@phdthesis{7196, abstract = {In this thesis we study certain mathematical aspects of evolution. The two primary forces that drive an evolutionary process are mutation and selection. Mutation generates new variants in a population. Selection chooses among the variants depending on the reproductive rates of individuals. Evolutionary processes are intrinsically random – a new mutation that is initially present in the population at low frequency can go extinct, even if it confers a reproductive advantage. The overall rate of evolution is largely determined by two quantities: the probability that an invading advantageous mutation spreads through the population (called fixation probability) and the time until it does so (called fixation time). Both those quantities crucially depend not only on the strength of the invading mutation but also on the population structure. In this thesis, we aim to understand how the underlying population structure affects the overall rate of evolution. Specifically, we study population structures that increase the fixation probability of advantageous mutants (called amplifiers of selection). Broadly speaking, our results are of three different types: We present various strong amplifiers, we identify regimes under which only limited amplification is feasible, and we propose population structures that provide different tradeoffs between high fixation probability and short fixation time.}, author = {Tkadlec, Josef}, issn = {2663-337X}, pages = {144}, publisher = {Institute of Science and Technology Austria}, title = {{A role of graphs in evolutionary processes}}, doi = {10.15479/AT:ISTA:7196}, year = {2020}, } @inproceedings{10190, abstract = {The verification of concurrent programs remains an open challenge, as thread interaction has to be accounted for, which leads to state-space explosion. Stateless model checking battles this problem by exploring traces rather than states of the program. As there are exponentially many traces, dynamic partial-order reduction (DPOR) techniques are used to partition the trace space into equivalence classes, and explore a few representatives from each class. The standard equivalence that underlies most DPOR techniques is the happens-before equivalence, however recent works have spawned a vivid interest towards coarser equivalences. The efficiency of such approaches is a product of two parameters: (i) the size of the partitioning induced by the equivalence, and (ii) the time spent by the exploration algorithm in each class of the partitioning. In this work, we present a new equivalence, called value-happens-before and show that it has two appealing features. First, value-happens-before is always at least as coarse as the happens-before equivalence, and can be even exponentially coarser. Second, the value-happens-before partitioning is efficiently explorable when the number of threads is bounded. We present an algorithm called value-centric DPOR (VCDPOR), which explores the underlying partitioning using polynomial time per class. Finally, we perform an experimental evaluation of VCDPOR on various benchmarks, and compare it against other state-of-the-art approaches. Our results show that value-happens-before typically induces a significant reduction in the size of the underlying partitioning, which leads to a considerable reduction in the running time for exploring the whole partitioning.}, author = {Chatterjee, Krishnendu and Pavlogiannis, Andreas and Toman, Viktor}, booktitle = {Proceedings of the 34th ACM International Conference on Object-Oriented Programming, Systems, Languages, and Applications}, issn = {2475-1421}, keywords = {safety, risk, reliability and quality, software}, location = {Athens, Greece}, publisher = {ACM}, title = {{Value-centric dynamic partial order reduction}}, doi = {10.1145/3360550}, volume = {3}, year = {2019}, } @phdthesis{6825, abstract = {The solving of complex tasks requires the functions of more than one brain area and their interaction. Whilst spatial navigation and memory is dependent on the hippocampus, flexible behavior relies on the medial prefrontal cortex (mPFC). To further examine the roles of the hippocampus and mPFC, we recorded their neural activity during a task that depends on both of these brain regions. With tetrodes, we recorded the extracellular activity of dorsal hippocampal CA1 (HPC) and mPFC neurons in Long-Evans rats performing a rule-switching task on the plus-maze. The plus-maze task had a spatial component since it required navigation along one of the two start arms and at the maze center a choice between one of the two goal arms. Which goal contained a reward depended on the rule currently in place. After an uncued rule change the animal had to abandon the old strategy and switch to the new rule, testing cognitive flexibility. Investigating the coordination of activity between the HPC and mPFC allows determination during which task stages their interaction is required. Additionally, comparing neural activity patterns in these two brain regions allows delineation of the specialized functions of the HPC and mPFC in this task. We analyzed neural activity in the HPC and mPFC in terms of oscillatory interactions, rule coding and replay. We found that theta coherence between the HPC and mPFC is increased at the center and goals of the maze, both when the rule was stable or has changed. Similar results were found for locking of HPC and mPFC neurons to HPC theta oscillations. However, no