@article{1441, abstract = {Optogenetics and photopharmacology enable the spatio-temporal control of cell and animal behavior by light. Although red light offers deep-tissue penetration and minimal phototoxicity, very few red-light-sensitive optogenetic methods are currently available. We have now developed a red-light-induced homodimerization domain. We first showed that an optimized sensory domain of the cyanobacterial phytochrome 1 can be expressed robustly and without cytotoxicity in human cells. We then applied this domain to induce the dimerization of two receptor tyrosine kinases—the fibroblast growth factor receptor 1 and the neurotrophin receptor trkB. This new optogenetic method was then used to activate the MAPK/ERK pathway non-invasively in mammalian tissue and in multicolor cell-signaling experiments. The light-controlled dimerizer and red-light-activated receptor tyrosine kinases will prove useful to regulate a variety of cellular processes with light. Go deep with red: The sensory domain (S) of the cyanobacterial phytochrome 1 (CPH1) was repurposed to induce the homodimerization of proteins in living cells by red light. By using this domain, light-activated protein kinases were engineered that can be activated orthogonally from many fluorescent proteins and through mammalian tissue. Pr/Pfr=red-/far-red-absorbing state of CPH1.}, author = {Gschaider-Reichhart, Eva and Inglés Prieto, Álvaro and Tichy, Alexandra-Madelaine and Mckenzie, Catherine and Janovjak, Harald L}, journal = {Angewandte Chemie - International Edition}, number = {21}, pages = {6339 -- 6342}, publisher = {Wiley}, title = {{A phytochrome sensory domain permits receptor activation by red light}}, doi = {10.1002/anie.201601736}, volume = {55}, year = {2016}, } @article{1358, abstract = {Gene regulation relies on the specificity of transcription factor (TF)–DNA interactions. Limited specificity may lead to crosstalk: a regulatory state in which a gene is either incorrectly activated due to noncognate TF–DNA interactions or remains erroneously inactive. As each TF can have numerous interactions with noncognate cis-regulatory elements, crosstalk is inherently a global problem, yet has previously not been studied as such. We construct a theoretical framework to analyse the effects of global crosstalk on gene regulation. We find that crosstalk presents a significant challenge for organisms with low-specificity TFs, such as metazoans. Crosstalk is not easily mitigated by known regulatory schemes acting at equilibrium, including variants of cooperativity and combinatorial regulation. Our results suggest that crosstalk imposes a previously unexplored global constraint on the functioning and evolution of regulatory networks, which is qualitatively distinct from the known constraints that act at the level of individual gene regulatory elements.}, author = {Friedlander, Tamar and Prizak, Roshan and Guet, Calin C and Barton, Nicholas H and Tkacik, Gasper}, journal = {Nature Communications}, publisher = {Nature Publishing Group}, title = {{Intrinsic limits to gene regulation by global crosstalk}}, doi = {10.1038/ncomms12307}, volume = {7}, year = {2016}, } @article{1346, abstract = {ATP production requires the establishment of an electrochemical proton gradient across the inner mitochondrial membrane. Mitochondrial uncouplers dissipate this proton gradient and disrupt numerous cellular processes, including vesicular trafficking, mainly through energy depletion. Here we show that Endosidin9 (ES9), a novel mitochondrial uncoupler, is a potent inhibitor of clathrin-mediated endocytosis (CME) in different systems and that ES9 induces inhibition of CME not because of its effect on cellular ATP, but rather due to its protonophore activity that leads to cytoplasm acidification. We show that the known tyrosine kinase inhibitor tyrphostinA23, which is routinely used to block CME, displays similar properties, thus questioning its use as a specific inhibitor of cargo recognition by the AP-2 adaptor complex via tyrosine motif-based endocytosis signals. Furthermore, we show that cytoplasm acidification dramatically affects the dynamics and recruitment of clathrin and associated adaptors, and leads to reduction of phosphatidylinositol 4,5-biphosphate from the plasma membrane.}, author = {Dejonghe, Wim and Kuenen, Sabine and Mylle, Evelien and Vasileva, Mina K and Keech, Olivier and Viotti, Corrado and Swerts, Jef and Fendrych, Matyas and Ortiz Morea, Fausto and Mishev, Kiril and Delang, Simon and Scholl, Stefan and Zarza, Xavier and Heilmann, Mareike and Kourelis, Jiorgos and Kasprowicz, Jaroslaw and Nguyen, Le and Drozdzecki, Andrzej and Van Houtte, Isabelle and Szatmári, Anna and Majda, Mateusz and Baisa, Gary and Bednarek, Sebastian and Robert, Stéphanie and Audenaert, Dominique and Testerink, Christa and Munnik, Teun and Van Damme, Daniël and Heilmann, Ingo and Schumacher, Karin and Winne, Johan and Friml, Jirí and Verstreken, Patrik and Russinova, Eugenia}, journal = {Nature Communications}, publisher = {Nature Publishing Group}, title = {{Mitochondrial uncouplers inhibit clathrin-mediated endocytosis largely through cytoplasmic acidification}}, doi = {10.1038/ncomms11710}, volume = {7}, year = {2016}, } @article{1328, abstract = {Hole spins have gained considerable interest in the past few years due to their potential for fast electrically controlled qubits. Here, we study holes confined in Ge hut wires, a so-far unexplored type of nanostructure. Low-temperature magnetotransport measurements reveal a large anisotropy between the in-plane and out-of-plane g-factors of up to 18. Numerical simulations verify that this large anisotropy originates from a confined wave function of heavy-hole character. A light-hole admixture of less than 1% is estimated for the states of lowest energy, leading to a surprisingly large reduction of the out-of-plane g-factors compared with those for pure heavy holes. Given this tiny light-hole contribution, the spin lifetimes are expected to be very long, even in isotopically nonpurified samples.}, author = {Watzinger, Hannes and Kloeffel, Christoph and Vukusic, Lada and Rossell, Marta and Sessi, Violetta and Kukucka, Josip and Kirchschlager, Raimund and Lausecker, Elisabeth and Truhlar, Alisha and Glaser, Martin and Rastelli, Armando and Fuhrer, Andreas and Loss, Daniel and Katsaros, Georgios}, journal = {Nano Letters}, number = {11}, pages = {6879 -- 6885}, publisher = {American Chemical Society}, title = {{Heavy-hole states in germanium hut wires}}, doi = {10.1021/acs.nanolett.6b02715}, volume = {16}, year = {2016}, } @inproceedings{1205, abstract = {In this paper, we present a formal model-driven engineering approach to establishing a safety-assured implementation of Multifunction vehicle bus controller (MVBC) based on the generic reference models and requirements described in the International Electrotechnical Commission (IEC) standard IEC-61375. First, the generic models described in IEC-61375 are translated into a network of timed automata, and some safety requirements tested in IEC-61375 are formalized as timed computation tree logic (TCTL) formulas. With the help of Uppaal, we check and debug whether the timed automata satisfy the formulas or not. Within this step, several logic inconsistencies in the original standard are detected and corrected. Then, we apply the tool Times to generate C code from the verified model, which was later synthesized into a real MVBC chip. Finally, the runtime verification tool RMOR is applied to verify some safety requirements at the implementation level. We set up a real platform with worldwide mostly used MVBC D113, and verify the correctness and the scalability of the synthesized MVBC chip more comprehensively. The errors in the standard has been confirmed and the resulted MVBC has been deployed in real train communication network.}, author = {Jiang, Yu and Liu, Han and Song, Houbing and Kong, Hui and Gu, Ming and Sun, Jiaguang and Sha, Lui}, location = {Limassol, Cyprus}, pages = {757 -- 763}, publisher = {Springer}, title = {{Safety assured formal model driven design of the multifunction vehicle bus controller}}, doi = {10.1007/978-3-319-48989-6_47}, volume = {9995}, year = {2016}, } @inproceedings{1193, abstract = {We consider the recent formulation of the Algorithmic Lovász Local Lemma [1], [2] for finding objects that avoid "bad features", or "flaws". It extends the Moser-Tardos resampling algorithm [3] to more general discrete spaces. At each step the method picks a flaw present in the current state and "resamples" it using a "resampling oracle" provided by the user. However, it is less flexible than the Moser-Tardos method since [1], [2] require a specific flaw selection rule, whereas [3] allows an arbitrary rule (and thus can potentially be implemented more efficiently). We formulate a new "commutativity" condition, and prove that it is sufficient for an arbitrary rule to work. It also enables an efficient parallelization under an additional assumption. We then show that existing resampling oracles for perfect matchings and permutations do satisfy this condition. Finally, we generalize the precondition in [2] (in the case of symmetric potential causality graphs). This unifies special cases that previously were treated separately.}, author = {Kolmogorov, Vladimir}, booktitle = {Proceedings - Annual IEEE Symposium on Foundations of Computer Science}, location = {New Brunswick, NJ, USA }, publisher = {IEEE}, title = {{Commutativity in the algorithmic Lovasz local lemma}}, doi = {10.1109/FOCS.2016.88}, volume = {2016-December}, year = {2016}, } @inproceedings{1438, abstract = {In this paper, we consider termination of probabilistic programs with real-valued variables. The questions concerned are: (a) qualitative ones that ask (i) whether the program terminates with probability 1 (almost-sure termination) and (ii) whether the expected termination time is finite (finite termination); (b) quantitative ones that ask (i) to approximate the expected termination time (expectation problem) and (ii) to compute a bound B such that the probability to terminate after B steps decreases exponentially (concentration problem). To solve these questions, we utilize the notion of ranking supermartingales which is a powerful approach for proving termination of probabilistic programs. In detail, we focus on algorithmic synthesis of linear ranking-supermartingales over affine probabilistic programs (APP's) with both angelic and demonic non-determinism. An important subclass of APP's is LRAPP which is defined as the class of all APP's over which a linear ranking-supermartingale exists. Our main contributions are as follows. Firstly, we show that the membership problem of LRAPP (i) can be decided in polynomial time for APP's with at most demonic non-determinism, and (ii) is NP-hard and in PSPACE for APP's with angelic non-determinism; moreover, the NP-hardness result holds already for APP's without probability and demonic non-determinism. Secondly, we show that the concentration problem over LRAPP can be solved in the same complexity as for the membership problem of LRAPP. Finally, we show that the expectation problem over LRAPP can be solved in 2EXPTIME and is PSPACE-hard even for APP's without probability and non-determinism (i.e., deterministic programs). Our experimental results demonstrate the effectiveness of our approach to answer the qualitative and quantitative questions over APP's with at most demonic non-determinism.}, author = {Chatterjee, Krishnendu and Fu, Hongfei and Novotny, Petr and Hasheminezhad, Rouzbeh}, location = {St. Petersburg, FL, USA}, pages = {327 -- 342}, publisher = {ACM}, title = {{Algorithmic analysis of qualitative and quantitative termination problems for affine probabilistic programs}}, doi = {10.1145/2837614.2837639}, volume = {20-22}, year = {2016}, } @misc{9710, abstract = {Much of quantitative genetics is based on the ‘infinitesimal model’, under which selection has a negligible effect on the genetic variance. This is typically justified by assuming a very large number of loci with additive effects. However, it applies even when genes interact, provided that the number of loci is large enough that selection on each of them is weak relative to random drift. In the long term, directional selection will change allele frequencies, but even then, the effects of epistasis on the ultimate change in trait mean due to selection may be modest. Stabilising selection can maintain many traits close to their optima, even when the underlying alleles are weakly selected. However, the number of traits that can be optimised is apparently limited to ~4Ne by the ‘drift load’, and this is hard to reconcile with the apparent complexity of many organisms. Just as for the mutation load, this limit can be evaded by a particular form of negative epistasis. A more robust limit is set by the variance in reproductive success. This suggests that selection accumulates information most efficiently in the infinitesimal regime, when selection on individual alleles is weak, and comparable with random drift. A review of evidence on selection strength suggests that although most variance in fitness may be because of alleles with large Nes, substantial amounts of adaptation may be because of alleles in the infinitesimal regime, in which epistasis has modest effects.}, author = {Barton, Nicholas H}, publisher = {Dryad}, title = {{Data from: How does epistasis influence the response to selection?}}, doi = {10.5061/dryad.s5s7r}, year = {2016}, } @misc{9864, abstract = {Viral capsids are structurally constrained by interactions among the amino acids (AAs) of their constituent proteins. Therefore, epistasis is expected to evolve among physically interacting sites and to influence the rates of substitution. To study the evolution of epistasis, we focused on the major structural protein of the ϕX174 phage family by, first, reconstructing the ancestral protein sequences of 18 species using a Bayesian statistical framework. The inferred ancestral reconstruction differed at eight AAs, for a total of 256 possible ancestral haplotypes. For each ancestral haplotype and the extant species, we estimated, in silico, the distribution of free energies and epistasis of the capsid structure. We found that free energy has not significantly increased but epistasis has. We decomposed epistasis up to fifth order and found that higher-order epistasis sometimes compensates pairwise interactions making the free energy seem additive. The dN/dS ratio is low, suggesting strong purifying selection, and that structure is under stabilizing selection. We synthesized phages carrying ancestral haplotypes of the coat protein gene and measured their fitness experimentally. Our findings indicate that stabilizing mutations can have higher fitness, and that fitness optima do not necessarily coincide with energy minima.}, author = {Fernandes Redondo, Rodrigo A and de Vladar, Harold and Włodarski, Tomasz and Bollback, Jonathan P}, publisher = {The Royal Society}, title = {{Data from evolutionary interplay between structure, energy and epistasis in the coat protein of the ϕX174 phage family}}, doi = {10.6084/m9.figshare.4315652.v1}, year = {2016}, } @inproceedings{1165, abstract = {We show that c-planarity is solvable in quadratic time for flat clustered graphs with three clusters if the combinatorial embedding of the underlying graph is fixed. In simpler graph-theoretical terms our result can be viewed as follows. Given a graph G with the vertex set partitioned into three parts embedded on a 2-sphere, our algorithm decides if we can augment G by adding edges without creating an edge-crossing so that in the resulting spherical graph the vertices of each part induce a connected sub-graph. We proceed by a reduction to the problem of testing the existence of a perfect matching in planar bipartite graphs. We formulate our result in a slightly more general setting of cyclic clustered graphs, i.e., the simple graph obtained by contracting each cluster, where we disregard loops and multi-edges, is a cycle.}, author = {Fulek, Radoslav}, location = {Athens, Greece}, pages = {94 -- 106}, publisher = {Springer}, title = {{C-planarity of embedded cyclic c-graphs}}, doi = {10.1007/978-3-319-50106-2_8}, volume = {9801 }, year = {2016}, } @inproceedings{1378, abstract = {We give a detailed and easily accessible proof of Gromov's Topological Overlap Theorem. Let X be a finite simplicial complex or, more generally, a finite polyhedral cell complex of dimension d. Informally, the theorem states that if X has sufficiently strong higher-dimensional expansion properties (which generalize edge expansion of graphs and are defined in terms of cellular cochains of X) then X has the following topological overlap property: for every continuous map X → ℝd there exists a point p ∈ ℝd whose preimage intersects a positive fraction μ > 0 of the d-cells of X. More generally, the conclusion holds if ℝd is replaced by any d-dimensional piecewise-linear (PL) manifold M, with a constant μ that depends only on d and on the expansion properties of X, but not on M.}, author = {Dotterrer, Dominic and Kaufman, Tali and Wagner, Uli}, location = {Medford, MA, USA}, pages = {35.1 -- 35.10}, publisher = {Schloss Dagstuhl- Leibniz-Zentrum fur Informatik GmbH, Dagstuhl Publishing}, title = {{On expansion and topological overlap}}, doi = {10.4230/LIPIcs.SoCG.2016.35}, volume = {51}, year = {2016}, } @article{1616, abstract = {The hippocampus plays a key role in learning and memory. Previous studies suggested that the main types of principal neurons, dentate gyrus granule cells (GCs), CA3 pyramidal neurons, and CA1 pyramidal neurons, differ in their activity pattern, with sparse firing in GCs and more frequent firing in CA3 and CA1 pyramidal neurons. It has been assumed but never shown that such different activity may be caused by differential synaptic excitation. To test this hypothesis, we performed high-resolution whole-cell patch-clamp recordings in anesthetized rats in vivo. In contrast to previous in vitro data, both CA3 and CA1 pyramidal neurons fired action potentials spontaneously, with a frequency of ∼3–6 Hz, whereas GCs were silent. Furthermore, both CA3 and CA1 cells primarily fired in bursts. To determine the underlying mechanisms, we quantitatively assessed the frequency of spontaneous excitatory synaptic input, the passive membrane properties, and the active membrane characteristics. Surprisingly, GCs showed comparable synaptic excitation to CA3 and CA1 cells and the highest ratio of excitation versus hyperpolarizing inhibition. Thus, differential synaptic excitation is not responsible for differences in firing. Moreover, the three types of hippocampal neurons markedly differed in their passive properties. While GCs showed the most negative membrane potential, CA3 pyramidal neurons had the highest input resistance and the slowest membrane time constant. The three types of neurons also differed in the active membrane characteristics. GCs showed the highest action potential threshold, but displayed the largest gain of the input-output curves. In conclusion, our results reveal that differential firing of the three main types of hippocampal principal neurons in vivo is not primarily caused by differences in the characteristics of the synaptic input, but by the distinct properties of synaptic integration and input-output transformation.