@misc{5436, abstract = {Recently there has been a significant effort to handle quantitative properties in formal verification and synthesis. While weighted automata over finite and infinite words provide a natural and flexible framework to express quantitative properties, perhaps surprisingly, some basic system properties such as average response time cannot be expressed using weighted automata, nor in any other know decidable formalism. In this work, we introduce nested weighted automata as a natural extension of weighted automata which makes it possible to express important quantitative properties such as average response time. In nested weighted automata, a master automaton spins off and collects results from weighted slave automata, each of which computes a quantity along a finite portion of an infinite word. Nested weighted automata can be viewed as the quantitative analogue of monitor automata, which are used in run-time verification. We establish an almost complete decidability picture for the basic decision problems about nested weighted automata, and illustrate their applicability in several domains. In particular, nested weighted automata can be used to decide average response time properties.}, author = {Chatterjee, Krishnendu and Henzinger, Thomas A and Otop, Jan}, issn = {2664-1690}, pages = {29}, publisher = {IST Austria}, title = {{Nested weighted automata}}, doi = {10.15479/AT:IST-2015-170-v2-2}, year = {2015}, } @inproceedings{1659, abstract = {The target discounted-sum problem is the following: Given a rational discount factor 0 < λ < 1 and three rational values a, b, and t, does there exist a finite or an infinite sequence w ε(a, b)∗ or w ε(a, b)w, such that Σ|w| i=0 w(i)λi equals t? The problem turns out to relate to many fields of mathematics and computer science, and its decidability question is surprisingly hard to solve. We solve the finite version of the problem, and show the hardness of the infinite version, linking it to various areas and open problems in mathematics and computer science: β-expansions, discounted-sum automata, piecewise affine maps, and generalizations of the Cantor set. We provide some partial results to the infinite version, among which are solutions to its restriction to eventually-periodic sequences and to the cases that λ λ 1/2 or λ = 1/n, for every n ε N. We use our results for solving some open problems on discounted-sum automata, among which are the exact-value problem for nondeterministic automata over finite words and the universality and inclusion problems for functional automata.}, author = {Boker, Udi and Henzinger, Thomas A and Otop, Jan}, booktitle = {LICS}, issn = {1043-6871 }, location = {Kyoto, Japan}, pages = {750 -- 761}, publisher = {IEEE}, title = {{The target discounted-sum problem}}, doi = {10.1109/LICS.2015.74}, year = {2015}, } @inproceedings{1610, abstract = {The edit distance between two words w1, w2 is the minimal number of word operations (letter insertions, deletions, and substitutions) necessary to transform w1 to w2. The edit distance generalizes to languages L1,L2, where the edit distance is the minimal number k such that for every word from L1 there exists a word in L2 with edit distance at most k. We study the edit distance computation problem between pushdown automata and their subclasses. The problem of computing edit distance to pushdown automata is undecidable, and in practice, the interesting question is to compute the edit distance from a pushdown automaton (the implementation, a standard model for programs with recursion) to a regular language (the specification). In this work, we present a complete picture of decidability and complexity for deciding whether, for a given threshold k, the edit distance from a pushdown automaton to a finite automaton is at most k.