@inproceedings{9678, abstract = {We introduce a new graph problem, the token dropping game, and we show how to solve it efficiently in a distributed setting. We use the token dropping game as a tool to design an efficient distributed algorithm for stable orientations and more generally for locally optimal semi-matchings. The prior work by Czygrinow et al. (DISC 2012) finds a stable orientation in O(Δ^5) rounds in graphs of maximum degree Δ, while we improve it to O(Δ^4) and also prove a lower bound of Ω(Δ). For the more general problem of locally optimal semi-matchings, the prior upper bound is O(S^5) and our new algorithm runs in O(C · S^4) rounds, which is an improvement for C = o(S); here C and S are the maximum degrees of customers and servers, respectively.}, author = {Brandt, Sebastian and Keller, Barbara and Rybicki, Joel and Suomela, Jukka and Uitto, Jara}, booktitle = {Annual ACM Symposium on Parallelism in Algorithms and Architectures}, isbn = {9781450380706}, location = { Virtual Event, United States}, pages = {129--139}, title = {{Efficient load-balancing through distributed token dropping}}, doi = {10.1145/3409964.3461785}, year = {2021}, } @article{8286, abstract = {We consider the following dynamic load-balancing process: given an underlying graph G with n nodes, in each step t≥ 0, one unit of load is created, and placed at a randomly chosen graph node. In the same step, the chosen node picks a random neighbor, and the two nodes balance their loads by averaging them. We are interested in the expected gap between the minimum and maximum loads at nodes as the process progresses, and its dependence on n and on the graph structure. Variants of the above graphical balanced allocation process have been studied previously by Peres, Talwar, and Wieder [Peres et al., 2015], and by Sauerwald and Sun [Sauerwald and Sun, 2015]. These authors left as open the question of characterizing the gap in the case of cycle graphs in the dynamic case, where weights are created during the algorithm’s execution. For this case, the only known upper bound is of 𝒪(n log n), following from a majorization argument due to [Peres et al., 2015], which analyzes a related graphical allocation process. In this paper, we provide an upper bound of 𝒪 (√n log n) on the expected gap of the above process for cycles of length n. We introduce a new potential analysis technique, which enables us to bound the difference in load between k-hop neighbors on the cycle, for any k ≤ n/2. We complement this with a "gap covering" argument, which bounds the maximum value of the gap by bounding its value across all possible subsets of a certain structure, and recursively bounding the gaps within each subset. We provide analytical and experimental evidence that our upper bound on the gap is tight up to a logarithmic factor. }, author = {Alistarh, Dan-Adrian and Nadiradze, Giorgi and Sabour, Amirmojtaba}, issn = {1432-0541}, journal = {Algorithmica}, location = {Virtual, Online; Germany}, publisher = {Springer Nature}, title = {{Dynamic averaging load balancing on cycles}}, doi = {10.1007/s00453-021-00905-9}, year = {2021}, } @phdthesis{9733, abstract = {This thesis is the result of the research carried out by the author during his PhD at IST Austria between 2017 and 2021. It mainly focuses on the Fröhlich polaron model, specifically to its regime of strong coupling. This model, which is rigorously introduced and discussed in the introduction, has been of great interest in condensed matter physics and field theory for more than eighty years. It is used to describe an electron interacting with the atoms of a solid material (the strength of this interaction is modeled by the presence of a coupling constant α in the Hamiltonian of the system). The particular regime examined here, which is mathematically described by considering the limit α →∞, displays many interesting features related to the emergence of classical behavior, which allows for a simplified effective description of the system under analysis. The properties, the range of validity and a quantitative analysis of the precision of such classical approximations are the main object of the present work. We specify our investigation to the study of the ground state energy of the system, its dynamics and its effective mass. For each of these problems, we provide in the introduction an overview of the previously known results and a detailed account of the original contributions by the author.}, author = {Feliciangeli, Dario}, issn = {2663-337X}, pages = {180}, publisher = {Institute of Science and Technology Austria}, title = {{The polaron at strong coupling}}, doi = {10.15479/at:ista:9733}, year = {2021}, } @article{9571, abstract = {As the size and complexity of models and datasets grow, so does the need for communication-efficient variants of stochastic gradient descent that can be deployed to perform parallel model training. One popular communication-compression method for data-parallel SGD is QSGD (Alistarh et al., 2017), which quantizes and encodes gradients to reduce communication costs. The baseline variant of QSGD provides strong theoretical guarantees, however, for practical purposes, the authors proposed a heuristic variant which we call QSGDinf, which demonstrated impressive empirical gains for distributed training of large neural networks. In this paper, we build on this work to propose a new gradient quantization scheme, and show that it has both stronger theoretical guarantees than QSGD, and matches and exceeds the empirical performance of the QSGDinf heuristic and of other compression methods.}, author = {Ramezani-Kebrya, Ali and Faghri, Fartash and Markov, Ilya and Aksenov, Vitalii and Alistarh, Dan-Adrian and Roy, Daniel M.}, issn = {15337928}, journal = {Journal of Machine Learning Research}, number = {114}, pages = {1−43}, publisher = {Journal of Machine Learning Research}, title = {{NUQSGD: Provably communication-efficient data-parallel SGD via nonuniform quantization}}, volume = {22}, year = {2021}, } @article{8544, abstract = {The synaptotrophic hypothesis posits that synapse formation stabilizes dendritic branches, yet this hypothesis has not been causally tested in vivo in the mammalian brain. Presynaptic ligand cerebellin-1 (Cbln1) and postsynaptic receptor GluD2 mediate synaptogenesis between granule cells and Purkinje cells in the molecular layer of the cerebellar cortex. Here we show that sparse but not global knockout of GluD2 causes under-elaboration of Purkinje cell dendrites in the deep molecular layer and overelaboration in the superficial molecular layer. Developmental, overexpression, structure-function, and genetic epistasis analyses indicate that dendrite morphogenesis defects result from competitive synaptogenesis in a Cbln1/GluD2-dependent manner. A generative model of dendritic growth based on competitive synaptogenesis largely recapitulates GluD2 sparse and global knockout phenotypes. Our results support the synaptotrophic hypothesis at initial stages of dendrite development, suggest a second mode in which cumulative synapse formation inhibits further dendrite growth, and highlight the importance of competition in dendrite morphogenesis.}, author = {Takeo, Yukari H. and Shuster, S. Andrew and Jiang, Linnie and Hu, Miley and Luginbuhl, David J. and Rülicke, Thomas and Contreras, Ximena and Hippenmeyer, Simon and Wagner, Mark J. and Ganguli, Surya and Luo, Liqun}, issn = {1097-4199}, journal = {Neuron}, number = {4}, pages = {P629--644.E8}, publisher = {Elsevier}, title = {{GluD2- and Cbln1-mediated competitive synaptogenesis shapes the dendritic arbors of cerebellar Purkinje cells}}, doi = {10.1016/j.neuron.2020.11.028}, volume = {109}, year = {2021}, } @unpublished{9791, abstract = {We provide a definition of the effective mass for the classical polaron described by the Landau-Pekar equations. It is based on a novel variational principle, minimizing the energy functional over states with given (initial) velocity. The resulting formula for the polaron's effective mass agrees with the prediction by Landau and Pekar.}, author = {Feliciangeli, Dario and Rademacher, Simone Anna Elvira and Seiringer, Robert}, booktitle = {arXiv}, title = {{The effective mass problem for the Landau-Pekar equations}}, year = {2021}, } @article{7553, abstract = {Normative theories and statistical inference provide complementary approaches for the study of biological systems. A normative theory postulates that organisms have adapted to efficiently solve essential tasks, and proceeds to mathematically work out testable consequences of such optimality; parameters that maximize the hypothesized organismal function can be derived ab initio, without reference to experimental data. In contrast, statistical inference focuses on efficient utilization of data to learn model parameters, without reference to any a priori notion of biological function, utility, or fitness. Traditionally, these two approaches were developed independently and applied separately. Here we unify them in a coherent Bayesian framework that embeds a normative theory into a family of maximum-entropy “optimization priors.” This family defines a smooth interpolation between a data-rich inference regime (characteristic of “bottom-up” statistical models), and a data-limited ab inito prediction regime (characteristic of “top-down” normative theory). We demonstrate the applicability of our framework using data from the visual cortex, and argue that the flexibility it affords is essential to address a number of fundamental challenges relating to inference and prediction in complex, high-dimensional biological problems.}, author = {Mlynarski, Wiktor F and Hledik, Michal and Sokolowski, Thomas R and Tkačik, Gašper}, journal = {Neuron}, number = {7}, pages = {1227--1241.e5}, publisher = {Cell Press}, title = {{Statistical analysis and optimality of neural systems}}, doi = {10.1016/j.neuron.2021.01.020}, volume = {109}, year = {2021}, } @inproceedings{10598, abstract = { We consider the problem of estimating a signal from measurements obtained via a generalized linear model. We focus on estimators based on approximate message passing (AMP), a family of iterative algorithms with many appealing features: the performance of AMP in the high-dimensional limit can be succinctly characterized under suitable model assumptions; AMP can also be tailored to the empirical distribution of the signal entries, and for a wide class of estimation problems, AMP is conjectured to be optimal among all polynomial-time algorithms. However, a major issue of AMP is that in many models (such as phase retrieval), it requires an initialization correlated with the ground-truth signal and independent from the measurement matrix. Assuming that such an initialization is available is typically not realistic. In this paper, we solve this problem by proposing an AMP algorithm initialized with a spectral estimator. With such an initialization, the standard AMP analysis fails since the spectral estimator depends in a complicated way on the design matrix. Our main contribution is a rigorous characterization of the performance of AMP with spectral initialization in the high-dimensional limit. The key technical idea is to define and analyze a two-phase artificial AMP algorithm that first produces the spectral estimator, and then closely approximates the iterates of the true AMP. We also provide numerical results that demonstrate the validity of the proposed approach. }, author = {Mondelli, Marco and Venkataramanan, Ramji}, booktitle = {Proceedings of The 24th International Conference on Artificial Intelligence and Statistics}, editor = {Banerjee, Arindam and Fukumizu, Kenji}, issn = {2640-3498}, location = {Virtual, San Diego, CA, United States}, pages = {397--405}, publisher = {ML Research Press}, title = {{Approximate message passing with spectral initialization for generalized linear models}}, volume = {130}, year = {2021}, } @article{8196, abstract = {This paper aims to obtain a strong convergence result for a Douglas–Rachford splitting method with inertial extrapolation step for finding a zero of the sum of two set-valued maximal monotone operators without any further assumption of uniform monotonicity on any of the involved maximal monotone operators. Furthermore, our proposed method is easy to implement and the inertial factor in our proposed method is a natural choice. Our method of proof is of independent interest. Finally, some numerical implementations are given to confirm the theoretical analysis.}, author = {Shehu, Yekini and Dong, Qiao-Li and Liu, Lu-Lu and Yao, Jen-Chih}, issn = {1573-2924}, journal = {Optimization and Engineering}, pages = {2627--2653}, publisher = {Springer Nature}, title = {{New strong convergence method for the sum of two maximal monotone operators}}, doi = {10.1007/s11081-020-09544-5}, volume = {22}, year = {2021}, } @article{8911, abstract = {In the worldwide endeavor for disruptive quantum technologies, germanium is emerging as a versatile material to realize devices capable of encoding, processing, or transmitting quantum information. These devices leverage special properties of the germanium valence-band states, commonly known as holes, such as their inherently strong spin-orbit coupling and the ability to host superconducting pairing correlations. In this Review, we initially introduce the physics of holes in low-dimensional germanium structures with key insights from a theoretical perspective. We then examine the material science progress underpinning germanium-based planar heterostructures and nanowires. We review the most significant experimental results demonstrating key building blocks for quantum technology, such as an electrically driven universal quantum gate set with spin qubits in quantum dots and superconductor-semiconductor devices for hybrid quantum systems. We conclude by identifying the most promising prospects toward scalable quantum information processing. }, author = {Scappucci, Giordano and Kloeffel, Christoph and Zwanenburg, Floris A. and Loss, Daniel and Myronov, Maksym and Zhang, Jian-Jun and Franceschi, Silvano De and Katsaros, Georgios and Veldhorst, Menno}, issn = {2058-8437}, journal = {Nature Reviews Materials}, pages = {926–943 }, publisher = {Springer Nature}, title = {{The germanium quantum information route}}, doi = {10.1038/s41578-020-00262-z}, volume = {6}, year = {2021}, } @article{8338, abstract = {Canonical parametrisations of classical confocal coordinate systems are introduced and exploited to construct non-planar analogues of incircular (IC) nets on individual quadrics and systems of confocal quadrics. Intimate connections with classical deformations of quadrics that are isometric along asymptotic lines and circular cross-sections of quadrics are revealed. The existence of octahedral webs of surfaces of Blaschke type generated by asymptotic and characteristic lines that are diagonally related to lines of curvature is proved theoretically and established constructively. Appropriate samplings (grids) of these webs lead to three-dimensional extensions of non-planar IC nets. Three-dimensional octahedral grids composed of planes and spatially extending (checkerboard) IC-nets are shown to arise in connection with systems of confocal quadrics in Minkowski space. In this context, the Laguerre geometric notion of conical octahedral grids of planes is introduced. The latter generalise the octahedral grids derived from systems of confocal quadrics in Minkowski space. An explicit construction of conical octahedral grids is presented. The results are accompanied by various illustrations which are based on the explicit formulae provided by the theory.}, author = {Akopyan, Arseniy and Bobenko, Alexander I. and Schief, Wolfgang K. and Techter, Jan}, issn = {1432-0444}, journal = {Discrete and Computational Geometry}, pages = {938--976}, publisher = {Springer Nature}, title = {{On mutually diagonal nets on (confocal) quadrics and 3-dimensional webs}}, doi = {10.1007/s00454-020-00240-w}, volume = {66}, year = {2021}, } @article{7939, abstract = {We design fast deterministic algorithms for distance computation in the Congested Clique model. Our key contributions include: A (2+ϵ)-approximation for all-pairs shortest paths in O(log2n/ϵ) rounds on unweighted undirected graphs. With a small additional additive factor, this also applies for weighted graphs. This is the first sub-polynomial constant-factor approximation for APSP in this model. A (1+ϵ)-approximation for multi-source shortest paths from O(n−−√) sources in O(log2n/ϵ) rounds on weighted undirected graphs. This is the first sub-polynomial algorithm obtaining this approximation for a set of sources of polynomial size. Our main techniques are new distance tools that are obtained via improved algorithms for sparse matrix multiplication, which we leverage to construct efficient hopsets and shortest paths. Furthermore, our techniques extend to additional distance problems for which we improve upon the state-of-the-art, including diameter approximation, and an exact single-source shortest paths algorithm for weighted undirected graphs in O~(n1/6) rounds. }, author = {Censor-Hillel, Keren and Dory, Michal and Korhonen, Janne and Leitersdorf, Dean}, issn = {1432-0452}, journal = {Distributed Computing}, pages = {463--487}, publisher = {Springer Nature}, title = {{Fast approximate shortest paths in the congested clique}}, doi = {10.1007/s00446-020-00380-5}, volume = {34}, year = {2021}, } @article{8248, abstract = {We consider the following setting: suppose that we are given a manifold M in Rd with positive reach. Moreover assume that we have an embedded simplical complex A without boundary, whose vertex set lies on the manifold, is sufficiently dense and such that all simplices in A have sufficient quality. We prove that if, locally, interiors of the projection of the simplices onto the tangent space do not intersect, then A is a triangulation of the manifold, that is, they are homeomorphic.}, author = {Boissonnat, Jean-Daniel and Dyer, Ramsay and Ghosh, Arijit and Lieutier, Andre and Wintraecken, Mathijs}, issn = {1432-0444}, journal = {Discrete and Computational Geometry}, pages = {666--686}, publisher = {Springer Nature}, title = {{Local conditions for triangulating submanifolds of Euclidean space}}, doi = {10.1007/s00454-020-00233-9}, volume = {66}, year = {2021}, } @article{7883, abstract = {All vertebrates have a spinal cord with dimensions and shape specific to their species. Yet how species‐specific organ size and shape are achieved is a fundamental unresolved question in biology. The formation and sculpting of organs begins during embryonic development. As it develops, the spinal cord extends in anterior–posterior direction in synchrony with the overall growth of the body. The dorsoventral (DV) and apicobasal lengths of the spinal cord neuroepithelium also change, while at the same time a characteristic pattern of neural progenitor subtypes along the DV axis is established and elaborated. At the basis of these changes in tissue size and shape are biophysical determinants, such as the change in cell number, cell size and shape, and anisotropic tissue growth. These processes are controlled by global tissue‐scale regulators, such as morphogen signaling gradients as well as mechanical forces. Current challenges in the field are to uncover how these tissue‐scale regulatory mechanisms are translated to the cellular and molecular level, and how regulation of distinct cellular processes gives rise to an overall defined size. Addressing these questions will help not only to achieve a better understanding of how size is controlled, but also of how tissue size is coordinated with the specification of pattern.}, author = {Kuzmicz-Kowalska, Katarzyna and Kicheva, Anna}, issn = {17597692}, journal = {Wiley Interdisciplinary Reviews: Developmental Biology}, publisher = {Wiley}, title = {{Regulation of size and scale in vertebrate spinal cord development}}, doi = {10.1002/wdev.383}, year = {2021}, } @article{7905, abstract = {We investigate a sheaf-theoretic interpretation of stratification learning from geometric and topological perspectives. Our main result is the construction of stratification learning algorithms framed in terms of a sheaf on a partially ordered set with the Alexandroff topology. We prove that the resulting decomposition is the unique minimal stratification for which the strata are homogeneous and the given sheaf is constructible. In particular, when we choose to work with the local homology sheaf, our algorithm gives an alternative to the local homology transfer algorithm given in Bendich et al. (Proceedings of the 23rd Annual ACM-SIAM Symposium on Discrete Algorithms, pp. 1355–1370, ACM, New York, 2012), and the cohomology stratification algorithm given in Nanda (Found. Comput. Math. 20(2), 195–222, 2020). Additionally, we give examples of stratifications based on the geometric techniques of Breiding et al. (Rev. Mat. Complut. 31(3), 545–593, 2018), illustrating how the sheaf-theoretic approach can be used to study stratifications from both topological and geometric perspectives. This approach also points toward future applications of sheaf theory in the study of topological data analysis by illustrating the utility of the language of sheaf theory in generalizing existing algorithms.}, author = {Brown, Adam and Wang, Bei}, issn = {1432-0444}, journal = {Discrete and Computational Geometry}, pages = {1166--1198}, publisher = {Springer Nature}, title = {{Sheaf-theoretic stratification learning from geometric and topological perspectives}}, doi = {10.1007/s00454-020-00206-y}, volume = {65}, year = {2021}, } @article{8601, abstract = {We consider large non-Hermitian real or complex random matrices X with independent, identically distributed centred entries. We prove that their local eigenvalue statistics near the spectral edge, the unit circle, coincide with those of the Ginibre ensemble, i.e. when the matrix elements of X are Gaussian. This result is the non-Hermitian counterpart of the universality of the Tracy–Widom distribution at the spectral edges of the Wigner ensemble.}, author = {Cipolloni, Giorgio and Erdös, László and Schröder, Dominik J}, issn = {14322064}, journal = {Probability Theory and Related Fields}, publisher = {Springer Nature}, title = {{Edge universality for non-Hermitian random matrices}}, doi = {10.1007/s00440-020-01003-7}, year = {2021}, } @article{7925, abstract = {In this paper, we introduce a relaxed CQ method with alternated inertial step for solving split feasibility problems. We give convergence of the sequence generated by our method under some suitable assumptions. Some numerical implementations from sparse signal and image deblurring are reported to show the efficiency of our method.