@article{1945, abstract = {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.}, author = {Sazanov, Leonid A and Zaǐtsev, Sergei}, issn = {0006-2979}, journal = {Biochemistry (Moscow)}, number = {10}, pages = {1443 -- 1460}, publisher = {Izdatel'stvo Nauka}, title = {{Effect of superlow doses (10(-18)-10-(-14) M) of biologically active substances: general rules, features, and possible mechanisms}}, volume = {57}, year = {1992}, } @article{2486, abstract = {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.}, author = {Shigemoto, Ryuichi and Nakanishi, Shigetada and Mizuno, Noboru}, issn = {0021-9967}, journal = {Journal of Comparative Neurology}, number = {1}, pages = {121 -- 135}, publisher = {Wiley-Blackwell}, title = {{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}}, doi = {10.1002/cne.903220110}, volume = {322}, year = {1992}, } @article{2485, abstract = {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.}, author = {Hori, Seiji and Komatsu, Yasato and Shigemoto, Ryuichi and Mizuno, Noboru and Nakanishi, Shigetada}, issn = {0013-7227}, journal = {Endocrinology}, number = {4}, pages = {1885 -- 1895}, publisher = {The Endocrine Society}, title = {{Distinct tissue distribution and cellular localization of two messenger ribonucleic acids encoding different subtypes of rat endothelin receptors}}, doi = {10.1210/endo.130.4.1312429}, volume = {130}, year = {1992}, } @article{2484, abstract = {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.}, author = {Tanabe, Yasuto and Masu, Masayuki and Ishii, Takahiro and Shigemoto, Ryuichi and Nakanishi, Shigetada}, issn = {0896-6273}, journal = {Neuron}, number = {1}, pages = {169 -- 179}, publisher = {Elsevier}, title = {{A family of metabotropic glutamate receptors}}, doi = {10.1016/0896-6273(92)90118-W}, volume = {8}, year = {1992}, } @article{2533, abstract = {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.}, author = {Abe, Takaaki and Sugihara, Hidemitsu and Nawa, Hiroyuki and Shigemoto, Ryuichi and Mizuno, Noboru and Nakanishi, Shigetada}, issn = {0021-9258}, journal = {Journal of Biological Chemistry}, number = {19}, pages = {13361 -- 13368}, publisher = {American Society for Biochemistry and Molecular Biology}, title = {{Molecular characterization of a novel metabotropic glutamate receptor mGluR5 coupled to inositol phosphate/Ca2+ signal transduction}}, doi = {10.1016/S0021-9258(18)42219-3}, volume = {267}, year = {1992}, } @article{2535, abstract = {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.}, author = {Sasai, Yoshiki and Kageyama, Ryoichiro and Tagawa, Yoshiaki and Shigemoto, Ryuichi and Nakanishi, Shigetada}, issn = {0890-9369}, journal = {Genes and Development}, number = {12 B}, pages = {2620 -- 2634}, publisher = {Cold Spring Harbor Laboratory Press}, title = {{Two mammalian helix-loop-helix factors structurally related to Drosophila hairy and Enhancer of split}}, doi = {10.1101/gad.6.12b.2620}, volume = {6}, year = {1992}, } @article{2532, abstract = {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.}, author = {Nishioka, Tatsuya and Oda, Yoshifumi and Seino, Yutaka and Yamamoto, Taizo and Inagaki, Nobuya and Yano, Hideki and Imura, Hiroo and Shigemoto, Ryuichi and Kikuchi, Haruhiko}, issn = {0008-5472}, journal = {Cancer Research}, number = {14}, pages = {3972 -- 3979}, publisher = {American Association for Cancer Research}, title = {{Distribution of the glucose transporters in human brain tumors}}, volume = {52}, year = {1992}, } @article{2534, abstract = {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.}, author = {Ishihara, Takeshi and Shigemoto, Ryuichi and Mori, Kensaku and Takahashi, Kenji and Nagata, Shigekazu}, issn = {0896-6273}, journal = {Neuron}, number = {4}, pages = {811 -- 819}, publisher = {Elsevier}, title = {{Functional expression and tissue distribution of a novel receptor for vasoactive intestinal polypeptide}}, doi = {10.1016/0896-6273(92)90101-I}, volume = {8}, year = {1992}, } @article{2531, abstract = {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.