TY - JOUR AB - We analyze a disordered central spin model, where a central spin interacts equally with each spin in a periodic one-dimensional (1D) random-field Heisenberg chain. If the Heisenberg chain is initially in the many-body localized (MBL) phase, we find that the coupling to the central spin suffices to delocalize the chain for a substantial range of coupling strengths. We calculate the phase diagram of the model and identify the phase boundary between the MBL and ergodic phase. Within the localized phase, the central spin significantly enhances the rate of the logarithmic entanglement growth and its saturation value. We attribute the increase in entanglement entropy to a nonextensive enhancement of magnetization fluctuations induced by the central spin. Finally, we demonstrate that correlation functions of the central spin can be utilized to distinguish between MBL and ergodic phases of the 1D chain. Hence, we propose the use of a central spin as a possible experimental probe to identify the MBL phase. AU - Hetterich, Daniel AU - Yao, Norman AU - Serbyn, Maksym AU - Pollmann, Frank AU - Trauzettel, Björn ID - 46 IS - 16 JF - Physical Review B TI - Detection and characterization of many-body localization in central spin models VL - 98 ER - TY - JOUR AB - Migrating cells penetrate tissue barriers during development, inflammatory responses, and tumor metastasis. We study if migration in vivo in such three-dimensionally confined environments requires changes in the mechanical properties of the surrounding cells using embryonic Drosophila melanogaster hemocytes, also called macrophages, as a model. We find that macrophage invasion into the germband through transient separation of the apposing ectoderm and mesoderm requires cell deformations and reductions in apical tension in the ectoderm. Interestingly, the genetic pathway governing these mechanical shifts acts downstream of the only known tumor necrosis factor superfamily member in Drosophila, Eiger, and its receptor, Grindelwald. Eiger-Grindelwald signaling reduces levels of active Myosin in the germband ectodermal cortex through the localization of a Crumbs complex component, Patj (Pals-1-associated tight junction protein). We therefore elucidate a distinct molecular pathway that controls tissue tension and demonstrate the importance of such regulation for invasive migration in vivo. AU - Ratheesh, Aparna AU - Biebl, Julia AU - Smutny, Michael AU - Veselá, Jana AU - Papusheva, Ekaterina AU - Krens, Gabriel AU - Kaufmann, Walter AU - György, Attila AU - Casano, Alessandra M AU - Siekhaus, Daria E ID - 308 IS - 3 JF - Developmental Cell TI - Drosophila TNF modulates tissue tension in the embryo to facilitate macrophage invasive migration VL - 45 ER - TY - JOUR AB - Creeping flow of polymeric fluid without inertia exhibits elastic instabilities and elastic turbulence accompanied by drag enhancement due to elastic stress produced by flow-stretched polymers. However, in inertia-dominated flow at high Re and low fluid elasticity El, a reduction in turbulent frictional drag is caused by an intricate competition between inertial and elastic stresses. Here we explore the effect of inertia on the stability of viscoelastic flow in a broad range of control parameters El and (Re,Wi). We present the stability diagram of observed flow regimes in Wi-Re coordinates and find that the instabilities' onsets show an unexpectedly nonmonotonic dependence on El. Further, three distinct regions in the diagram are identified based on El. Strikingly, for high-elasticity fluids we discover a complete relaminarization of flow at Reynolds number in the range of 1 to 10, different from a well-known turbulent drag reduction. These counterintuitive effects may be explained by a finite polymer extensibility and a suppression of vorticity at high Wi. Our results call for further theoretical and numerical development to uncover the role of inertial effect on elastic turbulence in a viscoelastic flow. AU - Varshney, Atul AU - Steinberg, Victor ID - 17 IS - 10 JF - Physical Review Fluids TI - Drag enhancement and drag reduction in viscoelastic flow VL - 3 ER - TY - JOUR AB - Although cells respond specifically to environments, how environmental identity is encoded intracellularly is not understood. Here, we study this organization of information in budding yeast by estimating the mutual information between environmental transitions and the dynamics of nuclear translocation for 10 transcription factors. Our method of estimation is general, scalable, and based on decoding from single cells. The dynamics of the transcription factors are necessary to encode the highest amounts of extracellular information, and we show that information is transduced through two channels: Generalists (Msn2/4, Tod6 and Dot6, Maf1, and Sfp1) can encode the nature of multiple stresses, but only if stress is high; specialists (Hog1, Yap1, and Mig1/2) encode one particular stress, but do so more quickly and for a wider range of magnitudes. In particular, Dot6 encodes almost as much information as Msn2, the master regulator of the environmental stress response. Each transcription factor reports differently, and it is only their collective behavior that distinguishes between multiple environmental states. Changes in the dynamics of the localization of transcription factors thus constitute a precise, distributed internal representation of extracellular change. We predict that such multidimensional representations are common in cellular decision-making. AU - Granados, Alejandro AU - Pietsch, Julian AU - Cepeda Humerez, Sarah A AU - Farquhar, Isebail AU - Tkacik, Gasper AU - Swain, Peter ID - 281 IS - 23 JF - PNAS TI - Distributed and dynamic intracellular organization of extracellular information VL - 115 ER - TY - JOUR AB - Clathrin-mediated endocytosis requires the coordinated assembly of various endocytic proteins and lipids at the plasma membrane. Accumulating evidence demonstrates a crucial role for phosphatidylinositol-4,5-bisphosphate (PtdIns(4,5)P2) in endocytosis, but specific roles for PtdIns(4)P other than as the biosynthetic precursor of PtdIns(4,5)P2 have not been clarified. In this study we investigated the role of PtdIns(4)P or PtdIns(4,5)P2 in receptor-mediated endocytosis through the construction of temperature-sensitive (ts) mutants for the PI 4-kinases Stt4p and Pik1p and the PtdIns(4) 5-kinase Mss4p. Quantitative analyses of endocytosis revealed that both the stt4(ts)pik1(ts) and mss4(ts) mutants have a severe defect in endocytic internalization. Live-cell imaging of endocytic protein dynamics in stt4(ts)pik1(ts) and mss4(ts) mutants revealed that PtdIns(4)P is required for the recruitment of the alpha-factor receptor Ste2p to clathrin-coated pits whereas PtdIns(4,5)P2 is required for membrane internalization. We also found that the localization to endocytic sites of the ENTH/ANTH domain-bearing clathrin adaptors, Ent1p/Ent2p and Yap1801p/Yap1802p, is significantly impaired in the stt4(ts)pik1(ts) mutant, but not in the mss4(ts) mutant. These results suggest distinct roles in successive steps for PtdIns(4)P and PtdIns(4,5)P2 during receptor-mediated endocytosis. AU - Yamamoto, Wataru AU - Wada, Suguru AU - Nagano, Makoto AU - Aoshima, Kaito AU - Siekhaus, Daria E AU - Toshima, Junko AU - Toshima, Jiro ID - 620 IS - 1 JF - Journal of Cell Science TI - Distinct roles for plasma membrane PtdIns 4 P and PtdIns 4 5 P2 during yeast receptor mediated endocytosis VL - 131 ER - TY - CONF AB - We describe a new algorithm for the parametric identification problem for signal temporal logic (STL), stated as follows. Given a densetime real-valued signal w and a parameterized temporal logic formula φ, compute the subset of the parameter space that renders the formula satisfied by the signal. Unlike previous solutions, which were based on search in the parameter space or quantifier elimination, our procedure works recursively on φ and computes the evolution over time of the set of valid parameter assignments. This procedure is similar to that of monitoring or computing the robustness of φ relative to w. Our implementation and experiments demonstrate that this approach can work well in practice. AU - Bakhirkin, Alexey AU - Ferrere, Thomas AU - Maler, Oded ID - 182 SN - 978-1-4503-5642-8 T2 - Proceedings of the 21st International Conference on Hybrid Systems TI - Efficient parametric identification for STL ER - TY - CONF AB - Vector Addition Systems with States (VASS) provide a well-known and fundamental model for the analysis of concurrent processes, parameterized systems, and are also used as abstract models of programs in resource bound analysis. In this paper we study the problem of obtaining asymptotic bounds on the termination time of a given VASS. In particular, we focus on the practically important case of obtaining polynomial bounds on termination time. Our main contributions are as follows: First, we present a polynomial-time algorithm for deciding whether a given VASS has a linear asymptotic complexity. We also show that if the