@article{7097, abstract = {Early endosomes, also called sorting endosomes, are known to mature into late endosomesvia the Rab5-mediated endolysosomal trafficking pathway. Thus, early endosome existence isthought to be maintained by the continual fusion of transport vesicles from the plasmamembrane and thetrans-Golgi network (TGN). Here we show instead that endocytosis isdispensable and post-Golgi vesicle transport is crucial for the formation of endosomes andthe subsequent endolysosomal traffic regulated by yeast Rab5 Vps21p. Fittingly, all threeproteins required for endosomal nucleotide exchange on Vps21p arefirst recruited to theTGN before transport to the endosome, namely the GEF Vps9p and the epsin-relatedadaptors Ent3/5p. The TGN recruitment of these components is distinctly controlled, withVps9p appearing to require the Arf1p GTPase, and the Rab11s, Ypt31p/32p. These resultsprovide a different view of endosome formation and identify the TGN as a critical location forregulating progress through the endolysosomal trafficking pathway.}, author = {Nagano, Makoto and Toshima, Junko Y. and Siekhaus, Daria E and Toshima, Jiro}, issn = {2399-3642}, journal = {Communications Biology}, number = {1}, publisher = {Springer Nature}, title = {{Rab5-mediated endosome formation is regulated at the trans-Golgi network}}, doi = {10.1038/s42003-019-0670-5}, volume = {2}, year = {2019}, } @article{7099, author = {Kasugai, Yu and Vogel, Elisabeth and Hörtnagl, Heide and Schönherr, Sabine and Paradiso, Enrica and Hauschild, Markus and Göbel, Georg and Milenkovic, Ivan and Peterschmitt, Yvan and Tasan, Ramon and Sperk, Günther and Shigemoto, Ryuichi and Sieghart, Werner and Singewald, Nicolas and Lüthi, Andreas and Ferraguti, Francesco}, issn = {0896-6273}, journal = {Neuron}, number = {4}, pages = {781--794.e4}, publisher = {Elsevier}, title = {{Structural and functional remodeling of amygdala GABAergic synapses in associative fear learning}}, doi = {10.1016/j.neuron.2019.08.013}, volume = {104}, year = {2019}, } @article{7100, abstract = {We present microscopic derivations of the defocusing two-dimensional cubic nonlinear Schrödinger equation and the Gross–Pitaevskii equation starting froman interacting N-particle system of bosons. We consider the interaction potential to be given either by Wβ(x)=N−1+2βW(Nβx), for any β>0, or to be given by VN(x)=e2NV(eNx), for some spherical symmetric, nonnegative and compactly supported W,V∈L∞(R2,R). In both cases we prove the convergence of the reduced density corresponding to the exact time evolution to the projector onto the solution of the corresponding nonlinear Schrödinger equation in trace norm. For the latter potential VN we show that it is crucial to take the microscopic structure of the condensate into account in order to obtain the correct dynamics.}, author = {Jeblick, Maximilian and Leopold, Nikolai K and Pickl, Peter}, issn = {1432-0916}, journal = {Communications in Mathematical Physics}, number = {1}, pages = {1--69}, publisher = {Springer Nature}, title = {{Derivation of the time dependent Gross–Pitaevskii equation in two dimensions}}, doi = {10.1007/s00220-019-03599-x}, volume = {372}, year = {2019}, } @article{7103, abstract = {Origin and functions of intermittent transitions among sleep stages, including short awakenings and arousals, constitute a challenge to the current homeostatic framework for sleep regulation, focusing on factors modulating sleep over large time scales. Here we propose that the complex micro-architecture characterizing the sleep-wake cycle results from an underlying non-equilibrium critical dynamics, bridging collective behaviors across spatio-temporal scales. We investigate θ and δ wave dynamics in control rats and in rats with lesions of sleep-promoting neurons in the parafacial zone. We demonstrate that intermittent bursts in θ and δ rhythms exhibit a complex temporal organization, with long-range power-law correlations and a robust duality of power law (θ-bursts, active phase) and exponential-like (δ-bursts, quiescent phase) duration distributions, typical features of non-equilibrium systems self-organizing at criticality. Crucially, such temporal organization relates to anti-correlated coupling between θ- and δ-bursts, and is independent of the dominant physiologic state and lesions, a solid indication of a basic principle in sleep dynamics.}, author = {Wang, Jilin W. J. L. and Lombardi, Fabrizio and Zhang, Xiyun and Anaclet, Christelle and Ivanov, Plamen Ch.}, issn = {1553-7358}, journal = {PLoS Computational Biology}, number = {11}, publisher = {Public Library of Science}, title = {{Non-equilibrium critical dynamics of bursts in θ and δ rhythms as fundamental characteristic of sleep and wake micro-architecture}}, doi = {10.1371/journal.pcbi.1007268}, volume = {15}, year = {2019}, } @article{7105, abstract = {Cell migration is hypothesized to involve a cycle of behaviours beginning with leading edge extension. However, recent evidence suggests that the leading edge may be dispensable for migration, raising the question of what actually controls cell directionality. Here, we exploit the embryonic migration of Drosophila macrophages to bridge the different temporal scales of the behaviours controlling motility. This approach reveals that edge fluctuations during random motility are not persistent and are weakly correlated with motion. In contrast, flow of the actin network behind the leading edge is highly persistent. Quantification of actin flow structure during migration reveals a stable organization and asymmetry in the cell-wide flowfield that strongly correlates with cell directionality. This organization is regulated by a gradient of actin network compression and destruction, which is controlled by myosin contraction and cofilin-mediated disassembly. It is this stable actin-flow polarity, which integrates rapid fluctuations of the leading edge, that controls inherent cellular persistence.