@article{469, abstract = {Spontaneous release of glutamate is important for maintaining synaptic strength and controlling spike timing in the brain. Mechanisms regulating spontaneous exocytosis remain poorly understood. Extracellular calcium concentration ([Ca2+]o) regulates Ca2+ entry through voltage-activated calcium channels (VACCs) and consequently is a pivotal determinant of action potential-evoked vesicle fusion. Extracellular Ca 2+ also enhances spontaneous release, but via unknown mechanisms. Here we report that external Ca2+ triggers spontaneous glutamate release more weakly than evoked release in mouse neocortical neurons. Blockade of VACCs has no effect on the spontaneous release rate or its dependence on [Ca2+]o. Intracellular [Ca2+] slowly increases in a minority of neurons following increases in [Ca2+]o. Furthermore, the enhancement of spontaneous release by extracellular calcium is insensitive to chelation of intracellular calcium by BAPTA. Activation of the calcium-sensing receptor (CaSR), a G-protein-coupled receptor present in nerve terminals, by several specific agonists increased spontaneous glutamate release. The frequency of spontaneous synaptic transmission was decreased in CaSR mutant neurons. The concentration-effect relationship for extracellular calcium regulation of spontaneous release was well described by a combination of CaSR-dependent and CaSR-independent mechanisms. Overall these results indicate that extracellular Ca2+ does not trigger spontaneous glutamate release by simply increasing calcium influx but stimulates CaSR and thereby promotes resting spontaneous glutamate release. }, author = {Vyleta, Nicholas and Smith, Stephen}, journal = {European Journal of Neuroscience}, number = {12}, pages = {4593 -- 4606}, publisher = {Wiley-Blackwell}, title = {{Spontaneous glutamate release is independent of calcium influx and tonically activated by the calcium-sensing receptor}}, doi = {10.1523/JNEUROSCI.6398-10.2011}, volume = {31}, year = {2011}, } @article{490, abstract = {BioSig is an open source software library for biomedical signal processing. The aim of the BioSig project is to foster research in biomedical signal processing by providing free and open source software tools for many different application areas. Some of the areas where BioSig can be employed are neuroinformatics, brain-computer interfaces, neurophysiology, psychology, cardiovascular systems, and sleep research. Moreover, the analysis of biosignals such as the electroencephalogram (EEG), electrocorticogram (ECoG), electrocardiogram (ECG), electrooculogram (EOG), electromyogram (EMG), or respiration signals is a very relevant element of the BioSig project. Specifically, BioSig provides solutions for data acquisition, artifact processing, quality control, feature extraction, classification, modeling, and data visualization, to name a few. In this paper, we highlight several methods to help students and researchers to work more efficiently with biomedical signals. }, author = {Schlögl, Alois and Vidaurre, Carmen and Sander, Tilmann}, journal = {Computational Intelligence and Neuroscience}, publisher = {Hindawi Publishing Corporation}, title = {{BioSig: The free and open source software library for biomedical signal processing}}, doi = {10.1155/2011/935364}, volume = {2011}, year = {2011}, } @article{491, abstract = {In their search for antigens, lymphocytes continuously shuttle among blood vessels, lymph vessels, and lymphatic tissues. Chemokines mediate entry of lymphocytes into lymphatic tissues, and sphingosine 1-phosphate (S1P) promotes localization of lymphocytes to the vasculature. Both signals are sensed through G protein-coupled receptors (GPCRs). Most GPCRs undergo ligand-dependent homologous receptor desensitization, a process that decreases their signaling output after previous exposure to high ligand concentration. Such desensitization can explain why lymphocytes do not take an intermediate position between two signals but rather oscillate between them. The desensitization of S1P receptor 1 (S1PR1) is mediated by GPCR kinase 2 (GRK2). Deletion of GRK2 in lymphocytes compromises desensitization by high vascular S1P concentrations, thereby reducing responsiveness to the chemokine signal and trapping the cells in the vascular compartment. The desensitization kinetics of S1PR1 allows lymphocytes to dynamically shuttle between vasculature and lymphatic tissue, although the positional information in both compartments is static.