complexity of a VASS is not linear, it is at least quadratic. Second, we classify VASS according to quantitative properties of their cycles. We show that certain singularities in these properties are the key reason for non-polynomial asymptotic complexity of VASS. In absence of singularities, we show that the asymptotic complexity is always polynomial and of the form Θ(nk), for some integer k d, where d is the dimension of the VASS. We present a polynomial-time algorithm computing the optimal k. For general VASS, the same algorithm, which is based on a complete technique for the construction of ranking functions in VASS, produces a valid lower bound, i.e., a k such that the termination complexity is (nk). Our results are based on new insights into the geometry of VASS dynamics, which hold the potential for further applicability to VASS analysis. AU - Brázdil, Tomáš AU - Chatterjee, Krishnendu AU - Kučera, Antonín AU - Novotny, Petr AU - Velan, Dominik AU - Zuleger, Florian ID - 143 SN - 978-1-4503-5583-4 TI - Efficient algorithms for asymptotic bounds on termination time in VASS VL - F138033 ER - TY - CONF AB - The accuracy of information retrieval systems is often measured using complex loss functions such as the average precision (AP) or the normalized discounted cumulative gain (NDCG). Given a set of positive and negative samples, the parameters of a retrieval system can be estimated by minimizing these loss functions. However, the non-differentiability and non-decomposability of these loss functions does not allow for simple gradient based optimization algorithms. This issue is generally circumvented by either optimizing a structured hinge-loss upper bound to the loss function or by using asymptotic methods like the direct-loss minimization framework. Yet, the high computational complexity of loss-augmented inference, which is necessary for both the frameworks, prohibits its use in large training data sets. To alleviate this deficiency, we present a novel quicksort flavored algorithm for a large class of non-decomposable loss functions. We provide a complete characterization of the loss functions that are amenable to our algorithm, and show that it includes both AP and NDCG based loss functions. Furthermore, we prove that no comparison based algorithm can improve upon the computational complexity of our approach asymptotically. We demonstrate the effectiveness of our approach in the context of optimizing the structured hinge loss upper bound of AP and NDCG loss for learning models for a variety of vision tasks. We show that our approach provides significantly better results than simpler decomposable loss functions, while requiring a comparable training time. AU - Mohapatra, Pritish AU - Rolinek, Michal AU - Jawahar, C V AU - Kolmogorov, Vladimir AU - Kumar, M Pawan ID - 273 SN - 9781538664209 T2 - 2018 IEEE/CVF Conference on Computer Vision and Pattern Recognition TI - Efficient optimization for rank-based loss functions ER - TY - JOUR AB - We report on quantum capacitance measurements of high quality, graphite- and hexagonal boron nitride encapsulated Bernal stacked trilayer graphene devices. At zero applied magnetic field, we observe a number of electron density- and electrical displacement-tuned features in the electronic compressibility associated with changes in Fermi surface topology. At high displacement field and low density, strong trigonal warping gives rise to emergent Dirac gullies centered near the corners of the hexagonal Brillouin and related by three fold rotation symmetry. At low magnetic fields of B=1.25~T, the gullies manifest as a change in the degeneracy of the Landau levels from two to three. Weak incompressible states are also observed at integer filling within these triplets Landau levels, which a Hartree-Fock analysis indicates are associated with Coulomb-driven nematic phases that spontaneously break rotation symmetry. AU - Zibrov, Alexander AU - Peng, Rao AU - Kometter, Carlos AU - Li, Jia AU - Dean, Cory AU - Taniguchi, Takashi AU - Watanabe, Kenji AU - Serbyn, Maksym AU - Young, Andrea ID - 289 IS - 16 JF - Physical Review Letters TI - Emergent dirac gullies and gully-symmetry-breaking quantum hall states in ABA trilayer graphene VL - 121 ER - TY - JOUR AB - In this paper, we discuss biological effects of electromagnetic (EM) fields in the context of cancer biology. In particular, we review the nanomechanical properties of microtubules (MTs), the latter being one of the most successful targets for cancer therapy. We propose an investigation on the coupling of electromagnetic radiation to mechanical vibrations of MTs as an important basis for biological and medical applications. In our opinion, optomechanical methods can accurately monitor and control the mechanical properties of isolated MTs in a liquid environment. Consequently, studying nanomechanical properties of MTs may give useful information for future applications to diagnostic and therapeutic technologies involving non-invasive externally applied physical fields. For example, electromagnetic fields or high intensity ultrasound can be used therapeutically avoiding harmful side effects of chemotherapeutic agents or classical radiation therapy. AU - Salari, Vahid AU - Barzanjeh, Shabir AU - Cifra, Michal AU - Simon, Christoph AU - Scholkmann, Felix AU - Alirezaei, Zahra AU - Tuszynski, Jack ID - 287 IS - 8 JF - Frontiers in Bioscience - Landmark TI - Electromagnetic fields and optomechanics In cancer diagnostics and treatment VL - 23 ER - TY - JOUR AB - We show that the following algorithmic problem is decidable: given a 2-dimensional simplicial complex, can it be embedded (topologically, or equivalently, piecewise linearly) in R3? By a known reduction, it suffices to decide the embeddability of a given triangulated 3-manifold X into the 3-sphere S3. The main step, which allows us to simplify X and recurse, is in proving that if X can be embedded in S3, then there is also an embedding in which X has a short meridian, that is, an essential curve in the boundary of X bounding a disk in S3 \ X with length bounded by a computable function of the number of tetrahedra of X. AU - Matoušek, Jiří AU - Sedgwick, Eric AU - Tancer, Martin AU - Wagner, Uli ID - 425 IS - 1 JF - Journal of the ACM TI - Embeddability in the 3-Sphere is decidable VL - 65 ER - TY - JOUR AB - Maladapted individuals can only colonise a new habitat if they can evolve a positive growth rate fast enough to avoid extinction, a process known as evolutionary rescue. We treat log fitness at low density in the new habitat as a single polygenic trait and thus use the infinitesimal model to follow the evolution of the growth rate; this assumes that the trait values of offspring of a sexual union are normally distributed around the mean of the parents’ trait values, with variance that depends only on the parents’ relatedness. The probability that a single migrant can establish depends on just two parameters: the mean and genetic variance of the trait in the source population. The chance of success becomes small if migrants come from a population with mean growth rate in the new habitat more than a few standard deviations below zero; this chance depends roughly equally on the probability that the initial founder is unusually fit, and on the subsequent increase in growth rate of its offspring as a result of selection. The loss of genetic variation during the founding event is substantial, but highly variable. With continued migration at rate M, establishment is inevitable; when migration is rare, the expected time to establishment decreases inversely with M. However, above a threshold migration rate, the population may be trapped in a ‘sink’ state, in which adaptation is held back by gene flow; above this threshold, the expected time to establishment increases exponentially with M. This threshold behaviour is captured by a deterministic approximation, which assumes a Gaussian distribution of the trait in the founder population with mean and variance evolving deterministically. By assuming a constant genetic variance, we also develop a diffusion approximation for the joint distribution of population size and trait mean, which extends to include stabilising selection and density regulation. Divergence of the population from its ancestors causes partial reproductive isolation, which we measure through the reproductive value of migrants into the newly established population. AU - Barton, Nicholas H AU - Etheridge, Alison ID - 564 IS - 7 JF - Theoretical Population Biology TI - Establishment in a new habitat by polygenic adaptation VL - 122 ER - TY - JOUR AB - Social dilemmas occur when incentives for individuals are misaligned with group interests 1-7 . According to the 'tragedy of the commons', these misalignments can lead to overexploitation and collapse of public resources. The resulting behaviours can be analysed with the tools of game theory 8 . The theory of direct reciprocity 9-15 suggests that repeated interactions can alleviate such dilemmas, but previous work has assumed that the