TY - THES AB - Neuronal networks in the brain consist of two main types of neuron, glutamatergic principal neurons and GABAergic interneurons. Although these interneurons only represent 10–20% of the whole population, they mediate feedback and feedforward inhibition and are involved in the generation of high-frequency network oscillations. A hallmark functional property of GABAergic interneurons, especially of the parvalbumin‑expressing (PV+) subtypes, is the speed of signaling at their output synapse across species and brain regions. Several molecular and subcellular factors may underlie the submillisecond signaling at GABAergic synapses. Such as the selective use of P/Q type Ca2+ channels and the tight coupling between Ca2+ channels and Ca2+ sensors of exocytosis. However, whether the molecular identity of the release sensor contributes to these signaling properties remains unclear. Besides, these interneurons are mainly show depression in response to train of stimuli. How could they keep sufficient release to control the activity of postsynaptic principal neurons during high network activity, is largely elusive. For my Ph.D. work, we firstly examined the Ca2+ sensor of exocytosis at the GABAergic basket cell (BC) to Purkinje cell (PC) synapse in the cerebellum. Immunolabeling suggested that BC terminals selectively expressed synaptotagmin 2 (Syt2), whereas synaptotagmin 1 (Syt1) was enriched in excitatory terminals. Genetic elimination of Syt2 reduced action potential-evoked release to ~10% compared to the wild-type control, identifying Syt2 as the major Ca2+ sensor at BC‑PC synapses. Differential adenovirus-mediated rescue revealed Syt2 triggered release with shorter latency and higher temporal precision, and mediated faster vesicle pool replenishment than Syt1. Furthermore, deletion of Syt2 severely reduced and delayed disynaptic inhibition following parallel fiber stimulation. Thus, the selective use of Syt2 as the release sensor at BC–PC synapse ensures fast feedforward inhibition in cerebellar microcircuits. Additionally, we tested the function of another synaptotagmin member, Syt7, for inhibitory synaptic transmission at the BC–PC synapse. Syt7 is thought to be a Ca2+ sensor that mediates asynchronous transmitter release and facilitation at synapses. However, it is strongly expressed in fast-spiking, PV+ GABAergic interneurons and the output synapses of these neurons produce only minimal asynchronous release and show depression rather than facilitation. How could Syt7, a facilitation sensor, contribute to the depressed inhibitory synaptic transmission needs to be further investigated and understood. Our results indicated that at the BC–PC synapse, Syt7 contributes to asynchronous release, pool replenishment and facilitation. In combination, these three effects ensure efficient transmitter release during high‑frequency activity and guarantee frequency independence of inhibition. Taken together, our results confirmed that Syt2, which has the fastest kinetic properties among all synaptotagmin members, is mainly used by the inhibitory BC‑PC synapse for synaptic transmission, contributing to the speed and temporal precision of transmitter release. Furthermore, we showed that Syt7, another highly expressed synaptotagmin member in the output synapses of cerebellar BCs, is used for ensuring efficient inhibitor synaptic transmission during high activity. AU - Chen, Chong ID - 324 SN - 2663-337X TI - Synaptotagmins ensure speed and efficiency of inhibitory neurotransmitter release ER - TY - JOUR AB - We give a detailed and easily accessible proof of Gromov’s Topological Overlap Theorem. Let X be a finite simplicial complex or, more generally, a finite polyhedral cell complex of dimension d. Informally, the theorem states that if X has sufficiently strong higher-dimensional expansion properties (which generalize edge expansion of graphs and are defined in terms of cellular cochains of X) then X has the following topological overlap property: for every continuous map (Formula presented.) there exists a point (Formula presented.) that is contained in the images of a positive fraction (Formula presented.) of the d-cells of X. More generally, the conclusion holds if (Formula presented.) is replaced by any d-dimensional piecewise-linear manifold M, with a constant (Formula presented.) that depends only on d and on the expansion properties of X, but not on M. AU - Dotterrer, Dominic AU - Kaufman, Tali AU - Wagner, Uli ID - 742 IS - 1 JF - Geometriae Dedicata TI - On expansion and topological overlap VL - 195 ER - TY - JOUR AB - We consider the totally asymmetric simple exclusion