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
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 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 -
TY - CONF
AU - Thomas Henzinger
AU - Manna, Zohar
AU - Pnueli,Amir
ID - 4504
TI - What good are digital clocks?
VL - 623
ER -
TY - CONF
AB - We describe finite-state programs over real-numbered time in a guarded-command language with real-valued clocks or, equivalently, as finite automata with real-valued clocks. Model checking answers the question which states of a real-time program satisfy a branching-time specification (given in an extension of CTL with clock variables). We develop an algorithm that computes this set of states symbolically as a fixpoint of a functional on state predicates, without constructing the state space.
For this purpose, we introduce a mu-calculus on computation trees over real-numbered time. Unfortunately, many standard program properties, such as response for all nonzeno execution sequences (during which time diverges), cannot be characterized by fixpoints: we show that the expressiveness of the timed mu-calculus is incomparable to the expressiveness of timed CTL. Fortunately, this result does not impair the symbolic verification of "implementable" real-time programs--those whose safety constraints are machine-closed with respect to diverging time and whose fairness constraints are restricted to finite upper bounds on clock values. All timed CTL properties of such programs are shown to be computable as finitely approximable fixpoints in a simple decidable theory.
AU - Thomas Henzinger
AU - Nicollin, Xavier
AU - Sifakis, Joseph
AU - Yovine, Sergio
ID - 4505
TI - Symbolic model checking for real-time systems
ER -
TY - CHAP
AB - We incorporate time into an interleaving model of concurrency. In timed transition systems, the qualitative fairness requirements of traditional transition system are replaced (and superseded) by quantitative lower-bound and upperbound timing constraints on transitions. The purpose of this paper is to explore the scope of applicability for the abstract model of timed transition systems. We demonstrate that the model can represent a wide variety of phenomena that routinely occur in conjunction with the timed execution of concurrent processes. Our treatment covers both processes that are executed in parallel on separate processors and communicate either through shared variables or by message passing, and processes that time-share a limited number of processors under a given scheduling policy. Often it is this scheduling policy that determines if a system meets its real-time requirements. Thus we explicitly address such questions as time-outs, interrupts, static and dynamic priorities.
AU - Thomas Henzinger
AU - Manna, Zohar
AU - Pnueli,Amir
ID - 4507
T2 - Real Time: Theory in Practice
TI - Timed transition systems
VL - 600
ER -
TY - JOUR
AB - It has been observed repeatedly that the standard safety-liveness classification for properties of reactive systems does not fit for real-time properties. This is because the implicit “liveliness” of time shifts the spectrum towards the safety side. While, for example, response—that “something good” will happen eventually—is a classical liveness property, bounded response—that “something good” will happen soon, within a certain amount of time—has many characteristics of safety. We account for this phenomenon formally by defining safety and liveness relative to a given condition, such as the progress of time.
AU - Thomas Henzinger
ID - 4517
IS - 3
JF - Information Processing Letters
TI - Sooner Is Safer Than Later
VL - 43
ER -
TY - CHAP
AB - We survey logic-based and automata-based languages and techniques for the specification and verification of real-time systems. In particular, we discuss three syntactic extensions of temporal logic: time-bounded operators, freeze quantification, and time variables. We also discuss the extension of finite-state machines with clocks and the extension of transition systems with time bounds on the transitions. All of the resulting notations can be interpreted over a variety of different models of time and computation, including linear and branching time, interleaving and true concurrency, discrete and continuous time. For each choice of syntax and semantics, we summarize the results that are known about expressive power, algorithmic finite-state verification, and deductive verification.
