TY - CONF AB - We show that the framework of topological data analysis can be extended from metrics to general Bregman divergences, widening the scope of possible applications. Examples are the Kullback - Leibler divergence, which is commonly used for comparing text and images, and the Itakura - Saito divergence, popular for speech and sound. In particular, we prove that appropriately generalized čech and Delaunay (alpha) complexes capture the correct homotopy type, namely that of the corresponding union of Bregman balls. Consequently, their filtrations give the correct persistence diagram, namely the one generated by the uniformly growing Bregman balls. Moreover, we show that unlike the metric setting, the filtration of Vietoris-Rips complexes may fail to approximate the persistence diagram. We propose algorithms to compute the thus generalized čech, Vietoris-Rips and Delaunay complexes and experimentally test their efficiency. Lastly, we explain their surprisingly good performance by making a connection with discrete Morse theory. AU - Edelsbrunner, Herbert AU - Wagner, Hubert ID - 688 SN - 18688969 TI - Topological data analysis with Bregman divergences VL - 77 ER - TY - JOUR AB - Pursuing the similarity between the Kontsevich-Soibelman construction of the cohomological Hall algebra (CoHA) of BPS states and Lusztig's construction of canonical bases for quantum enveloping algebras, and the similarity between the integrality conjecture for motivic Donaldson-Thomas invariants and the PBW theorem for quantum enveloping algebras, we build a coproduct on the CoHA associated to a quiver with potential. We also prove a cohomological dimensional reduction theorem, further linking a special class of CoHAs with Yangians, and explaining how to connect the study of character varieties with the study of CoHAs. AU - Davison, Ben ID - 687 IS - 2 JF - Quarterly Journal of Mathematics SN - 00335606 TI - The critical CoHA of a quiver with potential VL - 68 ER - TY - JOUR AB - Tissues are thought to behave like fluids with a given surface tension. Differences in tissue surface tension (TST) have been proposed to trigger cell sorting and tissue envelopment. D'Arcy Thompson in his seminal book ‘On Growth and Form’ has introduced this concept of differential TST as a key physical mechanism dictating tissue formation and organization within the developing organism. Over the past century, many studies have picked up the concept of differential TST and analyzed the role and cell biological basis of TST in development, underlining the importance and influence of this concept in developmental biology. AU - Heisenberg, Carl-Philipp J ID - 686 JF - Mechanisms of Development SN - 09254773 TI - D'Arcy Thompson's ‘on growth and form’: From soap bubbles to tissue self organization VL - 145 ER - TY - JOUR AB - Rett syndrome modeling in monkey mirrors the human disorder. AU - Novarino, Gaia ID - 689 IS - 393 JF - Science Translational Medicine SN - 19466234 TI - Rett syndrome modeling goes simian VL - 9 ER - TY - JOUR AB - Many central synapses contain a single presynaptic active zone and a single postsynaptic density. Vesicular release statistics at such “simple synapses” indicate that they contain a small complement of docking sites where vesicles repetitively dock and fuse. In this work, we investigate functional and morphological aspects of docking sites at simple synapses made between cerebellar parallel fibers and molecular layer interneurons. Using immunogold labeling of SDS-treated freeze-fracture replicas, we find that Cav2.1 channels form several clusters per active zone with about nine channels per cluster. The mean value and range of intersynaptic variation are similar for Cav2.1 cluster numbers and for functional estimates of docking-site numbers obtained from the maximum numbers of released vesicles per action potential. Both numbers grow in relation with synaptic size and decrease by a similar extent with age between 2 wk and 4 wk postnatal. Thus, the mean docking-site numbers were 3.15 at 2 wk (range: 1–10) and 2.03 at 4 wk (range: 1–4), whereas the mean numbers of Cav2.1 clusters were 2.84 at 2 wk (range: 1–8) and 2.37 at 4 wk (range: 1–5). These changes were accompanied by decreases of miniature current amplitude (from 93 pA to 56 pA), active-zone surface area (from 0.0427 μm2 to 0.0234 μm2), and initial success rate (from 0.609 to 0.353), indicating a tightening of synaptic transmission with development. Altogether, these results suggest a close correspondence between the number of functionally defined vesicular docking sites and that of clusters of voltage-gated calcium channels. AU - Miki, Takafumi AU - Kaufmann, Walter AU - Malagon, Gerardo AU - Gomez, Laura AU - Tabuchi, Katsuhiko AU - Watanabe, Masahiko AU - Shigemoto, Ryuichi AU - Marty, Alain ID - 693 IS - 26 JF - PNAS SN - 00278424 TI - Numbers of presynaptic Ca2+ channel clusters match those of functionally defined vesicular docking sites in single central synapses VL - 114 ER - TY - JOUR AB - A change regarding the extent of adhesion - hereafter referred to as adhesion plasticity - between adhesive and less-adhesive states of mammalian cells is important for their behavior. To investigate adhesion plasticity, we have selected a stable isogenic subpopulation of human MDA-MB-468 breast carcinoma cells growing in suspension. These suspension cells are unable to re-adhere to various matrices or to contract three-dimensional collagen lattices. By using transcriptome analysis, we identified the focal adhesion protein tensin3 (Tns3) as a determinant of adhesion plasticity. Tns3 is strongly reduced at mRNA and protein levels in suspension cells. Furthermore, by transiently challenging breast cancer cells to grow under non-adherent conditions markedly reduces Tns3 protein expression, which is regained upon re-adhesion. Stable knockdown of Tns3 in parental MDA-MB-468 cells results in defective adhesion, spreading and migration. Tns3-knockdown cells display impaired structure and dynamics of focal adhesion complexes as determined by immunostaining. Restoration of Tns3 protein expression in suspension cells partially rescues adhesion and focal contact composition. Our work identifies Tns3 as a crucial focal adhesion component regulated by, and functionally contributing to, the switch between adhesive and non-adhesive states in MDA-MB-468 cancer cells. AU - Veß, Astrid AU - Blache, Ulrich AU - Leitner, Laura AU - Kurz, Angela AU - Ehrenpfordt, Anja AU - Sixt, Michael K AU - Posern, Guido ID - 694 IS - 13 JF - Journal of Cell Science SN - 00219533 TI - A dual phenotype of MDA MB 468 cancer cells reveals mutual regulation of tensin3 and adhesion plasticity VL - 130 ER - TY - CONF AB - De, Trevisan and Tulsiani [CRYPTO 2010] show that every distribution over n-bit strings which has constant statistical distance to uniform (e.g., the output of a pseudorandom generator mapping n-1 to n bit strings), can be distinguished from the uniform distribution with advantage epsilon by a circuit of size O( 2^n epsilon^2). We generalize this result, showing that a distribution which has less than k bits of min-entropy, can be distinguished from any distribution with k bits of delta-smooth min-entropy with advantage epsilon by a circuit of size O(2^k epsilon^2/delta^2). As a special case, this implies that any distribution with support at most 2^k (e.g., the output of a pseudoentropy generator mapping k to n bit strings) can be distinguished from any given distribution with min-entropy k+1 with advantage epsilon by a circuit of size O(2^k epsilon^2). Our result thus shows that pseudoentropy distributions face basically the same non-uniform attacks as pseudorandom distributions. AU - Pietrzak, Krzysztof Z AU - Skórski, Maciej ID - 697 SN - 18688969 TI - Non uniform attacks against pseudoentropy VL - 80 ER - TY - JOUR AB - Extracellular matrix signals from the microenvironment regulate gene expression patterns and cell behavior. Using a combination of experiments and geometric models, we demonstrate correlations between cell geometry, three-dimensional (3D) organization of chromosome territories, and gene expression. Fluorescence in situ hybridization experiments showed that micropatterned fibroblasts cultured on anisotropic versus isotropic substrates resulted in repositioning of specific chromosomes, which contained genes that were differentially regulated by cell geometries. Experiments combined with ellipsoid packing models revealed that the mechanosensitivity of chromosomes was correlated with their orientation in the nucleus. Transcription inhibition experiments suggested that the intermingling degree was more sensitive to global changes in transcription than to chromosome radial positioning and its orientations. These results suggested that cell geometry modulated 3D chromosome arrangement, and their neighborhoods correlated with gene expression patterns in a predictable manner. This is central to understanding geometric control of genetic programs involved in cellular homeostasis and the associated diseases. AU - Wang, Yejun AU - Nagarajan, Mallika AU - Uhler, Caroline AU - Shivashankar, Gv ID - 698 IS - 14 JF - Molecular Biology of the Cell SN - 10591524 TI - Orientation and repositioning of chromosomes correlate with cell geometry dependent gene expression VL - 28 ER - TY - JOUR AB - In antagonistic symbioses, such as host–parasite interactions, one population’s success is the other’s loss. In mutualistic symbioses, such as division of labor, both parties can gain, but they might have different preferences over the possible mutualistic arrangements. The rates of evolution of the two populations in a