@inproceedings{299, abstract = {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.}, author = {Nickovic, Dejan and Lebeltel, Olivier and Maler, Oded and Ferrere, Thomas and Ulus, Dogan}, editor = {Beyer, Dirk and Huisman, Marieke}, location = {Thessaloniki, Greece}, pages = {303 -- 319}, publisher = {Springer}, title = {{AMT 2.0: Qualitative and quantitative trace analysis with extended signal temporal logic}}, doi = {10.1007/978-3-319-89963-3_18}, volume = {10806}, year = {2018}, } @article{413, abstract = {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.}, author = {Konrad, Matthias and Pull, Christopher and Metzler, Sina and Seif, Katharina and Naderlinger, Elisabeth and Grasse, Anna V and Cremer, Sylvia}, journal = {PNAS}, number = {11}, pages = {2782 -- 2787}, publisher = {National Academy of Sciences}, title = {{Ants avoid superinfections by performing risk-adjusted sanitary care}}, doi = {10.1073/pnas.1713501115}, volume = {115}, year = {2018}, } @article{195, abstract = {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.}, author = {Yakaboylu, Enderalp and Lemeshko, Mikhail}, journal = {Physical Review B - Condensed Matter and Materials Physics}, number = {4}, publisher = {American Physical Society}, title = {{Anyonic statistics of quantum impurities in two dimensions}}, doi = {10.1103/PhysRevB.98.045402}, volume = {98}, year = {2018}, } @inproceedings{144, abstract = {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.}, author = {Ferrere, Thomas and Henzinger, Thomas A and Saraç, Ege}, location = {Oxford, UK}, pages = {394 -- 403}, publisher = {IEEE}, title = {{A theory of register monitors}}, doi = {10.1145/3209108.3209194}, volume = {Part F138033}, year = {2018}, } @article{203, abstract = {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.}, author = {Abbas, Mohamad and Hernández, García J and Pollmann, Stephan and Samodelov, Sophia L and Kolb, Martina and Friml, Jirí and Hammes, Ulrich Z and Zurbriggen, Matias D and Blázquez, Miguel and Alabadí, David}, journal = {PNAS}, number = {26}, pages = {6864--6869}, publisher = {National Academy of Sciences}, title = {{Auxin methylation is required for differential growth in Arabidopsis}}, doi = {10.1073/pnas.1806565115}, volume = {115}, year = {2018}, } @article{399, abstract = {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.}, author = {Napiórkowski, Marcin M and Reuvers, Robin and Solovej, Jan}, journal = {EPL}, number = {1}, publisher = {IOP Publishing Ltd.}, title = {{Calculation of the critical temperature of a dilute Bose gas in the Bogoliubov approximation}}, doi = {10.1209/0295-5075/121/10007}, volume = {121}, year = {2018}, } @article{5830, abstract = {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.}, author = {Zhang, Luosha and Shi, Xiong and Zhang, Yutao and Wang, Jiajing and Yang, Jingwei and Ishida, Takashi and Jiang, Wenqian and Han, Xiangyu and Kang, Jingke and Wang, Xuening and Pan, Lixia and Lv, Shuo and Cao, Bing and Zhang, Yonghong and Wu, Jinbin and Han, Huibin and Hu, Zhubing and Cui, Langjun and Sawa, Shinichiro and He, Junmin and Wang, Guodong}, issn = {01407791}, journal = {Plant Cell and Environment}, publisher = {Wiley}, title = {{CLE9 peptide-induced stomatal closure is mediated by abscisic acid, hydrogen peroxide, and nitric oxide in arabidopsis thaliana}}, doi = {10.1111/pce.13475}, year = {2018}, } @article{288, abstract = {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.}, author = {Lilja, Anna and Rodilla, Veronica and Huyghe, Mathilde and Hannezo, Edouard B and Landragin, Camille and Renaud, Olivier and Leroy, Olivier and Rulands, Steffen and Simons, Benjamin and Fré, Silvia}, journal = {Nature Cell Biology}, number = {6}, pages = {677 -- 687}, publisher = {Nature Publishing Group}, title = {{Clonal analysis of Notch1-expressing cells reveals the existence of unipotent stem cells that retain long-term plasticity in the embryonic mammary gland}}, doi = {10.1038/s41556-018-0108-1}, volume = {20}, year = {2018}, } @article{304, abstract = {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.}, author = {Auzinger, Thomas and Heidrich, Wolfgang and Bickel, Bernd}, journal = {ACM Transactions on Graphics}, number = {4}, publisher = {ACM}, title = {{Computational design of nanostructural color for additive manufacturing}}, doi = {10.1145/3197517.3201376}, volume = {37}, year = {2018}, } @article{12, abstract = {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.}, author = {Nakashima, Kazutaka and Auzinger, Thomas and Iarussi, Emmanuel and Zhang, Ran and Igarashi, Takeo and Bickel, Bernd}, journal = {ACM Transaction on Graphics}, number = {4}, publisher = {ACM}, title = {{CoreCavity: Interactive shell decomposition for fabrication with two-piece rigid molds}}, doi = {10.1145/3197517.3201341}, volume = {37}, year = {2018}, } @article{454, abstract = {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.}, author = {Reiter, Johannes and Hilbe, Christian and Rand, David and Chatterjee, Krishnendu and Nowak, Martin}, journal = {Nature Communications}, number = {1}, publisher = {Nature Publishing Group}, title = {{Crosstalk in concurrent repeated games impedes direct reciprocity and requires stronger levels of forgiveness}}, doi = {10.1038/s41467-017-02721-8}, volume = {9}, year = {2018}, } @article{320, abstract = {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. }, author = {Hu, Hua and Roth, Fabian and Vandael, David H and Jonas, Peter M}, journal = {Neuron}, number = {1}, pages = {156 -- 165}, publisher = {Elsevier}, title = {{Complementary tuning of Na+ and K+ channel gating underlies fast and energy-efficient action potentials in GABAergic interneuron axons}}, doi = {10.1016/j.neuron.2018.02.024}, volume = {98}, year = {2018}, } @article{423, abstract = {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.