@article{8517,
abstract = {We consider the evolution of a connected set on the plane carried by a space periodic incompressible stochastic flow. While for almost every realization of the stochastic flow at time t most of the particles are at a distance of order equation image away from the origin, there is a measure zero set of points that escape to infinity at the linear rate. We study the set of points visited by the original set by time t and show that such a set, when scaled down by the factor of t, has a limiting nonrandom shape.},
author = {Dolgopyat, Dmitry and Kaloshin, Vadim and Koralov, Leonid},
issn = {0010-3640},
journal = {Communications on Pure and Applied Mathematics},
keywords = {Applied Mathematics, General Mathematics},
number = {9},
pages = {1127--1158},
publisher = {Wiley},
title = {{A limit shape theorem for periodic stochastic dispersion}},
doi = {10.1002/cpa.20032},
volume = {57},
year = {2004},
}
@article{8518,
author = {Koralov, Leonid and Kaloshin, Vadim and Dolgopyat, Dmitry},
issn = {0091-1798},
journal = {The Annals of Probability},
number = {1A},
pages = {1--27},
publisher = {Institute of Mathematical Statistics},
title = {{Sample path properties of the stochastic flows}},
doi = {10.1214/aop/1078415827},
volume = {32},
year = {2004},
}
@article{864,
abstract = {We present a method for prediction of functional sites in a set of aligned protein sequences. The method selects sites which are both well conserved and clustered together in space, as inferred from the 3D structures of proteins included in the alignment. We tested the method using 86 alignments from the NCBI CDD database, where the sites of experimentally determined ligand and/or macromolecular interactions are annotated. In agreement with earlier investigations, we found that functional site predictions are most successful when overall background sequence conservation is low, such that sites under evolutionary constraint become apparent. In addition, we found that averaging of conservation values across spatially clustered sites improves predictions under certain conditions: that is, when overall conservation is relatively high and when the site in question involves a large macromolecular binding interface. Under these conditions it is better to look for clusters of conserved sites than to look for particular conserved sites.},
author = {Panchenko, Anna R and Fyodor Kondrashov and Bryant, Stephen H},
journal = {Protein Science},
number = {4},
pages = {884 -- 892},
publisher = {Wiley-Blackwell},
title = {{Prediction of functional sites by analysis of sequence and structure conservation}},
doi = {10.1110/ps.03465504},
volume = {13},
year = {2004},
}
@article{870,
abstract = {Only a fraction of eukaryotic genes affect the phenotype drastically. We compared 18 parameters in 1273 human morbid genes, known to cause diseases, and in the remaining 16 580 unambiguous human genes. Morbid genes evolve more slowly, have wider phylogenetic distributions, are more similar to essential genes of Drosophila melanogaster, code for longer proteins containing more alanine and glycine and less histidine, lysine and methionine, possess larger numbers of longer introns with more accurate splicing signals and have higher and broader expressions. These differences make it possible to classify as non-morbid 34% of human genes with unknown morbidity, when only 5% of known morbid genes are incorrectly classified as non-morbid. This classification can help to identify disease-causing genes among multiple candidates.},
author = {Fyodor Kondrashov and Ogurtsov, Aleksey Yu and Kondrashov, Alexey S},
journal = {Nucleic Acids Research},
number = {5},
pages = {1731 -- 1737},
publisher = {Oxford University Press},
title = {{Bioinformatical assay of human gene morbidity}},
doi = {10.1093/nar/gkh330},
volume = {32},
year = {2004},
}
@article{875,
abstract = {The dominance of wild-type alleles and the concomitant recessivity of deleterious mutant alleles might have evolved by natural selection or could be a by-product of the molecular and physiological mechanisms of gene action. We compared the properties of human haplosufficient genes, whose wild-type alleles are dominant over loss-of-function alleles, with haploinsufficient (recessive wild-type) genes, which produce an abnormal phenotype when heterozygous for a loss-of-function allele. The fraction of haplosufficient genes is the highest among the genes that encode enzymes, which is best compatible with the physiological theory. Haploinsufficient genes, on average, have more paralogs than haplosufficient genes, supporting the idea that gene dosage could be important for the initial fixation of duplications. Thus, haplo(in)sufficiency of a gene and its propensity for duplication might have a common evolutionary basis.},
author = {Fyodor Kondrashov and Koonin, Eugene V},
journal = {Trends in Genetics},
number = {7},
pages = {287 -- 291},
publisher = {Elsevier},
title = {{A common framework for understanding the origin of genetic dominance and evolutionary fates of gene duplications}},
doi = {10.1016/j.tig.2004.05.001},
volume = {20},
year = {2004},
}
@article{1963,
abstract = {The mechanism coupling electron transfer and proton pumping in respiratory complex I (NADH-ubiquinone oxidoreductase) has not been established, but it has been suggested that it involves conformational changes. Here, the influence of substrates on the conformation of purified complex I from Escherichia coli was studied by cross-linking and electron microscopy. When a zero-length cross-linking reagent was used, the presence of NAD(P)H, in contrast to that of NAD+, prevented the formation of cross-links between the hydrophilic subunits of the complex, including NuoB, NuoI, and NuoCD. Comparisons using different cross-linkers suggested that NuoB, which is likely to coordinate the key iron-sulfur cluster N2, is the most mobile subunit. The presence of NAD(P)H led also to enhanced proteolysis of subunit NuoG. These data indicate that upon NAD(P)H binding, the peripheral arm of the complex adopts a more open conformation, with increased distances between subunits. Single particle analysis showed the nature of this conformational change. The enzyme retains its L-shape in the presence of NADH, but exhibits a significantly more open or expanded structure both in the peripheral arm and, unexpectedly, in the membrane domain also.},
author = {Mamedova, Aygun A and Holt, Peter J and Carroll, Joe D and Leonid Sazanov},
journal = {Journal of Biological Chemistry},
number = {22},
pages = {23830 -- 23836},
publisher = {American Society for Biochemistry and Molecular Biology},
title = {{Substrate-induced conformational change in bacterial complex I}},
doi = {10.1074/jbc.M401539200},
volume = {279},
year = {2004},
}
@article{209,
author = {Timothy Browning and Heath-Brown, Roger},
journal = {Inventiones Mathematicae},
number = {3},
pages = {553 -- 573},
publisher = {Unknown},
title = {{Equal sums of three powers}},
doi = {10.1007/s00222-004-0360-9},
volume = {157},
year = {2004},
}
@article{7333,
abstract = {The analysis of the complete H2/air polymer electrolyte fuel cell system shows that process air humidification is one of the biggest obstacles for a high performance portable system in the kW range. Therefore, a new concept, with passive process air humidification integrated into the stack, has been developed. Humidification in each cell makes the process independent from the number of cells and the operation mode, thus making the concept fully scalable. Without external humidification the system is simpler, smaller, and cheaper. The humidification of the process air is achieved by transfer of product water from the exhaust air, through part of the membrane, to the dry intake air. Tests have shown that cells using the concept of internal humidification and operated with dry air at 70 ° have almost the same performance as when operated with external humidification. A 42‐cell stack with this internal humidification concept was built and integrated into a portable 1 kW power generator system.},
author = {Santis, M. and Schmid, D. and Ruge, M. and Freunberger, Stefan Alexander and Büchi, F.N.},
issn = {1615-6846},
journal = {Fuel Cells},
number = {3},
pages = {214--218},
publisher = {Wiley},
title = {{Modular stack-internal air humidification concept-verification in a 1 kW stack}},
doi = {10.1002/fuce.200400028},
volume = {4},
year = {2004},
}
@article{7334,