process in a critical scaling parametrized by a≥0, which creates a shock in the particle density of order aT−1/3, T the observation time. When starting from step initial data, we provide bounds on the limiting law which in particular imply that in the double limit lima→∞limT→∞ one recovers the product limit law and the degeneration of the correlation length observed at shocks of order 1. This result is shown to apply to a general last-passage percolation model. We also obtain bounds on the two-point functions of several airy processes. AU - Nejjar, Peter ID - 70 IS - 2 JF - Latin American Journal of Probability and Mathematical Statistics SN - 1980-0436 TI - Transition to shocks in TASEP and decoupling of last passage times VL - 15 ER - TY - JOUR AB - Recent realization of a kinetically constrained chain of Rydberg atoms by Bernien et al., [Nature (London) 551, 579 (2017)] resulted in the observation of unusual revivals in the many-body quantum dynamics. In our previous work [C. J. Turner et al., Nat. Phys. 14, 745 (2018)], such dynamics was attributed to the existence of “quantum scarred” eigenstates in the many-body spectrum of the experimentally realized model. Here, we present a detailed study of the eigenstate properties of the same model. We find that the majority of the eigenstates exhibit anomalous thermalization: the observable expectation values converge to their Gibbs ensemble values, but parametrically slower compared to the predictions of the eigenstate thermalization hypothesis (ETH). Amidst the thermalizing spectrum, we identify nonergodic eigenstates that strongly violate the ETH, whose number grows polynomially with system size. Previously, the same eigenstates were identified via large overlaps with certain product states, and were used to explain the revivals observed in experiment. Here, we find that these eigenstates, in addition to highly atypical expectation values of local observables, also exhibit subthermal entanglement entropy that scales logarithmically with the system size. Moreover, we identify an additional class of quantum scarred eigenstates, and discuss their manifestations in the dynamics starting from initial product states. We use forward scattering approximation to describe the structure and physical properties of quantum scarred eigenstates. Finally, we discuss the stability of quantum scars to various perturbations. We observe that quantum scars remain robust when the introduced perturbation is compatible with the forward scattering approximation. In contrast, the perturbations which most efficiently destroy quantum scars also lead to the restoration of “canonical” thermalization. AU - Turner, C J AU - Michailidis, Alexios AU - Abanin, D A AU - Serbyn, Maksym AU - Papić, Z ID - 44 IS - 15 JF - Physical Review B TI - Quantum scarred eigenstates in a Rydberg atom chain: Entanglement, breakdown of thermalization, and stability to perturbations VL - 98 ER - TY - JOUR AB - The drag of turbulent flows can be drastically decreased by adding small amounts of high molecular weight polymers. While drag reduction initially increases with polymer concentration, it eventually saturates to what is known as the maximum drag reduction (MDR) asymptote; this asymptote is generally attributed to the dynamics being reduced to a marginal yet persistent state of subdued turbulent motion. Contrary to this accepted view, we show that, for an appropriate choice of parameters, polymers can reduce the drag beyond the suggested asymptotic limit, eliminating turbulence and giving way to laminar flow. At higher polymer concentrations, however, the laminar state becomes unstable, resulting in a fluctuating flow with the characteristic drag of the MDR asymptote. Our findings indicate that the asymptotic state is hence dynamically disconnected from ordinary turbulence. © 2018 American Physical Society. AU - Choueiri, George H AU - Lopez Alonso, Jose M AU - Hof, Björn ID - 328 IS - 12 JF - Physical Review Letters TI - Exceeding the asymptotic limit of polymer drag reduction VL - 120 ER - TY - JOUR AB - Recent studies suggest that unstable, nonchaotic solutions of the Navier-Stokes equation may provide deep insights into fluid turbulence. In this article, we present a combined experimental and numerical study exploring the dynamical role of unstable equilibrium solutions and their invariant manifolds in a weakly turbulent, electromagnetically driven, shallow fluid layer. Identifying instants when turbulent evolution slows down, we compute 31 unstable equilibria of a realistic two-dimensional model of the flow. We establish the dynamical relevance of these unstable