@article{3917, abstract = {Male dimorphism is not genetically determined, but is induced by environmental conditions particularly decreasing temperature and density.}, author = {Cremer, Sylvia and Heinze, Jürgen}, journal = {Blick in die Wissenschaft}, number = {15}, pages = {32 -- 36}, publisher = {Schnell und Steiner}, title = {{Zwischen Hochzeitsflug und Brudermord: reproduktive Taktiken bei Ameisenmännchen}}, volume = {12}, year = {2003}, } @phdthesis{4416, abstract = {Methods for the formal specification and verification of systems are indispensible for the development of complex yet correct systems. In formal verification, the designer describes the system in a modeling language with a well-defined semantics, and this system description is analyzed against a set of correctness requirements. Model checking is an algorithmic technique to check that a system description indeed satisfies correctness requirements given as logical specifications. While successful in hardware verification, the potential for model checking for software and embedded systems has not yet been realized. This is because traditional model checking focuses on systems modeled as finite state-transition graphs. While a natural model for hardware (especially synchronous hardware), state-transition graphs often do not capture software and embedded systems at an appropriate level of granularity. This dissertation considers two orthogonal extensions to finite state-transition graphs making model checking techniques applicable to both a wider class of systems and a wider class of properties. The first direction is an extension to infinite-state structures finitely represented using constraints and operations on constraints. Infinite state arises when we wish to model variables with unbounded range (e.g., integers), or data structures, or real time. We provide a uniform framework of symbolic region algebras to study model checking of infinite-state systems. We also provide sufficient language-independent termination conditions for symbolic model checking algorithms on infinite state systems. The second direction supplements verification with game theoretic reasoning. Games are natural models for interactions between components. We study game theoretic behavior with winning conditions given by temporal logic objectives both in the deterministic and in the probabilistic context. For deterministic games, we provide an extremal model characterization of fixpoint algorithms that link solutions of verification problems to solutions for games. For probabilistic games we study fixpoint characterization of winning probabilities for games with omega-regular winning objectives, and construct (epsilon-)optimal winning strategies.}, author = {Majumdar, Ritankar}, pages = {1 -- 201}, publisher = {University of California, Berkeley}, title = {{Symbolic algorithms for verification and control}}, year = {2003}, } @phdthesis{4425, abstract = {Giotto provides a time-triggered programmer’s model for the implementation of embedded control systems with hard real-time constraints. Giotto’s precise semantics and predictabil- ity make it suitable for safety-critical applications. Giotto is based around the idea that time-triggered task invocation together with time-triggered mode switching can form a useful programming model for real-time systems. To substantiate this claim, we describe the use of Giotto to refactor the software of a small, autonomous helicopter. The ease with which Giotto expresses the existing software provides evidence that Giotto is an appropriate programming language for control systems. Since Giotto is a real-time programming language, ensuring that Giotto programs meet their deadlines is crucial. To study precedence-constrained Giotto scheduling, we first examine single-mode, single-processor scheduling. We extend to an infinite, periodic setting the classical problem of meeting deadlines for a set of tasks with release times, deadlines, precedence constraints, and preemption. We then develop an algorithm for scheduling Giotto programs on a single processor by representing Giotto programs as instances of the extended scheduling problem. Next, we study multi-mode, single-processor Giotto scheduling. This problem is different from classical scheduling problems, since in our precedence-constrained approach, the deadlines of tasks may vary depending on the mode switching behavior of the program. We present conditional scheduling models which capture this varying-deadline behavior. We develop polynomial-time algorithms for some conditional scheduling models, and prove oth- ers to be computationally hard. We show how to represent multi-mode Giotto programs as instances of the model, resulting in an algorithm for scheduling multi-mode Giotto programs on a single processor. Finally, we show that the problem of scheduling Giotto programs for multiple net- worked processors is strongly NP-hard.