TY - GEN AB - This dataset contains a GitHub repository containing all the data, analysis, Nextflow workflows and Jupyter notebooks to replicate the manuscript titled "Fast and accurate large multiple sequence alignments with a root-to-leaf regressive method". It also contains the Multiple Sequence Alignments (MSAs) generated and well as the main figures and tables from the manuscript. The repository is also available at GitHub (https://github.com/cbcrg/dpa-analysis) release `v1.2`. For details on how to use the regressive alignment algorithm, see the T-Coffee software suite (https://github.com/cbcrg/tcoffee). AU - Garriga, Edgar AU - di Tommaso, Paolo AU - Magis, Cedrik AU - Erb, Ionas AU - Mansouri, Leila AU - Baltzis, Athanasios AU - Laayouni, Hafid AU - Kondrashov, Fyodor AU - Floden, Evan AU - Notredame, Cedric ID - 13059 TI - Fast and accurate large multiple sequence alignments with a root-to-leaf regressive method ER - TY - THES AB - Nowadays, quantum computation is receiving more and more attention as an alternative to the classical way of computing. For realizing a quantum computer, different devices are investigated as potential quantum bits. In this thesis, the focus is on Ge hut wires, which turned out to be promising candidates for implementing hole spin quantum bits. The advantages of Ge as a material system are the low hyperfine interaction for holes and the strong spin orbit coupling, as well as the compatibility with the highly developed CMOS processes in industry. In addition, Ge can also be isotopically purified which is expected to boost the spin coherence times. The strong spin orbit interaction for holes in Ge on the one hand enables the full electrical control of the quantum bit and on the other hand should allow short spin manipulation times. Starting with a bare Si wafer, this work covers the entire process reaching from growth over the fabrication and characterization of hut wire devices up to the demonstration of hole spin resonance. From experiments with single quantum dots, a large g-factor anisotropy between the in-plane and the out-of-plane direction was found. A comparison to a theoretical model unveiled the heavy-hole character of the lowest energy states. The second part of the thesis addresses double quantum dot devices, which were realized by adding two gate electrodes to a hut wire. In such devices, Pauli spin blockade was observed, which can serve as a read-out mechanism for spin quantum bits. Applying oscillating electric fields in spin blockade allowed the demonstration of continuous spin rotations and the extraction of a lower bound for the spin dephasing time. Despite the strong spin orbit coupling in Ge, the obtained value for the dephasing time is comparable to what has been recently reported for holes in Si. All in all, the presented results point out the high potential of Ge hut wires as a platform for long-lived, fast and fully electrically tunable hole spin quantum bits. AU - Watzinger, Hannes ID - 49 SN - 2663-337X TI - Ge hut wires - from growth to hole spin resonance ER - TY - THES AB - We describe arrangements of three-dimensional spheres from a geometrical and topological point of view. Real data (fitting this setup) often consist of soft spheres which show certain degree of deformation while strongly packing against each other. In this context, we answer the following questions: If we model a soft packing of spheres by hard spheres that are allowed to overlap, can we measure the volume in the overlapped areas? Can we be more specific about the overlap volume, i.e. quantify how much volume is there covered exactly twice, three times, or k times? What would be a good optimization criteria that rule the arrangement of soft spheres while making a good use of the available space? Fixing a particular criterion, what would be the optimal sphere configuration? The first result of this thesis are short formulas for the computation of volumes covered by at least k of the balls. The formulas exploit information contained in the order-k Voronoi diagrams and its closely related Level-k complex. The used complexes lead to a natural generalization into poset diagrams, a theoretical formalism that contains the order-k and degree-k diagrams as special cases. In parallel, we define different criteria to determine what could be considered an optimal arrangement from a geometrical point of view. Fixing a criterion, we find optimal soft packing configurations in 2D and 3D where the ball centers lie on a lattice. As a last step, we use tools from computational topology on real physical data, to show the potentials of higher-order diagrams in the description of melting crystals. The results of the experiments leaves us with an open window to apply the theories developed in this thesis in real applications. AU - Iglesias Ham, Mabel ID - 201 SN - 2663-337X TI - Multiple covers with balls ER - TY - THES AB - The most common assumption made in statistical learning theory is the assumption of the independent and identically distributed (i.i.d.) data. While being very convenient mathematically, it is often very clearly violated in practice. This disparity between the machine learning theory and applications underlies a growing demand in the development of algorithms that learn from dependent data and theory that can provide generalization guarantees similar to the independent situations. This thesis is dedicated to two variants of dependencies that can arise in practice. One is a dependence on the level of samples in a single learning task. Another dependency type arises in the multi-task setting when the tasks are dependent on each other even though the data for them can be i.i.d. In both cases we model the data (samples or tasks) as stochastic processes and introduce new algorithms for both settings that take into account and exploit the resulting dependencies. We prove the theoretical guarantees on the performance of the introduced algorithms under different evaluation criteria and, in addition, we compliment the theoretical study by the empirical one, where we evaluate some of the algorithms on two real world datasets to highlight their practical applicability. AU - Zimin, Alexander ID - 68 SN - 2663-337X TI - Learning from dependent data ER - TY - THES AB - A proof system is a protocol between a prover and a verifier over a common input in which an honest prover convinces the verifier of the validity of true statements. Motivated by the success of decentralized cryptocurrencies, exemplified by Bitcoin, the focus of this thesis will be on proof systems which found applications in some sustainable alternatives to Bitcoin, such as the Spacemint and Chia cryptocurrencies. In particular, we focus on proofs of space and proofs of sequential work. Proofs of space (PoSpace) were suggested as more ecological, economical, and egalitarian alternative to the energy-wasteful proof-of-work mining of Bitcoin. However, the state-of-the-art constructions of PoSpace are based on sophisticated graph pebbling lower bounds, and are therefore complex. Moreover, when these PoSpace are used in cryptocurrencies like Spacemint, miners can only start mining after ensuring that a commitment to their space is already added in a special transaction to the blockchain. Proofs of sequential work (PoSW) are proof systems in which a prover, upon receiving a statement x and a time parameter T, computes a proof which convinces the verifier that T time units had passed since x was received. Whereas Spacemint assumes synchrony to retain some interesting Bitcoin dynamics, Chia requires PoSW with unique proofs, i.e., PoSW in which it is hard to come up with more than one accepting proof for any true statement. In this thesis we construct simple and practically-efficient PoSpace and PoSW. When using our PoSpace in cryptocurrencies, miners can start mining on the fly, like in Bitcoin, and unlike current constructions of PoSW, which either achieve efficient verification of sequential work, or faster-than-recomputing verification of correctness