symbiosis are important determinants of which population will be more successful: Faster evolution is thought to be favored in antagonistic symbioses (the “Red Queen effect”), but disfavored in certain mutualistic symbioses (the “Red King effect”). However, it remains unclear which biological parameters drive these effects. Here, we analyze the effects of the various determinants of evolutionary rate: generation time, mutation rate, population size, and the intensity of natural selection. Our main results hold for the case where mutation is infrequent. Slower evolution causes a long-term advantage in an important class of mutualistic interactions. Surprisingly, less intense selection is the strongest driver of this Red King effect, whereas relative mutation rates and generation times have little effect. In antagonistic interactions, faster evolution by any means is beneficial. Our results provide insight into the demographic evolution of symbionts. AU - Veller, Carl AU - Hayward, Laura AU - Nowak, Martin AU - Hilbe, Christian ID - 699 IS - 27 JF - PNAS SN - 00278424 TI - The red queen and king in finite populations VL - 114 ER - TY - JOUR AB - Microtubules provide the mechanical force required for chromosome separation during mitosis. However, little is known about the dynamic (high-frequency) mechanical properties of microtubules. Here, we theoretically propose to control the vibrations of a doubly clamped microtubule by tip electrodes and to detect its motion via the optomechanical coupling between the vibrational modes of the microtubule and an optical cavity. In the presence of a red-detuned strong pump laser, this coupling leads to optomechanical-induced transparency of an optical probe field, which can be detected with state-of-the art technology. The center frequency and line width of the transparency peak give the resonance frequency and damping rate of the microtubule, respectively, while the height of the peak reveals information about the microtubule-cavity field coupling. Our method opens the new possibilities to gain information about the physical properties of microtubules, which will enhance our capability to design physical cancer treatment protocols as alternatives to chemotherapeutic drugs. AU - Barzanjeh, Shabir AU - Salari, Vahid AU - Tuszynski, Jack AU - Cifra, Michal AU - Simon, Christoph ID - 700 IS - 1 JF - Physical Review E Statistical Nonlinear and Soft Matter Physics SN - 24700045 TI - Optomechanical proposal for monitoring microtubule mechanical vibrations VL - 96 ER - TY - JOUR AB - A d-dimensional simplex S is called a k-reptile (or a k-reptile simplex) if it can be tiled by k simplices with disjoint interiors that are all mutually congruent and similar to S. For d = 2, triangular k-reptiles exist for all k of the form a^2, 3a^2 or a^2+b^2 and they have been completely characterized by Snover, Waiveris, and Williams. On the other hand, the only k-reptile simplices that are known for d ≥ 3, have k = m^d, where m is a positive integer. We substantially simplify the proof by Matoušek and the second author that for d = 3, k-reptile tetrahedra can exist only for k = m^3. We then prove a weaker analogue of this result for d = 4 by showing that four-dimensional k-reptile simplices can exist only for k = m^2. AU - Kynčl, Jan AU - Patakova, Zuzana ID - 701 IS - 3 JF - The Electronic Journal of Combinatorics SN - 10778926 TI - On the nonexistence of k reptile simplices in ℝ^3 and ℝ^4 VL - 24 ER - TY - JOUR AB - Leading autism-associated mutation in mouse partially mimics human disorder. AU - Novarino, Gaia ID - 702 IS - 399 JF - Science Translational Medicine SN - 19466234 TI - The riddle of CHD8 haploinsufficiency in autism spectrum disorder VL - 9 ER - TY - JOUR AB - A hippocampal mossy fiber synapse has a complex structure and is implicated in learning and memory. In this synapse, the mossy fiber boutons attach to the dendritic shaft by puncta adherentia junctions and wrap around a multiply-branched spine, forming synaptic junctions. We have recently shown using transmission electron microscopy, immunoelectron microscopy and serial block face-scanning electron microscopy that atypical puncta adherentia junctions are formed in the afadin-deficient mossy fiber synapse and that the complexity of postsynaptic spines and mossy fiber boutons, the number of spine heads, the area of postsynaptic densities and the density of synaptic vesicles docked to active zones are decreased in the afadin-deficient synapse. We investigated here the roles of afadin in the functional differentiations of the mossy fiber synapse using the afadin-deficient mice. The electrophysiological studies showed that both the release probability of glutamate and the postsynaptic responsiveness to glutamate were markedly reduced, but not completely lost, in the afadin-deficient mossy