TY - JOUR AB - Recently it was shown that anyons on the two-sphere naturally arise from a system of molecular impurities exchanging angular momentum with a many-particle bath (Phys. Rev. Lett. 126, 015301 (2021)). Here we further advance this approach and rigorously demonstrate that in the experimentally realized regime the lowest spectrum of two linear molecules immersed in superfluid helium corresponds to the spectrum of two anyons on the sphere. We develop the formalism within the framework of the recently experimentally observed angulon quasiparticle AU - Brooks, Morris AU - Lemeshko, Mikhail AU - Lundholm, Douglas AU - Yakaboylu, Enderalp ID - 10585 IS - 4 JF - Atoms KW - anyons KW - quasiparticles KW - Quantum Hall Effect KW - topological states of matter TI - Emergence of anyons on the two-sphere in molecular impurities VL - 9 ER - TY - CONF AB - We investigate fast and communication-efficient algorithms for the classic problem of minimizing a sum of strongly convex and smooth functions that are distributed among n different nodes, which can communicate using a limited number of bits. Most previous communication-efficient approaches for this problem are limited to first-order optimization, and therefore have \emph{linear} dependence on the condition number in their communication complexity. We show that this dependence is not inherent: communication-efficient methods can in fact have sublinear dependence on the condition number. For this, we design and analyze the first communication-efficient distributed variants of preconditioned gradient descent for Generalized Linear Models, and for Newton’s method. Our results rely on a new technique for quantizing both the preconditioner and the descent direction at each step of the algorithms, while controlling their convergence rate. We also validate our findings experimentally, showing faster convergence and reduced communication relative to previous methods. AU - Alimisis, Foivos AU - Davies, Peter AU - Alistarh, Dan-Adrian ID - 13147 SN - 9781713845065 T2 - Proceedings of the 38th International Conference on Machine Learning TI - Communication-efficient distributed optimization with quantized preconditioners VL - 139 ER - TY - CONF AB - A recent line of work has analyzed the theoretical properties of deep neural networks via the Neural Tangent Kernel (NTK). In particular, the smallest eigenvalue of the NTK has been related to the memorization capacity, the global convergence of gradient descent algorithms and the generalization of deep nets. However, existing results either provide bounds in the two-layer setting or assume that the spectrum of the NTK matrices is bounded away from 0 for multi-layer networks. In this paper, we provide tight bounds on the smallest eigenvalue of NTK matrices for deep ReLU nets, both in the limiting case of infinite widths and for finite widths. In the finite-width setting, the network architectures we consider are fairly general: we require the existence of a wide layer with roughly order of N neurons, N being the number of data samples; and the scaling of the remaining layer widths is arbitrary (up to logarithmic factors). To obtain our results, we analyze various quantities of independent interest: we give lower bounds on the smallest singular value of hidden feature matrices, and upper bounds on the Lipschitz constant of input-output feature maps. AU - Nguyen, Quynh AU - Mondelli, Marco AU - Montufar, Guido ID - 13146 SN - 9781713845065 T2 - Proceedings of the 38th International Conference on Machine Learning TI - Tight bounds on the smallest Eigenvalue of the neural tangent kernel for deep ReLU networks VL - 139 ER - TY - CONF AB - 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. AU - Henzinger, Thomas A AU - Lechner, Mathias AU - Zikelic, Dorde ID - 10665 IS - 5A SN - 2159-5399 T2 - Proceedings of the AAAI Conference on Artificial Intelligence TI - Scalable verification of quantized neural networks VL - 35 ER - TY - CONF AB - Bayesian neural networks (BNNs) place distributions over the weights of a neural network to model uncertainty in the data and the network's prediction. We consider the problem of verifying safety when running a Bayesian neural network policy in a feedback loop with infinite time horizon systems. Compared to the existing sampling-based approaches, which are inapplicable to the infinite time horizon setting, we train a separate deterministic neural network that serves as an infinite time horizon safety certificate. In particular, we show that the certificate network guarantees the safety of the system over a subset of the BNN weight posterior's support. Our method first computes a safe weight set and then alters the BNN's weight posterior to reject samples outside this set. Moreover, we show how to extend our approach to a safe-exploration reinforcement learning setting, in order to avoid unsafe trajectories during the training of the policy. We evaluate our approach on a series of reinforcement learning benchmarks, including non-Lyapunovian safety specifications. AU - Lechner, Mathias AU - Žikelić, Ðorđe AU - Chatterjee, Krishnendu AU - Henzinger, Thomas A ID - 10667 T2 - 35th Conference on Neural Information Processing Systems TI - Infinite time horizon safety of Bayesian neural networks ER - TY - JOUR AB - DNA nanotechnology offers a versatile toolbox for precise spatial and temporal manipulation of matter on the nanoscale. However, rendering DNA-based systems responsive to light has remained challenging. Herein, we describe the remote manipulation of native (non-photoresponsive) chiral plasmonic molecules (CPMs) using light. Our strategy is based on the use of a photoresponsive medium comprising a merocyanine-based photoacid. Upon exposure to visible light, the medium decreases its pH, inducing the formation of DNA triplex links, leading to a spatial reconfiguration of the CPMs. The process can be reversed simply by turning the light off and it can be repeated for multiple cycles. The degree of the overall chirality change in an ensemble of CPMs depends on the CPM fraction undergoing reconfiguration, which, remarkably, depends on and can be tuned by the intensity of incident light. Such a dynamic, remotely controlled system could aid in further advancing DNA-based devices and nanomaterials. AU - Ryssy, Joonas AU - Natarajan, Ashwin K. AU - Wang, Jinhua AU - Lehtonen, Arttu J. AU - Nguyen, Minh‐Kha AU - Klajn, Rafal AU - Kuzyk, Anton ID - 13358 IS - 11 JF - Angewandte Chemie International Edition KW - General Chemistry KW - Catalysis SN - 1433-7851 TI - Light‐responsive dynamic DNA‐origami‐based plasmonic assemblies VL - 60 ER - TY - CHAP AB - Inorganic nanoparticles (NPs) exhibit a wide range of fascinating physicochemical properties, many of which can be controlled by modulating the NP–NP coupling. Controlling the self-assembly of NPs using light has traditionally been achieved by functionalizing their surfaces with monolayers of photoswitchable molecules, which can be reversibly isomerized between two or more states upon exposure to different wavelengths of light. NPs whose assembly can be controlled by light in a reversible fashion can find interesting applications. The chapter deals with systems comprising mixtures of non-photoswitchable NPs and small-molecule photoacids and photobases. Examples of light-controlled self-assembly of NPs hitherto reported have been categorized into six distinct approaches. These are: functionalizing NPs with monolayers of photoswitchable molecules, light-controlled adsorption/desorption of photoswitchable molecules onto NPs, and light-induced electron transfer between the particle's inorganic core and the NP-bound ligands. AU - Bian, Tong AU - Chu, Zonglin AU - Klajn, Rafal ED - Giuseppone, Nicolas ED - Walther, Andreas ID - 13360 SN - 9783527346158 T2 - Out‐of‐Equilibrium (Supra)molecular Systems and Materials TI - Controlling Self‐Assembly of Nanoparticles Using Light ER - TY - JOUR AB - Coulombic interactions can be used to assemble charged nanoparticles into higher-order structures, but the process requires oppositely charged partners that are similarly sized. The ability to mediate the assembly of such charged nanoparticles using structurally simple small molecules would greatly facilitate the fabrication of nanostructured materials and harnessing their applications in catalysis, sensing and photonics. Here we show that small molecules with as few as three electric charges can effectively induce attractive interactions between oppositely charged nanoparticles in water. These interactions can guide the assembly of charged nanoparticles into colloidal crystals of a quality previously only thought to result from their co-crystallization with oppositely charged nanoparticles of a similar size. Transient nanoparticle assemblies can be generated using positively charged nanoparticles and multiply charged anions that are enzymatically hydrolysed into mono- and/or dianions. Our findings demonstrate an approach for the facile fabrication, manipulation and further investigation of static and dynamic nanostructured materials in aqueous environments. AU - Bian, Tong AU - Gardin, Andrea AU - Gemen, Julius AU - Houben, Lothar AU - Perego, Claudio AU - Lee, Byeongdu AU - Elad, Nadav AU - Chu, Zonglin AU - Pavan, Giovanni M. AU - Klajn, Rafal ID - 13357 IS - 10 JF - Nature Chemistry KW - General Chemical Engineering KW - General Chemistry SN - 1755-4330 TI - Electrostatic co-assembly of nanoparticles with oppositely charged small molecules into static and dynamic superstructures VL - 13 ER - TY - GEN AB - CpGs and corresponding mean weights for DNAm-based prediction of cognitive abilities (6 traits) AU - McCartney, Daniel L AU - Hillary, Robert F AU - Conole, Eleanor LS AU - Trejo Banos, Daniel AU - Gadd, Danni A AU - Walker, Rosie M AU - Nangle, Cliff AU - Flaig, Robin AU - Campbell, Archie AU - Murray, Alison D AU - Munoz Maniega, Susana AU - del C Valdes-Hernandez, Maria AU - Harris, Mathew A AU - Bastin, Mark E AU - Wardlaw, Joanna M AU - Harris, Sarah E AU - Porteous, David J AU - Tucker-Drob, Elliot M AU - McIntosh, Andrew M AU - Evans, Kathryn L AU - Deary, Ian J AU - Cox, Simon R AU - Robinson, Matthew Richard AU - Marioni, Riccardo E ID - 13072 TI - Blood-based epigenome-wide analyses of cognitive abilities ER - TY - GEN AB - Source data and source code for the graphs in "Spatiotemporal dynamics of self-organized branching pancreatic cancer-derived organoids". AU - Randriamanantsoa, Samuel AU - Papargyriou, Aristeidis AU - Maurer, Carlo AU - Peschke, Katja AU - Schuster, Maximilian AU - Zecchin, Giulia AU - Steiger, Katja AU - Öllinger, Rupert AU - Saur, Dieter AU - Scheel, Christina AU - Rad, Roland AU - Hannezo, Edouard B AU - Reichert, Maximilian AU - Bausch, Andreas R. ID - 13068 TI - Spatiotemporal dynamics of self-organized branching in pancreas-derived organoids ER - TY - JOUR AB - Novelty facilitates formation of memories. The detection of novelty and storage of contextual memories are both mediated by the hippocampus, yet the mechanisms that link these two functions remain to be defined. Dentate granule cells (GCs) of the dorsal hippocampus fire upon novelty exposure forming engrams of contextual memory. However, their key excitatory inputs from the entorhinal cortex are not responsive to novelty and are insufficient to make dorsal GCs fire reliably. Here we uncover a powerful glutamatergic pathway to dorsal GCs from ventral hippocampal mossy cells (MCs) that relays novelty, and is necessary and sufficient for driving dorsal GCs activation. Furthermore, manipulation of ventral MCs activity bidirectionally regulates novelty-induced contextual memory acquisition. Our results show that ventral MCs activity controls memory formation through an intra-hippocampal interaction mechanism gated by novelty. AU - Fredes Tolorza, Felipe A AU - Silva Sifuentes, Maria A AU - Koppensteiner, Peter AU - Kobayashi, Kenta AU - Jösch, Maximilian A AU - Shigemoto, Ryuichi ID - 7551 IS - 1 JF - Current Biology TI - Ventro-dorsal hippocampal pathway gates novelty-induced contextual memory formation VL - 31 ER - TY - JOUR AB - Resting-state brain activity is characterized by the presence of neuronal avalanches showing absence of characteristic size. Such evidence has been interpreted in the context of criticality and associated with the normal functioning of the brain. A distinctive attribute of systems at criticality is the presence of long-range correlations. Thus, to verify the hypothesis that the brain operates close to a critical point and consequently assess deviations from criticality for diagnostic purposes, it is of primary importance to robustly and reliably characterize correlations in resting-state brain activity. Recent works focused on the analysis of narrow-band electroencephalography (EEG) and magnetoencephalography (MEG) signal amplitude envelope, showing evidence of long-range temporal correlations (LRTC) in neural oscillations. However, brain activity is a broadband phenomenon, and a significant piece of information useful to precisely discriminate between normal (critical) and pathological behavior (non-critical), may be encoded in the broadband spatio-temporal cortical dynamics. Here we propose to characterize the temporal correlations in the broadband brain activity through the lens of neuronal avalanches. To this end, we consider resting-state EEG and long-term MEG recordings, extract the corresponding neuronal avalanche sequences, and study their temporal correlations. We demonstrate that the broadband resting-state brain activity consistently exhibits long-range power-law correlations in both EEG and MEG recordings, with similar values of the scaling exponents. Importantly, although we observe that the avalanche size distribution depends on scale parameters, scaling exponents characterizing long-range correlations are quite robust. In particular, they are independent of the temporal binning (scale of analysis), indicating that our analysis captures intrinsic characteristics of the underlying dynamics. Because neuronal avalanches constitute a fundamental feature of neural systems with universal characteristics, the proposed approach may serve as a general, systems- and experiment-independent procedure to infer the existence of underlying long-range correlations in extended neural systems, and identify pathological behaviors in the complex spatio-temporal interplay of cortical rhythms. AU - Lombardi, Fabrizio AU - Shriki, Oren AU - Herrmann, Hans J AU - de Arcangelis, Lucilla ID - 7463 JF - Neurocomputing SN - 0925-2312 TI - Long-range temporal correlations in the broadband resting state activity of the human brain revealed by neuronal avalanches VL - 461 ER - TY - GEN AB - Human brain organoids represent a powerful tool for the study of human neurological diseases particularly those that impact brain growth and structure. However, many neurological diseases lack obvious anatomical abnormalities, yet significantly impact neural network functions, raising the question of whether organoids possess sufficient neural network architecture and complexity to model these conditions. Here, we explore the network level functions of brain organoids using calcium sensor imaging and extracellular recording approaches that together reveal the existence of complex oscillatory network behaviors reminiscent of intact brain preparations. We further demonstrate strikingly abnormal epileptiform network activity in organoids derived from a Rett Syndrome patient despite only modest anatomical differences from isogenically matched controls, and rescue with an unconventional neuromodulatory drug Pifithrin-α. Together, these findings provide an essential foundation for the utilization of human brain organoids to study intact and disordered human brain network formation and illustrate their utility in therapeutic discovery. AU - Samarasinghe, Ranmal A. AU - Miranda, Osvaldo AU - Buth, Jessie