public resource remains constant over time. Here we introduce the idea that the public resource is instead changeable and depends on the strategic choices of individuals. An intuitive scenario is that cooperation increases the public resource, whereas defection decreases it. Thus, cooperation allows the possibility of playing a more valuable game with higher payoffs, whereas defection leads to a less valuable game. We analyse this idea using the theory of stochastic games 16-19 and evolutionary game theory. We find that the dependence of the public resource on previous interactions can greatly enhance the propensity for cooperation. For these results, the interaction between reciprocity and payoff feedback is crucial: neither repeated interactions in a constant environment nor single interactions in a changing environment yield similar cooperation rates. Our framework shows which feedbacks between exploitation and environment - either naturally occurring or designed - help to overcome social dilemmas. AU - Hilbe, Christian AU - Šimsa, Štepán AU - Chatterjee, Krishnendu AU - Nowak, Martin ID - 157 IS - 7713 JF - Nature TI - Evolution of cooperation in stochastic games VL - 559 ER - TY - JOUR AB - Can orthologous proteins differ in terms of their ability to be secreted? To answer this question, we investigated the distribution of signal peptides within the orthologous groups of Enterobacterales. Parsimony analysis and sequence comparisons revealed a large number of signal peptide gain and loss events, in which signal peptides emerge or disappear in the course of evolution. Signal peptide losses prevail over gains, an effect which is especially pronounced in the transition from the free-living or commensal to the endosymbiotic lifestyle. The disproportionate decline in the number of signal peptide-containing proteins in endosymbionts cannot be explained by the overall reduction of their genomes. Signal peptides can be gained and lost either by acquisition/elimination of the corresponding N-terminal regions or by gradual accumulation of mutations. The evolutionary dynamics of signal peptides in bacterial proteins represents a powerful mechanism of functional diversification. AU - Hönigschmid, Peter AU - Bykova, Nadya AU - Schneider, René AU - Ivankov, Dmitry AU - Frishman, Dmitrij ID - 384 IS - 3 JF - Genome Biology and Evolution TI - Evolutionary interplay between symbiotic relationships and patterns of signal peptide gain and loss VL - 10 ER - TY - JOUR AB - In continuous populations with local migration, nearby pairs of individuals have on average more similar genotypes than geographically well separated pairs. A barrier to gene flow distorts this classical pattern of isolation by distance. Genetic similarity is decreased for sample pairs on different sides of the barrier and increased for pairs on the same side near the barrier. Here, we introduce an inference scheme that utilizes this signal to detect and estimate the strength of a linear barrier to gene flow in two-dimensions. We use a diffusion approximation to model the effects of a barrier on the geographical spread of ancestry backwards in time. This approach allows us to calculate the chance of recent coalescence and probability of identity by descent. We introduce an inference scheme that fits these theoretical results to the geographical covariance structure of bialleleic genetic markers. It can estimate the strength of the barrier as well as several demographic parameters. We investigate the power of our inference scheme to detect barriers by applying it to a wide range of simulated data. We also showcase an example application to a Antirrhinum majus (snapdragon) flower color hybrid zone, where we do not detect any signal of a strong genome wide barrier to gene flow. AU - Ringbauer, Harald AU - Kolesnikov, Alexander AU - Field, David AU - Barton, Nicholas H ID - 563 IS - 3 JF - Genetics TI - Estimating barriers to gene flow from distorted isolation-by-distance patterns VL - 208 ER - TY - JOUR AB - The Fluid Implicit Particle method (FLIP) reduces numerical dissipation by combining particles with grids. To improve performance, the subsequent narrow band FLIP method (NB‐FLIP) uses a FLIP‐based fluid simulation only near the liquid surface and a traditional grid‐based fluid simulation away from the surface. This spatially‐limited FLIP simulation significantly reduces the number of particles and alleviates a computational bottleneck. In this paper, we extend the NB‐FLIP idea even further, by allowing a simulation to transition between a FLIP‐like fluid simulation and a grid‐based simulation in arbitrary locations, not just near the surface. This approach leads to even more savings in memory and computation, because we can concentrate the particles only in areas where they are needed. More importantly, this new method allows us to seamlessly transition to smooth implicit surface geometry wherever the particle‐based simulation is unnecessary. Consequently, our method leads to a practical algorithm for avoiding the noisy surface artifacts associated with particle‐based liquid simulations, while simultaneously maintaining the benefits of a FLIP simulation in regions of dynamic motion. AU - Sato, Takahiro AU - Wojtan, Christopher J AU - Thuerey, Nils AU - Igarashi, Takeo AU - Ando, Ryoichi ID - 135 IS - 2 JF - Computer Graphics Forum SN - 0167-7055 TI - Extended narrow band FLIP for liquid simulations VL - 37 ER - TY - JOUR AB - Self-incompatibility (SI) is a genetically based recognition system that functions to prevent self-fertilization and mating among related plants. An enduring puzzle in SI is how the high diversity observed in nature arises and is maintained. Based on the underlying recognition mechanism, SI can be classified into two main groups: self- and non-self recognition. Most work has focused on diversification within self-recognition systems despite expected differences between the two groups in the evolutionary pathways and outcomes of diversification. Here, we use a deterministic population genetic model and stochastic simulations to investigate how novel S-haplotypes evolve in a gametophytic non-self recognition (SRNase/S Locus F-box (SLF)) SI system. For this model the pathways for diversification involve either the maintenance or breakdown of SI and can vary in the order of mutations of the female (SRNase) and male (SLF) components. We show analytically that diversification can occur with high inbreeding depression and self-pollination, but this varies with evolutionary pathway and level of completeness (which determines the number of potential mating partners in the population), and in general is more likely for lower haplotype number. The conditions for diversification are broader in stochastic simulations of finite population size. However, the number of haplotypes observed under high inbreeding and moderate to high self-pollination is less than that commonly observed in nature. Diversification was observed through pathways that maintain SI as well as through self-compatible intermediates. Yet the lifespan of diversified haplotypes was sensitive to their level of completeness. By examining diversification in a non-self recognition SI system, this model extends our understanding of the evolution and maintenance of haplotype diversity observed in a self recognition system common in flowering plants. AU - Bodova, Katarina AU - Priklopil, Tadeas AU - Field, David AU - Barton, Nicholas H AU - Pickup, Melinda ID - 316 IS - 3 JF - Genetics TI - Evolutionary pathways for the generation of new self-incompatibility haplotypes in a non-self recognition system VL - 209 ER - TY - JOUR AB - The German cockroach, Blattella germanica, is a worldwide pest that infests buildings, including homes, restaurants, and hospitals, often living in unsanitary conditions. As a disease vector and producer of allergens, this species has major health and economic impacts on humans. Factors contributing to the success of the German cockroach include its resistance to a broad range of insecticides, immunity to many pathogens, and its ability, as an extreme generalist omnivore, to survive on most food sources. The recently published genome shows that B. germanica has an exceptionally high number of protein coding genes. In this study, we investigate the functions of the 93 significantly expanded gene families with the aim to better understand the success of B. germanica as a major pest despite such inhospitable conditions. We find major expansions in gene families with functions related to the detoxification of insecticides and allelochemicals, defense against pathogens, digestion, sensory perception, and gene regulation. These expansions might have allowed B. germanica to develop multiple resistance mechanisms to insecticides and pathogens, and enabled a broad, flexible diet, thus explaining its success in unsanitary conditions and under recurrent chemical control. The findings and resources presented here provide insights for better understanding molecular mechanisms that will facilitate