@inproceedings{11857, abstract = {Two edges e/sub 1/ and e/sub 2/ of an undirected graph are cycle-equivalent iff all cycles that contain e/sub 1/ also contain e/sub 2/, i.e., iff e/sub 1/ and e/sub 2/ are a cut-edge pair. The cycle-equivalence classes of the control-flow graph are used in optimizing compilers to speed up existing control-flow and data-flow algorithms. While the cycle-equivalence classes can be computed in linear time, we present the first fully dynamic algorithm for maintaining the cycle-equivalence relation. In an n-node graph our data structure executes an edge insertion or deletion in O(/spl radic/n log n) time and answers the query whether two given edges are cycle-equivalent in O(log/sup 2/ n) time. We also present an algorithm for plane graphs with O(log n) update and query time and for planar graphs with O(log n) insertion time and O(log/sup 2/ n) query and deletion time. Additionally, we show a lower bound of /spl Omega/(log n/log log n) for the amortized time per operation for the dynamic cycle-equivalence problem in the cell probe model.< >}, author = {Henzinger, Monika H}, booktitle = {35th Annual Symposium on Foundations of Computer Science}, isbn = {0-8186-6580-7}, location = {Santa Fe, NM, United States}, pages = {744 -- 755}, publisher = {Institute of Electrical and Electronics Engineers}, title = {{Fully dynamic cycle-equivalence in graphs}}, doi = {10.1109/sfcs.1994.365718}, year = {1994}, } @article{2488, abstract = {Substance P receptor-expressing neurons in the rat cerebral neocortex were examined by single- and double-immunolabeling methods with an affinity-purified specific antibody to substance P receptor. Substance P receptor immunoreactivity was observed exclusively in non-pyramidal neurons. About a quarter of these substance P receptor-positive neocortical neurons showed intense immunoreactivity, and the other three quarters displayed weak substance P receptor immunoreactivity. The neurons showing intense substance P receptor immunoreactivity were large multipolar cells with a few long aspiny or sparsely-spiny dendrites, and were scattered throughout the neocortical layers except for layer I, and also in the underlying white matter. The weakly immunoreactive neurons were medium-sized multipolar cells with oval to round somata and aspiny varicose dendrites, and were distributed in all cortical layers with a bias to layers II-III and the superficial part of layer V. The double-immunofluorescence study revealed that almost all substance P receptor-positive neurons were immunoreactive for GABA, but negative for glutaminase. Substance P receptor immunoreactivity in GABAergic neocortical neurons were further examined by the double-immunofluorescence method with antibodies to markers for subgroups of GABAergic neurons. Somatostatin immunoreactivity was found in 89% of neurons with intense substance P receptor immunoreactivity, and in 1.5% of neurons with weak substance P receptor immunoreactivity. Neuropeptide Y immunoreactivity was also observed in 92% of neurons with intense immunoreactivity for substance P receptor, and in 1.6% of neurons with weak immunoreactivity for substance P receptor. In contrast, parvalbumin immunoreactivity was seen in 1.3% of neurons with intense substance P receptor immunoreactivity, and in 59% of weak substance P receptor immunoreactivity. Calbindin D28k immunoreactivity was found in 12 and 19% of neurons, respectively, with weak and intense immunoreactivities for substance P receptor. Virtually no cells showing substance P receptor immunoreactivity displayed immunoreactivity for vasoactive intestinal polypeptide or choline acetyltransferase. These results indicate that the neocortical neurons expressing substance P receptor constitute a subpopulation of GABAergic non-pyramidal cells, and are segregated into neurons with intense immunoreactivity and those with weak immunoreactivity for substance P receptor; the vast majority of neurons with intense substance P receptor immunoreactivity contain somatostatin and neuropeptide Y, and the majority of neurons with weak substance P receptor immunoreactivity have parvalbumin.