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In this thesis, a new concept to prove Mosco convergence of gradient-type Dirichlet forms within the \(L^2\)-framework of K.~Kuwae and T.~Shioya for varying reference measures is developed.
The goal is, to impose as little additional conditions as possible on the sequence of reference measure \({(\mu_N)}_{N\in \mathbb N}\), apart from weak convergence of measures.
Our approach combines the method of Finite Elements from numerical analysis with the topic of Mosco convergence.
We tackle the problem first on a finite-dimensional substructure of the \(L^2\)-framework, which is induced by finitely many basis functions on the state space \(\mathbb R^d\).
These are shifted and rescaled versions of the archetype tent function \(\chi^{(d)}\).
For \(d=1\) the archetype tent function is given by
\[\chi^{(1)}(x):=\big((-x+1)\land(x+1)\big)\lor 0,\quad x\in\mathbb R.\]
For \(d\geq 2\) we define a natural generalization of \(\chi^{(1)}\) as
\[\chi^{(d)}(x):=\Big(\min_{i,j\in\{1,\dots,d\}}\big(\big\{1+x_i-x_j,1+x_i,1-x_i\big\}\big)\Big)_+,\quad x\in\mathbb R^d.\]
Our strategy to obtain Mosco convergence of
\(\mathcal E^N(u,v)=\int_{\mathbb R^d}\langle\nabla u,\nabla v\rangle_\text{euc}d\mu_N\) towards \(\mathcal E(u,v)=\int_{\mathbb R^d}\langle\nabla u,\nabla v\rangle_\text{euc}d\mu\) for \(N\to\infty\)
involves as a preliminary step to restrict those bilinear forms to arguments \(u,v\) from the vector space spanned by the finite family \(\{\chi^{(d)}(\frac{\,\cdot\,}{r}-\alpha)\) \(|\alpha\in Z\}\) for
a finite index set \(Z\subset\mathbb Z^d\) and a scaling parameter \(r\in(0,\infty)\).
In a diagonal procedure, we consider a zero-sequence of scaling parameters and a sequence of index sets exhausting \(\mathbb Z^d\).
The original problem of Mosco convergence, \(\mathcal E^N\) towards \(\mathcal E\) w.r.t.~arguments \(u,v\) form the respective minimal closed form domains extending the pre-domain \(C_b^1(\mathbb R^d)\), can be solved
by such a diagonal procedure if we ask for some additional conditions on the Radon-Nikodym derivatives \(\rho_N(x)=\frac{d\mu_N(x)}{d x}\), \(N\in\mathbb N\). The essential requirement reads
\[\frac{1}{(2r)^d}\int_{[-r,r]^d}|\rho_N(x)- \rho_N(x+y)|d y \quad \overset{r\to 0}{\longrightarrow} \quad 0 \quad \text{in } L^1(d x),\,
\text{uniformly in } N\in\mathbb N.\]
As an intermediate step towards a setting with an infinite-dimensional state space, we let $E$ be a Suslin space and analyse the Mosco convergence of
\(\mathcal E^N(u,v)=\int_E\int_{\mathbb R^d}\langle\nabla_x u(z,x),\nabla_x v(z,x)\rangle_\text{euc}d\mu_N(z,x)\) with reference measure \(\mu_N\) on \(E\times\mathbb R^d\) for \(N\in\mathbb N\).
The form \(\mathcal E^N\) can be seen as a superposition of gradient-type forms on \(\mathbb R^d\).
Subsequently, we derive an abstract result on Mosco convergence for classical gradient-type Dirichlet forms
\(\mathcal E^N(u,v)=\int_E\langle \nabla u,\nabla v\rangle_Hd\mu_N\) with reference measure \(\mu_N\) on a Suslin space $E$ and a tangential Hilbert space \(H\subseteq E\).
The preceding analysis of superposed gradient-type forms can be used on the component forms \(\mathcal E^{N}_k\), which provide the decomposition
\(\mathcal E^{N}=\sum_k\mathcal E^{N}_k\). The index of the component \(k\) runs over a suitable orthonormal basis of admissible elements in \(H\).
For the asymptotic form \(\mathcal E\) and its component forms \(\mathcal E^k\), we have to assume \(D(\mathcal E)=\bigcap_kD(\mathcal E^k)\) regarding their domains, which is equivalent to the Markov uniqueness of \(\mathcal E\).
The abstract results are tested on an example from statistical mechanics.
Under a scaling limit, tightness of the family of laws for a microscopic dynamical stochastic interface model over \((0,1)^d\) is shown and its asymptotic Dirichlet form identified.
The considered model is based on a sequence of weakly converging Gaussian measures \({(\mu_N)}_{N\in\mathbb N}\) on \(L^2((0,1)^d)\), which are
perturbed by a class of physically relevant non-log-concave densities.
Colorectal cancer (CRC) is among the most frequent cancer entities worldwide. Multiple factors are causally associated with CRC development, such as genetic and epigenetic alterations,
inflammatory bowel disease, lifestyle and dietary factors. During malignant transformation,the cellular energy metabolism is reprogrammed in order to promote cancer cell growth and
proliferation. In this review, we first describe the main alterations of the energy metabolism found in CRC, revealing the critical impact of oncogenic signaling and driver mutations in key metabolic
enzymes. Then, the central role of mitochondria and the tricarboxylic acid (TCA) cycle in this process is highlighted, also considering the metabolic crosstalk between tumor and stromal cells in the
tumor microenvironment. The identified cancer-specific metabolic transformations provided new therapeutic targets for the development of small molecule inhibitors. Promising agents are in clinical
trials and are directed against enzymes of the TCA cycle, including isocitrate dehydrogenase, pyruvate dehydrogenase kinase, pyruvate dehydrogenase complex (PDC) and α-ketoglutarate dehydrogenase
(KGDH). Finally, we focus on the α-lipoic acid derivative CPI-613, an inhibitor of both PDC and KGDH, and delineate its anti-tumor effects for targeted therapy.
Heme oxygenase-1 (HO-1) is an enzyme located at the endoplasmic reticulum, which is responsible for the degradation of cellular heme into ferrous iron, carbon monoxide and biliverdin-IXa. In addition to this main function, the enzyme is involved in many other homeostatic, toxic and cancer-related mechanisms. In this review, we first summarize the importance of HO-1 in
physiology and pathophysiology with a focus on the digestive system. We then detail its structure and function, followed by a section on the regulatory mechanisms that control HO-1 expression and activity. Moreover, HO-2 as important further HO isoform is discussed, highlighting the similarities
and differences with regard to HO-1. Subsequently, we describe the direct and indirect cytoprotective functions of HO-1 and its breakdown products carbon monoxide and biliverdin-IXa, but also highlight possible pro-inflammatory effects. Finally, we address the role of HO-1 in cancer with a particular
focus on colorectal cancer. Here, relevant pathways and mechanisms are presented, through which HO-1 impacts tumor induction and tumor progression. These include oxidative stress and DNA damage, ferroptosis, cell cycle progression and apoptosis as well as migration, proliferation, and
epithelial-mesenchymal transition.