@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{2851, abstract = {The number of possible activity patterns in a population of neurons grows exponentially with the size of the population. Typical experiments explore only a tiny fraction of the large space of possible activity patterns in the case of populations with more than 10 or 20 neurons. It is thus impossible, in this undersampled regime, to estimate the probabilities with which most of the activity patterns occur. As a result, the corresponding entropy - which is a measure of the computational power of the neural population - cannot be estimated directly. We propose a simple scheme for estimating the entropy in the undersampled regime, which bounds its value from both below and above. The lower bound is the usual 'naive' entropy of the experimental frequencies. The upper bound results from a hybrid approximation of the entropy which makes use of the naive estimate, a maximum entropy fit, and a coverage adjustment. We apply our simple scheme to artificial data, in order to check their accuracy; we also compare its performance to those of several previously defined entropy estimators. We then apply it to actual measurements of neural activity in populations with up to 100 cells. Finally, we discuss the similarities and differences between the proposed simple estimation scheme and various earlier methods. © 2013 IOP Publishing Ltd and SISSA Medialab srl.}, author = {Berry, Michael and Tkacik, Gasper and Dubuis, Julien and Marre, Olivier and Da Silveira, Ravá}, journal = {Journal of Statistical Mechanics Theory and Experiment}, number = {3}, publisher = {IOP Publishing Ltd.}, title = {{A simple method for estimating the entropy of neural activity}}, doi = {10.1088/1742-5468/2013/03/P03015}, volume = {2013}, year = {2013}, } @article{2857, abstract = {In the vibrant field of optogenetics, optics and genetic targeting are combined to commandeer cellular functions, such as the neuronal action potential, by optically stimulating light-sensitive ion channels expressed in the cell membrane. One broadly applicable manifestation of this approach are covalently attached photochromic tethered ligands (PTLs) that allow activating ligand-gated ion channels with outstanding spatial and temporal resolution. Here, we describe all steps towards the successful development and application of PTL-gated ion channels in cell lines and primary cells. The basis for these experiments forms a combination of molecular modeling, genetic engineering, cell culture, and electrophysiology. The light-gated glutamate receptor (LiGluR), which consists of the PTL-functionalized GluK2 receptor, serves as a model.}, author = {Szobota, Stephanie and Mckenzie, Catherine and Janovjak, Harald L}, journal = {Methods in Molecular Biology}, pages = {417 -- 435}, publisher = {Springer}, title = {{Optical control of ligand-gated ion channels}}, doi = {10.1007/978-1-62703-351-0_32}, volume = {998}, year = {2013}, } @article{2860, abstract = {In the hippocampus, cell assemblies forming mnemonic representations of space are thought to arise as a result of changes in functional connections of pyramidal cells. We have found that CA1 interneuron circuits are also reconfigured during goal-oriented spatial learning through modification of inputs from pyramidal cells. As learning progressed, new pyramidal assemblies expressed in theta cycles alternated with previously established ones, and eventually overtook them. The firing patterns of interneurons developed a relationship to new, learning-related assemblies: some interneurons associated their activity with new pyramidal assemblies while some others dissociated from them. These firing associations were explained by changes in the weight of monosynaptic inputs received by interneurons from new pyramidal assemblies, as these predicted the associational changes. Spatial learning thus engages circuit modifications in the hippocampus that incorporate a redistribution of inhibitory activity that might assist in the segregation of competing pyramidal cell assembly patterns in space and time.}, author = {Dupret, David and O'Neill, Joseph and Csicsvari, Jozsef L}, journal = {Neuron}, number = {1}, pages = {166 -- 180}, publisher = {Elsevier}, title = {{Dynamic reconfiguration of hippocampal interneuron circuits during spatial learning}}, doi = {10.1016/j.neuron.2013.01.033}, volume = {78}, 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}, } @article{2859, abstract = {Given a continuous function f:X-R on a topological space, we consider the preimages of intervals and their homology groups and show how to read the ranks of these groups from the extended persistence diagram of f. In addition, we quantify the robustness of the homology classes under perturbations of f using well groups, and we show how to read the ranks of these groups from the same extended persistence diagram. The special case X=R3 has ramifications in the fields of medical imaging and scientific visualization.}, author = {Bendich, Paul and Edelsbrunner, Herbert and Morozov, Dmitriy and Patel, Amit}, journal = {Homology, Homotopy and Applications}, number = {1}, pages = {51 -- 72}, publisher = {International Press}, title = {{Homology and robustness of level and interlevel sets}}, doi = {10.4310/HHA.2013.v15.n1.a3}, volume = {15}, year = {2013}, } @article{2863, abstract = {Neural populations encode information about their stimulus in a collective fashion, by joint activity patterns of spiking and silence. A full account of this mapping from stimulus to neural activity is given by the conditional probability distribution over neural codewords given the sensory input. For large populations, direct sampling of these distributions is impossible, and so we must rely on constructing appropriate models. We show here that in a population of 100 retinal ganglion cells in the salamander retina responding to temporal white-noise stimuli, dependencies between cells play an important encoding role. We introduce the stimulus-dependent maximum entropy (SDME) model—a minimal extension of the canonical linear-nonlinear model of a single neuron, to a pairwise-coupled neural population. We find that the SDME model gives a more accurate account of single cell responses and in particular significantly outperforms uncoupled models in reproducing the distributions of population codewords emitted in response to a stimulus. We show how the SDME model, in conjunction with static maximum entropy models of population vocabulary, can be used to estimate information-theoretic quantities like average surprise and information transmission in a neural population.}, author = {Granot Atedgi, Einat and Tkacik, Gasper and Segev, Ronen and Schneidman, Elad}, journal = {PLoS Computational Biology}, number = {3}, publisher = {Public Library of Science}, title = {{Stimulus-dependent maximum entropy models of neural population codes}}, doi = {10.1371/journal.pcbi.1002922}, volume = {9}, year = {2013}, } @article{2862, abstract = {Motile cilia perform crucial functions during embryonic development and throughout adult life. Development of organs containing motile cilia involves regulation of cilia formation (ciliogenesis) and formation of a luminal space (lumenogenesis) in which cilia generate fluid flows. Control of ciliogenesis and lumenogenesis is not yet fully understood, and it remains unclear whether these processes are coupled. In the zebrafish embryo, lethal giant larvae 2 (lgl2) is expressed prominently in ciliated organs. Lgl proteins are involved in establishing cell polarity and have been implicated in vesicle trafficking. Here, we identified a role for Lgl2 in development of ciliated epithelia in Kupffer's vesicle, which directs left-right asymmetry of the embryo; the otic vesicles, which give rise to the inner ear; and the pronephric ducts of the kidney. Using Kupffer's vesicle as a model ciliated organ, we found that depletion of Lgl2 disrupted lumen formation and reduced cilia number and length. Immunofluorescence and time-lapse imaging of Kupffer's vesicle morphogenesis in Lgl2-deficient embryos suggested cell adhesion defects and revealed loss of the adherens junction component E-cadherin at lateral membranes. Genetic interaction experiments indicate that Lgl2 interacts with Rab11a to regulate E-cadherin and mediate lumen formation that is uncoupled from cilia formation. These results uncover new roles and interactions for Lgl2 that are crucial for both lumenogenesis and ciliogenesis and indicate that these processes are genetically separable in zebrafish.}, author = {Tay, Hwee and Schulze, Sabrina and Compagnon, Julien and Foley, Fiona and Heisenberg, Carl-Philipp J and Yost, H Joseph and Abdelilah Seyfried, Salim and Amack, Jeffrey}, journal = {Development}, number = {7}, pages = {1550 -- 1559}, publisher = {Company of Biologists}, title = {{Lethal giant larvae 2 regulates development of the ciliated organ Kupffer’s vesicle}}, doi = {10.1242/dev.087130}, volume = {140}, year = {2013}, } @article{2861, abstract = {We consider a two-parameter family of piecewise linear maps in which the moduli of the two slopes take different values. We provide numerical evidence of the existence of some parameter regions in which the Lyapunov exponent and the topological entropy remain constant. Analytical proof of this phenomenon is also given for certain cases. Surprisingly however, the systems with that property are not conjugate as we prove by using kneading theory.}, author = {Botella Soler, Vicente and Oteo, José and Ros, Javier and Glendinning, Paul}, journal = {Journal of Physics A: Mathematical and Theoretical}, number = {12}, publisher = {IOP Publishing Ltd.}, title = {{Lyapunov exponent and topological entropy plateaus in piecewise linear maps}}, doi = {10.1088/1751-8113/46/12/125101}, volume = {46}, year = {2013}, } @article{2877, abstract = {Premise of the study: To reach favorable conditions for photosynthesis, seedlings grow upward when deprived of light upon underground germination. To direct their growth, they use their negative gravitropic capacity. Negative gravitropism is under tight control of multiple hormones. • Methods: By counting the number of standing plants in a population or by real time monitoring of the reorientation of gravistimulated seedlings of Arabidopsis thaliana, we evaluated the negative gravitropism of ethylene or brassinosteroid (BR) treated plants. Meta-analysis of transcriptomic data on AUX / IAA genes was gathered, and subsequent mutant analysis was performed. • Key results: Ethylene and BR have opposite effects in regulating shoot gravitropism. Lack of BR enhances gravitropic reorientation in 2-d-old seedlings, whereas ethylene does not. Lack of ethylene signaling results in enhanced BR sensitivity. Ethylene and BRs regulate overlapping sets of AUX / IAA genes. BRs regulate a wider range of auxin signaling components than ethylene. • Conclusions: Upward growth in seedlings depends strongly on the internal hormonal balance. Endogenous ethylene stimulates, whereas BRs reduce negative gravitropism in a manner that depends on the function of different, yet overlapping sets of auxin signaling components.}, author = {Vandenbussche, Filip and Callebert, Pieter and Žádníková, Petra and Eva Benková and Van Der Straeten, Dominique}, journal = {American Journal of Botany}, number = {1}, pages = {215 -- 225}, publisher = {Botanical Society of America}, title = {{Brassinosteroid control of shoot gravitropism interacts with ethylene and depends on auxin signaling components}}, doi = {10.3732/ajb.1200264}, volume = {100}, year = {2013}, } @article{2883, abstract = {Plant architecture is influenced by the polar, cell-to-cell transport of auxin that is primarily provided and regulated by plasma membrane efflux catalysts of the PIN-FORMED and B family of ABC transporter (ABCB) classes. The latter were shown to require the functionality of the FK506 binding protein42 TWISTED DWARF1 (TWD1), although underlying mechanisms are unclear. By genetic manipulation of TWD1 expression, we show here that TWD1 affects shootward root auxin reflux and, thus, downstream developmental traits, such as epidermal twisting and gravitropism of the root. Using immunological assays, we demonstrate a predominant lateral, mainly outward-facing, plasma membrane location for TWD1 in the root epidermis characterized by the lateral marker ABC transporter G36/PLEIOTROPIC DRUG-RESISTANCE8/PENETRATION3. At these epidermal plasma membrane domains, TWD1 colocalizes with nonpolar ABCB1. In planta bioluminescence resonance energy transfer analysis was used to verify specific ABC transporter B1 (ABCB1)-TWD1 interaction. Our data support a model in which TWD1 promotes lateral ABCB-mediated auxin efflux via protein-protein interaction at the plasma membrane, minimizing reflux from the root apoplast into the cytoplasm.}, author = {Wang, Bangjun and Bailly, Aurélien and Zwiewk, Marta and Henrichs, Sina and Azzarello, Elisa and Mancuso, Stefano and Maeshima, Masayoshi and Friml, Jirí and Schulz, Alexander and Geisler, Markus}, journal = {Plant Cell}, number = {1}, pages = {202 -- 214}, publisher = {American Society of Plant Biologists}, title = {{Arabidopsis TWISTED DWARF1 functionally interacts with auxin exporter ABCB1 on the root plasma membrane}}, doi = {10.1105/tpc.112.105999}, volume = {25}, year = {2013}, } @article{2880, abstract = {Lateral root (LR) formation is initiated when pericycle cells accumulate auxin, thereby acquiring founder cell (FC) status and triggering asymmetric cell divisions, giving rise to a new primordium. How this auxin maximum in pericycle cells builds up and remains focused is not understood. We report that the endodermis plays an active role in the regulation of auxin accumulation and is instructive for FCs to progress during the LR initiation (LRI) phase. We describe the functional importance of a PIN3 (PIN-formed) auxin efflux carrier-dependent hormone reflux pathway between overlaying endodermal and pericycle FCs. Disrupting this reflux pathway causes dramatic defects in the progress of FCs towards the next initiation phase. Our data identify an unexpected regulatory function for the endodermis in LRI as part of the fine-tuning mechanism that appears to act as a check point in LR organogenesis after FCs are specified.}, author = {Marhavy, Peter and Vanstraelen, Marleen and De Rybel, Bert and Zhaojun, Ding and Bennett, Malcolm and Beeckman, Tom and Benková, Eva}, journal = {EMBO Journal}, number = {1}, pages = {149 -- 158}, publisher = {Wiley-Blackwell}, title = {{Auxin reflux between the endodermis and pericycle promotes lateral root initiation}}, doi = {10.1038/emboj.2012.303}, volume = {32}, year = {2013}, } @article{2882, abstract = {Gravitropic bending of plant organs is mediated by an asymmetric signaling of the plant hormone auxin between the upper and lower side of the respective organ. Here, we show that also another plant hormone, gibberellic acid (GA), shows asymmetric action during gravitropic responses. Immunodetection using an antibody against GA and monitoring GA signaling output by downstream degradation of DELLA proteins revealed an asymmetric GA distribution and response with the maximum at the lower side of gravistimulated roots. Genetic or pharmacological manipulation of GA levels or response affects gravity-mediated auxin redistribution and root bending response. The higher GA levels at the lower side of the root correlate with increased amounts of PIN-FORMED2 (PIN2) auxin transporter at the plasma membrane. The observed increase in PIN2 stability is caused by a specific GA effect on trafficking of PIN proteins to lytic vacuoles that presumably occurs downstream of brefeldin A-sensitive endosomes. Our results suggest that asymmetric auxin distribution instructive for gravity-induced differential growth is consolidated by the asymmetric action of GA that stabilizes the PIN-dependent auxin stream along the lower side of gravistimulated roots.}, author = {Löfke, Christian and Zwiewka, Marta and Heilmann, Ingo and Van Montagu, Marc and Teichmann, Thomas and Friml, Jirí}, journal = {PNAS}, number = {9}, pages = {3627 -- 3632}, publisher = {National Academy of Sciences}, title = {{Asymmetric gibberellin signaling regulates vacuolar trafficking of PIN auxin transporters during root gravitropism}}, doi = {10.1073/pnas.1300107110}, volume = {110}, year = {2013}, } @proceedings{2885, abstract = {This volume contains the post-proceedings of the 8th Doctoral Workshop on Mathematical and Engineering Methods in Computer Science, MEMICS 2012, held in Znojmo, Czech Republic, in October, 2012. The 13 thoroughly revised papers were carefully selected out of 31 submissions and are presented together with 6 invited papers. The topics covered by the papers include: computer-aided analysis and verification, applications of game theory in computer science, networks and security, modern trends of graph theory in computer science, electronic systems design and testing, and quantum information processing.