}, author = {Kowalski, Janina and Gan, Jian and Jonas, Peter M and Pernia-Andrade, Alejandro}, issn = {1098-1063}, journal = {Hippocampus}, number = {5}, pages = {668 -- 682}, publisher = {Wiley}, title = {{Intrinsic membrane properties determine hippocampal differential firing pattern in vivo in anesthetized rats}}, doi = {10.1002/hipo.22550}, volume = {26}, year = {2016}, } @article{1794, abstract = {We consider Conditional random fields (CRFs) with pattern-based potentials defined on a chain. In this model the energy of a string (labeling) (Formula presented.) is the sum of terms over intervals [i, j] where each term is non-zero only if the substring (Formula presented.) equals a prespecified pattern w. Such CRFs can be naturally applied to many sequence tagging problems. We present efficient algorithms for the three standard inference tasks in a CRF, namely computing (i) the partition function, (ii) marginals, and (iii) computing the MAP. Their complexities are respectively (Formula presented.), (Formula presented.) and (Formula presented.) where L is the combined length of input patterns, (Formula presented.) is the maximum length of a pattern, and D is the input alphabet. This improves on the previous algorithms of Ye et al. (NIPS, 2009) whose complexities are respectively (Formula presented.), (Formula presented.) and (Formula presented.), where (Formula presented.) is the number of input patterns. In addition, we give an efficient algorithm for sampling, and revisit the case of MAP with non-positive weights.}, author = {Kolmogorov, Vladimir and Takhanov, Rustem}, journal = {Algorithmica}, number = {1}, pages = {17 -- 46}, publisher = {Springer}, title = {{Inference algorithms for pattern-based CRFs on sequence data}}, doi = {10.1007/s00453-015-0017-7}, volume = {76}, year = {2016}, } @article{510, abstract = {The CLE (CLAVATA3/Embryo Surrounding Region-related) peptides are small secreted signaling peptides that are primarily involved in the regulation of stem cell homeostasis in different plant meristems. Particularly, the characterization of the CLE41-PXY/TDR signaling pathway has greatly advanced our understanding on the potential roles of CLE peptides in vascular development and wood formation. Nevertheless, our knowledge on this gene family in a tree species is limited. In a recent study, we reported on a systematically investigation of the CLE gene family in Populus trichocarpa . The potential roles of PtCLE genes were studied by comparative analysis and transcriptional pro fi ling. Among fi fty PtCLE members, many PtCLE proteins share identical CLE motifs or contain the same CLE motif as that of AtCLEs, while PtCLE genes exhibited either comparable or distinct expression patterns comparing to their Arabidopsis counterparts. These fi ndings indicate the existence of both functional conservation and functional divergence between PtCLEs and their AtCLE orthologues. Our results provide valuable resources for future functional investigations of these critical signaling molecules in woody plants. }, author = {Liu, Zhijun and Yang, Nan and Lv, Yanting and Pan, Lixia and Lv, Shuo and Han, Huibin and Wang, Guodong}, journal = {Plant Signaling & Behavior}, number = {6}, publisher = {Taylor & Francis}, title = {{The CLE gene family in Populus trichocarpa}}, doi = {10.1080/15592324.2016.1191734}, volume = {11}, year = {2016}, } @article{1263, abstract = {Linking classical microwave electrical circuits to the optical telecommunication band is at the core of modern communication. Future quantum information networks will require coherent microwave-to-optical conversion to link electronic quantum processors and memories via low-loss optical telecommunication networks. Efficient conversion can be achieved with electro-optical modulators operating at the single microwave photon level. In the standard electro-optic modulation scheme, this is impossible because both up- and down-converted sidebands are necessarily present. Here, we demonstrate true single-sideband up- or down-conversion in a triply resonant whispering gallery mode resonator by explicitly addressing modes with asymmetric free spectral range. Compared to previous experiments, we show a 3 orders of magnitude improvement of the electro-optical conversion efficiency, reaching 0.1% photon number conversion for a 10 GHz microwave tone at 0.42 mW of optical pump power. The presented scheme is fully compatible with existing superconducting 3D circuit quantum electrodynamics technology and can be used for nonclassical state conversion and communication. Our conversion bandwidth is larger than 1 MHz and is not fundamentally limited.}, author = {Rueda, Alfredo and Sedlmeir, Florian and Collodo, Michele and Vogl, Ulrich and Stiller, Birgit and Schunk, Gerhard and Strekalov, Dmitry and Marquardt, Christoph and Fink, Johannes M and Painter, Oskar and Leuchs, Gerd and Schwefel, Harald}, journal = {Optica}, number = {6}, pages = {597 -- 604}, publisher = {Optica Publishing Group}, title = {{Efficient microwave to optical photon conversion: An electro-optical realization}}, doi = {10.1364/OPTICA.3.000597}, volume = {3}, year = {2016}, } @article{1287, abstract = {A planar waveguide with an impedance boundary, composed of nonperfect metallic plates, and with passive or active dielectric filling, is considered. We show the possibility of selective mode guiding and amplification when a homogeneous pump is added to the dielectric and analyze differences in TE and TM mode propagation. Such a non-conservative system is also shown to feature exceptional points for specific and experimentally tunable parameters, which are described for a particular case of transparent dielectric.}, author = {Midya, Bikashkali and Konotop, Vladimir}, journal = {Optics Letters}, number = {20}, pages = {4621 -- 4624}, publisher = {Optica Publishing Group}, title = {{Modes and exceptional points in waveguides with impedance boundary conditions}}, doi = {10.1364/OL.41.004621}, volume = {41}, year = {2016}, } @article{1274, abstract = {Synchronized tissue polarization during regeneration or de novo vascular tissue formation is a plant-specific example of intercellular communication and coordinated development. According to the canalization hypothesis, the plant hormone auxin serves as polarizing signal that mediates directional channel formation underlying the spatio-temporal vasculature patterning. A necessary part of canalization is a positive feedback between auxin signaling and polarity of the intercellular auxin flow. The cellular and molecular mechanisms of this process are still poorly understood, not the least, because of a lack of a suitable model system. We show that the main genetic model plant, Arabidopsis (Arabidopsis thaliana) can be used to study the canalization during vascular cambium regeneration and new vasculature formation. We monitored localized auxin responses, directional auxin-transport channels formation, and establishment of new vascular cambium polarity during regenerative processes after stem wounding. The increased auxin response above and around the wound preceded the formation of PIN1 auxin transporter-marked channels from the primarily homogenous tissue and the transient, gradual changes in PIN1 localization preceded the polarity of newly formed vascular tissue. Thus, Arabidopsis is a useful model for studies of coordinated tissue polarization and vasculature formation after wounding allowing for genetic and mechanistic dissection of the canalization hypothesis.}, author = {Mazur, Ewa and Benková, Eva and Friml, Jirí}, journal = {Scientific Reports}, publisher = {Nature Publishing Group}, title = {{Vascular cambium regeneration and vessel formation in wounded inflorescence stems of Arabidopsis}}, doi = {10.1038/srep33754}, volume = {6}, year = {2016}, } @article{1253, abstract = {This article provides an introduction to the role of microRNAs in the nervous system and outlines their potential involvement in the pathophysiology of schizophrenia, which is hypothesized to arise owing to environmental factors and genetic predisposition.}, author = {Tsai, Lihuei and Siegert, Sandra}, issn = {2168-622X}, journal = {JAMA Psychiatry}, number = {4}, pages = {409 -- 410}, publisher = {American Medical Association}, title = {{How MicroRNAs Are involved in splitting the mind}}, doi = {10.1001/jamapsychiatry.2015.3144}, volume = {73}, year = {2016}, } @misc{5452, author = {Pavlogiannis, Andreas and Tkadlec, Josef and Chatterjee, Krishnendu and Nowak, Martin}, issn = {2664-1690}, pages = {32}, publisher = {IST Austria}, title = {{Arbitrarily strong amplifiers of natural selection}}, doi = {10.15479/AT:IST-2017-728-v2-1}, year = {2016}, } @misc{5550, abstract = {We collected flower colour information on species in the tribe Antirrhineae from taxonomic literature. We also retreived molecular data from GenBank for as many of these species as possible to estimate phylogenetic relationships among these taxa. We then used the R package 'diversitree' to examine patterns of evolutionary transitions between anthocyanin and yellow pigmentation across the phylogeny. For full details of the methods see: Ellis TJ and Field DL "Repeated gains in yellow and anthocyanin pigmentation in flower colour transitions in the Antirrhineae”, Annals of Botany (in press)}, author = {Ellis, Thomas and Field, David}, publisher = {Institute of Science and Technology Austria}, title = {{Flower colour data and phylogeny (NEXUS) files}}, doi = {10.15479/AT:ISTA:34}, year = {2016}, } @misc{5555, abstract = {This FIJI script calculates the population average of the migration speed as a function of time of all cells from wide field microscopy movies.}, author = {Hauschild, Robert}, keywords = {cell migration, wide field microscopy, FIJI}, publisher = {Institute of Science and Technology Austria}, title = {{Fiji script to determine average speed and direction of migration of cells}}, doi = {10.15479/AT:ISTA:44}, year = {2016}, } @misc{5557, abstract = {Small synthetic discrete tomography problems. Sizes are 32x32, 64z64 and 256x256. Projection angles are 2, 4, and 6. Number of labels are 3 and 5.}, author = {Swoboda, Paul}, keywords = {discrete tomography}, publisher = {Institute of Science and Technology Austria}, title = {{Synthetic discrete tomography problems}}, doi = {10.15479/AT:ISTA:46}, year = {2016}, } @phdthesis{1122, abstract = {Computer graphics is an extremely exciting field for two reasons. On the one hand, there is a healthy injection of pragmatism coming from the visual effects industry that want robust algorithms that work so they can produce results at an increasingly frantic pace. On the other hand, they must always try to push the envelope and achieve the impossible to wow their audiences in the next blockbuster, which means that the industry has not succumb to conservatism, and there is plenty of room to try out new and crazy ideas if there is a chance that it will pan into something useful. Water simulation has been in visual effects for decades, however it still remains extremely challenging because of its high computational cost and difficult artdirectability. The work in this thesis tries to address some of these difficulties. Specifically, we make the following three novel contributions to the state-of-the-art in water simulation for visual effects. First, we develop the first algorithm that can convert any sequence of closed surfaces in time into a moving triangle mesh. State-of-the-art methods at the time could only handle surfaces with fixed connectivity, but we are the first to be able to handle surfaces that merge and split apart. This is important for water simulation practitioners, because it allows them to convert splashy water surfaces extracted from particles or simulated using grid-based level sets into triangle meshes that can be either textured and enhanced with extra surface dynamics as a post-process. We also apply our algorithm to other phenomena that merge and split apart, such as morphs and noisy reconstructions of human performances. Second, we formulate a surface-based energy that measures the deviation of a water surface froma physically valid state. Such discrepancies arise when there is a mismatch in the degrees of freedom between the water surface and the underlying physics solver. This commonly happens when practitioners use a moving triangle mesh with a grid-based physics solver, or when high-resolution grid-based surfaces are combined with low-resolution physics. Following the direction of steepest descent on our surface-based energy, we can either smooth these artifacts or turn them into high-resolution waves by interpreting the energy as a physical potential. Third, we extend state-of-the-art techniques in non-reflecting boundaries to handle spatially and time-varying background flows. This allows a novel new workflow where practitioners can re-simulate part of an existing simulation, such as removing a solid obstacle, adding a new splash or locally changing the resolution. Such changes can easily lead to new waves in the re-simulated region that would reflect off of the new simulation boundary, effectively ruining the illusion of a seamless simulation boundary between the existing and new simulations. Our non-reflecting boundaries makes sure that such waves are absorbed.}, author = {Bojsen-Hansen, Morten}, issn = {2663-337X}, pages = {114}, publisher = {Institute of Science and Technology Austria}, title = {{Tracking, correcting and absorbing water surface waves}}, doi = {10.15479/AT:ISTA:th_640}, year = {2016}, } @phdthesis{1398, abstract = {Hybrid zones represent evolutionary laboratories, where recombination brings together alleles in combinations which have not previously been tested by selection. This provides an excellent opportunity to test the effect of molecular variation on fitness, and how this variation is able to spread through populations in a natural context. The snapdragon Antirrhinum majus is polymorphic in the wild for two loci controlling the distribution of yellow and magenta floral pigments. Where the yellow A. m. striatum and the magenta A. m. pseudomajus meet along a valley in the Spanish Pyrenees they form a stable hybrid zone Alleles at these loci recombine to give striking transgressive variation for flower colour. The sharp transition in phenotype over ~1km implies strong selection maintaining the hybrid zone. An indirect assay of pollinator visitation in the field found that pollinators forage in a positive-frequency dependent manner on Antirrhinum, matching previous data on fruit set. Experimental arrays and paternity analysis of wild-pollinated seeds demonstrated assortative mating for pigmentation alleles, and that pollinator behaviour alone is sufficient to explain this pattern. Selection by pollinators should be sufficiently strong to maintain the hybrid zone, although other mechanisms may be at work. At a broader scale I examined evolutionary transitions between yellow and anthocyanin pigmentation in the tribe Antirrhinae, and found that selection has acted strate that pollinators are a major determinant of reproductive success and mating patterns in wild Antirrhinum.}, author = {Ellis, Thomas}, issn = {2663-337X}, pages = {130}, publisher = {Institute of Science and Technology Austria}, title = {{The role of pollinator-mediated selection in the maintenance of a flower color polymorphism in an Antirrhinum majus hybrid zone}}, doi = {10.15479/AT:ISTA:TH_526 }, year = {2016}, } @phdthesis{1131, abstract = {Evolution of gene regulation is important for phenotypic evolution and diversity. Sequence-specific binding of regulatory proteins is one of the key regulatory mechanisms determining gene expression. Although there has been intense interest in evolution of regulatory binding sites in the last decades, a theoretical understanding is far from being complete. In this thesis, I aim at a better understanding of the evolution of transcriptional regulatory binding sequences by using biophysical and population genetic models. In the first part of the thesis, I discuss how to formulate the evolutionary dynamics of binding se- quences in a single isolated binding site and in promoter/enhancer regions. I develop a theoretical framework bridging between a thermodynamical model for transcription and a mutation-selection-drift model for monomorphic populations. I mainly address the typical evolutionary rates, and how they de- pend on biophysical parameters (e.g. binding length and specificity) and population genetic parameters (e.g. population size and selection strength). In the second part of the thesis, I analyse empirical data for a better evolutionary and biophysical understanding of sequence-specific binding of bacterial RNA polymerase. First, I infer selection on regulatory and non-regulatory binding sites of RNA polymerase in the E. coli K12 genome. Second, I infer the chemical potential of RNA polymerase, an important but unknown physical parameter defining the threshold energy for strong binding. Furthermore, I try to understand the relation between the lac promoter sequence diversity and the LacZ activity variation among 20 bacterial isolates by constructing a simple but biophysically motivated gene expression model. Lastly, I lay out a statistical framework to predict adaptive point mutations in de novo promoter evolution in a selection experiment.}, author = {Tugrul, Murat}, issn = {2663-337X}, pages = {89}, publisher = {Institute of Science and Technology Austria}, title = {{Evolution of transcriptional regulatory sequences}}, year = {2016}, } @misc{5553, abstract = {Genotypic, phenotypic and demographic data for 2128 wild snapdragons and 1127 open-pollinated progeny from a natural hybrid zone, collected as part of Tom Ellis' PhD thesis (submitted) February 2016). Tissue samples were sent to LGC Genomics in Berlin for DNA extraction, and genotyping at 70 SNP markers by KASPR genotyping. 29 of these SNPs failed to amplify reliably, and have been removed from this dataset. Other data were retreived from an online database of this population at www.antspec.org.