abstract = {Fundamental and phenomenological models for cells, stacks, and complete systems of PEFC and SOFC are reviewed and their predictive power is assessed by comparing model simulations against experiments. Computationally efficient models suited for engineering design include the (1+1) dimensionality approach, which decouples the membrane in-plane and through-plane processes, and the volume-averaged-method (VAM) that considers only the lumped effect of pre-selected system components. The former model was shown to capture the measured lateral current density inhomogeneities in a PEFC and the latter was used for the optimization of commercial SOFC systems. State Space Modeling (SSM) was used to identify the main reaction pathways in SOFC and, in conjunction with the implementation of geometrically well-defined electrodes, has opened a new direction for the understanding of electrochemical reactions. Furthermore, SSM has advanced the understanding of the COpoisoning-induced anode impedance in PEFC. Detailed numerical models such as the Lattice Boltzmann (LB) method for transport in porous media and the full 3-D Computational Fluid Dynamics (CFD) Navier-Stokes simulations are addressed. These models contain all components of the relevant physics and they can improve the understanding of the related phenomena, a necessary condition for the development of both appropriate simplified models as well as reliable technologies. Within the LB framework, a technique for the characterization and computer-reconstruction of the porous electrode structure was developed using advanced pattern recognition algorithms. In CFD modeling, 3-D simulations were used to investigate SOFC with internal methane steam reforming and have exemplified the significance of porous and novel fractal channel distributors for the fuel and oxidant delivery, as well as for the cooling of PEFC. As importantly, the novel concept has been put forth of functionally designed, fractal-shaped fuel cells, showing promise of significant performance improvements over the conventional rectangular shaped units. Thermo-economic modeling for the optimization of PEFC is finally addressed. },
author = {Mantzaras, John and Freunberger, Stefan Alexander and Büchi, Felix N. and Roos, Markus and Brandstätter, Wilhelm and Prestat, Michel and Gauckler, Ludwig J. and Andreaus, Bernhard and Hajbolouri, Faegheh and Senn, Stephan M. and Poulikakos, Dimos and Chaniotis, Andreas K. and Larrain, Diego and Autissier, Nordahl and Maréchal, François},
issn = {0009-4293},
journal = {CHIMIA International Journal for Chemistry},
number = {12},
pages = {857--868},
publisher = {Swiss Chemical Society},
title = {{Fuel cell modeling and simulations}},
doi = {10.2533/000942904777677029},
volume = {58},
year = {2004},
}
@article{7706,
abstract = {The Sir2 deacetylase modulates organismal life-span in various species. However, the molecular mechanisms by which Sir2 increases longevity are largely unknown. We show that in mammalian cells, the Sir2 homolog SIRT1 appears to control the cellular response to stress by regulating the FOXO family of Forkhead transcription factors, a family of proteins that function as sensors of the insulin signaling pathway and as regulators of organismal longevity. SIRT1 and the FOXO transcription factor FOXO3 formed a complex in cells in response to oxidative stress, and SIRT1 deacetylated FOXO3 in vitro and within cells. SIRT1 had a dual effect on FOXO3 function: SIRT1 increased FOXO3's ability to induce cell cycle arrest and resistance to oxidative stress but inhibited FOXO3's ability to induce cell death. Thus, one way in which members of the Sir2 family of proteins may increase organismal longevity is by tipping FOXO-dependent responses away from apoptosis and toward stress resistance.},
author = {Brunet, Anne and Sweeney, Lora Beatrice Jaeger and Sturgill, J Fitzhugh and Chua, Katrin and Greer, Paul and Lin, Yingxi and Tran, Hien and Ross, Sarah and Mostoslavsky, Raul and Cohen, Haim and Hu, Linda and Chen, Hwei-Ling and Jedrychowski, Mark and Gygi, Steven and Sinclair, David and Alt, Frederick and Greenberg, Michael},
issn = {0036-8075},
journal = {Science},
number = {5666},
pages = {2011--2015},
publisher = {American Association for the Advancement of Science},
title = {{Stress-dependent regulation of FOXO transcription factors by the SIRT1 deacetylase}},
doi = {10.1126/science.1094637},
volume = {303},
year = {2004},
}
@inproceedings{4629,
abstract = {Temporal logic is two-valued: a property is either true or false. When applied to the analysis of stochastic systems, or systems with imprecise formal models, temporal logic is therefore fragile: even small changes in the model can lead to opposite truth values for a specification. We present a generalization of the branching-time logic Ctl which achieves robustness with respect to model perturbations by giving a quantitative interpretation to predicates and logical operators, and by discounting the importance of events according to how late they occur. In every state, the value of a formula is a real number in the interval [0,1], where 1 corresponds to truth and 0 to falsehood. The boolean operators and and or are replaced by min and max, the path quantifiers ∃ and ∀ determine sup and inf over all paths from a given state, and the temporal operators and □ specify sup and inf over a given path; a new operator averages all values along a path. Furthermore, all path operators are discounted by a parameter that can be chosen to give more weight to states that are closer to the beginning of the path. We interpret the resulting logic Dctl over transition systems, Markov chains, and Markov decision processes. We present two semantics for Dctl: a path semantics, inspired by the standard interpretation of state and path formulas in CTL, and a fixpoint semantics, inspired by the μ-calculus evaluation of CTL formulas. We show that, while these semantics coincide for CTL, they differ for Dctl, and we provide model-checking algorithms for both semantics.},
author = {de Alfaro, Luca and Faella, Marco and Thomas Henzinger and Majumdar, Ritankar S and Stoelinga, Mariëlle},
pages = {77 -- 92},
publisher = {Springer},
title = {{Model checking discounted temporal properties}},
doi = {10.1007/978-3-540-24730-2_6},
volume = {2988},
year = {2004},
}
@article{6155,
abstract = {The genome of the nematode Caenorhabditis elegans encodes seven soluble guanylate cyclases (sGCs) [1]. In mammals, sGCs function as α/β heterodimers activated by gaseous ligands binding to a haem prosthetic group 2, 3. The principal activator is nitric oxide, which acts through sGCs to regulate diverse cellular events. In C. elegans the function of sGCs is mysterious: the worm genome does not appear to encode nitric oxide synthase, and all C. elegans sGC subunits are more closely related to mammalian β than α subunits [1]. Here, we show that two of the seven C. elegans sGCs, GCY-35 and GCY-36, promote aggregation behavior. gcy-35 and gcy-36 are expressed in a small number of neurons. These include the body cavity neurons AQR, PQR, and URX, which are directly exposed to the blood equivalent of C. elegans and regulate aggregation behavior [4]. We show that GCY-35 and GCY-36 act as α-like and β-like sGC subunits and that their function in the URX sensory neurons is sufficient for strong nematode aggregation. Neither GCY-35 nor GCY-36 is absolutely required for C. elegans to aggregate. Instead, these molecules may transduce one of several pathways that induce C. elegans to aggregate or may modulate aggregation by responding to cues in C. elegans body fluid.},
author = {Cheung, Benny H.H and Arellano-Carbajal, Fausto and Rybicki, Irene and de Bono, Mario},
issn = {0960-9822},
journal = {Current Biology},
number = {12},
pages = {1105--1111},
publisher = {Elsevier},
title = {{Soluble guanylate cyclases act in neurons exposed to the body fluid to promote C. elegans aggregation behavior}},
doi = {10.1016/j.cub.2004.06.027},
volume = {14},
year = {2004},
}
@article{1456,
abstract = {We study the space of L2 harmonic forms on complete manifolds with metrics of fibred boundary or fibred cusp type. These metrics generalize the geometric structures at infinity of several different well-known classes of metrics, including asymptotically locally Euclidean manifolds, the (known types of) gravitational instantons, and also Poincaré metrics on ℚ-rank 1 ends of locally symmetric spaces and on the complements of smooth divisors in Kähler manifolds. The answer in all cases is given in terms of intersection cohomology of a stratified compactification of the manifold. The L2 signature formula implied by our result is closely related to the one proved by Dai and more generally by Vaillant and identifies Dai's τ-invariant directly in terms of intersection cohomology of differing perversities. This work is also closely related to a recent paper of Carron and the forthcoming paper of Cheeger and Dai. We apply our results to a number of examples, gravitational instantons among them, arising in predictions about L2 harmonic forms in duality theories in string theory.},
author = {Tamas Hausel and Hunsicker, Eugénie and Mazzeo, Rafe R},
journal = {Duke Mathematical Journal},
number = {3},
pages = {485 -- 548},
publisher = {Duke University Press},
title = {{Hodge cohomology of gravitational instantons}},
doi = {10.1215/S0012-7094-04-12233-X},
volume = {122},
year = {2004},
}
@article{1464,
abstract = {The moduli space of stable vector bundles on a Riemann surface is smooth when the rank and degree are coprime, and is diffeomorphic to the space of unitary connections of central constant curvature. A classic result of Newstead and Atiyah and Bott asserts that its rational cohomology ring is generated by the universal classes, that is, by the Kunneth components of the Chern classes of the universal bundle.