equilibria by showing that they are closely visited by the turbulent flow. We also establish the dynamical relevance of unstable manifolds by verifying that they are shadowed by turbulent trajectories departing from the neighborhoods of unstable equilibria over large distances in state space. AU - Suri, Balachandra AU - Tithof, Jeffrey AU - Grigoriev, Roman AU - Schatz, Michael ID - 136 IS - 2 JF - Physical Review E TI - Unstable equilibria and invariant manifolds in quasi-two-dimensional Kolmogorov-like flow VL - 98 ER - TY - JOUR AB - Background: Transport protein particle (TRAPP) is a multisubunit complex that regulates membrane trafficking through the Golgi apparatus. The clinical phenotype associated with mutations in various TRAPP subunits has allowed elucidation of their functions in specific tissues. The role of some subunits in human disease, however, has not been fully established, and their functions remain uncertain. Objective: We aimed to expand the range of neurodevelopmental disorders associated with mutations in TRAPP subunits by exome sequencing of consanguineous families. Methods: Linkage and homozygosity mapping and candidate gene analysis were used to identify homozygous mutations in families. Patient fibroblasts were used to study splicing defect and zebrafish to model the disease. Results: We identified six individuals from three unrelated families with a founder homozygous splice mutation in TRAPPC6B, encoding a core subunit of the complex TRAPP I. Patients manifested a neurodevelopmental disorder characterised by microcephaly, epilepsy and autistic features, and showed splicing defect. Zebrafish trappc6b morphants replicated the human phenotype, displaying decreased head size and neuronal hyperexcitability, leading to a lower seizure threshold. Conclusion: This study provides clinical and functional evidence of the role of TRAPPC6B in brain development and function. AU - Marin Valencia, Isaac AU - Novarino, Gaia AU - Johansen, Anide AU - Rosti, Başak AU - Issa, Mahmoud AU - Musaev, Damir AU - Bhat, Gifty AU - Scott, Eric AU - Silhavy, Jennifer AU - Stanley, Valentina AU - Rosti, Rasim AU - Gleeson, Jeremy AU - Imam, Farhad AU - Zaki, Maha AU - Gleeson, Joseph ID - 691 IS - 1 JF - Journal of Medical Genetics SN - 0022-2593 TI - A homozygous founder mutation in TRAPPC6B associates with a neurodevelopmental disorder characterised by microcephaly epilepsy and autistic features VL - 55 ER - TY - JOUR AB - Borel probability measures living on metric spaces are fundamental mathematical objects. There are several meaningful distance functions that make the collection of the probability measures living on a certain space a metric space. We are interested in the description of the structure of the isometries of such metric spaces. We overview some of the recent results of the topic and we also provide some new ones concerning the Wasserstein distance. More specifically, we consider the space of all Borel probability measures on the unit sphere of a Euclidean space endowed with the Wasserstein metric W_p for arbitrary p >= 1, and we show that the action of a Wasserstein isometry on the set of Dirac measures is induced by an isometry of the underlying unit sphere. AU - Virosztek, Daniel ID - 284 IS - 1-2 JF - Acta Scientiarum Mathematicarum SN - 0001-6969 TI - Maps on probability measures preserving certain distances - a survey and some new results VL - 84 ER - TY - JOUR AB - In this paper we define and study the classical Uniform Electron Gas (UEG), a system of infinitely many electrons whose density is constant everywhere in space. The UEG is defined differently from Jellium, which has a positive constant background but no constraint on the density. We prove that the UEG arises in Density Functional Theory in the limit of a slowly varying density, minimizing the indirect Coulomb energy. We also construct the quantum UEG and compare it to the classical UEG at low density. AU - Lewi, Mathieu AU - Lieb, Élliott AU - Seiringer, Robert ID - 180 JF - Journal de l'Ecole Polytechnique - Mathematiques SN - 2429-7100 TI - Statistical mechanics of the uniform electron gas VL - 5 ER - TY - JOUR AB - For ultrafast fixation of biological samples to avoid artifacts, high-pressure freezing (HPF) followed by freeze substitution (FS) is preferred over chemical fixation at room temperature. After HPF, samples are maintained at low temperature during dehydration and fixation, while avoiding damaging recrystallization. This is a notoriously slow process. McDonald and Webb demonstrated, in 2011, that sample agitation during FS dramatically reduces the necessary time. Then, in 