fiber synapse, whereas neither long-term potentiation nor long-term depression was affected. These results indicate that afadin plays roles in the functional differentiations of the presynapse and the postsynapse of the hippocampal mossy fiber synapse. AU - Geng, Xiaoqi AU - Maruo, Tomohiko AU - Mandai, Kenji AU - Supriyanto, Irwan AU - Miyata, Muneaki AU - Sakakibara, Shotaro AU - Mizoguchi, Akira AU - Takai, Yoshimi AU - Mori, Masahiro ID - 706 IS - 8 JF - Genes to Cells SN - 13569597 TI - Roles of afadin in functional differentiations of hippocampal mossy fiber synapse VL - 22 ER - TY - JOUR AB - We answer a question of M. Gromov on the waist of the unit ball. AU - Akopyan, Arseniy AU - Karasev, Roman ID - 707 IS - 4 JF - Bulletin of the London Mathematical Society SN - 00246093 TI - A tight estimate for the waist of the ball VL - 49 ER - TY - JOUR AB - In the developing and adult brain, oligodendrocyte precursor cells (OPCs) are influenced by neuronal activity: they are involved in synaptic signaling with neurons, and their proliferation and differentiation into myelinating glia can be altered by transient changes in neuronal firing. An important question that has been unanswered is whether OPCs can discriminate different patterns of neuronal activity and respond to them in a distinct way. Here, we demonstrate in brain slices that the pattern of neuronal activity determines the functional changes triggered at synapses between axons and OPCs. Furthermore, we show that stimulation of the corpus callosum at different frequencies in vivo affects proliferation and differentiation of OPCs in a dissimilar way. Our findings suggest that neurons do not influence OPCs in “all-or-none” fashion but use their firing pattern to tune the response and behavior of these nonneuronal cells. AU - Nagy, Balint AU - Hovhannisyan, Anahit AU - Barzan, Ruxandra AU - Chen, Ting AU - Kukley, Maria ID - 708 IS - 8 JF - PLoS Biology SN - 15449173 TI - Different patterns of neuronal activity trigger distinct responses of oligodendrocyte precursor cells in the corpus callosum VL - 15 ER - TY - JOUR AB - Adipose tissues play key roles in energy homeostasis. Brown adipocytes and beige adipocytes in white adipose tissue (WAT) share the similar characters of thermogenesis, both of them could be potential targets for obesity management. Several thermo-sensitive transient receptor potential channels (thermoTRPs) are shown to be involved in adipocyte biology. However, the expression pattern of thermoTRPs in adipose tissues from obese mice is still unknown. The mRNA expression of thermoTRPs in subcutaneous WAT (sWAT) and interscapular brown adipose tissue (iBAT) from lean and obese mice were measured using reverse transcriptase-quantitative PCRs (RT-qPCR). The results demonstrated that all 10 thermoTRPs are expressed in both iBAT and sWAT, and without significant difference in the mRNA expression level of thermoTRPs between these two tissues. Moreover, Trpv1 and Trpv3 mRNA expression levels in both iBAT and sWAT were significantly decreased in high fat diet (HFD)-induced obese mice and db/db (leptin receptor deficient) mice. Trpm2 mRNA expression level was significantly decreased only in sWAT from HFD-induced obese mice and db/db mice. On the other hand, Trpv2 and Trpv4 mRNA expression levels in iBAT and sWAT were significantly increased in HFD-induced obese mice and db/db mice. Taken together, we conclude that all 10 thermoTRPs are expressed in iBAT and sWAT. And several thermoTRPs differentially expressed in adipose tissues from HFD-induced obese mice and db/db mice, suggesting a potential involvement in anti-obesity regulations. AU - Sun, Wuping AU - Li, Chen AU - Zhang, Yonghong AU - Jiang, Changyu AU - Zhai, Ming-Zhu AU - Zhou, Qian AU - Xiao, Lizu AU - Deng, Qiwen ID - 709 IS - 8 JF - Cell Biology International SN - 10656995 TI - Gene expression changes of thermo sensitive transient receptor potential channels in obese mice VL - 41 ER - TY - CONF AB - We revisit the problem of estimating entropy of discrete distributions from independent samples, studied recently by Acharya, Orlitsky, Suresh and Tyagi (SODA 2015), improving their upper and lower bounds on the necessary sample size n. For estimating Renyi entropy of order alpha, up to constant accuracy and error probability, we show the following * Upper bounds n = O(1) 2^{(1-1/alpha)H_alpha} for integer alpha>1, as the worst case over distributions with Renyi entropy equal to H_alpha. * Lower bounds n = Omega(1) K^{1-1/alpha} for any real alpha>1, with the constant being an inverse polynomial of the accuracy, as the worst case over all distributions on K elements. Our upper bounds essentially replace the alphabet size by a factor exponential in the entropy, which offers improvements especially in low or medium entropy regimes (interesting for