}, author = {Yolland, Lawrence and Burki, Mubarik and Marcotti, Stefania and Luchici, Andrei and Kenny, Fiona N. and Davis, John Robert and Serna-Morales, Eduardo and Müller, Jan and Sixt, Michael K and Davidson, Andrew and Wood, Will and Schumacher, Linus J. and Endres, Robert G. and Miodownik, Mark and Stramer, Brian M.}, issn = {1476-4679}, journal = {Nature Cell Biology}, number = {11}, pages = {1370--1381}, publisher = {Springer Nature}, title = {{Persistent and polarized global actin flow is essential for directionality during cell migration}}, doi = {10.1038/s41556-019-0411-5}, volume = {21}, year = {2019}, } @article{7106, abstract = {PIN-FORMED (PIN) transporters mediate directional, intercellular movement of the phytohormone auxin in land plants. To elucidate the evolutionary origins of this developmentally crucial mechanism, we analysed the single PIN homologue of a simple green alga Klebsormidium flaccidum. KfPIN functions as a plasma membrane-localized auxin exporter in land plants and heterologous models. While its role in algae remains unclear, PIN-driven auxin export is probably an ancient and conserved trait within streptophytes.}, author = {Skokan, Roman and Medvecká, Eva and Viaene, Tom and Vosolsobě, Stanislav and Zwiewka, Marta and Müller, Karel and Skůpa, Petr and Karady, Michal and Zhang, Yuzhou and Janacek, Dorina P. and Hammes, Ulrich Z. and Ljung, Karin and Nodzyński, Tomasz and Petrášek, Jan and Friml, Jiří}, issn = {2055-0278}, journal = {Nature Plants}, number = {11}, pages = {1114--1119}, publisher = {Springer Nature}, title = {{PIN-driven auxin transport emerged early in streptophyte evolution}}, doi = {10.1038/s41477-019-0542-5}, volume = {5}, year = {2019}, } @article{7108, abstract = {We prove that for every d ≥ 2, deciding if a pure, d-dimensional, simplicial complex is shellable is NP-hard, hence NP-complete. This resolves a question raised, e.g., by Danaraj and Klee in 1978. Our reduction also yields that for every d ≥ 2 and k ≥ 0, deciding if a pure, d-dimensional, simplicial complex is k-decomposable is NP-hard. For d ≥ 3, both problems remain NP-hard when restricted to contractible pure d-dimensional complexes. Another simple corollary of our result is that it is NP-hard to decide whether a given poset is CL-shellable.}, author = {Goaoc, Xavier and Patak, Pavel and Patakova, Zuzana and Tancer, Martin and Wagner, Uli}, issn = {0004-5411}, journal = {Journal of the ACM}, number = {3}, publisher = {ACM}, title = {{Shellability is NP-complete}}, doi = {10.1145/3314024}, volume = {66}, year = {2019}, } @article{7109, abstract = {We show how to construct temporal testers for the logic MITL, a prominent linear-time logic for real-time systems. A temporal tester is a transducer that inputs a signal holding the Boolean value of atomic propositions and outputs the truth value of a formula along time. Here we consider testers over continuous-time Boolean signals that use clock variables to enforce duration constraints, as in timed automata. We first rewrite the MITL formula into a “simple” formula using a limited set of temporal modalities. We then build testers for these specific modalities and show how to compose testers for simple formulae into complex ones. Temporal testers can be turned into acceptors, yielding a compositional translation from MITL to timed automata. This construction is much simpler than previously known and remains asymptotically optimal. It supports both past and future operators and can easily be extended.}, author = {Ferrere, Thomas and Maler, Oded and Ničković, Dejan and Pnueli, Amir}, issn = {0004-5411}, journal = {Journal of the ACM}, number = {3}, publisher = {ACM}, title = {{From real-time logic to timed automata}}, doi = {10.1145/3286976}, volume = {66}, year = {2019}, } @article{7117, abstract = {We propose a novel generic shape optimization method for CAD models based on the eXtended Finite Element Method (XFEM). Our method works directly on the intersection between the model and a regular simulation grid, without the need to mesh or remesh, thus removing a bottleneck of classical shape optimization strategies. This is made possible by a novel hierarchical integration scheme that accurately integrates finite element quantities with sub-element precision. For optimization, we efficiently compute analytical shape derivatives of the entire framework, from model intersection to integration rule generation and XFEM simulation. Moreover, we describe a differentiable projection of shape parameters onto a constraint manifold spanned by user-specified shape preservation, consistency, and manufacturability constraints. We demonstrate the utility of our approach by optimizing mass distribution, strength-to-weight ratio, and inverse elastic shape design objectives directly on parameterized 3D CAD models.