E. AU - Mitchell, Simon AU - Ferando, Isabella AU - Watanabe, Momoko AU - Kurdian, Arinnae AU - Golshani, Peyman AU - Plath, Kathrin AU - Lowry, William E. AU - Parent, Jack M. AU - Mody, Istvan AU - Novitch, Bennett G. ID - 6995 SN - 1097-6256 TI - Identification of neural oscillations and epileptiform changes in human brain organoids VL - 24 ER - TY - JOUR AB - The central object of investigation of this paper is the Hirzebruch class, a deformation of the Todd class, given by Hirzebruch (for smooth varieties). The generalization for singular varieties is due to Brasselet–Schürmann–Yokura. Following the work of Weber, we investigate its equivariant version for (possibly singular) toric varieties. The local decomposition of the Hirzebruch class to the fixed points of the torus action and a formula for the local class in terms of the defining fan are recalled. After this review part, we prove the positivity of local Hirzebruch classes for all toric varieties, thus proving false the alleged counterexample given by Weber. AU - Rychlewicz, Kamil P ID - 6965 IS - 2 JF - Bulletin of the London Mathematical Society SN - 0024-6093 TI - The positivity of local equivariant Hirzebruch class for toric varieties VL - 53 ER - TY - JOUR AB - Brains process information in spiking neural networks. Their intricate connections shape the diverse functions these networks perform. In comparison, the functional capabilities of models of spiking networks are still rudimentary. This shortcoming is mainly due to the lack of insight and practical algorithms to construct the necessary connectivity. Any such algorithm typically attempts to build networks by iteratively reducing the error compared to a desired output. But assigning credit to hidden units in multi-layered spiking networks has remained challenging due to the non-differentiable nonlinearity of spikes. To avoid this issue, one can employ surrogate gradients to discover the required connectivity in spiking network models. However, the choice of a surrogate is not unique, raising the question of how its implementation influences the effectiveness of the method. Here, we use numerical simulations to systematically study how essential design parameters of surrogate gradients impact learning performance on a range of classification problems. We show that surrogate gradient learning is robust to different shapes of underlying surrogate derivatives, but the choice of the derivative’s scale can substantially affect learning performance. When we combine surrogate gradients with a suitable activity regularization technique, robust information processing can be achieved in spiking networks even at the sparse activity limit. Our study provides a systematic account of the remarkable robustness of surrogate gradient learning and serves as a practical guide to model functional spiking neural networks. AU - Zenke, Friedemann AU - Vogels, Tim P ID - 8253 IS - 4 JF - Neural Computation SN - 0899-7667 TI - The remarkable robustness of surrogate gradient learning for instilling complex function in spiking neural networks VL - 33 ER - TY - JOUR AB - We investigate how the critical driving amplitude at the Floquet many-body localized (MBL) to ergodic phase transition differs between smooth and nonsmooth drives. To this end, we numerically study a disordered spin-1/2 chain which is periodically driven by a sine or square-wave drive over a wide range of driving frequencies. In both cases the critical driving amplitude increases monotonically with the frequency, and at large frequencies it is identical for the two drives. However, at low and intermediate frequencies the critical amplitude of the square-wave drive depends strongly on the frequency, while that of the sinusoidal drive is almost constant over a wide frequency range. By analyzing the density of drive-induced resonances we conclude that this difference is due to resonances induced by the higher harmonics which are present (absent) in the Fourier spectrum of the square-wave (sine) drive. Furthermore, we suggest a numerically efficient method for estimating the frequency dependence of the critical driving amplitudes for different drives which is based on calculating the density of drive-induced resonances. We conclude that delocalization occurs once the density of drive-induced resonances reaches a critical value determined only by the static system. AU - Diringer, Asaf A. AU - Gulden, Tobias ID - 8198 IS - 21 JF - Physical Review B SN - 24699950 TI - Impact of drive harmonics on the stability of Floquet many-body localization VL - 103 ER - TY - JOUR AB - It is well known that special Kubo-Ando operator means admit divergence center interpretations, moreover, they are also mean squared error estimators for certain metrics on positive definite operators. In this paper we give a divergence center interpretation for every symmetric Kubo-Ando mean. This characterization of the symmetric means naturally leads to a definition of weighted and multivariate versions of a large class of symmetric Kubo-Ando means. We study elementary properties of these weighted multivariate means, and note in particular that in the special case of the geometric mean we recover the weighted A#H-mean introduced by Kim, Lawson, and Lim. AU - Pitrik, József AU - Virosztek, Daniel ID - 8373 JF - Linear Algebra and its Applications KW - Kubo-Ando mean KW - weighted multivariate mean KW - barycenter SN - 0024-3795 TI - A divergence center interpretation of general symmetric Kubo-Ando means, and related weighted multivariate operator means VL - 609 ER - TY - JOUR AB - When can a polyomino piece of paper be folded into a unit cube? Prior work studied tree-like polyominoes, but polyominoes with holes remain an intriguing open problem. We present sufficient conditions for a polyomino with one or several holes to fold into a cube, and conditions under which cube folding is impossible. In particular, we show that all but five special “basic” holes guarantee foldability. AU - Aichholzer, Oswin AU - Akitaya, Hugo A. AU - Cheung, Kenneth C. AU - Demaine, Erik D. AU - Demaine, Martin L. AU - Fekete, Sándor P. AU - Kleist, Linda AU - Kostitsyna, Irina AU - Löffler, Maarten AU - Masárová, Zuzana AU - Mundilova, Klara AU - Schmidt, Christiane ID - 8317 JF - Computational Geometry: Theory and Applications SN - 09257721 TI - Folding polyominoes with holes into a cube VL - 93 ER - TY - JOUR AB - We consider a gas of interacting bosons trapped in a box of side length one in the Gross–Pitaevskii limit. We review the proof of the validity of Bogoliubov’s prediction for the ground state energy and the low-energy excitation spectrum. This note is based on joint work with C. Brennecke, S. Cenatiempo and B. Schlein. AU - Boccato, Chiara ID - 7685 IS - 1 JF - Reviews in Mathematical Physics SN - 0129-055X TI - The excitation spectrum of the Bose gas in the Gross-Pitaevskii regime VL - 33 ER - TY - JOUR AB - Cell and tissue polarization is fundamental for plant growth and morphogenesis. The polar, cellular localization of Arabidopsis PIN‐FORMED (PIN) proteins is crucial for their function in directional auxin transport. The clustering of PIN polar cargoes within the plasma membrane has been proposed to be important for the maintenance of their polar distribution. However, the more detailed features of PIN clusters and the cellular requirements of cargo clustering remain unclear. Here, we characterized PIN clusters in detail by means of multiple advanced microscopy and quantification methods, such as 3D quantitative imaging or freeze‐fracture replica labeling. The size and aggregation types of PIN clusters were determined by electron microscopy at the nanometer level at different polar domains and at different developmental stages, revealing a strong preference for clustering at the polar domains. Pharmacological and genetic studies revealed that PIN clusters depend on phosphoinositol pathways, cytoskeletal structures and specific cell‐wall components as well as connections between the cell wall and the plasma membrane. This study identifies the role of different cellular processes and structures in polar cargo clustering and provides initial mechanistic insight into the maintenance of polarity in plants and other systems. AU - Li, Hongjiang AU - von Wangenheim, Daniel AU - Zhang, Xixi AU - Tan, Shutang AU - Darwish-Miranda, Nasser AU - Naramoto, Satoshi AU - Wabnik, Krzysztof T AU - de Rycke, Riet AU - Kaufmann, Walter AU - Gütl, Daniel J AU - Tejos, Ricardo AU - Grones, Peter AU - Ke, Meiyu AU - Chen, Xu AU - Dettmer, Jan AU - Friml, Jiří ID - 8582 IS - 1 JF - New Phytologist SN - 0028646X TI - Cellular requirements for PIN polar cargo clustering in Arabidopsis thaliana VL - 229 ER - TY - JOUR AB - Brain neurons arise from relatively few progenitors generating an enormous diversity of neuronal types. Nonetheless, a cardinal feature of mammalian brain neurogenesis is thought to be that excitatory and inhibitory neurons derive from separate, spatially segregated progenitors. Whether bi-potential progenitors with an intrinsic capacity to generate both lineages exist and how such a fate decision may be regulated are unknown. Using cerebellar development as a model, we discover that individual progenitors can give rise to both inhibitory and excitatory lineages. Gradations of Notch activity determine the fates of the progenitors and their daughters. Daughters with the highest levels of Notch activity retain the progenitor fate, while intermediate levels of Notch activity generate inhibitory neurons, and daughters with very low levels of Notch signaling adopt the excitatory fate. Therefore, Notch-mediated binary cell fate choice is a mechanism for regulating the ratio of excitatory to inhibitory neurons from common progenitors. AU - Zhang, Tingting AU - Liu, Tengyuan AU - Mora, Natalia AU - Guegan, Justine AU - Bertrand, Mathilde AU - Contreras, Ximena AU - Hansen, Andi H AU - Streicher, Carmen AU - Anderle, Marica AU - Danda, Natasha AU - Tiberi, Luca AU - Hippenmeyer, Simon AU - Hassan, Bassem A. ID - 8546 IS - 10 JF - Cell Reports TI - Generation of excitatory and inhibitory neurons from common progenitors via Notch signaling in the cerebellum VL - 35 ER - TY - JOUR AB - While recent advancements in computation and modelling have improved the analysis of complex traits, our understanding of the genetic basis of the time at symptom onset remains limited. Here, we develop a Bayesian approach (BayesW) that provides probabilistic inference of the genetic architecture of age-at-onset phenotypes in a sampling scheme that facilitates biobank-scale time-to-event analyses. We show in extensive simulation work the benefits BayesW provides in terms of number of discoveries, model performance and genomic prediction. In the UK Biobank, we find many thousands of common genomic regions underlying the age-at-onset of high blood pressure (HBP), cardiac disease (CAD), and type-2 diabetes (T2D), and for the genetic basis of onset reflecting the underlying genetic liability to disease. Age-at-menopause and age-at-menarche are also highly polygenic, but with higher variance contributed by low frequency variants. Genomic prediction into the Estonian Biobank data shows that BayesW gives higher prediction accuracy than other approaches. AU - Ojavee, Sven E AU - Kousathanas, Athanasios AU - Trejo Banos, Daniel AU - Orliac, Etienne J AU - Patxot, Marion AU - Lall, Kristi AU - Magi, Reedik AU - Fischer, Krista AU - Kutalik, Zoltan AU - Robinson, Matthew Richard ID - 8430 IS - 1 JF - Nature Communications TI - Genomic architecture and prediction of censored time-to-event phenotypes with a Bayesian genome-wide analysis VL - 12 ER - TY - JOUR AB - 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. AU - Boocock, Daniel R AU - Hino, Naoya AU - Ruzickova, Natalia AU - Hirashima, Tsuyoshi AU - Hannezo, Edouard B ID - 8602 JF - Nature Physics SN - 17452473 TI - Theory of mechanochemical patterning and optimal migration in cell monolayers VL - 17 ER - TY - JOUR AB - We consider the Fröhlich polaron model in the strong coupling limit. It is well‐known that to leading order the ground state energy is given by the (classical) Pekar energy. In this work, we establish the subleading correction, describing quantum fluctuation about the classical limit. Our proof applies to a model of a confined polaron, where both the electron and the polarization field are restricted to a set of finite volume, with linear size determined by the natural length scale of the Pekar problem. AU - Frank, Rupert AU - Seiringer, Robert ID - 8603 IS - 3 JF - Communications on Pure and Applied Mathematics SN - 00103640 TI - Quantum corrections to the Pekar asymptotics of a strongly coupled polaron VL - 74 ER - TY - JOUR AB - The leaf is a crucial organ evolved with remarkable morphological diversity to maximize plant photosynthesis. The leaf shape is a key trait that affects photosynthesis, flowering rates, disease resistance, and yield. Although many genes regulating leaf development have been identified in the past years, the precise regulatory architecture underlying the generation of diverse leaf shapes remains to be elucidated. We used cotton as a reference model to probe the genetic framework underlying divergent leaf forms. Comparative transcriptome analysis revealed that the GhARF16‐1 and GhKNOX2‐1 genes might be potential regulators of leaf shape. We functionally characterized the auxin‐responsive factor ARF16‐1 acting upstream of GhKNOX2‐1 to determine leaf morphology in cotton. The transcription of GhARF16‐1 was significantly higher in lobed‐leaved cotton than in smooth‐leaved cotton. Furthermore, the overexpression of GhARF16‐1 led to the upregulation of GhKNOX2‐1 and resulted in more and deeper serrations in cotton leaves, similar to the leaf shape of cotton plants overexpressing GhKNOX2‐1. We found that GhARF16‐1 specifically bound to the promoter of GhKNOX2‐1 to induce its expression. The heterologous expression of GhARF16‐1 and GhKNOX2‐1 in Arabidopsis led to lobed and curly leaves, and a genetic analysis revealed that GhKNOX2‐1 is epistatic to GhARF16‐1 in Arabidopsis, suggesting that the GhARF16‐1 and GhKNOX2‐1 interaction paradigm also functions to regulate leaf shape in Arabidopsis. To our knowledge, our results uncover a novel mechanism by which auxin, through the key component ARF16‐1 and its downstream‐activated gene KNOX2‐1, determines leaf morphology in eudicots. AU - He, P AU - Zhang, Yuzhou AU - Li, H AU - Fu, X AU - Shang, H AU - Zou, C AU - Friml, Jiří AU - Xiao, G ID - 8606 IS - 3 JF - Plant Biotechnology Journal SN - 1467-7644 TI - GhARF16-1 modulates leaf development by transcriptionally regulating the GhKNOX2-1 gene in cotton VL - 19 ER - TY - JOUR AB - The Mytilus complex of marine mussel species forms a mosaic of hybrid zones, found across temperate regions of the globe. This allows us to study ‘replicated’ instances of secondary contact between closely related species. Previous work on this complex has shown that local introgression is both widespread and highly heterogeneous, and has identified SNPs that are outliers of differentiation between lineages. Here, we developed an ancestry‐informative panel of such SNPs. We then compared their frequencies in newly sampled populations, including samples from within the hybrid zones, and parental populations at different distances from the contact. Results show that close to the hybrid zones, some outlier loci are near to fixation for the heterospecific allele, suggesting enhanced local introgression, or the local sweep of a shared ancestral allele. Conversely, genomic cline analyses, treating local parental populations as the reference, reveal a globally high concordance among loci, albeit with a few signals of asymmetric introgression. Enhanced local introgression at specific loci is consistent with the early transfer of adaptive variants after contact, possibly including asymmetric