2015, we (H.G. and S.R.) introduced an agitation module into the cryochamber of an automated FS unit and demonstrated that the preparation of algae could be shortened from days to a couple of hours. We argued that variability in the processing, reproducibility, and safety issues are better addressed using automated FS units. For dissemination, we started low-cost manufacturing of agitation modules for two of the most widely used FS units, the Automatic Freeze Substitution Systems, AFS(1) and AFS2, from Leica Microsystems, using three dimensional (3D)-printing of the major components. To test them, several labs independently used the modules on a wide variety of specimens that had previously been processed by manual agitation, or without agitation. We demonstrate that automated processing with sample agitation saves time, increases flexibility with respect to sample requirements and protocols, and produces data of at least as good quality as other approaches. AU - Reipert, Siegfried AU - Goldammer, Helmuth AU - Richardson, Christine AU - Goldberg, Martin AU - Hawkins, Timothy AU - Hollergschwandtner, Elena AU - Kaufmann, Walter AU - Antreich, Sebastian AU - Stierhof, York ID - 163 IS - 12 JF - Journal of Histochemistry and Cytochemistry SN - 0022-1554 TI - Agitation modules: Flexible means to accelerate automated freeze substitution VL - 66 ER - TY - CONF AB - We present an approach to identify concise equations from data using a shallow neural network approach. In contrast to ordinary black-box regression, this approach allows understanding functional relations and generalizing them from observed data to unseen parts of the parameter space. We show how to extend the class of learnable equations for a recently proposed equation learning network to include divisions, and we improve the learning and model selection strategy to be useful for challenging real-world data. For systems governed by analytical expressions, our method can in many cases identify the true underlying equation and extrapolate to unseen domains. We demonstrate its effectiveness by experiments on a cart-pendulum system, where only 2 random rollouts are required to learn the forward dynamics and successfully achieve the swing-up task. AU - Sahoo, Subham AU - Lampert, Christoph AU - Martius, Georg S ID - 6012 T2 - Proceedings of the 35th International Conference on Machine Learning TI - Learning equations for extrapolation and control VL - 80 ER - TY - CONF AB - We establish a data-dependent notion of algorithmic stability for Stochastic Gradient Descent (SGD), and employ it to develop novel generalization bounds. This is in contrast to previous distribution-free algorithmic stability results for SGD which depend on the worst-case constants. By virtue of the data-dependent argument, our bounds provide new insights into learning with SGD on convex and non-convex problems. In the convex case, we show that the bound on the generalization error depends on the risk at the initialization point. In the non-convex case, we prove that the expected curvature of the objective function around the initialization point has crucial influence on the generalization error. In both cases, our results suggest a simple data-driven strategy to stabilize SGD by pre-screening its initialization. As a corollary, our results allow us to show optimistic generalization bounds that exhibit fast convergence rates for SGD subject to a vanishing empirical risk and low noise of stochastic gradient. AU - Kuzborskij, Ilja AU - Lampert, Christoph ID - 6011 T2 - Proceedings of the 35 th International Conference on Machine Learning TI - Data-dependent stability of stochastic gradient descent VL - 80 ER - TY - GEN AU - Danowski, Patrick ID - 5686 TI - An Austrian proposal for the Classification of Open Access Tuples (COAT) - Distinguish different Open Access types beyond colors ER - TY - CONF AB - Distributed training of massive machine learning models, in particular deep neural networks, via Stochastic Gradient Descent (SGD) is becoming commonplace. Several families of communication-reduction methods, such as quantization, large-batch methods, and gradient sparsification, have been proposed. To date, gradient sparsification methods--where each node sorts gradients by magnitude, and only communicates a subset of the components, accumulating the rest locally--are known to yield some of the largest practical gains. Such methods can reduce the amount of communication per step by up to \emph{three orders of magnitude}, while preserving model accuracy. Yet, this family of methods currently has no theoretical justification. This is the question we