}, author = {Horowitz, Benjamin}, pages = {1 -- 237}, publisher = {University of California, Berkeley}, title = {{Giotto: A time-triggered language for embedded programming}}, year = {2003}, } @article{576, abstract = {We study the free expansion of a pancake-shaped Bose-condensed gas, which is initially trapped under harmonic confinement and containing a vortex at its centre. In the case of a radial expansion holding the axial confinement fixed we consider various models for the interactions, depending on the thickness of the condensate relative to the value of the scattering length. We are thus able to evaluate different scattering regimes ranging from quasi-three-dimensional (Q3D) to strictly two-dimensional (2D). We find that as the system goes from Q3D to 2D the expansion rate of the condensate increases whereas that of the vortex core decreases. In the Q3D scattering regime we also examine a fully free expansion in 3D and find oscillatory behaviour for the vortex core radius: an initial fast expansion of the vortex core is followed by a slowing down. Such a nonuniform expansion rate of the vortex core implies that the timing of its observation should be chosen appropriately.}, author = {Onur Hosten and Vignolo, Patrizia and Minguzzi, Anna and Tanatar, Bilal and Tosi, Mario P}, journal = {Journal of Physics B: Atomic, Molecular and Optical Physics}, number = {12}, pages = {2455 -- 2463}, publisher = {IOP Publishing Ltd.}, title = {{Free expansion of two-dimensional condensates with a vortex}}, doi = {10.1088/0953-4075/36/12/306}, volume = {36}, year = {2003}, } @article{6156, abstract = {Social and solitary feeding in natural Caenorhabditis elegans isolates are associated with two alleles of the orphan G-protein-coupled receptor (GPCR) NPR-1: social feeders contain NPR-1 215F, whereas solitary feeders contain NPR-1 215V. Here we identify FMRFamide-related neuropeptides (FaRPs) encoded by the flp-18 and flp-21 genes as NPR-1 ligands and show that these peptides can differentially activate the NPR-1 215F and NPR-1 215V receptors. Multicopy overexpression of flp-21 transformed wild social animals into solitary feeders. Conversely, a flp-21 deletion partially phenocopied the npr-1(null) phenotype, which is consistent with NPR-1 activation by FLP-21 in vivo but also implicates other ligands for NPR-1. Phylogenetic studies indicate that the dominant npr-1 215V allele likely arose from an ancestral npr-1 215F gene in C. elegans. Our data suggest a model in which solitary feeding evolved in an ancestral social strain of C. elegans by a gain-of-function mutation that modified the response of NPR-1 to FLP-18 and FLP-21 ligands.}, author = {Rogers, Candida and Reale, Vincenzina and Kim, Kyuhyung and Chatwin, Heather and Li, Chris and Evans, Peter and de Bono, Mario}, issn = {1097-6256}, journal = {Nature Neuroscience}, number = {11}, pages = {1178--1185}, publisher = {Springer Nature}, title = {{Inhibition of Caenorhabditis elegans social feeding by FMRFamide-related peptide activation of NPR-1}}, doi = {10.1038/nn1140}, volume = {6}, year = {2003}, } @article{6157, abstract = {In many animal species individuals aggregate to live in groups. A range of experimental approaches in different animals, including studies of social feeding in nematodes, maternal behavior in rats and sheep, and pair-bonding in voles, are providing insights into the neural bases for these behaviors. These studies are delineating multiple neural circuits and gene networks in the brain that interact in ways that are as yet poorly understood to coordinate social behavior.}, author = {de Bono, Mario}, issn = {0022-3034}, journal = {Journal of Neurobiology}, number = {1}, pages = {78--92}, publisher = {Wiley}, title = {{Molecular approaches to aggregation behavior and social attachment}}, doi = {10.1002/neu.10162}, volume = {54}, year = {2003}, } @article{847, abstract = {The accumulation of genome-wide information on single nucleotide polymorphisms in humans provides an unprecedented opportunity to detect the evolutionary forces responsible for heterogeneity of the level of genetic variability across loci. Previous studies have shown that history of recombination events has produced long haplotype blocks in the human genome, which contribute to this heterogeneity. Other factors, however, such as natural selection or the heterogeneity of mutation rates across loci, may also lead to heterogeneity of genetic variability. We compared synonymous and non-synonymous