AU - Alur, Rajeev
AU - Thomas Henzinger
ID - 4593
T2 - Real Time: Theory in Practice
TI - Logics and models of real time: A survey
VL - 600
ER -
TY - CONF
AB - The authors introduce two-way timed automata-timed automata that can move back and forth while reading a timed word. Two-wayness in its unrestricted form leads, like nondeterminism, to the undecidability of language inclusion. However, if they restrict the number of times an input symbol may be revisited, then two-wayness is both harmless and desirable. The authors show that the resulting class of bounded two-way deterministic timed automata is closed under all boolean operations, has decidable (PSPACE-complete) emptiness and inclusion problems, and subsumes all decidable real-time logics we know. They obtain a strict hierarchy of real-time properties: deterministic timed automata can accept more languages as the bound on the number of times an input symbol may be revisited is increased. This hierarchy is also enforced by the number of alternations between past and future operators in temporal logic. The combination of the results leads to a decision procedure for a real-time logic with past operators
AU - Alur, Rajeev
AU - Thomas Henzinger
ID - 4594
TI - Back to the future: Towards a theory of timed regular languages
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 - Glutamate-operated ion channels (GluR channels) of the L-alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)-kainate subtype are found in both neurons and glial cells of the central nervous system. These channels are assembled from the GluR-A, -B, -C, and -D subunits; channels containing a GluR-B subunit show an outwardly rectifying current-voltage relation and low calcium permeability, whereas channels lacking the GluR-B subunit are characterized by a doubly rectifying current-voltage relation and high calcium permeability. Most cell types in the central nervous system coexpress several subunits, including GluR-B. However, Bergmann glia in rat cerebellum do not express GluR-B subunit genes. In a subset of cultured cerebellar glial cells, likely derived from Bergmann glial cells. GluR channels exhibit doubly rectifying current-voltage relations and high calcium permeability, whereas GluR channels of cerebellar neurons have low calcium permeability. Thus, differential expression of the GluR-B subunit gene in neurons and glia is one mechanism by which functional properties of native GluR channels are regulated.
AU - Burnashev, Nail A
AU - Khodorova, Alla
AU - Peter Jonas
AU - Helm, P. J.
AU - Wisden, William
AU - Monyer, Hannah
AU - Seeburg, Peter H
AU - Sakmann, Bert
ID - 3469
IS - 5063
JF - Science
TI - Calcium-permeable AMPA-kainate receptors in fusiform cerebellar glial cells.
VL - 256
ER -
TY - JOUR
AB - Currents activated by glutamate receptor (GluR) agonists were recorded from outside-out patches isolated from the soma of visually identified pyramidal neurones of the (CA3 and CA1 region of rat hippocampal slices. α-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA). L-glutamate (L-Glu), and kainate (KA) were delivered either by bath application through perfusion of the recording chamber or by rapid application via a piezo-driven two-barrelled fast application system. 2. Bath application of each of the three agonists activated inward currents in all patches (n = 134) at holding potentials of -50 or -60 mV. The current amplitude increased in size between 3 to 30 μM-AMPA and 100 μM to 1 mM-KA. With this slow mode of bath application, the responses showed no apparent desensitization even at saturating concentrations of AMPA (30 μM) and KA (1 mM). 3. The ratio of currents activated by 30 μM-AMPA and 300 μM-KA showed a characteristic difference between CA3 and CA1 neurones. The ratio was 0.242 ± 0.028 (mean ± S.E.M., n = 16) for CA3 cell patches and 0.097 ± 0.012 (n = 8) for CA1 cell patches indicating that GluRs in the two cell populations are different. 4. The steady-state current-voltage relations (I-Vs) for AMPA- and KA-activated currents showed pronounced outward rectification for both cell types (when the main cations are Na+ in the bath and Cs+ in the pipette solution). The current reversed close to 0 mV and the ratio of chord conductances 80 mV on either side of the reversal potential was 2.66 for KA-activated currents in CA3 cell patches and 2.60 in CA1 cell patches. AMPA-activated currents showed a time-dependent increase after steps to positive membrane potentials and a decrease after steps to negative voltages, indicating that a gating process is responsible for outward rectification of the steady-state I-IV. 5. The permeability (P) of GluR channels was high for Na+ as compared to Cs+ for both cell types (P(Na)/P(Cs) = 0.88 and 0.84). The permeability was low for N-methyl-D-glucamine+ (P(NMG)/P(Cs) ≤ 0.03) and Ca2+ (P(Ca)/P(Cs) ≤0.05). 