@article{289, abstract = {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.}, author = {Zibrov, Alexander and Peng, Rao and Kometter, Carlos and Li, Jia and Dean, Cory and Taniguchi, Takashi and Watanabe, Kenji and Serbyn, Maksym and Young, Andrea}, journal = {Physical Review Letters}, number = {16}, publisher = {American Physical Society}, title = {{Emergent dirac gullies and gully-symmetry-breaking quantum hall states in ABA trilayer graphene}}, doi = {10.1103/PhysRevLett.121.167601}, volume = {121}, year = {2018}, } @article{287, abstract = {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.}, author = {Salari, Vahid and Barzanjeh, Shabir and Cifra, Michal and Simon, Christoph and Scholkmann, Felix and Alirezaei, Zahra and Tuszynski, Jack}, journal = {Frontiers in Bioscience - Landmark}, number = {8}, pages = {1391 -- 1406}, publisher = {Frontiers in Bioscience}, title = {{Electromagnetic fields and optomechanics In cancer diagnostics and treatment}}, doi = {10.2741/4651}, volume = {23}, year = {2018}, } @article{425, abstract = {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.}, author = {Matoušek, Jiří and Sedgwick, Eric and Tancer, Martin and Wagner, Uli}, journal = {Journal of the ACM}, number = {1}, publisher = {ACM}, title = {{Embeddability in the 3-Sphere is decidable}}, doi = {10.1145/3078632}, volume = {65}, year = {2018}, } @article{564, abstract = {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.}, author = {Barton, Nicholas H and Etheridge, Alison}, journal = {Theoretical Population Biology}, number = {7}, pages = {110--127}, publisher = {Academic Press}, title = {{Establishment in a new habitat by polygenic adaptation}}, doi = {10.1016/j.tpb.2017.11.007}, volume = {122}, year = {2018}, } @article{157, abstract = {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.}, author = {Hilbe, Christian and Šimsa, Štepán and Chatterjee, Krishnendu and Nowak, Martin}, journal = {Nature}, number = {7713}, pages = {246 -- 249}, publisher = {Nature Publishing Group}, title = {{Evolution of cooperation in stochastic games}}, doi = {10.1038/s41586-018-0277-x}, volume = {559}, year = {2018}, } @article{384, abstract = {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.}, author = {Hönigschmid, Peter and Bykova, Nadya and Schneider, René and Ivankov, Dmitry and Frishman, Dmitrij}, journal = {Genome Biology and Evolution}, number = {3}, pages = {928 -- 938}, publisher = {Oxford University Press}, title = {{Evolutionary interplay between symbiotic relationships and patterns of signal peptide gain and loss}}, doi = {10.1093/gbe/evy049}, volume = {10}, year = {2018}, } @article{563, abstract = {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.}, author = {Ringbauer, Harald and Kolesnikov, Alexander and Field, David and Barton, Nicholas H}, journal = {Genetics}, number = {3}, pages = {1231--1245}, publisher = {Genetics Society of America}, title = {{Estimating barriers to gene flow from distorted isolation-by-distance patterns}}, doi = {10.1534/genetics.117.300638}, volume = {208}, year = {2018}, } @article{135, abstract = {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.}, author = {Sato, Takahiro and Wojtan, Christopher J and Thuerey, Nils and Igarashi, Takeo and Ando, Ryoichi}, issn = {0167-7055}, journal = {Computer Graphics Forum}, number = {2}, pages = {169 -- 177}, publisher = {Wiley}, title = {{Extended narrow band FLIP for liquid simulations}}, doi = {10.1111/cgf.13351}, volume = {37}, year = {2018}, } @article{316, abstract = {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.}, author = {Bodova, Katarina and Priklopil, Tadeas and Field, David and Barton, Nicholas H and Pickup, Melinda}, journal = {Genetics}, number = {3}, pages = {861--883}, publisher = {Genetics Society of America}, title = {{Evolutionary pathways for the generation of new self-incompatibility haplotypes in a non-self recognition system}}, doi = {10.1534/genetics.118.300748}, volume = {209}, year = {2018}, } @article{190, abstract = {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.