@article{678, abstract = {The seminal observation that mechanical signals can elicit changes in biochemical signalling within cells, a process commonly termed mechanosensation and mechanotransduction, has revolutionized our understanding of the role of cell mechanics in various fundamental biological processes, such as cell motility, adhesion, proliferation and differentiation. In this Review, we will discuss how the interplay and feedback between mechanical and biochemical signals control tissue morphogenesis and cell fate specification in embryonic development.}, author = {Petridou, Nicoletta and Spiro, Zoltan P and Heisenberg, Carl-Philipp J}, issn = {14657392}, journal = {Nature Cell Biology}, number = {6}, pages = {581 -- 588}, publisher = {Nature Publishing Group}, title = {{Multiscale force sensing in development}}, doi = {10.1038/ncb3524}, volume = {19}, year = {2017}, } @article{681, abstract = {Two-player games on graphs provide the theoretical framework for many important problems such as reactive synthesis. While the traditional study of two-player zero-sum games has been extended to multi-player games with several notions of equilibria, they are decidable only for perfect-information games, whereas several applications require imperfect-information. In this paper we propose a new notion of equilibria, called doomsday equilibria, which is a strategy profile where all players satisfy their own objective, and if any coalition of players deviates and violates even one of the players' objective, then the objective of every player is violated. We present algorithms and complexity results for deciding the existence of doomsday equilibria for various classes of ω-regular objectives, both for imperfect-information games, and for perfect-information games. We provide optimal complexity bounds for imperfect-information games, and in most cases for perfect-information games.}, author = {Chatterjee, Krishnendu and Doyen, Laurent and Filiot, Emmanuel and Raskin, Jean}, issn = {08905401}, journal = {Information and Computation}, pages = {296 -- 315}, publisher = {Elsevier}, title = {{Doomsday equilibria for omega-regular games}}, doi = {10.1016/j.ic.2016.10.012}, volume = {254}, year = {2017}, } @inproceedings{6841, abstract = {In classical machine learning, regression is treated as a black box process of identifying a suitable function from a hypothesis set without attempting to gain insight into the mechanism connecting inputs and outputs. In the natural sciences, however, finding an interpretable function for a phenomenon is the prime goal as it allows to understand and generalize results. This paper proposes a novel type of function learning network, called equation learner (EQL), that can learn analytical expressions and is able to extrapolate to unseen domains. It is implemented as an end-to-end differentiable feed-forward network and allows for efficient gradient based training. Due to sparsity regularization concise interpretable expressions can be obtained. Often the true underlying source expression is identified.}, author = {Martius, Georg S and Lampert, Christoph}, booktitle = {5th International Conference on Learning Representations, ICLR 2017 - Workshop Track Proceedings}, location = {Toulon, France}, publisher = {International Conference on Learning Representations}, title = {{Extrapolation and learning equations}}, year = {2017}, } @article{684, abstract = {We generalize winning conditions in two-player games by adding a structural acceptance condition called obligations. Obligations are orthogonal to the linear winning conditions that define whether a play is winning. Obligations are a declaration that player 0 can achieve a certain value from a configuration. If the obligation is met, the value of that configuration for player 0 is 1. We define the value in such games and show that obligation games are determined. For Markov chains with Borel objectives and obligations, and finite turn-based stochastic parity games with obligations we give an alternative and simpler characterization of the value function. Based on this simpler definition we show that the decision problem of winning finite turn-based stochastic parity games with obligations is in NP∩co-NP. We also show that obligation games provide a game framework for reasoning about p-automata. © 2017 The Association for Symbolic Logic.}, author = {Chatterjee, Krishnendu and Piterman, Nir}, issn = {1943-5886}, journal = {Journal of Symbolic Logic}, number = {2}, pages = {420 -- 452}, publisher = {Cambridge University Press}, title = {{Obligation blackwell games and p-automata}}, doi = {10.1017/jsl.2016.71}, volume = {82}, year = {2017}, } @article{685, abstract = {By applying methods and principles from the physical sciences to biological problems, D'Arcy Thompson's On Growth and Form demonstrated how mathematical reasoning reveals elegant, simple explanations for seemingly complex processes. This has had a profound influence on subsequent generations of developmental biologists. We discuss how this influence can be traced through twentieth century morphologists, embryologists and theoreticians to current research that explores the molecular and cellular mechanisms of tissue growth and patterning, including our own studies of the vertebrate neural tube.}, author = {Briscoe, James and Kicheva, Anna}, issn = {09254773}, journal = {Mechanisms of Development}, pages = {26 -- 31}, publisher = {Elsevier}, title = {{The physics of development 100 years after D'Arcy Thompson's “on growth and form”}}, doi = {10.1016/j.mod.2017.03.005}, volume = {145}, year = {2017}, } @inproceedings{688, abstract = {We show that the framework of topological data analysis can be extended from metrics to general Bregman divergences, widening the scope of possible applications. Examples are the Kullback - Leibler divergence, which is commonly used for comparing text and images, and the Itakura - Saito divergence, popular for speech and sound. In particular, we prove that appropriately generalized čech and Delaunay (alpha) complexes capture the correct homotopy type, namely that of the corresponding union of Bregman balls. Consequently, their filtrations give the correct persistence diagram, namely the one generated by the uniformly growing Bregman balls. Moreover, we show that unlike the metric setting, the filtration of Vietoris-Rips complexes may fail to approximate the persistence diagram. We propose algorithms to compute the thus generalized čech, Vietoris-Rips and Delaunay complexes and experimentally test their efficiency. Lastly, we explain their surprisingly good performance by making a connection with discrete Morse theory. }, author = {Edelsbrunner, Herbert and Wagner, Hubert}, issn = {18688969}, location = {Brisbane, Australia}, pages = {391--3916}, publisher = {Schloss Dagstuhl - Leibniz-Zentrum für Informatik}, title = {{Topological data analysis with Bregman divergences}}, doi = {10.4230/LIPIcs.SoCG.2017.39}, volume = {77}, year = {2017}, } @article{687, abstract = {Pursuing the similarity between the Kontsevich-Soibelman construction of the cohomological Hall algebra (CoHA) of BPS states and Lusztig's construction of canonical bases for quantum enveloping algebras, and the similarity between the integrality conjecture for motivic Donaldson-Thomas invariants and the PBW theorem for quantum enveloping algebras, we build a coproduct on the CoHA associated to a quiver with potential. We also prove a cohomological dimensional reduction theorem, further linking a special class of CoHAs with Yangians, and explaining how to connect the study of character varieties with the study of CoHAs.