}, author = {Payne, Pavel and Geyrhofer, Lukas and Barton, Nicholas H and Bollback, Jonathan P}, journal = {eLife}, publisher = {eLife Sciences Publications}, title = {{CRISPR-based herd immunity can limit phage epidemics in bacterial populations}}, doi = {10.7554/eLife.32035}, volume = {7}, year = {2018}, } @inproceedings{5791, abstract = {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 ε>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 ε-perturbation, for every ε>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.}, author = {Fulek, Radoslav and Tóth, Csaba D.}, isbn = {9783030044138}, location = {Barcelona, Spain}, pages = {229--241}, publisher = {Springer}, title = {{Crossing minimization in perturbed drawings}}, doi = {10.1007/978-3-030-04414-5_16}, volume = {11282 }, year = {2018}, } @article{291, abstract = {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.}, author = {Budanur, Nazmi B and Hof, Björn}, journal = {Physical Review Fluids}, number = {5}, publisher = {American Physical Society}, title = {{Complexity of the laminar-turbulent boundary in pipe flow}}, doi = {10.1103/PhysRevFluids.3.054401}, volume = {3}, year = {2018}, } @article{58, abstract = {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.}, author = {Akopyan, Arseniy and Segal Halevi, Erel}, journal = {SIAM Journal on Discrete Mathematics}, number = {3}, pages = {2242 -- 2257}, publisher = {Society for Industrial and Applied Mathematics }, title = {{Counting blanks in polygonal arrangements}}, doi = {10.1137/16M110407X}, volume = {32}, year = {2018}, } @misc{9840, abstract = {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.}, author = {Payne, Pavel and Geyrhofer, Lukas and Barton, Nicholas H and Bollback, Jonathan P}, publisher = {Dryad}, title = {{Data from: CRISPR-based herd immunity limits phage epidemics in bacterial populations}}, doi = {10.5061/dryad.42n44}, year = {2018}, } @article{616, abstract = {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.}, author = {Pull, Christopher and Ugelvig, Line V and Wiesenhofer, Florian and Grasse, Anna V and Tragust, Simon and Schmitt, Thomas and Brown, Mark and Cremer, Sylvia}, journal = {eLife}, publisher = {eLife Sciences Publications}, title = {{Destructive disinfection of infected brood prevents systemic disease spread in ant colonies}}, doi = {10.7554/eLife.32073}, volume = {7}, year = {2018}, } @article{132, abstract = {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.}, author = {Sznurkowska, Magdalena and Hannezo, Edouard B and Azzarelli, Roberta and Rulands, Steffen and Nestorowa, Sonia and Hindley, Christopher and Nichols, Jennifer and Göttgens, Berthold and Huch, Meritxell and Philpott, Anna and Simons, Benjamin}, journal = {Developmental Cell}, number = {3}, pages = {360 -- 375}, publisher = {Cell Press}, title = {{Defining lineage potential and fate behavior of precursors during pancreas development}}, doi = {10.1016/j.devcel.2018.06.028}, volume = {46}, year = {2018}, } @article{42, abstract = {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.}, author = {Cucinotta, Mara and Manrique, Silvia and Cuesta, Candela and Benková, Eva and Novák, Ondřej and Colombo, Lucia}, journal = {Journal of Experimental Botany}, number = {21}, pages = {5169 -- 5176}, publisher = {Oxford University Press}, title = {{Cup-shaped Cotyledon1 (CUC1) and CU2 regulate cytokinin homeostasis to determine ovule number in arabidopsis}}, doi = {10.1093/jxb/ery281}, volume = {69}, year = {2018}, } @article{407, abstract = {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.}, author = {Kubiasová, Karolina and Mik, Václav and Nisler, Jaroslav and Hönig, Martin and Husičková, Alexandra and Spíchal, Lukáš and Pěkná, Zuzana and Šamajová, Olga and Doležal, Karel and Plíhal, Ondřej and Benková, Eva and Strnad, Miroslav and Plíhalová, Lucie}, journal = {Phytochemistry}, pages = {1--11}, publisher = {Elsevier}, title = {{Design, synthesis and perception of fluorescently labeled isoprenoid cytokinins}}, doi = {10.1016/j.phytochem.2018.02.015}, volume = {150}, year = {2018}, } @article{46, abstract = {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.}, author = {Hetterich, Daniel and Yao, Norman and Serbyn, Maksym and Pollmann, Frank and Trauzettel, Björn}, journal = {Physical Review B}, number = {16}, publisher = {American Physical Society}, title = {{Detection and characterization of many-body localization in central spin models}}, doi = {10.1103/PhysRevB.98.161122}, volume = {98}, year = {2018}, } @article{308, abstract = {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.}, author = {Ratheesh, Aparna and Biebl, Julia and Smutny, Michael and Veselá, Jana and Papusheva, Ekaterina and Krens, Gabriel and Kaufmann, Walter and György, Attila and Casano, Alessandra M and Siekhaus, Daria E}, journal = {Developmental Cell}, number = {3}, pages = {331 -- 346}, publisher = {Elsevier}, title = {{Drosophila TNF modulates tissue tension in the embryo to facilitate macrophage invasive migration}}, doi = {10.1016/j.devcel.2018.04.002}, volume = {45}, year = {2018}, } @article{17, abstract = {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.}, author = {Varshney, Atul and Steinberg, Victor}, journal = {Physical Review Fluids}, number = {10}, publisher = {American Physical Society}, title = {{Drag enhancement and drag reduction in viscoelastic flow}}, doi = {10.1103/PhysRevFluids.3.103302}, volume = {3}, year = {2018}, } @article{281, abstract = {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.}, author = {Granados, Alejandro and Pietsch, Julian and Cepeda Humerez, Sarah A and Farquhar, Isebail and Tkacik, Gasper and Swain, Peter}, journal = {PNAS}, number = {23}, pages = {6088 -- 6093}, publisher = {National Academy of Sciences}, title = {{Distributed and dynamic intracellular organization of extracellular information}}, doi = {10.1073/pnas.1716659115}, volume = {115}, year = {2018}, } @article{620, abstract = {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.