bi‐stable variants (Dobzhansky‐Muller incompatibilities), or haplotypes loaded with fewer deleterious mutations. Having escaped one barrier, however, these variants can be trapped or delayed at the next barrier, confining the introgression locally. These results shed light on the decay of species barriers during phases of contact. AU - Simon, Alexis AU - Fraisse, Christelle AU - El Ayari, Tahani AU - Liautard‐Haag, Cathy AU - Strelkov, Petr AU - Welch, John J AU - Bierne, Nicolas ID - 8708 IS - 1 JF - Journal of Evolutionary Biology SN - 1010061X TI - How do species barriers decay? Concordance and local introgression in mosaic hybrid zones of mussels VL - 34 ER - TY - JOUR AB - Deep learning at scale is dominated by communication time. Distributing samples across nodes usually yields the best performance, but poses scaling challenges due to global information dissemination and load imbalance across uneven sample lengths. State-of-the-art decentralized optimizers mitigate the problem, but require more iterations to achieve the same accuracy as their globally-communicating counterparts. We present Wait-Avoiding Group Model Averaging (WAGMA) SGD, a wait-avoiding stochastic optimizer that reduces global communication via subgroup weight exchange. The key insight is a combination of algorithmic changes to the averaging scheme and the use of a group allreduce operation. We prove the convergence of WAGMA-SGD, and empirically show that it retains convergence rates similar to Allreduce-SGD. For evaluation, we train ResNet-50 on ImageNet; Transformer for machine translation; and deep reinforcement learning for navigation at scale. Compared with state-of-the-art decentralized SGD variants, WAGMA-SGD significantly improves training throughput (e.g., 2.1× on 1,024 GPUs for reinforcement learning), and achieves the fastest time-to-solution (e.g., the highest score using the shortest training time for Transformer). AU - Li, Shigang AU - Tal Ben-Nun, Tal Ben-Nun AU - Nadiradze, Giorgi AU - Girolamo, Salvatore Di AU - Dryden, Nikoli AU - Alistarh, Dan-Adrian AU - Hoefler, Torsten ID - 8723 IS - 7 JF - IEEE Transactions on Parallel and Distributed Systems SN - 10459219 TI - Breaking (global) barriers in parallel stochastic optimization with wait-avoiding group averaging VL - 32 ER - TY - JOUR AB - Montane cloud forests are areas of high endemism, and are one of the more vulnerable terrestrial ecosystems to climate change. Thus, understanding how they both contribute to the generation of biodiversity, and will respond to ongoing climate change, are important and related challenges. The widely accepted model for montane cloud forest dynamics involves upslope forcing of their range limits with global climate warming. However, limited climate data provides some support for an alternative model, where range limits are forced downslope with climate warming. Testing between these two models is challenging, due to the inherent limitations of climate and pollen records. We overcome this with an alternative source of historical information, testing between competing model predictions using genomic data and demographic analyses for a species of beetle tightly associated to an oceanic island cloud forest. Results unequivocally support the alternative model: populations that were isolated at higher elevation peaks during the Last Glacial Maximum are now in contact and hybridizing at lower elevations. Our results suggest that genomic data are a rich source of information to further understand how montane cloud forest biodiversity originates, and how it is likely to be impacted by ongoing climate change. AU - Salces-Castellano, Antonia AU - Stankowski, Sean AU - Arribas, Paula AU - Patino, Jairo AU - Karger, Dirk N. AU - Butlin, Roger AU - Emerson, Brent C. ID - 8743 IS - 2 JF - Evolution SN - 0014-3820 TI - Long-term cloud forest response to climate warming revealed by insect speciation history VL - 75 ER - TY - JOUR AB - In RuCl3, inelastic neutron scattering and Raman spectroscopy reveal a continuum of non-spin-wave excitations that persists to high temperature, suggesting the presence of a spin liquid state on a honeycomb lattice. In the context of the Kitaev model, finite magnetic fields introduce interactions between the elementary excitations, and thus the effects of high magnetic fields that are comparable to the spin-exchange energy scale must be explored. Here, we report measurements of the magnetotropic coefficient—the thermodynamic coefficient associated with magnetic anisotropy—over a wide range of magnetic fields and temperatures. We find that magnetic field and temperature compete to determine the magnetic response in a way that is independent of the large intrinsic exchange-interaction energy. This emergent scale-invariant magnetic anisotropy provides evidence for a high degree of exchange frustration that favours the formation of a spin liquid state in RuCl3. AU - Modic, Kimberly A AU - McDonald, Ross D. AU - Ruff, J.P.C. AU - Bachmann, Maja D. AU - Lai, You AU - Palmstrom, Johanna C. AU - Graf, David AU - Chan, Mun K. AU - Balakirev, F.F. AU - Betts, J.B. AU - Boebinger, G.S. AU - Schmidt, Marcus AU - Lawler, Michael J. AU - Sokolov, D.A. AU - Moll, Philip J.W. AU - Ramshaw, B.J. AU - Shekhter, Arkady ID - 8673 JF - Nature Physics SN - 17452473 TI - Scale-invariant magnetic anisotropy in RuCl3 at high magnetic fields VL - 17 ER - TY - JOUR AB - Traditional scientific conferences and seminar events have been hugely disrupted by the COVID-19 pandemic, paving the way for virtual forms of scientific communication to take hold and be put to the test. AU - Bozelos, Panagiotis AU - Vogels, Tim P ID - 8757 IS - 1 JF - Nature Reviews Neuroscience SN - 1471003X TI - Talking science, online VL - 22 ER - TY - JOUR AB - We study optimal election sequences for repeatedly selecting a (very) small group of leaders among a set of participants (players) with publicly known unique ids. In every time slot, every player has to select exactly one player that it considers to be the current leader, oblivious to the selection of the other players, but with the overarching goal of maximizing a given parameterized global (“social”) payoff function in the limit. We consider a quite generic model, where the local payoff achieved by a given player depends, weighted by some arbitrary but fixed real parameter, on the number of different leaders chosen in a round, the number of players that choose the given player as the leader, and whether the chosen leader has changed w.r.t. the previous round or not. The social payoff can be the maximum, average or minimum local payoff of the players. Possible applications include quite diverse examples such as rotating coordinator-based distributed algorithms and long-haul formation flying of social birds. Depending on the weights and the particular social payoff, optimal sequences can be very different, from simple round-robin where all players chose the same leader alternatingly every time slot to very exotic patterns, where a small group of leaders (at most 2) is elected in every time slot. Moreover, we study the question if and when a single player would not benefit w.r.t. its local payoff when deviating from the given optimal sequence, i.e., when our optimal sequences are Nash equilibria in the restricted strategy space of oblivious strategies. As this is the case for many parameterizations of our model, our results reveal that no punishment is needed to make it rational for the players to optimize the social payoff. AU - Zeiner, Martin AU - Schmid, Ulrich AU - Chatterjee, Krishnendu ID - 8793 IS - 1 JF - Discrete Applied Mathematics SN - 0166218X TI - Optimal strategies for selecting coordinators VL - 289 ER - TY - JOUR AB - Area-dependent quantum field theory is a modification of two-dimensional topological quantum field theory, where one equips each connected component of a bordism with a positive real number—interpreted as area—which behaves additively under glueing. As opposed to topological theories, in area-dependent theories the state spaces can be infinite-dimensional. We introduce the notion of regularised Frobenius algebras in Hilbert spaces and show that area-dependent theories are in one-to-one correspondence to commutative regularised Frobenius algebras. We also provide a state sum construction for area-dependent theories. Our main example is two-dimensional Yang–Mills theory with compact gauge group, which we treat in detail. AU - Runkel, Ingo AU - Szegedy, Lorant ID - 8816 IS - 1 JF - Communications in Mathematical Physics SN - 00103616 TI - Area-dependent quantum field theory VL - 381 ER - TY - JOUR AB - The hippocampus has a major role in encoding and consolidating long-term memories, and undergoes plastic changes during sleep1. These changes require precise homeostatic control by subcortical neuromodulatory structures2. The underlying mechanisms of this phenomenon, however, remain unknown. Here, using multi-structure recordings in macaque monkeys, we show that the brainstem transiently modulates hippocampal network events through phasic pontine waves known as pontogeniculooccipital waves (PGO waves). Two physiologically distinct types of PGO wave appear to occur sequentially, selectively influencing high-frequency ripples and low-frequency theta events, respectively. The two types of PGO wave are associated with opposite hippocampal spike-field coupling, prompting periods of high neural synchrony of neural populations during periods of ripple and theta instances. The coupling between PGO waves and ripples, classically associated with distinct sleep stages, supports the notion that a global coordination mechanism of hippocampal sleep dynamics by cholinergic pontine transients may promote systems and synaptic memory consolidation as well as synaptic homeostasis. AU - Ramirez Villegas, Juan F AU - Besserve, Michel AU - Murayama, Yusuke AU - Evrard, Henry C. AU - Oeltermann, Axel AU - Logothetis, Nikos K. ID - 8818 IS - 7840 JF - Nature SN - 00280836 TI - Coupling of hippocampal theta and ripples with pontogeniculooccipital waves VL - 589 ER - TY - JOUR AB - Let g be a complex semisimple Lie algebra. We give a classification of contravariant forms on the nondegenerate Whittaker g-modules Y(χ,η) introduced by Kostant. We prove that the set of all contravariant forms on Y(χ,η) forms a vector space whose dimension is given by the cardinality of the Weyl group of g. We also describe a procedure for parabolically inducing contravariant forms. As a corollary, we deduce the existence of the Shapovalov form on a Verma module, and provide a formula for the dimension of the space of contravariant forms on the degenerate Whittaker modules M(χ,η) introduced by McDowell. AU - Brown, Adam AU - Romanov, Anna ID - 8773 IS - 1 JF - Proceedings of the American Mathematical Society KW - Applied Mathematics KW - General Mathematics SN - 0002-9939 TI - Contravariant forms on Whittaker modules VL - 149 ER - TY - JOUR AB - This paper is concerned with a non-isothermal Cahn-Hilliard model based on a microforce balance. The model was derived by A. Miranville and G. Schimperna starting from the two fundamental laws of Thermodynamics, following M. Gurtin's two-scale approach. The main working assumptions are made on the behaviour of the heat flux as the absolute temperature tends to zero and to infinity. A suitable Ginzburg-Landau free energy is considered. Global-in-time existence for the initial-boundary value problem associated to the entropy formulation and, in a subcase, also to the weak formulation of the model is proved by deriving suitable a priori estimates and by showing weak sequential stability of families of approximating solutions. At last, some highlights are given regarding a possible approximation scheme compatible with the a-priori estimates available for the system. AU - Marveggio, Alice AU - Schimperna, Giulio ID - 8792 IS - 2 JF - Journal of Differential Equations SN - 00220396 TI - On a non-isothermal Cahn-Hilliard model based on a microforce balance VL - 274 ER - TY - JOUR AB - For automata, synchronization, the problem of bringing an automaton to a particular state regardless of its initial state, is important. It has several applications in practice and is related to a fifty-year-old conjecture on the length of the shortest synchronizing word. Although using shorter words increases the effectiveness in practice, finding a shortest one (which is not necessarily unique) is NP-hard. For this reason, there exist various heuristics in the literature. However, high-quality heuristics such as SynchroP producing relatively shorter sequences are very expensive and can take hours when the automaton has tens of thousands of states. The SynchroP heuristic has been frequently used as a benchmark to evaluate the performance of the new heuristics. In this work, we first improve the runtime of SynchroP and its variants by using algorithmic techniques. We then focus on adapting SynchroP for many-core architectures, and overall, we obtain more than 1000× speedup on GPUs compared to naive sequential implementation that has been frequently used as a benchmark to evaluate new heuristics in the literature. We also propose two SynchroP variants and evaluate their performance. AU - Sarac, Naci E AU - Altun, Ömer Faruk AU - Atam, Kamil Tolga AU - Karahoda, Sertac AU - Kaya, Kamer AU - Yenigün, Hüsnü ID - 8912 IS - 4 JF - Expert Systems with Applications SN - 09574174 TI - Boosting expensive synchronizing heuristics VL - 167 ER - TY - JOUR AB - Domestication is a human‐induced selection process that imprints the genomes of domesticated populations over a short evolutionary time scale and that occurs in a given demographic context. Reconstructing historical gene flow, effective population size changes and their timing is therefore of fundamental interest to understand how plant demography and human selection jointly shape genomic divergence during domestication. Yet, the comparison under a single statistical framework of independent domestication histories across different crop species has been little evaluated so far. Thus, it is unclear whether domestication leads to convergent demographic changes that similarly affect crop genomes. To address this question, we used existing and new transcriptome data on three crop species of Solanaceae (eggplant, pepper and tomato), together with their close wild relatives. We fitted twelve demographic models of increasing complexity on the unfolded joint allele frequency spectrum for each wild/crop pair, and we found evidence for both shared and species‐specific demographic processes between species. A convergent history of domestication with gene flow was inferred for all three species, along with evidence of strong reduction in the effective population size during the cultivation stage of tomato and pepper. The absence of any reduction in size of the crop in eggplant stands out from the classical view of the domestication process; as does the existence of a “protracted period” of management before cultivation. Our results also suggest divergent management strategies of modern cultivars among species as their current demography substantially differs. Finally, the timing of domestication is species‐specific and supported by the few historical records available. AU - Arnoux, Stéphanie AU - Fraisse, Christelle AU - Sauvage, Christopher ID - 8928 IS - 2 JF - Journal of Evolutionary Biology SN - 1010061X TI - Genomic inference of complex domestication histories in three Solanaceae species VL - 34 ER - TY - JOUR AB - The phytohormone auxin plays a central role in shaping plant growth and development. With decades of genetic and biochemical studies, numerous core molecular components and their networks, underlying auxin biosynthesis, transport, and signaling, have been identified. Notably, protein phosphorylation, catalyzed by kinases and oppositely hydrolyzed by phosphatases, has been emerging to be a crucial