TY - CHAP
AB - We introduce the framework of hybrid automata as a model and specification language for hybrid systems. Hybrid automata can be viewed as a generalization of timed automata, in which the behavior of variables is governed in each state by a set of differential equations. We show that many of the examples considered in the workshop can be defined by hybrid automata. While the reachability problem is undecidable even for very restricted classes of hybrid automata, we present two semidecision procedures for verifying safety properties of piecewiselinear hybrid automata, in which all variables change at constant rates. The two procedures are based, respectively, on minimizing and computing fixpoints on generally infinite state spaces. We show that if the procedures terminate, then they give correct answers. We then demonstrate that for many of the typical workshop examples, the procedures do terminate and thus provide an automatic way for verifying their properties.
AU - Alur, Rajeev
AU - Courcoubetis, Costas
AU - Thomas Henzinger
AU - Ho, Pei-Hsin
ED - Grossman, Robert L.
ED - Nerode, Anil
ED - Ravn, Anders P
ED - Rischel, Hans
ID - 4618
T2 - Hybrid Systems
TI - Hybrid automata: An algorithmic approach to the specification and verification of hybrid systems
VL - 736
ER -
TY - CONF
AB - Traditional approaches to the algorithmic verification of real-time systems are limited to checking program correctness with respect to concrete timing properties (e.g., "message delivery within 10 milliseconds"). We address the more realistic and more ambitious problem of deriving symbolic constraints on the timing properties required of real-time systems (e.g., "message delivery within the time it takes to execute two assignment statements"). To model this problem, we introduce parametric timed automata -- finite-state machines whose transitions are constrained with parametric timing requirements. The emptiness question for parametric timed automata is central to the verification problem. On the negative side, we show that in general this question is undecidable. On the positive side, we provide algorithms for checking the emptiness of restricted classes of parametric timed automata. The practical relevance of these classes is illustrated with several verification examples. There remains a gap between the automata classes for which we know that emptiness is decidable and undecidable, respectively, and this gap is related to various hard and open problems of logic and automata theory.
AU - Alur, Rajeev
AU - Thomas Henzinger
AU - Vardi, Moshe Y
ID - 4619
TI - Parametric real-time reasoning
ER -
TY - CONF
AB - We present a verification algorithm for duration properties of finite-state real-time systems. While simple real-time properties constrain the total elapsed time between events, duration properties constrain the accumulated time during which certain state predicates hold. We formalize the concept of durations by introducing duration measures for (dense-time) timed automata. Given a timed automaton with a duration measure, a start and a target state, and a duration constraint, the duration-bounded reachability problem asks if there is a run of the automaton from the start state to the target state such that the accumulated duration along the run satisfies the constraint. Our main result is a novel decision procedure for solving the duration-bounded reachability problem. We also prove that the problem is PSPACE-complete and demonstrate how the solution can be used to verify interesting duration properties of real-time systems.
AU - Alur, Rajeev
AU - Courcoubetis, Costas
AU - Thomas Henzinger
ID - 4620
TI - Computing accumulated delays in real-time systems
VL - 697
ER -
TY - JOUR
AB - This paper presents a randomized incremental algorithm for computing a single face in an arrangement of n line segments in the plane that is fairly simple to implement. The expected running time of the algorithm is O(nα(n)log n). The analysis of the algorithm uses a novel approach that generalizes and extends the Clarkson-Shor analysis technique [in Discrete Comput. Geom., 4(1989), pp. 387-421]. A few extensions of the technique, obtaining efficient randomized incremental algorithms for constructing the entire arrangement of a collection of line segments and for computing a single face in an arrangement of Jordan arcs are also presented.
AU - Chazelle, Bernard
AU - Herbert Edelsbrunner
AU - Guibas, Leonidas
AU - Sharir, Micha
AU - Snoeyink, Jack
ID - 4036
IS - 6
JF - SIAM Journal on Computing
TI - Computing a face in an arrangement of line segments and related problems
VL - 22
ER -
TY - JOUR
AB - A plane geometric graph C in ℝ2 conforms to another such graph G if each edge of G is the union of some edges of C. It is proved that, for every G with n vertices and m edges, there is a completion of a Delaunay triangulation of O(m2 n) points that conforms to G. The algorithm that constructs the points is also described.
AU - Herbert Edelsbrunner
AU - Tan, Tiow Seng
ID - 4040
IS - 1
JF - Discrete & Computational Geometry
TI - An upper bound for conforming Delaunay triangulations
VL - 10
ER -
TY - JOUR
AB - The zone theorem for an arrangement of n hyperplanes in d-dimensional real space says that the total number of faces bounding the cells intersected by another hyperplane is O(n(d-1)). This result is the basis of a time-optimal incremental algorithm that constructs a hyperplane arrangement and has a host of other algorithmic and combinatorial applications. Unfortunately, the original proof of the zone theorem, for d greater-than-or-equal-to 3, turned out to contain a serious and irreparable error. This paper presents a new proof of the theorem. The proof is based on an inductive argument, which also applies in the case of pseudohyperplane arrangements. The fallacies of the old proof along with some ways of partially saving that approach are briefly discussed.
AU - Herbert Edelsbrunner
AU - Seidel, Raimund
AU - Sharir, Micha
ID - 4041
IS - 2
JF - SIAM Journal on Computing
TI - On the zone theorem for hyperplane arrangements
VL - 22
ER -
TY - JOUR
AB - It is shown that a triangulation of a set of n points in the plane that minimizes the maximum edge length can be computed in time 0(n2). The algorithm is reasonably easy to implement and is based on the theorem that there is a triangulation with minmax edge length that contains the relative neighborhood graph of the points as a subgraph. With minor modifications the algorithm works for arbitrary normed metrics.