differences in HPC-mPFC theta coordination were observed between the spatially- and cue-guided rule. Phase locking of HPC and mPFC neurons to HPC gamma oscillations was not modulated by maze position or rule type. We found that the HPC coded for the two different rules with cofiring relationships between cell pairs. However, we could not find conclusive evidence for rule coding in the mPFC. Spatially-selective firing in the mPFC generalized between the two start and two goal arms. With Bayesian positional decoding, we found that the mPFC reactivated non-local positions during awake immobility periods. Replay of these non-local positions could represent entire behavioral trajectories resembling trajectory replay of the HPC. Furthermore, mPFC trajectory-replay at the goal positively correlated with rule-switching performance. Finally, HPC and mPFC trajectory replay occurred independently of each other. These results show that the mPFC can replay ordered patterns of activity during awake immobility, possibly underlying its role in flexible behavior. }, author = {Käfer, Karola}, issn = {2663-337X}, pages = {89}, publisher = {Institute of Science and Technology Austria}, title = {{The hippocampus and medial prefrontal cortex during flexible behavior}}, doi = {10.15479/AT:ISTA:6825}, year = {2019}, } @article{19544, abstract = {Medicinal bioinorganic chemistry is a thriving field of drug research for cancer treatment. Transition metal complexes coordinated to essential biological scaffolds represent a highly promising class of compounds for design of novel target-specific therapeutics. We report here the biological evaluation of a novel Isatin-Schiff base derivative and its Cu(II) complex in several tumor cell lines by assessing their effects on cellular metabolism, real-time cell proliferation and induction of apoptosis. Further, the impact of compounds on the p53 protein and expression of its target genes, including MDM2, p21/CDKN1A, and PUMA was evaluated. Results obtained in this study provide further evidence in support of our prior data suggesting the p53-mediated mechanism of action for Isatin-Schiff base derivatives and their complexes and also shed light on potential use of these compounds for stimulation of apoptosis in breast cancer cells via activation of the pro-apoptotic PUMA gene.}, author = {Bulatov, Emil and Sayarova, Regina and Mingaleeva, Rimma and Miftakhova, Regina and Gomzikova, Marina and Ignatev, Iurii and Petukhov, Alexey and Davidovich, Pavel and Rizvanov, Albert and Barlev, Nickolai A.}, issn = {2058-7716}, journal = {Cell Death Discovery}, publisher = {Springer Nature}, title = {{Isatin-Schiff base-copper (II) complex induces cell death in p53-positive tumors}}, doi = {10.1038/s41420-018-0120-z}, volume = {4}, year = {2018}, } @article{104, abstract = {The biotrophic pathogen Ustilago maydis, the causative agent of corn smut disease, infects one of the most important crops worldwide – Zea mays. To successfully colonize its host, U. maydis secretes proteins, known as effectors, that suppress plant defense responses and facilitate the establishment of biotrophy. In this work, we describe the U. maydis effector protein Cce1. Cce1 is essential for virulence and is upregulated during infection. Through microscopic analysis and in vitro assays, we show that Cce1 is secreted from hyphae during filamentous growth of the fungus. Strikingly, Δcce1 mutants are blocked at early stages of infection and induce callose deposition as a plant defense response. Cce1 is highly conserved among smut fungi and the Ustilago bromivora ortholog complemented the virulence defect of the SG200Δcce1 deletion strain. These data indicate that Cce1 is a core effector with apoplastic localization that is essential for U. maydis to infect its host.}, author = {Seitner, Denise and Uhse, Simon and Gallei, Michelle C and Djamei, Armin}, journal = {Molecular Plant Pathology}, number = {10}, pages = {2277 -- 2287}, publisher = {Wiley}, title = {{The core effector Cce1 is required for early infection of maize by Ustilago maydis}}, doi = {10.1111/mpp.12698}, volume = {19}, year = {2018}, } @phdthesis{69, abstract = {A qubit, a unit of quantum information, is essentially any quantum mechanical two-level system which can be coherently controlled. Still, to be used for computation, it has to fulfill criteria. Qubits, regardless of the system in which they are realized, suffer from decoherence. This leads to loss of the information stored in the qubit. The upper bound of the time scale on which decoherence happens is set by the spin relaxation time. In this thesis I studied a two-level system consisting of a Zeeman-split hole spin confined in a quantum dot formed in a Ge hut wire. Such Ge hut wires have emerged as a promising material system for the realization of spin qubits, due to the combination of two significant properties: long spin coherence time as expected for group IV semiconductors due to the low hyperfine interaction and a strong valence band spin-orbit coupling. Here, I present how to fabricate quantum dot devices suitable for electrical transport measurements. Coupled quantum dot devices allowed the realization of a charge sensor, which is electrostatically and tunnel coupled to a quantum dot. By integrating the charge sensor into a radio-frequency reflectometry setup, I performed for the first time single-shot readout measurements of hole spins and extracted the hole spin relaxation times in Ge hut wires.