TY - JOUR AB - Turbulence is ubiquitous in nature, yet even for the case of ordinary Newtonian fluids like water, our understanding of this phenomenon is limited. Many liquids of practical importance are more complicated (e.g., blood, polymer melts, paints), however; they exhibit elastic as well as viscous characteristics, and the relation between stress and strain is nonlinear. We demonstrate here for a model system of such complex fluids that at high shear rates, turbulence is not simply modified as previously believed but is suppressed and replaced by a different type of disordered motion, elasto-inertial turbulence. Elasto-inertial turbulence is found to occur at much lower Reynolds numbers than Newtonian turbulence, and the dynamical properties differ significantly. The friction scaling observed coincides with the so-called "maximum drag reduction" asymptote, which is exhibited by a wide range of viscoelastic fluids. AU - Samanta, Devranjan AU - Dubief, Yves AU - Holzner, Markus AU - Schäfer, Christof AU - Morozov, Alexander AU - Wagner, Christian AU - Hof, Björn ID - 2813 IS - 26 JF - PNAS TI - Elasto-inertial turbulence VL - 110 ER - TY - CONF AB - We consider the problem of deciding whether the persistent homology group of a simplicial pair (K, L) can be realized as the homology H* (X) of some complex X with L ⊂ X ⊂ K. We show that this problem is NP-complete even if K is embedded in ℝ3. As a consequence, we show that it is NP-hard to simplify level and sublevel sets of scalar functions on S3 within a given tolerance constraint. This problem has relevance to the visualization of medical images by isosurfaces. We also show an implication to the theory of well groups of scalar functions: not every well group can be realized by some level set, and deciding whether a well group can be realized is NP-hard. AU - Attali, Dominique AU - Bauer, Ulrich AU - Devillers, Olivier AU - Glisse, Marc AU - Lieutier, André ID - 2812 T2 - Proceedings of the 29th annual symposium on Computational Geometry TI - Homological reconstruction and simplification in R3 ER - TY - JOUR AB - The basic idea of evolutionary game theory is that payoff determines reproductive rate. Successful individuals have a higher payoff and produce more offspring. But in evolutionary and ecological situations there is not only reproductive rate but also carrying capacity. Individuals may differ in their exposure to density limiting effects. Here we explore an alternative approach to evolutionary game theory by assuming that the payoff from the game determines the carrying capacity of individual phenotypes. Successful strategies are less affected by density limitation (crowding) and reach higher equilibrium abundance. We demonstrate similarities and differences between our framework and the standard replicator equation. Our equation is defined on the positive orthant, instead of the simplex, but has the same equilibrium points as the replicator equation. Linear stability analysis produces the classical conditions for asymptotic stability of pure strategies, but the stability properties of internal equilibria can differ in the two frameworks. For example, in a two-strategy game with an internal equilibrium that is always stable under the replicator equation, the corresponding equilibrium can be unstable in the new framework resulting in a limit cycle. AU - Novak, Sebastian AU - Chatterjee, Krishnendu AU - Nowak, Martin ID - 2817 JF - Journal of Theoretical Biology TI - Density games VL - 334 ER - TY - CONF AB - We introduce quantatitive timed refinement metrics and quantitative timed simulation functions, incorporating zenoness checks, for timed systems. These functions assign positive real numbers between zero and infinity which quantify the timing mismatches between two timed systems, amongst non-zeno runs. We quantify timing mismatches in three ways: (1) the maximum timing mismatch that can arise, (2) the "steady-state" maximum timing mismatches, where initial transient timing mismatches are ignored; and (3) the (long-run) average timing mismatches amongst two systems. These three kinds of mismatches constitute three important types of timing differences. Our event times are the global times, measured from the start of the system execution, not just the time durations of individual steps. We present algorithms over timed automata for computing the three quantitative simulation functions to within any desired degree of accuracy. In order to compute the values of the quantitative simulation functions, we use a game theoretic formulation. We introduce two new kinds of objectives for two player games on finite state game graphs: (1) eventual debit-sum level objectives, and (2) average debit-sum level objectives. We present algorithms for computing the optimal values for these objectives for player 1, and then use these algorithms to