TY - JOUR AB - The physical conditions giving rise to high escape fractions of ionizing radiation (LyC fesc) in star-forming galaxies – most likely protagonists of cosmic reionization – are not yet fully understood. Using the VLT/MUSE observations of ∼1400 Ly α emitters at 2.9 &lt; z &lt; 6.7, we compare stacked rest-frame UV spectra of candidates for LyC leakers and non-leakers selected based on their Ly α profiles. We find that the stacks of potential LyC leakers, i.e. galaxies with narrow, symmetric Ly α profiles with small peak separation, generally show (i) strong nebular O iii]λ1666, [Si iii]λ1883, and [C iii]λ1907 +C iii]λ1909 emission, indicating a high-ionization state of the interstellar medium (ISM); (ii) high equivalent widths of He iiλ1640 (∼1 − 3 Å), suggesting the presence of hard ionizing radiation fields; (iii) Si ii*λ1533 emission, revealing substantial amounts of neutral hydrogen off the line of sight; (iv) high C ivλλ1548,1550 to [C iii]λ1907 +C iii]λ1909 ratios (C iv/C iii] ≳0.75) , signalling the presence of low column density channels in the ISM. In contrast, the stacks with broad, asymmetric Ly α profiles with large peak separation show weak nebular emission lines, low He iiλ1640 equivalent widths (≲1 Å), and low C iv/C iii] (≲0.25), implying low-ionization states and high-neutral hydrogen column densities. Our results suggest that C iv/C iii] might be sensitive to the physical conditions that govern LyC photon escape, providing a promising tool for identification of ionizing sources among star-forming galaxies in the epoch of reionization. AU - Kramarenko, Ivan AU - Kerutt, J AU - Verhamme, A AU - Oesch, P A AU - Barrufet, L AU - Matthee, Jorryt J AU - Kusakabe, H AU - Goovaerts, I AU - Thai, T T ID - 14852 IS - 4 JF - Monthly Notices of the Royal Astronomical Society KW - Space and Planetary Science KW - Astronomy and Astrophysics SN - 0035-8711 TI - Linking UV spectral properties of MUSE Ly α emitters at z ≳ 3 to Lyman continuum escape VL - 527 ER - TY - THES AB - In nature, different species find their niche in a range of environments, each with its unique characteristics. While some thrive in uniform (homogeneous) landscapes where environmental conditions stay relatively consistent across space, others traverse the complexities of spatially heterogeneous terrains. Comprehending how species are distributed and how they interact within these landscapes holds the key to gaining insights into their evolutionary dynamics while also informing conservation and management strategies. For species inhabiting heterogeneous landscapes, when the rate of dispersal is low compared to spatial fluctuations in selection pressure, localized adaptations may emerge. Such adaptation in response to varying selection strengths plays an important role in the persistence of populations in our rapidly changing world. Hence, species in nature are continuously in a struggle to adapt to local environmental conditions, to ensure their continued survival. Natural populations can often adapt in time scales short enough for evolutionary changes to influence ecological dynamics and vice versa, thereby creating a feedback between evolution and demography. The analysis of this feedback and the relative contributions of gene flow, demography, drift, and natural selection to genetic variation and differentiation has remained a recurring theme in evolutionary biology. Nevertheless, the effective role of these forces in maintaining variation and shaping patterns of diversity is not fully understood. Even in homogeneous environments devoid of local adaptations, such understanding remains elusive. Understanding this feedback is crucial, for example in determining the conditions under which extinction risk can be mitigated in peripheral populations subject to deleterious mutation accumulation at the edges of species’ ranges as well as in highly fragmented populations. In this thesis we explore both uniform and spatially heterogeneous metapopulations, investigating and providing theoretical insights into the dynamics of local adaptation in the latter and examining the dynamics of load and extinction as well as the impact of joint ecological and evolutionary (eco-evolutionary) dynamics in the former. The thesis is divided into 5 chapters. Chapter 1 provides a general introduction into the subject matter, clarifying concepts and ideas used throughout the thesis. In chapter 2, we explore how fast a species distributed across a heterogeneous landscape adapts to changing conditions marked by alterations in carrying capacity, selection pressure, and migration rate. In chapter 3, we investigate how migration selection and drift influences adaptation and the maintenance of variation in a metapopulation with three habitats, an extension of previous models of adaptation in two habitats. We further develop analytical approximations for the critical threshold required for polymorphism to persist. The focus of chapter 4 of the thesis is on understanding the interplay between ecology and evolution as coupled processes. We investigate how eco-evolutionary feedback between migration, selection, drift, and demography influences eco-evolutionary outcomes in marginal populations subject to deleterious mutation accumulation. Using simulations as well as theoretical approximations of the coupled dynamics of population size and allele frequency, we analyze how gene flow from a large mainland source influences genetic load and population size on an island (i.e., in a marginal population) under genetically realistic assumptions. Analyses of this sort are important because small isolated populations, are repeatedly affected by complex interactions between ecological and evolutionary processes, which can lead to their death. Understanding these interactions can therefore provide an insight into the conditions under which extinction risk can be mitigated in peripheral populations thus, contributing to conservation and restoration efforts. Chapter 5 extends the analysis in chapter 4 to consider the dynamics of load (due to deleterious mutation accumulation) and extinction risk in a metapopulation. We explore the role of gene flow, selection, and dominance on load and extinction risk and further pinpoint critical thresholds required for metapopulation persistence. Overall this research contributes to our understanding of ecological and evolutionary mechanisms that shape species’ persistence in fragmented landscapes, a crucial foundation for successful conservation efforts and biodiversity management. AU - Olusanya, Oluwafunmilola O ID - 14711 SN - 2663 - 337X TI - Local adaptation, genetic load and extinction in metapopulations ER - TY - THES AU - Chiossi, Heloisa ID - 14821 SN - 2663 - 337X TI - Adaptive hierarchical representations in the hippocampus ER - TY - JOUR AB - Global services like navigation, communication, and Earth observation have increased dramatically in the 21st century due to advances in outer space industries. But as orbits become increasingly crowded with both satellites and inevitable space debris pollution, continued operations become endangered by the heightened risks of debris collisions in orbit. Kessler Syndrome is the term for when a critical threshold of orbiting debris triggers a runaway positive feedback loop of debris collisions, creating debris congestion that can render orbits unusable. As this potential tipping point becomes more widely recognized, there have been renewed calls for debris mitigation and removal. Here, we combine complex systems and social-ecological systems approaches to study how these efforts may affect space debris accumulation and the likelihood of reaching Kessler Syndrome. Specifically, we model how debris levels are affected by future launch rates, cleanup activities, and collisions between extant debris. We contextualize and interpret our dynamic model within a discussion of existing space debris governance and other social, economic, and geopolitical factors that may influence effective collective management of the orbital commons. In line with previous studies, our model finds that debris congestion may be reached in less than 200 years, though a holistic management strategy combining removal and mitigation actions can avoid such outcomes while continuing space activities. Moreover, although active debris removal may be particularly effective, the current lack of market and governance support may impede its implementation. Research into these critical dynamics and the multi-faceted variables that influence debris outcomes can support policymakers in curating impactful governance strategies and realistic transition pathways to sustaining debris-free orbits. Overall, our study is useful for communicating about space debris sustainability in policy and education settings by providing an exploration of policy portfolio options supported by a simple and clear social-ecological modeling approach. AU - Nomura, Keiko AU - Rella, Simon AU - Merritt, Haily AU - Baltussen, Mathieu AU - Bird, Darcy AU - Tjuka, Annika AU - Falk, Dan ID - 14901 IS - 1 JF - International Journal of the Commons KW - Sociology and Political Science SN - 1875-0281 TI - Tipping points of space debris in low earth orbit VL - 18 ER - TY - DATA AB - Since the commercialization of brine shrimp (genus Artemia) in the 1950s, this lineage, and in particular the model species Artemia franciscana, has been the subject of extensive research. However, our understanding of the genetic mechanisms underlying various aspects of their reproductive biology, including sex determination, are still lacking. This is partly due to the scarcity of genomic resources for Artemia species and crustaceans in general. Here, we present a chromosome-level genome assembly of Artemia franciscana (Kellogg 1906), from the Great Salt Lake, USA. The genome is 1GB, and the majority of the genome (81%) is scaffolded into 21 linkage groups using a previously published high-density linkage map. We performed coverage and FST analyses using male and female genomic and transcriptomic reads to quantify the extent of differentiation between the Z and W chromosomes. Additionally, we quantified the expression levels in male and female heads and gonads and found further evidence for dosage compensation in this species. AU - Elkrewi, Marwan N ID - 14705 KW - sex chromosome evolution KW - genome assembly KW - dosage compensation TI - Data from "Chromosome-level assembly of Artemia franciscana sheds light on sex-chromosome differentiation" ER - TY - JOUR AB - Key innovations are fundamental to biological diversification, but their genetic basis is poorly understood. A recent transition from egg-laying to live-bearing in marine snails (Littorina spp.) provides the opportunity to study the genetic architecture of an innovation that has evolved repeatedly across animals. Individuals do not cluster by reproductive mode in a genome-wide phylogeny, but local genealogical analysis revealed numerous small genomic regions where all live-bearers carry the same core haplotype. Candidate regions show evidence for live-bearer–specific positive selection and are enriched for genes that are differentially expressed between egg-laying and live-bearing reproductive systems. Ages of selective sweeps suggest that live-bearer–specific alleles accumulated over more than 200,000 generations. Our results suggest that new functions evolve through the recruitment of many alleles rather than in a single evolutionary step. AU - Stankowski, Sean AU - Zagrodzka, Zuzanna B. AU - Garlovsky, Martin D. AU - Pal, Arka AU - Shipilina, Daria AU - Garcia Castillo, Diego Fernando AU - Lifchitz, Hila AU - Le Moan, Alan AU - Leder, Erica AU - Reeve, James AU - Johannesson, Kerstin AU - Westram, Anja M AU - Butlin, Roger K. ID - 14796 IS - 6678 JF - Science TI - The genetic basis of a recent transition to live-bearing in marine snails VL - 383 ER - TY - THES AB - This thesis consists of four distinct pieces of work within theoretical biology, with two themes in common: the concept of optimization in biological systems, and the use of information-theoretic tools to quantify biological stochasticity and statistical uncertainty. Chapter 2 develops a statistical framework for studying biological systems which we believe to be optimized for a particular utility function, such as retinal neurons conveying information about visual stimuli. We formalize such beliefs as maximum-entropy Bayesian priors, constrained by the expected utility. We explore how such priors aid inference of system parameters with limited data and enable optimality hypothesis testing: is the utility higher than by chance? Chapter 3 examines the ultimate biological optimization process: evolution by natural selection. As some individuals survive and reproduce more successfully than others, populations evolve towards fitter genotypes and phenotypes. We formalize this as accumulation of genetic information, and use population genetics theory to study how much such information can be accumulated per generation and maintained in the face of random mutation and genetic drift. We identify the population size and fitness variance as the key quantities that control information accumulation and maintenance. Chapter 4 reuses the concept of genetic information from Chapter 3, but from a different perspective: we ask how much genetic information organisms actually need, in particular in the context of gene regulation. For example, how much information is needed to bind transcription factors at correct locations within the genome? Population genetics provides us with a refined answer: with an increasing population size, populations achieve higher fitness by maintaining more genetic information. Moreover, regulatory parameters experience selection pressure to optimize the fitness-information trade-off, i.e. minimize the information needed for a given fitness. This provides an evolutionary derivation of the optimization priors introduced in Chapter 2. Chapter 5 proves an upper bound on mutual information between a signal and a communication channel output (such as neural activity). Mutual information is an important utility measure for biological systems, but its practical use can be difficult due to the large dimensionality of many biological channels. Sometimes, a lower bound on mutual information is computed by replacing the high-dimensional channel outputs with decodes (signal estimates). Our result provides a corresponding upper bound, provided that the decodes are the maximum posterior estimates of the signal. AU - Hledik, Michal ID - 15020 KW - Theoretical biology KW - Optimality KW - Evolution KW - Information SN - 2663 - 337X TI - Genetic information and biological optimization ER - TY - THES AU - Chen, JingJing ID - 15101 SN - 2663 - 337X TI - Developmental transformation of nanodomain coupling between Ca2+ channels and release sensors at a central GABAergic synapse ER - TY - JOUR AB - Given a fixed finite metric space (V,μ), the {\em minimum 0-extension problem}, denoted as 0-Ext[μ], is equivalent to the following optimization problem: minimize function of the form minx∈Vn∑ifi(xi)+∑ijcijμ(xi,xj) where cij,cvi are given nonnegative costs and fi:V→R are functions given by fi(xi)=∑v∈Vcviμ(xi,v). The computational complexity of 0-Ext[μ] has been recently established by Karzanov and by Hirai: if metric μ is {\em orientable modular} then 0-Ext[μ] can be solved in polynomial time, otherwise 0-Ext[μ] is NP-hard. To prove the tractability part, Hirai developed a theory of discrete convex functions on orientable modular graphs generalizing several known classes of functions in discrete convex analysis, such as L♮-convex functions. We consider a more general version of the problem in which unary functions fi(xi) can additionally have terms of the form cuv;iμ(xi,{u,v}) for {u,v}∈F, where set F⊆(V2) is fixed. We extend the complexity classification above by providing an explicit condition on (μ,F) for the problem to be tractable. In order to prove the tractability part, we generalize Hirai's theory and define a larger class of discrete convex functions. It covers, in particular, another well-known class of functions, namely submodular functions on an integer lattice. Finally, we improve the complexity of Hirai's algorithm for solving 0-Ext on orientable modular graphs. AU - Dvorak, Martin AU - Kolmogorov, Vladimir ID - 10045 JF - Mathematical Programming KW - minimum 0-extension problem KW - metric labeling problem KW - discrete metric spaces KW - metric extensions KW - computational complexity KW - valued constraint satisfaction problems KW - discrete convex analysis KW - L-convex functions SN - 0025-5610 TI - Generalized minimum 0-extension problem and discrete convexity ER - TY - THES AB - Point sets, geometric networks, and arrangements of hyperplanes are fundamental objects in discrete geometry that have captivated mathematicians for centuries, if not millennia. This thesis seeks to cast new light on these structures by illustrating specific instances where a topological perspective, specifically through discrete Morse theory and persistent homology, provides valuable insights. At first glance, the topology of these geometric objects might seem uneventful: point sets essentially lack of topology, arrangements of hyperplanes are a decomposition of Rd, which is a contractible space, and the topology of a network primarily involves the enumeration of connected components and cycles within the network. However, beneath this apparent simplicity, there lies an array of intriguing structures, a small subset of which will be uncovered in this thesis. Focused on three case studies, each addressing one of the mentioned objects, this work will showcase connections that intertwine topology with diverse fields such as combinatorial geometry, algorithms and data structures, and emerging applications like spatial biology. AU - Cultrera di Montesano, Sebastiano ID - 15094 SN - 2663 - 337X TI - Persistence and Morse theory for discrete geometric structures ER - TY - CONF AB - Turn-based stochastic games (aka simple stochastic games) are two-player zero-sum games played on directed graphs with probabilistic transitions. The goal of player-max is to maximize the probability to reach a target state against the adversarial player-min. These games lie in NP ∩ coNP and are among the rare combinatorial problems that belong to this complexity class for which the existence of polynomial-time algorithm is a major open question. While randomized sub-exponential time algorithm exists, all known deterministic algorithms require exponential time in the worst-case. An important open question has been whether faster algorithms can be obtained parametrized by the treewidth of the game graph. Even deterministic sub-exponential time algorithm for constant treewidth turn-based stochastic games has remain elusive. In this work our main result is a deterministic algorithm to solve turn-based stochastic games that, given a game with n states, treewidth at most t, and the bit-complexity of the probabilistic transition function log D, has running time O ((tn2 log D)t log n). In particular, our algorithm is quasi-polynomial time for games with constant or poly-logarithmic treewidth. AU - Chatterjee, Krishnendu AU - Meggendorfer, Tobias AU - Saona Urmeneta, Raimundo J AU - Svoboda, Jakub ID - 12676 SN - 9781611977554 T2 - Proceedings of the 2023 Annual ACM-SIAM Symposium on Discrete Algorithms TI - Faster algorithm for turn-based stochastic games with bounded treewidth ER - TY - GEN AB - Although a wide variety of handcrafted concurrent data structures have been proposed, there is considerable interest in universal approaches (Universal Constructions or UCs) for building concurrent data structures. UCs (semi-)automatically convert a sequential data structure into a concurrent one. The simplest approach uses locks [3, 6] that protect a sequential data structure and allow only one process to access it at a time. However, the resulting data structure is blocking. Most work on UCs instead focuses on obtaining non-blocking progress guarantees such as obstruction-freedom, lock-freedom or wait-freedom. Many non-blocking UCs have appeared. Key examples include the seminal wait-free UC [2] by Herlihy, a NUMA-aware UC [10] by Yi et al., and an efficient UC for large objects [1] by Fatourou et al. AU - Aksenov, Vitaly AU - Brown, Trevor A AU - Fedorov, Alexander AU - Kokorin, Ilya ID - 12736 SN - 9798400700156 T2 - Proceedings of the ACM SIGPLAN Symposium on Principles and Practice of Parallel Programming TI - Unexpected scaling in path copying trees ER - TY - THES AB - The process of detecting and evaluating sensory information to guide behaviour is termed perceptual decision-making (PDM), and is critical for the ability of an organism to interact with its external world. Individuals with autism, a neurodevelopmental condition primarily characterised by social and communication difficulties, frequently exhibit altered sensory processing and PDM difficulties are widely reported. Recent technological advancements have pushed forward our understanding of the genetic changes accompanying this condition, however our understanding of how these mutations affect the function of specific neuronal circuits and bring about the corresponding behavioural changes remains limited. Here, we use an innate PDM task, the looming avoidance response (LAR) paradigm, to identify a convergent behavioural abnormality across three molecularly distinct genetic mouse models of autism (Cul3, Setd5 and Ptchd1). Although mutant mice can rapidly detect threatening visual stimuli, their responses are consistently delayed, requiring longer to initiate an appropriate response than their wild-type siblings. Mutant animals show abnormal adaptation in both their stimulus- evoked escape responses and exploratory dynamics following repeated stimulus presentations. Similarly delayed behavioural responses are observed in wild-type animals when faced with more ambiguous threats, suggesting the mutant phenotype could arise from a dysfunction in the flexible control of this PDM process. Our knowledge of the core neuronal circuitry mediating the LAR facilitated a detailed dissection of the neuronal mechanisms underlying the behavioural impairment. In vivo extracellular recording revealed that visual responses were unaffected within a key brain region for the rapid processing