}, author = {Eichner, Alexander and Sixt, Michael K}, journal = {Science Signaling}, number = {198}, publisher = {American Association for the Advancement of Science}, title = {{Setting the clock for recirculating lymphocytes}}, doi = {10.1126/scisignal.2002617}, volume = {4}, year = {2011}, } @article{518, abstract = {Cancer stem cells or cancer initiating cells are believed to contribute to cancer recurrence after therapy. MicroRNAs (miRNAs) are short RNA molecules with fundamental roles in gene regulation. The role of miRNAs in cancer stem cells is only poorly understood. Here, we report miRNA expression profiles of glioblastoma stem cell-containing CD133 + cell populations. We find that miR-9, miR-9 * (referred to as miR-9/9 *), miR-17 and miR-106b are highly abundant in CD133 + cells. Furthermore, inhibition of miR-9/9 * or miR-17 leads to reduced neurosphere formation and stimulates cell differentiation. Calmodulin-binding transcription activator 1 (CAMTA1) is a putative transcription factor, which induces the expression of the anti-proliferative cardiac hormone natriuretic peptide A (NPPA). We identify CAMTA1 as an miR-9/9 * and miR-17 target. CAMTA1 expression leads to reduced neurosphere formation and tumour growth in nude mice, suggesting that CAMTA1 can function as tumour suppressor. Consistently, CAMTA1 and NPPA expression correlate with patient survival. Our findings could provide a basis for novel strategies of glioblastoma therapy.}, author = {Schraivogel, Daniel and Weinmann, Lasse and Beier, Dagmar and Tabatabai, Ghazaleh and Eichner, Alexander and Zhu, Jia and Anton, Martina and Sixt, Michael K and Weller, Michael and Beier, Christoph and Meister, Gunter}, journal = {EMBO Journal}, number = {20}, pages = {4309 -- 4322}, publisher = {Wiley-Blackwell}, title = {{CAMTA1 is a novel tumour suppressor regulated by miR-9/9 * in glioblastoma stem cells}}, doi = {10.1038/emboj.2011.301}, volume = {30}, year = {2011}, } @article{531, abstract = {Software transactional memories (STM) are described in the literature with assumptions of sequentially consistent program execution and atomicity of high level operations like read, write, and abort. However, in a realistic setting, processors use relaxed memory models to optimize hardware performance. Moreover, the atomicity of operations depends on the underlying hardware. This paper presents the first approach to verify STMs under relaxed memory models with atomicity of 32 bit loads and stores, and read-modify-write operations. We describe RML, a simple language for expressing concurrent programs. We develop a semantics of RML parametrized by a relaxed memory model. We then present our tool, FOIL, which takes as input the RML description of an STM algorithm restricted to two threads and two variables, and the description of a memory model, and automatically determines the locations of fences, which if inserted, ensure the correctness of the restricted STM algorithm under the given memory model. We use FOIL to verify DSTM, TL2, and McRT STM under the memory models of sequential consistency, total store order, partial store order, and relaxed memory order for two threads and two variables. Finally, we extend the verification results for DSTM and TL2 to an arbitrary number of threads and variables by manually proving that the structural properties of STMs are satisfied at the hardware level of atomicity under the considered relaxed memory models.}, author = {Guerraoui, Rachid and Henzinger, Thomas A and Singh, Vasu}, journal = {Formal Methods in System Design}, number = {3}, pages = {297 -- 331}, publisher = {Springer}, title = {{Verification of STM on relaxed memory models}}, doi = {10.1007/s10703-011-0131-3}, volume = {39}, year = {2011}, } @misc{5379, abstract = {Computing the winning set for Büchi objectives in alternating games on graphs is a central problem in computer aided verification with a large number of applications. The long standing best known upper bound for solving the problem is ̃O(n·m), where n is the number of vertices and m is the number of edges in the graph. We are the first to break the ̃O(n·m) boundary by presenting a new technique that reduces the running time to O(n2). This bound also leads to O(n2) time algorithms for computing the set of almost-sure winning vertices for Büchi objectives (1) in alternating games with probabilistic transitions (improving an earlier bound of O(n·m)), (2) in concurrent graph games with constant actions (improving an earlier bound of O(n3)), and (3) in Markov decision processes (improving for m > n4/3 an earlier bound of O(min(m1.5, m·n2/3)). We also show that the same technique can be used to compute the maximal end-component decomposition of a graph in time O(n2), which is an improvement over earlier bounds for m > n4/3. Finally, we show how to maintain the winning set for Büchi objectives in alternating games under a sequence of edge insertions or a sequence of edge deletions in O(n) amortized time per operation. This is the first dynamic algorithm for this problem.