@inproceedings{183, abstract = {Fault-localization is considered to be a very tedious and time-consuming activity in the design of complex Cyber-Physical Systems (CPS). This laborious task essentially requires expert knowledge of the system in order to discover the cause of the fault. In this context, we propose a new procedure that AIDS designers in debugging Simulink/Stateflow hybrid system models, guided by Signal Temporal Logic (STL) specifications. The proposed method relies on three main ingredients: (1) a monitoring and a trace diagnostics procedure that checks whether a tested behavior satisfies or violates an STL specification, localizes time segments and interfaces variables contributing to the property violations; (2) a slicing procedure that maps these observable behavior segments to the internal states and transitions of the Simulink model; and (3) a spectrum-based fault-localization method that combines the previous analysis from multiple tests to identify the internal states and/or transitions that are the most likely to explain the fault. We demonstrate the applicability of our approach on two Simulink models from the automotive and the avionics domain.}, author = {Bartocci, Ezio and Ferrere, Thomas and Manjunath, Niveditha and Nickovic, Dejan}, location = {Porto, Portugal}, pages = {197 -- 206}, publisher = {Association for Computing Machinery, Inc}, title = {{Localizing faults in simulink/stateflow models with STL}}, doi = {10.1145/3178126.3178131}, year = {2018}, } @article{566, abstract = {We consider large random matrices X with centered, independent entries which have comparable but not necessarily identical variances. Girko's circular law asserts that the spectrum is supported in a disk and in case of identical variances, the limiting density is uniform. In this special case, the local circular law by Bourgade et. al. [11,12] shows that the empirical density converges even locally on scales slightly above the typical eigenvalue spacing. In the general case, the limiting density is typically inhomogeneous and it is obtained via solving a system of deterministic equations. Our main result is the local inhomogeneous circular law in the bulk spectrum on the optimal scale for a general variance profile of the entries of X. }, author = {Alt, Johannes and Erdös, László and Krüger, Torben H}, journal = {Annals Applied Probability }, number = {1}, pages = {148--203}, publisher = {Institute of Mathematical Statistics}, title = {{Local inhomogeneous circular law}}, doi = {10.1214/17-AAP1302}, volume = {28}, year = {2018}, } @article{106, abstract = {The goal of this article is to introduce the reader to the theory of intrinsic geometry of convex surfaces. We illustrate the power of the tools by proving a theorem on convex surfaces containing an arbitrarily long closed simple geodesic. Let us remind ourselves that a curve in a surface is called geodesic if every sufficiently short arc of the curve is length minimizing; if, in addition, it has no self-intersections, we call it simple geodesic. A tetrahedron with equal opposite edges is called isosceles. The axiomatic method of Alexandrov geometry allows us to work with the metrics of convex surfaces directly, without approximating it first by a smooth or polyhedral metric. Such approximations destroy the closed geodesics on the surface; therefore it is difficult (if at all possible) to apply approximations in the proof of our theorem. On the other hand, a proof in the smooth or polyhedral case usually admits a translation into Alexandrov’s language; such translation makes the result more general. In fact, our proof resembles a translation of the proof given by Protasov. Note that the main theorem implies in particular that a smooth convex surface does not have arbitrarily long simple closed geodesics. However we do not know a proof of this corollary that is essentially simpler than the one presented below.}, author = {Akopyan, Arseniy and Petrunin, Anton}, journal = {Mathematical Intelligencer}, number = {3}, pages = {26 -- 31}, publisher = {Springer}, title = {{Long geodesics on convex surfaces}}, doi = {10.1007/s00283-018-9795-5}, volume = {40}, year = {2018}, } @misc{9810, author = {Chaudhry, Waqas and Pleska, Maros and Shah, Nilang and Weiss, Howard and Mccall, Ingrid and Meyer, Justin and Gupta, Animesh and Guet, Calin C and Levin, Bruce}, publisher = {Public Library of Science}, title = {{Numerical data used in figures}}, doi = {10.1371/journal.pbio.2005971.s008}, year = {2018}, } @article{275, abstract = {Lymphatic endothelial cells (LECs) release extracellular chemokines to guide the migration of dendritic cells. In this study, we report that LECs also release basolateral exosome-rich endothelial vesicles (EEVs) that are secreted in greater numbers in the presence of inflammatory cytokines and accumulate in the perivascular stroma of small lymphatic vessels in human chronic inflammatory diseases. Proteomic analyses of EEV fractions identified > 1,700 cargo proteins and revealed a dominant motility-promoting protein signature. In vitro and ex vivo EEV fractions augmented cellular protrusion formation in a CX3CL1/fractalkine-dependent fashion and enhanced the directional migratory response of human dendritic cells along guidance cues. We conclude that perilymphatic LEC exosomes enhance exploratory behavior and thus promote directional migration of CX3CR1-expressing cells in complex tissue environments.}, author = {Brown, Markus and Johnson, Louise and Leone, Dario and Májek, Peter and Vaahtomeri, Kari and Senfter, Daniel and Bukosza, Nora and Schachner, Helga and Asfour, Gabriele and Langer, Brigitte and Hauschild, Robert and Parapatics, Katja and Hong, Young and Bennett, Keiryn and Kain, Renate and Detmar, Michael and Sixt, Michael K and Jackson, David and Kerjaschki, Dontscho}, journal = {Journal of Cell Biology}, number = {6}, pages = {2205 -- 2221}, publisher = {Rockefeller University Press}, title = {{Lymphatic exosomes promote dendritic cell migration along guidance cues}}, doi = {10.1083/jcb.201612051}, volume = {217}, year = {2018}, } @article{158, abstract = {The angiosperm seed is composed of three genetically distinct tissues: the diploid embryo that originates from the fertilized egg cell, the triploid endosperm that is produced from the fertilized central cell, and the maternal sporophytic integuments that develop into the seed coat1. At the onset of embryo development in Arabidopsis thaliana, the zygote divides asymmetrically, producing a small apical embryonic cell and a larger basal cell that connects the embryo to the maternal tissue2. The coordinated and synchronous development of the embryo and the surrounding integuments, and the alignment of their growth axes, suggest communication between maternal tissues and the embryo. In contrast to animals, however, where a network of maternal factors that direct embryo patterning have been identified3,4, only a few maternal mutations have been described to affect embryo development in plants5–7. Early embryo patterning in Arabidopsis requires accumulation of the phytohormone auxin in the apical cell by directed transport from the suspensor8–10. However, the origin of this auxin has remained obscure. Here we investigate the source of auxin for early embryogenesis and provide evidence that the mother plant coordinates seed development by supplying auxin to the early embryo from the integuments of the ovule. We show that auxin response increases in ovules after fertilization, due to upregulated auxin biosynthesis in the integuments, and this maternally produced auxin is required for correct embryo development.}, author = {Robert, Hélène and Park, Chulmin and Gutièrrez, Carla and Wójcikowska, Barbara and Pěnčík, Aleš and Novák, Ondřej and Chen, Junyi and Grunewald, Wim and Dresselhaus, Thomas and Friml, Jirí and Laux, Thomas}, journal = {Nature Plants}, number = {8}, pages = {548 -- 553}, publisher = {Nature Publishing Group}, title = {{Maternal auxin supply contributes to early embryo patterning in Arabidopsis}}, doi = {10.1038/s41477-018-0204-z}, volume = {4}, year = {2018}, } @article{152, abstract = {Complex I has an essential role in ATP production by coupling electron transfer from NADH to quinone with translocation of protons across the inner mitochondrial membrane. Isolated complex I deficiency is a frequent cause of mitochondrial inherited diseases. Complex I has also been implicated in cancer, ageing, and neurodegenerative conditions. Until recently, the understanding of complex I deficiency on the molecular level was limited due to the lack of high-resolution structures of the enzyme. However, due to developments in single particle cryo-electron microscopy (cryo-EM), recent studies have reported nearly atomic resolution maps and models of mitochondrial complex I. These structures significantly add to our understanding of complex I mechanism and assembly. The disease-causing mutations are discussed here in their structural context.