@article{1083, abstract = { Cholecystokinin-expressing interneurons (CCK-INs) mediate behavior state-dependent inhibition in cortical circuits and themselves receive strong GABAergic input. However, it remains unclear to what extent GABABreceptors (GABABRs) contribute to their inhibitory control. Using immunoelectron microscopy, we found that CCK-INs in the rat hippocampus possessed high levels of dendritic GABABRs and KCTD12 auxiliary proteins, whereas postsynaptic effector Kir3 channels were present at lower levels. Consistently, whole-cell recordings revealed slow GABABR-mediated inhibitory postsynaptic currents (IPSCs) in most CCK-INs. In spite of the higher surface density of GABABRs in CCK-INs than in CA1 principal cells, the amplitudes of IPSCs were comparable, suggesting that the expression of Kir3 channels is the limiting factor for the GABABR currents in these INs. Morphological analysis showed that CCK-INs were diverse, comprising perisomatic-targeting basket cells (BCs), as well as dendrite-targeting (DT) interneurons, including a previously undescribed DT type. GABABR-mediated IPSCs in CCK-INs were large in BCs, but small in DT subtypes. In response to prolonged activation, GABABR-mediated currents displayed strong desensitization, which was absent in KCTD12-deficient mice. This study highlights that GABABRs differentially control CCK-IN subtypes, and the kinetics and desensitization of GABABR-mediated currents are modulated by KCTD12 proteins. }, author = {Booker, Sam and Althof, Daniel and Gross, Anna and Loreth, Desiree and Müller, Johanna and Unger, Andreas and Fakler, Bernd and Varro, Andrea and Watanabe, Masahiko and Gassmann, Martin and Bettler, Bernhard and Shigemoto, Ryuichi and Vida, Imre and Kulik, Ákos}, journal = {Cerebral Cortex}, number = {3}, pages = {2318 -- 2334}, publisher = {Oxford University Press}, title = {{KCTD12 auxiliary proteins modulate kinetics of GABAB receptor-mediated inhibition in Cholecystokinin-containing interneurons}}, doi = {10.1093/cercor/bhw090}, volume = {27}, year = {2016}, } @article{1088, abstract = {Cell geometry is tightly coupled to gene expression patterns within the tissue microenvironment. This perspective synthesizes evidence that the 3D organization of chromosomes is a critical intermediate for geometric control of genomic programs. Using a combination of experiments and modeling we outline approaches to decipher the mechano-genomic code that governs cellular homeostasis and reprogramming.}, author = {Uhler, Caroline and Shivashankar, G V}, journal = {BioArchitecture}, number = {4}, pages = {76 -- 84}, publisher = {Taylor & Francis}, title = {{Geometric control and modeling of genome reprogramming}}, doi = {10.1080/19490992.2016.1201620}, volume = {6}, year = {2016}, } @inproceedings{1090, abstract = { While weighted automata provide a natural framework to express quantitative properties, many basic properties like average response time cannot be expressed with weighted automata. Nested weighted automata extend weighted automata and consist of a master automaton and a set of slave automata that are invoked by the master automaton. Nested weighted automata are strictly more expressive than weighted automata (e.g., average response time can be expressed with nested weighted automata), but the basic decision questions have higher complexity (e.g., for deterministic automata, the emptiness question for nested weighted automata is PSPACE-hard, whereas the corresponding complexity for weighted automata is PTIME). We consider a natural subclass of nested weighted automata where at any point at most a bounded number k of slave automata can be active. We focus on automata whose master value function is the limit average. We show that these nested weighted automata with bounded width are strictly more expressive than weighted automata (e.g., average response time with no overlapping requests can be expressed with bound k=1, but not with non-nested weighted automata). We show that the complexity of the basic decision problems (i.e., emptiness and universality) for the subclass with k constant matches the complexity for weighted automata. Moreover, when k is part of the input given in unary we establish PSPACE-completeness.