}, author = {Yamamoto, Wataru and Wada, Suguru and Nagano, Makoto and Aoshima, Kaito and Siekhaus, Daria E and Toshima, Junko and Toshima, Jiro}, journal = {Journal of Cell Science}, number = {1}, publisher = {Company of Biologists}, title = {{Distinct roles for plasma membrane PtdIns 4 P and PtdIns 4 5 P2 during yeast receptor mediated endocytosis}}, doi = {10.1242/jcs.207696}, volume = {131}, year = {2018}, } @inproceedings{182, abstract = {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.}, author = {Bakhirkin, Alexey and Ferrere, Thomas and Maler, Oded}, booktitle = {Proceedings of the 21st International Conference on Hybrid Systems}, isbn = {978-1-4503-5642-8 }, location = {Porto, Portugal}, pages = {177 -- 186}, publisher = {ACM}, title = {{Efficient parametric identification for STL}}, doi = {10.1145/3178126.3178132}, year = {2018}, } @inproceedings{143, abstract = {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.}, author = {Brázdil, Tomáš and Chatterjee, Krishnendu and Kučera, Antonín and Novotny, Petr and Velan, Dominik and Zuleger, Florian}, isbn = {978-1-4503-5583-4}, location = {Oxford, United Kingdom}, pages = {185 -- 194}, publisher = {IEEE}, title = {{Efficient algorithms for asymptotic bounds on termination time in VASS}}, doi = {10.1145/3209108.3209191}, volume = {F138033}, year = {2018}, } @inproceedings{273, abstract = {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.}, author = {Mohapatra, Pritish and Rolinek, Michal and Jawahar, C V and Kolmogorov, Vladimir and Kumar, M Pawan}, booktitle = {2018 IEEE/CVF Conference on Computer Vision and Pattern Recognition}, isbn = {9781538664209}, location = {Salt Lake City, UT, USA}, pages = {3693--3701}, publisher = {IEEE}, title = {{Efficient optimization for rank-based loss functions}}, doi = {10.1109/cvpr.2018.00389}, year = {2018}, } @article{289, abstract = {We report on quantum capacitance measurements of high quality, graphite- and hexagonal boron nitride encapsulated Bernal stacked trilayer graphene devices. At zero applied magnetic field, we observe a number of electron density- and electrical displacement-tuned features in the electronic compressibility associated with changes in Fermi surface topology. At high displacement field and low density, strong trigonal warping gives rise to emergent Dirac gullies centered near the corners of the hexagonal Brillouin and related by three fold rotation symmetry. At low magnetic fields of B=1.25~T, the gullies manifest as a change in the degeneracy of the Landau levels from two to three. Weak incompressible states are also observed at integer filling within these triplets Landau levels, which a Hartree-Fock analysis indicates are associated with Coulomb-driven nematic phases that spontaneously break rotation symmetry.}, author = {Zibrov, Alexander and Peng, Rao and Kometter, Carlos and Li, Jia and Dean, Cory and Taniguchi, Takashi and Watanabe, Kenji and Serbyn, Maksym and Young, Andrea}, journal = {Physical Review Letters}, number = {16}, publisher = {American Physical Society}, title = {{Emergent dirac gullies and gully-symmetry-breaking quantum hall states in ABA trilayer graphene}}, doi = {10.1103/PhysRevLett.121.167601}, volume = {121}, year = {2018}, } @article{287, abstract = {In this paper, we discuss biological effects of electromagnetic (EM) fields in the context of cancer biology. In particular, we review the nanomechanical properties of microtubules (MTs), the latter being one of the most successful targets for cancer therapy. We propose an investigation on the coupling of electromagnetic radiation to mechanical vibrations of MTs as an important basis for biological and medical applications. In our opinion, optomechanical methods can accurately monitor and control the mechanical properties of isolated MTs in a liquid environment. Consequently, studying nanomechanical properties of MTs may give useful information for future applications to diagnostic and therapeutic technologies involving non-invasive externally applied physical fields. For example, electromagnetic fields or high intensity ultrasound can be used therapeutically avoiding harmful side effects of chemotherapeutic agents or classical radiation therapy.}, author = {Salari, Vahid and Barzanjeh, Shabir and Cifra, Michal and Simon, Christoph and Scholkmann, Felix and Alirezaei, Zahra and Tuszynski, Jack}, journal = {Frontiers in Bioscience - Landmark}, number = {8}, pages = {1391 -- 1406}, publisher = {Frontiers in Bioscience}, title = {{Electromagnetic fields and optomechanics In cancer diagnostics and treatment}}, doi = {10.2741/4651}, volume = {23}, year = {2018}, } @article{425, abstract = {We show that the following algorithmic problem is decidable: given a 2-dimensional simplicial complex, can it be embedded (topologically, or equivalently, piecewise linearly) in R3? By a known reduction, it suffices to decide the embeddability of a given triangulated 3-manifold X into the 3-sphere S3. The main step, which allows us to simplify X and recurse, is in proving that if X can be embedded in S3, then there is also an embedding in which X has a short meridian, that is, an essential curve in the boundary of X bounding a disk in S3 \ X with length bounded by a computable function of the number of tetrahedra of X.