type of post-translational modification, regulating physiological and developmental auxin output at all levels. In this review, we comprehensively discuss earlier and recent advances in our understanding of genetics, biochemistry, and cell biology of the kinases and phosphatases participating in auxin action. We provide insights into the mechanisms by which reversible protein phosphorylation defines developmental auxin responses, discuss current challenges, and provide our perspectives on future directions involving the integration of the control of protein phosphorylation into the molecular auxin network. AU - Tan, Shutang AU - Luschnig, Christian AU - Friml, Jiří ID - 8992 IS - 1 JF - Molecular Plant SN - 16742052 TI - Pho-view of auxin: Reversible protein phosphorylation in auxin biosynthesis, transport and signaling VL - 14 ER - TY - JOUR AB - The differentiation of cells depends on a precise control of their internal organization, which is the result of a complex dynamic interplay between the cytoskeleton, molecular motors, signaling molecules, and membranes. For example, in the developing neuron, the protein ADAP1 (ADP-ribosylation factor GTPase-activating protein [ArfGAP] with dual pleckstrin homology [PH] domains 1) has been suggested to control dendrite branching by regulating the small GTPase ARF6. Together with the motor protein KIF13B, ADAP1 is also thought to mediate delivery of the second messenger phosphatidylinositol (3,4,5)-trisphosphate (PIP3) to the axon tip, thus contributing to PIP3 polarity. However, what defines the function of ADAP1 and how its different roles are coordinated are still not clear. Here, we studied ADAP1’s functions using in vitro reconstitutions. We found that KIF13B transports ADAP1 along microtubules, but that PIP3 as well as PI(3,4)P2 act as stop signals for this transport instead of being transported. We also demonstrate that these phosphoinositides activate ADAP1’s enzymatic activity to catalyze GTP hydrolysis by ARF6. Together, our results support a model for the cellular function of ADAP1, where KIF13B transports ADAP1 until it encounters high PIP3/PI(3,4)P2 concentrations in the plasma membrane. Here, ADAP1 disassociates from the motor to inactivate ARF6, promoting dendrite branching. AU - Düllberg, Christian F AU - Auer, Albert AU - Canigova, Nikola AU - Loibl, Katrin AU - Loose, Martin ID - 8988 IS - 1 JF - PNAS SN - 00278424 TI - In vitro reconstitution reveals phosphoinositides as cargo-release factors and activators of the ARF6 GAP ADAP1 VL - 118 ER - TY - JOUR AB - The recent outbreak of coronavirus disease 2019 (COVID‐19), caused by the Severe Acute Respiratory Syndrome Coronavirus‐2 (SARS‐CoV‐2) has resulted in a world‐wide pandemic. Disseminated lung injury with the development of acute respiratory distress syndrome (ARDS) is the main cause of mortality in COVID‐19. Although liver failure does not seem to occur in the absence of pre‐existing liver disease, hepatic involvement in COVID‐19 may correlate with overall disease severity and serve as a prognostic factor for the development of ARDS. The spectrum of liver injury in COVID‐19 may range from direct infection by SARS‐CoV‐2, indirect involvement by systemic inflammation, hypoxic changes, iatrogenic causes such as drugs and ventilation to exacerbation of underlying liver disease. This concise review discusses the potential pathophysiological mechanisms for SARS‐CoV‐2 hepatic tropism as well as acute and possibly long‐term liver injury in COVID‐19. AU - Nardo, Alexander D. AU - Schneeweiss-Gleixner, Mathias AU - Bakail, May M AU - Dixon, Emmanuel D. AU - Lax, Sigurd F. AU - Trauner, Michael ID - 8927 IS - 1 JF - Liver International SN - 14783223 TI - Pathophysiological mechanisms of liver injury in COVID-19 VL - 41 ER - TY - JOUR AB - Self-assembly of nanoparticles can be mediated by polymers, but has so far led almost exclusively to nanoparticle aggregates that are amorphous. Here, we employed Coulombic interactions to generate a range of composite materials from mixtures of charged nanoparticles and oppositely charged polymers. The assembly behavior of these nanoparticle/polymer composites depends on their order of addition: polymers added to nanoparticles give rise to stable aggregates, but nanoparticles added to polymers disassemble the initially formed aggregates. The amorphous aggregates were transformed into crystalline ones by transiently increasing the ionic strength of the solution. The morphology of the resulting crystals depended on the length of the polymer: short polymer chains mediated the self-assembly of nanoparticles into strongly faceted crystals, whereas long chains led to pseudospherical nanoparticle/polymer assemblies, within which the crystalline order of nanoparticles was retained. AU - Bian, Tong AU - Klajn, Rafal ID - 13356 IS - 1 JF - Annals of the New York Academy of Sciences KW - History and Philosophy of Science KW - General Biochemistry KW - Genetics and Molecular Biology KW - General Neuroscience SN - 0077-8923 TI - Morphology control in crystalline nanoparticle–polymer aggregates VL - 1505 ER - TY - JOUR AB - Dissipative self-assembly is ubiquitous in nature, where it gives rise to complex structures and functions such as self-healing, homeostasis, and camouflage. These phenomena are enabled by the continuous conversion of energy stored in chemical fuels, such as ATP. Over the past decade, an increasing number of synthetic chemically driven systems have been reported that mimic the features of their natural counterparts. At the same time, it has been shown that dissipative self-assembly can also be fueled by light; these optically fueled systems have been developed in parallel to the chemically fueled ones. In this perspective, we critically compare these two classes of systems. Despite the complementarity and fundamental differences between these two modes of dissipative self-assembly, our analysis reveals that multiple analogies exist between chemically and light-fueled systems. We hope that these considerations will facilitate further development of the field of dissipative self-assembly. AU - Weißenfels, Maren AU - Gemen, Julius AU - Klajn, Rafal ID - 13359 IS - 1 JF - Chem KW - Materials Chemistry KW - Biochemistry (medical) KW - General Chemical Engineering KW - Environmental Chemistry KW - Biochemistry KW - General Chemistry SN - 2451-9294 TI - Dissipative self-assembly: Fueling with chemicals versus light VL - 7 ER - TY - JOUR AB - 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. AU - Schauer, Alexandra AU - Heisenberg, Carl-Philipp J ID - 8966 JF - Developmental Biology KW - Developmental Biology KW - Cell Biology KW - Molecular Biology SN - 0012-1606 TI - Reassembling gastrulation VL - 474 ER - TY - JOUR AB - N-1-naphthylphthalamic acid (NPA) is a key inhibitor of directional (polar) transport of the hormone auxin in plants. For decades, it has been a pivotal tool in elucidating the unique polar auxin transport-based processes underlying plant growth and development. Its exact mode of action has long been sought after and is still being debated, with prevailing mechanistic schemes describing only indirect connections between NPA and the main transporters responsible for directional transport, namely PIN auxin exporters. Here we present data supporting a model in which NPA associates with PINs in a more direct manner than hitherto postulated. We show that NPA inhibits PIN activity in a heterologous oocyte system and that expression of NPA-sensitive PINs in plant, yeast, and oocyte membranes leads to specific saturable NPA binding. We thus propose that PINs are a bona fide NPA target. This offers a straightforward molecular basis for NPA inhibition of PIN-dependent auxin transport and a logical parsimonious explanation for the known physiological effects of NPA on plant growth, as well as an alternative hypothesis to interpret past and future results. We also introduce PIN dimerization and describe an effect of NPA on this, suggesting that NPA binding could be exploited to gain insights into structural aspects of PINs related to their transport mechanism. AU - Abas, Lindy AU - Kolb, Martina AU - Stadlmann, Johannes AU - Janacek, Dorina P. AU - Lukic, Kristina AU - Schwechheimer, Claus AU - Sazanov, Leonid A AU - Mach, Lukas AU - Friml, Jiří AU - Hammes, Ulrich Z. ID - 8993 IS - 1 JF - PNAS SN - 00278424 TI - Naphthylphthalamic acid associates with and inhibits PIN auxin transporters VL - 118 ER - TY - JOUR AB - In many basic shear flows, such as pipe, Couette, and channel flow, turbulence does not arise from an instability of the laminar state, and both dynamical states co-exist. With decreasing flow speed (i.e., decreasing Reynolds number) the fraction of fluid in laminar motion increases while turbulence recedes and eventually the entire flow relaminarizes. The first step towards understanding the nature of this transition is to determine if the phase change is of either first or second order. In the former case, the turbulent fraction would drop discontinuously to zero as the Reynolds number decreases while in the latter the process would be continuous. For Couette flow, the flow between two parallel plates, earlier studies suggest a discontinuous scenario. In the present study we realize a Couette flow between two concentric cylinders which allows studies to be carried out in large aspect ratios and for extensive observation times. The presented measurements show that the transition in this circular Couette geometry is continuous suggesting that former studies were limited by finite size effects. A further characterization of this transition, in particular its relation to the directed percolation universality class, requires even larger system sizes than presently available. AU - Avila, Kerstin AU - Hof, Björn ID - 8999 IS - 1 JF - Entropy TI - Second-order phase transition in counter-rotating taylor-couette flow experiment VL - 23 ER - TY - JOUR AB - Studies on the experimental realization of two-dimensional anyons in terms of quasiparticles have been restricted, so far, to only anyons on the plane. It is known, however, that the geometry and topology of space can have significant effects on quantum statistics for particles moving on it. Here, we have undertaken the first step toward realizing the emerging fractional statistics for particles restricted to move on the sphere instead of on the plane. We show that such a model arises naturally in the context of quantum impurity problems. In particular, we demonstrate a setup in which the lowest-energy spectrum of two linear bosonic or fermionic molecules immersed in a quantum many-particle environment can coincide with the anyonic spectrum on the sphere. This paves the way toward the experimental realization of anyons on the sphere using molecular impurities. Furthermore, since a change in the alignment of the molecules corresponds to the exchange of the particles on the sphere, such a realization reveals a novel type of exclusion principle for molecular impurities, which could also be of use as a powerful technique to measure the statistics parameter. Finally, our approach opens up a simple numerical route to investigate the spectra of many anyons on the sphere. Accordingly, we present the spectrum of two anyons on the sphere in the presence of a Dirac monopole field. AU - Brooks, Morris AU - Lemeshko, Mikhail AU - Lundholm, D. AU - Yakaboylu, Enderalp ID - 9005 IS - 1 JF - Physical Review Letters SN - 00319007 TI - Molecular impurities as a realization of anyons on the two-sphere VL - 126 ER - TY - JOUR AB - Recent advancements in live cell imaging technologies have identified the phenomenon of intracellular propagation of late apoptotic events, such as cytochrome c release and caspase activation. The mechanism, prevalence, and speed of apoptosis propagation remain unclear. Additionally, no studies have demonstrated propagation of the pro-apoptotic protein, BAX. To evaluate the role of BAX in intracellular apoptotic propagation, we used high speed live-cell imaging to visualize fluorescently tagged-BAX recruitment to mitochondria in four immortalized cell lines. We show that propagation of mitochondrial BAX recruitment occurs in parallel to cytochrome c and SMAC/Diablo release and is affected by cellular morphology, such that cells with processes are more likely to exhibit propagation. The initiation of propagation events is most prevalent in the distal tips of processes, while the rate of propagation is influenced by the 2-dimensional width of the process. Propagation was rarely observed in the cell soma, which exhibited near synchronous recruitment of BAX. Propagation velocity is not affected by mitochondrial volume in segments of processes, but is negatively affected by mitochondrial density. There was no evidence of a propagating wave of increased levels of intracellular calcium ions. Alternatively, we did observe a uniform increase in superoxide build-up in cellular mitochondria, which was released as a propagating wave simultaneously with the propagating recruitment of BAX to the mitochondrial outer membrane. AU - Grosser, Joshua A. AU - Maes, Margaret E AU - Nickells, Robert W. ID - 9009 IS - 2 JF - Apoptosis SN - 1360-8185 TI - Characteristics of intracellular propagation of mitochondrial BAX recruitment during apoptosis VL - 26 ER - TY - JOUR AB - Layered materials in which individual atomic layers are bonded by weak van der Waals forces (vdW materials) constitute one of the most prominent platforms for materials research. Particularly, polar vdW crystals, such as hexagonal boron nitride (h-BN), alpha-molybdenum trioxide (α-MoO3) or alpha-vanadium pentoxide (α-V2O5), have received significant attention in nano-optics, since they support phonon polaritons (PhPs)―light coupled to lattice vibrations― with strong electromagnetic confinement and low optical losses. Recently, correlative far- and near-field studies of α-MoO3 have been demonstrated as an effective strategy to accurately extract the permittivity of this material. Here, we use this accurately characterized and low-loss polaritonic material to sense its local dielectric environment, namely silica (SiO2), one of the most widespread substrates in nanotechnology. By studying the propagation of PhPs on α-MoO3 flakes with different thicknesses laying on SiO2 substrates via near-field microscopy (s-SNOM), we extract locally the infrared permittivity of SiO2. Our work reveals PhPs nanoimaging as a versatile method for the quantitative characterization of the local optical properties of dielectric substrates, crucial for understanding and predicting the response of nanomaterials and for the future scalability of integrated nanophotonic devices. AU - Aguilar-Merino, Patricia AU - Álvarez-Pérez, Gonzalo AU - Taboada-Gutiérrez, Javier AU - Duan, Jiahua AU - Prieto Gonzalez, Ivan AU - Álvarez-Prado, Luis Manuel AU - Nikitin, Alexey Y. AU - Martín-Sánchez, Javier AU - Alonso-González, Pablo ID - 9038 IS - 1 JF - Nanomaterials TI - Extracting the infrared permittivity of SiO2 substrates locally by near-field imaging of phonon polaritons in a van der Waals crystal VL - 11 ER - TY - JOUR AB - We study dynamics and thermodynamics of ion transport in narrow, water-filled channels, considered as effective 1D Coulomb systems. The long range nature of the inter-ion interactions comes about due to the dielectric constants mismatch between the water and the surrounding medium, confining the electric filed to stay mostly within the water-filled channel. Statistical mechanics of such Coulomb systems is dominated by entropic effects which may be accurately accounted for by mapping onto an effective quantum mechanics. In presence of multivalent ions the corresponding quantum mechanics appears to be non-Hermitian. In this review we discuss a framework for semiclassical calculations for the effective non-Hermitian Hamiltonians. Non-Hermiticity elevates WKB action integrals