}, author = {Chatterjee, Krishnendu and Henzinger, Thomas A and Otop, Jan}, location = {Krakow; Poland}, publisher = {Schloss Dagstuhl - Leibniz-Zentrum für Informatik}, title = {{Nested weighted limit-average automata of bounded width}}, doi = {10.4230/LIPIcs.MFCS.2016.24}, volume = {58}, year = {2016}, } @inproceedings{1093, abstract = {We introduce a general class of distances (metrics) between Markov chains, which are based on linear behaviour. This class encompasses distances given topologically (such as the total variation distance or trace distance) as well as by temporal logics or automata. We investigate which of the distances can be approximated by observing the systems, i.e. by black-box testing or simulation, and we provide both negative and positive results. }, author = {Daca, Przemyslaw and Henzinger, Thomas A and Kretinsky, Jan and Petrov, Tatjana}, location = {Quebec City; Canada}, publisher = {Schloss Dagstuhl - Leibniz-Zentrum für Informatik}, title = {{Linear distances between Markov chains}}, doi = {10.4230/LIPIcs.CONCUR.2016.20}, volume = {59}, year = {2016}, } @inbook{1094, abstract = {Immunogold labeling of freeze-fracture replicas has recently been used for high-resolution visualization of protein localization in electron microscopy. This method has higher labeling efficiency than conventional immunogold methods for membrane molecules allowing precise quantitative measurements. However, one of the limitations of freeze-fracture replica immunolabeling is difficulty in keeping structural orientation and identifying labeled profiles in complex tissues like brain. The difficulty is partly due to fragmentation of freeze-fracture replica preparations during labeling procedures and limited morphological clues on the replica surface. To overcome these issues, we introduce here a grid-glued replica method combined with SEM observation. This method allows histological staining before dissolving the tissue and easy handling of replicas during immunogold labeling, and keeps the whole replica surface intact without fragmentation. The procedure described here is also useful for matched double-replica analysis allowing further identification of labeled profiles in corresponding P-face and E-face.}, author = {Harada, Harumi and Shigemoto, Ryuichi}, booktitle = {High-Resolution Imaging of Cellular Proteins}, issn = {1611-3349}, pages = {203 -- 216}, publisher = {Springer}, title = {{Immunogold protein localization on grid-glued freeze-fracture replicas}}, doi = {10.1007/978-1-4939-6352-2_12}, volume = {1474}, year = {2016}, } @inproceedings{1095, abstract = { The semantics of concurrent data structures is usually given by a sequential specification and a consistency condition. Linearizability is the most popular consistency condition due to its simplicity and general applicability. Nevertheless, for applications that do not require all guarantees offered by linearizability, recent research has focused on improving performance and scalability of concurrent data structures by relaxing their semantics. In this paper, we present local linearizability, a relaxed consistency condition that is applicable to container-type concurrent data structures like pools, queues, and stacks. While linearizability requires that the effect of each operation is observed by all threads at the same time, local linearizability only requires that for each thread T, the effects of its local insertion operations and the effects of those removal operations that remove values inserted by T are observed by all threads at the same time. We investigate theoretical and practical properties of local linearizability and its relationship to many existing consistency conditions. We present a generic implementation method for locally linearizable data structures that uses existing linearizable data structures as building blocks. Our implementations show performance and scalability improvements over the original building blocks and outperform the fastest existing container-type implementations. }, author = {Haas, Andreas and Henzinger, Thomas A and Holzer, Andreas and Kirsch, Christoph and Lippautz, Michael and Payer, Hannes and Sezgin, Ali and Sokolova, Ana and Veith, Helmut}, booktitle = {Leibniz International Proceedings in Informatics}, location = {Quebec City; Canada}, publisher = {Schloss Dagstuhl - Leibniz-Zentrum für Informatik}, title = {{Local linearizability for concurrent container-type data structures}}, doi = {10.4230/LIPIcs.CONCUR.2016.6}, volume = {59}, year = {2016}, } @article{1096, author = {Schwayer, Cornelia and Sikora, Mateusz K and Slovakova, Jana and Kardos, Roland and Heisenberg, Carl-Philipp