Matching Items (40)

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The Ketogenic Diet Alters the Hypoxic Response and Affects Expression of Proteins Associated with Angiogenesis, Invasive Potential and Vascular Permeability in a Mouse Glioma Model

Description

Background
The successful treatment of malignant gliomas remains a challenge despite the current standard of care, which consists of surgery, radiation and temozolomide. Advances in the survival of brain cancer

Background
The successful treatment of malignant gliomas remains a challenge despite the current standard of care, which consists of surgery, radiation and temozolomide. Advances in the survival of brain cancer patients require the design of new therapeutic approaches that take advantage of common phenotypes such as the altered metabolism found in cancer cells. It has therefore been postulated that the high-fat, low-carbohydrate, adequate protein ketogenic diet (KD) may be useful in the treatment of brain tumors. We have demonstrated that the KD enhances survival and potentiates standard therapy in a mouse model of malignant glioma, yet the mechanisms are not fully understood.
Methods
To explore the effects of the KD on various aspects of tumor growth and progression, we used the immunocompetent, syngeneic GL261-Luc2 mouse model of malignant glioma.
Results
Tumors from animals maintained on KD showed reduced expression of the hypoxia marker carbonic anhydrase 9, hypoxia inducible factor 1-alpha, and decreased activation of nuclear factor kappa B. Additionally, tumors from animals maintained on KD had reduced tumor microvasculature and decreased expression of vascular endothelial growth factor receptor 2, matrix metalloproteinase-2 and vimentin. Peritumoral edema was significantly reduced in animals fed the KD and protein analyses showed altered expression of zona occludens-1 and aquaporin-4.
Conclusions
The KD directly or indirectly alters the expression of several proteins involved in malignant progression and may be a useful tool for the treatment of gliomas.

Contributors

Agent

Created

Date Created
  • 2015-06-17

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Mathematical Analysis of Glioma Growth in a Murine Model

Description

Five immunocompetent C57BL/6-cBrd/cBrd/Cr (albino C57BL/6) mice were injected with GL261-luc2 cells, a cell line sharing characteristics of human glioblastoma multiforme (GBM). The mice were imaged using magnetic resonance (MR) at

Five immunocompetent C57BL/6-cBrd/cBrd/Cr (albino C57BL/6) mice were injected with GL261-luc2 cells, a cell line sharing characteristics of human glioblastoma multiforme (GBM). The mice were imaged using magnetic resonance (MR) at five separate time points to characterize growth and development of the tumor. After 25 days, the final tumor volumes of the mice varied from 12 mm[superscript 3] to 62 mm[superscript 3], even though mice were inoculated from the same tumor cell line under carefully controlled conditions. We generated hypotheses to explore large variances in final tumor size and tested them with our simple reaction-diffusion model in both a 3-dimensional (3D) finite difference method and a 2-dimensional (2D) level set method. The parameters obtained from a best-fit procedure, designed to yield simulated tumors as close as possible to the observed ones, vary by an order of magnitude between the three mice analyzed in detail. These differences may reflect morphological and biological variability in tumor growth, as well as errors in the mathematical model, perhaps from an oversimplification of the tumor dynamics or nonidentifiability of parameters. Our results generate parameters that match other experimental in vitro and in vivo measurements. Additionally, we calculate wave speed, which matches with other rat and human measurements.

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Agent

Created

Date Created
  • 2017-05-31

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Accurate state estimation from uncertain data and models: an application of data assimilation to mathematical models of human brain tumors

Description

Background
Data assimilation refers to methods for updating the state vector (initial condition) of a complex spatiotemporal model (such as a numerical weather model) by combining new observations with one

Background
Data assimilation refers to methods for updating the state vector (initial condition) of a complex spatiotemporal model (such as a numerical weather model) by combining new observations with one or more prior forecasts. We consider the potential feasibility of this approach for making short-term (60-day) forecasts of the growth and spread of a malignant brain cancer (glioblastoma multiforme) in individual patient cases, where the observations are synthetic magnetic resonance images of a hypothetical tumor.
Results
We apply a modern state estimation algorithm (the Local Ensemble Transform Kalman Filter), previously developed for numerical weather prediction, to two different mathematical models of glioblastoma, taking into account likely errors in model parameters and measurement uncertainties in magnetic resonance imaging. The filter can accurately shadow the growth of a representative synthetic tumor for 360 days (six 60-day forecast/update cycles) in the presence of a moderate degree of systematic model error and measurement noise.
Conclusions
The mathematical methodology described here may prove useful for other modeling efforts in biology and oncology. An accurate forecast system for glioblastoma may prove useful in clinical settings for treatment planning and patient counseling.

