@misc{9192, abstract = {Here are the research data underlying the publication " Effects of fine-scale population structure on inbreeding in a long-term study of snapdragons (Antirrhinum majus)." Further information are summed up in the README document.}, author = {Surendranadh, Parvathy and Arathoon, Louise S and Baskett, Carina and Field, David and Pickup, Melinda and Barton, Nicholas H}, publisher = {Institute of Science and Technology Austria}, title = {{Effects of fine-scale population structure on the distribution of heterozygosity in a long-term study of Antirrhinum majus}}, doi = {10.15479/AT:ISTA:9192}, year = {2021}, } @misc{9949, author = {Vicoso, Beatriz}, publisher = {Institute of Science and Technology Austria}, title = {{Data from Hyulmans et al 2021, "Transitions to asexuality and evolution of gene expression in Artemia brine shrimp"}}, doi = {10.15479/AT:ISTA:9949}, year = {2021}, } @article{8997, abstract = {Phenomenological relations such as Ohm’s or Fourier’s law have a venerable history in physics but are still scarce in biology. This situation restrains predictive theory. Here, we build on bacterial “growth laws,” which capture physiological feedback between translation and cell growth, to construct a minimal biophysical model for the combined action of ribosome-targeting antibiotics. Our model predicts drug interactions like antagonism or synergy solely from responses to individual drugs. We provide analytical results for limiting cases, which agree well with numerical results. We systematically refine the model by including direct physical interactions of different antibiotics on the ribosome. In a limiting case, our model provides a mechanistic underpinning for recent predictions of higher-order interactions that were derived using entropy maximization. We further refine the model to include the effects of antibiotics that mimic starvation and the presence of resistance genes. We describe the impact of a starvation-mimicking antibiotic on drug interactions analytically and verify it experimentally. Our extended model suggests a change in the type of drug interaction that depends on the strength of resistance, which challenges established rescaling paradigms. We experimentally show that the presence of unregulated resistance genes can lead to altered drug interaction, which agrees with the prediction of the model. While minimal, the model is readily adaptable and opens the door to predicting interactions of second and higher-order in a broad range of biological systems.}, author = {Kavcic, Bor and Tkačik, Gašper and Bollenbach, Tobias}, issn = {1553-7358}, journal = {PLOS Computational Biology}, keywords = {Modelling and Simulation, Genetics, Molecular Biology, Antibiotics, Drug interactions}, publisher = {Public Library of Science}, title = {{Minimal biophysical model of combined antibiotic action}}, doi = {10.1371/journal.pcbi.1008529}, volume = {17}, year = {2021}, } @article{9283, abstract = {Gene expression levels are influenced by multiple coexisting molecular mechanisms. Some of these interactions such as those of transcription factors and promoters have been studied extensively. However, predicting phenotypes of gene regulatory networks (GRNs) remains a major challenge. Here, we use a well-defined synthetic GRN to study in Escherichia coli how network phenotypes depend on local genetic context, i.e. the genetic neighborhood of a transcription factor and its relative position. We show that one GRN with fixed topology can display not only quantitatively but also qualitatively different phenotypes, depending solely on the local genetic context of its components. Transcriptional read-through is the main molecular mechanism that places one transcriptional unit (TU) within two separate regulons without the need for complex regulatory sequences. We propose that relative order of individual TUs, with its potential for combinatorial complexity, plays an important role in shaping phenotypes of GRNs.}, author = {Nagy-Staron, Anna A and Tomasek, Kathrin and Caruso Carter, Caroline and Sonnleitner, Elisabeth and Kavcic, Bor and Paixão, Tiago and Guet, Calin C}, issn = {2050-084X}, journal = {eLife}, keywords = {Genetics and Molecular Biology}, publisher = {eLife Sciences Publications}, title = {{Local genetic context shapes the function of a gene regulatory network}}, doi = {10.7554/elife.65993}, volume = {10}, year = {2021}, } @article{10184, abstract = {We introduce a novel technique to automatically decompose an input object’s volume into a set of parts that can be represented by two opposite height fields. Such decomposition enables the manufacturing of individual parts using two-piece reusable rigid molds. Our decomposition strategy relies on a new energy formulation that utilizes a pre-computed signal on the mesh volume representing the accessibility for a predefined set of extraction directions. Thanks to this novel formulation, our method allows for efficient optimization of a fabrication-aware partitioning of volumes in a completely automatic way. We demonstrate the efficacy of our approach by generating valid volume partitionings for a wide range of complex objects and physically reproducing several of them.}, author = {Alderighi, Thomas and Malomo, Luigi and Bickel, Bernd and Cignoni, Paolo and Pietroni, Nico}, issn = {1557-7368 }, journal = {ACM Transactions on Graphics}, number = {6}, publisher = {Association for Computing Machinery}, title = {{Volume decomposition for two-piece rigid casting}}, doi = {10.1145/3478513.3480555}, volume = {40}, year = {2021}, } @article{9541, abstract = {The Massively Parallel Computation (MPC) model is an emerging model that distills core aspects of distributed and parallel computation, developed as a tool to solve combinatorial (typically graph) problems in systems of many machines with limited space. Recent work has focused on the regime in which machines have sublinear (in n, the number of nodes in the input graph) space, with randomized algorithms presented for the fundamental problems of Maximal Matching and Maximal Independent Set. However, there have been no prior corresponding deterministic algorithms. A major challenge underlying the sublinear space