}, author = {Matoušek, Jiří and Sedgwick, Eric and Tancer, Martin and Wagner, Uli}, journal = {Journal of the ACM}, number = {1}, publisher = {ACM}, title = {{Embeddability in the 3-Sphere is decidable}}, doi = {10.1145/3078632}, volume = {65}, year = {2018}, } @article{564, abstract = {Maladapted individuals can only colonise a new habitat if they can evolve a positive growth rate fast enough to avoid extinction, a process known as evolutionary rescue. We treat log fitness at low density in the new habitat as a single polygenic trait and thus use the infinitesimal model to follow the evolution of the growth rate; this assumes that the trait values of offspring of a sexual union are normally distributed around the mean of the parents’ trait values, with variance that depends only on the parents’ relatedness. The probability that a single migrant can establish depends on just two parameters: the mean and genetic variance of the trait in the source population. The chance of success becomes small if migrants come from a population with mean growth rate in the new habitat more than a few standard deviations below zero; this chance depends roughly equally on the probability that the initial founder is unusually fit, and on the subsequent increase in growth rate of its offspring as a result of selection. The loss of genetic variation during the founding event is substantial, but highly variable. With continued migration at rate M, establishment is inevitable; when migration is rare, the expected time to establishment decreases inversely with M. However, above a threshold migration rate, the population may be trapped in a ‘sink’ state, in which adaptation is held back by gene flow; above this threshold, the expected time to establishment increases exponentially with M. This threshold behaviour is captured by a deterministic approximation, which assumes a Gaussian distribution of the trait in the founder population with mean and variance evolving deterministically. By assuming a constant genetic variance, we also develop a diffusion approximation for the joint distribution of population size and trait mean, which extends to include stabilising selection and density regulation. Divergence of the population from its ancestors causes partial reproductive isolation, which we measure through the reproductive value of migrants into the newly established population.}, author = {Barton, Nicholas H and Etheridge, Alison}, journal = {Theoretical Population Biology}, number = {7}, pages = {110--127}, publisher = {Academic Press}, title = {{Establishment in a new habitat by polygenic adaptation}}, doi = {10.1016/j.tpb.2017.11.007}, volume = {122}, year = {2018}, } @article{157, abstract = {Social dilemmas occur when incentives for individuals are misaligned with group interests 1-7 . According to the 'tragedy of the commons', these misalignments can lead to overexploitation and collapse of public resources. The resulting behaviours can be analysed with the tools of game theory 8 . The theory of direct reciprocity 9-15 suggests that repeated interactions can alleviate such dilemmas, but previous work has assumed that the public resource remains constant over time. Here we introduce the idea that the public resource is instead changeable and depends on the strategic choices of individuals. An intuitive scenario is that cooperation increases the public resource, whereas defection decreases it. Thus, cooperation allows the possibility of playing a more valuable game with higher payoffs, whereas defection leads to a less valuable game. We analyse this idea using the theory of stochastic games 16-19 and evolutionary game theory. We find that the dependence of the public resource on previous interactions can greatly enhance the propensity for cooperation. For these results, the interaction between reciprocity and payoff feedback is crucial: neither repeated interactions in a constant environment nor single interactions in a changing environment yield similar cooperation rates. Our framework shows which feedbacks between exploitation and environment - either naturally occurring or designed - help to overcome social dilemmas.}, author = {Hilbe, Christian and Šimsa, Štepán and Chatterjee, Krishnendu and Nowak, Martin}, journal = {Nature}, number = {7713}, pages = {246 -- 249}, publisher = {Nature Publishing Group}, title = {{Evolution of cooperation in stochastic games}}, doi = {10.1038/s41586-018-0277-x}, volume = {559}, year = {2018}, } @article{384, abstract = {Can orthologous proteins differ in terms of their ability to be secreted? To answer this question, we investigated the distribution of signal peptides within the orthologous groups of Enterobacterales. Parsimony analysis and sequence comparisons revealed a large number of signal peptide gain and loss events, in which signal peptides emerge or disappear in the course of evolution. Signal peptide losses prevail over gains, an effect which is especially pronounced in the transition from the free-living or commensal to the endosymbiotic lifestyle. The disproportionate decline in the number of signal peptide-containing proteins in endosymbionts cannot be explained by the overall reduction of their genomes. Signal peptides can be gained and lost either by acquisition/elimination of the corresponding N-terminal regions or by gradual accumulation of mutations. The evolutionary dynamics of signal peptides in bacterial proteins represents a powerful mechanism of functional diversification.}, author = {Hönigschmid, Peter and Bykova, Nadya and Schneider, René and Ivankov, Dmitry and Frishman, Dmitrij}, journal = {Genome Biology and Evolution}, number = {3}, pages = {928 -- 938}, publisher = {Oxford University Press}, title = {{Evolutionary interplay between symbiotic relationships and patterns of signal peptide gain and loss}}, doi = {10.1093/gbe/evy049}, volume = {10}, year = {2018}, } @article{563, abstract = {In continuous populations with local migration, nearby pairs of individuals have on average more similar genotypes than geographically well separated pairs. A barrier to gene flow distorts this classical pattern of isolation by distance. Genetic similarity is decreased for sample pairs on different sides of the barrier and increased for pairs on the same side near the barrier. Here, we introduce an inference scheme that utilizes this signal to detect and estimate the strength of a linear barrier to gene flow in two-dimensions. We use a diffusion approximation to model the effects of a barrier on the geographical spread of ancestry backwards in time. This approach allows us to calculate the chance of recent coalescence and probability of identity by descent. We introduce an inference scheme that fits these theoretical results to the geographical covariance structure of bialleleic genetic markers. It can estimate the strength of the barrier as well as several demographic parameters. We investigate the power of our inference scheme to detect barriers by applying it to a wide range of simulated data. We also showcase an example application to a Antirrhinum majus (snapdragon) flower color hybrid zone, where we do not detect any signal of a strong genome wide barrier to gene flow.