This paper studies the larger, non-compact moduli space of Higgs bundles, as introduced by Hitchin and Simpson, with values in the canonical bundle K. This is diffeomorphic to the space of all connections of central constant curvature, whether unitary or not. The main result of the paper is that, in the rank 2 case, the rational cohomology ring of this space is again generated by universal classes.
The spaces of Higgs bundles with values in K(n) for n > 0 turn out to be essential to the story. Indeed, we show that their direct limit has the homotopy type of the classifying space of the gauge group, and hence has cohomology generated by universal classes. 2000 Mathematics Subject Classification 14H60 (primary), 14D20, 14H81, 32Q55, 58D27 (secondary). },
author = {Tamas Hausel and Thaddeus, Michael},
journal = {Proceedings of the London Mathematical Society},
number = {3},
pages = {632 -- 658},
publisher = {Oxford University Press},
title = {{Generators for the cohomology ring of the moduli space of rank 2 higgs bundles}},
doi = {10.1112/S0024611503014618},
volume = {88},
year = {2004},
}
@article{889,
abstract = {The function of protein and RNA molecules depends on complex epistatic interactions between sites. Therefore, the deleterious effect of a mutation can be suppressed by a compensatory second-site substitution. In relating a list of 86 pathogenic mutations in human IRNAs encoded by mitochondrial genes to the sequences of their mammalian orthologs, we noted that 52 pathogenic mutations were present in normal tRNAs of one or several nonhuman mammals. We found at least five mechanisms of compensation for 32 pathogenic mutations that destroyed a Watson-Crick pair in one of the four tRNA stems: restoration of the affected Watson-Crick interaction (25 cases), strengthening of another pair (4 cases), creation of a new pair (8 cases), changes of multiple interactions in the affected stem (11 cases) and changes involving the interaction between the loop and stem structures (3 cases). A pathogenic mutation and its compensating substitution are fixed in a lineage in rapid succession, and often a compensatory interaction evolves convergently in different clades. At least 10%, and perhaps as many as 50%, of all nucleotide substitutions in evolving mammalian (RNAs participate in such interactions, indicating that the evolution of tRNAs proceeds along highly epistatic fitness ridges.},
author = {Kern, Andrew D and Fyodor Kondrashov},
journal = {Nature Genetics},
number = {11},
pages = {1207 -- 1212},
publisher = {Nature Publishing Group},
title = {{Mechanisms and convergence of compensatory evolution in mammalian mitochondrial tRNAs}},
doi = {10.1038/ng1451},
volume = {36},
year = {2004},
}
@article{898,
abstract = {New alleles become fixed owing to random drift of nearly neutral mutations or to positive selection of substantially advantageous mutations. After decades of debate, the fraction of fixations driven by selection remains uncertain. Within 9,390 genes, we analysed 28,196 codons at which rat and mouse differ from each other at two nucleotide sites and 1,982 codons with three differences. At codons where rat-mouse divergence involved two non-synonymous substitutions, both of them occurred in the same lineage, either rat or mouse, in 64% of cases; however, independent substitutions would occur in the same lineage with a probability of only 50%. All three non-synonymous substitutions occurred in the same lineage for 46% of codons, instead of the 25% expected. Furthermore, comparison of 12 pairs of prokaryotic genomes also shows clumping of multiple non-synonymous substitutions in the same lineage. This pattern cannot be explained by correlated mutation or episodes of relaxed negative selection, but instead indicates that positive selection acts at many sites of rapid, successive amino acid replacement.},
author = {Bazykin, Georgii A and Fyodor Kondrashov and Ogurtsov, Aleksey Yu and Sunyaev, Shamil R and Kondrashov, Alexey S},
journal = {Nature},
number = {6991},
pages = {558 -- 562},
publisher = {Nature Publishing Group},
title = {{Positive selection at sites of multiple amino acid replacements since rat-mouse divergence}},
doi = {10.1038/nature02601},
volume = {429},
year = {2004},
}
@article{902,
abstract = {We compare the functional spectrum of protein evolution in two separate animal lineages with respect to two hypotheses: (1) rates of divergence are distributed similarly among functional classes within both lineages, indicating that selective pressure on the proteome is largely independent of organismic-level biological requirements; and (2) rates of divergence are distributed differently among functional classes within each lineage, indicating species-specific selective regimes impact genome-wide substitutional patterns. Integrating comparative genome sequence with data from tissue-specific expressed-sequence-tag (EST) libraries and detailed database annotations, we find a functional genomic signature of rapid evolution and selective constraint shared between mammalian and nematode lineages despite their extensive morphological and ecological differences and distant common ancestry. In both phyla, we find evidence of accelerated evolution among components of molecular systems involved in coevolutionary change. In mammals, lineage-specific fast evolving genes include those involved in reproduction, immunity, and possibly, maternal-fetal conflict. Likelihood ratio tests provide evidence for positive selection in these rapidly evolving functional categories in mammals. In contrast, slowly evolving genes, in terms of amino acid or insertion/deletion (indel) change, in both phyla are involved in core molecular processes such as transcription, translation, and protein transport. Thus, strong purifying selection appears to act on the same core cellular processes in both mammalian and nematode lineages, whereas positive and/or relaxed selection acts on different biological processes in each lineage.},
author = {Castillo-Davis, Cristian I and Fyodor Kondrashov and Hartl, Daniel L and Kulathinal, Rob J},
journal = {Genome Research},
number = {5},
pages = {802 -- 811},
publisher = {Cold Spring Harbor Laboratory Press},
title = {{The functional genomic distribution of protein divergence in two animal phyla: Coevolution, genomic conflict, and constraint}},
doi = {10.1101/gr.2195604},
volume = {14},
year = {2004},
}
@article{3805,
abstract = {The operation of neuronal networks crucially depends on a fast time course of signaling in inhibitory interneurons. Synapses that excite interneurons generate fast currents, owing to the expression of glutamate receptors of specific subunit composition. Interneurons generate brief action potentials in response to transient synaptic activation and discharge repetitively at very high frequencies during sustained stimulation. The ability to generate short-duration action potentials at high frequencies depends on the expression of specific voltage-gated K+ channels. Factors facilitating fast action potential initiation following synaptic excitation include depolarized interneuron resting potential, subthreshold conductances and active dendrites. Finally, GABA release at interneuron output synapses is rapid and highly synchronized, leading to a faster inhibition in postsynaptic interneurons than in principal cells. Thus, the expression of distinct transmitter receptors and voltage-gated ion channels ensures that interneurons operate with high speed and temporal precision.},
author = {Peter Jonas and Bischofberger, Josef and Fricker, Desdemona and Miles, Richard},
journal = {Trends in Neurosciences},
number = {1},
pages = {30 -- 40},
publisher = {Elsevier},
title = {{Interneuron Diversity series: Fast in, fast out--temporal and spatial signal processing in hippocampal interneurons}},
doi = {doi:10.1016/j.tins.2003.10.010},
volume = {27},
year = {2004},
}
@article{3807,