}, author = {Shehu, Yekini and Gibali, Aviv}, issn = {1862-4480}, journal = {Optimization Letters}, pages = {2109--2126}, publisher = {Springer Nature}, title = {{New inertial relaxed method for solving split feasibilities}}, doi = {10.1007/s11590-020-01603-1}, volume = {15}, year = {2021}, } @article{15151, abstract = {Eukaryotic DNA-binding proteins operate in the context of chromatin, where nucleosomes are the elementary building blocks. Nucleosomal DNA is wrapped around a histone core, thereby rendering a large fraction of the DNA surface inaccessible to DNA-binding proteins. Nevertheless, first responders in DNA repair and sequence-specific transcription factors bind DNA target sites obstructed by chromatin. While early studies examined protein binding to histone-free DNA, it is only now beginning to emerge how DNA sequences are interrogated on nucleosomes. These readout strategies range from the release of nucleosomal DNA from histones, to rotational/translation register shifts of the DNA motif, and nucleosome-specific DNA binding modes that differ from those observed on naked DNA. Since DNA motif engagement on nucleosomes strongly depends on position and orientation, we argue that motif location and nucleosome positioning co-determine protein access to DNA in transcription and DNA repair.}, author = {Michael, Alicia and Thomä, Nicolas H.}, issn = {0092-8674}, journal = {Cell}, keywords = {General Biochemistry, Genetics and Molecular Biology}, number = {14}, pages = {3599--3611}, publisher = {Elsevier}, title = {{Reading the chromatinized genome}}, doi = {10.1016/j.cell.2021.05.029}, volume = {184}, year = {2021}, } @article{9438, abstract = {Rigorous investigation of synaptic transmission requires analysis of unitary synaptic events by simultaneous recording from presynaptic terminals and postsynaptic target neurons. However, this has been achieved at only a limited number of model synapses, including the squid giant synapse and the mammalian calyx of Held. Cortical presynaptic terminals have been largely inaccessible to direct presynaptic recording, due to their small size. Here, we describe a protocol for improved subcellular patch-clamp recording in rat and mouse brain slices, with the synapse in a largely intact environment. Slice preparation takes ~2 h, recording ~3 h and post hoc morphological analysis 2 d. Single presynaptic hippocampal mossy fiber terminals are stimulated minimally invasively in the bouton-attached configuration, in which the cytoplasmic content remains unperturbed, or in the whole-bouton configuration, in which the cytoplasmic composition can be precisely controlled. Paired pre–postsynaptic recordings can be integrated with biocytin labeling and morphological analysis, allowing correlative investigation of synapse structure and function. Paired recordings can be obtained from mossy fiber terminals in slices from both rats and mice, implying applicability to genetically modified synapses. Paired recordings can also be performed together with axon tract stimulation or optogenetic activation, allowing comparison of unitary and compound synaptic events in the same target cell. Finally, paired recordings can be combined with spontaneous event analysis, permitting collection of miniature events generated at a single identified synapse. In conclusion, the subcellular patch-clamp techniques detailed here should facilitate analysis of biophysics, plasticity and circuit function of cortical synapses in the mammalian central nervous system.}, author = {Vandael, David H and Okamoto, Yuji and Borges Merjane, Carolina and Vargas Barroso, Victor M and Suter, Benjamin and Jonas, Peter M}, issn = {17502799}, journal = {Nature Protocols}, number = {6}, pages = {2947–2967}, publisher = {Springer Nature}, title = {{Subcellular patch-clamp techniques for single-bouton stimulation and simultaneous pre- and postsynaptic recording at cortical synapses}}, doi = {10.1038/s41596-021-00526-0}, volume = {16}, year = {2021}, } @phdthesis{9992, abstract = {Blood – this is what animals use to heal wounds fast and efficient. Plants do not have blood circulation and their cells cannot move. However, plants have evolved remarkable capacities to regenerate tissues and organs preventing further damage. In my PhD research, I studied the wound healing in the Arabidopsis root. I used a UV laser to ablate single cells in the root tip and observed the consequent wound healing. Interestingly, the inner adjacent cells induced a division plane switch and subsequently adopted the cell type of the killed cell to replace it. We termed this form of wound healing “restorative divisions”. This initial observation triggered the questions of my PhD studies: How and why do cells orient their division planes, how do they feel the wound and why does this happen only in inner adjacent cells. For answering these questions, I used a quite simple experimental setup: 5 day - old seedlings were stained with propidium iodide to visualize cell walls and dead cells; ablation was carried out using a special laser cutter and a confocal microscope. Adaptation of the novel vertical microscope system made it possible to observe wounds in real time. This revealed that restorative divisions occur at increased frequency compared to normal divisions. Additionally, the major plant hormone auxin accumulates in wound adjacent cells and drives the expression of the wound-stress responsive transcription factor ERF115. Using this as a marker gene for wound responses, we found that an important part of wound signalling is the sensing of the collapse of the ablated cell. The collapse causes a radical pressure drop, which results in strong tissue deformations. These deformations manifest in an invasion of the now free spot specifically by the inner adjacent cells within seconds, probably because of higher pressure of the inner tissues. Long-term imaging revealed that those deformed cells continuously expand towards the wound hole and that this is crucial for the restorative division. These wound-expanding cells exhibit an abnormal, biphasic polarity of microtubule arrays before the division. Experiments inhibiting cell expansion suggest that it is the biphasic stretching that induces those MT arrays. Adapting the micromanipulator aspiration system from animal scientists at our institute confirmed the hypothesis that stretching influences microtubule stability. In conclusion, this shows that microtubules react to tissue deformation and this facilitates the observed division plane switch. This puts mechanical cues and tensions at the most prominent position for explaining the growth and wound healing properties of plants. Hence, it shines light onto the importance of understanding mechanical signal transduction. }, author = {Hörmayer, Lukas}, issn = {2663-337X}, pages = {168}, publisher = {Institute of Science and Technology Austria}, title = {{Wound healing in the Arabidopsis root meristem}}, doi = {10.15479/at:ista:9992}, year = {2021}, } @article{10816, abstract = {Pattern separation is a fundamental brain computation that converts small differences in input patterns into large differences in output patterns. Several synaptic mechanisms of pattern separation have been proposed, including code expansion, inhibition and plasticity; however, which of these mechanisms play a role in the entorhinal cortex (EC)–dentate gyrus (DG)–CA3 circuit, a classical pattern separation circuit, remains unclear. Here we show that a biologically realistic, full-scale EC–DG–CA3 circuit model, including granule cells (GCs) and parvalbumin-positive inhibitory interneurons (PV+-INs) in the DG, is an efficient pattern separator. Both external gamma-modulated inhibition and internal lateral inhibition mediated by PV+-INs substantially contributed to pattern separation. Both local connectivity and fast signaling at GC–PV+-IN synapses were important for maximum effectiveness. Similarly, mossy fiber synapses with conditional detonator properties contributed to pattern separation. By contrast, perforant path synapses with Hebbian synaptic plasticity and direct EC–CA3 connection shifted the network towards pattern completion. Our results demonstrate that the specific properties of cells and synapses optimize higher-order computations in biological networks and might be useful to improve the deep learning capabilities of technical networks.}, author = {Guzmán, José and Schlögl, Alois and Espinoza Martinez, Claudia and Zhang, Xiaomin and Suter, Benjamin and Jonas, Peter M}, issn = {2662-8457}, journal = {Nature Computational Science}, keywords = {general medicine}, number = {12}, pages = {830--842}, publisher = {Springer Nature}, title = {{How connectivity rules and synaptic properties shape the efficacy of pattern separation in the entorhinal cortex–dentate gyrus–CA3 network}}, doi = {10.1038/s43588-021-00157-1}, volume = {1}, year = {2021}, } @misc{10110, abstract = {Pattern separation is a fundamental brain computation that converts small differences in input patterns into large differences in output patterns. Several synaptic mechanisms of pattern separation have been proposed, including code expansion, inhibition and plasticity; however, which of these mechanisms play a role in the entorhinal cortex (EC)–dentate gyrus (DG)–CA3 circuit, a classical pattern separation circuit, remains unclear. Here we show that a biologically realistic, full-scale EC–DG–CA3 circuit model, including granule cells (GCs) and parvalbumin-positive inhibitory interneurons (PV+-INs) in the DG, is an efficient pattern separator. Both external gamma-modulated inhibition and internal lateral inhibition mediated by PV+-INs substantially contributed to pattern separation. Both local connectivity and fast signaling at GC–PV+-IN synapses were important for maximum effectiveness. Similarly, mossy fiber synapses with conditional detonator properties contributed to pattern separation. By contrast, perforant path synapses with Hebbian synaptic plasticity and direct EC–CA3 connection shifted the network towards pattern completion. Our results demonstrate that the specific properties of cells and synapses optimize higher-order computations in biological networks and might be useful to improve the deep learning capabilities of technical networks.}, author = {Guzmán, José and Schlögl, Alois and Espinoza Martinez, Claudia and Zhang, Xiaomin and Suter, Benjamin and Jonas, Peter M}, publisher = {IST Austria}, title = {{How connectivity rules and synaptic properties shape the efficacy of pattern separation in the entorhinal cortex–dentate gyrus–CA3 network}}, doi = {10.15479/AT:ISTA:10110}, year = {2021}, } @unpublished{10077, abstract = {Although much is known about how single neurons in the hippocampus represent an animal’s position, how cell-cell interactions contribute to spatial coding remains poorly understood. Using a novel statistical estimator and theoretical modeling, both developed in the framework of maximum entropy models, we reveal highly structured cell-to-cell interactions whose statistics depend on familiar vs. novel environment. In both conditions the circuit interactions optimize the encoding of spatial information, but for regimes that differ in the signal-to-noise ratio of their spatial inputs. Moreover, the topology of the interactions facilitates linear decodability, making the information easy to read out by downstream circuits. These findings suggest that the efficient coding hypothesis is not applicable only to individual neuron properties in the sensory periphery, but also to neural interactions in the central brain.}, author = {Nardin, Michele and Csicsvari, Jozsef L and Tkačik, Gašper and Savin, Cristina}, booktitle = {bioRxiv}, publisher = {Cold Spring Harbor Laboratory}, title = {{The structure of hippocampal CA1 interactions optimizes spatial coding across experience}}, doi = {10.1101/2021.09.28.460602}, year = {2021}, } @article{9250, abstract = {Aprotic alkali metal–O2 batteries face two major obstacles to their chemistry occurring efficiently, the insulating nature of the formed alkali superoxides/peroxides and parasitic reactions that are caused by the highly reactive singlet oxygen (1O2). Redox mediators are recognized to be key for improving rechargeability. However, it is unclear how they affect 1O2 formation, which hinders strategies for their improvement. Here we clarify the mechanism of mediated peroxide and superoxide oxidation and thus explain how redox mediators either enhance or suppress 1O2 formation. We show that charging commences with peroxide oxidation to a superoxide intermediate and that redox potentials above ~3.5 V versus Li/Li+ drive 1O2 evolution from superoxide oxidation, while disproportionation always generates some 1O2. We find that 1O2 suppression requires oxidation to be faster than the generation of 1O2 from disproportionation. Oxidation rates decrease with growing driving force following Marcus inverted-region behaviour, establishing a region of maximum rate.}, author = {Petit, Yann K. and Mourad, Eléonore and Prehal, Christian and Leypold, Christian and Windischbacher, Andreas and Mijailovic, Daniel and Slugovc, Christian and Borisov, Sergey M. and Zojer, Egbert and Brutti, Sergio and Fontaine, Olivier and Freunberger, Stefan Alexander}, issn = {1755-4349}, journal = {Nature Chemistry}, keywords = {General Chemistry, General Chemical Engineering}, number = {5}, pages = {465--471}, publisher = {Springer Nature}, title = {{Mechanism of mediated alkali peroxide oxidation and triplet versus singlet oxygen formation}}, doi = {10.1038/s41557-021-00643-z}, volume = {13}, year = {2021}, } @phdthesis{9623, abstract = {Cytoplasmic reorganizations are essential for morphogenesis. In large cells like oocytes, these reorganizations become crucial in patterning the oocyte for later stages of embryonic development. Ascidians oocytes reorganize their cytoplasm (ooplasm) in a spectacular manner. Ooplasmic reorganization is initiated at fertilization with the contraction of the actomyosin cortex along the animal-vegetal axis of the oocyte, driving the accumulation of cortical endoplasmic reticulum (cER), maternal mRNAs associated to it and a mitochondria-rich subcortical layer – the myoplasm – in a region of the vegetal pole termed contraction pole (CP). Here we have used the species Phallusia mammillata to investigate the changes in cell shape that accompany these reorganizations and the mechanochemical mechanisms underlining CP formation. We report that the length of the animal-vegetal (AV) axis oscillates upon fertilization: it first undergoes a cycle of fast elongation-lengthening followed by a slow expansion of mainly the vegetal pole (VP) of the cell. We show that the fast oscillation corresponds to a dynamic polarization of the actin cortex as a result of a fertilization-induced increase in cortical tension in the oocyte that triggers a rupture of the cortex at the animal pole and the establishment of vegetal-directed cortical flows. These flows are responsible for the vegetal accumulation of actin causing the VP to flatten. We find that the slow expansion of the VP, leading to CP formation, correlates with a relaxation of the vegetal cortex and that the myoplasm plays a role in the expansion. We show that the myoplasm is a solid-like layer that buckles under compression forces arising from the contracting actin cortex at the VP. Straightening of the myoplasm when actin flows stops, facilitates the expansion of the VP and the CP. Altogether, our results present a previously unrecognized role for the myoplasm in ascidian ooplasmic segregation. }, author = {Caballero Mancebo, Silvia}, isbn = {978-3-99078-012-1}, issn = {2663-337X}, pages = {111}, publisher = {Institute of Science and Technology Austria}, title = {{Fertilization-induced deformations are controlled by the actin cortex and a mitochondria-rich subcortical layer in ascidian oocytes}}, doi = {10.15479/at:ista:9623}, year = {2021}, } @article{9006, abstract = {Cytoplasm is a gel-like crowded environment composed of various macromolecules, organelles, cytoskeletal networks, and cytosol. The structure of the cytoplasm is highly organized and heterogeneous due to the crowding of its constituents and their effective compartmentalization. In such an environment, the diffusive dynamics of the molecules are restricted, an effect that is further amplified by clustering and anchoring of molecules. Despite the crowded nature of the cytoplasm at the microscopic scale, large-scale reorganization of the cytoplasm is essential for important cellular functions, such as cell division and polarization. How such mesoscale reorganization of the cytoplasm is achieved, especially for large cells such as oocytes or syncytial tissues that can span hundreds of micrometers in size, is only beginning to be understood. In this review, we will discuss recent advances in elucidating the molecular, cellular, and biophysical mechanisms by which the cytoskeleton drives cytoplasmic reorganization across different scales, structures, and species.}, author = {Shamipour, Shayan and Caballero Mancebo, Silvia and Heisenberg, Carl-Philipp J}, issn = {18781551}, journal = {Developmental Cell}, number = {2}, pages = {P213--226}, publisher = {Elsevier}, title = {{Cytoplasm's got moves}}, doi = {10.1016/j.devcel.2020.12.002}, volume = {56}, year = {2021}, } @article{9429, abstract = {De novo loss of function mutations in the ubiquitin ligase-encoding gene Cullin3 lead to autism spectrum disorder (ASD). In mouse, constitutive haploinsufficiency leads to motor coordination deficits as well as ASD-relevant social and cognitive impairments. However, induction of Cul3 haploinsufficiency later in life does not lead to ASD-relevant behaviors, pointing to an important role of Cul3 during a critical developmental window. Here we show that Cul3 is essential to regulate neuronal migration and, therefore, constitutive Cul3 heterozygous mutant mice display cortical lamination abnormalities. At the molecular level, we found that Cul3 controls neuronal migration by tightly regulating the amount of Plastin3 (Pls3), a previously unrecognized player of neural migration. Furthermore, we found that Pls3 cell-autonomously regulates cell migration by regulating actin cytoskeleton organization, and its levels are inversely proportional to neural migration speed. Finally, we provide evidence that cellular phenotypes associated with autism-linked gene haploinsufficiency can be rescued by transcriptional activation of the intact allele in vitro, offering a proof of concept for a potential therapeutic approach for ASDs.}, author = {Morandell, Jasmin and Schwarz, Lena A and Basilico, Bernadette and Tasciyan, Saren and Dimchev, Georgi A and Nicolas, Armel and Sommer, Christoph M and Kreuzinger, Caroline and Dotter, Christoph and Knaus, Lisa and Dobler, Zoe and Cacci, Emanuele and Schur, Florian KM and Danzl, Johann G and Novarino, Gaia}, issn = {2041-1723}, journal = {Nature Communications}, keywords = {General Biochemistry, Genetics and Molecular Biology}, number = {1}, publisher = {Springer Nature}, title = {{Cul3 regulates cytoskeleton protein homeostasis and cell migration during a critical window of brain development}}, doi = {10.1038/s41467-021-23123-x}, volume = {12}, year = {2021}, } @phdthesis{10058, abstract = {Quantum information and computation has become a vast field paved with opportunities for researchers and investors. As large multinational companies and international funds are heavily investing in quantum technologies it is still a question which platform is best suited for the task of realizing a scalable quantum processor. In this work we investigate hole spins in Ge quantum wells. These hold great promise as they possess several favorable properties: a small effective mass, a strong spin-orbit coupling, long relaxation time and an inherent immunity to hyperfine noise. All these characteristics helped Ge hole spin qubits to evolve from a single qubit to a fully entangled four qubit processor in only 3 years. Here, we investigated a qubit approach leveraging the large out-of-plane g-factors of heavy hole states in Ge quantum dots. We found this qubit to be reproducibly operable at extremely low magnetic field and at large speeds while maintaining coherence. This was possible because large differences of g-factors in adjacent dots can be achieved in the out-of-plane direction. In the in-plane direction the small g-factors, on the other hand, can be altered very effectively by the confinement potentials. Here, we found that this can even lead to a sign change of the g-factors. The resulting g-factor difference alters the dynamics of the system drastically and produces effects typically attributed to a spin-orbit induced spin-flip term. The investigations carried out in this thesis give further insights into the possibilities of holes in Ge and reveal new physical properties that need to be considered when designing future spin qubit experiments.}, author = {Jirovec, Daniel}, issn = {2663-337X}, keywords = {qubits, quantum computing, holes}, pages = {151}, publisher = {Institute of Science and Technology Austria}, title = {{Singlet-Triplet qubits and spin-orbit interaction in 2-dimensional Ge hole gases}}, doi = {10.15479/at:ista:10058}, year = {2021}, } @article{8909, abstract = {Spin qubits are considered to be among the most promising candidates for building a quantum processor. Group IV hole spin qubits have moved into the focus of interest due to the ease of operation and compatibility with Si technology. In addition, Ge offers the option for monolithic superconductor-semiconductor integration. Here we demonstrate a hole spin qubit operating at fields below 10 mT, the critical field of Al, by exploiting the large out-of-plane hole g-factors in planar Ge and by encoding the qubit into the singlet-triplet states of a double quantum dot. We observe electrically controlled X and Z-rotations with tunable frequencies exceeding 100 MHz and dephasing times of 1μs which we extend beyond 15μs with echo techniques. These results show that Ge hole singlet triplet qubits outperform their electronic Si and GaAs based counterparts in speed and coherence, respectively. In addition, they are on par with Ge single spin qubits, but can be operated at much lower fields underlining their potential for on chip integration with superconducting technologies.}, author = {Jirovec, Daniel and Hofmann, Andrea C and Ballabio, Andrea and Mutter, Philipp M. and Tavani, Giulio and Botifoll, Marc and Crippa, Alessandro and Kukucka, Josip and Sagi, Oliver and Martins, Frederico and Saez Mollejo, Jaime and Prieto Gonzalez, Ivan and Borovkov, Maksim and Arbiol, Jordi and Chrastina, Daniel and Isella, Giovanni and Katsaros, Georgios}, issn = {1476-4660}, journal = {Nature Materials}, number = {8}, pages = {1106–1112}, publisher = {Springer Nature}, title = {{A singlet triplet hole spin qubit in planar Ge}}, doi = {10.1038/s41563-021-01022-2}, volume = {20}, year = {2021}, } @phdthesis{9397, abstract = {Accumulation of interstitial fluid (IF) between embryonic cells is a common phenomenon in vertebrate embryogenesis. Unlike other model systems, where these accumulations coalesce into a large central cavity – the blastocoel, in zebrafish, IF is more uniformly distributed between the deep cells (DC) before the onset of gastrulation. This is likely due to the presence of a large extraembryonic structure – the yolk cell (YC) at the position where the blastocoel typically forms in other model organisms. IF has long been speculated to play a role in tissue morphogenesis during embryogenesis, but direct evidence supporting such function is still sparse. Here we show that the relocalization of IF to the interface between the YC and DC/epiblast is critical for axial mesendoderm (ME) cell protrusion formation and migration along this interface, a key process in embryonic axis formation. We further demonstrate that axial ME cell migration and IF relocalization engage in a positive feedback loop, where axial ME migration triggers IF accumulation ahead of the advancing axial ME tissue by mechanically compressing the overlying epiblast cell layer. Upon compression, locally induced flow relocalizes the IF through the porous epiblast tissue resulting in an IF accumulation ahead of the leading axial ME. This IF accumulation, in turn, promotes cell protrusion formation and migration of the leading axial ME cells, thereby facilitating axial ME extension. Our findings reveal a central role of dynamic IF relocalization in orchestrating germ layer morphogenesis during gastrulation.