@article{2826, abstract = {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.}, author = {Tran Viet, Khanh and Powell, Caldwell and Barathi, Veluchamy and Klemm, Thomas and Maurer Stroh, Sebastian and Limviphuvadh, Vachiranee and Soler, Vincent and Ho, Candice and Yanovitch, Tammy and Schneider, Georg and Li, Yi and Nading, Erica and Metlapally, Ravikanth and Saw, Seang and Goh, Liang and Rozen, Steve and Young, Terri}, journal = {American Journal of Human Genetics}, number = {5}, pages = {820 -- 826}, publisher = {Cell Press}, title = {{Mutations in SCO2 are associated with autosomal-dominant high-grade myopia}}, doi = {10.1016/j.ajhg.2013.04.005}, volume = {92}, year = {2013}, } @article{2827, abstract = {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.}, author = {Du, Yunlong and Tejos, Ricardo and Beck, Martina and Himschoot, Ellie and Li, Hongjiang and Robatzek, Silke and Vanneste, Steffen and Friml, Jirí}, journal = {PNAS}, number = {19}, pages = {7946 -- 7951}, publisher = {National Academy of Sciences}, title = {{Salicylic acid interferes with clathrin-mediated endocytic protein trafficking}}, doi = {10.1073/pnas.1220205110}, volume = {110}, year = {2013}, } @article{2828, abstract = {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.}, author = {Kolmogorov, Vladimir and Živný, Stanislav}, journal = {Journal of the ACM}, number = {2}, publisher = {ACM}, title = {{The complexity of conservative valued CSPs}}, doi = {10.1145/2450142.2450146}, volume = {60}, year = {2013}, } @article{2829, abstract = {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.}, author = {Shi, Liang and Avila, Marc and Hof, Björn}, journal = {Physical Review Letters}, number = {20}, publisher = {American Physical Society}, title = {{Scale invariance at the onset of turbulence in couette flow}}, doi = {10.1103/PhysRevLett.110.204502}, volume = {110}, year = {2013}, } @article{2831, abstract = {We consider Markov decision processes (MDPs) with Büchi (liveness) objectives. We consider the problem of computing the set of almost-sure winning states from where the objective can be ensured with probability 1. Our contributions are as follows: First, we present the first subquadratic symbolic algorithm to compute the almost-sure winning set for MDPs with Büchi objectives; our algorithm takes O(n · √ m) symbolic steps as compared to the previous known algorithm that takes O(n 2) symbolic steps, where n is the number of states and m is the number of edges of the MDP. In practice MDPs have constant out-degree, and then our symbolic algorithm takes O(n · √ n) symbolic steps, as compared to the previous known O(n 2) symbolic steps algorithm. Second, we present a new algorithm, namely win-lose algorithm, with the following two properties: (a) the algorithm iteratively computes subsets of the almost-sure winning set and its complement, as compared to all previous algorithms that discover the almost-sure winning set upon termination; and (b) requires O(n · √ K) symbolic steps, where K is the maximal number of edges of strongly connected components (scc's) of the MDP. The win-lose algorithm requires symbolic computation of scc's. Third, we improve the algorithm for symbolic scc computation; the previous known algorithm takes linear symbolic steps, and our new algorithm improves the constants associated with the linear number of steps. In the worst case the previous known algorithm takes 5×n symbolic steps, whereas our new algorithm takes 4×n symbolic steps.}, author = {Chatterjee, Krishnendu and Henzinger, Monika H and Joglekar, Manas and Shah, Nisarg}, journal = {Formal Methods in System Design}, number = {3}, pages = {301 -- 327}, publisher = {Springer}, title = {{Symbolic algorithms for qualitative analysis of Markov decision processes with Büchi objectives}}, doi = {10.1007/s10703-012-0180-2}, volume = {42}, year = {2013}, } @article{2832, abstract = {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.}, author = {Tanaka, Hirokazu and Kitakura, Saeko and Rakusová, Hana and Uemura, Tomohiro and Feraru, Mugurel and De Rycke, Riet and Robert, Stéphanie and Kakimoto, Tatsuo and Friml, Jirí}, journal = {PLoS Genetics}, number = {5}, publisher = {Public Library of Science}, title = {{Cell polarity and patterning by PIN trafficking through early endosomal compartments in arabidopsis thaliana}}, doi = {10.1371/journal.pgen.1003540}, volume = {9}, year = {2013}, } @article{2834, abstract = {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.