@inproceedings{10665, abstract = {Formal verification of neural networks is an active topic of research, and recent advances have significantly increased the size of the networks that verification tools can handle. However, most methods are designed for verification of an idealized model of the actual network which works over real arithmetic and ignores rounding imprecisions. This idealization is in stark contrast to network quantization, which is a technique that trades numerical precision for computational efficiency and is, therefore, often applied in practice. Neglecting rounding errors of such low-bit quantized neural networks has been shown to lead to wrong conclusions about the network’s correctness. Thus, the desired approach for verifying quantized neural networks would be one that takes these rounding errors into account. In this paper, we show that verifying the bitexact implementation of quantized neural networks with bitvector specifications is PSPACE-hard, even though verifying idealized real-valued networks and satisfiability of bit-vector specifications alone are each in NP. Furthermore, we explore several practical heuristics toward closing the complexity gap between idealized and bit-exact verification. In particular, we propose three techniques for making SMT-based verification of quantized neural networks more scalable. Our experiments demonstrate that our proposed methods allow a speedup of up to three orders of magnitude over existing approaches.}, author = {Henzinger, Thomas A and Lechner, Mathias and Zikelic, Dorde}, booktitle = {Proceedings of the AAAI Conference on Artificial Intelligence}, isbn = {978-1-57735-866-4}, issn = {2374-3468}, location = {Virtual}, number = {5A}, pages = {3787--3795}, publisher = {AAAI Press}, title = {{Scalable verification of quantized neural networks}}, doi = {10.1609/aaai.v35i5.16496}, volume = {35}, year = {2021}, } @inproceedings{10671, abstract = {We introduce a new class of time-continuous recurrent neural network models. Instead of declaring a learning system’s dynamics by implicit nonlinearities, we construct networks of linear first-order dynamical systems modulated via nonlinear interlinked gates. The resulting models represent dynamical systems with varying (i.e., liquid) time-constants coupled to their hidden state, with outputs being computed by numerical differential equation solvers. These neural networks exhibit stable and bounded behavior, yield superior expressivity within the family of neural ordinary differential equations, and give rise to improved performance on time-series prediction tasks. To demonstrate these properties, we first take a theoretical approach to find bounds over their dynamics, and compute their expressive power by the trajectory length measure in a latent trajectory space. We then conduct a series of time-series prediction experiments to manifest the approximation capability of Liquid Time-Constant Networks (LTCs) compared to classical and modern RNNs.}, author = {Hasani, Ramin and Lechner, Mathias and Amini, Alexander and Rus, Daniela and Grosu, Radu}, booktitle = {Proceedings of the AAAI Conference on Artificial Intelligence}, isbn = {978-1-57735-866-4}, issn = {2374-3468}, location = {Virtual}, number = {9}, pages = {7657--7666}, publisher = {AAAI Press}, title = {{Liquid time-constant networks}}, doi = {10.1609/aaai.v35i9.16936}, volume = {35}, year = {2021}, } @inproceedings{11436, abstract = {Asynchronous distributed algorithms are a popular way to reduce synchronization costs in large-scale optimization, and in particular for neural network training. However, for nonsmooth and nonconvex objectives, few convergence guarantees exist beyond cases where closed-form proximal operator solutions are available. As training most popular deep neural networks corresponds to optimizing nonsmooth and nonconvex objectives, there is a pressing need for such convergence guarantees. In this paper, we analyze for the first time the convergence of stochastic asynchronous optimization for this general class of objectives. In particular, we focus on stochastic subgradient methods allowing for block variable partitioning, where the shared model is asynchronously updated by concurrent processes. To this end, we use a probabilistic model which captures key features of real asynchronous scheduling between concurrent processes. Under this model, we establish convergence with probability one to an invariant set for stochastic subgradient methods with momentum. From a practical perspective, one issue with the family of algorithms that we consider is that they are not efficiently supported by machine learning frameworks, which mostly focus on distributed data-parallel strategies. To address this, we propose a new implementation strategy for shared-memory based training of deep neural networks for a partitioned but shared model in single- and multi-GPU settings. Based on this implementation, we achieve on average1.2x speed-up in comparison to state-of-the-art training methods for popular image classification tasks, without compromising accuracy.