TY - CONF AB - We automatically compute a new class of environment assumptions in two-player turn-based finite graph games which characterize an “adequate cooperation” needed from the environment to allow the system player to win. Given an ω-regular winning condition Φ for the system player, we compute an ω-regular assumption Ψ for the environment player, such that (i) every environment strategy compliant with Ψ allows the system to fulfill Φ (sufficiency), (ii) Ψ can be fulfilled by the environment for every strategy of the system (implementability), and (iii) Ψ does not prevent any cooperative strategy choice (permissiveness). For parity games, which are canonical representations of ω-regular games, we present a polynomial-time algorithm for the symbolic computation of adequately permissive assumptions and show that our algorithm runs faster and produces better assumptions than existing approaches—both theoretically and empirically. To the best of our knowledge, for ω -regular games, we provide the first algorithm to compute sufficient and implementable environment assumptions that are also permissive. AU - Anand, Ashwani AU - Mallik, Kaushik AU - Nayak, Satya Prakash AU - Schmuck, Anne Kathrin ID - 13141 SN - 0302-9743 T2 - TACAS 2023: Tools and Algorithms for the Construction and Analysis of Systems TI - Computing adequately permissive assumptions for synthesis VL - 13994 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 - JOUR AB - We present a simple algorithm for computing higher-order Delaunay mosaics that works in Euclidean spaces of any finite dimensions. The algorithm selects the vertices of the order-k mosaic from incrementally constructed lower-order mosaics and uses an algorithm for weighted first-order Delaunay mosaics as a black-box to construct the order-k mosaic from its vertices. Beyond this black-box, the algorithm uses only combinatorial operations, thus facilitating easy implementation. We extend this algorithm to compute higher-order α-shapes and provide open-source implementations. We present experimental results for properties of higher-order Delaunay mosaics of random point sets. AU - Edelsbrunner, Herbert AU - Osang, Georg F ID - 12086 JF - Algorithmica SN - 0178-4617 TI - A simple algorithm for higher-order Delaunay mosaics and alpha shapes VL - 85 ER - TY - JOUR AB - We study ergodic decompositions of Dirichlet spaces under intertwining via unitary order isomorphisms. We show that the ergodic decomposition of a quasi-regular Dirichlet space is unique up to a unique isomorphism of the indexing space. Furthermore, every unitary order isomorphism intertwining two quasi-regular Dirichlet spaces is decomposable over their ergodic decompositions up to conjugation via an isomorphism of the corresponding indexing spaces. AU - Dello Schiavo, Lorenzo AU - Wirth, Melchior ID - 12104 IS - 1 JF - Journal of Evolution Equations SN - 1424-3199 TI - Ergodic decompositions of Dirichlet forms under order isomorphisms VL - 23 ER - TY - JOUR AB - The Indian summer monsoon rainfall (ISMR) has been declining since the 1950s. However, since 2002 it is reported to have revived. For these observed changes in the ISMR, several explanations have been reported. Among these explanations, however, the role of the eastern equatorial Indian Ocean (EEIO) is missing despite being one of the warmest regions in the Indian Ocean, and monotonously warming. A recent study reported that EEIO warming impacts the rainfall over northern India. Here we report that warming in the EEIO weakens the low-level Indian summer monsoon circulation and reduces ISMR. A warm EEIO drives easterly winds in the Indo–Pacific sector as a Gill response. The warm EEIO also enhances nocturnal convection offshore the western coast of Sumatra. The latent heating associated with the increased convection augments the Gill response and the resultant circulation opposes the monsoon low-level circulation and weakens the seasonal rainfall. AU - Goswami, Bidyut B ID - 11434 JF - Climate Dynamics SN - 0930-7575 TI - Role of the eastern equatorial Indian Ocean warming in the Indian summer monsoon rainfall trend VL - 60 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 - JOUR AB - Writing concurrent code that is both correct and efficient is notoriously difficult. Thus, programmers often prefer to use synchronization abstractions, which render code simpler and easier to reason about. Despite a wealth of work on this topic, there is still a gap between the rich semantics provided by synchronization abstractions in modern programming languages—specifically, fair FIFO ordering of synchronization requests and support for abortable operations—and frameworks for implementing it correctly and efficiently. Supporting such semantics is critical given the rising popularity of constructs for asynchronous programming, such as coroutines, which abort frequently and are cheaper to suspend and resume compared to native threads. This paper introduces a new framework called CancellableQueueSynchronizer (CQS), which enables simple yet efficient implementations of a wide range of fair and abortable synchronization primitives: mutexes, semaphores, barriers, count-down latches, and blocking pools. Our main contribution is algorithmic, as implementing both fairness and abortability efficiently at this level of generality is non-trivial. Importantly, all our algorithms, including the CQS framework and the primitives built on top of it, come with formal proofs in the Iris framework for Coq for many of their properties. These proofs are modular, so it is easy to show correctness for new primitives implemented on top of CQS. From a practical perspective, implementation of CQS for native threads on the JVM improves throughput by up to two orders of magnitude over Java’s AbstractQueuedSynchronizer, the only practical abstraction offering similar semantics. Further, we successfully integrated CQS as a core component of the popular Kotlin Coroutines library, validating the framework’s practical impact and expressiveness in a real-world environment. In sum, CancellableQueueSynchronizer is the first framework to combine expressiveness with formal guarantees and solid practical performance. Our approach should be extensible to other languages and families of synchronization primitives. AU - Koval, Nikita AU - Khalanskiy, Dmitry AU - Alistarh, Dan-Adrian ID - 13179 JF - Proceedings of the ACM on Programming Languages TI - CQS: A formally-verified framework for fair and abortable synchronization VL - 7 ER - TY - JOUR AB - We study the density of everywhere locally soluble diagonal quadric surfaces, parameterised by rational points that lie on a split quadric surface AU - Browning, Timothy D AU - Lyczak, Julian AU - Sarapin, Roman ID - 13180 IS - 2 JF - Involve SN - 1944-4176 TI - Local solubility for a family of quadrics over a split quadric surface VL - 16 ER - TY - GEN AU - Elefante, Stefano AU - Stadlbauer, Stephan AU - Alexander, Michael F AU - Schlögl, Alois ID - 13162 T2 - ASHPC23 - Austrian-Slovenian HPC Meeting 2023 TI - Cryo-EM software packages: A sys-admins point of view ER - TY - GEN AU - Schlögl, Alois AU - Elefante, Stefano AU - Hodirnau, Victor-Valentin ID - 13161 T2 - ASHPC23 - Austrian-Slovenian HPC Meeting 2023 TI - Running Windows-applications on a Linux HPC cluster using WINE ER - TY - JOUR AB - A rotating organic cation and