more effective cockroach control. AU - Harrison, Mark AU - Arning, Nicolas AU - Kremer, Lucas AU - Ylla, Guillem AU - Belles, Xavier AU - Bornberg Bauer, Erich AU - Huylmans, Ann K AU - Jongepier, Evelien AU - Puilachs, Maria AU - Richards, Stephen AU - Schal, Coby ID - 190 JF - Journal of Experimental Zoology Part B: Molecular and Developmental Evolution TI - Expansions of key protein families in the German cockroach highlight the molecular basis of its remarkable success as a global indoor pest VL - 330 ER - TY - JOUR AB - We construct martingale solutions to stochastic thin-film equations by introducing a (spatial) semidiscretization and establishing convergence. The discrete scheme allows for variants of the energy and entropy estimates in the continuous setting as long as the discrete energy does not exceed certain threshold values depending on the spatial grid size $h$. Using a stopping time argument to prolongate high-energy paths constant in time, arbitrary moments of coupled energy/entropy functionals can be controlled. Having established Hölder regularity of approximate solutions, the convergence proof is then based on compactness arguments---in particular on Jakubowski's generalization of Skorokhod's theorem---weak convergence methods, and recent tools on martingale convergence. AU - Fischer, Julian L AU - Grün, Günther ID - 404 IS - 1 JF - SIAM Journal on Mathematical Analysis TI - Existence of positive solutions to stochastic thin-film equations VL - 50 ER - TY - GEN AB - File S1 contains figures that clarify the following features: (i) effect of population size on the average number/frequency of SI classes, (ii) changes in the minimal completeness deficit in time for a single class, and (iii) diversification diagrams for all studied pathways, including the summary figure for k = 8. File S2 contains the code required for a stochastic simulation of the SLF system with an example. This file also includes the output in the form of figures and tables. AU - Bod'ová, Katarína AU - Priklopil, Tadeas AU - Field, David AU - Barton, Nicholas H AU - Pickup, Melinda ID - 9813 TI - Supplemental material for Bodova et al., 2018 ER - TY - JOUR AB - Bioluminescence is found across the entire tree of life, conferring a spectacular set of visually oriented functions from attracting mates to scaring off predators. Half a dozen different luciferins, molecules that emit light when enzymatically oxidized, are known. However, just one biochemical pathway for luciferin biosynthesis has been described in full, which is found only in bacteria. Here, we report identification of the fungal luciferase and three other key enzymes that together form the biosynthetic cycle of the fungal luciferin from caffeic acid, a simple and widespread metabolite. Introduction of the identified genes into the genome of the yeast Pichia pastoris along with caffeic acid biosynthesis genes resulted in a strain that is autoluminescent in standard media. We analyzed evolution of the enzymes of the luciferin biosynthesis cycle and found that fungal bioluminescence emerged through a series of events that included two independent gene duplications. The retention of the duplicated enzymes of the luciferin pathway in nonluminescent fungi shows that the gene duplication was followed by functional sequence divergence of enzymes of at least one gene in the biosynthetic pathway and suggests that the evolution of fungal bioluminescence proceeded through several closely related stepping stone nonluminescent biochemical reactions with adaptive roles. The availability of a complete eukaryotic luciferin biosynthesis pathway provides several applications in biomedicine and bioengineering. AU - Kotlobay, Alexey A. AU - Sarkisyan, Karen AU - Mokrushina, Yuliana A. AU - Marcet-Houben, Marina AU - Serebrovskaya, Ekaterina O. AU - Markina, Nadezhda M. AU - Gonzalez Somermeyer, Louisa AU - Gorokhovatsky, Andrey Y. AU - Vvedensky, Andrey AU - Purtov, Konstantin V. AU - Petushkov, Valentin N. AU - Rodionova, Natalja S. AU - Chepurnyh, Tatiana V. AU - Fakhranurova, Liliia AU - Guglya, Elena B. AU - Ziganshin, Rustam AU - Tsarkova, Aleksandra S. AU - Kaskova, Zinaida M. AU - Shender, Victoria AU - Abakumov, Maxim AU - Abakumova, Tatiana O. AU - Povolotskaya, Inna S. AU - Eroshkin, Fedor M. AU - Zaraisky, Andrey G. AU - Mishin, Alexander S. AU - Dolgov, Sergey V. AU - Mitiouchkina, Tatiana Y. AU - Kopantzev, Eugene P. AU - Waldenmaier, Hans E. AU - Oliveira, Anderson G. AU - Oba, Yuichi AU - Barsova, Ekaterina AU - Bogdanova, Ekaterina A. AU - Gabaldón, Toni AU - Stevani, Cassius V. AU - Lukyanov, Sergey AU - Smirnov, Ivan V. AU - Gitelson, Josef I. AU - Kondrashov, Fyodor AU - Yampolsky, Ilia V. ID - 5780 IS - 50 JF - Proceedings of the National Academy of Sciences of the United States of America SN - 00278424 TI - Genetically encodable bioluminescent system from fungi VL - 115 ER - TY - JOUR AB - The plant hormone gibberellic acid (GA) is a crucial regulator of growth and development. The main paradigm of GA signaling puts forward transcriptional regulation via the degradation of DELLA transcriptional repressors. GA has also been shown to regulate tropic responses by modulation of the plasma membrane incidence of PIN auxin transporters by an unclear mechanism. Here we uncovered the cellular and molecular mechanisms by which GA redirects protein trafficking and thus regulates cell surface functionality. Photoconvertible reporters revealed that GA balances the protein traffic between the vacuole degradation route and recycling back to the cell surface. Low GA levels promote vacuolar delivery and degradation of multiple cargos, including PIN proteins, whereas high GA levels promote their recycling to the plasma membrane. This GA effect requires components of the retromer complex, such as Sorting Nexin 1 (SNX1) and its interacting, microtubule (MT)-associated protein, the Cytoplasmic Linker-Associated Protein (CLASP1). Accordingly, GA regulates the subcellular distribution of SNX1 and CLASP1, and the intact MT cytoskeleton is essential for the GA effect on trafficking. This GA cellular action occurs through DELLA proteins that regulate the MT and retromer presumably via their interaction partners Prefoldins (PFDs). Our study identified a branching of the GA signaling pathway at the level of DELLA proteins, which, in parallel to regulating transcription, also target by a nontranscriptional mechanism the retromer complex acting at the intersection of the degradation and recycling trafficking routes. By this mechanism, GA can redirect receptors and transporters to the cell surface, thus coregulating multiple processes, including PIN-dependent auxin fluxes during tropic responses. AU - Salanenka, Yuliya AU - Verstraeten, Inge AU - Löfke, Christian AU - Tabata, Kaori AU - Naramoto, Satoshi AU - Glanc, Matous AU - Friml, Jirí ID - 428 IS - 14 JF - PNAS TI - Gibberellin DELLA signaling targets the retromer complex to redirect protein trafficking to the plasma membrane VL - 115 ER - TY - JOUR AB - Imaging is a dominant strategy for data collection in neuroscience, yielding stacks of images that often scale to gigabytes of data for a single experiment. Machine learning algorithms from computer vision can serve as a pair of virtual eyes that tirelessly processes these images, automatically detecting and identifying microstructures. Unlike learning methods, our Flexible Learning-free Reconstruction of Imaged Neural volumes (FLoRIN) pipeline exploits structure-specific contextual clues and requires no training. This approach generalizes across different modalities, including serially-sectioned scanning electron microscopy (sSEM) of genetically labeled and contrast enhanced processes, spectral confocal reflectance (SCoRe) microscopy, and high-energy synchrotron X-ray microtomography (μCT) of large tissue volumes. We deploy the FLoRIN pipeline on newly published and novel mouse datasets, demonstrating the high biological fidelity of the pipeline’s reconstructions. FLoRIN reconstructions are of sufficient quality for preliminary biological study, for example examining the distribution and morphology of cells or extracting single axons from functional data. Compared to existing supervised learning methods, FLoRIN is one to two orders of magnitude faster and produces high-quality reconstructions that are tolerant to noise and artifacts, as is shown qualitatively and quantitatively. AU - Shabazi, Ali AU - Kinnison, Jeffery AU - Vescovi, Rafael AU - Du, Ming AU - Hill, Robert AU - Jösch, Maximilian A AU - Takeno, Marc AU - Zeng, Hongkui AU - Da Costa, Nuno AU - Grutzendler, Jaime AU - Kasthuri, Narayanan AU - Scheirer, Walter ID - 62 IS - 1 JF - Scientific Reports TI - Flexible learning-free segmentation and reconstruction of neural volumes VL - 8 ER - TY - JOUR AB - Dendritic cells (DCs) are sentinels of the adaptive immune system that reside in peripheral organs of mammals. Upon pathogen encounter, they undergo maturation and up-regulate the chemokine receptor CCR7 that guides them along gradients of its chemokine