AU - Herbert Edelsbrunner
AU - Tan, Tiow Seng
ID - 4042
IS - 3
JF - SIAM Journal on Computing
TI - A quadratic time algorithm for the minmax length triangulation
VL - 22
ER -
TY - JOUR
AB - Edge insertion iteratively improves a triangulation of a finite point set in ℜ2 by adding a new edge, deleting old edges crossing the new edge, and retriangulating the polygonal regions on either side of the new edge. This paper presents an abstract view of the edge insertion paradigm, and then shows that it gives polynomial-time algorithms for several types of optimal triangulations, including minimizing the maximum slope of a piecewise-linear interpolating surface.
AU - Bern, Marshall
AU - Herbert Edelsbrunner
AU - Eppstein, David
AU - Mitchell, Stephen
AU - Tan, Tiow Seng
ID - 4044
IS - 1
JF - Discrete & Computational Geometry
TI - Edge insertion for optimal triangulations
VL - 10
ER -
TY - JOUR
AB - We apply Megiddo's parametric searching technique to several geometric optimization problems and derive significantly improved solutions for them. We obtain, for any fixed ε>0, an O(n1+ε) algorithm for computing the diameter of a point set in 3-space, an O(8/5+ε) algorithm for computing the width of such a set, and on O(n8/5+ε) algorithm for computing the closest pair in a set of n lines in space. All these algorithms are deterministic.
AU - Chazelle, Bernard
AU - Herbert Edelsbrunner
AU - Guibas, Leonidas
AU - Sharir, Micha
ID - 4045
IS - 1
JF - Discrete & Computational Geometry
TI - Diameter, width, closest line pair, and parametric searching
VL - 10
ER -
TY - JOUR
AB - We have studied the effects of different neurotrophins on the survival and proliferation of rat cerebellar granule cells in culture. These neurons express trkB and trkC, the putative neuronal receptors for brain-derived neurotrophic factor (BDNF) and neurotrophin-3 (NT-3) respectively. Binding studies using iodinated BDNF and NT-3 demonstrated that both BDNF and NT-3 bind to the cerebellar granule neurons with a similar affinity of approximately 2 x 10(-9) M. The number of receptors per granule cell was surprisingly high, approximately 30 x 10(-4) and 2 x 10(5) for BDNF and NT-3, respectively. Both NT-3 and BDNF elevated c-fos mRNA in the granule neurons, but only BDNF up-regulated the mRNA encoding the low-affinity neurotrophin receptor (p75). In contrast to NT-3, BDNF acted as a survival factor for the granule neurons. BDNF also induced sprouting of the granule neurons and significantly protected them against neurotoxicity induced by high (1 mM) glutamate concentrations. Cultured granule neurons also expressed low levels of BDNF mRNA which were increased by kainic acid, a glutamate receptor agonist. Thus, BDNF, but not NT-3, is a survival factor for cultured cerebellar granule neurons and activation of glutamate receptor(s) up-regulates BDNF expression in these cells.
AU - Lindholm, Dan
AU - Dechant, Georg
AU - Heisenberg, Carl-Philipp J
AU - Thoenen, Hans
ID - 4175
IS - 11
JF - European Journal of Neuroscience
TI - Brain-derived neurotrophic factor is a survival factor for cultured rat cerebellar granule neurons and protects them against glutamate-induced neurotoxicity
VL - 5
ER -
TY - JOUR
AB - Thyroid hormones play an important role in brain development, but the mechanism(s) by which triiodothyronine (T3) mediates neuronal differentiation is poorly understood. Here we demonstrate that T3 regulates the neurotrophic factor, neurotrophin-3 (NT-3), in developing rat cerebellar granule cells both in cell culture and in vivo. In situ hybridization experiments showed that developing Purkinje cells do not express NT-3 mRNA but do express trkC, the putative neuronal receptor for NT-3. Addition of recombinant NT-3 to cerebellar cultures from embryonic rat brain induces hypertrophy and neurite sprouting of Purkinje cells, and upregulates the mRNA encoding the calcium-binding protein, calbindin-28 kD. The present study demonstrates a novel interaction between cerebellar granule neurons and developing Purkinje cells in which NT-3 induced by T3 in the granule cells promotes Purkinje cell differentiation.
AU - Lindholm, Dan
AU - Castrén, Eero
AU - Tsoulfas, Pantelis
AU - Kolbeck, Roland
AU - Berzaghi, Maria
AU - Leingärtner, Axel
AU - Heisenberg, Carl-Philipp J
AU - Tesarollo, Lino
AU - Parada, Luis
AU - Thoenen, Hans
ID - 4177
IS - 2
JF - Journal of Cell Biology
TI - Neurotrophin-3 induced by tri-iodothyronine in cerebellar granule cells promotes Purkinje cell differentiation
VL - 122
ER -
TY - JOUR
AB - Evolutionary explanations of ageing fall into two classes. Organisms might have evolved the optimal life history, in which survival and fertility late in life are sacrificed for the sake of early reproduction and survival. Alternatively, the life history might be depressed below this optimal compromise by deleterious mutations: because selection against late-acting mutations is weaker, these will impose a greater load on late life. Evidence for the importance of both is emerging, and unravelling their relative importance presents experimentalists with a major challenge.