}, editor = {Kucera, Antonin and Henzinger, Thomas A and Nesetril, Jaroslav and Vojnar, Tomas and Antos, David}, location = {Znojmo, Czech Republic}, pages = {1 -- 228}, publisher = {Springer}, title = {{Mathematical and Engineering Methods in Computer Science}}, doi = {10.1007/978-3-642-36046-6}, volume = {7721}, year = {2013}, } @article{2881, abstract = {The puzzle piece-shaped Arabidopsis leaf pavement cells (PCs) with interdigitated lobes and indents is a good model system to investigate the mechanisms that coordinate cell polarity and shape formation within a tissue. Auxin has been shown to coordinate the interdigitation by activating ROP GTPase-dependent signaling pathways. To identify additional components or mechanisms, we screened for mutants with abnormal PC morphogenesis and found that cytokinin signaling regulates the PC interdigitation pattern. Reduction in cytokinin accumulation and defects in cytokinin signaling (such as in ARR7-over-expressing lines, the ahk3cre1 cytokinin receptor mutant, and the ahp12345 cytokinin signaling mutant) enhanced PC interdigitation, whereas over-production of cytokinin and over-activation of cytokinin signaling in an ARR20 over-expression line delayed or abolished PC interdigitation throughout the cotyledon. Genetic and biochemical analyses suggest that cytokinin signaling acts upstream of ROPs to suppress the formation of interdigitated pattern. Our results provide novel mechanistic understanding of the pathways controlling PC shape and uncover a new role for cytokinin signaling in cell morphogenesis.}, author = {Hongjiang Li and Xu, Tongda and Lin, Deshu and Wen, Mingzhang and Xie, Mingtang and Duclercq, Jérôme and Bielach, Agnieszka and Kim, Jungmook and Reddy, G Venugopala and Zuo, Jianru and Eva Benková and Jirí Friml and Guo, Hongwei and Yang, Zhenbiao}, journal = {Cell Research}, number = {2}, pages = {290 -- 299}, publisher = {Nature Publishing Group}, title = {{Cytokinin signaling regulates pavement cell morphogenesis in Arabidopsis}}, doi = {10.1038/cr.2012.146}, volume = {23}, year = {2013}, } @article{2884, author = {Maître, Jean-Léon and Berthoumieux, Hélène and Krens, Gabriel and Salbreux, Guillaume and Julicher, Frank and Paluch, Ewa and Heisenberg, Carl-Philipp J}, journal = {Medecine Sciences}, number = {2}, pages = {147 -- 150}, publisher = {Éditions Médicales et Scientifiques}, title = {{Cell adhesion mechanics of zebrafish gastrulation}}, doi = {10.1051/medsci/2013292011}, volume = {29}, year = {2013}, } @inproceedings{2886, abstract = {We focus on the realizability problem of Message Sequence Graphs (MSG), i.e. the problem whether a given MSG specification is correctly distributable among parallel components communicating via messages. This fundamental problem of MSG is known to be undecidable. We introduce a well motivated restricted class of MSG, so called controllable-choice MSG, and show that all its models are realizable and moreover it is decidable whether a given MSG model is a member of this class. In more detail, this class of MSG specifications admits a deadlock-free realization by overloading existing messages with additional bounded control data. We also show that the presented class is the largest known subclass of MSG that allows for deadlock-free realization.}, author = {Chmelik, Martin and Řehák, Vojtěch}, location = {Znojmo, Czech Republic}, pages = {118 -- 130}, publisher = {Springer}, title = {{Controllable-choice message sequence graphs}}, doi = {10.1007/978-3-642-36046-6_12}, volume = {7721}, year = {2013}, } @article{2887, abstract = {Root system growth and development is highly plastic and is influenced by the surrounding environment. Roots frequently grow in heterogeneous environments that include interactions from neighboring plants and physical impediments in the rhizosphere. To investigate how planting density and physical objects affect root system growth, we grew rice in a transparent gel system in close proximity with another plant or a physical object. Root systems were imaged and reconstructed in three dimensions. Root-root interaction strength was calculated using quantitative metrics that characterize the extent towhich the reconstructed root systems overlap each other. Surprisingly, we found the overlap of root systems of the same genotype was significantly higher than that of root systems of different genotypes. Root systems of the same genotype tended to grow toward each other but those of different genotypes appeared to avoid each other. Shoot separation experiments excluded the possibility of aerial interactions, suggesting root communication. Staggered plantings indicated that interactions likely occur at root tips in close proximity. Recognition of obstacles also occurred through root tips, but through physical contact in a size-dependent manner. These results indicate that root systems use two different forms of communication to recognize objects and alter root architecture: root-root recognition, possibly mediated through root exudates, and root-object recognition mediated by physical contact at the root tips. This finding suggests that root tips act as local sensors that integrate rhizosphere information into global root architectural changes.}, author = {Fang, Suqin and Clark, Randy and Zheng, Ying and Iyer Pascuzzi, Anjali and Weitz, Joshua and Kochian, Leon and Edelsbrunner, Herbert and Liao, Hong and Benfey, Philip}, journal = {PNAS}, number = {7}, pages = {2670 -- 2675}, publisher = {National Academy of Sciences}, title = {{Genotypic recognition and spatial responses by rice roots}}, doi = {10.1073/pnas.1222821110}, volume = {110}, year = {2013}, } @inproceedings{2901, abstract = { We introduce the M-modes problem for graphical models: predicting the M label configurations of highest probability that are at the same time local maxima of the probability landscape. M-modes have multiple possible applications: because they are intrinsically diverse, they provide a principled alternative to non-maximum suppression techniques for structured prediction, they can act as codebook vectors for quantizing the configuration space, or they can form component centers for mixture model approximation. We present two algorithms for solving the M-modes problem. The first algorithm solves the problem in polynomial time when the underlying graphical model is a simple chain. The second algorithm solves the problem for junction chains. In synthetic and real dataset, we demonstrate how M-modes can improve the performance of prediction. We also use the generated modes as a tool to understand the topography of the probability distribution of configurations, for example with relation to the training set size and amount of noise in the data. }, author = {Chen, Chao and Kolmogorov, Vladimir and Yan, Zhu and Metaxas, Dimitris and Lampert, Christoph}, location = {Scottsdale, AZ, United States}, pages = {161 -- 169}, publisher = {JMLR}, title = {{Computing the M most probable modes of a graphical model}}, volume = {31}, year = {2013}, } @article{2900, author = {Azevedo, Ricardo B and Lohaus, Rolf and Tiago Paixao}, journal = {Evolution & Development}, number = {5}, pages = {514 -- 515}, publisher = {Wiley-Blackwell}, title = {{Networking networks}}, volume = {10}, year = {2013}, } @inproceedings{2906, abstract = {Motivated by an application in cell biology, we describe an extension of the kinetic data structures framework from Delaunay triangulations to fixed-radius alpha complexes. Our algorithm is implemented using CGAL, following the exact geometric computation paradigm. We report on several techniques to accelerate the computation that turn our implementation applicable to the underlying biological problem.}, author = {Kerber, Michael and Edelsbrunner, Herbert}, booktitle = {2013 Proceedings of the 15th Workshop on Algorithm Engineering and Experiments}, location = {New Orleans, LA, United States}, pages = {70 -- 77}, publisher = {Society of Industrial and Applied Mathematics}, title = {{3D kinetic alpha complexes and their implementation}}, doi = {10.1137/1.9781611972931.6}, year = {2013}, } @article{2910, abstract = {Coalescent simulation has become an indispensable tool in population genetics and many complex evolutionary scenarios have been incorporated into the basic algorithm. Despite many years of intense interest in spatial structure, however, there are no available methods to simulate the ancestry of a sample of genes that occupy a spatial continuum. This is mainly due to the severe technical problems encountered by the classical model of isolation by distance. A recently introduced model solves these technical problems and provides a solid theoretical basis for the study of populations evolving in continuous space. We present a detailed algorithm to simulate the coalescent process in this model, and provide an efficient implementation of a generalised version of this algorithm as a freely available Python module.}, author = {Kelleher, Jerome and Barton, Nicholas H and Etheridge, Alison}, journal = {Bioinformatics}, number = {7}, pages = {955 -- 956}, publisher = {Oxford University Press}, title = {{Coalescent simulation in continuous space}}, doi = {10.1093/bioinformatics/btt067}, volume = {29}, year = {2013}, } @article{2909, abstract = {We survey a class of models for spatially structured populations which we have called spatial Λ-Fleming–Viot processes. They arise from a flexible framework for modelling in which the key innovation is that random genetic drift is driven by a Poisson point process of spatial ‘events’. We demonstrate how this overcomes some of the obstructions to modelling populations which evolve in two- (and higher-) dimensional spatial continua, how its predictions match phenomena observed in data and how it fits with classical models. Finally we outline some directions for future research.}, author = {Barton, Nicholas H and Etheridge, Alison and Véber, Amandine}, journal = {Journal of Statistical Mechanics Theory and Experiment}, number = {1}, publisher = {IOP Publishing Ltd.}, title = {{Modelling evolution in a spatial continuum}}, doi = {10.1088/1742-5468/2013/01/P01002}, volume = {2013}, year = {2013}, } @article{2908, abstract = {Hybridization is an almost inevitable component of speciation, and its study can tell us much about that process. However, hybridization itself may have a negligible influence on the origin of species: on the one hand, universally favoured alleles spread readily across hybrid zones, whilst on the other, spatially heterogeneous selection causes divergence despite gene flow. Thus, narrow hybrid zones or occasional hybridisation may hardly affect the process of divergence.}, author = {Barton, Nicholas H}, journal = {Journal of Evolutionary Biology}, number = {2}, pages = {267 -- 269}, publisher = {Wiley-Blackwell}, title = {{Does hybridisation influence speciation? }}, doi = {10.1111/jeb.12015}, volume = {26}, year = {2013}, } @inbook{2907, abstract = {Sex and recombination are among the most striking features of the living world, and they play a crucial role in allowing the evolution of complex adaptation. The sharing of genomes through the sexual union of different individuals requires elaborate behavioral and physiological adaptations. At the molecular level, the alignment of two DNA double helices, followed by their precise cutting and rejoining, is an extraordinary feat. Sex and recombination have diverse—and often surprising—evolutionary consequences: distinct sexes, elaborate mating displays, selfish genetic elements, and so on.}, author = {Barton, Nicholas H}, booktitle = {The Princeton Guide to Evolution}, isbn = {9780691149776}, pages = {328 -- 333}, publisher = {Princeton University Press}, title = {{Recombination and sex}}, year = {2013}, } @article{2913, abstract = {The ability of an organism to distinguish between various stimuli is limited by the structure and noise in the population code of its sensory neurons. Here we infer a distance measure on the stimulus space directly from the recorded activity of 100 neurons in the salamander retina. In contrast to previously used measures of stimulus similarity, this "neural metric" tells us how distinguishable a pair of stimulus clips is to the retina, based on the similarity between the induced distributions of population responses. We show that the retinal distance strongly deviates from Euclidean, or any static metric, yet has a simple structure: we identify the stimulus features that the neural population is jointly sensitive to, and show the support-vector-machine- like kernel function relating the stimulus and neural response spaces. We show that the non-Euclidean nature of the retinal distance has important consequences for neural decoding.}, author = {Tkacik, Gasper and Granot Atedgi, Einat and Segev, Ronen and Schneidman, Elad}, journal = {Physical Review Letters}, number = {5}, publisher = {American Physical Society}, title = {{Retinal metric: a stimulus distance measure derived from population neural responses}}, doi = {10.1103/PhysRevLett.110.058104}, volume = {110}, year = {2013}, } @article{2918, abstract = {Oriented mitosis is essential during tissue morphogenesis. The Wnt/planar cell polarity (Wnt/PCP) pathway orients mitosis in a number of developmental systems, including dorsal epiblast cell divisions along the animal-vegetal (A-V) axis during zebrafish gastrulation. How Wnt signalling orients the mitotic plane is, however, unknown. Here we show that, in dorsal epiblast cells, anthrax toxin receptor 2a (Antxr2a) accumulates in a polarized cortical cap, which is aligned with the embryonic A-V axis and forecasts the division plane. Filamentous actin (F-actin) also forms an A-V polarized cap, which depends on Wnt/PCP and its effectors RhoA and Rock2. Antxr2a is recruited to the cap by interacting with actin. Antxr2a also interacts with RhoA and together they activate the diaphanous-related formin zDia2. Mechanistically, Antxr2a functions as a Wnt-dependent polarized determinant, which, through the action of RhoA and zDia2, exerts torque on the spindle to align it with the A-V axis. }, author = {Castanon, Irinka and Abrami, Laurence and Holtzer, Laurent and Heisenberg, Carl-Philipp J and Van Der Goot, Françoise and González Gaitán, Marcos}, journal = {Nature Cell Biology}, number = {1}, pages = {28 -- 39}, publisher = {Nature Publishing Group}, title = {{Anthrax toxin receptor 2a controls mitotic spindle positioning}}, doi = {10.1038/ncb2632}, volume = {15}, year = {2013}, } @article{2919, abstract = {The distribution of the phytohormone auxin regulates many aspects of plant development including growth response to gravity. Gravitropic root curvature involves coordinated and asymmetric cell elongation between the lower and upper side of the root, mediated by differential cellular auxin levels. The asymmetry in the auxin distribution is established and maintained by a spatio-temporal regulation of the PIN-FORMED (PIN) auxin transporter activity. We provide novel insights into the complex regulation of PIN abundance and activity during root gravitropism. We show that PIN2 turnover is differentially regulated on the upper and lower side of gravistimulated roots by distinct but partially overlapping auxin feedback mechanisms. In addition to regulating transcription and clathrin-mediated internalization, auxin also controls PIN abundance at the plasma membrane by promoting their vacuolar targeting and degradation. This effect of elevated auxin levels requires the activity of SKP-Cullin-F-box TIR1/AFB (SCF TIR1/AFB)-dependent pathway. Importantly, also suboptimal auxin levels mediate PIN degradation utilizing the same signalling pathway. These feedback mechanisms are functionally important during gravitropic response and ensure fine-tuning of auxin fluxes for maintaining as well as terminating asymmetric growth.}, author = {Baster, Pawel and Robert, Stéphanie and Kleine Vehn, Jürgen and Vanneste, Steffen and Kania, Urszula and Grunewald, Wim and De Rybel, Bert and Beeckman, Tom and Friml, Jirí}, journal = {EMBO Journal}, number = {2}, pages = {260 -- 274}, publisher = {Wiley-Blackwell}, title = {{SCF^TIR1 AFB-auxin signalling regulates PIN vacuolar trafficking and auxin fluxes during root gravitropism}}, doi = {10.1038/emboj.2012.310}, volume = {32}, year = {2013}, } @article{2920, abstract = {Cell polarisation in development is a common and fundamental process underlying embryo patterning and morphogenesis, and has been extensively studied over the past years. Our current knowledge of cell polarisation in development is predominantly based on studies that have analysed polarisation of single cells, such as eggs, or cellular aggregates with a stable polarising interface, such as cultured epithelial cells (St Johnston and Ahringer, 2010). However, in embryonic development, particularly of vertebrates, cell polarisation processes often encompass large numbers of cells that are placed within moving and proliferating tissues, and undergo mesenchymal-to-epithelial transitions with a highly complex spatiotemporal choreography. How such intricate cell polarisation processes in embryonic development are achieved has only started to be analysed. By using live imaging of neurulation in the transparent zebrafish embryo, Buckley et al (2012) now describe a novel polarisation strategy by which cells assemble an apical domain in the part of their cell body that intersects with the midline of the forming neural rod. This mechanism, along with the previously described mirror-symmetric divisions (Tawk et al, 2007), is thought to trigger formation of both neural rod midline and lumen.