}, author = {Davison, Ben}, issn = {00335606}, journal = {Quarterly Journal of Mathematics}, number = {2}, pages = {635 -- 703}, publisher = {Oxford University Press}, title = {{The critical CoHA of a quiver with potential}}, doi = {10.1093/qmath/haw053}, volume = {68}, year = {2017}, } @article{686, abstract = {Tissues are thought to behave like fluids with a given surface tension. Differences in tissue surface tension (TST) have been proposed to trigger cell sorting and tissue envelopment. D'Arcy Thompson in his seminal book ‘On Growth and Form’ has introduced this concept of differential TST as a key physical mechanism dictating tissue formation and organization within the developing organism. Over the past century, many studies have picked up the concept of differential TST and analyzed the role and cell biological basis of TST in development, underlining the importance and influence of this concept in developmental biology.}, author = {Heisenberg, Carl-Philipp J}, issn = {09254773}, journal = {Mechanisms of Development}, pages = {32 -- 37}, publisher = {Elsevier}, title = {{D'Arcy Thompson's ‘on growth and form’: From soap bubbles to tissue self organization}}, doi = {10.1016/j.mod.2017.03.006}, volume = {145}, year = {2017}, } @article{689, abstract = {Rett syndrome modeling in monkey mirrors the human disorder.}, author = {Novarino, Gaia}, issn = {19466234}, journal = {Science Translational Medicine}, number = {393}, publisher = {American Association for the Advancement of Science}, title = {{Rett syndrome modeling goes simian}}, doi = {10.1126/scitranslmed.aan8196}, volume = {9}, year = {2017}, } @article{693, abstract = {Many central synapses contain a single presynaptic active zone and a single postsynaptic density. Vesicular release statistics at such “simple synapses” indicate that they contain a small complement of docking sites where vesicles repetitively dock and fuse. In this work, we investigate functional and morphological aspects of docking sites at simple synapses made between cerebellar parallel fibers and molecular layer interneurons. Using immunogold labeling of SDS-treated freeze-fracture replicas, we find that Cav2.1 channels form several clusters per active zone with about nine channels per cluster. The mean value and range of intersynaptic variation are similar for Cav2.1 cluster numbers and for functional estimates of docking-site numbers obtained from the maximum numbers of released vesicles per action potential. Both numbers grow in relation with synaptic size and decrease by a similar extent with age between 2 wk and 4 wk postnatal. Thus, the mean docking-site numbers were 3.15 at 2 wk (range: 1–10) and 2.03 at 4 wk (range: 1–4), whereas the mean numbers of Cav2.1 clusters were 2.84 at 2 wk (range: 1–8) and 2.37 at 4 wk (range: 1–5). These changes were accompanied by decreases of miniature current amplitude (from 93 pA to 56 pA), active-zone surface area (from 0.0427 μm2 to 0.0234 μm2), and initial success rate (from 0.609 to 0.353), indicating a tightening of synaptic transmission with development. Altogether, these results suggest a close correspondence between the number of functionally defined vesicular docking sites and that of clusters of voltage-gated calcium channels. }, author = {Miki, Takafumi and Kaufmann, Walter and Malagon, Gerardo and Gomez, Laura and Tabuchi, Katsuhiko and Watanabe, Masahiko and Shigemoto, Ryuichi and Marty, Alain}, issn = {00278424}, journal = {PNAS}, number = {26}, pages = {E5246 -- E5255}, publisher = {National Academy of Sciences}, title = {{Numbers of presynaptic Ca2+ channel clusters match those of functionally defined vesicular docking sites in single central synapses}}, doi = {10.1073/pnas.1704470114}, volume = {114}, year = {2017}, } @article{694, abstract = {A change regarding the extent of adhesion - hereafter referred to as adhesion plasticity - between adhesive and less-adhesive states of mammalian cells is important for their behavior. To investigate adhesion plasticity, we have selected a stable isogenic subpopulation of human MDA-MB-468 breast carcinoma cells growing in suspension. These suspension cells are unable to re-adhere to various matrices or to contract three-dimensional collagen lattices. By using transcriptome analysis, we identified the focal adhesion protein tensin3 (Tns3) as a determinant of adhesion plasticity. Tns3 is strongly reduced at mRNA and protein levels in suspension cells. Furthermore, by transiently challenging breast cancer cells to grow under non-adherent conditions markedly reduces Tns3 protein expression, which is regained upon re-adhesion. Stable knockdown of Tns3 in parental MDA-MB-468 cells results in defective adhesion, spreading and migration. Tns3-knockdown cells display impaired structure and dynamics of focal adhesion complexes as determined by immunostaining. Restoration of Tns3 protein expression in suspension cells partially rescues adhesion and focal contact composition. Our work identifies Tns3 as a crucial focal adhesion component regulated by, and functionally contributing to, the switch between adhesive and non-adhesive states in MDA-MB-468 cancer cells.}, author = {Veß, Astrid and Blache, Ulrich and Leitner, Laura and Kurz, Angela and Ehrenpfordt, Anja and Sixt, Michael K and Posern, Guido}, issn = {00219533}, journal = {Journal of Cell Science}, number = {13}, pages = {2172 -- 2184}, publisher = {Company of Biologists}, title = {{A dual phenotype of MDA MB 468 cancer cells reveals mutual regulation of tensin3 and adhesion plasticity}}, doi = {10.1242/jcs.200899}, volume = {130}, year = {2017}, } @inproceedings{697, abstract = {De, Trevisan and Tulsiani [CRYPTO 2010] show that every distribution over n-bit strings which has constant statistical distance to uniform (e.g., the output of a pseudorandom generator mapping n-1 to n bit strings), can be distinguished from the uniform distribution with advantage epsilon by a circuit of size O( 2^n epsilon^2). We generalize this result, showing that a distribution which has less than k bits of min-entropy, can be distinguished from any distribution with k bits of delta-smooth min-entropy with advantage epsilon by a circuit of size O(2^k epsilon^2/delta^2). As a special case, this implies that any distribution with support at most 2^k (e.g., the output of a pseudoentropy generator mapping k to n bit strings) can be distinguished from any given distribution with min-entropy k+1 with advantage epsilon by a circuit of size O(2^k epsilon^2). Our result thus shows that pseudoentropy distributions face basically the same non-uniform attacks as pseudorandom distributions. }, author = {Pietrzak, Krzysztof Z and Skórski, Maciej}, issn = {18688969}, location = {Warsaw, Poland}, publisher = {Schloss Dagstuhl - Leibniz-Zentrum für Informatik}, title = {{Non uniform attacks against pseudoentropy}}, doi = {10.4230/LIPIcs.ICALP.2017.39}, volume = {80}, year = {2017}, } @article{698, abstract = {Extracellular matrix signals from the microenvironment regulate gene expression patterns and cell behavior. Using a combination of experiments and geometric models, we demonstrate correlations between cell geometry, three-dimensional (3D) organization of chromosome territories, and gene expression. Fluorescence in situ hybridization experiments showed that micropatterned fibroblasts cultured on anisotropic versus isotropic substrates resulted in repositioning of specific chromosomes, which contained genes that were differentially regulated by cell geometries. Experiments combined with ellipsoid packing models revealed that the mechanosensitivity of chromosomes was correlated with their orientation in the nucleus. Transcription inhibition experiments suggested that the intermingling degree was more sensitive to global changes in transcription than to chromosome radial positioning and its orientations. These results suggested that cell geometry modulated 3D chromosome arrangement, and their neighborhoods correlated with gene expression patterns in a predictable manner. This is central to understanding geometric control of genetic programs involved in cellular homeostasis and the associated diseases. }, author = {Wang, Yejun and Nagarajan, Mallika and Uhler, Caroline and Shivashankar, Gv}, issn = {10591524}, journal = {Molecular Biology of the Cell}, number = {14}, pages = {1997 -- 2009}, publisher = {American