address in this paper. We prove that, under analytic assumptions, sparsifying gradients by magnitude with local error correction provides convergence guarantees, for both convex and non-convex smooth objectives, for data-parallel SGD. The main insight is that sparsification methods implicitly maintain bounds on the maximum impact of stale updates, thanks to selection by magnitude. Our analysis and empirical validation also reveal that these methods do require analytical conditions to converge well, justifying existing heuristics. AU - Alistarh, Dan-Adrian AU - Hoefler, Torsten AU - Johansson, Mikael AU - Konstantinov, Nikola H AU - Khirirat, Sarit AU - Renggli, Cedric ID - 6589 T2 - Advances in Neural Information Processing Systems 31 TI - The convergence of sparsified gradient methods VL - Volume 2018 ER - TY - JOUR AB - Animal social networks are shaped by multiple selection pressures, including the need to ensure efficient communication and functioning while simultaneously limiting disease transmission. Social animals could potentially further reduce epidemic risk by altering their social networks in the presence of pathogens, yet there is currently no evidence for such pathogen-triggered responses. We tested this hypothesis experimentally in the ant Lasius niger using a combination of automated tracking, controlled pathogen exposure, transmission quantification, and temporally explicit simulations. Pathogen exposure induced behavioral changes in both exposed ants and their nestmates, which helped contain the disease by reinforcing key transmission-inhibitory properties of the colony's contact network. This suggests that social network plasticity in response to pathogens is an effective strategy for mitigating the effects of disease in social groups. AU - Stroeymeyt, Nathalie AU - Grasse, Anna V AU - Crespi, Alessandro AU - Mersch, Danielle AU - Cremer, Sylvia AU - Keller, Laurent ID - 7 IS - 6417 JF - Science SN - 1095-9203 TI - Social network plasticity decreases disease transmission in a eusocial insect VL - 362 ER - TY - JOUR AB - Bacteria regulate genes to survive antibiotic stress, but regulation can be far from perfect. When regulation is not optimal, mutations that change gene expression can contribute to antibiotic resistance. It is not systematically understood to what extent natural gene regulation is or is not optimal for distinct antibiotics, and how changes in expression of specific genes quantitatively affect antibiotic resistance. Here we discover a simple quantitative relation between fitness, gene expression, and antibiotic potency, which rationalizes our observation that a multitude of genes and even innate antibiotic defense mechanisms have expression that is critically nonoptimal under antibiotic treatment. First, we developed a pooled-strain drug-diffusion assay and screened Escherichia coli overexpression and knockout libraries, finding that resistance to a range of 31 antibiotics could result from changing expression of a large and functionally diverse set of genes, in a primarily but not exclusively drug-specific manner. Second, by synthetically controlling the expression of single-drug and multidrug resistance genes, we observed that their fitness-expression functions changed dramatically under antibiotic treatment in accordance with a log-sensitivity relation. Thus, because many genes are nonoptimally expressed under antibiotic treatment, many regulatory mutations can contribute to resistance by altering expression and by activating latent defenses. AU - Palmer, Adam AU - Chait, Remy P AU - Kishony, Roy ID - 19 IS - 11 JF - Molecular Biology and Evolution SN - 0737-4038 TI - Nonoptimal gene expression creates latent potential for antibiotic resistance VL - 35 ER - TY - JOUR AB - Lesion and electrode location verification are traditionally done via histological examination of stained brain slices, a time-consuming procedure that requires manual estimation. Here, we describe a simple, straightforward method for quantifying lesions and locating electrodes in the brain that is less laborious and yields more detailed results. Whole brains are stained with osmium tetroxide, embedded in resin, and imaged with a micro-CT scanner. The scans result in 3D digital volumes of the brains with resolutions and virtual section thicknesses dependent on the sample size (12-15 and 5-6 µm per voxel for rat and zebra finch brains, respectively). Surface and deep lesions can be characterized, and single tetrodes, tetrode arrays, electrolytic lesions, and silicon probes can also be localized. Free and proprietary software allows experimenters to examine the sample