6. The current noise level increased during application of AMPA or KA. Apparent single-channel conductances obtained from fluctuation analysis were higher for AMPA than for KA, but similar for both cell types. In CA3 cell patches, AMPA activated channels with an apparent chord conductance of 7.2 pS, KA of 3.0 pS conductance. 7. Fast agonist application revealed desensitization of GluR channels which was dependent on the type of agonist, currents activated by AMPA and L-Glu rose rapidly to a peak and then desensitized to a steady-state current. In contrast, currents activated by fast application of KA rose to a plateau and did not desensitize. The steady state current expressed as a percentage of the peak current was higher for L-Glu than for AMPA and slightly higher for CA3 than for CA1 cell patches. For CA3 cell patches, this fraction amounted to 6.2 %, with 300 μM-L-Glu and 2.8%, with 300 μM-AMPA. For CA1 cell patches, corresponding values were 3.6 and 1.9 % 8. The dose response relations for the peak current activated by AMPA and L-Glu and the steady-state current activated by KA were similar for CA3 and CA1 cell patches. The order of potency was AMPA > L-Glu ≃ KA for both cell types EC50 values 189, 342 and 344 μM for CA3 cell patches and 183, 424 and 474 μM for CA1 cell patches). In all cases, the Hill coefficients ranged between 12 and 1.7. 8. The rise of AMPA and L-Glu-activated currents became faster with increasing agonist concentration for both cell types. With L-Glu, rise times decreased from about 3 ms at 100 μM to 500 μs at 3 mM. The delay for agonist concentrations ≥ 300 μM was described by the sum of two exponential functions. The time constant of the predominant fast component was slightly concentration dependent and decreased from about 12 ms at 300 μM to 8 ms at 3 mM-L-Glu. 10. The current voltage relations of the peak currents activated by 300 μM-AMPA were linear for both cell types with a reversal potential close to OmV. 11. It is concluded that the GluR channels in pyramidal cells of hippocampal CA3 and CA1 regions are distinet but share many pharmacological and functional properties. Comparison of the properties of native and recombinant GluRs suggests that in both CA3 and CA1 regions GluR channels are hetero-oligomers containing the GluR-B subunit.
AU - Peter Jonas
AU - Sakmann, Bert
ID - 3470
JF - Journal of Physiology
TI - Glutamate receptor channels in isolated patches from CA1 and CA3 pyramidal cells of rat hippocampal slices
VL - 455
ER -
TY - JOUR
AB - 1. Outside-out patches were isolated from granule cells of dentate gyrus and pyramidal cells of CA3 and CA1 regions of rat hippocampal slices. Patches were exposed briefly to L-glutamate using a piezo-driven double-barrelled application pipette. 2. Applications of glutamate (1 mM) of 1 ms duration activated patch currents which rose and decayed rapidly. The 20-80% rise time of these glutamate receptor (GluR)-mediated currents was usually 0.2-0.6 ms. At -50 mV the peak current varied from 10 to 500 pA in different patches. 3. The peak current-voltage relation for brief pulses of 1 mM glutamate was virtually linear in normal extracellular solution for patches from the three cell types (-100 to 60 mV). 4. The permeability of GluR channels activated at the peak to Ca2+, relative to K+, was less than 0.1 for all three cell types (under bi-ionic conditions with Ca2+ on the extracellular side and K+ on the intracellular side of the membrane). 5. The offset decay time constant of the current following 1 ms pulses of 1 mM glutamate was brief, with mean values of 3.0 +/- 0.8, 2.5 +/- 0.7, and 2.3 +/- 0.7 ms for dentate, CA3 and CA1 cell patches, respectively. Offset time constants were independent of membrane potential and independent of glutamate concentration (200 microM and 1 mM) for the three cell types. 6. Applications of 1 mM glutamate of 100 ms duration showed that glutamate responses desensitized rapidly. The time constants for desensitization were 9.4 +/- 2.7, 11.3 +/- 2.8, and 9.3 +/- 2.8 ms for patches from dentate, CA3 and CA1 cells respectively. Desensitization time constants were only weakly dependent on glutamate concentration (200 microM and 1 mM) for the three cell types. Thus offset time constants are about four times faster than desensitization time constants for both glutamate concentrations. 7. Double pulse application of glutamate indicated that even a 1 ms pulse of 1 mM glutamate causes partial (about 60%) desensitization of GluR channels. The time course of recovery from desensitization was slower in dentate gyrus granule cell patches than in CA3 or CA1 pyramidal cell patches. 8. Desensitization was studied at equilibrium by exposing patches to low glutamate concentrations for at least 15 s before a 1 ms test pulse of 1 mM glutamate.
