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 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
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 -
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 -