J}, journal = {Developmental Cell}, number = {6}, pages = {493 -- 506}, publisher = {Cell Press}, title = {{Actin rings of power}}, doi = {10.1016/j.devcel.2016.05.024}, volume = {37}, year = {2016}, } @inproceedings{1097, abstract = {We present an interactive system for computational design, optimization, and fabrication of multicopters. Our computational approach allows non-experts to design, explore, and evaluate a wide range of different multicopters. We provide users with an intuitive interface for assembling a multicopter from a collection of components (e.g., propellers, motors, and carbon fiber rods). Our algorithm interactively optimizes shape and controller parameters of the current design to ensure its proper operation. In addition, we allow incorporating a variety of other metrics (such as payload, battery usage, size, and cost) into the design process and exploring tradeoffs between them. We show the efficacy of our method and system by designing, optimizing, fabricating, and operating multicopters with complex geometries and propeller configurations. We also demonstrate the ability of our optimization algorithm to improve the multicopter performance under different metrics.}, author = {Du, Tao and Schulz, Adriana and Zhu, Bo and Bickel, Bernd and Matusik, Wojciech}, location = {Macao, China}, number = {6}, publisher = {ACM}, title = {{Computational multicopter design}}, doi = {10.1145/2980179.2982427}, volume = {35}, year = {2016}, } @inproceedings{1098, abstract = {Better understanding of the potential benefits of information transfer and representation learning is an important step towards the goal of building intelligent systems that are able to persist in the world and learn over time. In this work, we consider a setting where the learner encounters a stream of tasks but is able to retain only limited information from each encountered task, such as a learned predictor. In contrast to most previous works analyzing this scenario, we do not make any distributional assumptions on the task generating process. Instead, we formulate a complexity measure that captures the diversity of the observed tasks. We provide a lifelong learning algorithm with error guarantees for every observed task (rather than on average). We show sample complexity reductions in comparison to solving every task in isolation in terms of our task complexity measure. Further, our algorithmic framework can naturally be viewed as learning a representation from encountered tasks with a neural network.}, author = {Pentina, Anastasia and Urner, Ruth}, location = {Barcelona, Spain}, pages = {3619--3627}, publisher = {Neural Information Processing Systems}, title = {{Lifelong learning with weighted majority votes}}, volume = {29}, year = {2016}, } @inproceedings{1099, abstract = {We present FlexMolds, a novel computational approach to automatically design flexible, reusable molds that, once 3D printed, allow us to physically fabricate, by means of liquid casting, multiple copies of complex shapes with rich surface details and complex topology. The approach to design such flexible molds is based on a greedy bottom-up search of possible cuts over an object, evaluating for each possible cut the feasibility of the resulting mold. We use a dynamic simulation approach to evaluate candidate molds, providing a heuristic to generate forces that are able to open, detach, and remove a complex mold from the object it surrounds. We have tested the approach with a number of objects with nontrivial shapes and topologies.}, author = {Malomo, Luigi and Pietroni, Nico and Bickel, Bernd and Cignoni, Paolo}, location = {Macao, China}, number = {6}, publisher = {ACM}, title = {{FlexMolds: Automatic design of flexible shells for molding}}, doi = {10.1145/2980179.2982397}, volume = {35}, year = {2016}, } @article{1100, abstract = {During metazoan development, the temporal pattern of morphogen signaling is critical for organizing cell fates in space and time. Yet, tools for temporally controlling morphogen signaling within the embryo are still scarce. Here, we developed a photoactivatable Nodal receptor to determine how the temporal pattern of Nodal signaling affects cell fate specification during zebrafish gastrulation. By using this receptor to manipulate the duration of Nodal signaling in vivo by light, we show that extended Nodal signaling within the organizer promotes prechordal plate specification and suppresses endoderm differentiation. Endoderm differentiation is suppressed by extended Nodal signaling inducing expression of the transcriptional repressor goosecoid (gsc) in prechordal plate progenitors, which in turn restrains Nodal signaling from upregulating the endoderm differentiation gene sox17 within these cells. Thus, optogenetic manipulation of Nodal signaling identifies a critical role of Nodal signaling duration for organizer cell fate specification during gastrulation.