from the real line to closed cycles on a complex Riemann surfaces where direct calculations are not attainable. We circumvent this issue by applying tools from algebraic topology, such as the Picard-Fuchs equation. We discuss how its solutions relate to the thermodynamics and correlation functions of multivalent solutions within narrow, water-filled channels. AU - Gulden, Tobias AU - Kamenev, Alex ID - 9020 IS - 1 JF - Entropy TI - Dynamics of ion channels via non-hermitian quantum mechanics VL - 23 ER - TY - JOUR AB - We continue our study of ‘no‐dimension’ analogues of basic theorems in combinatorial and convex geometry in Banach spaces. We generalize some results of the paper (Adiprasito, Bárány and Mustafa, ‘Theorems of Carathéodory, Helly, and Tverberg without dimension’, Proceedings of the Thirtieth Annual ACM‐SIAM Symposium on Discrete Algorithms (Society for Industrial and Applied Mathematics, San Diego, California, 2019) 2350–2360) and prove no‐dimension versions of the colored Tverberg theorem, the selection lemma and the weak 𝜀 ‐net theorem in Banach spaces of type 𝑝>1 . To prove these results, we use the original ideas of Adiprasito, Bárány and Mustafa for the Euclidean case, our no‐dimension version of the Radon theorem and slightly modified version of the celebrated Maurey lemma. AU - Ivanov, Grigory ID - 9037 IS - 2 JF - Bulletin of the London Mathematical Society SN - 00246093 TI - No-dimension Tverberg's theorem and its corollaries in Banach spaces of type p VL - 53 ER - TY - JOUR AU - Römhild, Roderich AU - Andersson, Dan I. ID - 9046 IS - 1 JF - PLoS Pathogens SN - 15537366 TI - Mechanisms and therapeutic potential of collateral sensitivity to antibiotics VL - 17 ER - TY - JOUR AB - This work analyzes the latency of the simplified successive cancellation (SSC) decoding scheme for polar codes proposed by Alamdar-Yazdi and Kschischang. It is shown that, unlike conventional successive cancellation decoding, where latency is linear in the block length, the latency of SSC decoding is sublinear. More specifically, the latency of SSC decoding is O(N1−1/μ) , where N is the block length and μ is the scaling exponent of the channel, which captures the speed of convergence of the rate to capacity. Numerical results demonstrate the tightness of the bound and show that most of the latency reduction arises from the parallel decoding of subcodes of rate 0 or 1. AU - Mondelli, Marco AU - Hashemi, Seyyed Ali AU - Cioffi, John M. AU - Goldsmith, Andrea ID - 9047 IS - 1 JF - IEEE Transactions on Wireless Communications SN - 15361276 TI - Sublinear latency for simplified successive cancellation decoding of polar codes VL - 20 ER - TY - JOUR AB - In this short note, we prove that the square root of the quantum Jensen-Shannon divergence is a true metric on the cone of positive matrices, and hence in particular on the quantum state space. AU - Virosztek, Daniel ID - 9036 IS - 3 JF - Advances in Mathematics KW - General Mathematics SN - 0001-8708 TI - The metric property of the quantum Jensen-Shannon divergence VL - 380 ER - TY - JOUR AB - Behavioral predispositions are innate tendencies of animals to behave in a given way without the input of learning. They increase survival chances and, due to environmental and ecological challenges, may vary substantially even between closely related taxa. These differences are likely to be especially pronounced in long-lived species like crocodilians. This order is particularly relevant for comparative cognition due to its phylogenetic proximity to birds. Here we compared early life behavioral predispositions in two Alligatoridae species. We exposed American alligator and spectacled caiman hatchlings to three different novel situations: a novel object, a novel environment that was open and a novel environment with a shelter. This was then repeated a week later. During exposure to the novel environments, alligators moved around more and explored a larger range of the arena than the caimans. When exposed to the novel object, the alligators reduced the mean distance to the novel object in the second phase, while the caimans further increased it, indicating diametrically opposite ontogenetic development in behavioral predispositions. Although all crocodilian hatchlings face comparable challenges, e.g., high predation pressure, the effectiveness of parental protection might explain the observed pattern. American alligators are apex predators capable of protecting their offspring against most dangers, whereas adult spectacled caimans are frequently predated themselves. Their distancing behavior might be related to increased predator avoidance and also explain the success of invasive spectacled caimans in the natural habitats of other crocodilians. AU - Reber, Stephan A. AU - Oh, Jinook AU - Janisch, Judith AU - Stevenson, Colin AU - Foggett, Shaun AU - Wilkinson, Anna ID - 9101 IS - 4 JF - Animal Cognition SN - 14359448 TI - Early life differences in behavioral predispositions in two Alligatoridae species VL - 24 ER - TY - JOUR AB - Marine environments are inhabited by a broad representation of the tree of life, yet our understanding of speciation in marine ecosystems is extremely limited compared with terrestrial and freshwater environments. Developing a more comprehensive picture of speciation in marine environments requires that we 'dive under the surface' by studying a wider range of taxa and ecosystems is necessary for a more comprehensive picture of speciation. Although studying marine evolutionary processes is often challenging, recent technological advances in different fields, from maritime engineering to genomics, are making it increasingly possible to study speciation of marine life forms across diverse ecosystems and taxa. Motivated by recent research in the field, including the 14 contributions in this issue, we highlight and discuss six axes of research that we think will deepen our understanding of speciation in the marine realm: (a) study a broader range of marine environments and organisms; (b) identify the reproductive barriers driving speciation between marine taxa; (c) understand the role of different genomic architectures underlying reproductive isolation; (d) infer the evolutionary history of divergence using model‐based approaches; (e) study patterns of hybridization and introgression between marine taxa; and (f) implement highly interdisciplinary, collaborative research programmes. In outlining these goals, we hope to inspire researchers to continue filling this critical knowledge gap surrounding the origins of marine biodiversity. AU - Faria, Rui AU - Johannesson, Kerstin AU - Stankowski, Sean ID - 9100 IS - 1 JF - Journal of Evolutionary Biology SN - 1010061X TI - Speciation in marine environments: Diving under the surface VL - 34 ER - TY - JOUR AB - We employ the Gross-Pitaevskii equation to study acoustic emission generated in a uniform Bose gas by a static impurity. The impurity excites a sound-wave packet, which propagates through the gas. We calculate the shape of this wave packet in the limit of long wave lengths, and argue that it is possible to extract properties of the impurity by observing this shape. We illustrate here this possibility for a Bose gas with a trapped impurity atom -- an example of a relevant experimental setup. Presented results are general for all one-dimensional systems described by the nonlinear Schrödinger equation and can also be used in nonatomic systems, e.g., to analyze light propagation in nonlinear optical media. Finally, we calculate the shape of the sound-wave packet for a three-dimensional Bose gas assuming a spherically symmetric perturbation. AU - Marchukov, Oleksandr AU - Volosniev, Artem ID - 9093 IS - 2 JF - SciPost Physics SN - 2542-4653 TI - Shape of a sound wave in a weakly-perturbed Bose gas VL - 10 ER - TY - JOUR AB - This paper continues the discussion started in [CK19] concerning Arnold's legacy on classical KAM theory and (some of) its modern developments. We prove a detailed and explicit `global' Arnold's KAM Theorem, which yields, in particular, the Whitney conjugacy of a non{degenerate, real{analytic, nearly-integrable Hamiltonian system to an integrable system on a closed, nowhere dense, positive measure subset of the phase space. Detailed measure estimates on the Kolmogorov's set are provided in the case the phase space is: (A) a uniform neighbourhood of an arbitrary (bounded) set times the d-torus and (B) a domain with C2 boundary times the d-torus. All constants are explicitly given. AU - Chierchia, Luigi AU - Koudjinan, Edmond ID - 8689 IS - 1 JF - Regular and Chaotic Dynamics KW - Nearly{integrable Hamiltonian systems KW - perturbation theory KW - KAM Theory KW - Arnold's scheme KW - Kolmogorov's set KW - primary invariant tori KW - Lagrangian tori KW - measure estimates KW - small divisors KW - integrability on nowhere dense sets KW - Diophantine frequencies. SN - 1560-3547 TI - V.I. Arnold's ''Global'' KAM theorem and geometric measure estimates VL - 26 ER - TY - JOUR AB - We show that on an Abelian variety over an algebraically closed field of positive characteristic, the obstruction to lifting an automorphism to a field of characteristic zero as a morphism vanishes if and only if it vanishes for lifting it as a derived autoequivalence. We also compare the deformation space of these two types of deformations. AU - Srivastava, Tanya K ID - 9099 IS - 5 JF - Archiv der Mathematik SN - 0003889X TI - Lifting automorphisms on Abelian varieties as derived autoequivalences VL - 116 ER - TY - JOUR AB - We study properties of the volume of projections of the n-dimensional cross-polytope $\crosp^n = \{ x \in \R^n \mid |x_1| + \dots + |x_n| \leqslant 1\}.$ We prove that the projection of $\crosp^n$ onto a k-dimensional coordinate subspace has the maximum possible volume for k=2 and for k=3. We obtain the exact lower bound on the volume of such a projection onto a two-dimensional plane. Also, we show that there exist local maxima which are not global ones for the volume of a projection of $\crosp^n$ onto a k-dimensional subspace for any n>k⩾2. AU - Ivanov, Grigory ID - 9098 IS - 5 JF - Discrete Mathematics SN - 0012365X TI - On the volume of projections of the cross-polytope VL - 344 ER - TY - JOUR AB - Genomic imprinting is an epigenetic mechanism that results in parental allele-specific expression of ~1% of all genes in mouse and human. Imprinted genes are key developmental regulators and play pivotal roles in many biological processes such as nutrient transfer from the mother to offspring and neuronal development. Imprinted genes are also involved in human disease, including neurodevelopmental disorders, and often occur in clusters that are regulated by a common imprint control region (ICR). In extra-embryonic tissues ICRs can act over large distances, with the largest surrounding Igf2r spanning over 10 million base-pairs. Besides classical imprinted expression that shows near exclusive maternal or paternal expression, widespread biased imprinted expression has been identified mainly in brain. In this review we discuss recent developments mapping cell type specific imprinted expression in extra-embryonic tissues and neocortex in the mouse. We highlight the advantages of using an inducible uniparental chromosome disomy (UPD) system to generate cells carrying either two maternal or two paternal copies of a specific chromosome to analyze the functional consequences of genomic imprinting. Mosaic Analysis with Double Markers (MADM) allows fluorescent labeling and concomitant induction of UPD sparsely in specific cell types, and thus to over-express or suppress all imprinted genes on that chromosome. To illustrate the utility of this technique, we explain how MADM-induced UPD revealed new insights about the function of the well-studied Cdkn1c imprinted gene, and how MADM-induced UPDs led to identification of highly cell type specific phenotypes related to perturbed imprinted expression in the mouse neocortex. Finally, we give an outlook on how MADM could be used to probe cell type specific imprinted expression in other tissues in mouse, particularly in extra-embryonic tissues. AU - Pauler, Florian AU - Hudson, Quanah AU - Laukoter, Susanne AU - Hippenmeyer, Simon ID - 9188 IS - 5 JF - Neurochemistry International KW - Cell Biology KW - Cellular and Molecular Neuroscience SN - 0197-0186 TI - Inducible uniparental chromosome disomy to probe genomic imprinting at single-cell level in brain and beyond VL - 145 ER - TY - JOUR AB - While several tools have been developed to study the ground state of many-body quantum spin systems, the limitations of existing techniques call for the exploration of new approaches. In this manuscript we develop an alternative analytical and numerical framework for many-body quantum spin ground states, based on the disentanglement formalism. In this approach, observables are exactly expressed as Gaussian-weighted functional integrals over scalar fields. We identify the leading contribution to these integrals, given by the saddle point of a suitable effective action. Analytically, we develop a field-theoretical expansion of the functional integrals, performed by means of appropriate Feynman rules. The expansion can be truncated to a desired order to obtain analytical approximations to observables. Numerically, we show that the disentanglement approach can be used to compute ground state expectation values from classical stochastic processes. While the associated fluctuations grow exponentially with imaginary time and the system size, this growth can be mitigated by means of an importance sampling scheme based on knowledge of the saddle point configuration. We illustrate the advantages and limitations of our methods by considering the quantum Ising model in 1, 2 and 3 spatial dimensions. Our analytical and numerical approaches are applicable to a broad class of systems, bridging concepts from quantum lattice models, continuum field theory, and classical stochastic processes. AU - De Nicola, Stefano ID - 9158 IS - 1 JF - Journal of Statistical Mechanics: Theory and Experiment KW - Statistics KW - Probability and Uncertainty KW - Statistics and Probability KW - Statistical and Nonlinear Physics SN - 1742-5468 TI - Disentanglement approach to quantum spin ground states: Field theory and stochastic simulation VL - 2021 ER - TY - JOUR AB - Cesium lead halides have intrinsically unstable crystal lattices and easily transform within perovskite and nonperovskite structures. In this work, we explore the conversion of the perovskite CsPbBr3 into Cs4PbBr6 in the presence of PbS at 450 °C to produce doped nanocrystal-based composites with embedded Cs4PbBr6 nanoprecipitates. We show that PbBr2 is extracted from CsPbBr3 and diffuses into the PbS lattice with a consequent increase in the concentration of free charge carriers. This new doping strategy enables the adjustment of the density of charge carriers between 1019 and 1020 cm–3, and it may serve as a general strategy for doping other nanocrystal-based semiconductors. AU - Calcabrini, Mariano AU - Genc, Aziz AU - Liu, Yu AU - Kleinhanns, Tobias AU - Lee, Seungho AU - Dirin, Dmitry N. AU - Akkerman, Quinten A. AU - Kovalenko, Maksym V. AU - Arbiol, Jordi AU - Ibáñez, Maria ID - 9118 IS - 2 JF - ACS Energy Letters TI - Exploiting the lability of metal halide perovskites for doping semiconductor nanocomposites VL - 6 ER - TY - JOUR AB - Interspecific crossing experiments have shown that sex chromosomes play a major role in reproductive isolation between many pairs of species. However, their ability to act as reproductive barriers, which hamper interspecific genetic exchange, has rarely been evaluated quantitatively compared to Autosomes. This genome-wide limitation of gene flow is essential for understanding the complete separation of species, and thus speciation. Here, we develop a mainland-island model of secondary contact between hybridizing species of an