compute the values of the quantitative timed simulation functions. AU - Chatterjee, Krishnendu AU - Prabhu, Vinayak ID - 2819 T2 - Proceedings of the 16th International Conference on Hybrid Systems: Computation and Control TI - Quantitative timed simulation functions and refinement metrics for real-time systems VL - 1 ER - TY - JOUR AB - Models of neural responses to stimuli with complex spatiotemporal correlation structure often assume that neurons are selective for only a small number of linear projections of a potentially high-dimensional input. In this review, we explore recent modeling approaches where the neural response depends on the quadratic form of the input rather than on its linear projection, that is, the neuron is sensitive to the local covariance structure of the signal preceding the spike. To infer this quadratic dependence in the presence of arbitrary (e.g., naturalistic) stimulus distribution, we review several inference methods, focusing in particular on two information theory–based approaches (maximization of stimulus energy and of noise entropy) and two likelihood-based approaches (Bayesian spike-triggered covariance and extensions of generalized linear models). We analyze the formal relationship between the likelihood-based and information-based approaches to demonstrate how they lead to consistent inference. We demonstrate the practical feasibility of these procedures by using model neurons responding to a flickering variance stimulus. AU - Rajan, Kanaka AU - Marre, Olivier AU - Tkacik, Gasper ID - 2818 IS - 7 JF - Neural Computation TI - Learning quadratic receptive fields from neural responses to natural stimuli VL - 25 ER - TY - JOUR AB - Myopia, or near-sightedness, is an ocular refractive error of unfocused image quality in front of the retinal plane. Individuals with high-grade myopia (dioptric power greater than -6.00) are predisposed to ocular morbidities such as glaucoma, retinal detachment, and myopic maculopathy. Nonsyndromic, high-grade myopia is highly heritable, and to date multiple gene loci have been reported. We performed exome sequencing in 4 individuals from an 11-member family of European descent from the United States. Affected individuals had a mean dioptric spherical equivalent of -22.00 sphere. A premature stop codon mutation c.157C>T (p.Gln53*) cosegregating with disease was discovered within SCO2 that maps to chromosome 22q13.33. Subsequent analyses identified three additional mutations in three highly myopic unrelated individuals (c.341G>A, c.418G>A, and c.776C>T). To determine differential gene expression in a developmental mouse model, we induced myopia by applying a -15.00D lens over one eye. Messenger RNA levels of SCO2 were significantly downregulated in myopic mouse retinae. Immunohistochemistry in mouse eyes confirmed SCO2 protein localization in retina, retinal pigment epithelium, and sclera. SCO2 encodes for a copper homeostasis protein influential in mitochondrial cytochrome c oxidase activity. Copper deficiencies have been linked with photoreceptor loss and myopia with increased scleral wall elasticity. Retinal thinning has been reported with an SC02 variant. Human mutation identification with support from an induced myopic animal provides biological insights of myopic development. AU - Tran Viet, Khanh AU - Powell, Caldwell AU - Barathi, Veluchamy AU - Klemm, Thomas AU - Maurer Stroh, Sebastian AU - Limviphuvadh, Vachiranee AU - Soler, Vincent AU - Ho, Candice AU - Yanovitch, Tammy AU - Schneider, Georg AU - Li, Yi AU - Nading, Erica AU - Metlapally, Ravikanth AU - Saw, Seang AU - Goh, Liang AU - Rozen, Steve AU - Young, Terri ID - 2826 IS - 5 JF - American Journal of Human Genetics TI - Mutations in SCO2 are associated with autosomal-dominant high-grade myopia VL - 92 ER - TY - JOUR AB - Identification of genes that control root system architecture in crop plants requires innovations that enable high-throughput and accurate measurements of root system architecture through time. We demonstrate the ability of a semiautomated 3D in vivo imaging and digital phenotyping pipeline to interrogate the quantitative genetic basis of root system growth in a rice biparental mapping population, Bala x Azucena. We phenotyped >1,400 3D root models and >57,000 2D images for a suite of 25 traits that quantified the distribution, shape, extent of exploration, and the intrinsic size of root networks at days 12, 14, and 16 of growth in a gellan gum medium. From these data we identified 89 quantitative trait loci, some of which correspond to those found previously in soil-grown plants, and provide evidence for genetic tradeoffs in root growth allocations, such as between the extent and thoroughness of exploration. We also developed a multivariate method for generating and mapping central root architecture phenotypes and used it to identify five major