}, author = {Fiedorczuk, Karol and Sazanov, Leonid A}, journal = {Trends in Cell Biology}, number = {10}, pages = {835 -- 867}, publisher = {Elsevier}, title = {{Mammalian mitochondrial complex I structure and disease causing mutations}}, doi = {10.1016/j.tcb.2018.06.006}, volume = {28}, year = {2018}, } @inproceedings{310, abstract = {A model of computation that is widely used in the formal analysis of reactive systems is symbolic algorithms. In this model the access to the input graph is restricted to consist of symbolic operations, which are expensive in comparison to the standard RAM operations. We give lower bounds on the number of symbolic operations for basic graph problems such as the computation of the strongly connected components and of the approximate diameter as well as for fundamental problems in model checking such as safety, liveness, and coliveness. Our lower bounds are linear in the number of vertices of the graph, even for constant-diameter graphs. For none of these problems lower bounds on the number of symbolic operations were known before. The lower bounds show an interesting separation of these problems from the reachability problem, which can be solved with O(D) symbolic operations, where D is the diameter of the graph. Additionally we present an approximation algorithm for the graph diameter which requires Õ(n/D) symbolic steps to achieve a (1 +ϵ)-approximation for any constant > 0. This compares to O(n/D) symbolic steps for the (naive) exact algorithm and O(D) symbolic steps for a 2-approximation. Finally we also give a refined analysis of the strongly connected components algorithms of [15], showing that it uses an optimal number of symbolic steps that is proportional to the sum of the diameters of the strongly connected components.}, author = {Chatterjee, Krishnendu and Dvorák, Wolfgang and Henzinger, Monika H and Loitzenbauer, Veronika}, location = {New Orleans, Louisiana, United States}, pages = {2341 -- 2356}, publisher = {ACM}, title = {{Lower bounds for symbolic computation on graphs: Strongly connected components, liveness, safety, and diameter}}, doi = {10.1137/1.9781611975031.151}, year = {2018}, } @article{436, abstract = {There has been significant interest recently in using complex quantum systems to create effective nonreciprocal dynamics. Proposals have been put forward for the realization of artificial magnetic fields for photons and phonons; experimental progress is fast making these proposals a reality. Much work has concentrated on the use of such systems for controlling the flow of signals, e.g., to create isolators or directional amplifiers for optical signals. In this Letter, we build on this work but move in a different direction. We develop the theory of and discuss a potential realization for the controllable flow of thermal noise in quantum systems. We demonstrate theoretically that the unidirectional flow of thermal noise is possible within quantum cascaded systems. Viewing an optomechanical platform as a cascaded system we show here that one can ultimately control the direction of the flow of thermal noise. By appropriately engineering the mechanical resonator, which acts as an artificial reservoir, the flow of thermal noise can be constrained to a desired direction, yielding a thermal rectifier. The proposed quantum thermal noise rectifier could potentially be used to develop devices such as a thermal modulator, a thermal router, and a thermal amplifier for nanoelectronic devices and superconducting circuits.}, author = {Barzanjeh, Shabir and Aquilina, Matteo and Xuereb, André}, journal = {Physical Review Letters}, number = {6}, publisher = {American Physical Society}, title = {{Manipulating the flow of thermal noise in quantum devices}}, doi = {10.1103/PhysRevLett.120.060601}, volume = {120}, year = {2018}, } @article{5858, abstract = {Spatial patterns are ubiquitous on the subcellular, cellular and tissue level, and can be studied using imaging techniques such as light and fluorescence microscopy. Imaging data provide quantitative information about biological systems; however, mechanisms causing spatial patterning often remain elusive. In recent years, spatio-temporal mathematical modelling has helped to overcome this problem. Yet, outliers and structured noise limit modelling of whole imaging data, and models often consider spatial summary statistics. Here, we introduce an integrated data-driven modelling approach that can cope with measurement artefacts and whole imaging data. Our approach combines mechanistic models of the biological processes with robust statistical models of the measurement process. The parameters of the integrated model are calibrated using a maximum-likelihood approach. We used this integrated modelling approach to study in vivo gradients of the chemokine (C-C motif) ligand 21 (CCL21). CCL21 gradients guide dendritic cells and are important in the adaptive immune response. Using artificial data, we verified that the integrated modelling approach provides reliable parameter estimates in the presence of measurement noise and that bias and variance of these estimates are reduced compared to conventional approaches. The application to experimental data allowed the parametrization and subsequent refinement of the model using additional mechanisms. Among other results, model-based hypothesis testing predicted lymphatic vessel-dependent concentration of heparan sulfate, the binding partner of CCL21. The selected model provided an accurate description of the experimental data and was partially validated using published data. Our findings demonstrate that integrated statistical modelling of whole imaging data is computationally feasible and can provide novel biological insights.}, author = {Hross, Sabrina and Theis, Fabian J. and Sixt, Michael K and Hasenauer, Jan}, issn = {17425689}, journal = {Journal of the Royal Society Interface}, number = {149}, publisher = {Royal Society Publishing}, title = {{Mechanistic description of spatial processes using integrative modelling of noise-corrupted imaging data}}, doi = {10.1098/rsif.2018.0600}, volume = {15}, year = {2018}, } @article{16, abstract = {We report quantitative evidence of mixing-layer elastic instability in a viscoelastic fluid flow between two widely spaced obstacles hindering a channel flow at Re 1 and Wi 1. Two mixing layers with nonuniform shear velocity profiles are formed in the region between the obstacles. The mixing-layer instability arises in the vicinity of an inflection point on the shear velocity profile with a steep variation in the elastic stress. The instability results in an intermittent appearance of small vortices in the mixing layers and an amplification of spatiotemporal averaged vorticity in the elastic turbulence regime. The latter is characterized through scaling of friction factor with Wi and both pressure and velocity spectra. Furthermore, the observations reported provide improved understanding of the stability of the mixing layer in a viscoelastic fluid at large elasticity, i.e., Wi 1 and Re 1 and oppose the current view of suppression of vorticity solely by polymer additives.}, author = {Varshney, Atul and Steinberg, Victor}, journal = {Physical Review Fluids}, number = {10}, publisher = {American Physical Society}, title = {{Mixing layer instability and vorticity amplification in a creeping viscoelastic flow}}, doi = {10.1103/PhysRevFluids.3.103303}, volume = {3}, year = {2018}, } @article{43, abstract = {The initial amount of pathogens required to start an infection within a susceptible host is called the infective dose and is known to vary to a large extent between different pathogen species. We investigate the hypothesis that the differences in infective doses are explained by the mode of action in the underlying mechanism of pathogenesis: Pathogens with locally acting mechanisms tend to have smaller infective doses than pathogens with distantly acting mechanisms. While empirical evidence tends to support the hypothesis, a formal theoretical explanation has been lacking. We give simple analytical models to gain insight into this phenomenon and also investigate a stochastic, spatially explicit, mechanistic within-host model for toxin-dependent bacterial infections. The model shows that pathogens secreting locally acting toxins have smaller infective doses than pathogens secreting diffusive toxins, as hypothesized. While local pathogenetic mechanisms require smaller infective doses, pathogens with distantly acting toxins tend to spread faster and may cause more damage to the host. The proposed model can serve as a basis for the spatially explicit analysis of various virulence factors also in the context of other problems in infection dynamics.