XY (or ZW) sexual system. We obtain theoretical predictions for the frequency of introgressed alleles, and the strength of the barrier to neutral gene flow for the two types of chromosomes carrying multiple interspecific barrier loci. Theoretical predictions are obtained for scenarios where introgressed alleles are rare. We show that the same analytical expressions apply for sex chromosomes and autosomes, but with different sex-averaged effective parameters. The specific features of sex chromosomes (hemizygosity and absence of recombination in the heterogametic sex) lead to reduced levels of introgression on the X (or Z) compared to autosomes. This effect can be enhanced by certain types of sex-biased forces, but it remains overall small (except when alleles causing incompatibilities are recessive). We discuss these predictions in the light of empirical data comprising model-based tests of introgression and cline surveys in various biological systems. AU - Fraisse, Christelle AU - Sachdeva, Himani ID - 9168 IS - 2 JF - Genetics SN - 1943-2631 TI - The rates of introgression and barriers to genetic exchange between hybridizing species: Sex chromosomes vs autosomes VL - 217 ER - TY - JOUR AB - “Hydrogen economy” could enable a carbon-neutral sustainable energy chain. However, issues with safety, storage, and transport of molecular hydrogen impede its realization. Alcohols as liquid H2 carriers could be enablers, but state-of-the-art reforming is difficult, requiring high temperatures >200 °C and pressures >25 bar, and the resulting H2 is carbonized beyond tolerance levels for direct use in fuel cells. Here, we demonstrate ambient temperature and pressure alcohol reforming in a fuel cell (ARFC) with a simultaneous electrical power output. The alcohol is oxidized at the alkaline anode, where the resulting CO2 is sequestrated as carbonate. Carbon-free H2 is liberated at the acidic cathode. The neutralization energy between the alkaline anode and the acidic cathode drives the process, particularly the unusually high entropy gain (1.27-fold ΔH). The significantly positive temperature coefficient of the resulting electromotive force allows us to harvest a large fraction of the output energy from the surrounding, achieving a thermodynamic efficiency as high as 2.27. MoS2 as the cathode catalyst allows alcohol reforming even under open-air conditions, a challenge that state-of-the-art alcohol reforming failed to overcome. We further show reforming of a wide range of alcohols. The ARFC offers an unprecedented route toward hydrogen economy as CO2 is simultaneously captured and pure H2 produced at mild conditions. AU - Manzoor Bhat, Zahid Manzoor AU - Thimmappa, Ravikumar AU - Dargily, Neethu Christudas AU - Raafik, Abdul AU - Kottaichamy, Alagar Raja AU - Devendrachari, Mruthyunjayachari Chattanahalli AU - Itagi, Mahesh AU - Makri Nimbegondi Kotresh, Harish AU - Freunberger, Stefan Alexander AU - Ottakam Thotiyl, Musthafa ID - 9113 IS - 8 JF - ACS Sustainable Chemistry and Engineering TI - Ambient condition alcohol reforming to hydrogen with electricity output VL - 9 ER - TY - JOUR AB - We present DILS, a deployable statistical analysis platform for conducting demographic inferences with linked selection from population genomic data using an Approximate Bayesian Computation framework. DILS takes as input single‐population or two‐population data sets (multilocus fasta sequences) and performs three types of analyses in a hierarchical manner, identifying: (a) the best demographic model to study the importance of gene flow and population size change on the genetic patterns of polymorphism and divergence, (b) the best genomic model to determine whether the effective size Ne and migration rate N, m are heterogeneously distributed along the genome (implying linked selection) and (c) loci in genomic regions most associated with barriers to gene flow. Also available via a Web interface, an objective of DILS is to facilitate collaborative research in speciation genomics. Here, we show the performance and limitations of DILS by using simulations and finally apply the method to published data on a divergence continuum composed by 28 pairs of Mytilus mussel populations/species. AU - Fraisse, Christelle AU - Popovic, Iva AU - Mazoyer, Clément AU - Spataro, Bruno AU - Delmotte, Stéphane AU - Romiguier, Jonathan AU - Loire, Étienne AU - Simon, Alexis AU - Galtier, Nicolas AU - Duret, Laurent AU - Bierne, Nicolas AU - Vekemans, Xavier AU - Roux, Camille ID - 9119 JF - Molecular Ecology Resources SN - 1755098X TI - DILS: Demographic inferences with linked selection by using ABC VL - 21 ER - TY - JOUR AB - We show that Hilbert schemes of points on supersingular Enriques surface in characteristic 2, Hilbn(X), for n ≥ 2 are simply connected, symplectic varieties but are not irreducible symplectic as the hodge number h2,0 > 1, even though a supersingular Enriques surface is an irreducible symplectic variety. These are the classes of varieties which appear only in characteristic 2 and they show that the hodge number formula for G¨ottsche-Soergel does not hold over haracteristic 2. It also gives examples of varieties with trivial canonical class which are neither irreducible symplectic nor Calabi-Yau, thereby showing that there are strictly more classes of simply connected varieties with trivial canonical class in characteristic 2 than over C as given by Beauville-Bogolomov decomposition theorem. AU - Srivastava, Tanya K ID - 9173 IS - 03 JF - Bulletin des Sciences Mathematiques SN - 0007-4497 TI - Pathologies of the Hilbert scheme of points of a supersingular Enriques surface VL - 167 ER - TY - CONF AB - Formal design of embedded and cyber-physical systems relies on mathematical modeling. In this paper, we consider the model class of hybrid automata whose dynamics are defined by affine differential equations. Given a set of time-series data, we present an algorithmic approach to synthesize a hybrid automaton exhibiting behavior that is close to the data, up to a specified precision, and changes in synchrony with the data. A fundamental problem in our synthesis algorithm is to check membership of a time series in a hybrid automaton. Our solution integrates reachability and optimization techniques for affine dynamical systems to obtain both a sufficient and a necessary condition for membership, combined in a refinement framework. The algorithm processes one time series at a time and hence can be interrupted, provide an intermediate result, and be resumed. We report experimental results demonstrating the applicability of our synthesis approach. AU - Garcia Soto, Miriam AU - Henzinger, Thomas A AU - Schilling, Christian ID - 9200 KW - hybrid automaton KW - membership KW - system identification SN - 9781450383394 T2 - HSCC '21: Proceedings of the 24th International Conference on Hybrid Systems: Computation and Control TI - Synthesis of hybrid automata with affine dynamics from time-series data ER - TY - JOUR AB - Cryo-EM grid preparation is an important bottleneck in protein structure determination, especially for membrane proteins, typically requiring screening of a large number of conditions. We systematically investigated the effects of buffer components, blotting conditions and grid types on the outcome of grid preparation of five different membrane protein samples. Aggregation was the most common type of problem which was addressed by changing detergents, salt concentration or reconstitution of proteins into nanodiscs or amphipols. We show that the optimal concentration of detergent is between 0.05 and 0.4% and that the presence of a low concentration of detergent with a high critical micellar concentration protects the proteins from denaturation at the air-water interface. Furthermore, we discuss the strategies for achieving an adequate ice thickness, particle coverage and orientation distribution on free ice and on support films. Our findings provide a clear roadmap for comprehensive screening of conditions for cryo-EM grid preparation of membrane proteins. AU - Kampjut, Domen AU - Steiner, Julia AU - Sazanov, Leonid A ID - 9205 IS - 3 JF - iScience TI - Cryo-EM grid optimization for membrane proteins VL - 24 ER - TY - JOUR AB - In this paper we experimentally study the transitional range of Reynolds numbers in plane Couette–Poiseuille flow, focusing our attention on the localized turbulent structures triggered by a strong impulsive jet and the large-scale flow generated around these structures. We present a detailed investigation of the large-scale flow and show how its amplitude depends on Reynolds number and amplitude perturbation. In addition, we characterize the initial dynamics of the localized turbulent spot, which includes the coupling between the small and large scales, as well as the dependence of the advection speed on the large-scale flow generated around the spot. Finally, we provide the first experimental measurements of the large-scale flow around an oblique turbulent band. AU - Klotz, Lukasz AU - Pavlenko, A. M. AU - Wesfreid, J. E. ID - 9207 JF - Journal of Fluid Mechanics SN - 0022-1120 TI - Experimental measurements in plane Couette-Poiseuille flow: Dynamics of the large- and small-scale flow VL - 912 ER - TY - JOUR AB - The precise engineering of thermoelectric materials using nanocrystals as their building blocks has proven to be an excellent strategy to increase energy conversion efficiency. Here we present a synthetic route to produce Sb-doped PbS colloidal nanoparticles. These nanoparticles are then consolidated into nanocrystalline PbS:Sb using spark plasma sintering. We demonstrate that the introduction of Sb significantly influences the size, geometry, crystal lattice and especially the carrier concentration of PbS. The increase of charge carrier concentration achieved with the introduction of Sb translates into an increase of the electrical and thermal conductivities and a decrease of the Seebeck coefficient. Overall, PbS:Sb nanomaterial were characterized by two-fold higher thermoelectric figures of merit than undoped PbS. AU - Cadavid, Doris AU - Wei, Kaya AU - Liu, Yu AU - Zhang, Yu AU - Li, Mengyao AU - Genç, Aziz AU - Berestok, Taisiia AU - Ibáñez, Maria AU - Shavel, Alexey AU - Nolas, George S. AU - Cabot, Andreu ID - 9206 IS - 4 JF - Materials TI - Synthesis, bottom up assembly and thermoelectric properties of Sb-doped PbS nanocrystal building blocks VL - 14 ER - TY - JOUR AB - Half a century after Lewis Wolpert's seminal conceptual advance on how cellular fates distribute in space, we provide a brief historical perspective on how the concept of positional information emerged and influenced the field of developmental biology and beyond. We focus on a modern interpretation of this concept in terms of information theory, largely centered on its application to cell specification in the early Drosophila embryo. We argue that a true physical variable (position) is encoded in local concentrations of patterning molecules, that this mapping is stochastic, and that the processes by which positions and corresponding cell fates are determined based on these concentrations need to take such stochasticity into account. With this approach, we shift the focus from biological mechanisms, molecules, genes and pathways to quantitative systems-level questions: where does positional information reside, how it is transformed and accessed during development, and what fundamental limits it is subject to? AU - Tkačik, Gašper AU - Gregor, Thomas ID - 9226 IS - 2 JF - Development TI - The many bits of positional information VL - 148 ER - TY - JOUR AB - A stochastic PDE, describing mesoscopic fluctuations in systems of weakly interacting inertial particles of finite volume, is proposed and analysed in any finite dimension . It is a regularised and inertial version of the Dean–Kawasaki model. A high-probability well-posedness theory for this model is developed. This theory improves significantly on the spatial scaling restrictions imposed in an earlier work of the same authors, which applied only to significantly larger particles in one dimension. The well-posedness theory now applies in d-dimensions when the particle-width ϵ is proportional to for and N is the number of particles. This scaling is optimal in a certain Sobolev norm. Key tools of the analysis are fractional Sobolev spaces, sharp bounds on Bessel functions, separability of the regularisation in the d-spatial dimensions, and use of the Faà di Bruno's formula. AU - Cornalba, Federico AU - Shardlow, Tony AU - Zimmer, Johannes ID - 9240 IS - 5 JF - Journal of Differential Equations SN - 0022-0396 TI - Well-posedness for a regularised inertial Dean–Kawasaki model for slender particles in several space dimensions VL - 284 ER - TY - CONF AB - In March 2020, the Austrian government introduced a widespread lock-down in response to the COVID-19 pandemic. Based on subjective impressions and anecdotal evidence, Austrian public and private life came to a sudden halt. Here we assess the effect of the lock-down quantitatively for all regions in Austria and present an analysis of daily changes of human mobility throughout Austria using near-real-time anonymized mobile phone data. We describe an efficient data aggregation pipeline and analyze the mobility by quantifying mobile-phone traffic at specific point of interests (POIs), analyzing individual trajectories and investigating the cluster structure of the origin-destination graph. We found a reduction of commuters at Viennese metro stations of over 80% and the number of devices with a radius of gyration of less than 500 m almost doubled. The results of studying crowd-movement behavior highlight considerable changes in the structure of mobility networks, revealed by a higher modularity and an increase from 12 to 20 detected communities. We demonstrate the relevance of mobility data for epidemiological studies by showing a significant correlation of the outflow from the town of Ischgl (an early COVID-19 hotspot) and the reported COVID-19 cases with an 8-day time lag. This research indicates that mobile phone usage data permits the moment-by-moment quantification of mobility behavior for a whole country. We emphasize the need to improve the availability of such data in anonymized form to empower rapid response to combat COVID-19 and future pandemics. AU - Heiler, Georg AU - Reisch, Tobias AU - Hurt, Jan AU - Forghani, Mohammad AU - Omani, Aida AU - Hanbury, Allan AU - Karimipour, Farid ID - 9253 SN - 9781728162515 T2 - 2020 IEEE International Conference on Big Data TI - Country-wide mobility changes observed using mobile phone data during COVID-19 pandemic ER - TY - JOUR AB - Legacy conferences are costly and time consuming, and exclude scientists lacking various resources or abilities. During the 2020 pandemic, we created an online conference platform, Neuromatch Conferences (NMC), aimed at developing technological and cultural changes to make conferences more democratic, scalable, and accessible. We discuss the lessons we learned. AU - Achakulvisut, Titipat AU - Ruangrong, Tulakan AU - Mineault, Patrick AU - Vogels, Tim P AU - Peters, Megan A.K. AU - Poirazi, Panayiota AU - Rozell, Christopher AU - Wyble, Brad AU - Goodman, Dan F.M. AU - Kording, Konrad Paul ID - 9228 IS - 4 JF - Trends in Cognitive Sciences SN - 1364-6613 TI - Towards democratizing and automating online conferences: Lessons from the Neuromatch Conferences VL - 25 ER - TY - JOUR AB - We re-examine attempts to study the many-body localization transition using measures that are physically natural on the ergodic/quantum chaotic regime of the phase diagram. Using simple scaling arguments and an analysis of various models for which rigorous results are available, we find that these measures can be particularly adversely affected by the strong finite-size effects observed in nearly all numerical studies of many-body localization. This severely impacts their utility in probing the