}, author = {Field, David and Ellis, Thomas}, keywords = {paternity assignment, pedigree, matting patterns, assortative mating, Antirrhinum majus, frequency-dependent selection, plant-pollinator interaction}, publisher = {Institute of Science and Technology Austria}, title = {{Inference of mating patterns among wild snapdragons in a natural hybrid zone in 2012}}, doi = {10.15479/AT:ISTA:37}, year = {2016}, } @misc{5551, abstract = {Data from array experiments investigating pollinator behaviour on snapdragons in controlled conditions, and their effect on plant mating. Data were collected as part of Tom Ellis' PhD thesis , submitted February 2016. We placed a total of 36 plants in a grid inside a closed organza tent, with a single hive of commercially bred bumblebees (Bombus hortorum). We used only the yellow-flowered Antirrhinum majus striatum and the magenta-flowered Antirrhinum majus pseudomajus, at ratios of 6:36, 12:24, 18:18, 24:12 and 30:6. After 24 hours to learn how to deal with snapdragons, I observed pollinators foraging on plants, and recorded the transitions between plants. Thereafter seeds on plants were allowed to develops. A sample of these were grown to maturity when their flower colour could be determined, and they were scored as yellow, magenta, or hybrid.}, author = {Ellis, Thomas}, publisher = {Institute of Science and Technology Austria}, title = {{Data on pollinator observations and offpsring phenotypes}}, doi = {10.15479/AT:ISTA:35}, year = {2016}, } @misc{5552, abstract = {Data on pollinator visitation to wild snapdragons in a natural hybrid zone, collected as part of Tom Ellis' PhD thesis (submitted February 2016). Snapdragon flowers have a mouth-like structure which pollinators must open to access nectar. We placed 5mm cellophane tags in these mouths, which are held in place by the pressure of the flower until a pollinator visits. When she opens the flower, the tag drops out, and one can infer a visit. We surveyed plants over multiple days in 2010, 2011 and 2012. Also included are data on phenotypic and demographic variables which may be explanatory variables for pollinator visitation.}, author = {Ellis, Thomas}, publisher = {Institute of Science and Technology Austria}, title = {{Pollinator visitation data for wild Antirrhinum majus plants, with phenotypic and frequency data.}}, doi = {10.15479/AT:ISTA:36}, year = {2016}, } @misc{5554, abstract = {The data stored here is used in Murat Tugrul's PhD thesis (Chapter 3), which is related to the evolution of bacterial RNA polymerase binding. Magdalena Steinrueck (PhD Student in Calin Guet's group at IST Austria) performed the experiments and created the data on de novo promoter evolution. Fabienne Jesse (PhD Student in Jon Bollback's group at IST Austria) performed the experiments and created the data on lac promoter evolution.}, author = {Tugrul, Murat}, keywords = {RNAP binding, de novo promoter evolution, lac promoter}, publisher = {Institute of Science and Technology Austria}, title = {{Experimental Data for Binding Site Evolution of Bacterial RNA Polymerase}}, doi = {10.15479/AT:ISTA:43}, year = {2016}, } @misc{5558, abstract = {PhD thesis LaTeX source code}, author = {Bojsen-Hansen, Morten}, publisher = {Institute of Science and Technology Austria}, title = {{Tracking, Correcting and Absorbing Water Surface Waves}}, doi = {10.15479/AT:ISTA:48}, year = {2016}, } @misc{5556, abstract = {MATLAB code and processed datasets available for reproducing the results in: Lukačišin, M.*, Landon, M.*, Jajoo, R*. (2016) Sequence-Specific Thermodynamic Properties of Nucleic Acids Influence Both Transcriptional Pausing and Backtracking in Yeast. *equal contributions}, author = {Lukacisin, Martin and Landon, Matthieu and Jajoo, Rishi}, keywords = {transcription, pausing, backtracking, polymerase, RNA, NET-seq, nucleosome, basepairing}, publisher = {Institute of Science and Technology Austria}, title = {{MATLAB analysis code for 'Sequence-Specific Thermodynamic Properties of Nucleic Acids Influence Both Transcriptional Pausing and Backtracking in Yeast'}}, doi = {10.15479/AT:ISTA:45}, year = {2016}, } @inproceedings{15245, abstract = {eXTP is a science mission designed to study the state of matter under extreme conditions of density, gravity and magnetism. Primary goals are the determination of the equation of state of matter at supra-nuclear density, the measurement of QED effects in highly magnetized star, and the study of accretion in the strong-field regime of gravity. Primary targets include isolated and binary neutron stars, strong magnetic field systems like magnetars, and stellar-mass and supermassive black holes. The mission carries a unique and unprecedented suite of state-of-the-art scientific instruments enabling for the first time ever the simultaneous spectral-timing-polarimetry studies of cosmic sources in the energy range from 0.5-30 keV (and beyond). Key elements of the payload are: the Spectroscopic Focusing Array (SFA) - a set of 11 X-ray optics for a total effective area of ∼0.9 m2 and 0.6 m2 at 2 keV and 6 keV respectively, equipped with Silicon Drift Detectors offering <180 eV spectral resolution; the Large Area Detector (LAD) - a deployable set of 640 Silicon Drift Detectors, for a total effective area of ∼3.4 m2, between 6 and 10 keV, and spectral resolution better than 250 eV; the Polarimetry Focusing Array (PFA) - a set of 2 X-ray telescope, for a total effective area of 250 cm2 at 2 keV, equipped with imaging gas pixel photoelectric polarimeters; the Wide Field Monitor (WFM) - a set of 3 coded mask wide field units, equipped with position-sensitive Silicon Drift Detectors, each covering a 90 degrees x 90 degrees field of view. The eXTP international consortium includes major institutions of the Chinese Academy of Sciences and Universities in China, as well as major institutions in several European countries and the United States. The predecessor of eXTP, the XTP mission concept, has been selected and funded as one of the so-called background missions in the Strategic Priority Space Science Program of the Chinese Academy of Sciences since 2011. The strong European participation has significantly enhanced the scientific capabilities of eXTP. The planned launch date of the mission is earlier than 2025.}, author = {Zhang, S. N. and Feroci, M. and Santangelo, A. and Dong, Y. W. and Feng, H. and Lu, F. J. and Nandra, K. and Wang, Z. S. and Zhang, S. and Bozzo, E. and Brandt, S. and De Rosa, A. and Gou, L. J. and Hernanz, M. and van der Klis, M. and Li, X. D. and Liu, Y. and Orleanski, P. and Pareschi, G. and Pohl, M. and Poutanen, J. and Qu, J. L. and Schanne, S. and Stella, L. and Uttley, P. and Watts, A. and Xu, R. X. and Yu, W. F. and in ’t Zand, J. J. M. and Zane, S. and Alvarez, L. and Amati, L. and Baldini, L. and Bambi, C. and Basso, S. and Bhattacharyya, S. and Bellazzini, R. and Belloni, T. and Bellutti, P. and Bianchi, S. and Brez, A. and Bursa, M. and Burwitz, V. and Budtz-Jørgensen, C. and Caiazzo, Ilaria and Campana, R. and Cao, X. L. and Casella, P. and Chen, C. Y. and Chen, L. and Chen, T. and Chen, Y. and Chen, Y. and Chen, Y. P. and Civitani, M. and Coti Zelati, F. and Cui, W. and Cui, W. W. and Dai, Z. G. and Del Monte, E. and de Martino, D. and Di Cosimo, S. and Diebold, S. and Dovciak, M. and Donnarumma, I. and Doroshenko, V. and Esposito, P. and Evangelista, Y. and Favre, Y. and Friedrich, P. and Fuschino, F. and Galvez, J. L. and Gao, Z. L. and Ge, M. Y. and Gevin, O. and Goetz, D. and Han, D. W. and Heyl, J. and Horak, J. and Hu, W. and Huang, F. and Huang, Q. S. and Hudec, R. and Huppenkothen, D. and Israel, G. L. and Ingram, A. and Karas, V. and Karelin, D. and Jenke, P. A. and Ji, L. and Korpela, S. and Kunneriath, D. and Labanti, C. and Li, G. and Li, X. and Li, Z. S. and Liang, E. W. and Limousin, O. and Lin, L. and Ling, Z. X. and Liu, H. B. and Liu, H. W. and Liu, Z. and Lu, B. and Lund, N. and Lai, D. and Luo, B. and Luo, T. and Ma, B. and Mahmoodifar, S. and Marisaldi, M. and Martindale, A. and Meidinger, N. and Men, Y. P. and Michalska, M. and Mignani, R. and Minuti, M. and Motta, S. and Muleri, F. and Neilsen, J. and Orlandini, M. and Pan, A. T. and Patruno, A. and Perinati, E. and Picciotto, A. and Piemonte, C. and Pinchera, M. and Rachevski, A. and Rapisarda, M. and Rea, N. and Rossi, E. M. R. and Rubini, A. and Sala, G. and Shu, X. W. and Sgro, C. and Shen, Z. X. and Soffitta, P. and Song, L. M. and Spandre, G. and Stratta, G. and Strohmayer, T. E. and Sun, L. and Svoboda, J. and Tagliaferri, G. and Tenzer, C. and Hong, T. and Taverna, R. and Torok, G. and Turolla, R. and Vacchi, S. and Wang, J. and Walton, D. and Wang, K. and Wang, J. F. and Wang, R. J. and Wang, Y. F. and Weng, S. S. and Wilms, J. and Winter, B. and Wu, X. and Wu, X. F. and Xiong, S. L. and Xu, Y. P. and Xue, Y. Q. and Yan, Z. and Yang, S. and Yang, X. and Yang, Y. J. and Yuan, F. and Yuan, W. M. and Yuan, Y. F. and Zampa, G. and Zampa, N. and Zdziarski, A. and Zhang, C. and Zhang, C. L. and Zhang, L. and Zhang, X. and Zhang, Z. and Zhang, W. D. and Zheng, S. J. and Zhou, P. and Zhou, X. L.}, booktitle = {Proceedings of the SPIE}, issn = {0277-786X}, publisher = {SPIE}, title = {{eXTP: Enhanced X-ray timing and polarization mission}}, doi = {10.1117/12.2232034}, volume = {9905}, year = {2016}, } @article{1183, abstract = {Autism spectrum disorders (ASD) are a group of genetic disorders often overlapping with other neurological conditions. We previously described abnormalities in the branched-chain amino acid (BCAA) catabolic pathway as a cause of ASD. Here, we show that the solute carrier transporter 7a5 (SLC7A5), a large neutral amino acid transporter localized at the blood brain barrier (BBB), has an essential role in maintaining normal levels of brain BCAAs. In mice, deletion of Slc7a5 from the endothelial cells of the BBB leads to atypical brain amino acid profile, abnormal mRNA translation, and severe neurological abnormalities. Furthermore, we identified several patients with autistic traits and motor delay carrying deleterious homozygous mutations in the SLC7A5 gene. Finally, we demonstrate that BCAA intracerebroventricular administration ameliorates abnormal behaviors in adult mutant mice. Our data elucidate a neurological syndrome defined by SLC7A5 mutations and support an essential role for the BCAA in human brain function.}, author = {Tarlungeanu, Dora-Clara and Deliu, Elena and Dotter, Christoph and Kara, Majdi and Janiesch, Philipp and Scalise, Mariafrancesca and Galluccio, Michele and Tesulov, Mateja and Morelli, Emanuela and Sönmez, Fatma and Bilgüvar, Kaya and Ohgaki, Ryuichi and Kanai, Yoshikatsu and Johansen, Anide and Esharif, Seham and Ben Omran, Tawfeg and Topcu, Meral and Schlessinger, Avner and Indiveri, Cesare and Duncan, Kent and Caglayan, Ahmet and Günel, Murat and Gleeson, Joseph and Novarino, Gaia}, journal = {Cell}, number = {6}, pages = {1481 -- 1494}, publisher = {Cell Press}, title = {{Impaired amino acid transport at the blood brain barrier is a cause of autism spectrum disorder}}, doi = {10.1016/j.cell.2016.11.013}, volume = {167}, year = {2016}, } @article{1321, abstract = {Most migrating cells extrude their front by the force of actin polymerization. Polymerization requires an initial nucleation step, which is mediated by factors establishing either parallel filaments in the case of filopodia or branched filaments that form the branched lamellipodial network. Branches are considered essential for regular cell motility and are initiated by the Arp2/3 complex, which in turn is activated by nucleation-promoting factors of the WASP and WAVE families. Here we employed rapid amoeboid crawling leukocytes and found that deletion of the WAVE complex eliminated actin branching and thus lamellipodia formation. The cells were left with parallel filaments at the leading edge, which translated, depending on the differentiation status of the cell, into a unipolar pointed cell shape or cells with multiple filopodia. Remarkably, unipolar cells migrated with increased speed and enormous directional persistence, while they were unable to turn towards chemotactic gradients. Cells with multiple filopodia retained chemotactic activity but their migration was progressively impaired with increasing geometrical complexity of the extracellular environment. These findings establish that diversified leading edge protrusions serve as explorative structures while they slow down actual locomotion.}, author = {Leithner, Alexander F and Eichner, Alexander and Müller, Jan and Reversat, Anne and Brown, Markus and Schwarz, Jan and Merrin, Jack and De Gorter, David and Schur, Florian and Bayerl, Jonathan and De Vries, Ingrid and Wieser, Stefan and Hauschild, Robert and Lai, Frank and Moser, Markus and Kerjaschki, Dontscho and Rottner, Klemens and Small, Victor and Stradal, Theresia and Sixt, Michael K}, journal = {Nature Cell Biology}, pages = {1253 -- 1259}, publisher = {Nature Publishing Group}, title = {{Diversified actin protrusions promote environmental exploration but are dispensable for locomotion of leukocytes}}, doi = {10.1038/ncb3426}, volume = {18}, 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}, } @inproceedings{1437, abstract = {We study algorithmic questions for concurrent systems where the transitions are labeled from a complete, closed semiring, and path properties are algebraic with semiring operations. 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 Goharshady, Amir and Ibsen-Jensen, Rasmus and Pavlogiannis, Andreas}, location = {St. Petersburg, FL, USA}, pages = {733 -- 747}, publisher = {ACM}, title = {{Algorithms for algebraic path properties in concurrent systems of constant treewidth components}}, doi = {10.1145/2837614.2837624}, volume = {20-22}, year = {2016}, } @inproceedings{1386, abstract = {We consider nondeterministic probabilistic programs with the most basic liveness property of termination. We present efficient methods for termination analysis of nondeterministic probabilistic programs with polynomial guards and assignments. Our approach is through synthesis of polynomial ranking supermartingales, that on one hand significantly generalizes linear ranking supermartingales and on the other hand is a counterpart of polynomial ranking-functions for proving termination of nonprobabilistic programs. The approach synthesizes polynomial ranking-supermartingales through Positivstellensatz's, yielding an efficient method which is not only sound, but also semi-complete over a large subclass of programs. We show experimental results to demonstrate that our approach can handle several classical programs with complex polynomial guards and assignments, and can synthesize efficient quadratic ranking-supermartingales when a linear one does not exist even for simple affine programs.}, author = {Chatterjee, Krishnendu and Fu, Hongfei and Goharshady, Amir}, location = {Toronto, Canada}, pages = {3 -- 22}, publisher = {Springer}, title = {{Termination analysis of probabilistic programs through Positivstellensatz's}}, doi = {10.1007/978-3-319-41528-4_1}, volume = {9779}, year = {2016}, } @inproceedings{10748, abstract = {The study of fluxoid states and fluxoid dynamics in mesoscopic iron-based superconducting rings is valuable for characterizing the basic properties of the superconductor, and may also provide important insight into the superconducting paring symmetry. We report the fabrications of micron-sized rings and disks from thin films of Fe(Se, Te) grown by molecular beam epitaxy. In order to study fluxoid states in rings we developed a custom-tailored version of magnetic force microscopy (MFM). This technique has a number of qualitative advantages for working with mesoscopic superconducting samples in comparison to the conventional MFM and other imaging techniques. We observed metastable fluxoid states in rings of different sizes. Thermally activated fluxoid dynamics of these states was studied and modeled. In addition, we found different regimes of interaction between Fe(Se, Te) ring and MFM tip which are explained. Possibilities of the existence of exotic vortex states and proposals for experiments to test the symmetry of the superconducting order parameter in iron based superconductors are analyzed.}, author = {Polshyn, Hryhoriy and Zhang, Can and Naibert, Tyler and Eckstein, James and Budakian, Raffi}, booktitle = {APS March Meeting 2015}, issn = {0003-0503}, location = {San Antonio, TX, United States}, number = {1}, publisher = {American Physical Society}, title = {{Study of Fe (Se, Te) micron-sized rings by magnetic force microscopy}}, volume = {60}, year = {2015}, } @article{10794, abstract = {Mathematical models are of fundamental importance in the understanding of complex population dynamics. For instance, they can be used to predict the population evolution starting from different initial conditions or to test how a system responds to external perturbations. For this analysis to be meaningful in real applications, however, it is of paramount importance to choose an appropriate model structure and to infer the model parameters from measured data. While many parameter inference methods are available for models based on deterministic ordinary differential equations, the same does not hold for more detailed individual-based models. Here we consider, in particular, stochastic models in which the time evolution of the species abundances is described by a continuous-time Markov chain. These models are governed by a master equation that is typically difficult to solve. Consequently, traditional inference methods that rely on iterative evaluation of parameter likelihoods are computationally intractable. The aim of this paper is to present recent advances in parameter inference for continuous-time Markov chain models, based on a moment closure approximation of the parameter likelihood, and to investigate how these results can help in understanding, and ultimately controlling, complex systems in ecology. Specifically, we illustrate through an agricultural pest case study how parameters of a stochastic individual-based model can be identified from measured data and how the resulting model can be used to solve an optimal control problem in a stochastic setting. In particular, we show how the matter of determining the optimal combination of two different pest control methods can be formulated as a chance constrained optimization problem where the control action is modeled as a state reset, leading to a hybrid system formulation.