AU - Partridge, Linda
AU - Nicholas Barton
ID - 4300
JF - Nature
TI - Optimality, mutation and the evolution of ageing
VL - 362
ER -
TY - CHAP
AU - Nicholas Barton
AU - Gale, Katherine S
ED - Harrison, Richard G
ID - 4301
T2 - Hybrid zones and the evolutionary process
TI - Genetic analysis of hybrid zones
ER -
TY - GEN
AU - Nicholas Barton
ID - 4302
IS - 1
T2 - Genetical Research
TI - Review of "The causes of molecular evolution" by J.H. Gillespie
VL - 62
ER -
TY - JOUR
AB - In a stably subdivided population with symmetric migration, the chance that a favoured allele will be fixed is independent of population structure. However, random extinction introduces an extra component of sampling drift, and reduces the probability of fixation. In this paper, the fixation probability is calculated using the diffusion approximation; comparison with exact solution of the discrete model shows this to be accurate. The key parameters are the rates of selection, migration and extinction, scaled relative to population size (S = 4Ns, M = 4Nm, Λ = 4Nλ); results apply to a haploid model, or to diploids with additive selection. If new colonies derive from many demes, the fixation probability cannot be reduced by more than half. However, if colonies are initially homogeneous, fixation probability can be much reduced. In the limit of low migration and extinction rates (M, Λ 1), it is 2s/{1 + (Λ/MS)(1 −exp(−S))}, whilst in the opposite limit (S 1), it is 4sM/{Λ(Λ + M)}. In the limit of weak selection (M, Λ 1), it is 4sM/{Λ(Λ + M)}. These factors are not the same as the reduction in effective population size (Ne/N), showing that the effects of population structure on selected alleles cannot be understood from the behaviour of neutral markers.
AU - Nicholas Barton
ID - 4303
IS - 2
JF - Genetical Research
TI - The probability of fixation of a favoured allele in a subdivided population
VL - 62
ER -
TY - GEN
AU - Nicholas Barton
ID - 4304
IS - 11
T2 - Current Biology
TI - Why species and subspecies?
VL - 3
ER -
TY - CHAP
AB - We propose a formal framework for designing hybrid systems by stepwise refinement. Starting with a specification in hybrid temporal logic, we make successively more transitions explicit until we obtain an executable system.
AU - Thomas Henzinger
AU - Manna, Zohar
AU - Pnueli,Amir
ED - Grossman, Robert L.
ED - Nerode, Anil
ED - Ravn, Anders P
ED - Rischel, Hans
ID - 4506
T2 - Hybrid Systems
TI - Towards refining temporal specifications into hybrid systems
VL - 736
ER -
TY - JOUR
AB - The theory of the natural numbers with linear order and monadic predicates underlies propositional linear temporal logic. To study temporal logics that are suitable for reasoning about real-time systems, we combine this classical theory of infinite state sequences with a theory of discrete time, via a monotonic function that maps every state to its time. The resulting theory of timed state sequences is shown to be decidable, albeit nonelementary, and its expressive power is characterized by ω-regular sets. Several more expressive variants are proved to be highly undecidable. This framework allows us to classify a wide variety of real-time logics according to their complexity and expressiveness. Indeed, it follows that most formalisms proposed in the literature cannot be decided. We are, however, able to identify two elementary real-time temporal logics as expressively complete fragments of the theory of timed state sequences, and we present tableau-based decision procedures for checking validity. Consequently, these two formalisms are well-suited for the specification and verification of real-time systems.
Copyright © 1993 Academic Press. All rights reserved.
AU - Alur, Rajeev
AU - Thomas Henzinger
ID - 4589
IS - 1
JF - Information and Computation
TI - Real-time logics: Complexity and expressiveness
VL - 104
ER -
TY - JOUR
AB - An effective character recognition procedure implemented on a new type of hardware system and using a new architecture called CNND is proposed. This CNND contains one or more analog cellular neural networks (CNNs) and some digital logic, combining the advantages of the fast analog CNN signal processing and the fast and easy decision capability of digital logic. It is shown that the CNND system can be used for recognition of multifont printed or handwritten characters and could recognize 100,000 char/s with a recognition rate of more than 95%. The more advantage of the system over competing types is that there is not an extra feature extraction procedure implemented in slow hardware
AU - Sziranyi, Tamas
AU - Jozsef Csicsvari
ID - 3446
IS - 3
JF - IEEE Transactions on Circuits and Systems II: Analog and Digital Signal Processing
TI - High-speed character recognition using a dual cellular neural network architecture (CNND)
VL - 40
ER -
TY - CHAP
AU - Peter Jonas
ID - 3451
T2 - Molecular Basis of Ion Channels and Receptors Involved in Nerve Excitation, Synaptic Transmission, and Muscle Contraction
TI - Glutamate receptors in the central nervous system
VL - 707
ER -
TY - CHAP
AB - In recent years, considerable progress in our understanding of the molecular events underlying excitatory synaptic transmission has been made. This progress was mainly achieved by technical advances, among them the patch-clamp technique in brain slices (Edwards et al., 1989), fast application of agonists (Franke et al., 1987), and cloning and functional expression of GluR channels of the nonNMDA type (e.g., Hollmann et al., 1989). A suitable model for studying excitatory postsynaptic currents (EPSCs) in the brain slice with patch-clamp techniques is the mossy fiber synapse on CA3 pyramidal cells of rat hippocampus (MF-CA3 synapse). This synapse is located close to the cell soma and should provide almost ideal space-clamp conditions. A comparison of MF-CA3 EPSCs with the currents activated by fast application of glutamate on membrane patches isolated from CA3 cell somata suggests that the concentration of glutamate in the synaptic cleft during excitatory synaptic transmission is high (about 1 mM) and that the transmitter remains in the synaptic cleft only briefly (about 1 ms). It seems likely that desensitization influences the peak amplitude of the EPSC in several ways. Brief pulses of glutamate cause desensitization, from which the glutamate receptor channels recover only slowly, and micromolar ambient glutamate concentrations produce desensitization at equilibrium. From the functional properties of recombinant GluR channels, in situ hybridization data, and patch-clamp experiments on different neuronal and nonneuronal cell types, a picture of the molecular identity of native channels emerges. In neurons of the hippocampus the pharmacological features of these channels were similar to recombinant channels assembled from subunits of the AMPA/kainate subtype which are strongly expressed in these cells. The native channels are characterized by outward rectification of the steady-state I-V and low Ca permeability, similar to recombinant channels containing the GluR-B subunit. This is consistent with the ubiquitous expression of this subunit in hippocampal neurones. In contrast, GluR channels from cerebellar glial cells, which uniquely in the central nervous system lack the expression of GluR-B subunits, show double rectification and high Ca permeability. The results suggest that the native functional nonNMDA glutamate receptor channels in the CNS are assembled form subunits of the AMPA/kainate subtype in a cell-specific way, with the functional properties of GluR channels in neurones being dominated by the GluR-B subunit.