}, author = {Shigemoto, Ryuichi and Ohishi, Hitoshi and Nakanishi, Shigetada and Mizuno, Noboru}, issn = {0304-3940}, journal = {Neuroscience Letters}, number = {1-2}, pages = {229 -- 232}, publisher = {Elsevier}, title = {{Expression of the mRNA for the rat NMDA receptor (NMDAR1) in the sensory and autonomic ganglion neurons}}, doi = {10.1016/0304-3940(92)90756-W}, volume = {144}, year = {1992}, } @article{2714, author = {Erdös, László}, issn = {0001-5954}, journal = {Acta Mathematica Hungarica}, number = {1-2}, pages = {11 -- 24}, publisher = {Springer}, title = {{On some problems of P. Turán concerning power sums of complex numbers}}, doi = {10.1007/BF00052086}, volume = {59}, year = {1992}, } @article{2722, abstract = {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).}, author = {Erdös, László and Tuyen, Dao}, issn = {0010-3616}, journal = {Communications in Mathematical Physics}, number = {3}, pages = {451 -- 466}, publisher = {Springer}, title = {{Central limit theorems for the one-dimensional Rayleigh gas with semipermeable barriers}}, doi = {10.1007/BF02099260}, volume = {143}, year = {1992}, } @article{3470, abstract = {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.}, author = {Jonas, Peter M and Sakmann, Bert}, issn = {0022-3751}, journal = {Journal of Physiology}, pages = {143 -- 171}, publisher = {Wiley-Blackwell}, title = {{Glutamate receptor channels in isolated patches from CA1 and CA3 pyramidal cells of rat hippocampal slices}}, doi = {10.1113/jphysiol.1992.sp019294 }, volume = {455}, year = {1992}, } @article{3471, abstract = {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.}, author = {Colquhoun, D. and Jonas, Peter M and Sakmann, Bert}, issn = {0022-3751}, journal = {Journal of Physiology}, pages = {261 -- 287}, publisher = {Wiley-Blackwell}, title = {{Action of brief pulses of glutamate on AMPA/kainate receptors in patches from different neurones of rat hippocampal slices}}, doi = {10.1113/jphysiol.1992.sp019417}, volume = {458}, year = {1992}, } @article{3472, abstract = {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.}, author = {Koh, Duk and Jonas, Peter M and Bräu, Michael and Vogel, Werner}, issn = {0022-2631}, journal = {Journal of Membrane Biology}, pages = {149 -- 162}, publisher = {Springer}, title = {{A TEA-insensitive flickering potassium channel active around the resting potential in myelinated nerve}}, doi = {10.1007/BF00231893}, volume = {130}, year = {1992}, } @article{4053, abstract = {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.}, author = {Aronov, Boris and Edelsbrunner, Herbert and Guibas, Leonidas and Sharir, Micha}, issn = {0209-9683}, journal = {Combinatorica}, number = {3}, pages = {261 -- 274}, publisher = {Springer}, title = {{The number of edges of many faces in a line segment arrangement}}, doi = {10.1007/BF01285815}, volume = {12}, year = {1992}, } @article{4050, author = {Edelsbrunner, Herbert}, journal = {Discrete & Computational Geometry}, number = {1}, pages = {217 -- 217}, publisher = {Springer}, title = {{Guest editor's foreword}}, doi = {10.1007/BF02293046}, volume = {8}, year = {1992}, } @article{4195, abstract = {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.}, author = {Heisenberg, Carl-Philipp J and Thoenen, Hans and Lindholm, Dan}, issn = {1473-558X}, journal = {Neuroreport}, number = {8}, pages = {685 -- 688}, publisher = {Lippincott, Williams & Wilkins}, title = {{Triiodothyronine Regulates Survival and Differentiation of Rat Cerebellar Granule Neurons}}, doi = {10.1097/00001756-199208000-00008 }, volume = {3}, year = {1992}, } @article{4305, abstract = {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.}, author = {Hatfield, Todd and Barton, Nicholas H and Searle, Jeremy}, issn = {1558-5646}, journal = {Evolution; International Journal of Organic Evolution}, number = {4}, pages = {1129 -- 1145}, publisher = {Wiley-Blackwell}, title = {{A model of a hybrid zone between two chromosomal races of the common shrew (Sorex araneus)}}, doi = {10.1111/j.1558-5646.1992.tb00624.x}, volume = {46}, year = {1992}, } @article{4308, author = {Barton, Nicholas H}, issn = {1558-5646}, journal = {Evolution; International Journal of Organic Evolution}, number = {2}, pages = {551 -- 557}, publisher = {Wiley-Blackwell}, title = {{On the spread of new gene combinations in the