}, author = {Rybicki, Joel and Kisdi, Eva and Anttila, Jani}, journal = {PNAS}, number = {42}, pages = {10690 -- 10695}, publisher = {National Academy of Sciences}, title = {{Model of bacterial toxin-dependent pathogenesis explains infective dose}}, doi = {10.1073/pnas.1721061115}, volume = {115}, year = {2018}, } @article{13, abstract = {We propose a new method for fabricating digital objects through reusable silicone molds. Molds are generated by casting liquid silicone into custom 3D printed containers called metamolds. Metamolds automatically define the cuts that are needed to extract the cast object from the silicone mold. The shape of metamolds is designed through a novel segmentation technique, which takes into account both geometric and topological constraints involved in the process of mold casting. Our technique is simple, does not require changing the shape or topology of the input objects, and only requires off-the- shelf materials and technologies. We successfully tested our method on a set of challenging examples with complex shapes and rich geometric detail. © 2018 Association for Computing Machinery.}, author = {Alderighi, Thomas and Malomo, Luigi and Giorgi, Daniela and Pietroni, Nico and Bickel, Bernd and Cignoni, Paolo}, journal = {ACM Trans. Graph.}, number = {4}, publisher = {ACM}, title = {{Metamolds: Computational design of silicone molds}}, doi = {10.1145/3197517.3201381}, volume = {37}, year = {2018}, } @article{137, abstract = {Fluorescent sensors are an essential part of the experimental toolbox of the life sciences, where they are used ubiquitously to visualize intra- and extracellular signaling. In the brain, optical neurotransmitter sensors can shed light on temporal and spatial aspects of signal transmission by directly observing, for instance, neurotransmitter release and spread. Here we report the development and application of the first optical sensor for the amino acid glycine, which is both an inhibitory neurotransmitter and a co-agonist of the N-methyl-d-aspartate receptors (NMDARs) involved in synaptic plasticity. Computational design of a glycine-specific binding protein allowed us to produce the optical glycine FRET sensor (GlyFS), which can be used with single and two-photon excitation fluorescence microscopy. We took advantage of this newly developed sensor to test predictions about the uneven spatial distribution of glycine in extracellular space and to demonstrate that extracellular glycine levels are controlled by plasticity-inducing stimuli.}, author = {Zhang, William and Herde, Michel and Mitchell, Joshua and Whitfield, Jason and Wulff, Andreas and Vongsouthi, Vanessa and Sanchez Romero, Inmaculada and Gulakova, Polina and Minge, Daniel and Breithausen, Björn and Schoch, Susanne and Janovjak, Harald L and Jackson, Colin and Henneberger, Christian}, journal = {Nature Chemical Biology}, number = {9}, pages = {861 -- 869}, publisher = {Nature Publishing Group}, title = {{Monitoring hippocampal glycine with the computationally designed optical sensor GlyFS}}, doi = {10.1038/s41589-018-0108-2}, volume = {14}, year = {2018}, } @inbook{153, abstract = {Cells migrating in multicellular organisms steadily traverse complex three-dimensional (3D) environments. To decipher the underlying cell biology, current experimental setups either use simplified 2D, tissue-mimetic 3D (e.g., collagen matrices) or in vivo environments. While only in vivo experiments are truly physiological, they do not allow for precise manipulation of environmental parameters. 2D in vitro experiments do allow mechanical and chemical manipulations, but increasing evidence demonstrates substantial differences of migratory mechanisms in 2D and 3D. Here, we describe simple, robust, and versatile “pillar forests” to investigate cell migration in complex but fully controllable 3D environments. Pillar forests are polydimethylsiloxane-based setups, in which two closely adjacent surfaces are interconnected by arrays of micrometer-sized pillars. Changing the pillar shape, size, height and the inter-pillar distance precisely manipulates microenvironmental parameters (e.g., pore sizes, micro-geometry, micro-topology), while being easily combined with chemotactic cues, surface coatings, diverse cell types and advanced imaging techniques. Thus, pillar forests combine the advantages of 2D cell migration assays with the precise definition of 3D environmental parameters.}, author = {Renkawitz, Jörg and Reversat, Anne and Leithner, Alexander F and Merrin, Jack and Sixt, Michael K}, booktitle = {Methods in Cell Biology}, issn = {0091679X}, pages = {79 -- 91}, publisher = {Academic Press}, title = {{Micro-engineered “pillar forests” to study cell migration in complex but controlled 3D environments}}, doi = {10.1016/bs.mcb.2018.07.004}, volume = {147}, year = {2018}, } @article{54, abstract = {During epithelial tissue development, repair, and homeostasis, adherens junctions (AJs) ensure intercellular adhesion and tissue integrity while allowing for cell and tissue dynamics. Mechanical forces play critical roles in AJs’ composition and dynamics. Recent findings highlight that beyond a well-established role in reinforcing cell-cell adhesion, AJ mechanosensitivity promotes junctional remodeling and polarization, thereby regulating critical processes such as cell intercalation, division, and collective migration. Here, we provide an integrated view of mechanosensing mechanisms that regulate cell-cell contact composition, geometry, and integrity under tension and highlight pivotal roles for mechanosensitive AJ remodeling in preserving epithelial integrity and sustaining tissue dynamics.}, author = {Nunes Pinheiro, Diana C and Bellaïche, Yohanns}, journal = {Developmental Cell}, number = {1}, pages = {3 -- 19}, publisher = {Cell Press}, title = {{Mechanical force-driven adherents junction remodeling and epithelial dynamics}}, doi = {10.1016/j.devcel.2018.09.014}, volume = {47}, year = {2018}, } @article{276, abstract = {Directed migration of cells relies on their ability to sense directional guidance cues and to interact with pericellular structures in order to transduce contractile cytoskeletal- into mechanical forces. These biomechanical processes depend highly on microenvironmental factors such as exposure to 2D surfaces or 3D matrices. In vivo, the majority of cells are exposed to 3D environments. Data on 3D cell migration are mostly derived from intravital microscopy or collagen-based in vitro assays. Both approaches offer only limited controlla-bility of experimental conditions. Here, we developed an automated microfluidic system that allows positioning of cells in 3D microenvironments containing highly controlled diffusion-based chemokine gradients. Tracking migration in such gradients was feasible in real time at the single cell level. Moreover, the setup allowed on-chip immunocytochemistry and thus linking of functional with phenotypical properties in individual cells. Spatially defined retrieval of cells from the device allows down-stream off-chip analysis. Using dendritic cells as a model, our setup specifically allowed us for the first time to quantitate key migration characteristics of cells exposed to identical gradients of the chemokine CCL19 yet placed on 2D vs in 3D environments. Migration properties between 2D and 3D migration were distinct. Morphological features of cells migrating in an in vitro 3D environment were similar to those of cells migrating in animal tissues, but different from cells migrating on a surface. Our system thus offers a highly controllable in vitro-mimic of a 3D environment that cells traffic in vivo.