}, author = {Compagnon, Julien and Heisenberg, Carl-Philipp J}, journal = {EMBO Journal}, number = {1}, pages = {1 -- 3}, publisher = {Wiley-Blackwell}, title = {{Neurulation coordinating cell polarisation and lumen formation}}, doi = {10.1038/emboj.2012.325}, volume = {32}, year = {2013}, } @inproceedings{2940, abstract = {A chain rule for an entropy notion H(.) states that the entropy H(X) of a variable X decreases by at most l if conditioned on an l-bit string A, i.e., H(X|A)>= H(X)-l. More generally, it satisfies a chain rule for conditional entropy if H(X|Y,A)>= H(X|Y)-l. All natural information theoretic entropy notions we are aware of (like Shannon or min-entropy) satisfy some kind of chain rule for conditional entropy. Moreover, many computational entropy notions (like Yao entropy, unpredictability entropy and several variants of HILL entropy) satisfy the chain rule for conditional entropy, though here not only the quantity decreases by l, but also the quality of the entropy decreases exponentially in l. However, for the standard notion of conditional HILL entropy (the computational equivalent of min-entropy) the existence of such a rule was unknown so far. In this paper, we prove that for conditional HILL entropy no meaningful chain rule exists, assuming the existence of one-way permutations: there exist distributions X,Y,A, where A is a distribution over a single bit, but $H(X|Y)>>H(X|Y,A)$, even if we simultaneously allow for a massive degradation in the quality of the entropy. The idea underlying our construction is based on a surprising connection between the chain rule for HILL entropy and deniable encryption. }, author = {Krenn, Stephan and Pietrzak, Krzysztof Z and Wadia, Akshay}, editor = {Sahai, Amit}, location = {Tokyo, Japan}, pages = {23 -- 39}, publisher = {Springer}, title = {{A counterexample to the chain rule for conditional HILL entropy, and what deniable encryption has to do with it}}, doi = {10.1007/978-3-642-36594-2_2}, volume = {7785}, year = {2013}, } @inproceedings{2948, abstract = {Many visual datasets are traditionally used to analyze the performance of different learning techniques. The evaluation is usually done within each dataset, therefore it is questionable if such results are a reliable indicator of true generalization ability. We propose here an algorithm to exploit the existing data resources when learning on a new multiclass problem. Our main idea is to identify an image representation that decomposes orthogonally into two subspaces: a part specific to each dataset, and a part generic to, and therefore shared between, all the considered source sets. This allows us to use the generic representation as un-biased reference knowledge for a novel classification task. By casting the method in the multi-view setting, we also make it possible to use different features for different databases. We call the algorithm MUST, Multitask Unaligned Shared knowledge Transfer. Through extensive experiments on five public datasets, we show that MUST consistently improves the cross-datasets generalization performance.}, author = {Tommasi, Tatiana and Quadrianto, Novi and Caputo, Barbara and Lampert, Christoph}, location = {Daejeon, Korea}, pages = {1 -- 15}, publisher = {Springer}, title = {{Beyond dataset bias: Multi-task unaligned shared knowledge transfer}}, doi = {10.1007/978-3-642-37331-2_1}, volume = {7724}, year = {2013}, } @inproceedings{2973, abstract = {Efficient zero-knowledge proofs of knowledge (ZK-PoK) are basic building blocks of many practical cryptographic applications such as identification schemes, group signatures, and secure multiparty computation. Currently, first applications that critically rely on ZK-PoKs are being deployed in the real world. The most prominent example is Direct Anonymous Attestation (DAA), which was adopted by the Trusted Computing Group (TCG) and implemented as one of the functionalities of the cryptographic Trusted Platform Module (TPM) chip. Implementing systems using ZK-PoK turns out to be challenging, since ZK-PoK are, loosely speaking, significantly more complex than standard crypto primitives, such as encryption and signature schemes. As a result, implementation cycles of ZK-PoK are time-consuming and error-prone, in particular for developers with minor or no cryptographic skills. In this paper we report on our ongoing and future research vision with the goal to bring ZK-PoK to practice by making them accessible to crypto and security engineers. To this end we are developing compilers and related tools that support and partially automate the design, implementation, verification and secure implementation of ZK-PoK protocols.}, author = {Bangerter, Endre and Barzan, Stefania and Stephan Krenn and Sadeghi, Ahmad-Reza and Schneider, Thomas and Tsay, Joe-Kai}, editor = {Christianson, Bruce and Malcolm, James A. and Matyas, Vashek and Roe, Michael}, pages = {51 -- 62}, publisher = {Springer}, title = {{Bringing Zero-Knowledge Proofs of Knowledge to Practice}}, doi = {10.1007/978-3-642-36213-2_9}, volume = {7028}, year = {2013}, } @article{3116, abstract = {Multithreaded programs coordinate their interaction through synchronization primitives like mutexes and semaphores, which are managed by an OS-provided resource manager. We propose algorithms for the automatic construction of code-aware resource managers for multithreaded embedded applications. Such managers use knowledge about the structure and resource usage (mutex and semaphore usage) of the threads to guarantee deadlock freedom and progress while managing resources in an efficient way. Our algorithms compute managers as winning strategies in certain infinite games, and produce a compact code description of these strategies. We have implemented the algorithms in the tool Cynthesis. Given a multithreaded program in C, the tool produces C code implementing a code-aware resource manager. We show in experiments that Cynthesis produces compact resource managers within a few minutes on a set of embedded benchmarks with up to 6 threads. © 2012 Springer Science+Business Media, LLC.}, author = {Chatterjee, Krishnendu and De Alfaro, Luca and Faella, Marco and Majumdar, Ritankar and Raman, Vishwanath}, journal = {Formal Methods in System Design}, number = {2}, pages = {142 -- 174}, publisher = {Springer}, title = {{Code aware resource management}}, doi = {10.1007/s10703-012-0170-4}, volume = {42}, year = {2013}, } @article{2815, abstract = {The fact that a sum of isotropic Gaussian kernels can have more modes than kernels is surprising. Extra (ghost) modes do not exist in ℝ1 and are generally not well studied in higher dimensions. We study a configuration of n+1 Gaussian kernels for which there are exactly n+2 modes. We show that all modes lie on a finite set of lines, which we call axes, and study the restriction of the Gaussian mixture to these axes in order to discover that there are an exponential number of critical points in this configuration. Although the existence of ghost modes remained unknown due to the difficulty of finding examples in ℝ2, we show that the resilience of ghost modes grows like the square root of the dimension. In addition, we exhibit finite configurations of isotropic Gaussian kernels with superlinearly many modes.}, author = {Edelsbrunner, Herbert and Fasy, Brittany Terese and Rote, Günter}, issn = {1432-0444}, journal = {Discrete & Computational Geometry}, number = {4}, pages = {797 -- 822}, publisher = {Springer}, title = {{Add isotropic Gaussian kernels at own risk: More and more resilient modes in higher dimensions}}, doi = {10.1007/s00454-013-9517-x}, volume = {49}, year = {2013}, } @article{2939, abstract = {In this paper, we present the first output-sensitive algorithm to compute the persistence diagram of a filtered simplicial complex. For any Γ > 0, it returns only those homology classes with persistence at least Γ. Instead of the classical reduction via column operations, our algorithm performs rank computations on submatrices of the boundary matrix. For an arbitrary constant δ ∈ (0, 1), the running time is O (C (1 - δ) Γ R d (n) log n), where C (1 - δ) Γ is the number of homology classes with persistence at least (1 - δ) Γ, n is the total number of simplices in the complex, d its dimension, and R d (n) is the complexity of computing the rank of an n × n matrix with O (d n) nonzero entries. Depending on the choice of the rank algorithm, this yields a deterministic O (C (1 - δ) Γ n 2.376) algorithm, an O (C (1 - δ) Γ n 2.28) Las-Vegas algorithm, or an O (C (1 - δ) Γ n 2 + ε{lunate}) Monte-Carlo algorithm for an arbitrary ε{lunate} > 0. The space complexity of the Monte-Carlo version is bounded by O (d n) = O (n log n).}, author = {Chen, Chao and Kerber, Michael}, journal = {Computational Geometry: Theory and Applications}, number = {4}, pages = {435 -- 447}, publisher = {Elsevier}, title = {{An output sensitive algorithm for persistent homology}}, doi = {10.1016/j.comgeo.2012.02.010}, volume = {46}, year = {2013}, } @article{344, abstract = {Copper-based selenides are attracting increasing interest due to their outstanding optoelectronic and thermoelectric properties. Herein a novel colloidal synthetic route to prepare Cu2SnSe3 nanocrystals with controlled size, shape and composition is presented. The high yield of the developed procedure allowed its up-scaling to the production of grams of colloidal Cu2SnSe3 nanocrystals. These nanocrystals were used as building blocks for the production of Cu2SnSe3 bulk nanostructured materials by spark plasma sintering. The thermoelectric properties of the prepared nanocrystalline Cu2SnSe3 pellets were characterized in the temperature range from 300 to 720 K. The obtained results show the bottom-up production of nanocrystalline materials from solution-processed nanocrystals to be a potentially advantageous alternative to conventional methods of production of efficient thermoelectric materials.}, author = {Ibáñez, Maria and Cadavid, Doris and Anselmi Tamburini, Umberto and Zamani, Reza and Gorsse, Stéphane and Li, Wenhua and López, Antonio and Morante, Joan and Arbiol, Jordi and Cabot, Andreu}, journal = {Journal of Materials Chemistry A}, number = {4}, pages = {1421 -- 1426}, publisher = {Royal Society of Chemistry}, title = {{Colloidal synthesis and thermoelectric properties of Cu 2SnSe3 nanocrystals}}, doi = {10.1039/C2TA00419D}, volume = {1}, year = {2013}, } @article{352, abstract = {The presence of organic ligands on the surface of colloidal nanoparticles strongly limits their performance in technological applications where charge carrier transfer/transport plays an important role. We use metal salts, matched with the nanoparticle composition, to eliminate the surface organic ligands without introducing extrinsic impurities in the final nanomaterial. The potential of the simple, general and scalable processes presented here is demonstrated by characterizing the thermoelectric properties of nanostructured Ag2Te produced by the bottom up assembly of Ag2Te nanocrystals. A 6-fold increase of the thermoelectric figure of merit of Ag2Te was obtained when organic ligands were displaced by AgNO3. The same procedure can enhance the performance of nanocrystals and nanocrystal-based devices in a broad range of applications, from photovoltaics and thermoelectrics to catalysis.}, author = {Cadavid, Doris and Ibáñez, Maria and Shavel, Alexey and Durá, Oscar and López De La Torre, Marco and Cabot, Andreu}, journal = {Journal of Materials Chemistry A}, number = {15}, pages = {4864 -- 4870}, publisher = {Royal Society of Chemistry}, title = {{Organic ligand displacement by metal salts to enhance nanoparticle functionality: Thermoelectric properties of Ag inf 2 inf Te}}, doi = {10.1039/C3TA01455J}, volume = {1}, year = {2013}, } @article{378, abstract = {Until recently, to prepare nanocrystals of a new material, scientists searched their shelves for the appropriate molecular precursors, surfactants, and solvents. They then optimized the reaction conditions for the atoms to self-assemble into monodisperse nanocrystals (1). This approach is being replaced by a simpler strategy, in which preformed nanocrystals serve as templates to produce nanoparticles with a different composition through chemical transformation. On page 964 of this issue, Oh et al. (2) report a powerful mechanism that allows the composition of oxide nanoparticles to be transformed in solution and at low temperatures.}, author = {Ibáñez, Maria and Cabot, Andreu}, journal = {Science}, number = {6135}, pages = {935 -- 936}, publisher = {American Association for the Advancement of Science}, title = {{All change for nanocrystals}}, doi = {10.1126/science.1239221}, volume = {340}, year = {2013}, } @article{3261, abstract = {Cells in a developing embryo have no direct way of "measuring" their physical position. Through a variety of processes, however, the expression levels of multiple genes come to be correlated with position, and these expression levels thus form a code for "positional information." We show how to measure this information, in bits, using the gap genes in the Drosophila embryo as an example. Individual genes carry nearly two bits of information, twice as much as expected if the expression patterns consisted only of on/off domains separated by sharp boundaries. Taken together, four gap genes carry enough information to define a cell's location with an error bar of ~1% along the anterior-posterior axis of the embryo. This precision is nearly enough for each cell to have a unique identity, which is the maximum information the system can use, and is nearly constant along the length of the embryo. We argue that this constancy is a signature of optimality in the transmission of information from primary morphogen inputs to the output of the gap gene network.}, author = {Dubuis, Julien and Tkacik, Gasper and Wieschaus, Eric and Gregor, Thomas and Bialek, William}, journal = {PNAS}, number = {41}, pages = {16301 -- 16308}, publisher = {National Academy of Sciences}, title = {{Positional information, in bits}}, doi = {10.1073/pnas.1315642110}, volume = {110}, year = {2013}, } @article{331, abstract = {We report a procedure to prepare highly monodisperse copper telluride nanocubes, nanoplates, and nanorods. The procedure is based on the reaction of a copper salt with trioctylphosphine telluride in the presence of lithium bis(trimethylsilyl)amide and oleylamine. CuTe nanocrystals display a strong near-infrared optical absorption associated with localized surface plasmon resonances. We exploit this plasmon resonance for the design of surface-enhanced Raman scattering sensors for unconventional optical probes. Furthermore, we also report here our preliminary analysis of the use of CuTe nanocrystals as cytotoxic and photothermal agents.}, author = {Li, Wenhua and Zamani, Reza and Rivera Gil, Pilar and Pelaz, Beatriz and Ibáñez, Maria and Cadavid, Doris and Shavel, Alexey and Alvarez Puebla, Ramon and Parak, Wolfgang and Arbiol, Jordi and Cabot, Andreu}, journal = {Journal of the American Chemical Society}, number = {19}, pages = {7098 -- 7101}, publisher = {ACS}, title = {{CuTe nanocrystals: Shape and size control, plasmonic properties, and use as SERS probes and photothermal agents}}, doi = {10.1021/ja401428e}, volume = {135}, year = {2013}, } @misc{3321, author = {Quadrianto, Novi and Lampert, Christoph}, booktitle = {Encyclopedia of Systems Biology}, editor = {Dubitzky, Werner and Wolkenhauer, Olaf and Cho, Kwang and Yokota, Hiroki}, pages = {1069 -- 1069}, publisher = {Springer}, title = {{Kernel based learning}}, doi = {10.1007/978-1-4419-9863-7_604}, volume = {3}, 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{342, abstract = {Morphology is a key parameter in the design of novel nanocrystals and nanomaterials with controlled functional properties. Here, we demonstrate the potential of foreign metal ions to tune the morphology of colloidal semiconductor nanoparticles. We illustrate the underlying mechanism by preparing copper selenide nanocubes in the presence of Al ions. We further characterize the plasmonic properties of the obtained nanocrystals and demonstrate their potential as a platform to produce cubic nanoparticles with different composition by cation exchange. © 2013 American Chemical Society.