of proofs, but not both at the same time, ours achieve the best of these two worlds. AU - Abusalah, Hamza M ID - 83 SN - 2663-337X TI - Proof systems for sustainable decentralized cryptocurrencies ER - TY - THES AB - Modern computer vision systems heavily rely on statistical machine learning models, which typically require large amounts of labeled data to be learned reliably. Moreover, very recently computer vision research widely adopted techniques for representation learning, which further increase the demand for labeled data. However, for many important practical problems there is relatively small amount of labeled data available, so it is problematic to leverage full potential of the representation learning methods. One way to overcome this obstacle is to invest substantial resources into producing large labelled datasets. Unfortunately, this can be prohibitively expensive in practice. In this thesis we focus on the alternative way of tackling the aforementioned issue. We concentrate on methods, which make use of weakly-labeled or even unlabeled data. Specifically, the first half of the thesis is dedicated to the semantic image segmentation task. We develop a technique, which achieves competitive segmentation performance and only requires annotations in a form of global image-level labels instead of dense segmentation masks. Subsequently, we present a new methodology, which further improves segmentation performance by leveraging tiny additional feedback from a human annotator. By using our methods practitioners can greatly reduce the amount of data annotation effort, which is required to learn modern image segmentation models. In the second half of the thesis we focus on methods for learning from unlabeled visual data. We study a family of autoregressive models for modeling structure of natural images and discuss potential applications of these models. Moreover, we conduct in-depth study of one of these applications, where we develop the state-of-the-art model for the probabilistic image colorization task. AU - Kolesnikov, Alexander ID - 197 SN - 2663-337X TI - Weakly-Supervised Segmentation and Unsupervised Modeling of Natural Images ER - TY - JOUR AB - A central problem of algebraic topology is to understand the homotopy groups 𝜋𝑑(𝑋) of a topological space X. For the computational version of the problem, it is well known that there is no algorithm to decide whether the fundamental group 𝜋1(𝑋) of a given finite simplicial complex X is trivial. On the other hand, there are several algorithms that, given a finite simplicial complex X that is simply connected (i.e., with 𝜋1(𝑋) trivial), compute the higher homotopy group 𝜋𝑑(𝑋) for any given đ‘‘â‰„2 . However, these algorithms come with a caveat: They compute the isomorphism type of 𝜋𝑑(𝑋) , đ‘‘â‰„2 as an abstract finitely generated abelian group given by generators and relations, but they work with very implicit representations of the elements of 𝜋𝑑(𝑋) . Converting elements of this abstract group into explicit geometric maps from the d-dimensional sphere 𝑆𝑑 to X has been one of the main unsolved problems in the emerging field of computational homotopy theory. Here we present an algorithm that, given a simply connected space X, computes 𝜋𝑑(𝑋) and represents its elements as simplicial maps from a suitable triangulation of the d-sphere 𝑆𝑑 to X. For fixed d, the algorithm runs in time exponential in size(𝑋) , the number of simplices of X. Moreover, we prove that this is optimal: For every fixed đ‘‘â‰„2 , we construct a family of simply connected spaces X such that for any simplicial map representing a generator of 𝜋𝑑(𝑋) , the size of the triangulation of 𝑆𝑑 on which the map is defined, is exponential in size(𝑋) . AU - FilakovskĂœ, Marek AU - Franek, Peter AU - Wagner, Uli AU - Zhechev, Stephan Y ID - 6774 IS - 3-4 JF - Journal of Applied and Computational Topology SN - 2367-1726 TI - Computing simplicial representatives of homotopy group elements VL - 2 ER - TY - CONF AB - Synchronous programs are easy to specify because the side effects of an operation are finished by the time the invocation of the operation returns to the caller. Asynchronous programs, on the other hand, are difficult to specify because there are side effects due to pending computation scheduled as a result of the invocation of an operation. They are also difficult to verify because of the large number of possible interleavings of concurrent computation threads. We present synchronization, a new proof rule that simplifies the verification of asynchronous programs by introducing the fiction, for proof purposes, that asynchronous operations complete synchronously. Synchronization summarizes an asynchronous computation as immediate atomic effect. Modular verification is enabled via pending asynchronous calls in atomic summaries, and a complementary proof rule that eliminates pending asynchronous calls when components and their specifications are composed. We evaluate synchronization in the context of a multi-layer refinement verification methodology on a collection of benchmark programs. AU - Kragl, Bernhard AU - Qadeer, Shaz AU - Henzinger, Thomas A ID - 133 SN - 18688969 TI - Synchronizing the asynchronous VL - 118 ER - TY - CONF AB - Given a locally finite X ⊆ ℝd and a radius r ≄ 0, the k-fold cover of X and r consists of all points in ℝd that have k or more points of X within distance r. We consider two filtrations - one in scale obtained by fixing k and increasing r, and the other in depth obtained by fixing r and decreasing k - and we compute the persistence diagrams of both. While standard methods suffice for the filtration in scale, we need novel geometric and topological concepts for the filtration in depth. In particular, we introduce a rhomboid tiling in ℝd+1 whose horizontal integer slices are the order-k Delaunay mosaics of X, and construct a zigzag module from Delaunay mosaics that is isomorphic to the persistence module of the multi-covers. AU - Edelsbrunner, Herbert AU - Osang, Georg F ID - 187 TI - The multi-cover persistence of Euclidean balls VL - 99 ER - TY - JOUR AB - We consider families of confocal conics and two pencils of Apollonian circles having the same foci. We will show that these families of curves generate trivial 3-webs and find the exact formulas describing them. AU - Akopyan, Arseniy ID - 692 IS - 1 JF - Geometriae Dedicata TI - 3-Webs generated by confocal conics and circles VL - 194 ER - TY - JOUR AB - Holes confined in quantum dots have gained considerable interest in the past few years due to their potential as spin qubits. Here we demonstrate two-axis control of a spin 3/2 qubit in natural Ge. The qubit is formed in a hut wire double quantum dot device. The Pauli spin blockade principle allowed us to demonstrate electric dipole spin resonance by applying a radio frequency electric field to one of the electrodes defining the double quantum dot. Coherent hole spin oscillations with Rabi frequencies reaching 140 MHz are demonstrated and dephasing times of 130 ns are measured. The reported results emphasize the potential of Ge as a platform for fast and electrically tunable hole spin qubit devices. AU - Watzinger, Hannes AU - Kukucka, Josip AU - Vukusic, Lada AU - Gao, Fei AU - Wang, Ting AU - SchĂ€ffler, Friedrich AU - Zhang, Jian AU - Katsaros, Georgios ID - 77 IS - 3902 JF - Nature Communications TI - A germanium hole spin qubit VL - 9 ER - TY - JOUR AB - The actomyosin cytoskeleton, a key stress-producing unit in epithelial cells, oscillates spontaneously in a wide variety of systems. Although much of the signal cascade regulating myosin activity has been characterized, the origin of such oscillatory behavior is still unclear. Here, we show that basal myosin II oscillation in Drosophila ovarian epithelium is not controlled by actomyosin cortical tension, but instead relies on a biochemical oscillator involving ROCK and myosin phosphatase. Key to this oscillation is a diffusive ROCK flow, linking junctional Rho1 to medial actomyosin cortex, and dynamically maintained by