L4

Heterogeneity is a fundamental feature of biological systems. Oncology is one of the fields in which this feature is most evident, as its key players are characterised by mutability, plasticity, and often “uncontrolled” dynamics. Whether heterogeneity arises from spatial structure, environmental variability, or cellular traits, effective therapeutic strategies must explicitly account for it in order to eradicate or control tumours.

From a modern perspective, this requires balancing the hit-hard / keep-it-sensitive trade-off, while also considering not only medical but also broader patient-related side effects of treatments. Contemporary medicine is increasingly exploring ways to exploit the very characteristics that have historically made cancer so dangerous, turning them into potential advantages for therapy.

The multiscale nature of tumour systems, together with the need to predict the combined effects of multiple, non-parallelisable processes, makes the development of optimised mathematical tools particularly compelling. Such tools can address questions that are both scientifically challenging and highly relevant from a clinical and humanitarian perspective.

In this seminar, we will analyse tumour masses from a structured population perspective, focusing on the role of heterogeneity in shaping therapeutic strategies. We will first discuss how heterogeneity in phenotypic composition and nutrient distribution influences the eco-evolutionary dynamics of tumour growth. We will then consider more specifically its impact on radiotherapy.

In particular, we will highlight the advantages of mathematically rigorous modelling in bridging theory and biology. We will also adopt a more exploratory perspective, using these models to illustrate how mathematics can serve as a potential decision-support tool for the selection and optimisation of treatment protocols, within an image- and model-driven framework.

The final part of the seminar will focus on potential future developments, with the aim of fostering an open and collaborative discussion on novel perspectives to improve understanding, prediction, and therapeutic optimisation.

Prostate cancer progression and therapeutic resistance present significant clinical challenges, particularly in the transition to castration-resistant disease. Although androgen deprivation therapy and second-generation drugs have improved patient outcomes, resistance frequently develops, reflecting tumour heterogeneity and the influence of its microenvironment. This talk presents two interdisciplinary studies that address these issues through data-driven mathematical approaches. We show how integrating experimental data with mathematical and statistical modelling can improve our understanding of prostate cancer dynamics and inform more effective, context-specific therapeutic strategies. The first study examines drug resistance and tumour evolution under treatment. We develop a multi-scale hybrid modelling framework to capture processes occurring across different temporal scales. Partial differential equations describe the behaviour of drugs and other chemicals in the tumour microenvironment (over the ‘fast’ timescale), while a cellular automaton captures the dynamics of tumour cells (over the ‘slow’ timescale). Through computational analysis of the model solutions, we examine the spatial dynamics of tumour cells, assess the efficacy of different drug therapies in inhibiting prostate cancer growth, and identify effective drug combinations and treatment schedules to limit tumour progression and prevent metastasis. The second study focuses on the role of host–microbiome interactions in obesity-associated prostate cancer. Using data from experiments with the TRAMP mouse model, we apply statistical and machine learning methods, including generalised linear models, Granger causality, and support vector regression, to characterise microbial dynamics and their responses to treatment. These findings are incorporated into a dynamical systems framework that captures microbiome–tumour co-evolution under therapeutic and dietary perturbations, providing insight into how dietary fat and combination therapies involving enzalutamide and phytocannabinoids influence tumour progression and gut microbiota composition.

Reaction systems are continuos-time dynamical systems with polynomial right-hand side, and are very common in biochemistry, cell signaling, population dynamics, and many other biological applications. We discuss global stability (i.e., the existence of a globally attracting point) and persistence (i.e., robust absence of extinction) for large classes of reaction systems. In particular, we describe recent progress on the proof of the Global Attractor Conjecture (which says that vertex-balanced reaction systems are globally stable) and the Persistence Conjecture (which says that weakly-reversible reaction systems are persistent), and how these results can be extended outside their classical setting using the notion of “disguised reaction systems". We will also discuss analogous results for the case where reaction systems are replaced by generalized Lotka-Volterra systems of arbitrary degree. 

