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 -