@article{612, abstract = {Metabotropic GABAB receptors mediate slow inhibitory effects presynaptically and postsynaptically through the modulation of different effector signalling pathways. Here, we analysed the distribution of GABAB receptors using highly sensitive SDS-digested freeze-fracture replica labelling in mouse cerebellar Purkinje cells. Immunoreactivity for GABAB1 was observed on presynaptic and, more abundantly, on postsynaptic compartments, showing both scattered and clustered distribution patterns. Quantitative analysis of immunoparticles revealed a somato-dendritic gradient, with the density of immunoparticles increasing 26-fold from somata to dendritic spines. To understand the spatial relationship of GABAB receptors with two key effector ion channels, the G protein-gated inwardly rectifying K+ (GIRK/Kir3) channel and the voltage-dependent Ca2+ channel, biochemical and immunohistochemical approaches were performed. Co-immunoprecipitation analysis demonstrated that GABAB receptors co-assembled with GIRK and CaV2.1 channels in the cerebellum. Using double-labelling immunoelectron microscopic techniques, co-clustering between GABAB1 and GIRK2 was detected in dendritic spines, whereas they were mainly segregated in the dendritic shafts. In contrast, co-clustering of GABAB1 and CaV2.1 was detected in dendritic shafts but not spines. Presynaptically, although no significant co-clustering of GABAB1 and GIRK2 or CaV2.1 channels was detected, inter-cluster distance for GABAB1 and GIRK2 was significantly smaller in the active zone than in the dendritic shafts, and that for GABAB1 and CaV2.1 was significantly smaller in the active zone than in the dendritic shafts and spines. Thus, GABAB receptors are associated with GIRK and CaV2.1 channels in different subcellular compartments. These data provide a better framework for understanding the different roles played by GABAB receptors and their effector ion channels in the cerebellar network.}, author = {Luján, Rafael and Aguado, Carolina and Ciruela, Francisco and Cózar, Javier and Kleindienst, David and De La Ossa, Luis and Bettler, Bernhard and Wickman, Kevin and Watanabe, Masahiko and Shigemoto, Ryuichi and Fukazawa, Yugo}, journal = {Brain Structure and Function}, number = {3}, pages = {1565 -- 1587}, publisher = {Springer}, title = {{Differential association of GABAB receptors with their effector ion channels in Purkinje cells}}, doi = {10.1007/s00429-017-1568-y}, volume = {223}, year = {2018}, } @article{21, abstract = {Parvalbumin-positive (PV+) GABAergic interneurons in hippocampal microcircuits are thought to play a key role in several higher network functions, such as feedforward and feedback inhibition, network oscillations, and pattern separation. Fast lateral inhibition mediated by GABAergic interneurons may implement a winner-takes-all mechanism in the hippocampal input layer. However, it is not clear whether the functional connectivity rules of granule cells (GCs) and interneurons in the dentate gyrus are consistent with such a mechanism. Using simultaneous patch-clamp recordings from up to seven GCs and up to four PV+ interneurons in the dentate gyrus, we find that connectivity is structured in space, synapse-specific, and enriched in specific disynaptic motifs. In contrast to the neocortex, lateral inhibition in the dentate gyrus (in which a GC inhibits neighboring GCs via a PV+ interneuron) is ~ 10-times more abundant than recurrent inhibition (in which a GC inhibits itself). Thus, unique connectivity rules may enable the dentate gyrus to perform specific higher-order computations}, author = {Espinoza Martinez, Claudia and Guzmán, José and Zhang, Xiaomin and Jonas, Peter M}, journal = {Nature Communications}, number = {1}, publisher = {Nature Publishing Group}, title = {{Parvalbumin+ interneurons obey unique connectivity rules and establish a powerful lateral-inhibition microcircuit in dentate gyrus}}, doi = {10.1038/s41467-018-06899-3}, volume = {9}, year = {2018}, } @inproceedings{66, abstract = {Crypto-currencies are digital assets designed to work as a medium of exchange, e.g., Bitcoin, but they are susceptible to attacks (dishonest behavior of participants). A framework for the analysis of attacks in crypto-currencies requires (a) modeling of game-theoretic aspects to analyze incentives for deviation from honest behavior; (b) concurrent