}, author = {Ringbauer, Harald and Kolesnikov, Alexander and Field, David and Barton, Nicholas H}, journal = {Genetics}, number = {3}, pages = {1231--1245}, publisher = {Genetics Society of America}, title = {{Estimating barriers to gene flow from distorted isolation-by-distance patterns}}, doi = {10.1534/genetics.117.300638}, volume = {208}, year = {2018}, } @article{135, abstract = {The Fluid Implicit Particle method (FLIP) reduces numerical dissipation by combining particles with grids. To improve performance, the subsequent narrow band FLIP method (NB‐FLIP) uses a FLIP‐based fluid simulation only near the liquid surface and a traditional grid‐based fluid simulation away from the surface. This spatially‐limited FLIP simulation significantly reduces the number of particles and alleviates a computational bottleneck. In this paper, we extend the NB‐FLIP idea even further, by allowing a simulation to transition between a FLIP‐like fluid simulation and a grid‐based simulation in arbitrary locations, not just near the surface. This approach leads to even more savings in memory and computation, because we can concentrate the particles only in areas where they are needed. More importantly, this new method allows us to seamlessly transition to smooth implicit surface geometry wherever the particle‐based simulation is unnecessary. Consequently, our method leads to a practical algorithm for avoiding the noisy surface artifacts associated with particle‐based liquid simulations, while simultaneously maintaining the benefits of a FLIP simulation in regions of dynamic motion.}, author = {Sato, Takahiro and Wojtan, Christopher J and Thuerey, Nils and Igarashi, Takeo and Ando, Ryoichi}, issn = {0167-7055}, journal = {Computer Graphics Forum}, number = {2}, pages = {169 -- 177}, publisher = {Wiley}, title = {{Extended narrow band FLIP for liquid simulations}}, doi = {10.1111/cgf.13351}, volume = {37}, year = {2018}, } @article{316, abstract = {Self-incompatibility (SI) is a genetically based recognition system that functions to prevent self-fertilization and mating among related plants. An enduring puzzle in SI is how the high diversity observed in nature arises and is maintained. Based on the underlying recognition mechanism, SI can be classified into two main groups: self- and non-self recognition. Most work has focused on diversification within self-recognition systems despite expected differences between the two groups in the evolutionary pathways and outcomes of diversification. Here, we use a deterministic population genetic model and stochastic simulations to investigate how novel S-haplotypes evolve in a gametophytic non-self recognition (SRNase/S Locus F-box (SLF)) SI system. For this model the pathways for diversification involve either the maintenance or breakdown of SI and can vary in the order of mutations of the female (SRNase) and male (SLF) components. We show analytically that diversification can occur with high inbreeding depression and self-pollination, but this varies with evolutionary pathway and level of completeness (which determines the number of potential mating partners in the population), and in general is more likely for lower haplotype number. The conditions for diversification are broader in stochastic simulations of finite population size. However, the number of haplotypes observed under high inbreeding and moderate to high self-pollination is less than that commonly observed in nature. Diversification was observed through pathways that maintain SI as well as through self-compatible intermediates. Yet the lifespan of diversified haplotypes was sensitive to their level of completeness. By examining diversification in a non-self recognition SI system, this model extends our understanding of the evolution and maintenance of haplotype diversity observed in a self recognition system common in flowering plants.}, author = {Bodova, Katarina and Priklopil, Tadeas and Field, David and Barton, Nicholas H and Pickup, Melinda}, journal = {Genetics}, number = {3}, pages = {861--883}, publisher = {Genetics Society of America}, title = {{Evolutionary pathways for the generation of new self-incompatibility haplotypes in a non-self recognition system}}, doi = {10.1534/genetics.118.300748}, volume = {209}, year = {2018}, } @article{190, abstract = {The German cockroach, Blattella germanica, is a worldwide pest that infests buildings, including homes, restaurants, and hospitals, often living in unsanitary conditions. As a disease vector and producer of allergens, this species has major health and economic impacts on humans. Factors contributing to the success of the German cockroach include its resistance to a broad range of insecticides, immunity to many pathogens, and its ability, as an extreme generalist omnivore, to survive on most food sources. The recently published genome shows that B. germanica has an exceptionally high number of protein coding genes. In this study, we investigate the functions of the 93 significantly expanded gene families with the aim to better understand the success of B. germanica as a major pest despite such inhospitable conditions. We find major expansions in gene families with functions related to the detoxification of insecticides and allelochemicals, defense against pathogens, digestion, sensory perception, and gene regulation. These expansions might have allowed B. germanica to develop multiple resistance mechanisms to insecticides and pathogens, and enabled a broad, flexible diet, thus explaining its success in unsanitary conditions and under recurrent chemical control. The findings and resources presented here provide insights for better understanding molecular mechanisms that will facilitate more effective cockroach control.