ligands CCL19 and 21 to the next draining lymph node. There, DCs present peripherally acquired antigen to naïve T cells, thereby triggering adaptive immunity. AU - Leithner, Alexander F AU - Renkawitz, Jörg AU - De Vries, Ingrid AU - Hauschild, Robert AU - Haecker, Hans AU - Sixt, Michael K ID - 437 IS - 6 JF - European Journal of Immunology TI - Fast and efficient genetic engineering of hematopoietic precursor cells for the study of dendritic cell migration VL - 48 ER - TY - JOUR AB - Insects are exposed to a variety of potential pathogens in their environment, many of which can severely impact fitness and health. Consequently, hosts have evolved resistance and tolerance strategies to suppress or cope with infections. Hosts utilizing resistance improve fitness by clearing or reducing pathogen loads, and hosts utilizing tolerance reduce harmful fitness effects per pathogen load. To understand variation in, and selective pressures on, resistance and tolerance, we asked to what degree they are shaped by host genetic background, whether plasticity in these responses depends upon dietary environment, and whether there are interactions between these two factors. Females from ten wild-type Drosophila melanogaster genotypes were kept on high- or low-protein (yeast) diets and infected with one of two opportunistic bacterial pathogens, Lactococcus lactis or Pseudomonas entomophila. We measured host resistance as the inverse of bacterial load in the early infection phase. The relationship (slope) between fly fecundity and individual-level bacteria load provided our fecundity tolerance measure. Genotype and dietary yeast determined host fecundity and strongly affected survival after infection with pathogenic P. entomophila. There was considerable genetic variation in host resistance, a commonly found phenomenon resulting from for example varying resistance costs or frequency-dependent selection. Despite this variation and the reproductive cost of higher P. entomophila loads, fecundity tolerance did not vary across genotypes. The absence of genetic variation in tolerance may suggest that at this early infection stage, fecundity tolerance is fixed or that any evolved tolerance mechanisms are not expressed under these infection conditions. AU - Kutzer, Megan AU - Kurtz, Joachim AU - Armitage, Sophie ID - 617 IS - 1 JF - Journal of Evolutionary Biology SN - 1010-061X TI - Genotype and diet affect resistance, survival, and fecundity but not fecundity tolerance VL - 31 ER - TY - JOUR AB - Despite the remarkable number of scientific breakthroughs of the last 100 years, the treatment of neurodevelopmental disorders (e.g., autism spectrum disorder, intellectual disability) remains a great challenge. Recent advancements in genomics, such as whole-exome or whole-genome sequencing, have enabled scientists to identify numerous mutations underlying neurodevelopmental disorders. Given the few hundred risk genes that have been discovered, the etiological variability and the heterogeneous clinical presentation, the need for genotype — along with phenotype- based diagnosis of individual patients has become a requisite. In this review we look at recent advancements in genomic analysis and their translation into clinical practice. AU - Tarlungeanu, Dora-Clara AU - Novarino, Gaia ID - 5888 IS - 8 JF - Experimental & Molecular Medicine SN - 2092-6413 TI - Genomics in neurodevelopmental disorders: an avenue to personalized medicine VL - 50 ER - TY - JOUR AB - We prove upper and lower bounds on the ground-state energy of the ideal two-dimensional anyon gas. Our bounds are extensive in the particle number, as for fermions, and linear in the statistics parameter (Formula presented.). The lower bounds extend to Lieb–Thirring inequalities for all anyons except bosons. AU - Lundholm, Douglas AU - Seiringer, Robert ID - 295 IS - 11 JF - Letters in Mathematical Physics TI - Fermionic behavior of ideal anyons VL - 108 ER - TY - JOUR AB - Conventional wisdom has it that proteins fold and assemble into definite structures, and that this defines their function. Glycosaminoglycans (GAGs) are different. In most cases the structures they form have a low degree of order, even when interacting with proteins. Here, we discuss how physical features common to all GAGs — hydrophilicity, charge, linearity and semi-flexibility — underpin the overall properties of GAG-rich matrices. By integrating soft matter physics concepts (e.g. polymer brushes and phase separation) with our molecular understanding of GAG–protein interactions, we can better comprehend how GAG-rich matrices assemble, what their properties are, and how they function. Taking perineuronal nets (PNNs) — a GAG-rich matrix enveloping neurons — as a relevant example, we propose that microphase separation determines the holey PNN anatomy that is pivotal to PNN functions. AU - Richter, Ralf AU - Baranova, Natalia AU - Day, Anthony AU - Kwok, Jessica ID - 555 JF - Current Opinion in Structural Biology TI - Glycosaminoglycans in extracellular matrix organisation: Are concepts from soft matter physics key to understanding the formation of perineuronal nets? VL - 50 ER - TY - JOUR AB - Around 150 million years ago, eusocial termites evolved from within the cockroaches, 50 million years before eusocial Hymenoptera, such as bees and ants, appeared. Here, we report the 2-Gb genome of the German cockroach, Blattella germanica, and the 1.3-Gb genome of the drywood termite Cryptotermes secundus. We show evolutionary signatures of termite eusociality by comparing the genomes and transcriptomes of three termites and the cockroach against the background of 16 other eusocial and non-eusocial insects. Dramatic adaptive changes in genes underlying the production and perception of pheromones confirm the importance of chemical communication in the termites. These are accompanied by major changes in gene regulation and the molecular evolution of caste determination. Many of these results parallel molecular mechanisms of eusocial evolution in Hymenoptera. However, the specific solutions are remarkably different, thus revealing a striking case of convergence in one of the major evolutionary transitions in biological complexity. AU - Harrison, Mark AU - Jongepier, Evelien AU - Robertson, Hugh AU - Arning, Nicolas AU - Bitard Feildel, Tristan AU - Chao, Hsu AU - Childers, Christopher AU - Dinh, Huyen AU - Doddapaneni, Harshavardhan AU - Dugan, Shannon AU - Gowin, Johannes AU - Greiner, Carolin AU - Han, Yi AU - Hu, Haofu AU - Hughes, Daniel AU - Huylmans, Ann K AU - Kemena, Karsten AU - Kremer, Lukas AU - Lee, Sandra AU - López Ezquerra, Alberto AU - Mallet, Ludovic AU - Monroy Kuhn, Jose AU - Moser, Annabell AU - Murali, Shwetha AU - Muzny, Donna AU - Otani, Saria AU - Piulachs, Maria AU - Poelchau, Monica AU - Qu, Jiaxin AU - Schaub, Florentine AU - Wada Katsumata, Ayako AU - Worley, Kim AU - Xie, Qiaolin AU - Ylla, Guillem AU - Poulsen, Michael AU - Gibbs, Richard AU - Schal, Coby AU - Richards, Stephen AU - Belles, Xavier AU - Korb, Judith AU - Bornberg Bauer, Erich ID - 448 IS - 3 JF - Nature Ecology and Evolution TI - Hemimetabolous genomes reveal molecular basis of termite eusociality VL - 2 ER - TY - JOUR AB - Escaping local optima is one of the major obstacles to function optimisation. Using the metaphor of a fitness landscape, local optima correspond to hills separated by fitness valleys that have to be overcome. We define a class of fitness valleys of tunable difficulty by considering their length, representing the Hamming path between the two optima and their depth, the drop in fitness. For this function class we present a runtime comparison between stochastic search algorithms using different search strategies. The (1+1) EA is a simple and well-studied evolutionary algorithm that has to jump across the valley to a point of higher fitness because it does not accept worsening moves (elitism). In contrast, the Metropolis algorithm and the Strong Selection Weak Mutation (SSWM) algorithm, a famous process in population genetics, are both able to cross the fitness valley by accepting worsening moves. We show that the runtime of the (1+1) EA depends critically on the length of the valley while the runtimes of the non-elitist algorithms depend crucially on the depth of the valley. Moreover, we show that both SSWM and Metropolis can also efficiently optimise a rugged function consisting of consecutive valleys. AU - Oliveto, Pietro AU - Paixao, Tiago AU - Pérez Heredia, Jorge AU - Sudholt, Dirk AU - Trubenova, Barbora ID - 723 IS - 5 JF - Algorithmica TI - How to escape local optima in black box optimisation when non elitism outperforms elitism VL - 80 ER - TY - JOUR AB - The twelve papers in this special section focus on learning systems with shared information for computer vision and multimedia communication analysis. In the real world, a realistic setting for computer vision or multimedia recognition problems is that we have some classes containing lots of training data and many classes containing a small amount of training data. Therefore, how