a dynamically disordered soft inorganic cage are the hallmark features of organic-inorganic lead-halide perovskites. Understanding the interplay between these two subsystems is a challenging problem, but it is this coupling that is widely conjectured to be responsible for the unique behavior of photocarriers in these materials. In this work, we use the fact that the polarizability of the organic cation strongly depends on the ambient electrostatic environment to put the molecule forward as a sensitive probe of the local crystal fields inside the lattice cell. We measure the average polarizability of the C/N–H bond stretching mode by means of infrared spectroscopy, which allows us to deduce the character of the motion of the cation molecule, find the magnitude of the local crystal field, and place an estimate on the strength of the hydrogen bond between the hydrogen and halide atoms. Our results pave the way for understanding electric fields in lead-halide perovskites using infrared bond spectroscopy. AU - Wei, Yujing AU - Volosniev, Artem AU - Lorenc, Dusan AU - Zhumekenov, Ayan A. AU - Bakr, Osman M. AU - Lemeshko, Mikhail AU - Alpichshev, Zhanybek ID - 13251 IS - 27 JF - The Journal of Physical Chemistry Letters KW - General Materials Science KW - Physical and Theoretical Chemistry TI - Bond polarizability as a probe of local crystal fields in hybrid lead-halide perovskites VL - 14 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 - JOUR AB - Recent experimental advances have inspired the development of theoretical tools to describe the non-equilibrium dynamics of quantum systems. Among them an exact representation of quantum spin systems in terms of classical stochastic processes has been proposed. Here we provide first steps towards the extension of this stochastic approach to bosonic systems by considering the one-dimensional quantum quartic oscillator. We show how to exactly parameterize the time evolution of this prototypical model via the dynamics of a set of classical variables. We interpret these variables as stochastic processes, which allows us to propose a novel way to numerically simulate the time evolution of the system. We benchmark our findings by considering analytically solvable limits and providing alternative derivations of known results. AU - Tucci, Gennaro AU - De Nicola, Stefano AU - Wald, Sascha AU - Gambassi, Andrea ID - 13277 IS - 2 JF - SciPost Physics Core KW - Statistical and Nonlinear Physics KW - Atomic and Molecular Physics KW - and Optics KW - Nuclear and High Energy Physics KW - Condensed Matter Physics SN - 2666-9366 TI - Stochastic representation of the quantum quartic oscillator VL - 6 ER - TY - JOUR AB - We introduce a generic and accessible implementation of an exact diagonalization method for studying few-fermion models. Our aim is to provide a testbed for the newcomers to the field as well as a stepping stone for trying out novel optimizations and approximations. This userguide consists of a description of the algorithm, and several examples in varying orders of sophistication. In particular, we exemplify our routine using an effective-interaction approach that fixes the low-energy physics. We benchmark this approach against the existing data, and show that it is able to deliver state-of-the-art numerical results at a significantly reduced computational cost. AU - Rammelmüller, Lukas AU - Huber, David AU - Volosniev, Artem ID - 13276 JF - SciPost Physics Codebases SN - 2949-804X TI - A modular implementation of an effective interaction approach for harmonically trapped fermions in 1D ER - TY - GEN AB - We introduce a generic and accessible implementation of an exact diagonalization method for studying few-fermion models. Our aim is to provide a testbed for the newcomers to the field as well as a stepping stone for trying out novel optimizations and approximations. This userguide consists of a description of the algorithm, and several examples in varying orders of sophistication. In particular, we exemplify our routine using an effective-interaction approach that fixes the low-energy physics. We benchmark this approach against the existing data, and show that it is able to deliver state-of-the-art numerical results at a significantly reduced computational cost. AU - Rammelmüller, Lukas AU - Huber, David AU - Volosniev, Artem ID - 13275 TI - Codebase release 1.0 for FermiFCI 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 - Understanding population divergence that eventually leads to speciation is essential for evolutionary biology. High species diversity in the sea was regarded as a paradox when strict allopatry was considered necessary for most speciation events because geographical barriers seemed largely absent in the sea, and many marine species have high dispersal capacities. Combining genome-wide data with demographic modelling to infer the demographic history of divergence has introduced new ways to address this classical issue. These models assume an ancestral population that splits into two subpopulations diverging according to different scenarios that allow tests for periods of gene flow. Models can also test for heterogeneities in population sizes and migration rates along the genome to account, respectively, for background selection and selection against introgressed ancestry. To investigate how barriers to gene flow arise in the sea, we compiled studies modelling the demographic history of divergence in marine organisms and extracted preferred demographic scenarios together with estimates of demographic parameters. These studies show that geographical barriers to gene flow do exist in the sea but that divergence can also occur without strict isolation. Heterogeneity of gene flow was detected in most population pairs suggesting the predominance of semipermeable barriers during divergence. We found a weak positive relationship between the fraction of the genome experiencing reduced gene flow and levels of genome-wide differentiation. Furthermore, we found that the upper bound of the ‘grey zone of speciation’ for our dataset extended beyond that found before, implying that gene flow between diverging taxa is possible at higher levels of divergence than previously thought. Finally, we list recommendations for further strengthening the use of demographic modelling in speciation research. These include a more balanced representation of taxa, more consistent and comprehensive modelling, clear reporting of results and simulation studies to rule out nonbiological explanations for general results. AU - De Jode, Aurélien AU - Le Moan, Alan AU - Johannesson, Kerstin AU - Faria, Rui AU - Stankowski, Sean AU - Westram, Anja M AU - Butlin, Roger K. AU - Rafajlović, Marina AU - Fraisse, Christelle ID - 11479 IS - 2 JF - Evolutionary Applications TI - Ten years of demographic modelling of divergence and speciation in the sea VL - 16 ER - TY - JOUR AB - In this article, we develop two independent and new approaches to model epidemic spread in a network. Contrary to the most studied models, those developed here allow for contacts with different probabilities of transmitting the disease (transmissibilities). We then examine each of these models using some mean field type approximations. The first model looks at the late-stage effects of an epidemic outbreak and allows for the computation of the probability that a given vertex