}, author = {Avila, Marc and Mellibovsky, Fernando and Roland, Nicolas and Hof, Björn}, journal = {Physical Review Letters}, number = {22}, publisher = {American Physical Society}, title = {{Streamwise-localized solutions at the onset of turbulence in pipe flow}}, doi = {10.1103/PhysRevLett.110.224502}, volume = {110}, year = {2013}, } @article{2835, abstract = {The phytohormone auxin regulates virtually every aspect of plant development. To identify new genes involved in auxin activity, a genetic screen was performed for Arabidopsis (Arabidopsis thaliana) mutants with altered expression of the auxin-responsive reporter DR5rev:GFP. One of the mutants recovered in the screen, designated as weak auxin response3 (wxr3), exhibits much lower DR5rev:GFP expression when treated with the synthetic auxin 2,4-dichlorophenoxyacetic acid and displays severe defects in root development. The wxr3 mutant decreases polar auxin transport and results in a disruption of the asymmetric auxin distribution. The levels of the auxin transporters AUXIN1 and PIN-FORMED are dramatically reduced in the wxr3 root tip. Molecular analyses demonstrate that WXR3 is ROOT ULTRAVIOLET B-SENSITIVE1 (RUS1), a member of the conserved Domain of Unknown Function647 protein family found in diverse eukaryotic organisms. Our data suggest that RUS1/WXR3 plays an essential role in the regulation of polar auxin transport by maintaining the proper level of auxin transporters on the plasma membrane.}, author = {Yu, Hong and Karampelias, Michael and Robert, Stéphanie and Peer, Wendy and Swarup, Ranjan and Ye, Songqing and Ge, Lei and Cohen, Jerry and Murphy, Angus and Friml, Jirí and Estelle, Mark}, journal = {Plant Physiology}, number = {2}, pages = {965 -- 976}, publisher = {American Society of Plant Biologists}, title = {{Root ultraviolet b-sensitive1/weak auxin response3 is essential for polar auxin transport in arabidopsis}}, doi = {10.1104/pp.113.217018}, volume = {162}, year = {2013}, } @article{2836, abstract = {We study the automatic synthesis of fair non-repudiation protocols, a class of fair exchange protocols, used for digital contract signing. First, we show how to specify the objectives of the participating agents and the trusted third party as path formulas in linear temporal logic and prove that the satisfaction of these objectives imply fairness; a property required of fair exchange protocols. We then show that weak (co-operative) co-synthesis and classical (strictly competitive) co-synthesis fail, whereas assume-guarantee synthesis (AGS) succeeds. We demonstrate the success of AGS as follows: (a) any solution of AGS is attack-free; no subset of participants can violate the objectives of the other participants; (b) the Asokan-Shoup-Waidner certified mail protocol that has known vulnerabilities is not a solution of AGS; (c) the Kremer-Markowitch non-repudiation protocol is a solution of AGS; and (d) AGS presents a new and symmetric fair non-repudiation protocol that is attack-free. To our knowledge this is the first application of synthesis to fair non-repudiation protocols, and our results show how synthesis can both automatically discover vulnerabilities in protocols and generate correct protocols. The solution to AGS can be computed efficiently as the secure equilibrium solution of three-player graph games. }, author = {Chatterjee, Krishnendu and Raman, Vishwanath}, journal = {Formal Aspects of Computing}, number = {4}, pages = {825 -- 859}, publisher = {Springer}, title = {{Assume-guarantee synthesis for digital contract signing}}, doi = {10.1007/s00165-013-0283-6}, volume = {26}, year = {2013}, } @article{2837, abstract = {We consider a general class of N × N random matrices whose entries hij are independent up to a symmetry constraint, but not necessarily identically distributed. Our main result is a local semicircle law which improves previous results [17] both in the bulk and at the edge. The error bounds are given in terms of the basic small parameter of the model, maxi,j E|hij|2. As a consequence, we prove the universality of the local n-point correlation functions in the bulk spectrum for a class of matrices whose entries do not have comparable variances, including random band matrices with band width W ≫N1-εn with some εn > 0 and with a negligible mean-field component. In addition, we provide a coherent and pedagogical proof of the local semicircle law, streamlining and strengthening previous arguments from [17, 19, 6].