Society for Cell Biology}, title = {{Orientation and repositioning of chromosomes correlate with cell geometry dependent gene expression}}, doi = {10.1091/mbc.E16-12-0825}, volume = {28}, year = {2017}, } @article{699, abstract = {In antagonistic symbioses, such as host–parasite interactions, one population’s success is the other’s loss. In mutualistic symbioses, such as division of labor, both parties can gain, but they might have different preferences over the possible mutualistic arrangements. The rates of evolution of the two populations in a symbiosis are important determinants of which population will be more successful: Faster evolution is thought to be favored in antagonistic symbioses (the “Red Queen effect”), but disfavored in certain mutualistic symbioses (the “Red King effect”). However, it remains unclear which biological parameters drive these effects. Here, we analyze the effects of the various determinants of evolutionary rate: generation time, mutation rate, population size, and the intensity of natural selection. Our main results hold for the case where mutation is infrequent. Slower evolution causes a long-term advantage in an important class of mutualistic interactions. Surprisingly, less intense selection is the strongest driver of this Red King effect, whereas relative mutation rates and generation times have little effect. In antagonistic interactions, faster evolution by any means is beneficial. Our results provide insight into the demographic evolution of symbionts. }, author = {Veller, Carl and Hayward, Laura and Nowak, Martin and Hilbe, Christian}, issn = {00278424}, journal = {PNAS}, number = {27}, pages = {E5396 -- E5405}, publisher = {National Academy of Sciences}, title = {{The red queen and king in finite populations}}, doi = {10.1073/pnas.1702020114}, volume = {114}, year = {2017}, } @article{700, abstract = {Microtubules provide the mechanical force required for chromosome separation during mitosis. However, little is known about the dynamic (high-frequency) mechanical properties of microtubules. Here, we theoretically propose to control the vibrations of a doubly clamped microtubule by tip electrodes and to detect its motion via the optomechanical coupling between the vibrational modes of the microtubule and an optical cavity. In the presence of a red-detuned strong pump laser, this coupling leads to optomechanical-induced transparency of an optical probe field, which can be detected with state-of-the art technology. The center frequency and line width of the transparency peak give the resonance frequency and damping rate of the microtubule, respectively, while the height of the peak reveals information about the microtubule-cavity field coupling. Our method opens the new possibilities to gain information about the physical properties of microtubules, which will enhance our capability to design physical cancer treatment protocols as alternatives to chemotherapeutic drugs.}, author = {Barzanjeh, Shabir and Salari, Vahid and Tuszynski, Jack and Cifra, Michal and Simon, Christoph}, issn = {24700045}, journal = { Physical Review E Statistical Nonlinear and Soft Matter Physics }, number = {1}, publisher = {American Institute of Physics}, title = {{Optomechanical proposal for monitoring microtubule mechanical vibrations}}, doi = {10.1103/PhysRevE.96.012404}, volume = {96}, year = {2017}, } @article{701, abstract = {A d-dimensional simplex S is called a k-reptile (or a k-reptile simplex) if it can be tiled by k simplices with disjoint interiors that are all mutually congruent and similar to S. For d = 2, triangular k-reptiles exist for all k of the form a^2, 3a^2 or a^2+b^2 and they have been completely characterized by Snover, Waiveris, and Williams. On the other hand, the only k-reptile simplices that are known for d ≥ 3, have k = m^d, where m is a positive integer. We substantially simplify the proof by Matoušek and the second author that for d = 3, k-reptile tetrahedra can exist only for k = m^3. We then prove a weaker analogue of this result for d = 4 by showing that four-dimensional k-reptile simplices can exist only for k = m^2.}, author = {Kynčl, Jan and Patakova, Zuzana}, issn = {10778926}, journal = {The Electronic Journal of Combinatorics}, number = {3}, pages = {1--44}, publisher = {International Press}, title = {{On the nonexistence of k reptile simplices in ℝ^3 and ℝ^4}}, volume = {24}, year = {2017}, } @article{702, abstract = {Leading autism-associated mutation in mouse partially mimics human disorder. }, author = {Novarino, Gaia}, issn = {19466234}, journal = {Science Translational Medicine}, number = {399}, pages = {eaao0972}, publisher = {American Association for the Advancement of Science}, title = {{The riddle of CHD8 haploinsufficiency in autism spectrum disorder}}, doi = {10.1126/scitranslmed.aao0972}, volume = {9}, year = {2017}, } @article{706, abstract = {A hippocampal mossy fiber synapse has a complex structure and is implicated in learning and memory. In this synapse, the mossy fiber boutons attach to the dendritic shaft by puncta adherentia junctions and wrap around a multiply-branched spine, forming synaptic junctions. We have recently shown using transmission electron microscopy, immunoelectron microscopy and serial block face-scanning electron microscopy that atypical puncta adherentia junctions are formed in the afadin-deficient mossy fiber synapse and that the complexity of postsynaptic spines and mossy fiber boutons, the number of spine heads, the area of postsynaptic densities and the density of synaptic vesicles docked to active zones are decreased in the afadin-deficient synapse. We investigated here the roles of afadin in the functional differentiations of the mossy fiber synapse using the afadin-deficient mice. The electrophysiological studies showed that both the release probability of glutamate and the postsynaptic responsiveness to glutamate were markedly reduced, but not completely lost, in the afadin-deficient mossy fiber synapse, whereas neither long-term potentiation nor long-term depression was affected. These results indicate that afadin plays roles in the functional differentiations of the presynapse and the postsynapse of the hippocampal mossy fiber synapse.}, author = {Geng, Xiaoqi and Maruo, Tomohiko and Mandai, Kenji and Supriyanto, Irwan and Miyata, Muneaki and Sakakibara, Shotaro and Mizoguchi, Akira and Takai, Yoshimi and Mori, Masahiro}, issn = {13569597}, journal = {Genes to Cells}, number = {8}, pages = {715 -- 722}, publisher = {Wiley-Blackwell}, title = {{Roles of afadin in functional differentiations of hippocampal mossy fiber synapse}}, doi = {10.1111/gtc.12508}, volume = {22}, year = {2017}, } @article{707, abstract = {We answer a question of M. Gromov on the waist of the unit ball.}, author = {Akopyan, Arseniy and Karasev, Roman}, issn = {00246093}, journal = {Bulletin of the London Mathematical Society}, number = {4}, pages = {690 -- 693}, publisher = {Wiley-Blackwell}, title = {{A tight estimate for the waist of the ball }}, doi = {10.1112/blms.12062}, volume = {49}, year = {2017}, } @article{708, abstract = {In the developing and adult brain, oligodendrocyte precursor cells (OPCs) are influenced by neuronal activity: they are involved in synaptic signaling with neurons, and their proliferation and differentiation into myelinating glia can be altered by transient changes in neuronal firing. An important question that has been unanswered is whether OPCs can discriminate different patterns of neuronal activity and respond to them in a distinct way. Here, we demonstrate in brain slices that the pattern of neuronal activity determines the functional changes triggered at synapses between axons and OPCs. Furthermore, we show that stimulation of the corpus callosum at different frequencies in vivo affects proliferation and differentiation of OPCs in a dissimilar way. Our findings suggest that neurons do not influence OPCs in “all-or-none” fashion but use their firing pattern to tune the response and behavior of these nonneuronal cells.