TY - JOUR
AB - The tra-1 gene is the terminal global selector of somatic sex in Caenorhabditis elegans: High tra-1 activity elicits female somatic development while low tra-1 activity elicits male development. Previous genetic studies defined a cascade of negatively interacting genes that regulates tra-1 activity in response to the primary sex-determining signal. Here, we investigate the last step in this regulatory cascade, by studying rare gain-of-function (gf) mutations of tra-1 that direct female somatic development irrespective of the upstream sex-determining signal. These mutations appear to abolish negative regulation of tra-1 in male tissues. We identify the lesions associated with 29 of these mutations and find that all affect a short stretch of amino acid residues present in both protein products of the tra-1 gene. Twenty-six alleles are associated with single nonconservative amino acid substitutions. Two alleles affect tra-1 RNA splicing and generate messages that omit part or all of the exon encoding this short stretch. These results suggest that sexual regulation of tra-1 is achieved post-translationally, by an inhibitory protein-protein interaction. The amino acid stretch altered by the tra-1(gf) mutations may define a site of interaction for negative regulators of tra-1. The stretch includes a potential phosphorylation site for glycogen synthase kinase 3 and may be conserved in the human gene GLI3, a homolog of tra-1 identified previously.
AU - de Bono, Mario
AU - Zarkower, D.
AU - Hodgkin, J.
ID - 6162
IS - 2
JF - Genes and Development
SN - 08909369
TI - Dominant feminizing mutations implicate protein-protein interactions as the main mode of regulation of the nematode sex-determining gene tra-1
VL - 9
ER -
TY - JOUR
AB - Efficient algorithms are described for computing topological, combinatorial, and metric properties of the union of finitely many spherical balls in R(d) These algorithms are based on a simplicial complex dual to a decomposition of the union of balls using Voronoi cells, and on short inclusion-exclusion formulas derived from this complex. The algorithms are most relevant in R(3) where unions of finitely many balls are commonly used as models of molecules.
AU - Herbert Edelsbrunner
ID - 4028
IS - 1
JF - Discrete & Computational Geometry
TI - The union of balls and its dual shape
VL - 13
ER -
TY - JOUR
AB - A general and direct method for computing the Betti numbers of a finite simplicial complex in Bd is given. This method is complete for d less than or equal to 3, where versions of this method run in time O(n alpha(n)) and O(n), n the number of simplices. An implementation of the algorithm is applied to alpha shapes, which is a novel geometric modeling tool.
AU - Delfinado, Cecil J
AU - Herbert Edelsbrunner
ID - 4029
IS - 7
JF - Computer Aided Geometric Design
TI - An incremental algorithm for Betti numbers of simplicial complexes on the 3-sphere
VL - 12
ER -
TY - CONF
AB - Any arbitrary polyhedron P contained as a subset within Rd can be written as algebraic sum of simple terms, each an integer multiple of the intersection of d or fewer half-spaces defined by facets of P. P can be non-convex and can have holes of any kind. Among the consequences of this result are a short boolean formula for P, a fast parallel algorithm for point classification, and a new proof of the Gram-Sommerville angle relation.
AU - Herbert Edelsbrunner
ID - 4034
TI - Algebraic decomposition of non-convex polyhedra
ER -
TY - JOUR
AB - Let S be a set of n points in ℝd . A set W is a weak ε-net for (convex ranges of)S if, for any T⊆S containing εn points, the convex hull of T intersects W. We show the existence of weak ε-nets of size {Mathematical expression}, where β2=0, β3=1, and βd ≈0.149·2d-1(d-1)!, improving a previous bound of Alon et al. Such a net can be computed effectively. We also consider two special cases: when S is a planar point set in convex position, we prove the existence of a net of size O((1/ε) log1.6(1/ε)). In the case where S consists of the vertices of a regular polygon, we use an argument from hyperbolic geometry to exhibit an optimal net of size O(1/ε), which improves a previous bound of Capoyleas.
AU - Chazelle, Bernard
AU - Herbert Edelsbrunner
AU - Grigni, Michelangelo
AU - Guibas, Leonidas
AU - Sharir, Micha
AU - Welzl, Emo
ID - 4035
IS - 1
JF - Discrete & Computational Geometry
TI - Improved bounds on weak ε-nets for convex sets
VL - 13
ER -
TY - JOUR
AU - Ransom, D.
AU - Brownlie, Alison
AU - Haffter, Pascal
AU - Odenthal, Jörg
AU - Kelsh, Robert
AU - Brand, Michael
AU - Furutani Seiki, Makoto
AU - Granato, Michael
AU - Hammerschmidt, Matthias
AU - Heisenberg, Carl-Philipp J
AU - Jiang, Yunjin
AU - Kane, David
AU - Mullins, Mary
AU - Van Eden, Fredericus
AU - Warga, Rachel
AU - Nüsslein Volhard, Christiane
AU - Zon, L.