}, author = {Erdös, László and Knowles, Antti and Yau, Horng and Yin, Jun}, journal = {Electronic Journal of Probability}, number = {59}, pages = {1--58}, publisher = {Institute of Mathematical Statistics}, title = {{The local semicircle law for a general class of random matrices}}, doi = {10.1214/EJP.v18-2473}, volume = {18}, year = {2013}, } @article{2838, abstract = {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.}, author = {Arquè Fuste, Gloria and Casanovas, Anna and Dierssen, Mara}, journal = {PLoS One}, number = {1}, publisher = {Public Library of Science}, title = {{Dyrk1A is dynamically expressed on subsets of motor neurons and in the neuromuscular junction: Possible role in Down syndrome}}, doi = {10.1371/journal.pone.0054285}, volume = {8}, year = {2013}, } @article{2839, abstract = {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.}, author = {Weber, Michele and Hauschild, Robert and Schwarz, Jan and Moussion, Christine and De Vries, Ingrid and Legler, Daniel and Luther, Sanjiv and Bollenbach, Mark Tobias and Sixt, Michael K}, journal = {Science}, number = {6117}, pages = {328 -- 332}, publisher = {American Association for the Advancement of Science}, title = {{Interstitial dendritic cell guidance by haptotactic chemokine gradients}}, doi = {10.1126/science.1228456}, volume = {339}, year = {2013}, } @article{2842, abstract = {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.}, author = {Barton, Nicholas H and Etheridge, Alison and Kelleher, Jerome and Véber, Amandine}, journal = {Theoretical Population Biology}, number = {1}, pages = {105 -- 119}, publisher = {Elsevier}, title = {{Inference in two dimensions: Allele frequencies versus lengths of shared sequence blocks}}, doi = {10.1016/j.tpb.2013.03.001}, volume = {87}, year = {2013}, } @article{2846, abstract = {The Red Queen hypothesis proposes that coevolving parasites select for outcrossing in the host. Outcrossing relies on males, which often show lower immune investment due to, for example, sexual selection. Here, we demonstrate that such sex differences in immunity interfere with parasite-mediated selection for outcrossing. Two independent coevolution experiments with Caenorhabditis elegans and its microparasite Bacillus thuringiensis produced decreased yet stable frequencies of outcrossing male hosts. A subsequent systematic analysis verified that male C. elegans suffered from a direct selective disadvantage under parasite pressure (i.e. lower resistance, decreased sexual activity, increased escape behaviour), which can reduce outcrossing and thus male frequencies. At the same time, males offered an indirect selective benefit, because male-mediated outcrossing increased offspring resistance, thus favouring male persistence in the evolving populations. As sex differences in immunity are widespread, such interference of opposing selective constraints is likely of central importance during host adaptation to a coevolving parasite.}, author = {El Masri, Leila and Schulte, Rebecca and Timmermeyer, Nadine and Thanisch, Stefanie and Crummenerl, Lena and Jansen, Gunther and Michiels, Nico and Schulenburg, Hinrich}, journal = {Ecology Letters}, number = {4}, pages = {461 -- 468}, publisher = {Wiley-Blackwell}, title = {{Sex differences in host defence interfere with parasite-mediated selection for outcrossing during host-parasite coevolution}}, doi = {10.1111/ele.12068}, volume = {16}, year = {2013}, } @inproceedings{2847, abstract = {Depth-Bounded Systems form an expressive class of well-structured transition systems. They can model a wide range of concurrent infinite-state systems including those with dynamic thread creation, dynamically changing communication topology, and complex shared heap structures. We present the first method to automatically prove fair termination of depth-bounded systems. Our method uses a numerical abstraction of the system, which we obtain by systematically augmenting an over-approximation of the system’s reachable states with a finite set of counters. This numerical abstraction can be analyzed with existing termination provers. What makes our approach unique is the way in which it exploits the well-structuredness of the analyzed system. We have implemented our work in a prototype tool and used it to automatically prove liveness properties of complex concurrent systems, including nonblocking algorithms such as Treiber’s stack and several distributed processes. Many of these examples are beyond the scope of termination analyses that are based on traditional counter abstractions.