abstract = {The time course of Mg(2+) block and unblock of NMDA receptors (NMDARs) determines the extent they are activated by depolarization. Here, we directly measure the rate of NMDAR channel opening in response to depolarizations at different times after brief (1 ms) and sustained (4.6 s) applications of glutamate to nucleated patches from neocortical pyramidal neurons. The kinetics of Mg(2+) unblock were found to be non-instantaneous and complex, consisting of a prominent fast component (time constant approximately 100 micros) and slower components (time constants 4 and approximately 300 ms), the relative amplitudes of which depended on the timing of the depolarizing pulse. Fitting a kinetic model to these data indicated that Mg(2+) not only blocks the NMDAR channel, but reduces both the open probability and affinity for glutamate, while enhancing desensitization. These effects slow the rate of NMDAR channel opening in response to depolarization in a time-dependent manner such that the slower components of Mg(2+) unblock are enhanced during depolarizations at later times after glutamate application. One physiological consequence of this is that brief depolarizations occurring earlier in time after glutamate application are better able to open NMDAR channels. This finding has important implications for spike-timing-dependent synaptic plasticity (STDP), where the precise (millisecond) timing of action potentials relative to synaptic inputs determines the magnitude and sign of changes in synaptic strength. Indeed, we find that STDP timing curves of NMDAR channel activation elicited by realistic dendritic action potential waveforms are narrower than expected assuming instantaneous Mg(2+) unblock, indicating that slow Mg(2+) unblock of NMDAR channels makes the STDP timing window more precise.},
author = {Kampa, Bjorn M and Clements, John and Peter Jonas and Stuart, Greg J},
journal = {Journal of Physiology},
number = {Pt 2},
pages = {337 -- 45},
publisher = {Wiley-Blackwell},
title = {{Kinetics of Mg(2+) unblock of NMDA receptors: implications for spike-timing dependent synaptic plasticity}},
doi = {10.1113/jphysiol.2003.058842 },
volume = {556},
year = {2004},
}
@article{3809,
abstract = {Neural stem cells in various regions of the vertebrate brain continuously generate neurons throughout life. In the mammalian hippocampus, a region important for spatial and episodic memory, thousands of new granule cells are produced per day, with the exact number depending on environmental conditions and physical exercise. The survival of these neurons is improved by learning and conversely learning may be promoted by neurogenesis. Although it has been suggested that newly generated neurons may have specific properties to facilitate learning, the cellular and synaptic mechanisms of plasticity in these neurons are largely unknown. Here we show that young granule cells in the adult hippocampus differ substantially from mature granule cells in both active and passive membrane properties. In young neurons, T-type Ca2+ channels can generate isolated Ca2+ spikes and boost fast Na+ action potentials, contributing to the induction of synaptic plasticity. Associative long-term potentiation can be induced more easily in young neurons than in mature neurons under identical conditions. Thus, newly generated neurons express unique mechanisms to facilitate synaptic plasticity, which may be important for the formation of new memories.},
author = {Schmidt-Hieber, Christoph and Peter Jonas and Bischofberger, Josef},
journal = {Nature},
number = {6988},
pages = {184 -- 7},
publisher = {Nature Publishing Group},
title = {{Enhanced synaptic plasticity in newly generated granule cells of the adult hippocampus}},
doi = {10.1038/nature02553},
volume = {429},
year = {2004},
}
@article{3810,
abstract = {Voltage-gated potassium (Kv) channels control action potential repolarization, interspike membrane potential, and action potential frequency in excitable cells. It is thought that the combinatorial association between distinct alpha and beta subunits determines whether Kv channels function as non-inactivating delayed rectifiers or as rapidly inactivating A-type channels. We show that membrane lipids can convert A-type channels into delayed rectifiers and vice versa. Phosphoinositides remove N-type inactivation from A-type channels by immobilizing the inactivation domains. Conversely, arachidonic acid and its amide anandamide endow delayed rectifiers with rapid voltage-dependent inactivation. The bidirectional control of Kv channel gating by lipids may provide a mechanism for the dynamic regulation of electrical signaling in the nervous system.},
author = {Oliver, Dominik and Lien, Cheng-Chang and Soom, Malle and Baukrowitz, Thomas and Peter Jonas and Fakler, Bernd},
journal = {Science},
number = {5668},
pages = {265 -- 70},
publisher = {American Association for the Advancement of Science},
title = {{Functional conversion between A-type and delayed rectifier K+ channels by membrane lipids}},
doi = {10.1126/science.1094113},
volume = {304},
year = {2004},
}
@inproceedings{3894,
abstract = {We study infinite stochastic games played by n-players on a finite graph with goals given by sets of infinite traces. The games are stochastic (each player simultaneously and independently chooses an action at each round, and the next state is determined by a probability distribution depending on the current state and the chosen actions), infinite (the game continues for an infinite number of rounds), nonzero sum (the players' goals are not necessarily conflicting), and undiscounted. We show that if each player has a reachability objective, that is, if the goal for each player i is to visit some subset R-i of the states, then there exists an epsilon-Nash equilibrium in memoryless strategies, for every epsilon > 0. However, exact Nash equilibria need not exist. We study the complexity of finding such Nash equilibria, and show that the payoff of some epsilon-Nash equilibrium in memoryless strategies can be epsilon-approximated in NP. We study the important subclass of n-player turn-based probabilistic games, where at each state at most one player has a nontrivial choice of moves. For turn-based probabilistic games, we show the existence of epsilon-Nash equilibria in pure strategies for games where the objective of player i is a Borel set B-i of infinite traces. However, exact Nash equilibria may not exist. For the special case of omega-regular objectives, we show exact Nash equilibria exist, and can be computed in NP when the omega-regular objectives are expressed as parity objectives.},
author = {Krishnendu Chatterjee and Majumdar, Ritankar S and Jurdziński, Marcin},
pages = {26 -- 40},
publisher = {Springer},
title = {{On Nash equilibria in stochastic games}},
doi = {10.1007/978-3-540-30124-0_6},
volume = {3210},
year = {2004},
}
@inproceedings{3895,
abstract = {In 2-player non-zero-sum games, Nash equilibria capture the options for rational behavior if each player attempts to maximize her payoff. In contrast to classical game theory, we consider lexicographic objectives: first, each player tries to maximize her own payoff, and then, the player tries to minimize the opponent's payoff. Such objectives arise naturally in the verification of systems with multiple components. There, instead of proving that each component satisfies its specification no matter how the other components behave, it often suffices to prove that each component satisfies its specification provided that the other components satisfy their specifications. We say that a Nash equilibrium is secure if it is an equilibrium with respect to the lexicographic objectives of both players. We prove that in graph games with Borel objectives, which include the games that arise in verification, there may be several Nash equilibria, but there is always a unique maximal payoff profile of secure equilibria. We show how this equilibrium can be computed in the case of omega-regular objectives, and we characterize the memory requirements of strategies that achieve the equilibrium.},
author = {Krishnendu Chatterjee and Thomas Henzinger and Jurdziński, Marcin},
pages = {160 -- 169},
publisher = {IEEE},
title = {{Games with secure equilibria}},
doi = {10.1109/LICS.2004.1319610},
year = {2004},
}
@article{3918,