}, author = {Sako, Keisuke and Pradhan, Saurabh and Barone, Vanessa and Inglés Prieto, Álvaro and Mueller, Patrick and Ruprecht, Verena and Capek, Daniel and Galande, Sanjeev and Janovjak, Harald L and Heisenberg, Carl-Philipp J}, journal = {Cell Reports}, number = {3}, pages = {866 -- 877}, publisher = {Cell Press}, title = {{Optogenetic control of nodal signaling reveals a temporal pattern of nodal signaling regulating cell fate specification during gastrulation}}, doi = {10.1016/j.celrep.2016.06.036}, volume = {16}, year = {2016}, } @article{1101, abstract = {Optical sensors based on the phenomenon of Förster resonance energy transfer (FRET) are powerful tools that have advanced the study of small molecules in biological systems. However, sensor construction is not trivial and often requires multiple rounds of engineering or an ability to screen large numbers of variants. A method that would allow the accurate rational design of FRET sensors would expedite the production of biologically useful sensors. Here, we present Rangefinder, a computational algorithm that allows rapid in silico screening of dye attachment sites in a ligand-binding protein for the conjugation of a dye molecule to act as a Förster acceptor for a fused fluorescent protein. We present three ratiometric fluorescent sensors designed with Rangefinder, including a maltose sensor with a dynamic range of >300% and the first sensors for the most abundant sialic acid in human cells, N-acetylneuraminic acid. Provided a ligand-binding protein exists, it is our expectation that this model will facilitate the design of an optical sensor for any small molecule of interest.}, author = {Mitchell, Joshua and Whitfield, Jason and Zhang, William and Henneberger, Christian and Janovjak, Harald L and O'Mara, Megan and Jackson, Colin}, journal = {ACS SENSORS}, number = {11}, pages = {1286 -- 1290}, publisher = {American Chemical Society}, title = {{Rangefinder: A semisynthetic FRET sensor design algorithm}}, doi = {10.1021/acssensors.6b00576}, volume = {1}, year = {2016}, } @inproceedings{1102, abstract = {Weakly-supervised object localization methods tend to fail for object classes that consistently co-occur with the same background elements, e.g. trains on tracks. We propose a method to overcome these failures by adding a very small amount of model-specific additional annotation. The main idea is to cluster a deep network\'s mid-level representations and assign object or distractor labels to each cluster. Experiments show substantially improved localization results on the challenging ILSVC2014 dataset for bounding box detection and the PASCAL VOC2012 dataset for semantic segmentation.}, author = {Kolesnikov, Alexander and Lampert, Christoph}, booktitle = {Proceedings of the British Machine Vision Conference 2016}, location = {York, United Kingdom}, pages = {92.1--92.12}, publisher = {BMVA Press}, title = {{Improving weakly-supervised object localization by micro-annotation}}, doi = {10.5244/C.30.92}, volume = {2016-September}, year = {2016}, } @inproceedings{1103, abstract = {We propose two parallel state-space-exploration algorithms for hybrid automaton (HA), with the goal of enhancing performance on multi-core shared-memory systems. The first uses the parallel, breadth-first-search algorithm (PBFS) of the SPIN model checker, when traversing the discrete modes of the HA, and enhances it with a parallel exploration of the continuous states within each mode. We show that this simple-minded extension of PBFS does not provide the desired load balancing in many HA benchmarks. The second algorithm is a task-parallel BFS algorithm (TP-BFS), which uses a cheap precomputation of the cost associated with the post operations (both continuous and discrete) in order to improve load balancing. We illustrate the TP-BFS and the cost precomputation of the post operators on a support-function-based algorithm for state-space exploration. The performance comparison of the two algorithms shows that, in general, TP-BFS provides a better utilization/load-balancing of the CPU. Both algorithms are implemented in the model checker XSpeed. Our experiments show a maximum speed-up of more than 2000 χ on a navigation benchmark, with respect to SpaceEx LGG scenario. In order to make the comparison fair, we employed an equal number of post operations in both tools. To the best of our knowledge, this paper represents the first attempt to provide parallel, reachability-analysis algorithms for HA.