AU - Colquhoun, D.
AU - Peter Jonas
AU - Sakmann, Bert
ID - 3471
JF - Journal of Physiology
TI - Action of brief pulses of glutamate on AMPA/kainate receptors in patches from different neurones of rat hippocampal slices
VL - 458
ER -
TY - JOUR
AB - A novel potassium-selective channel which is active at membrane potentials between -100 mV and +40 mV has been identified in peripheral myelinated axons of Xenopus laevis using the patch-clamp technique. At negative potentials with 105 mM-K on both sides of the membrane, the channel at 1 kHz resolution showed a series of brief openings and closings interrupted by longer closings, resulting in a flickery bursting activity. Measurements with resolution up to 10 kHz revealed a single-channel conductance of 49 pS with 105 mM-K and 17 pS with 2.5 mM-K on the outer side of the membrane. The channel was selective for K ions over Na ions (PNa/PK = 0.033). The probability of being within a burst in outside-out patches varied from patch to patch (> 0.2, but often > 0.9), and was independent of membrane potential. Open-time histograms were satisfactorily described with a single exponential (tau o = 0.09 msec), closed times with the sum of three exponentials (tau c = 0.13, 5.9, and 36.6 msec). Sensitivity to external tetraethylammonium was comparatively low (IC50 = 19.0 mM). External Cs ions reduced the apparent unitary conductance for inward currents at Em = -90 mV (IC50 = 1.1 mM). Ba and, more potently, Zn ions lowered not only the apparent single-channel conductance but also open probability. The local anesthetic bupivacaine with high potency reduced probability of being within a burst (IC50 = 165 nM). The flickering K channel is clearly different from the other five types of K channels identified so far in the same preparation. We suggest that this channel may form the molecular basis of the resting potential in vertebrate myelinated axons.
AU - Koh, Duk S
AU - Peter Jonas
AU - Bräu, Michael E
AU - Vogel, Werner
ID - 3472
JF - Journal of Membrane Biology
TI - A TEA-insensitive flickering potassium channel active around the resting potential in myelinated nerve
VL - 130
ER -
TY - JOUR
AU - Chazelle, Bernard
AU - Herbert Edelsbrunner
AU - Guibas, Leonidas J
AU - Pollack, Richard
AU - Seidel, Raimund
AU - Sharir, Micha
AU - Snoeyink, Jack
ID - 3581
IS - 6
JF - Computational Geometry: Theory and Applications
TI - Counting and cutting cycles of lines and rods in space
VL - 1
ER -
TY - JOUR
AB - Three components of mating call (pulse duration, cycle length, and fundamental frequency) were measured and six diagnostic enzyme loci scored across the hybrid zone between the toads Bombina bombina and B. variegata. All three call components differ significantly, but only cycle length is diagnostic. The clines in call coincide with those for enzymes, and have similar widths. This suggests that there is no strong selection on any of these characters. There are significant correlations between electrophoretic markers and call components, but these are no stronger than would be expected if the electrophoretic loci and the genes causing mating call were neutral. The selection differential on the call is no greater than 6% of the difference in mean cycle length between the two taxa. There is a substantial increase in the variance of cycle length in the center of the zone, suggesting that a small number of loci are involved (≈ three). Recombination between these loci will hinder the evolution of reinforcement and may partly be responsible for the lack of premating isolation between B. bombina and B. variegata.