abstract = {Wingless (ergatoid) males of the tramp ant Cardiocondyla minutior attack and kill their young ergatoid rivals and thus attempt to monopolize mating with female sexuals reared in the colony. Because of the different strength of local mate competition in colonies with one or several reproductive queens, we expected the production of new ergatoid males to vary with queen number. Sex ratios were mostly female-biased, but in contrast to the sympatric species C. obscurior (Cremer and Heinze, 2002) neither the percentage of ergatoid males nor of female sexuals among the first 20 sexuals produced varied considerably with queen number. As in C. obscurior, experimental colony fragmentation led to the production of winged males, whereas in unfragmented control colonies only ergatoid males eclosed.},
author = {Heinze, Jürgen and Böttcher, A. and Cremer, Sylvia},
journal = {Insectes Sociaux},
number = {3},
pages = {275 -- 278},
publisher = {Springer},
title = {{Production of winged and wingless males in the ant, Cardiocondyla minutior}},
doi = {10.1007/s00040-004-0740-6},
volume = {51},
year = {2004},
}
@article{3929,
abstract = {The Nef protein of human and simian immunodeficiency virus (HIV/SIV) is believed to interfere with T cell activation signals by forming a signaling complex at the plasma membrane. Composition and function of the complex are not fully understood. Here we report that Nef recruits the Polycomb Group (PcG) protein Eed, so far known as a nuclear factor and repressor of transcription, to the membrane of cells. The Nef-induced translocation of Eed led to a potent stimulation of Tat-dependent HIV transcription, implying that Eed removal from the nucleus is required for optimal Tat function. Similar to Nef action, activation of integrin receptors recruited Eed to the plasma membrane, also leading to enhanced Tat/Nef-mediated transcription. Our results suggest a link between membrane-associated activation processes and transcriptional derepression and demonstrate how HIV exploits this mechanism.},
author = {Witte, Vanessa and Laffert, Bernd and Rosorius, Olaf and Lischka, Peter and Blume, Katja and Galler, Gunther and Stilper, Andrea and Willbold, Dieter and D'Aloja, Paola and Michael Sixt and Kolanus, Johanna and Ott, Melanie and Kolanus, Waldemar and Schuler, Gerold and Baur, Andreas S},
journal = {Molecular Cell},
number = {2},
pages = {179 -- 190},
publisher = {Cell Press},
title = {{HIV-1 Nef mimics an integrin receptor signal that recruits the polycomb group protein Eed to the plasma membrane}},
doi = {10.1016/S1097-2765(04)00004-8},
volume = {13},
year = {2004},
}
@article{3931,
abstract = {Hyaluronan is an unsulfated glycosaminoglycan (GAG) that is ubiquitously expressed in the extracellular matrix (ECM) of all vertebrates, where hyaluronan rich matrices constitute a particular permissive environment for the development of complex biological structures and also for tumor progression. Because of its conserved structure and ubiquitous expression, antibodies for its histochemical detection cannot be produced. We have engineered a fusion protein, neurocan-GFP, and expressed it as a secreted molecule in mammalian cells. Neurocan-GFP fusion protein specifically binds to hyaluronan and directly visualizes hyaluronan on tissue sections, revealing a very detailed picture of hyaluronan distribution. The fluorescent fusion protein can be used in combination with antibodies and nuclear markers for double or triple staining. In addition, it is suitable to visualize hyaluronan on living cells by time-lapse video microscopy. The successful production and application of the neurocan-GFP fusion protein opens up new perspectives for using GFP fusion proteins as detection tools in histological and cytological studies complementing conventional antibody and biotin/avidin techniques.},
author = {Zhang, Hui and Baader, Stephan L and Michael Sixt and Kappler, Joachim and Rauch, Uwe},
journal = {Journal of Histochemistry and Cytochemistry},
number = {7},
pages = {915 -- 922},
publisher = {Histochemical Society},
title = {{Neurocan-GFP fusion protein: a new approach to detect hyaluronan on tissue sections and living cells}},
doi = {10.1369/jhc.3A6221.2004},
volume = {52},
year = {2004},
}
@article{3984,
abstract = {We combine topological and geometric methods to construct a multiresolution representation for a function over a two-dimensional domain. In a preprocessing stage, we create the Morse-Smale complex of the function and progressively simplify its topology by cancelling pairs of critical points. Based on a simple notion of dependency among these cancellations, we construct a hierarchical data structure supporting traversal and reconstruction operations similarly to traditional geometry-based representations. We use this data structure to extract topologically valid approximations that satisfy error bounds provided at runtime.},
author = {Bremer, Peer-Timo and Herbert Edelsbrunner and Hamann, Bernd and Pascucci, Valerio},
journal = {IEEE Transactions on Visualization and Computer Graphics},
number = {4},
pages = {385 -- 396},
publisher = {IEEE},
title = {{A topological hierarchy for functions on triangulated surfaces}},
doi = {10.1109/TVCG.2004.3},
volume = {10},
year = {2004},
}
@article{3985,
abstract = {Given a Morse function f over a 2-manifold with or without boundary, the Reeb graph is obtained by contracting the connected components of the level sets to points. We prove tight upper and lower bounds on the number of loops in the Reeb graph that depend on the genus, the number of boundary components, and whether or not the 2-manifold is orientable. We also give an algorithm that constructs the Reeb graph in time O(n log n), where n is the number of edges in the triangulation used to represent the 2-manifold and the Morse function.},
author = {Cole-McLaughlin, Kree and Herbert Edelsbrunner and Harer, John and Natarajan, Vijay and Pascucci, Valerio},
journal = {Discrete & Computational Geometry},
number = {2},
pages = {231 -- 244},
publisher = {Springer},
title = {{Loops in Reeb graphs of 2-manifolds}},
doi = {10.1007/s00454-004-1122-6},
volume = {32},
year = {2004},
}
@article{3986,
abstract = {The motion of a biomolecule greatly depends on the engulfing solution, which is mostly water. Instead of representing individual water molecules, it is desirable to develop implicit solvent models that nevertheless accurately represent the contribution of the solvent interaction to the motion. In such models, hydrophobicity is expressed as a weighted sum of atomic surface areas. The derivatives of these weighted areas contribute to the force that drives the motion. In this paper we give formulas for the weighted and unweighted area derivatives of a molecule modeled as a space-filling diagram made up of balls in motion. Other than the radii and the centers of the balls, the formulas are given in terms of the sizes of circular arcs of the boundary and edges of the power diagram. We also give inclusion-exclusion formulas for these sizes.},
author = {Bryant, Robert and Herbert Edelsbrunner and Koehl, Patrice and Levitt, Michael},
journal = {Discrete & Computational Geometry},
number = {3},
pages = {293 -- 308},
publisher = {Springer},
title = {{The area derivative of a space-filling diagram}},
doi = {10.1007/s00454-004-1099-1},
volume = {32},
year = {2004},
}
@article{3987,
abstract = {We consider scientific data sets that describe density functions over three-dimensional geometric domains. Such data sets are often large and coarsened representations are needed for visualization and analysis. Assuming a tetrahedral mesh representation, we construct such representations with a simplification algorithm that combines three goals: the approximation of the function, the preservation of the mesh topology, and the improvement of the mesh quality. The third goal is achieved with a novel extension of the well-known quadric error metric. We perform a number of computational experiments to understand the effect of mesh quality improvement on the density map approximation. In addition, we study the effect of geometric simplification on the topological features of the function by monitoring its critical points.},