}, author = {Gurung, Amit and Deka, Arup and Bartocci, Ezio and Bogomolov, Sergiy and Grosu, Radu and Ray, Rajarshi}, location = {Kanpur, India }, publisher = {IEEE}, title = {{Parallel reachability analysis for hybrid systems}}, doi = {10.1109/MEMCOD.2016.7797741}, year = {2016}, } @inproceedings{1105, abstract = {Jointly characterizing neural responses in terms of several external variables promises novel insights into circuit function, but remains computationally prohibitive in practice. Here we use gaussian process (GP) priors and exploit recent advances in fast GP inference and learning based on Kronecker methods, to efficiently estimate multidimensional nonlinear tuning functions. Our estimator require considerably less data than traditional methods and further provides principled uncertainty estimates. We apply these tools to hippocampal recordings during open field exploration and use them to characterize the joint dependence of CA1 responses on the position of the animal and several other variables, including the animal\'s speed, direction of motion, and network oscillations.Our results provide an unprecedentedly detailed quantification of the tuning of hippocampal neurons. The model\'s generality suggests that our approach can be used to estimate neural response properties in other brain regions.}, author = {Savin, Cristina and Tkacik, Gasper}, location = {Barcelona; Spain}, pages = {3610--3618}, publisher = {Neural Information Processing Systems}, title = {{Estimating nonlinear neural response functions using GP priors and Kronecker methods}}, volume = {29}, year = {2016}, } @article{11069, abstract = {Repeated rounds of nuclear envelope (NE) rupture and repair have been observed in laminopathy and cancer cells and result in intermittent loss of nucleus compartmentalization. Currently, the causes of NE rupture are unclear. Here, we show that NE rupture in cancer cells relies on the assembly of contractile actin bundles that interact with the nucleus via the linker of nucleoskeleton and cytoskeleton (LINC) complex. We found that the loss of actin bundles or the LINC complex did not rescue nuclear lamina defects, a previously identified determinant of nuclear membrane stability, but did decrease the number and size of chromatin hernias. Finally, NE rupture inhibition could be rescued in cells treated with actin-depolymerizing drugs by mechanically constraining nucleus height. These data suggest a model of NE rupture where weak membrane areas, caused by defects in lamina organization, rupture because of an increase in intranuclear pressure from actin-based nucleus confinement.}, author = {Hatch, Emily M. and HETZER, Martin W}, issn = {0021-9525}, journal = {Journal of Cell Biology}, keywords = {Cell Biology}, number = {1}, pages = {27--36}, publisher = {Rockefeller University Press}, title = {{Nuclear envelope rupture is induced by actin-based nucleus confinement}}, doi = {10.1083/jcb.201603053}, volume = {215}, year = {2016}, } @article{11070, abstract = {The organization of the genome in the three-dimensional space of the nucleus is coupled with cell type-specific gene expression. However, how nuclear architecture influences transcription that governs cell identity remains unknown. Here, we show that nuclear pore complex (NPC) components Nup93 and Nup153 bind superenhancers (SE), regulatory structures that drive the expression of key genes that specify cell identity. We found that nucleoporin-associated SEs localize preferentially to the nuclear periphery, and absence of Nup153 and Nup93 results in dramatic transcriptional changes of SE-associated genes. Our results reveal a crucial role of NPC components in the regulation of cell type-specifying genes and highlight nuclear architecture as a regulatory layer of genome functions in cell fate.