example in anomaly detection). As for the lower bounds, our proof explicitly shows how the complexity depends on both alphabet and accuracy, partially solving the open problem posted in previous works. The argument for upper bounds derives a clean identity for the variance of falling-power sum of a multinomial distribution. Our approach for lower bounds utilizes convex optimization to find a distribution with possibly worse estimation performance, and may be of independent interest as a tool to work with Le Cam’s two point method. AU - Obremski, Maciej AU - Skórski, Maciej ID - 710 SN - 18688969 TI - Renyi entropy estimation revisited VL - 81 ER - TY - JOUR AB - To determine the dynamics of allelic-specific expression during mouse development, we analyzed RNA-seq data from 23 F1 tissues from different developmental stages, including 19 female tissues allowing X chromosome inactivation (XCI) escapers to also be detected. We demonstrate that allelic expression arising from genetic or epigenetic differences is highly tissue-specific. We find that tissue-specific strain-biased gene expression may be regulated by tissue-specific enhancers or by post-transcriptional differences in stability between the alleles. We also find that escape from X-inactivation is tissue-specific, with leg muscle showing an unexpectedly high rate of XCI escapers. By surveying a range of tissues during development, and performing extensive validation, we are able to provide a high confidence list of mouse imprinted genes including 18 novel genes. This shows that cluster size varies dynamically during development and can be substantially larger than previously thought, with the Igf2r cluster extending over 10 Mb in placenta. AU - Andergassen, Daniel AU - Dotter, Christoph AU - Wenzel, Dyniel AU - Sigl, Verena AU - Bammer, Philipp AU - Muckenhuber, Markus AU - Mayer, Daniela AU - Kulinski, Tomasz AU - Theussl, Hans AU - Penninger, Josef AU - Bock, Christoph AU - Barlow, Denise AU - Pauler, Florian AU - Hudson, Quanah ID - 713 JF - eLife SN - 2050084X TI - Mapping the mouse Allelome reveals tissue specific regulation of allelic expression VL - 6 ER - TY - CONF AB - Nested weighted automata (NWA) present a robust and convenient automata-theoretic formalism for quantitative specifications. Previous works have considered NWA that processed input words only in the forward direction. It is natural to allow the automata to process input words backwards as well, for example, to measure the maximal or average time between a response and the preceding request. We therefore introduce and study bidirectional NWA that can process input words in both directions. First, we show that bidirectional NWA can express interesting quantitative properties that are not expressible by forward-only NWA. Second, for the fundamental decision problems of emptiness and universality, we establish decidability and complexity results for the new framework which match the best-known results for the special case of forward-only NWA. Thus, for NWA, the increased expressiveness of bidirectionality is achieved at no additional computational complexity. This is in stark contrast to the unweighted case, where bidirectional finite automata are no more expressive but exponentially more succinct than their forward-only counterparts. AU - Chatterjee, Krishnendu AU - Henzinger, Thomas A AU - Otop, Jan ID - 711 SN - 18688969 TI - Bidirectional nested weighted automata VL - 85 ER - TY - JOUR AB - We establish a weak–strong uniqueness principle for solutions to entropy-dissipating reaction–diffusion equations: As long as a strong solution to the reaction–diffusion equation exists, any weak solution and even any renormalized solution must coincide with this strong solution. Our assumptions on the reaction rates are just the entropy condition and local Lipschitz continuity; in particular, we do not impose any growth restrictions on the reaction rates. Therefore, our result applies to any single reversible reaction with mass-action kinetics as well as to systems of reversible reactions with mass-action kinetics satisfying the detailed balance condition. Renormalized solutions are known to exist globally in time for reaction–diffusion equations with entropy-dissipating reaction rates; in contrast, the global-in-time existence of weak solutions is in general still an open problem–even for smooth data–, thereby motivating the study of renormalized solutions. The key ingredient of our result is a careful adjustment of the usual relative entropy functional, whose evolution cannot be controlled properly for weak solutions or renormalized solutions. AU - Fischer, Julian L ID - 712 JF - Nonlinear Analysis: Theory, Methods and Applications SN - 0362546X TI - Weak–strong uniqueness of solutions to entropy dissipating reaction–diffusion equations VL - 159 ER -