was infected. This computation is based on a mean field approximation and only depends on the number of contacts and their transmissibilities. This approach shares many similarities with percolation models in networks. The second model we develop is a dynamic model which we analyze using a mean field approximation which highly reduces the dimensionality of the system. In particular, the original system which individually analyses each vertex of the network is reduced to one with as many equations as different transmissibilities. Perhaps the greatest contribution of this article is the observation that, in both these models, the existence and size of an epidemic outbreak are linked to the properties of a matrix which we call the R-matrix. This is a generalization of the basic reproduction number which more precisely characterizes the main routes of infection. AU - Gómez, Arturo AU - Oliveira, Goncalo ID - 12329 JF - Scientific Reports TI - New approaches to epidemic modeling on networks VL - 13 ER - TY - JOUR AB - We determine an asymptotic formula for the number of integral points of bounded height on a blow-up of P3 outside certain planes using universal torsors. AU - Wilsch, Florian Alexander ID - 9034 IS - 8 JF - International Mathematics Research Notices SN - 1073-7928 TI - Integral points of bounded height on a log Fano threefold VL - 2023 ER - TY - JOUR AB - Hosts can carry many viruses in their bodies, but not all of them cause disease. We studied ants as a social host to determine both their overall viral repertoire and the subset of actively infecting viruses across natural populations of three subfamilies: the Argentine ant (Linepithema humile, Dolichoderinae), the invasive garden ant (Lasius neglectus, Formicinae) and the red ant (Myrmica rubra, Myrmicinae). We used a dual sequencing strategy to reconstruct complete virus genomes by RNA-seq and to simultaneously determine the small interfering RNAs (siRNAs) by small RNA sequencing (sRNA-seq), which constitute the host antiviral RNAi immune response. This approach led to the discovery of 41 novel viruses in ants and revealed a host ant-specific RNAi response (21 vs. 22 nt siRNAs) in the different ant species. The efficiency of the RNAi response (sRNA/RNA read count ratio) depended on the virus and the respective ant species, but not its population. Overall, we found the highest virus abundance and diversity per population in Li. humile, followed by La. neglectus and M. rubra. Argentine ants also shared a high proportion of viruses between populations, whilst overlap was nearly absent in M. rubra. Only one of the 59 viruses was found to infect two of the ant species as hosts, revealing high host-specificity in active infections. In contrast, six viruses actively infected one ant species, but were found as contaminants only in the others. Disentangling spillover of disease-causing infection from non-infecting contamination across species is providing relevant information for disease ecology and ecosystem management. AU - Viljakainen, Lumi AU - Fürst, Matthias AU - Grasse, Anna V AU - Jurvansuu, Jaana AU - Oh, Jinook AU - Tolonen, Lassi AU - Eder, Thomas AU - Rattei, Thomas AU - Cremer, Sylvia ID - 12469 JF - Frontiers in Microbiology TI - Antiviral immune response reveals host-specific virus infections in natural ant populations VL - 14 ER - TY - JOUR AB - We present criteria for establishing a triangulation of a manifold. Given a manifold M, a simplicial complex A, and a map H from the underlying space of A to M, our criteria are presented in local coordinate charts for M, and ensure that H is a homeomorphism. These criteria do not require a differentiable structure, or even an explicit metric on M. No Delaunay property of A is assumed. The result provides a triangulation guarantee for algorithms that construct a simplicial complex by working in local coordinate patches. Because the criteria are easily verified in such a setting, they are expected to be of general use. AU - Boissonnat, Jean-Daniel AU - Dyer, Ramsay AU - Ghosh, Arijit AU - Wintraecken, Mathijs ID - 12287 JF - Discrete & Computational Geometry KW - Computational Theory and Mathematics KW - Discrete Mathematics and Combinatorics KW - Geometry and Topology KW - Theoretical Computer Science SN - 0179-5376 TI - Local criteria for triangulating general manifolds VL - 69 ER - TY - JOUR AB - It may come as a surprise that a phenomenon as ubiquitous and prominent as the transition from laminar to turbulent flow has resisted combined efforts by physicists, engineers and mathematicians, and remained unresolved for almost one and a half centuries. In recent years, various studies have proposed analogies to directed percolation, a well-known universality class in statistical mechanics, which describes a non-equilibrium phase transition from a fluctuating active phase into an absorbing state. It is this unlikely relation between the multiscale, high-dimensional dynamics that signify the transition process in virtually all flows of practical relevance, and the arguably most basic non-equilibrium phase transition, that so far has mainly been the subject of model studies, which I review in this Perspective. AU - Hof, Björn ID - 12165 JF - Nature Reviews Physics KW - General Physics and Astronomy TI - Directed percolation and the transition to turbulence VL - 5 ER - TY - JOUR AB - The actin cytoskeleton plays a key role in cell migration and cellular morphodynamics in most eukaryotes. The ability of the actin cytoskeleton to assemble and disassemble in a spatiotemporally controlled manner allows it to form higher-order structures, which can generate forces required for a cell to explore and navigate through its environment. It is regulated not only via a complex synergistic and competitive interplay between actin-binding proteins (ABP), but also by filament biochemistry and filament geometry. The lack of structural insights into how geometry and ABPs regulate the actin cytoskeleton limits our understanding of the molecular mechanisms that define actin cytoskeleton remodeling and, in turn, impact emerging cell migration characteristics. With the advent of cryo-electron microscopy (cryo-EM) and advanced computational methods, it is now possible to define these molecular mechanisms involving actin and its interactors at both atomic and ultra-structural levels in vitro and in cellulo. In this review, we will provide an overview of the available cryo-EM methods, applicable to further our understanding of the actin cytoskeleton, specifically in the context of cell migration. We will discuss how these methods have been employed to elucidate ABP- and geometry-defined regulatory mechanisms in initiating, maintaining, and disassembling cellular actin networks in migratory protrusions. AU - Fäßler, Florian AU - Javoor, Manjunath AU - Schur, Florian KM ID - 12421 IS - 1 JF - Biochemical Society Transactions KW - Biochemistry SN - 0300-5127 TI - Deciphering the molecular mechanisms of actin cytoskeleton regulation in cell migration using cryo-EM VL - 51 ER - TY - JOUR AB - Data-driven dimensionality reduction methods such as proper orthogonal decomposition and dynamic mode decomposition have proven to be useful for exploring complex phenomena within fluid dynamics and beyond. A well-known challenge for these techniques is posed by the continuous symmetries, e.g. translations