quantitative trait loci (r2 = 24-37%), two of which were not identified by our univariate analysis. Our imaging and analytical platform provides a means to identify genes with high potential for improving root traits and agronomic qualities of crops. AU - Topp, Christopher AU - Iyer Pascuzzi, Anjali AU - Anderson, Jill AU - Lee, Cheng AU - Zurek, Paul AU - Symonova, Olga AU - Zheng, Ying AU - Bucksch, Alexander AU - Mileyko, Yuriy AU - Galkovskyi, Taras AU - Moore, Brad AU - Harer, John AU - Edelsbrunner, Herbert AU - Mitchell Olds, Thomas AU - Weitz, Joshua AU - Benfey, Philip ID - 2822 IS - 18 JF - PNAS TI - 3D phenotyping and quantitative trait locus mapping identify core regions of the rice genome controlling root architecture VL - 110 ER - TY - JOUR AB - Many key aspects of plant development are regulated by the polarized transport of the phytohormone auxin. Cellular auxin efflux, the rate-limiting step in this process, has been shown to rely on the coordinated action of PIN-formed (PIN) and B-type ATP binding cassette (ABCB) carriers. Here, we report that polar auxin transport in the Arabidopsis thaliana root also requires the action of a Major Facilitator Superfamily (MFS) transporter, Zinc-Induced Facilitator-Like 1 (ZIFL1). Sequencing, promoter-reporter, and fluorescent protein fusion experiments indicate that the full-length ZIFL1.1 protein and a truncated splice isoform, ZIFL1.3, localize to the tonoplast of root cells and the plasma membrane of leaf stomatal guard cells, respectively. Using reverse genetics, we show that the ZIFL1.1 transporter regulates various root auxin-related processes, while the ZIFL1.3 isoform mediates drought tolerance by regulating stomatal closure. Auxin transport and immunolocalization assays demonstrate that ZIFL1.1 indirectly modulates cellular auxin efflux during shootward auxin transport at the root tip, likely by regulating plasma membrane PIN2 abundance. Finally, heterologous expression in yeast revealed that ZIFL1.1 and ZIFL1.3 share H+-coupled K+ transport activity. Thus, by determining the subcellular and tissue distribution of two isoforms, alternative splicing dictates a dual function for the ZIFL1 transporter. We propose that this MFS carrier regulates stomatal movements and polar auxin transport by modulating potassium and proton fluxes in Arabidopsis cells. AU - Remy, Estelle AU - Cabrito, Tânia AU - Baster, Pawel AU - Batista, Rita AU - Teixeira, Miguel AU - Friml, Jirí AU - Sá Correia, Isabel AU - Duque, Paula ID - 2821 IS - 3 JF - Plant Cell TI - A major facilitator superfamily transporter plays a dual role in polar auxin transport and drought stress tolerance in Arabidopsis VL - 25 ER - TY - JOUR AB - Removal of cargos from the cell surface via endocytosis is an efficient mechanism to regulate activities of plasma membrane (PM)-resident proteins, such as receptors or transporters. Salicylic acid (SA) is an important plant hormone that is traditionally associated with pathogen defense. Here, we describe an unanticipated effect of SA on subcellular endocytic cycling of proteins. Both exogenous treatments and endogenously enhanced SA levels repressed endocytosis of different PM proteins. The SA effect on endocytosis did not involve transcription or known components of the SA signaling pathway for transcriptional regulation. SA likely targets an endocytic mechanism that involves the coat protein clathrin, because SA interfered with the clathrin incidence at the PM and clathrin-deficient mutants were less sensitive to the impact of SA on the auxin distribution and root bending during the gravitropic response. By contrast, SA did not affect the ligand-induced endocytosis of the FLAGELLIN SENSING2 (FLS2) receptor during pathogen responses. Our data suggest that the established SA impact on transcription in plant immunity and the nontranscriptional effect of SA on clathrin-mediated endocytosis are independent mechanisms by which SA regulates distinct aspects of plant physiology. AU - Du, Yunlong AU - Tejos, Ricardo AU - Beck, Martina AU - Himschoot, Ellie AU - Li, Hongjiang AU - Robatzek, Silke AU - Vanneste, Steffen AU - Friml, Jirí ID - 2827 IS - 19 JF - PNAS TI - Salicylic acid interferes with clathrin-mediated endocytic protein trafficking VL - 110 ER - TY - JOUR AB - The primary goal of restoration is to create self-sustaining ecological communities that are resilient to periodic disturbance. Currently, little is known about how restored communities respond to disturbance events such as fire and how this response compares to remnant vegetation. Following the 2003 fires in south-eastern Australia we examined the post-fire response of revegetation plantings and compared this to remnant vegetation. Ten burnt and 10 unburnt (control) sites were assessed for each of three types of vegetation (direct seeding revegetation, revegetation using nursery