author = {Natarajan, Vijay and Herbert Edelsbrunner},
journal = {IEEE Transactions on Visualization and Computer Graphics},
number = {5},
pages = {587 -- 597},
publisher = {IEEE},
title = {{Simplification of three-dimensional density maps}},
doi = {10.1109/TVCG.2004.32},
volume = {10},
year = {2004},
}
@inproceedings{3988,
abstract = {We give an algorithm that locally improves the fit between two proteins modeled as space-filling diagrams. The algorithm defines the fit in purely geometric terms and improves by applying a rigid motion to one of the two proteins. Our implementation of the algorithm takes between three and ten seconds and converges with high likelihood to the correct docked configuration, provided it starts at a position away from the correct one by at most 18 degrees of rotation and at most 3.0Angstrom of translation. The speed and convergence radius make this an attractive algorithm to use in combination with a coarse sampling of the six-dimensional space of rigid motions.},
author = {Choi, Vicky and Agarwal, Pankaj K and Herbert Edelsbrunner and Rudolph, Johannes},
pages = {218 -- 229},
publisher = {Springer},
title = {{Local search heuristic for rigid protein docking}},
doi = {10.1007/978-3-540-30219-3_19},
volume = {3240},
year = {2004},
}
@inproceedings{3989,
abstract = {We introduce local and global comparison measures for a collection of k less than or equal to d real-valued smooth functions on a common d-dimensional Riemannian manifold. For k = d = 2 we relate the measures to the set of critical points of one function restricted to the level sets of the other. The definition of the measures extends to piecewise linear functions for which they ace easy to compute. The computation of the measures forms the centerpiece of a software tool which we use to study scientific datasets.},
author = {Herbert Edelsbrunner and Harer, John and Natarajan, Vijay and Pascucci, Valerio},
pages = {275 -- 280},
publisher = {IEEE},
title = {{Local and global comparison of continuous functions}},
doi = {10.1109/VISUAL.2004.68},
year = {2004},
}
@article{3990,
abstract = {The writhing number measures the global geometry of a closed space curve or knot. We show that this measure is related to the average winding number of its Gauss map. Using this relationship, we give an algorithm for computing the writhing number for a polygonal knot with n edges in time roughly proportional to n(1.6). We also implement a different, simple algorithm and provide experimental evidence for its practical efficiency.},
author = {Agarwal, Pankaj K and Herbert Edelsbrunner and Wang, Yusu},
journal = {Discrete & Computational Geometry},
number = {1},
pages = {37 -- 53},
publisher = {Springer},
title = {{Computing the writhing number of a polygonal knot}},
doi = {10.1007/s00454-004-2864-x},
volume = {32},
year = {2004},
}
@article{4172,
abstract = {During vertebrate gastrulation, a relatively limited number of blastodermal cells undergoes a stereotypical set of cellular movements that leads to formation of the three germ layers: ectoderm, mesoderm and endoderm. Gastrulation, therefore, provides a unique developmental system in which to study cell movements in vivo in a fairly simple cellular context. Recent advances have been made in elucidating the cellular and molecular mechanisms that underlie cell movements during zebrafish gastrulation. These findings can be compared with observations made in other model systems to identify potential general mechanisms of cell migration during development.},
author = {Montero, Juan and Heisenberg, Carl-Philipp J},
journal = {Trends in Cell Biology},
number = {11},
pages = {620 -- 627},
publisher = {Cell Press},
title = {{Gastrulation dynamics: cells move into focus}},
doi = {10.1016/j.tcb.2004.09.008},
volume = {14},
year = {2004},
}
@article{4224,
abstract = {Developing cells acquire positional information by reading the graded distribution of morphogens. In Drosophila, the Dpp morphogen forms a long-range concentration gradient by spreading from a restricted source in the developing wing. It has been assumed that Dpp spreads by extracellular diffusion. Under this assumption, the main role of endocytosis in gradient formation is to downregulate receptors at the cell surface. These surface receptors bind to the ligand and thereby interfere with its long-range movement. Recent experiments indicate that Dpp spreading is mediated by Dynamin-dependent endocytosis in the target tissue, suggesting that extracellular diffusion alone cannot account for Dpp dispersal. Here, we perform a theoretical study of a model for morphogen spreading based on extracellular diffusion, which takes into account receptor binding and trafficking. We compare profiles of ligand and surface receptors obtained in this model with experimental data. To this end, we monitored directly the pool of surface receptors and extracellular Dpp with specific antibodies. We conclude that current models considering pure extracellular diffusion cannot explain the observed role of endocytosis during Dpp long-range movement.},
author = {Kruse, Karsten and Pantazis, Periklis and Bollenbach, Mark Tobias and Julicher, Frank and Gonzalez Gaitan, Marcos},
journal = {Development},
number = {19},
pages = {4843 -- 4856},
publisher = {Company of Biologists},
title = {{Dpp gradient formation by dynamin-dependent endocytosis: receptor trafficking and the diffusion model}},
doi = {10.1242/dev.01335},
volume = {131},
year = {2004},
}
@inbook{4230,
author = {Harold Vladar and Cipriani, Roberto and Scharifker, Benjamin and Bubis, Jose},
booktitle = {Life in the Universe From the Miller Experiment to the Search for Life on Other Worlds},
editor = {Hanslmeier,A. and Kempe,S. and Seckbach,J.},
pages = {83 -- 87},
publisher = {Springer},
title = {{A mechanism for the prebiotic emergence of proteins}},
year = {2004},
}
@phdthesis{4236,
author = {de Vladar, Harold},
publisher = {Centro de estudios avazados, IVIC},
title = {{Métodos no lineales y sus aplicaciones en dinámicas aleatorias de poblaciones celulares}},
doi = {3810},
year = {2004},
}
@article{4238,
abstract = {The dynamical basis of tumoral growth has been controversial. Many models have been proposed to explain cancer development. The descriptions employ exponential, potential, logistic or Gompertzian growth laws. Some of these models are concerned with the interaction between cancer and the immunological, system. Among other properties, these models are concerned with the microscopic behavior of tumors and the emergence of cancer. We propose a modification of a previous model by Stepanova, which describes the specific immunological response against cancer. The modification consists of the substitution of a Gompertian law for the exponential rate used for tumoral growth. This modification is motivated by the numerous works confirming that Gompertz's equation correctly describes solid tumor growth. The modified model predicts that near zero, tumors always tend to grow. Immunological contraposition never suffices to induce a complete regression of the tumor. Instead, a stable microscopic equilibrium between cancer and immunological activity can be attained. In other words, our model predicts that the theory of immune surveillance is plausible. A macroscopic equilibrium in which the system develops cancer is also possible. In this case, immunological activity is depleted. This is consistent with the phenomena of cancer tolerance. Both equilibrium points can coexist or can exist without the other. In all cases the fixed point at zero tumor size is unstable. Since immunity cannot induce a complete tumor regression, a therapy is required. We include constant-dose therapies and show that they are insufficient. Final levels of immunocompetent cells and tumoral cells are finite, thus post-treatment regrowth of the tumor is certain. We also evaluate late-intensification therapies which are successful. They induce an asymptotic regression to zero tumor size. Immune response is also suppressed by the therapy, and thus plays a negligible role in the remission. We conclude that treatment evaluation should be successful without taking into account immunological effects. (C) 2003 Elsevier Ltd. All rights reserved.},