}, author = {Huljev, Karla}, issn = {2663-337X}, pages = {101}, publisher = {Institute of Science and Technology Austria}, title = {{Coordinated spatiotemporal reorganization of interstitial fluid is required for axial mesendoderm migration in zebrafish gastrulation}}, doi = {10.15479/at:ista:9397}, year = {2021}, } @unpublished{10066, abstract = {The potential of Si and SiGe-based devices for the scaling of quantum circuits is tainted by device variability. Each device needs to be tuned to operation conditions. We give a key step towards tackling this variability with an algorithm that, without modification, is capable of tuning a 4-gate Si FinFET, a 5-gate GeSi nanowire and a 7-gate SiGe heterostructure double quantum dot device from scratch. We achieve tuning times of 30, 10, and 92 minutes, respectively. The algorithm also provides insight into the parameter space landscape for each of these devices. These results show that overarching solutions for the tuning of quantum devices are enabled by machine learning.}, author = {Severin, B. and Lennon, D. T. and Camenzind, L. C. and Vigneau, F. and Fedele, F. and Jirovec, Daniel and Ballabio, A. and Chrastina, D. and Isella, G. and Kruijf, M. de and Carballido, M. J. and Svab, S. and Kuhlmann, A. V. and Braakman, F. R. and Geyer, S. and Froning, F. N. M. and Moon, H. and Osborne, M. A. and Sejdinovic, D. and Katsaros, Georgios and Zumbühl, D. M. and Briggs, G. A. D. and Ares, N.}, booktitle = {arXiv}, title = {{Cross-architecture tuning of silicon and SiGe-based quantum devices using machine learning}}, doi = {10.48550/arXiv.2107.12975}, year = {2021}, } @article{9437, abstract = {The synaptic connection from medial habenula (MHb) to interpeduncular nucleus (IPN) is critical for emotion-related behaviors and uniquely expresses R-type Ca2+ channels (Cav2.3) and auxiliary GABAB receptor (GBR) subunits, the K+-channel tetramerization domain-containing proteins (KCTDs). Activation of GBRs facilitates or inhibits transmitter release from MHb terminals depending on the IPN subnucleus, but the role of KCTDs is unknown. We therefore examined the localization and function of Cav2.3, GBRs, and KCTDs in this pathway in mice. We show in heterologous cells that KCTD8 and KCTD12b directly bind to Cav2.3 and that KCTD8 potentiates Cav2.3 currents in the absence of GBRs. In the rostral IPN, KCTD8, KCTD12b, and Cav2.3 co-localize at the presynaptic active zone. Genetic deletion indicated a bidirectional modulation of Cav2.3-mediated release by these KCTDs with a compensatory increase of KCTD8 in the active zone in KCTD12b-deficient mice. The interaction of Cav2.3 with KCTDs therefore scales synaptic strength independent of GBR activation.}, author = {Bhandari, Pradeep and Vandael, David H and Fernández-Fernández, Diego and Fritzius, Thorsten and Kleindienst, David and Önal, Hüseyin C and Montanaro-Punzengruber, Jacqueline-Claire and Gassmann, Martin and Jonas, Peter M and Kulik, Akos and Bettler, Bernhard and Shigemoto, Ryuichi and Koppensteiner, Peter}, issn = {2050-084X}, journal = {eLife}, publisher = {eLife Sciences Publications}, title = {{GABAB receptor auxiliary subunits modulate Cav2.3-mediated release from medial habenula terminals}}, doi = {10.7554/ELIFE.68274}, volume = {10}, year = {2021}, } @phdthesis{9562, abstract = {Left-right asymmetries can be considered a fundamental organizational principle of the vertebrate central nervous system. The hippocampal CA3-CA1 pyramidal cell synaptic connection shows an input-side dependent asymmetry where the hemispheric location of the presynaptic CA3 neuron determines the synaptic properties. Left-input synapses terminating on apical dendrites in stratum radiatum have a higher density of NMDA receptor subunit GluN2B, a lower density of AMPA receptor subunit GluA1 and smaller areas with less often perforated PSDs. On the other hand, left-input synapses terminating on basal dendrites in stratum oriens have lower GluN2B densities than right-input ones. Apical and basal synapses further employ different signaling pathways involved in LTP. SDS-digested freeze-fracture replica labeling can visualize synaptic membrane proteins with high sensitivity and resolution, and has been used to reveal the asymmetry at the electron microscopic level. However, it requires time-consuming manual demarcation of the synaptic surface for quantitative measurements. To facilitate the analysis of replica labeling, I first developed a software named Darea, which utilizes deep-learning to automatize this demarcation. With Darea I characterized the synaptic distribution of NMDA and AMPA receptors as well as the voltage-gated Ca2+ channels in CA1 stratum radiatum and oriens. Second, I explored the role of GluN2B and its carboxy-terminus in the establishment of input-side dependent hippocampal asymmetry. In conditional knock-out mice lacking GluN2B expression in CA1 and GluN2B-2A swap mice, where GluN2B carboxy-terminus was exchanged to that of GluN2A, no significant asymmetries of GluN2B, GluA1 and PSD area were detected. We further discovered a previously unknown functional asymmetry of GluN2A, which was also lost in the swap mouse. These results demonstrate that GluN2B carboxy-terminus plays a critical role in normal formation of input-side dependent asymmetry.}, author = {Kleindienst, David}, issn = {2663-337X}, pages = {124}, publisher = {Institute of Science and Technology Austria}, title = {{2B or not 2B: Hippocampal asymmetries mediated by NMDA receptor subunit GluN2B C-terminus and high-throughput image analysis by Deep-Learning}}, doi = {10.15479/at:ista:9562}, year = {2021}, } @phdthesis{8934, abstract = {In this thesis, we consider several of the most classical and fundamental problems in static analysis and formal verification, including invariant generation, reachability analysis, termination analysis of probabilistic programs, data-flow analysis, quantitative analysis of Markov chains and Markov decision processes, and the problem of data packing in cache management. We use techniques from parameterized complexity theory, polyhedral geometry, and real algebraic geometry to significantly improve the state-of-the-art, in terms of both scalability and completeness guarantees, for the mentioned problems. In some cases, our results are the first theoretical improvements for the respective problems in two or three decades.}, author = {Goharshady, Amir Kafshdar}, issn = {2663-337X}, pages = {278}, publisher = {Institute of Science and Technology Austria}, title = {{Parameterized and algebro-geometric advances in static program analysis}}, doi = {10.15479/AT:ISTA:8934}, year = {2021}, } @phdthesis{10307, abstract = {Bacteria-host interactions represent a continuous trade-off between benefit and risk. Thus, the host immune response is faced with a non-trivial problem – accommodate beneficial commensals and remove harmful pathogens. This is especially difficult as molecular patterns, such as lipopolysaccharide or specific surface organelles such as pili, are conserved in both, commensal and pathogenic bacteria. Type 1 pili, tightly regulated by phase variation, are considered an important virulence factor of pathogenic bacteria as they facilitate invasion into host cells. While invasion represents a de facto passive mechanism for pathogens to escape the host immune response, we demonstrate a fundamental role of type 1 pili as active modulators of the innate and adaptive immune response.}, author = {Tomasek, Kathrin}, issn = {2663-337X}, pages = {73}, publisher = {Institute of Science and Technology Austria}, title = {{Pathogenic Escherichia coli hijack the host immune response}}, doi = {10.15479/at:ista:10307}, year = {2021}, } @unpublished{10316, abstract = {A key attribute of persistent or recurring bacterial infections is the ability of the pathogen to evade the host’s immune response. Many Enterobacteriaceae express type 1 pili, a pre-adapted virulence trait, to invade host epithelial cells and establish persistent infections. However, the molecular mechanisms and strategies by which bacteria actively circumvent the immune response of the host remain poorly understood. Here, we identified CD14, the major co-receptor for lipopolysaccharide detection, on dendritic cells as a previously undescribed binding partner of FimH, the protein located at the tip of the type 1 pilus of Escherichia coli. The FimH amino acids involved in CD14 binding are highly conserved across pathogenic and non-pathogenic strains. Binding of pathogenic bacteria to CD14 lead to reduced dendritic cell migration and blunted expression of co-stimulatory molecules, both rate-limiting factors of T cell activation. While defining an active molecular mechanism of immune evasion by pathogens, the interaction between FimH and CD14 represents a potential target to interfere with persistent and recurrent infections, such as urinary tract infections or Crohn’s disease.}, author = {Tomasek, Kathrin and Leithner, Alexander F and Glatzová, Ivana and Lukesch, Michael S. and Guet, Calin C and Sixt, Michael K}, booktitle = {bioRxiv}, publisher = {Cold Spring Harbor Laboratory}, title = {{Type 1 piliated uropathogenic Escherichia coli hijack the host immune response by binding to CD14}}, doi = {10.1101/2021.10.18.464770}, year = {2021}, } @article{9010, abstract = {Availability of the essential macronutrient nitrogen in soil plays a critical role in plant growth, development, and impacts agricultural productivity. Plants have evolved different strategies for sensing and responding to heterogeneous nitrogen distribution. Modulation of root system architecture, including primary root growth and branching, is among the most essential plant adaptions to ensure adequate nitrogen acquisition. However, the immediate molecular pathways coordinating the adjustment of root growth in response to distinct nitrogen sources, such as nitrate or ammonium, are poorly understood. Here, we show that growth as manifested by cell division and elongation is synchronized by coordinated auxin flux between two adjacent outer tissue layers of the root. This coordination is achieved by nitrate‐dependent dephosphorylation of the PIN2 auxin efflux carrier at a previously uncharacterized phosphorylation site, leading to subsequent PIN2 lateralization and thereby regulating auxin flow between adjacent tissues. A dynamic computer model based on our experimental data successfully recapitulates experimental observations. Our study provides mechanistic insights broadening our understanding of root growth mechanisms in dynamic environments.}, author = {Ötvös, Krisztina and Marconi, Marco and Vega, Andrea and O’Brien, Jose and Johnson, Alexander J and Abualia, Rashed and Antonielli, Livio and Montesinos López, Juan C and Zhang, Yuzhou and Tan, Shutang and Cuesta, Candela and Artner, Christina and Bouguyon, Eleonore and Gojon, Alain and Friml, Jiří and Gutiérrez, Rodrigo A. and Wabnik, Krzysztof T and Benková, Eva}, issn = {14602075}, journal = {EMBO Journal}, number = {3}, publisher = {Embo Press}, title = {{Modulation of plant root growth by nitrogen source-defined regulation of polar auxin transport}}, doi = {10.15252/embj.2020106862}, volume = {40}, year = {2021}, } @article{9913, abstract = {Nitrate commands genome-wide gene expression changes that impact metabolism, physiology, plant growth, and development. In an effort to identify new components involved in nitrate responses in plants, we analyze the Arabidopsis thaliana root phosphoproteome in response to nitrate treatments via liquid chromatography coupled to tandem mass spectrometry. 176 phosphoproteins show significant changes at 5 or 20 min after nitrate treatments. Proteins identified by 5 min include signaling components such as kinases or transcription factors. In contrast, by 20 min, proteins identified were associated with transporter activity or hormone metabolism functions, among others. The phosphorylation profile of NITRATE TRANSPORTER 1.1 (NRT1.1) mutant plants was significantly altered as compared to wild-type plants, confirming its key role in nitrate signaling pathways that involves phosphorylation changes. Integrative bioinformatics analysis highlights auxin transport as an important mechanism modulated by nitrate signaling at the post-translational level. We validated a new phosphorylation site in PIN2 and provide evidence that it functions in primary and lateral root growth responses to nitrate.}, author = {Vega, Andrea and Fredes, Isabel and O’Brien, José and Shen, Zhouxin and Ötvös, Krisztina and Abualia, Rashed and Benková, Eva and Briggs, Steven P. and Gutiérrez, Rodrigo A.}, issn = {1469-3178}, journal = {EMBO Reports}, number = {9}, publisher = {Wiley}, title = {{Nitrate triggered phosphoproteome changes and a PIN2 phosphosite modulating root system architecture}}, doi = {10.15252/embr.202051813}, volume = {22}, year = {2021}, } @phdthesis{10303, abstract = {Nitrogen is an essential macronutrient determining plant growth, development and affecting agricultural productivity. Root, as a hub that perceives and integrates local and systemic signals on the plant’s external and endogenous nitrogen resources, communicates with other plant organs to consolidate their physiology and development in accordance with actual nitrogen balance. Over the last years, numerous studies demonstrated that these comprehensive developmental adaptations rely on the interaction between pathways controlling nitrogen homeostasis and hormonal networks acting globally in the plant body. However, molecular insights into how the information about the nitrogen status is translated through hormonal pathways into specific developmental output are lacking. In my work, I addressed so far poorly understood mechanisms underlying root-to-shoot communication that lead to a rapid re-adjustment of shoot growth and development after nitrate provision. Applying a combination of molecular, cell, and developmental biology approaches, genetics and grafting experiments as well as hormonal analytics, I identified and characterized an unknown molecular framework orchestrating shoot development with a root nitrate sensory system. }, author = {Abualia, Rashed}, issn = {2663-337X}, pages = {139}, publisher = {Institute of Science and Technology Austria}, title = {{Role of hormones in nitrate regulated growth}}, doi = {10.15479/at:ista:10303}, year = {2021}, } @phdthesis{9962, abstract = {The brain is one of the largest and most complex organs and it is composed of billions of neurons that communicate together enabling e.g. consciousness. The cerebral cortex is the largest site of neural integration in the central nervous system. Concerted radial migration of newly born cortical projection neurons, from their birthplace to their final position, is a key step in the assembly of the cerebral cortex. The cellular and molecular mechanisms regulating radial neuronal migration in vivo are however still unclear. Recent evidence suggests that distinct signaling cues act cell-autonomously but differentially at certain steps during the overall migration process. Moreover, functional analysis of genetic mosaics (mutant neurons present in wild-type/heterozygote environment) using the MADM (Mosaic Analysis with Double Markers) analyses in comparison to global knockout also indicate a significant degree of non-cell-autonomous and/or community effects in the control of cortical neuron migration. The interactions of cell-intrinsic (cell-autonomous) and cell-extrinsic (non-cell-autonomous) components are largely unknown. In part of this thesis work we established a MADM-based experimental strategy for the quantitative analysis of cell-autonomous gene function versus non-cell-autonomous and/or community effects. The direct comparison of mutant neurons from the genetic mosaic (cell-autonomous) to mutant neurons in the conditional and/or global knockout (cell-autonomous + non-cell-autonomous) allows to quantitatively analyze non-cell-autonomous effects. Such analysis enable the high-resolution analysis of projection neuron migration dynamics in distinct environments with concomitant isolation of genomic and proteomic profiles. Using these experimental paradigms and in combination with computational modeling we show and characterize the nature of non-cell-autonomous effects to coordinate radial neuron migration. Furthermore, this thesis discusses recent developments in neurodevelopment with focus on neuronal polarization and non-cell-autonomous mechanisms in neuronal migration.}, author = {Hansen, Andi H}, issn = {2663-337X}, keywords = {Neuronal migration, Non-cell-autonomous, Cell-autonomous, Neurodevelopmental disease}, pages = {182}, publisher = {Institute of Science and Technology Austria}, title = {{Cell-autonomous gene function and non-cell-autonomous effects in radial projection neuron migration}}, doi = {10.15479/at:ista:9962}, year = {2021}, } @article{9428, abstract = {Thermalization is the inevitable fate of many complex quantum systems, whose dynamics allow them to fully explore the vast configuration space regardless of the initial state---the behaviour known as quantum ergodicity. In a quest for experimental realizations of coherent long-time dynamics, efforts have focused on ergodicity-breaking mechanisms, such as integrability and localization. The recent discovery of persistent revivals in quantum simulators based on Rydberg atoms have pointed to the existence of a new type of behaviour where the system rapidly relaxes for most initial conditions, while certain initial states give rise to non-ergodic dynamics. This collective effect has been named ”quantum many-body scarring’by analogy with a related form of weak ergodicity breaking that occurs for a single particle inside a stadium billiard potential. In this Review, we provide a pedagogical introduction to quantum many-body scars and highlight the emerging connections with the semiclassical quantization of many-body systems. We discuss the relation between scars and more general routes towards weak violations of ergodicity due to embedded algebras and non-thermal eigenstates, and highlight possible applications of scars in quantum technology.}, author = {Serbyn, Maksym and Abanin, Dmitry A. and Papić, Zlatko}, issn = {1745-2481}, journal = {Nature Physics}, number = {6}, pages = {675–685}, publisher = {Nature Research}, title = {{Quantum many-body scars and weak breaking of ergodicity}}, doi = {10.1038/s41567-021-01230-2}, volume = {17}, year = {2021}, } @article{8931, abstract = {Auxin is a major plant growth regulator, but current models on auxin perception and signaling cannot explain the whole plethora of auxin effects, in particular those associated with rapid responses. A possible candidate for a component of additional auxin perception mechanisms is the AUXIN BINDING PROTEIN 1 (ABP1), whose function in planta remains unclear. Here we combined expression analysis with gain- and loss-of-function approaches to analyze the role of ABP1 in plant development. ABP1 shows a broad expression largely overlapping with, but not regulated by, transcriptional auxin response activity. Furthermore, ABP1 activity is not essential for the transcriptional auxin signaling. Genetic in planta analysis revealed that abp1 loss-of-function mutants show largely normal development with minor defects in bolting. On the other hand, ABP1 gain-of-function alleles show a broad range of growth and developmental defects, including root and hypocotyl growth and bending, lateral root and leaf development, bolting, as well as response to heat stress. At the cellular level, ABP1 gain-of-function leads to impaired auxin effect on PIN polar distribution and affects BFA-sensitive PIN intracellular aggregation. The gain-of-function analysis suggests a broad, but still mechanistically unclear involvement of ABP1 in plant development, possibly masked in abp1 loss-of-function mutants by a functional redundancy.