TY - THES
AB - In the first part of the thesis we consider Hermitian random matrices. Firstly, we consider sample covariance matrices XX∗ with X having independent identically distributed (i.i.d.) centred entries. We prove a Central Limit Theorem for differences of linear statistics of XX∗ and its minor after removing the first column of X. Secondly, we consider Wigner-type matrices and prove that the eigenvalue statistics near cusp singularities of the limiting density of states are universal and that they form a Pearcey process. Since the limiting eigenvalue distribution admits only square root (edge) and cubic root (cusp) singularities, this concludes the third and last remaining case of the Wigner-Dyson-Mehta universality conjecture. The main technical ingredients are an optimal local law at the cusp, and the proof of the fast relaxation to equilibrium of the Dyson Brownian motion in the cusp regime.
In the second part we consider non-Hermitian matrices X with centred i.i.d. entries. We normalise the entries of X to have variance N −1. It is well known that the empirical eigenvalue density converges to the uniform distribution on the unit disk (circular law). In the first project, we prove universality of the local eigenvalue statistics close to the edge of the spectrum. This is the non-Hermitian analogue of the TracyWidom universality at the Hermitian edge. Technically we analyse the evolution of the spectral distribution of X along the Ornstein-Uhlenbeck flow for very long time
(up to t = +∞). In the second project, we consider linear statistics of eigenvalues for macroscopic test functions f in the Sobolev space H2+ϵ and prove their convergence to the projection of the Gaussian Free Field on the unit disk. We prove this result for non-Hermitian matrices with real or complex entries. The main technical ingredients are: (i) local law for products of two resolvents at different spectral parameters, (ii) analysis of correlated Dyson Brownian motions.
In the third and final part we discuss the mathematically rigorous application of supersymmetric techniques (SUSY ) to give a lower tail estimate of the lowest singular value of X − z, with z ∈ C. More precisely, we use superbosonisation formula to give an integral representation of the resolvent of (X − z)(X − z)∗ which reduces to two and three contour integrals in the complex and real case, respectively. The rigorous analysis of these integrals is quite challenging since simple saddle point analysis cannot be applied (the main contribution comes from a non-trivial manifold). Our result
improves classical smoothing inequalities in the regime |z| ≈ 1; this result is essential to prove edge universality for i.i.d. non-Hermitian matrices.
AU - Cipolloni, Giorgio
ID - 9022
TI - Fluctuations in the spectrum of random matrices
ER -
TY - THES
AB - In this thesis we study persistence of multi-covers of Euclidean balls and the geometric structures underlying their computation, in particular Delaunay mosaics and Voronoi tessellations.
The k-fold cover for some discrete input point set consists of the space where at least k balls of radius r around the input points overlap. Persistence is a notion that captures, in some sense, the topology of the shape underlying the input. While persistence is usually computed for the union of balls, the k-fold cover is of interest as it captures local density,
and thus might approximate the shape of the input better if the input data is noisy. To compute persistence of these k-fold covers, we need a discretization that is provided by higher-order Delaunay mosaics.
We present and implement a simple and efficient algorithm for the computation of higher-order Delaunay mosaics, and use it to give experimental results for their combinatorial properties. The algorithm makes use of a new geometric structure, the rhomboid tiling. It contains the higher-order Delaunay mosaics as slices, and by introducing a filtration
function on the tiling, we also obtain higher-order α-shapes as slices. These allow us to compute persistence of the multi-covers for varying radius r; the computation for varying k is less straight-foward and involves the rhomboid tiling directly. We apply our algorithms to experimental sphere packings to shed light on their structural properties. Finally, inspired by periodic structures in packings and materials, we propose and implement an algorithm for periodic Delaunay triangulations to be integrated into the Computational Geometry Algorithms Library (CGAL), and discuss
the implications on persistence for periodic data sets.