a self-activation loop reliant on ROCK kinase activity. In response to the resulting myosin II recruitment, myosin phosphatase is locally enriched and shuts off ROCK and myosin II signals. Coupling Drosophila genetics, live imaging, modeling, and optogenetics, we uncover an intrinsic biochemical oscillator at the core of myosin II regulatory network, shedding light on the spatio-temporal dynamics of force generation. AU - Qin, Xiang AU - Hannezo, Edouard B AU - Mangeat, Thomas AU - Liu, Chang AU - Majumder, Pralay AU - Liu, Jjiaying AU - Choesmel Cadamuro, Valerie AU - Mcdonald, Jocelyn AU - Liu, Yinyao AU - Yi, Bin AU - Wang, Xiaobo ID - 401 IS - 1 JF - Nature Communications TI - A biochemical network controlling basal myosin oscillation VL - 9 ER - TY - JOUR AB - The insect’s fat body combines metabolic and immunological functions. In this issue of Developmental Cell, Franz et al. (2018) show that in Drosophila, cells of the fat body are not static, but can actively “swim” toward sites of epithelial injury, where they physically clog the wound and locally secrete antimicrobial peptides. AU - Casano, Alessandra M AU - Sixt, Michael K ID - 318 IS - 4 JF - Developmental Cell TI - A fat lot of good for wound healing VL - 44 ER - TY - JOUR AB - Lesion verification and quantification is traditionally done via histological examination of sectioned brains, a time-consuming process that relies heavily on manual estimation. Such methods are particularly problematic in posterior cortical regions (e.g. visual cortex), where sectioning leads to significant damage and distortion of tissue. Even more challenging is the post hoc localization of micro-electrodes, which relies on the same techniques, suffers from similar drawbacks and requires even higher precision. Here, we propose a new, simple method for quantitative lesion characterization and electrode localization that is less labor-intensive and yields more detailed results than conventional methods. We leverage staining techniques standard in electron microscopy with the use of commodity micro-CT imaging. We stain whole rat and zebra finch brains in osmium tetroxide, embed these in resin and scan entire brains in a micro-CT machine. The scans result in 3D reconstructions of the brains with section thickness dependent on sample size (12–15 and 5–6 microns for rat and zebra finch respectively) that can be segmented manually or automatically. Because the method captures the entire intact brain volume, comparisons within and across studies are more tractable, and the extent of lesions and electrodes may be studied with higher accuracy than with current methods. AU - MasĂ­s, Javier AU - Mankus, David AU - Wolff, Steffen AU - Guitchounts, Grigori AU - Jösch, Maximilian A AU - Cox, David ID - 410 IS - 1 JF - Scientific Reports TI - A micro-CT-based method for quantitative brain lesion characterization and electrode localization VL - 8 ER - TY - JOUR AB - Arabidopsis and human ARM protein interact with telomerase. Deregulated mRNA levels of DNA repair and ribosomal protein genes in an Arabidopsis arm mutant suggest non-telomeric ARM function. The human homolog ARMC6 interacts with hTRF2. Abstract: Telomerase maintains telomeres and has proposed non-telomeric functions. We previously identified interaction of the C-terminal domain of Arabidopsis telomerase reverse transcriptase (AtTERT) with an armadillo/ÎČ-catenin-like repeat (ARM) containing protein. Here we explore protein–protein interactions of the ARM protein, AtTERT domains, POT1a, TRF-like family and SMH family proteins, and the chromatin remodeling protein CHR19 using bimolecular fluorescence complementation (BiFC), yeast two-hybrid (Y2H) analysis, and co-immunoprecipitation. The ARM protein interacts with both the N- and C-terminal domains of AtTERT in different cellular compartments. ARM interacts with CHR19 and TRF-like I family proteins that also bind AtTERT directly or through interaction with POT1a. The putative human ARM homolog co-precipitates telomerase activity and interacts with hTRF2 protein in vitro. Analysis of Arabidopsis arm mutants shows no obvious changes in telomere length or telomerase activity, suggesting that ARM is not essential for telomere maintenance. The observed interactions with telomerase and Myb-like domain proteins (TRF-like family I) may therefore reflect possible non-telomeric functions. Transcript levels of several DNA repair and ribosomal genes are affected in arm mutants, and ARM, likely in association with other proteins, suppressed expression of XRCC3 and RPSAA promoter constructs in luciferase reporter assays. In conclusion, ARM can participate in non-telomeric functions of telomerase, and can also perform its own telomerase-independent functions. AU - DoklĂĄdal, Ladislav AU - BenkovĂĄ, Eva AU - Honys, David AU - DuplĂĄkovĂĄ, Nikoleta AU - Lee, Lan AU - Gelvin, Stanton AU - SĂœkorovĂĄ, Eva ID - 277 IS - 5 JF - Plant Molecular Biology TI - An armadillo-domain protein participates in a telomerase interaction network VL - 97 ER - TY - CONF AB - We introduce in this paper AMT 2.0 , a tool for qualitative and quantitative analysis of hybrid continuous and Boolean signals that combine numerical values and discrete events. The evaluation of the signals is based on rich temporal specifications expressed in extended Signal Temporal Logic (xSTL), which integrates Timed Regular Expressions (TRE) within Signal Temporal Logic (STL). The tool features qualitative monitoring (property satisfaction checking), trace diagnostics for explaining and justifying property violations and specification-driven measurement of quantitative features of the signal. AU - Nickovic, Dejan AU - Lebeltel, Olivier AU - Maler, Oded AU - Ferrere, Thomas AU - Ulus, Dogan ED - Beyer, Dirk ED - Huisman, Marieke ID - 299 TI - AMT 2.0: Qualitative and quantitative trace analysis with extended signal temporal logic VL - 10806 ER - TY - JOUR AB - Being cared for when sick is a benefit of sociality that can reduce disease and improve survival of group members. However, individuals providing care risk contracting infectious diseases themselves. If they contract a low pathogen dose, they may develop low-level infections that do not cause disease but still affect host immunity by either decreasing or increasing the host’s vulnerability to subsequent infections. Caring for contagious individuals can thus significantly alter the future disease susceptibility of caregivers. Using ants and their fungal pathogens as a model system, we tested if the altered disease susceptibility of experienced caregivers, in turn, affects their expression of sanitary care behavior. We found that low-level infections contracted during sanitary care had protective or neutral effects on secondary exposure to the same (homologous) pathogen but consistently caused high mortality on superinfection with a different (heterologous) pathogen. In response to this risk, the ants selectively adjusted the expression of their sanitary care. Specifically, the ants performed less grooming and more antimicrobial disinfection when caring for nestmates contaminated with heterologous pathogens compared with homologous ones. By modulating the components of sanitary care in this way the ants acquired less infectious particles of the heterologous pathogens, resulting in reduced superinfection. The performance of risk-adjusted sanitary care reveals the remarkable capacity of ants to react to changes in their disease susceptibility, according to their own infection history and to flexibly adjust collective care to individual risk. AU - Konrad, Matthias AU - Pull, Christopher AU - Metzler, Sina AU - Seif, Katharina AU - Naderlinger, Elisabeth AU - Grasse, Anna V AU - Cremer, Sylvia ID - 413 IS - 11 JF - PNAS TI - Ants avoid superinfections by performing risk-adjusted sanitary care VL - 115 ER - TY - JOUR AB - We demonstrate that identical impurities immersed in a two-dimensional many-particle bath can be viewed as flux-tube-charged-particle composites described by fractional statistics. In