seedlings (tubestock) and remnant woodland). Sixty sampling sites were surveyed 6months after fire to quantify the initial survival of mid- and overstorey plant species in each type of vegetation. Three and 5years after fire all sites were resurveyed to assess vegetation structure, species diversity and vigour, as well as indicators of soil function. Overall, revegetation showed high (>60%) post-fire survival, but this varied among species depending on regeneration strategy (obligate seeder or resprouter). The native ground cover, mid- and overstorey in both types of plantings showed rapid recovery of vegetation structure and cover within 3years of fire. This recovery was similar to the burnt remnant woodlands. Non-native (exotic) ground cover initially increased after fire, but was no different in burnt and unburnt sites 5years after fire. Fire had no effect on species richness, but burnt direct seeding sites had reduced species diversity (Simpson's Diversity Index) while diversity was higher in burnt remnant woodlands. Indices of soil function in all types of vegetation had recovered to levels found in unburnt sites 5years after fire. These results indicate that even young revegetation (stands <10years old) showed substantial recovery from disturbance by fire. This suggests that revegetation can provide an important basis for restoring woodland communities in the fire-prone Australian environment. AU - Pickup, Melinda AU - Wilson, Susie AU - Freudenberger, David AU - Nicholls, Nick AU - Gould, Lori AU - Hnatiuk, Sarah AU - Delandre, Jeni ID - 2823 IS - 3 JF - Austral Ecology TI - Post-fire recovery of revegetated woodland communities in south-eastern Australia VL - 38 ER - TY - JOUR AB - We study synthesis of controllers for real-time systems, where the objective is to stay in a given safe set. The problem is solved by obtaining winning strategies in the setting of concurrent two player timed automaton games with safety objectives. To prevent a player from winning by blocking time, we restrict each player to strategies that ensure that the player cannot be responsible for causing a Zeno run. We construct winning strategies for the controller which require access only to (1) the system clocks (thus, controllers which require their own internal infinitely precise clocks are not necessary), and (2) a logarithmic (in the number of clocks) number of memory bits (i.e. a linear number of memory states). Precisely, we show that for safety objectives, a memory of size (3 + lg (| C | + 1)) bits suffices for winning controller strategies, where C is the set of clocks of the timed automaton game, significantly improving the previous known exponential memory states bound. We also settle the open question of whether winning region-based strategies require memory for safety objectives by showing with an example the necessity of memory for such strategies to win for safety objectives. Finally, we show that the decision problem of determining if there exists a receptive player-1 winning strategy for safety objectives is EXPTIME-complete over timed automaton games. AU - Chatterjee, Krishnendu AU - Prabhu, Vinayak ID - 2824 JF - Information and Computation TI - Synthesis of memory-efficient, clock-memory free, and non-Zeno safety controllers for timed systems VL - 228-229 ER - TY - JOUR AB - PIN-FORMED (PIN) proteins localize asymmetrically at the plasma membrane and mediate intercellular polar transport of the plant hormone auxin that is crucial for a multitude of developmental processes in plants. PIN localization is under extensive control by environmental or developmental cues, but mechanisms regulating PIN localization are not fully understood. Here we show that early endosomal components ARF GEF BEN1 and newly identified Sec1/Munc18 family protein BEN2 are involved in distinct steps of early endosomal trafficking. BEN1 and BEN2 are collectively required for polar PIN localization, for their dynamic repolarization, and consequently for auxin activity gradient formation and auxin-related developmental processes including embryonic patterning, organogenesis, and vasculature venation patterning. These results show that early endosomal trafficking is crucial for cell polarity and auxin-dependent regulation of plant architecture. AU - Tanaka, Hirokazu AU - Kitakura, Saeko AU - Rakusová, Hana AU - Uemura, Tomohiro AU - Feraru, Mugurel AU - De Rycke, Riet AU - Robert, Stéphanie AU - Kakimoto, Tatsuo AU - Friml, Jirí ID - 2832 IS - 5 JF - PLoS Genetics TI - Cell polarity and patterning by PIN trafficking through early endosomal compartments in arabidopsis thaliana VL - 9 ER - TY - JOUR AB - We study the complexity of valued constraint satisfaction problems (VCSPs) parametrized by a constraint language, a fixed set of cost functions over a finite domain. An instance of the problem is specified by a sum of cost