AU - Osang, Georg F
ID - 9056
SN - 2663-337X
TI - Multi-cover persistence and Delaunay mosaics
ER -
TY - THES
AB - In this thesis, we consider several of the most classical and fundamental problems in static analysis and formal verification, including invariant generation, reachability analysis, termination analysis of probabilistic programs, data-flow analysis, quantitative analysis of Markov chains and Markov decision processes, and the problem of data packing in cache management.
We use techniques from parameterized complexity theory, polyhedral geometry, and real algebraic geometry to significantly improve the state-of-the-art, in terms of both scalability and completeness guarantees, for the mentioned problems. In some cases, our results are the first theoretical improvements for the respective problems in two or three decades.
AU - Goharshady, Amir Kafshdar
ID - 8934
SN - 2663-337X
TI - Parameterized and algebro-geometric advances in static program analysis
ER -
TY - THES
AB - Quantum computation enables the execution of algorithms that have exponential complexity. This might open the path towards the synthesis of new materials or medical drugs, optimization of transport or financial strategies etc., intractable on even the fastest classical computers. A quantum computer consists of interconnected two level quantum systems, called qubits, that satisfy DiVincezo’s criteria. Worldwide, there are ongoing efforts to find the qubit architecture which will unite quantum error correction compatible single and two qubit fidelities, long distance qubit to qubit coupling and
calability. Superconducting qubits have gone the furthest in this race, demonstrating an algorithm running on 53 coupled qubits, but still the fidelities are not even close to those required for realizing a single logical qubit. emiconductor qubits offer extremely good characteristics, but they are currently investigated across different platforms. Uniting those good characteristics into a single platform might be a big step towards the quantum computer realization.
Here we describe the implementation of a hole spin qubit hosted in a Ge hut wire double quantum dot. The high and tunable spin-orbit coupling together with a heavy hole state character is expected to allow fast spin manipulation and long coherence times. Furthermore large lever arms, for hut wire devices, should allow good coupling to superconducting resonators enabling efficient long distance spin to spin coupling and a sensitive gate reflectometry spin readout. The developed cryogenic setup (printed circuit board sample holders, filtering, high-frequency wiring) enabled us to perform low temperature spin dynamics experiments. Indeed, we measured the fastest single spin qubit Rabi frequencies reported so far, reaching 140 MHz, while the dephasing times of 130 ns oppose the long decoherence predictions. In order to further investigate this, a double quantum dot gate was connected directly to a lumped element
resonator which enabled gate reflectometry readout. The vanishing inter-dot transition signal, for increasing external magnetic field, revealed the spin nature of the measured quantity.
AU - Kukucka, Josip
ID - 7996
TI - Implementation of a hole spin qubit in Ge hut wires and dispersive spin sensing
ER -
TY - THES
AB - Algorithms in computational 3-manifold topology typically take a triangulation as an input and return topological information about the underlying 3-manifold. However, extracting the desired information from a triangulation (e.g., evaluating an invariant) is often computationally very expensive. In recent years this complexity barrier has been successfully tackled in some cases by importing ideas from the theory of parameterized algorithms into the realm of 3-manifolds. Various computationally hard problems were shown to be efficiently solvable for input triangulations that are sufficiently “tree-like.”
In this thesis we focus on the key combinatorial parameter in the above context: we consider the treewidth of a compact, orientable 3-manifold, i.e., the smallest treewidth of the dual graph of any triangulation thereof. By building on the work of Scharlemann–Thompson and Scharlemann–Schultens–Saito on generalized Heegaard splittings, and on the work of Jaco–Rubinstein on layered triangulations, we establish quantitative relations between the treewidth and classical topological invariants of a 3-manifold. In particular, among other results, we show that the treewidth of a closed, orientable, irreducible, non-Haken 3-manifold is always within a constant factor of its Heegaard genus.