variability within human genes with their divergence from murine orthologs. We separately analyzed the non-synonymous variants predicted to damage protein structure or function and the variants predicted to be functionally benign. The predictions were based on comparative sequence analysis and, in some cases, on the analysis of protein structure. A strong correlation between non-synonymous, benign variability and non-synonymous human-mouse divergence suggests that selection played an important role in shaping the pattern of variability in coding regions of human genes. However, the lack of correlation between deleterious variability and evolutionary divergence shows that a substantial proportion of the observed non-synonymous single-nucleotide polymorphisms reduces fitness and never reaches fixation. Evolutionary and medical implications of the impact of selection on human polymorphisms are discussed.}, author = {Sunyaev, Shamil R and Fyodor Kondrashov and Bork, Peer and Ramensky, Vasily}, journal = {Human Molecular Genetics}, number = {24}, pages = {3325 -- 3330}, publisher = {Oxford University Press}, title = {{Impact of selection, mutation rate and genetic drift on human genetic variation}}, doi = {10.1093/hmg/ddg359}, volume = {12}, year = {2003}, } @article{876, abstract = {Alternative splicing is thought to be a major source of functional diversity in animal proteins. We analyzed the evolutionary conservation of proteins encoded by alternatively spliced genes and predicted the ancestral state for 73 cases of alternative splicing (25 insertions and 48 deletions). The amino acid sequences of most of the inserts in proteins produced by alternative splicing are as conserved as the surrounding sequences. Thus, alternative splicing often creates novel isoforms by the insertion of new, functional protein sequences that probably originated from noncoding sequences of introns.}, author = {Fyodor Kondrashov and Koonin, Eugene V}, journal = {Trends in Genetics}, number = {3}, pages = {115 -- 119}, publisher = {Elsevier}, title = {{Evolution of alternative splicing: Deletions, insertions and origin of functional parts of proteins from intron sequences}}, doi = {10.1016/S0168-9525(02)00029-X}, volume = {19}, year = {2003}, } @article{9495, abstract = {RNA interference is a conserved process in which double-stranded RNA is processed into 21–25 nucleotide siRNAs that trigger posttranscriptional gene silencing. In addition, plants display a phenomenon termed RNA-directed DNA methylation (RdDM) in which DNA with sequence identity to silenced RNA is de novo methylated at its cytosine residues. This methylation is not only at canonical CpG sites but also at cytosines in CpNpG and asymmetric sequence contexts. In this report, we study the role of the DRM and CMT3 DNA methyltransferase genes in the initiation and maintenance of RdDM. Neither drm nor cmt3 mutants affected the maintenance of preestablished RNA-directed CpG methylation. However, drm mutants showed a nearly complete loss of asymmetric methylation and a partial loss of CpNpG methylation. The remaining asymmetric and CpNpG methylation was dependent on the activity of CMT3, showing that DRM and CMT3 act redundantly to maintain non-CpG methylation. These DNA methyltransferases appear to act downstream of siRNAs, since drm1 drm2 cmt3 triple mutants show a lack of non-CpG methylation but elevated levels of siRNAs. Finally, we demonstrate that DRM activity is required for the initial establishment of RdDM in all sequence contexts including CpG, CpNpG, and asymmetric sites.}, author = {Cao, Xiaofeng and Aufsatz, Werner and Zilberman, Daniel and Mette, M.Florian and Huang, Michael S. and Matzke, Marjori and Jacobsen, Steven E.}, issn = {1879-0445}, journal = {Current Biology}, number = {24}, pages = {2212--2217}, publisher = {Elsevier}, title = {{Role of the DRM and CMT3 methyltransferases in RNA-directed DNA methylation}}, doi = {10.1016/j.cub.2003.11.052}, volume = {13}, year = {2003}, } @article{8519, author = {Kaloshin, Vadim}, issn = {0020-9910}, journal = {Inventiones mathematicae}, keywords = {General Mathematics}, number = {3}, pages = {451--512}, publisher = {Springer Nature}, title = {{The existential Hilbert 16-th problem and an estimate for cyclicity of elementary polycycles}}, doi = {10.1007/s00222-002-0244-9}, volume = {151}, year = {2003}, } @article{9455, abstract = {Proteins of the ARGONAUTE family are important in diverse posttranscriptional RNA-mediated gene-silencing systems as well as in transcriptional gene silencing in Drosophila and fission yeast and in programmed DNA elimination in Tetrahymena. We cloned ARGONAUTE4 (AGO4) from a screen for mutants that suppress silencing of the Arabidopsis SUPERMAN(SUP) gene. The ago4-1 mutant reactivated silentSUP alleles and decreased CpNpG and asymmetric DNA methylation as well as histone H3 lysine-9 methylation. In addition,ago4-1 blocked histone and DNA methylation and the accumulation of 25-nucleotide small interfering RNAs (siRNAs) that correspond to the retroelement AtSN1. These results suggest that AGO4 and long siRNAs direct chromatin modifications, including histone methylation and non-CpG DNA methylation.