}, author = {Kungurtsev, Vyacheslav and Egan, Malcolm and Chatterjee, Bapi and Alistarh, Dan-Adrian}, booktitle = {35th AAAI Conference on Artificial Intelligence, AAAI 2021}, isbn = {9781713835974}, issn = {2374-3468}, location = {Virtual, Online}, number = {9B}, pages = {8209--8216}, publisher = {AAAI Press}, title = {{Asynchronous optimization methods for efficient training of deep neural networks with guarantees}}, doi = {10.1609/aaai.v35i9.16999}, volume = {35}, year = {2021}, } @inproceedings{10669, abstract = {We show that Neural ODEs, an emerging class of timecontinuous neural networks, can be verified by solving a set of global-optimization problems. For this purpose, we introduce Stochastic Lagrangian Reachability (SLR), an abstraction-based technique for constructing a tight Reachtube (an over-approximation of the set of reachable states over a given time-horizon), and provide stochastic guarantees in the form of confidence intervals for the Reachtube bounds. SLR inherently avoids the infamous wrapping effect (accumulation of over-approximation errors) by performing local optimization steps to expand safe regions instead of repeatedly forward-propagating them as is done by deterministic reachability methods. To enable fast local optimizations, we introduce a novel forward-mode adjoint sensitivity method to compute gradients without the need for backpropagation. Finally, we establish asymptotic and non-asymptotic convergence rates for SLR.}, author = {Grunbacher, Sophie and Hasani, Ramin and Lechner, Mathias and Cyranka, Jacek and Smolka, Scott A and Grosu, Radu}, booktitle = {Proceedings of the AAAI Conference on Artificial Intelligence}, isbn = {978-1-57735-866-4}, issn = {2374-3468}, location = {Virtual}, number = {13}, pages = {11525--11535}, publisher = {AAAI Press}, title = {{On the verification of neural ODEs with stochastic guarantees}}, doi = {10.1609/aaai.v35i13.17372}, volume = {35}, year = {2021}, } @phdthesis{10429, abstract = {The scalability of concurrent data structures and distributed algorithms strongly depends on reducing the contention for shared resources and the costs of synchronization and communication. We show how such cost reductions can be attained by relaxing the strict consistency conditions required by sequential implementations. In the first part of the thesis, we consider relaxation in the context of concurrent data structures. Specifically, in data structures such as priority queues, imposing strong semantics renders scalability impossible, since a correct implementation of the remove operation should return only the element with highest priority. Intuitively, attempting to invoke remove operations concurrently creates a race condition. This bottleneck can be circumvented by relaxing semantics of the affected data structure, thus allowing removal of the elements which are no longer required to have the highest priority. We prove that the randomized implementations of relaxed data structures provide provable guarantees on the priority of the removed elements even under concurrency. Additionally, we show that in some cases the relaxed data structures can be used to scale the classical algorithms which are usually implemented with the exact ones. In the second part, we study parallel variants of the stochastic gradient descent (SGD) algorithm, which distribute computation among the multiple processors, thus reducing the running time. Unfortunately, in order for standard parallel SGD to succeed, each processor has to maintain a local copy of the necessary model parameter, which is identical to the local copies of other processors; the overheads from this perfect consistency in terms of communication and synchronization can negate the speedup gained by distributing the computation. We show that the consistency conditions required by SGD can be relaxed, allowing the algorithm to be more flexible in terms of tolerating quantized communication, asynchrony, or even crash faults, while its convergence remains asymptotically the same.}, author = {Nadiradze, Giorgi}, issn = {2663-337X}, pages = {132}, publisher = {Institute of Science and Technology Austria}, title = {{On achieving scalability through relaxation}}, doi = {10.15479/at:ista:10429}, year = {2021}, } @inproceedings{10432, abstract = {One key element behind the recent progress of machine learning has been the ability to train machine learning models in large-scale distributed shared-memory and message-passing environments. Most of these models are trained employing variants of stochastic gradient descent (SGD) based optimization, but most methods involve some type of consistency relaxation relative to sequential SGD, to mitigate its large communication or synchronization costs at scale. In this paper, we introduce a general consistency condition covering communication-reduced and asynchronous distributed SGD implementations. Our framework, called elastic consistency, decouples the system-specific aspects of the implementation from the SGD convergence requirements, giving a general way to obtain convergence bounds for a wide variety of distributed SGD methods used in practice. Elastic consistency can be used to re-derive or improve several previous convergence bounds in message-passing and shared-memory settings, but also to analyze new models and distribution schemes. As a direct application, we propose and analyze a new synchronization-avoiding scheduling scheme for distributed SGD, and show that it can be used to efficiently train deep convolutional models for image classification.