transition and the localized phase. In light of this analysis, we discuss a recent study (Šuntajs et al., 2020) of the behaviour of the Thouless energy and level repulsion in disordered spin chains, and its implications for the question of whether MBL is a true phase of matter. AU - Abanin, D. A. AU - Bardarson, J. H. AU - De Tomasi, G. AU - Gopalakrishnan, S. AU - Khemani, V. AU - Parameswaran, S. A. AU - Pollmann, F. AU - Potter, A. C. AU - Serbyn, Maksym AU - Vasseur, R. ID - 9224 IS - 4 JF - Annals of Physics SN - 00034916 TI - Distinguishing localization from chaos: Challenges in finite-size systems VL - 427 ER - TY - JOUR AB - A graph game proceeds as follows: two players move a token through a graph to produce a finite or infinite path, which determines the payoff of the game. We study bidding games in which in each turn, an auction determines which player moves the token. Bidding games were largely studied in combination with two variants of first-price auctions called “Richman” and “poorman” bidding. We study taxman bidding, which span the spectrum between the two. The game is parameterized by a constant : portion τ of the winning bid is paid to the other player, and portion to the bank. While finite-duration (reachability) taxman games have been studied before, we present, for the first time, results on infinite-duration taxman games: we unify, generalize, and simplify previous equivalences between bidding games and a class of stochastic games called random-turn games. AU - Avni, Guy AU - Henzinger, Thomas A AU - Žikelić, Đorđe ID - 9239 IS - 8 JF - Journal of Computer and System Sciences SN - 0022-0000 TI - Bidding mechanisms in graph games VL - 119 ER - TY - JOUR AB - Organ function depends on tissues adopting the correct architecture. However, insights into organ architecture are currently hampered by an absence of standardized quantitative 3D analysis. We aimed to develop a robust technology to visualize, digitalize, and segment the architecture of two tubular systems in 3D: double resin casting micro computed tomography (DUCT). As proof of principle, we applied DUCT to a mouse model for Alagille syndrome (Jag1Ndr/Ndr mice), characterized by intrahepatic bile duct paucity, that can spontaneously generate a biliary system in adulthood. DUCT identified increased central biliary branching and peripheral bile duct tortuosity as two compensatory processes occurring in distinct regions of Jag1Ndr/Ndr liver, leading to full reconstitution of wild-type biliary volume and phenotypic recovery. DUCT is thus a powerful new technology for 3D analysis, which can reveal novel phenotypes and provide a standardized method of defining liver architecture in mouse models. AU - Hankeova, Simona AU - Salplachta, Jakub AU - Zikmund, Tomas AU - Kavkova, Michaela AU - Van Hul, Noémi AU - Brinek, Adam AU - Smekalova, Veronika AU - Laznovsky, Jakub AU - Dawit, Feven AU - Jaros, Josef AU - Bryja, Vítězslav AU - Lendahl, Urban AU - Ellis, Ewa AU - Nemeth, Antal AU - Fischler, Björn AU - Hannezo, Edouard B AU - Kaiser, Jozef AU - Andersson, Emma Rachel ID - 9244 JF - eLife TI - DUCT reveals architectural mechanisms contributing to bile duct recovery in a mouse model for alagille syndrome VL - 10 ER - TY - JOUR AB - Volumetric light transport is a pervasive physical phenomenon, and therefore its accurate simulation is important for a broad array of disciplines. While suitable mathematical models for computing the transport are now available, obtaining the necessary material parameters needed to drive such simulations is a challenging task: direct measurements of these parameters from material samples are seldom possible. Building on the inverse scattering paradigm, we present a novel measurement approach which indirectly infers the transport parameters from extrinsic observations of multiple-scattered radiance. The novelty of the proposed approach lies in replacing structured illumination with a structured reflector bonded to the sample, and a robust fitting procedure that largely compensates for potential systematic errors in the calibration of the setup. We show the feasibility of our approach by validating simulations of complex 3D compositions of the measured materials against physical prints, using photo-polymer resins. As presented in this paper, our technique yields colorspace data suitable for accurate appearance reproduction in the area of 3D printing. Beyond that, and without fundamental changes to the basic measurement methodology, it could equally well be used to obtain spectral measurements that are useful for other application areas. AU - Elek, Oskar AU - Zhang, Ran AU - Sumin, Denis AU - Myszkowski, Karol AU - Bickel, Bernd AU - Wilkie, Alexander AU - Křivánek, Jaroslav AU - Weyrich, Tim ID - 9241 IS - 5 JF - Optics Express TI - Robust and practical measurement of volume transport parameters in solid photo-polymer materials for 3D printing VL - 29 ER - TY - JOUR AB - Peptidoglycan is an essential component of the bacterial cell envelope that surrounds the cytoplasmic membrane to protect the cell from osmotic lysis. Important antibiotics such as β-lactams and glycopeptides target peptidoglycan biosynthesis. Class A penicillin-binding proteins (PBPs) are bifunctional membrane-bound peptidoglycan synthases that polymerize glycan chains and connect adjacent stem peptides by transpeptidation. How these enzymes work in their physiological membrane environment is poorly understood. Here, we developed a novel Förster resonance energy transfer-based assay to follow in real time both reactions of class A PBPs reconstituted in liposomes or supported lipid bilayers and applied this assay with PBP1B homologues from Escherichia coli, Pseudomonas aeruginosa, and Acinetobacter baumannii in the presence or absence of their cognate lipoprotein activator. Our assay will allow unravelling the mechanisms of peptidoglycan synthesis in a lipid-bilayer environment and can be further developed to be used for high-throughput screening for new antimicrobials. AU - Hernández-Rocamora, Víctor M. AU - Baranova, Natalia S. AU - Peters, Katharina AU - Breukink, Eefjan AU - Loose, Martin AU - Vollmer, Waldemar ID - 9243 JF - eLife TI - Real time monitoring of peptidoglycan synthesis by membrane-reconstituted penicillin binding proteins VL - 10 ER - TY - JOUR AB - We consider the Fröhlich Hamiltonian in a mean-field limit where many bosonic particles weakly couple to the quantized phonon field. For large particle numbers and a suitably small coupling, we show that the dynamics of the system is approximately described by the Landau–Pekar equations. These describe a Bose–Einstein condensate interacting with a classical polarization field, whose dynamics is effected by the condensate, i.e., the back-reaction of the phonons that are created by the particles during the time evolution is of leading order. AU - Leopold, Nikolai K AU - Mitrouskas, David Johannes AU - Seiringer, Robert ID - 9246 JF - Archive for Rational Mechanics and Analysis SN - 00039527 TI - Derivation of the Landau–Pekar equations in a many-body mean-field limit VL - 240 ER - TY - JOUR AB - We consider the ferromagnetic quantum Heisenberg model in one dimension, for any spin S≥1/2. We give upper and lower bounds on the free energy, proving that at low temperature it is asymptotically equal to the one of an ideal Bose gas of magnons, as predicted by the spin-wave approximation. The trial state used in the upper bound yields an analogous estimate also in the case of two spatial dimensions, which is believed to be sharp at low temperature. AU - Napiórkowski, Marcin M AU - Seiringer, Robert ID - 9256 IS - 2 JF - Letters in Mathematical Physics SN - 03779017 TI - Free energy asymptotics of the quantum Heisenberg spin chain VL - 111 ER - TY - JOUR AB - In the recent years important experimental advances in resonant electro-optic modulators as high-efficiency sources for coherent frequency combs and as devices for quantum information transfer have been realized, where strong optical and microwave mode coupling were achieved. These features suggest electro-optic-based devices as candidates for entangled optical frequency comb sources. In the present work, I study the generation of entangled optical frequency combs in millimeter-sized resonant electro-optic modulators. These devices profit from the experimentally proven advantages such as nearly constant optical free spectral ranges over several gigahertz, and high optical and microwave quality factors. The generation of frequency multiplexed quantum channels with spectral bandwidth in the MHz range for conservative parameter values paves the way towards novel uses in long-distance hybrid quantum networks, quantum key distribution, enhanced optical metrology, and quantum computing. AU - Rueda Sanchez, Alfredo R ID - 9242 IS - 2 JF - Physical Review A SN - 2469-9926 TI - Frequency-multiplexed hybrid optical entangled source based on the Pockels effect VL - 103 ER - TY - JOUR AB - The inverse problem of designing component interactions to target emergent structure is fundamental to numerous applications in biotechnology, materials science, and statistical physics. Equally important is the inverse problem of designing emergent kinetics, but this has received considerably less attention. Using recent advances in automatic differentiation, we show how kinetic pathways can be precisely designed by directly differentiating through statistical physics models, namely free energy calculations and molecular dynamics simulations. We consider two systems that are crucial to our understanding of structural self-assembly: bulk crystallization and small nanoclusters. In each case, we are able to assemble precise dynamical features. Using gradient information, we manipulate interactions among constituent particles to tune the rate at which these systems yield specific structures of interest. Moreover, we use this approach to learn nontrivial features about the high-dimensional design space, allowing us to accurately predict when multiple kinetic features can be simultaneously and independently controlled. These results provide a concrete and generalizable foundation for studying nonstructural self-assembly, including kinetic properties as well as other complex emergent properties, in a vast array of systems. AU - Goodrich, Carl Peter AU - King, Ella M. AU - Schoenholz, Samuel S. AU - Cubuk, Ekin D. AU - Brenner, Michael P. ID - 9257 IS - 10 JF - Proceedings of the National Academy of Sciences SN - 0027-8424 TI - Designing self-assembling kinetics with differentiable statistical physics models VL - 118 ER - TY - JOUR AB - Sequence-specific oligomers with predictable folding patterns, i.e., foldamers, provide new opportunities to mimic α-helical peptides and design inhibitors of protein-protein interactions. One major hurdle of this strategy is to retain the correct orientation of key side chains involved in protein surface recognition. Here, we show that the structural plasticity of a foldamer backbone may notably contribute to the required spatial adjustment for optimal interaction with the protein surface. By using oligoureas as α helix mimics, we designed a foldamer/peptide hybrid inhibitor of histone chaperone ASF1, a key regulator of chromatin dynamics. The crystal structure of its complex with ASF1 reveals a notable plasticity of the urea backbone, which adapts to the ASF1 surface to maintain the same binding interface. One additional benefit of generating ASF1 ligands with nonpeptide oligourea segments is the resistance to proteolysis in human plasma, which was highly improved compared to the cognate α-helical peptide. AU - Mbianda, Johanne AU - Bakail, May M AU - André, Christophe AU - Moal, Gwenaëlle AU - Perrin, Marie E. AU - Pinna, Guillaume AU - Guerois, Raphaël AU - Becher, Francois AU - Legrand, Pierre AU - Traoré, Seydou AU - Douat, Céline AU - Guichard, Gilles AU - Ochsenbein, Françoise ID - 9262 IS - 12 JF - Science Advances SN - 2375-2548 TI - Optimal anchoring of a foldamer inhibitor of ASF1 histone chaperone through backbone plasticity VL - 7 ER - TY - JOUR AB - Gradients of chemokines and growth factors guide migrating cells and morphogenetic processes. Migration of antigen-presenting dendritic cells from the interstitium into the lymphatic system is dependent on chemokine CCL21, which is secreted by endothelial cells of the lymphatic capillary, binds heparan sulfates and forms gradients decaying into the interstitium. Despite the importance of CCL21 gradients, and chemokine gradients in general, the mechanisms of gradient formation are unclear. Studies on fibroblast growth factors have shown that limited diffusion is crucial for gradient formation. Here, we used the mouse dermis as a model tissue to address the necessity of CCL21 anchoring to lymphatic capillary heparan sulfates in the formation of interstitial CCL21 gradients. Surprisingly, the absence of lymphatic endothelial heparan sulfates resulted only in a modest decrease of CCL21 levels at the lymphatic capillaries and did neither affect interstitial CCL21 gradient shape nor dendritic cell migration toward lymphatic capillaries. Thus, heparan sulfates at the level of the lymphatic endothelium are dispensable for the formation of a functional CCL21 gradient. AU - Vaahtomeri, Kari AU - Moussion, Christine AU - Hauschild, Robert AU - Sixt, Michael K ID - 9259 JF - Frontiers in Immunology TI - Shape and function of interstitial chemokine CCL21 gradients are independent of heparan sulfates produced by lymphatic endothelium VL - 12 ER - TY - JOUR AB - Auxin is a key regulator of plant growth and development. Local auxin biosynthesis and intercellular transport generates regional gradients in the root that are instructive for processes such as specification of developmental zones that maintain root growth and tropic responses. Here we present a toolbox to study auxin-mediated root development that features: (i) the ability to control auxin synthesis with high spatio-temporal resolution and (ii) single-cell nucleus tracking and morphokinetic analysis infrastructure. Integration of these two features enables cutting-edge analysis of root development at single-cell resolution based on morphokinetic parameters under normal growth conditions and during cell-type-specific induction of auxin biosynthesis. We show directional auxin flow in the root and refine the contributions of key players in this process. In addition, we determine the quantitative kinetics of Arabidopsis root meristem skewing, which depends on local auxin gradients but does not require PIN2 and AUX1 auxin transporter activities. Beyond the mechanistic insights into root development, the tools developed here will enable biologists to study kinetics and morphology of various critical processes at the single cell-level in whole organisms. AU - Hu, Yangjie AU - Omary, Moutasem AU - Hu, Yun AU - Doron, Ohad AU - Hörmayer, Lukas AU - Chen, Qingguo AU - Megides, Or AU - Chekli, Ori AU - Ding, Zhaojun AU - Friml, Jiří AU - Zhao, Yunde AU - Tsarfaty, Ilan AU - Shani, Eilon ID - 9254 JF - Nature Communications TI - Cell kinetics of auxin transport and activity in Arabidopsis root growth and skewing VL - 12 ER - TY - JOUR AB - Our ability to trust that a random number is truly random is essential for fields as diverse as cryptography and fundamental tests of quantum mechanics. Existing solutions both come with drawbacks—device-independent quantum random number generators (QRNGs) are highly impractical and standard semi-device-independent QRNGs are limited to a specific physical implementation and level of trust. Here we propose a framework for semi-device-independent randomness certification, using a source of trusted vacuum in the form of a signal shutter. It employs a flexible set of assumptions and levels of trust, allowing it to be applied in a wide range of physical scenarios involving both quantum and classical entropy sources. We experimentally