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Agent

Created

Date Created
  • 2011-12-21

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Kalman filter data assimilation: Targeting observations and parameter estimation

Description

This paper studies the effect of targeted observations on state and parameter estimates determined with Kalman filter data assimilation (DA) techniques. We first provide an analytical result demonstrating that targeting

This paper studies the effect of targeted observations on state and parameter estimates determined with Kalman filter data assimilation (DA) techniques. We first provide an analytical result demonstrating that targeting observations within the Kalman filter for a linear model can significantly reduce state estimation error as opposed to fixed or randomly located observations. We next conduct observing system simulation experiments for a chaotic model of meteorological interest, where we demonstrate that the local ensemble transform Kalman filter (LETKF) with targeted observations based on largest ensemble variance is skillful in providing more accurate state estimates than the LETKF with randomly located observations. Additionally, we find that a hybrid ensemble Kalman filter parameter estimation method accurately updates model parameters within the targeted observation context to further improve state estimation.

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Agent

Created

Date Created
  • 2014-06-01

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A Numerical and Analytical Study of Wave Reflection and Transmission across the Tropopause

Description

A numerical study of wave-induced momentum transport across the tropopause in the presence of a stably stratified thin inversion layer is presented and discussed. This layer consists of a shar

A numerical study of wave-induced momentum transport across the tropopause in the presence of a stably stratified thin inversion layer is presented and discussed. This layer consists of a sharp increase in static stability within the tropopause. The wave propagation is modeled by numerically solving the Taylor-Goldstein equation, which governs the dynamics of internal waves in stably stratified shear flows. The waves are forced by a flow over a bell shaped mountain placed at the lower boundary of the domain. A perfectly radiating condition based on the group velocity of mountain waves is imposed at the top to avoid artificial wave reflection. A validation for the numerical method through comparisons with the corresponding analytical solutions will be provided. Then, the method is applied to more realistic profiles of the stability to study the impact of these profiles on wave propagation through the tropopause.

Contributors

Created

Date Created
  • 2017-05

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Computations on Spherical Domains

Description

The main goal of this project is to study approximations of functions on circular and spherical domains using the cubed sphere discretization. On each subdomain, the function is approximated by

The main goal of this project is to study approximations of functions on circular and spherical domains using the cubed sphere discretization. On each subdomain, the function is approximated by windowed Fourier expansions. Of particular interest is the dependence of accuracy on the different choices of windows and the size of the overlapping regions. We use Matlab to manipulate each of the variables involved in these computations as well as the overall error, thus enabling us to decide which specific values produce the most accurate results. This work is motivated by problems arising in atmospheric research.

Contributors

Created

Date Created
  • 2018-05

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Statistical Properties of Coherent Structures in Two Dimensional Turbulence

Description

Coherent vortices are ubiquitous structures in natural flows that affect mixing and transport of substances and momentum/energy. Being able to detect these coherent structures is important for pollutant mitigation, ecological

Coherent vortices are ubiquitous structures in natural flows that affect mixing and transport of substances and momentum/energy. Being able to detect these coherent structures is important for pollutant mitigation, ecological conservation and many other aspects. In recent years, mathematical criteria and algorithms have been developed to extract these coherent structures in turbulent flows. In this study, we will apply these tools to extract important coherent structures and analyze their statistical properties as well as their implications on kinematics and dynamics of the flow. Such information will aide representation of small-scale nonlinear processes that large-scale models of natural processes may not be able to resolve.