AU - Huszár, Kristóf
ID - 8032
SN - 2663-337X
TI - Combinatorial width parameters for 3-dimensional manifolds
ER -
TY - THES
AB - In the thesis we focus on the interplay of the biophysics and evolution of gene regulation. We start by addressing how the type of prokaryotic gene regulation – activation and repression – affects spurious binding to DNA, also known as
transcriptional crosstalk. We propose that regulatory interference caused by excess regulatory proteins in the dense cellular medium – global crosstalk – could be a factor in determining which type of gene regulatory network is evolutionarily preferred. Next,we use a normative approach in eukaryotic gene regulation to describe minimal
non-equilibrium enhancer models that optimize so-called regulatory phenotypes. We find a class of models that differ from standard thermodynamic equilibrium models by a single parameter that notably increases the regulatory performance. Next chapter addresses the question of genotype-phenotype-fitness maps of higher dimensional phenotypes. We show that our biophysically realistic approach allows us to understand how the mechanisms of promoter function constrain genotypephenotype maps, and how they affect the evolutionary trajectories of promoters.
In the last chapter we ask whether the intrinsic instability of gene duplication and amplification provides a generic alternative to canonical gene regulation. Using mathematical modeling, we show that amplifications can tune gene expression in many environments, including those where transcription factor-based schemes are
hard to evolve or maintain.
AU - Grah, Rok
ID - 8155
SN - 2663-337X
TI - Gene regulation across scales – how biophysical constraints shape evolution
ER -
TY - THES
AB - We present solutions to several problems originating from geometry and discrete mathematics: existence of equipartitions, maps without Tverberg multiple points, and inscribing quadrilaterals. Equivariant obstruction theory is the natural topological approach to these type of questions. However, for the specific problems we consider it had yielded only partial or no results. We get our results by complementing equivariant obstruction theory with other techniques from topology and geometry.
AU - Avvakumov, Sergey
ID - 8156
TI - Topological methods in geometry and discrete mathematics
ER -
TY - THES
AB - Designing and verifying concurrent programs is a notoriously challenging, time consuming, and error prone task, even for experts. This is due to the sheer number of possible interleavings of a concurrent program, all of which have to be tracked and accounted for in a formal proof. Inventing an inductive invariant that captures all interleavings of a low-level implementation is theoretically possible, but practically intractable. We develop a refinement-based verification framework that provides mechanisms to simplify proof construction by decomposing the verification task into smaller subtasks.
In a first line of work, we present a foundation for refinement reasoning over structured concurrent programs. We introduce layered concurrent programs as a compact notation to represent multi-layer refinement proofs. A layered concurrent program specifies a sequence of connected concurrent programs, from most concrete to most abstract, such that common parts of different programs are written exactly once. Each program in this sequence is expressed as structured concurrent program, i.e., a program over (potentially recursive) procedures, imperative control flow, gated atomic actions, structured parallelism, and asynchronous concurrency. This is in contrast to existing refinement-based verifiers, which represent concurrent systems as flat transition relations. We present a powerful refinement proof rule that decomposes refinement checking over structured programs into modular verification conditions. Refinement checking is supported by a new form of modular, parameterized invariants, called yield invariants, and a linear permission system to enhance local reasoning.
In a second line of work, we present two new reduction-based program transformations that target asynchronous programs. These transformations reduce the number of interleavings that need to be considered, thus reducing the complexity of invariants. Synchronization simplifies the verification of asynchronous programs by introducing the fiction, for proof purposes, that asynchronous operations complete synchronously. Synchronization summarizes an asynchronous computation as immediate atomic effect. Inductive sequentialization establishes sequential reductions that captures every behavior of the original program up to reordering of coarse-grained commutative actions. A sequential reduction of a concurrent program is easy to reason about since it corresponds to a simple execution of the program in an idealized synchronous environment, where processes act in a fixed order and at the same speed.
Our approach is implemented the CIVL verifier, which has been successfully used for the verification of several complex concurrent programs. In our methodology, the overall correctness of a program is established piecemeal by focusing on the invariant required for each refinement step separately. While the programmer does the creative work of specifying the chain of programs and the inductive invariant justifying each link in the chain, the tool automatically constructs the verification conditions underlying each refinement step.