}, author = {Nagy, Balint and Hovhannisyan, Anahit and Barzan, Ruxandra and Chen, Ting and Kukley, Maria}, issn = {15449173}, journal = {PLoS Biology}, number = {8}, publisher = {Public Library of Science}, title = {{Different patterns of neuronal activity trigger distinct responses of oligodendrocyte precursor cells in the corpus callosum}}, doi = {10.1371/journal.pbio.2001993}, volume = {15}, year = {2017}, } @article{709, abstract = {Adipose tissues play key roles in energy homeostasis. Brown adipocytes and beige adipocytes in white adipose tissue (WAT) share the similar characters of thermogenesis, both of them could be potential targets for obesity management. Several thermo-sensitive transient receptor potential channels (thermoTRPs) are shown to be involved in adipocyte biology. However, the expression pattern of thermoTRPs in adipose tissues from obese mice is still unknown. The mRNA expression of thermoTRPs in subcutaneous WAT (sWAT) and interscapular brown adipose tissue (iBAT) from lean and obese mice were measured using reverse transcriptase-quantitative PCRs (RT-qPCR). The results demonstrated that all 10 thermoTRPs are expressed in both iBAT and sWAT, and without significant difference in the mRNA expression level of thermoTRPs between these two tissues. Moreover, Trpv1 and Trpv3 mRNA expression levels in both iBAT and sWAT were significantly decreased in high fat diet (HFD)-induced obese mice and db/db (leptin receptor deficient) mice. Trpm2 mRNA expression level was significantly decreased only in sWAT from HFD-induced obese mice and db/db mice. On the other hand, Trpv2 and Trpv4 mRNA expression levels in iBAT and sWAT were significantly increased in HFD-induced obese mice and db/db mice. Taken together, we conclude that all 10 thermoTRPs are expressed in iBAT and sWAT. And several thermoTRPs differentially expressed in adipose tissues from HFD-induced obese mice and db/db mice, suggesting a potential involvement in anti-obesity regulations.}, author = {Sun, Wuping and Li, Chen and Zhang, Yonghong and Jiang, Changyu and Zhai, Ming-Zhu and Zhou, Qian and Xiao, Lizu and Deng, Qiwen}, issn = {10656995}, journal = {Cell Biology International}, number = {8}, pages = {908 -- 913}, publisher = {Wiley-Blackwell}, title = {{Gene expression changes of thermo sensitive transient receptor potential channels in obese mice}}, doi = {10.1002/cbin.10783}, volume = {41}, year = {2017}, } @inproceedings{710, abstract = {We revisit the problem of estimating entropy of discrete distributions from independent samples, studied recently by Acharya, Orlitsky, Suresh and Tyagi (SODA 2015), improving their upper and lower bounds on the necessary sample size n. For estimating Renyi entropy of order alpha, up to constant accuracy and error probability, we show the following * Upper bounds n = O(1) 2^{(1-1/alpha)H_alpha} for integer alpha>1, as the worst case over distributions with Renyi entropy equal to H_alpha. * Lower bounds n = Omega(1) K^{1-1/alpha} for any real alpha>1, with the constant being an inverse polynomial of the accuracy, as the worst case over all distributions on K elements. Our upper bounds essentially replace the alphabet size by a factor exponential in the entropy, which offers improvements especially in low or medium entropy regimes (interesting for example in anomaly detection). As for the lower bounds, our proof explicitly shows how the complexity depends on both alphabet and accuracy, partially solving the open problem posted in previous works. The argument for upper bounds derives a clean identity for the variance of falling-power sum of a multinomial distribution. Our approach for lower bounds utilizes convex optimization to find a distribution with possibly worse estimation performance, and may be of independent interest as a tool to work with Le Cam’s two point method. }, author = {Obremski, Maciej and Skórski, Maciej}, issn = {18688969}, location = {Berkeley, USA}, publisher = {Schloss Dagstuhl - Leibniz-Zentrum für Informatik}, title = {{Renyi entropy estimation revisited}}, doi = {10.4230/LIPIcs.APPROX-RANDOM.2017.20}, volume = {81}, year = {2017}, } @article{713, abstract = {To determine the dynamics of allelic-specific expression during mouse development, we analyzed RNA-seq data from 23 F1 tissues from different developmental stages, including 19 female tissues allowing X chromosome inactivation (XCI) escapers to also be detected. We demonstrate that allelic expression arising from genetic or epigenetic differences is highly tissue-specific. We find that tissue-specific strain-biased gene expression may be regulated by tissue-specific enhancers or by post-transcriptional differences in stability between the alleles. We also find that escape from X-inactivation is tissue-specific, with leg muscle showing an unexpectedly high rate of XCI escapers. By surveying a range of tissues during development, and performing extensive validation, we are able to provide a high confidence list of mouse imprinted genes including 18 novel genes. This shows that cluster size varies dynamically during development and can be substantially larger than previously thought, with the Igf2r cluster extending over 10 Mb in placenta.}, author = {Andergassen, Daniel and Dotter, Christoph and Wenzel, Dyniel and Sigl, Verena and Bammer, Philipp and Muckenhuber, Markus and Mayer, Daniela and Kulinski, Tomasz and Theussl, Hans and Penninger, Josef and Bock, Christoph and Barlow, Denise and Pauler, Florian and Hudson, Quanah}, issn = {2050084X}, journal = {eLife}, publisher = {eLife Sciences Publications}, title = {{Mapping the mouse Allelome reveals tissue specific regulation of allelic expression}}, doi = {10.7554/eLife.25125}, volume = {6}, year = {2017}, } @inproceedings{711, abstract = {Nested weighted automata (NWA) present a robust and convenient automata-theoretic formalism for quantitative specifications. Previous works have considered NWA that processed input words only in the forward direction. It is natural to allow the automata to process input words backwards as well, for example, to measure the maximal or average time between a response and the preceding request. We therefore introduce and study bidirectional NWA that can process input words in both directions. First, we show that bidirectional NWA can express interesting quantitative properties that are not expressible by forward-only NWA. Second, for the fundamental decision problems of emptiness and universality, we establish decidability and complexity results for the new framework which match the best-known results for the special case of forward-only NWA. Thus, for NWA, the increased expressiveness of bidirectionality is achieved at no additional computational complexity. This is in stark contrast to the unweighted case, where bidirectional finite automata are no more expressive but exponentially more succinct than their forward-only counterparts.}, author = {Chatterjee, Krishnendu and Henzinger, Thomas A and Otop, Jan}, issn = {18688969}, location = {Berlin, Germany}, publisher = {Schloss Dagstuhl - Leibniz-Zentrum für Informatik}, title = {{Bidirectional nested weighted automata}}, doi = {10.4230/LIPIcs.CONCUR.2017.5}, volume = {85}, year = {2017}, } @article{712, abstract = {We establish a weak–strong uniqueness principle for solutions to entropy-dissipating reaction–diffusion equations: As long as a strong solution to the reaction–diffusion equation exists, any weak solution and even any renormalized solution must coincide with this strong solution. Our assumptions on the reaction rates are just the entropy condition and local Lipschitz continuity; in particular, we do not impose any growth restrictions on the reaction rates. Therefore, our result applies to any single reversible reaction with mass-action kinetics as well as to systems of reversible reactions with mass-action kinetics satisfying the detailed balance condition. Renormalized solutions are known to exist globally in time for reaction–diffusion equations with entropy-dissipating reaction rates; in contrast, the global-in-time existence of weak solutions is in general still an open problem–even for smooth data–, thereby motivating the study of renormalized solutions. The key ingredient of our result is a careful adjustment of the usual relative entropy functional, whose evolution cannot be controlled properly for weak solutions or renormalized solutions.