized in terms of scaling arguments. The mappings considered produce a mixed structure in the phase space in the sense that, depending on the combination of the control parameters and initial conditions, KAM islands which are surrounded by chaotic seas that are limited by invariant tori are observed. Some dynamical properties for the largest component of the chaotic sea are obtained and described in terms of the control parameters. The average value and the deviation of the average value for chaotic components of a dynamical variable are described in terms of scaling laws, therefore critical exponents characterizing a scaling function that describes a phase transition are obtained and then classes of universality are characterized. The three models considered are: The Fermi-Ulam accelerator model, a periodically corrugate waveguide, and variant of the standard nontwist map.

ON THE JOINT APPLICATION OF THE COLLOCATION BOUNDARY ELEMENT METHOD AND THE FOURIER METHOD FOR SOLVING PROBLEMS OF HEAT CONDUCTION IN FINITE CYLINDERS WITH SMOOTH DIRECTRICES

2021 ◽  
pp. 15-38
Author(s):  
D.Y. Ivanov ◽  
Keyword(s):  
Fourier Series ◽  
Boundary Element Method ◽  
Boundary Conditions ◽  
Boundary Element ◽  
Initial Conditions ◽  
Fourier Method ◽  
Time Interval ◽  
Cylindrical Domain ◽  
Two Dimensional ◽  
Element Method

Here we consider the initial-boundary value problems in a homogeneous cylindrical domain YI Ω ×+ ( Ω+ is an open two-dimensional bounded simply connected domain with a boundary 5 ∂Ω ∈C , 2 \ Ω≡ Ω − + R is the open exterior of the domain Ω+ , [0, ] YI ≡ Y is the height of the cylinder) on a time interval [0, ] TI ≡ T . The initial conditions and the boundary conditions on the bases of the cylinder are zero, and the boundary conditions on the lateral surface of the cylinder are given by the function 1 2 wx x yt ( , , ,) ( 1 2 (, ) x x ∈∂Ω , Y y ∈ I , T t I ∈ ). An approximate solution of such problems is obtained through the combined use of the Fourier method and the collocation boundary element method based on piecewise quadratic interpolation (PQI). The solution to the problem in the cylinder is expanded in a Fourier series in terms of eigenfunctions of the operator 2 By yy ≡ ∂ with the corresponding zero boundary conditions. The coefficients of such a Fourier series are solutions of problems for two-dimensional heat equations 2 2 t ∇ =∂ + u u ku . With a low smoothness of the functions w in the variable y, the weight of solutions at large values of k increases and the accuracy of solving the problem in the cylinder decreases. To maintain accuracy on a uniform grid, the step of discretization of the boundary function w with respect to the variable y is decreased by a factor of j. Here j is an averaged value of the quantity Y k π depending on the function w. In addition, the steps of discretization of functions ( ) 2 exp − τ k with respect to the variable τ in domains τ≤πT k are reduced by a factor of 2 2 k π . The steps in the remaining ranges of values τ and the steps by the other variables remain unchanged. The approximate solutions obtained on the basis of this procedure converge stably to exact solutions in the 2 ( ) LI I Y T × -norm with a cubic velocity uniformly with respect to sets of functions w, bounded by norm of functions with low smoothness in the variable y, uniformly along the length of the generatrix of the cylinder Y , and uniformly in the domain Ω . The latter is also associated with the use of PQI along the curve ∂Ω over the variable 2 2 ρ≡ − r d , which is carried out at small values of r ( d and r are the distances from the observed point of the domain Ω to the boundary ∂Ω and to the current point of integration along ∂Ω , respectively). The theoretical conclusions are confirmed by the results of the numerical solution of the problem in a circular cylinder, where the dependence of the boundary functions w on y is given by the normalized eigenfunctions of the differential operator By which vary in a sufficiently large range of values of k .

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