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#### Fachbereich / Organisatorische Einheit

- Fachbereich Mathematik (1042) (entfernen)

SDE-driven modeling of phenotypically heterogeneous tumors: The influence of cancer cell stemness
(2018)

We deduce cell population models describing the evolution of a tumor (possibly interacting with its
environment of healthy cells) with the aid of differential equations. Thereby, different subpopulations
of cancer cells allow accounting for the tumor heterogeneity. In our settings these include cancer
stem cells known to be less sensitive to treatment and differentiated cancer cells having a higher
sensitivity towards chemo- and radiotherapy. Our approach relies on stochastic differential equations
in order to account for randomness in the system, arising e.g., by the therapy-induced decreasing
number of clonogens, which renders a pure deterministic model arguable. The equations are deduced
relying on transition probabilities characterizing innovations of the two cancer cell subpopulations,
and similarly extended to also account for the evolution of normal tissue. Several therapy approaches
are introduced and compared by way of tumor control probability (TCP) and uncomplicated tumor
control probability (UTCP). A PDE approach allows to assess the evolution of tumor and normal
tissue with respect to time and to cell population densities which can vary continuously in a given set
of states. Analytical approximations of solutions to the obtained PDE system are provided as well.

Optimal control of partial differential equations is an important task in applied mathematics where it is used in order to optimize, for example, industrial or medical processes. In this thesis we investigate an optimal control problem with tracking type cost functional for the Cattaneo equation with distributed control, that is, \(\tau y_{tt} + y_t - \Delta y = u\). Our focus is on the theoretical and numerical analysis of the limit process \(\tau \to 0\) where we prove the convergence of solutions of the Cattaneo equation to solutions of the heat equation.
We start by deriving both the Cattaneo and the classical heat equation as well as introducing our notation and some functional analytic background. Afterwards, we prove the well-posedness of the Cattaneo equation for homogeneous Dirichlet boundary conditions, that is, we show the existence and uniqueness of a weak solution together with its continuous dependence on the data. We need this in the following, where we investigate the optimal control problem for the Cattaneo equation: We show the existence and uniqueness of a global minimizer for an optimal control problem with tracking type cost functional and the Cattaneo equation as a constraint. Subsequently, we do an asymptotic analysis for \(\tau \to 0\) for both the forward equation and the aforementioned optimal control problem and show that the solutions of these problems for the Cattaneo equation converge strongly to the ones for the heat equation. Finally, we investigate these problems numerically, where we examine the different behaviour of the models and also consider the limit \(\tau \to 0\), suggesting a linear convergence rate.

In modern algebraic geometry solutions of polynomial equations are studied from a qualitative point of view using highly sophisticated tools such as cohomology, \(D\)-modules and Hodge structures. The latter have been unified in Saito’s far-reaching theory of mixed Hodge modules, that has shown striking applications including vanishing theorems for cohomology. A mixed Hodge module can be seen as a special type of filtered \(D\)-module, which is an algebraic counterpart of a system of linear differential equations. We present the first algorithmic approach to Saito’s theory. To this end, we develop a Gröbner basis theory for a new class of algebras generalizing PBW-algebras.
The category of mixed Hodge modules satisfies Grothendieck’s six-functor formalism. In part these functors rely on an additional natural filtration, the so-called \(V\)-filtration. A key result of this thesis is an algorithm to compute the \(V\)-filtration in the filtered setting. We derive from this algorithm methods for the computation of (extraordinary) direct image functors under open embeddings of complements of pure codimension one subvarieties. As side results we show
how to compute vanishing and nearby cycle functors and a quasi-inverse of Kashiwara’s equivalence for mixed Hodge modules.
Describing these functors in terms of local coordinates and taking local sections, we reduce the corresponding computations to algorithms over certain bifiltered algebras. It leads us to introduce the class of so-called PBW-reduction-algebras, a generalization of the class of PBW-algebras. We establish a comprehensive Gröbner basis framework for this generalization representing the involved filtrations by weight vectors.

Certain brain tumours are very hard to treat with radiotherapy due to their irregular shape caused by the infiltrative nature of the tumour cells. To enhance the estimation of the tumour extent one may use a mathematical model. As the brain structure plays an important role for the cell migration, it has to be included in such a model. This is done via diffusion-MRI data. We set up a multiscale model class accounting among others for integrin-mediated movement of cancer cells in the brain tissue, and the integrin-mediated proliferation. Moreover, we model a novel chemotherapy in combination with standard radiotherapy.
Thereby, we start on the cellular scale in order to describe migration. Then we deduce mean-field equations on the mesoscopic (cell density) scale on which we also incorporate cell proliferation. To reduce the phase space of the mesoscopic equation, we use parabolic scaling and deduce an effective description in the form of a reaction-convection-diffusion equation on the macroscopic spatio-temporal scale. On this scale we perform three dimensional numerical simulations for the tumour cell density, thereby incorporating real diffusion tensor imaging data. To this aim, we present programmes for the data processing taking the raw medical data and processing it to the form to be included in the numerical simulation. Thanks to the reduction of the phase space, the numerical simulations are fast enough to enable application in clinical practice.