}, author = {Harrison, Mark and Arning, Nicolas and Kremer, Lucas and Ylla, Guillem and Belles, Xavier and Bornberg Bauer, Erich and Huylmans, Ann K and Jongepier, Evelien and Puilachs, Maria and Richards, Stephen and Schal, Coby}, journal = {Journal of Experimental Zoology Part B: Molecular and Developmental Evolution}, pages = {254--264}, publisher = {Wiley}, title = {{Expansions of key protein families in the German cockroach highlight the molecular basis of its remarkable success as a global indoor pest}}, doi = {10.1002/jez.b.22824}, volume = {330}, year = {2018}, } @article{404, abstract = {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. }, author = {Fischer, Julian L and Grün, Günther}, journal = {SIAM Journal on Mathematical Analysis}, number = {1}, pages = {411 -- 455}, publisher = {Society for Industrial and Applied Mathematics }, title = {{Existence of positive solutions to stochastic thin-film equations}}, doi = {10.1137/16M1098796}, volume = {50}, year = {2018}, } @misc{9813, abstract = {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.}, author = {Bod'ová, Katarína and Priklopil, Tadeas and Field, David and Barton, Nicholas H and Pickup, Melinda}, publisher = {Genetics Society of America}, title = {{Supplemental material for Bodova et al., 2018}}, doi = {10.25386/genetics.6148304.v1}, year = {2018}, } @article{5780, abstract = {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.}, author = {Kotlobay, Alexey A. and Sarkisyan, Karen and Mokrushina, Yuliana A. and Marcet-Houben, Marina and Serebrovskaya, Ekaterina O. and Markina, Nadezhda M. and Gonzalez Somermeyer, Louisa and Gorokhovatsky, Andrey Y. and Vvedensky, Andrey and Purtov, Konstantin V. and Petushkov, Valentin N. and Rodionova, Natalja S. and Chepurnyh, Tatiana V. and Fakhranurova, Liliia and Guglya, Elena B. and Ziganshin, Rustam and Tsarkova, Aleksandra S. and Kaskova, Zinaida M. and Shender, Victoria and Abakumov, Maxim and Abakumova, Tatiana O. and Povolotskaya, Inna S. and Eroshkin, Fedor M. and Zaraisky, Andrey G. and Mishin, Alexander S. and Dolgov, Sergey V. and Mitiouchkina, Tatiana Y. and Kopantzev, Eugene P. and Waldenmaier, Hans E. and Oliveira, Anderson G. and Oba, Yuichi and Barsova, Ekaterina and Bogdanova, Ekaterina A. and Gabaldón, Toni and Stevani, Cassius V. and Lukyanov, Sergey and Smirnov, Ivan V. and Gitelson, Josef I. and Kondrashov, Fyodor and Yampolsky, Ilia V.}, issn = {00278424}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, number = {50}, pages = {12728--12732}, publisher = {National Academy of Sciences}, title = {{Genetically encodable bioluminescent system from fungi}}, doi = {10.1073/pnas.1803615115}, volume = {115}, year = {2018}, } @article{428, abstract = {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.}, author = {Salanenka, Yuliya and Verstraeten, Inge and Löfke, Christian and Tabata, Kaori and Naramoto, Satoshi and Glanc, Matous and Friml, Jirí}, journal = {PNAS}, number = {14}, pages = { 3716 -- 3721}, publisher = {National Academy of Sciences}, title = {{Gibberellin DELLA signaling targets the retromer complex to redirect protein trafficking to the plasma membrane}}, doi = {10.1073/pnas.1721760115}, volume = {115}, year = {2018}, } @article{62, abstract = {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.}, author = {Shabazi, Ali and Kinnison, Jeffery and Vescovi, Rafael and Du, Ming and Hill, Robert and Jösch, Maximilian A and Takeno, Marc and Zeng, Hongkui and Da Costa, Nuno and Grutzendler, Jaime and Kasthuri, Narayanan and Scheirer, Walter}, journal = {Scientific Reports}, number = {1}, publisher = {Nature Publishing Group}, title = {{Flexible learning-free segmentation and reconstruction of neural volumes}}, doi = {10.1038/s41598-018-32628-3}, volume = {8}, year = {2018}, } @article{437, abstract = {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.}, author = {Leithner, Alexander F and Renkawitz, Jörg and De Vries, Ingrid and Hauschild, Robert and Haecker, Hans and Sixt, Michael K}, journal = {European Journal of Immunology}, number = {6}, pages = {1074 -- 1077}, publisher = {Wiley-Blackwell}, title = {{Fast and efficient genetic engineering of hematopoietic precursor cells for the study of dendritic cell migration}}, doi = {10.1002/eji.201747358}, volume = {48}, year = {2018}, } @article{617, abstract = {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.