of visual threats, the superior colliculus (SC), indicating that the behavioural delay was unlikely to originate from sensory impairments. Delayed behavioural responses were recapitulated in the Setd5 model following optogenetic stimulation of the excitatory output neurons of the SC, which are known to mediate escape initiation through the activation of cells in the underlying dorsal periaqueductal grey (dPAG). In vitro patch-clamp recordings of dPAG cells uncovered a stark hypoexcitability phenotype in two out of the three genetic models investigated (Setd5 and Ptchd1), that in Setd5, is mediated by the misregulation of voltage-gated potassium channels. Overall, our results show that the ability to use visual information to drive efficient escape responses is impaired in three diverse genetic mouse models of autism and that, in one of the models studied, this behavioural delay likely originates from differences in the intrinsic excitability of a key subcortical node, the dPAG. Furthermore, this work showcases the use of an innate behavioural paradigm to mechanistically dissect PDM processes in autism. AU - Burnett, Laura ID - 12716 SN - 2663-337X TI - To flee, or not to flee? Using innate defensive behaviours to investigate rapid perceptual decision-making through subcortical circuits in mouse models of autism ER - TY - GEN AB - We present a formula for the signed area of a spherical polygon via prequantization. In contrast to the traditional formula based on the Gauss-Bonnet theorem that requires measuring angles, the new formula mimics Green's theorem and is applicable to a wider range of degenerate spherical curves and polygons. AU - Chern, Albert AU - Ishida, Sadashige ID - 12846 T2 - arXiv TI - Area formula for spherical polygons via prequantization ER - TY - THES AB - Understanding the mechanisms of learning and memory formation has always been one of the main goals in neuroscience. Already Pavlov (1927) in his early days has used his classic conditioning experiments to study the neural mechanisms governing behavioral adaptation. What was not known back then was that the part of the brain that is largely responsible for this type of associative learning is the cerebellum. Since then, plenty of theories on cerebellar learning have emerged. Despite their differences, one thing they all have in common is that learning relies on synaptic and intrinsic plasticity. The goal of my PhD project was to unravel the molecular mechanisms underlying synaptic plasticity in two synapses that have been shown to be implicated in motor learning, in an effort to understand how learning and memory formation are processed in the cerebellum. One of the earliest and most well-known cerebellar theories postulates that motor learning largely depends on long-term depression at the parallel fiber-Purkinje cell (PC-PC) synapse. However, the discovery of other types of plasticity in the cerebellar circuitry, like long-term potentiation (LTP) at the PC-PC synapse, potentiation of molecular layer interneurons (MLIs), and plasticity transfer from the cortex to the cerebellar/ vestibular nuclei has increased the popularity of the idea that multiple sites of plasticity might be involved in learning. Still a lot remains unknown about the molecular mechanisms responsible for these types of plasticity and whether they occur during physiological learning. In the first part of this thesis we have analyzed the variation and nanodistribution of voltagegated calcium channels (VGCCs) and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid type glutamate receptors (AMPARs) on the parallel fiber-Purkinje cell synapse after vestibuloocular reflex phase reversal adaptation, a behavior that has been suggested to rely on PF-PC LTP. We have found that on the last day of adaptation there is no learning trace in form of VGCCs nor AMPARs variation at the PF-PC synapse, but instead a decrease in the number of PF-PC synapses. These data seem to support the view that learning is only stored in the cerebellar cortex in an initial learning phase, being transferred later to the vestibular nuclei. Next, we have studied the role of MLIs in motor learning using a relatively simple and well characterized behavioral paradigm – horizontal optokinetic reflex (HOKR) adaptation. We have found behavior-induced MLI potentiation in form of release probability increase that could be explained by the increase of VGCCs at the presynaptic side. Our results strengthen the idea of distributed cerebellar plasticity contributing to learning and provide a novel mechanism for release probability increase. AU - Alcarva, Catarina ID - 12809 SN - 2663 - 337X TI - Plasticity in the cerebellum: What molecular mechanisms are behind physiological learning ER - TY - CONF AB - Deep neural networks (DNNs) often have to be compressed, via pruning and/or quantization, before they can be deployed in practical settings. In this work we propose a new compression-aware minimizer dubbed CrAM that modifies the optimization step in a principled way, in order to produce models whose local loss behavior is stable under compression operations such as pruning. Thus, dense models trained via CrAM should be compressible post-training, in a single step, without significant accuracy loss. Experimental results on standard benchmarks, such as residual networks for ImageNet classification and BERT models for language modelling, show that CrAM produces dense models that can be more accurate than the standard SGD/Adam-based baselines, but which are stable under weight pruning: specifically, we can prune models in one-shot to 70-80% sparsity with almost no accuracy loss, and to 90% with reasonable (∼1%) accuracy loss, which is competitive with gradual compression methods. Additionally, CrAM can produce sparse models which perform well for transfer learning, and it also works for semi-structured 2:4 pruning patterns supported by GPU hardware. The code for reproducing the results is available at this https URL . AU - Peste, Elena-Alexandra AU - Vladu, Adrian AU - Kurtic, Eldar AU - Lampert, Christoph AU - Alistarh, Dan-Adrian ID - 13053 T2 - 11th International Conference on Learning Representations TI - CrAM: A Compression-Aware Minimizer ER - TY - THES AB - During navigation, animals can infer the structure of the environment by computing the optic flow cues elicited by their own movements, and subsequently use this information to instruct proper locomotor actions. These computations require a panoramic assessment of the visual environment in order to disambiguate similar sensory experiences that may require distinct behavioral responses. The estimation of the global motion patterns is therefore essential for successful navigation. Yet, our understanding of the algorithms and implementations that enable coherent panoramic visual perception remains scarce. Here I pursue this problem by dissecting the functional aspects of interneuronal communication in the lobula plate tangential cell network in Drosophila melanogaster. The results presented in the thesis demonstrate that the basis for effective interpretation of the optic flow in this circuit are stereotyped synaptic connections that mediate the formation of distinct subnetworks, each extracting a particular pattern of global motion. Firstly, I show that gap junctions are essential for a correct interpretation of binocular motion cues by horizontal motion-sensitive cells. HS cells form electrical synapses with contralateral H2 neurons that are involved in detecting yaw rotation and translation. I developed an FlpStop-mediated mutant of a gap junction protein ShakB that disrupts these electrical synapses. While the loss of electrical synapses does not affect the tuning of the direction selectivity in HS neurons, it severely alters their sensitivity to horizontal motion in the contralateral side. These physiological changes result in an inappropriate integration of binocular motion cues in walking animals. While wild-type flies form a binocular perception of visual motion by non-linear integration of monocular optic flow cues, the mutant flies sum the monocular inputs linearly. These results indicate that rather than averaging signals in neighboring neurons, gap-junctions operate in conjunction with chemical synapses to mediate complex non-linear optic flow computations. Secondly, I show that stochastic manipulation of neuronal activity in the lobula plate tangential cell network is a powerful approach to study the neuronal implementation of optic flow-based navigation in flies. Tangential neurons form multiple subnetworks, each mediating course-stabilizing response to a particular global pattern of visual motion. Application of genetic mosaic techniques can provide sparse optogenetic activation of HS cells in numerous combinations. These distinct combinations of activated neurons drive an array of distinct behavioral responses, providing important insights into how visuomotor transformation is performed in the lobula plate tangential cell network. This approach can be complemented by stochastic silencing of tangential neurons, enabling direct assessment of the functional role of individual tangential neurons in the processing of specific visual motion patterns. Taken together, the findings presented in this thesis suggest that establishing specific activity patterns of tangential cells via stereotyped synaptic connectivity is a key to efficient optic flow-based navigation in Drosophila melanogaster. AU - Pokusaeva, Victoria ID - 12826 SN - 2663 - 337X TI - Neural control of optic flow-based navigation in Drosophila melanogaster ER - TY - CONF AB - Safety and liveness are elementary concepts of computation, and the foundation of many verification paradigms. The safety-liveness classification of boolean properties characterizes whether a given property can be falsified by observing a finite prefix of an infinite computation trace (always for safety, never for liveness). In quantitative specification and verification, properties assign not truth values, but quantitative values to infinite traces (e.g., a cost, or the distance to a boolean property). We introduce quantitative safety and liveness, and we prove that our definitions induce conservative quantitative generalizations of both (1)~the safety-progress hierarchy of boolean properties and (2)~the safety-liveness decomposition of boolean properties. In particular, we show that every quantitative property can be written as the pointwise minimum of a quantitative safety property and a quantitative liveness property. Consequently, like boolean properties, also quantitative properties can be min-decomposed into safety and liveness parts, or alternatively, max-decomposed into co-safety and co-liveness parts. Moreover, quantitative properties can be approximated naturally. We prove that every quantitative property that has both safe and co-safe approximations can be monitored arbitrarily precisely by a monitor that uses only a finite number of states. AU - Henzinger, Thomas A AU - Mazzocchi, Nicolas Adrien AU - Sarac, Naci E ID - 12467 SN - 0302-9743 T2 - 26th International Conference Foundations of Software Science and Computation Structures TI - Quantitative safety and liveness VL - 13992 ER - TY - CONF AB - The operator precedence languages (OPLs) represent the largest known subclass of the context-free languages which enjoys all desirable closure and decidability properties. This includes the decidability of language inclusion, which is the ultimate verification problem. Operator precedence grammars, automata, and logics have been investigated and used, for example, to verify programs with arithmetic expressions and exceptions (both of which are deterministic pushdown but lie outside the scope of the visibly pushdown languages). In this paper, we complete the picture and give, for the first time, an algebraic characterization of the class of OPLs in the form of a syntactic congruence that has finitely many equivalence classes exactly for the operator precedence languages. This is a generalization of the celebrated Myhill-Nerode theorem for the regular languages to OPLs. As one of the consequences, we show that universality and language inclusion for nondeterministic operator precedence automata can be solved by an antichain algorithm. Antichain algorithms avoid determinization and complementation through an explicit subset construction, by leveraging a quasi-order on words, which allows the pruning of the search space for counterexample words without sacrificing completeness. Antichain algorithms can be implemented symbolically, and these implementations are today the best-performing algorithms in practice for the inclusion of finite automata. We give a generic construction of the quasi-order needed for antichain algorithms from a finite syntactic congruence. This yields the first antichain algorithm for OPLs, an algorithm that solves the ExpTime-hard language inclusion problem for OPLs in exponential time. AU - Henzinger, Thomas A AU - Kebis, Pavol AU - Mazzocchi, Nicolas Adrien AU - Sarac, Naci E ID - 13292 SN - 9783959772785 T2 - 50th International Colloquium on Automata, Languages, and Programming TI - Regular methods for operator precedence languages VL - 261 ER - TY - CONF AB - Determining the degree of inherent parallelism in classical sequential algorithms and leveraging it for fast parallel execution is a key topic in parallel computing, and detailed analyses are known for a wide range of classical algorithms. In this paper, we perform the first such analysis for the fundamental Union-Find problem, in which we are given a graph as a sequence of edges, and must maintain its connectivity structure under edge additions. We prove that classic sequential algorithms for this problem are well-parallelizable under reasonable assumptions, addressing a conjecture by [Blelloch, 2017]. More precisely, we show via a new potential argument that, under uniform random edge ordering, parallel union-find operations are unlikely to interfere: T concurrent threads processing the graph in parallel will encounter memory contention O(T2 · log |V| · log |E|) times in expectation, where |E| and |V| are the number of edges and nodes in the graph, respectively. We leverage this result to design a new parallel Union-Find algorithm that is both internally deterministic, i.e., its results are guaranteed to match those of a sequential execution, but also work-efficient and scalable, as long as the number of threads T is O(|E|1 over 3 - ε), for an arbitrarily small constant ε > 0, which holds for most large real-world graphs. We present lower bounds which show that our analysis is close to optimal, and experimental results suggesting that the performance cost of internal determinism is limited. AU - Fedorov, Alexander AU - Hashemi, Diba AU - Nadiradze, Giorgi AU - Alistarh, Dan-Adrian ID - 13262 SN - 9781450395458 T2 - Proceedings of the 35th ACM Symposium on Parallelism in Algorithms and Architectures TI - Provably-efficient and internally-deterministic parallel Union-Find ER - TY - JOUR AB - We study active surface wetting using a minimal model of bacteria that takes into account the intrinsic motility diversity of living matter. A mixture of “fast” and “slow” self-propelled Brownian particles is considered in the presence of a wall. The evolution of the wetting layer thickness shows an overshoot before stationarity and its composition evolves in two stages, equilibrating after a slow elimination of excess particles. Nonmonotonic evolutions are shown to arise from delayed avalanches towards the dilute phase combined with the emergence of a transient particle front. AU - Rojas Vega, Mauricio Nicolas AU - De Castro, Pablo AU - Soto, Rodrigo ID - 12545 IS - 1 JF - Physical Review E SN - 2470-0045 TI - Wetting dynamics by mixtures of fast and slow self-propelled particles VL - 107 ER - TY - JOUR AB - Lead halide perovskites enjoy a number of remarkable optoelectronic properties. To explain their origin, it is necessary to study how electromagnetic fields interact with these systems. We address this problem here by studying two classical quantities: Faraday rotation and the complex refractive index in a paradigmatic perovskite CH3NH3PbBr3 in a broad wavelength range. We find that the minimal coupling of electromagnetic fields to the k⋅p Hamiltonian is insufficient to describe the observed data even on the qualitative level. To amend this, we demonstrate that there exists a relevant atomic-level coupling between electromagnetic fields and the spin degree of freedom. This spin-electric coupling allows for quantitative description of a number of previous as well as present experimental data. In particular, we use it here to show that the Faraday effect in lead halide perovskites is dominated by the Zeeman splitting of the energy levels and has a substantial beyond-Becquerel contribution. Finally, we present general symmetry-based phenomenological arguments that in the low-energy limit our effective model includes all basis coupling terms to the electromagnetic field in the linear order. AU - Volosniev, Artem AU - Shiva Kumar, Abhishek AU - Lorenc, Dusan AU - Ashourishokri, Younes AU - Zhumekenov, Ayan A. AU - Bakr, Osman M. AU - Lemeshko, Mikhail AU - Alpichshev, Zhanybek ID - 12723 IS - 10 JF - Physical Review Letters KW - General Physics and Astronomy SN - 0031-9007 TI - Spin-electric coupling in lead halide perovskites VL - 130 ER - TY - JOUR AB - We use general symmetry-based arguments to construct an effective model suitable for studying optical properties of lead halide perovskites. To build the model, we identify an atomic-level interaction between electromagnetic fields and the spin degree of freedom that should be added to a minimally coupled k⋅p Hamiltonian. As a first application, we study two basic optical characteristics of the material: the Verdet constant and the refractive index. Beyond these linear characteristics of the material, the model is suitable for calculating nonlinear effects such as the third-order optical susceptibility. Analysis of this quantity shows that the geometrical properties of the spin-electric term imply isotropic optical response of the system, and that optical anisotropy of lead halide perovskites is a manifestation of hopping of charge carriers. To illustrate this, we discuss third-harmonic generation. AU - Volosniev, Artem AU - Shiva Kumar, Abhishek AU - Lorenc, Dusan AU - Ashourishokri, Younes AU - Zhumekenov, Ayan AU - Bakr, Osman M. AU - Lemeshko, Mikhail AU - Alpichshev, Zhanybek ID - 12724 IS - 12 JF - Physical Review B SN - 2469-9950 TI - Effective model for studying optical properties of lead halide perovskites VL - 107 ER - TY - JOUR AB - Brachyury, a member of T-box gene family, is widely known for its major role in mesoderm specification in bilaterians. It is also present in non-bilaterian metazoans, such as cnidarians, where it acts as a component of an axial patterning system. In this study, we present a phylogenetic analysis of Brachyury genes within phylum Cnidaria, investigate differential expression and address a functional framework of Brachyury paralogs in hydrozoan Dynamena pumila. Our analysis indicates two duplication events of Brachyury within the cnidarian lineage. The first duplication likely appeared in the medusozoan ancestor, resulting in two copies in medusozoans, while the second duplication arose in the hydrozoan ancestor, resulting in three copies in hydrozoans. Brachyury1 and 2 display a conservative expression pattern marking the oral pole of the body axis in D. pumila. On the contrary, Brachyury3 expression was detected in scattered presumably nerve cells of the D. pumila larva. Pharmacological modulations indicated that Brachyury3 is not under regulation of cWnt signaling in contrast to the other two Brachyury genes. Divergence in expression patterns and regulation suggest neofunctionalization of Brachyury3 in hydrozoans. AU - Vetrova, Alexandra A. AU - Kupaeva, Daria M. AU - Kizenko, Alena AU - Lebedeva, Tatiana S. AU - Walentek, Peter AU - Tsikolia, Nikoloz AU - Kremnyov, Stanislav V. ID - 13166 JF - Scientific Reports TI - The evolutionary history of Brachyury genes in Hydrozoa involves duplications, divergence, and neofunctionalization VL - 13 ER - TY - JOUR AB - We consider the spin- 1 2 Heisenberg chain (XXX model) weakly perturbed away from integrability by an isotropic next-to-nearest neighbor exchange interaction. Recently, it was conjectured that this model possesses an infinite tower of quasiconserved integrals of motion (charges) [D. Kurlov et al., Phys. Rev. B 105, 104302 (2022)]. In this work we first test this conjecture by investigating how the norm of the adiabatic gauge potential (AGP) scales with the system size, which is known to be a remarkably accurate measure of chaos. We find that for the perturbed XXX chain the behavior of the AGP norm corresponds to neither an integrable nor a chaotic regime, which supports the conjectured quasi-integrability of the model. We then prove the conjecture and explicitly construct the infinite set of quasiconserved charges. Our proof relies on the fact that the XXX chain perturbed by next-to-nearest exchange interaction can be viewed as a truncation of an integrable long-range deformation of the Heisenberg spin chain. AU - Orlov, Pavel AU - Tiutiakina, Anastasiia AU - Sharipov, Rustem AU - Petrova, Elena AU - Gritsev, Vladimir AU - Kurlov, Denis V. ID - 13138 IS - 18 JF - Physical Review B SN - 2469-9950 TI - Adiabatic eigenstate deformations and weak integrability breaking of Heisenberg chain VL - 107 ER - TY - THES AB - Most energy in humans is produced in form of ATP by the mitochondrial respiratory chain consisting of several protein assemblies embedded into lipid membrane (complexes I-V). Complex I is the first and the largest enzyme of the respiratory chain which is essential for energy production. It couples the transfer of two electrons from NADH to ubiquinone with proton translocation across bacterial or inner mitochondrial membrane. The coupling mechanism between electron transfer and proton translocation is one of the biggest enigma in bioenergetics and structural biology. Even though the enzyme has been studied for decades, only recent technological advances in cryo-EM allowed its extensive structural investigation. Complex I from E.coli appears to be of special importance because it is a perfect model system