to use frequent classes to help learning rare classes for which it is harder to collect the training data is an open question. Learning with shared information is an emerging topic in machine learning, computer vision and multimedia analysis. There are different levels of components that can be shared during concept modeling and machine learning stages, such as sharing generic object parts, sharing attributes, sharing transformations, sharing regularization parameters and sharing training examples, etc. Regarding the specific methods, multi-task learning, transfer learning and deep learning can be seen as using different strategies to share information. These learning with shared information methods are very effective in solving real-world large-scale problems. AU - Darrell, Trevor AU - Lampert, Christoph AU - Sebe, Nico AU - Wu, Ying AU - Yan, Yan ID - 321 IS - 5 JF - IEEE Transactions on Pattern Analysis and Machine Intelligence TI - Guest editors' introduction to the special section on learning with Shared information for computer vision and multimedia analysis VL - 40 ER - TY - GEN AB - Around 150 million years ago, eusocial termites evolved from within the cockroaches, 50 million years before eusocial Hymenoptera, such as bees and ants, appeared. Here, we report the 2-Gb genome of the German cockroach, Blattella germanica, and the 1.3-Gb genome of the drywood termite Cryptotermes secundus. We show evolutionary signatures of termite eusociality by comparing the genomes and transcriptomes of three termites and the cockroach against the background of 16 other eusocial and non-eusocial insects. Dramatic adaptive changes in genes underlying the production and perception of pheromones confirm the importance of chemical communication in the termites. These are accompanied by major changes in gene regulation and the molecular evolution of caste determination. Many of these results parallel molecular mechanisms of eusocial evolution in Hymenoptera. However, the specific solutions are remarkably different, thus revealing a striking case of convergence in one of the major evolutionary transitions in biological complexity. AU - Harrison, Mark C. AU - Jongepier, Evelien AU - Robertson, Hugh M. AU - Arning, Nicolas AU - Bitard-Feildel, Tristan AU - Chao, Hsu AU - Childers, Christopher P. AU - Dinh, Huyen AU - Doddapaneni, Harshavardhan AU - Dugan, Shannon AU - Gowin, Johannes AU - Greiner, Carolin AU - Han, Yi AU - Hu, Haofu AU - Hughes, Daniel S. T. AU - Huylmans, Ann K AU - Kemena, Carsten AU - Kremer, Lukas P. M. AU - Lee, Sandra L. AU - Lopez-Ezquerra, Alberto AU - Mallet, Ludovic AU - Monroy-Kuhn, Jose M. AU - Moser, Annabell AU - Murali, Shwetha C. AU - Muzny, Donna M. AU - Otani, Saria AU - Piulachs, Maria-Dolors AU - Poelchau, Monica AU - Qu, Jiaxin AU - Schaub, Florentine AU - Wada-Katsumata, Ayako AU - Worley, Kim C. AU - Xie, Qiaolin AU - Ylla, Guillem AU - Poulsen, Michael AU - Gibbs, Richard A. AU - Schal, Coby AU - Richards, Stephen AU - Belles, Xavier AU - Korb, Judith AU - Bornberg-Bauer, Erich ID - 9841 TI - Data from: Hemimetabolous genomes reveal molecular basis of termite eusociality ER - TY - JOUR AB - The functional role of AMPA receptor (AMPAR)-mediated synaptic signaling between neurons and oligodendrocyte precursor cells (OPCs) remains enigmatic. We modified the properties of AMPARs at axon-OPC synapses in the mouse corpus callosum in vivo during the peak of myelination by targeting the GluA2 subunit. Expression of the unedited (Ca2+ permeable) or the pore-dead GluA2 subunit of AMPARs triggered proliferation of OPCs and reduced their differentiation into oligodendrocytes. Expression of the cytoplasmic C-terminal (GluA2(813-862)) of the GluA2 subunit (C-tail), a modification designed to affect the interaction between GluA2 and AMPAR-binding proteins and to perturb trafficking of GluA2-containing AMPARs, decreased the differentiation of OPCs without affecting their proliferation. These findings suggest that ionotropic and non-ionotropic properties of AMPARs in OPCs, as well as specific aspects of AMPAR-mediated signaling at axon-OPC synapses in the mouse corpus callosum, are important for balancing the response of OPCs to proliferation and differentiation cues. In the brain, oligodendrocyte precursor cells (OPCs) receive glutamatergic AMPA-receptor-mediated synaptic input from neurons. Chen et al. show that modifying AMPA-receptor properties at axon-OPC synapses alters proliferation and differentiation of OPCs. This expands the traditional view of synaptic transmission by suggesting neurons also use synapses to modulate behavior of glia. AU - Chen, Ting AU - Kula, Bartosz AU - Nagy, Balint AU - Barzan, Ruxandra AU - Gall, Andrea AU - Ehrlich, Ingrid AU - Kukley, Maria ID - 32 IS - 4 JF - Cell Reports TI - In Vivo regulation of Oligodendrocyte processor cell proliferation and differentiation by the AMPA-receptor Subunit GluA2 VL - 25 ER - TY - JOUR AB - The release of IgM is the first line of an antibody response and precedes the generation of high affinity IgG in germinal centers. Once secreted by freshly activated plasmablasts, IgM is released into the efferent lymph of reactive lymph nodes as early as 3 d after immunization. As pentameric IgM has an enormous size of 1,000 kD, its diffusibility is low, and one might wonder how it can pass through the densely lymphocyte-packed environment of a lymph node parenchyma in order to reach its exit. In this issue of JEM, Thierry et al. show that, in order to reach the blood stream, IgM molecules take a specific micro-anatomical route via lymph node conduits. AU - Reversat, Anne AU - Sixt, Michael K ID - 5672 IS - 12 JF - Journal of Experimental Medicine SN - 00221007 TI - IgM's exit route VL - 215 ER - TY - JOUR AB - We consider congruences of straight lines in a plane with the combinatorics of the square grid, with all elementary quadrilaterals possessing an incircle. It is shown that all the vertices of such nets (we call them incircular or IC-nets) lie on confocal conics. Our main new results are on checkerboard IC-nets in the plane. These are congruences of straight lines in the plane with the combinatorics of the square grid, combinatorially colored as a checkerboard, such that all black coordinate quadrilaterals possess inscribed circles. We show how this larger class of IC-nets appears quite naturally in Laguerre geometry of oriented planes and spheres and leads to new remarkable incidence theorems. Most of our results are valid in hyperbolic and spherical geometries as well. We present also generalizations in spaces of higher dimension, called checkerboard IS-nets. The construction of these nets is based on a new 9 inspheres incidence theorem. AU - Akopyan, Arseniy AU - Bobenko, Alexander ID - 458 IS - 4 JF - Transactions of the American Mathematical Society TI - Incircular nets and confocal conics VL - 370 ER - TY - CONF AB - In two-player games on graphs, the players move a token through a graph to produce an infinite path, which determines the winner or payoff of the game. Such games are central in formal verification since they model the interaction between a non-terminating system and its environment. We study bidding games in which the players bid for the right to move the token. Two bidding rules have been defined. In Richman bidding, in each round, the players simultaneously submit bids, and the higher bidder moves the token and pays the other player. Poorman bidding is similar except that the winner of the bidding pays the “bank” rather than the other player. While poorman reachability games have been studied before, we present, for the first time, results on infinite-duration poorman games. A central quantity in these games is the ratio between the two players’ initial budgets. The questions we study concern a necessary and sufficient ratio with which a player can achieve a goal. For reachability objectives, such threshold ratios are known to exist for both bidding rules. We show that the properties of poorman reachability games extend to complex qualitative objectives such as parity, similarly to the Richman case. Our most interesting results concern quantitative poorman games, namely poorman mean-payoff games, where we construct optimal strategies depending on the initial ratio, by showing a connection with random-turn based games. The connection in itself is interesting, because it does not hold for reachability poorman games. We also solve the complexity problems that arise in poorman bidding games. AU - Avni, Guy AU - Henzinger, Thomas A AU - Ibsen-Jensen, Rasmus ID - 5788 SN - 03029743 TI - Infinite-duration poorman-bidding games VL - 11316 ER - TY - JOUR AB - A short, 14-amino-acid segment called SP1, located in the Gag structural protein1, has a critical role during the formation of the HIV-1 virus particle. During virus assembly, the SP1 peptide and seven preceding residues fold into a six-helix bundle, which holds together the Gag hexamer and facilitates the formation of a curved immature hexagonal lattice underneath the viral membrane2,3. Upon