and rotations, of the system under consideration, as drifts in the data dominate the modal expansions without providing an insight into the dynamics of the problem. In the present study, we address this issue for fluid flows in rectangular channels by formulating a continuous symmetry reduction method that eliminates the translations in the streamwise and spanwise directions simultaneously. We demonstrate our method by computing the symmetry-reduced dynamic mode decomposition (SRDMD) of sliding windows of data obtained from the transitional plane-Couette and turbulent plane-Poiseuille flow simulations. In the former setting, SRDMD captures the dynamics in the vicinity of the invariant solutions with translation symmetries, i.e. travelling waves and relative periodic orbits, whereas in the latter, our calculations reveal episodes of turbulent time evolution that can be approximated by a low-dimensional linear expansion. AU - Marensi, Elena AU - Yalniz, Gökhan AU - Hof, Björn AU - Budanur, Nazmi B ID - 12105 JF - Journal of Fluid Mechanics SN - 0022-1120 TI - Symmetry-reduced dynamic mode decomposition of near-wall turbulence VL - 954 ER - TY - JOUR AB - The concept of a “speciation continuum” has gained popularity in recent decades. It emphasizes speciation as a continuous process that may be studied by comparing contemporary population pairs that show differing levels of divergence. In their recent perspective article in Evolution, Stankowski and Ravinet provided a valuable service by formally defining the speciation continuum as a continuum of reproductive isolation, based on opinions gathered from a survey of speciation researchers. While we agree that the speciation continuum has been a useful concept to advance the understanding of the speciation process, some intrinsic limitations exist. Here, we advocate for a multivariate extension, the speciation hypercube, first proposed by Dieckmann et al. in 2004, but rarely used since. We extend the idea of the speciation cube and suggest it has strong conceptual and practical advantages over a one-dimensional model. We illustrate how the speciation hypercube can be used to visualize and compare different speciation trajectories, providing new insights into the processes and mechanisms of speciation. A key strength of the speciation hypercube is that it provides a unifying framework for speciation research, as it allows questions from apparently disparate subfields to be addressed in a single conceptual model. AU - Bolnick, Daniel I. AU - Hund, Amanda K. AU - Nosil, Patrik AU - Peng, Foen AU - Ravinet, Mark AU - Stankowski, Sean AU - Subramanian, Swapna AU - Wolf, Jochen B.W. AU - Yukilevich, Roman ID - 12514 IS - 1 JF - Evolution: International journal of organic evolution TI - A multivariate view of the speciation continuum VL - 77 ER - TY - CONF AB - The limited exchange between human communities is a key factor in preventing the spread of COVID-19. This paper introduces a digital framework that combines an integration of real mobility data at the country scale with a series of modeling techniques and visual capabilities that highlight mobility patterns before and during the pandemic. The findings not only significantly exhibit mobility trends and different degrees of similarities at regional and local levels but also provide potential insight into the emergence of a pandemic on human behavior patterns and their likely socio-economic impacts. AU - Forghani, Mohammad AU - Claramunt, Christophe AU - Karimipour, Farid AU - Heiler, Georg ID - 12548 T2 - 2022 IEEE International Conference on Data Mining Workshops TI - Visual analytics of mobility network changes observed using mobile phone data during COVID-19 pandemic ER - TY - JOUR AB - he approximate graph coloring problem, whose complexity is unresolved in most cases, concerns finding a c-coloring of a graph that is promised to be k-colorable, where c≥k. This problem naturally generalizes to promise graph homomorphism problems and further to promise constraint satisfaction problems. The complexity of these problems has recently been studied through an algebraic approach. In this paper, we introduce two new techniques to analyze the complexity of promise CSPs: one is based on topology and the other on adjunction. We apply these techniques, together with the previously introduced algebraic approach, to obtain new unconditional NP-hardness results for a significant class of approximate graph coloring and promise graph homomorphism problems. AU - Krokhin, Andrei AU - Opršal, Jakub AU - Wrochna, Marcin AU - Živný, Stanislav ID - 12563 IS - 1 JF - SIAM Journal on Computing KW - General Mathematics KW - General Computer Science SN - 0097-5397 TI - Topology and adjunction in promise constraint satisfaction VL - 52 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 - Let k be a number field and X a smooth, geometrically integral quasi-projective variety over k. For any linear algebraic group G over k and any G-torsor g : Z → X, we observe that if the étale-Brauer obstruction is the only one for strong approximation off a finite set of places S for all twists of Z by elements in H^1(k, G), then the étale-Brauer obstruction is the only one for strong approximation off a finite set of places S for X. As an application, we show that any homogeneous space of the form G/H with G a connected linear algebraic group over k satisfies strong approximation off the infinite places with étale-Brauer obstruction, under some compactness assumptions when k is totally real. We also prove more refined strong approximation results for homogeneous spaces of the form G/H with G semisimple simply connected and H finite, using the theory of torsors and descent. AU - Balestrieri, Francesca ID - 12427 IS - 3 JF - Proceedings of the American Mathematical Society SN - 0002-9939 TI - Some remarks on strong approximation and applications to homogeneous spaces of linear algebraic groups VL - 151 ER - TY - JOUR AB - In this issue of Neuron, Espinosa-Medina et al.1 present the TEMPO (Temporal Encoding and Manipulation in a Predefined Order) system, which enables the marking and genetic manipulation of sequentially generated cell lineages in vertebrate species in vivo. AU - Villalba Requena, Ana AU - Hippenmeyer, Simon ID - 12542 IS - 3 JF - Neuron TI - Going back in time with TEMPO VL - 111 ER - TY - JOUR AB - Single-molecule localization microscopy (SMLM) greatly advances structural studies of diverse biological tissues. For example, presynaptic active zone (AZ) nanotopology is resolved in increasing detail. Immunofluorescence imaging of AZ proteins usually relies on epitope preservation using aldehyde-based immunocompetent fixation. Cryofixation techniques, such as high-pressure freezing (HPF) and freeze substitution (FS), are widely used for ultrastructural studies of presynaptic architecture in electron microscopy (EM). HPF/FS demonstrated nearer-to-native preservation of AZ ultrastructure, e.g., by facilitating single filamentous structures. Here, we present a protocol combining the advantages of HPF/FS and direct stochastic optical reconstruction microscopy (dSTORM) to quantify nanotopology of the AZ scaffold protein Bruchpilot (Brp) at neuromuscular junctions (NMJs) of Drosophila melanogaster. Using this standardized model, we tested for preservation of Brp clusters in different FS protocols compared to