with a rich mutant library, however the structure of the entire complex was unknown. In this thesis I have resolved structures of the minimal complex I version from E. coli in different states including reduced, inhibited, under reaction turnover and several others. Extensive structural analyses of these structures and comparison to structures from other species allowed to derive general features of conformational dynamics and propose a universal coupling mechanism. The mechanism is straightforward, robust and consistent with decades of experimental data available for complex I from different species. Cyanobacterial NDH (cyanobacterial complex I) is a part of broad complex I superfamily and was studied as well in this thesis. It plays an important role in cyclic electron transfer (CET), during which electrons are cycled within PSI through ferredoxin and plastoquinone to generate proton gradient without NADPH production. Here, I solved structure of NDH and revealed additional state, which was not observed before. The novel “resting” state allowed to propose the mechanism of CET regulation. Moreover, conformational dynamics of NDH resembles one in complex I which suggest more broad universality of the proposed coupling mechanism. In summary, results presented here helped to interpret decades of experimental data for complex I and contributed to fundamental mechanistic understanding of protein function. AU - Kravchuk, Vladyslav ID - 12781 SN - 2663-337X TI - Structural and mechanistic study of bacterial complex I and its cyanobacterial ortholog ER - TY - THES AB - Deep learning has become an integral part of a large number of important applications, and many of the recent breakthroughs have been enabled by the ability to train very large models, capable to capture complex patterns and relationships from the data. At the same time, the massive sizes of modern deep learning models have made their deployment to smaller devices more challenging; this is particularly important, as in many applications the users rely on accurate deep learning predictions, but they only have access to devices with limited memory and compute power. One solution to this problem is to prune neural networks, by setting as many of their parameters as possible to zero, to obtain accurate sparse models with lower memory footprint. Despite the great research progress in obtaining sparse models that preserve accuracy, while satisfying memory and computational constraints, there are still many challenges associated with efficiently training sparse models, as well as understanding their generalization properties. The focus of this thesis is to investigate how the training process of sparse models can be made more efficient, and to understand the differences between sparse and dense models in terms of how well they can generalize to changes in the data distribution. We first study a method for co-training sparse and dense models, at a lower cost compared to regular training. With our method we can obtain very accurate sparse networks, and dense models that can recover the baseline accuracy. Furthermore, we are able to more easily analyze the differences, at prediction level, between the sparse-dense model pairs. Next, we investigate the generalization properties of sparse neural networks in more detail, by studying how well different sparse models trained on a larger task can adapt to smaller, more specialized tasks, in a transfer learning scenario. Our analysis across multiple pruning methods and sparsity levels reveals that sparse models provide features that can transfer similarly to or better than the dense baseline. However, the choice of the pruning method plays an important role, and can influence the results when the features are fixed (linear finetuning), or when they are allowed to adapt to the new task (full finetuning). Using sparse models with fixed masks for finetuning on new tasks has an important practical advantage, as it enables training neural networks on smaller devices. However, one drawback of current pruning methods is that the entire training cycle has to be repeated to obtain the initial sparse model, for every sparsity target; in consequence, the entire training process is costly and also multiple models need to be stored. In the last part of the thesis we propose a method that can train accurate dense models that are compressible in a single step, to multiple sparsity levels, without additional finetuning. Our method results in sparse models that can be competitive with existing pruning methods, and which can also successfully generalize to new tasks. AU - Peste, Elena-Alexandra ID - 13074 SN - 2663-337X TI - Efficiency and generalization of sparse neural networks ER - TY - THES AB - Pattern formation is of great importance for its contribution across different biological behaviours. During developmental processes for example, patterns of chemical gradients are established to determine cell fate and complex tissue patterns emerge to define structures such as limbs and vascular networks. Patterns are also seen in collectively migrating groups, for instance traveling waves of density emerging in moving animal flocks as well as collectively migrating cells and tissues. To what extent these biological patterns arise spontaneously through the local interaction of individual constituents or are dictated by higher level instructions is still an open question however there is evidence for the involvement of both types of process. Where patterns arise spontaneously there is a long standing interest in how far the interplay of mechanics, e.g. force generation and deformation, and chemistry, e.g. gene regulation and signaling, contributes to the behaviour. This is because many systems are able to both chemically regulate mechanical force production and chemically sense mechanical deformation, forming mechano-chemical feedback loops which can potentially become unstable towards spatio and/or temporal patterning. We work with experimental collaborators to investigate the possibility that this type of interaction drives pattern formation in biological systems at different scales. We focus first on tissue-level ERK-density waves observed during the wound healing response across different systems where many previous studies have proposed that patterns depend on polarized cell migration and arise from a mechanical flocking-like mechanism. By combining theory with mechanical and optogenetic perturbation experiments on in vitro monolayers we instead find evidence for mechanochemical pattern formation involving only scalar bilateral feedbacks between ERK signaling and cell contraction. We perform further modeling and experiment to study how this instability couples with polar cell migration in order to produce a robust and efficient wound healing response. In a following chapter we implement ERK-density coupling and cell migration in a 2D active vertex model to investigate the interaction of ERK-density patterning with different tissue rheologies and find that the spatio-temporal dynamics are able to both locally and globally fluidize a tissue across the solid-fluid glass transition. In a last chapter we move towards lower spatial scales in the context of subcellular patterning of the cell cytoskeleton where we investigate the transition between phases of spatially homogeneous temporal oscillations and chaotic spatio-temporal patterning in the dynamics of myosin and ROCK activities (a motor component of the actomyosin cytoskeleton and its activator). Experimental evidence supports an intrinsic chemical oscillator which we encode in a reaction model and couple to a contractile active gel description of the cell cortex. The model exhibits phases of chemical oscillations and contractile spatial patterning which reproduce many features of the dynamics seen in Drosophila oocyte epithelia in vivo. However, additional pharmacological perturbations to inhibit myosin contractility leaves the role of contractile instability unclear. We discuss alternative hypotheses and investigate the possibility of reaction-diffusion instability. AU - Boocock, Daniel R ID - 12964 SN - 2663-337X TI - Mechanochemical pattern formation across biological scales ER - TY - THES AB - High-performance semiconductors rely upon precise control of heat and charge transport. This can be achieved by precisely engineering defects in polycrystalline solids. There are multiple approaches to preparing such polycrystalline semiconductors, and the transformation of solution-processed colloidal nanoparticles is appealing because colloidal nanoparticles combine low cost with structural and compositional tunability along with rich surface chemistry. However, the multiple processes from nanoparticle synthesis to the final bulk nanocomposites are very complex. They involve nanoparticle purification, post-synthetic modifications, and finally consolidation (thermal treatments and densification). All these properties dictate the final material’s composition and microstructure, ultimately affecting its functional properties. This thesis explores the synthesis, surface chemistry and consolidation of colloidal semiconductor nanoparticles into dense solids. In particular, the transformations that take place during these processes, and their effect on the material’s transport properties are evaluated. AU - Calcabrini, Mariano ID - 12885 SN - 2663-337X TI - Nanoparticle-based semiconductor solids: From synthesis to consolidation ER - TY - JOUR AB - Differentiated X chromosomes are expected to have higher rates of adaptive divergence than autosomes, if new beneficial mutations are recessive (the “faster-X effect”), largely because these mutations are immediately exposed to selection in males. The evolution of X chromosomes after they stop recombining in males, but before they become hemizygous, has not been well explored theoretically. We use the diffusion approximation to infer substitution rates of beneficial and deleterious mutations under such a scenario. Our results show that selection is less efficient on diploid X loci than on autosomal and hemizygous X loci under a wide range of parameters. This “slower-X” effect is stronger for genes affecting primarily (or only) male fitness, and for sexually antagonistic genes. These unusual dynamics suggest that some of the peculiar features of X chromosomes, such as the differential accumulation of genes with sex-specific functions, may start arising earlier than previously appreciated. AU - Mrnjavac, Andrea AU - Khudiakova, Kseniia AU - Barton, Nicholas H AU - Vicoso, Beatriz ID - 12521 IS - 1 JF - Evolution Letters KW - Genetics KW - Ecology KW - Evolution KW - Behavior and Systematics SN - 2056-3744 TI - Slower-X: Reduced efficiency of selection in the early stages of X chromosome evolution VL - 7 ER - TY - JOUR AB - Neurons in the brain are wired into adaptive networks that exhibit collective dynamics as diverse as scale-specific oscillations and scale-free neuronal avalanches. Although existing models account for oscillations and avalanches separately, they typically do not explain both phenomena, are too complex to analyze analytically or intractable to infer from data rigorously. Here we propose a feedback-driven Ising-like class of neural networks that captures avalanches and oscillations simultaneously and quantitatively. In the simplest yet fully microscopic model version, we can analytically compute the phase diagram and make direct contact with human brain resting-state activity recordings via tractable inference of the model’s two essential parameters. The inferred model quantitatively captures the dynamics over a broad range of scales, from single sensor oscillations to collective behaviors of extreme events and neuronal avalanches. Importantly, the inferred parameters indicate that the co-existence of scale-specific (oscillations) and scale-free (avalanches) dynamics occurs close to a non-equilibrium critical point at the onset of self-sustained oscillations. AU - Lombardi, Fabrizio AU - Pepic, Selver AU - Shriki, Oren AU - Tkačik, Gašper AU - De Martino, Daniele ID - 12762 JF - Nature Computational Science TI - Statistical modeling of adaptive neural networks explains co-existence of avalanches and oscillations in resting human brain VL - 3 ER - TY - THES AB - The tight spatiotemporal coordination of signaling activity determining embryo patterning and the physical processes driving embryo morphogenesis renders embryonic development robust, such that key developmental processes can unfold relatively normally even outside of the full embryonic context. For instance, embryonic stem cell cultures can recapitulate the hallmarks of gastrulation, i.e. break symmetry leading to germ layer formation and morphogenesis, in a very reduced environment. This leads to questions on specific contributions of embryo-specific features, such as the presence of extraembryonic tissues, which are inherently involved in gastrulation in the full embryonic context. To address this, we established zebrafish embryonic explants without the extraembryonic yolk cell, an important player as a signaling source and for morphogenesis during gastrulation, as a model of ex vivo development. We found that dorsal-marginal determinants are required and sufficient in these explants to form and pattern all three germ layers. However, formation of tissues, which require the highest Nodal-signaling levels, is variable, demonstrating a contribution of extraembryonic tissues for reaching peak Nodal signaling levels. Blastoderm explants also undergo gastrulation-like axis elongation. We found that this elongation movement shows hallmarks of oriented mesendoderm cell intercalations typically associated with dorsal tissues in the intact embryo. These are disrupted by uniform upregulation of BMP signaling activity and concomitant explant ventralization, suggesting that tight spatial control of BMP signaling is a prerequisite for explant morphogenesis. This control is achieved by Nodal signaling, which is critical for effectively downregulating BMP signaling in the mesendoderm, highlighting that Nodal signaling is not only directly required for mesendoderm cell fate specification and morphogenesis, but also by maintaining low levels of BMP signaling at the dorsal side. Collectively, we provide insights into the capacity and organization of signaling and morphogenetic domains to recapitulate features of zebrafish gastrulation outside of the full embryonic context. AU - Schauer, Alexandra ID - 12891 SN - 2663 - 337X TI - Mesendoderm formation in zebrafish gastrulation: The role of extraembryonic tissues ER - TY - THES AB - About a 100 years ago, we discovered that our universe is inherently noisy, that is, measuring any physical quantity with a precision beyond a certain point is not possible because of an omnipresent inherent noise. We call this - the quantum noise. Certain physical processes allow this quantum noise to get correlated in conjugate physical variables. These quantum correlations can be used to go beyond the potential of our inherently noisy universe and obtain a quantum advantage over the classical applications. Quantum noise being inherent also means that, at the fundamental level, the physical quantities are not well defined and therefore, objects can stay in multiple states at the same time. For example, the position of a particle not being well defined means that the particle is in multiple positions at the same time. About 4 decades ago, we started exploring the possibility of using objects which can be in multiple states at the same time to increase the dimensionality in computation. Thus, the field of quantum computing was born. We discovered that using quantum entanglement, a property closely related to quantum correlations, can be used to speed up computation of certain problems, such as factorisation of large numbers, faster than any known classical algorithm. Thus began the pursuit to make quantum computers a reality. Till date, we have explored quantum control over many physical systems including photons, spins, atoms, ions and even simple circuits made up of superconducting material. However, there persists one ubiquitous theme. The more readily a system interacts with an external field or matter, the more easily we can control it. But this also means that such a system can easily interact with a noisy environment and quickly lose its coherence. Consequently, such systems like electron spins need to be protected from the environment to ensure the longevity of their coherence. Other systems like nuclear spins are naturally protected as they do not interact easily with the environment. But, due to the same reason, it is harder to interact with such systems. After decades of experimentation with various systems, we are convinced that no one type of quantum system would be the best for all the quantum applications. We would need hybrid systems which are all interconnected - much like the current internet where all sorts of devices can all talk to each other - but now for quantum devices. A quantum internet. Optical photons are the best contenders to carry information for the quantum internet. They can carry quantum information cheaply and without much loss - the same reasons which has made them the backbone of our current internet. Following this direction, many systems, like trapped ions, have already demonstrated successful quantum links over a large distances using optical photons. However, some of the most promising contenders for quantum computing which are based on microwave frequencies have been left behind. This is because high energy optical photons can adversely affect fragile low-energy microwave systems. In this thesis, we present substantial progress on this missing quantum link between microwave and optics using electrooptical nonlinearities in lithium niobate. The nonlinearities are enhanced by using resonant cavities for all the involved modes leading to observation of strong direct coupling between optical and microwave frequencies. With this strong coupling we are not only able to achieve almost 100\% internal conversion efficiency with low added noise, thus presenting a quantum-enabled transducer, but also we are able to observe novel effects such as cooling of a microwave mode using optics. The strong coupling regime also leads to direct observation of dynamical backaction effect between microwave and optical frequencies which are studied in detail here. Finally, we also report first observation of microwave-optics entanglement in form of two-mode squeezed vacuum squeezed 0.7dB below vacuum level. With this new bridge between microwave and optics, the microwave-based quantum technologies can finally be a part of a quantum network which is based on optical photons - putting us one step closer to a future with quantum internet. AU - Sahu, Rishabh ID - 13175 KW - quantum optics KW - electrooptics KW - quantum networks KW - quantum communication KW - transduction SN - 2663 - 337X TI - Cavity quantum electrooptics ER - TY - THES AB - About a 100 years ago, we discovered that our universe is inherently noisy, that is, measuring any physical quantity with a precision beyond a certain point is not possible because of an omnipresent inherent noise. We call this - the quantum noise. Certain physical processes allow this quantum noise to get correlated in conjugate physical variables. These quantum correlations can be used to go beyond the potential of our inherently noisy universe and obtain a quantum advantage over the classical applications. Quantum noise being inherent also means that, at the fundamental level, the physical quantities are not well defined and therefore, objects can stay in multiple states at the same time. For example, the position of a particle not being well defined means that the particle is in multiple positions at the same time. About 4 decades ago, we started exploring the possibility of using objects which can be in multiple states at the same time to increase the dimensionality in computation. Thus, the field of quantum computing was born. We discovered that using quantum entanglement, a property closely related to quantum correlations, can be used to speed up computation of certain problems, such as factorisation of large numbers, faster than any known classical algorithm. Thus began the pursuit to make quantum computers a reality. Till date, we have explored quantum control over many physical systems including photons, spins, atoms, ions and even simple circuits made up of superconducting material. However, there persists one ubiquitous theme. The more readily a system interacts with an external field or matter, the more easily we can control it. But this also means that such a system can easily interact with a noisy environment and quickly lose its coherence. Consequently, such systems like electron spins need to be protected from the environment to ensure the longevity of their coherence. Other systems like nuclear spins are naturally protected as they do not interact easily with the environment. But, due to the same reason, it is harder to interact with such systems. After decades of experimentation with various systems, we are convinced that no one type of quantum system would be the best for all the quantum applications. We would need hybrid systems which are all interconnected - much like the current internet where all sorts of devices can all talk to each other - but now for quantum devices. A quantum internet. Optical photons are the best contenders to carry information for the quantum internet. They can carry quantum information cheaply and without much loss - the same reasons which has made them the backbone of our current internet. Following this direction, many systems, like trapped ions, have already demonstrated successful quantum links over a large distances using optical photons. However, some of the most promising contenders for quantum computing which are based on microwave frequencies have been left behind. This is because high energy optical photons can adversely affect fragile low-energy microwave systems. In this thesis, we present substantial progress on this missing quantum link between microwave and optics using electrooptical nonlinearities in lithium niobate. The nonlinearities are enhanced by using resonant cavities for all the involved modes leading to observation of strong direct coupling between optical