third phase of Wright's shifting balance}}, volume = {46}, year = {1992}, } @inbook{4307, author = {Barton, Nicholas H}, booktitle = {Animal dispersal: small mammals as a model}, editor = {Stenseth, Nils and Lidicker, William}, pages = {37 -- 60}, publisher = {Chapman Hall}, title = {{The genetic consequences of dispersal}}, doi = {10.1007/978-94-011-2338-9_3}, year = {1992}, } @misc{4306, author = {Barton, Nicholas H and Goldman, Nick}, booktitle = {Nature}, pages = {440 -- 441}, publisher = {Nature Publishing Group}, title = {{Genetics and geography}}, doi = {10.1038/357440a0}, volume = {357}, year = {1992}, } @article{3469, abstract = {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.}, author = {Burnashev, Nail and Khodorova, Alla and Jonas, Peter M and Helm, P. and Wisden, William and Monyer, Hannah and Seeburg, Peter and Sakmann, Bert}, issn = {0036-8075}, journal = {Science}, number = {5063}, pages = {1566 -- 1570}, publisher = {American Association for the Advancement of Science}, title = {{Calcium-permeable AMPA-kainate receptors in fusiform cerebellar glial cells.}}, doi = {10.1126/science.1317970}, volume = {256}, year = {1992}, } @article{3581, abstract = {A number of rendering algorithms in computer graphics sort three-dimensional objects by depth and assume that there is no cycle that makes the sorting impossible. One way to resolve the problem caused by cycles is to cut the objects into smaller pieces. In this paper we address the problem of estimating how many such cuts arc always sufficient. We also consider a few related algorithmic and combinatorial geometry problems. For example, we demonstrate that n lines in space can be sorted in randomized expected time O(n4’st’), provided that they define no cycle. We also prove an 0(n7’4) upper bound on the number of points in space so that there are n lines with the property that for each point there are at least three noncoplanar lines that contain it. }, author = {Chazelle, Bernard and Edelsbrunner, Herbert and Guibas, Leonidas and Pollack, Richard and Seidel, Raimund and Sharir, Micha and Snoeyink, Jack}, issn = {0925-7721}, journal = {Computational Geometry: Theory and Applications}, number = {6}, pages = {305 -- 323}, publisher = {Elsevier}, title = {{Counting and cutting cycles of lines and rods in space}}, doi = {10.1016/0925-7721(92)90009-H}, volume = {1}, year = {1992}, } @article{3645, abstract = {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.}, author = {Sanderson, Neil and Szymura, Jacek and Barton, Nicholas H}, issn = {0014-3820}, journal = {Evolution}, number = {3}, pages = {595 -- 607}, publisher = {Wiley-Blackwell}, title = {{Variation in mating call across the hybrid zone between the fire-bellied toads Bombina bombina and B. variegata}}, doi = {10.1111/j.1558-5646.1992.tb02068.x}, volume = {46}, year = {1992}, } @inproceedings{4049, abstract = {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.}, author = {Bern, Marshall and Edelsbrunner, Herbert and Eppstein, David and Mitchell, Stephen and Tan, Tiow}, booktitle = {1st Latin American Symposium on Theoretical Informatics}, editor = {Simon, Imre}, isbn = {978-3-540-55284-0}, location = {São Paulo, Brazil}, pages = {46 -- 60}, publisher = {Springer}, title = {{Edge insertion for optimal triangulations}}, doi = {10.1007/BFb0023816}, volume = {583}, year = {1992}, } @article{4047, abstract = {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.}, author = {Edelsbrunner, Herbert and Guibas, Leonidas and Pach, János and Pollack, Richard and Seidel, Raimund and Sharir, Micha}, issn = {0304-3975}, journal = {Theoretical Computer Science}, number = {2}, pages = {319 -- 336}, publisher = {Elsevier}, title = {{Arrangements of curves in the plane - topology, combinatorics, and algorithms}}, doi = {10.1016/0304-3975(92)90319-B}, volume = {92}, year = {1992}, } @article{4046, abstract = {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.}, author = {Chazelle, Bernard and Edelsbrunner, Herbert}, issn = {1557-735X}, journal = {Journal of the ACM}, number = {1}, pages = {1 -- 54}, publisher = {ACM}, title = {{An optimal algorithm for intersecting line segments in the plane}}, doi = {10.1145/147508.147511}, volume = {39}, year = {1992}, } @article{4043, abstract = {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.