AU - Peter Jonas
ED - Siemen, Detlef
ID - 3452
T2 - Nonselective cation channels: Pharmacology, Physiology and Biophysics.
TI - AMPA-type glutamate receptors - nonselective cation channels mediating fast excitatory transmission in the CNS
VL - 66
ER -
TY - JOUR
AB - Sixteen different K+ channel subtypes have been cloned from mammalian tissue. Considering their sequence homology to Drosophila Shaker, Shab, Shaw and Shal channels, they were classified into four corresponding classes Kv1-4. All K+ channels belonging to these classes consist of four subunits with each six hydrophobic segments (S1-S6) and a characteristic structure-function relationship of certain domains in their amino acid sequence. These domains are, the inactivation gate in the N-terminal region of the sequence, the voltage sensor in the fourth hydrophobic segment (S4), and the pore-region in the H5 segment between S5 and S6. In some functional properties K+ channels cloned from the mammalian brain, however, differ from Drosophila K+ channels. These are pharmacological differences, differences in the threshold of activation and in regulation of inactivation. Part of these differences are important to understand their physiological role in the brain. Based on their functional characteristics the expression pattern of cloned K+ channels in the rat brain can be correlated with the properties of K+ currents measured in central neurones.
Copyright © 1993 S. Karger AG, Basel
AU - Ruppersberg, Peter
AU - Ermler, Mamfred
AU - Knopf, Martin
AU - Kues, Wilfried
AU - Peter Jonas
AU - Koenen, Michael
ID - 3473
JF - Cellular Physiology and Biochemistry
TI - Properties of Shaker-homologous potassium channels expressed in the mammalian brain.
VL - 3
ER -
TY - JOUR
AB - 1. Excitatory postsynaptic currents (EPSCs) were recorded in CA3 pyramidal cells of hippocampal slices of 15- to 24-day-old rats (22 degrees C) using the whole-cell configuration of the patch clamp technique. 2. Composite EPSCs were evoked by extracellular stimulation of the mossy fibre tract. Using the selective blockers 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) and D-2-amino-5-phosphonopentanoic acid (APV), a major alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate (AMPA)/kainate receptor-mediated component and a minor NMDA receptor-mediated component with slower time course were distinguished. For the AMPA/kainate receptor-mediated component, the peak current-voltage (I-V) relation was linear, with a reversal potential close to 0 mV. The half-maximal blocking concentration of CNQX was 353 nM. 3. Unitary EPSCs of the mossy fibre terminal (MF)-CA3 pyramidal cell synapse were evoked at membrane potentials of -70 to -90 mV by low-intensity extracellular stimulation of granule cell somata using fine-tipped pipettes. The EPSC peak amplitude as a function of stimulus intensity showed all-or-none behaviour. The region of low threshold was restricted to a few micrometres. This suggests that extracellular stimulation was focal, and that the stimulus-evoked EPSCs were unitary. 4. Latency and rise time histograms of EPSCs evoked by granule cell stimulation showed narrow unimodal distributions within each experiment. The mean latency was 4.2 +/- 1.0 ms, and the mean 20-80% rise time was 0.6 +/- 0.1 ms (23 cells). When fitted within the range 0.7 ms to 20 ms after the peak, the decay of the EPSCs with the fastest rise (rise time 0.5 ms or less) could be described by a single exponential function; the mean time constant was in the range 3.0-6.6 ms with a mean of 4.8 ms (8 cells). 5. Peak amplitudes of the EPSCs evoked by suprathreshold granule cell stimulation fluctuated between trials. The apparent EPSC peak conductance in normal extracellular solution (2 mM Ca2+, 1 mM Mg2+), excluding failures, was 1 nS. Reducing the Ca2+ concentration and increasing the Mg2+ concentration reduced the mean peak amplitude in a concentration-dependent manner. 6. Peaks in EPSC peak amplitude distributions were apparent in low Ca2+ and high Mg2+. Using the criteria of equidistance and the presence of peaks and dips in the autocorrelation function, five of nine EPSC peak amplitude distributions were judged to be quantal.