AU - Sanderson, Neil
AU - Szymura, Jacek M
AU - Nicholas Barton
ID - 3645
IS - 3
JF - Evolution
TI - Variation in mating call across the hybrid zone between the fire-bellied toads Bombina bombina and B. variegata
VL - 46
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 complementary DNA of a metabotropic glutamate receptor coupled to inositol phosphate/Ca2+ signal transduction has been cloned and characterized. This receptor shows no sequence similarity to conventional G protein-coupled receptors and has a unique structure with large hydrophilic sequences at both sides of seven putative membrane-spanning domains. Abundant expression of this messenger RNA is observed in neuronal cells in hippocampal dentate gyrus and CA2-3 and in cerebellar Purkinje cells, suggesting the importance of this receptor in specific hippocampal and cerebellar functions.
AU - Masu, Masayuki
AU - Tanabe, Yasuto
AU - Tsuchida, Kunihiro
AU - Ryuichi Shigemoto
AU - Nakanishi, Shigetada
ID - 2482
IS - 6312
JF - Nature
TI - Sequence and expression of a metabotropic glutamate receptor
VL - 349
ER -
TY - JOUR
AB - A complementary DNA encoding the rat NMDA receptor has been cloned and characterized. The single protein encoded by the cDNA forms a receptor-channel complex that has electrophysiological and pharmacological properties characteristic of the NMDA receptor. This protein has a significant sequence similarity to the AMPA/kainate receptors and contains four putative transmembrane segments following a large extracellular domain. The NMDA receptor messenger RNA is expressed in neuronal cells throughout the brain regions, particularly in the hippocampus, cerebral cortex and cerebellum.
AU - Moriyoshi, Koki
AU - Masu, Masayuki
AU - Ishii, Takahiro
AU - Ryuichi Shigemoto
AU - Mizuno, Noboru
AU - Nakanishi, Shigetada
ID - 2483
IS - 6348
JF - Nature
TI - Molecular cloning and characterization of the rat NMDA receptor
VL - 353
ER -
TY - JOUR
AB - The distribution of cerebral cortical neurons sending projection fibers to the nucleus of the solitary tract (NST), and the topographical distribution of axon terminals of cortico-NST fibers within the NST were examined in the cat by two sets of experiments with horseradish peroxidase (HRP) and HRP conjugated with wheat germ agglutinin (WGA-HRP). First, HRP was injected into the NST. In the cerebral cortex of these cats, neuronal cell bodies were labeled retrogradely in the deep pyramidal cell layer (layer V): After HRP injection centered on the rostral or middle part of the NST, HRP-labeled neuronal cell bodies were distributed mainly in the orbital gyrus and caudal part of the intralimbic cortex, and additionally in the rostral part of the anterior sylvian gyrus. After HRP injection centered on the caudal part of the NST, labeled neuronal cell bodies were seen mainly in the caudoventral part of the intralimbic cortex, and additionally in the orbital gyrus, posterior sigmoid gyrus and rostral part of the anterior sylvian gyrus. The labeling in the intralimbic cortex, orbital gyrus and anterior sylvian gyrus was bilateral with a predominantly ipsilateral distribution, while that in the posterior sigmoid gyrus was bilateral with a clear-cut contralateral dominance. In the second set of experiments, WGA-HRP was injected into the cerebral cortical regions where neuronal cell bodies had been retrogradely labeled with HRP injected into the NST: after WGA-HRP injection into the orbital gyrus, presumed axon terminals in the NST were labeled in the rostral two thirds of the nucleus bilaterally with an ipsilateral predominance. After WGA-HRP injection into the rostral part of the anterior sylvian gyrus, a moderate number of presumed axon terminals were labeled throughout the whole rostrocaudal extent of the NST bilaterally with a slight ipsilateral dominance. After WGA-HRP injection into the middle and caudal parts of the anterior sylvian gyrus, no labeling was found in the NST. After WGA-HRP injection into the caudal part of the intralimbic cortex, presumed terminal labeling in the NST was seen throughout the whole rostrocaudal extent of the nucleus bilaterally with a dominant ipsilateral distribution. After WGA-HRP injection into the posterior sigmoid gyrus, however, no terminal labeling was found in the NST. The results indicate that cortico-NST fibers from the orbital gyrus terminate in the rostral two thirds of the NST, while those from the intralimbic cortex and the rostral part of the anterior sylvian gyrus project to the whole rostrocaudal extent of the NST.