completion of assembly and budding, proteolytic cleavage of Gag leads to virus maturation, in which the immature lattice is broken down; the liberated CA domain of Gag then re-assembles into the mature conical capsid that encloses the viral genome and associated enzymes. Folding and proteolysis of the six-helix bundle are crucial rate-limiting steps of both Gag assembly and disassembly, and the six-helix bundle is an established target of HIV-1 inhibitors4,5. Here, using a combination of structural and functional analyses, we show that inositol hexakisphosphate (InsP6, also known as IP6) facilitates the formation of the six-helix bundle and assembly of the immature HIV-1 Gag lattice. IP6 makes ionic contacts with two rings of lysine residues at the centre of the Gag hexamer. Proteolytic cleavage then unmasks an alternative binding site, where IP6 interaction promotes the assembly of the mature capsid lattice. These studies identify IP6 as a naturally occurring small molecule that promotes both assembly and maturation of HIV-1. AU - Dick, Robert AU - Zadrozny, Kaneil K AU - Xu, Chaoyi AU - Schur, Florian AU - Lyddon, Terri D AU - Ricana, Clifton L AU - Wagner, Jonathan M AU - Perilla, Juan R AU - Ganser, Pornillos Barbie K AU - Johnson, Marc C AU - Pornillos, Owen AU - Vogt, Volker ID - 150 IS - 7719 JF - Nature TI - Inositol phosphates are assembly co-factors for HIV-1 VL - 560 ER - TY - JOUR AB - The theory of tropical series, that we develop here, firstly appeared in the study of the growth of pluriharmonic functions. Motivated by waves in sandpile models we introduce a dynamic on the set of tropical series, and it is experimentally observed that this dynamic obeys a power law. So, this paper serves as a compilation of results we need for other articles and also introduces several objects interesting by themselves. AU - Kalinin, Nikita AU - Shkolnikov, Mikhail ID - 303 IS - 6 JF - Discrete and Continuous Dynamical Systems- Series A TI - Introduction to tropical series and wave dynamic on them VL - 38 ER - TY - CONF AB - Approximating a probability density in a tractable manner is a central task in Bayesian statistics. Variational Inference (VI) is a popular technique that achieves tractability by choosing a relatively simple variational family. Borrowing ideas from the classic boosting framework, recent approaches attempt to \emph{boost} VI by replacing the selection of a single density with a greedily constructed mixture of densities. In order to guarantee convergence, previous works impose stringent assumptions that require significant effort for practitioners. Specifically, they require a custom implementation of the greedy step (called the LMO) for every probabilistic model with respect to an unnatural variational family of truncated distributions. Our work fixes these issues with novel theoretical and algorithmic insights. On the theoretical side, we show that boosting VI satisfies a relaxed smoothness assumption which is sufficient for the convergence of the functional Frank-Wolfe (FW) algorithm. Furthermore, we rephrase the LMO problem and propose to maximize the Residual ELBO (RELBO) which replaces the standard ELBO optimization in VI. These theoretical enhancements allow for black box implementation of the boosting subroutine. Finally, we present a stopping criterion drawn from the duality gap in the classic FW analyses and exhaustive experiments to illustrate the usefulness of our theoretical and algorithmic contributions. AU - Locatello, Francesco AU - Dresdner, Gideon AU - Khanna, Rajiv AU - Valera, Isabel AU - Rätsch, Gunnar ID - 14202 SN - 9781510884472 T2 - Advances in Neural Information Processing Systems TI - Boosting black box variational inference VL - 31 ER - TY - CONF AB - Variational inference is a popular technique to approximate a possibly intractable Bayesian posterior with a more tractable one. Recently, boosting variational inference has been proposed as a new paradigm to approximate the posterior by a mixture of densities by greedily adding components to the mixture. However, as is the case with many other variational inference algorithms, its theoretical properties have not been studied. In the present work, we study the convergence properties of this approach from a modern optimization viewpoint by establishing connections to the classic Frank-Wolfe algorithm. Our analyses yields novel theoretical insights regarding the sufficient conditions for convergence, explicit rates, and algorithmic simplifications. Since a lot of focus in previous works for variational inference has been on tractability, our work is especially important as a much needed attempt to bridge the gap between probabilistic models and their corresponding theoretical properties. AU - Locatello, Francesco AU - Khanna, Rajiv AU - Ghosh, Joydeep AU - Rätsch, Gunnar ID - 14201 T2 - Proceedings of the 21st International Conference on Artificial Intelligence and Statistics TI - Boosting variational inference: An optimization perspective VL - 84 ER - TY - CONF AB - High-dimensional time series are common in many domains. Since human cognition is not optimized to work well in high-dimensional spaces, these areas could benefit from interpretable low-dimensional representations. However, most representation learning algorithms for time series data are difficult to interpret. This is due to non-intuitive mappings from data features to salient properties of the representation and non-smoothness over time. To address this problem, we propose a new representation learning framework building on ideas from interpretable discrete dimensionality reduction and deep generative modeling. This framework allows us to learn discrete representations of time series, which give rise to smooth and interpretable embeddings with superior clustering performance. We introduce a new way to overcome the non-differentiability in discrete representation learning and present a gradient-based version of the traditional self-organizing map algorithm that is more performant than the original. Furthermore, to allow for a probabilistic interpretation of our method, we integrate a Markov model in the representation space. This model uncovers the temporal transition structure, improves clustering performance even further and provides additional explanatory insights as well as a natural representation of uncertainty. We evaluate our model in terms of clustering performance and interpretability on static (Fashion-)MNIST data, a time series of linearly interpolated (Fashion-)MNIST images, a chaotic Lorenz attractor system with two macro states, as well as on a challenging real world medical time series application on the eICU data set. Our learned representations compare favorably with competitor methods and facilitate downstream tasks on the real world data. AU - Fortuin, Vincent AU - Hüser, Matthias AU - Locatello, Francesco AU - Strathmann, Heiko AU - Rätsch, Gunnar ID - 14198 T2 - International Conference on Learning Representations TI - SOM-VAE: Interpretable discrete representation learning on time series ER - TY - CONF AB - We propose a conditional gradient framework for a composite convex minimization template with broad applications. Our approach combines smoothing and homotopy techniques under the CGM framework, and provably achieves the optimal O(1/k−−√) convergence rate. We demonstrate that the same rate holds if the linear subproblems are solved approximately with additive or multiplicative error. In contrast with the relevant work, we are able to characterize the convergence when the non-smooth term is an indicator function. Specific applications of our framework include the non-smooth minimization, semidefinite programming, and minimization with linear inclusion constraints over a compact domain. Numerical evidence demonstrates the benefits of our framework. AU - Yurtsever, Alp AU - Fercoq, Olivier AU - Locatello, Francesco AU - Cevher, Volkan ID - 14203 T2 - Proceedings of the 35th International Conference on Machine Learning TI - A conditional gradient framework for composite convex minimization with applications to semidefinite programming VL - 80 ER - TY - JOUR AB - Adaptive introgression is common in nature and can be driven by selection acting on multiple, linked genes. We explore the effects of polygenic selection on introgression under the infinitesimal model with linkage. This model assumes that the introgressing block has an effectively infinite number of genes, each with an infinitesimal effect on the trait under selection. The block is assumed to introgress under directional selection within a native population that is genetically homogeneous. We use individual-based simulations and a branching process approximation to compute various statistics of the introgressing block, and explore how these depend on parameters such as the map length and initial trait value associated with the introgressing block, the genetic variability along the block, and the strength of selection. Our results show that the introgression dynamics of a block under infinitesimal