AU - Peter Jonas
AU - Major, Guy
AU - Sakmann, Bert
ID - 3474
JF - Journal of Physiology
TI - Quantal components of unitary EPSCs at the mossy fibre synapse on CA3 pyramidal cells of rat hippocampus
VL - 472
ER -
TY - CHAP
AU - Herbert Edelsbrunner
ID - 3568
T2 - Handbook of Convex Geometry
TI - Geometric algorithms
ER -
TY - CHAP
AU - Herbert Edelsbrunner
ID - 3569
T2 - Current Trends in Theoretical Computer Science, Essays and Tutorials
TI - Computational geometry
ER -
TY - JOUR
AB - We investigate the establishment and spread of new adaptive peaks within Wright's ‘shifting balance’. The third phase of the ‘shifting balance’ involves a kind of group selection, since demes in which a superior peak has been established contain more individuals, and so send out more migrants. We assume that population size, N, increases with mean fitness, , according to the exponential relation, . Here, k is a measure of the weakness of density-dependent regulation, and equals the inverse of the regression of log (fitness) on log(N). In the island model, we find that just as with soft selection (k = 0), two distinct types of behaviour exist: group selection makes no qualitative difference. With low numbers of migrants, demes fluctuate almost independently, and only one equilibrium exists. With large numbers of migrants, all the demes evolve towards the same adaptive peak, and so the whole population can move towards one or other of the peaks. Group selection can be understood in terms of an effective mean fitness function. Its main consequence is to increase the effect of selection relative to drift (Ns), and so increase the bias towards the fitter peak. However, this increased bias depends on the ratio between k and the deme size (k/N), and so is very small when density-dependence is reasonably strong.
AU - Rouhani, Shahin
AU - Nicholas Barton
ID - 3643
IS - 2
JF - Genetical Research
TI - Group selection and the 'shifting balance'
VL - 61
ER -
TY - JOUR
AU - Nicholas Barton
AU - Rouhani, Shahin
ID - 3644
IS - 1
JF - Genetical Research
TI - Adaptation and the 'shifting balance'
VL - 61
ER -
TY - JOUR
AB - Three cDNA clones, mGluR2, mGluR3, and mGluR4, were isolated from a rat brain cDNA library by cross-hybridization with the cDNA for a metabotropic glutamate receptor (mGluR1). The cloned receptors show considerable sequence similarity with mGluR1 and possess a large extracellular domain preceding the seven putative membrane-spanning segments. mGluR2 is expressed in some particular neuronal cells different from those expressing mGluR1 and mediates an efficient inhibition of forskolin-stimulated cAMP formation in cDNA- transfected cells. The mGluRs thus form a novel family of G protein-coupled receptors that differ in their signal transduction and expression patterns.
AU - Tanabe, Yasuto
AU - Masu, Masayuki
AU - Ishii, Takahiro
AU - Ryuichi Shigemoto
AU - Nakanishi, Shigetada
ID - 2484
IS - 1
JF - Neuron
TI - A family of metabotropic glutamate receptors
VL - 8
ER -
TY - JOUR
AB - Endothelins (ETs) are very potent vasoconstrictive peptides and have diverse functions in both vascular and nonvascular tissues. This investigation concerns the tissue distribution and cellular localization of rat mRNAs encoding two different subtypes of ET receptors (ET(A) and ET(B)). We isolated 46 cDNA clones from a rat lung cDNA library by hybridization with the bovine ET(A) cDNA. The characterization of these cDNA clones indicated that they represent either the ET(A) or ET(B) cDNA. In situ and blot hybridization analyses revealed that the rat ET(A) mRNA is predominantly expressed in vascular smooth muscle cells of a variety of tissues, bronchial smooth muscle cells, myocardium, and the pituitary gland. There is no significant expression of ET(B) mRNA in vascular smooth muscle cells, and ET(A), thus, plays a primary role in ET-induced vascular contraction. ET(B) mRNA is more widely distributed in various cell types of many tissues. Its prominent expression is seen in glial cells throughout the brain regions, epithelial cells of the choroid plexus, ependymal cells lining the ventricle, myocardium, endothelial cells of glomeruli, and epithelial cells of the thin segments of Henle's loops. Our investigation demonstrates that the mRNAs for the two subtypes of rat ET receptors show specialized expression patterns of cell types in both brain and peripheral tissues.
AU - Hori, Seiji
AU - Komatsu, Yasato
AU - Ryuichi Shigemoto
AU - Mizuno, Noboru
AU - Nakanishi, Shigetada
ID - 2485
IS - 4
JF - Endocrinology
TI - Distinct tissue distribution and cellular localization of two messenger ribonucleic acids encoding different subtypes of rat endothelin receptors
VL - 130
ER -
TY - JOUR
AB - Distribution of the mRNA for a metabotropic glutamate receptor (mGluR1), which is linked to phosphoinositide (PI) hydrolysis, was investigated in adult and developing rat central nervous system (CNS) by in situ hybridization. Transcripts of mGluR1 were specifically localized to neurons and widely distributed throughout the adult rat brain. Most intensely labeled neurons were Purkinje cells of the cerebellum, mitral and tufted cells of the olfactory bulb, and neurons in the hippocampus, lateral septum, thalamus, globus pallidus, entopeduncular nucleus, ventral pallidum, magnocellular preoptic nucleus, substantia nigra, and dorsal cochlear nucleus. Moderately labeled neurons were seen in high density in the dentate gyrus, striatum, islands of Calleja, superficial layers of the retrosplenial, cingulate and entorhinal cortices, mammillary nuclei, red nucleus, and superior colliculus. In the developing rat brain, the level of mGluR1 expression gradually increased during early postnatal days in accordance with the maturation of neuronal elements. These results show prominent expression of mGluR1 in the major targets of putative glutamatergic pathways and unique distribution pattern of mGluR1 distinct from those reported for ionotropic subtypes of glutamate receptors, suggesting specific roles of mGluR1 in the glutamatergic system.