}, author = {Li, Wenhua and Zamani, Reza and Ibáñez, Maria and Cadavid, Doris and Shavel, Alexey and Morante, Joan and Arbiol, Jordi and Cabot, Andreu}, journal = {Journal of the American Chemical Society}, number = {12}, pages = {4664 -- 4667}, publisher = {American Chemical Society}, title = {{Metal ions to control the morphology of semiconductor nanoparticles: Copper selenide nanocubes}}, doi = {10.1021/ja400472m}, volume = {135}, year = {2013}, } @article{343, abstract = {The bottom-up assembly of nanocrystals provides access to a three-dimensional composition control at the nanoscale not attainable by any other technology. In particular, colloidal nanoheterostructures, with intrinsic multiphase organization, are especially appealing building blocks for the bottom-up production of nanocomposites. In the present work, we use PbTe-PbS as the model material system and thermoelectricity as the paradigmatic application to investigate the potential of the bottom-up assembly of core-shell nanoparticles to produce functional nanocomposites. With this goal in mind, a rapid, high-yield and scalable colloidal synthetic route to prepare grams of PbTe@PbS core-shell nanoparticles with unprecedented narrow size distributions and exceptional composition control is detailed. PbTe@PbS nanoparticles were used as building blocks for the bottom-up production of PbTe-PbS nanocomposites with tuned composition. In such PbTe-PbS nanocomposites, synergistic nanocrystal doping effects result in up to 10-fold higher electrical conductivities than in pure PbTe and PbS nanomaterials. At the same time, the acoustic impedance mismatch between PbTe and PbS phases and a partial phase alloying provide PbTe-PbS nanocomposites with strongly reduced thermal conductivities. As a result, record thermoelectric figures of merit (ZT) of ∼1.1 were obtained from undoped PbTe and PbS phases at 710 K. These high ZT values prove the potential of the proposed processes to produce efficient functional nanomaterials with programmable properties. © 2013 American Chemical Society.}, author = {Ibáñez, Maria and Zamani, Reza and Gorsse, Stéphane and Fan, Jiandong and Ortega, Silvia and Cadavid, Doris and Morante, Joan and Arbiol, Jordi and Cabot, Andreu}, journal = {ACS Nano}, number = {3}, pages = {2573 -- 2586}, publisher = {American Chemical Society}, title = {{Core shell nanoparticles as building blocks for the bottom-up production of functional nanocomposites: PbTe PbS thermoelectric properties}}, doi = {10.1021/nn305971v}, volume = {7}, year = {2013}, } @article{351, abstract = {A multistrategy approach to overcome the main challenges of nanoparticle-based solution-processed Cu2ZnSnSe4 thin film solar cells is presented. We developed an efficient ligand exchange strategy, using an antimony salt, to displace organic ligands from the surface of Cu 2ZnSnS4 nanoparticles. An automated pulsed spray-deposition system was used to deposit the nanoparticles into homogeneous and crack-free films with controlled thickness. After annealing the film in a Se-rich atmosphere, carbon-free and crystalline Cu2ZnSnSe4 absorber layers were obtained. Not only was crystallization promoted by the complete removal of organics, but also Sb itself played a critical role. The Sb-assisted crystal growth is associated with the formation of a Sb-based compound at the grain boundaries, which locally reduces the melting point, thus promoting the film diffusion-limited crystallization. }, author = {Carrete, Alex and Shavel, Alexey and Fontané, Xavier and Montserrat, Joana and Fan, Jiandong and Ibáñez, Maria and Saucedo, Edgardo and Pérez Rodríguez, Alejandro and Cabot, Andreu}, journal = {Journal of the American Chemical Society}, number = {43}, pages = {15982 -- 15985}, publisher = {American Chemical Society}, title = {{Antimony-based ligand exchange to promote crystallization in spray-deposited Cu2ZnSnSe4 solar cells}}, doi = {10.1021/ja4068639}, volume = {135}, year = {2013}, } @article{353, abstract = {We report a procedure to prepare highly monodisperse copper telluride nanocubes, nanoplates, and nanorods. The procedure is based on the reaction of a copper salt with trioctylphosphine telluride in the presence of lithium bis(trimethylsilyl)amide and oleylamine. CuTe nanocrystals display a strong near-infrared optical absorption associated with localized surface plasmon resonances. We exploit this plasmon resonance for the design of surface-enhanced Raman scattering sensors for unconventional optical probes. Furthermore, we also report here our preliminary analysis of the use of CuTe nanocrystals as cytotoxic and photothermal agents.}, author = {Li, Wenhua and Zamani, Reza and Rivera Gil, Pilar and Pelaz, Beatriz and Ibáñez, Maria and Cadavid, Doris and Shavel, Alexey and Alvarez Puebla, Ramon and Parak, Wolfgang and Arbiol, Jordi and Cabot, Andreu}, journal = {Journal of the American Chemical Society}, number = {19}, pages = {7098 -- 7101}, publisher = {American Chemical Society}, title = {{CuTe nanocrystals: Shape and size control, plasmonic properties, and use as SERS probes and photothermal agents}}, doi = {10.1021/ja401428e}, volume = {135}, year = {2013}, } @article{376, abstract = {The compositional versatility of I2–II–IV–VI4 tetrahedrally-coordinated compounds allows for accommodating their functional properties to numerous technological applications. Among them, Cu2ZnSnSe4 is an emerging photovoltaic material and Cu2CdSnSe4 displays excellent thermoelectric properties. The third compound of this family, Cu2HgSnSe4, remains relatively unexplored. Herein, a synthetic route to produce Cu2HgSnSe4 nanoparticles with narrow size distribution and controlled composition is presented. Cu2HgSnSe4 nanoparticles were subsequently used as building blocks to produce bulk nanocrystalline materials, whose thermoelectric properties were analyzed. A very preliminary adjustment of the material composition yielded Seebeck coefficients up to 160 μV K−1, electrical conductivities close to 104 S m−1 and thermal conductivities down to 0.5 W m−1 K−1.}, author = {Li, Wenhua and Ibáñez, Maria and Zamani, Reza and García Castelló, Nuria and Stéphane, Grosse and Cadavid, Doris and Prades, Joan and Arbiol, Jordi and Cabot, Andreu}, journal = {CrystEngComm}, pages = {8966 -- 8971}, publisher = {Royal Society of Chemistry}, title = {{Cu2HgSnSe4 nanoparticles: synthesis and thermoelectric properties}}, doi = {10.1039/C3CE41583J}, volume = {44}, year = {2013}, } @article{450, abstract = {Understanding the relative importance of heterosis and outbreeding depression over multiple generations is a key question in evolutionary biology and is essential for identifying appropriate genetic sources for population and ecosystem restoration. Here we use 2455 experimental crosses between 12 population pairs of the rare perennial plant Rutidosis leptorrhynchoides (Asteraceae) to investigate the multi-generational (F1, F2, F3) fitness outcomes of inter-population hybridization. We detected no evidence of outbreeding depression, with inter-population hybrids and backcrosses showing either similar fitness or significant heterosis for fitness components across the three generations. Variation in heterosis among population pairs was best explained by characteristics of the foreign source or home population, and was greatest when the source population was large, with high genetic diversity and low inbreeding, and the home population was small and inbred. Our results indicate that the primary consideration for maximizing progeny fitness following population augmentation or restoration is the use of seed from large, genetically diverse populations.}, author = {Pickup, Melinda and Field, David and Rowell, David and Young, Andrew}, journal = {Proceedings of the Royal Society of London Series B Biological Sciences}, number = {1750}, publisher = {Royal Society, The}, title = {{Source population characteristics affect heterosis following genetic rescue of fragmented plant populations}}, doi = {10.1098/rspb.2012.2058}, volume = {280}, year = {2013}, } @article{476, abstract = {Maternal exposure to infection occurring mid-gestation produces a three-fold increase in the risk of schizophrenia in the offspring. The critical initiating factor appears to be the maternal immune activation (MIA) that follows infection. This process can be induced in rodents by exposure of pregnant dams to the viral mimic Poly I:C, which triggers an immune response that results in structural, functional, behavioral, and electrophysiological phenotypes in the adult offspring that model those seen in schizophrenia. We used this model to explore the role of synchronization in brain neural networks, a process thought to be dysfunctional in schizophrenia and previously associated with positive, negative, and cognitive symptoms of schizophrenia. Exposure of pregnant dams to Poly I:C on GD15 produced an impairment in long-range neural synchrony in adult offspring between two regions implicated in schizophrenia pathology; the hippocampus and the medial prefrontal cortex (mPFC). This reduction in synchrony was ameliorated by acute doses of the antipsychotic clozapine. MIA animals have previously been shown to have impaired pre-pulse inhibition (PPI), a gold-standard measure of schizophrenia-like deficits in animal models. Our data showed that deficits in synchrony were positively correlated with the impairments in PPI. Subsequent analysis of LFP activity during the PPI response also showed that reduced coupling between the mPFC and the hippocampus following processing of the pre-pulse was associated with reduced PPI. The ability of the MIA intervention to model neurodevelopmental aspects of schizophrenia pathology provides a useful platform from which to investigate the ontogeny of aberrant synchronous processes. Further, the way in which the model expresses translatable deficits such as aberrant synchrony and reduced PPI will allow researchers to explore novel intervention strategies targeted to these changes. }, author = {Dickerson, Desiree and Bilkey, David}, journal = {Frontiers in Behavioral Neuroscience}, number = {DEC}, publisher = {Frontiers Research Foundation}, title = {{Aberrant neural synchrony in the maternal immune activation model: Using translatable measures to explore targeted interventions}}, doi = {10.3389/fnbeh.2013.00217}, volume = {7}, year = {2013}, } @article{499, abstract = {Exposure of an isogenic bacterial population to a cidal antibiotic typically fails to eliminate a small fraction of refractory cells. Historically, fractional killing has been attributed to infrequently dividing or nondividing "persisters." Using microfluidic cultures and time-lapse microscopy, we found that Mycobacterium smegmatis persists by dividing in the presence of the drug isoniazid (INH). Although persistence in these studies was characterized by stable numbers of cells, this apparent stability was actually a dynamic state of balanced division and death. Single cells expressed catalase-peroxidase (KatG), which activates INH, in stochastic pulses that were negatively correlated with cell survival. These behaviors may reflect epigenetic effects, because KatG pulsing and death were correlated between sibling cells. Selection of lineages characterized by infrequent KatG pulsing could allow nonresponsive adaptation during prolonged drug exposure.}, author = {Wakamoto, Yurichi and Dhar, Neraaj and Chait, Remy P and Schneider, Katrin and Signorino Gelo, François and Leibler, Stanislas and Mckinney, John}, journal = {Science}, number = {6115}, pages = {91 -- 95}, publisher = {American Association for the Advancement of Science}, title = {{Dynamic persistence of antibiotic-stressed mycobacteria}}, doi = {10.1126/science.1229858}, volume = {339}, year = {2013}, } @article{500, abstract = {Background: Reassortment between the RNA segments encoding haemagglutinin (HA) and neuraminidase (NA), the major antigenic influenza proteins, produces viruses with novel HA and NA subtype combinations and has preceded the emergence of pandemic strains. It has been suggested that productive viral infection requires a balance in the level of functional activity of HA and NA, arising from their closely interacting roles in the viral life cycle, and that this functional balance could be mediated by genetic changes in the HA and NA. Here, we investigate how the selective pressure varies for H7 avian influenza HA on different NA subtype backgrounds. Results: By extending Bayesian stochastic mutational mapping methods to calculate the ratio of the rate of non-synonymous change to the rate of synonymous change (d N/d S), we found the average d N/d S across the avian influenza H7 HA1 region to be significantly greater on an N2 NA subtype background than on an N1, N3 or N7 background. Observed differences in evolutionary rates of H7 HA on different NA subtype backgrounds could not be attributed to underlying differences between avian host species or virus pathogenicity. Examination of d N/d S values for each subtype on a site-by-site basis indicated that the elevated d N/d S on the N2 NA background was a result of increased selection, rather than a relaxation of selective constraint. Conclusions: Our results are consistent with the hypothesis that reassortment exposes influenza HA to significant changes in selective pressure through genetic interactions with NA. Such epistatic effects might be explicitly accounted for in future models of influenza evolution.}, author = {Ward, Melissa and Lycett, Samantha and Avila, Dorita and Bollback, Jonathan P and Leigh Brown, Andrew}, journal = {BMC Evolutionary Biology}, number = {1}, publisher = {BioMed Central}, title = {{Evolutionary interactions between haemagglutinin and neuraminidase in avian influenza}}, doi = {10.1186/1471-2148-13-222}, volume = {13}, year = {2013}, } @article{501, abstract = {All known species of extant tapirs are allopatric: 1 in southeastern Asia and 3 in Central and South America. The fossil record for tapirs, however, is much wider in geographical range, including Europe, Asia, and North and South America, going back to the late Oligocene, making the present distribution a relict of the original one. We here describe a new species of living Tapirus from the Amazon rain forest, the 1st since T. bairdii Gill, 1865, and the 1st new Perissodactyla in more than 100 years, from both morphological and molecular characters. It is shorter in stature than T. terrestris (Linnaeus, 1758) and has distinctive skull morphology, and it is basal to the clade formed by T. terrestris and T. pinchaque (Roulin, 1829). This highlights the unrecognized biodiversity in western Amazonia, where the biota faces increasing threats. Local peoples have long recognized our new species, suggesting a key role for traditional knowledge in understanding the biodiversity of the region.}, author = {Cozzuol, Mario and Clozato, Camila and Holanda, Elizete and Rodrigues, Flávio and Nienow, Samuel and De Thoisy, Benoit and Fernandes Redondo, Rodrigo A and Santos, Fabrício}, journal = {Journal of Mammalogy}, number = {6}, pages = {1331 -- 1345}, publisher = {Oxford University Press}, title = {{A new species of tapir from the Amazon}}, doi = {10.1644/12-MAMM-A-169.1}, volume = {94}, year = {2013}, } @article{505, abstract = {Alkyd resins are polyesters containing unsaturated fatty acids that are used as binding agents in paints and coatings. Chemical drying of these polyesters is based on heavy metal catalyzed cross-linking of the unsaturated fatty acid moieties. Among the heavy-metal catalysts, cobalt complexes are the most effective, yet they have been proven to be carcinogenic. Therefore, strategies to replace the cobalt-based catalyst by environmentally friendlier and less toxic alternatives are under development. Here, we demonstrate for the first time that a laccase-mediator system can effectively replace the heavy-metal catalyst and cross-link alkyd resins. Interestingly, the biocatalytic reaction does not only work in aqueous media, but also in a solid film, where enzyme diffusion is limited. Within the catalytic cycle, the mediator oxidizes the alkyd resin and is regenerated by the laccase, which is uniformly distributed within the drying film as evidenced by confocal laser scanning microscopy. During gradual build-up of molecular weight, there is a concomitant decrease of the oxygen content in the film. A new optical sensor to follow oxygen consumption during the cross-linking reaction was developed and validated with state of the art techniques. A remarkable feature is the low sample amount required, which allows faster screening of new catalysts.