and microwave frequencies. With this strong coupling we are not only able to achieve almost 100\% internal conversion efficiency with low added noise, thus presenting a quantum-enabled transducer, but also we are able to observe novel effects such as cooling of a microwave mode using optics. The strong coupling regime also leads to direct observation of dynamical backaction effect between microwave and optical frequencies which are studied in detail here. Finally, we also report first observation of microwave-optics entanglement in form of two-mode squeezed vacuum squeezed 0.7dB below vacuum level. With this new bridge between microwave and optics, the microwave-based quantum technologies can finally be a part of a quantum network which is based on optical photons - putting us one step closer to a future with quantum internet. AU - Sahu, Rishabh ID - 12900 KW - quantum optics KW - electrooptics KW - quantum networks KW - quantum communication KW - transduction SN - 2663 - 337X TI - Cavity quantum electrooptics ER - TY - CONF AB - Machine-learned systems are in widespread use for making decisions about humans, and it is important that they are fair, i.e., not biased against individuals based on sensitive attributes. We present runtime verification of algorithmic fairness for systems whose models are unknown, but are assumed to have a Markov chain structure. We introduce a specification language that can model many common algorithmic fairness properties, such as demographic parity, equal opportunity, and social burden. We build monitors that observe a long sequence of events as generated by a given system, and output, after each observation, a quantitative estimate of how fair or biased the system was on that run until that point in time. The estimate is proven to be correct modulo a variable error bound and a given confidence level, where the error bound gets tighter as the observed sequence gets longer. Our monitors are of two types, and use, respectively, frequentist and Bayesian statistical inference techniques. While the frequentist monitors compute estimates that are objectively correct with respect to the ground truth, the Bayesian monitors compute estimates that are correct subject to a given prior belief about the system’s model. Using a prototype implementation, we show how we can monitor if a bank is fair in giving loans to applicants from different social backgrounds, and if a college is fair in admitting students while maintaining a reasonable financial burden on the society. Although they exhibit different theoretical complexities in certain cases, in our experiments, both frequentist and Bayesian monitors took less than a millisecond to update their verdicts after each observation. AU - Henzinger, Thomas A AU - Karimi, Mahyar AU - Kueffner, Konstantin AU - Mallik, Kaushik ID - 13310 SN - 0302-9743 T2 - Computer Aided Verification TI - Monitoring algorithmic fairness VL - 13965 ER - TY - JOUR AB - In this work, a generalized, adapted Numerov implementation capable of determining band structures of periodic quantum systems is outlined. Based on the input potential, the presented approach numerically solves the Schrödinger equation in position space at each momentum space point. Thus, in addition to the band structure, the method inherently provides information about the state functions and probability densities in position space at each momentum space point considered. The generalized, adapted Numerov framework provided reliable estimates for a variety of increasingly complex test suites in one, two, and three dimensions. The accuracy of the proposed methodology was benchmarked against results obtained for the analytically solvable Kronig-Penney model. Furthermore, the presented numerical solver was applied to a model potential representing a 2D optical lattice being a challenging application relevant, for example, in the field of quantum computing. AU - Gamper, Jakob AU - Kluibenschedl, Florian AU - Weiss, Alexander K.H. AU - Hofer, Thomas S. ID - 14261 IS - 33 JF - Journal of Physical Chemistry Letters TI - Accessing position space wave functions in band structure calculations of periodic systems - a generalized, adapted numerov implementation for one-, two-, and three-dimensional quantum problems VL - 14 ER - TY - THES AB - Nonergodic systems, whose out-of-equilibrium dynamics fail to thermalize, provide a fascinating research direction both for fundamental reasons and for application in state of the art quantum devices. Going beyond the description of statistical mechanics, ergodicity breaking yields a new paradigm in quantum many-body physics, introducing novel phases of matter with no counterpart at equilibrium. In this Thesis, we address different open questions in the field, focusing on disorder-induced many-body localization (MBL) and on weak ergodicity breaking in kinetically constrained models. In particular, we contribute to the debate about transport in kinetically constrained models, studying the effect of $U(1)$ conservation and inversion-symmetry breaking in a family of quantum East models. Using tensor network techniques, we analyze the dynamics of large MBL systems beyond the limit of exact numerical methods. In this setting, we approach the debated topic of the coexistence of localized and thermal eigenstates separated by energy thresholds known as many-body mobility edges. Inspired by recent experiments, our work further investigates the localization of a small bath induced by the coupling to a large localized chain, the so-called MBL proximity effect. In the first Chapter, we introduce a family of particle-conserving kinetically constrained models, inspired by the quantum East model. The system we study features strong inversion-symmetry breaking, due to the nature of the correlated hopping. We show that these models host so-called quantum Hilbert space fragmentation, consisting of disconnected subsectors in an entangled basis, and further provide an analytical description of this phenomenon. We further probe its effect on dynamics of simple product states, showing revivals in fidelity and local observalbes. The study of dynamics within the largest subsector reveals an anomalous transient superdiffusive behavior crossing over to slow logarithmic dynamics at later times. This work suggests that particle conserving constrained models with inversion-symmetry breaking realize new universality classes of dynamics and invite their further theoretical and experimental studies. Next, we use kinetic constraints and disorder to design a model with many-body mobility edges in particle density. This feature allows to study the dynamics of localized and thermal states in large systems beyond the limitations of previous studies. The time-evolution shows typical signatures of localization at small densities, replaced by thermal behavior at larger densities. Our results provide evidence in favor of the stability of many-body mobility edges, which was recently challenged by a theoretical argument. To support our findings, we probe the mechanism proposed as a cause of delocalization in many-body localized systems with mobility edges suggesting its ineffectiveness in the model studied. In the last Chapter of this Thesis, we address the topic of many-body localization proximity effect. We study a model inspired by recent experiments, featuring Anderson localized coupled to a small bath of free hard-core bosons. The interaction among the two particle species results in non-trivial dynamics, which we probe using tensor network techniques. Our simulations show convincing evidence of many-body localization proximity effect when the bath is composed by a single free particle and interactions are strong. We furthter observe an anomalous entanglement dynamics, which we explain through a phenomenological theory. Finally, we extract highly excited eigenstates of large systems, providing supplementary evidence in favor of our findings. AU - Brighi, Pietro ID - 12732 SN - 2663-337X TI - Ergodicity breaking in disordered and kinetically constrained quantum many-body systems ER - TY - CONF AB - We formalized general (i.e., type-0) grammars using the Lean 3 proof assistant. We defined basic notions of rewrite rules and of words derived by a grammar, and used grammars to show closure of the class of type-0 languages under four operations: union, reversal, concatenation, and the Kleene star. The literature mostly focuses on Turing machine arguments, which are possibly more difficult to formalize. For the Kleene star, we could not follow the literature and came up with our own grammar-based construction. AU - Dvorak, Martin AU - Blanchette, Jasmin ID - 13120 SN - 9783959772846 T2 - 14th International Conference on Interactive Theorem Proving TI - Closure properties of general grammars - formally verified VL - 268 ER - TY - THES AB - During development, tissues undergo changes in size and shape to form functional organs. Distinct cellular processes such as cell division and cell rearrangements underlie tissue morphogenesis. Yet how the distinct processes are controlled and coordinated, and how they contribute to morphogenesis is poorly understood. In our study, we addressed these questions using the developing mouse neural tube. This epithelial organ transforms from a flat epithelial sheet to an epithelial tube while increasing in size and undergoing morpho-gen-mediated patterning. The extent and mechanism of neural progenitor rearrangement within the developing mouse neuroepithelium is unknown. To investigate this, we per-formed high resolution lineage tracing analysis to quantify the extent of epithelial rear-rangement at different stages of neural tube development. We quantitatively described the relationship between apical cell size with cell cycle dependent interkinetic nuclear migra-tions (IKNM) and performed high cellular resolution live imaging of the neuroepithelium to study the dynamics of junctional remodeling. Furthermore, developed a vertex model of the neuroepithelium to investigate the quantitative contribution of cell proliferation, cell differentiation and mechanical properties to the epithelial rearrangement dynamics and validated the model predictions through functional experiments. Our analysis revealed that at early developmental stages, the apical cell area kinetics driven by IKNM induce high lev-els of cell rearrangements in a regime of high junctional tension and contractility. After E9.5, there is a sharp decline in the extent of cell rearrangements, suggesting that the epi-thelium transitions from a fluid-like to a solid-like state. We found that this transition is regulated by the growth rate of the tissue, rather than by changes in cell-cell adhesion and contractile forces. Overall, our study provides a quantitative description of the relationship between tissue growth, cell cycle dynamics, epithelia rearrangements and the emergent tissue material properties, and novel insights on how epithelial cell dynamics influences tissue morphogenesis. AU - Bocanegra, Laura ID - 13081 SN - 2663 - 337X TI - Epithelial dynamics during mouse neural tube development ER - TY - JOUR AB - Statistics of natural scenes are not uniform - their structure varies dramatically from ground to sky. It remains unknown whether these non-uniformities are reflected in the large-scale organization of the early visual system and what benefits such adaptations would confer. Here, by relying on the efficient coding hypothesis, we predict that changes in the structure of receptive fields across visual space increase the efficiency of sensory coding. We show experimentally that, in agreement with our predictions, receptive fields of retinal ganglion cells change their shape along the dorsoventral retinal axis, with a marked surround asymmetry at the visual horizon. Our work demonstrates that, according to principles of efficient coding, the panoramic structure of natural scenes is exploited by the retina across space and cell-types. AU - Gupta, Divyansh AU - Mlynarski, Wiktor F AU - Sumser, Anton L AU - Symonova, Olga AU - Svaton, Jan AU - Jösch, Maximilian A ID - 12349 JF - Nature Neuroscience SN - 1097-6256 TI - Panoramic visual statistics shape retina-wide organization of receptive fields VL - 26 ER - TY - DATA AB - Statistics of natural scenes are not uniform - their structure varies dramatically from ground to sky. It remains unknown whether these non-uniformities are reflected in the large-scale organization of the early visual system and what benefits such adaptations would confer. Here, by relying on the efficient coding hypothesis, we predict that changes in the structure of receptive fields across visual space increase the efficiency of sensory coding. We show experimentally that, in agreement with our predictions, receptive fields of retinal ganglion cells change their shape along the dorsoventral retinal axis, with a marked surround asymmetry at the visual horizon. Our work demonstrates that, according to principles of efficient coding, the panoramic structure of natural scenes is exploited by the retina across space and cell-types. AU - Gupta, Divyansh AU - Sumser, Anton L AU - Jösch, Maximilian A ID - 12370 TI - Research Data for: Panoramic visual statistics shape retina-wide organization of receptive fields ER - TY - THES AB - The extension of extremal combinatorics to the setting of exterior algebra is a work in progress that gained attention recently. In this thesis, we study the combinatorial structure of exterior algebra by introducing a dictionary that translates the notions from the set systems into the framework of exterior algebra. We show both generalizations of celebrated Erdös--Ko--Rado theorem and Hilton--Milner theorem to the setting of exterior algebra in the simplest non-trivial case of two-forms. AU - Köse, Seyda ID - 13331 SN - 2791-4585 TI - Exterior algebra and combinatorics ER - TY - JOUR AB - The celebrated Erdős–Ko–Rado theorem about the maximal size of an intersecting family of r-element subsets of was extended to the setting of exterior algebra in [5, Theorem 2.3] and in [6, Theorem 1.4]. However, the equality case has not been settled yet. In this short note, we show that the extension of the Erdős–Ko–Rado theorem and the characterization of the equality case therein, as well as those of the Hilton–Milner theorem to the setting of exterior algebra in the simplest non-trivial case of two-forms follow from a folklore puzzle about possible arrangements of an intersecting family of lines. AU - Ivanov, Grigory AU - Köse, Seyda ID - 12680 IS - 6 JF - Discrete Mathematics SN - 0012-365X TI - Erdős-Ko-Rado and Hilton-Milner theorems for two-forms VL - 346 ER - TY - CONF AB - The safety-liveness dichotomy is a fundamental concept in formal languages which plays a key role in verification. Recently, this dichotomy has been lifted to quantitative properties, which are arbitrary functions from infinite words to partially-ordered domains. We look into harnessing the dichotomy for the specific classes of quantitative properties expressed by quantitative automata. These automata contain finitely many states and rational-valued transition weights, and their common value functions Inf, Sup, LimInf, LimSup, LimInfAvg, LimSupAvg, and DSum map infinite words into the totallyordered domain of real numbers. In this automata-theoretic setting, we establish a connection between quantitative safety and topological continuity and provide an alternative characterization of quantitative safety and liveness in terms of their boolean counterparts. For all common value functions, we show how the safety closure of a quantitative automaton can be constructed in PTime, and we provide PSpace-complete checks of whether a given quantitative automaton is safe or live, with the exception of LimInfAvg and LimSupAvg automata, for which the safety check is in ExpSpace. Moreover, for deterministic Sup, LimInf, and LimSup automata, we give PTime decompositions into safe and live automata. These decompositions enable the separation of techniques for safety and liveness verification for quantitative specifications. AU - Boker, Udi AU - Henzinger, Thomas A AU - Mazzocchi, Nicolas Adrien AU - Sarac, Naci E ID - 13221 SN - 9783959772990 T2 - 34th International Conference on Concurrency Theory TI - Safety and liveness of quantitative automata VL - 279 ER - TY - JOUR AB - Let X be a sufficiently large positive integer. We prove that one may choose a subset S of primes with cardinality O(logX) such that a positive proportion of integers less than X can be represented by x2+py2 for at least one p∈S. AU - Diao, Yijie ID - 12406 JF - Acta Arithmetica KW - Algebra KW - Number Theory SN - 0065-1036 TI - Density of the union of positive diagonal binary quadratic forms VL - 207 ER - TY - THES AB - Animals exhibit a remarkable ability to learn and remember new behaviors, skills, and associations throughout their lifetime. These capabilities are made possible thanks to a variety of changes in the brain throughout adulthood, regrouped under the term "plasticity". Some cells in the brain —neurons— and specifically changes in the connections between neurons, the synapses, were shown to be crucial for the formation, selection, and consolidation of memories from past experiences. These ongoing changes of synapses across time are called synaptic plasticity. Understanding how a myriad of biochemical processes operating at individual synapses can somehow work in concert to give rise to meaningful changes in behavior is a fascinating problem and an active area of research. However, the experimental search for the precise plasticity mechanisms at play in the brain is daunting, as it is difficult to control and observe synapses during learning. Theoretical approaches have thus been the default method to probe the plasticity-behavior connection. Such studies attempt to extract unifying principles across synapses and model all observed synaptic changes using plasticity rules: equations that govern the evolution of synaptic strengths across time in neuronal network models. These rules can use many relevant quantities to determine the magnitude of synaptic changes, such as the precise timings of pre- and postsynaptic action potentials, the recent neuronal activity levels, the state of neighboring synapses, etc. However, analytical studies rely heavily on human intuition and are forced to make simplifying assumptions about plasticity rules. In this thesis, we aim to assist and augment human intuition in this search for plasticity rules. We explore whether a numerical approach could automatically discover the plasticity rules that elicit desired behaviors in large networks of interconnected neurons. This approach is dubbed meta-learning synaptic plasticity: learning plasticity rules which themselves will make neuronal networks learn how to solve a desired task. We first write all the potential plasticity mechanisms to consider using a single expression with adjustable parameters. We then optimize these plasticity parameters using evolutionary strategies or Bayesian inference on tasks known to involve synaptic plasticity, such as familiarity detection and network stabilization. We show that these automated approaches are powerful tools, able to complement established analytical methods. By comprehensively screening plasticity rules at all synapse types in realistic, spiking neuronal network models, we discover entire sets of degenerate plausible plasticity rules that reliably elicit memory-related behaviors. Our approaches allow for more robust experimental predictions, by abstracting out the idiosyncrasies of individual plasticity rules, and provide fresh insights on synaptic plasticity in spiking network models. AU - Confavreux, Basile J ID - 14422 SN - 2663 - 337X TI - Synapseek: Meta-learning synaptic plasticity rules ER - TY - THES AB - Superconductivity has many important applications ranging from levitating trains over qubits to MRI scanners. The phenomenon is successfully modeled by Bardeen-Cooper-Schrieffer (BCS) theory. From a mathematical perspective, BCS theory has been studied extensively for systems without boundary. However, little is known in the presence of boundaries. With the help of numerical methods physicists observed that the critical temperature may increase in the presence of a boundary. The goal of this thesis is to understand the influence of boundaries on the critical temperature in BCS theory and to give a first rigorous justification of these observations. On the way, we also study two-body Schrödinger operators on domains with boundaries and prove additional results for superconductors without boundary. BCS theory is based on a non-linear functional, where the minimizer indicates whether the system is superconducting or in the normal, non-superconducting state. By considering the Hessian of the BCS functional at the normal state, one can analyze whether the normal state is possibly a minimum of the BCS functional and estimate the critical temperature. The Hessian turns out to be a linear operator resembling a Schrödinger operator for two interacting particles, but with more complicated kinetic energy. As a first step, we study the two-body Schrödinger operator in the presence of boundaries. For Neumann boundary conditions, we prove that the addition of a boundary can create new eigenvalues, which correspond to the two particles forming a bound state close to the boundary. Second, we need to understand superconductivity in the translation invariant setting. While in three dimensions this has been extensively studied, there is no mathematical literature for the one and two dimensional cases. In dimensions one and two, we compute the weak coupling asymptotics of the critical temperature and the energy gap in the translation invariant setting. We also prove that their ratio is independent of the microscopic details of the model in the weak coupling limit; this property is referred to as universality. In the third part, we study the critical temperature of superconductors in the presence of boundaries. We start by considering the one-dimensional case of a half-line with contact interaction. Then, we generalize the results to generic interactions and half-spaces in one, two and three dimensions. Finally, we compare the critical temperature of a quarter space in two dimensions to the critical temperatures of a half-space and of the full space. AU - Roos, Barbara ID - 14374 SN - 2663 - 337X TI - Boundary superconductivity in BCS theory ER - TY - JOUR AB - We consider the linear BCS equation, determining the BCS critical temperature, in the presence of a boundary, where Dirichlet boundary conditions are imposed. In the one-dimensional case with point interactions, we prove that the critical temperature is strictly larger than the bulk value, at least at weak coupling. In particular, the Cooper-pair wave function localizes near the boundary, an effect that cannot be modeled by effective Neumann boundary conditions on the order parameter as often imposed in Ginzburg–Landau theory. We also show that the relative shift in critical temperature vanishes if the coupling constant either goes to zero or to infinity. AU - Hainzl, Christian AU - Roos, Barbara AU - Seiringer, Robert ID - 13207 IS - 4 JF - Journal of Spectral Theory SN - 1664-039X TI - Boundary superconductivity in the BCS model VL - 12 ER - TY - CONF AB - Batching is a technique that stores multiple keys/values in each node of a data structure. In sequential search data structures, batching reduces latency by reducing the number of cache misses and shortening the chain of pointers to dereference. Applying batching to concurrent data structures is challenging, because it is difficult to maintain the search property and keep contention low in the presence of batching. In this paper, we present a general methodology for leveraging batching in concurrent search data structures, called BatchBoost. BatchBoost builds a search data structure from distinct "data" and "index" layers. The data layer’s purpose is to store a batch of key/value pairs in each of its nodes. The index layer uses an unmodified concurrent search data structure to route operations to a position in the data layer that is "close" to where the corresponding key should exist. The requirements on the index and data layers are low: with minimal effort, we were able to compose three highly scalable concurrent search data structures based on three original data structures as the index layers with a batched version of the Lazy List as the data layer. The resulting BatchBoost data structures provide significant performance improvements over their original counterparts. AU - Aksenov, Vitaly AU - Anoprenko, Michael AU - Fedorov, Alexander AU - Spear, Michael ID - 14485 SN - 1868-8969 T2 - 37th International Symposium on Distributed Computing TI - Brief announcement: BatchBoost: Universal batching for concurrent data structures VL - 281 ER - TY - DATA AB - We introduce a stochastic cellular automaton as a model for culture and border formation. The model can be conceptualized as a game where the expansion rate of cultures is quantified in terms of their area and perimeter in such a way that approximately round cultures get a competitive advantage. We first analyse the model with periodic boundary conditions, where we study how the model can end up in a fixed state, i.e. freezes. Then we implement the model on the European geography with mountains and rivers. We see how the model reproduces some qualitative features of European culture formation, namely that rivers and mountains are more frequently borders between cultures, mountainous regions tend to have higher cultural diversity and the central European plain has less clear cultural borders. AU - Klausen, Frederik Ravn AU - Lauritsen, Asbjørn Bækgaard ID - 12869 TI - Research data for: A stochastic cellular automaton model of culture formation ER - TY - JOUR AB - We introduce a stochastic cellular automaton as a model for culture and border formation. The model can be conceptualized as a game where the expansion rate of cultures is quantified in terms of their area and perimeter in such a way that approximately geometrically round cultures get a competitive advantage. We first analyze the model with periodic boundary conditions, where we study how the model can end up in a fixed state, i.e., freezes. Then we implement the model on the European geography with mountains and rivers. We see how the model reproduces some qualitative features of European culture formation, namely, that rivers and mountains are more frequently borders between cultures, mountainous regions tend to have higher cultural diversity, and the central European plain has less clear cultural borders. AU - Klausen, Frederik Ravn AU - Lauritsen, Asbjørn Bækgaard ID - 12890 IS - 5 JF - Physical Review E SN - 2470-0045 TI - Stochastic cellular automaton model of culture formation VL - 108 ER - TY - JOUR AB - The acyl-CoA-binding domain-containing protein 6 (ACBD6) is ubiquitously expressed, plays a role in the acylation of lipids and proteins, and regulates the N-myristoylation of proteins via N-myristoyltransferase enzymes (NMTs). However, its precise function in cells is still unclear, as is the consequence of ACBD6 defects on human pathophysiology. Utilizing exome sequencing and extensive international data sharing efforts, we identified 45 affected individuals from 28 unrelated families (consanguinity 93%) with bi-allelic pathogenic, predominantly loss-of-function (18/20) variants in ACBD6. We generated zebrafish and Xenopus tropicalis acbd6 knockouts by CRISPR/Cas9 and characterized the role of ACBD6 on protein N-myristoylation with YnMyr chemical proteomics in the model organisms and human cells, with the latter also being subjected further to ACBD6 peroxisomal localization studies. The affected individuals (23 males and 22 females), with ages ranging from 1 to 50 years old, typically present with a complex and progressive disease involving moderate-to-severe global developmental delay/intellectual disability (100%) with significant expressive language impairment (98%), movement disorders (97%), facial dysmorphism (95%), and mild cerebellar ataxia (85%) associated with gait impairment (94%), limb spasticity/hypertonia (76%), oculomotor (71%) and behavioural abnormalities (65%), overweight (59%), microcephaly (39%) and epilepsy (33%). The most conspicuous and common movement disorder was dystonia (94%), frequently leading to early-onset progressive postural deformities (97%), limb dystonia (55%), and cervical dystonia (31%). A jerky tremor in the upper limbs (63%), a mild head tremor (59%), parkinsonism/hypokinesia developing with advancing age (32%), and simple motor and vocal tics were among other frequent movement disorders. Midline brain malformations including corpus callosum abnormalities (70%), hypoplasia/agenesis of the anterior commissure (66%), short midbrain and small inferior cerebellar vermis (38% each), as well as hypertrophy of the clava (24%) were common neuroimaging findings. acbd6-deficient zebrafish and Xenopus models effectively recapitulated many clinical phenotypes reported in patients including movement disorders, progressive neuromotor impairment, seizures, microcephaly, craniofacial dysmorphism, and midbrain defects accompanied by developmental delay with increased mortality over time. Unlike ACBD5, ACBD6 did not show a peroxisomal localisation and ACBD6-deficiency was not associated with altered peroxisomal parameters in patient fibroblasts. Significant differences in YnMyr-labelling were observed for 68 co- and 18 post-translationally N-myristoylated proteins in patient-derived fibroblasts. N-Myristoylation was similarly affected in acbd6-deficient zebrafish and Xenopus tropicalis models, including Fus, Marcks, and Chchd-related proteins implicated in neurological diseases. The present study provides evidence that bi-allelic pathogenic variants in ACBD6 lead to a distinct neurodevelopmental syndrome accompanied by complex and progressive cognitive and movement disorders. AU - Kaiyrzhanov, Rauan AU - Rad, Aboulfazl AU - Lin, Sheng-Jia AU - Bertoli-Avella, Aida AU - Kallemeijn, Wouter W AU - Godwin, Annie AU - Zaki, Maha S AU - Huang, Kevin AU - Lau, Tracy AU - Petree, Cassidy AU - Efthymiou, Stephanie AU - Ghayoor Karimiani, Ehsan AU - Hempel, Maja AU - Normand, Elizabeth A AU - Rudnik-Schöneborn, Sabine AU - Schatz, Ulrich A AU - Baggelaar, Marc P AU - Ilyas, Muhammad AU - Sultan, Tipu AU - Alvi, Javeria Raza AU - Ganieva, Manizha AU - Fowler, Ben AU - Aanicai, Ruxandra AU - Akay Tayfun, Gulsen AU - Al Saman, Abdulaziz AU - Alswaid, Abdulrahman AU - Amiri, Nafise AU - Asilova, Nilufar AU - Shotelersuk, Vorasuk AU - Yeetong, Patra AU - Azam, Matloob AU - Babaei, Meisam AU - Bahrami Monajemi, Gholamreza AU - Mohammadi, Pouria AU - Samie, Saeed AU - Banu, Selina Husna AU - Basto, Jorge Pinto AU - Kortüm, Fanny AU - Bauer, Mislen AU - Bauer, Peter AU - Beetz, Christian AU - Garshasbi, Masoud AU - Hameed Issa, Awatif AU - Eyaid, Wafaa AU - Ahmed, Hind AU - Hashemi, Narges AU - Hassanpour, Kazem AU - Herman, Isabella AU - Ibrohimov, Sherozjon AU - Abdul-Majeed, Ban A AU - Imdad, Maria AU - Isrofilov, Maksudjon AU - Kaiyal, Qassem AU - Khan, Suliman AU - Kirmse, Brian AU - Koster, Janet AU - Lourenço, Charles Marques AU - Mitani, Tadahiro AU - Moldovan, Oana AU - Murphy, David AU - Najafi, Maryam AU - Pehlivan, Davut AU - Rocha, Maria Eugenia AU - Salpietro, Vincenzo AU - Schmidts, Miriam AU - Shalata, Adel AU - Mahroum, Mohammad AU - Talbeya, Jawabreh Kassem AU - Taylor, Robert W AU - Vazquez, Dayana AU - Vetro, Annalisa AU - Waterham, Hans R AU - Zaman, Mashaya AU - Schrader, Tina A AU - Chung, Wendy K AU - Guerrini, Renzo AU - Lupski, James R AU - Gleeson, Joseph AU - Suri, Mohnish AU - Jamshidi, Yalda AU - Bhatia, Kailash P AU - Vona, Barbara AU - Schrader, Michael AU - Severino, Mariasavina AU - Guille, Matthew AU - Tate, Edward W AU - Varshney, Gaurav K AU - Houlden, Henry AU - Maroofian, Reza ID - 14543 JF - Brain KW - Neurology (clinical) SN - 0006-8950 TI - Bi-allelic ACBD6 variants lead to a neurodevelopmental syndrome with progressive and complex movement disorders ER - TY - JOUR AB - It is a remarkable property of BCS theory that the ratio of the energy gap at zero temperature Ξ and the critical temperature Tc is (approximately) given by a universal constant, independent of the microscopic details of the fermionic interaction. This universality has rigorously been proven quite recently in three spatial dimensions and three different limiting regimes: weak coupling, low density and high density. The goal of this short note is to extend the universal behavior to lower dimensions d=1,2 and give an exemplary proof in the weak coupling limit. AU - Henheik, Sven Joscha AU - Lauritsen, Asbjørn Bækgaard AU - Roos, Barbara ID - 14542 JF - Reviews in Mathematical Physics SN - 0129-055X TI - Universality in low-dimensional BCS theory ER - TY - THES AB - Payment channel networks are a promising approach to improve the scalability bottleneck of cryptocurrencies. Two design principles behind payment channel networks are efficiency and privacy. Payment channel networks improve efficiency by allowing users to transact in a peer-to-peer fashion along multi-hop routes in the network, avoiding the lengthy process of consensus on the blockchain. Transacting over payment channel networks also improves privacy as these transactions are not broadcast to the blockchain. Despite the influx of recent protocols built on top of payment channel networks and their analysis, a common shortcoming of many of these protocols is that they typically focus only on either improving efficiency or privacy, but not both. Another limitation on the efficiency front is that the models used to model actions, costs and utilities of users are limited or come with unrealistic assumptions. This thesis aims to address some of the shortcomings of recent protocols and algorithms on payment channel networks, particularly in their privacy and efficiency aspects. We first present a payment route discovery protocol based on hub labelling and private information retrieval that hides the route query and is also efficient. We then present a rebalancing protocol that formulates the rebalancing problem as a linear program and solves the linear program using multiparty computation so as to hide the channel balances. The rebalancing solution as output by our protocol is also globally optimal. We go on to develop more realistic models of the action space, costs, and utilities of both existing and new users that want to join the network. In each of these settings, we also develop algorithms to optimise the utility of these users with good guarantees on the approximation and competitive ratios. AU - Yeo, Michelle X ID - 14506 SN - 2663 - 337X TI - Advances in efficiency and privacy in payment channel network analysis ER - TY - THES AB - Most motions of many-body systems at any scale in nature with sufficient degrees of freedom tend to be chaotic; reaching from the orbital motion of planets, the air currents in our atmosphere, down to the water flowing through our pipelines or the movement of a population of bacteria. To the observer it is therefore intriguing when a moving collective exhibits order. Collective motion of flocks of birds, schools of fish or swarms of self-propelled particles or robots have been studied extensively over the past decades but the mechanisms involved in the transition from chaos to order remain unclear. Here, the interactions, that in most systems give rise to chaos, sustain order. In this thesis we investigate mechanisms that preserve, destabilize or lead to the ordered state. We show that endothelial cells migrating in circular confinements transition to a collective rotating state and concomitantly synchronize the frequencies of nucleating actin waves within individual cells. Consequently, the frequency dependent cell migration speed uniformizes across the population. Complementary to the WAVE dependent nucleation of traveling actin waves, we show that in leukocytes the actin polymerization depending on WASp generates pushing forces locally at stationary patches. Next, in pipe flows, we study methods to disrupt the self–sustaining cycle of turbulence and therefore relaminarize the flow. While we find in pulsating flow conditions that turbulence emerges through a helical instability during the decelerating phase. Finally, we show quantitatively in brain slices of mice that wild-type control neurons can compensate the migratory deficits of a genetically modified neuronal sub–population in the developing cortex. AU - Riedl, Michael ID - 12726 SN - 2663-337X TI - Synchronization in collectively moving active matter ER - TY - THES AB - Most motions of many-body systems at any scale in nature with sufficient degrees of freedom tend to be chaotic; reaching from the orbital motion of planets, the air currents in our atmosphere, down to the water flowing through our pipelines or the movement of a population of bacteria. To the observer it is therefore intriguing when a moving collective exhibits order. Collective motion of flocks of birds, schools of fish or swarms of self-propelled particles or robots have been studied extensively over the past decades but the mechanisms involved in the transition from chaos to order remain unclear. Here, the interactions, that in most systems give rise to chaos, sustain order. In this thesis we investigate mechanisms that preserve, destabilize or lead to the ordered state. We show that endothelial cells migrating in circular confinements transition to a collective rotating state and concomitantly synchronize the frequencies of nucleating actin waves within individual cells. Consequently, the frequency dependent cell migration speed uniformizes across the population. Complementary to the WAVE dependent nucleation of traveling actin waves, we show that in leukocytes the actin polymerization depending on WASp generates pushing forces locally at stationary patches. Next, in pipe flows, we study methods to disrupt the self--sustaining cycle of turbulence and therefore relaminarize the flow. While we find in pulsating flow conditions that turbulence emerges through a helical instability during the decelerating phase. Finally, we show quantitatively in brain slices of mice that wild-type control neurons can compensate the migratory deficits of a genetically modified neuronal sub--population in the developing cortex. AU - Riedl, Michael ID - 14530 KW - Synchronization KW - Collective Movement KW - Active Matter KW - Cell Migration KW - Active Colloids SN - 2663 - 337X TI - Synchronization in collectively moving active matter ER - TY - THES AB - Superconductor-semiconductor heterostructures currently capture a significant amount of research interest and they serve as the physical platform in many proposals towards topological quantum computation. Despite being under extensive investigations, historically using transport techniques, the basic properties of the interface between the superconductor and the semiconductor remain to be understood. In this thesis, two separate studies on the Al-InAs heterostructures are reported with the first focusing on the physics of the material motivated by the emergence of a new phase, the Bogoliubov-Fermi surface. The second focuses on a technological application, a gate-tunable Josephson parametric amplifier. In the first study, we investigate the hypothesized unconventional nature of the induced superconductivity at the interface between the Al thin film and the InAs quantum well. We embed a two-dimensional Al-InAs hybrid system in a resonant microwave circuit allowing measurements of change in inductance. The behaviour of the resonance in a range of temperature and in-plane magnetic field has been studied and compared with the theory of conventional s-wave superconductor and a two-component theory that includes both contribution of the $s$-wave pairing in Al and the intraband $p \pm ip$ pairing in InAs. Measuring the temperature dependence of resonant frequency, no discrepancy is found between data and the conventional theory. We observe the breakdown of superconductivity due to an applied magnetic field which contradicts the conventional theory. In contrast, the data can be captured quantitatively by fitting to a two-component model. We find the evidence of the intraband $p \pm ip$ pairing in the InAs and the emergence of the Bogoliubov-Fermi surfaces due to magnetic field with the characteristic value $B^* = 0.33~\mathrm{T}$. From the fits, the sheet resistance of Al, the carrier density and mobility in InAs are determined. By systematically studying the anisotropy of the circuit response, we find weak anisotropy for $B < B^*$ and increasingly strong anisotropy for $B > B^*$ resulting in a pronounced two-lobe structure in polar plot of frequency versus field angle. Strong resemblance between the field dependence of dissipation and superfluid density hints at a hidden signature of the Bogoliubov-Fermi surface that is burried in the dissipation data. In the second study, we realize a parametric amplifier with a Josephson field effect transistor as the active element. The device's modest construction consists of a gated SNS weak link embedded at the center of a coplanar waveguide resonator. By applying a gate voltage, the resonant frequency is field-effect tunable over a range of 2 GHz. Modelling the JoFET minimally as a parallel RL circuit, the dissipation introduced by the JoFET can be quantitatively related to the gate voltage. We observed gate-tunable Kerr nonlinearity qualitatively in line with expectation. The JoFET amplifier has 20 dB of gain, 4 MHz of instantaneous bandwidth, and a 1dB compression point of -125.5 dBm when operated at a fixed resonant frequency. In general, the signal-to-noise ratio is improved by 5-7 dB when the JoFET amplifier is activated compared. The noise of the measurement chain and insertion loss of relevant circuit elements are calibrated to determine the expected and the real noise performance of the JoFET amplifier. As a quantification of the noise performance, the measured total input-referred noise of the JoFET amplifier is in good agreement with the estimated expectation which takes device loss into account. We found that the noise performance of the device reported in this document approaches one photon of total input-referred added noise which is the quantum limit imposed in nondegenerate parametric amplifier. AU - Phan, Duc T ID - 14547 KW - superconductor-semiconductor KW - superconductivity KW - Al KW - InAs KW - p-wave KW - superconductivity KW - JPA KW - microwave SN - 2663 - 337X TI - Resonant microwave spectroscopy of Al-InAs ER - TY - JOUR AB - We introduce a compact, intuitive procedural graph representation for cellular metamaterials, which are small-scale, tileable structures that can be architected to exhibit many useful material properties. Because the structures’ “architectures” vary widely—with elements such as beams, thin shells, and solid bulks—it is difficult to explore them using existing representations. Generic approaches like voxel grids are versatile, but it is cumbersome to represent and edit individual structures; architecture-specific approaches address these issues, but are incompatible with one another. By contrast, our procedural graph succinctly represents the construction process for any structure using a simple skeleton annotated with spatially varying thickness. To express the highly constrained triply periodic minimal surfaces (TPMS) in this manner, we present the first fully automated version of the conjugate surface construction method, which allows novices to create complex TPMS from intuitive input. We demonstrate our representation’s expressiveness, accuracy, and compactness by constructing a wide range of established structures and hundreds of novel structures with diverse architectures and material properties. We also conduct a user study to verify our representation’s ease-of-use and ability to expand engineers’ capacity for exploration. AU - Makatura, Liane AU - Wang, Bohan AU - Chen, Yi-Lu AU - Deng, Bolei AU - Wojtan, Christopher J AU - Bickel, Bernd AU - Matusik, Wojciech ID - 14628 IS - 5 JF - ACM Transactions on Graphics KW - Computer Graphics and Computer-Aided Design SN - 0730-0301 TI - Procedural metamaterials: A unified procedural graph for metamaterial design VL - 42 ER - TY - JOUR AB - Mass spectrometry imaging (MSI) is a powerful analytical technique for the two-dimensional (2D) localization of chemicals on surfaces. Conventional MSI experiments require to predefine the surface of interest based on photographic or microscopic images. Typically, these boundaries can no longer be changed or adjusted