AU - Ryuichi Shigemoto
AU - Nakanishi, Shigetada
AU - Mizuno, Noboru
ID - 2486
IS - 1
JF - Journal of Comparative Neurology
TI - Distribution of the mRNA for a metabotropic glutamate receptor (mGluR1) in the central nervous system: An in situ hybridization study in adult and developing rat
VL - 322
ER -
TY - JOUR
AB - The distribution of NMDA receptor (NMDAR1) on neurons in the peripheral ganglia was examined in the adult rat by in situ hybridization. NMDAR1 mRNA was expressed in all neurons in the sensory and autonomic ganglia examined; in the dorsal root, trigeminal, nodose, superior cervical, and sphenopalatine ganglia. Possible roles of the NMDA receptor on the sensory and autonomic ganglion neurons are discussed.
AU - Ryuichi Shigemoto
AU - Ohishi, Hitoshi
AU - Nakanishi, Shigetada
AU - Mizuno, Noboru
ID - 2531
IS - 1-2
JF - Neuroscience Letters
TI - Expression of the mRNA for the rat NMDA receptor (NMDAR1) in the sensory and autonomic ganglion neurons
VL - 144
ER -
TY - JOUR
AB - In the present study, we have investigated the expression of both the erythrocyte-type (GLUT1) and the brain-type (GLUT3) glucose transporter isoforms in primary human brain tumors. In situ hybridization made it possible to localize and semiquantify both GLUT1 and GLUT3 mRNAs of individual cells in all 18 samples examined. More signals for GLUT3 mRNA than for GLUT1 mRNA were found over astrocytoma cells, while the reverse was the case in all 6 meningiomas. In astrocytomas, for both mRNAs, the density of silver grains over tumor cells was well correlated with the malignancy of the cells. This correlation was, as was also confirmed by Northern blot analysis, more marked with GLUT3 mRNA than with GLUT1 mRNA. In 2 of 5 anaplastic astrocytomas and in all 3 glioblastomas, numerous tumor cells with large amounts of both mRNAs tended to surround the perivascular regions. 'Tumor vessels' with endothelial proliferation, an almost pathognomonic feature of glioblastomas, expressed much GLUT3 mRNA but no significant GLUT1 mRNA, while a single- or a few-layered capillary endothelium expressed much GLUT1 mRNA. The distribution of both mRNAs was in good accordance with that of both proteins. Our results suggest that the expression of both glucose transporter isoforms may contribute to the maintenance of human brain tumors and that the expression of the GLUT3 isoform may be closely related to the malignant change of astrocytomas and particularly related to the aberrant neovascularization which accompanies glioblastomas.
AU - Nishioka, Tatsuya
AU - Oda, Yoshifumi
AU - Seino, Yutaka
AU - Yamamoto, Taizo
AU - Inagaki, Nobuya
AU - Yano, Hideki
AU - Imura, Hiroo
AU - Ryuichi Shigemoto
AU - Kikuchi, Haruhiko
ID - 2532
IS - 14
JF - Cancer Research
TI - Distribution of the glucose transporters in human brain tumors
VL - 52
ER -
TY - JOUR
AB - A cDNA clone for a new metabotropic glutamate receptor, mGluR5, was isolated through polymerase chain reaction-mediated DNA amplification by using primer sequences conserved among the metabotropic glutamate receptor (mGluR) family and by the subsequent screening of a rat brain cDNA library. The cloned receptor consists of 1171 amino acid residues and exhibits a structural architecture common to the mGluR family, possessing a large extracellular domain preceding the seven putative membrane-spanning segments. mGluR5 shows the highest sequence similarity to mGluR1 among the mGluR members and is coupled to the stimulation of phosphatidylinositol hydrolysis/ Ca2+ signal transduction in Chinese hamster ovary cells transfected with the cloned cDNA. This receptor also resembles mGluR1 in its agonist selectivity and antagonist responses; the potency rank order of agonists for mGluR5 was determined to be quisqualate > L-glutamate ≥ ibotenate > trans-1-aminocyclopentane-1,3-dicarboxylate. Blot and in situ hybridization analyses indicated that mGluR5 mRNA is widely distributed in neuronal cells of the central nervous system and is expressed differently from mGluR1 mRNA in many brain regions. This investigation thus demonstrates that there is an additional mGluR subtype which closely resembles mGluR1 in its signal transduction and pharmacological properties and is expressed in specialized neuronal cells in the central nervous system.
AU - Abe, Takaaki
AU - Sugihara, Hidemitsu
AU - Nawa, Hiroyuki
AU - Ryuichi Shigemoto
AU - Mizuno, Noboru
AU - Nakanishi, Shigetada
ID - 2533
IS - 19
JF - Journal of Biological Chemistry
TI - Molecular characterization of a novel metabotropic glutamate receptor mGluR5 coupled to inositol phosphate/Ca2+ signal transduction
VL - 267
ER -
TY - JOUR
AB - Vasoactive intestinal polypeptide (VIP), a 28 amino acid peptide hormone, plays many physiological roles in the peripheral and central nerve systems. A functional cDNA clone of the VIP receptor was isolated from a rat lung cDNA library by cross-hybridization with the secretin receptor cDNA. VIP bound the cloned VIP receptor expressed in mouse COP cells and stimulated adenylate cyclase through the cloned receptor. The rat VIP receptor consists of 459 amino acids with a calculated Mr of 52,054 and contains seven transmembrane segments. It is structurally related to the secretin, calcitonin, and parathyroid hormone receptors, suggesting that they constitute a new subfamily of the G5 protein - coupled receptors. VIP receptor mRNA was detected in various rat tissues including liver, lung, intestines, and brain. In situ hybridization revealed that VIP receptor mRNA is widely distributed in neuronal cells of the adult rat brain, with a relatively high expression in the cerebral cortex and hippocampus.