particular, we find that the bath manifests itself as an external magnetic flux tube with respect to the impurities, and hence the time-reversal symmetry is broken for the effective Hamiltonian describing the impurities. The emerging flux tube acts as a statistical gauge field after a certain critical coupling. This critical coupling corresponds to the intersection point between the quasiparticle state and the phonon wing, where the angular momentum is transferred from the impurity to the bath. This amounts to a novel configuration with emerging anyons. The proposed setup paves the way to realizing anyons using electrons interacting with superfluid helium or lattice phonons, as well as using atomic impurities in ultracold gases. AU - Yakaboylu, Enderalp AU - Lemeshko, Mikhail ID - 195 IS - 4 JF - Physical Review B - Condensed Matter and Materials Physics TI - Anyonic statistics of quantum impurities in two dimensions VL - 98 ER - TY - CONF AB - The task of a monitor is to watch, at run-time, the execution of a reactive system, and signal the occurrence of a safety violation in the observed sequence of events. While finite-state monitors have been studied extensively, in practice, monitoring software also makes use of unbounded memory. We define a model of automata equipped with integer-valued registers which can execute only a bounded number of instructions between consecutive events, and thus can form the theoretical basis for the study of infinite-state monitors. We classify these register monitors according to the number k of available registers, and the type of register instructions. In stark contrast to the theory of computability for register machines, we prove that for every k 1, monitors with k + 1 counters (with instruction set 〈+1, =〉) are strictly more expressive than monitors with k counters. We also show that adder monitors (with instruction set 〈1, +, =〉) are strictly more expressive than counter monitors, but are complete for monitoring all computable safety -languages for k = 6. Real-time monitors are further required to signal the occurrence of a safety violation as soon as it occurs. The expressiveness hierarchy for counter monitors carries over to real-time monitors. We then show that 2 adders cannot simulate 3 counters in real-time. Finally, we show that real-time adder monitors with inequalities are as expressive as real-time Turing machines. AU - Ferrere, Thomas AU - Henzinger, Thomas A AU - Saraç, Ege ID - 144 TI - A theory of register monitors VL - Part F138033 ER - TY - JOUR AB - Asymmetric auxin distribution is instrumental for the differential growth that causes organ bending on tropic stimuli and curvatures during plant development. Local differences in auxin concentrations are achieved mainly by polarized cellular distribution of PIN auxin transporters, but whether other mechanisms involving auxin homeostasis are also relevant for the formation of auxin gradients is not clear. Here we show that auxin methylation is required for asymmetric auxin distribution across the hypocotyl, particularly during its response to gravity. We found that loss-of-function mutants in Arabidopsis IAA CARBOXYL METHYLTRANSFERASE1 (IAMT1) prematurely unfold the apical hook, and that their hypocotyls are impaired in gravitropic reorientation. This defect is linked to an auxin-dependent increase in PIN gene expression, leading to an increased polar auxin transport and lack of asymmetric distribution of PIN3 in the iamt1 mutant. Gravitropic reorientation in the iamt1 mutant could be restored with either endodermis-specific expression of IAMT1 or partial inhibition of polar auxin transport, which also results in normal PIN gene expression levels. We propose that IAA methylation is necessary in gravity-sensing cells to restrict polar auxin transport within the range of auxin levels that allow for differential responses. AU - Abbas, Mohamad AU - HernĂĄndez, GarcĂ­a J AU - Pollmann, Stephan AU - Samodelov, Sophia L AU - Kolb, Martina AU - Friml, JirĂ­ AU - Hammes, Ulrich Z AU - Zurbriggen, Matias D AU - BlĂĄzquez, Miguel AU - AlabadĂ­, David ID - 203 IS - 26 JF - PNAS TI - Auxin methylation is required for differential growth in Arabidopsis VL - 115 ER - TY - JOUR AB - Following an earlier calculation in 3D, we calculate the 2D critical temperature of a dilute, translation-invariant Bose gas using a variational formulation of the Bogoliubov approximation introduced by Critchley and Solomon in 1976. This provides the first analytical calculation of the Kosterlitz-Thouless transition temperature that includes the constant in the logarithm. AU - NapiĂłrkowski, Marcin M AU - Reuvers, Robin AU - Solovej, Jan ID - 399 IS - 1 JF - EPL TI - Calculation of the critical temperature of a dilute Bose gas in the Bogoliubov approximation VL - 121 ER - TY - JOUR AB - CLE peptides have been implicated in various developmental processes of plants and mediate their responses to environmental stimuli. However, the biological relevance of most CLE genes remains to be functionally characterized. Here, we report that CLE9, which is expressed in stomata, acts as an essential regulator in the induction of stomatal closure. Exogenous application of CLE9 peptides or overexpression of CLE9 effectively led to stomatal closure and enhanced drought tolerance, whereas CLE9 loss-of-function mutants were sensitivity to drought stress. CLE9-induced stomatal closure was impaired in abscisic acid (ABA)-deficient mutants, indicating that ABA is required for CLE9-medaited guard cell signalling. We further deciphered that two guard cell ABA-signalling components, OST1 and SLAC1, were responsible for CLE9-induced stomatal closure. MPK3 and MPK6 were activated by the CLE9 peptide, and CLE9 peptides failed to close stomata in mpk3 and mpk6 mutants. In addition, CLE9 peptides stimulated the induction of hydrogen peroxide (H2O2) and nitric oxide (NO) synthesis associated with stomatal closure, which was abolished in the NADPH oxidase-deficient mutants or nitric reductase mutants, respectively. Collectively, our results reveal a novel ABA-dependent function of CLE9 in the regulation of stomatal apertures, thereby suggesting a potential role of CLE9 in the stress acclimatization of plants. AU - Zhang, Luosha AU - Shi, Xiong AU - Zhang, Yutao AU - Wang, Jiajing AU - Yang, Jingwei AU - Ishida, Takashi AU - Jiang, Wenqian AU - Han, Xiangyu AU - Kang, Jingke AU - Wang, Xuening AU - Pan, Lixia AU - Lv, Shuo AU - Cao, Bing AU - Zhang, Yonghong AU - Wu, Jinbin AU - Han, Huibin AU - Hu, Zhubing AU - Cui, Langjun AU - Sawa, Shinichiro AU - He, Junmin AU - Wang, Guodong ID - 5830 JF - Plant Cell and Environment SN - 01407791 TI - CLE9 peptide-induced stomatal closure is mediated by abscisic acid, hydrogen peroxide, and nitric oxide in arabidopsis thaliana ER - TY - JOUR AB - Recent lineage tracing studies have revealed that mammary gland homeostasis relies on unipotent stem cells. However, whether and when lineage restriction occurs during embryonic mammary development, and which signals orchestrate cell fate specification, remain unknown. Using a combination of in vivo clonal analysis with whole mount immunofluorescence and mathematical modelling of clonal dynamics, we found that embryonic multipotent mammary cells become lineage-restricted surprisingly early in development, with evidence for unipotency as early as E12.5 and no statistically discernable bipotency after E15.5. To gain insights into the mechanisms governing the switch from multipotency to unipotency, we used gain-of-function Notch1 mice and demonstrated that Notch activation cell autonomously dictates luminal cell fate specification to both embryonic and basally committed mammary cells. These functional studies have important implications for understanding the signals underlying cell plasticity and serve to clarify how reactivation of embryonic programs in adult cells can lead to cancer. AU - Lilja, Anna AU - Rodilla, Veronica AU - Huyghe, Mathilde AU - Hannezo, Edouard B AU - Landragin, Camille AU - Renaud, Olivier