}, author = {Gelová, Zuzana and Gallei, Michelle C and Pernisová, Markéta and Brunoud, Géraldine and Zhang, Xixi and Glanc, Matous and Li, Lanxin and Michalko, Jaroslav and Pavlovicova, Zlata and Verstraeten, Inge and Han, Huibin and Hajny, Jakub and Hauschild, Robert and Čovanová, Milada and Zwiewka, Marta and Hörmayer, Lukas and Fendrych, Matyas and Xu, Tongda and Vernoux, Teva and Friml, Jiří}, issn = {0168-9452}, journal = {Plant Science}, keywords = {Agronomy and Crop Science, Plant Science, Genetics, General Medicine}, publisher = {Elsevier}, title = {{Developmental roles of auxin binding protein 1 in Arabidopsis thaliana}}, doi = {10.1016/j.plantsci.2020.110750}, volume = {303}, year = {2021}, } @article{9287, abstract = {The phytohormone auxin and its directional transport through tissues are intensively studied. However, a mechanistic understanding of auxin-mediated feedback on endocytosis and polar distribution of PIN auxin transporters remains limited due to contradictory observations and interpretations. Here, we used state-of-the-art methods to reexamine the auxin effects on PIN endocytic trafficking. We used high auxin concentrations or longer treatments versus lower concentrations and shorter treatments of natural (IAA) and synthetic (NAA) auxins to distinguish between specific and nonspecific effects. Longer treatments of both auxins interfere with Brefeldin A-mediated intracellular PIN2 accumulation and also with general aggregation of endomembrane compartments. NAA treatment decreased the internalization of the endocytic tracer dye, FM4-64; however, NAA treatment also affected the number, distribution, and compartment identity of the early endosome/trans-Golgi network (EE/TGN), rendering the FM4-64 endocytic assays at high NAA concentrations unreliable. To circumvent these nonspecific effects of NAA and IAA affecting the endomembrane system, we opted for alternative approaches visualizing the endocytic events directly at the plasma membrane (PM). Using Total Internal Reflection Fluorescence (TIRF) microscopy, we saw no significant effects of IAA or NAA treatments on the incidence and dynamics of clathrin foci, implying that these treatments do not affect the overall endocytosis rate. However, both NAA and IAA at low concentrations rapidly and specifically promoted endocytosis of photo-converted PIN2 from the PM. These analyses identify a specific effect of NAA and IAA on PIN2 endocytosis, thus contributing to its polarity maintenance and furthermore illustrate that high auxin levels have nonspecific effects on trafficking and endomembrane compartments. }, author = {Narasimhan, Madhumitha and Gallei, Michelle C and Tan, Shutang and Johnson, Alexander J and Verstraeten, Inge and Li, Lanxin and Rodriguez Solovey, Lesia and Han, Huibin and Himschoot, E and Wang, R and Vanneste, S and Sánchez-Simarro, J and Aniento, F and Adamowski, Maciek and Friml, Jiří}, issn = {1532-2548}, journal = {Plant Physiology}, number = {2}, pages = {1122–1142}, publisher = {Oxford University Press}, title = {{Systematic analysis of specific and nonspecific auxin effects on endocytosis and trafficking}}, doi = {10.1093/plphys/kiab134}, volume = {186}, year = {2021}, } @phdthesis{10083, abstract = {Plant motions occur across a wide spectrum of timescales, ranging from seed dispersal through bursting (milliseconds) and stomatal opening (minutes) to long-term adaptation of gross architecture. Relatively fast motions include water-driven growth as exemplified by root cell expansion under abiotic/biotic stresses or during gravitropism. A showcase is a root growth inhibition in 30 seconds triggered by the phytohormone auxin. However, the cellular and molecular mechanisms are still largely unknown. This thesis covers the studies about this topic as follows. By taking advantage of microfluidics combined with live imaging, pharmaceutical tools, and transgenic lines, we examined the kinetics of and causal relationship among various auxininduced rapid cellular changes in root growth, apoplastic pH, cytosolic Ca2+, cortical microtubule (CMT) orientation, and vacuolar morphology. We revealed that CMT reorientation and vacuolar constriction are the consequence of growth itself instead of responding directly to auxin. In contrast, auxin induces apoplast alkalinization to rapidly inhibit root growth in 30 seconds. This auxin-triggered apoplast alkalinization results from rapid H+- influx that is contributed by Ca2+ inward channel CYCLIC NUCLEOTIDE-GATED CHANNEL 14 (CNGC14)-dependent Ca2+ signaling. To dissect which auxin signaling mediates the rapid apoplast alkalinization, we combined microfluidics and genetic engineering to verify that TIR1/AFB receptors conduct a non-transcriptional regulation on Ca2+ and H+ -influx. This non-canonical pathway is mostly mediated by the cytosolic portion of TIR1/AFB. On the other hand, we uncovered, using biochemical and phospho-proteomic analysis, that auxin cell surface signaling component TRANSMEMBRANE KINASE 1 (TMK1) plays a negative role during auxin-trigger apoplast alkalinization and root growth inhibition through directly activating PM H+ -ATPases. Therefore, we discovered that PM H+ -ATPases counteract instead of mediate the auxintriggered rapid H+ -influx, and that TIR1/AFB and TMK1 regulate root growth antagonistically. This opposite effect of TIR1/AFB and TMK1 is consistent during auxin-induced hypocotyl elongation, leading us to explore the relation of two signaling pathways. Assisted with biochemistry and fluorescent imaging, we verified for the first time that TIR1/AFB and TMK1 can interact with each other. The ability of TIR1/AFB binding to membrane lipid provides a basis for the interaction of plasma membrane- and cytosol-localized proteins. Besides, transgenic analysis combined with genetic engineering and biochemistry showed that vi they do function in the same pathway. Particularly, auxin-induced TMK1 increase is TIR1/AFB dependent, suggesting TIR1/AFB regulation on TMK1. Conversely, TMK1 also regulates TIR1/AFB protein levels and thus auxin canonical signaling. To follow the study of rapid growth regulation, we analyzed another rapid growth regulator, signaling peptide RALF1. We showed that RALF1 also triggers a rapid and reversible growth inhibition caused by H + influx, highly resembling but not dependent on auxin. Besides, RALF1 promotes auxin biosynthesis by increasing expression of auxin biosynthesis enzyme YUCCAs and thus induces auxin signaling in ca. 1 hour, contributing to the sustained RALF1-triggered growth inhibition. These studies collectively contribute to understanding rapid regulation on plant cell growth, novel auxin signaling pathway as well as auxin-peptide crosstalk. }, author = {Li, Lanxin}, issn = {2663-337X}, publisher = {Institute of Science and Technology Austria}, title = {{Rapid cell growth regulation in Arabidopsis}}, doi = {10.15479/at:ista:10083}, year = {2021}, } @article{10015, abstract = {Auxin plays a dual role in growth regulation and, depending on the tissue and concentration of the hormone, it can either promote or inhibit division and expansion processes in plants. Recent studies have revealed that, beyond transcriptional reprogramming, alternative auxincontrolled mechanisms regulate root growth. Here, we explored the impact of different concentrations of the synthetic auxin NAA that establish growth-promoting and -repressing conditions on the root tip proteome and phosphoproteome, generating a unique resource. From the phosphoproteome data, we pinpointed (novel) growth regulators, such as the RALF34-THE1 module. Our results, together with previously published studies, suggest that auxin, H+-ATPases, cell wall modifications and cell wall sensing receptor-like kinases are tightly embedded in a pathway regulating cell elongation. Furthermore, our study assigned a novel role to MKK2 as a regulator of primary root growth and a (potential) regulator of auxin biosynthesis and signalling, and suggests the importance of the MKK2 Thr31 phosphorylation site for growth regulation in the Arabidopsis root tip.}, author = {Nikonorova, N and Murphy, E and Fonseca de Lima, CF and Zhu, S and van de Cotte, B and Vu, LD and Balcerowicz, D and Li, Lanxin and Kong, X and De Rop, G and Beeckman, T and Friml, Jiří and Vissenberg, K and Morris, PC and Ding, Z and De Smet, I}, issn = {2073-4409}, journal = {Cells}, keywords = {primary root, (phospho)proteomics, auxin, (receptor) kinase}, publisher = {MDPI}, title = {{The Arabidopsis root tip (phospho)proteomes at growth-promoting versus growth-repressing conditions reveal novel root growth regulators}}, doi = {10.3390/cells10071665}, volume = {10}, year = {2021}, } @unpublished{10095, abstract = {Growth regulation tailors plant development to its environment. A showcase is response to gravity, where shoots bend up and roots down1. This paradox is based on opposite effects of the phytohormone auxin, which promotes cell expansion in shoots, while inhibiting it in roots via a yet unknown cellular mechanism2. Here, by combining microfluidics, live imaging, genetic engineering and phospho-proteomics in Arabidopsis thaliana, we advance our understanding how auxin inhibits root growth. We show that auxin activates two distinct, antagonistically acting signalling pathways that converge on the rapid regulation of the apoplastic pH, a causative growth determinant. Cell surface-based TRANSMEMBRANE KINASE1 (TMK1) interacts with and mediates phosphorylation and activation of plasma membrane H+-ATPases for apoplast acidification, while intracellular canonical auxin signalling promotes net cellular H+-influx, causing apoplast alkalinisation. The simultaneous activation of these two counteracting mechanisms poises the root for a rapid, fine-tuned growth modulation while navigating complex soil environment.}, author = {Li, Lanxin and Verstraeten, Inge and Roosjen, Mark and Takahashi, Koji and Rodriguez Solovey, Lesia and Merrin, Jack and Chen, Jian and Shabala, Lana and Smet, Wouter and Ren, Hong and Vanneste, Steffen and Shabala, Sergey and De Rybel, Bert and Weijers, Dolf and Kinoshita, Toshinori and Gray, William M. and Friml, Jiří}, booktitle = {Research Square}, issn = {2693-5015}, title = {{Cell surface and intracellular auxin signalling for H+-fluxes in root growth}}, doi = {10.21203/rs.3.rs-266395/v3}, year = {2021}, } @phdthesis{10293, abstract = {Indirect reciprocity in evolutionary game theory is a prominent mechanism for explaining the evolution of cooperation among unrelated individuals. In contrast to direct reciprocity, which is based on individuals meeting repeatedly, and conditionally cooperating by using their own experiences, indirect reciprocity is based on individuals’ reputations. If a player helps another, this increases the helper’s public standing, benefitting them in the future. This lets cooperation in the population emerge without individuals having to meet more than once. While the two modes of reciprocity are intertwined, they are difficult to compare. Thus, they are usually studied in isolation. Direct reciprocity can maintain cooperation with simple strategies, and is robust against noise even when players do not remember more than their partner’s last action. Meanwhile, indirect reciprocity requires its successful strategies, or social norms, to be more complex. Exhaustive search previously identified eight such norms, called the “leading eight”, which excel at maintaining cooperation. However, as the first result of this thesis, we show that the leading eight break down once we remove the fundamental assumption that information is synchronized and public, such that everyone agrees on reputations. Once we consider a more realistic scenario of imperfect information, where reputations are private, and individuals occasionally misinterpret or miss observations, the leading eight do not promote cooperation anymore. Instead, minor initial disagreements can proliferate, fragmenting populations into subgroups. In a next step, we consider ways to mitigate this issue. We first explore whether introducing “generosity” can stabilize cooperation when players use the leading eight strategies in noisy environments. This approach of modifying strategies to include probabilistic elements for coping with errors is known to work well in direct reciprocity. However, as we show here, it fails for the more complex norms of indirect reciprocity. Imperfect information still prevents cooperation from evolving. On the other hand, we succeeded to show in this thesis that modifying the leading eight to use “quantitative assessment”, i.e. tracking reputation scores on a scale beyond good and bad, and making overall judgments of others based on a threshold, is highly successful, even when noise increases in the environment. Cooperation can flourish when reputations are more nuanced, and players have a broader understanding what it means to be “good.” Finally, we present a single theoretical framework that unites the two modes of reciprocity despite their differences. Within this framework, we identify a novel simple and successful strategy for indirect reciprocity, which can cope with noisy environments and has an analogue in direct reciprocity. We can also analyze decision making when different sources of information are available. Our results help highlight that for sustaining cooperation, already the most simple rules of reciprocity can be sufficient.}, author = {Schmid, Laura}, issn = {2663-337X}, pages = {171}, publisher = {Institute of Science and Technology Austria}, title = {{Evolution of cooperation via (in)direct reciprocity under imperfect information}}, doi = {10.15479/at:ista:10293}, year = {2021}, } @article{9997, abstract = {Indirect reciprocity is a mechanism for the evolution of cooperation based on social norms. This mechanism requires that individuals in a population observe and judge each other’s behaviors. Individuals with a good reputation are more likely to receive help from others. Previous work suggests that indirect reciprocity is only effective when all relevant information is reliable and publicly available. Otherwise, individuals may disagree on how to assess others, even if they all apply the same social norm. Such disagreements can lead to a breakdown of cooperation. Here we explore whether the predominantly studied ‘leading eight’ social norms of indirect reciprocity can be made more robust by equipping them with an element of generosity. To this end, we distinguish between two kinds of generosity. According to assessment generosity, individuals occasionally assign a good reputation to group members who would usually be regarded as bad. According to action generosity, individuals occasionally cooperate with group members with whom they would usually defect. Using individual-based simulations, we show that the two kinds of generosity have a very different effect on the resulting reputation dynamics. Assessment generosity tends to add to the overall noise and allows defectors to invade. In contrast, a limited amount of action generosity can be beneficial in a few cases. However, even when action generosity is beneficial, the respective simulations do not result in full cooperation. Our results suggest that while generosity can favor cooperation when individuals use the most simple strategies of reciprocity, it is disadvantageous when individuals use more complex social norms.}, author = {Schmid, Laura and Shati, Pouya and Hilbe, Christian and Chatterjee, Krishnendu}, issn = {2045-2322}, journal = {Scientific Reports}, keywords = {Multidisciplinary}, number = {1}, publisher = {Springer Nature}, title = {{The evolution of indirect reciprocity under action and assessment generosity}}, doi = {10.1038/s41598-021-96932-1}, volume = {11}, year = {2021}, } @article{9402, abstract = {Direct and indirect reciprocity are key mechanisms for the evolution of cooperation. Direct reciprocity means that individuals use their own experience to decide whether to cooperate with another person. Indirect reciprocity means that they also consider the experiences of others. Although these two mechanisms are intertwined, they are typically studied in isolation. Here, we introduce a mathematical framework that allows us to explore both kinds of reciprocity simultaneously. We show that the well-known ‘generous tit-for-tat’ strategy of direct reciprocity has a natural analogue in indirect reciprocity, which we call ‘generous scoring’. Using an equilibrium analysis, we characterize under which conditions either of the two strategies can maintain cooperation. With simulations, we additionally explore which kind of reciprocity evolves when members of a population engage in social learning to adapt to their environment. Our results draw unexpected connections between direct and indirect reciprocity while highlighting important differences regarding their evolvability.}, author = {Schmid, Laura and Chatterjee, Krishnendu and Hilbe, Christian and Nowak, Martin A.}, issn = {2397-3374}, journal = {Nature Human Behaviour}, number = {10}, pages = {1292–1302}, publisher = {Springer Nature}, title = {{A unified framework of direct and indirect reciprocity}}, doi = {10.1038/s41562-021-01114-8}, volume = {5}, year = {2021}, } @article{9817, abstract = {Elastic bending of initially flat slender elements allows the realization and economic fabrication of intriguing curved shapes. In this work, we derive an intuitive but rigorous geometric characterization of the design space of plane elastic rods with variable stiffness. It enables designers to determine which shapes are physically viable with active bending by visual inspection alone. Building on these insights, we propose a method for efficiently designing the geometry of a flat elastic rod that realizes a target equilibrium curve, which only requires solving a linear program. We implement this method in an interactive computational design tool that gives feedback about the feasibility of a design, and computes the geometry of the structural elements necessary to realize it within an instant. The tool also offers an iterative optimization routine that improves the fabricability of a model while modifying it as little as possible. In addition, we use our geometric characterization to derive an algorithm for analyzing and recovering the stability of elastic curves that would otherwise snap out of their unstable equilibrium shapes by buckling. We show the efficacy of our approach by designing and manufacturing several physical models that are assembled from flat elements.}, author = {Hafner, Christian and Bickel, Bernd}, issn = {1557-7368}, journal = {ACM Transactions on Graphics}, keywords = {Computing methodologies, shape modeling, modeling and simulation, theory of computation, computational geometry, mathematics of computing, mathematical optimization}, location = {Virtual}, number = {4}, publisher = {Association for Computing Machinery}, title = {{The design space of plane elastic curves}}, doi = {10.1145/3450626.3459800}, volume = {40}, year = {2021}, } @phdthesis{10135, abstract = {Plants maintain the capacity to develop new organs e.g. lateral roots post-embryonically throughout their whole life and thereby flexibly adapt to ever-changing environmental conditions. Plant hormones auxin and cytokinin are the main regulators of the lateral root organogenesis. Additionally to their solo activities, the interaction between auxin and cytokinin plays crucial role in fine-tuning of lateral root development and growth. In particular, cytokinin modulates auxin distribution within the developing lateral root by affecting the endomembrane trafficking of auxin transporter PIN1 and promoting its vacuolar degradation (Marhavý et al., 2011, 2014). This effect is independent of transcription and translation. Therefore, it suggests novel, non-canonical cytokinin activity occuring possibly on the posttranslational level. Impact of cytokinin and other plant hormones on auxin transporters (including PIN1) on the posttranslational level is described in detail in the introduction part of this thesis in a form of a review (Semeradova et al., 2020). To gain insights into the molecular machinery underlying cytokinin effect on the endomembrane trafficking in the plant cell, in particular on the PIN1 degradation, we conducted two large proteomic screens: 1) Identification of cytokinin binding proteins using chemical proteomics. 2) Monitoring of proteomic and phosphoproteomic changes upon cytokinin treatment. In the first screen, we identified DYNAMIN RELATED PROTEIN 2A (DRP2A). We found that DRP2A plays a role in cytokinin regulated processes during the plant growth and that cytokinin treatment promotes destabilization of DRP2A protein. However, the role of DRP2A in the PIN1 degradation remains to be elucidated. In the second screen, we found VACUOLAR PROTEIN SORTING 9A (VPS9A). VPS9a plays crucial role in plant’s response to cytokin and in cytokinin mediated PIN1 degradation. Altogether, we identified proteins, which bind to cytokinin and proteins that in response to cytokinin exhibit significantly changed abundance or phosphorylation pattern. By combining information from these two screens, we can pave our way towards understanding of noncanonical cytokinin effects.}, author = {Semerádová, Hana}, isbn = {978-3-99078-014-5}, issn = {2663-337X}, publisher = {Institute of Science and Technology Austria}, title = {{Molecular mechanisms of the cytokinin-regulated endomembrane trafficking to coordinate plant organogenesis}}, doi = {10.15479/at:ista:10135}, year = {2021}, } @phdthesis{9728, abstract = {Most real-world flows are multiphase, yet we know little about them compared to their single-phase counterparts. Multiphase flows are more difficult to investigate as their dynamics occur in large parameter space and involve complex phenomena such as preferential concentration, turbulence modulation, non-Newtonian rheology, etc. Over the last few decades, experiments in particle-laden flows have taken a back seat in favour of ever-improving computational resources. However, computers are still not powerful enough to simulate a real-world fluid with millions of finite-size particles. Experiments are essential not only because they offer a reliable way to investigate real-world multiphase flows but also because they serve to validate numerical studies and steer the research in a relevant direction. In this work, we have experimentally investigated particle-laden flows in pipes, and in particular, examined the effect of particles on the laminar-turbulent transition and the drag scaling in turbulent flows. For particle-laden pipe flows, an earlier study [Matas et al., 2003] reported how the sub-critical (i.e., hysteretic) transition that occurs via localised turbulent structures called puffs is affected by the addition of particles. In this study, in addition to this known transition, we found a super-critical transition to a globally fluctuating state with increasing particle concentration. At the same time, the Newtonian-type transition via puffs is delayed to larger Reynolds numbers. At an even higher concentration, only the globally fluctuating state is found. The dynamics of particle-laden flows are hence determined by two competing instabilities that give rise to three flow regimes: Newtonian-type turbulence at low, a particle-induced globally fluctuating state at high, and a coexistence state at intermediate concentrations. The effect of particles on turbulent drag is ambiguous, with studies reporting drag reduction, no net change, and even drag increase. The ambiguity arises because, in addition to particle concentration, particle shape, size, and density also affect the net drag. Even similar particles might affect the flow dissimilarly in different Reynolds number and concentration ranges. In the present study, we explored a wide range of both Reynolds number and concentration, using spherical as well as cylindrical particles. We found that the spherical particles do not reduce drag while the cylindrical particles are drag-reducing within a specific Reynolds number interval. The interval strongly depends on the particle concentration and the relative size of the pipe and particles. Within this interval, the magnitude of drag reduction reaches a maximum. These drag reduction maxima appear to fall onto a distinct power-law curve irrespective of the pipe diameter and particle concentration, and this curve can be considered as the maximum drag reduction asymptote for a given fibre shape. Such an asymptote is well known for polymeric flows but had not been identified for particle-laden flows prior to this work.}, author = {Agrawal, Nishchal}, issn = {2663-337X}, keywords = {Drag Reduction, Transition to Turbulence, Multiphase Flows, particle Laden Flows, Complex Flows, Experiments, Fluid Dynamics}, pages = {118}, publisher = {Institute of Science and Technology Austria}, title = {{Transition to turbulence and drag reduction in particle-laden pipe flows}}, doi = {10.15479/at:ista:9728}, year = {2021}, } @article{10336, abstract = {Biological membranes can dramatically accelerate the aggregation of normally soluble protein molecules into amyloid fibrils and alter the fibril morphologies, yet the molecular mechanisms through which this accelerated nucleation takes place are not yet understood. Here, we develop a coarse-grained model to systematically explore the effect that the structural properties of the lipid membrane and the nature of protein–membrane interactions have on the nucleation rates of amyloid fibrils. We identify two physically distinct nucleation pathways—protein-rich and lipid-rich—and quantify how the membrane fluidity and protein–membrane affinity control the relative importance of those molecular pathways. We find that the membrane’s susceptibility to reshaping and being incorporated into the fibrillar aggregates is a key determinant of its ability to promote protein aggregation. We then characterize the rates and the free-energy profile associated with this heterogeneous nucleation process, in which the surface itself participates in the aggregate structure. Finally, we compare quantitatively our data to experiments on membrane-catalyzed amyloid aggregation of α-synuclein, a protein implicated in Parkinson’s disease that predominately nucleates on membranes. More generally, our results provide a framework for understanding macromolecular aggregation on lipid membranes in a broad biological and biotechnological context.