functions from the language and the goal is to minimize the sum. Under the unique games conjecture, the approximability of finite-valued VCSPs is well understood, see Raghavendra [2008]. However, there is no characterization of finite-valued VCSPs, let alone general-valued VCSPs, that can be solved exactly in polynomial time, thus giving insights from a combinatorial optimization perspective. We consider the case of languages containing all possible unary cost functions. In the case of languages consisting of only {0, ∞}-valued cost functions (i.e., relations), such languages have been called conservative and studied by Bulatov [2003, 2011] and recently by Barto [2011]. Since we study valued languages, we call a language conservative if it contains all finite-valued unary cost functions. The computational complexity of conservative valued languages has been studied by Cohen et al. [2006] for languages over Boolean domains, by Deineko et al. [2008] for {0, 1}-valued languages (a.k.a Max-CSP), and by Takhanov [2010a] for {0, ∞}-valued languages containing all finite-valued unary cost functions (a.k.a. Min-Cost-Hom). We prove a Schaefer-like dichotomy theorem for conservative valued languages: if all cost functions in the language satisfy a certain condition (specified by a complementary combination of STP and MJN multimor-phisms), then any instance can be solved in polynomial time (via a new algorithm developed in this article), otherwise the language is NP-hard. This is the first complete complexity classification of general-valued constraint languages over non-Boolean domains. It is a common phenomenon that complexity classifications of problems over non-Boolean domains are significantly harder than the Boolean cases. The polynomial-time algorithm we present for the tractable cases is a generalization of the submodular minimization problem and a result of Cohen et al. [2008]. Our results generalize previous results by Takhanov [2010a] and (a subset of results) by Cohen et al. [2006] and Deineko et al. [2008]. Moreover, our results do not rely on any computer-assisted search as in Deineko et al. [2008], and provide a powerful tool for proving hardness of finite-valued and general-valued languages. AU - Kolmogorov, Vladimir AU - Živný, Stanislav ID - 2828 IS - 2 JF - Journal of the ACM TI - The complexity of conservative valued CSPs VL - 60 ER - TY - JOUR AB - Laminar-turbulent intermittency is intrinsic to the transitional regime of a wide range of fluid flows including pipe, channel, boundary layer, and Couette flow. In the latter turbulent spots can grow and form continuous stripes, yet in the stripe-normal direction they remain interspersed by laminar fluid. We carry out direct numerical simulations in a long narrow domain and observe that individual turbulent stripes are transient. In agreement with recent observations in pipe flow, we find that turbulence becomes sustained at a distinct critical point once the spatial proliferation outweighs the inherent decaying process. By resolving the asymptotic size distributions close to criticality we can for the first time demonstrate scale invariance at the onset of turbulence. AU - Shi, Liang AU - Avila, Marc AU - Hof, Björn ID - 2829 IS - 20 JF - Physical Review Letters TI - Scale invariance at the onset of turbulence in couette flow VL - 110 ER - TY - JOUR AB - Although the equations governing fluid flow are well known, there are no analytical expressions that describe the complexity of turbulent motion. A recent proposition is that in analogy to low dimensional chaotic systems, turbulence is organized around unstable solutions of the governing equations which provide the building blocks of the disordered dynamics. We report the discovery of periodic solutions which just like intermittent turbulence are spatially localized and show that turbulent transients arise from one such solution branch. AU - Avila, Marc AU - Mellibovsky, Fernando AU - Roland, Nicolas AU - Hof, Björn ID - 2834 IS - 22 JF - Physical Review Letters TI - Streamwise-localized solutions at the onset of turbulence in pipe flow VL - 110 ER - TY - JOUR AB - During development, mechanical forces cause changes in size, shape, number, position, and gene expression of cells. They are therefore integral to any morphogenetic processes. Force generation by actin-myosin networks and force transmission through adhesive complexes are two self-organizing phenomena driving tissue morphogenesis. Coordination and integration of forces by long-range force transmission and mechanosensing of cells within tissues produce large-scale tissue shape changes. Extrinsic mechanical forces also control tissue patterning by modulating cell fate specification and differentiation. Thus, the interplay between tissue mechanics and biochemical signaling orchestrates tissue morphogenesis and patterning in