AU - Yasui, Yukihiko
AU - Itoh, Kazuo
AU - Kaneko, Takeshi
AU - Ryuichi Shigemoto
AU - Mizuno, Noboru
ID - 2529
IS - 1
JF - Experimental Brain Research
TI - Topographical projections from the cerebral cortex to the nucleus of the solitary tract in the cat
VL - 85
ER -
TY - JOUR
AU - Nakanishi, Shigetada
AU - Ohkubo, Hiroaki
AU - Kakizuka, Akira
AU - Yokota, Yoshifumi
AU - Ryuichi Shigemoto
AU - Sasai, Yoshiki
AU - Takumi, Toru
ID - 2530
IS - 1
JF - Recent Progress in Hormone Research
TI - Molecular characterization of mammalian tachykinin receptors and a possible epithelial potassium channel
VL - 46
ER -
TY - JOUR
AB - An algorithm is presented that constructs the convex hull of a set of n points in three dimensions in worst-case time O(n log2h) and storage O(n), where h is the number of extreme points. This is an improvement of the O(nh) time gift-wrapping algorithm and, for certain values of h, of the O(n log n) time divide-and-conquer algorithm.
AU - Herbert Edelsbrunner
AU - Shi, Weiping
ID - 4051
IS - 2
JF - SIAM Journal on Computing
TI - An O(n log^2 h) time algorithm for the three-dimensional convex hull problem
VL - 20
ER -
TY - JOUR
AB - This paper describes an effective procedure for stratifying a real semi-algebraic set into cells of constant description size. The attractive feature of our method is that the number of cells produced is singly exponential in the number of input variables. This compares favorably with the doubly exponential size of Collins' decomposition. Unlike Collins' construction, however, our scheme does not produce a cell complex but only a smooth stratification. Nevertheless, we are able to apply our results in interesting ways to problems of point location and geometric optimization.
AU - Chazelle, Bernard
AU - Herbert Edelsbrunner
AU - Guibas, Leonidas J
AU - Sharir, Micha
ID - 4052
IS - 1
JF - Theoretical Computer Science
TI - A singly exponential stratification scheme for real semi-algebraic varieties and its applications
VL - 84
ER -
TY - CONF
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 ge 3, turned out to contain a serious and irreparable error. This paper presents a new proof of the theorem. Our proof is based on an inductive argument, which also applies in the case of pseudo-hyperplane arrangements. We also briefly discuss the fallacies of the old proof along with some ways of partially saving that approach.
AU - Herbert Edelsbrunner
AU - Seidel, Raimund
AU - Sharir, Micha
ID - 4054
TI - On the zone theorem for hyperplane arrangements
VL - 555
ER -
TY - CONF
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 O(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 - 4055
TI - A quadratic time algorithm for the minmax length triangulation
ER -
TY - JOUR
AB - This paper proves that for every n ≥ 4 there is a convex n-gon such that the vertices of 2n - 7 vertex pairs are one unit of distance apart. This improves the previously best lower bound of ⌊ (5n - 5) 3⌋ given by Erdo{combining double acute accent}s and Moser if n ≥ 17.
AU - Herbert Edelsbrunner
AU - Hajnal, Péter
ID - 4056
IS - 2
JF - Journal of Combinatorial Theory Series A
TI - A lower bound on the number of unit distances between the vertices of a convex polygon
VL - 56
ER -
TY - JOUR
AU - Herbert Edelsbrunner
ID - 4057
IS - 2
JF - Journal of Computer and System Sciences
TI - Corrigendum
VL - 42
ER -
TY - CONF
AB - We present 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.