}, author = {Greimel, Katrin and Perz, Veronika and Koren, Klaus and Feola, Roland and Temel, Armin and Sohar, Christian and Herrero Acero, Enrique and Klimant, Ingo and Guebitz, Georg}, journal = {Green Chemistry}, number = {2}, pages = {381 -- 388}, publisher = {Royal Society of Chemistry}, title = {{Banning toxic heavy-metal catalysts from paints: Enzymatic cross-linking of alkyd resins}}, doi = {10.1039/c2gc36666e}, volume = {15}, year = {2013}, } @article{502, abstract = {Blind signatures allow users to obtain signatures on messages hidden from the signer; moreover, the signer cannot link the resulting message/signature pair to the signing session. This paper presents blind signature schemes, in which the number of interactions between the user and the signer is minimal and whose blind signatures are short. Our schemes are defined over bilinear groups and are proved secure in the common-reference-string model without random oracles and under standard assumptions: CDH and the decision-linear assumption. (We also give variants over asymmetric groups based on similar assumptions.) The blind signatures are Waters signatures, which consist of 2 group elements. Moreover, we instantiate partially blind signatures, where the message consists of a part hidden from the signer and a commonly known public part, and schemes achieving perfect blindness. We propose new variants of blind signatures, such as signer-friendly partially blind signatures, where the public part can be chosen by the signer without prior agreement, 3-party blind signatures, as well as blind signatures on multiple aggregated messages provided by independent sources. We also extend Waters signatures to non-binary alphabets by proving a new result on the underlying hash function. }, author = {Blazy, Olivier and Fuchsbauer, Georg and Pointcheval, David and Vergnaud, Damien}, journal = {Journal of Computer Security}, number = {5}, pages = {627 -- 661}, publisher = {IOS Press}, title = {{Short blind signatures}}, doi = {10.3233/JCS-130477}, volume = {21}, year = {2013}, } @article{508, abstract = {The phagocyte NADPH oxidase catalyzes the reduction of O2 to reactive oxygen species with microbicidal activity. It is composed of two membrane-spanning subunits, gp91-phox and p22-phox (encoded by CYBB and CYBA, respectively), and three cytoplasmic subunits, p40-phox, p47-phox, and p67-phox (encoded by NCF4, NCF1, and NCF2, respectively). Mutations in any of these genes can result in chronic granulomatous disease, a primary immunodeficiency characterized by recurrent infections. Using evolutionary mapping, we determined that episodes of adaptive natural selection have shaped the extracellular portion of gp91-phox during the evolution of mammals, which suggests that this region may have a function in host-pathogen interactions. On the basis of a resequencing analysis of approximately 35 kb of CYBB, CYBA, NCF2, and NCF4 in 102 ethnically diverse individuals (24 of African ancestry, 31 of European ancestry, 24 of Asian/Oceanians, and 23 US Hispanics), we show that the pattern of CYBA diversity is compatible with balancing natural selection, perhaps mediated by catalase-positive pathogens. NCF2 in Asian populations shows a pattern of diversity characterized by a differentiated haplotype structure. Our study provides insight into the role of pathogen-driven natural selection in an innate immune pathway and sheds light on the role of CYBA in endothelial, nonphagocytic NADPH oxidases, which are relevant in the pathogenesis of cardiovascular and other complex diseases.}, author = {Tarazona Santos, Eduardo and Machado, Moara and Magalhães, Wagner and Chen, Renee and Lyon, Fernanda and Burdett, Laurie and Crenshaw, Andrew and Fabbri, Cristina and Pereira, Latife and Pinto, Laelia and Fernandes Redondo, Rodrigo A and Sestanovich, Ben and Yeager, Meredith and Chanock, Stephen}, journal = {Molecular Biology and Evolution}, number = {9}, pages = {2157 -- 2167}, publisher = {Oxford University Press}, title = {{Evolutionary dynamics of the human NADPH oxidase genes CYBB, CYBA, NCF2, and NCF4: Functional implications}}, doi = {10.1093/molbev/mst119}, volume = {30}, year = {2013}, } @article{509, abstract = {Clathrin-mediated endocytosis (CME) regulates many aspects of plant development, including hormone signaling and responses to environmental stresses. Despite the importance of this process, the machinery that regulates CME in plants is largely unknown. In mammals, the heterotetrameric ADAPTOR PROTEIN COMPLEX-2 (AP-2) is required for the formation of clathrin-coated vesicles at the plasma membrane (PM). Although the existence of AP-2 has been predicted in Arabidopsis thaliana, the biochemistry and functionality of the complex is still uncharacterized. Here, we identified all the subunits of the Arabidopsis AP-2 by tandem affinity purification and found that one of the large AP-2 subunits, AP2A1, localized at the PM and interacted with clathrin. Furthermore, endocytosis of the leucine-rich repeat receptor kinase, BRASSINOSTEROID INSENSITIVE1 (BRI1), was shown to depend on AP-2. Knockdown of the two Arabidopsis AP2A genes or overexpression of a dominant-negative version of the medium AP-2 subunit, AP2M, impaired BRI1 endocytosis and enhanced the brassinosteroid signaling. Our data reveal that the CME machinery in Arabidopsis is evolutionarily conserved and that AP-2 functions in receptormediated endocytosis. }, author = {Di Rubbo, Simone and Irani, Niloufer and Kim, Soo and Xu, Zheng and Gadeyne, Astrid and Dejonghe, Wim and Vanhoutte, Isabelle and Persiau, Geert and Eeckhout, Dominique and Simon, Sibu and Song, Kyungyoung and Kleine Vehn, Jürgen and Friml, Jirí and De Jaeger, Geert and Van Damme, Daniël and Hwang, Inhwan and Russinova, Eugenia}, journal = {Plant Cell}, number = {8}, pages = {2986 -- 2997}, publisher = {American Society of Plant Biologists}, title = {{The clathrin adaptor complex AP-2 mediates endocytosis of brassinosteroid INSENSITIVE1 in arabidopsis}}, doi = {10.1105/tpc.113.114058}, volume = {25}, year = {2013}, } @article{507, abstract = {Fertilization in flowering plants requires the temporal and spatial coordination of many developmental processes, including pollen production, anther dehiscence, ovule production, and pollen tube elongation. However, it remains elusive as to how this coordination occurs during reproduction. Here, we present evidence that endocytosis, involving heterotetrameric adaptor protein complex 2 (AP-2), plays a crucial role in fertilization. An Arabidopsis thaliana mutant ap2m displays multiple defects in pollen production and viability, as well as elongation of staminal filaments and pollen tubes, all of which are pivotal processes needed for fertilization. Of these abnormalities, the defects in elongation of staminal filaments and pollen tubes were partially rescued by exogenous auxin. Moreover, DR5rev:GFP (for green fluorescent protein) expression was greatly reduced in filaments and anthers in ap2m mutant plants. At the cellular level, ap2m mutants displayed defects in both endocytosis of N-(3-triethylammonium-propyl)-4- (4-diethylaminophenylhexatrienyl) pyridinium dibromide, a lypophilic dye used as an endocytosis marker, and polar localization of auxin-efflux carrier PIN FORMED2 (PIN2) in the stamen filaments. Moreover, these defects were phenocopied by treatment with Tyrphostin A23, an inhibitor of endocytosis. Based on these results, we propose that AP-2-dependent endocytosis plays a crucial role in coordinating the multiple developmental aspects of male reproductive organs by modulating cellular auxin level through the regulation of the amount and polarity of PINs.}, author = {Kim, Soo and Xu, Zheng and Song, Kyungyoung and Kim, Dae and Kang, Hyangju and Reichardt, Ilka and Sohn, Eun and Friml, Jirí and Juergens, Gerd and Hwang, Inhwan}, journal = {Plant Cell}, number = {8}, pages = {2970 -- 2985}, publisher = {American Society of Plant Biologists}, title = {{Adaptor protein complex 2-mediated endocytosis is crucial for male reproductive organ development in arabidopsis}}, doi = {10.1105/tpc.113.114264}, volume = {25}, year = {2013}, } @article{511, abstract = {The native auxin, indole-3-acetic acid (IAA), is a major regulator of plant growth and development. Its nonuniform distribution between cells and tissues underlies the spatiotemporal coordination of many developmental events and responses to environmental stimuli. The regulation of auxin gradients and the formation of auxin maxima/minima most likely involve the regulation of both metabolic and transport processes. In this article, we have demonstrated that 2-oxindole-3-acetic acid (oxIAA) is a major primary IAA catabolite formed in Arabidopsis thaliana root tissues. OxIAA had little biological activity and was formed rapidly and irreversibly in response to increases in auxin levels. We further showed that there is cell type-specific regulation of oxIAA levels in the Arabidopsis root apex. We propose that oxIAA is an important element in the regulation of output from auxin gradients and, therefore, in the regulation of auxin homeostasis and response mechanisms.}, author = {Pěnčík, Aleš and Simonovik, Biljana and Petersson, Sara and Henyková, Eva and Simon, Sibu and Greenham, Kathleen and Zhang, Yi and Kowalczyk, Mariusz and Estelle, Mark and Zažímalová, Eva and Novák, Ondřej and Sandberg, Göran and Ljung, Karin}, journal = {Plant Cell}, number = {10}, pages = {3858 -- 3870}, publisher = {American Society of Plant Biologists}, title = {{Regulation of auxin homeostasis and gradients in Arabidopsis roots through the formation of the indole-3-acetic acid catabolite 2-oxindole-3-acetic acid}}, doi = {10.1105/tpc.113.114421}, volume = {25}, year = {2013}, } @article{516, abstract = {In plants, changes in local auxin concentrations can trigger a range of developmental processes as distinct tissues respond differently to the same auxin stimulus. However, little is known about how auxin is interpreted by individual cell types. We performed a transcriptomic analysis of responses to auxin within four distinct tissues of the Arabidopsis thaliana root and demonstrate that different cell types show competence for discrete responses. The majority of auxin‐responsive genes displayed a spatial bias in their induction or repression. The novel data set was used to examine how auxin influences tissue‐specific transcriptional regulation of cell‐identity markers. Additionally, the data were used in combination with spatial expression maps of the root to plot a transcriptomic auxin‐response gradient across the apical and basal meristem. The readout revealed a strong correlation for thousands of genes between the relative response to auxin and expression along the longitudinal axis of the root. This data set and comparative analysis provide a transcriptome‐level spatial breakdown of the response to auxin within an organ where this hormone mediates many aspects of development.}, author = {Bargmann, Bastiaan and Vanneste, Steffen and Krouk, Gabriel and Nawy, Tal and Efroni, Idan and Shani, Eilon and Choe, Goh and Friml, Jirí and Bergmann, Dominique and Estelle, Mark and Birnbaum, Kenneth}, journal = {Molecular Systems Biology}, number = {1}, publisher = {Nature Publishing Group}, title = {{A map of cell type‐specific auxin responses}}, doi = {10.1038/msb.2013.40}, volume = {9}, year = {2013}, } @article{522, abstract = {Podoplanin, a mucin-like plasma membrane protein, is expressed by lymphatic endothelial cells and responsible for separation of blood and lymphatic circulation through activation of platelets. Here we show that podoplanin is also expressed by thymic fibroblastic reticular cells (tFRC), a novel thymic medulla stroma cell type associated with thymic conduits, and involved in development of natural regulatory T cells (nTreg). Young mice deficient in podoplanin lack nTreg owing to retardation of CD4+CD25+ thymocytes in the cortex and missing differentiation of Foxp3+ thymocytes in the medulla. This might be due to CCL21 that delocalizes upon deletion of the CCL21-binding podoplanin from medullar tFRC to cortex areas. The animals do not remain devoid of nTreg but generate them delayed within the first month resulting in Th2-biased hypergammaglobulinemia but not in the death-causing autoimmune phenotype of Foxp3-deficient Scurfy mice.}, author = {Fuertbauer, Elke and Zaujec, Jan and Uhrin, Pavel and Raab, Ingrid and Weber, Michele and Schachner, Helga and Bauer, Miroslav and Schütz, Gerhard and Binder, Bernd and Sixt, Michael K and Kerjaschki, Dontscho and Stockinger, Hannes}, journal = {Immunology Letters}, number = {1-2}, pages = {31 -- 41}, publisher = {Elsevier}, title = {{Thymic medullar conduits-associated podoplanin promotes natural regulatory T cells}}, doi = {10.1016/j.imlet.2013.07.007}, volume = {154}, year = {2013}, } @inproceedings{2279, abstract = {We consider two-player games played on weighted directed graphs with mean-payoff and total-payoff objectives, two classical quantitative objectives. While for single-dimensional games the complexity and memory bounds for both objectives coincide, we show that in contrast to multi-dimensional mean-payoff games that are known to be coNP-complete, multi-dimensional total-payoff games are undecidable. We introduce conservative approximations of these objectives, where the payoff is considered over a local finite window sliding along a play, instead of the whole play. For single dimension, we show that (i) if the window size is polynomial, deciding the winner takes polynomial time, and (ii) the existence of a bounded window can be decided in NP ∩ coNP, and is at least as hard as solving mean-payoff games. For multiple dimensions, we show that (i) the problem with fixed window size is EXPTIME-complete, and (ii) there is no primitive-recursive algorithm to decide the existence of a bounded window.}, author = {Chatterjee, Krishnendu and Doyen, Laurent and Randour, Mickael and Raskin, Jean}, location = {Hanoi, Vietnam}, pages = {118 -- 132}, publisher = {Springer}, title = {{Looking at mean-payoff and total-payoff through windows}}, doi = {10.1007/978-3-319-02444-8_10}, volume = {8172}, year = {2013}, } @article{528, abstract = {Establishment of the embryonic axis foreshadows the main body axis of adults both in plants and in animals, but underlying mechanisms are considered distinct. Plants utilize directional, cell-to-cell transport of the growth hormone auxin [1, 2] to generate an asymmetric auxin response that specifies the embryonic apical-basal axis [3-6]. The auxin flow directionality depends on the polarized subcellular localization of PIN-FORMED (PIN) auxin transporters [7, 8]. It remains unknown which mechanisms and spatial cues guide cell polarization and axis orientation in early embryos. Herein, we provide conceptually novel insights into the formation of embryonic axis in Arabidopsis by identifying a crucial role of localized tryptophan-dependent auxin biosynthesis [9-12]. Local auxin production at the base of young embryos and the accompanying PIN7-mediated auxin flow toward the proembryo are required for the apical auxin response maximum and the specification of apical embryonic structures. Later in embryogenesis, the precisely timed onset of localized apical auxin biosynthesis mediates PIN1 polarization, basal auxin response maximum, and specification of the root pole. Thus, the tight spatiotemporal control of distinct local auxin sources provides a necessary, non-cell-autonomous trigger for the coordinated cell polarization and subsequent apical-basal axis orientation during embryogenesis and, presumably, also for other polarization events during postembryonic plant life [13, 14].}, author = {Robert, Hélène and Grones, Peter and Stepanova, Anna and Robles, Linda and Lokerse, Annemarie and Alonso, Jose and Weijers, Dolf and Friml, Jirí}, journal = {Current Biology}, number = {24}, pages = {2506 -- 2512}, publisher = {Cell Press}, title = {{Local auxin sources orient the apical basal axis in arabidopsis embryos}}, doi = {10.1016/j.cub.2013.09.039}, volume = {23}, year = {2013}, } @article{527, abstract = {The apical-basal axis of the early plant embryo determines the body plan of the adult organism. To establish a polarized embryonic axis, plants evolved a unique mechanism that involves directional, cell-to-cell transport of the growth regulator auxin. Auxin transport relies on PIN auxin transporters [1], whose polar subcellular localization determines the flow directionality. PIN-mediated auxin transport mediates the spatial and temporal activity of the auxin response machinery [2-7] that contributes to embryo patterning processes, including establishment of the apical (shoot) and basal (root) embryo poles [8]. However, little is known of upstream mechanisms guiding the (re)polarization of auxin fluxes during embryogenesis [9]. Here, we developed a model of plant embryogenesis that correctly generates emergent cell polarities and auxin-mediated sequential initiation of apical-basal axis of plant embryo. The model relies on two precisely localized auxin sources and a feedback between auxin and the polar, subcellular PIN transporter localization. Simulations reproduced PIN polarity and auxin distribution, as well as previously unknown polarization events during early embryogenesis. The spectrum of validated model predictions suggests that our model corresponds to a minimal mechanistic framework for initiation and orientation of the apical-basal axis to guide both embryonic and postembryonic plant development.}, author = {Wabnik, Krzysztof T and Robert, Hélène and Smith, Richard and Friml, Jirí}, journal = {Current Biology}, number = {24}, pages = {2513 -- 2518}, publisher = {Cell Press}, title = {{Modeling framework for the establishment of the apical-basal embryonic axis in plants}}, doi = {10.1016/j.cub.2013.10.038}, volume = {23}, year = {2013}, } @misc{5399, abstract = {In this work we present a flexible tool for tumor progression, which simulates the evolutionary dynamics of cancer. Tumor progression implements a multi-type branching process where the key parameters are the fitness landscape, the mutation rate, and the average time of cell division. The fitness of a cancer cell depends on the mutations it has accumulated. The input to our tool could be any fitness landscape, mutation rate, and cell division time, and the tool produces the growth dynamics and all relevant statistics.