}, author = {Parise, Francesca and Lygeros, John and Ruess, Jakob}, issn = {2296-665X}, journal = {Frontiers in Environmental Science}, keywords = {General Environmental Science}, publisher = {Frontiers}, title = {{Bayesian inference for stochastic individual-based models of ecological systems: a pest control simulation study}}, doi = {10.3389/fenvs.2015.00042}, volume = {3}, year = {2015}, } @article{11079, abstract = {Aging is a major risk factor for many human diseases, and in vitro generation of human neurons is an attractive approach for modeling aging-related brain disorders. However, modeling aging in differentiated human neurons has proved challenging. We generated neurons from human donors across a broad range of ages, either by iPSC-based reprogramming and differentiation or by direct conversion into induced neurons (iNs). While iPSCs and derived neurons did not retain aging-associated gene signatures, iNs displayed age-specific transcriptional profiles and revealed age-associated decreases in the nuclear transport receptor RanBP17. We detected an age-dependent loss of nucleocytoplasmic compartmentalization (NCC) in donor fibroblasts and corresponding iNs and found that reduced RanBP17 impaired NCC in young cells, while iPSC rejuvenation restored NCC in aged cells. These results show that iNs retain important aging-related signatures, thus allowing modeling of the aging process in vitro, and they identify impaired NCC as an important factor in human aging.}, author = {Mertens, Jerome and Paquola, Apuã C.M. and Ku, Manching and Hatch, Emily and Böhnke, Lena and Ladjevardi, Shauheen and McGrath, Sean and Campbell, Benjamin and Lee, Hyungjun and Herdy, Joseph R. and Gonçalves, J. Tiago and Toda, Tomohisa and Kim, Yongsung and Winkler, Jürgen and Yao, Jun and HETZER, Martin W and Gage, Fred H.}, issn = {1934-5909}, journal = {Cell Stem Cell}, keywords = {Cell Biology, Genetics, Molecular Medicine}, number = {6}, pages = {705--718}, publisher = {Elsevier}, title = {{Directly reprogrammed human neurons retain aging-associated transcriptomic signatures and reveal age-related nucleocytoplasmic defects}}, doi = {10.1016/j.stem.2015.09.001}, volume = {17}, year = {2015}, } @article{11077, abstract = {Nucleoporins (Nups) are a family of proteins best known as the constituent building blocks of nuclear pore complexes (NPCs), membrane-embedded channels that mediate nuclear transport across the nuclear envelope. Recent evidence suggests that several Nups have additional roles in controlling the activation and silencing of developmental genes; however, the mechanistic details of these functions remain poorly understood. Here, we show that depletion of Nup153 in mouse embryonic stem cells (mESCs) causes the derepression of developmental genes and induction of early differentiation. This loss of stem cell identity is not associated with defects in the nuclear import of key pluripotency factors. Rather, Nup153 binds around the transcriptional start site (TSS) of developmental genes and mediates the recruitment of the polycomb-repressive complex 1 (PRC1) to a subset of its target loci. Our results demonstrate a chromatin-associated role of Nup153 in maintaining stem cell pluripotency by functioning in mammalian epigenetic gene silencing.}, author = {Jacinto, Filipe V. and Benner, Chris and HETZER, Martin W}, issn = {1549-5477}, journal = {Genes & Development}, keywords = {Developmental Biology, Genetics}, number = {12}, pages = {1224--1238}, publisher = {Cold Spring Harbor Laboratory}, title = {{The nucleoporin Nup153 regulates embryonic stem cell pluripotency through gene silencing}}, doi = {10.1101/gad.260919.115}, volume = {29}, year = {2015}, } @article{11078, abstract = {Aging is associated with the decline of protein, cell, and organ function. Here, we use an integrated approach to characterize gene expression, bulk translation, and cell biology in the brains and livers of young and old rats. We identify 468 differences in protein abundance between young and old animals. The majority are a consequence of altered translation output, that is, the combined effect of changes in transcript abundance and translation efficiency. In addition, we identify 130 proteins whose overall abundance remains unchanged but whose sub-cellular localization, phosphorylation state, or splice-form varies. While some protein-level differences appear to be a generic property of the rats’ chronological age, the majority are specific to one organ. These may be a consequence of the organ’s physiology or the chronological age of the cells within the tissue. Taken together, our study provides an initial view of the proteome at the molecular, sub-cellular, and organ level in young and old rats.}, author = {Ori, Alessandro and Toyama, Brandon H. and Harris, Michael S. and Bock, Thomas and Iskar, Murat and Bork, Peer and Ingolia, Nicholas T. and HETZER, Martin W and Beck, Martin}, issn = {2405-4712}, journal = {Cell Systems}, keywords = {Cell Biology, Histology, Pathology and Forensic Medicine}, number = {3}, pages = {P224--237}, publisher = {Elsevier}, title = {{Integrated transcriptome and proteome analyses reveal organ-specific proteome deterioration in old rats}}, doi = {10.1016/j.cels.2015.08.012}, volume = {1}, year = {2015}, } @article{11076, abstract = {Nuclear pore complexes (NPCs) are composed of several copies of ∼30 different proteins called nucleoporins (Nups). NPCs penetrate the nuclear envelope (NE) and regulate the nucleocytoplasmic trafficking of macromolecules. Beyond this vital role, NPC components influence genome functions in a transport-independent manner. Nups play an evolutionarily conserved role in gene expression regulation that, in metazoans, extends into the nuclear interior. Additionally, in proliferative cells, Nups play a crucial role in genome integrity maintenance and mitotic progression. Here we discuss genome-related functions of Nups and their impact on essential DNA metabolism processes such as transcription, chromosome duplication, and segregation.}, author = {Ibarra, Arkaitz and HETZER, Martin W}, issn = {1549-5477}, journal = {Genes & Development}, keywords = {Developmental Biology, Genetics}, number = {4}, pages = {337--349}, publisher = {Cold Spring Harbor Laboratory}, title = {{Nuclear pore proteins and the control of genome functions}}, doi = {10.1101/gad.256495.114}, volume = {29}, year = {2015}, } @article{11073, abstract = {Human cancer cells bear complex chromosome rearrangements that can be potential drivers of cancer development. However, the molecular mechanisms underlying these rearrangements have been unclear. Zhang et al. use a new technique combining live-cell imaging and single-cell sequencing to demonstrate that chromosomes mis-segregated to micronuclei frequently undergo chromothripsis-like rearrangements in the subsequent cell cycle.}, author = {Hatch, Emily M. and HETZER, Martin W}, issn = {0092-8674}, journal = {Cell}, keywords = {General Biochemistry, Genetics and Molecular Biology}, number = {7}, pages = {1502--1504}, publisher = {Elsevier}, title = {{Linking micronuclei to chromosome fragmentation}}, doi = {10.1016/j.cell.2015.06.005}, volume = {161}, year = {2015}, } @article{11074, author = {Hatch, Emily M. and HETZER, Martin W}, issn = {0960-9822}, journal = {Current Biology}, keywords = {General Agricultural and Biological Sciences, General Biochemistry, Genetics and Molecular Biology}, number = {10}, pages = {PR397--R399}, publisher = {Elsevier}, title = {{Chromothripsis}}, doi = {10.1016/j.cub.2015.02.033}, volume = {25}, year = {2015}, } @article{11519, abstract = {Faint Lyα emitters become increasingly rarer toward the reionization epoch (z ∼ 6–7). However, observations from a very large (∼5 deg2) Lyα narrow-band survey at z = 6.6 show that this is not the case for the most luminous emitters, capable of ionizing their own local bubbles. Here we present follow-up observations of the two most luminous Lyα candidates in the COSMOS field: “MASOSA” and “CR7.” We used X-SHOOTER, SINFONI, and FORS2 on the Very Large Telescope, and DEIMOS on Keck, to confirm both candidates beyond any doubt. We find redshifts of z = 6.541 and z = 6.604 for “MASOSA” and “CR7,” respectively. MASOSA has a strong detection in Lyα with a line width of 386 ± 30 km s−1 (FWHM) and with very high EW0 (>200 Å), but undetected in the continuum, implying very low stellar mass and a likely young, metal-poor stellar population. “CR7,” with an observed Lyα luminosity of 1043.92±0.05 erg s−1 is the most luminous Lyα emitter ever found at z > 6 and is spatially extended (∼16 kpc). “CR7” reveals a narrow Lyα line with 266 ± 15 km s−1 FWHM, being detected in the near-infrared (NIR) (rest-frame UV; β = −2.3 ± 0.1) and in IRAC/Spitzer. We detect a narrow He II 1640 Å emission line (6σ, FWHM = 130 ± 30 km s−1 ) in CR7 which can explain the clear excess seen in the J-band photometry (EW0 ∼ 80 Å). We find no other emission lines from the UV to the NIR in our X-SHOOTER spectra (He II/O III] 1663 Å > 3 and He II/C III] 1908 Å > 2.5). We conclude that CR7 is best explained by a combination of a PopIII-like population, which dominates the rest-frame UV and the nebular emission, and a more normal stellar population, which presumably dominates the mass. Hubble Space Telescope/WFC3 observations show that the light is indeed spatially separated between a very blue component, coincident with Lyα and He II emission, and two red components (∼5 kpc away), which dominate the mass. Our findings are consistent with theoretical predictions of a PopIII wave, with PopIII star formation migrating away from the original sites of star formation.}, author = {Sobral, David and Matthee, Jorryt J and Darvish, Behnam and Schaerer, Daniel and Mobasher, Bahram and Röttgering, Huub and Santos, Sérgio and Hemmati, Shoubaneh}, issn = {1538-4357}, journal = {The Astrophysical Journal}, keywords = {Space and Planetary Science, Astronomy and Astrophysics, dark ages, reionization, first stars – early universe – galaxies: evolution}, number = {2}, pages = {139}, publisher = {IOP Publishing}, title = {{Evidence for PopIII-like stellar populations in the most luminous Lyα emitters at the epoch of reionisation: Spectroscopic confirmation}}, doi = {10.1088/0004-637X/808/2/139}, volume = {808}, year = {2015}, } @article{11580, abstract = {We present results from the largest contiguous narrow-band survey in the near-infrared. We have used the wide-field infrared camera/Canada–France–Hawaii Telescope and the lowOH2 filter (1.187 ± 0.005 μm) to survey ≈10 deg2 of contiguous extragalactic sky in the SA22 field. A total of ∼6000 candidate emission-line galaxies are found. We use deep ugrizJK data to obtain robust photometric redshifts. We combine our data with the High-redshift(Z) Emission Line Survey (HiZELS), explore spectroscopic surveys (VVDS, VIPERS) and obtain our own spectroscopic follow-up with KMOS, FMOS and MOSFIRE to derive large samples of high-redshift emission-line selected galaxies: 3471 Hα emitters at z = 0.8, 1343 [O III] + Hβ emitters at z = 1.4 and 572 [O II] emitters at z = 2.2. We probe comoving volumes of >106 Mpc3 and find significant overdensities, including an 8.5σ (spectroscopically confirmed) overdensity of Hα emitters at z = 0.81. We derive Hα, [O III] + Hβ and [O II] luminosity functions at z = 0.8, 1.4, 2.2, respectively, and present implications for future surveys such as Euclid. Our uniquely large volumes/areas allow us to subdivide the samples in thousands of randomized combinations of areas and provide a robust empirical measurement of sample/cosmic variance. We show that surveys for star-forming/emission-line galaxies at a depth similar to ours can only overcome cosmic-variance (errors <10 per cent) if they are based on volumes >5 × 105 Mpc3; errors on L* and ϕ* due to sample (cosmic) variance on surveys probing ∼104 and ∼105 Mpc3 are typically very high: ∼300 and ∼40–60 per cent, respectively.}, author = {Sobral, D. and Matthee, Jorryt J and Best, P. N. and Smail, I. and Khostovan, A. A. and Milvang-Jensen, B. and Kim, J.-W. and Stott, J. and Calhau, J. and Nayyeri, H. and Mobasher, B.}, issn = {1365-2966}, journal = {Monthly Notices of the Royal Astronomical Society}, keywords = {Space and Planetary Science, Astronomy and Astrophysics, galaxies: evolution, galaxies: formation, galaxies: luminosity function, mass function, cosmology: observations, early Universe, large-scale structure of Universe}, number = {3}, pages = {2303--2323}, publisher = {Oxford University Press}, title = {{CF-HiZELS, an ∼10 deg2 emission-line survey with spectroscopic follow-up: Hα, [O III] + Hβ and [O II] luminosity functions at z = 0.8, 1.4 and 2.2 }}, doi = {10.1093/mnras/stv1076}, volume = {451}, year = {2015}, } @article{11581, abstract = {Using wide-field narrow-band surveys, we provide a new measurement of the z = 6.6 Lymanα emitter (LAE) luminosity function (LF), which constraints the bright end for the first time. We use a combination of archival narrow-band NB921 data in UDS and new NB921 measurements in SA22 and COSMOS/UltraVISTA, all observed with the Subaru telescope, with a total area of ∼5 deg2. We exclude lower redshift interlopers by using broad-band optical and near-infrared photometry and also exclude three supernovae with data split over multiple epochs. Combining the UDS and COSMOS samples, we find no evolution of the bright end of the Lyα LF between z = 5.7 and 6.6, which is supported by spectroscopic follow-up, and conclude that sources with Himiko-like luminosity are not as rare as previously thought, with number densities of ∼1.5 × 10−5 Mpc−3. Combined with our wide-field SA22 measurements, our results indicate a non-Schechter-like bright end of the LF at z = 6.6 and a different evolution of observed faint and bright LAEs, overcoming cosmic variance. This differential evolution is also seen in the spectroscopic follow-up of UV-selected galaxies and is now also confirmed for LAEs, and we argue that it may be an effect of reionization. Using a toy model, we show that such differential evolution of the LF is expected, since brighter sources are able to ionize their surroundings earlier, such that Lyα photons are able to escape. Our targets are excellent candidates for detailed follow-up studies and provide the possibility to give a unique view on the earliest stages in the formation of galaxies and reionization process.}, author = {Matthee, Jorryt J and Sobral, David and Santos, Sérgio and Röttgering, Huub and Darvish, Behnam and Mobasher, Bahram}, issn = {1365-2966}, journal = {Monthly Notices of the Royal Astronomical Society}, keywords = {Space and Planetary Science, Astronomy and Astrophysics}, number = {1}, pages = {400--417}, publisher = {Oxford University Press}, title = {{Identification of the brightest Lyα emitters at z = 6.6: implications for the evolution of the luminosity function in the reionization era}}, doi = {10.1093/mnras/stv947}, volume = {451}, year = {2015}, } @article{11579, abstract = {CR7 is the brightest z = 6.6 Ly α emitter (LAE) known to date, and spectroscopic follow-up by Sobral et al. suggests that CR7 might host Population (Pop) III stars. We examine this interpretation using cosmological hydrodynamical simulations. Several simulated galaxies show the same ‘Pop III wave’ pattern observed in CR7. However, to reproduce the extreme CR7 Ly α/He II1640 line luminosities (⁠Lα/HeII⁠) a top-heavy initial mass function and a massive ( ≳ 107 M⊙) Pop III burst with age ≲ 2 Myr are required. Assuming that the observed properties of Ly α and He II emission are typical for Pop III, we predict that in the COSMOS/UDS/SA22 fields, 14 out of the 30 LAEs at z = 6.6 with Lα > 1043.3 erg s−1 should also host Pop III stars producing an observable LHeII≳1042.7ergs−1⁠. As an alternate explanation, we explore the possibility that CR7 is instead powered by accretion on to a direct collapse black hole. Our model predicts Lα, LHeII⁠, and X-ray luminosities that are in agreement with the observations. In any case, the observed properties of CR7 indicate that this galaxy is most likely powered by sources formed from pristine gas. We propose that further X-ray observations can distinguish between the two above scenarios.}, author = {Pallottini, A. and Ferrara, A. and Pacucci, F. and Gallerani, S. and Salvadori, S. and Schneider, R. and Schaerer, D. and Sobral, D. and Matthee, Jorryt J}, issn = {1365-2966}, journal = {Monthly Notices of the Royal Astronomical Society}, keywords = {Space and Planetary Science, Astronomy and Astrophysics, black hole physics, stars: Population III, galaxies: high-redshift}, number = {3}, pages = {2465--2470}, publisher = {Oxford University Press}, title = {{The brightest Lyα emitter: Pop III or black hole?}}, doi = {10.1093/mnras/stv1795}, volume = {453}, year = {2015}, } @article{11668, abstract = {We study multiple keyword sponsored search auctions with budgets. Each keyword has multiple ad slots with a click-through rate. The bidders have additive valuations, which are linear in the click-through rates, and budgets, which are restricting their overall payments. Additionally, the number of slots per keyword assigned to a bidder is bounded. We show the following results: (1) We give the first mechanism for multiple keywords, where click-through rates differ among slots. Our mechanism is incentive compatible in expectation, individually rational in expectation, and Pareto optimal. (2) We study the combinatorial setting, where each bidder is only interested in a subset of the keywords. We give an incentive compatible, individually rational, Pareto-optimal, and deterministic mechanism for identical click-through rates. (3) We give an impossibility result for incentive compatible, individually rational, Pareto-optimal, and deterministic mechanisms for bidders with diminishing marginal valuations.}, author = {Colini-Baldeschi, Riccardo and Leonardi, Stefano and Henzinger, Monika H and Starnberger, Martin}, issn = {2167-8383}, journal = {ACM Transactions on Economics and Computation}, keywords = {Algorithms, Economics, Clinching ascending auction, auctions with budgets, Sponsored search auctions}, number = {1}, publisher = {Association for Computing Machinery}, title = {{On multiple keyword sponsored search auctions with budgets}}, doi = {10.1145/2818357}, volume = {4}, year = {2015}, } @article{11669, abstract = {We study individual rational, Pareto-optimal, and incentive compatible mechanisms for auctions with heterogeneous items and budget limits. We consider settings with multiunit demand and additive valuations. For single-dimensional valuations we prove a positive result for randomized mechanisms, and a negative result for deterministic mechanisms. While the positive result allows for private budgets, the negative result is for public budgets. For multidimensional valuations and public budgets we prove an impossibility result that applies to deterministic and randomized mechanisms. Taken together this shows the power of randomization in certain settings with heterogeneous items, but it also shows its limitations.