classical aldehyde fixation. In HPF/FS samples, presynaptic boutons were structurally well preserved with ~22% smaller Brp clusters that allowed quantification of subcluster topology. In summary, we established a standardized near-to-native preparation and immunohistochemistry protocol for SMLM analyses of AZ protein clusters in a defined model synapse. Our protocol could be adapted to study protein arrangements at single-molecule resolution in other intact tissue preparations. AU - Mrestani, Achmed AU - Lichter, Katharina AU - Sirén, Anna Leena AU - Heckmann, Manfred AU - Paul, Mila M. AU - Pauli, Martin ID - 12567 IS - 3 JF - International Journal of Molecular Sciences TI - Single-molecule localization microscopy of presynaptic active zones in Drosophila melanogaster after rapid cryofixation VL - 24 ER - TY - JOUR AB - Approximate agreement is one of the few variants of consensus that can be solved in a wait-free manner in asynchronous systems where processes communicate by reading and writing to shared memory. In this work, we consider a natural generalisation of approximate agreement on arbitrary undirected connected graphs. Each process is given a node of the graph as input and, if non-faulty, must output a node such that – all the outputs are within distance 1 of one another, and – each output value lies on a shortest path between two input values. From prior work, it is known that there is no wait-free algorithm among processes for this problem on any cycle of length , by reduction from 2-set agreement (Castañeda et al., 2018). In this work, we investigate the solvability of this task on general graphs. We give a new, direct proof of the impossibility of approximate agreement on cycles of length , via a generalisation of Sperner's Lemma to convex polygons. We also extend the reduction from 2-set agreement to a larger class of graphs, showing that approximate agreement on these graphs is unsolvable. On the positive side, we present a wait-free algorithm for a different class of graphs, which properly contains the class of chordal graphs. AU - Alistarh, Dan-Adrian AU - Ellen, Faith AU - Rybicki, Joel ID - 12566 IS - 2 JF - Theoretical Computer Science SN - 0304-3975 TI - Wait-free approximate agreement on graphs VL - 948 ER - TY - JOUR AB - The dissolution of minute concentration of polymers in wall-bounded flows is well-known for its unparalleled ability to reduce turbulent friction drag. Another phenomenon, elasto-inertial turbulence (EIT), has been far less studied even though elastic instabilities have already been observed in dilute polymer solutions before the discovery of polymer drag reduction. EIT is a chaotic state driven by polymer dynamics that is observed across many orders of magnitude in Reynolds number. It involves energy transfer from small elastic scales to large flow scales. The investigation of the mechanisms of EIT offers the possibility to better understand other complex phenomena such as elastic turbulence and maximum drag reduction. In this review, we survey recent research efforts that are advancing the understanding of the dynamics of EIT. We highlight the fundamental differences between EIT and Newtonian/inertial turbulence from the perspective of experiments, numerical simulations, instabilities, and coherent structures. Finally, we discuss the possible links between EIT and elastic turbulence and polymer drag reduction, as well as the remaining challenges in unraveling the self-sustaining mechanism of EIT. AU - Dubief, Yves AU - Terrapon, Vincent E. AU - Hof, Björn ID - 12681 IS - 1 JF - Annual Review of Fluid Mechanics SN - 0066-4189 TI - Elasto-inertial turbulence VL - 55 ER - TY - JOUR AB - Since the seminal studies by Osborne Reynolds in the nineteenth century, pipe flow has served as a primary prototype for investigating the transition to turbulence in wall-bounded flows. Despite the apparent simplicity of this flow, various facets of this problem have occupied researchers for more than a century. Here we review insights from three distinct perspectives: (a) stability and susceptibility of laminar flow, (b) phase transition and spatiotemporal dynamics, and (c) dynamical systems analysis of the Navier—Stokes equations. We show how these perspectives have led to a profound understanding of the onset of turbulence in pipe flow. Outstanding open points, applications to flows of complex fluids, and similarities with other wall-bounded flows are discussed. AU - Avila, Marc AU - Barkley, Dwight AU - Hof, Björn ID - 12682 JF - Annual Review of Fluid Mechanics SN - 0066-4189 TI - Transition to turbulence in pipe flow VL - 55 ER - TY - JOUR AB - Self-organisation is the spontaneous emergence of spatio-temporal structures and patterns from the interaction of smaller individual units. Examples are found across many scales in very different systems and scientific disciplines, from physics, materials science and robotics to biology, geophysics and astronomy. Recent research has highlighted how self-organisation can be both mediated and controlled by confinement. Confinement is an action over a system that limits its units’ translational and rotational degrees of freedom, thus also influencing the system's phase space probability density; it can function as either a catalyst or inhibitor of self-organisation. Confinement can then become a means to actively steer the emergence or suppression of collective phenomena in space and time. Here, to provide a common framework and perspective for future research, we examine the role of confinement in the self-organisation of soft-matter systems and identify overarching scientific challenges that need to be addressed to harness its full scientific and technological potential in soft matter and related fields. By drawing analogies with other disciplines, this framework will accelerate a common deeper understanding of self-organisation and trigger the development of innovative strategies to steer it using confinement, with impact on, e.g., the design of smarter materials, tissue engineering for biomedicine and in guiding active matter. AU - Araújo, Nuno A.M. AU - Janssen, Liesbeth M.C. AU - Barois, Thomas AU - Boffetta, Guido AU - Cohen, Itai AU - Corbetta, Alessandro AU - Dauchot, Olivier AU - Dijkstra, Marjolein AU - Durham, William M. AU - Dussutour, Audrey AU - Garnier, Simon AU - Gelderblom, Hanneke AU - Golestanian, Ramin AU - Isa, Lucio AU - Koenderink, Gijsje H. AU - Löwen, Hartmut AU - Metzler, Ralf AU - Polin, Marco AU - Royall, C. Patrick AU - Šarić, Anđela AU - Sengupta, Anupam AU - Sykes, Cécile AU - Trianni, Vito AU - Tuval, Idan AU - Vogel, Nicolas AU - Yeomans, Julia M. AU - Zuriguel, Iker AU - Marin, Alvaro AU - Volpe, Giorgio ID - 12708 JF - Soft Matter SN - 1744-683X TI - Steering self-organisation through confinement VL - 19 ER - TY - JOUR AB - Hydrocarbon mixtures are extremely abundant in the Universe, and diamond formation from them can play a crucial role in shaping the interior structure and evolution of planets. With first-principles accuracy, we first estimate the melting line of diamond, and then reveal the nature of chemical bonding in hydrocarbons at extreme conditions. We finally establish the pressure-temperature phase boundary where it is thermodynamically possible for diamond to form from hydrocarbon mixtures with different atomic fractions of carbon. Notably, here we show a