}, author = {Chatterjee, Krishnendu and Henzinger, Thomas A and Ibsen-Jensen, Rasmus and Otop, Jan}, booktitle = {42nd International Colloquium}, isbn = {978-3-662-47665-9}, location = {Kyoto, Japan}, number = {Part II}, pages = {121 -- 133}, publisher = {Springer Nature}, title = {{Edit distance for pushdown automata}}, doi = {10.1007/978-3-662-47666-6_10}, volume = {9135}, year = {2015}, } @misc{5437, abstract = {We consider the core algorithmic problems related to verification of systems with respect to three classical quantitative properties, namely, the mean-payoff property, the ratio property, and the minimum initial credit for energy property. The algorithmic problem given a graph and a quantitative property asks to compute the optimal value (the infimum value over all traces) from every node of the graph. We consider graphs with constant treewidth, and it is well-known that the control-flow graphs of most programs have constant treewidth. Let $n$ denote the number of nodes of a graph, $m$ the number of edges (for constant treewidth graphs $m=O(n)$) and $W$ the largest absolute value of the weights. Our main theoretical results are as follows. First, for constant treewidth graphs we present an algorithm that approximates the mean-payoff value within a multiplicative factor of $\epsilon$ in time $O(n \cdot \log (n/\epsilon))$ and linear space, as compared to the classical algorithms that require quadratic time. Second, for the ratio property we present an algorithm that for constant treewidth graphs works in time $O(n \cdot \log (|a\cdot b|))=O(n\cdot\log (n\cdot W))$, when the output is $\frac{a}{b}$, as compared to the previously best known algorithm with running time $O(n^2 \cdot \log (n\cdot W))$. Third, for the minimum initial credit problem we show that (i)~for general graphs the problem can be solved in $O(n^2\cdot m)$ time and the associated decision problem can be solved in $O(n\cdot m)$ time, improving the previous known $O(n^3\cdot m\cdot \log (n\cdot W))$ and $O(n^2 \cdot m)$ bounds, respectively; and (ii)~for constant treewidth graphs we present an algorithm that requires $O(n\cdot \log n)$ time, improving the previous known $O(n^4 \cdot \log (n \cdot W))$ bound. We have implemented some of our algorithms and show that they present a significant speedup on standard benchmarks. }, author = {Chatterjee, Krishnendu and Ibsen-Jensen, Rasmus and Pavlogiannis, Andreas}, issn = {2664-1690}, pages = {27}, publisher = {IST Austria}, title = {{Faster algorithms for quantitative verification in constant treewidth graphs}}, doi = {10.15479/AT:IST-2015-330-v2-1}, year = {2015}, } @misc{5430, abstract = {We consider the core algorithmic problems related to verification of systems with respect to three classical quantitative properties, namely, the mean- payoff property, the ratio property, and the minimum initial credit for energy property. The algorithmic problem given a graph and a quantitative property asks to compute the optimal value (the infimum value over all traces) from every node of the graph. We consider graphs with constant treewidth, and it is well-known that the control-flow graphs of most programs have constant treewidth. Let n denote the number of nodes of a graph, m the number of edges (for constant treewidth graphs m = O ( n ) ) and W the largest absolute value of the weights. Our main theoretical results are as follows. First, for constant treewidth graphs we present an algorithm that approximates the mean-payoff value within a mul- tiplicative factor of ∊ in time O ( n · log( n/∊ )) and linear space, as compared to the classical algorithms that require quadratic time. Second, for the ratio property we present an algorithm that for constant treewidth graphs works in time O ( n · log( | a · b · n | )) = O ( n · log( n · W )) , when the output is a b , as compared to the previously best known algorithm with running time O ( n 2 · log( n · W )) . Third, for the minimum initial credit problem we show that (i) for general graphs the problem can be solved in O ( n 2 · m ) time and the associated decision problem can be solved in O ( n · m ) time, improving the previous known O ( n 3 · m · log( n · W )) and O ( n 2 · m ) bounds, respectively; and (ii) for constant treewidth graphs we present an algorithm that requires O ( n · log n ) time, improving the previous known O ( n 4 · log( n · W )) bound. We have implemented some of our algorithms and show that they present a significant speedup on standard benchmarks.