}, author = {Bansal, Kshitij and Koskinen, Eric and Wies, Thomas and Zufferey, Damien}, editor = {Piterman, Nir and Smolka, Scott}, location = {Rome, Italy}, pages = {62 -- 77}, publisher = {Springer}, title = {{Structural Counter Abstraction}}, doi = {10.1007/978-3-642-36742-7_5}, volume = {7795}, year = {2013}, } @article{2850, abstract = {Recent work emphasizes that the maximum entropy principle provides a bridge between statistical mechanics models for collective behavior in neural networks and experiments on networks of real neurons. Most of this work has focused on capturing the measured correlations among pairs of neurons. Here we suggest an alternative, constructing models that are consistent with the distribution of global network activity, i.e. the probability that K out of N cells in the network generate action potentials in the same small time bin. The inverse problem that we need to solve in constructing the model is analytically tractable, and provides a natural 'thermodynamics' for the network in the limit of large N. We analyze the responses of neurons in a small patch of the retina to naturalistic stimuli, and find that the implied thermodynamics is very close to an unusual critical point, in which the entropy (in proper units) is exactly equal to the energy. © 2013 IOP Publishing Ltd and SISSA Medialab srl. }, author = {Tkacik, Gasper and Marre, Olivier and Mora, Thierry and Amodei, Dario and Berry, Michael and Bialek, William}, journal = {Journal of Statistical Mechanics Theory and Experiment}, number = {3}, publisher = {IOP Publishing Ltd.}, title = {{The simplest maximum entropy model for collective behavior in a neural network}}, doi = {10.1088/1742-5468/2013/03/P03011}, volume = {2013}, year = {2013}, } @article{2853, abstract = {High relatedness among interacting individuals has generally been considered a precondition for the evolution of altruism. However, kin-selection theory also predicts the evolution of altruism when relatedness is low, as long as the cost of the altruistic act is minor compared with its benefit. Here, we demonstrate evidence for a low-cost altruistic act in bacteria. We investigated Escherichia coli responding to the attack of an obligately lytic phage by committing suicide in order to prevent parasite transmission to nearby relatives. We found that bacterial suicide provides large benefits to survivors at marginal costs to committers. The cost of suicide was low, because infected cells are moribund, rapidly dying upon phage infection, such that no more opportunity for reproduction remains. As a consequence of its marginal cost, host suicide was selectively favoured even when relatedness between committers and survivors approached zero. Altogether, our findings demonstrate that low-cost suicide can evolve with ease, represents an effective host-defence strategy, and seems to be widespread among microbes. Moreover, low-cost suicide might also occur in higher organisms as exemplified by infected social insect workers leaving the colony to die in isolation.}, author = {Refardt, Dominik and Bergmiller, Tobias and Kümmerli, Rolf}, issn = {1471-2954}, journal = {Proceedings of the Royal Society of London Series B Biological Sciences}, number = {1759}, publisher = {The Royal Society}, title = {{Altruism can evolve when relatedness is low: Evidence from bacteria committing suicide upon phage infection}}, doi = {10.1098/rspb.2012.3035}, volume = {280}, year = {2013}, } @article{2854, abstract = {We consider concurrent games played on graphs. At every round of a game, each player simultaneously and independently selects a move; the moves jointly determine the transition to a successor state. Two basic objectives are the safety objective to stay forever in a given set of states, and its dual, the reachability objective to reach a given set of states. First, we present a simple proof of