AU - Ishihara, Takeshi
AU - Ryuichi Shigemoto
AU - Mori, Kensaku
AU - Takahashi, Kenji
AU - Nagata, Shigekazu
ID - 2534
IS - 4
JF - Neuron
TI - Functional expression and tissue distribution of a novel receptor for vasoactive intestinal polypeptide
VL - 8
ER -
TY - JOUR
AB - We report the molecular characterization of two novel rat helix-loop-helix (HLH) proteins, designated HES-1 and HES-3, that show structural homology to the Drosophila hairy and Enhancer of split [E(spl)] proteins, both of which are required for normal neurogenesis. HES-1 mRNA, expressed in various tissues of both embryos and adults, is present at a high level in the epithelial cells, including the embryonal neuroepithelial cells, as well as in the mesoderm-derived tissues such as the embryonal muscle. In contrast, HES-3 mRNA is produced exclusively in cerebellar Purkinje cells. HES-1 represses transcription by binding to the N box, which is a recognition sequence of E(spl) proteins. Interestingly, neither HES-1 nor HES-3 alone interacts efficiently with the E box, but each protein decreases the transcription induced by E-box-binding HLH activators such as E47. Furthermore, HES-1 also inhibits the functions of MyoD and MASH1 and effectively diminishes the myogenic conversion of C3H10T1/2 cells induced by MyoD. These results suggest that HES-1 may play an important role in mammalian development by negatively acting on the two different sequences while HES-3 acts as a repressor in a specific type of neurons.
AU - Sasai, Yoshiki
AU - Kageyama, Ryoichiro
AU - Tagawa, Yoshiaki
AU - Ryuichi Shigemoto
AU - Nakanishi, Shigetada
ID - 2535
IS - 12 B
JF - Genes and Development
TI - Two mammalian helix-loop-helix factors structurally related to Drosophila hairy and Enhancer of split
VL - 6
ER -
TY - JOUR
AU - László Erdös
ID - 2714
IS - 1-2
JF - Acta Mathematica Hungarica
TI - On some problems of P. Turán concerning power sums of complex numbers
VL - 59
ER -
TY - JOUR
AB - A version of the one-dimensional Rayleigh gas is considered: a point particle of mass M (molecule), confined to the unit interval [0,1], is surrounded by an infinite ideal gas of point particles of mass 1 (atoms). The molecule interacts with the atoms and with the walls via elastic collision. Central limit theorems are proved for a wide class of additive functionals of this system (e.g. the number of collisions with the walls and the total length of the molecular path).
AU - László Erdös
AU - Tuyen, Dao Quang
ID - 2722
IS - 3
JF - Communications in Mathematical Physics
TI - Central limit theorems for the one-dimensional Rayleigh gas with semipermeable barriers
VL - 143
ER -
TY - JOUR
AB - The effects of ultra-low (10(-18)-10(-14) M) doses (ULD) of biologically active substances have been reviewed in terms of common regularities of ULD effects and peculiarities of action of various groups of compounds. The most common and at the same time paradoxical regularities of ULD action are bi- or polymodal patterns of dose dependence, absence or presence of an inverse effect at higher doses, and instability of ULD effect. Possible mechanisms of ULD action including the mechanism based on the adaptation theory are discussed.
AU - Leonid Sazanov
AU - Zaǐtsev, Sergei V
ID - 1945
IS - 10
JF - Biokhimiya
TI - Effect of superlow doses (10(-18)-10-(-14) M) of biologically active substances: general rules, features, and possible mechanisms
VL - 57
ER -
TY - JOUR
AB - It is shown that a triangulation of a set of n points in the plane that minimizes the maximum angle can be computed in time O(n2 log n) and space O(n). The algorithm is fairly easy to implement and is based on the edge-insertion scheme that iteratively improves an arbitrary initial triangulation. It can be extended to the case where edges are prescribed, and, within the same time- and space-bounds, it can lexicographically minimize the sorted angle vector if the point set is in general position. Experimental results on the efficiency of the algorithm and the quality of the triangulations obtained are included.
AU - Herbert Edelsbrunner
AU - Tan, Tiow Seng
AU - Waupotitsch, Roman
ID - 4043
IS - 4
JF - SIAM Journal on Scientific Computing
TI - An O(n^2 log n) time algorithm for the MinMax angle triangulation
VL - 13
ER -
TY - JOUR
AB - The main contribution of this work is an O(n log n + k)-time algorithm for computing all k intersections among n line segments in the plane. This time complexity is easily shown to be optimal. Within the same asymptotic cost, our algorithm can also construct the subdivision of the plane defined by the segments and compute which segment (if any) lies right above (or below) each intersection and each endpoint. The algorithm has been implemented and performs very well. The storage requirement is on the order of n + k in the worst case, but it is considerably lower in practice. To analyze the complexity of the algorithm, an amortization argument based on a new combinatorial theorem on line arrangements is used.
AU - Chazelle, Bernard
AU - Herbert Edelsbrunner
ID - 4046
IS - 1
JF - Journal of the ACM
TI - An optimal algorithm for intersecting line segments in the plane
VL - 39
ER -
TY - JOUR
AB - Arrangements of curves in the plane are fundamental to many problems in computational and combinatorial geometry (e.g. motion planning, algebraic cell decomposition, etc.). In this paper we study various topological and combinatorial properties of such arrangements under some mild assumptions on the shape of the curves, and develop basic tools for the construction, manipulation, and analysis of these arrangements. Our main results include a generalization of the zone theorem of Edelsbrunner (1986) and Chazelle (1985) to arrangements of curves (in which we show that the combinatorial complexity of the zone of a curve is nearly linear in the number of curves) and an application of that theorem to obtain a nearly quadratic incremental algorithm for the construction of such arrangements.