}, author = {Nadiradze, Giorgi and Markov, Ilia and Chatterjee, Bapi and Kungurtsev, Vyacheslav and Alistarh, Dan-Adrian}, booktitle = {Proceedings of the AAAI Conference on Artificial Intelligence}, location = {Virtual}, number = {10}, pages = {9037--9045}, title = {{Elastic consistency: A practical consistency model for distributed stochastic gradient descent}}, doi = {10.1609/aaai.v35i10.17092}, volume = {35}, year = {2021}, } @unpublished{12077, abstract = {We compare the Manin-type conjecture for Campana points recently formulated by Pieropan, Smeets, Tanimoto and V\'{a}rilly-Alvarado with an alternative prediction of Browning and Van Valckenborgh in the special case of the orbifold $(\mathbb{P}^1,D)$, where $D =\frac{1}{2}[0]+\frac{1}{2}[1]+\frac{1}{2}[\infty]$. We find that the two predicted leading constants do not agree, and we discuss whether thin sets could explain this discrepancy. Motivated by this, we provide a counterexample to the Manin-type conjecture for Campana points, by considering orbifolds corresponding to squareful values of binary quadratic forms.}, author = {Shute, Alec L}, booktitle = {arXiv}, title = {{On the leading constant in the Manin-type conjecture for Campana points}}, doi = {10.48550/arXiv.2104.14946}, year = {2021}, } @article{9558, abstract = {We show that turbulent dynamics that arise in simulations of the three-dimensional Navier--Stokes equations in a triply-periodic domain under sinusoidal forcing can be described as transient visits to the neighborhoods of unstable time-periodic solutions. Based on this description, we reduce the original system with more than 10^5 degrees of freedom to a 17-node Markov chain where each node corresponds to the neighborhood of a periodic orbit. The model accurately reproduces long-term averages of the system's observables as weighted sums over the periodic orbits. }, author = {Yalniz, Gökhan and Hof, Björn and Budanur, Nazmi B}, issn = {1079-7114}, journal = {Physical Review Letters}, number = {24}, publisher = {American Physical Society}, title = {{Coarse graining the state space of a turbulent flow using periodic orbits}}, doi = {10.1103/PhysRevLett.126.244502}, volume = {126}, year = {2021}, } @inproceedings{10408, abstract = {Key trees are often the best solution in terms of transmission cost and storage requirements for managing keys in a setting where a group needs to share a secret key, while being able to efficiently rotate the key material of users (in order to recover from a potential compromise, or to add or remove users). Applications include multicast encryption protocols like LKH (Logical Key Hierarchies) or group messaging like the current IETF proposal TreeKEM. A key tree is a (typically balanced) binary tree, where each node is identified with a key: leaf nodes hold users’ secret keys while the root is the shared group key. For a group of size N, each user just holds log(N) keys (the keys on the path from its leaf to the root) and its entire key material can be rotated by broadcasting 2log(N) ciphertexts (encrypting each fresh key on the path under the keys of its parents). In this work we consider the natural setting where we have many groups with partially overlapping sets of users, and ask if we can find solutions where the cost of rotating a key is better than in the trivial one where we have a separate key tree for each group. We show that in an asymptotic setting (where the number m of groups is fixed while the number N of users grows) there exist more general key graphs whose cost converges to the cost of a single group, thus saving a factor linear in the number of groups over the trivial solution. As our asymptotic “solution” converges very slowly and performs poorly on concrete examples, we propose an algorithm that uses a natural heuristic to compute a key graph for any given group structure. Our algorithm combines two greedy algorithms, and is thus very efficient: it first converts the group structure into a “lattice graph”, which is then turned into a key graph by repeatedly applying the algorithm for constructing a Huffman code. To better understand how far our proposal is from an optimal solution, we prove lower bounds on the update cost of continuous group-key agreement and multicast encryption in a symbolic model admitting (asymmetric) encryption, pseudorandom generators, and secret sharing as building blocks.