}, author = {Dütting, Paul and Henzinger, Monika H and Starnberger, Martin}, issn = {2167-8383}, journal = {ACM Transactions on Economics and Computation}, keywords = {Algorithmic game theory, auction theory, Clinching auction, Pareto optimality, Budget limits}, number = {1}, publisher = {Association for Computing Machinery}, title = {{Auctions for heterogeneous items and budget limits}}, doi = {10.1145/2818351}, volume = {4}, year = {2015}, } @inproceedings{11774, abstract = {Combinatorial auctions (CA) are a well-studied area in algorithmic mechanism design. However, contrary to the standard model, empirical studies suggest that a bidder’s valuation often does not depend solely on the goods assigned to him. For instance, in adwords auctions an advertiser might not want his ads to be displayed next to his competitors’ ads. In this paper, we propose and analyze several natural graph-theoretic models that incorporate such negative externalities, in which bidders form a directed conflict graph with maximum out-degree Δ. We design algorithms and truthful mechanisms for social welfare maximization that attain approximation ratios depending on Δ. For CA, our results are twofold: (1) A lottery that eliminates conflicts by discarding bidders/items independent of the bids. It allows to apply any truthful 𝛼-approximation mechanism for conflict-free valuations and yields an 𝒪(𝛼Δ)-approximation mechanism. (2) For fractionally sub-additive valuations, we design a rounding algorithm via a novel combination of a semi-definite program and a linear program, resulting in a cone program; the approximation ratio is 𝒪((ΔloglogΔ)/logΔ). The ratios are almost optimal given existing hardness results. For adwords auctions, we present several algorithms for the most relevant scenario when the number of items is small. In particular, we design a truthful mechanism with approximation ratio 𝑜(Δ) when the number of items is only logarithmic in the number of bidders.}, author = {Cheung, Yun Kuen and Henzinger, Monika H and Hoefer, Martin and Starnberger, Martin}, booktitle = {11th International Conference on Web and Internet Economics}, isbn = {9783662489949}, issn = {0302-9743}, location = {Amsterdam, Netherlands}, pages = {230–243}, publisher = {Springer Nature}, title = {{Combinatorial auctions with conflict-based externalities}}, doi = {10.1007/978-3-662-48995-6_17}, volume = {9470}, year = {2015}, } @inproceedings{11773, abstract = {Ad exchanges are an emerging platform for trading advertisement slots on the web with billions of dollars revenue per year. Every time a user visits a web page, the publisher of that web page can ask an ad exchange to auction off the ad slots on this page to determine which advertisements are shown at which price. Due to the high volume of traffic, ad networks typically act as mediators for individual advertisers at ad exchanges. If multiple advertisers in an ad network are interested in the ad slots of the same auction, the ad network might use a “local” auction to resell the obtained ad slots among its advertisers. In this work we want to deepen the theoretical understanding of these new markets by analyzing them from the viewpoint of combinatorial auctions. Prior work studied mostly single-item auctions, while we allow the advertisers to express richer preferences over multiple items. We develop a game-theoretic model for the entanglement of the central auction at the ad exchange with the local auctions at the ad networks. We consider the incentives of all three involved parties and suggest a three-party competitive equilibrium, an extension of the Walrasian equilibrium that ensures envy-freeness for all participants. We show the existence of a three-party competitive equilibrium and a polynomial-time algorithm to find one for gross-substitute bidder valuations.}, author = {Ben-Zwi, Oren and Henzinger, Monika H and Loitzenbauer, Veronika}, booktitle = {11th International Conference on Web and Internet Economics}, isbn = {9783662489949}, issn = {0302-9743}, location = {Amsterdam, Netherlands}, pages = {104–117}, publisher = {Springer Nature}, title = {{Ad exchange: Envy-free auctions with mediators}}, doi = {10.1007/978-3-662-48995-6_8}, volume = {9470}, year = {2015}, } @inproceedings{11785, abstract = {Recently we presented the first algorithm for maintaining the set of nodes reachable from a source node in a directed graph that is modified by edge deletions with 𝑜(𝑚𝑛) total update time, where 𝑚 is the number of edges and 𝑛 is the number of nodes in the graph [Henzinger et al. STOC 2014]. The algorithm is a combination of several different algorithms, each for a different 𝑚 vs. 𝑛 trade-off. For the case of 𝑚=Θ(𝑛1.5) the running time is 𝑂(𝑛2.47), just barely below 𝑚𝑛=Θ(𝑛2.5). In this paper we simplify the previous algorithm using new algorithmic ideas and achieve an improved running time of 𝑂̃ (min(𝑚7/6𝑛2/3,𝑚3/4𝑛5/4+𝑜(1),𝑚2/3𝑛4/3+𝑜(1)+𝑚3/7𝑛12/7+𝑜(1))). This gives, e.g., 𝑂(𝑛2.36) for the notorious case 𝑚=Θ(𝑛1.5). We obtain the same upper bounds for the problem of maintaining the strongly connected components of a directed graph undergoing edge deletions. Our algorithms are correct with high probabililty against an oblivious adversary.}, author = {Henzinger, Monika H and Krinninger, Sebastian and Nanongkai, Danupon}, booktitle = {42nd International Colloquium on Automata, Languages and Programming}, isbn = {9783662476710}, issn = {0302-9743}, location = {Kyoto, Japan}, pages = {725 -- 736}, publisher = {Springer Nature}, title = {{Improved algorithms for decremental single-source reachability on directed graphs}}, doi = {10.1007/978-3-662-47672-7_59}, volume = {9134}, year = {2015}, } @inproceedings{11787, abstract = {We present faster algorithms for computing the 2-edge and 2-vertex strongly connected components of a directed graph. While in undirected graphs the 2-edge and 2-vertex connected components can be found in linear time, in directed graphs with m edges and n vertices only rather simple O(m n)-time algorithms were known. We use a hierarchical sparsification technique to obtain algorithms that run in time 𝑂(𝑛2). For 2-edge strongly connected components our algorithm gives the first running time improvement in 20 years. Additionally we present an 𝑂(𝑚2/log𝑛)-time algorithm for 2-edge strongly connected components, and thus improve over the O(m n) running time also when 𝑚=𝑂(𝑛). Our approach extends to k-edge and k-vertex strongly connected components for any constant k with a running time of 𝑂(𝑛2log𝑛) for k-edge-connectivity and 𝑂(𝑛3) for k-vertex-connectivity.}, author = {Henzinger, Monika H and Krinninger, Sebastian and Loitzenbauer, Veronika}, booktitle = {2nd International Colloquium on Automata, Languages and Programming}, isbn = {9783662476710}, issn = {0302-9743}, location = {Kyoto, Japan}, pages = {713 -- 724}, publisher = {Springer Nature}, title = {{Finding 2-edge and 2-vertex strongly connected components in quadratic time}}, doi = {10.1007/978-3-662-47672-7_58}, volume = {9134}, year = {2015}, } @inproceedings{11788, abstract = {Ad exchanges are becoming an increasingly popular way to sell advertisement slots on the internet. An ad exchange is basically a spot market for ad impressions. A publisher who has already signed contracts reserving advertisement impressions on his pages can choose between assigning a new ad impression for a new page view to a contracted advertiser or to sell it at an ad exchange. This leads to an online revenue maximization problem for the publisher. Given a new impression to sell decide whether (a) to assign it to a contracted advertiser and if so to which one or (b) to sell it at the ad exchange and if so at which reserve price. We make no assumptions about the distribution of the advertiser valuations that participate in the ad exchange and show that there exists a simple primal-dual based online algorithm, whose lower bound for the revenue converges to 𝑅𝐴𝐷𝑋+𝑅𝐴(1−1/𝑒), where 𝑅𝐴𝐷𝑋 is the revenue that the optimum algorithm achieves from the ad exchange and 𝑅𝐴 is the revenue that the optimum algorithm achieves from the contracted advertisers.}, author = {Dvořák, Wolfgang and Henzinger, Monika H}, booktitle = {12th International Workshop of Approximation and Online Algorithms}, issn = {0302-9743}, location = {Wroclaw, Poland}, pages = {156–167}, publisher = {Springer Nature}, title = {{Online ad assignment with an ad exchange}}, doi = {10.1007/978-3-319-18263-6_14}, volume = {8952}, year = {2015}, } @inproceedings{11786, abstract = {In this paper, we develop a dynamic version of the primal-dual method for optimization problems, and apply it to obtain the following results. (1) For the dynamic set-cover problem, we maintain an 𝑂(𝑓2)-approximately optimal solution in 𝑂(𝑓⋅log(𝑚+𝑛)) amortized update time, where 𝑓 is the maximum “frequency” of an element, 𝑛 is the number of sets, and 𝑚 is the maximum number of elements in the universe at any point in time. (2) For the dynamic 𝑏-matching problem, we maintain an 𝑂(1)-approximately optimal solution in 𝑂(log3𝑛) amortized update time, where 𝑛 is the number of nodes in the graph.}, author = {Bhattacharya, Sayan and Henzinger, Monika H and Italiano, Giuseppe F.}, booktitle = {42nd International Colloquium on Automata, Languages and Programming}, isbn = {9783662476710}, issn = {0302-9743}, location = {Kyoto, Japan}, pages = {206 -- 218}, publisher = {Springer Nature}, title = {{Design of dynamic algorithms via primal-dual method}}, doi = {10.1007/978-3-662-47672-7_17}, volume = {9134}, year = {2015}, } @article{11845, abstract = {Phylogenetic diversity (PD) is a measure of biodiversity based on the evolutionary history of species. Here, we discuss several optimization problems related to the use of PD, and the more general measure split diversity (SD), in conservation prioritization. Depending on the conservation goal and the information available about species, one can construct optimization routines that incorporate various conservation constraints. We demonstrate how this information can be used to select sets of species for conservation action. Specifically, we discuss the use of species' geographic distributions, the choice of candidates under economic pressure, and the use of predator–prey interactions between the species in a community to define viability constraints. Despite such optimization problems falling into the area of NP hard problems, it is possible to solve them in a reasonable amount of time using integer programming. We apply integer linear programming to a variety of models for conservation prioritization that incorporate the SD measure. We exemplarily show the results for two data sets: the Cape region of South Africa and a Caribbean coral reef community. Finally, we provide user-friendly software at http://www.cibiv.at/software/pda.}, author = {Chernomor, Olga and Minh, Bui Quang and Forest, Félix and Klaere, Steffen and Ingram, Travis and Henzinger, Monika H and von Haeseler, Arndt}, issn = {2041-210X}, journal = {Methods in Ecology and Evolution}, number = {1}, pages = {83--91}, publisher = {Wiley}, title = {{Split diversity in constrained conservation prioritization using integer linear programming}}, doi = {10.1111/2041-210x.12299}, volume = {6}, year = {2015}, } @inproceedings{11868, abstract = {Consider the following Online Boolean Matrix-Vector Multiplication problem: We are given an n x n matrix M and will receive n column-vectors of size n, denoted by v1, ..., vn, one by one. After seeing each vector vi, we have to output the product Mvi before we can see the next vector. A naive algorithm can solve this problem using O(n3) time in total, and its running time can be slightly improved to O(n3/log2 n) [Williams SODA'07]. We show that a conjecture that there is no truly subcubic (O(n3-ε)) time algorithm for this problem can be used to exhibit the underlying polynomial time hardness shared by many dynamic problems. For a number of problems, such as subgraph connectivity, Pagh's problem, d-failure connectivity, decremental single-source shortest paths, and decremental transitive closure, this conjecture implies tight hardness results. Thus, proving or disproving this conjecture will be very interesting as it will either imply several tight unconditional lower bounds or break through a common barrier that blocks progress with these problems. This conjecture might also be considered as strong evidence against any further improvement for these problems since refuting it will imply a major breakthrough for combinatorial Boolean matrix multiplication and other long-standing problems if the term "combinatorial algorithms" is interpreted as "Strassen-like algorithms" [Ballard et al. SPAA'11]. The conjecture also leads to hardness results for problems that were previously based on diverse problems and conjectures -- such as 3SUM, combinatorial Boolean matrix multiplication, triangle detection, and multiphase -- thus providing a uniform way to prove polynomial hardness results for dynamic algorithms; some of the new proofs are also simpler or even become trivial. The conjecture also leads to stronger and new, non-trivial, hardness results, e.g., for the fully-dynamic densest subgraph and diameter problems.}, author = {Henzinger, Monika H and Krinninger, Sebastian and Nanongkai, Danupon and Saranurak, Thatchaphol}, booktitle = {47th Annual ACM Symposium on Theory of Computing}, isbn = {978-145033536-2}, issn = {0737.8017}, location = {Portland, OR, United States}, publisher = {Association for Computing Machinery}, title = {{Unifying and strengthening hardness for dynamic problems via the online matrix-vector multiplication conjecture}}, doi = {10.1145/2746539.2746609}, year = {2015}, } @inproceedings{11869, abstract = {While in many graph mining applications it is crucial to handle a stream of updates efficiently in terms of both time and space, not much was known about achieving such type of algorithm. In this paper we study this issue for a problem which lies at the core of many graph mining applications called densest subgraph problem. We develop an algorithm that achieves time- and space-efficiency for this problem simultaneously. It is one of the first of its kind for graph problems to the best of our knowledge. Given an input graph, the densest subgraph is the subgraph that maximizes the ratio between the number of edges and the number of nodes. For any ε>0, our algorithm can, with high probability, maintain a (4+ε)-approximate solution under edge insertions and deletions using ~O(n) space and ~O(1) amortized time per update; here, $n$ is the number of nodes in the graph and ~O hides the O(polylog_{1+ε} n) term. The approximation ratio can be improved to (2+ε) with more time. It can be extended to a (2+ε)-approximation sublinear-time algorithm and a distributed-streaming algorithm. Our algorithm is the first streaming algorithm that can maintain the densest subgraph in one pass. Prior to this, no algorithm could do so even in the special case of an incremental stream and even when there is no time restriction. The previously best algorithm in this setting required O(log n) passes [BahmaniKV12]. The space required by our algorithm is tight up to a polylogarithmic factor.}, author = {Bhattacharya, Sayan and Henzinger, Monika H and Nanongkai, Danupon and Tsourakakis, Charalampos}, booktitle = {47th Annual ACM Symposium on Theory of Computing}, isbn = {978-145033536-2}, issn = {0737-8017}, location = {Portland, OR, United States}, pages = {173 -- 182}, publisher = {Association for Computing Machinery}, title = {{Space- and time-efficient algorithm for maintaining dense subgraphs on one-pass dynamic streams}}, doi = {10.1145/2746539.2746592}, year = {2015}, } @inproceedings{11837, abstract = {Online social networks allow the collection of large amounts of data about the influence between users connected by a friendship-like relationship. When distributing items among agents forming a social network, this information allows us to exploit network externalities that each agent receives from his neighbors that get the same item. In this paper we consider Friends-of-Friends (2-hop) network externalities, i.e., externalities that not only depend on the neighbors that get the same item but also on neighbors of neighbors. For these externalities we study a setting where multiple different items are assigned to unit-demand agents. Specifically, we study the problem of welfare maximization under different types of externality functions. Let n be the number of agents and m be the number of items. Our contributions are the following: (1) We show that welfare maximization is APX-hard; we show that even for step functions with 2-hop (and also with 1-hop) externalities it is NP-hard to approximate social welfare better than (1-1/e). (2) On the positive side we present (i) an O(sqrt n)-approximation algorithm for general concave externality functions, (ii) an O(\log m)-approximation algorithm for linear externality functions, and (iii) an (1-1/e)\frac{1}{6}-approximation algorithm for 2-hop step function externalities. We also improve the result from [6] for 1-hop step function externalities by giving a (1-1/e)/2-approximation algorithm.}, author = {Bhattacharya, Sayan and Dvorák, Wolfgang and Henzinger, Monika H and Starnberger, Martin}, booktitle = {32nd International Symposium on Theoretical Aspects of Computer Science}, isbn = {978-3-939897-78-1}, issn = {1868-8969}, location = {Garching, Germany}, pages = {90--102}, publisher = {Schloss Dagstuhl - Leibniz-Zentrum für Informatik}, title = {{Welfare maximization with friends-of-friends network externalities}}, doi = {10.4230/LIPICS.STACS.2015.90}, volume = {30}, year = {2015}, } @article{11901, abstract = {We consider auctions of indivisible items to unit-demand bidders with budgets. This setting was suggested as an expressive model for single sponsored search auctions. Prior work presented mechanisms that compute bidder-optimal outcomes and are truthful for a restricted set of inputs, i.e., inputs in so-called general position. This condition is easily violated. We provide the first mechanism that is truthful in expectation for all inputs and achieves for each bidder no worse utility than the bidder-optimal outcome. Additionally we give a complete characterization for which inputs mechanisms that compute bidder-optimal outcomes are truthful.}, author = {Henzinger, Monika H and Loitzenbauer, Veronika}, issn = {0304-3975}, journal = {Theoretical Computer Science}, pages = {1--15}, publisher = {Elsevier}, title = {{Truthful unit-demand auctions with budgets revisited}}, doi = {10.1016/j.tcs.2015.01.033}, volume = {573}, year = {2015}, } @article{121, abstract = {We show that the simplest building blocks of origami-based materials - rigid, degree-four vertices - are generically multistable. The existence of two distinct branches of folding motion emerging from the flat state suggests at least bistability, but we show how nonlinearities in the folding motions allow generic vertex geometries to have as many as five stable states. In special geometries with collinear folds and symmetry, more branches emerge leading to as many as six stable states. Tuning the fold energy parameters, we show how monostability is also possible. Finally, we show how to program the stability features of a single vertex into a periodic fold tessellation. The resulting metasheets provide a previously unanticipated functionality - tunable and switchable shape and size via multistability.