}, author = {Kaneko, Takeshi and Shigemoto, Ryuichi and Nakanishi, Shigetada and Mizuno, Noboru}, issn = {0306-4522}, journal = {Neuroscience}, number = {1}, pages = {199 -- 211}, publisher = {Elsevier}, title = {{Morphological and chemical characteristics of substance P receptor immunoreactive neurons in the rat neocortex}}, doi = {10.1016/0306-4522(94)90215-1}, volume = {60}, year = {1994}, } @article{2489, abstract = {Five N-methyl-D-aspartate (NMDA) receptor subunits have been identified thus far: NR1, NR2A, NR2B, NR2C, and NR2D. Here, we have analyzed the expression patterns of mRNAs for the NMDA receptor subunits in the developing and adult rats by in situ hybridization. The developmental changes of the expression patterns were most salient in the cerebellum. In the external granular layer, hybridization signals of mRNAs for NR1, NR2A, NR2B, and NR2C appeared by postnatal day 3, but no NR2D mRNA was expressed at any developmental stage examined. The NR1 mRNA was expressed in all cerebellar neurons at all developmental stages examined. The signals for the NR2A mRNA appeared in Purkinje cells and granule cells during the second postnatal week. The signals for the NR2B mRNA in granule cells were seen transiently during the first 2 weeks after birth. The signals for NR2C mRNA appeared in granule cells and glial cells during the second postnatal week. The signals for NR2D mRNA appeared transiently in Purkinje cells during the first 8 postnatal days; in adult rats, these were seen in stellate and Golgi cells. In the cerebellar nuclei, mRNAs for NR1, NR2A, NR2B, and NR2D were more or less expressed on postnatal day 0, while expression signals for the NR2C mRNA were first detected in postnatal day 14. Thus, the most conspicuous changes of expression patterns were observed in the cerebellar cortex during the first 2 weeks after birth, when development and maturation of the cerebellum proceed most rapidly.}, author = {Akazawa, Chihiro and Shigemoto, Ryuichi and Bessho, Yasumasa and Nakanishi, Shigetada and Mizuno, Noboru}, issn = {0021-9967}, journal = {Journal of Comparative Neurology}, number = {1}, pages = {150 -- 160}, publisher = {Wiley-Blackwell}, title = {{Differential expression of five N-methyl-D-aspartate receptor subunit mRNAs in the cerebellum of developing and adult rats}}, doi = {10.1002/cne.903470112}, volume = {347}, year = {1994}, } @article{2490, abstract = {Distribution of the messenger RNA for the prostaglandin E receptor subtype EP3 was investigated by in situ hybridization in the nervous system of the mouse. The hybridization signals for EP3 were widely distributed in the brain and sensory ganglia and specifically localized to neurons. In the dorsal root and trigeminal ganglia, about half of the neurons were labeled intensely. In the brain, intensely labeled neurons were found in Ammon's horn, the preoptic nuclei, lateral hypothalamic area, dorsomedial hypothalamic nucleus, lateral mammillary nucleus, entopeduncular nucleus, substantia nigra pars compacta, locus coeruleus and raphe nuclei. Moderately labeled neurons were seen in the mitral cell layer of the main olfactory bulb, layer V of the entorhinal and parasubicular cortices, layers V and VI of the cerebral neocortex, nuclei of the diagonal band, magnocellular preoptic nucleus, globus pallidus and lateral parabrachial nucleus. In the thalamus, moderately labeled neurons were distributed in the anterior, ventromedial, laterodorsal, paraventricular and central medial nuclei. Based on these distributions, we suggest that EP3 not only mediates prostaglandin E2 signals evoked by blood-borne cytokines in the areas poor in the blood-brain barrier, but also responds to those formed intrinsically within the brain to modulate various neuronal activities. Possible EP3 actions are discussed in relation to the reported neuronal activities of prostaglandin E2 in the brain.}, author = {Sugimoto, Yukihiko and Shigemoto, Ryuichi and Namba, Tsunehisa and Negishi, Manabu and Mizuno, Noboru and Narumiya, Shuh and Ichikawa, Atsushi}, issn = {0306-4522}, journal = {Neuroscience}, number = {3}, pages = {919 -- 928}, publisher = {Elsevier}, title = {{Distribution of the messenger rna for the prostaglandin e receptor subtype ep3 in the mouse nervous system}}, doi = {10.1016/0306-4522(94)90483-9}, volume = {62}, year = {1994}, } @inbook{2545, abstract = {Glutamate receptors play an important role in many integrative brain functions and in neuronal development. We report the molecular diversity of NMDA receptors and metabotropic glutamate receptors on the basis of our studies of molecular cloning and characterization of the diverse members of these receptors. The NMDA receptors consist of two distinct types of subunits. NMDAR1 possesses all properties characteristic of the NMDA receptor-channel complex, whereas the four NMDAR2 subunits, termed NMDAR2A-2D, show no channel activity but potentiate the NMDAR1 activity and confer functional variability by different heteromeric formations. The NMDA receptor subunits are considerably divergent from the other ligand-gated ion channels, and the structural architecture of these subunits remains elusive. The mGluRs form a family of at