}, author = {Kutzer, Megan and Kurtz, Joachim and Armitage, Sophie}, issn = {1420-9101}, journal = {Journal of Evolutionary Biology}, number = {1}, pages = {159 -- 171}, publisher = {Wiley}, title = {{Genotype and diet affect resistance, survival, and fecundity but not fecundity tolerance}}, doi = {10.1111/jeb.13211}, volume = {31}, year = {2018}, } @article{5888, abstract = {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.}, author = {Tarlungeanu, Dora-Clara and Novarino, Gaia}, issn = {2092-6413}, journal = {Experimental & Molecular Medicine}, number = {8}, publisher = {Springer Nature}, title = {{Genomics in neurodevelopmental disorders: an avenue to personalized medicine}}, doi = {10.1038/s12276-018-0129-7}, volume = {50}, year = {2018}, } @article{295, abstract = {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.}, author = {Lundholm, Douglas and Seiringer, Robert}, journal = {Letters in Mathematical Physics}, number = {11}, pages = {2523--2541}, publisher = {Springer}, title = {{Fermionic behavior of ideal anyons}}, doi = {10.1007/s11005-018-1091-y}, volume = {108}, year = {2018}, } @article{555, abstract = {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.}, author = {Richter, Ralf and Baranova, Natalia and Day, Anthony and Kwok, Jessica}, journal = {Current Opinion in Structural Biology}, pages = {65 -- 74}, publisher = {Elsevier}, title = {{Glycosaminoglycans in extracellular matrix organisation: Are concepts from soft matter physics key to understanding the formation of perineuronal nets?}}, doi = {10.1016/j.sbi.2017.12.002}, volume = {50}, year = {2018}, } @article{448, abstract = {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.}, author = {Harrison, Mark and Jongepier, Evelien and Robertson, Hugh and Arning, Nicolas and Bitard Feildel, Tristan and Chao, Hsu and Childers, Christopher and Dinh, Huyen and Doddapaneni, Harshavardhan and Dugan, Shannon and Gowin, Johannes and Greiner, Carolin and Han, Yi and Hu, Haofu and Hughes, Daniel and Huylmans, Ann K and Kemena, Karsten and Kremer, Lukas and Lee, Sandra and López Ezquerra, Alberto and Mallet, Ludovic and Monroy Kuhn, Jose and Moser, Annabell and Murali, Shwetha and Muzny, Donna and Otani, Saria and Piulachs, Maria and Poelchau, Monica and Qu, Jiaxin and Schaub, Florentine and Wada Katsumata, Ayako and Worley, Kim and Xie, Qiaolin and Ylla, Guillem and Poulsen, Michael and Gibbs, Richard and Schal, Coby and Richards, Stephen and Belles, Xavier and Korb, Judith and Bornberg Bauer, Erich}, journal = {Nature Ecology and Evolution}, number = {3}, pages = {557--566}, publisher = {Springer Nature}, title = {{Hemimetabolous genomes reveal molecular basis of termite eusociality}}, doi = {10.1038/s41559-017-0459-1}, volume = {2}, year = {2018}, } @article{723, abstract = {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.}, author = {Oliveto, Pietro and Paixao, Tiago and Pérez Heredia, Jorge and Sudholt, Dirk and Trubenova, Barbora}, journal = {Algorithmica}, number = {5}, pages = {1604 -- 1633}, publisher = {Springer}, title = {{How to escape local optima in black box optimisation when non elitism outperforms elitism}}, doi = {10.1007/s00453-017-0369-2}, volume = {80}, year = {2018}, } @article{321, abstract = {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.}, author = {Darrell, Trevor and Lampert, Christoph and Sebe, Nico and Wu, Ying and Yan, Yan}, journal = {IEEE Transactions on Pattern Analysis and Machine Intelligence}, number = {5}, pages = {1029 -- 1031}, publisher = {IEEE}, title = {{Guest editors' introduction to the special section on learning with Shared information for computer vision and multimedia analysis}}, doi = {10.1109/TPAMI.2018.2804998}, volume = {40}, year = {2018}, } @misc{9841, abstract = {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.}, author = {Harrison, Mark C. and Jongepier, Evelien and Robertson, Hugh M. and Arning, Nicolas and Bitard-Feildel, Tristan and Chao, Hsu and Childers, Christopher P. and Dinh, Huyen and Doddapaneni, Harshavardhan and Dugan, Shannon and Gowin, Johannes and Greiner, Carolin and Han, Yi and Hu, Haofu and Hughes, Daniel S. T. and Huylmans, Ann K and Kemena, Carsten and Kremer, Lukas P. M. and Lee, Sandra L. and Lopez-Ezquerra, Alberto and Mallet, Ludovic and Monroy-Kuhn, Jose M. and Moser, Annabell and Murali, Shwetha C. and Muzny, Donna M. and Otani, Saria and Piulachs, Maria-Dolors and Poelchau, Monica and Qu, Jiaxin and Schaub, Florentine and Wada-Katsumata, Ayako and Worley, Kim C. and Xie, Qiaolin and Ylla, Guillem and Poulsen, Michael and Gibbs, Richard A. and Schal, Coby and Richards, Stephen and Belles, Xavier and Korb, Judith and Bornberg-Bauer, Erich}, publisher = {Dryad}, title = {{Data from: Hemimetabolous genomes reveal molecular basis of termite eusociality}}, doi = {10.5061/dryad.51d4r}, year = {2018}, } @article{32, abstract = {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.