Composite materials are used in many modern tools and engineering applications and
consist of two or more materials that are intermixed. Features like inclusions in a matrix
material are often very small compared to the overall structure. Volume elements that
are characteristic for the microstructure can be simulated and their elastic properties are
then used as a homogeneous material on the macroscopic scale.
Moulinec and Suquet [2] solve the so-called Lippmann-Schwinger equation, a reformulation of the equations of elasticity in periodic homogenization, using truncated
trigonometric polynomials on a tensor product grid as ansatz functions.
In this thesis, we generalize their approach to anisotropic lattices and extend it to
anisotropic translation invariant spaces. We discretize the partial differential equation
on these spaces and prove the convergence rate. The speed of convergence depends on
the smoothness of the coefficients and the regularity of the ansatz space. The spaces of
translates unify the ansatz of Moulinec and Suquet with de la Vallée Poussin means and
periodic Box splines, including the constant finite element discretization of Brisard and
Dormieux [1].
For finely resolved images, sampling on a coarser lattice reduces the computational
effort. We introduce mixing rules as the means to transfer fine-grid information to the
smaller lattice.
Finally, we show the effect of the anisotropic pattern, the space of translates, and the
convergence of the method, and mixing rules on two- and three-dimensional examples.
References
[1] S. Brisard and L. Dormieux. “FFT-based methods for the mechanics of composites:
A general variational framework”. In: Computational Materials Science 49.3 (2010),
pp. 663–671. doi: 10.1016/j.commatsci.2010.06.009.
[2] H. Moulinec and P. Suquet. “A numerical method for computing the overall response
of nonlinear composites with complex microstructure”. In: Computer Methods in
Applied Mechanics and Engineering 157.1-2 (1998), pp. 69–94. doi: 10.1016/s00457825(97)00218-1.

Multiphase materials combine properties of several materials, which makes them interesting for high-performing components. This thesis considers a certain set of multiphase materials, namely silicon-carbide (SiC) particle-reinforced aluminium (Al) metal matrix composites and their modelling based on stochastic geometry models.
Stochastic modelling can be used for the generation of virtual material samples: Once we have fitted a model to the material statistics, we can obtain independent three-dimensional “samples” of the material under investigation without the need of any actual imaging. Additionally, by changing the model parameters, we can easily simulate a new material composition.
The materials under investigation have a rather complicated microstructure, as the system of SiC particles has many degrees of freedom: Size, shape, orientation and spatial distribution. Based on FIB-SEM images, that yield three-dimensional image data, we extract the SiC particle structure using methods of image analysis. Then we model the SiC particles by anisotropically rescaled cells of a random Laguerre tessellation that was fitted to the shapes of isotropically rescaled particles. We fit a log-normal distribution for the volume distribution of the SiC particles. Additionally, we propose models for the Al grain structure and the Aluminium-Copper (\({Al}_2{Cu}\)) precipitations occurring on the grain boundaries and on SiC-Al phase boundaries.
Finally, we show how we can estimate the parameters of the volume-distribution based on two-dimensional SEM images. This estimation is applied to two samples with different mean SiC particle diameters and to a random section through the model. The stereological estimations are within acceptable agreement with the parameters estimated from three-dimensional image data
as well as with the parameters of the model.

Using valuation theory we associate to a one-dimensional equidimensional semilocal Cohen-Macaulay ring \(R\) its semigroup of values, and to a fractional ideal of \(R\) we associate its value semigroup ideal. For a class of curve singularities (here called admissible rings) including algebroid curves the semigroups of values, respectively the value semigroup ideals, satisfy combinatorial properties defining good semigroups, respectively good semigroup ideals. Notably, the class of good semigroups strictly contains the class of value semigroups of admissible rings. On good semigroups we establish combinatorial versions of algebraic concepts on admissible rings which are compatible with their prototypes under taking values. Primarily we examine duality and quasihomogeneity.
We give a definition for canonical semigroup ideals of good semigroups which characterizes canonical fractional ideals of an admissible ring in terms of their value semigroup ideals. Moreover, a canonical semigroup ideal induces a duality on the set of good semigroup ideals of a good semigroup. This duality is compatible with the Cohen-Macaulay duality on fractional ideals under taking values.
The properties of the semigroup of values of a quasihomogeneous curve singularity lead to a notion of quasihomogeneity on good semigroups which is compatible with its algebraic prototype. We give a combinatorial criterion which allows to construct from a quasihomogeneous semigroup \(S\) a quasihomogeneous curve singularity having \(S\) as semigroup of values.
As an application we use the semigroup of values to compute endomorphism rings of maximal ideals of algebroid curves. This yields an explicit description of the intermediate rings in an algorithmic normalization of plane central arrangements of smooth curves based on a criterion by Grauert and Remmert. Applying this result to hyperplane arrangements we determine the number of steps needed to compute the normalization of a the arrangement in terms of its Möbius function.