the fact that in concurrent reachability games, for all ε>0, memoryless ε-optimal strategies exist. A memoryless strategy is independent of the history of plays, and an ε-optimal strategy achieves the objective with probability within ε of the value of the game. In contrast to previous proofs of this fact, our proof is more elementary and more combinatorial. Second, we present a strategy-improvement (a.k.a. policy-iteration) algorithm for concurrent games with reachability objectives. Finally, we present a strategy-improvement algorithm for turn-based stochastic games (where each player selects moves in turns) with safety objectives. Our algorithms yield sequences of player-1 strategies which ensure probabilities of winning that converge monotonically (from below) to the value of the game. © 2012 Elsevier Inc.}, author = {Chatterjee, Krishnendu and De Alfaro, Luca and Henzinger, Thomas A}, journal = {Journal of Computer and System Sciences}, number = {5}, pages = {640 -- 657}, publisher = {Elsevier}, title = {{Strategy improvement for concurrent reachability and turn based stochastic safety games}}, doi = {10.1016/j.jcss.2012.12.001}, volume = {79}, year = {2013}, } @article{2855, abstract = {Genomic imprinting leads to preferred expression of either the maternal or paternal alleles of a subset of genes. Imprinting is essential for mammalian development, and its deregulation causes many diseases. However, the functional relevance of imprinting at the cellular level is poorly understood for most imprinted genes. We used mosaic analysis with double markers (MADM) in mice to create uniparental disomies (UPDs) and to visualize imprinting effects with single-cell resolution. Although chromosome 12 UPD did not produce detectable phenotypes, chromosome 7 UPD caused highly significant paternal growth dominance in the liver and lung, but not in the brain or heart. A single gene on chromosome 7, encoding the secreted insulin-like growth factor 2 (IGF2), accounts for most of the paternal dominance effect. Mosaic analyses implied additional imprinted loci on chromosome 7 acting cell autonomously to transmit the IGF2 signal. Our study reveals chromosome- and cell-type specificity of genomic imprinting effects.}, author = {Hippenmeyer, Simon and Johnson, Randy and Luo, Liqun}, journal = {Cell Reports}, number = {3}, pages = {960 -- 967}, publisher = {Cell Press}, title = {{Mosaic analysis with double markers reveals cell type specific paternal growth dominance}}, doi = {10.1016/j.celrep.2013.02.002}, volume = {3}, year = {2013}, } @article{2856, abstract = {G protein–coupled receptors (GPCRs), the largest family of membrane signaling proteins, respond to neurotransmitters, hormones and small environmental molecules. The neuronal function of many GPCRs has been difficult to resolve because of an inability to gate them with subtype specificity, spatial precision, speed and reversibility. To address this, we developed an approach for opto-chemical engineering of native GPCRs. We applied this to the metabotropic glutamate receptors (mGluRs) to generate light-agonized and light-antagonized mGluRs (LimGluRs). The light-agonized LimGluR2, on which we focused, was fast, bistable and supported multiple rounds of on/off switching. Light gated two of the primary neuronal functions of mGluR2: suppression of excitability and inhibition of neurotransmitter release. We found that the light-antagonized tool LimGluR2-block was able to manipulate negative feedback of synaptically released glutamate on transmitter release. We generalized the optical control to two additional family members: mGluR3 and mGluR6. This system worked in rodent brain slices and in zebrafish in vivo, where we found that mGluR2 modulated the threshold for escape behavior. These light-gated mGluRs pave the way for determining the roles of mGluRs in synaptic plasticity, memory and disease.}, author = {Levitz, Joshua and Pantoja, Carlos and Gaub, Benjamin and Janovjak, Harald L and Reiner, Andreas and Hoagland, Adam and Schoppik, David and Kane, Brian and Stawski, Philipp and Schier, Alexander and Trauner, Dirk and Isacoff, Ehud}, journal = {Nature Neuroscience}, pages = {507 -- 516}, publisher = {Nature Publishing Group}, title = {{Optical control of metabotropic glutamate receptors}}, doi = {10.1038/nn.3346}, volume = {16}, year = {2013}, }