}, author = {Hafner, Christian and Schumacher, Christian and Knoop, Espen and Auzinger, Thomas and Bickel, Bernd and Bächer, Moritz}, issn = {0730-0301}, journal = {ACM Transactions on Graphics}, number = {6}, publisher = {ACM}, title = {{X-CAD: Optimizing CAD Models with Extended Finite Elements}}, doi = {10.1145/3355089.3356576}, volume = {38}, year = {2019}, } @inproceedings{7122, abstract = {Data-rich applications in machine-learning and control have motivated an intense research on large-scale optimization. Novel algorithms have been proposed and shown to have optimal convergence rates in terms of iteration counts. However, their practical performance is severely degraded by the cost of exchanging high-dimensional gradient vectors between computing nodes. Several gradient compression heuristics have recently been proposed to reduce communications, but few theoretical results exist that quantify how they impact algorithm convergence. This paper establishes and strengthens the convergence guarantees for gradient descent under a family of gradient compression techniques. For convex optimization problems, we derive admissible step sizes and quantify both the number of iterations and the number of bits that need to be exchanged to reach a target accuracy. Finally, we validate the performance of different gradient compression techniques in simulations. The numerical results highlight the properties of different gradient compression algorithms and confirm that fast convergence with limited information exchange is possible.}, author = {Khirirat, Sarit and Johansson, Mikael and Alistarh, Dan-Adrian}, booktitle = {2018 IEEE Conference on Decision and Control}, isbn = {9781538613955}, issn = {0743-1546}, location = {Miami Beach, FL, United States}, publisher = {IEEE}, title = {{Gradient compression for communication-limited convex optimization}}, doi = {10.1109/cdc.2018.8619625}, year = {2019}, } @phdthesis{7132, abstract = {A major challenge in neuroscience research is to dissect the circuits that orchestrate behavior in health and disease. Proteins from a wide range of non-mammalian species, such as microbial opsins, have been successfully transplanted to specific neuronal targets to override their natural communication patterns. The goal of our work is to manipulate synaptic communication in a manner that closely incorporates the functional intricacies of synapses by preserving temporal encoding (i.e. the firing pattern of the presynaptic neuron) and connectivity (i.e. target specific synapses rather than specific neurons). Our strategy to achieve this goal builds on the use of non-mammalian transplants to create a synthetic synapse. The mode of modulation comes from pre-synaptic uptake of a synthetic neurotransmitter (SN) into synaptic vesicles by means of a genetically targeted transporter selective for the SN. Upon natural vesicular release, exposure of the SN to the synaptic cleft will modify the post-synaptic potential through an orthogonal ligand gated ion channel. To achieve this goal we have functionally characterized a mixed cationic methionine-gated ion channel from Arabidopsis thaliana, designed a method to functionally characterize a synthetic transporter in isolated synaptic vesicles without the need for transgenic animals, identified and extracted multiple prokaryotic uptake systems that are substrate specific for methionine (Met), and established a primary/cell line co-culture system that would allow future combinatorial testing of this orthogonal transmitter-transporter-channel trifecta. Synthetic synapses will provide a unique opportunity to manipulate synaptic communication while maintaining the electrophysiological integrity of the pre-synaptic cell. In this way, information may be preserved that was generated in upstream circuits and that could be essential for concerted function and information processing.}, author = {Mckenzie, Catherine}, issn = {2663-337X}, pages = {95}, publisher = {Institute of Science and Technology Austria}, title = {{Design and characterization of methods and biological components to realize synthetic neurotransmission}}, doi = {10.15479/at:ista:7132}, year = {2019}, } @inproceedings{7136, abstract = {It is well established that the notion of min-entropy fails to satisfy the \emph{chain rule} of the form H(X,Y)=H(X|Y)+H(Y), known for Shannon Entropy. Such a property would help to analyze how min-entropy is split among smaller blocks. Problems of this kind arise for example when constructing extractors and dispersers. We show that any sequence of variables exhibits a very strong strong block-source structure (conditional distributions of blocks are nearly flat) when we \emph{spoil few correlated bits}. This implies, conditioned on the spoiled bits, that \emph{splitting-recombination properties} hold. In particular, we have many nice properties that min-entropy doesn't obey in general, for example strong chain rules, "information can't hurt" inequalities, equivalences of average and worst-case conditional entropy definitions and others. Quantitatively, for any sequence X1,…,Xt of random variables over an alphabet X we prove that, when conditioned on m=t⋅O(loglog|X|+loglog(1/ϵ)+logt) bits of auxiliary information, all conditional distributions of the form Xi|X