}, author = {Reiter, Johannes and Bozic, Ivana and Chatterjee, Krishnendu and Nowak, Martin}, issn = {2664-1690}, pages = {17}, publisher = {IST Austria}, title = {{TTP: Tool for Tumor Progression}}, doi = {10.15479/AT:IST-2013-104-v1-1}, year = {2013}, } @inproceedings{2295, abstract = {We consider partially observable Markov decision processes (POMDPs) with ω-regular conditions specified as parity objectives. The qualitative analysis problem given a POMDP and a parity objective asks whether there is a strategy to ensure that the objective is satisfied with probability 1 (resp. positive probability). While the qualitative analysis problems are known to be undecidable even for very special cases of parity objectives, we establish decidability (with optimal EXPTIME-complete complexity) of the qualitative analysis problems for POMDPs with all parity objectives under finite-memory strategies. We also establish asymptotically optimal (exponential) memory bounds.}, author = {Chatterjee, Krishnendu and Chmelik, Martin and Tracol, Mathieu}, location = {Torino, Italy}, pages = {165 -- 180}, publisher = {Schloss Dagstuhl - Leibniz-Zentrum für Informatik}, title = {{What is decidable about partially observable Markov decision processes with omega-regular objectives}}, doi = {10.4230/LIPIcs.CSL.2013.165}, volume = {23}, year = {2013}, } @misc{5403, abstract = {We consider concurrent games played by two-players on a finite state graph, where in every round the players simultaneously choose a move, and the current state along with the joint moves determine the successor state. We study the most fundamental objective for concurrent games, namely, mean-payoff or limit-average objective, where a reward is associated to every transition, and the goal of player 1 is to maximize the long-run average of the rewards, and the objective of player 2 is strictly the opposite (i.e., the games are zero-sum). The path constraint for player 1 could be qualitative, i.e., the mean-payoff is the maximal reward, or arbitrarily close to it; or quantitative, i.e., a given threshold between the minimal and maximal reward. We consider the computation of the almost-sure (resp. positive) winning sets, where player 1 can ensure that the path constraint is satisfied with probability 1 (resp. positive probability). Almost-sure winning with qualitative constraint exactly corresponds to the question whether there exists a strategy to ensure that the payoff is the maximal reward of the game. Our main results for qualitative path constraints are as follows: (1) we establish qualitative determinacy results that show for every state either player 1 has a strategy to ensure almost-sure (resp. positive) winning against all player-2 strategies or player 2 has a spoiling strategy to falsify almost-sure (resp. positive) winning against all player-1 strategies; (2) we present optimal strategy complexity results that precisely characterize the classes of strategies required for almost-sure and positive winning for both players; and (3) we present quadratic time algorithms to compute the almost-sure and the positive winning sets, matching the best known bound of the algorithms for much simpler problems (such as reachability objectives). For quantitative constraints we show that a polynomial time solution for the almost-sure or the positive winning set would imply a solution to a long-standing open problem (of solving the value problem of mean-payoff games) that is not known to be in polynomial time.}, author = {Chatterjee, Krishnendu and Ibsen-Jensen, Rasmus}, issn = {2664-1690}, pages = {33}, publisher = {IST Austria}, title = {{Qualitative analysis of concurrent mean-payoff games}}, doi = {10.15479/AT:IST-2013-126-v1-1}, year = {2013}, } @misc{5402, abstract = {Linearizability requires that the outcome of calls by competing threads to a concurrent data structure is the same as some sequential execution where each thread has exclusive access to the data structure. In an ordered data structure, such as a queue or a stack, linearizability is ensured by requiring threads commit in the order dictated by the sequential semantics of the data structure; e.g., in a concurrent queue implementation a dequeue can only remove the oldest element. In this paper, we investigate the impact of this strict ordering, by comparing what linearizability allows to what existing implementations do. We first give an operational definition for linearizability which allows us to build the most general linearizable implementation as a transition system for any given sequential specification. We then use this operational definition to categorize linearizable implementations based on whether they are bound or free. In a bound implementation, whenever all threads observe the same logical state, the updates to the logical state and the temporal order of commits coincide. All existing queue implementations we know of are bound. We then proceed to present, to the best of our knowledge, the first ever free queue implementation. Our experiments show that free implementations have the potential for better performance by suffering less from contention.}, author = {Henzinger, Thomas A and Sezgin, Ali}, issn = {2664-1690}, pages = {16}, publisher = {IST Austria}, title = {{How free is your linearizable concurrent data structure?}}, doi = {10.15479/AT:IST-2013-123-v1-1}, year = {2013}, } @misc{5400, abstract = {We consider partially observable Markov decision processes (POMDPs) with ω-regular conditions specified as parity objectives. The class of ω-regular languages extends regular languages to infinite strings and provides a robust specification language to express all properties used in verification, and parity objectives are canonical forms to express ω-regular conditions. The qualitative analysis problem given a POMDP and a parity objective asks whether there is a strategy to ensure that the objective is satis- fied with probability 1 (resp. positive probability). While the qualitative analysis problems are known to be undecidable even for very special cases of parity objectives, we establish decidability (with optimal complexity) of the qualitative analysis problems for POMDPs with all parity objectives under finite- memory strategies. We establish asymptotically optimal (exponential) memory bounds and EXPTIME- completeness of the qualitative analysis problems under finite-memory strategies for POMDPs with parity objectives.}, author = {Chatterjee, Krishnendu and Chmelik, Martin and Tracol, Mathieu}, issn = {2664-1690}, pages = {41}, publisher = {IST Austria}, title = {{What is decidable about partially observable Markov decision processes with ω-regular objectives}}, doi = {10.15479/AT:IST-2013-109-v1-1}, year = {2013}, } @misc{5404, abstract = {We study finite-state two-player (zero-sum) concurrent mean-payoff games played on a graph. We focus on the important sub-class of ergodic games where all states are visited infinitely often with probability 1. The algorithmic study of ergodic games was initiated in a seminal work of Hoffman and Karp in 1966, but all basic complexity questions have remained unresolved. Our main results for ergodic games are as follows: We establish (1) an optimal exponential bound on the patience of stationary strategies (where patience of a distribution is the inverse of the smallest positive probability and represents a complexity measure of a stationary strategy); (2) the approximation problem lie in FNP; (3) the approximation problem is at least as hard as the decision problem for simple stochastic games (for which NP and coNP is the long-standing best known bound). We show that the exact value can be expressed in the existential theory of the reals, and also establish square-root sum hardness for a related class of games.}, author = {Chatterjee, Krishnendu and Ibsen-Jensen, Rasmus}, issn = {2664-1690}, pages = {29}, publisher = {IST Austria}, title = {{The complexity of ergodic games}}, doi = {10.15479/AT:IST-2013-127-v1-1}, year = {2013}, } @techreport{5401, abstract = {This document is created as a part of the project “Repository for Research Data at IST Austria”. It summarises the actual initiatives, projects and standards related to the project. It supports the preparation of standards and specifications for the project, which should be considered and followed to ensure interoperability and visibility of the uploaded data.}, author = {Porsche, Jana}, publisher = {IST Austria}, title = {{Initiatives and projects related to RD}}, year = {2013}, } @misc{5405, abstract = {The theory of graph games is the foundation for modeling and synthesizing reactive processes. In the synthesis of stochastic processes, we use 2-1/2-player games where some transitions of the game graph are controlled by two adversarial players, the System and the Environment, and the other transitions are determined probabilistically. We consider 2-1/2-player games where the objective of the System is the conjunction of a qualitative objective (specified as a parity condition) and a quantitative objective (specified as a mean-payoff condition). We establish that the problem of deciding whether the System can ensure that the probability to satisfy the mean-payoff parity objective is at least a given threshold is in NP ∩ coNP, matching the best known bound in the special case of 2-player games (where all transitions are deterministic) with only parity objectives, or with only mean-payoff objectives. We present an algorithm running in time O(d · n^{2d}·MeanGame) to compute the set of almost-sure winning states from which the objective can be ensured with probability 1, where n is the number of states of the game, d the number of priorities of the parity objective, and MeanGame is the complexity to compute the set of almost-sure winning states in 2-1/2-player mean-payoff games. Our results are useful in the synthesis of stochastic reactive systems with both functional requirement (given as a qualitative objective) and performance requirement (given as a quantitative objective).}, author = {Chatterjee, Krishnendu and Doyen, Laurent and Gimbert, Hugo and Oualhadj, Youssouf}, issn = {2664-1690}, pages = {22}, publisher = {IST Austria}, title = {{Perfect-information stochastic mean-payoff parity games}}, doi = {10.15479/AT:IST-2013-128-v1-1}, year = {2013}, } @misc{5409, abstract = {The edit distance between two (untimed) traces is the minimum cost of a sequence of edit operations (insertion, deletion, or substitution) needed to transform one trace to the other. Edit distances have been extensively studied in the untimed setting, and form the basis for approximate matching of sequences in different domains such as coding theory, parsing, and speech recognition. In this paper, we lift the study of edit distances from untimed languages to the timed setting. We define an edit distance between timed words which incorporates both the edit distance between the untimed words and the absolute difference in timestamps. Our edit distance between two timed words is computable in polynomial time. Further, we show that the edit distance between a timed word and a timed language generated by a timed automaton, defined as the edit distance between the word and the closest word in the language, is PSPACE-complete. While computing the edit distance between two timed automata is undecidable, we show that the approximate version, where we decide if the edit distance between two timed automata is either less than a given parameter or more than delta away from the parameter, for delta>0, can be solved in exponential space and is EXPSPACE-hard. Our definitions and techniques can be generalized to the setting of hybrid systems, and we show analogous decidability results for rectangular automata.}, author = {Chatterjee, Krishnendu and Ibsen-Jensen, Rasmus and Majumdar, Rupak}, issn = {2664-1690}, pages = {12}, publisher = {IST Austria}, title = {{Edit distance for timed automata}}, doi = {10.15479/AT:IST-2013-144-v1-1}, year = {2013}, } @inproceedings{1376, abstract = {We consider the distributed synthesis problem for temporal logic specifications. Traditionally, the problem has been studied for LTL, and the previous results show that the problem is decidable iff there is no information fork in the architecture. We consider the problem for fragments of LTL and our main results are as follows: (1) We show that the problem is undecidable for architectures with information forks even for the fragment of LTL with temporal operators restricted to next and eventually. (2) For specifications restricted to globally along with non-nested next operators, we establish decidability (in EXPSPACE) for star architectures where the processes receive disjoint inputs, whereas we establish undecidability for architectures containing an information fork-meet structure. (3) Finally, we consider LTL without the next operator, and establish decidability (NEXPTIME-complete) for all architectures for a fragment that consists of a set of safety assumptions, and a set of guarantees where each guarantee is a safety, reachability, or liveness condition.}, author = {Chatterjee, Krishnendu and Henzinger, Thomas A and Otop, Jan and Pavlogiannis, Andreas}, booktitle = {13th International Conference on Formal Methods in Computer-Aided Design}, location = {Portland, OR, United States}, pages = {18 -- 25}, publisher = {IEEE}, title = {{Distributed synthesis for LTL fragments}}, doi = {10.1109/FMCAD.2013.6679386}, year = {2013}, } @misc{5406, abstract = {We consider the distributed synthesis problem fortemporal logic specifications. Traditionally, the problem has been studied for LTL, and the previous results show that the problem is decidable iff there is no information fork in the architecture. We consider the problem for fragments of LTLand our main results are as follows: (1) We show that the problem is undecidable for architectures with information forks even for the fragment of LTL with temporal operators restricted to next and eventually. (2) For specifications restricted to globally along with non-nested next operators, we establish decidability (in EXPSPACE) for star architectures where the processes receive disjoint inputs, whereas we establish undecidability for architectures containing an information fork-meet structure. (3)Finally, we consider LTL without the next operator, and establish decidability (NEXPTIME-complete) for all architectures for a fragment that consists of a set of safety assumptions, and a set of guarantees where each guarantee is a safety, reachability, or liveness condition.}, author = {Chatterjee, Krishnendu and Henzinger, Thomas A and Otop, Jan and Pavlogiannis, Andreas}, issn = {2664-1690}, pages = {11}, publisher = {IST Austria}, title = {{Distributed synthesis for LTL Fragments}}, doi = {10.15479/AT:IST-2013-130-v1-1}, year = {2013}, } @misc{5408, abstract = {We consider two-player partial-observation stochastic games where player 1 has partial observation and player 2 has perfect observation. The winning condition we study are omega-regular conditions specified as parity objectives. The qualitative analysis problem given a partial-observation stochastic game and a parity objective asks whether there is a strategy to ensure that the objective is satisfied with probability 1 (resp. positive probability). While the qualitative analysis problems are known to be undecidable even for very special cases of parity objectives, they were shown to be decidable in 2EXPTIME under finite-memory strategies. We improve the complexity and show that the qualitative analysis problems for partial-observation stochastic parity games under finite-memory strategies are EXPTIME-complete; and also establish optimal (exponential) memory bounds for finite-memory strategies required for qualitative analysis. }, author = {Chatterjee, Krishnendu and Doyen, Laurent and Nain, Sumit and Vardi, Moshe}, issn = {2664-1690}, pages = {17}, publisher = {IST Austria}, title = {{The complexity of partial-observation stochastic parity games with finite-memory strategies}}, doi = {10.15479/AT:IST-2013-141-v1-1}, year = {2013}, } @techreport{5407, abstract = {This document is created as a part of the project “Repository for Research Data at IST Austria”. It summarises the mandatory features, which need to be fulfilled to provide an institutional repository as a platform and also a service to the scientists at the institute. It also includes optional features, which would be of strong benefit for the scientists and would increase the usage of the repository, and hence the visibility of research at IST Austria.