AU - Chazelle, Bernard
AU - Herbert Edelsbrunner
AU - Guibas, Leonidas
AU - Sharir, Micha
AU - Snoeyink, Jack
ID - 4058
TI - Computing a face in an arrangement of line segments
ER -
TY - CONF
AB - Let P be a simple polygon with n vertices. We present a simple decomposition scheme that partitions the interior of P into O(n) so-called geodesic triangles, so that any line segment interior to P crosses at most 2 log n of these triangles. This decomposition can be used to preprocess P in time O(n log n) and storage O(n), so that any ray-shooting query can be answered in time O(log n).The algorithms are fairly simple and easy to implement. We also extend this technique to the case of ray-shooting amidst k polygonal obstacles with a total of n edges, so that a query can be answered in O(radicklog n) time.
AU - Chazelle, Bernard
AU - Herbert Edelsbrunner
AU - Grigni, Michelangelo
AU - Guibas, Leonidas
AU - Hershberger, John
AU - Sharir, Micha
AU - Snoeyink, Jack
ID - 4059
TI - Ray shooting in polygons using geodesic triangulations
VL - 510
ER -
TY - JOUR
AB - We present an algorithm to compute a Euclidean minimum spanning tree of a given set S of N points in Ed in time O(Fd (N,N) logd N), where Fd (n,m) is the time required to compute a bichromatic closest pair among n red and m green points in Ed . If Fd (N,N)=Ω(N1+ε), for some fixed e{open}>0, then the running time improves to O(Fd (N,N)). Furthermore, we describe a randomized algorithm to compute a bichromatic closest pair in expected time O((nm log n log m)2/3+m log2 n+n log2 m) in E3, which yields an O(N4/3 log4/3 N) expected time, algorithm for computing a Euclidean minimum spanning tree of N points in E3. In d≥4 dimensions we obtain expected time O((nm)1-1/([d/2]+1)+ε+m log n+n log m) for the bichromatic closest pair problem and O(N2-2/([d/2]+1)ε) for the Euclidean minimum spanning tree problem, for any positive e{open}.
AU - Agarwal, Pankaj K
AU - Herbert Edelsbrunner
AU - Schwarzkopf, Otfried
AU - Welzl, Emo
ID - 4061
IS - 1
JF - Discrete & Computational Geometry
TI - Euclidean minimum spanning trees and bichromatic closest pairs
VL - 6
ER -
TY - JOUR
AB - We prove that for any set S of n points in the plane and n3-α triangles spanned by the points in S there exists a point (not necessarily in S) contained in at least n3-3α/(c log5 n) of the triangles. This implies that any set of n points in three-dimensional space defines at most {Mathematical expression} halving planes.
AU - Aronov, Boris
AU - Chazelle, Bernard
AU - Herbert Edelsbrunner
AU - Guibas, Leonidas J
AU - Sharir, Micha
AU - Wenger, Rephael
ID - 4062
IS - 1
JF - Discrete & Computational Geometry
TI - Points and triangles in the plane and halving planes in space
VL - 6
ER -
TY - CONF
AB - We extend the specification language of temporal logic, the corresponding verification framework, and the underlying computational model to deal with real-time properties of concurrent and reactive systems. A global, discrete, and asynchronous clock is incorporated into the model by defining the abstract notion of a real-time transition system as a conservative extension of traditional transition systems: qualitative fairness requirements are replaced (and superseded) by quantitative lower-bound and upperbound real-time requirements for transitions. We show how to model real-time systems that communicate either through shared variables or by message passing, and how to represent the important real-time constructs of priorities (interrupts), scheduling, and timeouts in this framework. Two styles for the specification of real-time properties are presented. The first style uses bounded versions of the temporal operators; the real-time requirements expressed in this style are classified ...
AU - Thomas Henzinger
AU - Manna, Zohar
AU - Pnueli,Amir
ID - 4508
TI - Temporal proof methodologies for real-time systems
ER -
TY - THES
AU - Thomas Henzinger
ID - 4516
TI - The Temporal Specification and Verification of Real-time Systems
ER -