depletion zone at pressures above 200 GPa and temperatures below 3000 K-3500 K where diamond formation is thermodynamically favorable regardless of the carbon atomic fraction, due to a phase separation mechanism. The cooler condition of the interior of Neptune compared to Uranus means that the former is much more likely to contain the depletion zone. Our findings can help explain the dichotomy of the two ice giants manifested by the low luminosity of Uranus, and lead to a better understanding of (exo-)planetary formation and evolution. AU - Cheng, Bingqing AU - Hamel, Sebastien AU - Bethkenhagen, Mandy ID - 12702 JF - Nature Communications TI - Thermodynamics of diamond formation from hydrocarbon mixtures in planets VL - 14 ER - TY - JOUR AB - Background Epigenetic clocks can track both chronological age (cAge) and biological age (bAge). The latter is typically defined by physiological biomarkers and risk of adverse health outcomes, including all-cause mortality. As cohort sample sizes increase, estimates of cAge and bAge become more precise. Here, we aim to develop accurate epigenetic predictors of cAge and bAge, whilst improving our understanding of their epigenomic architecture. Methods First, we perform large-scale (N = 18,413) epigenome-wide association studies (EWAS) of chronological age and all-cause mortality. Next, to create a cAge predictor, we use methylation data from 24,674 participants from the Generation Scotland study, the Lothian Birth Cohorts (LBC) of 1921 and 1936, and 8 other cohorts with publicly available data. In addition, we train a predictor of time to all-cause mortality as a proxy for bAge using the Generation Scotland cohort (1214 observed deaths). For this purpose, we use epigenetic surrogates (EpiScores) for 109 plasma proteins and the 8 component parts of GrimAge, one of the current best epigenetic predictors of survival. We test this bAge predictor in four external cohorts (LBC1921, LBC1936, the Framingham Heart Study and the Women’s Health Initiative study). Results Through the inclusion of linear and non-linear age-CpG associations from the EWAS, feature pre-selection in advance of elastic net regression, and a leave-one-cohort-out (LOCO) cross-validation framework, we obtain cAge prediction with a median absolute error equal to 2.3 years. Our bAge predictor was found to slightly outperform GrimAge in terms of the strength of its association to survival (HRGrimAge = 1.47 [1.40, 1.54] with p = 1.08 × 10−52, and HRbAge = 1.52 [1.44, 1.59] with p = 2.20 × 10−60). Finally, we introduce MethylBrowsR, an online tool to visualise epigenome-wide CpG-age associations. Conclusions The integration of multiple large datasets, EpiScores, non-linear DNAm effects, and new approaches to feature selection has facilitated improvements to the blood-based epigenetic prediction of biological and chronological age. AU - Bernabeu, Elena AU - Mccartney, Daniel L. AU - Gadd, Danni A. AU - Hillary, Robert F. AU - Lu, Ake T. AU - Murphy, Lee AU - Wrobel, Nicola AU - Campbell, Archie AU - Harris, Sarah E. AU - Liewald, David AU - Hayward, Caroline AU - Sudlow, Cathie AU - Cox, Simon R. AU - Evans, Kathryn L. AU - Horvath, Steve AU - Mcintosh, Andrew M. AU - Robinson, Matthew Richard AU - Vallejos, Catalina A. AU - Marioni, Riccardo E. ID - 12719 JF - Genome Medicine TI - Refining epigenetic prediction of chronological and biological age VL - 15 ER - TY - JOUR AB - Adversarial training (i.e., training on adversarially perturbed input data) is a well-studied method for making neural networks robust to potential adversarial attacks during inference. However, the improved robustness does not come for free but rather is accompanied by a decrease in overall model accuracy and performance. Recent work has shown that, in practical robot learning applications, the effects of adversarial training do not pose a fair trade-off but inflict a net loss when measured in holistic robot performance. This work revisits the robustness-accuracy trade-off in robot learning by systematically analyzing if recent advances in robust training methods and theory in conjunction with adversarial robot learning, are capable of making adversarial training suitable for real-world robot applications. We evaluate three different robot learning tasks ranging from autonomous driving in a high-fidelity environment amenable to sim-to-real deployment to mobile robot navigation and gesture recognition. Our results demonstrate that, while these techniques make incremental improvements on the trade-off on a relative scale, the negative impact on the nominal accuracy caused by adversarial training still outweighs the improved robustness by an order of magnitude. We conclude that although progress is happening, further advances in robust learning methods are necessary before they can benefit robot learning tasks in practice. AU - Lechner, Mathias AU - Amini, Alexander AU - Rus, Daniela AU - Henzinger, Thomas A ID - 12704 IS - 3 JF - IEEE Robotics and Automation Letters TI - Revisiting the adversarial robustness-accuracy tradeoff in robot learning VL - 8 ER - TY - JOUR AB - The substitution of heavier, more metallic atoms into classical organic ligand frameworks provides an important strategy for tuning ligand properties, such as ligand bite and donor character, and is the basis for the emerging area of main-group supramolecular chemistry. In this paper, we explore two new ligands [E(2-Me-8-qy)3] [E = Sb (1), Bi (2); qy = quinolyl], allowing a fundamental comparison of their coordination behavior with classical tris(2-pyridyl) ligands of the type [E′(2-py)3] (E = a range of bridgehead atoms and groups, py = pyridyl). A range of new coordination modes to Cu+, Ag+, and Au+ is seen for 1 and 2, in the absence of steric constraints at the bridgehead and with their more remote N-donor atoms. A particular feature is the adaptive nature of these new ligands, with the ability to adjust coordination mode in response to the hard–soft character of coordinated metal ions, influenced also by the character of the bridgehead atom (Sb or Bi). These features can be seen in a comparison between [Cu2{Sb(2-Me-8-qy)3}2](PF6)2 (1·CuPF6) and [Cu{Bi(2-Me-8-qy)3}](PF6) (2·CuPF6), the first containing a dimeric cation in which 1 adopts an unprecedented intramolecular N,N,Sb-coordination mode while in the second, 2 adopts an unusual N,N,(π-)C coordination mode. In contrast, the previously reported analogous ligands [E(6-Me-2-py)3] (E = Sb, Bi; 2-py = 2-pyridyl) show a tris-chelating mode in their complexes with CuPF6, which is typical for the extensive tris(2-pyridyl) family with a range of metals. The greater polarity of the Bi–C bond in 2 results in ligand transfer reactions with Au(I). Although this reactivity is not in itself unusual, the characterization of several products by single-crystal X-ray diffraction provides snapshots of the ligand transfer reaction involved, with one of the products (the bimetallic complex [(BiCl){ClAu2(2-Me-8-qy)3}] (8)) containing a Au2Bi core in which the shortest Au → Bi donor–acceptor bond to date is observed. AU - García-Romero, Álvaro AU - Waters, Jessica E. AU - Jethwa, Rajesh B AU - Bond, Andrew D. AU - Colebatch, Annie L. AU - García-Rodríguez, Raúl AU - Wright, Dominic S. ID - 12737 IS - 11 JF - Inorganic Chemistry SN - 0020-1669 TI - Highly adaptive nature of group 15 tris(quinolyl) ligands─studies