In the present master’s thesis we investigate the connection between derivations and
homogeneities of complete analytic algebras. We prove a theorem, which describes a specific set of generators
for the module of derivations of an analytic algebra, which map the maximal ideal of R into itself. It turns out, that this set has a structure similar to a Cartan subalgebra and contains
information regarding multi-homogeneity. In order to prove
this theorem, we extend the notion of grading by Scheja and Wiebe to projective systems and state the connection between multi-gradings and pairwise
commuting diagonalizable derivations. We prove a theorem similar to Cartan’s Conjugacy Theorem in the setup of infinite-dimensional Lie algebras, which arise as projective limits of finite-dimensional Lie algebras. Using this result, we can show that the structure of the aforementioned set of generators is an intrinsic property of the analytic algebra. At the end we state an algorithm, which is theoretically able to compute the maximal multi-homogeneity of a complete analytic algebra.

In this thesis we integrate discrete dividends into the stock model, estimate
future outstanding dividend payments and solve different portfolio optimization
problems. Therefore, we discuss three well-known stock models, including
discrete dividend payments and evolve a model, which also takes early
announcement into account.
In order to estimate the future outstanding dividend payments, we develop a
general estimation framework. First, we investigate a model-free, no-arbitrage
methodology, which is based on the put-call parity for European options. Our
approach integrates all available option market data and simultaneously calculates
the market-implied discount curve. We illustrate our method using stocks
of European blue-chip companies and show within a statistical assessment that
the estimate performs well in practice.
As American options are more common, we additionally develop a methodology,
which is based on market prices of American at-the-money options.
This method relies on a linear combination of no-arbitrage bounds of the dividends,
where the corresponding optimal weight is determined via a historical
least squares estimation using realized dividends. We demonstrate our method
using all Dow Jones Industrial Average constituents and provide a robustness
check with respect to the used discount factor. Furthermore, we backtest our
results against the method using European options and against a so called
simple estimate.
In the last part of the thesis we solve the terminal wealth portfolio optimization
problem for a dividend paying stock. In the case of the logarithmic utility
function, we show that the optimal strategy is not a constant anymore but
connected to the Merton strategy. Additionally, we solve a special optimal
consumption problem, where the investor is only allowed to consume dividends.
We show that this problem can be reduced to the before solved terminal wealth
problem.

In this thesis, we deal with the finite group of Lie type \(F_4(2^n)\). The aim is to find information on the \(l\)-decomposition numbers of \(F_4(2^n)\) on unipotent blocks for \(l\neq2\) and \(n\in \mathbb{N}\) arbitrary and on the irreducible characters of the Sylow \(2\)-subgroup of \(F_4(2^n)\).
S. M. Goodwin, T. Le, K. Magaard and A. Paolini have found a parametrization of the irreducible characters of the unipotent subgroup \(U\) of \(F_4(q)\), a Sylow \(2\)-subgroup of \(F_4(q)\), of \(F_4(p^n)\), \(p\) a prime, for the case \(p\neq2\).
We managed to adapt their methods for the parametrization of the irreducible characters of the Sylow \(2\)-subgroup for the case \(p=2\) for the group \(F_4(q)\), \(q=p^n\). This gives a nearly complete parametrization of the irreducible characters of the unipotent subgroup \(U\) of \(F_4(q)\), namely of all irreducible characters of \(U\) arising from so-called abelian cores.
The general strategy we have applied to obtain information about the \(l\)-decomposition numbers on unipotent blocks is to induce characters of the unipotent subgroup \(U\) of \(F_4(q)\) and Harish-Chandra induce projective characters of proper Levi subgroups of \(F_4(q)\) to obtain projective characters of \(F_4(q)\). Via Brauer reciprocity, the multiplicities of the ordinary irreducible unipotent characters in these projective characters give us information on the \(l\)-decomposition numbers of the unipotent characters of \(F_4(q)\).
Sadly, the projective characters of \(F_4(q)\) we obtained were not sufficient to give the shape of the entire decomposition matrix.