}, author = {Frick, Corina and Dettinger, Philip and Renkawitz, Jörg and Jauch, Annaïse and Berger, Christoph and Recher, Mike and Schroeder, Timm and Mehling, Matthias}, journal = {PLoS One}, number = {6}, publisher = {Public Library of Science}, title = {{Nano-scale microfluidics to study 3D chemotaxis at the single cell level}}, doi = {10.1371/journal.pone.0198330}, volume = {13}, year = {2018}, } @article{283, abstract = {Light represents the principal signal driving circadian clock entrainment. However, how light influences the evolution of the clock remains poorly understood. The cavefish Phreatichthys andruzzii represents a fascinating model to explore how evolution under extreme aphotic conditions shapes the circadian clock, since in this species the clock is unresponsive to light. We have previously demonstrated that loss-of-function mutations targeting non-visual opsins contribute in part to this blind clock phenotype. Here, we have compared orthologs of two core clock genes that play a key role in photic entrainment, cry1a and per2, in both zebrafish and P. andruzzii. We encountered aberrantly spliced variants for the P. andruzzii per2 transcript. The most abundant transcript encodes a truncated protein lacking the C-terminal Cry binding domain and incorporating an intronic, transposon-derived coding sequence. We demonstrate that the transposon insertion leads to a predominantly cytoplasmic localization of the cavefish Per2 protein in contrast to the zebrafish ortholog which is distributed in both the nucleus and cytoplasm. Thus, it seems that during evolution in complete darkness, the photic entrainment pathway of the circadian clock has been subject to mutation at multiple levels, extending from opsin photoreceptors to nuclear effectors.}, author = {Ceinos, Rosa Maria and Frigato, Elena and Pagano, Cristina and Frohlich, Nadine and Negrini, Pietro and Cavallari, Nicola and Vallone, Daniela and Fuselli, Silvia and Bertolucci, Cristiano and Foulkes, Nicholas S}, journal = {Scientific Reports}, number = {1}, publisher = {Nature Publishing Group}, title = {{Mutations in blind cavefish target the light regulated circadian clock gene period 2}}, doi = {10.1038/s41598-018-27080-2}, volume = {8}, year = {2018}, } @inproceedings{81, abstract = {We solve the offline monitoring problem for timed propositional temporal logic (TPTL), interpreted over dense-time Boolean signals. The variant of TPTL we consider extends linear temporal logic (LTL) with clock variables and reset quantifiers, providing a mechanism to specify real-time constraints. We first describe a general monitoring algorithm based on an exhaustive computation of the set of satisfying clock assignments as a finite union of zones. We then propose a specialized monitoring algorithm for the one-variable case using a partition of the time domain based on the notion of region equivalence, whose complexity is linear in the length of the signal, thereby generalizing a known result regarding the monitoring of metric temporal logic (MTL). The region and zone representations of time constraints are known from timed automata verification and can also be used in the discrete-time case. Our prototype implementation appears to outperform previous discrete-time implementations of TPTL monitoring,}, author = {Elgyütt, Adrian and Ferrere, Thomas and Henzinger, Thomas A}, location = {Beijing, China}, pages = {53 -- 70}, publisher = {Springer}, title = {{Monitoring temporal logic with clock variables}}, doi = {10.1007/978-3-030-00151-3_4}, volume = {11022}, year = {2018}, } @article{76, abstract = {Consider a fully-connected synchronous distributed system consisting of n nodes, where up to f nodes may be faulty and every node starts in an arbitrary initial state. In the synchronous C-counting problem, all nodes need to eventually agree on a counter that is increased by one modulo C in each round for given C>1. In the self-stabilising firing squad problem, the task is to eventually guarantee that all non-faulty nodes have simultaneous responses to external inputs: if a subset of the correct nodes receive an external “go” signal as input, then all correct nodes should agree on a round (in the not-too-distant future) in which to jointly output a “fire” signal. Moreover, no node should generate a “fire” signal without some correct node having previously received a “go” signal as input. We present a framework reducing both tasks to binary consensus at very small cost. For example, we obtain a deterministic algorithm for self-stabilising Byzantine firing squads with optimal resilience f<n/3, asymptotically optimal stabilisation and response time O(f), and message size O(log f). As our framework does not restrict the type of consensus routines used, we also obtain efficient randomised solutions.}, author = {Lenzen, Christoph and Rybicki, Joel}, journal = {Distributed Computing}, publisher = {Springer}, title = {{Near-optimal self-stabilising counting and firing squads}}, doi = {10.1007/s00446-018-0342-6}, year = {2018}, } @article{530, abstract = {Inclusion–exclusion is an effective method for computing the volume of a union of measurable sets. We extend it to multiple coverings, proving short inclusion–exclusion formulas for the subset of Rn covered by at least k balls in a finite set. We implement two of the formulas in dimension n=3 and report on results obtained with our software.}, author = {Edelsbrunner, Herbert and Iglesias Ham, Mabel}, journal = {Computational Geometry: Theory and Applications}, pages = {119 -- 133}, publisher = {Elsevier}, title = {{Multiple covers with balls I: Inclusion–exclusion}}, doi = {10.1016/j.comgeo.2017.06.014}, volume = {68}, year = {2018}, } @article{307, abstract = {Spontaneous emission spectra of two initially excited closely spaced identical atoms are very sensitive to the strength and the direction of the applied magnetic field. We consider the relevant schemes that ensure the determination of the mutual spatial orientation of the atoms and the distance between them by entirely optical means. A corresponding theoretical description is given accounting for the dipole-dipole interaction between the two atoms in the presence of a magnetic field and for polarizations of the quantum field interacting with magnetic sublevels of the two-atom system. }, author = {Redchenko, Elena and Makarov, Alexander and Yudson, Vladimir}, journal = { Physical Review A - Atomic, Molecular, and Optical Physics}, number = {4}, publisher = {American Physical Society}, title = {{Nanoscopy of pairs of atoms by fluorescence in a magnetic field}}, doi = {10.1103/PhysRevA.97.043812}, volume = {97}, year = {2018}, } @article{279, abstract = {Background: Natural selection shapes cancer genomes. Previous studies used signatures of positive selection to identify genes driving malignant transformation. However, the contribution of negative selection against somatic mutations that affect essential tumor functions or specific domains remains a controversial topic. Results: Here, we analyze 7546 individual exomes from 26 tumor types from TCGA data to explore the portion of the cancer exome under negative selection. Although we find most of the genes neutrally evolving in a pan-cancer framework, we identify essential cancer genes and immune-exposed protein regions under significant negative selection. Moreover, our simulations suggest that the amount of negative selection is underestimated. We therefore choose an empirical approach to identify genes, functions, and protein regions under negative selection. We find that expression and mutation status of negatively selected genes is indicative of patient survival. Processes that are most strongly conserved are those that play fundamental cellular roles such as protein synthesis, glucose metabolism, and molecular transport. Intriguingly, we observe strong signals of selection in the immunopeptidome and proteins controlling peptide exposition, highlighting the importance of immune surveillance evasion. Additionally, tumor type-specific immune activity correlates with the strength of negative selection on human epitopes. Conclusions: In summary, our results show that negative selection is a hallmark of cell essentiality and immune response in cancer. The functional domains identified could be exploited therapeutically, ultimately allowing for the development of novel cancer treatments.}, author = {Zapata, Luis and Pich, Oriol and Serrano, Luis and Kondrashov, Fyodor and Ossowski, Stephan and Schaefer, Martin}, journal = {Genome Biology}, publisher = {BioMed Central}, title = {{Negative selection in tumor genome evolution acts on essential cellular functions and the immunopeptidome}}, doi = {10.1186/s13059-018-1434-0}, volume = {19}, year = {2018}, } @article{145, abstract = {Aged proteins can become hazardous to cellular function, by accumulating molecular damage. This implies that cells should preferentially rely on newly produced ones. We tested this hypothesis in cultured hippocampal neurons, focusing on synaptic transmission. We found that newly synthesized vesicle proteins were incorporated in the actively recycling pool of vesicles responsible for all neurotransmitter release during physiological activity. We observed this for the calcium sensor Synaptotagmin 1, for the neurotransmitter transporter VGAT, and for the fusion protein VAMP2 (Synaptobrevin 2). Metabolic labeling of proteins and visualization by secondary ion mass spectrometry enabled us to query the entire protein makeup of the actively recycling vesicles, which we found to be younger than that of non-recycling vesicles. The young vesicle proteins remained in use for up to ~ 24 h, during which they participated in recycling a few hundred times. They were afterward reluctant to release and were degraded after an additional ~ 24–48 h. We suggest that the recycling pool of synaptic vesicles relies on newly synthesized proteins, while the inactive reserve pool contains older proteins.