}, author = {Porsche, Jana}, publisher = {IST Austria}, title = {{Technical requirements and features}}, year = {2013}, } @misc{5410, abstract = {Board games, like Tic-Tac-Toe and CONNECT-4, play an important role not only in development of mathematical and logical skills, but also in emotional and social development. In this paper, we address the problem of generating targeted starting positions for such games. This can facilitate new approaches for bringing novice players to mastery, and also leads to discovery of interesting game variants. Our approach generates starting states of varying hardness levels for player 1 in a two-player board game, given rules of the board game, the desired number of steps required for player 1 to win, and the expertise levels of the two players. Our approach leverages symbolic methods and iterative simulation to efficiently search the extremely large state space. We present experimental results that include discovery of states of varying hardness levels for several simple grid-based board games. Also, the presence of such states for standard game variants like Tic-Tac-Toe on board size 4x4 opens up new games to be played that have not been played for ages since the default start state is heavily biased. }, author = {Ahmed, Umair and Chatterjee, Krishnendu and Gulwani, Sumit}, issn = {2664-1690}, pages = {13}, publisher = {IST Austria}, title = {{Automatic generation of alternative starting positions for traditional board games}}, doi = {10.15479/AT:IST-2013-146-v1-1}, year = {2013}, } @inproceedings{2327, abstract = {We define the model-measuring problem: given a model M and specification φ, what is the maximal distance ρ such that all models M′ within distance ρ from M satisfy (or violate) φ. The model measuring problem presupposes a distance function on models. We concentrate on automatic distance functions, which are defined by weighted automata. The model-measuring problem subsumes several generalizations of the classical model-checking problem, in particular, quantitative model-checking problems that measure the degree of satisfaction of a specification, and robustness problems that measure how much a model can be perturbed without violating the specification. We show that for automatic distance functions, and ω-regular linear-time and branching-time specifications, the model-measuring problem can be solved. We use automata-theoretic model-checking methods for model measuring, replacing the emptiness question for standard word and tree automata by the optimal-weight question for the weighted versions of these automata. We consider weighted automata that accumulate weights by maximizing, summing, discounting, and limit averaging. We give several examples of using the model-measuring problem to compute various notions of robustness and quantitative satisfaction for temporal specifications.}, author = {Henzinger, Thomas A and Otop, Jan}, location = {Buenos Aires, Argentina}, pages = {273 -- 287}, publisher = {Springer}, title = {{From model checking to model measuring}}, doi = {10.1007/978-3-642-40184-8_20}, volume = {8052}, year = {2013}, } @inproceedings{590, abstract = {We present two methods of creating two orthogonally-polarized focal points at customizable relative locations. These schemes may be critical for enhancing entanglement sources and other applications.}, author = {Schmid, David and Huang, Ting-Yu and Dirks, Radhika and Onur Hosten and Kwiat, Paul G}, publisher = {OSA}, title = {{Polarization dependent focusing}}, doi = {10.1364/QIM.2013.W6.23}, year = {2013}, } @article{5920, abstract = {We study chains of lattice ideals that are invariant under a symmetric group action. In our setting, the ambient rings for these ideals are polynomial rings which are increasing in (Krull) dimension. Thus, these chains will fail to stabilize in the traditional commutative algebra sense. However, we prove a theorem which says that “up to the action of the group”, these chains locally stabilize. We also give an algorithm, which we have implemented in software, for explicitly constructing these stabilization generators for a family of Laurent toric ideals involved in applications to algebraic statistics. We close with several open problems and conjectures arising from our theoretical and computational investigations.}, author = {Hillar, Christopher J. and Martin del Campo Sanchez, Abraham}, issn = {0747-7171}, journal = {Journal of Symbolic Computation}, pages = {314--334}, publisher = {Elsevier}, title = {{Finiteness theorems and algorithms for permutation invariant chains of Laurent lattice ideals}}, doi = {10.1016/j.jsc.2012.06.006}, volume = {50}, year = {2013}, } @article{591, abstract = {We present two methods for the precise independent focusing of orthogonal linear polarizations of light at arbitrary relative locations. Our first scheme uses a displaced lens in a polarization Sagnac interferometer to provide adjustable longitudinal and lateral focal displacements via simple geometry; the second uses uniaxial crystals to achieve the same effect in a compact collinear setup. We develop the theoretical applications and limitations of our schemes, and provide experimental confirmation of our calculations.}, author = {Schmid, David and Huang, Ting-Yu and Hazrat, Shiraz and Dirks, Radhika and Onur Hosten and Quint, Stephan and Thian, Dickson and Kwiat, Paul G}, journal = {Optics Express}, number = {13}, pages = {15538 -- 15552}, publisher = {Optical Society of America}, title = {{Adjustable and robust methods for polarization-dependent focusing}}, doi = {10.1364/OE.21.015538}, volume = {21}, year = {2013}, } @article{595, author = {Bernecky, Carrie A and Cramer, Patrick}, journal = {EMBO Journal}, number = {6}, pages = {771 -- 772}, publisher = {Wiley-Blackwell}, title = {{Struggling to let go: A non-coding RNA directs its own extension and destruction}}, doi = {10.1038/emboj.2013.36}, volume = {32}, year = {2013}, } @article{6128, abstract = {Different interoceptive systems must be integrated to ensure that multiple homeostatic insults evoke appropriate behavioral and physiological responses. Little is known about how this is achieved. Using C. elegans, we dissect cross-modulation between systems that monitor temperature, O2 and CO2. CO2 is less aversive to animals acclimated to 15°C than those grown at 22°C. This difference requires the AFD neurons, which respond to both temperature and CO2 changes. CO2 evokes distinct AFD Ca2+ responses in animals acclimated at 15°C or 22°C. Mutants defective in synaptic transmission can reprogram AFD CO2 responses according to temperature experience, suggesting reprogramming occurs cell autonomously. AFD is exquisitely sensitive to CO2. Surprisingly, gradients of 0.01% CO2/second evoke very different Ca2+ responses from gradients of 0.04% CO2/second. Ambient O2 provides further contextual modulation of CO2 avoidance. At 21% O2 tonic signalling from the O2-sensing neuron URX inhibits CO2 avoidance. This inhibition can be graded according to O2 levels. In a natural wild isolate, a switch from 21% to 19% O2 is sufficient to convert CO2 from a neutral to an aversive cue. This sharp tuning is conferred partly by the neuroglobin GLB-5. The modulatory effects of O2 on CO2 avoidance involve the RIA interneurons, which are post-synaptic to URX and exhibit CO2-evoked Ca2+ responses. Ambient O2 and acclimation temperature act combinatorially to modulate CO2 responsiveness. Our work highlights the integrated architecture of homeostatic responses in C. elegans.}, author = {Kodama-Namba, Eiji and Fenk, Lorenz A. and Bretscher, Andrew J. and Gross, Einav and Busch, K. Emanuel and de Bono, Mario}, issn = {1553-7404}, journal = {PLoS Genetics}, number = {12}, publisher = {Public Library of Science (PLoS)}, title = {{Cross-modulation of homeostatic responses to temperature, oxygen and carbon dioxide in C. elegans}}, doi = {10.1371/journal.pgen.1004011}, volume = {9}, year = {2013}, } @article{6130, abstract = {Cas9 is an RNA-guided double-stranded DNA nuclease that participates in clustered regularly interspaced short palindromic repeats (CRISPR)-mediated adaptive immunity in prokaryotes. CRISPR–Cas9 has recently been used to generate insertion and deletion mutations in Caenorhabditis elegans, but not to create tailored changes (knock-ins). We show that the CRISPR–CRISPR-associated (Cas) system can be adapted for efficient and precise editing of the C. elegans genome. The targeted double-strand breaks generated by CRISPR are substrates for transgene-instructed gene conversion. This allows customized changes in the C. elegans genome by homologous recombination: sequences contained in the repair template (the transgene) are copied by gene conversion into the genome. The possibility to edit the C. elegans genome at selected locations will facilitate the systematic study of gene function in this widely used model organism.}, author = {Chen, Changchun and Fenk, Lorenz A. and de Bono, Mario}, issn = {1362-4962}, journal = {Nucleic Acids Research}, number = {20}, publisher = {Oxford University Press}, title = {{Efficient genome editing in Caenorhabditis elegans by CRISPR-targeted homologous recombination}}, doi = {10.1093/nar/gkt805}, volume = {41}, year = {2013}, } @article{6133, abstract = {cGMP signaling is widespread in the nervous system. However, it has proved difficult to visualize and genetically probe endogenously evoked cGMP dynamics in neurons in vivo. Here, we combine cGMP and Ca2+ biosensors to image and dissect a cGMP signaling network in a Caenorhabditis elegans oxygen-sensing neuron. We show that a rise in O2 can evoke a tonic increase in cGMP that requires an atypical O2-binding soluble guanylate cyclase and that is sustained until oxygen levels fall. Increased cGMP leads to a sustained Ca2+ response in the neuron that depends on cGMP-gated ion channels. Elevated levels of cGMP and Ca2+ stimulate competing negative feedback loops that shape cGMP dynamics. Ca2+-dependent negative feedback loops, including activation of phosphodiesterase-1 (PDE-1), dampen the rise of cGMP. A different negative feedback loop, mediated by phosphodiesterase-2 (PDE-2) and stimulated by cGMP-dependent kinase (PKG), unexpectedly promotes cGMP accumulation following a rise in O2, apparently by keeping in check gating of cGMP channels and limiting activation of Ca2+-dependent negative feedback loops. Simultaneous imaging of Ca2+ and cGMP suggests that cGMP levels can rise close to cGMP channels while falling elsewhere. O2-evoked cGMP and Ca2+ responses are highly reproducible when the same neuron in an individual animal is stimulated repeatedly, suggesting that cGMP transduction has high intrinsic reliability. However, responses vary substantially across individuals, despite animals being genetically identical and similarly reared. This variability may reflect stochastic differences in expression of cGMP signaling components. Our work provides in vivo insights into the architecture of neuronal cGMP signaling.}, author = {Couto, A. and Oda, S. and Nikolaev, V. O. and Soltesz, Z. and de Bono, Mario}, issn = {0027-8424}, journal = {Proceedings of the National Academy of Sciences}, number = {35}, pages = {E3301--E3310}, publisher = {Proceedings of the National Academy of Sciences}, title = {{In vivo genetic dissection of O2-evoked cGMP dynamics in a Caenorhabditis elegans gas sensor}}, doi = {10.1073/pnas.1217428110}, volume = {110}, year = {2013}, } @article{6135, abstract = {Many organisms have stress response pathways, components of which share homology with players in complex human disease pathways. Research on stress response in the nematode worm Caenorhabditis elegans has provided detailed insights into the genetic and molecular mechanisms underlying complex human diseases. In this review we focus on four different types of environmental stress responses – heat shock, oxidative stress, hypoxia, and osmotic stress – and on how these can be used to study the genetics of complex human diseases. All four types of responses involve the genetic machineries that underlie a number of complex human diseases such as cancer and neurodegenerative diseases, including Alzheimer's and Parkinson's. We highlight the types of stress response experiments required to detect the genes and pathways underlying human disease and suggest that studying stress biology in worms can be translated to understanding human disease and provide potential targets for drug discovery.}, author = {Rodriguez, Miriam and Snoek, L. Basten and de Bono, Mario and Kammenga, Jan E.}, issn = {0168-9525}, journal = {Trends in Genetics}, number = {6}, pages = {367--374}, publisher = {Elsevier}, title = {{Worms under stress: C. elegans stress response and its relevance to complex human disease and aging}}, doi = {10.1016/j.tig.2013.01.010}, volume = {29}, year = {2013}, } @inbook{6132, author = {de Bono, Mario and Schafer, W.R. and Gottschalk, A.}, booktitle = {Optogenetics}, editor = {Hegemann, Peter and Sigrist, Stephan}, isbn = {9783110270723; 9783110270716}, pages = {61--78}, publisher = {Walter de Gruyter}, title = {{Optogenetic actuation, inhibition, modulation and readout for neuronal networks generating behavior in the nematode Caenorhabditis elegans}}, year = {2013}, } @article{6370, abstract = {The molecular and supramolecular origins of the superior nonlinear optical (NLO) properties observed in the organic phenolic triene material, OH1 (2-(3-(4-hydroxystyryl)-5,5-dimethylcyclohex-2-enylidene)malononitrile), are presented. The molecular charge-transfer distribution is topographically mapped, demonstrating that a uniformly delocalized passive electronic medium facilitates the charge-transfer between the phenolic electron donor and the cyano electron acceptors which lie at opposite ends of the molecule. Its ability to act as a “push–pull” π-conjugated molecule is quantified, relative to similar materials, by supporting empirical calculations; these include bond-length alternation and harmonic-oscillator stabilization energy (HOSE) tests. Such tests, together with frontier molecular orbital considerations, reveal that OH1 can exist readily in its aromatic (neutral) or quinoidal (charge-separated) state, thereby overcoming the “nonlinearity-thermal stability trade-off”. The HOSE calculation also reveals a correlation between the quinoidal resonance contribution to the overall structure of OH1 and the UV–vis absorption peak wavelength in the wider family of configurationally locked polyene framework materials. Solid-state tensorial coefficients of the molecular dipole, polarizability, and the first hyperpolarizability for OH1 are derived from the first-, second-, and third-order electronic moments of the experimental charge-density distribution. The overall solid-state molecular dipole moment is compared with those from gas-phase calculations, revealing that crystal field effects are very significant in OH1. The solid-state hyperpolarizability derived from this charge-density study affords good agreement with gas-phase calculations as well as optical measurements based on hyper-Rayleigh scattering (HRS) and electric-field-induced second harmonic (EFISH) generation. This lends support to the further use of charge-density studies to calculate solid-state hyperpolarizability coefficients in other organic NLO materials. Finally, this charge-density study is also employed to provide an advanced classification of hydrogen bonds in OH1, which requires more stringent criteria than those from conventional structure analysis. As a result, only the strongest OH···NC interaction is so classified as a true hydrogen bond. Indeed, it is this electrostatic interaction that influences the molecular charge transfer: the other four, weaker, nonbonded contacts nonetheless affect the crystal packing. Overall, the establishment of these structure–property relationships lays a blueprint for designing further, more NLO efficient, materials in this industrially leading organic family of compounds.}, author = {Lin, Tze-Chia and Cole, Jacqueline M. and Higginbotham, Andrew P and Edwards, Alison J. and Piltz, Ross O. and Pérez-Moreno, Javier and Seo, Ji-Youn and Lee, Seung-Chul and Clays, Koen and Kwon, O-Pil}, issn = {1932-7447}, journal = {The Journal of Physical Chemistry C}, number = {18}, pages = {9416--9430}, publisher = {American Chemical Society (ACS)}, title = {{Molecular origins of the high-performance nonlinear optical susceptibility in a phenolic polyene chromophore: Electron density distributions, hydrogen bonding, and ab initio calculations}}, doi = {10.1021/jp400648q}, volume = {117}, year = {2013}, } @misc{6440, abstract = {In order to guarantee that each method of a data structure updates the logical state exactly once, al-most all non-blocking implementations employ Compare-And-Swap (CAS) based synchronization. For FIFO queue implementations this translates into concurrent enqueue or dequeue methods competing among themselves to update the same variable, the tail or the head, respectively, leading to high contention and poor scalability. Recent non-blocking queue implementations try to alleviate high contentionby increasing the number of contention points, all the while using CAS-based synchronization. Furthermore, obtaining a wait-free implementation with competition is achieved by additional synchronization which leads to further degradation of performance.In this paper we formalize the notion of competitiveness of a synchronizing statement which can beused as a measure for the scalability of concurrent implementations. We present a new queue implementation, the Speculative Pairing (SP) queue, which, as we show, decreases competitiveness by using Fetch-And-Increment (FAI) instead of CAS. We prove that the SP queue is linearizable and lock-free.We also show that replacing CAS with FAI leads to wait-freedom for dequeue methods without an adverse effect on performance. In fact, our experiments suggest that the SP queue can perform and scale better than the state-of-the-art queue implementations.