}, author = {Fischer, Julian L}, issn = {0362546X}, journal = {Nonlinear Analysis: Theory, Methods and Applications}, pages = {181 -- 207}, publisher = {Elsevier}, title = {{Weak–strong uniqueness of solutions to entropy dissipating reaction–diffusion equations}}, doi = {10.1016/j.na.2017.03.001}, volume = {159}, year = {2017}, } @article{714, abstract = {Background HIV-1 infection and drug abuse are frequently co-morbid and their association greatly increases the severity of HIV-1-induced neuropathology. While nucleus accumbens (NAcc) function is severely perturbed by drugs of abuse, little is known about how HIV-1 infection affects NAcc. Methods We used calcium and voltage imaging to investigate the effect of HIV-1 trans-activator of transcription (Tat) on rat NAcc. Based on previous neuronal studies, we hypothesized that Tat modulates intracellular Ca2+ homeostasis of NAcc neurons. Results We provide evidence that Tat triggers a Ca2+ signaling cascade in NAcc medium spiny neurons (MSN) expressing D1-like dopamine receptors leading to neuronal depolarization. Firstly, Tat induced inositol 1,4,5-trisphsophate (IP3) receptor-mediated Ca2+ release from endoplasmic reticulum, followed by Ca2+ and Na+ influx via transient receptor potential canonical channels. The influx of cations depolarizes the membrane promoting additional Ca2+ entry through voltage-gated P/Q-type Ca2+ channels and opening of tetrodotoxin-sensitive Na+ channels. By activating this mechanism, Tat elicits a feed-forward depolarization increasing the excitability of D1-phosphatidylinositol-linked NAcc MSN. We previously found that cocaine targets NAcc neurons directly (independent of the inhibition of dopamine transporter) only when IP3-generating mechanisms are concomitantly initiated. When tested here, cocaine produced a dose-dependent potentiation of the effect of Tat on cytosolic Ca2+. Conclusion We describe for the first time a HIV-1 Tat-triggered Ca2+ signaling in MSN of NAcc involving TRPC and depolarization and a potentiation of the effect of Tat by cocaine, which may be relevant for the reward axis in cocaine-abusing HIV-1-positive patients.}, author = {Brailoiu, Gabriela and Deliu, Elena and Barr, Jeffrey and Console Bram, Linda and Ciuciu, Alexandra and Abood, Mary and Unterwald, Ellen and Brǎiloiu, Eugen}, issn = {03768716}, journal = {Drug and Alcohol Dependence}, pages = {7 -- 14}, publisher = {Elsevier}, title = {{HIV Tat excites D1 receptor-like expressing neurons from rat nucleus accumbens}}, doi = {10.1016/j.drugalcdep.2017.04.015}, volume = {178}, year = {2017}, } @article{715, abstract = {D-cycloserine ameliorates breathing abnormalities and survival rate in a mouse model of Rett syndrome.}, author = {Novarino, Gaia}, issn = {19466234}, journal = {Science Translational Medicine}, number = {405}, publisher = {American Association for the Advancement of Science}, title = {{More excitation for Rett syndrome}}, doi = {10.1126/scitranslmed.aao4218}, volume = {9}, year = {2017}, } @article{716, abstract = {Two-player games on graphs are central in many problems in formal verification and program analysis, such as synthesis and verification of open systems. In this work, we consider solving recursive game graphs (or pushdown game graphs) that model the control flow of sequential programs with recursion.While pushdown games have been studied before with qualitative objectives-such as reachability and ?-regular objectives- in this work, we study for the first time such games with the most well-studied quantitative objective, the mean-payoff objective. In pushdown games, two types of strategies are relevant: (1) global strategies, which depend on the entire global history; and (2) modular strategies, which have only local memory and thus do not depend on the context of invocation but rather only on the history of the current invocation of the module. Our main results are as follows: (1) One-player pushdown games with mean-payoff objectives under global strategies are decidable in polynomial time. (2) Two-player pushdown games with mean-payoff objectives under global strategies are undecidable. (3) One-player pushdown games with mean-payoff objectives under modular strategies are NP-hard. (4) Two-player pushdown games with mean-payoff objectives under modular strategies can be solved in NP (i.e., both one-player and two-player pushdown games with mean-payoff objectives under modular strategies are NP-complete). We also establish the optimal strategy complexity by showing that global strategies for mean-payoff objectives require infinite memory even in one-player pushdown games and memoryless modular strategies are sufficient in two-player pushdown games. Finally, we also show that all the problems have the same complexity if the stack boundedness condition is added, where along with the mean-payoff objective the player must also ensure that the stack height is bounded.}, author = {Chatterjee, Krishnendu and Velner, Yaron}, issn = {00045411}, journal = {Journal of the ACM}, number = {5}, pages = {34}, publisher = {ACM}, title = {{The complexity of mean-payoff pushdown games}}, doi = {10.1145/3121408}, volume = {64}, year = {2017}, } @article{717, abstract = {We consider finite-state and recursive game graphs with multidimensional mean-payoff objectives. In recursive games two types of strategies are relevant: global strategies and modular strategies. Our contributions are: (1) We show that finite-state multidimensional mean-payoff games can be solved in polynomial time if the number of dimensions and the maximal absolute value of weights are fixed; whereas for arbitrary dimensions the problem is coNP-complete. (2) We show that one-player recursive games with multidimensional mean-payoff objectives can be solved in polynomial time. Both above algorithms are based on hyperplane separation technique. (3) For recursive games we show that under modular strategies the multidimensional problem is undecidable. We show that if the number of modules, exits, and the maximal absolute value of the weights are fixed, then one-dimensional recursive mean-payoff games under modular strategies can be solved in polynomial time, whereas for unbounded number of exits or modules the problem is NP-hard.}, author = {Chatterjee, Krishnendu and Velner, Yaron}, journal = {Journal of Computer and System Sciences}, pages = {236 -- 259}, publisher = {Academic Press}, title = {{Hyperplane separation technique for multidimensional mean-payoff games}}, doi = {10.1016/j.jcss.2017.04.005}, volume = {88}, year = {2017}, } @article{719, abstract = {The ubiquity of computation in modern machines and devices imposes a need to assert the correctness of their behavior. Especially in the case of safety-critical systems, their designers need to take measures that enforce their safe operation. Formal methods has emerged as a research field that addresses this challenge: by rigorously proving that all system executions adhere to their specifications, the correctness of an implementation under concern can be assured. To achieve this goal, a plethora of techniques are nowadays available, all of which are optimized for different system types and application domains.