}, author = {Alwen, Joel F and Auerbach, Benedikt and Baig, Mirza Ahad and Cueto Noval, Miguel and Klein, Karen and Pascual Perez, Guillermo and Pietrzak, Krzysztof Z and Walter, Michael}, booktitle = {19th International Conference}, isbn = {9-783-0309-0455-5}, issn = {1611-3349}, location = {Raleigh, NC, United States}, pages = {222--253}, publisher = {Springer Nature}, title = {{Grafting key trees: Efficient key management for overlapping groups}}, doi = {10.1007/978-3-030-90456-2_8}, volume = {13044}, year = {2021}, } @phdthesis{10035, abstract = {Many security definitions come in two flavors: a stronger “adaptive” flavor, where the adversary can arbitrarily make various choices during the course of the attack, and a weaker “selective” flavor where the adversary must commit to some or all of their choices a-priori. For example, in the context of identity-based encryption, selective security requires the adversary to decide on the identity of the attacked party at the very beginning of the game whereas adaptive security allows the attacker to first see the master public key and some secret keys before making this choice. Often, it appears to be much easier to achieve selective security than it is to achieve adaptive security. A series of several recent works shows how to cleverly achieve adaptive security in several such scenarios including generalized selective decryption [Pan07][FJP15], constrained PRFs [FKPR14], and Yao’s garbled circuits [JW16]. Although the above works expressed vague intuition that they share a common technique, the connection was never made precise. In this work we present a new framework (published at Crypto ’17 [JKK+17a]) that connects all of these works and allows us to present them in a unified and simplified fashion. Having the framework in place, we show how to achieve adaptive security for proxy re-encryption schemes (published at PKC ’19 [FKKP19]) and provide the first adaptive security proofs for continuous group key agreement protocols (published at S&P ’21 [KPW+21]). Questioning optimality of our framework, we then show that currently used proof techniques cannot lead to significantly better security guarantees for "graph-building" games (published at TCC ’21 [KKPW21a]). These games cover generalized selective decryption, as well as the security of prominent constructions for constrained PRFs, continuous group key agreement, and proxy re-encryption. Finally, we revisit the adaptive security of Yao’s garbled circuits and extend the analysis of Jafargholi and Wichs in two directions: While they prove adaptive security only for a modified construction with increased online complexity, we provide the first positive results for the original construction by Yao (published at TCC ’21 [KKP21a]). On the negative side, we prove that the results of Jafargholi and Wichs are essentially optimal by showing that no black-box reduction can provide a significantly better security bound (published at Crypto ’21 [KKPW21c]).}, author = {Klein, Karen}, issn = {2663-337X}, pages = {276}, publisher = {Institute of Science and Technology Austria}, title = {{On the adaptive security of graph-based games}}, doi = {10.15479/at:ista:10035}, year = {2021}, } @inproceedings{9826, abstract = {Automated contract tracing aims at supporting manual contact tracing during pandemics by alerting users of encounters with infected people. There are currently many proposals for protocols (like the “decentralized” DP-3T and PACT or the “centralized” ROBERT and DESIRE) to be run on mobile phones, where the basic idea is to regularly broadcast (using low energy Bluetooth) some values, and at the same time store (a function of) incoming messages broadcasted by users in their proximity. In the existing proposals one can trigger false positives on a massive scale by an “inverse-Sybil” attack, where a large number of devices (malicious users or hacked phones) pretend to be the same user, such that later, just a single person needs to be diagnosed (and allowed to upload) to trigger an alert for all users who were in proximity to any of this large group of devices. We propose the first protocols that do not succumb to such attacks assuming the devices involved in the attack do not constantly communicate, which we observe is a necessary assumption. The high level idea of the protocols is to derive the values to be broadcasted by a hash chain, so that two (or more) devices who want to launch an inverse-Sybil attack will not be able to connect their respective chains and thus only one of them will be able to upload. Our protocols also achieve security against replay, belated replay, and one of them even against relay attacks.}, author = {Auerbach, Benedikt and Chakraborty, Suvradip and Klein, Karen and Pascual Perez, Guillermo and Pietrzak, Krzysztof Z and Walter, Michael and Yeo, Michelle X}, booktitle = {Topics in Cryptology – CT-RSA 2021}, isbn = {9783030755386}, issn = {1611-3349}, location = {Virtual Event}, pages = {399--421}, publisher = {Springer Nature}, title = {{Inverse-Sybil attacks in automated contact tracing}}, doi = {10.1007/978-3-030-75539-3_17}, volume = {12704}, year = {2021}, } @inproceedings{10049, abstract = {While messaging systems with strong security guarantees are widely used in practice, designing a protocol that scales efficiently to large groups and enjoys similar security guarantees remains largely open. The two existing proposals to date are ART (Cohn-Gordon et al., CCS18) and TreeKEM (IETF, The Messaging Layer Security Protocol, draft). TreeKEM is the currently considered candidate by the IETF MLS working group, but dynamic group operations (i.e. adding and removing users) can cause efficiency issues. In this paper we formalize and analyze a variant of TreeKEM which we term Tainted TreeKEM (TTKEM for short). The basic idea underlying TTKEM was suggested by Millican (MLS mailing list, February 2018). This version is more efficient than TreeKEM for some natural distributions of group operations, we quantify this through simulations.Our second contribution is two security proofs for TTKEM which establish post compromise and forward secrecy even against adaptive attackers. The security loss (to the underlying PKE) in the Random Oracle Model is a polynomial factor, and a quasipolynomial one in the Standard Model. Our proofs can be adapted to TreeKEM as well. Before our work no security proof for any TreeKEM-like protocol establishing tight security against an adversary who can adaptively choose the sequence of operations was known. We also are the first to prove (or even formalize) active security where the server can arbitrarily deviate from the protocol specification. Proving fully active security – where also the users can arbitrarily deviate – remains open.}, author = {Klein, Karen and Pascual Perez, Guillermo and Walter, Michael and Kamath Hosdurg, Chethan and Capretto, Margarita and Cueto Noval, Miguel and Markov, Ilia and Yeo, Michelle X and Alwen, Joel F and Pietrzak, Krzysztof Z}, booktitle = {2021 IEEE Symposium on Security and Privacy }, location = {San Francisco, CA, United States}, pages = {268--284}, publisher = {IEEE}, title = {{Keep the dirt: tainted TreeKEM, adaptively and actively secure continuous group key agreement}}, doi = {10.1109/sp40001.2021.00035}, year = {2021}, } @inproceedings{9345, abstract = {Modeling a crystal as a periodic point set, we present a fingerprint consisting of density functionsthat facilitates the efficient search for new materials and material properties. We prove invarianceunder isometries, continuity, and completeness in the generic case, which are necessary featuresfor the reliable comparison of crystals. The proof of continuity integrates methods from discretegeometry and lattice theory, while the proof of generic completeness combines techniques fromgeometry with analysis. The fingerprint has a fast algorithm based on Brillouin zones and relatedinclusion-exclusion formulae. We have implemented the algorithm and describe its application tocrystal structure prediction.}, author = {Edelsbrunner, Herbert and Heiss, Teresa and Kurlin , Vitaliy and Smith, Philip and Wintraecken, Mathijs}, booktitle = {37th International Symposium on Computational Geometry}, issn = {1868-8969}, location = {Virtual}, pages = {32:1--32:16}, publisher = {Schloss Dagstuhl - Leibniz-Zentrum für Informatik}, title = {{The density fingerprint of a periodic point set}}, doi = {10.4230/LIPIcs.SoCG.2021.32}, volume = {189}, year = {2021}, } @article{9928, abstract = {There are two elementary superconducting qubit types that derive directly from the quantum harmonic oscillator. In one, the inductor is replaced by a nonlinear Josephson junction to realize the widely used charge qubits with a compact phase variable and a discrete charge wave function. In the other, the junction is added in parallel, which gives rise to an extended phase variable, continuous wave functions, and a rich energy-level structure due to the loop topology. While the corresponding rf superconducting quantum interference device Hamiltonian was introduced as a quadratic quasi-one-dimensional potential approximation to describe the fluxonium qubit implemented with long Josephson-junction arrays, in this work we implement it directly using a linear superinductor formed by a single uninterrupted aluminum wire. We present a large variety of qubits, all stemming from the same circuit but with drastically different characteristic energy scales. This includes flux and fluxonium qubits but also the recently introduced quasicharge qubit with strongly enhanced zero-point phase fluctuations and a heavily suppressed flux dispersion. The use of a geometric inductor results in high reproducibility of the inductive energy as guaranteed by top-down lithography—a key ingredient for intrinsically protected superconducting qubits.