author = {de Vladar, Harold and González, J.},
journal = {Journal of Theoretical Biology},
number = {3},
pages = {335 -- 348},
publisher = {Elsevier},
title = {{Dynamic response of cancer under the influence of immunological activity and therapy}},
doi = {3801},
volume = {227},
year = {2004},
}
@inbook{4239,
author = {Harold Vladar and Cipriani, Roberto and Scharifker, Benjamin and Bubis, Jose},
booktitle = {Life in the Universe From the Miller Experiment to the Search for Life on Other Worlds},
editor = {Seckbach,J. and Chela-Flores,J. and Owen,T. and Raulin,F.},
pages = {83 -- 87},
publisher = {Springer},
title = {{A Mechanism for the Prebiotic Emergence of Proteins}},
doi = {3807},
volume = {7},
year = {2004},
}
@article{4253,
abstract = {We consider a single genetic locus which carries two alleles, labelled P and Q. This locus experiences selection and mutation. It is linked to a second neutral locus with recombination rate r. If r = 0, this reduces to the study of a single selected locus. Assuming a Moran model for the population dynamics, we pass to a diffusion approximation and, assuming that the allele frequencies at the selected locus have reached stationarity, establish the joint generating function for the genealogy of a sample from the population and the frequency of the P allele. In essence this is the joint generating function for a coalescent and the random background in which it evolves. We use this to characterize, for the diffusion approximation, the probability of identity in state at the neutral locus of a sample of two individuals (whose type at the selected locus is known) as solutions to a system of ordinary differential equations. The only subtlety is to find the boundary conditions for this system. Finally, numerical examples are presented that illustrate the accuracy and predictions of the diffusion approximation. In particular, a comparison is made between this approach and one in which the frequencies at the selected locus are estimated by their value in the absence of fluctuations and a classical structured coalescent model is used.},
author = {Nicholas Barton and Etheridge, Alison M and Sturm, Anja K},
journal = {Annals of Applied Probability},
number = {2},
pages = {754 -- 785},
publisher = {Institute of Mathematical Statistics},
title = {{Coalescence in a Random Background}},
volume = {14},
year = {2004},
}
@inproceedings{4372,
author = {Maler, Oded and Dejan Nickovic},
pages = {152 -- 166},
publisher = {Springer},
title = {{Monitoring Temporal Properties of Continuous Signals}},
doi = {1572},
year = {2004},
}
@phdthesis{4424,
abstract = {The enormous cost and ubiquity of software errors necessitates the need for techniques and tools that can precisely analyze large systems and prove that they meet given specifications, or if they don't, return counterexample behaviors showing how the system fails. Recent advances in model checking, decision procedures, program analysis and type systems, and a shift of focus to partial specifications common to several systems (e.g., memory safety and race freedom) have resulted in several practical verification methods. However, these methods are either precise or they are scalable, depending on whether they track the values of variables or only a fixed small set of dataflow facts (e.g., types), and are usually insufficient for precisely verifying large programs.
We describe a new technique called Lazy Abstraction (LA) which achieves both precision and scalability by localizing the use of precise information. LA automatically builds, explores and refines a single abstract model of the program in a way that different parts of the model exhibit different degrees of precision, namely just enough to verify the desired property. The algorithm automatically mines the information required by partitioning mechanical proofs of unsatisfiability of spurious counterexamples into Craig Interpolants. For multithreaded systems, we give a new technique based on analyzing the behavior of a single thread executing in a context which is an abstraction of the other (arbitrarily many) threads. We define novel context models and show how to automatically infer them and analyze the full system (thread + context) using LA.
LA is implemented in BLAST. We have run BLAST on Windows and Linux Device Drivers to verify API conformance properties, and have used it to find (or guarantee the absence of) data races in multithreaded Networked Embedded Systems (NESC) applications. BLAST is able to prove the absence of races in several cases where earlier methods, which depend on lock-based synchronization, fail.},
author = {Jhala, Ranjit},
pages = {1 -- 165},
publisher = {University of California, Berkeley},
title = {{Program verification by lazy abstraction}},
year = {2004},
}
@inproceedings{4445,
abstract = {We present a type system for E code, which is an assembly language that manages the release, interaction, and termination of real-time tasks. E code specifies a deadline for each task, and the type system ensures that the deadlines are path-insensitive. We show that typed E programs allow, for given worst-case execution times of tasks, a simple schedulability analysis. Moreover, the real-time programming language Giotto can be compiled into typed E~code. This shows that typed E~code identifies an easily schedulable yet expressive class of real-time programs. We have extended the Giotto compiler to generate typed E code, and enabled the run-time system for E code to perform a type and schedulability check before executing the code.},
author = {Thomas Henzinger and Kirsch, Christoph M},
pages = {104 -- 113},
publisher = {ACM},
title = {{A typed assembly language for real-time programs}},
doi = {10.1145/1017753.1017774},
year = {2004},
}
@inproceedings{4458,
abstract = {The success of model checking for large programs depends crucially on the ability to efficiently construct parsimonious abstractions. A predicate abstraction is parsimonious if at each control location, it specifies only relationships between current values of variables, and only those which are required for proving correctness. Previous methods for automatically refining predicate abstractions until sufficient precision is obtained do not systematically construct parsimonious abstractions: predicates usually contain symbolic variables, and are added heuristically and often uniformly to many or all control locations at once. We use Craig interpolation to efficiently construct, from a given abstract error trace which cannot be concretized, a parsominous abstraction that removes the trace. At each location of the trace, we infer the relevant predicates as an interpolant between the two formulas that define the past and the future segment of the trace. Each interpolant is a relationship between current values of program variables, and is relevant only at that particular program location. It can be found by a linear scan of the proof of infeasibility of the trace.We develop our method for programs with arithmetic and pointer expressions, and call-by-value function calls. For function calls, Craig interpolation offers a systematic way of generating relevant predicates that contain only the local variables of the function and the values of the formal parameters when the function was called. We have extended our model checker Blast with predicate discovery by Craig interpolation, and applied it successfully to C programs with more than 130,000 lines of code, which was not possible with approaches that build less parsimonious abstractions.},
author = {Thomas Henzinger and Jhala, Ranjit and Majumdar, Ritankar S and McMillan, Kenneth L},
pages = {232 -- 244},
publisher = {ACM},
title = {{Abstractions from proofs}},
doi = {10.1145/964001.964021},
year = {2004},
}
@inproceedings{4459,