}, author = {Chen, Ting and Kula, Bartosz and Nagy, Balint and Barzan, Ruxandra and Gall, Andrea and Ehrlich, Ingrid and Kukley, Maria}, journal = {Cell Reports}, number = {4}, pages = {852 -- 861.e7}, publisher = {Elsevier}, title = {{In Vivo regulation of Oligodendrocyte processor cell proliferation and differentiation by the AMPA-receptor Subunit GluA2}}, doi = {10.1016/j.celrep.2018.09.066}, volume = {25}, year = {2018}, } @article{5672, abstract = {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.}, author = {Reversat, Anne and Sixt, Michael K}, issn = {00221007}, journal = {Journal of Experimental Medicine}, number = {12}, pages = {2959--2961}, publisher = {Rockefeller University Press}, title = {{IgM's exit route}}, doi = {10.1084/jem.20181934}, volume = {215}, year = {2018}, } @article{458, abstract = {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.}, author = {Akopyan, Arseniy and Bobenko, Alexander}, journal = {Transactions of the American Mathematical Society}, number = {4}, pages = {2825 -- 2854}, publisher = {American Mathematical Society}, title = {{Incircular nets and confocal conics}}, doi = {10.1090/tran/7292}, volume = {370}, year = {2018}, } @inproceedings{5788, abstract = {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.}, author = {Avni, Guy and Henzinger, Thomas A and Ibsen-Jensen, Rasmus}, isbn = {9783030046118}, issn = {03029743}, location = {Oxford, UK}, pages = {21--36}, publisher = {Springer}, title = {{Infinite-duration poorman-bidding games}}, doi = {10.1007/978-3-030-04612-5_2}, volume = {11316}, year = {2018}, } @article{150, abstract = {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.}, author = {Dick, Robert and Zadrozny, Kaneil K and Xu, Chaoyi and Schur, Florian and Lyddon, Terri D and Ricana, Clifton L and Wagner, Jonathan M and Perilla, Juan R and Ganser, Pornillos Barbie K and Johnson, Marc C and Pornillos, Owen and Vogt, Volker}, issn = {1476-4687}, journal = {Nature}, number = {7719}, pages = {509–512}, publisher = {Nature Publishing Group}, title = {{Inositol phosphates are assembly co-factors for HIV-1}}, doi = {10.1038/s41586-018-0396-4}, volume = {560}, year = {2018}, } @article{303, abstract = {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.}, author = {Kalinin, Nikita and Shkolnikov, Mikhail}, journal = {Discrete and Continuous Dynamical Systems- Series A}, number = {6}, pages = {2827 -- 2849}, publisher = {AIMS}, title = {{Introduction to tropical series and wave dynamic on them}}, doi = {10.3934/dcds.2018120}, volume = {38}, year = {2018}, } @inproceedings{14202, abstract = {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.}, author = {Locatello, Francesco and Dresdner, Gideon and Khanna, Rajiv and Valera, Isabel and Rätsch, Gunnar}, booktitle = {Advances in Neural Information Processing Systems}, isbn = {9781510884472}, issn = {1049-5258}, location = {Montreal, Canada}, publisher = {Neural Information Processing Systems Foundation}, title = {{Boosting black box variational inference}}, volume = {31}, year = {2018}, } @inproceedings{14201, abstract = {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.}, author = {Locatello, Francesco and Khanna, Rajiv and Ghosh, Joydeep and Rätsch, Gunnar}, booktitle = {Proceedings of the 21st International Conference on Artificial Intelligence and Statistics}, location = {Playa Blanca, Lanzarote}, pages = {464--472}, publisher = {ML Research Press}, title = {{Boosting variational inference: An optimization perspective}}, volume = {84}, year = {2018}, } @inproceedings{14198, abstract = {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.}, author = {Fortuin, Vincent and Hüser, Matthias and Locatello, Francesco and Strathmann, Heiko and Rätsch, Gunnar}, booktitle = {International Conference on Learning Representations}, location = {New Orleans, LA, United States}, title = {{SOM-VAE: Interpretable discrete representation learning on time series}}, year = {2018}, } @inproceedings{14203, abstract = {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.