}, author = {Krausser, Johannes and Knowles, Tuomas P. J. and Šarić, Anđela}, issn = {1091-6490}, journal = {Proceedings of the National Academy of Sciences}, number = {52}, pages = {33090--33098}, publisher = {National Academy of Sciences}, title = {{Physical mechanisms of amyloid nucleation on fluid membranes}}, doi = {10.1073/pnas.2007694117}, volume = {117}, year = {2020}, } @article{10342, abstract = {The blood-brain barrier is made of polarized brain endothelial cells (BECs) phenotypically conditioned by the central nervous system (CNS). Although transport across BECs is of paramount importance for nutrient uptake as well as ridding the brain of waste products, the intracellular sorting mechanisms that regulate successful receptor-mediated transcytosis in BECs remain to be elucidated. Here, we used a synthetic multivalent system with tunable avidity to the low-density lipoprotein receptor–related protein 1 (LRP1) to investigate the mechanisms of transport across BECs. We used a combination of conventional and super-resolution microscopy, both in vivo and in vitro, accompanied with biophysical modeling of transport kinetics and membrane-bound interactions to elucidate the role of membrane-sculpting protein syndapin-2 on fast transport via tubule formation. We show that high-avidity cargo biases the LRP1 toward internalization associated with fast degradation, while mid-avidity augments the formation of syndapin-2 tubular carriers promoting a fast shuttling across.}, author = {Tian, Xiaohe and Leite, Diana M. and Scarpa, Edoardo and Nyberg, Sophie and Fullstone, Gavin and Forth, Joe and Matias, Diana and Apriceno, Azzurra and Poma, Alessandro and Duro-Castano, Aroa and Vuyyuru, Manish and Harker-Kirschneck, Lena and Šarić, Anđela and Zhang, Zhongping and Xiang, Pan and Fang, Bin and Tian, Yupeng and Luo, Lei and Rizzello, Loris and Battaglia, Giuseppe}, issn = {2375-2548}, journal = {Science Advances}, keywords = {multidisciplinary}, number = {48}, publisher = {American Association for the Advancement of Science}, title = {{On the shuttling across the blood-brain barrier via tubule formation: Mechanism and cargo avidity bias}}, doi = {10.1126/sciadv.abc4397}, volume = {6}, year = {2020}, } @article{10344, abstract = {In this study, we investigate the role of the surface patterning of nanostructures for cell membrane reshaping. To accomplish this, we combine an evolutionary algorithm with coarse-grained molecular dynamics simulations and explore the solution space of ligand patterns on a nanoparticle that promote efficient and reliable cell uptake. Surprisingly, we find that in the regime of low ligand number the best-performing structures are characterized by ligands arranged into long one-dimensional chains that pattern the surface of the particle. We show that these chains of ligands provide particles with high rotational freedom and they lower the free energy barrier for membrane crossing. Our approach reveals a set of nonintuitive design rules that can be used to inform artificial nanoparticle construction and the search for inhibitors of viral entry.}, author = {Forster, Joel C. and Krausser, Johannes and Vuyyuru, Manish R. and Baum, Buzz and Šarić, Anđela}, issn = {1079-7114}, journal = {Physical Review Letters}, number = {22}, publisher = {American Physical Society}, title = {{Exploring the design rules for efficient membrane-reshaping nanostructures}}, doi = {10.1103/physrevlett.125.228101}, volume = {125}, year = {2020}, } @article{10341, abstract = {Tracing the motion of macromolecules, viruses, and nanoparticles adsorbed onto cell membranes is currently the most direct way of probing the complex dynamic interactions behind vital biological processes, including cell signalling, trafficking, and viral infection. The resulting trajectories are usually consistent with some type of anomalous diffusion, but the molecular origins behind the observed anomalous behaviour are usually not obvious. Here we use coarse-grained molecular dynamics simulations to help identify the physical mechanisms that can give rise to experimentally observed trajectories of nanoscopic objects moving on biological membranes. We find that diffusion on membranes of high fluidities typically results in normal diffusion of the adsorbed nanoparticle, irrespective of the concentration of receptors, receptor clustering, or multivalent interactions between the particle and membrane receptors. Gel-like membranes on the other hand result in anomalous diffusion of the particle, which becomes more pronounced at higher receptor concentrations. This anomalous diffusion is characterised by local particle trapping in the regions of high receptor concentrations and fast hopping between such regions. The normal diffusion is recovered in the limit where the gel membrane is saturated with receptors. We conclude that hindered receptor diffusivity can be a common reason behind the observed anomalous diffusion of viruses, vesicles, and nanoparticles adsorbed on cell and model membranes. Our results enable direct comparison with experiments and offer a new route for interpreting motility experiments on cell membranes.}, author = {Debets, V. E. and Janssen, L. M. C. and Šarić, Anđela}, issn = {1744-683X}, journal = {Soft Matter}, keywords = {condensed matter physics, general chemistry}, number = {47}, pages = {10628--10639}, publisher = {Royal Society of Chemistry}, title = {{Characterising the diffusion of biological nanoparticles on fluid and cross-linked membranes}}, doi = {10.1039/d0sm00712a}, volume = {16}, year = {2020}, } @article{10346, abstract = {One of the most robust examples of self-assembly in living organisms is the formation of collagen architectures. Collagen type I molecules are a crucial component of the extracellular matrix, where they self-assemble into fibrils of well-defined axial striped patterns. This striped fibrillar pattern is preserved across the animal kingdom and is important for the determination of cell phenotype, cell adhesion, and tissue regulation and signaling. The understanding of the physical processes that determine such a robust morphology of self-assembled collagen fibrils is currently almost completely missing. Here, we develop a minimal coarse-grained computational model to identify the physical principles of the assembly of collagen-mimetic molecules. We find that screened electrostatic interactions can drive the formation of collagen-like filaments of well-defined striped morphologies. The fibril axial pattern is determined solely by the distribution of charges on the molecule and is robust to the changes in protein concentration, monomer rigidity, and environmental conditions. We show that the striped fibrillar pattern cannot be easily predicted from the interactions between two monomers but is an emergent result of multibody interactions. Our results can help address collagen remodeling in diseases and aging and guide the design of collagen scaffolds for biotechnological applications.}, author = {Hafner, Anne E. and Gyori, Noemi G. and Bench, Ciaran A. and Davis, Luke K. and Šarić, Anđela}, issn = {0006-3495}, journal = {Biophysical Journal}, keywords = {biophysics}, number = {9}, pages = {1791--1799}, publisher = {Cell Press}, title = {{Modeling fibrillogenesis of collagen-mimetic molecules}}, doi = {10.1016/j.bpj.2020.09.013}, volume = {119}, year = {2020}, } @article{10350, abstract = {The misfolding and aberrant aggregation of proteins into fibrillar structures is a key factor in some of the most prevalent human diseases, including diabetes and dementia. Low molecular weight oligomers are thought to be a central factor in the pathology of these diseases, as well as critical intermediates in the fibril formation process, and as such have received much recent attention. Moreover, on-pathway oligomeric intermediates are potential targets for therapeutic strategies aimed at interrupting the fibril formation process. However, a consistent framework for distinguishing on-pathway from off-pathway oligomers has hitherto been lacking and, in particular, no consensus definition of on- and off-pathway oligomers is available. In this paper, we argue that a non-binary definition of oligomers' contribution to fibril-forming pathways may be more informative and we suggest a quantitative framework, in which each oligomeric species is assigned a value between 0 and 1 describing its relative contribution to the formation of fibrils. First, we clarify the distinction between oligomers and fibrils, and then we use the formalism of reaction networks to develop a general definition for on-pathway oligomers, that yields meaningful classifications in the context of amyloid formation. By applying these concepts to Monte Carlo simulations of a minimal aggregating system, and by revisiting several previous studies of amyloid oligomers in light of our new framework, we demonstrate how to perform these classifications in practice. For each oligomeric species we obtain the degree to which it is on-pathway, highlighting the most effective pharmaceutical targets for the inhibition of amyloid fibril formation.}, author = {Dear, Alexander J. and Meisl, Georg and Šarić, Anđela and Michaels, Thomas C. T. and Kjaergaard, Magnus and Linse, Sara and Knowles, Tuomas P. J.}, issn = {2041-6539}, journal = {Chemical Science}, keywords = {general chemistry}, number = {24}, pages = {6236--6247}, publisher = {Royal Society of Chemistry}, title = {{Identification of on- and off-pathway oligomers in amyloid fibril formation}}, doi = {10.1039/c9sc06501f}, volume = {11}, year = {2020}, } @article{10349, abstract = {Sulfolobus acidocaldarius is the closest experimentally tractable archaeal relative of eukaryotes and, despite lacking obvious cyclin-dependent kinase and cyclin homologs, has an ordered eukaryote-like cell cycle with distinct phases of DNA replication and division. Here, in exploring the mechanism of cell division in S. acidocaldarius, we identify a role for the archaeal proteasome in regulating the transition from the end of one cell cycle to the beginning of the next. Further, we identify the archaeal ESCRT-III homolog, CdvB, as a key target of the proteasome and show that its degradation triggers division by allowing constriction of the CdvB1:CdvB2 ESCRT-III division ring. These findings offer a minimal mechanism for ESCRT-III–mediated membrane remodeling and point to a conserved role for the proteasome in eukaryotic and archaeal cell cycle control.}, author = {Tarrason Risa, Gabriel and Hurtig, Fredrik and Bray, Sian and Hafner, Anne E. and Harker-Kirschneck, Lena and Faull, Peter and Davis, Colin and Papatziamou, Dimitra and Mutavchiev, Delyan R. and Fan, Catherine and Meneguello, Leticia and Arashiro Pulschen, Andre and Dey, Gautam and Culley, Siân and Kilkenny, Mairi and Souza, Diorge P. and Pellegrini, Luca and de Bruin, Robertus A. M. and Henriques, Ricardo and Snijders, Ambrosius P. and Šarić, Anđela and Lindås, Ann-Christin and Robinson, Nicholas P. and Baum, Buzz}, issn = {1095-9203}, journal = {Science}, keywords = {multidisciplinary}, number = {6504}, publisher = {American Association for the Advancement of Science}, title = {{The proteasome controls ESCRT-III–mediated cell division in an archaeon}}, doi = {10.1126/science.aaz2532}, volume = {369}, year = {2020}, } @article{10347, abstract = {Understanding the mechanism of action of compounds capable of inhibiting amyloid-fibril formation is critical to the development of potential therapeutics against protein-misfolding diseases. A fundamental challenge for progress is the range of possible target species and the disparate timescales involved, since the aggregating proteins are simultaneously the reactants, products, intermediates, and catalysts of the reaction. It is a complex problem, therefore, to choose the states of the aggregating proteins that should be bound by the compounds to achieve the most potent inhibition. We present here a comprehensive kinetic theory of amyloid-aggregation inhibition that reveals the fundamental thermodynamic and kinetic signatures characterizing effective inhibitors by identifying quantitative relationships between the aggregation and binding rate constants. These results provide general physical laws to guide the design and optimization of inhibitors of amyloid-fibril formation, revealing in particular the important role of on-rates in the binding of the inhibitors.}, author = {Michaels, Thomas C. T. and Šarić, Anđela and Meisl, Georg and Heller, Gabriella T. and Curk, Samo and Arosio, Paolo and Linse, Sara and Dobson, Christopher M. and Vendruscolo, Michele and Knowles, Tuomas P. J.}, issn = {1091-6490}, journal = {Proceedings of the National Academy of Sciences}, keywords = {multidisciplinary}, number = {39}, pages = {24251--24257}, publisher = {National Academy of Sciences}, title = {{Thermodynamic and kinetic design principles for amyloid-aggregation inhibitors}}, doi = {10.1073/pnas.2006684117}, volume = {117}, year = {2020}, } @article{10351, abstract = {Oligomeric species populated during the aggregation of the Aβ42 peptide have been identified as potent cytotoxins linked to Alzheimer’s disease, but the fundamental molecular pathways that control their dynamics have yet to be elucidated. By developing a general approach that combines theory, experiment and simulation, we reveal, in molecular detail, the mechanisms of Aβ42 oligomer dynamics during amyloid fibril formation. Even though all mature amyloid fibrils must originate as oligomers, we found that most Aβ42 oligomers dissociate into their monomeric precursors without forming new fibrils. Only a minority of oligomers converts into fibrillar structures. Moreover, the heterogeneous ensemble of oligomeric species interconverts on timescales comparable to those of aggregation. Our results identify fundamentally new steps that could be targeted by therapeutic interventions designed to combat protein misfolding diseases.}, author = {Michaels, Thomas C. T. and Šarić, Anđela and Curk, Samo and Bernfur, Katja and Arosio, Paolo and Meisl, Georg and Dear, Alexander J. and Cohen, Samuel I. A. and Dobson, Christopher M. and Vendruscolo, Michele and Linse, Sara and Knowles, Tuomas P. J.}, issn = {1755-4349}, journal = {Nature Chemistry}, keywords = {general chemical engineering, general chemistry}, number = {5}, pages = {445--451}, publisher = {Springer Nature}, title = {{Dynamics of oligomer populations formed during the aggregation of Alzheimer’s Aβ42 peptide}}, doi = {10.1038/s41557-020-0452-1}, volume = {12}, year = {2020}, } @article{10348, abstract = {The endosomal sorting complex required for transport-III (ESCRT-III) catalyzes membrane fission from within membrane necks, a process that is essential for many cellular functions, from cell division to lysosome degradation and autophagy. How it breaks membranes, though, remains unknown. Here, we characterize a sequential polymerization of ESCRT-III subunits that, driven by a recruitment cascade and by continuous subunit-turnover powered by the ATPase Vps4, induces membrane deformation and fission. During this process, the exchange of Vps24 for Did2 induces a tilt in the polymer-membrane interface, which triggers transition from flat spiral polymers to helical filament to drive the formation of membrane protrusions, and ends with the formation of a highly constricted Did2-Ist1 co-polymer that we show is competent to promote fission when bound on the inside of membrane necks. Overall, our results suggest a mechanism of stepwise changes in ESCRT-III filament structure and mechanical properties via exchange of the filament subunits to catalyze ESCRT-III activity.}, author = {Pfitzner, Anna-Katharina and Mercier, Vincent and Jiang, Xiuyun and Moser von Filseck, Joachim and Baum, Buzz and Šarić, Anđela and Roux, Aurélien}, issn = {0092-8674}, journal = {Cell}, keywords = {general biochemistry, genetics and molecular biology}, number = {5}, pages = {1140--1155.e18}, publisher = {Elsevier}, title = {{An ESCRT-III polymerization sequence drives membrane deformation and fission}}, doi = {10.1016/j.cell.2020.07.021}, volume = {182}, year = {2020}, } @article{10352, abstract = {In the nuclear pore complex, intrinsically disordered nuclear pore proteins (FG Nups) form a selective barrier for transport into and out of the cell nucleus, in a way that remains poorly understood. The collective FG Nup behavior has long been conceptualized either as a polymer brush, dominated by entropic and excluded-volume (repulsive) interactions, or as a hydrogel, dominated by cohesive (attractive) interactions between FG Nups. Here we compare mesoscale computational simulations with a wide range of experimental data to demonstrate that FG Nups are at the crossover point between these two regimes. Specifically, we find that repulsive and attractive interactions are balanced, resulting in morphologies and dynamics that are close to those of ideal polymer chains. We demonstrate that this property of FG Nups yields sufficient cohesion to seal the transport barrier, and yet maintains fast dynamics at the molecular scale, permitting the rapid polymer rearrangements needed for transport events.}, author = {Davis, Luke K. and Ford, Ian J. and Šarić, Anđela and Hoogenboom, Bart W.}, issn = {2470-0053}, journal = {Physical Review E}, number = {2}, publisher = {American Physical Society}, title = {{Intrinsically disordered nuclear pore proteins show ideal-polymer morphologies and dynamics}}, doi = {10.1103/physreve.101.022420}, volume = {101}, year = {2020}, } @article{10353, abstract = {Experiments have suggested that bacterial mechanosensitive channels separate into 2D clusters, the role of which is unclear. By developing a coarse-grained computer model we find that clustering promotes the channel closure, which is highly dependent on the channel concentration and membrane stress. This behaviour yields a tightly regulated gating system, whereby at high tensions channels gate individually, and at lower tensions the channels spontaneously aggregate and inactivate. We implement this positive feedback into the model for cell volume regulation, and find that the channel clustering protects the cell against excessive loss of cytoplasmic content.}, author = {Paraschiv, Alexandru and Hegde, Smitha and Ganti, Raman and Pilizota, Teuta and Šarić, Anđela}, issn = {1079-7114}, journal = {Physical Review Letters}, keywords = {general physics and astronomy}, number = {4}, publisher = {American Physical Society}, title = {{Dynamic clustering regulates activity of mechanosensitive membrane channels}}, doi = {10.1103/physrevlett.124.048102}, volume = {124}, year = {2020}, } @misc{10557, abstract = {Data storage and retrieval systems, methods, and computer-readable media utilize a cryptographically verifiable data structure that facilitates verification of a transaction in a decentralized peer-to-peer environment using multi-hop backwards and forwards links. Backward links are cryptographic hashes of past records. Forward links are cryptographic signatures of future records that are added retroactively to records once the target block has been appended to the data structure.}, author = {Ford, Bryan and Gasse, Linus and Kokoris Kogias, Eleftherios and Jovanovic, Philipp}, title = {{Cryptographically verifiable data structure having multi-hop forward and backwards links and associated systems and methods}}, year = {2020}, } @article{10618, abstract = {Magnetism typically arises from the joint effect of Fermi statistics and repulsive Coulomb interactions, which favours ground states with non-zero electron spin. As a result, controlling spin magnetism with electric fields—a longstanding technological goal in spintronics and multiferroics1,2—can be achieved only indirectly. Here we experimentally demonstrate direct electric-field control of magnetic states in an orbital Chern insulator3,4,5,6, a magnetic system in which non-trivial band topology favours long-range order of orbital angular momentum but the spins are thought to remain disordered7,8,9,10,11,12,13,14. We use van der Waals heterostructures consisting of a graphene monolayer rotationally faulted with respect to a Bernal-stacked bilayer to realize narrow and topologically non-trivial valley-projected moiré minibands15,16,17. At fillings of one and three electrons per moiré unit cell within these bands, we observe quantized anomalous Hall effects18 with transverse resistance approximately equal to h/2e2 (where h is Planck’s constant and e is the charge on the electron), which is indicative of spontaneous polarization of the system into a single-valley-projected band with a Chern number equal to two. At a filling of three electrons per moiré unit cell, we find that the sign of the quantum anomalous Hall effect can be reversed via field-effect control of the chemical potential; moreover, this transition is hysteretic, which we use to demonstrate non-volatile electric-field-induced reversal of the magnetic state. A theoretical analysis19 indicates that the effect arises from the topological edge states, which drive a change in sign of the magnetization and thus a reversal in the favoured magnetic state. Voltage control of magnetic states can be used to electrically pattern non-volatile magnetic-domain structures hosting chiral edge states, with applications ranging from reconfigurable microwave circuit elements to ultralow-power magnetic memories.}, author = {Polshyn, Hryhoriy and Zhu, J. and Kumar, M. A. and Zhang, Y. and Yang, F. and Tschirhart, C. L. and Serlin, M. and Watanabe, K. and Taniguchi, T. and MacDonald, A. H. and Young, A. F.}, issn = {1476-4687}, journal = {Nature}, keywords = {multidisciplinary}, number = {7836}, pages = {66--70}, publisher = {Springer Nature}, title = {{Electrical switching of magnetic order in an orbital Chern insulator}}, doi = {10.1038/s41586-020-2963-8}, volume = {588}, year = {2020}, } @unpublished{10650, abstract = {The understanding of material systems with strong electron-electron interactions is the central problem in modern condensed matter physics. Despite this, the essential physics of many of these materials is still not understood and we have no overall perspective on their properties. Moreover, we have very little ability to make predictions in this class of systems. In this manuscript we share our personal views of what the major open problems are in correlated electron systems and we discuss some possible routes to make progress in this rich and fascinating field. This manuscript is the result of the vigorous discussions and deliberations that took place at Johns Hopkins University during a three-day workshop January 27, 28, and 29, 2020 that brought together six senior scientists and 46 more junior scientists. Our hope, is that the topics we have presented will provide inspiration for others working in this field and motivation for the idea that significant progress can be made on very hard problems if we focus our collective energies.