}, author = {Henzinger, Thomas A and Payer, Hannes and Sezgin, Ali}, issn = {2664-1690}, pages = {23}, publisher = {IST Austria}, title = {{Replacing competition with cooperation to achieve scalable lock-free FIFO queues }}, doi = {10.15479/AT:IST-2013-124-v1-1}, year = {2013}, } @article{6768, abstract = {The paper presents an algorithm that applies a stack filter simulating the Mean Curvature Motion equation via a finite difference scheme.}, author = {Mondelli, Marco}, issn = {2105-1232}, journal = {Image Processing On Line}, pages = {68--111}, publisher = {Image Processing On Line}, title = {{A finite difference scheme for the stack filter simulating the MCM}}, doi = {10.5201/ipol.2013.53}, volume = {3}, year = {2013}, } @inproceedings{2329, abstract = {Two-player games on graphs are central in many problems in formal verification and program analysis such as synthesis and verification of open systems. In this work, we consider both finite-state game graphs, and recursive game graphs (or pushdown game graphs) that model the control flow of sequential programs with recursion. The objectives we study are multidimensional mean-payoff objectives, where the goal of player 1 is to ensure that the mean-payoff is non-negative in all dimensions. In pushdown games two types of strategies are relevant: (1) global strategies, that depend on the entire global history; and (2) modular strategies, that have only local memory and thus do not depend on the context of invocation. Our main contributions are as follows: (1) We show that finite-state multidimensional mean-payoff games can be solved in polynomial time if the number of dimensions and the maximal absolute value of the weights are fixed; whereas if the number of dimensions is arbitrary, then the problem is known to be coNP-complete. (2) We show that pushdown graphs with multidimensional mean-payoff objectives can be solved in polynomial time. For both (1) and (2) our algorithms are based on hyperplane separation technique. (3) For pushdown games under global strategies both one and multidimensional mean-payoff objectives problems are known to be undecidable, and we show that under modular strategies the multidimensional problem is also undecidable; under modular strategies the one-dimensional problem is NP-complete. We show that if the number of modules, the number of exits, and the maximal absolute value of the weights are fixed, then pushdown games under modular strategies with one-dimensional mean-payoff objectives can be solved in polynomial time, and if either the number of exits or the number of modules is unbounded, then the problem is NP-hard. (4) Finally we show that a fixed parameter tractable algorithm for finite-state multidimensional mean-payoff games or pushdown games under modular strategies with one-dimensional mean-payoff objectives would imply the fixed parameter tractability of parity games.}, author = {Chatterjee, Krishnendu and Velner, Yaron}, location = {Buenos Aires, Argentinia}, pages = {500 -- 515}, publisher = {Springer}, title = {{Hyperplane separation technique for multidimensional mean-payoff games}}, doi = {10.1007/978-3-642-40184-8_35}, volume = {8052}, year = {2013}, } @article{7306, abstract = {Rechargeable lithium–air (O2) batteries are receiving intense interest because their high theoretical specific energy exceeds that of lithium-ion batteries. If the Li–O2 battery is ever to succeed, highly reversible formation/decomposition of Li2O2 must take place at the cathode on cycling. However, carbon, used ubiquitously as the basis of the cathode, decomposes during Li2O2 oxidation on charge and actively promotes electrolyte decomposition on cycling. Replacing carbon with a nanoporous gold cathode, when in contact with a dimethyl sulphoxide-based electrolyte, does seem to demonstrate better stability. However, nanoporous gold is not a suitable cathode; its high mass destroys the key advantage of Li–O2 over Li ion (specific energy), it is too expensive and too difficult to fabricate. Identifying a suitable cathode material for the Li–O2 cell is one of the greatest challenges at present. Here we show that a TiC-based cathode reduces greatly side reactions (arising from the electrolyte and electrode degradation) compared with carbon and exhibits better reversible formation/decomposition of Li2O2 even than nanoporous gold (>98% capacity retention after 100 cycles, compared with 95% for nanoporous gold); it is also four times lighter, of lower cost and easier to fabricate. The stability may originate from the presence of TiO2 (along with some TiOC) on the surface of TiC. In contrast to carbon or nanoporous gold, TiC seems to represent a more viable, stable, cathode for aprotic Li–O2 cells.}, author = {Ottakam Thotiyl, Muhammed M. and Freunberger, Stefan Alexander and Peng, Zhangquan and Chen, Yuhui and Liu, Zheng and Bruce, Peter G.}, issn = {1476-1122}, journal = {Nature Materials}, number = {11}, pages = {1050--1056}, publisher = {Springer Nature}, title = {{A stable cathode for the aprotic Li–O2 battery}}, doi = {10.1038/nmat3737}, volume = {12}, year = {2013}, } @article{7307, abstract = {The non-aqueous Li–air (O2) battery is receiving intense interest because its theoretical specific energy exceeds that of Li-ion batteries. Recharging the Li–O2 battery depends on oxidizing solid lithium peroxide (Li2O2), which is formed on discharge within the porous cathode. However, transporting charge between Li2O2 particles and the solid electrode surface is at best very difficult and leads to voltage polarization on charging, even at modest rates. This is a significant problem facing the non-aqueous Li–O2 battery. Here we show that incorporation of a redox mediator, tetrathiafulvalene (TTF), enables recharging at rates that are impossible for the cell in the absence of the mediator. On charging, TTF is oxidized to TTF+ at the cathode surface; TTF+ in turn oxidizes the solid Li2O2, which results in the regeneration of TTF. The mediator acts as an electron–hole transfer agent that permits efficient oxidation of solid Li2O2. The cell with the mediator demonstrated 100 charge/discharge cycles.}, author = {Chen, Yuhui and Freunberger, Stefan Alexander and Peng, Zhangquan and Fontaine, Olivier and Bruce, Peter G.}, issn = {1755-4330}, journal = {Nature Chemistry}, number = {6}, pages = {489--494}, publisher = {Springer Nature}, title = {{Charging a Li–O2 battery using a redox mediator}}, doi = {10.1038/nchem.1646}, volume = {5}, year = {2013}, } @article{7596, abstract = {Casein kinase1 (CK1) plays crucial roles in regulating growth and development via phosphorylating various substrates throughout the eukaryote kingdom. Blue light is crucial for normal growth of both plants and animals, and blue light receptor cryptochrome2 (CRY2) undergoes blue light–dependent phosphorylation and degradation in planta. To study the function of plant CK1s, systematic genetic analysis showed that deficiency of two paralogous Arabidopsis thaliana CK1s, CK1.3 and CK1.4, caused shortened hypocotyls, especially under blue light, while overexpression of either CK1.3 or CK1.4 resulted in the insensitive response to blue light and delayed flowering under long-day conditions. CK1.3 or CK1.4 act dependently on CRY2, and overexpression of CK1.3 or CK1.4 significantly suppresses the hypersensitive response to blue light by CRY2 overexpression. Biochemical studies showed that CK1.3 and CK1.4 directly phosphorylate CRY2 at Ser-587 and Thr-603 in vitro and negatively regulate CRY2 stability in planta, which are stimulated by blue light, further confirming the crucial roles of CK1.3 and CK1.4 in blue light responses through phosphorylating CRY2. Interestingly, expression of CK1.3 and CK1.4 is stimulated by blue light and feedback regulated by CRY2-mediated signaling. These results provide direct evidence for CRY2 phosphorylation and informative clues on the mechanisms of CRY2-mediated light responses.}, author = {Tan, Shutang and Dai, C. and Liu, H.-T. and Xue, H.-W.}, issn = {1040-4651}, journal = {The Plant Cell}, number = {7}, pages = {2618--2632}, publisher = {American Society of Plant Biologists}, title = {{Arabidopsis casein kinase1 proteins CK1.3 and CK1.4 phosphorylate cryptochrome2 to regulate blue light signaling}}, doi = {10.1105/tpc.113.114322}, volume = {25}, year = {2013}, } @article{7595, abstract = {Inositol 1,3,4-trisphosphate 5/6 kinase (ITPK) phosphorylates inositol 1,3,4-trisphosphate to form inositol 1,3,4,5-tetrakisphosphate and inositol 1,3,4,6-tetrakisphosphate which can be finally transferred to inositol hexaphosphate (IP6) and play important roles during plant growth and development. There are 4 putative ITPK members in Arabidopsis. Expression pattern analysis showed that ITPK2 is constitutively expressed in various tissues. A T-DNA knockout mutant of ITPK2 was identified and scanning electron microscopy (SEM) analysis showed that the epidermis structure of seed coat was irregularly formed in seeds of itpk2-1 mutant, resulting in the increased permeability of seed coat to tetrazolium salts. Further analysis by gas chromatography coupled with mass spectrometry of lipid polyester monomers in cell wall confirmed a dramatic decrease in composition of suberin and cutin, which relate to the permeability of seed coat and the formation of which is accompanied with seed coat development. These results indicate that ITPK2 plays an essential role in seed coat development and lipid polyester barrier formation.}, author = {Tang, Yong and Tan, Shutang and Xue, Hongwei}, issn = {1745-7270}, journal = {Acta Biochimica et Biophysica Sinica}, number = {7}, pages = {549--560}, publisher = {Oxford University Press}, title = {{Arabidopsis inositol 1,3,4-trisphosphate 5/6 kinase 2 is required for seed coat development}}, doi = {10.1093/abbs/gmt039}, volume = {45}, year = {2013}, } @inproceedings{765, abstract = {Renaming is a classic distributed coordination task in which a set of processes must pick distinct identifiers from a small namespace. In this paper, we consider the time complexity of this problem when the namespace is linear in the number of participants, a variant known as loose renaming. We give a non-adaptive algorithm with O(log log n) (individual) step complexity, where n is a known upper bound on contention, and an adaptive algorithm with step complexity O((log log k)2), where k is the actual contention in the execution. We also present a variant of the adaptive algorithm which requires O(k log log k) total process steps. All upper bounds hold with high probability against a strong adaptive adversary. We complement the algorithms with an ω(log log n) expected time lower bound on the complexity of randomized renaming using test-and-set operations and linear space. The result is based on a new coupling technique, and is the first to apply to non-adaptive randomized renaming. Since our algorithms use O(n) test-and-set objects, our results provide matching bounds on the cost of loose renaming in this setting.}, author = {Alistarh, Dan-Adrian and Aspnes, James and Giakkoupis, George and Woelfel, Philipp}, pages = {200 -- 209}, publisher = {ACM}, title = {{Randomized loose renaming in O(loglogn) time}}, doi = {10.1145/2484239.2484240}, year = {2013}, } @article{7745, abstract = {The underlying basis of genetic variation in quantitative traits, in terms of the number of causal variants and the size of their effects, is largely unknown in natural populations. The expectation is that complex quantitative trait variation is attributable to many, possibly interacting, causal variants, whose effects may depend upon the sex, age and the environment in which they are expressed. A recently developed methodology in animal breeding derives a value of relatedness among individuals from high‐density genomic marker data, to estimate additive genetic variance within livestock populations. Here, we adapt and test the effectiveness of these methods to partition genetic variation for complex traits across genomic regions within ecological study populations where individuals have varying degrees of relatedness. We then apply this approach for the first time to a natural population and demonstrate that genetic variation in wing length in the great tit (Parus major) reflects contributions from multiple genomic regions. We show that a polygenic additive mode of gene action best describes the patterns observed, and we find no evidence of dosage compensation for the sex chromosome. Our results suggest that most of the genomic regions that influence wing length have the same effects in both sexes. We found a limited amount of genetic variance in males that is attributed to regions that have no effects in females, which could facilitate the sexual dimorphism observed for this trait. Although this exploratory work focuses on one complex trait, the methodology is generally applicable to any trait for any laboratory or wild population, paving the way for investigating sex‐, age‐ and environment‐specific genetic effects and thus the underlying genetic architecture of phenotype in biological study systems.}, author = {Robinson, Matthew Richard and Santure, Anna W. and DeCauwer, Isabelle and Sheldon, Ben C. and Slate, Jon}, issn = {0962-1083}, journal = {Molecular Ecology}, number = {15}, pages = {3963--3980}, publisher = {Wiley}, title = {{Partitioning of genetic variation across the genome using multimarker methods in a wild bird population}}, doi = {10.1111/mec.12375}, volume = {22}, year = {2013}, } @article{7746, abstract = {Clutch size and egg mass are life history traits that have been extensively studied in wild bird populations, as life history theory predicts a negative trade‐off between them, either at the phenotypic or at the genetic level. Here, we analyse the genomic architecture of these heritable traits in a wild great tit (Parus major) population, using three marker‐based approaches – chromosome partitioning, quantitative trait locus (QTL) mapping and a genome‐wide association study (GWAS). The variance explained by each great tit chromosome scales with predicted chromosome size, no location in the genome contains genome‐wide significant QTL, and no individual SNPs are associated with a large proportion of phenotypic variation, all of which may suggest that variation in both traits is due to many loci of small effect, located across the genome. There is no evidence that any regions of the genome contribute significantly to both traits, which combined with a small, nonsignificant negative genetic covariance between the traits, suggests the absence of genetic constraints on the independent evolution of these traits. Our findings support the hypothesis that variation in life history traits in natural populations is likely to be determined by many loci of small effect spread throughout the genome, which are subject to continued input of variation by mutation and migration, although we cannot exclude the possibility of an additional input of major effect genes influencing either trait.}, author = {Santure, Anna W. and De Cauwer, Isabelle and Robinson, Matthew Richard and Poissant, Jocelyn and Sheldon, Ben C. and Slate, Jon}, issn = {0962-1083}, journal = {Molecular Ecology}, number = {15}, pages = {3949--3962}, publisher = {Wiley}, title = {{Genomic dissection of variation in clutch size and egg mass in a wild great tit (Parus major) population}}, doi = {10.1111/mec.12376}, volume = {22}, year = {2013}, } @article{7747, abstract = {Acquisition and allocation of resources are central to life‐history theory. However, empirical work typically focuses only on allocation despite the fact that relationships between fitness components may be governed by differences in the ability of individuals to acquire resources across environments. Here, we outline a statistical framework to partition the genetic basis of multivariate plasticity into independent axes of genetic variation, and quantify for the first time, the extent to which specific traits drive multitrait genotype–environment interactions. Our framework generalises to analyses of plasticity, growth and ageing. We apply this approach to a unique, large‐scale, multivariate study of acquisition, allocation and plasticity in the life history of the cricket, Gryllus firmus. We demonstrate that resource acquisition and allocation are genetically correlated, and that plasticity in trade‐offs between allocation to components of fitness is 90% dependent on genetic variance for total resource acquisition. These results suggest that genotype–environment effects for resource acquisition can maintain variation in life‐history components that are typically observed in the wild.}, author = {Robinson, Matthew Richard and Beckerman, Andrew P.}, issn = {1461-023X}, journal = {Ecology Letters}, number = {3}, pages = {281--290}, publisher = {Wiley}, title = {{Quantifying multivariate plasticity: Genetic variation in resource acquisition drives plasticity in resource allocation to components of life history}}, doi = {10.1111/ele.12047}, volume = {16}, year = {2013}, }