}, author = {Chatterjee, Krishnendu and Ibsen-Jensen, Rasmus and Pavlogiannis, Andreas}, issn = {2664-1690}, pages = {31}, publisher = {IST Austria}, title = {{Faster algorithms for quantitative verification in constant treewidth graphs}}, doi = {10.15479/AT:IST-2015-319-v1-1}, year = {2015}, } @misc{5439, abstract = {The target discounted-sum problem is the following: Given a rational discount factor 0 < λ < 1 and three rational values a, b, and t, does there exist a finite or an infinite sequence w ε(a, b)∗ or w ε(a, b)w, such that Σ|w| i=0 w(i)λi equals t? The problem turns out to relate to many fields of mathematics and computer science, and its decidability question is surprisingly hard to solve. We solve the finite version of the problem, and show the hardness of the infinite version, linking it to various areas and open problems in mathematics and computer science: β-expansions, discounted-sum automata, piecewise affine maps, and generalizations of the Cantor set. We provide some partial results to the infinite version, among which are solutions to its restriction to eventually-periodic sequences and to the cases that λ λ 1/2 or λ = 1/n, for every n ε N. We use our results for solving some open problems on discounted-sum automata, among which are the exact-value problem for nondeterministic automata over finite words and the universality and inclusion problems for functional automata. }, author = {Boker, Udi and Henzinger, Thomas A and Otop, Jan}, issn = {2664-1690}, pages = {20}, publisher = {IST Austria}, title = {{The target discounted-sum problem}}, doi = {10.15479/AT:IST-2015-335-v1-1}, year = {2015}, } @misc{5438, abstract = {The edit distance between two words w1, w2 is the minimal number of word operations (letter insertions, deletions, and substitutions) necessary to transform w1 to w2. The edit distance generalizes to languages L1, L2, where the edit distance is the minimal number k such that for every word from L1 there exists a word in L2 with edit distance at most k. We study the edit distance computation problem between pushdown automata and their subclasses. The problem of computing edit distance to a pushdown automaton is undecidable, and in practice, the interesting question is to compute the edit distance from a pushdown automaton (the implementation, a standard model for programs with recursion) to a regular language (the specification). In this work, we present a complete picture of decidability and complexity for deciding whether, for a given threshold k, the edit distance from a pushdown automaton to a finite automaton is at most k. }, author = {Chatterjee, Krishnendu and Henzinger, Thomas A and Ibsen-Jensen, Rasmus and Otop, Jan}, issn = {2664-1690}, pages = {15}, publisher = {IST Austria}, title = {{Edit distance for pushdown automata}}, doi = {10.15479/AT:IST-2015-334-v1-1}, year = {2015}, } @misc{5440, abstract = {Evolution occurs in populations of reproducing individuals. The structure of the population affects the outcome of the evolutionary process. Evolutionary graph theory is a powerful approach to study this phenomenon. There are two graphs. The interaction graph specifies who interacts with whom for payoff in the context of evolution. The replacement graph specifies who competes with whom for reproduction. The vertices of the two graphs are the same, and each vertex corresponds to an individual of the population. The fitness (or the reproductive rate) is a non-negative number, and depends on the payoff. A key quantity is the fixation probability of a new mutant. It is defined as the probability that a newly introduced mutant (on a single vertex) generates a lineage of offspring which eventually takes over the entire population of resident individuals. The basic computational questions are as follows: (i) the qualitative question asks whether the fixation probability is positive; and (ii) the quantitative approximation question asks for an approximation of the fixation probability. Our main results are as follows: First, we consider a special case of the general problem, where the residents do not reproduce. We show that the qualitative question is NP-complete, and the quantitative approximation question is #P-complete, and the hardness results hold even in the special case where the interaction and the replacement graphs coincide. Second, we show that in general both the qualitative and the quantitative approximation questions are PSPACE-complete. The PSPACE-hardness result for quantitative approximation holds even when the fitness is always positive.