@phdthesis{324, abstract = {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.}, author = {Chen, Chong}, issn = {2663-337X}, pages = {110}, publisher = {Institute of Science and Technology Austria}, title = {{Synaptotagmins ensure speed and efficiency of inhibitory neurotransmitter release}}, doi = {10.15479/AT:ISTA:th_997}, year = {2018}, } @article{742, abstract = {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.}, author = {Dotterrer, Dominic and Kaufman, Tali and Wagner, Uli}, journal = {Geometriae Dedicata}, number = {1}, pages = {307–317}, publisher = {Springer}, title = {{On expansion and topological overlap}}, doi = {10.1007/s10711-017-0291-4}, volume = {195}, year = {2018}, } @article{70, abstract = {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.}, author = {Nejjar, Peter}, issn = {1980-0436}, journal = {Latin American Journal of Probability and Mathematical Statistics}, number = {2}, pages = {1311--1334}, publisher = {Instituto Nacional de Matematica Pura e Aplicada}, title = {{Transition to shocks in TASEP and decoupling of last passage times}}, doi = {10.30757/ALEA.v15-49}, volume = {15}, year = {2018}, } @article{44, abstract = {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.}, author = {Turner, C J and Michailidis, Alexios and Abanin, D A and Serbyn, Maksym and Papić, Z}, journal = {Physical Review B}, number = {15}, publisher = {American Physical Society}, title = {{Quantum scarred eigenstates in a Rydberg atom chain: Entanglement, breakdown of thermalization, and stability to perturbations}}, doi = {10.1103/PhysRevB.98.155134}, volume = {98}, year = {2018}, } @article{328, abstract = {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.}, author = {Choueiri, George H and Lopez Alonso, Jose M and Hof, Björn}, journal = {Physical Review Letters}, number = {12}, publisher = {American Physical Society}, title = {{Exceeding the asymptotic limit of polymer drag reduction}}, doi = {10.1103/PhysRevLett.120.124501}, volume = {120}, year = {2018}, } @article{136, abstract = {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.}, author = {Suri, Balachandra and Tithof, Jeffrey and Grigoriev, Roman and Schatz, Michael}, journal = {Physical Review E}, number = {2}, publisher = {American Physical Society}, title = {{Unstable equilibria and invariant manifolds in quasi-two-dimensional Kolmogorov-like flow}}, doi = {10.1103/PhysRevE.98.023105}, volume = {98}, year = {2018}, } @article{691, abstract = {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.}, author = {Marin Valencia, Isaac and Novarino, Gaia and Johansen, Anide and Rosti, Başak and Issa, Mahmoud and Musaev, Damir and Bhat, Gifty and Scott, Eric and Silhavy, Jennifer and Stanley, Valentina and Rosti, Rasim and Gleeson, Jeremy and Imam, Farhad and Zaki, Maha and Gleeson, Joseph}, issn = {0022-2593}, journal = {Journal of Medical Genetics}, number = {1}, pages = {48 -- 54}, publisher = {BMJ Publishing Group}, title = {{A homozygous founder mutation in TRAPPC6B associates with a neurodevelopmental disorder characterised by microcephaly epilepsy and autistic features}}, doi = {10.1136/jmedgenet-2017-104627}, volume = {55}, year = {2018}, } @article{284, abstract = {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.}, author = {Virosztek, Daniel}, issn = {2064-8316}, journal = {Acta Scientiarum Mathematicarum}, number = {1-2}, pages = {65 -- 80}, publisher = {Springer Nature}, title = {{Maps on probability measures preserving certain distances - a survey and some new results}}, doi = {10.14232/actasm-018-753-y}, volume = {84}, year = {2018}, } @article{180, abstract = {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.}, author = {Lewi, Mathieu and Lieb, Élliott and Seiringer, Robert}, issn = {2270-518X}, journal = {Journal de l'Ecole Polytechnique - Mathematiques}, pages = {79 -- 116}, publisher = {Ecole Polytechnique}, title = {{Statistical mechanics of the uniform electron gas}}, doi = {10.5802/jep.64}, volume = {5}, year = {2018}, } @article{163, abstract = {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.}, author = {Reipert, Siegfried and Goldammer, Helmuth and Richardson, Christine and Goldberg, Martin and Hawkins, Timothy and Hollergschwandtner, Elena and Kaufmann, Walter and Antreich, Sebastian and Stierhof, York}, issn = {0022-1554}, journal = {Journal of Histochemistry and Cytochemistry}, number = {12}, pages = {903--921}, publisher = {SAGE Publications}, title = {{Agitation modules: Flexible means to accelerate automated freeze substitution}}, doi = {10.1369/0022155418786698}, volume = {66}, year = {2018}, }