}, author = {Vukušić, Lada}, issn = {2663-337X}, pages = {103}, publisher = {Institute of Science and Technology Austria}, title = {{Charge sensing and spin relaxation times of holes in Ge hut wires}}, doi = {10.15479/AT:ISTA:TH_1047}, year = {2018}, } @phdthesis{1398, abstract = {Hybrid zones represent evolutionary laboratories, where recombination brings together alleles in combinations which have not previously been tested by selection. This provides an excellent opportunity to test the effect of molecular variation on fitness, and how this variation is able to spread through populations in a natural context. The snapdragon Antirrhinum majus is polymorphic in the wild for two loci controlling the distribution of yellow and magenta floral pigments. Where the yellow A. m. striatum and the magenta A. m. pseudomajus meet along a valley in the Spanish Pyrenees they form a stable hybrid zone Alleles at these loci recombine to give striking transgressive variation for flower colour. The sharp transition in phenotype over ~1km implies strong selection maintaining the hybrid zone. An indirect assay of pollinator visitation in the field found that pollinators forage in a positive-frequency dependent manner on Antirrhinum, matching previous data on fruit set. Experimental arrays and paternity analysis of wild-pollinated seeds demonstrated assortative mating for pigmentation alleles, and that pollinator behaviour alone is sufficient to explain this pattern. Selection by pollinators should be sufficiently strong to maintain the hybrid zone, although other mechanisms may be at work. At a broader scale I examined evolutionary transitions between yellow and anthocyanin pigmentation in the tribe Antirrhinae, and found that selection has acted strate that pollinators are a major determinant of reproductive success and mating patterns in wild Antirrhinum.}, author = {Ellis, Thomas}, issn = {2663-337X}, pages = {130}, publisher = {Institute of Science and Technology Austria}, title = {{The role of pollinator-mediated selection in the maintenance of a flower color polymorphism in an Antirrhinum majus hybrid zone}}, doi = {10.15479/AT:ISTA:TH_526 }, year = {2016}, } @phdthesis{1130, abstract = {In this thesis we present a computer-aided programming approach to concurrency. Our approach helps the programmer by automatically fixing concurrency-related bugs, i.e. bugs that occur when the program is executed using an aggressive preemptive scheduler, but not when using a non-preemptive (cooperative) scheduler. Bugs are program behaviours that are incorrect w.r.t. a specification. We consider both user-provided explicit specifications in the form of assertion statements in the code as well as an implicit specification. The implicit specification is inferred from the non-preemptive behaviour. Let us consider sequences of calls that the program makes to an external interface. The implicit specification requires that any such sequence produced under a preemptive scheduler should be included in the set of sequences produced under a non-preemptive scheduler. We consider several semantics-preserving fixes that go beyond atomic sections typically explored in the synchronisation synthesis literature. Our synthesis is able to place locks, barriers and wait-signal statements and last, but not least reorder independent statements. The latter may be useful if a thread is released to early, e.g., before some initialisation is completed. We guarantee that our synthesis does not introduce deadlocks and that the synchronisation inserted is optimal w.r.t. a given objective function. We dub our solution trace-based synchronisation synthesis and it is loosely based on counterexample-guided inductive synthesis (CEGIS). The synthesis works by discovering a trace that is incorrect w.r.t. the specification and identifying ordering constraints crucial to trigger the specification violation. Synchronisation may be placed immediately (greedy approach) or delayed until all incorrect traces are found (non-greedy approach). For the non-greedy approach we construct a set of global constraints over synchronisation placements. Each model of the global constraints set corresponds to a correctness-ensuring synchronisation placement. The placement that is optimal w.r.t. the given objective function is chosen as the synchronisation solution. We evaluate our approach on a number of realistic (albeit simplified) Linux device-driver benchmarks. The benchmarks are versions of the drivers with known concurrency-related bugs. For the experiments with an explicit specification we added assertions that would detect the bugs in the experiments. Device drivers lend themselves to implicit specification, where the device and the operating system are the external interfaces. Our experiments demonstrate that our synthesis method is precise and efficient. We implemented objective functions for coarse-grained and fine-grained locking and observed that different synchronisation placements are produced for our experiments, favouring e.g. a minimal number of synchronisation operations or maximum concurrency.