}, author = {Alexandradinata, A and Armitage, N.P. and Baydin, Andrey and Bi, Wenli and Cao, Yue and Changlani, Hitesh J. and Chertkov, Eli and da Silva Neto, Eduardo H. and Delacretaz, Luca and El Baggari, Ismail and Ferguson, G.M. and Gannon, William J. and Ghorashi, Sayed Ali Akbar and Goodge, Berit H. and Goulko, Olga and Grissonnache, G. and Hallas, Alannah and Hayes, Ian M. and He, Yu and Huang, Edwin W. and Kogar, Anshu and Kumah, Divine and Lee, Jong Yeon and Legros, A. and Mahmood, Fahad and Maximenko, Yulia and Pellatz, Nick and Polshyn, Hryhoriy and Sarkar, Tarapada and Scheie, Allen and Seyler, Kyle L. and Shi, Zhenzhong and Skinner, Brian and Steinke, Lucia and Thirunavukkuarasu, K. and Trevisan, Thaís Victa and Vogl, Michael and Volkov, Pavel A. and Wang, Yao and Wang, Yishu and Wei, Di and Wei, Kaya and Yang, Shuolong and Zhang, Xian and Zhang, Ya-Hui and Zhao, Liuyan and Zong, Alfred}, booktitle = {arXiv}, pages = {55}, title = {{The future of the correlated electron problem}}, year = {2020}, } @inproceedings{10673, abstract = {We propose a neural information processing system obtained by re-purposing the function of a biological neural circuit model to govern simulated and real-world control tasks. Inspired by the structure of the nervous system of the soil-worm, C. elegans, we introduce ordinary neural circuits (ONCs), defined as the model of biological neural circuits reparameterized for the control of alternative tasks. We first demonstrate that ONCs realize networks with higher maximum flow compared to arbitrary wired networks. We then learn instances of ONCs to control a series of robotic tasks, including the autonomous parking of a real-world rover robot. For reconfiguration of the purpose of the neural circuit, we adopt a search-based optimization algorithm. Ordinary neural circuits perform on par and, in some cases, significantly surpass the performance of contemporary deep learning models. ONC networks are compact, 77% sparser than their counterpart neural controllers, and their neural dynamics are fully interpretable at the cell-level.}, author = {Hasani, Ramin and Lechner, Mathias and Amini, Alexander and Rus, Daniela and Grosu, Radu}, booktitle = {Proceedings of the 37th International Conference on Machine Learning}, issn = {2640-3498}, location = {Virtual}, pages = {4082--4093}, title = {{A natural lottery ticket winner: Reinforcement learning with ordinary neural circuits}}, year = {2020}, } @inproceedings{10693, abstract = {High quality graphene heterostructures host an array of fractional quantum Hall isospin ferromagnets with diverse spin and valley orders. While a variety of phase transitions have been observed, disentangling the isospin phase diagram of these states is hampered by the absence of direct probes of spin and valley order. I will describe nonlocal transport measurements based on launching spin waves from a gate defined lateral heterojunction, performed in ultra-clean Corbino geometry graphene devices. At high magnetic fields, we find that the spin-wave transport signal is detected in all FQH states between ν = 0 and 1; however, between ν = 1 and 2 only odd numerator FQH states show finite nonlocal transport, despite the identical ground state spin polarizations in odd- and even numerator states. The results reveal that the neutral spin-waves are both spin and sublattice polarized making them a sensitive probe of ground state sublattice structure. Armed with this understanding, we use nonlocal transport signal to a magnetic field tuned isospin phase transition, showing that the emergent even denominator state at ν = 1/2 in monolayer graphene is indeed a multicomponent state featuring equal populations on each sublattice.}, author = {Zhou, Haoxin and Polshyn, Hryhoriy and Tanaguchi, Takashi and Watanabe, Kenji and Young, Andrea}, booktitle = {APS March Meeting 2020}, issn = {0003-0503}, location = {Denver, CO, United States}, number = {1}, publisher = {American Physical Society}, title = {{Sublattice resolved spin wave transport through graphene fractional quantum Hall states as a probe of isospin order}}, volume = {65}, year = {2020}, } @inproceedings{10698, abstract = {This is the second of three talks describing the observation and characterization of a ferromagnetic moiré heterostructure based on twisted bilayer graphene aligned to hexagonal boron nitride. I will compare the qualitative and quantitative features of this observed quantum anomalous Hall state to traditional systems engineered from thin film (Bi,Sb)2Te3 topological insulators. In particular, we find that the measured electronic energy gap of ~30K is several times higher than the Curie temperature, consistent with a lack of disorder associated with magnetic dopants. In this system, the quantization arises from spontaneous ferromagnetic polarization into a single spin and valley moiré subband, which is topological despite the lack of spin orbit coupling. I will also discuss the observation of current induced switching, which allows the magnetic state of the heterostructure to be controllably reversed with currents as small as a few nanoamperes.}, author = {Serlin, Marec and Tschirhart, Charles and Polshyn, Hryhoriy and Zhang, Yuxuan and Zhu, Jiacheng and Huber, Martin E. and Balents, Leon and Watanabe, Kenji and Tanaguchi, Takashi and Young, Andrea}, booktitle = {APS March Meeting 2020}, location = {Denver, CO, United States}, number = {1}, publisher = {American Physical Society}, title = {{Intrinsic quantized anomalous Hall effect in a moiré heterostructure, part II: Temperature dependence and current switching}}, volume = {65}, year = {2020}, } @inproceedings{10699, abstract = {This is the third of three talks describing the observation and characterization of a ferromagnetic moiré heterostructure based on twisted bilayer graphene aligned to hexagonal boron nitride. In this segment I will present scanning probe magnetometry data acquired using a nanoSQUID-on-tip microscope, which provides ~150 nm spatial resolution and a field sensitivity of ~10 nT/rtHz. We study the distribution of magnetic domains within the device as a function of density, magnetic field training, and DC current. Our data allow us to constrain the magnitude of the orbital magnetic moment of the electrons in the QAH state. Comparison with simultaneously acquired transport data allows us to precisely correlate single domain dynamics with discrete jumps in the observed anomalous Hall signal.}, author = {Tschirhart, Charles and Serlin, Marec and Polshyn, Hryhoriy and Zhang, Yuxuan and Zhu, Jiacheng and Balents, Leon and Huber, Martin E. and Watanabe, Kenji and Tanaguchi, Takashi and Young, Andrea}, booktitle = {APS March Meeting 2020}, issn = {0003-0503}, location = {Denver, CO, United States}, number = {1}, publisher = {American Physical Society}, title = {{Intrinsic quantized anomalous Hall effect in a moiré heterostructure, part III: Scanning probe magnetometry}}, volume = {65}, year = {2020}, } @inproceedings{10697, abstract = {We report the observation of a quantized anomalous Hall effect in a moiré heterostructure consisting of twisted bilayer graphene aligned to an encapsulating hBN substrate. The effect occurs at a density of 3 electrons per superlattice unit cell, where we observe magnetic hysteresis and a Hall resistance quantized to within 0.1% of the resistance quantum at temperatures as high as 3K. In this first of 3 talks, I will describe the fabrication procedure for our device as well as basic transport characterization measurements. I will introduce the phenomenology of twisted bilayer graphene and present evidence for hBN alignment as manifested in the hierarchy of symmetry-breaking gaps and anomalous magnetoresistance.}, author = {Zhang, Yuxuan and Serlin, Marec and Tschirhart, Charles and Polshyn, Hryhoriy and Zhu, Jiacheng and Balents, Leon and Huber, Martin E. and Taniguchi, Takashi and Watanabe, Kenji and Young, Andrea}, booktitle = {APS March Meeting 2020}, location = {Denver, CO, United States}, number = {1}, publisher = {American Physical Society}, title = {{Intrinsic quantized anomalous Hall effect in a moiré heterostructure, part I: Device fabrication and transport}}, volume = {65}, year = {2020}, } @inproceedings{10696, abstract = {We experimentally investigate twisted van der Waals heterostructures of monolayer graphene rotated with respect to a bernal stacked graphene bilayer. We report transport measurements for devices with twist angles between 0.9 and 1.4°. The electric field allows efficient tuning of the width, isolation and the topology of the moiré bands in this system. By comparing magnetoresistance measurements to numerical simulations, we develop an understanding of the band structure. Finally, we observe correlated states at half- and quarter-fillings, which arise when narrow moire sublattice band is isolated by energy gaps from dispersive bands. We investigate the effects of in-plane and out-of-plane magnetic field on these states and discuss the implication for their spin- and valley- polarization.}, author = {Polshyn, Hryhoriy and Zhu, Jihang and Kumar, Manish and Taniguchi, Takashi and Watanabe, Kenji and MacDonald, Allan and Young, Andrea}, booktitle = {APS March Meeting 2020}, issn = {0003-0503}, location = {Denver, CO, United States}, number = {1}, publisher = {American Physical Society}, title = {{Correlated states and tunable topological bands in twisted monolayer-bilayer graphene heterostructures}}, volume = {65}, year = {2020}, } @article{10701, abstract = {Partially filled Landau levels host competing electronic orders. For example, electron solids may prevail close to integer filling of the Landau levels before giving way to fractional quantum Hall liquids at higher carrier density1,2. Here, we report the observation of an electron solid with non-collinear spin texture in monolayer graphene, consistent with solidification of skyrmions3—topological spin textures characterized by quantized electrical charge4,5. We probe the spin texture of the solids using a modified Corbino geometry that allows ferromagnetic magnons to be launched and detected6,7. We find that magnon transport is highly efficient when one Landau level is filled (ν=1), consistent with quantum Hall ferromagnetic spin polarization. However, even minimal doping immediately quenches the magnon signal while leaving the vanishing low-temperature charge conductivity unchanged. Our results can be understood by the formation of a solid of charged skyrmions near ν=1, whose non-collinear spin texture leads to rapid magnon decay. Data near fractional fillings show evidence of several fractional skyrmion solids, suggesting that graphene hosts a highly tunable landscape of coupled spin and charge orders.}, author = {Zhou, Haoxin and Polshyn, Hryhoriy and Taniguchi, Takashi and Watanabe, Kenji and Young, Andrea F.}, issn = {1745-2481}, journal = {Nature Physics}, number = {2}, pages = {154--158}, publisher = {Springer Nature}, title = {{Skyrmion solids in monolayer graphene}}, doi = {10.1038/s41567-019-0729-8}, volume = {16}, year = {2020}, } @article{11056, abstract = {Aging of the circulatory system correlates with the pathogenesis of a large spectrum of diseases. However, it is largely unknown which factors drive the age-dependent or pathological decline of the vasculature and how vascular defects relate to tissue aging. The goal of the study is to design a multianalytical approach to identify how the cellular microenvironment (i.e., fibroblasts) and serum from healthy donors of different ages or Alzheimer disease (AD) patients can modulate the functionality of organ-specific vascular endothelial cells (VECs). Long-living human microvascular networks embedding VECs and fibroblasts from skin biopsies are generated. RNA-seq, secretome analyses, and microfluidic assays demonstrate that fibroblasts from young donors restore the functionality of aged endothelial cells, an effect also achieved by serum from young donors. New biomarkers of vascular aging are validated in human biopsies and it is shown that young serum induces angiopoietin-like-4, which can restore compromised vascular barriers. This strategy is then employed to characterize transcriptional/functional changes induced on the blood–brain barrier by AD serum, demonstrating the importance of PTP4A3 in the regulation of permeability. Features of vascular degeneration during aging and AD are recapitulated, and a tool to identify novel biomarkers that can be exploited to develop future therapeutics modulating vascular function is established.}, author = {Bersini, Simone and Arrojo e Drigo, Rafael and Huang, Ling and Shokhirev, Maxim N. and HETZER, Martin W}, issn = {2366-7478}, journal = {Advanced Biosystems}, keywords = {General Biochemistry, Genetics and Molecular Biology, Biomedical Engineering, Biomaterials}, number = {5}, publisher = {Wiley}, title = {{Transcriptional and functional changes of the human microvasculature during physiological aging and Alzheimer disease}}, doi = {10.1002/adbi.202000044}, volume = {4}, year = {2020}, } @article{11055, abstract = {Vascular dysfunctions are a common feature of multiple age-related diseases. However, modeling healthy and pathological aging of the human vasculature represents an unresolved experimental challenge. Here, we generated induced vascular endothelial cells (iVECs) and smooth muscle cells (iSMCs) by direct reprogramming of healthy human fibroblasts from donors of different ages and Hutchinson-Gilford Progeria Syndrome (HGPS) patients. iVECs induced from old donors revealed upregulation of GSTM1 and PALD1, genes linked to oxidative stress, inflammation and endothelial junction stability, as vascular aging markers. A functional assay performed on PALD1 KD VECs demonstrated a recovery in vascular permeability. We found that iSMCs from HGPS donors overexpressed bone morphogenetic protein (BMP)−4, which plays a key role in both vascular calcification and endothelial barrier damage observed in HGPS. Strikingly, BMP4 concentrations are higher in serum from HGPS vs. age-matched mice. Furthermore, targeting BMP4 with blocking antibody recovered the functionality of the vascular barrier in vitro, hence representing a potential future therapeutic strategy to limit cardiovascular dysfunction in HGPS. These results show that iVECs and iSMCs retain disease-related signatures, allowing modeling of vascular aging and HGPS in vitro.}, author = {Bersini, Simone and Schulte, Roberta and Huang, Ling and Tsai, Hannah and HETZER, Martin W}, issn = {2050-084X}, journal = {eLife}, keywords = {General Immunology and Microbiology, General Biochemistry, Genetics and Molecular Biology, General Medicine, General Neuroscience}, publisher = {eLife Sciences Publications}, title = {{Direct reprogramming of human smooth muscle and vascular endothelial cells reveals defects associated with aging and Hutchinson-Gilford progeria syndrome}}, doi = {10.7554/elife.54383}, volume = {9}, year = {2020}, } @article{11054, abstract = {In recent years, the nuclear pore complex (NPC) has emerged as a key player in genome regulation and cellular homeostasis. New discoveries have revealed that the NPC has multiple cellular functions besides mediating the molecular exchange between the nucleus and the cytoplasm. In this review, we discuss non-transport aspects of the NPC focusing on the NPC-genome interaction, the extreme longevity of the NPC proteins, and NPC dysfunction in age-related diseases. The examples summarized herein demonstrate that the NPC, which first evolved to enable the biochemical communication between the nucleus and the cytoplasm, now doubles as the gatekeeper of cellular identity and aging.}, author = {Cho, Ukrae H. and HETZER, Martin W}, issn = {0896-6273}, journal = {Neuron}, keywords = {General Neuroscience}, number = {6}, pages = {899--911}, publisher = {Elsevier}, title = {{Nuclear periphery takes center stage: The role of nuclear pore complexes in cell identity and aging}}, doi = {10.1016/j.neuron.2020.05.031}, volume = {106}, year = {2020}, } @article{11057, abstract = {During mitosis, transcription of genomic DNA is dramatically reduced, before it is reactivated during nuclear reformation in anaphase/telophase. Many aspects of the underlying principles that mediate transcriptional memory and reactivation in the daughter cells remain unclear. Here, we used ChIP-seq on synchronized cells at different stages after mitosis to generate genome-wide maps of histone modifications. Combined with EU-RNA-seq and Hi-C analyses, we found that during prometaphase, promoters, enhancers, and insulators retain H3K4me3 and H3K4me1, while losing H3K27ac. Enhancers globally retaining mitotic H3K4me1 or locally retaining mitotic H3K27ac are associated with cell type-specific genes and their transcription factors for rapid transcriptional activation. As cells exit mitosis, promoters regain H3K27ac, which correlates with transcriptional reactivation. Insulators also gain H3K27ac and CCCTC-binding factor (CTCF) in anaphase/telophase. This increase of H3K27ac in anaphase/telophase is required for posttranscriptional activation and may play a role in the establishment of topologically associating domains (TADs). Together, our results suggest that the genome is reorganized in a sequential order, in which histone methylations occur first in prometaphase, histone acetylation, and CTCF in anaphase/telophase, transcription in cytokinesis, and long-range chromatin interactions in early G1. We thus provide insights into the histone modification landscape that allows faithful reestablishment of the transcriptional program and TADs during cell division.}, author = {Kang, Hyeseon and Shokhirev, Maxim N. and Xu, Zhichao and Chandran, Sahaana and Dixon, Jesse R. and HETZER, Martin W}, issn = {0890-9369}, journal = {Genes & Development}, keywords = {Developmental Biology, Genetics}, number = {13-14}, pages = {913--930}, publisher = {Cold Spring Harbor Laboratory Press}, title = {{Dynamic regulation of histone modifications and long-range chromosomal interactions during postmitotic transcriptional reactivation}}, doi = {10.1101/gad.335794.119}, volume = {34}, year = {2020}, } @article{11058, abstract = {Nucleoporin 93 (Nup93) expression inversely correlates with the survival of triple-negative breast cancer patients. However, our knowledge of Nup93 function in breast cancer besides its role as structural component of the nuclear pore complex is not understood. Combination of functional assays and genetic analyses suggested that chromatin interaction of Nup93 partially modulates the expression of genes associated with actin cytoskeleton remodeling and epithelial to mesenchymal transition, resulting in impaired invasion of triple-negative, claudin-low breast cancer cells. Nup93 depletion induced stress fiber formation associated with reduced cell migration/proliferation and impaired expression of mesenchymal-like genes. Silencing LIMCH1, a gene responsible for actin cytoskeleton remodeling and up-regulated upon Nup93 depletion, partially restored the invasive phenotype of cancer cells. Loss of Nup93 led to significant defects in tumor establishment/propagation in vivo, whereas patient samples revealed that high Nup93 and low LIMCH1 expression correlate with late tumor stage. Our approach identified Nup93 as contributor of triple-negative, claudin-low breast cancer cell invasion and paves the way to study the role of nuclear envelope proteins during breast cancer tumorigenesis.}, author = {Bersini, Simone and Lytle, Nikki K and Schulte, Roberta and Huang, Ling and Wahl, Geoffrey M and HETZER, Martin W}, issn = {2575-1077}, journal = {Life Science Alliance}, keywords = {Health, Toxicology and Mutagenesis, Plant Science, Biochemistry, Genetics and Molecular Biology (miscellaneous), Ecology}, number = {1}, publisher = {Life Science Alliance}, title = {{Nup93 regulates breast tumor growth by modulating cell proliferation and actin cytoskeleton remodeling}}, doi = {10.26508/lsa.201900623}, volume = {3}, year = {2020}, } @article{11503, abstract = {Context. The Lyα emitter (LAE) fraction, XLAE, is a potentially powerful probe of the evolution of the intergalactic neutral hydrogen gas fraction. However, uncertainties in the measurement of XLAE are still under debate. Aims. Thanks to deep data obtained with the integral field spectrograph Multi Unit Spectroscopic Explorer (MUSE), we can measure the evolution of the LAE fraction homogeneously over a wide redshift range of z ≈ 3–6 for UV-faint galaxies (down to UV magnitudes of M1500 ≈ −17.75). This is a significantly fainter range than in former studies (M1500 ≤ −18.75) and it allows us to probe the bulk of the population of high-redshift star-forming galaxies. Methods. We constructed a UV-complete photometric-redshift sample following UV luminosity functions and measured the Lyα emission with MUSE using the latest (second) data release from the MUSE Hubble Ultra Deep Field Survey. Results. We derived the redshift evolution of XLAE for M1500 ∈ [ − 21.75; −17.75] for the first time with a equivalent width range EW(Lyα) ≥ 65 Å and found low values of XLAE ≲ 30% at z ≲ 6. The best-fit linear relation is XLAE = 0.07+0.06−0.03z − 0.22+0.12−0.24. For M1500 ∈ [ − 20.25; −18.75] and EW(Lyα) ≥ 25 Å, our XLAE values are consistent with those in the literature within 1σ at z ≲ 5, but our median values are systematically lower than reported values over the whole redshift range. In addition, we do not find a significant dependence of XLAE on M1500 for EW(Lyα) ≥ 50 Å at z ≈ 3–4, in contrast with previous work. The differences in XLAE mainly arise from selection biases for Lyman Break Galaxies (LBGs) in the literature: UV-faint LBGs are more easily selected if they have strong Lyα emission, hence XLAE is biased towards higher values when those samples are used. Conclusions. Our results suggest either a lower increase of XLAE towards z ≈ 6 than previously suggested, or even a turnover of XLAE at z ≈ 5.5, which may be the signature of a late or patchy reionization process. We compared our results with predictions from a cosmological galaxy evolution model. We find that a model with a bursty star formation (SF) can reproduce our observed LAE fractions much better than models where SF is a smooth function of time.