}, author = {Chatterjee, Krishnendu and Ibsen-Jensen, Rasmus and Nowak, Martin}, issn = {2664-1690}, pages = {18}, publisher = {IST Austria}, title = {{The complexity of evolutionary games on graphs}}, doi = {10.15479/AT:IST-2015-323-v2-2}, year = {2015}, } @misc{5432, abstract = {Evolution occurs in populations of reproducing individuals. The structure of the population affects the outcome of the evolutionary process. Evolutionary graph theory is a powerful approach to study this phenomenon. There are two graphs. The interaction graph specifies who interacts with whom in the context of evolution.The replacement graph specifies who competes with whom for reproduction. The vertices of the two graphs are the same, and each vertex corresponds to an individual of the population. A key quantity is the fixation probability of a new mutant. It is defined as the probability that a newly introduced mutant (on a single vertex) generates a lineage of offspring which eventually takes over the entire population of resident individuals. The basic computational questions are as follows: (i) the qualitative question asks whether the fixation probability is positive; and (ii) the quantitative approximation question asks for an approximation of the fixation probability. Our main results are: (1) We show that the qualitative question is NP-complete and the quantitative approximation question is #P-hard in the special case when the interaction and the replacement graphs coincide and even with the restriction that the resident individuals do not reproduce (which corresponds to an invading population taking over an empty structure). (2) We show that in general the qualitative question is PSPACE-complete and the quantitative approximation question is PSPACE-hard and can be solved in exponential time. }, author = {Chatterjee, Krishnendu and Ibsen-Jensen, Rasmus and Nowak, Martin}, issn = {2664-1690}, pages = {29}, publisher = {IST Austria}, title = {{The complexity of evolutionary games on graphs}}, doi = {10.15479/AT:IST-2015-323-v1-1}, year = {2015}, } @misc{5444, abstract = {A comprehensive understanding of the clonal evolution of cancer is critical for understanding neoplasia. Genome-wide sequencing data enables evolutionary studies at unprecedented depth. However, classical phylogenetic methods often struggle with noisy sequencing data of impure DNA samples and fail to detect subclones that have different evolutionary trajectories. We have developed a tool, called Treeomics, that allows us to reconstruct the phylogeny of a cancer with commonly available sequencing technologies. Using Bayesian inference and Integer Linear Programming, robust phylogenies consistent with the biological processes underlying cancer evolution were obtained for pancreatic, ovarian, and prostate cancers. Furthermore, Treeomics correctly identified sequencing artifacts such as those resulting from low statistical power; nearly 7% of variants were misclassified by conventional statistical methods. These artifacts can skew phylogenies by creating illusory tumor heterogeneity among distinct samples. Importantly, we show that the evolutionary trees generated with Treeomics are mathematically optimal.}, author = {Reiter, Johannes and Makohon-Moore, Alvin and Gerold, Jeffrey and Bozic, Ivana and Chatterjee, Krishnendu and Iacobuzio-Donahue, Christine and Vogelstein, Bert and Nowak, Martin}, issn = {2664-1690}, pages = {25}, publisher = {IST Austria}, title = {{Reconstructing robust phylogenies of metastatic cancers}}, doi = {10.15479/AT:IST-2015-399-v1-1}, year = {2015}, } @misc{5443, abstract = {POMDPs are standard models for probabilistic planning problems, where an agent interacts with an uncertain environment. We study the problem of almost-sure reachability, where given a set of target states, the question is to decide whether there is a policy to ensure that the target set is reached with probability 1 (almost-surely). While in general the problem is EXPTIME-complete, in many practical cases policies with a small amount of memory suffice. Moreover, the existing solution to the problem is explicit, which first requires to construct explicitly an exponential reduction to a belief-support MDP. In this work, we first study the existence of observation-stationary strategies, which is NP-complete, and then small-memory strategies. We present a symbolic algorithm by an efficient encoding to SAT and using a SAT solver for the problem. We report experimental results demonstrating the scalability of our symbolic (SAT-based) approach.