}, author = {Zilberman, Daniel and Cao, Xiaofeng and Jacobsen, Steven E.}, issn = {1095-9203}, journal = {Science}, keywords = {Multidisciplinary}, number = {5607}, pages = {716--719}, publisher = {American Association for the Advancement of Science}, title = {{ARGONAUTE4 control of locus-specific siRNA accumulation and DNA and histone methylation}}, doi = {10.1126/science.1079695}, volume = {299}, year = {2003}, } @inproceedings{4628, abstract = {Discounting the future means that the value, today, of a unit payoffis 1 if the payoffo ccurs today, a if it occurs tomorrow, a 2 if it occurs the day after tomorrow, and so on, for some real-valued discount factor 0 < a < 1. Discounting (or inflation) is a key paradigm in economics and has been studied in Markov decision processes as well as game theory. We submit that discounting also has a natural place in systems engineering: for nonterminating systems, a potential bug in the far-away future is less troubling than a potential bug today. We therefore develop a systems theory with discounting. Our theory includes several basic elements: discounted versions of system properties that correspond to the ω-regular properties, fixpoint-based algorithms for checking discounted properties, and a quantitative notion of bisimilarity for capturing the difference between two states with respect to discounted properties. We present the theory in a general form that applies to probabilistic systems as well as multicomponent systems (games), but it readily specializes to classical transition systems. We show that discounting, besides its natural practical appeal, has also several mathematical benefits. First, the resulting theory is robust, in that small perturbations of a system can cause only small changes in the properties of the system. Second, the theory is computational, in that the values of discounted properties, as well as the discounted bisimilarity distance between states, can be computed to any desired degree of precision.}, author = {De Alfaro, Luca and Henzinger, Thomas A and Majumdar, Ritankar}, booktitle = {Proceedings of the 30th International Colloquium on Automata, Languages and Programming}, isbn = {9783540404934}, location = {Eindhoven, The Netherlands}, pages = {1022 -- 1037}, publisher = {Springer}, title = {{Discounting the future in systems theory}}, doi = {10.1007/3-540-45061-0_79}, volume = {2719}, year = {2003}, } @article{13436, abstract = {Cross-metathesis reactions of α,β-unsaturated sulfones and sulfoxides in the presence of molybdenum and ruthenium pre-catalysts were tested. A selective metahesis reaction was achieved between functionalized terminal olefins and vinyl sulfones by using the ‘second generation’ ruthenium catalysts 1c–h while the highly active Schrock catalyst 1b was found to be functional group incompatible with vinyl sulfones. The cross-metathesis products were isolated in good yields with an excellent (E)-selectivity. Both the molybdenum and ruthenium-based complexes were, however, incompatible with α,β- and β,γ-unsaturated sulfoxides.}, author = {Michrowska, Anna and Bieniek, Michał and Kim, Mikhail and Klajn, Rafal and Grela, Karol}, issn = {1464-5416}, journal = {Tetrahedron}, keywords = {Organic Chemistry, Drug Discovery, Biochemistry}, number = {25}, pages = {4525--4531}, publisher = {Elsevier}, title = {{Cross-metathesis reaction of vinyl sulfones and sulfoxides}}, doi = {10.1016/s0040-4020(03)00682-3}, volume = {59}, year = {2003}, } @inproceedings{4561, abstract = {We present a formalism for specifying component interfaces that expose component requirements on limited resources. The formalism permits an algorithmic check if two or more components, when put together, exceed the available resources. Moreover, the formalism can be used to compute the quantity of resources necessary for satisfying the requirements of a collection of components. The formalism can be instantiated in several ways. For example, several components may draw power from the same source. Then, the formalism supports compatibility checks such as: can two components, when put together, achieve their tasks without ever exceeding the available amount of peak power? or, can they achieve their tasks by