}, author = {Chatterjee, Krishnendu and Henzinger, Monika H}, issn = {2664-1690}, pages = {20}, publisher = {IST Austria}, title = {{An O(n2) time algorithm for alternating Büchi games}}, doi = {10.15479/AT:IST-2011-0009}, year = {2011}, } @misc{5380, abstract = {We consider 2-player games played on a finite state space for an infinite number of rounds. The games are concurrent: in each round, the two players (player 1 and player 2) choose their moves independently and simultaneously; the current state and the two moves determine the successor state. We study concurrent games with ω-regular winning conditions specified as parity objectives. We consider the qualitative analysis problems: the computation of the almost-sure and limit-sure winning set of states, where player 1 can ensure to win with probability 1 and with probability arbitrarily close to 1, respectively. In general the almost-sure and limit-sure winning strategies require both infinite-memory as well as infinite-precision (to describe probabilities). We study the bounded-rationality problem for qualitative analysis of concurrent parity games, where the strategy set for player 1 is restricted to bounded-resource strategies. In terms of precision, strategies can be deterministic, uniform, finite-precision or infinite-precision; and in terms of memory, strategies can be memoryless, finite-memory or infinite-memory. We present a precise and complete characterization of the qualitative winning sets for all combinations of classes of strategies. In particular, we show that uniform memoryless strategies are as powerful as finite-precision infinite-memory strategies, and infinite-precision memoryless strategies are as powerful as infinite-precision finite-memory strategies. We show that the winning sets can be computed in O(n2d+3) time, where n is the size of the game structure and 2d is the number of priorities (or colors), and our algorithms are symbolic. The membership problem of whether a state belongs to a winning set can be decided in NP ∩ coNP. While this complexity is the same as for the simpler class of turn-based parity games, where in each state only one of the two players has a choice of moves, our algorithms,that are obtained by characterization of the winning sets as μ-calculus formulas, are considerably more involved than those for turn-based games.}, author = {Chatterjee, Krishnendu}, issn = {2664-1690}, pages = {53}, publisher = {IST Austria}, title = {{Bounded rationality in concurrent parity games}}, doi = {10.15479/AT:IST-2011-0008}, year = {2011}, } @misc{5382, abstract = {We consider two-player stochastic games played on a finite state space for an infinite num- ber of rounds. The games are concurrent: in each round, the two players (player 1 and player 2) choose their moves independently and simultaneously; the current state and the two moves determine a probability distribution over the successor states. We also consider the important special case of turn-based stochastic games where players make moves in turns, rather than concurrently. We study concurrent games with ω-regular winning conditions specified as parity objectives. The value for player 1 for a parity objective is the maximal probability with which the player can guarantee the satisfaction of the objective against all strategies of the opponent. We study the problem of continuity and robustness of the value function in concurrent and turn-based stochastic parity games with respect to imprecision in the transition probabilities. We present quantitative bounds on the difference of the value function (in terms of the imprecision of the transition probabilities) and show the value continuity for structurally equivalent concurrent games (two games are structurally equivalent if the support of the transition func- tion is same and the probabilities differ). We also show robustness of optimal strategies for structurally equivalent turn-based stochastic parity games. Finally we show that the value continuity property breaks without the structurally equivalent assumption (even for Markov chains) and show that our quantitative bound is asymptotically optimal. Hence our results are tight (the assumption is both necessary and sufficient) and optimal (our quantitative bound is asymptotically optimal).}, author = {Chatterjee, Krishnendu}, issn = {2664-1690}, pages = {18}, publisher = {IST Austria}, title = {{Robustness of structurally equivalent concurrent parity games}}, doi = {10.15479/AT:IST-2011-0006}, year = {2011}, } @misc{5383, abstract = {We present a new decidable logic called TREX for expressing constraints about imperative tree data structures. In particular, TREX supports a transitive closure operator that can express reachability constraints, which often appear in data structure invariants. We show that our logic is closed under weakest precondition computation, which enables its use for automated software verification. We further show that satisfiability of formulas in TREX is decidable in NP. The low complexity makes it an attractive alternative to more expensive logics such as monadic second-order logic (MSOL) over trees, which have been traditionally used for reasoning about tree data structures.