}, author = {Chatterjee, Krishnendu and Chmelik, Martin and Davies, Jessica}, issn = {2664-1690}, pages = {23}, publisher = {IST Austria}, title = {{A symbolic SAT-based algorithm for almost-sure reachability with small strategies in POMDPs}}, doi = {10.15479/AT:IST-2015-325-v2-1}, year = {2015}, } @article{5804, abstract = {We present here the first integer-based algorithm for constructing a well-defined lattice sphere specified by integer radius and integer center. The algorithm evolves from a unique correspondence between the lattice points comprising the sphere and the distribution of sum of three square numbers in integer intervals. We characterize these intervals to derive a useful set of recurrences, which, in turn, aids in efficient computation. Each point of the lattice sphere is determined by resorting to only a few primitive operations in the integer domain. The symmetry of its quadraginta octants provides an added advantage by confining the computation to its prima quadraginta octant. Detailed theoretical analysis and experimental results have been furnished to demonstrate its simplicity and elegance.}, author = {Biswas, Ranita and Bhowmick, Partha}, issn = {0304-3975}, journal = {Theoretical Computer Science}, number = {4}, pages = {56--72}, publisher = {Elsevier}, title = {{From prima quadraginta octant to lattice sphere through primitive integer operations}}, doi = {10.1016/j.tcs.2015.11.018}, volume = {624}, year = {2015}, } @article{5807, author = {Biswas, Ranita and Bhowmick, Partha}, issn = {0304-3975}, journal = {Theoretical Computer Science}, number = {11}, pages = {146--163}, publisher = {Elsevier}, title = {{On different topological classes of spherical geodesic paths and circles inZ3}}, doi = {10.1016/j.tcs.2015.09.003}, volume = {605}, year = {2015}, } @article{5808, author = {Biswas, Ranita and Bhowmick, Partha}, issn = {0178-2789}, journal = {The Visual Computer}, number = {6-8}, pages = {787--797}, publisher = {Springer Nature}, title = {{Layer the sphere}}, doi = {10.1007/s00371-015-1101-3}, volume = {31}, year = {2015}, } @article{594, abstract = {Transcription of eukaryotic protein-coding genes commences with the assembly of a conserved initiation complex, which consists of RNA polymerase II (Pol II) and the general transcription factors, at promoter DNA. After two decades of research, the structural basis of transcription initiation is emerging. Crystal structures of many components of the initiation complex have been resolved, and structural information on Pol II complexes with general transcription factors has recently been obtained. Although mechanistic details await elucidation, available data outline how Pol II cooperates with the general transcription factors to bind to and open promoter DNA, and how Pol II directs RNA synthesis and escapes from the promoter.}, author = {Sainsbury, Sarah and Bernecky, Carrie A and Cramer, Patrick}, journal = {Nature Reviews Molecular Cell Biology}, number = {3}, pages = {129 -- 143}, publisher = {Nature Publishing Group}, title = {{Structural basis of transcription initiation by RNA polymerase II}}, doi = {10.1038/nrm3952}, volume = {16}, year = {2015}, } @inproceedings{1511, abstract = {The fact that the complete graph K_5 does not embed in the plane has been generalized in two independent directions. On the one hand, the solution of the classical Heawood problem for graphs on surfaces established that the complete graph K_n embeds in a closed surface M if and only if (n-3)(n-4) is at most 6b_1(M), where b_1(M) is the first Z_2-Betti number of M. On the other hand, Van Kampen and Flores proved that the k-skeleton of the n-dimensional simplex (the higher-dimensional analogue of K_{n+1}) embeds in R^{2k} if and only if n is less or equal to 2k+2. Two decades ago, Kuhnel conjectured that the k-skeleton of the n-simplex embeds in a compact, (k-1)-connected 2k-manifold with kth