once the experiment has been started. In terms of a more interactive approach we recently developed a pen-like ionization interface which is directly connected to the mass spectrometer. The device allows the user to ionize chemicals by desorption electrospray ionization (DESI) and to freely move the interface over a surface of interest. A mini camera, which is mounted on the tip of the pen, magnifies the desorption area and enables a simple positioning of the pen. The combination of optical data from the camera module and chemical data obtained by mass analysis facilitates a novel type of imaging experiment: interactive mass spectrometry imaging (IMSI). For this application, we present a novel approach for a robust, optical flow-based motion detection. While the live video stream from the camera is used to track the pen's motion across the surface a post-acquisition algorithm correlates the coordinates of the pen trajectory with respective mass spectra obtained from a simultaneous mass spectrometric data acquisition. This algorithm is no longer dependent on a single, manually applied optical marker on the sample surface, which has to be visible on all video frames throughout the analysis. The advanced DESI-IMSI method was successfully tested on inkjet-printed letters as well as mouse brain tissue samples. Validation of the results was done by comparing DESI-IMSI with standard DESI-MSI data. AU - Kluibenschedl, Florian AU - Ploner, Anna AU - Meisenbichler, Christina AU - Konrat, Robert AU - Müller, Thomas ID - 14653 JF - International Journal of Mass Spectrometry SN - 1387-3806 TI - Advanced motion tracking for interactive mass spectrometry imaging (IMSI) VL - 495 ER - TY - JOUR AB - Viscous flows through pipes and channels are steady and ordered until, with increasing velocity, the laminar motion catastrophically breaks down and gives way to turbulence. How this apparently discontinuous change from low- to high-dimensional motion can be rationalized within the framework of the Navier-Stokes equations is not well understood. Exploiting geometrical properties of transitional channel flow we trace turbulence to far lower Reynolds numbers (Re) than previously possible and identify the complete path that reversibly links fully turbulent motion to an invariant solution. This precursor of turbulence destabilizes rapidly with Re, and the accompanying explosive increase in attractor dimension effectively marks the transition between deterministic and de facto stochastic dynamics. AU - Paranjape, Chaitanya S AU - Yalniz, Gökhan AU - Duguet, Yohann AU - Budanur, Nazmi B AU - Hof, Björn ID - 13274 IS - 3 JF - Physical Review Letters KW - General Physics and Astronomy SN - 0031-9007 TI - Direct path from turbulence to time-periodic solutions VL - 131 ER - TY - THES AB - Females and males across species are subject to divergent selective pressures arising from di↵erent reproductive interests and ecological niches. This often translates into a intricate array of sex-specific natural and sexual selection on traits that have a shared genetic basis between both sexes, causing a genetic sexual conflict. The resolution of this conflict mostly relies on the evolution of sex-specific expression of the shared genes, leading to phenotypic sexual dimorphism. Such sex-specific gene expression is thought to evolve via modifications of the genetic networks ultimately linked to sex-determining transcription factors. Although much empirical and theoretical evidence supports this standard picture of the molecular basis of sexual conflict resolution, there still are a few open questions regarding the complex array of selective forces driving phenotypic di↵erentiation between the sexes, as well as the molecular mechanisms underlying sexspecific adaptation. I address some of these open questions in my PhD thesis. First, how do patterns of phenotypic sexual dimorphism vary within populations, as a response to the temporal and spatial changes in sex-specific selective forces? To tackle this question, I analyze the patterns of sex-specific phenotypic variation along three life stages and across populations spanning the whole geographical range of Rumex hastatulus, a wind-pollinated angiosperm, in the first Chapter of the thesis. Second, how do gene expression patterns lead to phenotypic dimorphism, and what are the molecular mechanisms underlying the observed transcriptomic variation? I address this question by examining the sex- and tissue-specific expression variation in newly-generated datasets of sex-specific expression in heads and gonads of Drosophila melanogaster. I additionally used two complementary approaches for the study of the genetic basis of sex di↵erences in gene expression in the second and third Chapters of the thesis. Third, how does intersex correlation, thought to be one of the main aspects constraining the ability for the two sexes to decouple, interact with the evolution of sexual dimorphism? I develop models of sex-specific stabilizing selection, mutation and drift to formalize common intuition regarding the patterns of covariation between intersex correlation and sexual dimorphism in the fourth Chapter of the thesis. Alltogether, the work described in this PhD thesis provides useful insights into the links between genetic, transcriptomic and phenotypic layers of sex-specific variation, and contributes to our general understanding of the dynamics of sexual dimorphism evolution. AU - Puixeu Sala, Gemma ID - 14058 SN - 2663-337X TI - The molecular basis of sexual dimorphism: Experimental and theoretical characterization of phenotypic, transcriptomic and genetic patterns of sex-specific adaptation ER - TY - JOUR AB - The regulatory architecture of gene expression is known to differ substantially between sexes in Drosophila, but most studies performed so far used whole-body data and only single crosses, which may have limited their scope to detect patterns that are robust across tissues and biological replicates. Here, we use allele-specific gene expression of parental and reciprocal hybrid crosses between 6 Drosophila melanogaster inbred lines to quantify cis- and trans-regulatory variation in heads and gonads of both sexes separately across 3 replicate crosses. Our results suggest that female and male heads, as well as ovaries, have a similar regulatory architecture. On the other hand, testes display more and substantially different cis-regulatory effects, suggesting that sex differences in the regulatory architecture that have been previously observed may largely derive from testis-specific effects. We also examine the difference in cis-regulatory variation of genes across different levels of sex bias in gonads and heads. Consistent with the idea that intersex correlations constrain expression and can lead to sexual antagonism, we find more cis variation in unbiased and moderately biased genes in heads. In ovaries, reduced cis variation is observed for male-biased genes, suggesting that cis variants acting on these genes in males do not lead to changes in ovary expression. Finally, we examine the dominance patterns of gene expression and find that sex- and tissue-specific patterns of inheritance as well as trans-regulatory variation are highly variable across biological crosses, although these were performed in highly controlled experimental conditions. This highlights the importance of using various genetic backgrounds to infer generalizable patterns. AU - Puixeu Sala, Gemma AU - Macon, Ariana AU - Vicoso, Beatriz ID - 14077 IS - 8 JF - G3: Genes, Genomes, Genetics KW - Genetics (clinical) KW - Genetics KW - Molecular Biology SN - 2160-1836 TI - Sex-specific estimation of cis and trans regulation of gene expression in heads and gonads of Drosophila melanogaster VL - 13 ER - TY - DATA AB - Datasets of the publication "Sex-specific estimation of cis and trans regulation of gene expression in heads and gonads of Drosophila melanogaster". AU - Puixeu Sala, Gemma ID - 12933 TI - Data from: Sex-specific estimation of cis and trans regulation of gene expression in heads and gonads of Drosophila melanogaster ER - TY - JOUR AB - The total energy of an eigenstate in a composite quantum system tends to be distributed equally among its constituents. We identify the quantum fluctuation around this equipartition principle in the simplest disordered quantum system consisting of linear combinations of Wigner matrices. As our main ingredient, we prove the Eigenstate Thermalisation Hypothesis and Gaussian fluctuation for general quadratic forms of the bulk eigenvectors of Wigner matrices with an arbitrary deformation. AU - Cipolloni, Giorgio AU - Erdös, László AU - Henheik, Sven Joscha AU - Kolupaiev, Oleksii ID - 14343 JF - Forum of Mathematics, Sigma TI - Gaussian fluctuations in the equipartition principle for Wigner matrices VL - 11 ER - TY - JOUR AB - Only recently has it been possible to construct a self-adjoint Hamiltonian that involves the creation of Dirac particles at a point source in 3d space. Its definition makes use of an interior-boundary condition. Here, we develop for this Hamiltonian a corresponding theory of the Bohmian configuration. That is, we (non-rigorously) construct a Markov jump process $(Q_t)_{t\in\mathbb{R}}$ in the configuration space of a variable number of particles that is $|\psi_t|^2$-distributed at every time t and follows Bohmian trajectories between the jumps. The jumps correspond to particle creation or annihilation events and occur either to or from a configuration with a particle located at the source. The process is the natural analog of Bell's jump process, and a central piece in its construction is the determination of the rate of particle creation. The construction requires an analysis of the asymptotic behavior of the Bohmian trajectories near the source. We find that the particle reaches the source with radial speed 0, but orbits around the source infinitely many times in finite time before absorption (or after emission). AU - Henheik, Sven Joscha AU - Tumulka, Roderich ID - 14421 IS - 44 JF - Journal of Physics A: Mathematical and Theoretical SN - 1751-8113 TI - Creation rate of Dirac particles at a point source VL - 56 ER - TY - JOUR AB - Water adsorption and dissociation processes on pristine low-index TiO2 interfaces are important but poorly understood outside the well-studied anatase (101) and rutile (110). To understand these, we construct three sets of machine learning potentials that are simultaneously applicable to various TiO2 surfaces, based on three density-functional-theory approximations. Here we show the water dissociation free energies on seven pristine TiO2 surfaces, and predict that anatase (100), anatase (110), rutile (001), and rutile (011) favor water dissociation, anatase (101) and rutile (100) have mostly molecular adsorption, while the simulations of rutile (110) sensitively depend on the slab thickness and molecular adsorption is preferred with thick slabs. Moreover, using an automated algorithm, we reveal that these surfaces follow different types of atomistic mechanisms for proton transfer and water dissociation: one-step, two-step, or both. These mechanisms can be rationalized based on the arrangements of water molecules on the different surfaces. Our finding thus demonstrates that the different pristine TiO2 surfaces react with water in distinct ways, and cannot be represented using just the low-energy anatase (101) and rutile (110) surfaces. AU - Zeng, Zezhu AU - Wodaczek, Felix AU - Liu, Keyang AU - Stein, Frederick AU - Hutter, Jürg AU - Chen, Ji AU - Cheng, Bingqing ID - 14425 JF - Nature Communications TI - Mechanistic insight on water dissociation on pristine low-index TiO2 surfaces from machine learning molecular dynamics simulations VL - 14 ER - TY - THES AU - Sack, Stefan ID - 14622 SN - 2663 - 337X TI - Improving variational quantum algorithms: Innovative initialization techniques and extensions to qudit systems ER - TY - THES AU - Stopp, Julian A ID - 14697 SN - 2663 - 337X TI - Neutrophils on the hunt: Migratory strategies employed by neutrophils to fulfill their effector function ER - TY - THES AB - For self-incompatibility (SI) to be stable in a population, theory predicts that sufficient inbreeding depression (ID) is required: the fitness of offspring from self-mated individuals must be low enough to prevent the spread of self-compatibility (SC). Reviews of natural plant populations have supported this theory, with SI species generally showing high levels of ID. However, there is thought to be an under-sampling of self-incompatible taxa in the current literature. In this thesis, I study inbreeding depression in the SI plant species Antirrhinum majus using both greenhouse crosses and a large collected field dataset. Additionally, the gametophytic S-locus of A. majus is highly heterozygous and polymorphic, thus making assembly and discovery of S-alleles very difficult. Here, 206 new alleles of the male component SLFs are presented, along with a phylogeny showing the high conservation with alleles from another Antirrhinum species. Lastly, selected sites within the protein structure of SLFs are investigated, with one site in particular highlighted as potentially being involved in the SI recognition mechanism. AU - Arathoon, Louise S ID - 14651 SN - 2663 - 337X TI - Investigating inbreeding depression and the self-incompatibility locus of Antirrhinum majus ER - TY - GEN AB - We present a discretization of the dynamic optimal transport problem for which we can obtain the convergence rate for the value of the transport cost to its continuous value when the temporal and spatial stepsize vanish. This convergence result does not require any regularity assumption on the measures, though experiments suggest that the rate is not sharp. Via an analysis of the duality gap we also obtain the convergence rates for the gradient of the optimal potentials and the velocity field under mild regularity assumptions. To obtain such rates we discretize the dual formulation of the dynamic optimal transport problem and use the mature literature related to the error due to discretizing the Hamilton-Jacobi equation. AU - Ishida, Sadashige AU - Lavenant, Hugo ID - 14703 KW - Optimal transport KW - Hamilton-Jacobi equation KW - convex optimization T2 - arXiv TI - Quantitative convergence of a discretization of dynamic optimal transport using the dual formulation ER - TY - CONF AB - Scaling blockchain protocols to perform on par with the expected needs of Web3.0 has been proven to be a challenging task with almost a decade of research. In the forefront of the current solution is the idea of separating the execution of the updates encoded in a block from the ordering of blocks. In order to achieve this, a new class of protocols called rollups has emerged. Rollups have as input a total ordering of valid and invalid transactions and as output a new valid state-transition. If we study rollups from a distributed computing perspective, we uncover that rollups take as input the output of a Byzantine Atomic Broadcast (BAB) protocol and convert it to a State Machine Replication (SMR) protocol. BAB and SMR, however, are considered equivalent as far as distributed computing is concerned and a solution to one can easily be retrofitted to solve the other simply by adding/removing an execution step before the validation of the input. This “easy” step of retrofitting an atomic broadcast solution to implement an SMR has, however, been overlooked in practice. In this paper, we formalize the problem and show that after BAB is solved, traditional impossibility results for consensus no longer apply towards an SMR. Leveraging this we propose a distributed execution protocol that allows reduced execution and storage cost per executor (O(log2n/n)) without relaxing the network assumptions of the underlying BAB protocol and providing censorship-resistance. Finally, we propose efficient non-interactive light client constructions that leverage our efficient execution protocols and do not require any synchrony assumptions or expensive ZK-proofs. AU - Stefo, Christos AU - Xiang, Zhuolun AU - Kokoris Kogias, Eleftherios ID - 14735 SN - 1611-3349 T2 - 27th International Conference on Financial Cryptography and Data Security TI - Executing and proving over dirty ledgers VL - 13950 ER - TY - THES AB - Stochastic systems provide a formal framework for modelling and quantifying uncertainty in systems and have been widely adopted in many application domains. Formal verification and control of finite state stochastic systems, a subfield of formal methods also known as probabilistic model checking, is well studied. In contrast, formal verification and control of infinite state stochastic systems have received comparatively less attention. However, infinite state stochastic systems commonly arise in practice. For instance, probabilistic models that contain continuous probability distributions such as normal or uniform, or stochastic dynamical systems which are a classical model for control under uncertainty, both give rise to infinite state systems. The goal of this thesis is to contribute to laying theoretical and algorithmic foundations of fully automated formal verification and control of infinite state stochastic systems, with a particular focus on systems that may be executed over a long or infinite time. We consider formal verification of infinite state stochastic systems in the setting of static analysis of probabilistic programs and formal control in the setting of controller synthesis in stochastic dynamical systems. For both problems, we present some of the first fully automated methods for probabilistic (a.k.a. quantitative) reachability and safety analysis applicable to infinite time horizon systems. We also advance the state of the art of probability 1 (a.k.a. qualitative) reachability analysis for both problems. Finally, for formal controller synthesis in stochastic dynamical systems, we present a novel framework for learning neural network control policies in stochastic dynamical systems with formal guarantees on correctness with respect to quantitative reachability, safety or reach-avoid specifications. AU - Zikelic, Dorde ID - 14539 SN - 2663 - 337X TI - Automated verification and control of infinite state stochastic systems ER - TY - GEN AU - Polesello, Andrea AU - Muller, Caroline J AU - Pasquero, Claudia AU - Meroni, Agostino N. ID - 14863 T2 - EGU General Assembly 2023 TI - Intensification mechanisms of tropical cyclones ER - TY - JOUR AB - We propose a computational design approach for covering a surface with individually addressable RGB LEDs, effectively forming a low-resolution surface screen. To achieve a low-cost and scalable approach, we propose creating designs from flat PCB panels bent in-place along the surface of a 3D printed core. Working with standard rigid PCBs enables the use of established PCB manufacturing services, allowing the fabrication of designs with several hundred LEDs. Our approach optimizes the PCB geometry for folding, and then jointly optimizes the LED packing, circuit and routing, solving a challenging layout problem under strict manufacturing requirements. Unlike paper, PCBs cannot bend beyond a certain point without breaking. Therefore, we introduce parametric cut patterns acting as hinges, designed to allow bending while remaining compact. To tackle the joint optimization of placement, circuit and routing, we propose a specialized algorithm that splits the global problem into one sub-problem per triangle, which is then individually solved. Our technique generates PCB blueprints in a completely automated way. After being fabricated by a PCB manufacturing service, the boards are bent and glued by the user onto the 3D printed support. We demonstrate our technique on a range of physical models and virtual examples, creating intricate surface light patterns from hundreds of LEDs. AU - Freire, Marco AU - Bhargava, Manas AU - Schreck, Camille AU - Hugron, Pierre-Alexandre AU - Bickel, Bernd AU - Lefebvre, Sylvain ID - 13049 IS - 4 JF - Transactions on Graphics KW - PCB design and layout KW - Mesh geometry models SN - 0730-0301 TI - PCBend: Light up your 3D shapes with foldable circuit boards VL - 42 ER - TY - JOUR AB - Arrays of Josephson junctions are governed by a competition between superconductivity and repulsive Coulomb interactions, and are expected to exhibit diverging low-temperature resistance when interactions exceed a critical level. Here we report a study of the transport and microwave response of Josephson arrays with interactions exceeding this level. Contrary to expectations, we observe that the array resistance drops dramatically as the temperature is decreased—reminiscent of superconducting behaviour—and then saturates at low temperature. Applying a magnetic field, we eventually observe a transition to a highly resistive regime. These observations can be understood within a theoretical picture that accounts for the effect of thermal fluctuations on the insulating phase. On the basis of the agreement between experiment and theory, we suggest that apparent superconductivity in our Josephson arrays arises from melting the zero-temperature insulator. AU - Mukhopadhyay, Soham AU - Senior, Jorden L AU - Saez Mollejo, Jaime AU - Puglia, Denise AU - Zemlicka, Martin AU - Fink, Johannes M AU - Higginbotham, Andrew P ID - 14032 JF - Nature Physics KW - General Physics and Astronomy SN - 1745-2473 TI - Superconductivity from a melted insulator in Josephson junction arrays VL - 19 ER - TY - JOUR AB - Given A⊆GL2(Fq), we prove that there exist disjoint subsets B,C⊆A such that A=B⊔C and their additive and multiplicative energies satisfying max{E+(B),E×(C)}≪|A|3/M(|A|), where M(|A|)=min{q4/3/|A|1/3(log|A|)2/3,|A|4/5/q13/5(log|A|)27/10}. We also study some related questions on moderate expanders over matrix rings, namely, for A,B,C⊆GL2(Fq), we have |AB+C|, |(A+B)C|≫q4, whenever |A||B||C|≫q10+1/2. These improve earlier results due to Karabulut, Koh, Pham, Shen, and Vinh ([2019], Expanding phenomena over matrix rings, ForumMath., 31, 951–970). AU - Mohammadi, Ali AU - Pham, Thang AU - Wang, Yiting ID - 13128 IS - 4 JF - Canadian Mathematical Bulletin SN - 0008-4395 TI - An energy decomposition theorem for matrices and related questions VL - 66 ER - TY - JOUR AB - Polar active matter of self-propelled particles sustain spontaneous flows through the full-integer topological defects. We study