AU - Leroy, Olivier AU - Rulands, Steffen AU - Simons, Benjamin AU - FrĂ©, Silvia ID - 288 IS - 6 JF - Nature Cell Biology TI - Clonal analysis of Notch1-expressing cells reveals the existence of unipotent stem cells that retain long-term plasticity in the embryonic mammary gland VL - 20 ER - TY - JOUR AB - Additive manufacturing has recently seen drastic improvements in resolution, making it now possible to fabricate features at scales of hundreds or even dozens of nanometers, which previously required very expensive lithographic methods. As a result, additive manufacturing now seems poised for optical applications, including those relevant to computer graphics, such as material design, as well as display and imaging applications. In this work, we explore the use of additive manufacturing for generating structural colors, where the structures are designed using a fabrication-aware optimization process. This requires a combination of full-wave simulation, a feasible parameterization of the design space, and a tailored optimization procedure. Many of these components should be re-usable for the design of other optical structures at this scale. We show initial results of material samples fabricated based on our designs. While these suffer from the prototype character of state-of-the-art fabrication hardware, we believe they clearly demonstrate the potential of additive nanofabrication for structural colors and other graphics applications. AU - Auzinger, Thomas AU - Heidrich, Wolfgang AU - Bickel, Bernd ID - 304 IS - 4 JF - ACM Transactions on Graphics TI - Computational design of nanostructural color for additive manufacturing VL - 37 ER - TY - JOUR AB - Molding is a popular mass production method, in which the initial expenses for the mold are offset by the low per-unit production cost. However, the physical fabrication constraints of the molding technique commonly restrict the shape of moldable objects. For a complex shape, a decomposition of the object into moldable parts is a common strategy to address these constraints, with plastic model kits being a popular and illustrative example. However, conducting such a decomposition requires considerable expertise, and it depends on the technical aspects of the fabrication technique, as well as aesthetic considerations. We present an interactive technique to create such decompositions for two-piece molding, in which each part of the object is cast between two rigid mold pieces. Given the surface description of an object, we decompose its thin-shell equivalent into moldable parts by first performing a coarse decomposition and then utilizing an active contour model for the boundaries between individual parts. Formulated as an optimization problem, the movement of the contours is guided by an energy reflecting fabrication constraints to ensure the moldability of each part. Simultaneously, the user is provided with editing capabilities to enforce aesthetic guidelines. Our interactive interface provides control of the contour positions by allowing, for example, the alignment of part boundaries with object features. Our technique enables a novel workflow, as it empowers novice users to explore the design space, and it generates fabrication-ready two-piece molds that can be used either for casting or industrial injection molding of free-form objects. AU - Nakashima, Kazutaka AU - Auzinger, Thomas AU - Iarussi, Emmanuel AU - Zhang, Ran AU - Igarashi, Takeo AU - Bickel, Bernd ID - 12 IS - 4 JF - ACM Transaction on Graphics TI - CoreCavity: Interactive shell decomposition for fabrication with two-piece rigid molds VL - 37 ER - TY - JOUR AB - Direct reciprocity is a mechanism for cooperation among humans. Many of our daily interactions are repeated. We interact repeatedly with our family, friends, colleagues, members of the local and even global community. In the theory of repeated games, it is a tacit assumption that the various games that a person plays simultaneously have no effect on each other. Here we introduce a general framework that allows us to analyze “crosstalk” between a player’s concurrent games. In the presence of crosstalk, the action a person experiences in one game can alter the person’s decision in another. We find that crosstalk impedes the maintenance of cooperation and requires stronger levels of forgiveness. The magnitude of the effect depends on the population structure. In more densely connected social groups, crosstalk has a stronger effect. A harsh retaliator, such as Tit-for-Tat, is unable to counteract crosstalk. The crosstalk framework provides a unified interpretation of direct and upstream reciprocity in the context of repeated games. AU - Reiter, Johannes AU - Hilbe, Christian AU - Rand, David AU - Chatterjee, Krishnendu AU - Nowak, Martin ID - 454 IS - 1 JF - Nature Communications TI - Crosstalk in concurrent repeated games impedes direct reciprocity and requires stronger levels of forgiveness VL - 9 ER - TY - JOUR AB - Fast-spiking, parvalbumin-expressing GABAergic interneurons (PV+-BCs) express a complex machinery of rapid signaling mechanisms, including specialized voltage-gated ion channels to generate brief action potentials (APs). However, short APs are associated with overlapping Na+ and K+ fluxes and are therefore energetically expensive. How the potentially vicious combination of high AP frequency and inefficient spike generation can be reconciled with limited energy supply is presently unclear. To address this question, we performed direct recordings from the PV+-BC axon, the subcellular structure where active conductances for AP initiation and propagation are located. Surprisingly, the energy required for the AP was, on average, only ∌1.6 times the theoretical minimum. High energy efficiency emerged from the combination of fast inactivation of Na+ channels and delayed activation of Kv3-type K+ channels, which minimized ion flux overlap during APs. Thus, the complementary tuning of axonal Na+ and K+ channel gating optimizes both fast signaling properties and metabolic efficiency. Hu et al. demonstrate that action potentials in parvalbumin-expressing GABAergic interneuron axons are energetically efficient, which is highly unexpected given their brief duration. High energy efficiency emerges from the combination of fast inactivation of voltage-gated Na+ channels and delayed activation of Kv3 channels in the axon. AU - Hu, Hua AU - Roth, Fabian AU - Vandael, David H AU - Jonas, Peter M ID - 320 IS - 1 JF - Neuron TI - Complementary tuning of Na+ and K+ channel gating underlies fast and energy-efficient action potentials in GABAergic interneuron axons VL - 98 ER - TY - JOUR AB - Herd immunity, a process in which resistant individuals limit the spread of a pathogen among susceptible hosts has been extensively studied in eukaryotes. Even though bacteria have evolved multiple immune systems against their phage pathogens, herd immunity in bacteria remains unexplored. Here we experimentally demonstrate that herd immunity arises during phage epidemics in structured and unstructured Escherichia coli populations consisting of differing frequencies of susceptible and resistant cells harboring CRISPR immunity. In addition, we develop a mathematical model that quantifies how herd immunity is affected by spatial population structure, bacterial growth rate, and phage replication rate. Using our model we infer a general epidemiological rule describing the relative speed of an epidemic in partially resistant spatially structured populations. Our experimental and theoretical findings indicate that herd immunity may be important in bacterial communities, allowing for stable coexistence of bacteria and their phages and the maintenance of polymorphism in bacterial immunity. AU - Payne, Pavel AU - Geyrhofer, Lukas AU - Barton, Nicholas H AU - Bollback, Jonathan P ID - 423 JF - eLife TI - CRISPR-based herd immunity can limit phage epidemics in bacterial populations VL - 7 ER - TY - CONF AB - Due to data compression or low resolution, nearby vertices and edges of a graph