}, author = {Yurtsever, Alp and Fercoq, Olivier and Locatello, Francesco and Cevher, Volkan}, booktitle = {Proceedings of the 35th International Conference on Machine Learning}, location = {Stockholm, Sweden}, pages = {5727--5736}, publisher = {ML Research Press}, title = {{A conditional gradient framework for composite convex minimization with applications to semidefinite programming}}, volume = {80}, year = {2018}, } @article{282, abstract = {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.}, author = {Sachdeva, Himani and Barton, Nicholas H}, journal = {Genetics}, number = {4}, pages = {1279 -- 1303}, publisher = {Genetics Society of America}, title = {{Introgression of a block of genome under infinitesimal selection}}, doi = {10.1534/genetics.118.301018}, volume = {209}, year = {2018}, } @inproceedings{108, abstract = {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.}, author = {Obremski, Marciej and Skorski, Maciej}, location = {Vail, CO, USA}, publisher = {IEEE}, title = {{Inverted leftover hash lemma}}, doi = {10.1109/ISIT.2018.8437654}, volume = {2018}, year = {2018}, } @inproceedings{14204, abstract = {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.}, author = {Locatello, Francesco and Raj, Anant and Karimireddy, Sai Praneeth and Rätsch, Gunnar and Schölkopf, Bernhard and Stich, Sebastian U. and Jaggi, Martin}, booktitle = {Proceedings of the 35th International Conference on Machine Learning}, pages = {3198--3207}, publisher = {ML Research Press}, title = {{On matching pursuit and coordinate descent}}, volume = {80}, year = {2018}, } @inproceedings{160, abstract = {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.}, author = {Kragl, Bernhard and Qadeer, Shaz}, location = {Oxford, UK}, pages = {79 -- 102}, publisher = {Springer}, title = {{Layered Concurrent Programs}}, doi = {10.1007/978-3-319-96145-3_5}, volume = {10981}, year = {2018}, } @article{82, abstract = {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.”.}, author = {Chaudhry, Waqas and Pleska, Maros and Shah, Nilang and Weiss, Howard and Mccall, Ingrid and Meyer, Justin and Gupta, Animesh and Guet, Calin C and Levin, Bruce}, journal = {PLoS Biology}, number = {8}, publisher = {Public Library of Science}, title = {{Leaky resistance and the conditions for the existence of lytic bacteriophage}}, doi = {10.1371/journal.pbio.2005971}, volume = {16}, year = {2018}, } @article{4, abstract = {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.}, author = {Umetani, Nobuyuki and Bickel, Bernd}, journal = {ACM Trans. Graph.}, number = {4}, publisher = {ACM}, title = {{Learning three-dimensional flow for interactive aerodynamic design}}, doi = {10.1145/3197517.3201325}, volume = {37}, year = {2018}, } @article{566, abstract = {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. }, author = {Alt, Johannes and Erdös, László and Krüger, Torben H}, journal = {Annals Applied Probability }, number = {1}, pages = {148--203}, publisher = {Institute of Mathematical Statistics}, title = {{Local inhomogeneous circular law}}, doi = {10.1214/17-AAP1302}, volume = {28}, year = {2018}, } @article{106, abstract = {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.}, author = {Akopyan, Arseniy and Petrunin, Anton}, journal = {Mathematical Intelligencer}, number = {3}, pages = {26 -- 31}, publisher = {Springer}, title = {{Long geodesics on convex surfaces}}, doi = {10.1007/s00283-018-9795-5}, volume = {40}, year = {2018}, } @article{275, abstract = {Lymphatic endothelial cells (LECs) release extracellular chemokines to guide the migration of dendritic cells. In this study, we report that LECs also release basolateral exosome-rich endothelial vesicles (EEVs) that are secreted in greater numbers in the presence of inflammatory cytokines and accumulate in the perivascular stroma of small lymphatic vessels in human chronic inflammatory diseases. Proteomic analyses of EEV fractions identified > 1,700 cargo proteins and revealed a dominant motility-promoting protein signature. In vitro and ex vivo EEV fractions augmented cellular protrusion formation in a CX3CL1/fractalkine-dependent fashion and enhanced the directional migratory response of human dendritic cells along guidance cues. We conclude that perilymphatic LEC exosomes enhance exploratory behavior and thus promote directional migration of CX3CR1-expressing cells in complex tissue environments.