}, author = {Truckenbrodt, Sven M and Viplav, Abhiyan and Jähne, Sebsatian and Vogts, Angela and Denker, Annette and Wildhagen, Hanna and Fornasiero, Eugenio and Rizzoli, Silvio}, issn = {0261-4189}, journal = {The EMBO Journal}, number = {15}, publisher = {Wiley}, title = {{Newly produced synaptic vesicle proteins are preferentially used in synaptic transmission}}, doi = {10.15252/embj.201798044}, volume = {37}, year = {2018}, } @article{462, abstract = {AtNHX5 and AtNHX6 are endosomal Na+,K+/H+ antiporters that are critical for growth and development in Arabidopsis, but the mechanism behind their action remains unknown. Here, we report that AtNHX5 and AtNHX6, functioning as H+ leak, control auxin homeostasis and auxin-mediated development. We found that nhx5 nhx6 exhibited growth variations of auxin-related defects. We further showed that nhx5 nhx6 was affected in auxin homeostasis. Genetic analysis showed that AtNHX5 and AtNHX6 were required for the function of the ER-localized auxin transporter PIN5. Although AtNHX5 and AtNHX6 were co-localized with PIN5 at ER, they did not interact directly. Instead, the conserved acidic residues in AtNHX5 and AtNHX6, which are essential for exchange activity, were required for PIN5 function. AtNHX5 and AtNHX6 regulated the pH in ER. Overall, AtNHX5 and AtNHX6 may regulate auxin transport across the ER via the pH gradient created by their transport activity. H+-leak pathway provides a fine-tuning mechanism that controls cellular auxin fluxes. }, author = {Fan, Ligang and Zhao, Lei and Hu, Wei and Li, Weina and Novák, Ondřej and Strnad, Miroslav and Simon, Sibu and Friml, Jirí and Shen, Jinbo and Jiang, Liwen and Qiu, Quan}, journal = {Plant, Cell and Environment}, pages = {850 -- 864}, publisher = {Wiley-Blackwell}, title = {{NHX antiporters regulate the pH of endoplasmic reticulum and auxin-mediated development}}, doi = {10.1111/pce.13153}, volume = {41}, year = {2018}, } @article{519, abstract = {This study treats with the influence of a symmetry-breaking transversal magnetic field on the nonlinear dynamics of ferrofluidic Taylor-Couette flow – flow confined between two concentric independently rotating cylinders. We detected alternating ‘flip’ solutions which are flow states featuring typical characteristics of slow-fast-dynamics in dynamical systems. The flip corresponds to a temporal change in the axial wavenumber and we find them to appear either as pure 2-fold axisymmetric (due to the symmetry-breaking nature of the applied transversal magnetic field) or involving non-axisymmetric, helical modes in its interim solution. The latter ones show features of typical ribbon solutions. In any case the flip solutions have a preferential first axial wavenumber which corresponds to the more stable state (slow dynamics) and second axial wavenumber, corresponding to the short appearing more unstable state (fast dynamics). However, in both cases the flip time grows exponential with increasing the magnetic field strength before the flip solutions, living on 2-tori invariant manifolds, cease to exist, with lifetime going to infinity. Further we show that ferrofluidic flow turbulence differ from the classical, ordinary (usually at high Reynolds number) turbulence. The applied magnetic field hinders the free motion of ferrofluid partials and therefore smoothen typical turbulent quantities and features so that speaking of mildly chaotic dynamics seems to be a more appropriate expression for the observed motion. }, author = {Altmeyer, Sebastian}, journal = {Journal of Magnetism and Magnetic Materials}, pages = {427 -- 441}, publisher = {Elsevier}, title = {{Non-linear dynamics and alternating ‘flip’ solutions in ferrofluidic Taylor-Couette flow}}, doi = {10.1016/j.jmmm.2017.12.073}, volume = {452}, year = {2018}, } @inproceedings{5679, abstract = {We study the almost-sure termination problem for probabilistic programs. First, we show that supermartingales with lower bounds on conditional absolute difference provide a sound approach for the almost-sure termination problem. Moreover, using this approach we can obtain explicit optimal bounds on tail probabilities of non-termination within a given number of steps. Second, we present a new approach based on Central Limit Theorem for the almost-sure termination problem, and show that this approach can establish almost-sure termination of programs which none of the existing approaches can handle. Finally, we discuss algorithmic approaches for the two above methods that lead to automated analysis techniques for almost-sure termination of probabilistic programs.}, author = {Huang, Mingzhang and Fu, Hongfei and Chatterjee, Krishnendu}, editor = {Ryu, Sukyoung}, isbn = {9783030027674}, issn = {03029743}, location = {Wellington, New Zealand}, pages = {181--201}, publisher = {Springer}, title = {{New approaches for almost-sure termination of probabilistic programs}}, doi = {10.1007/978-3-030-02768-1_11}, volume = {11275}, year = {2018}, } @article{546, abstract = {The precise control of neural stem cell (NSC) proliferation and differentiation is crucial for the development and function of the human brain. Here, we review the emerging links between the alteration of embryonic and adult neurogenesis and the etiology of neuropsychiatric disorders (NPDs) such as autism spectrum disorders (ASDs) and schizophrenia (SCZ), as well as the advances in stem cell-based modeling and the novel therapeutic targets derived from these studies.}, author = {Sacco, Roberto and Cacci, Emanuele and Novarino, Gaia}, journal = {Current Opinion in Neurobiology}, number = {2}, pages = {131 -- 138}, publisher = {Elsevier}, title = {{Neural stem cells in neuropsychiatric disorders}}, doi = {10.1016/j.conb.2017.12.005}, volume = {48}, year = {2018}, } @misc{9812, abstract = {This document contains the full list of genes with their respective significance and dN/dS values. (TXT 4499Â kb)}, author = {Zapata, Luis and Pich, Oriol and Serrano, Luis and Kondrashov, Fyodor and Ossowski, Stephan and Schaefer, Martin}, publisher = {Springer Nature}, title = {{Additional file 2: Of negative selection in tumor genome evolution acts on essential cellular functions and the immunopeptidome}}, doi = {10.6084/m9.figshare.6401414.v1}, year = {2018}, } @misc{9811, abstract = {This document contains additional supporting evidence presented as supplemental tables. (XLSX 50Â kb)}, author = {Zapata, Luis and Pich, Oriol and Serrano, Luis and Kondrashov, Fyodor and Ossowski, Stephan and Schaefer, Martin}, publisher = {Springer Nature}, title = {{Additional file 1: Of negative selection in tumor genome evolution acts on essential cellular functions and the immunopeptidome}}, doi = {10.6084/m9.figshare.6401390.v1}, year = {2018}, } @article{20, abstract = {Background: Norepinephrine (NE) signaling has a key role in white adipose tissue (WAT) functions, including lipolysis, free fatty acid liberation and, under certain conditions, conversion of white into brite (brown-in-white) adipocytes. However, acute effects of NE stimulation have not been described at the transcriptional network level. Results: We used RNA-seq to uncover a broad transcriptional response. The inference of protein-protein and protein-DNA interaction networks allowed us to identify a set of immediate-early genes (IEGs) with high betweenness, validating our approach and suggesting a hierarchical control of transcriptional regulation. In addition, we identified a transcriptional regulatory network with IEGs as master regulators, including HSF1 and NFIL3 as novel NE-induced IEG candidates. Moreover, a functional enrichment analysis and gene clustering into functional modules suggest a crosstalk between metabolic, signaling, and immune responses. Conclusions: Altogether, our network biology approach explores for the first time the immediate-early systems level response of human adipocytes to acute sympathetic activation, thereby providing a first network basis of early cell fate programs and crosstalks between metabolic and transcriptional networks required for proper WAT function.