theoretically the incompressible flow profiles around ±1 defects induced by polar and dipolar active forces. We show that dipolar forces induce vortical flows around the +1 defect, while the flow around the −1 defect has an 8-fold rotational symmetry. The vortical flow changes its chirality near the +1 defect core in the absence of the friction with a substrate. We show analytically that the flow induced by polar active forces is vortical near the +1 defect and is 4-fold symmetric near the −1 defect, while it becomes uniform in the far-field. For a pair of oppositely charged defects, this polar flow contributes to a mutual interaction force that depends only on the orientation of the defect pair relative to the background polarization, and that enhances defect pair annihilation. This is in contradiction with the effect of dipolar active forces which decay inversely proportional with the defect separation distance. As such, our analyses reveals a long-ranged mechanism for the pairwise interaction between topological defects in polar active matter. AU - Rønning, Jonas AU - Renaud, Julian B AU - Doostmohammadi, Amin AU - Angheluta, Luiza ID - 14087 JF - Soft Matter SN - 1744-683X TI - Spontaneous flows and dynamics of full-integer topological defects in polar active matter VL - 39 ER - TY - CONF AB - Machine learning models are vulnerable to adversarial perturbations, and a thought-provoking paper by Bubeck and Sellke has analyzed this phenomenon through the lens of over-parameterization: interpolating smoothly the data requires significantly more parameters than simply memorizing it. However, this "universal" law provides only a necessary condition for robustness, and it is unable to discriminate between models. In this paper, we address these gaps by focusing on empirical risk minimization in two prototypical settings, namely, random features and the neural tangent kernel (NTK). We prove that, for random features, the model is not robust for any degree of over-parameterization, even when the necessary condition coming from the universal law of robustness is satisfied. In contrast, for even activations, the NTK model meets the universal lower bound, and it is robust as soon as the necessary condition on over-parameterization is fulfilled. This also addresses a conjecture in prior work by Bubeck, Li and Nagaraj. Our analysis decouples the effect of the kernel of the model from an "interaction matrix", which describes the interaction with the test data and captures the effect of the activation. Our theoretical results are corroborated by numerical evidence on both synthetic and standard datasets (MNIST, CIFAR-10). AU - Bombari, Simone AU - Kiyani, Shayan AU - Mondelli, Marco ID - 12859 T2 - Proceedings of the 40th International Conference on Machine Learning TI - Beyond the universal law of robustness: Sharper laws for random features and neural tangent kernels VL - 202 ER - TY - THES AB - Within the human body, the brain exhibits the highest rate of energy consumption amongst all organs, with the majority of generated ATP being utilized to sustain neuronal activity. Therefore, the metabolism of the mature cerebral cortex is geared towards preserving metabolic homeostasis whilst generating significant amounts of energy. This requires a precise interplay between diverse metabolic pathways, spanning from a tissue-wide scale to the level of individual neurons. Disturbances to this delicate metabolic equilibrium, such as those resulting from maternal malnutrition or mutations affecting metabolic enzymes, often result in neuropathological variants of neurodevelopment. For instance, mutations in SLC7A5, a transporter of metabolically essential large neutral amino acids (LNAAs), have been associated with autism and microcephaly. However, despite recent progress in the field, the extent of metabolic restructuring that occurs within the developing brain and the corresponding alterations in nutrient demands during various critical periods remain largely unknown. To investigate this, we performed metabolomic profiling of the murine cerebral cortex to characterize the metabolic state of the forebrain at different developmental stages. We found that the developing cortex undergoes substantial metabolic reprogramming, with specific sets of metabolites displaying stage-specific changes. According to our observations, we determined a distinct temporal period in postnatal development during which the cortex displays heightened reliance on LNAAs. Hence, using a conditional knock-out mouse model, we deleted Slc7a5 in neural cells, allowing us to monitor the impact of a perturbed neuronal metabolic state across multiple developmental stages of corticogenesis. We found that manipulating the levels of essential LNAAs in cortical neurons in vivo affects one particular perinatal developmental period critical for cortical network refinement. Abnormally low intracellular LNAA levels result in cell-autonomous alterations in neuronal lipid metabolism, excitability, and survival during this particular time window. Although most of the effects of Slc7a5 deletion on neuronal physiology are transient, derailment of these processes during this brief but crucial window leads to long-term circuit dysfunction in mice. In conclusion, out data indicate that the cerebral cortex undergoes significant metabolic reorganization during development. This process involves the intricate integration of multiple metabolic pathways to ensure optimal neuronal function throughout different developmental stages. Our findings offer a paradigm for understanding how neurons synchronize the expression of nutrient-related genes with their activity to allow proper brain maturation. Further, our results demonstrate that disruptions in these precisely calibrated metabolic processes during critical periods of brain development may result in neuropathological outcomes in mice and in humans. AU - Knaus, Lisa ID - 13107 SN - 2663 - 337X TI - The metabolism of the developing brain : How large neutral amino acids modulate perinatal neuronal excitability and survival ER - TY - JOUR AB - The first long-lived turbulent structures observable in planar shear flows take the form of localized stripes, inclined with respect to the mean flow direction. The dynamics of these stripes is central to transition, and recent studies proposed an analogy to directed percolation where the stripes’ proliferation is ultimately responsible for the turbulence becoming sustained. In the present study we focus on the internal stripe dynamics as well as on the eventual stripe expansion, and we compare the underlying mechanisms in pressure- and shear-driven planar flows, respectively, plane-Poiseuille and plane-Couette flow. Despite the similarities of the overall laminar–turbulence patterns, the stripe proliferation processes in the two cases are fundamentally different. Starting from the growth and sustenance of individual stripes, we find that in plane-Couette flow new streaks are created stochastically throughout the stripe whereas in plane-Poiseuille flow streak creation is deterministic and occurs locally at the downstream tip. Because of the up/downstream symmetry, Couette stripes, in contrast to Poiseuille stripes, have two weak and two strong laminar turbulent interfaces. These differences in symmetry as well as in internal growth give rise to two fundamentally different stripe splitting mechanisms. In plane-Poiseuille flow splitting is connected to the elongational growth of the original stripe, and it results from a break-off/shedding of the stripe's tail. In plane-Couette flow splitting follows from a broadening of the original stripe and a division along the stripe into two slimmer stripes. AU - Marensi, Elena AU - Yalniz, Gökhan AU - Hof, Björn ID - 14466 JF - Journal of Fluid Mechanics KW - turbulence KW - transition to turbulence KW - patterns SN - 0022-1120 TI - Dynamics and proliferation of turbulent stripes in plane-Poiseuille and plane-Couette flows VL - 974 ER - TY - JOUR AB - The short history of research on Li-O2 batteries has seen a remarkable number of mechanistic U-turns over the years. From the initial use of carbonate electrolytes, that were then found to be entirely unsuitable, to the belief that (su)peroxide was solely responsible for degradation, before the more reactive singlet oxygen was found to form, to the hypothesis that capacity depends on a competing surface/solution mechanism before a practically exclusive solution mechanism was identified. Herein, we argue for an ever-fresh look at the reported data without bias towards supposedly established explanations. We explain how the latest findings on rate and capacity limits, as well as the origin of side reactions, are connected via the disproportionation (DISP) step in the (dis)charge mechanism. Therefrom, directions emerge for the design of electrolytes and mediators on how to suppress side reactions and to enable high rate and high reversible capacity. AU - Jethwa, Rajesh B AU - Mondal, Soumyadip AU - Pant, Bhargavi AU - Freunberger, Stefan Alexander ID - 14687 JF - Angewandte Chemie International Edition KW - General Chemistry KW - Catalysis SN - 1433-7851 TI - To DISP or not? The far‐reaching reaction mechanisms underpinning Lithium‐air batteries ER - TY - JOUR AB - Aromatic side chains are important reporters of the plasticity of proteins, and often form important contacts in protein--protein interactions. By studying a pair of structurally homologous cross-β amyloid fibrils, HET-s and HELLF, with a specific isotope-labeling approach and magic-angle-spinning (MAS) NMR, we have characterized the dynamic behavior of Phe and Tyr aromatic rings to show that the hydrophobic amyloid core is rigid, without any sign of "breathing motions" over hundreds of milliseconds at least. Aromatic residues exposed at the fibril surface have a rigid ring axis but undergo ring flips, on a variety of time scales from ns to µs. Our approach provides direct insight into hydrophobic-core motions, enabling a better evaluation of the conformational heterogeneity generated from a NMR structural ensemble of such amyloid cross-β architecture. AU - Becker, Lea Marie AU - Berbon, Mélanie AU - Vallet, Alicia AU - Grelard, Axelle AU - Morvan, Estelle AU - Bardiaux, Benjamin AU - Lichtenecker, Roman AU - Ernst, Matthias AU - Loquet, Antoine AU - Schanda, Paul ID - 12675 IS - 19 JF - Angewandte Chemie International Edition KW - General Chemistry KW - Catalysis SN - 1433-7851 TI - The rigid core and flexible surface of amyloid fibrils probed by Magic‐Angle Spinning NMR of aromatic residues VL - 62 ER - TY - DATA AB - Aromatic side chains are important reporters of the plasticity of proteins, and often form important contacts in protein–protein interactions. We studied aromatic residues in the two structurally homologous cross-β amyloid fibrils HET-s, and HELLF by employing a specific isotope-labeling approach and magic-angle-spinning NMR. The dynamic behavior of the aromatic residues Phe and Tyr indicates that the hydrophobic amyloid core is rigid, without any sign of "breathing motions" over hundreds of milliseconds at least. Aromatic residues exposed at the fibril surface have a rigid ring axis but undergo ring flips on a variety of time scales from nanoseconds to microseconds. Our approach provides direct insight into hydrophobic-core motions, enabling a better evaluation of the conformational heterogeneity generated from an NMR structural ensemble of such amyloid cross-β architecture. AU - Becker, Lea Marie AU - Schanda, Paul ID - 12497 KW - aromatic side chains KW - isotopic labeling KW - protein dynamics KW - ring flips KW - spin relaxation TI - Research data to: The rigid core and flexible surface of amyloid fibrils probed by magic-angle-spinning NMR spectroscopy of aromatic residues ER - TY - JOUR AB - The emergence of large-scale order in self-organized systems relies on local interactions between individual components. During bacterial cell division, FtsZ—a prokaryotic homologue of the eukaryotic protein tubulin—polymerizes into treadmilling filaments that further organize into a cytoskeletal ring. In vitro, FtsZ filaments can form dynamic chiral assemblies. However, how the active and passive properties of individual filaments relate to these large-scale self-organized structures remains poorly understood. Here we connect single-filament properties with the mesoscopic scale by combining minimal active matter simulations and biochemical reconstitution experiments. We show that the density and flexibility of active chiral filaments define their global order. At intermediate densities, curved, flexible filaments organize into chiral rings and polar bands. An effectively nematic organization dominates for high densities and for straight, mutant filaments with increased rigidity. Our predicted phase diagram quantitatively captures these features, demonstrating how the flexibility, density and chirality of the active filaments affect their collective behaviour. Our findings shed light on the fundamental properties of active chiral matter and explain how treadmilling FtsZ filaments organize during bacterial cell division. AU - Dunajova, Zuzana AU - Prats Mateu, Batirtze AU - Radler, Philipp AU - Lim, Keesiang AU - Brandis, Dörte AU - Velicky, Philipp AU - Danzl, Johann G AU - Wong, Richard W. AU - Elgeti, Jens AU - Hannezo, Edouard B AU - Loose, Martin ID - 13314 JF - Nature Physics SN - 1745-2473 TI - Chiral and nematic phases of flexible active filaments VL - 19 ER - TY - THES AB - Cell division in Escherichia coli is performed by the divisome, a multi-protein complex composed of more than 30 proteins. The divisome spans from the cytoplasm through the inner membrane to the cell wall and the outer membrane. Divisome assembly is initiated by a cytoskeletal structure, the so-called Z-ring, which localizes at the center of the E. coli cell and determines the position of the future cell septum. The Z-ring is composed of the highly conserved bacterial tubulin homologue FtsZ, which forms treadmilling filaments. These filaments are recruited to the inner membrane by FtsA, a highly conserved bacterial actin homologue. FtsA interacts with other proteins in the periplasm and thus connects the cytoplasmic and periplasmic components of the divisome. A previous model postulated that FtsA regulates maturation of the divisome by switching from an oligomeric, inactive state to a monomeric and active state. This model was based mostly on in vivo studies, as a biochemical characterization of FtsA has been hampered by difficulties in purifying the protein. Here, we studied FtsA using an in vitro reconstitution approach and aimed to answer two questions: (i) How are dynamics from cytoplasmic, treadmilling FtsZ filaments coupled to proteins acting in the periplasmic space and (ii) How does FtsA regulate the maturation of the divisome? We found that the cytoplasmic peptides of the transmembrane proteins FtsN and FtsQ interact directly with FtsA and can follow the spatiotemporal signal of FtsA/Z filaments. When we investigated the underlying mechanism by imaging single molecules of FtsNcyto, we found the peptide to interact transiently with FtsA. An in depth analysis of the single molecule trajectories helped to postulate a model where PG synthases follow the dynamics of FtsZ by a diffusion and capture mechanism. Following up on these findings we were interested in how the self-interaction of FtsA changes when it encounters FtsNcyto and if we can confirm the proposed oligomer-monomer switch. For this, we compared the behavior of the previously identified, hyperactive mutant FtsA R286W with wildtype FtsA. The mutant outperforms WT in mirroring and transmitting the spatiotemporal signal of treadmilling FtsZ filaments. Surprisingly however, we found that this was not due to a difference in the self-interaction strength of the two variants, but a difference in their membrane residence time. Furthermore, in contrast to our expectations, upon binding of FtsNcyto the measured self-interaction of FtsA actually increased. We propose that FtsNcyto induces a rearrangement of the oligomeric architecture of FtsA. In further consequence this change leads to more persistent FtsZ filaments which results in a defined signalling zone, allowing formation of the mature divisome. The observed difference between FtsA WT and R286W is due to the vastly different membrane turnover of the proteins. R286W cycles 5-10x faster compared to WT which allows to sample FtsZ filaments at faster frequencies. These findings can explain the observed differences in toxicity for overexpression of FtsA WT and R286W and help to understand how FtsA regulates divisome maturation. AU - Radler, Philipp ID - 14280 KW - Cell Division KW - Reconstitution KW - FtsZ KW - FtsA KW - Divisome KW - E.coli SN - 2663-337X TI - Spatiotemporal signaling during assembly of the bacterial divisome ER - TY - THES AB - Semiconductor-superconductor hybrid systems are the harbour of many intriguing mesoscopic phenomena. This material combination leads to spatial variations of the superconducting properties, which gives rise to Andreev bound states (ABSs). Some of these states might exhibit remarkable properties that render them highly desirable for topological quantum computing. The most prominent and hunted of such states are Majorana zero modes (MZMs), quasiparticles equals to their own quasiparticles that they follow non-abelian statistics. In this thesis, we first introduce the general framework of such hybrid systems and, then, we unveil a series of mesoscopic phenomena that we discovered. Firstly, we show tunneling spectroscopy experiments on full-shell nanowires (NWs) showing that unwanted quantum-dot states coupled to superconductors (Yu-Shiba-Rusinov states) can mimic MZMs signatures. Then, we introduce a novel protocol which allowed the integration of tunneling spectroscopy with Coulomb spectroscopy within the same device. Employing this approach on both full-shell NWs and partial-shell NWs, we demonstrated that longitudinally confined states reveal charge transport phenomenology similar to the one expected for MZMs. These findings shed light on the intricate interplay between superconductivity and quantum confinement, which brought us to explore another material platform, i.e. a two-dimensional Germanium hole gas. After developing a robust way to induce superconductivity in such system, we showed how to engineer the proximity effect and we revealed a superconducting hard gap. Finally, we created a superconducting radio frequency driven ideal diode and a generator of non-sinusoidal current-phase relations. Our results open the path for the exploration of protected superconducting qubits and more complex hybrid devices in planar Germanium, like Kitaev chains and hybrid qubit devices. AU - Valentini, Marco ID - 13286 SN - 2663 - 337X TI - Mesoscopic phenomena in hybrid semiconductor-superconductor nanodevices : From full-shell nanowires to two-dimensional hole gas in germanium ER - TY - CONF AB - This paper presents Lincheck, a new practical and user-friendly framework for testing concurrent algorithms on the Java Virtual Machine (JVM). Lincheck provides a simple and declarative way to write concurrent tests: instead of describing how to perform the test, users specify what to test by declaring all the operations to examine; the framework automatically handles the rest. As a result, tests written with Lincheck are concise and easy to understand. The framework automatically generates a set of concurrent scenarios, examines them using stress-testing or bounded model checking, and verifies that the results of each invocation are correct. Notably, if an error is detected via model checking, Lincheck provides an easy-to-follow trace to reproduce it, significantly simplifying the bug investigation. To the best of our knowledge, Lincheck is the first production-ready tool on the JVM that offers such a simple way of writing concurrent tests, without requiring special skills or expertise. We successfully integrated Lincheck in the development process of several large projects, such as Kotlin Coroutines, and identified new bugs in popular concurrency libraries, such as a race in Java’s standard ConcurrentLinkedDeque and a liveliness bug in Java’s AbstractQueuedSynchronizer framework, which is used in most of the synchronization primitives. We believe that Lincheck can significantly improve the quality and productivity of concurrent algorithms research and development and become the state-of-the-art tool for checking their correctness. AU - Koval, Nikita AU - Fedorov, Alexander AU - Sokolova, Maria AU - Tsitelov, Dmitry AU - Alistarh, Dan-Adrian ID - 14260 SN - 0302-9743 T2 - 35th International Conference on Computer Aided Verification TI - Lincheck: A practical framework for testing concurrent data structures on JVM VL - 13964 ER - TY - THES AB - Social insects fight disease using their individual immune systems and the cooperative sanitary behaviors of colony members. These social defenses are well explored against externally-infecting pathogens, but little is known about defense strategies against internally-infecting pathogens, such as viruses. Viruses are ubiquitous and in the last decades it has become evident that also many ant species harbor viruses. We present one of the first studies addressing transmission dynamics and collective disease defenses against viruses in ants on a mechanistic level. I successfully established an experimental ant host – viral pathogen system as a model for the defense strategies used by social insects against internal pathogen infections, as outlined in the third chapter. In particular, we studied how garden ants (Lasius neglectus) defend themselves and their colonies against the generalist insect virus CrPV (cricket paralysis virus). We chose microinjections of virus directly into the ants’ hemolymph because it allowed us to use a defined exposure dose. Here we show that this is a good model system, as the virus is replicating and thus infecting the host. The ants mount a clear individual immune response against the viral infection, which is characterized by a specific siRNA pattern, namely siRNAs mapping against the viral genome with a peak of 21 and 22 bp long fragments. The onset of this immune response is consistent with the timeline of viral replication that starts already within two days post injection. The