demonstrate our protocol with a photonic setup and generate secure random bits under three different assumptions with varying degrees of security and resulting data rates. AU - Pivoluska, Matej AU - Plesch, Martin AU - Farkas, Máté AU - Ruzickova, Natalia AU - Flegel, Clara AU - Valencia, Natalia Herrera AU - Mccutcheon, Will AU - Malik, Mehul AU - Aguilar, Edgar A. ID - 9255 JF - npj Quantum Information TI - Semi-device-independent random number generation with flexible assumptions VL - 7 ER - TY - JOUR AB - We study the density of rational points on a higher-dimensional orbifold (Pn−1,Δ) when Δ is a Q-divisor involving hyperplanes. This allows us to address a question of Tanimoto about whether the set of rational points on such an orbifold constitutes a thin set. Our approach relies on the Hardy–Littlewood circle method to first study an asymptotic version of Waring’s problem for mixed powers. In doing so we make crucial use of the recent resolution of the main conjecture in Vinogradov’s mean value theorem, due to Bourgain–Demeter–Guth and Wooley. AU - Browning, Timothy D AU - Yamagishi, Shuntaro ID - 9260 JF - Mathematische Zeitschrift SN - 0025-5874 TI - Arithmetic of higher-dimensional orbifolds and a mixed Waring problem VL - 299 ER - TY - JOUR AU - Pinkard, Henry AU - Stuurman, Nico AU - Ivanov, Ivan E. AU - Anthony, Nicholas M. AU - Ouyang, Wei AU - Li, Bin AU - Yang, Bin AU - Tsuchida, Mark A. AU - Chhun, Bryant AU - Zhang, Grace AU - Mei, Ryan AU - Anderson, Michael AU - Shepherd, Douglas P. AU - Hunt-Isaak, Ian AU - Dunn, Raymond L. AU - Jahr, Wiebke AU - Kato, Saul AU - Royer, Loïc A. AU - Thiagarajah, Jay R. AU - Eliceiri, Kevin W. AU - Lundberg, Emma AU - Mehta, Shalin B. AU - Waller, Laura ID - 9258 IS - 3 JF - Nature Methods SN - 1548-7091 TI - Pycro-Manager: Open-source software for customized and reproducible microscope control VL - 18 ER - TY - JOUR AB - Assemblies of actin and its regulators underlie the dynamic morphology of all eukaryotic cells. To understand how actin regulatory proteins work together to generate actin-rich structures such as filopodia, we analyzed the localization of diverse actin regulators within filopodia in Drosophila embryos and in a complementary in vitro system of filopodia-like structures (FLSs). We found that the composition of the regulatory protein complex where actin is incorporated (the filopodial tip complex) is remarkably heterogeneous both in vivo and in vitro. Our data reveal that different pairs of proteins correlate with each other and with actin bundle length, suggesting the presence of functional subcomplexes. This is consistent with a theoretical framework where three or more redundant subcomplexes join the tip complex stochastically, with any two being sufficient to drive filopodia formation. We provide an explanation for the observed heterogeneity and suggest that a mechanism based on multiple components allows stereotypical filopodial dynamics to arise from diverse upstream signaling pathways. AU - Dobramysl, Ulrich AU - Jarsch, Iris Katharina AU - Inoue, Yoshiko AU - Shimo, Hanae AU - Richier, Benjamin AU - Gadsby, Jonathan R. AU - Mason, Julia AU - Szałapak, Alicja AU - Ioannou, Pantelis Savvas AU - Correia, Guilherme Pereira AU - Walrant, Astrid AU - Butler, Richard AU - Hannezo, Edouard B AU - Simons, Benjamin D. AU - Gallop, Jennifer L. ID - 9306 IS - 4 JF - Journal of Cell Biology TI - Stochastic combinations of actin regulatory proteins are sufficient to drive filopodia formation VL - 220 ER - TY - JOUR AB - We establish finite time extinction with probability one for weak solutions of the Cauchy–Dirichlet problem for the 1D stochastic porous medium equation with Stratonovich transport noise and compactly supported smooth initial datum. Heuristically, this is expected to hold because Brownian motion has average spread rate O(t12) whereas the support of solutions to the deterministic PME grows only with rate O(t1m+1). The rigorous proof relies on a contraction principle up to time-dependent shift for Wong–Zakai type approximations, the transformation to a deterministic PME with two copies of a Brownian path as the lateral boundary, and techniques from the theory of viscosity solutions. AU - Hensel, Sebastian ID - 9307 JF - Stochastics and Partial Differential Equations: Analysis and Computations SN - 2194-0401 TI - Finite time extinction for the 1D stochastic porous medium equation with transport noise VL - 9 ER - TY - JOUR AB - We report the results of an experimental investigation into the decay of turbulence in plane Couette–Poiseuille flow using ‘quench’ experiments where the flow laminarises after a sudden reduction in Reynolds number Re. Specifically, we study the velocity field in the streamwise–spanwise plane. We show that the spanwise velocity containing rolls decays faster than the streamwise velocity, which displays elongated regions of higher or lower velocity called streaks. At final Reynolds numbers above 425, the decay of streaks displays two stages: first a slow decay when rolls are present and secondly a more rapid decay of streaks alone. The difference in behaviour results from the regeneration of streaks by rolls, called the lift-up effect. We define the turbulent fraction as the portion of the flow containing turbulence and this is estimated by thresholding the spanwise velocity component. It decreases linearly with time in the whole range of final Re. The corresponding decay slope increases linearly with final Re. The extrapolated value at which this decay slope vanishes is Reaz≈656±10, close to Reg≈670 at which turbulence is self-sustained. The decay of the energy computed from the spanwise velocity component is found to be exponential. The corresponding decay rate increases linearly with Re, with an extrapolated vanishing value at ReAz≈688±10. This value is also close to the value at which the turbulence is self-sustained, showing that valuable information on the transition can be obtained over a wide range of Re. AU - Liu, T. AU - Semin, B. AU - Klotz, Lukasz AU - Godoy-Diana, R. AU - Wesfreid, J. E. AU - Mullin, T. ID - 9297 JF - Journal of Fluid Mechanics SN - 0022-1120 TI - Decay of streaks and rolls in plane Couette-Poiseuille flow VL - 915 ER - TY - JOUR AB - Hill's Conjecture states that the crossing number cr(𝐾𝑛) of the complete graph 𝐾𝑛 in the plane (equivalently, the sphere) is 14⌊𝑛2⌋⌊𝑛−12⌋⌊𝑛−22⌋⌊𝑛−32⌋=𝑛4/64+𝑂(𝑛3) . Moon proved that the expected number of crossings in a spherical drawing in which the points are randomly distributed and joined by geodesics is precisely 𝑛4/64+𝑂(𝑛3) , thus matching asymptotically the conjectured value of cr(𝐾𝑛) . Let cr𝑃(𝐺) denote the crossing number of a graph 𝐺 in the projective plane. Recently, Elkies proved that the expected number of crossings in a naturally defined random projective plane drawing of 𝐾𝑛 is (𝑛4/8𝜋2)+𝑂(𝑛3) . In analogy with the relation of Moon's result to Hill's conjecture, Elkies asked if lim𝑛→∞ cr𝑃(𝐾𝑛)/𝑛4=1/8𝜋2 . We construct drawings of 𝐾𝑛 in the projective plane that disprove this. AU - Arroyo Guevara, Alan M AU - Mcquillan, Dan AU - Richter, R. Bruce AU - Salazar, Gelasio AU - Sullivan, Matthew ID - 9295 IS - 3 JF - Journal of Graph Theory SN - 0364-9024 TI - Drawings of complete graphs in the projective plane VL - 97 ER - TY - JOUR AB - In this issue of Developmental Cell, Doyle and colleagues identify periodic anterior contraction as a characteristic feature of fibroblasts and mesenchymal cancer cells embedded in 3D collagen gels. This contractile mechanism generates a matrix prestrain required for crawling in fibrous 3D environments. AU - Gärtner, Florian R AU - Sixt, Michael K ID - 9294 IS - 6 JF - Developmental Cell SN - 15345807 TI - Engaging the front wheels to drive through fibrous terrain VL - 56 ER - TY - JOUR AB - Background: To understand information coding in single neurons, it is necessary to analyze subthreshold synaptic events, action potentials (APs), and their interrelation in different behavioral states. However, detecting excitatory postsynaptic potentials (EPSPs) or currents (EPSCs) in behaving animals remains challenging, because of unfavorable signal-to-noise ratio, high frequency, fluctuating amplitude, and variable time course of synaptic events. New method: We developed a method for synaptic event detection, termed MOD (Machine-learning Optimal-filtering Detection-procedure), which combines concepts of supervised machine learning and optimal Wiener filtering. Experts were asked to manually score short epochs of data. The algorithm was trained to obtain the optimal filter coefficients of a Wiener filter and the optimal detection threshold. Scored and unscored data were then processed with the optimal filter, and events were detected as peaks above threshold. Results: We challenged MOD with EPSP traces in vivo in mice during spatial navigation and EPSC traces in vitro in slices under conditions of enhanced transmitter release. The area under the curve (AUC) of the receiver operating characteristics (ROC) curve was, on average, 0.894 for in vivo and 0.969 for in vitro data sets, indicating high detection accuracy and efficiency. Comparison with existing methods: When benchmarked using a (1 − AUC)−1 metric, MOD outperformed previous methods (template-fit, deconvolution, and Bayesian methods) by an average factor of 3.13 for in vivo data sets, but showed comparable (template-fit, deconvolution) or higher (Bayesian) computational efficacy. Conclusions: MOD may become an important new tool for large-scale, real-time analysis of synaptic activity. AU - Zhang, Xiaomin AU - Schlögl, Alois AU - Vandael, David H AU - Jonas, Peter M ID - 9329 IS - 6 JF - Journal of Neuroscience Methods SN - 0165-0270 TI - MOD: A novel machine-learning optimal-filtering method for accurate and efficient detection of subthreshold synaptic events in vivo VL - 357 ER - TY - JOUR AB - Embryo morphogenesis is impacted by dynamic changes in tissue material properties, which have been proposed to occur via processes akin to phase transitions (PTs). Here, we show that rigidity percolation provides a simple and robust theoretical framework to predict material/structural PTs of embryonic tissues from local cell connectivity. By using percolation theory, combined with directly monitoring dynamic changes in tissue rheology and cell contact mechanics, we demonstrate that the zebrafish blastoderm undergoes a genuine rigidity PT, brought about by a small reduction in adhesion-dependent cell connectivity below a critical value. We quantitatively predict and experimentally verify hallmarks of PTs, including power-law exponents and associated discontinuities of macroscopic observables. Finally, we show that this uniform PT depends on blastoderm cells undergoing meta-synchronous divisions causing random and, consequently, uniform changes in cell connectivity. Collectively, our theoretical and experimental findings reveal the structural basis of material PTs in an organismal context. AU - Petridou, Nicoletta AU - Corominas-Murtra, Bernat AU - Heisenberg, Carl-Philipp J AU - Hannezo, Edouard B ID - 9316 IS - 7 JF - Cell SN - 00928674 TI - Rigidity percolation uncovers a structural basis for embryonic tissue phase transitions VL - 184 ER - TY - JOUR AB - Given a locally finite X⊆Rd and a radius r≥0, the k-fold cover of X and r consists of all points in Rd that have k or more points of X within distance r. We consider two filtrations—one in scale obtained by fixing k and increasing r, and the other in depth obtained by fixing r and decreasing k—and we compute the persistence diagrams of both. While standard methods suffice for the filtration in scale, we need novel geometric and topological concepts for the filtration in depth. In particular, we introduce a rhomboid tiling in Rd+1 whose horizontal integer slices are the order-k Delaunay mosaics of X, and construct a zigzag module of Delaunay mosaics that is isomorphic to the persistence module of the multi-covers. AU - Edelsbrunner, Herbert AU - Osang, Georg F ID - 9317 JF - Discrete and Computational Geometry SN - 0179-5376 TI - The multi-cover persistence of Euclidean balls VL - 65 ER - TY - JOUR AB - We consider a system of N bosons in the mean-field scaling regime for a class of interactions including the repulsive Coulomb potential. We derive an asymptotic expansion of the low-energy eigenstates and the corresponding energies, which provides corrections to Bogoliubov theory to any order in 1/N. AU - Bossmann, Lea AU - Petrat, Sören P AU - Seiringer, Robert ID - 9318 JF - Forum of Mathematics, Sigma TI - Asymptotic expansion of low-energy excitations for weakly interacting bosons VL - 9 ER - TY - JOUR AB - Quantum entanglement has been generated and verified in cold-atom experiments and used to make atom-interferometric measurements below the shot-noise limit. However, current state-of-the-art cold-atom devices exploit separable (i.e., unentangled) atomic states. This perspective piece asks the question: can entanglement usefully improve cold-atom sensors, in the sense that it gives new sensing capabilities unachievable with current state-of-the-art devices? We briefly review the state-of-the-art in precision cold-atom sensing, focusing on clocks and inertial sensors, identifying the potential benefits entanglement could bring to these devices, and the challenges that need to be overcome to realize these benefits. We survey demonstrated methods of generating metrologically useful entanglement in cold-atom systems, note their relative strengths and weaknesses, and assess their prospects for near-to-medium term quantum-enhanced cold-atom sensing. AU - Szigeti, Stuart S. AU - Hosten, Onur AU - Haine, Simon A. ID - 9331 IS - 14 JF - Applied Physics Letters SN - 00036951 TI - Improving cold-atom sensors with quantum entanglement: Prospects and challenges VL - 118 ER - TY - JOUR AB - In nerve cells the genes encoding for α2δ subunits of voltage-gated calcium channels have been linked to synaptic functions and neurological disease. Here we show that α2δ subunits are essential for the formation and organization of glutamatergic synapses. Using a cellular α2δ subunit triple-knockout/knockdown model, we demonstrate a failure in presynaptic differentiation evidenced by defective presynaptic calcium channel clustering and calcium influx, smaller presynaptic active zones, and a strongly reduced accumulation of presynaptic vesicle-associated proteins (synapsin and vGLUT). The presynaptic defect is associated with the downscaling of postsynaptic AMPA receptors and the postsynaptic density. The role of α2δ isoforms as synaptic organizers is highly redundant, as each individual α2δ isoform can rescue presynaptic calcium channel trafficking and expression of synaptic proteins. Moreover, α2δ-2 and α2δ-3 with mutated metal ion-dependent adhesion sites can fully rescue presynaptic synapsin expression but only partially calcium channel trafficking, suggesting that the regulatory role of α2δ subunits is independent from its role as a calcium channel subunit. Our findings influence the current view on excitatory synapse formation. First, our study suggests that postsynaptic differentiation is secondary to presynaptic differentiation. Second, the dependence of presynaptic differentiation on α2δ implicates α2δ subunits as potential nucleation points for the organization of synapses. Finally, our results suggest that α2δ subunits act as transsynaptic organizers of glutamatergic synapses, thereby aligning the synaptic active zone with the postsynaptic density. AU - Schöpf, Clemens L. AU - Ablinger, Cornelia AU - Geisler, Stefanie M. AU - Stanika, Ruslan I. AU - Campiglio, Marta AU - Kaufmann, Walter AU - Nimmervoll, Benedikt AU - Schlick, Bettina AU - Brockhaus, Johannes AU - Missler, Markus AU - Shigemoto, Ryuichi AU - Obermair, Gerald J. ID - 9330 IS - 14 JF - PNAS TI - Presynaptic α2δ subunits are key organizers of glutamatergic synapses VL - 118 ER -