ID - 4153
IS - 10
JF - Blood
TI - Hematopoietic mutants identified in a saturation screen of the zebrafish genome
VL - 86
ER -
TY - JOUR
AB - Three replicate lines of Drosophila melanogaster were cultured at each of two temperatures (16.5⚬C and 25⚬C) in population cages for 4 yr. The lifespans of both sexes and the fecundity and fertility of the females were then measured at both experimental temperatures. The characters showed evidence of adaptation; flies of both sexes from each selection regime showed higher longevity, and females showed higher fecundity and fertility, than flies from the other selection regime when they were tested at the experimental temperature at which they had evolved. Calculation of intrinsic rates of increase under different assumptions about the rate of population increase showed that the difference between the lines from the two selection regimes became less the higher the rate of population increase, because the lines were more similar in early adulthood than they were later. Despite the increased adaptation of the low-temperature lines to the low temperature, like the high temperature lines they produced progeny at a higher rate at the higher temperature. The lines may have independently evolved adaptations to their respective thermal regimes during the experiment, or there may have been a trade-off between adaptation to the two temperatures, or mutation pressure may have lowered adaptation to the temperature that the flies no longer encountered.
AU - Partridge, Linda
AU - Barrie, Brian
AU - Nicholas Barton
AU - Fowler, Kevin
AU - French, Vernon
ID - 4296
IS - 3
JF - Evolution; International Journal of Organic Evolution
TI - Rapid laboratory evolution of adult life history traits in Drosophila melanogaster in response to temperature
VL - 49
ER -
TY - JOUR
AB - The F5 (2n = 34) and FM2 (2n = 44-46) chromosome races of the Sceloporus grammicus complex form a parapatric hybrid zone in the Mexican state of Hidalgo, characterized by steep concordant clines among three diagnostic chromosome markers across a straight-line distance of about 2 km. Here, we show that this zone is actually structured into local patches in which hybridization extends over an extremely irregular front. The distribution of hybrid-index (HI) scores across the transect reveals some hybridization at almost all localities mapped in a central 7 km x 3 km area. Pooling the central samples produces both a strong heterozygote deficit for all diagnostic markers and strong linkage disequilibria between all pairwise combinations of these (unlinked) markers. Moreover, a highly significant association exists between the habitat on which each individual was caught and its karyotype (F5 chromosomes are more likely to be found on oak). Analysis of genotype frequencies over a range of spatial scales shows that there is no significant heterozygote deficit or habitat association within local areas of less than about 200 m; however, there is significant linkage disequilibrium over the smallest scales (R = D (pquv)1/2 = 0.29, support limits, 0.18-0.36) over 100 m. These patterns suggest that lizards mate and choose habitats randomly within local patches. This conclusion is supported by mark-recapture estimates of dispersal (≈ 80 m in a generation) and by inference of matings from embryo and maternal karyotypes. Closer examination of the two-dimensional pattern reveals a convoluted cline for all three markers, with a width of 830 m (support limits 770 m-930 m). This cline width, combined with the strength of local linkage disequilibrium, implies a dispersal rate of σ = 160 m in a generation and an effective selection pressure of 30% on each chromosome marker. The proportion of inviable embryos is greater in females from the center of the hybrid zone; this is caused by effects associated with both karyotype and location. The hybrid zone is likely to be maintained by selection against chromosomal heterozygotes, by other kinds of selection against hybrids, and by selection adapting the chromosome races to different habitats. The structure of the contact may be caused by both random drift and by selection in relation to habitat.
AU - Sites, Jack W
AU - Nicholas Barton
AU - Reed, Kent M
ID - 4297
IS - 1
JF - Evolution; International Journal of Organic Evolution
TI - The genetic structure of a mosaic hybrid zone between two chromosome races of the Sceloporus grammicus complex (Sauria, Phrynosomatidae) in central Mexico
VL - 49
ER -
TY - JOUR
AU - Nicholas Barton
ID - 4298
JF - Evolution; International Journal of Organic Evolution
TI - Appendix to "The mixing of genotypes in hybrid zones: a simulation study of multilocus clines", by S J E Baird
VL - 49
ER -
TY - THES
AB - Hybrid systems are real-time systems that react to both discrete and continuous activities (such as analog signals, time, temperature, and speed). Typical examples of hybrid systems are embedded systems, timing-based communication protocols, and digital circuits at the transistor level. Due to the rapid development of microprocessor technology, hybrid systems directly control much of what we depend on in our daily lives. Consequently, the formal specification and verification of hybrid systems has become an active area of research. This dissertation presents the first general framework for the formal specification and verification of hybrid systems, as well as the first hybrid-system analysis tool--HyTech. The framework consists of a graphical finite-state-machine-like language for modeling hybrid systems, a temporal logic for modeling the requirements of hybrid systems, and a computer procedure that verifies modeled hybrid systems against modeled requirements. The tool HyTech is the implementation of the framework using C++ and Mathematica.