}, author = {Chatterjee, Krishnendu and Ehlers, Rüdiger}, issn = {00015903}, journal = {Acta Informatica}, number = {6}, pages = {543 -- 544}, publisher = {Springer}, title = {{Special issue: Synthesis and SYNT 2014}}, doi = {10.1007/s00236-017-0299-0}, volume = {54}, year = {2017}, } @article{720, abstract = {Advances in multi-unit recordings pave the way for statistical modeling of activity patterns in large neural populations. Recent studies have shown that the summed activity of all neurons strongly shapes the population response. A separate recent finding has been that neural populations also exhibit criticality, an anomalously large dynamic range for the probabilities of different population activity patterns. Motivated by these two observations, we introduce a class of probabilistic models which takes into account the prior knowledge that the neural population could be globally coupled and close to critical. These models consist of an energy function which parametrizes interactions between small groups of neurons, and an arbitrary positive, strictly increasing, and twice differentiable function which maps the energy of a population pattern to its probability. We show that: 1) augmenting a pairwise Ising model with a nonlinearity yields an accurate description of the activity of retinal ganglion cells which outperforms previous models based on the summed activity of neurons; 2) prior knowledge that the population is critical translates to prior expectations about the shape of the nonlinearity; 3) the nonlinearity admits an interpretation in terms of a continuous latent variable globally coupling the system whose distribution we can infer from data. Our method is independent of the underlying system’s state space; hence, it can be applied to other systems such as natural scenes or amino acid sequences of proteins which are also known to exhibit criticality.}, author = {Humplik, Jan and Tkacik, Gasper}, issn = {1553734X}, journal = {PLoS Computational Biology}, number = {9}, publisher = {Public Library of Science}, title = {{Probabilistic models for neural populations that naturally capture global coupling and criticality}}, doi = {10.1371/journal.pcbi.1005763}, volume = {13}, year = {2017}, } @article{721, abstract = {Let S be a positivity-preserving symmetric linear operator acting on bounded functions. The nonlinear equation -1/m=z+Sm with a parameter z in the complex upper half-plane ℍ has a unique solution m with values in ℍ. We show that the z-dependence of this solution can be represented as the Stieltjes transforms of a family of probability measures v on ℝ. Under suitable conditions on S, we show that v has a real analytic density apart from finitely many algebraic singularities of degree at most 3. Our motivation comes from large random matrices. The solution m determines the density of eigenvalues of two prominent matrix ensembles: (i) matrices with centered independent entries whose variances are given by S and (ii) matrices with correlated entries with a translation-invariant correlation structure. Our analysis shows that the limiting eigenvalue density has only square root singularities or cubic root cusps; no other singularities occur.}, author = {Ajanki, Oskari H and Krüger, Torben H and Erdös, László}, issn = {00103640}, journal = {Communications on Pure and Applied Mathematics}, number = {9}, pages = {1672 -- 1705}, publisher = {Wiley-Blackwell}, title = {{Singularities of solutions to quadratic vector equations on the complex upper half plane}}, doi = {10.1002/cpa.21639}, volume = {70}, year = {2017}, } @article{722, abstract = {Plants are sessile organisms rooted in one place. The soil resources that plants require are often distributed in a highly heterogeneous pattern. To aid foraging, plants have evolved roots whose growth and development are highly responsive to soil signals. As a result, 3D root architecture is shaped by myriad environmental signals to ensure resource capture is optimised and unfavourable environments are avoided. The first signals sensed by newly germinating seeds — gravity and light — direct root growth into the soil to aid seedling establishment. Heterogeneous soil resources, such as water, nitrogen and phosphate, also act as signals that shape 3D root growth to optimise uptake. Root architecture is also modified through biotic interactions that include soil fungi and neighbouring plants. This developmental plasticity results in a ‘custom-made’ 3D root system that is best adapted to forage for resources in each soil environment that a plant colonises.}, author = {Morris, Emily and Griffiths, Marcus and Golebiowska, Agata and Mairhofer, Stefan and Burr Hersey, Jasmine and Goh, Tatsuaki and Von Wangenheim, Daniel and Atkinson, Brian and Sturrock, Craig and Lynch, Jonathan and Vissenberg, Kris and Ritz, Karl and Wells, Darren and Mooney, Sacha and Bennett, Malcolm}, issn = {09609822}, journal = {Current Biology}, number = {17}, pages = {R919 -- R930}, publisher = {Cell Press}, title = {{Shaping 3D root system architecture}}, doi = {10.1016/j.cub.2017.06.043}, volume = {27}, year = {2017}, } @article{725, abstract = {Individual computations and social interactions underlying collective behavior in groups of animals are of great ethological, behavioral, and theoretical interest. While complex individual behaviors have successfully been parsed into small dictionaries of stereotyped behavioral modes, studies of collective behavior largely ignored these findings; instead, their focus was on inferring single, mode-independent social interaction rules that reproduced macroscopic and often qualitative features of group behavior. Here, we bring these two approaches together to predict individual swimming patterns of adult zebrafish in a group. We show that fish alternate between an “active” mode, in which they are sensitive to the swimming patterns of conspecifics, and a “passive” mode, where they ignore them. Using a model that accounts for these two modes explicitly, we predict behaviors of individual fish with high accuracy, outperforming previous approaches that assumed a single continuous computation by individuals and simple metric or topological weighing of neighbors’ behavior. At the group level, switching between active and passive modes is uncorrelated among fish, but correlated directional swimming behavior still emerges. Our quantitative approach for studying complex, multi-modal individual behavior jointly with emergent group behavior is readily extensible to additional behavioral modes and their neural correlates as well as to other species.}, author = {Harpaz, Roy and Tkacik, Gasper and Schneidman, Elad}, issn = {00278424}, journal = {PNAS}, number = {38}, pages = {10149 -- 10154}, publisher = {National Academy of Sciences}, title = {{Discrete modes of social information processing predict individual behavior of fish in a group}}, doi = {10.1073/pnas.1703817114}, volume = {114}, year = {2017}, } @article{724, abstract = {We investigate the stationary and dynamical behavior of an Anderson localized chain coupled to a single central bound state. Although this coupling partially dilutes the Anderson localized peaks towards nearly resonant sites, the most weight of the original peaks remains unchanged. This leads to multifractal wave functions with a frozen spectrum of fractal dimensions, which is characteristic for localized phases in models with power-law hopping. Using a perturbative approach we identify two different dynamical regimes. At weak couplings to the central site, the transport of particles and information is logarithmic in time, a feature usually attributed to many-body localization. We connect such transport to the persistence of the Poisson statistics of level spacings in parts of the spectrum. In contrast, at stronger couplings the level repulsion is established in the entire spectrum, the problem can be mapped to the Fano resonance, and the transport is ballistic.}, author = {Hetterich, Daniel and Serbyn, Maksym and Domínguez, Fernando and Pollmann, Frank and Trauzettel, Björn}, issn = {24699950}, journal = {Physical Review B}, number = {10}, publisher = {American Physical Society}, title = {{Noninteracting central site model localization and logarithmic entanglement growth}}, doi = {10.1103/PhysRevB.96.104203}, volume = {96}, year = {2017}, } @article{731, abstract = {Genetic variations in the oxytocin receptor gene affect patients with ASD and ADHD differently.