}, author = {Higareda Almaraz, Juan and Karbiener, Michael and Giroud, Maude and Pauler, Florian and Gerhalter, Teresa and Herzig, Stephan and Scheideler, Marcel}, issn = {1471-2164}, journal = {BMC Genomics}, number = {1}, publisher = {BioMed Central}, title = {{Norepinephrine triggers an immediate-early regulatory network response in primary human white adipocytes}}, doi = {10.1186/s12864-018-5173-0}, volume = {19}, year = {2018}, } @article{107, abstract = {We introduce the notion of “non-malleable codes” which relaxes the notion of error correction and error detection. Informally, a code is non-malleable if the message contained in a modified codeword is either the original message, or a completely unrelated value. In contrast to error correction and error detection, non-malleability can be achieved for very rich classes of modifications. We construct an efficient code that is non-malleable with respect to modifications that affect each bit of the codeword arbitrarily (i.e., leave it untouched, flip it, or set it to either 0 or 1), but independently of the value of the other bits of the codeword. Using the probabilistic method, we also show a very strong and general statement: there exists a non-malleable code for every “small enough” family F of functions via which codewords can be modified. Although this probabilistic method argument does not directly yield efficient constructions, it gives us efficient non-malleable codes in the random-oracle model for very general classes of tampering functions—e.g., functions where every bit in the tampered codeword can depend arbitrarily on any 99% of the bits in the original codeword. As an application of non-malleable codes, we show that they provide an elegant algorithmic solution to the task of protecting functionalities implemented in hardware (e.g., signature cards) against “tampering attacks.” In such attacks, the secret state of a physical system is tampered, in the hopes that future interaction with the modified system will reveal some secret information. This problem was previously studied in the work of Gennaro et al. in 2004 under the name “algorithmic tamper proof security” (ATP). We show that non-malleable codes can be used to achieve important improvements over the prior work. In particular, we show that any functionality can be made secure against a large class of tampering attacks, simply by encoding the secret state with a non-malleable code while it is stored in memory.}, author = {Dziembowski, Stefan and Pietrzak, Krzysztof Z and Wichs, Daniel}, journal = {Journal of the ACM}, number = {4}, publisher = {ACM}, title = {{Non-malleable codes}}, doi = {10.1145/3178432}, volume = {65}, year = {2018}, } @article{5676, abstract = {In epithelial tissues, cells tightly connect to each other through cell–cell junctions, but they also present the remarkable capacity of reorganizing themselves without compromising tissue integrity. Upon injury, simple epithelia efficiently resolve small lesions through the action of actin cytoskeleton contractile structures at the wound edge and cellular rearrangements. However, the underlying mechanisms and how they cooperate are still poorly understood. In this study, we combine live imaging and theoretical modeling to reveal a novel and indispensable role for occluding junctions (OJs) in this process. We demonstrate that OJ loss of function leads to defects in wound-closure dynamics: instead of contracting, wounds dramatically increase their area. OJ mutants exhibit phenotypes in cell shape, cellular rearrangements, and mechanical properties as well as in actin cytoskeleton dynamics at the wound edge. We propose that OJs are essential for wound closure by impacting on epithelial mechanics at the tissue level, which in turn is crucial for correct regulation of the cellular events occurring at the wound edge.}, author = {Carvalho, Lara and Patricio, Pedro and Ponte, Susana and Heisenberg, Carl-Philipp J and Almeida, Luis and Nunes, André S. and Araújo, Nuno A.M. and Jacinto, Antonio}, issn = {00219525}, journal = {Journal of Cell Biology}, number = {12}, pages = {4267--4283}, publisher = {Rockefeller University Press}, title = {{Occluding junctions as novel regulators of tissue mechanics during wound repair}}, doi = {10.1083/jcb.201804048}, volume = {217}, year = {2018}, } @inproceedings{14224, abstract = {Clustering is a cornerstone of unsupervised learning which can be thought as disentangling multiple generative mechanisms underlying the data. In this paper we introduce an algorithmic framework to train mixtures of implicit generative models which we particularize for variational autoencoders. Relying on an additional set of discriminators, we propose a competitive procedure in which the models only need to approximate the portion of the data distribution from which they can produce realistic samples. As a byproduct, each model is simpler to train, and a clustering interpretation arises naturally from the partitioning of the training points among the models. We empirically show that our approach splits the training distribution in a reasonable way and increases the quality of the generated samples.}, author = {Locatello, Francesco and Vincent, Damien and Tolstikhin, Ilya and Ratsch, Gunnar and Gelly, Sylvain and Scholkopf, Bernhard}, booktitle = {6th International Conference on Learning Representations}, location = {Vancouver, Canada}, title = {{Clustering meets implicit generative models}}, year = {2018}, } @misc{9807, abstract = {Table S1. Genes with highest betweenness. Table S2. Local and Master regulators up-regulated. Table S3. Local and Master regulators down-regulated (XLSX 23 kb).}, author = {Higareda Almaraz, Juan and Karbiener, Michael and Giroud, Maude and Pauler, Florian and Gerhalter, Teresa and Herzig, Stephan and Scheideler, Marcel}, publisher = {Springer Nature}, title = {{Additional file 1: Of Norepinephrine triggers an immediate-early regulatory network response in primary human white adipocytes}}, doi = {10.6084/m9.figshare.7295339.v1}, year = {2018}, } @misc{9808, abstract = {Table S4. Counts per Gene per Million Reads Mapped. (XLSX 2751 kb).}, author = {Higareda Almaraz, Juan and Karbiener, Michael and Giroud, Maude and Pauler, Florian and Gerhalter, Teresa and Herzig, Stephan and Scheideler, Marcel}, publisher = {Springer Nature}, title = {{Additional file 3: Of Norepinephrine triggers an immediate-early regulatory network response in primary human white adipocytes}}, doi = {10.6084/m9.figshare.7295369.v1}, year = {2018}, } @inproceedings{193, abstract = {We show attacks on five data-independent memory-hard functions (iMHF) that were submitted to the password hashing competition (PHC). Informally, an MHF is a function which cannot be evaluated on dedicated hardware, like ASICs, at significantly lower hardware and/or energy cost than evaluating a single instance on a standard single-core architecture. Data-independent means the memory access pattern of the function is independent of the input; this makes iMHFs harder to construct than data-dependent ones, but the latter can be attacked by various side-channel attacks. Following [Alwen-Blocki'16], we capture the evaluation of an iMHF as a directed acyclic graph (DAG). The cumulative parallel pebbling complexity of this DAG is a measure for the hardware cost of evaluating the iMHF on an ASIC. Ideally, one would like the complexity of a DAG underlying an iMHF to be as close to quadratic in the number of nodes of the graph as possible. Instead, we show that (the DAGs underlying) the following iMHFs are far from this bound: Rig.v2, TwoCats and Gambit each having an exponent no more than 1.75. Moreover, we show that the complexity of the iMHF modes of the PHC finalists Pomelo and Lyra2 have exponents at most 1.83 and 1.67 respectively. To show this we investigate a combinatorial property of each underlying DAG (called its depth-robustness. By establishing upper bounds on this property we are then able to apply the general technique of [Alwen-Block'16] for analyzing the hardware costs of an iMHF.