More specifically, our hybrid-system modeling language, Hybrid Automata, is an extension of timed automata with discrete and continuous variables whose dynamics are governed by differential equations. Our requirement modeling language, ICTL, is a branching-time temporal logic, and is an extension of TCTL with stop-watch variables. Our verification procedure is a symbolic model-checking procedure that verifies linear hybrid automata against ICTL formulas. To make HyTech more efficient and effective, we use model-checking strategies and abstract operators that can expedite the verification process. To enable HyTech to verify nonlinear hybrid automata, we introduce two translations from nonlinear hybrid automata to linear hybrid automata. We have applied HyTech to analyze more than 30 hybrid-system benchmarks. In this dissertation, we present the application of HyTech to three nontrivial hybrid systems taken from the literature.
AU - Ho, Pei
ID - 4428
TI - Automatic Analysis of Hybrid Systems
ER -
TY - CHAP
AB - This paper is addressed to potential users of HyTech, the Cornell Hybrid Technology Tool, an automatic tool for analyzing hybrid systems. We review the formal technologies that have been incorporated into HyTech, and we illustrate the use of HyTech with three nontrivial case studies.
AU - Thomas Henzinger
AU - Ho, Pei-Hsin
ED - Panos, Antsaklis
ED - Kohn, Wolf
ED - Nerode, Anil
ED - Sastry, Shankar
ID - 4447
T2 - Hybrid Systems II
TI - HyTech: The Cornell Hybrid Technology Tool
VL - 999
ER -
TY - CHAP
AB - We report on several abstract interpretation strategies that are designed to improve the performance of HyTech, a symbolic model checker for linear hybrid systems. We (1) simultaneously compute the target region from different directions, (2) conservatively approximate the target region by dropping constraints, and (3) iteratively refine the approximation until sufficient precision is obtained. We consider the standard abstract convex-hull operator and a novel abstract extrapolation operator.
AU - Thomas Henzinger
AU - Ho, Pei-Hsin
ED - Panos, Antsaklis
ED - Kohn, Wolf
ED - Nerode, Anil
ED - Sastry, Shankar
ID - 4448
T2 - Hybrid Systems II
TI - A note on abstract-interpretation strategies for hybrid automata
VL - 999
ER -
TY - CONF
AB - Hybrid systems model discrete programs that are embedded in continuous environments. Model-checking tools are available for the analysis of linear hybrid systems, whose continuous variables are bounded by piecewise-linear trajectories. Most embedded programs, however, operate in nonlinear environments. We present, analyze, and apply two algorithms for translating nonlinear hybrid systems into linear hybrid systems.
The clock translation replaces nonlinear variables by clock variables; the rate translation approximates nonlinear variables by piecewise-linear envelopes. Both translations are sound for reachability; that is, if we establish a safety property of the translated linear system, we may conclude that the original nonlinear system satisfies the property. The clock translation is also complete for reachability; that is, the original system and the translated system satisfy the same safety properties. The two translations apply to incomparable classes of nonlinear hybrid systems. From the clock translation we obtain a new decidability result for hybrid systems.
With the help of Hytech, a symbolic model checker for linear hybrid systems, we automatically verify a nonlinear railroad gate control program using the clock translation, and a nonlinear temperature control program using the rate translation.
AU - Thomas Henzinger
AU - Ho, Pei-Hsin
ID - 4450
TI - Algorithmic analysis of nonlinear hybrid systems
VL - 939
ER -
TY - CONF
AB - HyTech is a tool for the automated analysis of embedded systems. This document, designed for the first-time user of HyTech, guides the reader through the underlying system model, and through the input language for describing and analyzing systems. The guide gives several examples of usage, and some hints for gaining maximal computational efficiency from the tool.
The version of HyTech described in this guide was released in August 1995, and is available through anonymous ftp from ftp.cs.cornell.edu in the directory pub/tah/HyTech, and through the World-Wide Web via HyTech's home page http:/www.cs.cornell.edu/Info/People/tah/hytech.html.