drawing may be bundled to a common node or arc. We model such a “compromised” drawing by a piecewise linear map φ:G → ℝ. We wish to perturb φ by an arbitrarily small Δ>0 into a proper drawing (in which the vertices are distinct points, any two edges intersect in finitely many points, and no three edges have a common interior point) that minimizes the number of crossings. An Δ-perturbation, for every Δ>0, is given by a piecewise linear map (Formula Presented), where with ||·|| is the uniform norm (i.e., sup norm). We present a polynomial-time solution for this optimization problem when G is a cycle and the map φ has no spurs (i.e., no two adjacent edges are mapped to overlapping arcs). We also show that the problem becomes NP-complete (i) when G is an arbitrary graph and φ has no spurs, and (ii) when φ may have spurs and G is a cycle or a union of disjoint paths. AU - Fulek, Radoslav AU - TĂłth, Csaba D. ID - 5791 SN - 9783030044138 TI - Crossing minimization in perturbed drawings VL - 11282 ER - TY - JOUR AB - Over the past decade, the edge of chaos has proven to be a fruitful starting point for investigations of shear flows when the laminar base flow is linearly stable. Numerous computational studies of shear flows demonstrated the existence of states that separate laminar and turbulent regions of the state space. In addition, some studies determined invariant solutions that reside on this edge. In this paper, we study the unstable manifold of one such solution with the aid of continuous symmetry reduction, which we formulate here for the simultaneous quotiening of axial and azimuthal symmetries. Upon our investigation of the unstable manifold, we discover a previously unknown traveling-wave solution on the laminar-turbulent boundary with a relatively complex structure. By means of low-dimensional projections, we visualize different dynamical paths that connect these solutions to the turbulence. Our numerical experiments demonstrate that the laminar-turbulent boundary exhibits qualitatively different regions whose properties are influenced by the nearby invariant solutions. AU - Budanur, Nazmi B AU - Hof, Björn ID - 291 IS - 5 JF - Physical Review Fluids TI - Complexity of the laminar-turbulent boundary in pipe flow VL - 3 ER - TY - JOUR AB - Inside a two-dimensional region (``cake""), there are m nonoverlapping tiles of a certain kind (``toppings""). We want to expand the toppings while keeping them nonoverlapping, and possibly add some blank pieces of the same ``certain kind,"" such that the entire cake is covered. How many blanks must we add? We study this question in several cases: (1) The cake and toppings are general polygons. (2) The cake and toppings are convex figures. (3) The cake and toppings are axis-parallel rectangles. (4) The cake is an axis-parallel rectilinear polygon and the toppings are axis-parallel rectangles. In all four cases, we provide tight bounds on the number of blanks. AU - Akopyan, Arseniy AU - Segal Halevi, Erel ID - 58 IS - 3 JF - SIAM Journal on Discrete Mathematics TI - Counting blanks in polygonal arrangements VL - 32 ER - TY - GEN AB - Herd immunity, a process in which resistant individuals limit the spread of a pathogen among susceptible hosts has been extensively studied in eukaryotes. Even though bacteria have evolved multiple immune systems against their phage pathogens, herd immunity in bacteria remains unexplored. Here we experimentally demonstrate that herd immunity arises during phage epidemics in structured and unstructured Escherichia coli populations consisting of differing frequencies of susceptible and resistant cells harboring CRISPR immunity. In addition, we develop a mathematical model that quantifies how herd immunity is affected by spatial population structure, bacterial growth rate, and phage replication rate. Using our model we infer a general epidemiological rule describing the relative speed of an epidemic in partially resistant spatially structured populations. Our experimental and theoretical findings indicate that herd immunity may be important in bacterial communities, allowing for stable coexistence of bacteria and their phages and the maintenance of polymorphism in bacterial immunity. AU - Payne, Pavel AU - Geyrhofer, Lukas AU - Barton, Nicholas H AU - Bollback, Jonathan P ID - 9840 TI - Data from: CRISPR-based herd immunity limits phage epidemics in bacterial populations ER - TY - JOUR AB - Social insects protect their colonies from infectious disease through collective defences that result in social immunity. In ants, workers first try to prevent infection of colony members. Here, we show that if this fails and a pathogen establishes an infection, ants employ an efficient multicomponent behaviour − "destructive disinfection" − to prevent further spread of disease through the colony. Ants specifically target infected pupae during the pathogen's non-contagious incubation period, relying on chemical 'sickness cues' emitted by pupae. They then remove the pupal cocoon, perforate its cuticle and administer antimicrobial poison, which enters the body and prevents pathogen replication from the inside out. Like the immune system of a body that specifically targets and eliminates infected cells, this social immunity measure sacrifices infected brood to stop the pathogen completing its lifecycle, thus protecting the rest of the colony. Hence, the same principles of disease defence apply at different levels of biological organisation. AU - Pull, Christopher AU - Ugelvig, Line V AU - Wiesenhofer, Florian AU - Grasse, Anna V AU - Tragust, Simon AU - Schmitt, Thomas AU - Brown, Mark AU - Cremer, Sylvia ID - 616 JF - eLife TI - Destructive disinfection of infected brood prevents systemic disease spread in ant colonies VL - 7 ER - TY - JOUR AB - Pancreas development involves a coordinated process in which an early phase of cell segregation is followed by a longer phase of lineage restriction, expansion, and tissue remodeling. By combining clonal tracing and whole-mount reconstruction with proliferation kinetics and single-cell transcriptional profiling, we define the functional basis of pancreas morphogenesis. We show that the large-scale organization of mouse pancreas can be traced to the activity of self-renewing precursors positioned at the termini of growing ducts, which act collectively to drive serial rounds of stochastic ductal bifurcation balanced by termination. During this phase of branching morphogenesis, multipotent precursors become progressively fate-restricted, giving rise to self-renewing acinar-committed precursors that are conveyed with growing ducts, as well as ductal progenitors that expand the trailing ducts and give rise to delaminating endocrine cells. These findings define quantitatively how the functional behavior and lineage progression of precursor pools determine the large-scale patterning of pancreatic sub-compartments. AU - Sznurkowska, Magdalena AU - Hannezo, Edouard B AU - Azzarelli, Roberta AU - Rulands, Steffen AU - Nestorowa, Sonia AU - Hindley, Christopher AU - Nichols, Jennifer AU - Göttgens, Berthold AU - Huch, Meritxell AU - Philpott, Anna AU - Simons, Benjamin ID - 132 IS - 3 JF - Developmental Cell TI - Defining lineage potential and fate behavior of precursors during pancreas development VL - 46 ER - TY - JOUR AB - Seeds derive from ovules upon fertilization and therefore the total number of ovules determines the final seed yield, a fundamental trait in crop plants. Among the factors that co-ordinate the process of ovule formation, the transcription factors CUP-SHAPED COTYLEDON 1 (CUC1) and CUC2 and the hormone cytokinin (CK) have a particularly prominent role. Indeed, the absence of both CUC1 and CUC2 causes a severe reduction in ovule number, a phenotype that can be rescued by CK treatment. In this study, we combined CK quantification with an integrative genome-wide target identification approach to select Arabidopsis genes regulated by CUCs that are also involved in CK metabolism. We focused our attention on the functional