}, author = {Harrison, Mark and Arning, Nicolas and Kremer, Lucas and Ylla, Guillem and Belles, Xavier and Bornberg Bauer, Erich and Huylmans, Ann K and Jongepier, Evelien and Puilachs, Maria and Richards, Stephen and Schal, Coby}, journal = {Journal of Experimental Zoology Part B: Molecular and Developmental Evolution}, pages = {254--264}, publisher = {Wiley}, title = {{Expansions of key protein families in the German cockroach highlight the molecular basis of its remarkable success as a global indoor pest}}, doi = {10.1002/jez.b.22824}, volume = {330}, year = {2018}, } @article{404, abstract = {We construct martingale solutions to stochastic thin-film equations by introducing a (spatial) semidiscretization and establishing convergence. The discrete scheme allows for variants of the energy and entropy estimates in the continuous setting as long as the discrete energy does not exceed certain threshold values depending on the spatial grid size $h$. Using a stopping time argument to prolongate high-energy paths constant in time, arbitrary moments of coupled energy/entropy functionals can be controlled. Having established Hölder regularity of approximate solutions, the convergence proof is then based on compactness arguments---in particular on Jakubowski's generalization of Skorokhod's theorem---weak convergence methods, and recent tools on martingale convergence. }, author = {Fischer, Julian L and Grün, Günther}, journal = {SIAM Journal on Mathematical Analysis}, number = {1}, pages = {411 -- 455}, publisher = {Society for Industrial and Applied Mathematics }, title = {{Existence of positive solutions to stochastic thin-film equations}}, doi = {10.1137/16M1098796}, volume = {50}, year = {2018}, } @misc{9813, abstract = {File S1 contains figures that clarify the following features: (i) effect of population size on the average number/frequency of SI classes, (ii) changes in the minimal completeness deficit in time for a single class, and (iii) diversification diagrams for all studied pathways, including the summary figure for k = 8. File S2 contains the code required for a stochastic simulation of the SLF system with an example. This file also includes the output in the form of figures and tables.}, author = {Bod'ová, Katarína and Priklopil, Tadeas and Field, David and Barton, Nicholas H and Pickup, Melinda}, publisher = {Genetics Society of America}, title = {{Supplemental material for Bodova et al., 2018}}, doi = {10.25386/genetics.6148304.v1}, year = {2018}, } @article{5780, abstract = {Bioluminescence is found across the entire tree of life, conferring a spectacular set of visually oriented functions from attracting mates to scaring off predators. Half a dozen different luciferins, molecules that emit light when enzymatically oxidized, are known. However, just one biochemical pathway for luciferin biosynthesis has been described in full, which is found only in bacteria. Here, we report identification of the fungal luciferase and three other key enzymes that together form the biosynthetic cycle of the fungal luciferin from caffeic acid, a simple and widespread metabolite. Introduction of the identified genes into the genome of the yeast Pichia pastoris along with caffeic acid biosynthesis genes resulted in a strain that is autoluminescent in standard media. We analyzed evolution of the enzymes of the luciferin biosynthesis cycle and found that fungal bioluminescence emerged through a series of events that included two independent gene duplications. The retention of the duplicated enzymes of the luciferin pathway in nonluminescent fungi shows that the gene duplication was followed by functional sequence divergence of enzymes of at least one gene in the biosynthetic pathway and suggests that the evolution of fungal bioluminescence proceeded through several closely related stepping stone nonluminescent biochemical reactions with adaptive roles. The availability of a complete eukaryotic luciferin biosynthesis pathway provides several applications in biomedicine and bioengineering.}, author = {Kotlobay, Alexey A. and Sarkisyan, Karen and Mokrushina, Yuliana A. and Marcet-Houben, Marina and Serebrovskaya, Ekaterina O. and Markina, Nadezhda M. and Gonzalez Somermeyer, Louisa and Gorokhovatsky, Andrey Y. and Vvedensky, Andrey and Purtov, Konstantin V. and Petushkov, Valentin N. and Rodionova, Natalja S. and Chepurnyh, Tatiana V. and Fakhranurova, Liliia and Guglya, Elena B. and Ziganshin, Rustam and Tsarkova, Aleksandra S. and Kaskova, Zinaida M. and Shender, Victoria and Abakumov, Maxim and Abakumova, Tatiana O. and Povolotskaya, Inna S. and Eroshkin, Fedor M. and Zaraisky, Andrey G. and Mishin, Alexander S. and Dolgov, Sergey V. and Mitiouchkina, Tatiana Y. and Kopantzev, Eugene P. and Waldenmaier, Hans E. and Oliveira, Anderson G. and Oba, Yuichi and Barsova, Ekaterina and Bogdanova, Ekaterina A. and Gabaldón, Toni and Stevani, Cassius V. and Lukyanov, Sergey and Smirnov, Ivan V. and Gitelson, Josef I. and Kondrashov, Fyodor and Yampolsky, Ilia V.