@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}, } @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{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{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}, } @article{8966, abstract = {During development, a single cell is transformed into a highly complex organism through progressive cell division, specification and rearrangement. An important prerequisite for the emergence of patterns within the developing organism is to establish asymmetries at various scales, ranging from individual cells to the entire embryo, eventually giving rise to the different body structures. This becomes especially apparent during gastrulation, when the earliest major lineage restriction events lead to the formation of the different germ layers. Traditionally, the unfolding of the developmental program from symmetry breaking to germ layer formation has been studied by dissecting the contributions of different signaling pathways and cellular rearrangements in the in vivo context of intact embryos. Recent efforts, using the intrinsic capacity of embryonic stem cells to self-assemble and generate embryo-like structures de novo, have opened new avenues for understanding the many ways by which an embryo can be built and the influence of extrinsic factors therein. Here, we discuss and compare divergent and conserved strategies leading to germ layer formation in embryos as compared to in vitro systems, their upstream molecular cascades and the role of extrinsic factors in this process.}, author = {Schauer, Alexandra and Heisenberg, Carl-Philipp J}, issn = {0012-1606}, journal = {Developmental Biology}, keywords = {Developmental Biology, Cell Biology, Molecular Biology}, pages = {71--81}, publisher = {Elsevier}, title = {{Reassembling gastrulation}}, doi = {10.1016/j.ydbio.2020.12.014}, volume = {474}, year = {2021}, } @article{9349, abstract = {The way in which interactions between mechanics and biochemistry lead to the emergence of complex cell and tissue organization is an old question that has recently attracted renewed interest from biologists, physicists, mathematicians and computer scientists. Rapid advances in optical physics, microscopy and computational image analysis have greatly enhanced our ability to observe and quantify spatiotemporal patterns of signalling, force generation, deformation, and flow in living cells and tissues. Powerful new tools for genetic, biophysical and optogenetic manipulation are allowing us to perturb the underlying machinery that generates these patterns in increasingly sophisticated ways. Rapid advances in theory and computing have made it possible to construct predictive models that describe how cell and tissue organization and dynamics emerge from the local coupling of biochemistry and mechanics. Together, these advances have opened up a wealth of new opportunities to explore how mechanochemical patterning shapes organismal development. In this roadmap, we present a series of forward-looking case studies on mechanochemical patterning in development, written by scientists working at the interface between the physical and biological sciences, and covering a wide range of spatial and temporal scales, organisms, and modes of development. Together, these contributions highlight the many ways in which the dynamic coupling of mechanics and biochemistry shapes biological dynamics: from mechanoenzymes that sense force to tune their activity and motor output, to collectives of cells in tissues that flow and redistribute biochemical signals during development.}, author = {Lenne, Pierre François and Munro, Edwin and Heemskerk, Idse and Warmflash, Aryeh and Bocanegra, Laura and Kishi, Kasumi and Kicheva, Anna and Long, Yuchen and Fruleux, Antoine and Boudaoud, Arezki and Saunders, Timothy E. and Caldarelli, Paolo and Michaut, Arthur and Gros, Jerome and Maroudas-Sacks, Yonit and Keren, Kinneret and Hannezo, Edouard B and Gartner, Zev J. and Stormo, Benjamin and Gladfelter, Amy and Rodrigues, Alan and Shyer, Amy and Minc, Nicolas and Maître, Jean Léon and Di Talia, Stefano and Khamaisi, Bassma and Sprinzak, David and Tlili, Sham}, issn = {1478-3975}, journal = {Physical biology}, number = {4}, publisher = {IOP Publishing}, title = {{Roadmap for the multiscale coupling of biochemical and mechanical signals during development}}, doi = {10.1088/1478-3975/abd0db}, volume = {18}, 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 = {1750-2799}, 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}, } @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 = {1759-7692}, 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{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}, } @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}, } @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}, }