with coinage metals VL - 62 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 - Stereological methods for estimating the 3D particle size and density from 2D projections are essential to many research fields. These methods are, however, prone to errors arising from undetected particle profiles due to sectioning and limited resolution, known as ‘lost caps’. A potential solution developed by Keiding, Jensen, and Ranek in 1972, which we refer to as the Keiding model, accounts for lost caps by quantifying the smallest detectable profile in terms of its limiting ‘cap angle’ (ϕ), a size-independent measure of a particle’s distance from the section surface. However, this simple solution has not been widely adopted nor tested. Rather, model-independent design-based stereological methods, which do not explicitly account for lost caps, have come to the fore. Here, we provide the first experimental validation of the Keiding model by comparing the size and density of particles estimated from 2D projections with direct measurement from 3D EM reconstructions of the same tissue. We applied the Keiding model to estimate the size and density of somata, nuclei and vesicles in the cerebellum of mice and rats, where high packing density can be problematic for design-based methods. Our analysis reveals a Gaussian distribution for ϕ rather than a single value. Nevertheless, curve fits of the Keiding model to the 2D diameter distribution accurately estimate the mean ϕ and 3D diameter distribution. While systematic testing using simulations revealed an upper limit to determining ϕ, our analysis shows that estimated ϕ can be used to determine the 3D particle density from the 2D density under a wide range of conditions, and this method is potentially more accurate than minimum-size-based lost-cap corrections and disector methods. Our results show the Keiding model provides an efficient means of accurately estimating the size and density of particles from 2D projections even under conditions of a high density. AU - Rothman, Jason Seth AU - Borges Merjane, Carolina AU - Holderith, Noemi AU - Jonas, Peter M AU - Angus Silver, R. ID - 12759 IS - 3 March JF - PLoS ONE TI - Validation of a stereological method for estimating particle size and density from 2D projections with high accuracy VL - 18 ER - TY - JOUR AB - ESCRT-III family proteins form composite polymers that deform and cut membrane tubes in the context of a wide range of cell biological processes across the tree of life. In reconstituted systems, sequential changes in the composition of ESCRT-III polymers induced by the AAA–adenosine triphosphatase Vps4 have been shown to remodel membranes. However, it is not known how composite ESCRT-III polymers are organized and remodeled in space and time in a cellular context. Taking advantage of the relative simplicity of the ESCRT-III–dependent division system in Sulfolobus acidocaldarius, one of the closest experimentally tractable prokaryotic relatives of eukaryotes, we use super-resolution microscopy, electron microscopy, and computational modeling to show how CdvB/CdvB1/CdvB2 proteins form a precisely patterned composite ESCRT-III division ring, which undergoes stepwise Vps4-dependent disassembly and contracts to cut cells into two. These observations lead us to suggest sequential changes in a patterned composite polymer as a general mechanism of ESCRT-III–dependent membrane remodeling. AU - Hurtig, Fredrik AU - Burgers, Thomas C.Q. AU - Cezanne, Alice AU - Jiang, Xiuyun AU - Mol, Frank N. AU - Traparić, Jovan AU - Pulschen, Andre Arashiro AU - Nierhaus, Tim AU - Tarrason-Risa, Gabriel AU - Harker-Kirschneck, Lena AU - Löwe, Jan AU - Šarić, Anđela AU - Vlijm, Rifka AU - Baum, Buzz ID - 12756 IS - 11 JF - Science Advances TI - The patterned assembly and stepwise Vps4-mediated disassembly of composite ESCRT-III polymers drives archaeal cell division VL - 9 ER - TY - JOUR AB - AlphaFold changed the field of structural biology by achieving three-dimensional (3D) structure prediction from protein sequence at experimental quality. The astounding success even led to claims that the protein folding problem is “solved”. However, protein folding problem is more than just structure prediction from sequence. Presently, it is unknown if the AlphaFold-triggered revolution could help to solve other problems related to protein folding. Here we assay the ability of AlphaFold to predict the impact of single mutations on protein stability (ΔΔG) and function. To study the question we extracted the pLDDT and metrics from AlphaFold predictions before and after single mutation in a protein and correlated the predicted change with the experimentally known ΔΔG values. Additionally, we correlated the same AlphaFold pLDDT metrics with the impact of a single mutation on structure using a large scale dataset of single mutations in GFP with the experimentally assayed levels of fluorescence. We found a very weak or no correlation between AlphaFold output metrics and change of protein stability or fluorescence. Our results imply that AlphaFold may not be immediately applied to other problems or applications in protein folding. AU - Pak, Marina A. AU - Markhieva, Karina A. AU - Novikova, Mariia S. AU - Petrov, Dmitry S. AU - Vorobyev, Ilya S. AU - Maksimova, Ekaterina AU - Kondrashov, Fyodor AU - Ivankov, Dmitry N. ID - 12758 IS - 3 JF - PLoS ONE TI - Using AlphaFold to predict the impact of single mutations on protein stability and function VL - 18 ER - TY - JOUR AB - My group and myself have studied respiratory complex I for almost 30 years, starting in 1994 when it was known as a L-shaped giant ‘black box' of bioenergetics. First breakthrough was the X-ray structure of the peripheral arm, followed by structures of the membrane arm and finally the entire complex from Thermus thermophilus. The developments in cryo-EM technology allowed us to solve the first complete structure of the twice larger, ∼1 MDa mammalian enzyme in 2016. However, the mechanism coupling, over large distances, the transfer of two electrons to pumping of four protons across the membrane remained an enigma. Recently we have solved high-resolution structures of mammalian and bacterial complex I under a range of redox conditions, including catalytic turnover. This allowed us to propose a robust and universal mechanism for complex I and related protein families. Redox reactions initially drive conformational changes around the quinone cavity and a long-distance transfer of substrate protons. These set up a stage for a series of electrostatically driven proton transfers along the membrane arm (‘domino effect'), eventually resulting in proton expulsion from the distal antiporter-like subunit. The mechanism radically differs from previous suggestions, however, it naturally explains all the unusual structural features of complex I. In this review I discuss the state of knowledge on complex I, including the current most controversial issues. AU - Sazanov, Leonid A ID - 12757 IS - 5 JF - The Biochemical Journal SN - 0264-6021 TI - From the 'black box' to 'domino effect' mechanism: What have we learned from the structures of respiratory complex I VL - 480 ER - TY - JOUR AB - Populations evolve in spatially heterogeneous environments. While a certain trait might bring a fitness advantage in some patch of the environment, a different trait might be advantageous