}, author = {Wies, Thomas and Muñiz, Marco and Kuncak, Viktor}, issn = {2664-1690}, pages = {25}, publisher = {IST Austria}, title = {{On an efficient decision procedure for imperative tree data structures}}, doi = {10.15479/AT:IST-2011-0005}, year = {2011}, } @misc{5384, abstract = {We consider probabilistic automata on infinite words with acceptance defined by parity conditions. We consider three qualitative decision problems: (i) the positive decision problem asks whether there is a word that is accepted with positive probability; (ii) the almost decision problem asks whether there is a word that is accepted with probability 1; and (iii) the limit decision problem asks whether for every ε > 0 there is a word that is accepted with probability at least 1 − ε. We unify and generalize several decidability results for probabilistic automata over infinite words, and identify a robust (closed under union and intersection) subclass of probabilistic automata for which all the qualitative decision problems are decidable for parity conditions. We also show that if the input words are restricted to lasso shape words, then the positive and almost problems are decidable for all probabilistic automata with parity conditions.}, author = {Chatterjee, Krishnendu and Tracol, Mathieu}, issn = {2664-1690}, pages = {30}, publisher = {IST Austria}, title = {{Decidable problems for probabilistic automata on infinite words}}, doi = {10.15479/AT:IST-2011-0004}, year = {2011}, } @misc{5386, abstract = {We introduce TopoCut: a new way to integrate knowledge about topological properties (TPs) into random field image segmentation model. Instead of including TPs as additional constraints during minimization of the energy function, we devise an efficient algorithm for modifying the unary potentials such that the resulting segmentation is guaranteed with the desired properties. Our method is more flexible in the sense that it handles more topology constraints than previous methods, which were only able to enforce pairwise or global connectivity. In particular, our method is very fast, making it for the first time possible to enforce global topological properties in practical image segmentation tasks.}, author = {Chen, Chao and Freedman, Daniel and Lampert, Christoph}, issn = {2664-1690}, pages = {69}, publisher = {IST Austria}, title = {{Enforcing topological constraints in random field image segmentation}}, doi = {10.15479/AT:IST-2011-0002}, year = {2011}, } @misc{5387, abstract = {We consider Markov Decision Processes (MDPs) with mean-payoff parity and energy parity objectives. In system design, the parity objective is used to encode ω-regular specifications, and the mean-payoff and energy objectives can be used to model quantitative resource constraints. The energy condition re- quires that the resource level never drops below 0, and the mean-payoff condi- tion requires that the limit-average value of the resource consumption is within a threshold. While these two (energy and mean-payoff) classical conditions are equivalent for two-player games, we show that they differ for MDPs. We show that the problem of deciding whether a state is almost-sure winning (i.e., winning with probability 1) in energy parity MDPs is in NP ∩ coNP, while for mean- payoff parity MDPs, the problem is solvable in polynomial time, improving a recent PSPACE bound.}, author = {Chatterjee, Krishnendu and Doyen, Laurent}, issn = {2664-1690}, pages = {20}, publisher = {IST Austria}, title = {{Energy and mean-payoff parity Markov decision processes}}, doi = {10.15479/AT:IST-2011-0001}, year = {2011}, } @article{9483, abstract = {Imprinted genes are expressed primarily or exclusively from either the maternal or paternal allele, a phenomenon that occurs in flowering plants and mammals. Flowering plant imprinted gene expression has been described primarily in endosperm, a terminal nutritive tissue consumed by the embryo during seed development or after germination. Imprinted expression in Arabidopsis thaliana endosperm is orchestrated by differences in cytosine DNA methylation between the paternal and maternal genomes as well as by Polycomb group proteins. Currently, only 11 imprinted A. thaliana genes are known. Here, we use extensive sequencing of cDNA libraries to identify 9 paternally expressed and 34 maternally expressed imprinted genes in A. thaliana endosperm that are regulated by the DNA-demethylating glycosylase DEMETER, the DNA methyltransferase MET1, and/or the core Polycomb group protein FIE. These genes encode transcription factors, proteins involved in hormone signaling, components of the ubiquitin protein degradation pathway, regulators of histone and DNA methylation, and small RNA pathway proteins. We also identify maternally expressed genes that may be regulated by unknown mechanisms or deposited from maternal tissues. We did not detect any imprinted genes in the embryo. Our results show that imprinted gene expression is an extensive mechanistically complex phenomenon that likely affects multiple aspects of seed development.