AU - Herbert Edelsbrunner
AU - Guibas, Leonidas
AU - Pach, János
AU - Pollack, Richard
AU - Seidel, Raimund
AU - Sharir, Micha
ID - 4047
IS - 2
JF - Theoretical Computer Science
TI - Arrangements of curves in the plane - topology, combinatorics, and algorithms
VL - 92
ER -
TY - JOUR
AB - Given a sequence of n points that form the vertices of a simple polygon, we show that determining a closest pair requires OMEGA(n log n) time in the algebraic decision tree model. Together with the well-known O(n log n) upper bound for finding a closest pair, this settles an open problem of Lee and Preparata. We also extend this O(n log n) upper bound to the following problem: Given a collection of sets with a total of n points in the plane, find for each point a closest neighbor that does not belong to the same set.
AU - Aggarwal, Alok
AU - Herbert Edelsbrunner
AU - Raghavan, Prabhakar
AU - Tiwari, Prasoon
ID - 4048
IS - 1
JF - Information Processing Letters
TI - Optimal time bounds for some proximity problems in the plane
VL - 42
ER -
TY - CONF
AB - The edge-insertion paradigm improves a triangulation of a finite point set in R2
iteratively by adding a new edge, deleting intersecting old edges, and retriangulating
the resulting two polygonal regions. After presenting an abstract view of the paradigm,
this paper shows that it can be used to obtain polynomial time algorithms for several
types of optimal triangulations.
AU - Bern, Marshall
AU - Herbert Edelsbrunner
AU - Eppstein, David
AU - Mitchell, Stephen
AU - Tan, Tiow Seng
ID - 4049
TI - Edge insertion for optimal triangulations
VL - 583
ER -
TY - JOUR
AU - Herbert Edelsbrunner
ID - 4050
IS - 1
JF - Discrete & Computational Geometry
TI - Guest editor's foreword
VL - 8
ER -
TY - JOUR
AB - We show that the maximum number of edges bounding m faces in an arrangement of n line segments in the plane is O(m2/3n2/3+nα(n)+nlog m). This improves a previous upper bound of Edelsbrunner et al. [5] and almost matches the best known lower bound which is Ω(m2/3n2/3+nα(n)). In addition, we show that the number of edges bounding any m faces in an arrangement of n line segments with a total of t intersecting pairs is O(m2/3t1/3+nα(t/n)+nmin{log m,log t/n}), almost matching the lower bound of Ω(m2/3t1/3+nα(t/n)) demonstrated in this paper.
AU - Aronov, Boris
AU - Herbert Edelsbrunner
AU - Guibas, Leonidas J
AU - Sharir, Micha
ID - 4053
IS - 3
JF - Combinatorica
TI - The number of edges of many faces in a line segment arrangement
VL - 12
ER -
TY - JOUR
AB - The effects of tri-iodothyronine (T3), which are known to affect cerebellar development, were tested on neuronal survival and differentiation of cultured cerebellar granule neurons. T3 in physiological concentrations increased both granule neuron survival after three days in culture and synaptic vesicle protein formation, as shown by immunostaining with antibodies against synaptophysin. Likewise, T3 increased the mRNA level for synapsin(I), but not that for GAP43 in granule neurons. Antibodies against microtubule associated protein Tau, which is expressed in developing neurites, showed that T3 also enhanced neurite formation.
AU - Heisenberg, Carl-Philipp J
AU - Thoenen, Hans
AU - Lindholm, Dan
ID - 4195
IS - 8
JF - Neuroreport
TI - Triiodothyronine Regulates Survival and Differentiation of Rat Cerebellar Granule Neurons
VL - 3
ER -
TY - JOUR
AB - The common shrew (Sorex araneus) is subdivided into several karyotypic races in Britain. Two of these races meet near Oxford to form the "Oxford-Hermitage" hybrid zone. We present a model which describes this system as a "tension zone," i.e., a set of clines maintained by a balance between dispersal and selection against chromosomal heterozygotes. The Oxford and Hermitage races differ by Robertsonian fusions with monobrachial homology (kq, no versus ko), and so F1 hybrids between them would have low fertility. However, the acrocentric karyotype is found at high frequency within the hybrid zone, so that complex Robertsonian heterozygotes (kq no/q ko n) are replaced by more fertile combinations, such as (kq no/k q n o). This suggests that the hybrid zone has been modified so as to increase hybrid fitness. Mathematical analysis and simulation show that, if selection against complex heterozygotes is sufficiently strong relative to selection against simple heterozygotes, acrocentrics increase, and displace the clines for kq and no from the cline for ko. Superimposed on this separation is a tendency for the hybrid zone to move m favor of the Oxford (kq no) race. We compare the model with estimates of linkage disequilibrium and cline shape made from field data.
AU - Hatfield, Todd
AU - Nicholas Barton
AU - Searle, Jeremy B
ID - 4305
IS - 4
JF - Evolution; International Journal of Organic Evolution
TI - A model of a hybrid zone between two chromosomal races of the common shrew (Sorex araneus)
VL - 46
ER -
TY - GEN
AU - Nicholas Barton
AU - Goldman, Nick G
ID - 4306
T2 - Nature
TI - Genetics and geography
VL - 357
ER -
TY - CHAP
AU - Nicholas Barton
ED - Stenseth, Nils C
ED - Lidicker, William Z
ID - 4307
T2 - Animal dispersal: small mammals as a model
TI - The genetic consequences of dispersal
ER -
TY - JOUR
AU - Nicholas Barton
ID - 4308
IS - 2
JF - Evolution; International Journal of Organic Evolution
TI - On the spread of new gene combinations in the third phase of Wright's shifting balance
VL - 46
ER -