}, author = {Ibarra, Arkaitz and Benner, Chris and Tyagi, Swati and Cool, Jonah and HETZER, Martin W}, issn = {1549-5477}, journal = {Genes & Development}, keywords = {Developmental Biology, Genetics}, number = {20}, pages = {2253--2258}, publisher = {Cold Spring Harbor Laboratory}, title = {{Nucleoporin-mediated regulation of cell identity genes}}, doi = {10.1101/gad.287417.116}, volume = {30}, year = {2016}, } @article{11071, abstract = {Nuclear pore complexes (NPCs) emerged as nuclear transport channels in eukaryotic cells ∼1.5 billion years ago. While the primary role of NPCs is to regulate nucleo–cytoplasmic transport, recent research suggests that certain NPC proteins have additionally acquired the role of affecting gene expression at the nuclear periphery and in the nucleoplasm in metazoans. Here we identify a widely expressed variant of the transmembrane nucleoporin (Nup) Pom121 (named sPom121, for “soluble Pom121”) that arose by genomic rearrangement before the divergence of hominoids. sPom121 lacks the nuclear membrane-anchoring domain and thus does not localize to the NPC. Instead, sPom121 colocalizes and interacts with nucleoplasmic Nup98, a previously identified transcriptional regulator, at gene promoters to control transcription of its target genes in human cells. Interestingly, sPom121 transcripts appear independently in several mammalian species, suggesting convergent innovation of Nup-mediated transcription regulation during mammalian evolution. Our findings implicate alternate transcription initiation as a mechanism to increase the functional diversity of NPC components.}, author = {Franks, Tobias M. and Benner, Chris and Narvaiza, Iñigo and Marchetto, Maria C.N. and Young, Janet M. and Malik, Harmit S. and Gage, Fred H. and HETZER, Martin W}, issn = {1549-5477}, journal = {Genes & Development}, keywords = {Developmental Biology, Genetics}, number = {10}, pages = {1155--1171}, publisher = {Cold Spring Harbor Laboratory}, title = {{Evolution of a transcriptional regulator from a transmembrane nucleoporin}}, doi = {10.1101/gad.280941.116}, volume = {30}, year = {2016}, } @article{11072, abstract = {Spatiotemporal activation of RhoA and actomyosin contraction underpins cellular adhesion and division. Loss of cell–cell adhesion and chromosomal instability are cardinal events that drive tumour progression. Here, we show that p120-catenin (p120) not only controls cell–cell adhesion, but also acts as a critical regulator of cytokinesis. We find that p120 regulates actomyosin contractility through concomitant binding to RhoA and the centralspindlin component MKLP1, independent of cadherin association. In anaphase, p120 is enriched at the cleavage furrow where it binds MKLP1 to spatially control RhoA GTPase cycling. Binding of p120 to MKLP1 during cytokinesis depends on the N-terminal coiled-coil domain of p120 isoform 1A. Importantly, clinical data show that loss of p120 expression is a common event in breast cancer that strongly correlates with multinucleation and adverse patient survival. In summary, our study identifies p120 loss as a driver event of chromosomal instability in cancer. }, author = {van de Ven, Robert A.H. and de Groot, Jolien S. and Park, Danielle and van Domselaar, Robert and de Jong, Danielle and Szuhai, Karoly and van der Wall, Elsken and Rueda, Oscar M. and Ali, H. Raza and Caldas, Carlos and van Diest, Paul J. and HETZER, Martin W and Sahai, Erik and Derksen, Patrick W.B.}, issn = {2041-1723}, journal = {Nature Communications}, keywords = {General Physics and Astronomy, General Biochemistry, Genetics and Molecular Biology, General Chemistry}, publisher = {Springer Nature}, title = {{p120-catenin prevents multinucleation through control of MKLP1-dependent RhoA activity during cytokinesis}}, doi = {10.1038/ncomms13874}, volume = {7}, year = {2016}, } @inproceedings{1115, abstract = {We present a coherent microwave to telecom signal converter based on the electro-optical effect using a crystalline WGM-resonator coupled to a 3D microwave cavity, achieving high photon conversion efficiency of 0.1% with MHz bandwidth.}, author = {Rueda, Alfredo and Sedlmeir, Florian and Collodo, Michele and Vogl, Ulrich and Stiller, Birgit and Schunk, Georg and Strekalov, Dimitry and Marquardt, Christoph and Fink, Johannes M and Painter, Oskar and Leuchs, Gerd and Schwefel, Harald}, location = {San Jose, CA, USA}, publisher = {IEEE}, title = {{Efficient single sideband microwave to optical conversion using a LiNbO₃ WGM-resonator}}, doi = {10.1364/CLEO_SI.2016.SF2G.3}, year = {2016}, }