Z_2-Betti number b_k only if the following generalized Heawood inequality holds: binom{n-k-1}{k+1} is at most binom{2k+1}{k+1} b_k. This is a common generalization of the case of graphs on surfaces as well as the Van Kampen--Flores theorem. In the spirit of Kuhnel's conjecture, we prove that if the k-skeleton of the n-simplex embeds in a 2k-manifold with kth Z_2-Betti number b_k, then n is at most 2b_k binom{2k+2}{k} + 2k + 5. This bound is weaker than the generalized Heawood inequality, but does not require the assumption that M is (k-1)-connected. Our proof uses a result of Volovikov about maps that satisfy a certain homological triviality condition.}, author = {Goaoc, Xavier and Mabillard, Isaac and Paták, Pavel and Patakova, Zuzana and Tancer, Martin and Wagner, Uli}, location = {Eindhoven, Netherlands}, pages = {476 -- 490}, publisher = {Schloss Dagstuhl - Leibniz-Zentrum für Informatik}, title = {{On generalized Heawood inequalities for manifolds: A Van Kampen–Flores-type nonembeddability result}}, doi = {10.4230/LIPIcs.SOCG.2015.476}, volume = {34 }, year = {2015}, } @article{6118, abstract = {Carbon dioxide (CO2) gradients are ubiquitous and provide animals with information about their environment, such as the potential presence of prey or predators. The nematode Caenorhabditis elegans avoids elevated CO2, and previous work identified three neuron pairs called “BAG,” “AFD,” and “ASE” that respond to CO2 stimuli. Using in vivo Ca2+ imaging and behavioral analysis, we show that C. elegans can detect CO2 independently of these sensory pathways. Many of the C. elegans sensory neurons we examined, including the AWC olfactory neurons, the ASJ and ASK gustatory neurons, and the ASH and ADL nociceptors, respond to a rise in CO2 with a rise in Ca2+. In contrast, glial sheath cells harboring the sensory endings of C. elegans’ major chemosensory neurons exhibit strong and sustained decreases in Ca2+ in response to high CO2. Some of these CO2 responses appear to be cell intrinsic. Worms therefore may couple detection of CO2 to that of other cues at the earliest stages of sensory processing. We show that C. elegans persistently suppresses oviposition at high CO2. Hermaphrodite-specific neurons (HSNs), the executive neurons driving egg-laying, are tonically inhibited when CO2 is elevated. CO2 modulates the egg-laying system partly through the AWC olfactory neurons: High CO2 tonically activates AWC by a cGMP-dependent mechanism, and AWC output inhibits the HSNs. Our work shows that CO2 is a more complex sensory cue for C. elegans than previously thought, both in terms of behavior and neural circuitry.}, author = {Fenk, Lorenz A. and de Bono, Mario}, issn = {0027-8424}, journal = {Proceedings of the National Academy of Sciences}, number = {27}, pages = {E3525--E3534}, publisher = {National Academy of Sciences}, title = {{Environmental CO2 inhibits Caenorhabditis elegans egg-laying by modulating olfactory neurons and evokes widespread changes in neural activity}}, doi = {10.1073/pnas.1423808112}, volume = {112}, year = {2015}, } @article{6120, abstract = {Brains organize behavior and physiology to optimize the response to threats or opportunities. We dissect how 21% O2, an indicator of surface exposure, reprograms C. elegans' global state, inducing sustained locomotory arousal and altering expression of neuropeptides, metabolic enzymes, and other non-neural genes. The URX O2-sensing neurons drive arousal at 21% O2 by tonically activating the RMG interneurons. Stimulating RMG is sufficient to switch behavioral state. Ablating the ASH, ADL, or ASK sensory neurons connected to RMG by gap junctions does not disrupt arousal. However, disrupting cation currents in these neurons curtails RMG neurosecretion and arousal. RMG signals high O2 by peptidergic secretion. Neuropeptide reporters reveal neural circuit state, as neurosecretion stimulates neuropeptide expression. Neural imaging in unrestrained animals shows that URX and RMG encode O2 concentration rather than behavior, while the activity of downstream interneurons such as AVB and AIY reflect both O2 levels and the behavior being executed.