Contributors

Created

Date Created
  • 2018-05

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A New Numerical Method Based on Leapfrog for Atmospheric and Ocean Modeling

Description

A semi-implicit, fourth-order time-filtered leapfrog numerical scheme is investigated for accuracy and stability, and applied to several test cases, including one-dimensional advection and diffusion, the anelastic equations to simulate the

A semi-implicit, fourth-order time-filtered leapfrog numerical scheme is investigated for accuracy and stability, and applied to several test cases, including one-dimensional advection and diffusion, the anelastic equations to simulate the Kelvin-Helmholtz instability, and the global shallow water spectral model to simulate the nonlinear evolution of twin tropical cyclones. The leapfrog scheme leads to computational modes in the solutions to highly nonlinear systems, and time-filters are often used to damp these modes. The proposed filter damps the computational modes without appreciably degrading the physical mode. Its performance in these metrics is superior to the second-order time-filtered leapfrog scheme developed by Robert and Asselin.

Contributors

Created

Date Created
  • 2016-05

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Computations on Parameterized Surfaces with Chebfun2

Description

Chebfun is a collection of algorithms and an open-source software system in object-oriented Matlab that extends familiar powerful methods of numerical computation involving numbers to continuous or piecewise-continuous functions. The

Chebfun is a collection of algorithms and an open-source software system in object-oriented Matlab that extends familiar powerful methods of numerical computation involving numbers to continuous or piecewise-continuous functions. The success of this strategy is based on the mathematical fact that smooth functions can be represented very efficiently by polynomial interpolation at Chebyshev points or by trigonometric interpolation at equispaced points for periodic functions. More recently, the system has been extended to handle bivariate functions and vector fields. These two new classes of objects are called Chebfun2 and Chebfun2v, respectively. We will show that Chebfun2 and Chebfun2v, and can be used to accurately and efficiently perform various computations on parametric surfaces in two or three dimensions, including path trajectories and mean and Gaussian curvatures. More advanced surface computations such as mean curvature flows are also explored. This is also the first work to use the newly implemented trigonometric representation, namely Trigfun, for computations on surfaces.

Contributors

Created

Date Created
  • 2016-05

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Stochastic parameterization of the proliferation-diffusion model of brain cancer in a Murine model

Description

Glioblastoma multiforme (GBM) is a malignant, aggressive and infiltrative cancer of the central nervous system with a median survival of 14.6 months with standard care. Diagnosis of GBM is made

Glioblastoma multiforme (GBM) is a malignant, aggressive and infiltrative cancer of the central nervous system with a median survival of 14.6 months with standard care. Diagnosis of GBM is made using medical imaging such as magnetic resonance imaging (MRI) or computed tomography (CT). Treatment is informed by medical images and includes chemotherapy, radiation therapy, and surgical removal if the tumor is surgically accessible. Treatment seldom results in a significant increase in longevity, partly due to the lack of precise information regarding tumor size and location. This lack of information arises from the physical limitations of MR and CT imaging coupled with the diffusive nature of glioblastoma tumors. GBM tumor cells can migrate far beyond the visible boundaries of the tumor and will result in a recurring tumor if not killed or removed. Since medical images are the only readily available information about the tumor, we aim to improve mathematical models of tumor growth to better estimate the missing information. Particularly, we investigate the effect of random variation in tumor cell behavior (anisotropy) using stochastic parameterizations of an established proliferation-diffusion model of tumor growth. To evaluate the performance of our mathematical model, we use MR images from an animal model consisting of Murine GL261 tumors implanted in immunocompetent mice, which provides consistency in tumor initiation and location, immune response, genetic variation, and treatment. Compared to non-stochastic simulations, stochastic simulations showed improved volume accuracy when proliferation variability was high, but diffusion variability was found to only marginally affect tumor volume estimates. Neither proliferation nor diffusion variability significantly affected the spatial distribution accuracy of the simulations. While certain cases of stochastic parameterizations improved volume accuracy, they failed to significantly improve simulation accuracy overall. Both the non-stochastic and stochastic simulations failed to achieve over 75% spatial distribution accuracy, suggesting that the underlying structure of the model fails to capture one or more biological processes that affect tumor growth. Two biological features that are candidates for further investigation are angiogenesis and anisotropy resulting from differences between white and gray matter. Time-dependent proliferation and diffusion terms could be introduced to model angiogenesis, and diffusion weighed imaging (DTI) could be used to differentiate between white and gray matter, which might allow for improved estimates brain anisotropy.

Contributors

Agent

Created

Date Created
  • 2016-05