selection is qualitatively different from the dynamics of neutral introgression. We also find that in the long run, surviving descendant blocks are likely to have intermediate lengths, and clarify how the length is shaped by the interplay between linkage and infinitesimal selection. Our results suggest that it may be difficult to distinguish introgression of single loci from that of genomic blocks with multiple, tightly linked and weakly selected loci. AU - Sachdeva, Himani AU - Barton, Nicholas H ID - 282 IS - 4 JF - Genetics TI - Introgression of a block of genome under infinitesimal selection VL - 209 ER - TY - CONF AB - Universal hashing found a lot of applications in computer science. In cryptography the most important fact about universal families is the so called Leftover Hash Lemma, proved by Impagliazzo, Levin and Luby. In the language of modern cryptography it states that almost universal families are good extractors. In this work we provide a somewhat surprising characterization in the opposite direction. Namely, every extractor with sufficiently good parameters yields a universal family on a noticeable fraction of its inputs. Our proof technique is based on tools from extremal graph theory applied to the \'collision graph\' induced by the extractor, and may be of independent interest. We discuss possible applications to the theory of randomness extractors and non-malleable codes. AU - Obremski, Marciej AU - Skorski, Maciej ID - 108 TI - Inverted leftover hash lemma VL - 2018 ER - TY - CONF AB - Two popular examples of first-order optimization methods over linear spaces are coordinate descent and matching pursuit algorithms, with their randomized variants. While the former targets the optimization by moving along coordinates, the latter considers a generalized notion of directions. Exploiting the connection between the two algorithms, we present a unified analysis of both, providing affine invariant sublinear O(1/t) rates on smooth objectives and linear convergence on strongly convex objectives. As a byproduct of our affine invariant analysis of matching pursuit, our rates for steepest coordinate descent are the tightest known. Furthermore, we show the first accelerated convergence rate O(1/t2) for matching pursuit and steepest coordinate descent on convex objectives. AU - Locatello, Francesco AU - Raj, Anant AU - Karimireddy, Sai Praneeth AU - Rätsch, Gunnar AU - Schölkopf, Bernhard AU - Stich, Sebastian U. AU - Jaggi, Martin ID - 14204 T2 - Proceedings of the 35th International Conference on Machine Learning TI - On matching pursuit and coordinate descent VL - 80 ER - TY - CONF AB - We present layered concurrent programs, a compact and expressive notation for specifying refinement proofs of concurrent programs. A layered concurrent program specifies a sequence of connected concurrent programs, from most concrete to most abstract, such that common parts of different programs are written exactly once. These programs are expressed in the ordinary syntax of imperative concurrent programs using gated atomic actions, sequencing, choice, and (recursive) procedure calls. Each concurrent program is automatically extracted from the layered program. We reduce refinement to the safety of a sequence of concurrent checker programs, one each to justify the connection between every two consecutive concurrent programs. These checker programs are also automatically extracted from the layered program. Layered concurrent programs have been implemented in the CIVL verifier which has been successfully used for the verification of several complex concurrent programs. AU - Kragl, Bernhard AU - Qadeer, Shaz ID - 160 TI - Layered Concurrent Programs VL - 10981 ER - TY - JOUR AB - In experimental cultures, when bacteria are mixed with lytic (virulent) bacteriophage, bacterial cells resistant to the phage commonly emerge and become the dominant population of bacteria. Following the ascent of resistant mutants, the densities of bacteria in these simple communities become limited by resources rather than the phage. Despite the evolution of resistant hosts, upon which the phage cannot replicate, the lytic phage population is most commonly maintained in an apparently stable state with the resistant bacteria. Several mechanisms have been put forward to account for this result. Here we report the results of population dynamic/evolution experiments with a virulent mutant of phage Lambda, λVIR, and Escherichia coli in serial transfer cultures. We show that, following the ascent of λVIR-resistant bacteria, λVIRis maintained in the majority of cases in maltose-limited minimal media and in all cases in nutrient-rich broth. Using mathematical models and experiments, we show that the dominant mechanism responsible for maintenance of λVIRin these resource-limited populations dominated by resistant E. coli is a high rate of either phenotypic or genetic transition from resistance to susceptibility—a hitherto undemonstrated mechanism we term "leaky resistance." We discuss the implications of leaky resistance to our understanding of the conditions for the maintenance of phage in populations of bacteria—their “existence conditions.”. AU - Chaudhry, Waqas AU - Pleska, Maros AU - Shah, Nilang AU - Weiss, Howard AU - Mccall, Ingrid AU - Meyer, Justin AU - Gupta, Animesh AU - Guet, Calin C AU - Levin, Bruce ID - 82 IS - 8 JF - PLoS Biology TI - Leaky resistance and the conditions for the existence of lytic bacteriophage VL - 16 ER - TY - JOUR AB - We present a data-driven technique to instantly predict how fluid flows around various three-dimensional objects. Such simulation is useful for computational fabrication and engineering, but is usually computationally expensive since it requires solving the Navier-Stokes equation for many time steps. To accelerate the process, we propose a machine learning framework which predicts aerodynamic forces and velocity and pressure fields given a threedimensional shape input. Handling detailed free-form three-dimensional shapes in a data-driven framework is challenging because machine learning approaches usually require a consistent parametrization of input and output. We present a novel PolyCube maps-based parametrization that can be computed for three-dimensional shapes at interactive rates. This allows us to efficiently learn the nonlinear response of the flow using a Gaussian process regression. We demonstrate the effectiveness of our approach for the interactive design and optimization of a car body. AU - Umetani, Nobuyuki AU - Bickel, Bernd ID - 4 IS - 4 JF - ACM Trans. Graph. TI - Learning three-dimensional flow for interactive aerodynamic design VL - 37 ER - TY - JOUR AB - We consider large random matrices X with centered, independent entries which have comparable but not necessarily identical variances. Girko's circular law asserts that the spectrum is supported in a disk and in case of identical variances, the limiting density is uniform. In this special case, the local circular law by Bourgade et. al. [11,12] shows that the empirical density converges even locally on scales slightly above the typical eigenvalue spacing. In the general case, the limiting density is typically inhomogeneous and it is obtained via solving a system of deterministic equations. Our main result is the local inhomogeneous circular law in the bulk spectrum on the optimal scale for a general variance profile of the entries of X. AU - Alt, Johannes AU - Erdös, László AU - Krüger, Torben H ID - 566 IS - 1 JF - Annals Applied Probability TI - Local inhomogeneous circular law VL - 28 ER - TY - JOUR AB - The goal of this article is to introduce the reader to the theory of intrinsic geometry of convex surfaces. We illustrate the power of the tools by proving a theorem on convex surfaces containing an arbitrarily long closed simple geodesic. Let us remind ourselves that a curve in a surface is called geodesic if every sufficiently short arc of the curve is length minimizing; if, in addition, it has no self-intersections, we call it simple geodesic. A tetrahedron with equal opposite edges is called isosceles. The axiomatic method of Alexandrov geometry allows us to work with the metrics of convex surfaces directly, without approximating it first by a smooth or polyhedral metric. Such approximations destroy the closed geodesics on the surface; therefore it is difficult (if at all possible) to apply approximations in the proof of our theorem. On the other hand, a proof in the smooth or polyhedral case usually admits a translation into Alexandrov’s language; such translation makes the result more general. In fact, our proof resembles a translation of the proof given by Protasov. Note that the main theorem implies in particular that a smooth convex surface does not have arbitrarily long simple closed geodesics. However we do not know a proof of this corollary that is essentially simpler than the one presented below. AU - Akopyan, Arseniy AU - Petrunin, Anton ID - 106 IS - 3 JF - Mathematical Intelligencer TI - Long geodesics on convex surfaces VL - 40 ER -