}, author = {Alwen, Joel F and Gazi, Peter and Kamath Hosdurg, Chethan and Klein, Karen and Osang, Georg F and Pietrzak, Krzysztof Z and Reyzin, Lenoid and Rolinek, Michal and Rybar, Michal}, booktitle = {Proceedings of the 2018 on Asia Conference on Computer and Communication Security}, location = {Incheon, Republic of Korea}, pages = {51 -- 65}, publisher = {ACM}, title = {{On the memory hardness of data independent password hashing functions}}, doi = {10.1145/3196494.3196534}, year = {2018}, } @inproceedings{300, abstract = {We introduce a formal quantitative notion of “bit security” for a general type of cryptographic games (capturing both decision and search problems), aimed at capturing the intuition that a cryptographic primitive with k-bit security is as hard to break as an ideal cryptographic function requiring a brute force attack on a k-bit key space. Our new definition matches the notion of bit security commonly used by cryptographers and cryptanalysts when studying search (e.g., key recovery) problems, where the use of the traditional definition is well established. However, it produces a quantitatively different metric in the case of decision (indistinguishability) problems, where the use of (a straightforward generalization of) the traditional definition is more problematic and leads to a number of paradoxical situations or mismatches between theoretical/provable security and practical/common sense intuition. Key to our new definition is to consider adversaries that may explicitly declare failure of the attack. We support and justify the new definition by proving a number of technical results, including tight reductions between several standard cryptographic problems, a new hybrid theorem that preserves bit security, and an application to the security analysis of indistinguishability primitives making use of (approximate) floating point numbers. This is the first result showing that (standard precision) 53-bit floating point numbers can be used to achieve 100-bit security in the context of cryptographic primitives with general indistinguishability-based security definitions. Previous results of this type applied only to search problems, or special types of decision problems.}, author = {Micciancio, Daniele and Walter, Michael}, location = {Tel Aviv, Israel}, pages = {3 -- 28}, publisher = {Springer}, title = {{On the bit security of cryptographic primitives}}, doi = {10.1007/978-3-319-78381-9_1}, volume = {10820}, year = {2018}, } @article{312, abstract = {Motivated by biological questions, we study configurations of equal spheres that neither pack nor cover. Placing their centers on a lattice, we define the soft density of the configuration by penalizing multiple overlaps. Considering the 1-parameter family of diagonally distorted 3-dimensional integer lattices, we show that the soft density is maximized at the FCC lattice.}, author = {Edelsbrunner, Herbert and Iglesias Ham, Mabel}, issn = {08954801}, journal = {SIAM J Discrete Math}, number = {1}, pages = {750 -- 782}, publisher = {Society for Industrial and Applied Mathematics }, title = {{On the optimality of the FCC lattice for soft sphere packing}}, doi = {10.1137/16M1097201}, volume = {32}, year = {2018}, } @article{409, abstract = {We give a simple proof of T. Stehling's result [4], whereby in any normal tiling of the plane with convex polygons with number of sides not less than six, all tiles except a finite number are hexagons.}, author = {Akopyan, Arseniy}, issn = {1631073X}, journal = {Comptes Rendus Mathematique}, number = {4}, pages = {412--414}, publisher = {Elsevier}, title = {{On the number of non-hexagons in a planar tiling}}, doi = {10.1016/j.crma.2018.03.005}, volume = {356}, year = {2018}, } @article{419, abstract = {Reciprocity is a major factor in human social life and accounts for a large part of cooperation in our communities. Direct reciprocity arises when repeated interactions occur between the same individuals. The framework of iterated games formalizes this phenomenon. Despite being introduced more than five decades ago, the concept keeps offering beautiful surprises. Recent theoretical research driven by new mathematical tools has proposed a remarkable dichotomy among the crucial strategies: successful individuals either act as partners or as rivals. Rivals strive for unilateral advantages by applying selfish or extortionate strategies. Partners aim to share the payoff for mutual cooperation, but are ready to fight back when being exploited. Which of these behaviours evolves depends on the environment. Whereas small population sizes and a limited number of rounds favour rivalry, partner strategies are selected when populations are large and relationships stable. Only partners allow for evolution of cooperation, while the rivals’ attempt to put themselves first leads to defection. Hilbe et al. synthesize recent theoretical work on zero-determinant and ‘rival’ versus ‘partner’ strategies in social dilemmas. They describe the environments under which these contrasting selfish or cooperative strategies emerge in evolution.}, author = {Hilbe, Christian and Chatterjee, Krishnendu and Nowak, Martin}, journal = {Nature Human Behaviour}, pages = {469–477}, publisher = {Nature Publishing Group}, title = {{Partners and rivals in direct reciprocity}}, doi = {10.1038/s41562-018-0320-9}, volume = {2}, year = {2018}, } @inproceedings{78, abstract = {We provide a procedure for detecting the sub-segments of an incrementally observed Boolean signal ω that match a given temporal pattern ϕ. As a pattern specification language, we use timed regular expressions, a formalism well-suited for expressing properties of concurrent asynchronous behaviors embedded in metric time. We construct a timed automaton accepting the timed language denoted by ϕ and modify it slightly for the purpose of matching. We then apply zone-based reachability computation to this automaton while it reads ω, and retrieve all the matching segments from the results. Since the procedure is automaton based, it can be applied to patterns specified by other formalisms such as timed temporal logics reducible to timed automata or directly encoded as timed automata. The procedure has been implemented and its performance on synthetic examples is demonstrated.}, author = {Bakhirkin, Alexey and Ferrere, Thomas and Nickovic, Dejan and Maler, Oded and Asarin, Eugene}, isbn = {978-3-030-00150-6}, location = {Bejing, China}, pages = {215 -- 232}, publisher = {Springer}, title = {{Online timed pattern matching using automata}}, doi = {10.1007/978-3-030-00151-3_13}, volume = {11022}, year = {2018}, } @article{317, abstract = {We replace the established aluminium gates for the formation of quantum dots in silicon with gates made from palladium. We study the morphology of both aluminium and palladium gates with transmission electron microscopy. The native aluminium oxide is found to be formed all around the aluminium gates, which could lead to the formation of unintentional dots. Therefore, we report on a novel fabrication route that replaces aluminium and its native oxide by palladium with atomic-layer-deposition-grown aluminium oxide. Using this approach, we show the formation of low-disorder gate-defined quantum dots, which are reproducibly fabricated. Furthermore, palladium enables us to further shrink the gate design, allowing us to perform electron transport measurements in the few-electron regime in devices comprising only two gate layers, a major technological advancement. It remains to be seen, whether the introduction of palladium gates can improve the excellent results on electron and nuclear spin qubits defined with an aluminium gate stack.}, author = {Brauns, Matthias and Amitonov, Sergey and Spruijtenburg, Paul and Zwanenburg, Floris}, journal = {Scientific Reports}, number = {1}, publisher = {Nature Publishing Group}, title = {{Palladium gates for reproducible quantum dots in silicon}}, doi = {10.1038/s41598-018-24004-y}, volume = {8}, year = {2018}, } @article{194, abstract = {Ants are emerging model systems to study cellular signaling because distinct castes possess different physiologic phenotypes within the same colony. Here we studied the functionality of inotocin signaling, an insect ortholog of mammalian oxytocin (OT), which was recently discovered in ants. In Lasius ants, we determined that specialization within the colony, seasonal factors, and physiologic conditions down-regulated the expression of the OT-like signaling system. Given this natural variation, we interrogated its function using RNAi knockdowns. Next-generation RNA sequencing of OT-like precursor knock-down ants highlighted its role in the regulation of genes involved in metabolism. Knock-down ants exhibited higher walking activity and increased self-grooming in the brood chamber. We propose that OT-like signaling in ants is important for regulating metabolic processes and locomotion.