in another patch. Here, we study the Moran birth–death process with two types of individuals in a population stretched across two patches of size N, each patch favouring one of the two types. We show that the long-term fate of such populations crucially depends on the migration rate μ between the patches. To classify the possible fates, we use the distinction between polynomial (short) and exponential (long) timescales. We show that when μ is high then one of the two types fixates on the whole population after a number of steps that is only polynomial in N. By contrast, when μ is low then each type holds majority in the patch where it is favoured for a number of steps that is at least exponential in N. Moreover, we precisely identify the threshold migration rate μ⋆ that separates those two scenarios, thereby exactly delineating the situations that support long-term coexistence of the two types. We also discuss the case of various cycle graphs and we present computer simulations that perfectly match our analytical results. AU - Svoboda, Jakub AU - Tkadlec, Josef AU - Kaveh, Kamran AU - Chatterjee, Krishnendu ID - 12787 IS - 2271 JF - Proceedings of the Royal Society A: Mathematical, Physical and Engineering Sciences SN - 1364-5021 TI - Coexistence times in the Moran process with environmental heterogeneity VL - 479 ER - TY - JOUR AB - We show that the simplest of existing molecules—closed-shell diatomics not interacting with one another—host topological charges when driven by periodic far-off-resonant laser pulses. A periodically kicked molecular rotor can be mapped onto a “crystalline” lattice in angular momentum space. This allows us to define quasimomenta and the band structure in the Floquet representation, by analogy with the Bloch waves of solid-state physics. Applying laser pulses spaced by 1/3 of the molecular rotational period creates a lattice with three atoms per unit cell with staggered hopping. Within the synthetic dimension of the laser strength, we discover Dirac cones with topological charges. These Dirac cones, topologically protected by reflection and time-reversal symmetry, are reminiscent of (although not equivalent to) that seen in graphene. They—and the corresponding edge states—are broadly tunable by adjusting the laser strength and can be observed in present-day experiments by measuring molecular alignment and populations of rotational levels. This paves the way to study controllable topological physics in gas-phase experiments with small molecules as well as to classify dynamical molecular states by their topological invariants. AU - Karle, Volker AU - Ghazaryan, Areg AU - Lemeshko, Mikhail ID - 12788 IS - 10 JF - Physical Review Letters SN - 0031-9007 TI - Topological charges of periodically kicked molecules VL - 130 ER - TY - JOUR AB - Motivated by the recent discoveries of superconductivity in bilayer and trilayer graphene, we theoretically investigate superconductivity and other interaction-driven phases in multilayer graphene stacks. To this end, we study the density of states of multilayer graphene with up to four layers at the single-particle band structure level in the presence of a transverse electric field. Among the considered structures, tetralayer graphene with rhombohedral (ABCA) stacking reaches the highest density of states. We study the phases that can arise in ABCA graphene by tuning the carrier density and transverse electric field. For a broad region of the tuning parameters, the presence of strong Coulomb repulsion leads to a spontaneous spin and valley symmetry breaking via Stoner transitions. Using a model that incorporates the spontaneous spin and valley polarization, we explore the Kohn-Luttinger mechanism for superconductivity driven by repulsive Coulomb interactions. We find that the strongest superconducting instability is in the p-wave channel, and occurs in proximity to the onset of Stoner transitions. Interestingly, we find a range of densities and transverse electric fields where superconductivity develops out of a strongly corrugated, singly connected Fermi surface in each valley, leading to a topologically nontrivial chiral p+ip superconducting state with an even number of copropagating chiral Majorana edge modes. Our work establishes ABCA-stacked tetralayer graphene as a promising platform for observing strongly correlated physics and topological superconductivity. AU - Ghazaryan, Areg AU - Holder, Tobias AU - Berg, Erez AU - Serbyn, Maksym ID - 12790 IS - 10 JF - Physical Review B SN - 2469-9950 TI - Multilayer graphenes as a platform for interaction-driven physics and topological superconductivity VL - 107 ER - TY - JOUR AB - We investigate the capabilities of Physics-Informed Neural Networks (PINNs) to reconstruct turbulent Rayleigh–Bénard flows using only temperature information. We perform a quantitative analysis of the quality of the reconstructions at various amounts of low-passed-filtered information and turbulent intensities. We compare our results with those obtained via nudging, a classical equation-informed data assimilation technique. At low Rayleigh numbers, PINNs are able to reconstruct with high precision, comparable to the one achieved with nudging. At high Rayleigh numbers, PINNs outperform nudging and are able to achieve satisfactory reconstruction of the velocity fields only when data for temperature is provided with high spatial and temporal density. When data becomes sparse, the PINNs performance worsens, not only in a point-to-point error sense but also, and contrary to nudging, in a statistical sense, as can be seen in the probability density functions and energy spectra. AU - Clark Di Leoni, Patricio AU - Agasthya, Lokahith N AU - Buzzicotti, Michele AU - Biferale, Luca ID - 12791 IS - 3 JF - The European Physical Journal E SN - 1292-8941 TI - Reconstructing Rayleigh–Bénard flows out of temperature-only measurements using Physics-Informed Neural Networks VL - 46 ER - TY - JOUR AB - Interstitial fluid (IF) accumulation between embryonic cells is thought to be important for embryo patterning and morphogenesis. Here, we identify a positive mechanical feedback loop between cell migration and IF relocalization and find that it promotes embryonic axis formation during zebrafish gastrulation. We show that anterior axial mesendoderm (prechordal plate [ppl]) cells, moving in between the yolk cell and deep cell tissue to extend the embryonic axis, compress the overlying deep cell layer, thereby causing IF to flow from the deep cell layer to the boundary between the yolk cell and the deep cell layer, directly ahead of the advancing ppl. This IF relocalization, in turn, facilitates ppl cell protrusion formation and migration by opening up the space into which the ppl moves and, thereby, the ability of the ppl to trigger IF relocalization by pushing against the overlying deep cell layer. Thus, embryonic axis formation relies on a hydraulic feedback loop between cell migration and IF relocalization. AU - Huljev, Karla AU - Shamipour, Shayan AU - Nunes Pinheiro, Diana C AU - Preusser, Friedrich AU - Steccari, Irene AU - Sommer, Christoph M AU - Naik, Suyash AU - Heisenberg, Carl-Philipp J ID - 12830 IS - 7 JF - Developmental Cell SN - 1534-5807 TI - A hydraulic feedback loop between mesendoderm cell migration and interstitial fluid relocalization promotes embryonic axis formation in zebrafish VL - 58 ER -