interactions between participants; and (c) analysis of long-term monetary gains. Traditional game-theoretic approaches for the analysis of security protocols consider either qualitative temporal properties such as safety and termination, or the very special class of one-shot (stateless) games. However, to analyze general attacks on protocols for crypto-currencies, both stateful analysis and quantitative objectives are necessary. In this work our main contributions are as follows: (a) we show how a class of concurrent mean-payo games, namely ergodic games, can model various attacks that arise naturally in crypto-currencies; (b) we present the first practical implementation of algorithms for ergodic games that scales to model realistic problems for crypto-currencies; and (c) we present experimental results showing that our framework can handle games with thousands of states and millions of transitions.}, author = {Chatterjee, Krishnendu and Goharshady, Amir and Ibsen-Jensen, Rasmus and Velner, Yaron}, isbn = {978-3-95977-087-3}, location = {Beijing, China}, publisher = {Schloss Dagstuhl - Leibniz-Zentrum für Informatik}, title = {{Ergodic mean-payoff games for the analysis of attacks in crypto-currencies}}, doi = {10.4230/LIPIcs.CONCUR.2018.11}, volume = {118}, year = {2018}, } @inproceedings{311, abstract = {Smart contracts are computer programs that are executed by a network of mutually distrusting agents, without the need of an external trusted authority. Smart contracts handle and transfer assets of considerable value (in the form of crypto-currency like Bitcoin). Hence, it is crucial that their implementation is bug-free. We identify the utility (or expected payoff) of interacting with such smart contracts as the basic and canonical quantitative property for such contracts. We present a framework for such quantitative analysis of smart contracts. Such a formal framework poses new and novel research challenges in programming languages, as it requires modeling of game-theoretic aspects to analyze incentives for deviation from honest behavior and modeling utilities which are not specified as standard temporal properties such as safety and termination. While game-theoretic incentives have been analyzed in the security community, their analysis has been restricted to the very special case of stateless games. However, to analyze smart contracts, stateful analysis is required as it must account for the different program states of the protocol. Our main contributions are as follows: we present (i)~a simplified programming language for smart contracts; (ii)~an automatic translation of the programs to state-based games; (iii)~an abstraction-refinement approach to solve such games; and (iv)~experimental results on real-world-inspired smart contracts.}, author = {Chatterjee, Krishnendu and Goharshady, Amir and Velner, Yaron}, location = {Thessaloniki, Greece}, pages = {739 -- 767}, publisher = {Springer}, title = {{Quantitative analysis of smart contracts}}, doi = {10.1007/978-3-319-89884-1_26}, volume = {10801}, year = {2018}, } @inproceedings{6340, abstract = {We present a secure approach for maintaining andreporting credit history records on the Blockchain. Our ap-proach removes third-parties such as credit reporting agen-cies from the lending process and replaces them with smartcontracts. This allows customers to interact directly with thelenders or banks while ensuring the integrity, unmalleabilityand privacy of their credit data. Additionally, each customerhas full control over complete or selective disclosure of hercredit records, eliminating the risk of privacy violations or databreaches. Moreover, our approach provides strong guaranteesfor the lenders as well. A lender can check both correctness andcompleteness of the credit data disclosed to her. This is the firstapproach that can perform all credit reporting tasks withouta central authority or changing the financial mechanisms*.