}, author = {Waitukaitis, Scott R and Menaut, Rémi and Chen, Bryan and Van Hecke, Martin}, journal = {APS Physics, Physical Review Letters}, number = {5}, publisher = {American Physical Society}, title = {{Origami multistability: From single vertices to metasheets}}, doi = {10.1103/PhysRevLett.114.055503}, volume = {114}, year = {2015}, } @article{1383, abstract = {In plants, vacuolar H+-ATPase (V-ATPase) activity acidifies both the trans-Golgi network/early endosome (TGN/EE) and the vacuole. This dual V-ATPase function has impeded our understanding of how the pH homeostasis within the plant TGN/EE controls exo- and endocytosis. Here, we show that the weak V-ATPase mutant deetiolated3 (det3) displayed a pH increase in the TGN/EE, but not in the vacuole, strongly impairing secretion and recycling of the brassinosteroid receptor and the cellulose synthase complexes to the plasma membrane, in contrast to mutants lacking tonoplast-localized V-ATPase activity only. The brassinosteroid insensitivity and the cellulose deficiency defects in det3 were tightly correlated with reduced Golgi and TGN/EE motility. Thus, our results provide strong evidence that acidification of the TGN/EE, but not of the vacuole, is indispensable for functional secretion and recycling in plants.}, author = {Yu, Luo and Scholl, Stefan and Doering, Anett and Yi, Zhang and Irani, Niloufer and Di Rubbo, Simone and Neumetzler, Lutz and Krishnamoorthy, Praveen and Van Houtte, Isabelle and Mylle, Evelien and Bischoff, Volker and Vernhettes, Samantha and Winne, Johan and Friml, Jirí and Stierhof, York and Schumacher, Karin and Persson, Staffan and Russinova, Eugenia}, journal = {Nature Plants}, number = {7}, publisher = {Nature Publishing Group}, title = {{V-ATPase activity in the TGN/EE is required for exocytosis and recycling in Arabidopsis}}, doi = {10.1038/nplants.2015.94}, volume = {1}, year = {2015}, } @inproceedings{1425, abstract = {In this work we aim at extending the theoretical foundations of lifelong learning. Previous work analyzing this scenario is based on the assumption that learning tasks are sampled i.i.d. from a task environment or limited to strongly constrained data distributions. Instead, we study two scenarios when lifelong learning is possible, even though the observed tasks do not form an i.i.d. sample: first, when they are sampled from the same environment, but possibly with dependencies, and second, when the task environment is allowed to change over time in a consistent way. In the first case we prove a PAC-Bayesian theorem that can be seen as a direct generalization of the analogous previous result for the i.i.d. case. For the second scenario we propose to learn an inductive bias in form of a transfer procedure. We present a generalization bound and show on a toy example how it can be used to identify a beneficial transfer algorithm.}, author = {Pentina, Anastasia and Lampert, Christoph}, location = {Montreal, Canada}, pages = {1540 -- 1548}, publisher = {Neural Information Processing Systems}, title = {{Lifelong learning with non-i.i.d. tasks}}, volume = {2015}, year = {2015}, } @inproceedings{1424, abstract = {We consider the problem of statistical computations with persistence diagrams, a summary representation of topological features in data. These diagrams encode persistent homology, a widely used invariant in topological data analysis. While several avenues towards a statistical treatment of the diagrams have been explored recently, we follow an alternative route that is motivated by the success of methods based on the embedding of probability measures into reproducing kernel Hilbert spaces. In fact, a positive definite kernel on persistence diagrams has recently been proposed, connecting persistent homology to popular kernel-based learning techniques such as support vector machines. However, important properties of that kernel enabling a principled use in the context of probability measure embeddings remain to be explored. Our contribution is to close this gap by proving universality of a variant of the original kernel, and to demonstrate its effective use in twosample hypothesis testing on synthetic as well as real-world data.}, author = {Kwitt, Roland and Huber, Stefan and Niethammer, Marc and Lin, Weili and Bauer, Ulrich}, location = {Montreal, Canada}, pages = {3070 -- 3078}, publisher = {Neural Information Processing Systems}, title = {{Statistical topological data analysis-A kernel perspective}}, volume = {28}, year = {2015}, } @inproceedings{1430, abstract = {Evolutionary algorithms (EAs) form a popular optimisation paradigm inspired by natural evolution. In recent years the field of evolutionary computation has developed a rigorous analytical theory to analyse their runtime on many illustrative problems. Here we apply this theory to a simple model of natural evolution. In the Strong Selection Weak Mutation (SSWM) evolutionary regime the time between occurrence of new mutations is much longer than the time it takes for a new beneficial mutation to take over the population. In this situation, the population only contains copies of one genotype and evolution can be modelled as a (1+1)-type process where the probability of accepting a new genotype (improvements or worsenings) depends on the change in fitness. We present an initial runtime analysis of SSWM, quantifying its performance for various parameters and investigating differences to the (1+1) EA. We show that SSWM can have a moderate advantage over the (1+1) EA at crossing fitness valleys and study an example where SSWM outperforms the (1+1) EA by taking advantage of information on the fitness gradient.}, author = {Paixao, Tiago and Sudholt, Dirk and Heredia, Jorge and Trubenova, Barbora}, booktitle = {Proceedings of the 2015 Annual Conference on Genetic and Evolutionary Computation}, location = {Madrid, Spain}, pages = {1455 -- 1462}, publisher = {ACM}, title = {{First steps towards a runtime comparison of natural and artificial evolution}}, doi = {10.1145/2739480.2754758}, year = {2015}, } @inproceedings{1474, abstract = {Cryptographic access control offers selective access to encrypted data via a combination of key management and functionality-rich cryptographic schemes, such as attribute-based encryption. Using this approach, publicly available meta-data may inadvertently leak information on the access policy that is enforced by cryptography, which renders cryptographic access control unusable in settings where this information is highly sensitive. We begin to address this problem by presenting rigorous definitions for policy privacy in cryptographic access control. For concreteness we set our results in the model of Role-Based Access Control (RBAC), where we identify and formalize several different flavors of privacy, however, our framework should serve as inspiration for other models of access control. Based on our insights we propose a new system which significantly improves on the privacy properties of state-of-the-art constructions. Our design is based on a novel type of privacy-preserving attribute-based encryption, which we introduce and show how to instantiate. We present our results in the context of a cryptographic RBAC system by Ferrara et al. (CSF'13), which uses cryptography to control read access to files, while write access is still delegated to trusted monitors. We give an extension of the construction that permits cryptographic control over write access. Our construction assumes that key management uses out-of-band channels between the policy enforcer and the users but eliminates completely the need for monitoring read/write access to the data.}, author = {Ferrara, Anna and Fuchsbauer, Georg and Liu, Bin and Warinschi, Bogdan}, location = {Verona, Italy}, pages = {46--60}, publisher = {IEEE}, title = {{Policy privacy in cryptographic access control}}, doi = {10.1109/CSF.2015.11}, year = {2015}, } @misc{1473, abstract = {In this paper we survey geometric and arithmetic techniques to study the cohomology of semiprojective hyperkähler manifolds including toric hyperkähler varieties, Nakajima quiver varieties and moduli spaces of Higgs bundles on Riemann surfaces. The resulting formulae for their Poincaré polynomials are combinatorial and representation theoretical in nature. In particular we will look at their Betti numbers and will establish some results and state some expectations on their asymptotic shape.}, author = {Tamas Hausel and Rodríguez Villegas, Fernando}, booktitle = {Asterisque}, number = {370}, pages = {113 -- 156}, publisher = {Societe Mathematique de France}, title = {{Cohomology of large semiprojective hyperkähler varieties}}, volume = {2015}, year = {2015}, } @inproceedings{1483, abstract = {Topological data analysis offers a rich source of valuable information to study vision problems. Yet, so far we lack a theoretically sound connection to popular kernel-based learning techniques, such as kernel SVMs or kernel PCA. In this work, we establish such a connection by designing a multi-scale kernel for persistence diagrams, a stable summary representation of topological features in data. We show that this kernel is positive definite and prove its stability with respect to the 1-Wasserstein distance. Experiments on two benchmark datasets for 3D shape classification/retrieval and texture recognition show considerable performance gains of the proposed method compared to an alternative approach that is based on the recently introduced persistence landscapes.}, author = {Reininghaus, Jan and Huber, Stefan and Bauer, Ulrich and Kwitt, Roland}, location = {Boston, MA, USA}, pages = {4741 -- 4748}, publisher = {IEEE}, title = {{A stable multi-scale kernel for topological machine learning}}, doi = {10.1109/CVPR.2015.7299106}, year = {2015}, } @inproceedings{1498, abstract = {Fault-tolerant distributed algorithms play an important role in many critical/high-availability applications. These algorithms are notoriously difficult to implement correctly, due to asynchronous communication and the occurrence of faults, such as the network dropping messages or computers crashing. Nonetheless there is surprisingly little language and verification support to build distributed systems based on fault-tolerant algorithms. In this paper, we present some of the challenges that a designer has to overcome to implement a fault-tolerant distributed system. Then we review different models that have been proposed to reason about distributed algorithms and sketch how such a model can form the basis for a domain-specific programming language. Adopting a high-level programming model can simplify the programmer's life and make the code amenable to automated verification, while still compiling to efficiently executable code. We conclude by summarizing the current status of an ongoing language design and implementation project that is based on this idea.}, author = {Dragoi, Cezara and Henzinger, Thomas A and Zufferey, Damien}, isbn = {978-3-939897-80-4 }, location = {Asilomar, CA, United States}, pages = {90 -- 102}, publisher = {Schloss Dagstuhl - Leibniz-Zentrum für Informatik}, title = {{The need for language support for fault-tolerant distributed systems}}, doi = {10.4230/LIPIcs.SNAPL.2015.90}, volume = {32}, year = {2015}, } @article{1497, abstract = {Detecting allelic biases from high-throughput sequencing data requires an approach that maximises sensitivity while minimizing false positives. Here, we present Allelome.PRO, an automated user-friendly bioinformatics pipeline, which uses high-throughput sequencing data from reciprocal crosses of two genetically distinct mouse strains to detect allele-specific expression and chromatin modifications. Allelome.PRO extends approaches used in previous studies that exclusively analyzed imprinted expression to give a complete picture of the ‘allelome’ by automatically categorising the allelic expression of all genes in a given cell type into imprinted, strain-biased, biallelic or non-informative. Allelome.PRO offers increased sensitivity to analyze lowly expressed transcripts, together with a robust false discovery rate empirically calculated from variation in the sequencing data. We used RNA-seq data from mouse embryonic fibroblasts from F1 reciprocal crosses to determine a biologically relevant allelic ratio cutoff, and define for the first time an entire allelome. Furthermore, we show that Allelome.PRO detects differential enrichment of H3K4me3 over promoters from ChIP-seq data validating the RNA-seq results. This approach can be easily extended to analyze histone marks of active enhancers, or transcription factor binding sites and therefore provides a powerful tool to identify candidate cis regulatory elements genome wide.}, author = {Andergassen, Daniel and Dotter, Christoph and Kulinski, Tomasz and Guenzl, Philipp and Bammer, Philipp and Barlow, Denise and Pauler, Florian and Hudson, Quanah}, journal = {Nucleic Acids Research}, number = {21}, publisher = {Oxford University Press}, title = {{Allelome.PRO, a pipeline to define allele-specific genomic features from high-throughput sequencing data}}, doi = {10.1093/nar/gkv727}, volume = {43}, year = {2015}, } @inproceedings{1499, abstract = {We consider weighted automata with both positive and negative integer weights on edges and study the problem of synchronization using adaptive strategies that may only observe whether the current weight-level is negative or nonnegative. We show that the synchronization problem is decidable in polynomial time for deterministic weighted automata.}, author = {Kretinsky, Jan and Larsen, Kim and Laursen, Simon and Srba, Jiří}, location = {Madrid, Spain}, pages = {142 -- 154}, publisher = {Schloss Dagstuhl - Leibniz-Zentrum für Informatik}, title = {{Polynomial time decidability of weighted synchronization under partial observability}}, doi = {10.4230/LIPIcs.CONCUR.2015.142}, volume = {42}, year = {2015}, } @inproceedings{1495, abstract = {Motivated by biological questions, we study configurations of equal-sized disks in the Euclidean plane that neither pack nor cover. Measuring the quality by the probability that a random point lies in exactly one disk, we show that the regular hexagonal grid gives the maximum among lattice configurations. }, author = {Edelsbrunner, Herbert and Iglesias Ham, Mabel and Kurlin, Vitaliy}, booktitle = {Proceedings of the 27th Canadian Conference on Computational Geometry}, location = {Ontario, Canada}, pages = {128--135}, publisher = {Queen's University}, title = {{Relaxed disk packing}}, volume = {2015-August}, year = {2015}, } @article{1504, abstract = {Let Q = (Q1, . . . , Qn) be a random vector drawn from the uniform distribution on the set of all n! permutations of {1, 2, . . . , n}. Let Z = (Z1, . . . , Zn), where Zj is the mean zero variance one random variable obtained by centralizing and normalizing Qj , j = 1, . . . , n. Assume that Xi , i = 1, . . . ,p are i.i.d. copies of 1/√ p Z and X = Xp,n is the p × n random matrix with Xi as its ith row. Then Sn = XX is called the p × n Spearman's rank correlation matrix which can be regarded as a high dimensional extension of the classical nonparametric statistic Spearman's rank correlation coefficient between two independent random variables. In this paper, we establish a CLT for the linear spectral statistics of this nonparametric random matrix model in the scenario of high dimension, namely, p = p(n) and p/n→c ∈ (0,∞) as n→∞.We propose a novel evaluation scheme to estimate the core quantity in Anderson and Zeitouni's cumulant method in [Ann. Statist. 36 (2008) 2553-2576] to bypass the so-called joint cumulant summability. In addition, we raise a two-step comparison approach to obtain the explicit formulae for the mean and covariance functions in the CLT. Relying on this CLT, we then construct a distribution-free statistic to test complete independence for components of random vectors. Owing to the nonparametric property, we can use this test on generally distributed random variables including the heavy-tailed ones.}, author = {Bao, Zhigang and Lin, Liang and Pan, Guangming and Zhou, Wang}, journal = {Annals of Statistics}, number = {6}, pages = {2588 -- 2623}, publisher = {Institute of Mathematical Statistics}, title = {{Spectral statistics of large dimensional spearman s rank correlation matrix and its application}}, doi = {10.1214/15-AOS1353}, volume = {43}, year = {2015}, } @article{1503, abstract = {A Herman-Avila-Bochi type formula is obtained for the average sum of the top d Lyapunov exponents over a one-parameter family of double-struck G-cocycles, where double-struck G is the group that leaves a certain, non-degenerate Hermitian form of signature (c, d) invariant. The generic example of such a group is the pseudo-unitary group U(c, d) or, in the case c = d, the Hermitian-symplectic group HSp(2d) which naturally appears for cocycles related to Schrödinger operators. In the case d = 1, the formula for HSp(2d) cocycles reduces to the Herman-Avila-Bochi formula for SL(2, ℝ) cocycles.