}, author = {Hsieh, Tzung-Fu and Shin, Juhyun and Uzawa, Rie and Silva, Pedro and Cohen, Stephanie and Bauer, Matthew J. and Hashimoto, Meryl and Kirkbride, Ryan C. and Harada, John J. and Zilberman, Daniel and Fischer, Robert L.}, issn = {1091-6490}, journal = {Proceedings of the National Academy of Sciences}, number = {5}, pages = {1755--1762}, publisher = {National Academy of Sciences}, title = {{Regulation of imprinted gene expression in Arabidopsis endosperm}}, doi = {10.1073/pnas.1019273108}, volume = {108}, year = {2011}, } @misc{9522, abstract = {Little is known about chromatin remodeling events immediately after fertilization. A recent report by Autran et al. (2011) in Cell now shows that chromatin regulatory pathways that silence transposable elements are responsible for global delayed activation of gene expression in the early Arabidopsis embryo.}, author = {Zilberman, Daniel}, booktitle = {Developmental Cell}, issn = {1878-1551}, number = {6}, pages = {735--736}, publisher = {Elsevier}, title = {{Balancing parental contributions in plant embryonic gene activation}}, doi = {10.1016/j.devcel.2011.05.018}, volume = {20}, year = {2011}, } @inproceedings{9648, abstract = {In this paper, we establish a correspondence between the incremental algorithm for computing AT-models [8,9] and the one for computing persistent homology [6,14,15]. We also present a decremental algorithm for computing AT-models that allows to extend the persistence computation to a wider setting. Finally, we show how to combine incremental and decremental techniques for persistent homology computation.}, author = {Gonzalez-Diaz, Rocio and Ion, Adrian and Jimenez, Maria Jose and Poyatos, Regina}, booktitle = {Computer Analysis of Images and Patterns}, isbn = {9783642236716}, issn = {1611-3349}, location = {Seville, Spain}, pages = {286--293}, publisher = {Springer Nature}, title = {{Incremental-decremental algorithm for computing AT-models and persistent homology}}, doi = {10.1007/978-3-642-23672-3_35}, volume = {6854}, year = {2011}, } @misc{9762, abstract = {Defining population structure and genetic diversity levels is of the utmost importance for developing efficient conservation strategies. Overfishing has caused mean annual catches of the European spiny lobster (Palinurus elephas) to decrease alarmingly along its distribution area. In this context, there is a need for comprehensive studies to evaluate the genetic health of the exploited populations. The present work is based on a set of 10 nuclear markers amplified in 331 individuals from 10 different localities covering most of P. elephas distribution area. Samples from Atlantic and Mediterranean basins showed small but significant differences, indicating that P. elephas populations do not behave as a single panmictic unit but form two partially-overlapping groups. Despite intense overfishing, our dataset did not recover a recent bottleneck signal, and showed a large and stable historical effective size instead. This result could be accounted for by specific life history traits (reproduction and longevity) and the limitations of molecular markers in covering very recent timescales for non temporal samples. Our study emphasizes the necessity of integrating information on effective population sizes and life history parameters when evaluating population connectivity levels from genetic data.}, author = {Palero, Ferran and Abello, Pere and Macpherson, Enrique and Beaumont, Mark and Pascual, Marta}, publisher = {IST Austria}, title = {{Data from: Effect of oceanographic barriers and overfishing on the population genetic structure of the European spiny lobster (Palinurus elephas)}}, doi = {10.5061/dryad.299h8}, year = {2011}, } @article{6496, abstract = {We report the switching behavior of the full bacterial flagellum system that includes the filament and the motor in wild-type Escherichia coli cells. In sorting the motor behavior by the clockwise bias, we find that the distributions of the clockwise (CW) and counterclockwise (CCW) intervals are either exponential or nonexponential with long tails. At low bias, CW intervals are exponentially distributed and CCW intervals exhibit long tails. At intermediate CW bias (0.5) both CW and CCW intervals are mainly exponentially distributed. A simple model suggests that these two distinct switching behaviors are governed by the presence of signaling noise within the chemotaxis network. Low noise yields exponentially distributed intervals, whereas large noise yields nonexponential behavior with long tails. These drastically different motor statistics may play a role in optimizing bacterial behavior for a wide range of environmental conditions.