using no more than the initially available amount of energy (i.e., power accumulated over time)? The corresponding quantitative questions that our algorithms answer are the following: what is the amount of peak power needed for two components to be put together? what is the corresponding amount of initial energy? To solve these questions, we model interfaces with resource requirements as games with quantitative objectives. The games are played on state spaces where each state is labeled by a number (representing, e.g., power consumption), and a play produces an infinite path of labels. The objective may be, for example, to minimize the largest label that occurs during a play. We illustrate our approach by modeling compatibility questions for the components of robot control software, and of wireless sensor networks.}, author = {Chakrabarti, Arindam and De Alfaro, Luca and Henzinger, Thomas A and Stoelinga, Mariëlle}, booktitle = {Third International Conference on Embedded Software}, isbn = {9783540202233}, location = {Philadelphia, PA, USA}, pages = {117 -- 133}, publisher = {ACM}, title = {{Resource interfaces}}, doi = {10.1007/978-3-540-45212-6_9}, volume = {2855}, year = {2003}, } @inproceedings{4630, abstract = {We consider concurrent two-person games played in real time, in which the players decide both which action to play, and when to play it. Such timed games differ from untimed games in two essential ways. First, players can take each other by surprise, because actions are played with delays that cannot be anticipated by the opponent. Second, a player should not be able to win the game by preventing time from diverging. We present a model of timed games that preserves the element of surprise and accounts for time divergence in a way that treats both players symmetrically and applies to all ω-regular winning conditions. We prove that the ability to take each other by surprise adds extra power to the players. For the case that the games are specified in the style of timed automata, we provide symbolic algorithms for their solution with respect to all ω-regular winning conditions. We also show that for these timed games, memory strategies are more powerful than memoryless strategies already in the case of reachability objectives.}, author = {De Alfaro, Luca and Faella, Marco and Henzinger, Thomas A and Majumdar, Ritankar and Stoelinga, Mariëlle}, booktitle = {Proceedings of the 14th International Conference on Concurrency Theory}, isbn = {9783540407539}, location = {Marseille, France}, pages = {144 -- 158}, publisher = {Schloss Dagstuhl - Leibniz-Zentrum für Informatik}, title = {{The element of surprise in timed games}}, doi = {10.1007/978-3-540-45187-7_9}, volume = {2761}, year = {2003}, } @article{4468, abstract = {Giotto is a high-level programming language for time-triggered control applications. The authors begin with a conceptual overview of its methodology, discuss the Giotto helicopter project, and summarize available Giotto implementations.}, author = {Henzinger, Thomas A and Kirsch, Christoph and Sanvido, Marco and Pree, Wolfgang}, issn = {1066-033X }, journal = {IEEE Control Systems Magazine}, number = {1}, pages = {50 -- 64}, publisher = {IEEE}, title = {{From control models to real-time code using Giotto}}, doi = {10.1109/MCS.2003.1172829}, volume = {23}, year = {2003}, } @inbook{4465, abstract = {Giotto is a principled, tool-supported design methodology for implementing embedded control systems on platforms of possibly distributed sensors, actuators, CPUs, and networks. Giotto is based on the principle that time-triggered task invocations plus time-triggered mode switches can form the abstract essence of programming real-time control systems. Giotto consists of a programming language with a formal semantics, and a retargetable compiler and runtime library. Giotto supports the automation of control system design by strictly separating platform-independent functionality and timing concerns from platform-dependent scheduling and communication issues. The time-triggered predictability of Giotto makes it particularly suitable for safety-critical applications with hard real-time constraints. We illustrate the platform independence and time-triggered execution of Giotto by coordinating a heterogeneous flock of Intel x86 robots and Lego Mindstorms robots.