}, author = {Sadel, Christian}, journal = {Ergodic Theory and Dynamical Systems}, number = {5}, pages = {1582 -- 1591}, publisher = {Cambridge University Press}, title = {{A Herman-Avila-Bochi formula for higher-dimensional pseudo-unitary and Hermitian-symplectic-cocycles}}, doi = {10.1017/etds.2013.103}, volume = {35}, year = {2015}, } @inproceedings{1510, abstract = {The concept of well group in a special but important case captures homological properties of the zero set of a continuous map f from K to R^n on a compact space K that are invariant with respect to perturbations of f. The perturbations are arbitrary continuous maps within L_infty distance r from f for a given r > 0. The main drawback of the approach is that the computability of well groups was shown only when dim K = n or n = 1. Our contribution to the theory of well groups is twofold: on the one hand we improve on the computability issue, but on the other hand we present a range of examples where the well groups are incomplete invariants, that is, fail to capture certain important robust properties of the zero set. For the first part, we identify a computable subgroup of the well group that is obtained by cap product with the pullback of the orientation of R^n by f. In other words, well groups can be algorithmically approximated from below. When f is smooth and dim K < 2n-2, our approximation of the (dim K-n)th well group is exact. For the second part, we find examples of maps f, f' from K to R^n with all well groups isomorphic but whose perturbations have different zero sets. We discuss on a possible replacement of the well groups of vector valued maps by an invariant of a better descriptive power and computability status. }, author = {Franek, Peter and Krcál, Marek}, location = {Eindhoven, Netherlands}, pages = {842 -- 856}, publisher = {Schloss Dagstuhl - Leibniz-Zentrum für Informatik}, title = {{On computability and triviality of well groups}}, doi = {10.4230/LIPIcs.SOCG.2015.842}, volume = {34}, year = {2015}, } @article{1505, abstract = {This paper is aimed at deriving the universality of the largest eigenvalue of a class of high-dimensional real or complex sample covariance matrices of the form W N =Σ 1/2XX∗Σ 1/2 . Here, X = (xij )M,N is an M× N random matrix with independent entries xij , 1 ≤ i M,≤ 1 ≤ j ≤ N such that Exij = 0, E|xij |2 = 1/N . On dimensionality, we assume that M = M(N) and N/M → d ε (0, ∞) as N ∞→. For a class of general deterministic positive-definite M × M matrices Σ , under some additional assumptions on the distribution of xij 's, we show that the limiting behavior of the largest eigenvalue of W N is universal, via pursuing a Green function comparison strategy raised in [Probab. Theory Related Fields 154 (2012) 341-407, Adv. Math. 229 (2012) 1435-1515] by Erd″os, Yau and Yin for Wigner matrices and extended by Pillai and Yin [Ann. Appl. Probab. 24 (2014) 935-1001] to sample covariance matrices in the null case (&Epsi = I ). Consequently, in the standard complex case (Ex2 ij = 0), combing this universality property and the results known for Gaussian matrices obtained by El Karoui in [Ann. Probab. 35 (2007) 663-714] (nonsingular case) and Onatski in [Ann. Appl. Probab. 18 (2008) 470-490] (singular case), we show that after an appropriate normalization the largest eigenvalue of W N converges weakly to the type 2 Tracy-Widom distribution TW2 . Moreover, in the real case, we show that whenΣ is spiked with a fixed number of subcritical spikes, the type 1 Tracy-Widom limit TW1 holds for the normalized largest eigenvalue of W N , which extends a result of Féral and Péché in [J. Math. Phys. 50 (2009) 073302] to the scenario of nondiagonal Σ and more generally distributed X . In summary, we establish the Tracy-Widom type universality for the largest eigenvalue of generally distributed sample covariance matrices under quite light assumptions on &Sigma . Applications of these limiting results to statistical signal detection and structure recognition of separable covariance matrices are also discussed.}, author = {Bao, Zhigang and Pan, Guangming and Zhou, Wang}, journal = {Annals of Statistics}, number = {1}, pages = {382 -- 421}, publisher = {Institute of Mathematical Statistics}, title = {{Universality for the largest eigenvalue of sample covariance matrices with general population}}, doi = {10.1214/14-AOS1281}, volume = {43}, year = {2015}, } @article{1508, abstract = {We consider generalized Wigner ensembles and general β-ensembles with analytic potentials for any β ≥ 1. The recent universality results in particular assert that the local averages of consecutive eigenvalue gaps in the bulk of the spectrum are universal in the sense that they coincide with those of the corresponding Gaussian β-ensembles. In this article, we show that local averaging is not necessary for this result, i.e. we prove that the single gap distributions in the bulk are universal. In fact, with an additional step, our result can be extended to any C4(ℝ) potential.}, author = {Erdös, László and Yau, Horng}, journal = {Journal of the European Mathematical Society}, number = {8}, pages = {1927 -- 2036}, publisher = {European Mathematical Society}, title = {{Gap universality of generalized Wigner and β ensembles}}, doi = {10.4171/JEMS/548}, volume = {17}, year = {2015}, } @article{1506, abstract = {Consider the square random matrix An = (aij)n,n, where {aij:= a(n)ij , i, j = 1, . . . , n} is a collection of independent real random variables with means zero and variances one. Under the additional moment condition supn max1≤i,j ≤n Ea4ij <∞, we prove Girko's logarithmic law of det An in the sense that as n→∞ log | detAn| ? (1/2) log(n-1)! d/→√(1/2) log n N(0, 1).}, author = {Bao, Zhigang and Pan, Guangming and Zhou, Wang}, journal = {Bernoulli}, number = {3}, pages = {1600 -- 1628}, publisher = {Bernoulli Society for Mathematical Statistics and Probability}, title = {{The logarithmic law of random determinant}}, doi = {10.3150/14-BEJ615}, volume = {21}, year = {2015}, } @article{1513, abstract = {Insects of the order Hemiptera (true bugs) use a wide range of mechanisms of sex determination, including genetic sex determination, paternal genome elimination, and haplodiploidy. Genetic sex determination, the prevalent mode, is generally controlled by a pair of XY sex chromosomes or by an XX/X0 system, but different configurations that include additional sex chromosomes are also present. Although this diversity of sex determining systems has been extensively studied at the cytogenetic level, only the X chromosome of the model pea aphid Acyrthosiphon pisum has been analyzed at the genomic level, and little is known about X chromosome biology in the rest of the order. In this study, we take advantage of published DNA- and RNA-seq data from three additional Hemiptera species to perform a comparative analysis of the gene content and expression of the X chromosome throughout this clade. We find that, despite showing evidence of dosage compensation, the X chromosomes of these species show female-biased expression, and a deficit of male-biased genes, in direct contrast to the pea aphid X. We further detect an excess of shared gene content between these very distant species, suggesting that despite the diversity of sex determining systems, the same chromosomal element is used as the X throughout a large portion of the order. }, author = {Pal, Arka and Vicoso, Beatriz}, journal = {Genome Biology and Evolution}, number = {12}, pages = {3259 -- 3268}, publisher = {Oxford University Press}, title = {{The X chromosome of hemipteran insects: Conservation, dosage compensation and sex-biased expression}}, doi = {10.1093/gbe/evv215}, volume = {7}, year = {2015}, } @article{1517, abstract = {We study the large deviation rate functional for the empirical distribution of independent Brownian particles with drift. In one dimension, it has been shown by Adams, Dirr, Peletier and Zimmer that this functional is asymptotically equivalent (in the sense of Γ-convergence) to the Jordan-Kinderlehrer-Otto functional arising in the Wasserstein gradient flow structure of the Fokker-Planck equation. In higher dimensions, part of this statement (the lower bound) has been recently proved by Duong, Laschos and Renger, but the upper bound remained open, since the proof of Duong et al relies on regularity properties of optimal transport maps that are restricted to one dimension. In this note we present a new proof of the upper bound, thereby generalising the result of Adams et al to arbitrary dimensions. }, author = {Erbar, Matthias and Maas, Jan and Renger, Michiel}, journal = {Electronic Communications in Probability}, publisher = {Institute of Mathematical Statistics}, title = {{From large deviations to Wasserstein gradient flows in multiple dimensions}}, doi = {10.1214/ECP.v20-4315}, volume = {20}, year = {2015}, } @article{1519, abstract = {Evolutionary biologists have an array of powerful theoretical techniques that can accurately predict changes in the genetic composition of populations. Changes in gene frequencies and genetic associations between loci can be tracked as they respond to a wide variety of evolutionary forces. However, it is often less clear how to decompose these various forces into components that accurately reflect the underlying biology. Here, we present several issues that arise in the definition and interpretation of selection and selection coefficients, focusing on insights gained through the examination of selection coefficients in multilocus notation. Using this notation, we discuss how its flexibility-which allows different biological units to be identified as targets of selection-is reflected in the interpretation of the coefficients that the notation generates. In many situations, it can be difficult to agree on whether loci can be considered to be under "direct" versus "indirect" selection, or to quantify this selection. We present arguments for what the terms direct and indirect selection might best encompass, considering a range of issues, from viability and sexual selection to kin selection. We show how multilocus notation can discriminate between direct and indirect selection, and describe when it can do so.}, author = {Barton, Nicholas H and Servedio, Maria}, journal = {Evolution}, number = {5}, pages = {1101 -- 1112}, publisher = {Wiley}, title = {{The interpretation of selection coefficients}}, doi = {10.1111/evo.12641}, volume = {69}, year = {2015}, } @article{1525, abstract = {Based on 16 recommendations, efforts should be made to achieve the following goal: By 2025, all scholarly publication activity in Austria should be Open Access. In other words, the final versions of all scholarly publications resulting from the support of public resources must be freely accessible on the Internet without delay (Gold Open Access). The resources required to meet this obligation shall be provided to the authors, or the cost of the publication venues shall be borne directly by the research organisations.}, author = {Bauer, Bruno and Blechl, Guido and Bock, Christoph and Danowski, Patrick and Ferus, Andreas and Graschopf, Anton and König, Thomas and Mayer, Katja and Reckling, Falk and Rieck, Katharina and Seitz, Peter and Stöger, Herwig and Welzig, Elvira}, journal = {VÖB Mitteilungen}, number = {3}, pages = {580 -- 607}, publisher = {Verein Österreichischer Bibliothekare}, title = {{Arbeitsgruppe „Nationale Strategie“ des Open Access Network Austria OANA}}, doi = {10.5281/zenodo.33178}, volume = {68}, year = {2015}, } @article{1539, abstract = {Many stochastic models of biochemical reaction networks contain some chemical species for which the number of molecules that are present in the system can only be finite (for instance due to conservation laws), but also other species that can be present in arbitrarily large amounts. The prime example of such networks are models of gene expression, which typically contain a small and finite number of possible states for the promoter but an infinite number of possible states for the amount of mRNA and protein. One of the main approaches to analyze such models is through the use of equations for the time evolution of moments of the chemical species. Recently, a new approach based on conditional moments of the species with infinite state space given all the different possible states of the finite species has been proposed. It was argued that this approach allows one to capture more details about the full underlying probability distribution with a smaller number of equations. Here, I show that the result that less moments provide more information can only stem from an unnecessarily complicated description of the system in the classical formulation. The foundation of this argument will be the derivation of moment equations that describe the complete probability distribution over the finite state space but only low-order moments over the infinite state space. I will show that the number of equations that is needed is always less than what was previously claimed and always less than the number of conditional moment equations up to the same order. To support these arguments, a symbolic algorithm is provided that can be used to derive minimal systems of unconditional moment equations for models with partially finite state space. }, author = {Ruess, Jakob}, journal = {Journal of Chemical Physics}, number = {24}, publisher = {American Institute of Physics}, title = {{Minimal moment equations for stochastic models of biochemical reaction networks with partially finite state space}}, doi = {10.1063/1.4937937}, volume = {143}, year = {2015}, } @article{1534, abstract = {PIN proteins are auxin export carriers that direct intercellular auxin flow and in turn regulate many aspects of plant growth and development including responses to environmental changes. The Arabidopsis R2R3-MYB transcription factor FOUR LIPS (FLP) and its paralogue MYB88 regulate terminal divisions during stomatal development, as well as female reproductive development and stress responses. Here we show that FLP and MYB88 act redundantly but differentially in regulating the transcription of PIN3 and PIN7 in gravity-sensing cells of primary and lateral roots. On the one hand, FLP is involved in responses to gravity stimulation in primary roots, whereas on the other, FLP and MYB88 function complementarily in establishing the gravitropic set-point angles of lateral roots. Our results support a model in which FLP and MYB88 expression specifically determines the temporal-spatial patterns of PIN3 and PIN7 transcription that are closely associated with their preferential functions during root responses to gravity.}, author = {Wang, Hongzhe and Yang, Kezhen and Zou, Junjie and Zhu, Lingling and Xie, Zidian and Morita, Miyoterao and Tasaka, Masao and Friml, Jirí and Grotewold, Erich and Beeckman, Tom and Vanneste, Steffen and Sack, Fred and Le, Jie}, journal = {Nature Communications}, publisher = {Nature Publishing Group}, title = {{Transcriptional regulation of PIN genes by FOUR LIPS and MYB88 during Arabidopsis root gravitropism}}, doi = {10.1038/ncomms9822}, volume = {6}, year = {2015}, } @article{1538, abstract = {Systems biology rests on the idea that biological complexity can be better unraveled through the interplay of modeling and experimentation. However, the success of this approach depends critically on the informativeness of the chosen experiments, which is usually unknown a priori. Here, we propose a systematic scheme based on iterations of optimal experiment design, flow cytometry experiments, and Bayesian parameter inference to guide the discovery process in the case of stochastic biochemical reaction networks. To illustrate the benefit of our methodology, we apply it to the characterization of an engineered light-inducible gene expression circuit in yeast and compare the performance of the resulting model with models identified from nonoptimal experiments. In particular, we compare the parameter posterior distributions and the precision to which the outcome of future experiments can be predicted. Moreover, we illustrate how the identified stochastic model can be used to determine light induction patterns that make either the average amount of protein or the variability in a population of cells follow a desired profile. Our results show that optimal experiment design allows one to derive models that are accurate enough to precisely predict and regulate the protein expression in heterogeneous cell populations over extended periods of time.}, author = {Ruess, Jakob and Parise, Francesca and Milias Argeitis, Andreas and Khammash, Mustafa and Lygeros, John}, journal = {PNAS}, number = {26}, pages = {8148 -- 8153}, publisher = {National Academy of Sciences}, title = {{Iterative experiment design guides the characterization of a light-inducible gene expression circuit}}, doi = {10.1073/pnas.1423947112}, volume = {112}, year = {2015}, } @article{1535, abstract = {Neuronal and neuroendocrine L-type calcium channels (Cav1.2, Cav1.3) open readily at relatively low membrane potentials and allow Ca2+ to enter the cells near resting potentials. In this way, Cav1.2 and Cav1.3 shape the action potential waveform, contribute to gene expression, synaptic plasticity, neuronal differentiation, hormone secretion and pacemaker activity. In the chromaffin cells (CCs) of the adrenal medulla, Cav1.3 is highly expressed and is shown to support most of the pacemaking current that sustains action potential (AP) firings and part of the catecholamine secretion. Cav1.3 forms Ca2+-nanodomains with the fast inactivating BK channels and drives the resting SK currents. These latter set the inter-spike interval duration between consecutive spikes during spontaneous firing and the rate of spike adaptation during sustained depolarizations. Cav1.3 plays also a primary role in the switch from “tonic” to “burst” firing that occurs in mouse CCs when either the availability of voltage-gated Na channels (Nav) is reduced or the β2 subunit featuring the fast inactivating BK channels is deleted. Here, we discuss the functional role of these “neuronlike” firing modes in CCs and how Cav1.3 contributes to them. The open issue is to understand how these novel firing patterns are adapted to regulate the quantity of circulating catecholamines during resting condition or in response to acute and chronic stress.}, author = {Vandael, David H and Marcantoni, Andrea and Carbone, Emilio}, journal = {Current Molecular Pharmacology}, number = {2}, pages = {149 -- 161}, publisher = {Bentham Science Publishers}, title = {{Cav1.3 channels as key regulators of neuron-like firings and catecholamine release in chromaffin cells}}, doi = {10.2174/1874467208666150507105443}, volume = {8}, year = {2015}, } @article{1542, abstract = {The theory of population genetics and evolutionary computation have been evolving separately for nearly 30 years. Many results have been independently obtained in both fields and many others are unique to its respective field. We aim to bridge this gap by developing a unifying framework for evolutionary processes that allows both evolutionary algorithms and population genetics models to be cast in the same formal framework. The framework we present here decomposes the evolutionary process into its several components in order to facilitate the identification of similarities between different models. In particular, we propose a classification of evolutionary operators based on the defining properties of the different components. We cast several commonly used operators from both fields into this common framework. Using this, we map different evolutionary and genetic algorithms to different evolutionary regimes and identify candidates with the most potential for the translation of results between the fields. This provides a unified description of evolutionary processes and represents a stepping stone towards new tools and results to both fields. }, author = {Paixao, Tiago and Badkobeh, Golnaz and Barton, Nicholas H and Çörüş, Doğan and Dang, Duccuong and Friedrich, Tobias and Lehre, Per and Sudholt, Dirk and Sutton, Andrew and Trubenova, Barbora}, journal = { Journal of Theoretical Biology}, pages = {28 -- 43}, publisher = {Elsevier}, title = {{Toward a unifying framework for evolutionary processes}}, doi = {10.1016/j.jtbi.2015.07.011}, volume = {383}, year = {2015}, } @article{1546, abstract = {Synaptic efficacy and precision are influenced by the coupling of voltage-gated Ca2+ channels (VGCCs) to vesicles. But because the topography of VGCCs and their proximity to vesicles is unknown, a quantitative understanding of the determinants of vesicular release at nanometer scale is lacking. To investigate this, we combined freeze-fracture replica immunogold labeling of Cav2.1 channels, local [Ca2+] imaging, and patch pipette perfusion of EGTA at the calyx of Held. Between postnatal day 7 and 21, VGCCs formed variable sized clusters and vesicular release became less sensitive to EGTA, whereas fixed Ca2+ buffer properties remained constant. Experimentally constrained reaction-diffusion simulations suggest that Ca2+ sensors for vesicular release are located at the perimeter of VGCC clusters (<30nm) and predict that VGCC number per cluster determines vesicular release probability without altering release time course. This "perimeter release model" provides a unifying framework accounting for developmental changes in both synaptic efficacy and time course.