characterization of UDP-GLUCOSYL TRANSFERASE 85A3 (UGT85A3) and UGT73C1, which are up-regulated in the absence of CUC1 and CUC2 and encode enzymes able to catalyse CK inactivation by O-glucosylation. Our results demonstrate a role for these UGTs as a link between CUCs and CK homeostasis, and highlight the importance of CUCs and CKs in the determination of seed yield. AU - Cucinotta, Mara AU - Manrique, Silvia AU - Cuesta, Candela AU - BenkovĂĄ, Eva AU - NovĂĄk, Ondƙej AU - Colombo, Lucia ID - 42 IS - 21 JF - Journal of Experimental Botany TI - Cup-shaped Cotyledon1 (CUC1) and CU2 regulate cytokinin homeostasis to determine ovule number in arabidopsis VL - 69 ER - TY - JOUR AB - Isoprenoid cytokinins play a number of crucial roles in the regulation of plant growth and development. To study cytokinin receptor properties in plants, we designed and prepared fluorescent derivatives of 6-[(3-methylbut-2-en-1-yl)amino]purine (N6-isopentenyladenine, iP) with several fluorescent labels attached to the C2 or N9 atom of the purine moiety via a 2- or 6-carbon linker. The fluorescent labels included dansyl (DS), fluorescein (FC), 7-nitrobenzofurazan (NBD), rhodamine B (RhoB), coumarin (Cou), 7-(diethylamino)coumarin (DEAC) and cyanine 5 dye (Cy5). All prepared compounds were screened for affinity for the Arabidopsis thaliana cytokinin receptor (CRE1/AHK4). Although the attachment of the fluorescent labels to iP via the linkers mostly disrupted binding to the receptor, several fluorescent derivatives interacted well. For this reason, three derivatives, two rhodamine B and one 4-chloro-7-nitrobenzofurazan labeled iP were tested for their interaction with CRE1/AHK4 and Zea mays cytokinin receptors in detail. We further showed that the three derivatives were able to activate transcription of cytokinin response regulator ARR5 in Arabidopsis seedlings. The activity of fluorescently labeled cytokinins was compared with corresponding 6-dimethylaminopurine fluorescently labeled negative controls. Selected rhodamine B C2-labeled compounds 17, 18 and 4-chloro-7-nitrobenzofurazan N9-labeled compound 28 and their respective negative controls (19, 20 and 29, respectively) were used for in planta staining experiments in Arabidopsis thaliana cell suspension culture using live cell confocal microscopy. AU - KubiasovĂĄ, Karolina AU - Mik, VĂĄclav AU - Nisler, Jaroslav AU - Hönig, Martin AU - HusičkovĂĄ, Alexandra AU - SpĂ­chal, LukĂĄĆĄ AU - PěknĂĄ, Zuzana AU - Ć amajovĂĄ, Olga AU - DoleĆŸal, Karel AU - PlĂ­hal, Ondƙej AU - BenkovĂĄ, Eva AU - Strnad, Miroslav AU - PlĂ­halovĂĄ, Lucie ID - 407 JF - Phytochemistry TI - Design, synthesis and perception of fluorescently labeled isoprenoid cytokinins VL - 150 ER - 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 - VeselĂĄ, 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 - BrĂĄzdil, TomĂĄĆĄ AU - Chatterjee, Krishnendu AU - Kučera, AntonĂ­n 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 - MatouĆĄek, Jiƙí 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 - Ć imsa, Ć tepĂĄn 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, RenĂ© 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 - GrĂŒn, GĂŒnther 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'ovĂĄ, KatarĂ­na 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 - GabaldĂłn, 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, JirĂ­ 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 (ÎŒCT) 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 naĂŻve 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 - LĂłpez 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 - PĂ©rez 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 - CONF AB - Concurrent sets with range query operations are highly desirable in applications such as in-memory databases. However, few set implementations offer range queries. Known techniques for augmenting data structures with range queries (or operations that can be used to build range queries) have numerous problems that limit their usefulness. For example, they impose high overhead or rely heavily on garbage collection. In this work, we show how to augment data structures with highly efficient range queries, without relying on garbage collection. We identify a property of epoch-based memory reclamation algorithms that makes them ideal for implementing range queries, and produce three algorithms, which use locks, transactional memory and lock-free techniques, respectively. Our algorithms are applicable to more data structures than previous work, and are shown to be highly efficient on a large scale Intel system. AU - Arbel Raviv, Maya AU - Brown, Trevor A ID - 397 IS - 1 SN - 978-1-4503-4982-6 TI - Harnessing epoch-based reclamation for efficient range queries VL - 53 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 - Objective: To report long-term results after Pipeline Embolization Device (PED) implantation, characterize complex and standard aneurysms comprehensively, and introduce a modified flow disruption scale. Methods: We retrospectively reviewed a consecutive series of 40 patients harboring 59 aneurysms treated with 54 PEDs. Aneurysm complexity was assessed using our proposed classification. Immediate angiographic results were analyzed using previously published grading scales and our novel flow disruption scale. Results: According to our new definition, 46 (78%) aneurysms were classified as complex. Most PED interventions were performed in the paraophthalmic and cavernous internal carotid artery segments. Excellent neurologic outcome (modified Rankin Scale 0 and 1) was observed in 94% of patients. Our data showed low permanent procedure-related mortality (0%) and morbidity (3%) rates. Long-term angiographic follow-up showed complete occlusion in 81% and near-total obliteration in a further 14%. Complete obliteration after deployment of a single PED was achieved in all standard aneurysms with 1-year follow-up. Our new scale was an independent predictor of aneurysm occlusion in a multivariable analysis. All aneurysms with a high flow disruption grade showed complete occlusion at follow-up regardless of PED number or aneurysm complexity. Conclusions: Treatment with the PED should be recognized as a primary management strategy for a highly selected cohort with predominantly complex intracranial aneurysms. We further show that a priori assessment of aneurysm complexity and our new postinterventional angiographic flow disruption scale predict occlusion probability and may help to determine the adequate number of per-aneurysm devices. AU - Dodier, Philippe AU - Frischer, Josa AU - Wang, Wei AU - Auzinger, Thomas AU - Mallouhi, Ammar AU - Serles, Wolfgang AU - Gruber, Andreas AU - Knosp, Engelbert AU - Bavinzski, Gerhard ID - 398 JF - World Neurosurgery TI - Immediate flow disruption as a prognostic factor after flow diverter treatment long term experience with the pipeline embolization device VL - 13 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 - JOUR AB - Sperm cells are the most morphologically diverse cells across animal taxa. Within species, sperm and ejaculate traits have been suggested to vary with the male's competitive environment, e.g., level of sperm competition, female mating status and quality, and also with male age, body mass, physiological condition, and resource availability. Most previous studies have based their conclusions on the analysis of only one or a few ejaculates per male without investigating differences among the ejaculates of the same individual. This masks potential ejaculate-specific traits. Here, we provide data on the length, quantity, and viability of sperm ejaculated by wingless males of the ant Cardiocondyla obscurior. Males of this ant species are relatively long-lived and can mate with large numbers of female sexuals throughout their lives. We analyzed all ejaculates across the individuals' lifespan and manipulated the availability of mating partners. Our study shows that both the number and size of sperm cells transferred during copulations differ among