}, author = {Goharshady, Amir Kafshdar and Behrouz, Ali and Chatterjee, Krishnendu}, booktitle = {Proceedings of the IEEE International Conference on Blockchain}, isbn = {978-1-5386-7975-3 }, location = {Halifax, Canada}, pages = {1343--1348}, publisher = {IEEE}, title = {{Secure Credit Reporting on the Blockchain}}, doi = {10.1109/Cybermatics_2018.2018.00231}, year = {2018}, } @article{6009, abstract = {We study algorithmic questions wrt algebraic path properties in concurrent systems, where the transitions of the system are labeled from a complete, closed semiring. The algebraic path properties can model dataflow analysis problems, the shortest path problem, and many other natural problems that arise in program analysis. We consider that each component of the concurrent system is a graph with constant treewidth, a property satisfied by the controlflow graphs of most programs. We allow for multiple possible queries, which arise naturally in demand driven dataflow analysis. The study of multiple queries allows us to consider the tradeoff between the resource usage of the one-time preprocessing and for each individual query. The traditional approach constructs the product graph of all components and applies the best-known graph algorithm on the product. In this approach, even the answer to a single query requires the transitive closure (i.e., the results of all possible queries), which provides no room for tradeoff between preprocessing and query time. Our main contributions are algorithms that significantly improve the worst-case running time of the traditional approach, and provide various tradeoffs depending on the number of queries. For example, in a concurrent system of two components, the traditional approach requires hexic time in the worst case for answering one query as well as computing the transitive closure, whereas we show that with one-time preprocessing in almost cubic time, each subsequent query can be answered in at most linear time, and even the transitive closure can be computed in almost quartic time. Furthermore, we establish conditional optimality results showing that the worst-case running time of our algorithms cannot be improved without achieving major breakthroughs in graph algorithms (i.e., improving the worst-case bound for the shortest path problem in general graphs). Preliminary experimental results show that our algorithms perform favorably on several benchmarks. }, author = {Chatterjee, Krishnendu and Ibsen-Jensen, Rasmus and Goharshady, Amir Kafshdar and Pavlogiannis, Andreas}, issn = {0164-0925}, journal = {ACM Transactions on Programming Languages and Systems}, number = {3}, publisher = {Association for Computing Machinery (ACM)}, title = {{Algorithms for algebraic path properties in concurrent systems of constant treewidth components}}, doi = {10.1145/3210257}, volume = {40}, year = {2018}, } @inproceedings{5977, abstract = {We consider the stochastic shortest path (SSP)problem for succinct Markov decision processes(MDPs), where the MDP consists of a set of vari-ables, and a set of nondeterministic rules that up-date the variables. First, we show that several ex-amples from the AI literature can be modeled assuccinct MDPs. Then we present computationalapproaches for upper and lower bounds for theSSP problem: (a) for computing upper bounds, ourmethod is polynomial-time in the implicit descrip-tion of the MDP; (b) for lower bounds, we present apolynomial-time (in the size of the implicit descrip-tion) reduction to quadratic programming. Our ap-proach is applicable even to infinite-state MDPs.Finally, we present experimental results to demon-strate the effectiveness of our approach on severalclassical examples from the AI literature.}, author = {Chatterjee, Krishnendu and Fu, Hongfei and Goharshady, Amir and Okati, Nastaran}, booktitle = {Proceedings of the Twenty-Seventh International Joint Conference on Artificial Intelligence}, isbn = {978-099924112-7}, issn = {10450823}, location = {Stockholm, Sweden}, pages = {4700--4707}, publisher = {IJCAI}, title = {{Computational approaches for stochastic shortest path on succinct MDPs}}, doi = {10.24963/ijcai.2018/653}, volume = {2018}, year = {2018}, } @article{422, abstract = {We show that a rather simple, steady modification of the streamwise velocity profile in a pipe can lead to a complete collapse of turbulence and the flow fully relaminarizes. Two different devices, a stationary obstacle (inset) and a device which injects fluid through an annular gap close to the wall, are used to control the flow. Both devices modify the streamwise velocity profile such that the flow in the center of the pipe is decelerated and the flow in the near wall region is accelerated. We present measurements with stereoscopic particle image velocimetry to investigate and capture the development of