Let G be a finite Chevalley group, i.e., the group of F_q points of a reductive group over F_q. Virtual representations of G in defining characteristic can be constructed in two ways, either by Brauer-Nesbitt reduction of complex representations, or by restricting an algebraic representation. G. Lusztig conjectured the shape of formulas connecting the two procedures; I will discuss a realization of his proposal related to decomposition of the class of diagonal for G/B coming from summands in the push-forward of the structure sheaf under Frobenius. 

Time permitting I will discuss a different, unrelated at present, way to describe such virtual representations linking it to homology of an affine Springer fiber. This found application in the work of Tony Feng and Viet Bao Le Hung on Breuil-Mezard conjectures. 

Based on joint works with Finkelberg, Kazhdan and Morton-Ferguson and with Boixeda Alvarez, McBreen and Yun respectively.

Weighted flag varieties are generalizations of flag varieties and weighted projective spaces.  Although they are not usually homogeneous varieties, they are orbifolds and admit a torus action with isolated fixed points, and like ordinary flag varieties, their equivariant cohomology admits a Schubert basis.  This talk will be an introduction to weighted flag varieties, and will also discuss positivity.  Abe and Matsumura proved that the equivariant cohomology of weighted Grassmannians has a positivity property analogous to that for ordinary (non-weighted) flag varieties.  We prove a strengthened version of this result for arbitrary weighted flag varieties, along the way providing a geometric interpretation of the weighted roots of Abe and Matsumura.  This is joint work with Scott Larson.

In this talk, I present an explicit formula for the ADM mass of asymptotically locally Euclidean (ALE) almost Kähler manifolds. The formula expresses the mass in terms of the total Hermitian scalar curvature and topological data associated with the underlying almost complex structure, extending a result of Hein and LeBrun in the Kähler ALE case. The proof is based on a spin-c adaptation of Witten's proof of the positive mass conjecture in the spin case and is therefore distinct from previous complex-geometric methods. In dimension 4, I show that one can prove a positive mass theorem and a Penrose-type inequality for asymptotically Euclidean (AE) almost Kähler manifolds using this formula.

We describe the solution to two problems concerning indefinite integral ternary quadratic forms. The first about anisotropic forms was popularized by Margulis following his solution of the Oppenheim Conjecture. The second about the density of isotropic forms was raised by Serre. Joint work with A. Gamburd, A. Ghosh and J. Whang.

In the context of Fourier analysis on the real line, a \textit{one-sided problem} involves deducing properties of a function $f$ from some information about the restriction of its Fourier transform $\widehat{f}$ to a half-line, for instance to $\mathbb{R}_- := (-\infty, 0)$. A prototypical result, which is foundational to the theory of Hardy spaces on $\mathbb{R}$, asserts that if $f \in L^2(\mathbb{R})$ is non-zero and $\widehat{f}$ vanishes on a half-line, then $f$ satisfies the \textit{Szeg\H{o} condition} $\int_{-\infty}^\infty \frac{\log |f(x)|}{1+x^2} \, dx > -\infty$. 

Various problems in operator theory involve the study of functions $f$ satisfying a weaker condition of decay of $\widehat{f}$ on a half-line. In this setting, simple examples show that the Szeg\H{o} condition need not be satisfied. However, the following local Szeg\H{o}-type conditions hold: if the decay of $\widehat{f}$ is strong enough on a half-line, then the mass of the function $f \in L^2(\mathbb{R})$ must concentrate enough for the integral $\int_E \log |f(x)| dx$ to converge on a "massive" set $E$. 

In his talk, Bartosz Malman will describe this mass condensation phenomenon and its applications to operator-theoretic problems.

It is known for a long time, due to a celebrated theorem of Ornstein and Weiss, that (classical/plain) orbit equivalence offers no information about ergodic probability measure preserving actions of amenable groups. On the other hand, conjugacy is too intractable, and effectively hopeless to study in full generality. Quantitative orbit equivalence aims to bridge this gap by adding intermediate layers of rigidity— a strategy that has borne fruit already in the late 1960s but was used as a general framework only semi-recently. In this talk, Spyridon Petrakos will introduce aspects of quantitative orbit equivalence and present a complete picture of it for integer odometers. This is joint work with Petr Naryshkin.