development. AU - Heisenberg, Carl-Philipp J AU - Bellaïche, Yohanns ID - 2833 IS - 5 JF - Cell TI - Forces in tissue morphogenesis and patterning VL - 153 ER - TY - JOUR AU - Moussion, Christine AU - Sixt, Michael K ID - 2830 IS - 5 JF - Immunity TI - A conduit to amplify innate immunity VL - 38 ER - TY - JOUR AB - We outline two approaches to inference of neighbourhood size, N, and dispersal rate, σ2, based on either allele frequencies or on the lengths of sequence blocks that are shared between genomes. Over intermediate timescales (10-100 generations, say), populations that live in two dimensions approach a quasi-equilibrium that is independent of both their local structure and their deeper history. Over such scales, the standardised covariance of allele frequencies (i.e. pairwise FS T) falls with the logarithm of distance, and depends only on neighbourhood size, N, and a 'local scale', κ; the rate of gene flow, σ2, cannot be inferred. We show how spatial correlations can be accounted for, assuming a Gaussian distribution of allele frequencies, giving maximum likelihood estimates of N and κ. Alternatively, inferences can be based on the distribution of the lengths of sequence that are identical between blocks of genomes: long blocks (>0.1 cM, say) tell us about intermediate timescales, over which we assume a quasi-equilibrium. For large neighbourhood size, the distribution of long blocks is given directly by the classical Wright-Malécot formula; this relationship can be used to infer both N and σ2. With small neighbourhood size, there is an appreciable chance that recombinant lineages will coalesce back before escaping into the distant past. For this case, we show that if genomes are sampled from some distance apart, then the distribution of lengths of blocks that are identical in state is geometric, with a mean that depends on N and σ2. AU - Barton, Nicholas H AU - Etheridge, Alison AU - Kelleher, Jerome AU - Véber, Amandine ID - 2842 IS - 1 JF - Theoretical Population Biology TI - Inference in two dimensions: Allele frequencies versus lengths of shared sequence blocks VL - 87 ER - TY - JOUR AB - Individuals with Down syndrome (DS) present important motor deficits that derive from altered motor development of infants and young children. DYRK1A, a candidate gene for DS abnormalities has been implicated in motor function due to its expression in motor nuclei in the adult brain, and its overexpression in DS mouse models leads to hyperactivity and altered motor learning. However, its precise role in the adult motor system, or its possible involvement in postnatal locomotor development has not yet been clarified. During the postnatal period we observed time-specific expression of Dyrk1A in discrete subsets of brainstem nuclei and spinal cord motor neurons. Interestingly, we describe for the first time the presence of Dyrk1A in the presynaptic terminal of the neuromuscular junctions and its axonal transport from the facial nucleus, suggesting a function for Dyrk1A in these structures. Relevant to DS, Dyrk1A overexpression in transgenic mice (TgDyrk1A) produces motor developmental alterations possibly contributing to DS motor phenotypes and modifies the numbers of motor cholinergic neurons, suggesting that the kinase may have a role in the development of the brainstem and spinal cord motor system. AU - Arquè Fuste, Gloria AU - Casanovas, Anna AU - Dierssen, Mara ID - 2838 IS - 1 JF - PLoS One TI - Dyrk1A is dynamically expressed on subsets of motor neurons and in the neuromuscular junction: Possible role in Down syndrome VL - 8 ER - TY - JOUR AB - Directional guidance of cells via gradients of chemokines is considered crucial for embryonic development, cancer dissemination, and immune responses. Nevertheless, the concept still lacks direct experimental confirmation in vivo. Here, we identify endogenous gradients of the chemokine CCL21 within mouse skin and show that they guide dendritic cells toward lymphatic vessels. Quantitative imaging reveals depots of CCL21 within lymphatic endothelial cells and steeply decaying gradients within the perilymphatic interstitium. These gradients match the migratory patterns of the dendritic cells, which directionally approach vessels from a distance of up to 90-micrometers. Interstitial CCL21 is immobilized to heparan sulfates, and its experimental delocalization or swamping the endogenous gradients abolishes directed migration. These findings functionally establish the concept of haptotaxis, directed migration along immobilized gradients, in tissues. AU - Weber, Michele AU - Hauschild, Robert AU - Schwarz, Jan AU - Moussion, Christine AU - De Vries, Ingrid AU - Legler, Daniel AU - Luther, Sanjiv AU - Bollenbach, Mark Tobias AU - Sixt, Michael K ID - 2839 IS - 6117 JF - Science TI - Interstitial dendritic cell guidance by haptotactic chemokine gradients VL - 339 ER -