abstract = {Software model checking has been successful for sequential programs, where predicate abstraction offers suitable models, and counterexample-guided abstraction refinement permits the automatic inference of models. When checking concurrent programs, we need to abstract threads as well as the contexts in which they execute. Stateless context models, such as predicates on global variables, prove insufficient for showing the absence of race conditions in many examples. We therefore use richer context models, which combine (1) predicates for abstracting data state, (2) control flow quotients for abstracting control state, and (3) counters for abstracting an unbounded number of threads. We infer suitable context models automatically by a combination of counterexample-guided abstraction refinement, bisimulation minimization, circular assume-guarantee reasoning, and parametric reasoning about an unbounded number of threads. This algorithm, called CIRC, has been implemented in BLAST and succeeds in checking many examples of NESC code for data races. In particular, BLAST proves the absence of races in several cases where previous race checkers give false positives.},
author = {Thomas Henzinger and Jhala, Ranjit and Majumdar, Ritankar S},
pages = {1 -- 13},
publisher = {ACM},
title = {{Race checking by context inference}},
doi = {10.1145/996841.996844},
year = {2004},
}
@inbook{4461,
abstract = {One of the central axioms of extreme programming is the disciplined use of regression testing during stepwise software development. Due to recent progress in software model checking, it has become possible to supplement this process with automatic checks for behavioral safety properties of programs, such as conformance with locking idioms and other programming protocols and patterns. For efficiency reasons, all checks must be incremental, i.e., they must reuse partial results from previous checks in order to avoid all unnecessary repetition of expensive verification tasks. We show that the lazy-abstraction algorithm, and its implementation in Blast, can be extended to support the fully automatic and incremental checking of temporal safety properties during software development.},
author = {Thomas Henzinger and Jhala, Ranjit and Majumdar, Ritankar S and Sanvido, Marco A},
booktitle = {Verification: Theory and Practice},
pages = {332 -- 358},
publisher = {Springer},
title = {{Extreme model checking}},
doi = {10.1007/978-3-540-39910-0_16},
volume = {2772},
year = {2004},
}
@inproceedings{4525,
abstract = {We present a new high-level programming language, called xGiotto, for programming applications with hard real-time constraints. Like its predecessor, xGiotto is based on the LET (logical execution time) assumption: the programmer specifies when the outputs of a task become available, and the compiler checks if the specification can be implemented on a given platform. However, while the predecessor language xGiotto was purely time-triggered, xGiotto accommodates also asynchronous events. Indeed, through a mechanism called event scoping, events are the main structuring principle of the new language. The xGiotto compiler and run-time system implement event scoping through a tree-based event filter. The compiler also checks programs for determinism (absence of race conditions).},
author = {Ghosal, Arkadeb and Thomas Henzinger and Kirsch, Christoph M and Sanvido, Marco A},
pages = {167 -- 170},
publisher = {Springer},
title = {{Event-driven programming with logical execution times}},
doi = {10.1007/978-3-540-24743-2_24},
volume = {2993},
year = {2004},
}
@inproceedings{4555,
abstract = {Strategies in repeated games can be classified as to whether or not they use memory and/or randomization. We consider Markov decision processes and 2-player graph games, both of the deterministic and probabilistic varieties. We characterize when memory and/or randomization are required for winning with respect to various classes of w-regular objectives, noting particularly when the use of memory can be traded for the use of randomization. In particular, we show that Markov decision processes allow randomized memoryless optimal strategies for all M?ller objectives. Furthermore, we show that 2-player probabilistic graph games allow randomized memoryless strategies for winning with probability 1 those M?ller objectives which are upward-closed. Upward-closure means that if a set α of infinitely repeating vertices is winning, then all supersets of α are also winning.},
author = {Krishnendu Chatterjee and de Alfaro, Luca and Thomas Henzinger},
pages = {206 -- 217},
publisher = {IEEE},
title = {{Trading memory for randomness}},
doi = {10.1109/QEST.2004.10051},
year = {2004},
}
@article{4556,
abstract = {We study the problem of determining stack boundedness and the exact maximum stack size for three classes of interrupt-driven programs. Interrupt-driven programs are used in many real-time applications that require responsive interrupt handling. In order to ensure responsiveness, programmers often enable interrupt processing in the body of lower-priority interrupt handlers. In such programs a programming error can allow interrupt handlers to be interrupted in a cyclic fashion to lead to an unbounded stack, causing the system to crash. For a restricted class of interrupt-driven programs, we show that there is a polynomial-time procedure to check stack boundedness, while determining the exact maximum stack size is PSPACE-complete. For a larger class of programs, the two problems are both PSPACE-complete, and for the largest class of programs we consider, the two problems are PSPACE-hard and can be solved in exponential time. While the complexities are high, our algorithms are exponential only in the number of handlers, and polynomial in the size of the program.},
author = {Krishnendu Chatterjee and Ma, Di and Majumdar, Ritankar S and Zhao, Tian and Thomas Henzinger and Palsberg, Jens},
journal = {Information and Computation},
number = {2},
pages = {144 -- 174},
publisher = {Elsevier},
title = {{Stack size analysis for interrupt-driven programs}},
doi = {10.1016/j.ic.2004.06.001},
volume = {194},
year = {2004},
}
@inproceedings{4558,
abstract = {We study perfect-information stochastic parity games. These are two-player nonterminating games which are played on a graph with turn-based probabilistic transitions. A play results in an infinite path and the conflicting goals of the two players are ω-regular path properties, formalized as parity winning conditions. The qualitative solution of such a game amounts to computing the set of vertices from which a player has a strategy to win with probability 1 (or with positive probability). The quantitative solution amounts to computing the value of the game in every vertex, i.e., the highest probability with which a player can guarantee satisfaction of his own objective in a play that starts from the vertex.For the important special case of one-player stochastic parity games (parity Markov decision processes) we give polynomial-time algorithms both for the qualitative and the quantitative solution. The running time of the qualitative solution is O(d · m3/2) for graphs with m edges and d priorities. The quantitative solution is based on a linear-programming formulation.For the two-player case, we establish the existence of optimal pure memoryless strategies. This has several important ramifications. First, it implies that the values of the games are rational. This is in contrast to the concurrent stochastic parity games of de Alfaro et al.; there, values are in general algebraic numbers, optimal strategies do not exist, and ε-optimal strategies have to be mixed and with infinite memory. Second, the existence of optimal pure memoryless strategies together with the polynomial-time solution forone-player case implies that the quantitative two-player stochastic parity game problem is in NP ∩ co-NP. This generalizes a result of Condon for stochastic games with reachability objectives. It also constitutes an exponential improvement over the best previous algorithm, which is based on a doubly exponential procedure of de Alfaro and Majumdar for concurrent stochastic parity games and provides only ε-approximations of the values.},
author = {Krishnendu Chatterjee and Jurdziński, Marcin and Thomas Henzinger},
pages = {121 -- 130},
publisher = {SIAM},
title = {{Quantitative stochastic parity games}},
year = {2004},
}