}, author = {Edelsbrunner, Herbert and Tan, Tiow and Waupotitsch, Roman}, issn = {1095-7111}, journal = {SIAM Journal on Scientific Computing}, number = {4}, pages = {994 -- 1008}, publisher = {Society for Industrial and Applied Mathematics }, title = {{An O(n^2 log n) time algorithm for the MinMax angle triangulation}}, doi = {10.1137/0913058}, volume = {13}, year = {1992}, } @article{4048, abstract = {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.}, author = {Aggarwal, Alok and Edelsbrunner, Herbert and Raghavan, Prabhakar and Tiwari, Prasoon}, issn = {1872-6119}, journal = {Information Processing Letters}, number = {1}, pages = {55 -- 60}, publisher = {Elsevier}, title = {{Optimal time bounds for some proximity problems in the plane}}, doi = {10.1016/0020-0190(92)90133-G}, volume = {42}, year = {1992}, } @inproceedings{4505, abstract = {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.}, author = {Henzinger, Thomas A and Nicollin, Xavier and Sifakis, Joseph and Yovine, Sergio}, booktitle = {Proceedings of the 7th Annual IEEE Symposium on Logic in Computer Science}, isbn = {0-8186-2735-2}, location = {Santa Cruz, CA, United States of America}, pages = {394 -- 406}, publisher = {IEEE}, title = {{Symbolic model checking for real-time systems}}, doi = {10.1109/LICS.1992.185551}, year = {1992}, } @inproceedings{4504, abstract = {Real-time systems operate in “real,” continuous time and state changes may occur at any real-numbered time point. Yet many verification methods are based on the assumption that states are observed at integer time points only. What can we conclude if a real-time system has been shown “correct” for integral observations? Integer time verification techniques suffice if the problem of whether all real-numbered behaviors of a system satisfy a property can be reduced to the question of whether the integral observations satisfy a (possibly modified) property. We show that this reduction is possible for a large and important class of systems and properties: the class of systems includes all systems that can be modeled as timed transition systems; the class of properties includes time-bounded invariance and time-bounded response.}, author = {Henzinger, Thomas A and Manna, Zohar and Pnueli, Amir}, booktitle = {19th International Colloquium on Automata, Languages and Programming}, location = {Vienna, Austria}, pages = {545 -- 558}, publisher = {Springer}, title = {{What good are digital clocks?}}, doi = {10.1007/3-540-55719-9_103}, volume = {623}, year = {1992}, } @inbook{4507, abstract = {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.}, author = {Henzinger, Thomas A and Manna, Zohar and Pnueli, Amir}, booktitle = {Real Time: Theory in Practice}, pages = {226 -- 251}, publisher = {Springer}, title = {{Timed transition systems}}, doi = {10.1007/BFb0031995}, volume = {600}, year = {1992}, } @article{4517, abstract = {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.}, author = {Henzinger, Thomas A}, issn = {0020-0190}, journal = {Information Processing Letters}, number = {3}, pages = {135 -- 141}, publisher = {Elsevier}, title = {{Sooner Is Safer Than Later}}, doi = {10.1016/0020-0190(92)90005-G}, volume = {43}, year = {1992}, } @inproceedings{4593, abstract = {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.}, author = {Alur, Rajeev and Henzinger, Thomas A}, booktitle = {REX Workshop on Real Time: Theory in Practice}, location = {Mook, The Netherlands}, pages = {74 -- 106}, publisher = {Springer}, title = {{Logics and models of real time: A survey}}, doi = {10.1007/BFb0031984}, volume = {600}, year = {1992}, } @inproceedings{4594, abstract = {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 }, author = {Alur, Rajeev and Henzinger, Thomas A}, booktitle = {Proceedings of the 33rd Annual Symposium on Foundations of Computer Science}, location = {Pittsburgh, PA, United States of America}, pages = {177 -- 186}, publisher = {IEEE}, title = {{Back to the future: Towards a theory of timed regular languages}}, doi = {10.1109/SFCS.1992.267774}, year = {1992}, }