}, author = {Park, Heungwon and Oikonomou, Panos and Guet, Calin C and Cluzel, Philippe}, issn = {0006-3495}, journal = {Biophysical Journal}, number = {10}, pages = {2336--2340}, publisher = {Elsevier}, title = {{Noise underlies switching behavior of the bacterial flagellum}}, doi = {10.1016/j.bpj.2011.09.040}, volume = {101}, year = {2011}, } @inproceedings{3163, abstract = {We study multi-label prediction for structured output sets, a problem that occurs, for example, in object detection in images, secondary structure prediction in computational biology, and graph matching with symmetries. Conventional multilabel classification techniques are typically not applicable in this situation, because they require explicit enumeration of the label set, which is infeasible in case of structured outputs. Relying on techniques originally designed for single-label structured prediction, in particular structured support vector machines, results in reduced prediction accuracy, or leads to infeasible optimization problems. In this work we derive a maximum-margin training formulation for multi-label structured prediction that remains computationally tractable while achieving high prediction accuracy. It also shares most beneficial properties with single-label maximum-margin approaches, in particular formulation as a convex optimization problem, efficient working set training, and PAC-Bayesian generalization bounds.}, author = {Lampert, Christoph}, location = {Granada, Spain}, publisher = {Neural Information Processing Systems Foundation}, title = {{Maximum margin multi-label structured prediction}}, year = {2011}, } @inproceedings{3264, abstract = {Verification of programs with procedures, multi-threaded programs, and higher-order functional programs can be effectively au- tomated using abstraction and refinement schemes that rely on spurious counterexamples for abstraction discovery. The analysis of counterexam- ples can be automated by a series of interpolation queries, or, alterna- tively, as a constraint solving query expressed by a set of recursion free Horn clauses. (A set of interpolation queries can be formulated as a single constraint over Horn clauses with linear dependency structure between the unknown relations.) In this paper we present an algorithm for solving recursion free Horn clauses over a combined theory of linear real/rational arithmetic and uninterpreted functions. Our algorithm performs resolu- tion to deal with the clausal structure and relies on partial solutions to deal with (non-local) instances of functionality axioms.}, author = {Gupta, Ashutosh and Popeea, Corneliu and Rybalchenko, Andrey}, editor = {Yang, Hongseok}, location = {Kenting, Taiwan}, pages = {188 -- 203}, publisher = {Springer}, title = {{Solving recursion-free Horn clauses over LI+UIF}}, doi = {10.1007/978-3-642-25318-8_16}, volume = {7078}, year = {2011}, } @inproceedings{3266, abstract = {We present a joint image segmentation and labeling model (JSL) which, given a bag of figure-ground segment hypotheses extracted at multiple image locations and scales, constructs a joint probability distribution over both the compatible image interpretations (tilings or image segmentations) composed from those segments, and over their labeling into categories. The process of drawing samples from the joint distribution can be interpreted as first sampling tilings, modeled as maximal cliques, from a graph connecting spatially non-overlapping segments in the bag [1], followed by sampling labels for those segments, conditioned on the choice of a particular tiling. We learn the segmentation and labeling parameters jointly, based on Maximum Likelihood with a novel Incremental Saddle Point estimation procedure. The partition function over tilings and labelings is increasingly more accurately approximated by including incorrect configurations that a not-yet-competent model rates probable during learning. We show that the proposed methodologymatches the current state of the art in the Stanford dataset [2], as well as in VOC2010, where 41.7% accuracy on the test set is achieved.}, author = {Ion, Adrian and Carreira, Joao and Sminchisescu, Cristian}, booktitle = {NIPS Proceedings}, location = {Granada, Spain}, pages = {1827 -- 1835}, publisher = {Neural Information Processing Systems Foundation}, title = {{Probabilistic joint image segmentation and labeling}}, volume = {24}, year = {2011}, }