setting is that the local space of each machine might be too small to store all edges incident to a single node. This poses a considerable obstacle compared to classical models in which each node is assumed to know and have easy access to its incident edges. To overcome this barrier, we introduce a new graph sparsification technique that deterministically computes a low-degree subgraph, with the additional property that solving the problem on this subgraph provides significant progress towards solving the problem for the original input graph. Using this framework to derandomize the well-known algorithm of Luby [SICOMP’86], we obtain O(log Δ + log log n)-round deterministic MPC algorithms for solving the problems of Maximal Matching and Maximal Independent Set with O(nɛ) space on each machine for any constant ɛ > 0. These algorithms also run in O(log Δ) rounds in the closely related model of CONGESTED CLIQUE, improving upon the state-of-the-art bound of O(log 2Δ) rounds by Censor-Hillel et al. [DISC’17].}, author = {Czumaj, Artur and Davies, Peter and Parter, Merav}, issn = {1549-6333}, journal = {ACM Transactions on Algorithms}, number = {2}, publisher = {Association for Computing Machinery}, title = {{Graph sparsification for derandomizing massively parallel computation with low space}}, doi = {10.1145/3451992}, volume = {17}, year = {2021}, } @article{10134, abstract = {We investigate the effect of coupling between translational and internal degrees of freedom of composite quantum particles on their localization in a random potential. We show that entanglement between the two degrees of freedom weakens localization due to the upper bound imposed on the inverse participation ratio by purity of a quantum state. We perform numerical calculations for a two-particle system bound by a harmonic force in a 1D disordered lattice and a rigid rotor in a 2D disordered lattice. We illustrate that the coupling has a dramatic effect on localization properties, even with a small number of internal states participating in quantum dynamics.}, author = {Suzuki, Fumika and Lemeshko, Mikhail and Zurek, Wojciech H. and Krems, Roman V.}, issn = {1079-7114}, journal = {Physical Review Letters}, keywords = {General Physics and Astronomy}, number = {16}, publisher = {American Physical Society }, title = {{Anderson localization of composite particles}}, doi = {10.1103/physrevlett.127.160602}, volume = {127}, year = {2021}, } @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{9002, abstract = { We prove that, for the binary erasure channel (BEC), the polar-coding paradigm gives rise to codes that not only approach the Shannon limit but do so under the best possible scaling of their block length as a function of the gap to capacity. This result exhibits the first known family of binary codes that attain both optimal scaling and quasi-linear complexity of encoding and decoding. Our proof is based on the construction and analysis of binary polar codes with large kernels. When communicating reliably at rates within ε>0 of capacity, the code length n often scales as O(1/εμ), where the constant μ is called the scaling exponent. It is known that the optimal scaling exponent is μ=2, and it is achieved by random linear codes. The scaling exponent of conventional polar codes (based on the 2×2 kernel) on the BEC is μ=3.63. This falls far short of the optimal scaling guaranteed by random codes. Our main contribution is a rigorous proof of the following result: for the BEC, there exist ℓ×ℓ binary kernels, such that polar codes constructed from these kernels achieve scaling exponent μ(ℓ) that tends to the optimal value of 2 as ℓ grows. We furthermore characterize precisely how large ℓ needs to be as a function of the gap between μ(ℓ) and 2. The resulting binary codes maintain the recursive structure of conventional polar codes, and thereby achieve construction complexity O(n) and encoding/decoding complexity O(nlogn).}, author = {Fazeli, Arman and Hassani, Hamed and Mondelli, Marco and Vardy, Alexander}, issn = {1557-9654}, journal = {IEEE Transactions on Information Theory}, number = {9}, pages = {5693--5710}, publisher = {IEEE}, title = {{Binary linear codes with optimal scaling: Polar codes with large kernels}}, doi = {10.1109/TIT.2020.3038806}, volume = {67}, 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{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}, } @inbook{9756, abstract = {High-resolution visualization and quantification of membrane proteins contribute to the understanding of their functions and the roles they play in physiological and pathological conditions. Sodium dodecyl sulfate-digested freeze-fracture replica labeling (SDS-FRL) is a powerful electron microscopy method to study quantitatively the two-dimensional distribution of transmembrane proteins and their tightly associated proteins. During treatment with SDS, intracellular organelles and proteins not anchored to the replica are dissolved, whereas integral membrane proteins captured and stabilized by carbon/platinum deposition remain on the replica. Their intra- and extracellular domains become exposed on the surface of the replica, facilitating the accessibility of antibodies and, therefore, providing higher labeling efficiency than those obtained with other immunoelectron microscopy techniques. In this chapter, we describe the protocols of SDS-FRL adapted for mammalian brain samples, and optimization of the SDS treatment to increase the labeling efficiency for quantification of Cav2.1, the alpha subunit of P/Q-type voltage-dependent calcium channels utilizing deep learning algorithms.}, author = {Kaufmann, Walter and Kleindienst, David and Harada, Harumi and Shigemoto, Ryuichi}, booktitle = { Receptor and Ion Channel Detection in the Brain}, isbn = {9781071615218}, keywords = {Freeze-fracture replica: Deep learning, Immunogold labeling, Integral membrane protein, Electron microscopy}, pages = {267--283}, publisher = {Humana}, title = {{High-Resolution localization and quantitation of membrane proteins by SDS-digested freeze-fracture replica labeling (SDS-FRL)}}, doi = {10.1007/978-1-0716-1522-5_19}, volume = {169}, 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}, }