volume from any plane and segment the volume manually or automatically. Because this method generates whole brain volume, lesions and electrodes can be quantified to a much higher degree than in current methods, which will help standardize comparisons within and across studies. AU - Masís, Javier AU - Mankus, David AU - Wolff, Steffen AU - Guitchounts, Grigori AU - Jösch, Maximilian A AU - Cox, David ID - 6 JF - Journal of visualized experiments TI - A micro-CT-based method for characterising lesions and locating electrodes in small animal brains VL - 141 ER - TY - GEN AB - Dataset for manuscript 'Social network plasticity decreases disease transmission in a eusocial insect' Compared to previous versions: - raw image files added - correction of URLs within README.txt file AU - Stroeymeyt, Nathalie AU - Grasse, Anna V AU - Crespi, Alessandro AU - Mersch, Danielle AU - Cremer, Sylvia AU - Keller, Laurent ID - 13055 TI - Social network plasticity decreases disease transmission in a eusocial insect ER - TY - JOUR AB - Conventional ultra-high sensitivity detectors in the millimeter-wave range are usually cooled as their own thermal noise at room temperature would mask the weak received radiation. The need for cryogenic systems increases the cost and complexity of the instruments, hindering the development of, among others, airborne and space applications. In this work, the nonlinear parametric upconversion of millimeter-wave radiation to the optical domain inside high-quality (Q) lithium niobate whispering-gallery mode (WGM) resonators is proposed for ultra-low noise detection. We experimentally demonstrate coherent upconversion of millimeter-wave signals to a 1550 nm telecom carrier, with a photon conversion efficiency surpassing the state-of-the-art by 2 orders of magnitude. Moreover, a theoretical model shows that the thermal equilibrium of counterpropagating WGMs is broken by overcoupling the millimeter-wave WGM, effectively cooling the upconverted mode and allowing ultra-low noise detection. By theoretically estimating the sensitivity of a correlation radiometer based on the presented scheme, it is found that room-temperature radiometers with better sensitivity than state-of-the-art high-electron-mobility transistor (HEMT)-based radiometers can be designed. This detection paradigm can be used to develop room-temperature instrumentation for radio astronomy, earth observation, planetary missions, and imaging systems. AU - Botello, Gabriel AU - Sedlmeir, Florian AU - Rueda Sanchez, Alfredo R AU - Abdalmalak, Kerlos AU - Brown, Elliott AU - Leuchs, Gerd AU - Preu, Sascha AU - Segovia Vargas, Daniel AU - Strekalov, Dmitry AU - Munoz, Luis AU - Schwefel, Harald ID - 22 IS - 10 JF - Optica SN - 23342536 TI - Sensitivity limits of millimeter-wave photonic radiometers based on efficient electro-optic upconverters VL - 5 ER - TY - JOUR AB - Recently, contract-based design has been proposed as an “orthogonal” approach that complements system design methodologies proposed so far to cope with the complexity of system design. Contract-based design provides a rigorous scaffolding for verification, analysis, abstraction/refinement, and even synthesis. A number of results have been obtained in this domain but a unified treatment of the topic that can help put contract-based design in perspective was missing. This monograph intends to provide such a treatment where contracts are precisely defined and characterized so that they can be used in design methodologies with no ambiguity. In particular, this monograph identifies the essence of complex system design using contracts through a mathematical “meta-theory”, where all the properties of the methodology are derived from a very abstract and generic notion of contract. We show that the meta-theory provides deep and illuminating links with existing contract and interface theories, as well as guidelines for designing new theories. Our study encompasses contracts for both software and systems, with emphasis on the latter. We illustrate the use of contracts with two examples: requirement engineering for a parking garage management, and the development of contracts for timing and scheduling in the context of the Autosar methodology in use in the automotive sector. AU - Benveniste, Albert AU - Nickovic, Dejan AU - Caillaud, Benoît AU - Passerone, Roberto AU - Raclet, Jean Baptiste AU - Reinkemeier, Philipp AU - Sangiovanni-Vincentelli, Alberto AU - Damm, Werner AU - Henzinger, Thomas A AU - Larsen, Kim G. ID - 5677 IS - 2-3 JF - Foundations and Trends in Electronic Design Automation SN - 1551-3939 TI - Contracts for system design VL - 12 ER -