}, author = {Novarino, Gaia}, issn = {19466234}, journal = {Science Translational Medicine}, number = {411}, publisher = {American Association for the Advancement of Science}, title = {{The science of love in ASD and ADHD}}, doi = {10.1126/scitranslmed.aap8168}, volume = {9}, year = {2017}, } @article{7360, abstract = {Inflammation, which is a highly regulated host response against danger signals, may be harmful if it is excessive and deregulated. Ideally, anti-inflammatory therapy should autonomously commence as soon as possible after the onset of inflammation, should be controllable by a physician, and should not systemically block beneficial immune response in the long term. We describe a genetically encoded anti-inflammatory mammalian cell device based on a modular engineered genetic circuit comprising a sensor, an amplifier, a “thresholder” to restrict activation of a positive-feedback loop, a combination of advanced clinically used biopharmaceutical proteins, and orthogonal regulatory elements that linked modules into the functional device. This genetic circuit was autonomously activated by inflammatory signals, including endogenous cecal ligation and puncture (CLP)-induced inflammation in mice and serum from a systemic juvenile idiopathic arthritis (sIJA) patient, and could be reset externally by a chemical signal. The microencapsulated anti-inflammatory device significantly reduced the pathology in dextran sodium sulfate (DSS)-induced acute murine colitis, demonstrating a synthetic immunological approach for autonomous anti-inflammatory therapy.}, author = {Smole, Anže and Lainšček, Duško and Bezeljak, Urban and Horvat, Simon and Jerala, Roman}, issn = {1525-0016}, journal = {Molecular Therapy}, number = {1}, pages = {102--119}, publisher = {Elsevier}, title = {{A synthetic mammalian therapeutic gene circuit for sensing and suppressing inflammation}}, doi = {10.1016/j.ymthe.2016.10.005}, volume = {25}, year = {2017}, } @inproceedings{750, abstract = {Modern communication technologies allow first responders to contact thousands of potential volunteers simultaneously for support during a crisis or disaster event. However, such volunteer efforts must be well coordinated and monitored, in order to offer an effective relief to the professionals. In this paper we extend earlier work on optimally assigning volunteers to selected landmark locations. In particular, we emphasize the aspect that obtaining good assignments requires not only advanced computational tools, but also a realistic measure of distance between volunteers and landmarks. Specifically, we propose the use of the Open Street Map (OSM) driving distance instead of he previously used flight distance. We find the OSM driving distance to be better aligned with the interests of volunteers and first responders. Furthermore, we show that relying on the flying distance leads to a substantial underestimation of the number of required volunteers, causing negative side effects in case of an actual crisis situation.}, author = {Pielorz, Jasmin and Prandtstetter, Matthias and Straub, Markus and Lampert, Christoph}, booktitle = {2017 IEEE International Conference on Big Data}, isbn = {978-153862714-3}, location = {Boston, MA, United States}, pages = {3760 -- 3763}, publisher = {IEEE}, title = {{Optimal geospatial volunteer allocation needs realistic distances}}, doi = {10.1109/BigData.2017.8258375}, year = {2017}, } @article{795, abstract = {We introduce a common generalization of the strong Hanani–Tutte theorem and the weak Hanani–Tutte theorem: if a graph G has a drawing D in the plane where every pair of independent edges crosses an even number of times, then G has a planar drawing preserving the rotation of each vertex whose incident edges cross each other evenly in D. The theorem is implicit in the proof of the strong Hanani–Tutte theorem by Pelsmajer, Schaefer and Štefankovič. We give a new, somewhat simpler proof.}, author = {Fulek, Radoslav and Kynčl, Jan and Pálvölgyi, Dömötör}, issn = {10778926}, journal = {Electronic Journal of Combinatorics}, number = {3}, publisher = {International Press}, title = {{Unified Hanani Tutte theorem}}, doi = {10.37236/6663}, volume = {24}, year = {2017}, } @article{797, abstract = {Phasenübergänge helfen beim Verständnis von Vielteilchensystemen in der Festkörperphysik und Fluiddynamik bis hin zur Teilchenphysik. Unserer internationalen Kollaboration ist es gelungen, einen neuartigen Phasenübergang in einem Quantensystem zu beobachten [1]. In einem Mikrowellenresonator konnte erstmals die spontane Zustandsänderung von undurchsichtig zu transparent nachgewiesen werden.}, author = {Fink, Johannes M}, journal = {Physik in unserer Zeit}, number = {3}, pages = {111 -- 113}, publisher = {Wiley}, title = {{Photonenblockade aufgelöst}}, doi = {10.1002/piuz.201770305}, volume = {48}, year = {2017}, } @article{807, abstract = {On January the 1st, 2016 a new agreement between 32 Austrian scientific libraries and the publisher Springer took its effect: this deal covers accessing the licensed content on the one hand, and publishing open access on the other hand. More than 1000 papers by Austrian authors were published open access at Springer in the first year alone. The working group "Springer Compact Evaluierung" made the data for these articles available via the platform OpenAPC and would like to use this opportunity to give a short account of what this publishing agreement actually entails and the working group intends to do.}, author = {Andrae, Magdalena and Villányi, Márton}, issn = {10222588}, journal = {Mitteilungen der Vereinigung Österreichischer Bibliothekarinnen und Bibliothekare}, number = {2}, pages = {274 -- 280}, publisher = {VÖB}, title = {{Der Springer Compact-Deal – Ein erster Einblick in die Evaluierung einer Offsetting-Vereinbarung}}, doi = {10.31263/voebm.v70i2.1898}, volume = {70}, year = {2017}, } @article{825, abstract = {What data is needed about data? Describing the process to answer this question for the institutional data repository IST DataRep.}, author = {Petritsch, Barbara}, issn = {10222588}, journal = {Mitteilungen der Vereinigung Österreichischer Bibliothekarinnen & Bibliothekare}, number = {2}, pages = {200 -- 207}, publisher = {VÖB}, title = {{Metadata for research data in practice}}, doi = {10.31263/voebm.v70i2.1678}, volume = {70}, year = {2017}, } @article{9445, abstract = {Cytosine methylation regulates essential genome functions across eukaryotes, but the fundamental question of whether nucleosomal or naked DNA is the preferred substrate of plant and animal methyltransferases remains unresolved. Here, we show that genetic inactivation of a single DDM1/Lsh family nucleosome remodeler biases methylation toward inter-nucleosomal linker DNA in Arabidopsis thaliana and mouse. We find that DDM1 enables methylation of DNA bound to the nucleosome, suggesting that nucleosome-free DNA is the preferred substrate of eukaryotic methyltransferases in vivo. Furthermore, we show that simultaneous mutation of DDM1 and linker histone H1 in Arabidopsis reproduces the strong linker-specific methylation patterns of species that diverged from flowering plants and animals over a billion years ago. Our results indicate that in the absence of remodeling, nucleosomes are strong barriers to DNA methyltransferases. Linker-specific methylation can evolve simply by breaking the connection between nucleosome remodeling and DNA methylation.