}, author = {Henzinger, Thomas A and Horowitz, Benjamin and Kirsch, Christoph}, booktitle = {Software-Enabled Control: Information Technology for Dynamical Systems}, isbn = {9780471234364 }, pages = {123 -- 146}, publisher = {Wiley-Blackwell}, title = {{Embedded control systems development with Giotto}}, doi = {10.1002/047172288X.ch8}, year = {2003}, } @inproceedings{4466, abstract = {One source of complexity in the μ-calculus is its ability to specify an unbounded number of switches between universal (AX) and existential (EX) branching modes. We therefore study the problems of satisfiability, validity, model checking, and implication for the universal and existential fragments of the μ-calculus, in which only one branching mode is allowed. The universal fragment is rich enough to express most specifications of interest, and therefore improved algorithms are of practical importance. We show that while the satisfiability and validity problems become indeed simpler for the existential and universal fragments, this is, unfortunately, not the case for model checking and implication. We also show the corresponding results for the alternationfree fragment of the μ-calculus, where no alternations between least and greatest fixed points are allowed. Our results imply that efforts to find a polynomial-time model-checking algorithm for the μ-calculus can be replaced by efforts to find such an algorithm for the universal or existential fragment.}, author = {Henzinger, Thomas A and Kupferman, Orna and Majumdar, Ritankar}, booktitle = {Proceedings of the 9th International Conference on Tools and Algorithms for the Construction and Analysis of Systems }, isbn = {9783540008989}, location = {Warsaw, Poland}, pages = {49 -- 64}, publisher = {Springer}, title = {{On the universal and existential fragments of the mu-calculus}}, doi = {10.1007/3-540-36577-X_5}, volume = {2619}, year = {2003}, } @inproceedings{4467, abstract = {BLAST (the Berkeley Lazy Abstraction Software verification Tool) is a verification system for checking safety properties of C programs using automatic property-driven construction and model checking of software abstractions. Blast implements an abstract-model check-refine loop to check for reachability of a specified label in the program. The abstract model is built on the fly using predicate abstraction. This model is then checked for reachability. If there is no (abstract) path to the specified error label, Blast reports that the system is safe and produces a succinct proof. Otherwise, it checks if the path is feasible using symbolic execution of the program. If the path is feasible, Blast outputs the path as an error trace, otherwise, it uses the infeasibility of the path to refine the abstract model. Blast short-circuits the loop from abstraction to verification to refinement, integrating the three steps tightly through “lazy abstraction” [5]. This integration can offer significant advantages in performance by avoiding the repetition of work from one iteration of the loop to the next. }, author = {Henzinger, Thomas A and Jhala, Ranjit and Majumdar, Ritankar and Sutre, Grégoire}, booktitle = {Proceedings of the 10th International SPIN Workshop }, isbn = {9783540401179}, location = {Portland, OR, USA}, pages = {235 -- 239}, publisher = {Springer}, title = {{Software verification with BLAST}}, doi = {10.1007/3-540-44829-2_17}, volume = {2648}, year = {2003}, } @inproceedings{4463, abstract = {We present an algorithm called TAR (“Thread-modular Abstraction Refinement”) for model checking safety properties of concurrent software. The TAR algorithm uses thread-modular assume-guarantee reasoning to overcome the exponential complexity in the control state of multithreaded programs. Thread modularity means that TAR explores the state space of one thread at a time, making assumptions about how the environment can interfere. The TAR algorithm uses counterexample-guided predicate-abstraction refinement to overcome the usually infinite complexity in the data state of C programs. A successive approximation scheme automatically infers the necessary precision on data variables as well as suitable environment assumptions. The scheme is novel in that transition relations are approximated from above, while at the same time environment assumptions are approximated from below. In our software verification tool BLAST we have implemented a fully automatic race checker for multithreaded C programs which is based on the TAR algorithm. This tool has verified a wide variety of commonly used locking idioms, including locking schemes that are not amenable to existing dynamic and static race checkers such as ERASER or WARLOCK.}, author = {Henzinger, Thomas A and Jhala, Ranjit and Majumdar, Ritankar and Qadeer, Shaz}, booktitle = {Proceedings of the 15th International Conference on Computer Aided Verification}, isbn = {9783540405245}, location = {Boulder, CO, USA}, pages = {262 -- 274}, publisher = {Springer}, title = {{Thread-modular abstraction refinement}}, doi = {10.1007/978-3-540-45069-6_27}, volume = {2725}, year = {2003}, }