individuals and also among ejaculates of the same male. Sperm quality does not decrease with male age, but the variation in sperm number between ejaculates indicates that males need considerable time to replenish their sperm supplies. Producing many ejaculates in a short time appears to be traded-off against male longevity rather than sperm quality. AU - Metzler, Sina AU - Schrempf, Alexandra AU - Heinze, JĂŒrgen ID - 426 JF - Journal of Insect Physiology TI - Individual- and ejaculate-specific sperm traits in ant males VL - 107 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 - RĂ€tsch, 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 - RĂ€tsch, 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 - HĂŒser, Matthias AU - Locatello, Francesco AU - Strathmann, Heiko AU - RĂ€tsch, 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 - RĂ€tsch, 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 - Flowers have a species-specific functional life span that determines the time window in which pollination, fertilization and seed set can occur. The stigma tissue plays a key role in flower receptivity by intercepting pollen and initiating pollen tube growth toward the ovary. In this article, we show that a developmentally controlled cell death programme terminates the functional life span of stigma cells in Arabidopsis. We identified the leaf senescence regulator ORESARA1 (also known as ANAC092) and the previously uncharacterized KIRA1 (also known as ANAC074) as partially redundant transcription factors that modulate stigma longevity by controlling the expression of programmed cell death-associated genes. KIRA1 expression is sufficient to induce cell death and terminate floral receptivity, whereas lack of both KIRA1 and ORESARA1 substantially increases stigma life span. Surprisingly, the extension of stigma longevity is accompanied by only a moderate extension of flower receptivity, suggesting that additional processes participate in the control of the flower's receptive life span. AU - Gao, Zhen AU - Daneva, Anna AU - Salanenka, Yuliya AU - Van Durme, Matthias AU - Huysmans, Marlies AU - Lin, Zongcheng AU - De Winter, Freya AU - Vanneste, Steffen AU - Karimi, Mansour AU - Van De Velde, Jan AU - Vandepoele, Klaas AU - Van De Walle, Davy AU - Dewettinck, Koen AU - Lambrecht, Bart AU - Nowack, Moritz ID - 280 IS - 6 JF - Nature Plants TI - KIRA1 and ORESARA1 terminate flower receptivity by promoting cell death in the stigma of Arabidopsis VL - 4 ER - TY - JOUR AB - Buffers are essential for diluting bacterial cultures for flow cytometry analysis in order to study bacterial physiology and gene expression parameters based on fluorescence signals. Using a variety of constitutively expressed fluorescent proteins in Escherichia coli K-12 strain MG1655, we found strong artifactual changes in fluorescence levels after dilution into the commonly used flow cytometry buffer phosphate-buffered saline (PBS) and two other buffer solutions, Tris-HCl and M9 salts. These changes appeared very rapidly after dilution, and were linked to increased membrane permeability and loss in cell viability. We observed buffer-related effects in several different E. coli strains, K-12, C and W, but not E. coli B, which can be partially explained by differences in lipopolysaccharide (LPS) and outer membrane composition. Supplementing the buffers with divalent cations responsible for outer membrane stability, Mg2+ and Ca2+, preserved fluorescence signals, membrane integrity and viability of E. coli. Thus, stabilizing the bacterial outer membrane is essential for precise and unbiased measurements of fluorescence parameters using flow cytometry. AU - Tomasek, Kathrin AU - Bergmiller, Tobias AU - Guet, Calin C ID - 503 JF - Journal of Biotechnology TI - Lack of cations in flow cytometry buffers affect fluorescence signals by reducing membrane stability and viability of Escherichia coli strains VL - 268 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 - CONF AB - Fault-localization is considered to be a very tedious and time-consuming activity in the design of complex Cyber-Physical Systems (CPS). This laborious task essentially requires expert knowledge of the system in order to discover the cause of the fault. In this context, we propose a new procedure that AIDS designers in debugging Simulink/Stateflow hybrid system models, guided by Signal Temporal Logic (STL) specifications. The proposed method relies on three main ingredients: (1) a monitoring and a trace diagnostics procedure that checks whether a tested behavior satisfies or violates an STL specification, localizes time segments and interfaces variables contributing to the property violations; (2) a slicing procedure that maps these observable behavior segments to the internal states and transitions of the Simulink model; and (3) a spectrum-based fault-localization method that combines the previous analysis from multiple tests to identify the internal states and/or transitions that are the most likely to explain the fault. We demonstrate the applicability of our approach on two Simulink models from the automotive and the avionics domain. AU - Bartocci, Ezio AU - Ferrere, Thomas AU - Manjunath, Niveditha AU - Nickovic, Dejan ID - 183 TI - Localizing faults in simulink/stateflow models with STL 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, LĂĄszlĂł AU - KrĂŒger, 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 - TY - GEN 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 - 9810 TI - Numerical data used in figures ER - TY - JOUR AB - 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. AU - Brown, Markus AU - Johnson, Louise AU - Leone, Dario AU - MĂĄjek, Peter AU - Vaahtomeri, Kari AU - Senfter, Daniel AU - Bukosza, Nora AU - Schachner, Helga AU - Asfour, Gabriele AU - Langer, Brigitte AU - Hauschild, Robert AU - Parapatics, Katja AU - Hong, Young AU - Bennett, Keiryn AU - Kain, Renate AU - Detmar, Michael AU - Sixt, Michael K AU - Jackson, David AU - Kerjaschki, Dontscho ID - 275 IS - 6 JF - Journal of Cell Biology TI - Lymphatic exosomes promote dendritic cell migration along guidance cues VL - 217 ER - TY - JOUR AB - 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. AU - Robert, HĂ©lĂšne AU - Park, Chulmin AU - GutiĂšrrez, Carla AU - WĂłjcikowska, Barbara AU - Pěnčík, AleĆĄ AU - NovĂĄk, Ondƙej AU - Chen, Junyi AU - Grunewald, Wim AU - Dresselhaus, Thomas AU - Friml, JirĂ­ AU - Laux, Thomas ID - 158 IS - 8 JF - Nature Plants TI - Maternal auxin supply contributes to early embryo patterning in Arabidopsis VL - 4 ER - TY - JOUR AB - 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. AU - Fiedorczuk, Karol AU - Sazanov, Leonid A ID - 152 IS - 10 JF - Trends in Cell Biology TI - Mammalian mitochondrial complex I structure and disease causing mutations VL - 28 ER - TY - CONF AB - 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 +Ï”)-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. AU - Chatterjee, Krishnendu AU - DvorĂĄk, Wolfgang AU - Henzinger, Monika H AU - Loitzenbauer, Veronika ID - 310 TI - Lower bounds for symbolic computation on graphs: Strongly connected components, liveness, safety, and diameter ER - TY - JOUR AB - 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. AU - Barzanjeh, Shabir AU - Aquilina, Matteo AU - Xuereb, AndrĂ© ID - 436 IS - 6 JF - Physical Review Letters TI - Manipulating the flow of thermal noise in quantum devices VL - 120 ER - TY - JOUR AB - 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. AU - Hross, Sabrina AU - Theis, Fabian J. AU - Sixt, Michael K AU - Hasenauer, Jan ID - 5858 IS - 149 JF - Journal of the Royal Society Interface SN - 17425689 TI - Mechanistic description of spatial processes using integrative modelling of noise-corrupted imaging data VL - 15 ER - TY - JOUR AB - 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. AU - Varshney, Atul AU - Steinberg, Victor ID - 16 IS - 10 JF - Physical Review Fluids TI - Mixing layer instability and vorticity amplification in a creeping viscoelastic flow VL - 3 ER -