}, author = {Lyons, David B and Zilberman, Daniel}, issn = {2050-084X}, journal = {eLife}, publisher = {eLife Sciences Publications}, title = {{DDM1 and Lsh remodelers allow methylation of DNA wrapped in nucleosomes}}, doi = {10.7554/elife.30674}, volume = {6}, year = {2017}, } @inbook{957, abstract = {Small molecule biosensors based on Forster resonance energy transfer (FRET) enable small molecule signaling to be monitored with high spatial and temporal resolution in complex cellular environments. FRET sensors can be constructed by fusing a pair of fluorescent proteins to a suitable recognition domain, such as a member of the solute-binding protein (SBP) superfamily. However, naturally occurring SBPs may be unsuitable for incorporation into FRET sensors due to their low thermostability, which may preclude imaging under physiological conditions, or because the positions of their N- and C-termini may be suboptimal for fusion of fluorescent proteins, which may limit the dynamic range of the resulting sensors. Here, we show how these problems can be overcome using ancestral protein reconstruction and circular permutation. Ancestral protein reconstruction, used as a protein engineering strategy, leverages phylogenetic information to improve the thermostability of proteins, while circular permutation enables the termini of an SBP to be repositioned to maximize the dynamic range of the resulting FRET sensor. We also provide a protocol for cloning the engineered SBPs into FRET sensor constructs using Golden Gate assembly and discuss considerations for in situ characterization of the FRET sensors.}, author = {Clifton, Ben and Whitfield, Jason and Sanchez Romero, Inmaculada and Herde, Michel and Henneberger, Christian and Janovjak, Harald L and Jackson, Colin}, booktitle = {Synthetic Protein Switches}, editor = {Stein, Viktor}, issn = {10643745}, pages = {71 -- 87}, publisher = {Springer}, title = {{Ancestral protein reconstruction and circular permutation for improving the stability and dynamic range of FRET sensors}}, doi = {10.1007/978-1-4939-6940-1_5}, volume = {1596}, year = {2017}, } @inproceedings{963, abstract = {Network games are widely used as a model for selfish resource-allocation problems. In the classical model, each player selects a path connecting her source and target vertex. The cost of traversing an edge depends on the number of players that traverse it. Thus, it abstracts the fact that different users may use a resource at different times and for different durations, which plays an important role in defining the costs of the users in reality. For example, when transmitting packets in a communication network, routing traffic in a road network, or processing a task in a production system, the traversal of the network involves an inherent delay, and so sharing and congestion of resources crucially depends on time. We study timed network games , which add a time component to network games. Each vertex v in the network is associated with a cost function, mapping the load on v to the price that a player pays for staying in v for one time unit with this load. In addition, each edge has a guard, describing time intervals in which the edge can be traversed, forcing the players to spend time on vertices. Unlike earlier work that add a time component to network games, the time in our model is continuous and cannot be discretized. In particular, players have uncountably many strategies, and a game may have uncountably many pure Nash equilibria. We study properties of timed network games with cost-sharing or congestion cost functions: their stability, equilibrium inefficiency, and complexity. In particular, we show that the answer to the question whether we can restrict attention to boundary strategies, namely ones in which edges are traversed only at the boundaries of guards, is mixed. }, author = {Avni, Guy and Guha, Shibashis and Kupferman, Orna}, issn = {18688969}, location = {Aalborg, Denmark}, publisher = {Schloss Dagstuhl - Leibniz-Zentrum für Informatik}, title = {{Timed network games with clocks}}, doi = {10.4230/LIPIcs.MFCS.2017.37}, volume = {83}, year = {2017}, } @misc{9709, abstract = {Across the nervous system, certain population spiking patterns are observed far more frequently than others. A hypothesis about this structure is that these collective activity patterns function as population codewords–collective modes–carrying information distinct from that of any single cell. We investigate this phenomenon in recordings of ∼150 retinal ganglion cells, the retina’s output. We develop a novel statistical model that decomposes the population response into modes; it predicts the distribution of spiking activity in the ganglion cell population with high accuracy. We found that the modes represent localized features of the visual stimulus that are distinct from the features represented by single neurons. Modes form clusters of activity states that are readily discriminated from one another. When we repeated the same visual stimulus, we found that the same mode was robustly elicited. These results suggest that retinal ganglion cells’ collective signaling is endowed with a form of error-correcting code–a principle that may hold in brain areas beyond retina.}, author = {Prentice, Jason and Marre, Olivier and Ioffe, Mark and Loback, Adrianna and Tkačik, Gašper and Berry, Michael}, publisher = {Dryad}, title = {{Data from: Error-robust modes of the retinal population code}}, doi = {10.5061/dryad.1f1rc}, year = {2017}, } @article{541, abstract = {While we have good understanding of bacterial metabolism at the population level, we know little about the metabolic behavior of individual cells: do single cells in clonal populations sometimes specialize on different metabolic pathways? Such metabolic specialization could be driven by stochastic gene expression and could provide individual cells with growth benefits of specialization. We measured the degree of phenotypic specialization in two parallel metabolic pathways, the assimilation of glucose and arabinose. We grew Escherichia coli in chemostats, and used isotope-labeled sugars in combination with nanometer-scale secondary ion mass spectrometry and mathematical modeling to quantify sugar assimilation at the single-cell level. We found large variation in metabolic activities between single cells, both in absolute assimilation and in the degree to which individual cells specialize in the assimilation of different sugars. Analysis of transcriptional reporters indicated that this variation was at least partially based on cell-to-cell variation in gene expression. Metabolic differences between cells in clonal populations could potentially reduce metabolic incompatibilities between different pathways, and increase the rate at which parallel reactions can be performed.}, author = {Nikolic, Nela and Schreiber, Frank and Dal Co, Alma and Kiviet, Daniel and Bergmiller, Tobias and Littmann, Sten and Kuypers, Marcel and Ackermann, Martin}, issn = {15537390}, journal = {PLoS Genetics}, number = {12}, publisher = {Public Library of Science}, title = {{Cell-to-cell variation and specialization in sugar metabolism in clonal bacterial populations}}, doi = {10.1371/journal.pgen.1007122}, volume = {13}, year = {2017}, } @misc{9847, abstract = {information on culture conditions, phage mutagenesis, verification and lysate preparation; Raw data}, author = {Pleska, Maros and Guet, Calin C}, publisher = {The Royal Society}, title = {{Supplementary materials and methods; Full data set from effects of mutations in phage restriction sites during escape from restriction–modification}}, doi = {10.6084/m9.figshare.5633917.v1}, year = {2017}, } @misc{9845, abstract = {Estimates of 13 C-arabinose and 2 H-glucose uptake from the fractions of heavy isotopes measured in single cells}, author = {Nikolic, Nela and Schreiber, Frank and Dal Co, Alma and Kiviet, Daniel and Bergmiller, Tobias and Littmann, Sten and Kuypers, Marcel and Ackermann, Martin}, publisher = {Public Library of Science}, title = {{Mathematical model}}, doi = {10.1371/journal.pgen.1007122.s017}, year = {2017}, } @misc{9849, abstract = {This text provides additional information about the model, a derivation of the analytic results in Eq (4), and details about simulations of an additional parameter set.}, author = {Lukacisinova, Marta and Novak, Sebastian and Paixao, Tiago}, publisher = {Public Library of Science}, title = {{Modelling and simulation details}}, doi = {10.1371/journal.pcbi.1005609.s001}, year = {2017}, }