}, author = {Kusakabe, Haruka and Blaizot, Jérémy and Garel, Thibault and Verhamme, Anne and Bacon, Roland and Richard, Johan and Hashimoto, Takuya and Inami, Hanae and Conseil, Simon and Guiderdoni, Bruno and Drake, Alyssa B. and Christian Herenz, Edmund and Schaye, Joop and Oesch, Pascal and Matthee, Jorryt J and Anna Marino, Raffaella and Borello Schmidt, Kasper and Pelló, Roser and Maseda, Michael and Leclercq, Floriane and Kerutt, Josephine and Mahler, Guillaume}, issn = {1432-0746}, journal = {Astronomy & Astrophysics}, keywords = {Space and Planetary Science, Astronomy and Astrophysics, dark ages / reionization / first stars / early Universe / cosmology: observations / galaxies: evolution / galaxies: high-redshift / intergalactic medium}, publisher = {EDP Sciences}, title = {{The MUSE Hubble Ultra Deep Field Survey: XIV. Evolution of the Lyα emitter fraction from z = 3 to z = 6}}, doi = {10.1051/0004-6361/201937340}, volume = {638}, year = {2020}, } @article{11504, abstract = {We present spatially resolved maps of six individually-detected Lyman α haloes (LAHs) as well as a first statistical analysis of the Lyman α (Lyα) spectral signature in the circum-galactic medium of high-redshift star-forming galaxies (−17.5 >  MUV >  −21.5) using the Multi-Unit Spectroscopic Explorer. Our resolved spectroscopic analysis of the LAHs reveals significant intrahalo variations of the Lyα line profile. Using a three-dimensional two-component model for the Lyα emission, we measured the full width at half maximum (FWHM), the peak velocity shift, and the asymmetry of the Lyα line in the core and in the halo of 19 galaxies. We find that the Lyα line shape is statistically different in the halo compared to the core (in terms of width, peak wavelength, and asymmetry) for ≈40% of our galaxies. Similarly to object-by-object based studies and a recent resolved study using lensing, we find a correlation between the peak velocity shift and the width of the Lyα line both at the interstellar and circum-galactic scales. This trend has been predicted by radiative transfer simulations of galactic winds as a result of resonant scattering in outflows. While there is a lack of correlation between the spectral properties and the spatial scale lengths of our LAHs, we find a correlation between the width of the line in the LAH and the halo flux fraction. Interestingly, UV bright galaxies (MUV <  −20) show broader, more redshifted, and less asymmetric Lyα lines in their haloes. The most significant correlation found is for the FWHM of the line and the UV continuum slope of the galaxy, suggesting that the redder galaxies have broader Lyα lines. The generally broad and red line shapes found in the halo component suggest that the Lyα haloes are powered either by scattering processes through an outflowing medium, fluorescent emission from outflowing cold clumps of gas, or a mix of both. Considering the large diversity of the Lyα line profiles observed in our sample and the lack of strong correlation, the interpretation of our results is still broadly open and underlines the need for realistic spatially resolved models of the LAHs.}, author = {Leclercq, Floriane and Bacon, Roland and Verhamme, Anne and Garel, Thibault and Blaizot, Jérémy and Brinchmann, Jarle and Cantalupo, Sebastiano and Claeyssens, Adélaïde and Conseil, Simon and Contini, Thierry and Hashimoto, Takuya and Herenz, Edmund Christian and Kusakabe, Haruka and Marino, Raffaella Anna and Maseda, Michael and Matthee, Jorryt J and Mitchell, Peter and Pezzulli, Gabriele and Richard, Johan and Schmidt, Kasper Borello and Wisotzki, Lutz}, issn = {1432-0746}, journal = {Astronomy & Astrophysics}, keywords = {Space and Planetary Science, Astronomy and Astrophysics galaxies: high-redshift / galaxies: formation / galaxies: evolution / cosmology: observations}, publisher = {EDP Sciences}, title = {{The MUSE Hubble Ultra Deep field survey: XIII. Spatially resolved spectral properties of Lyman α haloes around star-forming galaxies at z > 3}}, doi = {10.1051/0004-6361/201937339}, volume = {635}, year = {2020}, } @article{11501, abstract = {We investigated the ultraviolet (UV) spectral properties of faint Lyman-α emitters (LAEs) in the redshift range 2.9 ≤ z ≤ 4.6, and we provide material to prepare future observations of the faint Universe. We used data from the MUSE Hubble Ultra Deep Survey to construct mean rest-frame spectra of continuum-faint (median MUV of −18 and down to MUV of −16), low stellar mass (median value of 108.4 M⊙ and down to 107 M⊙) LAEs at redshift z ≳ 3. We computed various averaged spectra of LAEs, subsampled on the basis of their observational (e.g., Lyα strength, UV magnitude and spectral slope) and physical (e.g., stellar mass and star-formation rate) properties. We searched for UV spectral features other than Lyα, such as higher ionization nebular emission lines and absorption features. We successfully observed the O III]λ1666 and [C III]λ1907+C III]λ1909 collisionally excited emission lines and the He IIλ1640 recombination feature, as well as the resonant C IVλλ1548,1551 doublet either in emission or P-Cygni. We compared the observed spectral properties of the different mean spectra and find the emission lines to vary with the observational and physical properties of the LAEs. In particular, the mean spectra of LAEs with larger Lyα equivalent widths, fainter UV magnitudes, bluer UV spectral slopes, and lower stellar masses show the strongest nebular emission. The line ratios of these lines are similar to those measured in the spectra of local metal-poor galaxies, while their equivalent widths are weaker compared to the handful of extreme values detected in individual spectra of z >  2 galaxies. This suggests that weak UV features are likely ubiquitous in high z, low-mass, and faint LAEs. We publicly released the stacked spectra, as they can serve as empirical templates for the design of future observations, such as those with the James Webb Space Telescope and the Extremely Large Telescope.}, author = {Feltre, Anna and Maseda, Michael V. and Bacon, Roland and Pradeep, Jayadev and Leclercq, Floriane and Kusakabe, Haruka and Wisotzki, Lutz and Hashimoto, Takuya and Schmidt, Kasper B. and Blaizot, Jeremy and Brinchmann, Jarle and Boogaard, Leindert and Cantalupo, Sebastiano and Carton, David and Inami, Hanae and Kollatschny, Wolfram and Marino, Raffaella A. and Matthee, Jorryt J and Nanayakkara, Themiya and Richard, Johan and Schaye, Joop and Tresse, Laurence and Urrutia, Tanya and Verhamme, Anne and Weilbacher, Peter M.}, issn = {1432-0746}, journal = {Astronomy & Astrophysics}, keywords = {Space and Planetary Science, Astronomy and Astrophysics, galaxies: evolution / galaxies: high-redshift / ISM: lines and bands / ultraviolet: ISM / ultraviolet: galaxies}, publisher = {EDP Sciences}, title = {{The MUSE Hubble Ultra Deep Field Survey: XV. The mean rest-UV spectra of Lyα emitters at z > 3}}, doi = {10.1051/0004-6361/202038133}, volume = {641}, year = {2020}, } @article{11513, abstract = {We report the spectroscopic confirmation of a new protocluster in the COSMOS field at z ∼ 2.2, COSMOS Cluster 2.2 (CC2.2), originally identified as an overdensity of narrowband selected Hα emitting candidates. With only two masks of Keck/MOSFIRE near-IR spectroscopy in both H (∼1.47–1.81 μm) and K (∼1.92–2.40 μm) bands (∼1.5 hr each), we confirm 35 unique protocluster members with at least two emission lines detected with S/N > 3. Combined with 12 extra members from the zCOSMOS-deep spectroscopic survey (47 in total), we estimate a mean redshift and a line-of-sight velocity dispersion of zmean = 2.23224 ± 0.00101 and σlos = 645 ± 69 km s−1 for this protocluster, respectively. Assuming virialization and spherical symmetry for the system, we estimate a total mass of Mvir ∼ (1–2) ×1014M⊙ for the structure. We evaluate a number density enhancement of δg ∼ 7 for this system and we argue that the structure is likely not fully virialized at z ∼ 2.2. However, in a spherical collapse model, δg is expected to grow to a linear matter enhancement of ∼1.9 by z = 0, exceeding the collapse threshold of 1.69, and leading to a fully collapsed and virialized Coma-type structure with a total mass of Mdyn(z = 0) ∼ 9.2 × 1014M⊙ by now. This observationally efficient confirmation suggests that large narrowband emission-line galaxy surveys, when combined with ancillary photometric data, can be used to effectively trace the large-scale structure and protoclusters at a time when they are mostly dominated by star-forming galaxies.}, author = {Darvish, Behnam and Scoville, Nick Z. and Martin, Christopher and Sobral, David and Mobasher, Bahram and Rettura, Alessandro and Matthee, Jorryt J and Capak, Peter and Chartab, Nima and Hemmati, Shoubaneh and Masters, Daniel and Nayyeri, Hooshang and O’Sullivan, Donal and Paulino-Afonso, Ana and Sattari, Zahra and Shahidi, Abtin and Salvato, Mara and Lemaux, Brian C. and Fèvre, Olivier Le and Cucciati, Olga}, issn = {1538-4357}, journal = {The Astrophysical Journal}, keywords = {Space and Planetary Science, Astronomy and Astrophysics}, number = {1}, publisher = {IOP Publishing}, title = {{Spectroscopic confirmation of a coma cluster progenitor at z ∼ 2.2}}, doi = {10.3847/1538-4357/ab75c3}, volume = {892}, year = {2020}, } @article{11528, abstract = {Ly α emission lines are typically found to be redshifted with respect to the systemic redshifts of galaxies, likely due to resonant scattering of Ly α photons. Here, we measure the average velocity offset for a sample of 96 z ≈ 3.3 Ly α emitters (LAEs) with a median Ly α flux (luminosity) of ≈10−17 erg cm−2 s−1 (⁠≈1042 erg s−1⁠) and a median star formation rate (SFR) of ≈1.3 M⊙ yr−1 (not corrected for possible dust extinction), detected by the Multi-Unit Spectroscopic Explorer as part of our MUSEQuBES circumgalactic medium (CGM) survey. By postulating that the stacked CGM absorption profiles of these LAEs, probed by eight background quasars, must be centred on the systemic redshift, we measure an average velocity offset, Voffset = 171\pm 8 km s−1, between the Ly α emission peak and the systemic redshift. The observed Voffset is lower by factors of ≈1.4 and ≈2.6 compared to the velocity offsets measured for narrow-band-selected LAEs and Lyman break galaxies, respectively, which probe galaxies with higher masses and SFRs. Consistent with earlier studies based on direct measurements for individual objects, we find that the Voffset is correlated with the full width at half-maximum of the red peak of the Ly α line, and anticorrelated with the rest-frame equivalent width. Moreover, we find that Voffset is correlated with SFR with a sub-linear scaling relation, Voffset∝SFR0.16±0.03⁠. Adopting the mass scaling for main-sequence galaxies, such a relation suggests that Voffset scales with the circular velocity of the dark matter haloes hosting the LAEs.}, author = {Muzahid, Sowgat and Schaye, Joop and Marino, Raffaella Anna and Cantalupo, Sebastiano and Brinchmann, Jarle and Contini, Thierry and Wendt, Martin and Wisotzki, Lutz and Zabl, Johannes and Bouché, Nicolas and Akhlaghi, Mohammad and Chen, Hsiao-Wen and Claeyssens, Adélaîde and Johnson, Sean and Leclercq, Floriane and Maseda, Michael and Matthee, Jorryt J and Richard, Johan and Urrutia, Tanya and Verhamme, Anne}, issn = {1365-2966}, journal = {Monthly Notices of the Royal Astronomical Society}, keywords = {Space and Planetary Science, Astronomy and Astrophysics, galaxies: haloes, galaxies: high-redshift, quasars: absorption lines}, number = {2}, pages = {1013--1022}, publisher = {Oxford University Press}, title = {{MUSEQuBES: Calibrating the redshifts of Lyα emitters using stacked circumgalactic medium absorption profiles}}, doi = {10.1093/mnras/staa1347}, volume = {496}, year = {2020}, } @article{11529, abstract = {CR7 is among the most luminous Ly α emitters (LAEs) known at z = 6.6 and consists of at least three UV components that are surrounded by Ly α emission. Previous studies have suggested that it may host an extreme ionizing source. Here, we present deep integral field spectroscopy of CR7 with VLT/Multi Unit Spectroscopic Explorer (MUSE). We measure extended emission with a similar halo scale length as typical LAEs at z ≈ 5. CR7’s Ly α halo is clearly elongated along the direction connecting the multiple components, likely tracing the underlying gas distribution. The Ly α emission originates almost exclusively from the brightest UV component, but we also identify a faint kinematically distinct Ly α emitting region nearby a fainter component. Combined with new near-infrared data, the MUSE data show that the rest-frame Ly α equivalent width (EW) is ≈100 Å. This is a factor 4 higher than the EW measured in low-redshift analogues with carefully matched Ly α profiles (and thus arguably H I column density), but this EW can plausibly be explained by star formation. Alternative scenarios requiring active galactic nucleus (AGN) powering are also disfavoured by the narrower and steeper Ly α spectrum and much smaller IR to UV ratio compared to obscured AGN in other Ly α blobs. CR7’s Ly α emission, while extremely luminous, resembles the emission in more common LAEs at lower redshifts very well and is likely powered by a young metal-poor starburst.}, author = {Matthee, Jorryt J and Pezzulli, Gabriele and Mackenzie, Ruari and Cantalupo, Sebastiano and Kusakabe, Haruka and Leclercq, Floriane and Sobral, David and Richard, Johan and Wisotzki, Lutz and Lilly, Simon and Boogaard, Leindert and Marino, Raffaella and Maseda, Michael and Nanayakkara, Themiya}, issn = {1365-2966}, journal = {Monthly Notices of the Royal Astronomical Society}, keywords = {Space and Planetary Science, Astronomy and Astrophysics, galaxies: evolution, galaxies: high-redshift, dark ages, reionization, first stars, cosmology: observations}, number = {2}, pages = {3043--3059}, publisher = {Oxford University Press}, title = {{The nature of CR7 revealed with MUSE: A young starburst powering extended Ly α emission at z = 6.6}}, doi = {10.1093/mnras/staa2550}, volume = {498}, year = {2020}, } @article{11533, abstract = {We explore deep rest-frame UV to FIR data in the COSMOS field to measure the individual spectral energy distributions (SED) of the ∼4000 SC4K (Sobral et al.) Lyman α (Ly α) emitters (LAEs) at z ∼ 2–6. We find typical stellar masses of 109.3 ± 0.6 M⊙ and star formation rates (SFR) of SFRSED=4.4+10.5−2.4 M⊙ yr−1 and SFRLyα=5.9+6.3−2.6 M⊙ yr−1, combined with very blue UV slopes of β=−2.1+0.5−0.4⁠, but with significant variations within the population. MUV and β are correlated in a similar way to UV-selected sources, but LAEs are consistently bluer. This suggests that LAEs are the youngest and/or most dust-poor subset of the UV-selected population. We also study the Ly α rest-frame equivalent width (EW0) and find 45 ‘extreme’ LAEs with EW0 > 240 Å (3σ), implying a low number density of (7 ± 1) × 10−7 Mpc−3. Overall, we measure little to no evolution of the Ly α EW0 and scale length parameter (w0), which are consistently high (EW0=140+280−70 Å, w0=129+11−11 Å) from z ∼ 6 to z ∼ 2 and below. However, w0 is anticorrelated with MUV and stellar mass. Our results imply that sources selected as LAEs have a high Ly α escape fraction (fesc,Ly α) irrespective of cosmic time, but fesc,Ly α is still higher for UV-fainter and lower mass LAEs. The least massive LAEs (<109.5 M⊙) are typically located above the star formation ‘main sequence’ (MS), but the offset from the MS decreases towards z ∼ 6 and towards 1010 M⊙. Our results imply a lack of evolution in the properties of LAEs across time and reveals the increasing overlap in properties of LAEs and UV-continuum selected galaxies as typical star-forming galaxies at high redshift effectively become LAEs.}, author = {Santos, S and Sobral, D and Matthee, Jorryt J and Calhau, J and da Cunha, E and Ribeiro, B and Paulino-Afonso, A and Arrabal Haro, P and Butterworth, J}, issn = {1365-2966}, journal = {Monthly Notices of the Royal Astronomical Society}, keywords = {Space and Planetary Science, Astronomy and Astrophysics, galaxies: evolution, galaxies: formation, galaxies: high-redshift, galaxies: star formation}, number = {1}, pages = {141--160}, publisher = {Oxford University Press}, title = {{The evolution of rest-frame UV properties, Ly α EWs, and the SFR–stellar mass relation at z ∼ 2–6 for SC4K LAEs}}, doi = {10.1093/mnras/staa093}, volume = {493}, year = {2020}, } @article{11534, abstract = {The observed properties of the Lyman-α (Ly α) emission line are a powerful probe of neutral gas in and around galaxies. We present spatially resolved Ly α spectroscopy with VLT/MUSE targeting VR7, a UV-luminous galaxy at z = 6.532 with moderate Ly α equivalent width (EW0 ≈ 38 Å). These data are combined with deep resolved [CII]158μm spectroscopy obtained with ALMA and UV imaging from HST and we also detect UV continuum with MUSE. Ly α emission is clearly detected with S/N ≈ 40 and FWHM of 374 km s−1. Ly α and [C II] are similarly extended beyond the UV, with effective radius reff = 2.1 ± 0.2 kpc for a single exponential model or reff,Lyα,halo=3.45+1.08−0.87 kpc when measured jointly with the UV continuum. The Ly α profile is broader and redshifted with respect to the [C II] line (by 213 km s−1), but there are spatial variations that are qualitatively similar in both lines and coincide with resolved UV components. This suggests that the emission originates from two components with plausibly different H I column densities. We place VR7 in the context of other galaxies at similar and lower redshift. The Ly α halo scale length is similar at different redshifts and velocity shifts with respect to the systemic are typically smaller. Overall, we find little indications of a more neutral vicinity at higher redshift. This means that the local (∼10 kpc) neutral gas conditions that determine the observed Ly α properties in VR7 resemble the conditions in post-reionization galaxies.}, author = {Matthee, Jorryt J and Sobral, David and Gronke, Max and Pezzulli, Gabriele and Cantalupo, Sebastiano and Röttgering, Huub and Darvish, Behnam and Santos, Sérgio}, issn = {1365-2966}, journal = {Monthly Notices of the Royal Astronomical Society}, keywords = {Space and Planetary Science, Astronomy and Astrophysics, galaxies: evolution, galaxies: high-redshift, dark ages, reionization, first stars, cosmology: observations}, number = {2}, pages = {1778--1790}, publisher = {Oxford University Press}, title = {{Resolved Lyman-α properties of a luminous Lyman-break galaxy in a large ionized bubble at z = 6.53 }}, doi = {10.1093/mnras/stz3554}, volume = {492}, year = {2020}, } @article{11531, abstract = {While low-luminosity galaxies dominate number counts at all redshifts, their contribution to cosmic reionization is poorly understood due to a lack of knowledge of their physical properties. We isolate a sample of 35 z ≈ 4–5 continuum-faint Lyman-α emitters from deep VLT/MUSE spectroscopy and directly measure their H α emission using stacked Spitzer/IRAC Ch. 1 photometry. Based on Hubble Space Telescope imaging, we determine that the average UV continuum magnitude is fainter than −16 (≈ 0.01 L⋆), implying a median Lyman-α equivalent width of 259 Å. By combining the H α measurement with the UV magnitude, we determine the ionizing photon production efficiency, ξion, a first for such faint galaxies. The measurement of log10 (ξion [Hz erg−1]) = 26.28 (⁠+0.28−0.40⁠) is in excess of literature measurements of both continuum- and emission line-selected samples, implying a more efficient production of ionizing photons in these lower luminosity, Lyman-α-selected systems. We conclude that this elevated efficiency can be explained by stellar populations with metallicities between 4 × 10−4 and 0.008, with light-weighted ages less than 3 Myr.}, author = {Maseda, Michael V and Bacon, Roland and Lam, Daniel and Matthee, Jorryt J and Brinchmann, Jarle and Schaye, Joop and Labbe, Ivo and Schmidt, Kasper B and Boogaard, Leindert and Bouwens, Rychard and Cantalupo, Sebastiano and Franx, Marijn and Hashimoto, Takuya and Inami, Hanae and Kusakabe, Haruka and Mahler, Guillaume and Nanayakkara, Themiya and Richard, Johan and Wisotzki, Lutz}, issn = {1365-2966}, journal = {Monthly Notices of the Royal Astronomical Society}, keywords = {Space and Planetary Science, Astronomy and Astrophysics, Galaxies: evolution, Galaxies: high-redshift, Galaxies: ISM}, number = {4}, pages = {5120--5130}, publisher = {Oxford University Press}, title = {{Elevated ionizing photon production efficiency in faint high-equivalent-width Lyman-α emitters}}, doi = {10.1093/mnras/staa622}, volume = {493}, year = {2020}, } @article{11530, abstract = {A prediction of the classic active galactic nucleus (AGN) unification model is the presence of ionization cones with different orientations depending on the AGN type. Confirmations of this model exist for present times, but it is less clear in the early Universe. Here, we use the morphology of giant Ly α nebulae around AGNs at redshift z ∼ 3 to probe AGN emission and therefore the validity of the AGN unification model at this redshift. We compare the spatial morphology of 19 nebulae previously found around type I AGNs with a new sample of four Ly α nebulae detected around type II AGNs. Using two independent techniques, we find that nebulae around type II AGNs are more asymmetric than around type I, at least at radial distances r > 30 physical kpc (pkpc) from the ionizing source. We conclude that the type I and type II AGNs in our sample show evidence of different surrounding ionizing geometries. This suggests that the classical AGN unification model is also valid for high-redshift sources. Finally, we discuss how the lack of asymmetry in the inner parts (r ≲ 30 pkpc) and the associated high values of the He II to Ly α ratios in these regions could indicate additional sources of (hard) ionizing radiation originating within or in proximity of the AGN host galaxies. This work demonstrates that the morphologies of giant Ly α nebulae can be used to understand and study the geometry of high-redshift AGNs on circumnuclear scales and it lays the foundation for future studies using much larger statistical samples.}, author = {den Brok, J S and Cantalupo, S and Mackenzie, R and Marino, R A and Pezzulli, G and Matthee, Jorryt J and Johnson, S D and Krumpe, M and Urrutia, T and Kollatschny, W}, issn = {1365-2966}, journal = {Monthly Notices of the Royal Astronomical Society}, keywords = {Space and Planetary Science, Astronomy and Astrophysics, galaxies: active, galaxies: high-redshift, intergalactic medium, quasars: emission lines, quasars: general}, number = {2}, pages = {1874--1887}, publisher = {Oxford University Press}, title = {{Probing the AGN unification model at redshift z ∼ 3 with MUSE observations of giant Lyα nebulae}}, doi = {10.1093/mnras/staa1269}, volume = {495}, year = {2020}, } @article{11539, abstract = {Despite recent progress in understanding Ly α emitters (LAEs), relatively little is known regarding their typical black hole activity across cosmic time. Here, we study the X-ray and radio properties of ∼4000 LAEs at 2.2 < z < 6 from the SC4K survey in the COSMOS field. We detect 254 (⁠6.8per cent±0.4per cent⁠) LAEs individually in the X-rays (S/N > 3) with an average luminosity of 1044.31±0.01ergs−1 and average black hole accretion rate (BHAR) of 0.72±0.01 M⊙ yr−1, consistent with moderate to high accreting active galactic neuclei (AGNs). We detect 120 sources in deep radio data (radio AGN fraction of 3.2per cent±0.3per cent⁠). The global AGN fraction (⁠8.6per cent±0.4per cent⁠) rises with Ly α luminosity and declines with increasing redshift. For X-ray-detected LAEs, Ly α luminosities correlate with the BHARs, suggesting that Ly α luminosity becomes a BHAR indicator. Most LAEs (⁠93.1per cent±0.6per cent⁠) at 2 < z < 6 have no detectable X-ray emission (BHARs < 0.017 M⊙ yr−1). The median star formation rate (SFR) of star-forming LAEs from Ly α and radio luminosities is 7.6+6.6−2.8 M⊙ yr−1. The black hole to galaxy growth ratio (BHAR/SFR) for LAEs is <0.0022, consistent with typical star-forming galaxies and the local BHAR/SFR relation. We conclude that LAEs at 2 < z < 6 include two different populations: an AGN population, where Ly α luminosity traces BHAR, and another with low SFRs which remain undetected in even the deepest X-ray stacks but is detected in the radio stacks.