}, author = {Nakamura, Yukihiro and Harada, Harumi and Kamasawa, Naomi and Matsui, Ko and Rothman, Jason and Shigemoto, Ryuichi and Silver, R Angus and Digregorio, David and Takahashi, Tomoyuki}, journal = {Neuron}, number = {1}, pages = {145 -- 158}, publisher = {Elsevier}, title = {{Nanoscale distribution of presynaptic Ca2+ channels and its impact on vesicular release during development}}, doi = {10.1016/j.neuron.2014.11.019}, volume = {85}, year = {2015}, } @inbook{1544, abstract = {Cell division in prokaryotes and eukaryotes is commonly initiated by the well-controlled binding of proteins to the cytoplasmic side of the cell membrane. However, a precise characterization of the spatiotemporal dynamics of membrane-bound proteins is often difficult to achieve in vivo. Here, we present protocols for the use of supported lipid bilayers to rebuild the cytokinetic machineries of cells with greatly different dimensions: the bacterium Escherichia coli and eggs of the vertebrate Xenopus laevis. Combined with total internal reflection fluorescence microscopy, these experimental setups allow for precise quantitative analyses of membrane-bound proteins. The protocols described to obtain glass-supported membranes from bacterial and vertebrate lipids can be used as starting points for other reconstitution experiments. We believe that similar biochemical assays will be instrumental to study the biochemistry and biophysics underlying a variety of complex cellular tasks, such as signaling, vesicle trafficking, and cell motility.}, author = {Nguyen, Phuong and Field, Christine and Groen, Aaron and Mitchison, Timothy and Loose, Martin}, booktitle = {Building a Cell from its Components Parts}, pages = {223 -- 241}, publisher = {Academic Press}, title = {{Using supported bilayers to study the spatiotemporal organization of membrane-bound proteins}}, doi = {10.1016/bs.mcb.2015.01.007}, volume = {128}, year = {2015}, } @article{1551, abstract = {Reciprocal coevolution between host and pathogen is widely seen as a major driver of evolution and biological innovation. Yet, to date, the underlying genetic mechanisms and associated trait functions that are unique to rapid coevolutionary change are generally unknown. We here combined experimental evolution of the bacterial biocontrol agent Bacillus thuringiensis and its nematode host Caenorhabditis elegans with large-scale phenotyping, whole genome analysis, and functional genetics to demonstrate the selective benefit of pathogen virulence and the underlying toxin genes during the adaptation process. We show that: (i) high virulence was specifically favoured during pathogen–host coevolution rather than pathogen one-sided adaptation to a nonchanging host or to an environment without host; (ii) the pathogen genotype BT-679 with known nematocidal toxin genes and high virulence specifically swept to fixation in all of the independent replicate populations under coevolution but only some under one-sided adaptation; (iii) high virulence in the BT-679-dominated populations correlated with elevated copy numbers of the plasmid containing the nematocidal toxin genes; (iv) loss of virulence in a toxin-plasmid lacking BT-679 isolate was reconstituted by genetic reintroduction or external addition of the toxins.We conclude that sustained coevolution is distinct from unidirectional selection in shaping the pathogen's genome and life history characteristics. To our knowledge, this study is the first to characterize the pathogen genes involved in coevolutionary adaptation in an animal host–pathogen interaction system.}, author = {El Masri, Leila and Branca, Antoine and Sheppard, Anna and Papkou, Andrei and Laehnemann, David and Guenther, Patrick and Prahl, Swantje and Saebelfeld, Manja and Hollensteiner, Jacqueline and Liesegang, Heiko and Brzuszkiewicz, Elzbieta and Daniel, Rolf and Michiels, Nico and Schulte, Rebecca and Kurtz, Joachim and Rosenstiel, Philip and Telschow, Arndt and Bornberg Bauer, Erich and Schulenburg, Hinrich}, journal = {PLoS Biology}, number = {6}, pages = {1 -- 30}, publisher = {Public Library of Science}, title = {{Host–pathogen coevolution: The selective advantage of Bacillus thuringiensis virulence and its cry toxin genes}}, doi = {10.1371/journal.pbio.1002169}, volume = {13}, year = {2015}, } @inbook{1549, abstract = {Nature has incorporated small photochromic molecules, colloquially termed 'photoswitches', in photoreceptor proteins to sense optical cues in photo-taxis and vision. While Nature's ability to employ light-responsive functionalities has long been recognized, it was not until recently that scientists designed, synthesized and applied synthetic photochromes to manipulate many of which open rapidly and locally in their native cell types, biological processes with the temporal and spatial resolution of light. Ion channels in particular have come to the forefront of proteins that can be put under the designer control of synthetic photochromes. Photochromic ion channel controllers are comprised of three classes, photochromic soluble ligands (PCLs), photochromic tethered ligands (PTLs) and photochromic crosslinkers (PXs), and in each class ion channel functionality is controlled through reversible changes in photochrome structure. By acting as light-dependent ion channel agonists, antagonist or modulators, photochromic controllers effectively converted a wide range of ion channels, including voltage-gated ion channels, 'leak channels', tri-, tetra- and pentameric ligand-gated ion channels, and temperaturesensitive ion channels, into man-made photoreceptors. Control by photochromes can be reversible, unlike in the case of 'caged' compounds, and non-invasive with high spatial precision, unlike pharmacology and electrical manipulation. Here, we introduce design principles of emerging photochromic molecules that act on ion channels and discuss the impact that these molecules are beginning to have on ion channel biophysics and neuronal physiology.}, author = {Mckenzie, Catherine and Sanchez Romero, Inmaculada and Janovjak, Harald L}, booktitle = {Novel chemical tools to study ion channel biology}, isbn = {978-1-4939-2844-6}, pages = {101 -- 117}, publisher = {Springer}, title = {{Flipping the photoswitch: Ion channels under light control}}, doi = {10.1007/978-1-4939-2845-3_6}, volume = {869}, year = {2015}, } @article{1548, abstract = {Reproduction within a host and transmission to the next host are crucial for the virulence and fitness of pathogens. Nevertheless, basic knowledge about such parameters is often missing from the literature, even for well-studied bacteria, such as Bacillus thuringiensis, an endospore-forming insect pathogen, which infects its hosts via the oral route. To characterize bacterial replication success, we made use of an experimental oral infection system for the red flour beetle Tribolium castaneum and developed a flow cytometric assay for the quantification of both spore ingestion by the individual beetle larvae and the resulting spore load after bacterial replication and resporulation within cadavers. On average, spore numbers increased 460-fold, showing that Bacillus thuringiensis grows and replicates successfully in insect cadavers. By inoculating cadaver-derived spores and spores from bacterial stock cultures into nutrient medium, we next investigated outgrowth characteristics of vegetative cells and found that cadaver- derived bacteria showed reduced growth compared to bacteria from the stock cultures. Interestingly, this reduced growth was a consequence of inhibited spore germination, probably originating from the host and resulting in reduced host mortality in subsequent infections by cadaver-derived spores. Nevertheless, we further showed that Bacillus thuringiensis transmission was possible via larval cannibalism when no other food was offered. These results contribute to our understanding of the ecology of Bacillus thuringiensis as an insect pathogen.}, author = {Milutinovic, Barbara and Höfling, Christina and Futo, Momir and Scharsack, Jörn and Kurtz, Joachim}, journal = {Applied and Environmental Microbiology}, number = {23}, pages = {8135 -- 8144}, publisher = {American Society for Microbiology}, title = {{Infection of Tribolium castaneum with Bacillus thuringiensis: Quantification of bacterial replication within cadavers, transmission via cannibalism, and inhibition of spore germination}}, doi = {10.1128/AEM.02051-15}, volume = {81}, year = {2015}, } @article{1550, abstract = {The medial ganglionic eminence (MGE) gives rise to the majority of mouse forebrain interneurons. Here, we examine the lineage relationship among MGE-derived interneurons using a replication-defective retroviral library containing a highly diverse set of DNA barcodes. Recovering the barcodes from the mature progeny of infected progenitor cells enabled us to unambiguously determine their respective lineal relationship. We found that clonal dispersion occurs across large areas of the brain and is not restricted by anatomical divisions. As such, sibling interneurons can populate the cortex, hippocampus striatum, and globus pallidus. The majority of interneurons appeared to be generated from asymmetric divisions of MGE progenitor cells, followed by symmetric divisions within the subventricular zone. Altogether, our findings uncover that lineage relationships do not appear to determine interneuron allocation to particular regions. As such, it is likely that clonally related interneurons have considerable flexibility as to the particular forebrain circuits to which they can contribute.}, author = {Mayer, Christian and Jaglin, Xavier and Cobbs, Lucy and Bandler, Rachel and Streicher, Carmen and Cepko, Constance and Hippenmeyer, Simon and Fishell, Gord}, journal = {Neuron}, number = {5}, pages = {989 -- 998}, publisher = {Elsevier}, title = {{Clonally related forebrain interneurons disperse broadly across both functional areas and structural boundaries}}, doi = {10.1016/j.neuron.2015.07.011}, volume = {87}, year = {2015}, } @article{1547, abstract = {Let G be a graph on the vertex set V(G) = {x1,…,xn} with the edge set E(G), and let R = K[x1,…, xn] be the polynomial ring over a field K. Two monomial ideals are associated to G, the edge ideal I(G) generated by all monomials xixj with {xi,xj} ∈ E(G), and the vertex cover ideal IG generated by monomials ∏xi∈Cxi for all minimal vertex covers C of G. A minimal vertex cover of G is a subset C ⊂ V(G) such that each edge has at least one vertex in C and no proper subset of C has the same property. Indeed, the vertex cover ideal of G is the Alexander dual of the edge ideal of G. In this paper, for an unmixed bipartite graph G we consider the lattice of vertex covers LG and we explicitly describe the minimal free resolution of the ideal associated to LG which is exactly the vertex cover ideal of G. Then we compute depth, projective dimension, regularity and extremal Betti numbers of R/I(G) in terms of the associated lattice.}, author = {Mohammadi, Fatemeh and Moradi, Somayeh}, issn = {2234-3016}, journal = {Bulletin of the Korean Mathematical Society}, number = {3}, pages = {977 -- 986}, publisher = {Korean Mathematical Society}, title = {{Resolution of unmixed bipartite graphs}}, doi = {10.4134/BKMS.2015.52.3.977}, volume = {52}, year = {2015}, } @article{1556, abstract = {The elongator complex subunit 2 (ELP2) protein, one subunit of an evolutionarily conserved histone acetyltransferase complex, has been shown to participate in leaf patterning, plant immune and abiotic stress responses in Arabidopsis thaliana. Here, its role in root development was explored. Compared to the wild type, the elp2 mutant exhibited an accelerated differentiation of its root stem cells and cell division was more active in its quiescent centre (QC). The key transcription factors responsible for maintaining root stem cell and QC identity, such as AP2 transcription factors PLT1 (PLETHORA1) and PLT2 (PLETHORA2), GRAS transcription factors such as SCR (SCARECROW) and SHR (SHORT ROOT) and WUSCHEL-RELATED HOMEOBOX5 transcription factor WOX5, were all strongly down-regulated in the mutant. On the other hand, expression of the G2/M transition activator CYCB1 was substantially induced in elp2. The auxin efflux transporters PIN1 and PIN2 showed decreased protein levels and PIN1 also displayed mild polarity alterations in elp2, which resulted in a reduced auxin content in the root tip. Either the acetylation or methylation level of each of these genes differed between the mutant and the wild type, suggesting that the ELP2 regulation of root development involves the epigenetic modification of a range of transcription factors and other developmental regulators.}, author = {Jia, Yuebin and Tian, Huiyu and Li, Hongjiang and Yu, Qianqian and Wang, Lei and Friml, Jirí and Ding, Zhaojun}, journal = {Journal of Experimental Botany}, number = {15}, pages = {4631 -- 4642}, publisher = {Oxford University Press}, title = {{The Arabidopsis thaliana elongator complex subunit 2 epigenetically affects root development}}, doi = {10.1093/jxb/erv230}, volume = {66}, year = {2015}, } @article{1555, abstract = {We show that incorporating spatial dispersal of individuals into a simple vaccination epidemic model may give rise to a model that exhibits rich dynamical behavior. Using an SIVS (susceptible-infected-vaccinated-susceptible) model as a basis, we describe the spread of an infectious disease in a population split into two regions. In each subpopulation, both forward and backward bifurcations can occur. This implies that for disconnected regions the two-patch system may admit several steady states. We consider traveling between the regions and investigate the impact of spatial dispersal of individuals on the model dynamics. We establish conditions for the existence of multiple nontrivial steady states in the system, and we study the structure of the equilibria. The mathematical analysis reveals an unusually rich dynamical behavior, not normally found in the simple epidemic models. In addition to the disease-free equilibrium, eight endemic equilibria emerge from backward transcritical and saddle-node bifurcation points, forming an interesting bifurcation diagram. Stability of steady states, their bifurcations, and the global dynamics are investigated with analytical tools, numerical simulations, and rigorous set-oriented numerical computations.}, author = {Knipl, Diána and Pilarczyk, Pawel and Röst, Gergely}, issn = {1536-0040}, journal = {SIAM Journal on Applied Dynamical Systems}, number = {2}, pages = {980 -- 1017}, publisher = {Society for Industrial and Applied Mathematics }, title = {{Rich bifurcation structure in a two patch vaccination model}}, doi = {10.1137/140993934}, volume = {14}, year = {2015}, } @article{1559, abstract = {There are deep, yet largely unexplored, connections between computer science and biology. Both disciplines examine how information proliferates in time and space. Central results in computer science describe the complexity of algorithms that solve certain classes of problems. An algorithm is deemed efficient if it can solve a problem in polynomial time, which means the running time of the algorithm is a polynomial function of the length of the input. There are classes of harder problems for which the fastest possible algorithm requires exponential time. Another criterion is the space requirement of the algorithm. There is a crucial distinction between algorithms that can find a solution, verify a solution, or list several distinct solutions in given time and space. The complexity hierarchy that is generated in this way is the foundation of theoretical computer science. Precise complexity results can be notoriously difficult. The famous question whether polynomial time equals nondeterministic polynomial time (i.e., P = NP) is one of the hardest open problems in computer science and all of mathematics. Here, we consider simple processes of ecological and evolutionary spatial dynamics. The basic question is: What is the probability that a new invader (or a new mutant)will take over a resident population?We derive precise complexity results for a variety of scenarios. We therefore show that some fundamental questions in this area cannot be answered by simple equations (assuming that P is not equal to NP).}, author = {Ibsen-Jensen, Rasmus and Chatterjee, Krishnendu and Nowak, Martin}, journal = {PNAS}, number = {51}, pages = {15636 -- 15641}, publisher = {National Academy of Sciences}, title = {{Computational complexity of ecological and evolutionary spatial dynamics}}, doi = {10.1073/pnas.1511366112}, volume = {112}, year = {2015}, } @article{1554, abstract = {The visualization of hormonal signaling input and output is key to understanding how multicellular development is regulated. The plant signaling molecule auxin triggers many growth and developmental responses, but current tools lack the sensitivity or precision to visualize these. We developed a set of fluorescent reporters that allow sensitive and semiquantitative readout of auxin responses at cellular resolution in Arabidopsis thaliana. These generic tools are suitable for any transformable plant species.}, author = {Liao, Cheyang and Smet, Wouter and Brunoud, Géraldine and Yoshida, Saiko and Vernoux, Teva and Weijers, Dolf}, journal = {Nature Methods}, number = {3}, pages = {207 -- 210}, publisher = {Nature Publishing Group}, title = {{Reporters for sensitive and quantitative measurement of auxin response}}, doi = {10.1038/nmeth.3279}, volume = {12}, year = {2015}, }