}, author = {Tarrach, Thorsten}, issn = {2663-337X}, pages = {151}, publisher = {Institute of Science and Technology Austria}, title = {{Automatic synthesis of synchronisation primitives for concurrent programs}}, doi = {10.15479/at:ista:1130}, year = {2016}, } @phdthesis{1401, abstract = {The human ability to recognize objects in complex scenes has driven research in the computer vision field over couple of decades. This thesis focuses on the object recognition task in images. That is, given the image, we want the computer system to be able to predict the class of the object that appears in the image. A recent successful attempt to bridge semantic understanding of the image perceived by humans and by computers uses attribute-based models. Attributes are semantic properties of the objects shared across different categories, which humans and computers can decide on. To explore the attribute-based models we take a statistical machine learning approach, and address two key learning challenges in view of object recognition task: learning augmented attributes as mid-level discriminative feature representation, and learning with attributes as privileged information. Our main contributions are parametric and non-parametric models and algorithms to solve these frameworks. In the parametric approach, we explore an autoencoder model combined with the large margin nearest neighbor principle for mid-level feature learning, and linear support vector machines for learning with privileged information. In the non-parametric approach, we propose a supervised Indian Buffet Process for automatic augmentation of semantic attributes, and explore the Gaussian Processes classification framework for learning with privileged information. A thorough experimental analysis shows the effectiveness of the proposed models in both parametric and non-parametric views.}, author = {Sharmanska, Viktoriia}, issn = {2663-337X}, pages = {144}, publisher = {Institute of Science and Technology Austria}, title = {{Learning with attributes for object recognition: Parametric and non-parametrics views}}, doi = {10.15479/at:ista:1401}, year = {2015}, } @phdthesis{1405, abstract = {Motivated by the analysis of highly dynamic message-passing systems, i.e. unbounded thread creation, mobility, etc. we present a framework for the analysis of depth-bounded systems. Depth-bounded systems are one of the most expressive known fragment of the π-calculus for which interesting verification problems are still decidable. Even though they are infinite state systems depth-bounded systems are well-structured, thus can be analyzed algorithmically. We give an interpretation of depth-bounded systems as graph-rewriting systems. This gives more flexibility and ease of use to apply depth-bounded systems to other type of systems like shared memory concurrency. First, we develop an adequate domain of limits for depth-bounded systems, a prerequisite for the effective representation of downward-closed sets. Downward-closed sets are needed by forward saturation-based algorithms to represent potentially infinite sets of states. Then, we present an abstract interpretation framework to compute the covering set of well-structured transition systems. Because, in general, the covering set is not computable, our abstraction over-approximates the actual covering set. Our abstraction captures the essence of acceleration based-algorithms while giving up enough precision to ensure convergence. We have implemented the analysis in the PICASSO tool and show that it is accurate in practice. Finally, we build some further analyses like termination using the covering set as starting point.}, author = {Zufferey, Damien}, issn = {2663-337X}, pages = {134}, publisher = {Institute of Science and Technology Austria}, title = {{Analysis of dynamic message passing programs}}, doi = {10.15479/at:ista:1405}, year = {2013}, } @phdthesis{2964, abstract = {CA3 pyramidal neurons are important for memory formation and pattern completion in the hippocampal network. These neurons receive multiple excitatory inputs from numerous sources. Therefore, the rules of spatiotemporal integration of multiple synaptic inputs and propagation of action potentials are important to understand how CA3 neurons contribute to higher brain functions at cellular level. By using confocally targeted patch-clamp recording techniques, we investigated the biophysical properties of rat CA3 pyramidal neuron dendrites. We found two distinct dendritic domains critical for action potential initiation and propagation: In the proximal domain, action potentials initiated in the axon backpropagate actively with large amplitude and fast time course. In the distal domain, Na+-channel mediated dendritic spikes are efficiently evoked by local dendritic depolarization or waveforms mimicking synaptic events. These findings can be explained by a high Na+-to-K+ conductance density ratio of CA3 pyramidal neuron dendrites. The results challenge the prevailing view that proximal mossy fiber inputs activate CA3 pyramidal neurons more efficiently than distal perforant inputs by showing that the distal synapses trigger a different form of activity represented by dendritic spikes. The high probability of dendritic spike initiation in the distal area may enhance the computational power of CA3 pyramidal neurons in the hippocampal network. }, author = {Kim, Sooyun}, issn = {2663-337X}, pages = {65}, publisher = {Institute of Science and Technology Austria}, title = {{Active properties of hippocampal CA3 pyramidal neuron dendrites}}, year = {2012}, } @phdthesis{3962, author = {Pflicke, Holger}, issn = {2663-337X}, publisher = {Institute of Science and Technology Austria}, title = {{Dendritic cell migration across basement membranes in the skin}}, year = {2010}, }