AU - Kragl, Bernhard
ID - 8332
SN - 2663-337X
TI - Verifying concurrent programs: Refinement, synchronization, sequentialization
ER -
TY - THES
AB - Mitochondria are sites of oxidative phosphorylation in eukaryotic cells. Oxidative phosphorylation operates by a chemiosmotic mechanism made possible by redox-driven proton pumping machines which establish a proton motive force across the inner mitochondrial membrane. This electrochemical proton gradient is used to drive ATP synthesis, which powers the majority of cellular processes such as protein synthesis, locomotion and signalling. In this thesis I investigate the structures and molecular mechanisms of two inner mitochondrial proton pumping enzymes, respiratory complex I and transhydrogenase. I present the first high-resolution structure of the full transhydrogenase from any species, and a significantly improved structure of complex I. Improving the resolution from 3.3 Å available previously to up to 2.3 Å in this thesis allowed us to model bound water molecules, crucial in the proton pumping mechanism. For both enzymes, up to five cryo-EM datasets with different substrates and inhibitors bound were solved to delineate the catalytic cycle and understand the proton pumping mechanism. In transhydrogenase, the proton channel is gated by reversible detachment of the NADP(H)-binding domain which opens the proton channel to the opposite sites of the membrane. In complex I, the proton channels are gated by reversible protonation of key glutamate and lysine residues and breaking of the water wire connecting the proton pumps with the quinone reduction site. The tight coupling between the redox and the proton pumping reactions in transhydrogenase is achieved by controlling the NADP(H) exchange which can only happen when the NADP(H)-binding domain interacts with the membrane domain. In complex I, coupling is achieved by cycling of the whole complex between the closed state, in which quinone can get reduced, and the open state, in which NADH can induce quinol ejection from the binding pocket. On the basis of these results I propose detailed mechanisms for catalytic cycles of transhydrogenase and complex I that are consistent with a large amount of previous work. In both enzymes, conformational and electrostatic mechanisms contribute to the overall catalytic process. Results presented here could be used for better understanding of the human pathologies arising from deficiencies of complex I or transhydrogenase and could be used to develop novel therapies.
AU - Kampjut, Domen
ID - 8340
SN - 978-3-99078-008-4
TI - Molecular mechanisms of mitochondrial redox-coupled proton pumping enzymes
ER -
TY - THES
AB - One of the most striking hallmarks of the eukaryotic cell is the presence of intracellular vesicles and organelles. Each of these membrane-enclosed compartments has a distinct composition of lipids and proteins, which is essential for accurate membrane traffic and homeostasis. Interestingly, their biochemical identities are achieved with the help
of small GTPases of the Rab family, which cycle between GDP- and GTP-bound forms on the selected membrane surface. While this activity switch is well understood for an individual protein, how Rab GTPases collectively transition between states to generate decisive signal propagation in space and time is unclear. In my PhD thesis, I present
in vitro reconstitution experiments with theoretical modeling to systematically study a minimal Rab5 activation network from bottom-up. We find that positive feedback based on known molecular interactions gives rise to bistable GTPase activity switching on system’s scale. Furthermore, we determine that collective transition near the critical
point is intrinsically stochastic and provide evidence that the inactive Rab5 abundance on the membrane can shape the network response. Finally, we demonstrate that collective switching can spread on the lipid bilayer as a traveling activation wave, representing a possible emergent activity pattern in endosomal maturation. Together, our
findings reveal new insights into the self-organization properties of signaling networks away from chemical equilibrium. Our work highlights the importance of systematic characterization of biochemical systems in well-defined physiological conditions. This way, we were able to answer long-standing open questions in the field and close the gap between regulatory processes on a molecular scale and emergent responses on system’s level.
AU - Bezeljak, Urban
ID - 8341
TI - In vitro reconstitution of a Rab activation switch
ER -