}, issn = {00278424}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, number = {50}, pages = {12728--12732}, publisher = {National Academy of Sciences}, title = {{Genetically encodable bioluminescent system from fungi}}, doi = {10.1073/pnas.1803615115}, volume = {115}, year = {2018}, } @article{428, abstract = {The plant hormone gibberellic acid (GA) is a crucial regulator of growth and development. The main paradigm of GA signaling puts forward transcriptional regulation via the degradation of DELLA transcriptional repressors. GA has also been shown to regulate tropic responses by modulation of the plasma membrane incidence of PIN auxin transporters by an unclear mechanism. Here we uncovered the cellular and molecular mechanisms by which GA redirects protein trafficking and thus regulates cell surface functionality. Photoconvertible reporters revealed that GA balances the protein traffic between the vacuole degradation route and recycling back to the cell surface. Low GA levels promote vacuolar delivery and degradation of multiple cargos, including PIN proteins, whereas high GA levels promote their recycling to the plasma membrane. This GA effect requires components of the retromer complex, such as Sorting Nexin 1 (SNX1) and its interacting, microtubule (MT)-associated protein, the Cytoplasmic Linker-Associated Protein (CLASP1). Accordingly, GA regulates the subcellular distribution of SNX1 and CLASP1, and the intact MT cytoskeleton is essential for the GA effect on trafficking. This GA cellular action occurs through DELLA proteins that regulate the MT and retromer presumably via their interaction partners Prefoldins (PFDs). Our study identified a branching of the GA signaling pathway at the level of DELLA proteins, which, in parallel to regulating transcription, also target by a nontranscriptional mechanism the retromer complex acting at the intersection of the degradation and recycling trafficking routes. By this mechanism, GA can redirect receptors and transporters to the cell surface, thus coregulating multiple processes, including PIN-dependent auxin fluxes during tropic responses.}, author = {Salanenka, Yuliya and Verstraeten, Inge and Löfke, Christian and Tabata, Kaori and Naramoto, Satoshi and Glanc, Matous and Friml, Jirí}, journal = {PNAS}, number = {14}, pages = { 3716 -- 3721}, publisher = {National Academy of Sciences}, title = {{Gibberellin DELLA signaling targets the retromer complex to redirect protein trafficking to the plasma membrane}}, doi = {10.1073/pnas.1721760115}, volume = {115}, year = {2018}, } @article{62, abstract = {Imaging is a dominant strategy for data collection in neuroscience, yielding stacks of images that often scale to gigabytes of data for a single experiment. Machine learning algorithms from computer vision can serve as a pair of virtual eyes that tirelessly processes these images, automatically detecting and identifying microstructures. Unlike learning methods, our Flexible Learning-free Reconstruction of Imaged Neural volumes (FLoRIN) pipeline exploits structure-specific contextual clues and requires no training. This approach generalizes across different modalities, including serially-sectioned scanning electron microscopy (sSEM) of genetically labeled and contrast enhanced processes, spectral confocal reflectance (SCoRe) microscopy, and high-energy synchrotron X-ray microtomography (μCT) of large tissue volumes. We deploy the FLoRIN pipeline on newly published and novel mouse datasets, demonstrating the high biological fidelity of the pipeline’s reconstructions. FLoRIN reconstructions are of sufficient quality for preliminary biological study, for example examining the distribution and morphology of cells or extracting single axons from functional data. Compared to existing supervised learning methods, FLoRIN is one to two orders of magnitude faster and produces high-quality reconstructions that are tolerant to noise and artifacts, as is shown qualitatively and quantitatively.}, author = {Shabazi, Ali and Kinnison, Jeffery and Vescovi, Rafael and Du, Ming and Hill, Robert and Jösch, Maximilian A and Takeno, Marc and Zeng, Hongkui and Da Costa, Nuno and Grutzendler, Jaime and Kasthuri, Narayanan and Scheirer, Walter}, journal = {Scientific Reports}, number = {1}, publisher = {Nature Publishing Group}, title = {{Flexible learning-free segmentation and reconstruction of neural volumes}}, doi = {10.1038/s41598-018-32628-3}, volume = {8}, year = {2018}, } @article{437, abstract = {Dendritic cells (DCs) are sentinels of the adaptive immune system that reside in peripheral organs of mammals. Upon pathogen encounter, they undergo maturation and up-regulate the chemokine receptor CCR7 that guides them along gradients of its chemokine ligands CCL19 and 21 to the next draining lymph node. There, DCs present peripherally acquired antigen to naïve T cells, thereby triggering adaptive immunity.}, author = {Leithner, Alexander F and Renkawitz, Jörg and De Vries, Ingrid and Hauschild, Robert and Haecker, Hans and Sixt, Michael K}, journal = {European Journal of Immunology}, number = {6}, pages = {1074 -- 1077}, publisher = {Wiley-Blackwell}, title = {{Fast and efficient genetic engineering of hematopoietic precursor cells for the study of dendritic cell migration}}, doi = {10.1002/eji.201747358}, volume = {48}, year = {2018}, } @article{617, abstract = {Insects are exposed to a variety of potential pathogens in their environment, many of which can severely impact fitness and health. Consequently, hosts have evolved resistance and tolerance strategies to suppress or cope with infections. Hosts utilizing resistance improve fitness by clearing or reducing pathogen loads, and hosts utilizing tolerance reduce harmful fitness effects per pathogen load. To understand variation in, and selective pressures on, resistance and tolerance, we asked to what degree they are shaped by host genetic background, whether plasticity in these responses depends upon dietary environment, and whether there are interactions between these two factors. Females from ten wild-type Drosophila melanogaster genotypes were kept on high- or low-protein (yeast) diets and infected with one of two opportunistic bacterial pathogens, Lactococcus lactis or Pseudomonas entomophila. We measured host resistance as the inverse of bacterial load in the early infection phase. The relationship (slope) between fly fecundity and individual-level bacteria load provided our fecundity tolerance measure. Genotype and dietary yeast determined host fecundity and strongly affected survival after infection with pathogenic P. entomophila. There was considerable genetic variation in host resistance, a commonly found phenomenon resulting from for example varying resistance costs or frequency-dependent selection. Despite this variation and the reproductive cost of higher P. entomophila loads, fecundity tolerance did not vary across genotypes. The absence of genetic variation in tolerance may suggest that at this early infection stage, fecundity tolerance is fixed or that any evolved tolerance mechanisms are not expressed under these infection conditions.