AU - Thomas Henzinger
AU - Ho, Pei-Hsin
AU - Wong-Toi, Howard
ID - 4497
TI - A user guide to HyTech
VL - 1019
ER -
TY - CONF
AB - We present algorithms for computing similarity relations of labeled graphs. Similarity relations have applications for the refinement and verification of reactive systems. For finite graphs, we present an O(mn) algorithm for computing the similarity relation of a graph with n vertices and m edges (assuming m⩾n). For effectively presented infinite graphs, we present a symbolic similarity-checking procedure that terminates if a finite similarity relation exists. We show that 2D rectangular automata, which model discrete reactive systems with continuous environments, define effectively presented infinite graphs with finite similarity relations. It follows that the refinement problem and the ∀CTL* model-checking problem are decidable for 2D rectangular automata
AU - Henzinger, Monika
AU - Thomas Henzinger
AU - Kopke, Peter W
ID - 4498
TI - Computing simulations on finite and infinite graphs
ER -
TY - CONF
AB - We describe a new implementation of HYTECH, a symbolic model checker for hybrid systems. Given a parametric description of an embedded system as a collection of communicating automata, HYTECH automatically computes the conditions on the parameters under which the system satisfies its safety and timing requirements. While the original HYTECH prototype was based on the symbolic algebra tool Mathematica, the new implementation is written in C++ and builds on geometric algorithms instead of formula manipulation. The new HYTECH offers a cleaner and more expressive input language, greater portability, superior performance (typically two to three orders of magnitude), and new features such as diagnostic error-trace generation. We illustrate the effectiveness of the new implementation by applying HYTECH to the automatic parametric analysis of the generic railroad crossing benchmark problem and to an active structure control algorithm
AU - Thomas Henzinger
AU - Ho, Pei-Hsin
AU - Wong-Toi, Howard
ID - 4499
TI - HyTech: The next generation
ER -
TY - CONF
AB - We investigate the expressive power of timing restrictions on labeled transition systems. In particular, we show how constraints on clock variables together with a uniform liveness condition—the divergence of time—can express Büchi, Muller, Streett, Rabin, and weak and strong fairness conditions on a given labeled transition system. We then consider the effect, on both timed and time-abstract expressiveness, of varying the following parameters: time domain (discrete or dense), number of clocks, number of states, and size of constants used in timing restrictions.
AU - Thomas Henzinger
AU - Kopke, Peter W
AU - Wong-Toi, Howard
ID - 4500
TI - The expressive power of clocks
VL - 944
ER -
TY - CONF
AB - Hybrid automata model systems with both digital and analog components, such as embedded control programs. Many verification tasks for such programs can be expressed as reachability problems for hybrid automata. By improving on previous decidability and undecidability results, we identify the precise boundary between decidability and undecidability of the reachability problem for hybrid automata.
On the positive side, we give an (optimal) PSPACE reachability algorithm for the case of initialized rectangular automata, where all analog variables follow trajectories within piecewise-linear envelopes and are reinitialized whenever the envelope changes. Our algorithm is based on the construction of a timed automaton that contains all reachability information about a given initialized rectangular automaton. The translation has practical significance for verification, because it guarantees the termination of symbolic procedures for the reachability analysis of initialized rectangular automata. The translation also preserves the omega-languages of initialized rectangular automata with bounded nondeterminism.
On the negative side, we show that several slight generalizations of initialized rectangular automata lead to an undecidable reachability problem. In particular, we prove that the reachability problem is undecidable for timed automata augmented with a single stopwatch.
AU - Thomas Henzinger
AU - Kopke, Peter W
AU - Puri, Anuj
AU - Varaiya,P.
ID - 4502
TI - What's decidable about hybrid automata?
ER -
TY - CONF
AB - The analysis, verification, and control of hybrid automata with finite bisimulations can be reduced to finite-state problems. We advocate a time-abstract, phase-based methodology for checking if a given hybrid automaton has a finite bisimulation. First, we factor the automaton into two components, a boolean automaton with a discrete dynamics on the finite state space B m and a euclidean automaton with a continuous dynamics on the infinite state space n . Second, we investigate the phase portrait of the euclidean component. In this fashion, we obtain new decidability results for hybrid systems as well as new, uniform proofs of known decidability results.
AU - Thomas Henzinger
ID - 4518
TI - Hybrid automata with finite bisimulations
VL - 944
ER -
TY - CONF
AB - We argue that the standard constraints on liveness conditions in nonblocking trace models—machine closure for closed systems, and receptiveness for open systems—are unnecessarily weak and complex, and that liveness should, instead, be specified by augmenting transition systems with acceptance conditions that satisfy a locality constraint. First, locality implies machine closure and receptiveness, and thus permits the composition and modular verification of live transition systems. Second, while machine closure and receptiveness are based on infinite games, locality is based on repeated finite games, and thus easier to check. Third, no expressive power is lost by the restriction to local liveness conditions. We illustrate the appeal of local liveness using the model of Fair Reactive Systems, a nonblocking trace model of communicating processes.
AU - Alur, Rajeev
AU - Thomas Henzinger
ID - 4587
TI - Local liveness for compositional modeling of fair reactive systems
VL - 939
ER -