disease manifests in decreased survival over a course of two to three weeks. Regarding group living, we find that infected ants show a strong individual immune response, but that their course of disease is little affected by nestmate presence, as described in chapter four. Hence, we do not find social immunity in the context of viral infections in ants. Nestmates, however, can contract the virus. Using Drosophila S2R+ cells in culture, we showed that 94 % of the nestmates contract active virus within four days of social contact to an infected individual. Virus is transmitted in low doses, thus not causing disease transmission within the colony. While virus can be transmitted during short direct contacts, we also assume transmission from deceased ants and show that the nestmates’ immune system gets activated after contracting a low viral dose. We find considerable potential for indirect transmission via the nest space. Virus is shed to the nest, where it stays viable for one week and is also picked up by other ants. Apart from that, we want to underline the potential of ant poison as antiviral agent. We determined that ant poison successfully inactivates CrPV in vitro. However, we found no evidence for effective poison use to sanitize the nest space. On the other hand, local application of ant poison by oral poison uptake, which is part of the ants prophylactic behavioral repertoire, probably contributes to keeping the gut of each individual sanitized. We hypothesize that oral poison uptake might be the reason why we did not find viable virus in the trophallactic fluid. The fifth chapter encompasses preliminary data on potential social immunization. However, our experiments do not confirm an actual survival benefit for the nestmates upon pathogen challenge under the given experimental settings. Nevertheless, we do not want to rule out the possibility for nestmate immunization, but rather emphasize that considering different experimental timelines and viral doses would provide a multitude of options for follow-up experiments. In conclusion, we find that prophylactic individual behaviors, such as oral poison uptake, might play a role in preventing viral disease transmission. Compared to colony defense against external pathogens, internal pathogen infections require a stronger component of individual physiological immunity than behavioral social immunity, yet could still lead to collective protection. AU - Franschitz, Anna ID - 13984 SN - 2663 - 337X TI - Individual and social immunity against viral infections in ants ER - TY - GEN AB - A crucial property for achieving secure, trustworthy and interpretable deep learning systems is their robustness: small changes to a system's inputs should not result in large changes to its outputs. Mathematically, this means one strives for networks with a small Lipschitz constant. Several recent works have focused on how to construct such Lipschitz networks, typically by imposing constraints on the weight matrices. In this work, we study an orthogonal aspect, namely the role of the activation function. We show that commonly used activation functions, such as MaxMin, as well as all piece-wise linear ones with two segments unnecessarily restrict the class of representable functions, even in the simplest one-dimensional setting. We furthermore introduce the new N-activation function that is provably more expressive than currently popular activation functions. We provide code at this https URL. AU - Prach, Bernd AU - Lampert, Christoph ID - 15039 T2 - arXiv TI - 1-Lipschitz neural networks are more expressive with N-activations ER - TY - THES AB - Morphogens are signaling molecules that are known for their prominent role in pattern formation within developing tissues. In addition to patterning, morphogens also control tissue growth. However, the underlying mechanisms are poorly understood. We studied the role of morphogens in regulating tissue growth in the developing vertebrate neural tube. In this system, opposing morphogen gradients of Shh and BMP establish the dorsoventral pattern of neural progenitor domains. Perturbations in these morphogen pathways result in alterations in tissue growth and cell cycle progression, however, it has been unclear what cellular process is affected. To address this, we analysed the rates of cell proliferation and cell death in mouse mutants in which signaling is perturbed, as well as in chick neural plate explants exposed to defined concentrations of signaling activators or inhibitors. Our results indicated that the rate of cell proliferation was not altered in these assays. By contrast, both the Shh and BMP signaling pathways had profound effects on neural progenitor survival. Our results indicate that these pathways synergise to promote cell survival within neural progenitors. Consistent with this, we found that progenitors within the intermediate region of the neural tube, where the combined levels of Shh and BMP are the lowest, are most prone to cell death when signaling activity is inhibited. In addition, we found that downregulation of Shh results in increased apoptosis within the roof plate, which is the dorsal source of BMP ligand production. This revealed a cross-interaction between the Shh and BMP morphogen signaling pathways that may be relevant for understanding how gradients scale in neural tubes with different overall sizes. We further studied the mechanism acting downstream of Shh in cell survival regulation using genetic and genomic approaches. We propose that Shh transcriptionally regulates a non-canonical apoptotic pathway. Altogether, our study points to a novel role of opposing morphogen gradients in tissue size regulation and provides new insights into complex interactions between Shh and BMP signaling gradients in the neural tube. AU - Kuzmicz-Kowalska, Katarzyna ID - 14323 SN - 2663 - 337X TI - Regulation of neural progenitor survival by Shh and BMP in the developing spinal cord ER - TY - THES AU - Hennessey-Wesen, Mike ID - 14641 KW - microfluidics KW - miceobiology KW - mutations KW - quorum sensing SN - 2663 - 337X TI - Adaptive mutation in E. coli modulated by luxS ER - TY - THES AB - This thesis concerns the application of variational methods to the study of evolution problems arising in fluid mechanics and in material sciences. The main focus is on weak-strong stability properties of some curvature driven interface evolution problems, such as the two-phase Navier–Stokes flow with surface tension and multiphase mean curvature flow, and on the phase-field approximation of the latter. Furthermore, we discuss a variational approach to the study of a class of doubly nonlinear wave equations. First, we consider the two-phase Navier–Stokes flow with surface tension within a bounded domain. The two fluids are immiscible and separated by a sharp interface, which intersects the boundary of the domain at a constant contact angle of ninety degree. We devise a suitable concept of varifolds solutions for the associated interface evolution problem and we establish a weak-strong uniqueness principle in case of a two dimensional ambient space. In order to focus on the boundary effects and on the singular geometry of the evolving domains, we work for simplicity in the regime of same viscosities for the two fluids. The core of the thesis consists in the rigorous proof of the convergence of the vectorial Allen-Cahn equation towards multiphase mean curvature flow for a suitable class of multi- well potentials and for well-prepared initial data. We even establish a rate of convergence. Our relative energy approach relies on the concept of gradient-flow calibration for branching singularities in multiphase mean curvature flow and thus enables us to overcome the limitations of other approaches. To the best of the author’s knowledge, our result is the first quantitative and unconditional one available in the literature for the vectorial/multiphase setting. This thesis also contains a first study of weak-strong stability for planar multiphase mean curvature flow beyond the singularity resulting from a topology change. Previous weak-strong results are indeed limited to time horizons before the first topology change of the strong solution. We consider circular topology changes and we prove weak-strong stability for BV solutions to planar multiphase mean curvature flow beyond the associated singular times by dynamically adapting the strong solutions to the weak one by means of a space-time shift. In the context of interface evolution problems, our proofs for the main results of this thesis are based on the relative energy technique, relying on novel suitable notions of relative energy functionals, which in particular measure the interface error. Our statements follow from the resulting stability estimates for the relative energy associated to the problem. At last, we introduce a variational approach to the study of nonlinear evolution problems. This approach hinges on the minimization of a parameter dependent family of convex functionals over entire trajectories, known as Weighted Inertia-Dissipation-Energy (WIDE) functionals. We consider a class of doubly nonlinear wave equations and establish the convergence, up to subsequences, of the associated WIDE minimizers to a solution of the target problem as the parameter goes to zero. AU - Marveggio, Alice ID - 14587 SN - 2663 - 337X TI - Weak-strong stability and phase-field approximation of interface evolution problems in fluid mechanics and in material sciences ER - TY - GEN AB - We prove a universal mesoscopic central limit theorem for linear eigenvalue statistics of a Wigner-type matrix inside the bulk of the spectrum with compactly supported twice continuously differentiable test functions. The main novel ingredient is an optimal local law for the two-point function $T(z,\zeta)$ and a general class of related quantities involving two resolvents at nearby spectral parameters. AU - Riabov, Volodymyr ID - 15128 T2 - arXiv TI - Mesoscopic eigenvalue statistics for Wigner-type matrices ER - TY - THES AB - The extracellular matrix (ECM) is a hydrated and complex three-dimensional network consisting of proteins, polysaccharides, and water. It provides structural scaffolding for the cells embedded within it and is essential in regulating numerous physiological processes, including cell migration and proliferation, wound healing, and stem cell fate. Despite extensive study, detailed structural knowledge of ECM components in physiologically relevant conditions is still rudimentary. This is due to methodological limitations in specimen preparation protocols which are incompatible with keeping large samples, such as the ECM, in their native state for subsequent imaging. Conventional electron microscopy (EM) techniques rely on fixation, dehydration, contrasting, and sectioning. This results in the alteration of a highly hydrated environment and the potential introduction of artifacts. Other structural biology techniques, such as nuclear magnetic resonance (NMR) spectroscopy and X-ray crystallography, allow high-resolution analysis of protein structures but only work on homogenous and purified samples, hence lacking contextual information. Currently, no approach exists for the ultrastructural and structural study of extracellular components under native conditions in a physiological, 3D environment. In this thesis, I have developed a workflow that allows for the ultrastructural analysis of the ECM in near-native conditions at molecular resolution. The developments I introduced include implementing a novel specimen preparation workflow for cell-derived matrices (CDMs) to render them compatible with ion-beam milling and subsequent high-resolution cryo-electron tomography (ET). To this end, I have established protocols to generate CDMs grown over several weeks on EM grids that are compatible with downstream cryo-EM sample preparation and imaging techniques. Characterization of these ECMs confirmed that they contain essential ECM components such as collagen I, collagen VI, and fibronectin I in high abundance and hence represent a bona fide biologically-relevant sample. I successfully optimized vitrification of these specimens by testing various vitrification techniques and cryoprotectants. In order to obtain high-resolution molecular insights into the ultrastructure and organization of CDMs, I established cryo-focused ion beam scanning electron microscopy (FIBSEM) on these challenging and complex specimens. I explored different approaches for the creation of thin cryo-lamellae by FIB milling and succeeded in optimizing the cryo-lift-out technique, resulting in high-quality lamellae of approximately 200 nm thickness. High-resolution Cryo-ET of these lamellae revealed for the first time the architecture of native CDM in the context of matrix-secreting cells. This allowed for the in situ visualization of fibrillar matrix proteins such as collagen, laying the foundation for future structural and ultrastructural characterization of these proteins in their near-native environment. In summary, in this thesis, I present a novel workflow that combines state-of-the-art cryo-EM specimen preparation and imaging technologies to permit characterization of the ECM, an important tissue component in higher organisms. This innovative and highly versatile workflow will enable addressing far-reaching questions on ECM architecture, composition, and reciprocal ECM-cell interactions. AU - Zens, Bettina ID - 12491 KW - cryo-EM KW - cryo-ET KW - FIB milling KW - method development KW - FIBSEM KW - extracellular matrix KW - ECM KW - cell-derived matrices KW - CDMs KW - cell culture KW - high pressure freezing KW - HPF KW - structural biology KW - tomography KW - collagen SN - 2663-337X TI - Ultrastructural characterization of natively preserved extracellular matrix by cryo-electron tomography ER - TY - THES AB - We introduce the notion of a Faustian interchange in a 1-parameter family of smooth functions to generalize the medial axis to critical points of index larger than 0. We construct and implement a general purpose algorithm for approximating such generalized medial axes. AU - Stephenson, Elizabeth R ID - 14226 SN - 2791-4585 TI - Generalizing medial axes with homology switches ER - TY - THES AB - The brain is an exceptionally sophisticated organ consisting of billions of cells and trillions of connections that orchestrate our cognition and behavior. To decode its complex connectivity, it is pivotal to disentangle its intricate architecture spanning from cm-sized circuits down to tens of nm-small synapses. To achieve this goal, I developed CATS – Comprehensive Analysis of nervous Tissue across Scales, a versatile toolbox for obtaining a holistic view of nervous tissue context with (superresolution) fluorescence microscopy. CATS combines comprehensive labeling of the extracellular space, that is compatible with chemical fixation, with information on molecular markers, superresolved data acquisition and machine-learning based data analysis for segmentation and synapse identification. I used CATS to analyze key features of nervous tissue connectivity, ranging from whole tissue architecture, neuronal in- and output-fields, down to synapse morphology. Focusing on the hippocampal circuitry, I quantified synaptic transmission properties of mossy fiber boutons and analyzed the connectivity pattern of dentate gyrus granule cells with CA3 pyramidal neurons. This shows that CATS is a viable tool to study hallmarks of neuronal connectivity with light microscopy. AU - Michalska, Julia M ID - 12470 SN - 2663-337X TI - A versatile toolbox for the comprehensive analysis of nervous tissue organization with light microscopy ER - TY - THES AB - All visual experiences of the vertebrates begin with light being converted into electrical signals by the eye retina. Retinal ganglion cells (RGCs) are the neurons of the innermost layer of the mammal retina, and they transmit visual information to the rest of the brain. It has been shown that RGCs vary in their morphology and genetic profiles, moreover they can be unambiguously grouped into subtypes that share the same morphological and/or molecular properties. However, in terms of RGCs function, it remains unclear how many distinct types there are and what response properties their typology relies on. Even given the recent studies that successfully classified RGCs in a patch of the retina [1] and in scotopic conditions [2], the question remains whether the found subtypes persist across the entire retina. In this work, using a novel imaging method, we show that, when sampled from a large portion of the retina, RGCs can not be clearly divided into functional subtypes. We found that in photopic conditions, which implies more prominent natural scene statistic differences across the visual field, response properties can be exhibited by cells differently depending on their location in the retina, which leads to formation of a gradient of features rather than distinct classes. This finding suggests that RGCs follow a global organization across the visual field of the animal, adapting each RGC subtype to the requirements imposed by the natural scene statistics. AU - Kirillova, Kseniia ID - 12531 SN - 2791-4585 TI - Panoramic functional gradients across the mouse retina ER - TY - THES AB - The evolutionary processes that brought about today’s plethora of living species and the many billions more ancient ones all underlie biology. Evolutionary pathways are neither directed nor deterministic, but rather an interplay between selection, migration, mutation, genetic drift and other environmental factors. Hybrid zones, as natural crossing experiments, offer a great opportunity to use cline analysis to deduce different evolutionary processes - for example, selection strength. Theoretical cline models, largely assuming uniform distribution of individuals, often lack the capability of incorporating population structure. Since in reality organisms mostly live in patchy distributions and their dispersal is hardly ever Gaussian, it is necessary to unravel the effect of these different elements of population structure on cline parameters and shape. In this thesis, I develop a simulation inspired by the A. majus hybrid zone of a single selected locus under frequency dependent selection. This simulation enables us to untangle the effects of different elements of population structure as for example a low-density center and long-range dispersal. This thesis is therefore a first step towards theoretically untangling the effects of different elements of population structure on cline parameters and shape. AU - Julseth, Mara ID - 12800 SN - 2791-4585 TI - The effect of local population structure on genetic variation at selected loci in the A. majus hybrid zone ER - TY - THES AU - Gnyliukh, Nataliia ID - 14510 KW - Clathrin-Mediated Endocytosis KW - vesicle scission KW - Dynamin-Related Protein 2 KW - SH3P2 KW - TPLATE complex KW - Total internal reflection fluorescence microscopy KW - Arabidopsis thaliana SN - 2663-337X TI - Mechanism of clathrin-coated vesicle formation during endocytosis in plants ER - TY - THES AB - Inverse design problems in fabrication-aware shape optimization are typically solved on discrete representations such as polygonal meshes. This thesis argues that there are benefits to treating these problems in the same domain as human designers, namely, the parametric one. One reason is that discretizing a parametric model usually removes the capability of making further manual changes to the design, because the human intent is captured by the shape parameters. Beyond this, knowledge about a design problem can sometimes reveal a structure that is present in a smooth representation, but is fundamentally altered by discretizing. In this case, working in the parametric domain may even simplify the optimization task. We present two lines of research that explore both of these aspects of fabrication-aware shape optimization on parametric representations. The first project studies the design of plane elastic curves and Kirchhoff rods, which are common mathematical models for describing the deformation of thin elastic rods such as beams, ribbons, cables, and hair. Our main contribution is a characterization of all curved shapes that can be attained by bending and twisting elastic rods having a stiffness that is allowed to vary across the length. Elements like these can be manufactured using digital fabrication devices such as 3d printers and digital cutters, and have applications in free-form architecture and soft robotics. We show that the family of curved shapes that can be produced this way admits geometric description that is concise and computationally convenient. In the case of plane curves, the geometric description is intuitive enough to allow a designer to determine whether a curved shape is physically achievable by visual inspection alone. We also present shape optimization algorithms that convert a user-defined curve in the plane or in three dimensions into the geometry of an elastic rod that will naturally deform to follow this curve when its endpoints are attached to a support structure. Implemented in an interactive software design tool, the rod geometry is generated in real time as the user edits a curve and enables fast prototyping. The second project tackles the problem of general-purpose shape optimization on CAD models using a novel variant of the extended finite element method (XFEM). Our goal is the decoupling between the simulation mesh and the CAD model, so no geometry-dependent meshing or remeshing needs to be performed when the CAD parameters change during optimization. This is achieved by discretizing the embedding space of the CAD model, and using a new high-accuracy numerical integration method to enable XFEM on free-form elements bounded by the parametric surface patches of the model. Our simulation is differentiable from the CAD parameters to the simulation output, which enables us to use off-the-shelf gradient-based optimization procedures. The result is a method that fits seamlessly into the CAD workflow because it works on the same representation as the designer, enabling the alternation of manual editing and fabrication-aware optimization at will. AU - Hafner, Christian ID - 12897 SN - 2663-337X TI - Inverse shape design with parametric representations: Kirchhoff Rods and parametric surface models ER -