}, author = {Brown, Markus and Johnson, Louise and Leone, Dario and Májek, Peter and Vaahtomeri, Kari and Senfter, Daniel and Bukosza, Nora and Schachner, Helga and Asfour, Gabriele and Langer, Brigitte and Hauschild, Robert and Parapatics, Katja and Hong, Young and Bennett, Keiryn and Kain, Renate and Detmar, Michael and Sixt, Michael K and Jackson, David and Kerjaschki, Dontscho}, journal = {Journal of Cell Biology}, number = {6}, pages = {2205 -- 2221}, publisher = {Rockefeller University Press}, title = {{Lymphatic exosomes promote dendritic cell migration along guidance cues}}, doi = {10.1083/jcb.201612051}, volume = {217}, year = {2018}, } @article{158, abstract = {The angiosperm seed is composed of three genetically distinct tissues: the diploid embryo that originates from the fertilized egg cell, the triploid endosperm that is produced from the fertilized central cell, and the maternal sporophytic integuments that develop into the seed coat1. At the onset of embryo development in Arabidopsis thaliana, the zygote divides asymmetrically, producing a small apical embryonic cell and a larger basal cell that connects the embryo to the maternal tissue2. The coordinated and synchronous development of the embryo and the surrounding integuments, and the alignment of their growth axes, suggest communication between maternal tissues and the embryo. In contrast to animals, however, where a network of maternal factors that direct embryo patterning have been identified3,4, only a few maternal mutations have been described to affect embryo development in plants5–7. Early embryo patterning in Arabidopsis requires accumulation of the phytohormone auxin in the apical cell by directed transport from the suspensor8–10. However, the origin of this auxin has remained obscure. Here we investigate the source of auxin for early embryogenesis and provide evidence that the mother plant coordinates seed development by supplying auxin to the early embryo from the integuments of the ovule. We show that auxin response increases in ovules after fertilization, due to upregulated auxin biosynthesis in the integuments, and this maternally produced auxin is required for correct embryo development.}, author = {Robert, Hélène and Park, Chulmin and Gutièrrez, Carla and Wójcikowska, Barbara and Pěnčík, Aleš and Novák, Ondřej and Chen, Junyi and Grunewald, Wim and Dresselhaus, Thomas and Friml, Jirí and Laux, Thomas}, journal = {Nature Plants}, number = {8}, pages = {548 -- 553}, publisher = {Nature Publishing Group}, title = {{Maternal auxin supply contributes to early embryo patterning in Arabidopsis}}, doi = {10.1038/s41477-018-0204-z}, volume = {4}, year = {2018}, } @article{152, abstract = {Complex I has an essential role in ATP production by coupling electron transfer from NADH to quinone with translocation of protons across the inner mitochondrial membrane. Isolated complex I deficiency is a frequent cause of mitochondrial inherited diseases. Complex I has also been implicated in cancer, ageing, and neurodegenerative conditions. Until recently, the understanding of complex I deficiency on the molecular level was limited due to the lack of high-resolution structures of the enzyme. However, due to developments in single particle cryo-electron microscopy (cryo-EM), recent studies have reported nearly atomic resolution maps and models of mitochondrial complex I. These structures significantly add to our understanding of complex I mechanism and assembly. The disease-causing mutations are discussed here in their structural context.