}, author = {Laurent, Patrick and Soltesz, Zoltan and Nelson, Geoffrey M and Chen, Changchun and Arellano-Carbajal, Fausto and Levy, Emmanuel and de Bono, Mario}, issn = {2050-084X}, journal = {eLife}, publisher = {eLife Sciences Publications}, title = {{Decoding a neural circuit controlling global animal state in C. elegans}}, doi = {10.7554/elife.04241}, volume = {4}, year = {2015}, } @inproceedings{1637, abstract = {An instance of the Valued Constraint Satisfaction Problem (VCSP) is given by a finite set of variables, a finite domain of labels, and a sum of functions, each function depending on a subset of the variables. Each function can take finite values specifying costs of assignments of labels to its variables or the infinite value, which indicates an infeasible assignment. The goal is to find an assignment of labels to the variables that minimizes the sum. We study, assuming that P ≠ NP, how the complexity of this very general problem depends on the set of functions allowed in the instances, the so-called constraint language. The case when all allowed functions take values in {0, ∞} corresponds to ordinary CSPs, where one deals only with the feasibility issue and there is no optimization. This case is the subject of the Algebraic CSP Dichotomy Conjecture predicting for which constraint languages CSPs are tractable (i.e. solvable in polynomial time) and for which NP-hard. The case when all allowed functions take only finite values corresponds to finite-valued CSP, where the feasibility aspect is trivial and one deals only with the optimization issue. The complexity of finite-valued CSPs was fully classified by Thapper and Zivny. An algebraic necessary condition for tractability of a general-valued CSP with a fixed constraint language was recently given by Kozik and Ochremiak. As our main result, we prove that if a constraint language satisfies this algebraic necessary condition, and the feasibility CSP (i.e. the problem of deciding whether a given instance has a feasible solution) corresponding to the VCSP with this language is tractable, then the VCSP is tractable. The algorithm is a simple combination of the assumed algorithm for the feasibility CSP and the standard LP relaxation. As a corollary, we obtain that a dichotomy for ordinary CSPs would imply a dichotomy for general-valued CSPs.}, author = {Kolmogorov, Vladimir and Krokhin, Andrei and Rolinek, Michal}, location = {Berkeley, CA, United States}, pages = {1246 -- 1258}, publisher = {IEEE}, title = {{The complexity of general-valued CSPs}}, doi = {10.1109/FOCS.2015.80}, year = {2015}, } @article{6507, abstract = {The osteoclast-associated receptor (OSCAR) is a collagen-binding immune receptor with important roles in dendritic cell maturation and activation of inflammatory monocytes as well as in osteoclastogenesis. The crystal structure of the OSCAR ectodomain is presented, both free and in complex with a consensus triple-helical peptide (THP). The structures revealed a collagen-binding site in each immunoglobulin-like domain (D1 and D2). The THP binds near a predicted collagen-binding groove in D1, but a more extensive interaction with D2 is facilitated by the unusually wide D1-D2 interdomain angle in OSCAR. Direct binding assays, combined with site-directed mutagenesis, confirm that the primary collagen-binding site in OSCAR resides in D2, in marked contrast to the related collagen receptors, glycoprotein VI (GPVI) and leukocyte-associated immunoglobulin-like receptor-1 (LAIR-1). Monomeric OSCAR D1D2 binds to the consensus THP with a KD of 28 µM measured in solution, but shows a higher affinity (KD 1.5 μM) when binding to a solid-phase THP, most likely due to an avidity effect. These data suggest a 2-stage model for the interaction of OSCAR with a collagen fibril, with transient, low-affinity interactions initiated by the membrane-distal D1, followed by firm adhesion to the primary binding site in D2.}, author = {Zhou, Long and Hinerman, J. M. and Blaszczyk, M. and Miller, J. L. C. and Conrady, D. G. and Barrow, A. D. and Chirgadze, D. Y. and Bihan, D. and Farndale, R. W. and Herr, A. B.}, issn = {0006-4971}, journal = {Blood}, number = {5}, pages = {529--537}, publisher = {American Society of Hematology}, title = {{Structural basis for collagen recognition by the immune receptor OSCAR}}, doi = {10.1182/blood-2015-08-667055}, volume = {127}, year = {2015}, }