}, author = {Kutzer, Megan and Kurtz, Joachim and Armitage, Sophie}, issn = {1420-9101}, journal = {Journal of Evolutionary Biology}, number = {1}, pages = {159 -- 171}, publisher = {Wiley}, title = {{Genotype and diet affect resistance, survival, and fecundity but not fecundity tolerance}}, doi = {10.1111/jeb.13211}, volume = {31}, year = {2018}, } @article{5888, abstract = {Despite the remarkable number of scientific breakthroughs of the last 100 years, the treatment of neurodevelopmental disorders (e.g., autism spectrum disorder, intellectual disability) remains a great challenge. Recent advancements in genomics, such as whole-exome or whole-genome sequencing, have enabled scientists to identify numerous mutations underlying neurodevelopmental disorders. Given the few hundred risk genes that have been discovered, the etiological variability and the heterogeneous clinical presentation, the need for genotype — along with phenotype- based diagnosis of individual patients has become a requisite. In this review we look at recent advancements in genomic analysis and their translation into clinical practice.}, author = {Tarlungeanu, Dora-Clara and Novarino, Gaia}, issn = {2092-6413}, journal = {Experimental & Molecular Medicine}, number = {8}, publisher = {Springer Nature}, title = {{Genomics in neurodevelopmental disorders: an avenue to personalized medicine}}, doi = {10.1038/s12276-018-0129-7}, volume = {50}, year = {2018}, } @article{295, abstract = {We prove upper and lower bounds on the ground-state energy of the ideal two-dimensional anyon gas. Our bounds are extensive in the particle number, as for fermions, and linear in the statistics parameter (Formula presented.). The lower bounds extend to Lieb–Thirring inequalities for all anyons except bosons.}, author = {Lundholm, Douglas and Seiringer, Robert}, journal = {Letters in Mathematical Physics}, number = {11}, pages = {2523--2541}, publisher = {Springer}, title = {{Fermionic behavior of ideal anyons}}, doi = {10.1007/s11005-018-1091-y}, volume = {108}, year = {2018}, } @article{555, abstract = {Conventional wisdom has it that proteins fold and assemble into definite structures, and that this defines their function. Glycosaminoglycans (GAGs) are different. In most cases the structures they form have a low degree of order, even when interacting with proteins. Here, we discuss how physical features common to all GAGs — hydrophilicity, charge, linearity and semi-flexibility — underpin the overall properties of GAG-rich matrices. By integrating soft matter physics concepts (e.g. polymer brushes and phase separation) with our molecular understanding of GAG–protein interactions, we can better comprehend how GAG-rich matrices assemble, what their properties are, and how they function. Taking perineuronal nets (PNNs) — a GAG-rich matrix enveloping neurons — as a relevant example, we propose that microphase separation determines the holey PNN anatomy that is pivotal to PNN functions.}, author = {Richter, Ralf and Baranova, Natalia and Day, Anthony and Kwok, Jessica}, journal = {Current Opinion in Structural Biology}, pages = {65 -- 74}, publisher = {Elsevier}, title = {{Glycosaminoglycans in extracellular matrix organisation: Are concepts from soft matter physics key to understanding the formation of perineuronal nets?}}, doi = {10.1016/j.sbi.2017.12.002}, volume = {50}, year = {2018}, } @article{448, abstract = {Around 150 million years ago, eusocial termites evolved from within the cockroaches, 50 million years before eusocial Hymenoptera, such as bees and ants, appeared. Here, we report the 2-Gb genome of the German cockroach, Blattella germanica, and the 1.3-Gb genome of the drywood termite Cryptotermes secundus. We show evolutionary signatures of termite eusociality by comparing the genomes and transcriptomes of three termites and the cockroach against the background of 16 other eusocial and non-eusocial insects. Dramatic adaptive changes in genes underlying the production and perception of pheromones confirm the importance of chemical communication in the termites. These are accompanied by major changes in gene regulation and the molecular evolution of caste determination. Many of these results parallel molecular mechanisms of eusocial evolution in Hymenoptera. However, the specific solutions are remarkably different, thus revealing a striking case of convergence in one of the major evolutionary transitions in biological complexity.}, author = {Harrison, Mark and Jongepier, Evelien and Robertson, Hugh and Arning, Nicolas and Bitard Feildel, Tristan and Chao, Hsu and Childers, Christopher and Dinh, Huyen and Doddapaneni, Harshavardhan and Dugan, Shannon and Gowin, Johannes and Greiner, Carolin and Han, Yi and Hu, Haofu and Hughes, Daniel and Huylmans, Ann K and Kemena, Karsten and Kremer, Lukas and Lee, Sandra and López Ezquerra, Alberto and Mallet, Ludovic and Monroy Kuhn, Jose and Moser, Annabell and Murali, Shwetha and Muzny, Donna and Otani, Saria and Piulachs, Maria and Poelchau, Monica and Qu, Jiaxin and Schaub, Florentine and Wada Katsumata, Ayako and Worley, Kim and Xie, Qiaolin and Ylla, Guillem and Poulsen, Michael and Gibbs, Richard and Schal, Coby and Richards, Stephen and Belles, Xavier and Korb, Judith and Bornberg Bauer, Erich}, journal = {Nature Ecology and Evolution}, number = {3}, pages = {557--566}, publisher = {Springer Nature}, title = {{Hemimetabolous genomes reveal molecular basis of termite eusociality}}, doi = {10.1038/s41559-017-0459-1}, volume = {2}, year = {2018}, }