}, author = {Liutkeviciute, Zita and Gil Mansilla, Esther and Eder, Thomas and Casillas Perez, Barbara E and Giulia Di Giglio, Maria and Muratspahić, Edin and Grebien, Florian and Rattei, Thomas and Muttenthaler, Markus and Cremer, Sylvia and Gruber, Christian}, issn = {08926638}, journal = {The FASEB Journal}, number = {12}, pages = {6808--6821}, publisher = {FASEB}, title = {{Oxytocin-like signaling in ants influences metabolic gene expression and locomotor activity}}, doi = {10.1096/fj.201800443}, volume = {32}, year = {2018}, } @article{159, abstract = {L-type Ca2+ channels (LTCCs) play a crucial role in excitation-contraction coupling and release of hormones from secretory cells. They are targets of antihypertensive and antiarrhythmic drugs such as diltiazem. Here, we present a photoswitchable diltiazem, FHU-779, which can be used to reversibly block endogenous LTCCs by light. FHU-779 is as potent as diltiazem and can be used to place pancreatic β-cell function and cardiac activity under optical control.}, author = {Fehrentz, Timm and Huber, Florian and Hartrampf, Nina and Bruegmann, Tobias and Frank, James and Fine, Nicholas and Malan, Daniela and Danzl, Johann G and Tikhonov, Denis and Sumser, Maritn and Sasse, Philipp and Hodson, David and Zhorov, Boris and Klocker, Nikolaj and Trauner, Dirk}, journal = {Nature Chemical Biology}, number = {8}, pages = {764 -- 767}, publisher = {Nature Publishing Group}, title = {{Optical control of L-type Ca2+ channels using a diltiazem photoswitch}}, doi = {10.1038/s41589-018-0090-8}, volume = {14}, year = {2018}, } @inproceedings{79, abstract = {Markov Decision Processes (MDPs) are a popular class of models suitable for solving control decision problems in probabilistic reactive systems. We consider parametric MDPs (pMDPs) that include parameters in some of the transition probabilities to account for stochastic uncertainties of the environment such as noise or input disturbances. We study pMDPs with reachability objectives where the parameter values are unknown and impossible to measure directly during execution, but there is a probability distribution known over the parameter values. We study for the first time computing parameter-independent strategies that are expectation optimal, i.e., optimize the expected reachability probability under the probability distribution over the parameters. We present an encoding of our problem to partially observable MDPs (POMDPs), i.e., a reduction of our problem to computing optimal strategies in POMDPs. We evaluate our method experimentally on several benchmarks: a motivating (repeated) learner model; a series of benchmarks of varying configurations of a robot moving on a grid; and a consensus protocol.}, author = {Arming, Sebastian and Bartocci, Ezio and Chatterjee, Krishnendu and Katoen, Joost P and Sokolova, Ana}, location = {Beijing, China}, pages = {53--70}, publisher = {Springer}, title = {{Parameter-independent strategies for pMDPs via POMDPs}}, doi = {10.1007/978-3-319-99154-2_4}, volume = {11024}, year = {2018}, } @unpublished{14327, abstract = {A common assumption in causal modeling posits that the data is generated by a set of independent mechanisms, and algorithms should aim to recover this structure. Standard unsupervised learning, however, is often concerned with training a single model to capture the overall distribution or aspects thereof. Inspired by clustering approaches, we consider mixtures of implicit generative models that ``disentangle'' the independent generative mechanisms underlying the data. Relying on an additional set of discriminators, we propose a competitive training procedure in which the models only need to capture the portion of the data distribution from which they can produce realistic samples. As a by-product, each model is simpler and faster to train. We empirically show that our approach splits the training distribution in a sensible way and increases the quality of the generated samples.}, author = {Locatello, Francesco and Vincent, Damien and Tolstikhin, Ilya and Rätsch, Gunnar and Gelly, Sylvain and Schölkopf, Bernhard}, booktitle = {arXiv}, title = {{Competitive training of mixtures of independent deep generative models}}, doi = {10.48550/arXiv.1804.11130}, year = {2018}, } @article{400, abstract = {We consider the two-dimensional BCS functional with a radial pair interaction. We show that the translational symmetry is not broken in a certain temperature interval below the critical temperature. In the case of vanishing angular momentum, our results carry over to the three-dimensional case.}, author = {Deuchert, Andreas and Geisinge, Alissa and Hainzl, Christian and Loss, Michael}, journal = {Annales Henri Poincare}, number = {5}, pages = {1507 -- 1527}, publisher = {Springer}, title = {{Persistence of translational symmetry in the BCS model with radial pair interaction}}, doi = {10.1007/s00023-018-0665-7}, volume = {19}, year = {2018}, } @article{406, abstract = {Recent developments in automated tracking allow uninterrupted, high-resolution recording of animal trajectories, sometimes coupled with the identification of stereotyped changes of body pose or other behaviors of interest. Analysis and interpretation of such data represents a challenge: the timing of animal behaviors may be stochastic and modulated by kinematic variables, by the interaction with the environment or with the conspecifics within the animal group, and dependent on internal cognitive or behavioral state of the individual. Existing models for collective motion typically fail to incorporate the discrete, stochastic, and internal-state-dependent aspects of behavior, while models focusing on individual animal behavior typically ignore the spatial aspects of the problem. Here we propose a probabilistic modeling framework to address this gap. Each animal can switch stochastically between different behavioral states, with each state resulting in a possibly different law of motion through space. Switching rates for behavioral transitions can depend in a very general way, which we seek to identify from data, on the effects of the environment as well as the interaction between the animals. We represent the switching dynamics as a Generalized Linear Model and show that: (i) forward simulation of multiple interacting animals is possible using a variant of the Gillespie’s Stochastic Simulation Algorithm; (ii) formulated properly, the maximum likelihood inference of switching rate functions is tractably solvable by gradient descent; (iii) model selection can be used to identify factors that modulate behavioral state switching and to appropriately adjust model complexity to data. To illustrate our framework, we apply it to two synthetic models of animal motion and to real zebrafish tracking data. }, author = {Bod’Ová, Katarína and Mitchell, Gabriel and Harpaz, Roy and Schneidman, Elad and Tkacik, Gasper}, journal = {PLoS One}, number = {3}, publisher = {Public Library of Science}, title = {{Probabilistic models of individual and collective animal behavior}}, doi = {10.1371/journal.pone.0193049}, volume = {13}, year = {2018}, } @article{457, abstract = {Temperate bacteriophages integrate in bacterial genomes as prophages and represent an important source of genetic variation for bacterial evolution, frequently transmitting fitness-augmenting genes such as toxins responsible for virulence of major pathogens. However, only a fraction of bacteriophage infections are lysogenic and lead to prophage acquisition, whereas the majority are lytic and kill the infected bacteria. Unless able to discriminate lytic from lysogenic infections, mechanisms of immunity to bacteriophages are expected to act as a double-edged sword and increase the odds of survival at the cost of depriving bacteria of potentially beneficial prophages. We show that although restriction-modification systems as mechanisms of innate immunity prevent both lytic and lysogenic infections indiscriminately in individual bacteria, they increase the number of prophage-acquiring individuals at the population level. We find that this counterintuitive result is a consequence of phage-host population dynamics, in which restriction-modification systems delay infection onset until bacteria reach densities at which the probability of lysogeny increases. These results underscore the importance of population-level dynamics as a key factor modulating costs and benefits of immunity to temperate bacteriophages}, author = {Pleska, Maros and Lang, Moritz and Refardt, Dominik and Levin, Bruce and Guet, Calin C}, journal = {Nature Ecology and Evolution}, number = {2}, pages = {359 -- 366}, publisher = {Springer Nature}, title = {{Phage-host population dynamics promotes prophage acquisition in bacteria with innate immunity}}, doi = {10.1038/s41559-017-0424-z}, volume = {2}, year = {2018}, }