the relaminarizing flow downstream these devices and the specific circumstances responsible for relaminarization. We find total relaminarization up to Reynolds numbers of 6000, where the skin friction in the far downstream distance is reduced by a factor of 3.4 due to relaminarization. In a smooth straight pipe the flow remains completely laminar downstream of the control. Furthermore, we show that transient (temporary) relaminarization in a spatially confined region right downstream the devices occurs also at much higher Reynolds numbers, accompanied by a significant local skin friction drag reduction. The underlying physical mechanism of relaminarization is attributed to a weakening of the near-wall turbulence production cycle.}, author = {Kühnen, Jakob and Scarselli, Davide and Schaner, Markus and Hof, Björn}, journal = {Flow Turbulence and Combustion}, number = {4}, pages = {919 -- 942}, publisher = {Springer}, title = {{Relaminarization by steady modification of the streamwise velocity profile in a pipe}}, doi = {10.1007/s10494-018-9896-4}, volume = {100}, year = {2018}, } @article{461, abstract = {Turbulence is the major cause of friction losses in transport processes and it is responsible for a drastic drag increase in flows over bounding surfaces. While much effort is invested into developing ways to control and reduce turbulence intensities, so far no methods exist to altogether eliminate turbulence if velocities are sufficiently large. We demonstrate for pipe flow that appropriate distortions to the velocity profile lead to a complete collapse of turbulence and subsequently friction losses are reduced by as much as 90%. Counterintuitively, the return to laminar motion is accomplished by initially increasing turbulence intensities or by transiently amplifying wall shear. Since neither the Reynolds number nor the shear stresses decrease (the latter often increase), these measures are not indicative of turbulence collapse. Instead, an amplification mechanism measuring the interaction between eddies and the mean shear is found to set a threshold below which turbulence is suppressed beyond recovery.}, author = {Kühnen, Jakob and Song, Baofang and Scarselli, Davide and Budanur, Nazmi B and Riedl, Michael and Willis, Ashley and Avila, Marc and Hof, Björn}, journal = {Nature Physics}, pages = {386--390}, publisher = {Nature Publishing Group}, title = {{Destabilizing turbulence in pipe flow}}, doi = {10.1038/s41567-017-0018-3}, volume = {14}, year = {2018}, } @article{449, abstract = {Auxin is unique among plant hormones due to its directional transport that is mediated by the polarly distributed PIN auxin transporters at the plasma membrane. The canalization hypothesis proposes that the auxin feedback on its polar flow is a crucial, plant-specific mechanism mediating multiple self-organizing developmental processes. Here, we used the auxin effect on the PIN polar localization in Arabidopsis thaliana roots as a proxy for the auxin feedback on the PIN polarity during canalization. We performed microarray experiments to find regulators of this process that act downstream of auxin. We identified genes that were transcriptionally regulated by auxin in an AXR3/IAA17- and ARF7/ARF19-dependent manner. Besides the known components of the PIN polarity, such as PID and PIP5K kinases, a number of potential new regulators were detected, among which the WRKY23 transcription factor, which was characterized in more detail. Gain- and loss-of-function mutants confirmed a role for WRKY23 in mediating the auxin effect on the PIN polarity. Accordingly, processes requiring auxin-mediated PIN polarity rearrangements, such as vascular tissue development during leaf venation, showed a higher WRKY23 expression and required the WRKY23 activity. Our results provide initial insights into the auxin transcriptional network acting upstream of PIN polarization and, potentially, canalization-mediated plant development.}, author = {Prat, Tomas and Hajny, Jakub and Grunewald, Wim and Vasileva, Mina K and Molnar, Gergely and Tejos, Ricardo and Schmid, Markus and Sauer, Michael and Friml, Jirí}, journal = {PLoS Genetics}, number = {1}, publisher = {Public Library of Science}, title = {{WRKY23 is a component of the transcriptional network mediating auxin feedback on PIN polarity}}, doi = {10.1371/journal.pgen.1007177}, volume = {14}, year = {2018}, }