}, author = {Fiedorczuk, Karol and Sazanov, Leonid A}, journal = {Trends in Cell Biology}, number = {10}, pages = {835 -- 867}, publisher = {Elsevier}, title = {{Mammalian mitochondrial complex I structure and disease causing mutations}}, doi = {10.1016/j.tcb.2018.06.006}, volume = {28}, year = {2018}, } @inproceedings{310, abstract = {A model of computation that is widely used in the formal analysis of reactive systems is symbolic algorithms. In this model the access to the input graph is restricted to consist of symbolic operations, which are expensive in comparison to the standard RAM operations. We give lower bounds on the number of symbolic operations for basic graph problems such as the computation of the strongly connected components and of the approximate diameter as well as for fundamental problems in model checking such as safety, liveness, and coliveness. Our lower bounds are linear in the number of vertices of the graph, even for constant-diameter graphs. For none of these problems lower bounds on the number of symbolic operations were known before. The lower bounds show an interesting separation of these problems from the reachability problem, which can be solved with O(D) symbolic operations, where D is the diameter of the graph. Additionally we present an approximation algorithm for the graph diameter which requires Õ(n/D) symbolic steps to achieve a (1 +ϵ)-approximation for any constant > 0. This compares to O(n/D) symbolic steps for the (naive) exact algorithm and O(D) symbolic steps for a 2-approximation. Finally we also give a refined analysis of the strongly connected components algorithms of [15], showing that it uses an optimal number of symbolic steps that is proportional to the sum of the diameters of the strongly connected components.}, author = {Chatterjee, Krishnendu and Dvorák, Wolfgang and Henzinger, Monika H and Loitzenbauer, Veronika}, location = {New Orleans, Louisiana, United States}, pages = {2341 -- 2356}, publisher = {ACM}, title = {{Lower bounds for symbolic computation on graphs: Strongly connected components, liveness, safety, and diameter}}, doi = {10.1137/1.9781611975031.151}, year = {2018}, } @article{436, abstract = {There has been significant interest recently in using complex quantum systems to create effective nonreciprocal dynamics. Proposals have been put forward for the realization of artificial magnetic fields for photons and phonons; experimental progress is fast making these proposals a reality. Much work has concentrated on the use of such systems for controlling the flow of signals, e.g., to create isolators or directional amplifiers for optical signals. In this Letter, we build on this work but move in a different direction. We develop the theory of and discuss a potential realization for the controllable flow of thermal noise in quantum systems. We demonstrate theoretically that the unidirectional flow of thermal noise is possible within quantum cascaded systems. Viewing an optomechanical platform as a cascaded system we show here that one can ultimately control the direction of the flow of thermal noise. By appropriately engineering the mechanical resonator, which acts as an artificial reservoir, the flow of thermal noise can be constrained to a desired direction, yielding a thermal rectifier. The proposed quantum thermal noise rectifier could potentially be used to develop devices such as a thermal modulator, a thermal router, and a thermal amplifier for nanoelectronic devices and superconducting circuits.}, author = {Barzanjeh, Shabir and Aquilina, Matteo and Xuereb, André}, journal = {Physical Review Letters}, number = {6}, publisher = {American Physical Society}, title = {{Manipulating the flow of thermal noise in quantum devices}}, doi = {10.1103/PhysRevLett.120.060601}, volume = {120}, year = {2018}, } @article{5858, abstract = {Spatial patterns are ubiquitous on the subcellular, cellular and tissue level, and can be studied using imaging techniques such as light and fluorescence microscopy. Imaging data provide quantitative information about biological systems; however, mechanisms causing spatial patterning often remain elusive. In recent years, spatio-temporal mathematical modelling has helped to overcome this problem. Yet, outliers and structured noise limit modelling of whole imaging data, and models often consider spatial summary statistics. Here, we introduce an integrated data-driven modelling approach that can cope with measurement artefacts and whole imaging data. Our approach combines mechanistic models of the biological processes with robust statistical models of the measurement process. The parameters of the integrated model are calibrated using a maximum-likelihood approach. We used this integrated modelling