}, author = {Peruzzo, Matilda and Hassani, Farid and Szep, Gregory and Trioni, Andrea and Redchenko, Elena and Zemlicka, Martin and Fink, Johannes M}, issn = {2691-3399}, journal = {PRX Quantum}, keywords = {quantum physics, mesoscale and nanoscale physics}, number = {4}, pages = {040341}, publisher = {American Physical Society}, title = {{Geometric superinductance qubits: Controlling phase delocalization across a single Josephson junction}}, doi = {10.1103/PRXQuantum.2.040341}, volume = {2}, year = {2021}, } @article{10067, abstract = {The search for novel entangled phases of matter has lead to the recent discovery of a new class of “entanglement transitions,” exemplified by random tensor networks and monitored quantum circuits. Most known examples can be understood as some classical ordering transitions in an underlying statistical mechanics model, where entanglement maps onto the free-energy cost of inserting a domain wall. In this paper we study the possibility of entanglement transitions driven by physics beyond such statistical mechanics mappings. Motivated by recent applications of neural-network-inspired variational Ansätze, we investigate under what conditions on the variational parameters these Ansätze can capture an entanglement transition. We study the entanglement scaling of short-range restricted Boltzmann machine (RBM) quantum states with random phases. For uncorrelated random phases, we analytically demonstrate the absence of an entanglement transition and reveal subtle finite-size effects in finite-size numerical simulations. Introducing phases with correlations decaying as 1/r^α in real space, we observe three regions with a different scaling of entanglement entropy depending on the exponent α. We study the nature of the transition between these regions, finding numerical evidence for critical behavior. Our work establishes the presence of long-range correlated phases in RBM-based wave functions as a required ingredient for entanglement transitions.}, author = {Medina Ramos, Raimel A and Vasseur, Romain and Serbyn, Maksym}, issn = {2469-9969}, journal = {Physical Review B}, number = {10}, publisher = {American Physical Society}, title = {{Entanglement transitions from restricted Boltzmann machines}}, doi = {10.1103/physrevb.104.104205}, volume = {104}, year = {2021}, } @article{10545, abstract = {Classical models with complex energy landscapes represent a perspective avenue for the near-term application of quantum simulators. Until now, many theoretical works studied the performance of quantum algorithms for models with a unique ground state. However, when the classical problem is in a so-called clustering phase, the ground state manifold is highly degenerate. As an example, we consider a 3-XORSAT model defined on simple hypergraphs. The degeneracy of classical ground state manifold translates into the emergence of an extensive number of Z2 symmetries, which remain intact even in the presence of a quantum transverse magnetic field. We establish a general duality approach that restricts the quantum problem to a given sector of conserved Z2 charges and use it to study how the outcome of the quantum adiabatic algorithm depends on the hypergraph geometry. We show that the tree hypergraph which corresponds to a classically solvable instance of the 3-XORSAT problem features a constant gap, whereas the closed hypergraph encounters a second-order phase transition with a gap vanishing as a power-law in the problem size. The duality developed in this work provides a practical tool for studies of quantum models with classically degenerate energy manifold and reveals potential connections between glasses and gauge theories.}, author = {Medina Ramos, Raimel A and Serbyn, Maksym}, issn = {2469-9934}, journal = {Physical Review A}, number = {6}, publisher = {American Physical Society}, title = {{Duality approach to quantum annealing of the 3-variable exclusive-or satisfiability problem (3-XORSAT)}}, doi = {10.1103/physreva.104.062423}, volume = {104}, 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}, } @article{8602, abstract = {Collective cell migration offers a rich field of study for non-equilibrium physics and cellular biology, revealing phenomena such as glassy dynamics, pattern formation and active turbulence. However, how mechanical and chemical signalling are integrated at the cellular level to give rise to such collective behaviours remains unclear. We address this by focusing on the highly conserved phenomenon of spatiotemporal waves of density and extracellular signal-regulated kinase (ERK) activation, which appear both in vitro and in vivo during collective cell migration and wound healing. First, we propose a biophysical theory, backed by mechanical and optogenetic perturbation experiments, showing that patterns can be quantitatively explained by a mechanochemical coupling between active cellular tensions and the mechanosensitive ERK pathway. Next, we demonstrate how this biophysical mechanism can robustly induce long-ranged order and migration in a desired orientation, and we determine the theoretically optimal wavelength and period for inducing maximal migration towards free edges, which fits well with experimentally observed dynamics. We thereby provide a bridge between the biophysical origin of spatiotemporal instabilities and the design principles of robust and efficient long-ranged migration.}, author = {Boocock, Daniel R and Hino, Naoya and Ruzickova, Natalia and Hirashima, Tsuyoshi and Hannezo, Edouard B}, issn = {1745-2481}, journal = {Nature Physics}, pages = {267--274}, publisher = {Springer Nature}, title = {{Theory of mechanochemical patterning and optimal migration in cell monolayers}}, doi = {10.1038/s41567-020-01037-7}, volume = {17}, 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}, } @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}, }