}, author = {Calhau, João and Sobral, David and Santos, Sérgio and Matthee, Jorryt J and Paulino-Afonso, Ana and Stroe, Andra and Simmons, Brooke and Barlow-Hall, Cassandra and Adams, Benjamin}, issn = {1365-2966}, journal = {Monthly Notices of the Royal Astronomical Society}, keywords = {Space and Planetary Science, Astronomy and Astrophysics, galaxies: active, galaxies: evolution, galaxies: high-redshift, quasars: supermassive black holes, galaxies: star formation, cosmology: observations, X-rays: galaxies}, number = {3}, pages = {3341--3362}, publisher = {Oxford University Press}, title = {{The X-ray and radio activity of typical and luminous Ly α emitters from z ∼ 2 to z ∼ 6: Evidence for a diverse, evolving population}}, doi = {10.1093/mnras/staa476}, volume = {493}, year = {2020}, } @inproceedings{11586, abstract = {Distant luminous Lyman-α emitters are excellent targets for detailed observations of galaxies in the epoch of reionisation. Spatially resolved observations of these galaxies allow us to simultaneously probe the emission from young stars, partially ionised gas in the interstellar medium and to constrain the properties of the surrounding hydrogen in the circumgalactic medium. We review recent results from (spectroscopic) follow-up studies of the rest-frame UV, Lyman-α and [CII] emission in luminous galaxies observed ∼500 Myr after the Big Bang with ALMA, HST/WFC3 and VLT/X-SHOOTER. These galaxies likely reside in early ionised bubbles and are complex systems, consisting of multiple well separated and resolved components where traces of metals are already present.}, author = {Matthee, Jorryt J and Sobral, David}, booktitle = {Proceedings of the International Astronomical Union}, issn = {1743-9221}, keywords = {Astronomy and Astrophysics, Space and Planetary Science, galaxies: formation, galaxies: evolution, galaxies: high-redshift}, number = {S352}, pages = {21--25}, publisher = {Cambridge University Press}, title = {{Unveiling the most luminous Lyman-α emitters in the epoch of reionisation}}, doi = {10.1017/s1743921319009451}, volume = {15}, year = {2020}, } @article{11610, abstract = {Studies of Galactic structure and evolution have benefited enormously from Gaia kinematic information, though additional, intrinsic stellar parameters like age are required to best constrain Galactic models. Asteroseismology is the most precise method of providing such information for field star populations en masse, but existing samples for the most part have been limited to a few narrow fields of view by the CoRoT and Kepler missions. In an effort to provide well-characterized stellar parameters across a wide range in Galactic position, we present the second data release of red giant asteroseismic parameters for the K2 Galactic Archaeology Program (GAP). We provide ${\nu }_{\max }$ and ${\rm{\Delta }}\nu $ based on six independent pipeline analyses; first-ascent red giant branch (RGB) and red clump (RC) evolutionary state classifications from machine learning; and ready-to-use radius and mass coefficients, κR and κM, which, when appropriately multiplied by a solar-scaled effective temperature factor, yield physical stellar radii and masses. In total, we report 4395 radius and mass coefficients, with typical uncertainties of 3.3% (stat.) ± 1% (syst.) for κR and 7.7% (stat.) ± 2% (syst.) for κM among RGB stars, and 5.0% (stat.) ± 1% (syst.) for κR and 10.5% (stat.) ± 2% (syst.) for κM among RC stars. We verify that the sample is nearly complete—except for a dearth of stars with ${\nu }_{\max }\lesssim 10\mbox{--}20\,\mu \mathrm{Hz}$—by comparing to Galactic models and visual inspection. Our asteroseismic radii agree with radii derived from Gaia Data Release 2 parallaxes to within 2.2% ± 0.3% for RGB stars and 2.0% ± 0.6% for RC stars.}, author = {Zinn, Joel C. and Stello, Dennis and Elsworth, Yvonne and García, Rafael A. and Kallinger, Thomas and Mathur, Savita and Mosser, Benoît and Bugnet, Lisa Annabelle and Jones, Caitlin and Hon, Marc and Sharma, Sanjib and Schönrich, Ralph and Warfield, Jack T. and Luger, Rodrigo and Pinsonneault, Marc H. and Johnson, Jennifer A. and Huber, Daniel and Aguirre, Victor Silva and Chaplin, William J. and Davies, Guy R. and Miglio, Andrea}, issn = {1538-4365}, journal = {The Astrophysical Journal Supplement Series}, keywords = {Space and Planetary Science, Astronomy and Astrophysics}, number = {2}, publisher = {IOP Publishing}, title = {{The K2 galactic archaeology program data release 2: Asteroseismic results from campaigns 4, 6, and 7}}, doi = {10.3847/1538-4365/abbee3}, volume = {251}, year = {2020}, } @article{11611, abstract = {Over the course of its history, the Milky Way has ingested multiple smaller satellite galaxies1. Although these accreted stellar populations can be forensically identified as kinematically distinct structures within the Galaxy, it is difficult in general to date precisely the age at which any one merger occurred. Recent results have revealed a population of stars that were accreted via the collision of a dwarf galaxy, called Gaia–Enceladus1, leading to substantial pollution of the chemical and dynamical properties of the Milky Way. Here we identify the very bright, naked-eye star ν Indi as an indicator of the age of the early in situ population of the Galaxy. We combine asteroseismic, spectroscopic, astrometric and kinematic observations to show that this metal-poor, alpha-element-rich star was an indigenous member of the halo, and we measure its age to be 11.0±0.7 (stat) ±0.8 (sys) billion years. The star bears hallmarks consistent with having been kinematically heated by the Gaia–Enceladus collision. Its age implies that the earliest the merger could have begun was 11.6 and 13.2 billion years ago, at 68% and 95% confidence, respectively. Computations based on hierarchical cosmological models slightly reduce the above limits.}, author = {Chaplin, William J. and Serenelli, Aldo M. and Miglio, Andrea and Morel, Thierry and Mackereth, J. Ted and Vincenzo, Fiorenzo and Kjeldsen, Hans and Basu, Sarbani and Ball, Warrick H. and Stokholm, Amalie and Verma, Kuldeep and Mosumgaard, Jakob Rørsted and Silva Aguirre, Victor and Mazumdar, Anwesh and Ranadive, Pritesh and Antia, H. M. and Lebreton, Yveline and Ong, Joel and Appourchaux, Thierry and Bedding, Timothy R. and Christensen-Dalsgaard, Jørgen and Creevey, Orlagh and García, Rafael A. and Handberg, Rasmus and Huber, Daniel and Kawaler, Steven D. and Lund, Mikkel N. and Metcalfe, Travis S. and Stassun, Keivan G. and Bazot, Michäel and Beck, Paul G. and Bell, Keaton J. and Bergemann, Maria and Buzasi, Derek L. and Benomar, Othman and Bossini, Diego and Bugnet, Lisa Annabelle and Campante, Tiago L. and Orhan, Zeynep Çelik and Corsaro, Enrico and González-Cuesta, Lucía and Davies, Guy R. and Di Mauro, Maria Pia and Egeland, Ricky and Elsworth, Yvonne P. and Gaulme, Patrick and Ghasemi, Hamed and Guo, Zhao and Hall, Oliver J. and Hasanzadeh, Amir and Hekker, Saskia and Howe, Rachel and Jenkins, Jon M. and Jiménez, Antonio and Kiefer, René and Kuszlewicz, James S. and Kallinger, Thomas and Latham, David W. and Lundkvist, Mia S. and Mathur, Savita and Montalbán, Josefina and Mosser, Benoit and Bedón, Andres Moya and Nielsen, Martin Bo and Örtel, Sibel and Rendle, Ben M. and Ricker, George R. and Rodrigues, Thaíse S. and Roxburgh, Ian W. and Safari, Hossein and Schofield, Mathew and Seager, Sara and Smalley, Barry and Stello, Dennis and Szabó, Róbert and Tayar, Jamie and Themeßl, Nathalie and Thomas, Alexandra E. L. and Vanderspek, Roland K. and van Rossem, Walter E. and Vrard, Mathieu and Weiss, Achim and White, Timothy R. and Winn, Joshua N. and Yıldız, Mutlu}, issn = {2397-3366}, journal = {Nature Astronomy}, keywords = {Astronomy and Astrophysics}, number = {4}, pages = {382--389}, publisher = {Springer Nature}, title = {{Age dating of an early Milky Way merger via asteroseismology of the naked-eye star ν Indi}}, doi = {10.1038/s41550-019-0975-9}, volume = {4}, year = {2020}, } @article{11612, abstract = {Since the onset of the "space revolution" of high-precision high-cadence photometry, asteroseismology has been demonstrated as a powerful tool for informing Galactic archeology investigations. The launch of the NASA Transiting Exoplanet Survey Satellite (TESS) mission has enabled seismic-based inferences to go full sky—providing a clear advantage for large ensemble studies of the different Milky Way components. Here we demonstrate its potential for investigating the Galaxy by carrying out the first asteroseismic ensemble study of red giant stars observed by TESS. We use a sample of 25 stars for which we measure their global asteroseimic observables and estimate their fundamental stellar properties, such as radius, mass, and age. Significant improvements are seen in the uncertainties of our estimates when combining seismic observables from TESS with astrometric measurements from the Gaia mission compared to when the seismology and astrometry are applied separately. Specifically, when combined we show that stellar radii can be determined to a precision of a few percent, masses to 5%–10%, and ages to the 20% level. This is comparable to the precision typically obtained using end-of-mission Kepler data.}, author = {Aguirre, Víctor Silva and Stello, Dennis and Stokholm, Amalie and Mosumgaard, Jakob R. and Ball, Warrick H. and Basu, Sarbani and Bossini, Diego and Bugnet, Lisa Annabelle and Buzasi, Derek and Campante, Tiago L. and Carboneau, Lindsey and Chaplin, William J. and Corsaro, Enrico and Davies, Guy R. and Elsworth, Yvonne and García, Rafael A. and Gaulme, Patrick and Hall, Oliver J. and Handberg, Rasmus and Hon, Marc and Kallinger, Thomas and Kang, Liu and Lund, Mikkel N. and Mathur, Savita and Mints, Alexey and Mosser, Benoit and Çelik Orhan, Zeynep and Rodrigues, Thaíse S. and Vrard, Mathieu and Yıldız, Mutlu and Zinn, Joel C. and Örtel, Sibel and Beck, Paul G. and Bell, Keaton J. and Guo, Zhao and Jiang, Chen and Kuszlewicz, James S. and Kuehn, Charles A. and Li, Tanda and Lundkvist, Mia S. and Pinsonneault, Marc and Tayar, Jamie and Cunha, Margarida S. and Hekker, Saskia and Huber, Daniel and Miglio, Andrea and F. G. Monteiro, Mario J. P. and Slumstrup, Ditte and Winther, Mark L. and Angelou, George and Benomar, Othman and Bódi, Attila and De Moura, Bruno L. and Deheuvels, Sébastien and Derekas, Aliz and Di Mauro, Maria Pia and Dupret, Marc-Antoine and Jiménez, Antonio and Lebreton, Yveline and Matthews, Jaymie and Nardetto, Nicolas and do Nascimento, Jose D. and Pereira, Filipe and Rodríguez Díaz, Luisa F. and Serenelli, Aldo M. and Spitoni, Emanuele and Stonkutė, Edita and Suárez, Juan Carlos and Szabó, Robert and Van Eylen, Vincent and Ventura, Rita and Verma, Kuldeep and Weiss, Achim and Wu, Tao and Barclay, Thomas and Christensen-Dalsgaard, Jørgen and Jenkins, Jon M. and Kjeldsen, Hans and Ricker, George R. and Seager, Sara and Vanderspek, Roland}, issn = {1538-4357}, journal = {The Astrophysical Journal Letters}, keywords = {Space and Planetary Science, Astronomy and Astrophysics}, number = {2}, publisher = {IOP Publishing}, title = {{Detection and characterization of oscillating red giants: First results from the TESS satellite}}, doi = {10.3847/2041-8213/ab6443}, volume = {889}, year = {2020}, } @inbook{11622, abstract = {The recent discovery of low-amplitude dipolar oscillation mixed modes in massive red giants indicates the presence of a missing physical process inside their cores. Stars more massive than ∼ 1.3 M⊙ are known to develop a convective core during the main-sequence: the dynamo process triggered by this convection could be the origin of a strong magnetic field inside the core of the star, trapped when it becomes stably stratified and for the rest of its evolution. The presence of highly magnetized white dwarfs strengthens the hypothesis of buried fossil magnetic fields inside the core of evolved low-mass stars. If such a fossil field exists, it should affect the mixed modes of red giants as they are sensitive to processes affecting the deepest layers of these stars. The impact of a magnetic field on dipolar oscillations modes was one of Pr. Michael J. Thompson’s research topics during the 90s when preparing the helioseismic SoHO space mission. As the detection of gravity modes in the Sun is still controversial, the investigation of the solar oscillation modes did not provide any hint of the existence of a magnetic field in the solar radiative core. Today we have access to the core of evolved stars thanks to the asteroseismic observation of mixed modes from CoRoT, Kepler, K2 and TESS missions. The idea of applying and generalizing the work done for the Sun came from discussions with Pr. Michael Thompson in early 2018 before we lost him. Following the path we drew together, we theoretically investigate the effect of a stable axisymmetric mixed poloidal and toroidal magnetic field, aligned with the rotation axis of the star, on the mixed modes frequencies of a typical evolved low-mass star. This enables us to estimate the magnetic perturbations to the eigenfrequencies of mixed dipolar modes, depending on the magnetic field strength and the evolutionary state of the star. We conclude that strong magnetic fields of ∼ 1MG should perturb the mixed-mode frequency pattern enough for its effects to be detectable inside current asteroseismic data.}, author = {Bugnet, Lisa Annabelle and Prat, V. and Mathis, S. and García, R. A. and Mathur, S. and Augustson, K. and Neiner, C. and Thompson, M. J.}, booktitle = {Dynamics of the Sun and Stars}, editor = {Monteiro, Mario and Garcia, Rafael A and Christensen-Dalsgaard, Jorgen and McIntosh, Scott W}, isbn = {978-3-030-55335-7}, issn = {1570-6605}, pages = {251--257}, publisher = {Springer Nature}, title = {{The impact of a fossil magnetic field on dipolar mixed-mode frequencies in sub- and red-giant stars}}, doi = {10.1007/978-3-030-55336-4_33}, volume = {57}, year = {2020}, } @article{11675, abstract = {We consider the problems of maintaining an approximate maximum matching and an approximate minimum vertex cover in a dynamic graph undergoing a sequence of edge insertions/deletions. Starting with the seminal work of Onak and Rubinfeld (in: Proceedings of the ACM symposium on theory of computing (STOC), 2010), this problem has received significant attention in recent years. Very recently, extending the framework of Baswana et al. (in: Proceedings of the IEEE symposium on foundations of computer science (FOCS), 2011) , Solomon (in: Proceedings of the IEEE symposium on foundations of computer science (FOCS), 2016) gave a randomized dynamic algorithm for this problem that has an approximation ratio of 2 and an amortized update time of O(1) with high probability. This algorithm requires the assumption of an oblivious adversary, meaning that the future sequence of edge insertions/deletions in the graph cannot depend in any way on the algorithm’s past output. A natural way to remove the assumption on oblivious adversary is to give a deterministic dynamic algorithm for the same problem in O(1) update time. In this paper, we resolve this question. We present a new deterministic fully dynamic algorithm that maintains a O(1)-approximate minimum vertex cover and maximum fractional matching, with an amortized update time of O(1). Previously, the best deterministic algorithm for this problem was due to Bhattacharya et al. (in: Proceedings of the ACM-SIAM symposium on discrete algorithms (SODA), 2015); it had an approximation ratio of (2+ε) and an amortized update time of O(logn/ε2). Our result can be generalized to give a fully dynamic O(f3)-approximate algorithm with O(f2) amortized update time for the hypergraph vertex cover and fractional hypergraph matching problem, where every hyperedge has at most f vertices.}, author = {Bhattacharya, Sayan and Chakrabarty, Deeparnab and Henzinger, Monika H}, issn = {1432-0541}, journal = {Algorithmica}, keywords = {Dynamic algorithms, Data structures, Graph algorithms, Matching, Vertex cover}, number = {4}, pages = {1057--1080}, publisher = {Springer Nature}, title = {{Deterministic dynamic matching in O(1) update time}}, doi = {10.1007/s00453-019-00630-4}, volume = {82}, year = {2020}, } @article{11674, abstract = {In this paper, we study the problem of opening centers to cluster a set of clients in a metric space so as to minimize the sum of the costs of the centers and of the cluster radii, in a dynamic environment where clients arrive and depart, and the solution must be updated efficiently while remaining competitive with respect to the current optimal solution. We call this dynamic sum-of-radii clustering problem. We present a data structure that maintains a solution whose cost is within a constant factor of the cost of an optimal solution in metric spaces with bounded doubling dimension and whose worst-case update time is logarithmic in the parameters of the problem.}, author = {Henzinger, Monika H and Leniowski, Dariusz and Mathieu, Claire}, issn = {1432-0541}, journal = {Algorithmica}, number = {11}, pages = {3183--3194}, publisher = {Springer Nature}, title = {{Dynamic clustering to minimize the sum of radii}}, doi = {10.1007/s00453-020-00721-7}, volume = {82}, year = {2020}, } @inproceedings{11818, abstract = {With input sizes becoming massive, coresets - small yet representative summary of the input - are relevant more than ever. A weighted set C_w that is a subset of the input is an ε-coreset if the cost of any feasible solution S with respect to C_w is within [1±ε] of the cost of S with respect to the original input. We give a very general technique to compute coresets in the fully-dynamic setting where input points can be added or deleted. Given a static (i.e., not dynamic) ε-coreset-construction algorithm that runs in time t(n, ε, λ) and computes a coreset of size s(n, ε, λ), where n is the number of input points and 1-λ is the success probability, we give a fully-dynamic algorithm that computes an ε-coreset with worst-case update time O((log n) ⋅ t(s(n, ε/log n, λ/n), ε/log n, λ/n)) (this bound is stated informally), where the success probability is 1-λ. Our technique is a fully-dynamic analog of the merge-and-reduce technique, which is due to Har-Peled and Mazumdar [Har-Peled and Mazumdar, 2004] and is based on a technique of Bentley and Saxe [Jon Louis Bentley and James B. Saxe, 1980], that applies to the insertion-only setting where points can only be added. Although, our space usage is O(n), our technique works in the presence of an adaptive adversary, and we show that Ω(n) space is required when adversary is adaptive. As a concrete implication of our technique, using the result of Braverman et al. [{Braverman} et al., 2016], we get fully-dynamic ε-coreset-construction algorithms for k-median and k-means with worst-case update time O(ε^{-2} k² log⁵ n log³ k) and coreset size O(ε^{-2} k log n log² k) ignoring log log n and log(1/ε) factors and assuming that ε = Ω(1/poly(n)) and λ = Ω(1/poly(n)) (which are very weak assumptions made only to make these bounds easy to parse). This results in the first fully-dynamic constant-approximation algorithms for k-median and k-means with update times O(poly(k, log n, ε^{-1})). Specifically, the dependence on k is only quadratic, and the bounds are worst-case. The best previous bound for both problems was amortized O(nlog n) by Cohen-Addad et al. [Cohen-Addad et al., 2019] via randomized O(1)-coresets in O(n) space. We also show that under the OMv conjecture [Monika Henzinger et al., 2015], a fully-dynamic (4 - δ)-approximation algorithm for k-means must either have an amortized update time of Ω(k^{1-γ}) or amortized query time of Ω(k^{2 - γ}), where γ > 0 is a constant.}, author = {Henzinger, Monika H and Kale, Sagar}, booktitle = {28th Annual European Symposium on Algorithms}, isbn = {9783959771627}, issn = {1868-8969}, location = {Pisa, Italy}, publisher = {Schloss Dagstuhl - Leibniz-Zentrum für Informatik}, title = {{Fully-dynamic coresets}}, doi = {10.4230/LIPIcs.ESA.2020.57}, volume = {173}, year = {2020}, } @inproceedings{11816, abstract = {In recent years, significant advances have been made in the design and analysis of fully dynamic maximal matching algorithms. However, these theoretical results have received very little attention from the practical perspective. Few of the algorithms are implemented and tested on real datasets, and their practical potential is far from understood. In this paper, we attempt to bridge the gap between theory and practice that is currently observed for the fully dynamic maximal matching problem. We engineer several algorithms and empirically study those algorithms on an extensive set of dynamic instances.}, author = {Henzinger, Monika H and Shahbaz, Khan and Paul, Richard and Schulz, Christian}, booktitle = {8th Annual European Symposium on Algorithms}, isbn = {9783959771627}, issn = {1868-8969}, location = {Pisa, Italy}, publisher = {Schloss Dagstuhl - Leibniz-Zentrum für Informatik}, title = {{Dynamic matching algorithms in practice}}, doi = {10.4230/LIPIcs.ESA.2020.58}, volume = {173}, year = {2020}, } @inproceedings{11824, abstract = {Independent set is a fundamental problem in combinatorial optimization. While in general graphs the problem is essentially inapproximable, for many important graph classes there are approximation algorithms known in the offline setting. These graph classes include interval graphs and geometric intersection graphs, where vertices correspond to intervals/geometric objects and an edge indicates that the two corresponding objects intersect. We present dynamic approximation algorithms for independent set of intervals, hypercubes and hyperrectangles in d dimensions. They work in the fully dynamic model where each update inserts or deletes a geometric object. All our algorithms are deterministic and have worst-case update times that are polylogarithmic for constant d and ε>0, assuming that the coordinates of all input objects are in [0, N]^d and each of their edges has length at least 1. We obtain the following results: - For weighted intervals, we maintain a (1+ε)-approximate solution. - For d-dimensional hypercubes we maintain a (1+ε)2^d-approximate solution in the unweighted case and a O(2^d)-approximate solution in the weighted case. Also, we show that for maintaining an unweighted (1+ε)-approximate solution one needs polynomial update time for d ≥ 2 if the ETH holds. - For weighted d-dimensional hyperrectangles we present a dynamic algorithm with approximation ratio (1+ε)log^{d-1}N.}, author = {Henzinger, Monika H and Neumann, Stefan and Wiese, Andreas}, booktitle = {36th International Symposium on Computational Geometry}, isbn = {9783959771436}, issn = {1868-8969}, location = {Zurich, Switzerland}, publisher = {Schloss Dagstuhl - Leibniz-Zentrum für Informatik}, title = {{Dynamic approximate maximum independent set of intervals, hypercubes and hyperrectangles}}, doi = {10.4230/LIPIcs.SoCG.2020.51}, volume = {164}, year = {2020}, }