approach to study in vivo gradients of the chemokine (C-C motif) ligand 21 (CCL21). CCL21 gradients guide dendritic cells and are important in the adaptive immune response. Using artificial data, we verified that the integrated modelling approach provides reliable parameter estimates in the presence of measurement noise and that bias and variance of these estimates are reduced compared to conventional approaches. The application to experimental data allowed the parametrization and subsequent refinement of the model using additional mechanisms. Among other results, model-based hypothesis testing predicted lymphatic vessel-dependent concentration of heparan sulfate, the binding partner of CCL21. The selected model provided an accurate description of the experimental data and was partially validated using published data. Our findings demonstrate that integrated statistical modelling of whole imaging data is computationally feasible and can provide novel biological insights.}, author = {Hross, Sabrina and Theis, Fabian J. and Sixt, Michael K and Hasenauer, Jan}, issn = {17425689}, journal = {Journal of the Royal Society Interface}, number = {149}, publisher = {Royal Society Publishing}, title = {{Mechanistic description of spatial processes using integrative modelling of noise-corrupted imaging data}}, doi = {10.1098/rsif.2018.0600}, volume = {15}, year = {2018}, } @article{16, abstract = {We report quantitative evidence of mixing-layer elastic instability in a viscoelastic fluid flow between two widely spaced obstacles hindering a channel flow at Re 1 and Wi 1. Two mixing layers with nonuniform shear velocity profiles are formed in the region between the obstacles. The mixing-layer instability arises in the vicinity of an inflection point on the shear velocity profile with a steep variation in the elastic stress. The instability results in an intermittent appearance of small vortices in the mixing layers and an amplification of spatiotemporal averaged vorticity in the elastic turbulence regime. The latter is characterized through scaling of friction factor with Wi and both pressure and velocity spectra. Furthermore, the observations reported provide improved understanding of the stability of the mixing layer in a viscoelastic fluid at large elasticity, i.e., Wi 1 and Re 1 and oppose the current view of suppression of vorticity solely by polymer additives.}, author = {Varshney, Atul and Steinberg, Victor}, journal = {Physical Review Fluids}, number = {10}, publisher = {American Physical Society}, title = {{Mixing layer instability and vorticity amplification in a creeping viscoelastic flow}}, doi = {10.1103/PhysRevFluids.3.103303}, volume = {3}, year = {2018}, } @article{43, abstract = {The initial amount of pathogens required to start an infection within a susceptible host is called the infective dose and is known to vary to a large extent between different pathogen species. We investigate the hypothesis that the differences in infective doses are explained by the mode of action in the underlying mechanism of pathogenesis: Pathogens with locally acting mechanisms tend to have smaller infective doses than pathogens with distantly acting mechanisms. While empirical evidence tends to support the hypothesis, a formal theoretical explanation has been lacking. We give simple analytical models to gain insight into this phenomenon and also investigate a stochastic, spatially explicit, mechanistic within-host model for toxin-dependent bacterial infections. The model shows that pathogens secreting locally acting toxins have smaller infective doses than pathogens secreting diffusive toxins, as hypothesized. While local pathogenetic mechanisms require smaller infective doses, pathogens with distantly acting toxins tend to spread faster and may cause more damage to the host. The proposed model can serve as a basis for the spatially explicit analysis of various virulence factors also in the context of other problems in infection dynamics.}, author = {Rybicki, Joel and Kisdi, Eva and Anttila, Jani}, journal = {PNAS}, number = {42}, pages = {10690 -- 10695}, publisher = {National Academy of Sciences}, title = {{Model of bacterial toxin-dependent pathogenesis explains infective dose}}, doi = {10.1073/pnas.1721061115}, volume = {115}, year = {2018}, }