least seven different subtypes termed mGluR1-mGluR7. These receptor subtypes have, seven transmembrane segments and possess a large extracellular domain at their N-terminal regions. The seven mGluR subtypes are classified into three subgroups according to their sequence similarities, signal transduction mechanisms and agonist selectivities: mGluR1/mGluR5, mGluR2/mGluR3 and mGluR4/mGluR6/mGluR7. On the basis of our knowledge of the molecular diversity of the NMDA receptors and mGluRs, we have studied the physiological roles of individual receptor subunits or subtypes. We have shown that K(+)-induced depolarization or NMDA treatment in primary cultures of neonatal cerebellar granule cells induces the functional NMDA receptor and specifically up-regulates NMDAR2A mRNA among the multiple NMDA receptor subunits through the increase in resting intracellular Ca2+ concentrations. Our study demonstrates that the regulation of the specific NMDA receptor subunit mRNA governs the NMDA receptor induction that is thought to play an important role in granule cell survival and death. Analysis of an agonist selectivity and an expression pattern of mGluR6 has indicated that mGluR6 is responsible for synaptic neurotransmission from photoreceptor cells to ON-bipolar cells in the visual system. We have also investigated the function of mGluR2 in granule cells of the accessory olfactory bulb by combining immunoelectron-microscopic analysis with slice-patch recordings on the basis of the identification of a new agonist selective for this receptor subtype. Our results demonstrate that mGluR2 is present at the presynaptic site of granule cells and modulates inhibitory GABA transmission from granule cells to mitral cells. This finding indicates that the mGluR2 activation relieves excited mitral cells from GABA inhibition but maintains the lateral inhibition of unexcited mitral cells, thus resulting in enhancement of the signal-to-noise ratio between the excited mitral cells and their neighboring unexcited mitral cells.}, author = {Nakanishi, Shigetada and Masu, Masayuki and Bessho, Yasumasa and Nakajima, Yoshiaki and Hayashi, Yasunori and Shigemoto, Ryuichi}, booktitle = {Experientia Supplementum}, isbn = {9783034873321}, pages = {71 -- 80}, publisher = {Birkhäuser}, title = {{Molecular diversity of glutamate receptors and their physiological functions}}, doi = {10.1007/978-3-0348-7330-7_8}, volume = {71}, year = {1994}, } @inproceedings{2548, abstract = {The induction mechanism of cerebellar long term depression (LTD) has been analysed in a cerebellar culture. Using nitr-5, a photolabile Ca chelator, we demonstrated that an increase in postsynaptic Ca together with glutamate application is sufficient to induce the LTD of glutamate responsiveness in Purkinje cells. It has also been shown that one subtype of genetically defined metabotropic glutamate receptor, mGluR1, is involved in the LTD induction. We raised antibodies which specifically recognized mGluR1 and inactivated its function. The antibodies suppressed the LTD induction in the cultured Purkinje cells.}, author = {Hirano, Tomoo and Kasono, Keizo and Ryuichi Shigemoto and Nakanishi, Shigetada}, number = {SUPPL. 1}, pages = {79 -- 81}, publisher = {Biomedical Research Foundation}, title = {{Induction mechanism of long term depression in cultured Purkinje neurons}}, volume = {15}, year = {1994}, } @article{2549, abstract = {In an attempt to reveal the function sites of substance P (SP) in the central nervous system (CNS), the distribution of SP receptor (SPR) was immunocytochemically investigated in adult rat and compared with that of SP- positive fibers. SPR-like immunoreactivity (LI) was mostly localized to neuronal cell bodies and dendrites. Neurons with intense SPR-LI were distributed densely in the cortical amygdaloid nucleus, hilus of the dentate gyrus, locus ceruleus, rostral half of the ambiguus nucleus, and intermediolateral nucleus of the thoracic cord; moderately in the caudatoputamen, nucleus accumbens, olfactory tubercle, median, pontine, and magnus raphe nuclei, laminae I and III of the caudal subnucleus of the spinal trigeminal nucleus, and lamina I of the spinal cord; and sparsely in the cerebral cortex, basal nucleus of Meynert, claustrum, gigantocellular reticular nucleus, and lobules IX and X of the cerebellar vermis. Neurons with weak to moderate SPR-LI were distributed more widely throughout the CNS. The regional patterns of distribution of SPR-LI were not necessarily the same as those of SP-positive fibers. The entopeduncular nucleus, substantia nigra, and lateral part of the interpeduncular nucleus showed intense SP-LI but displayed almost no SPR-LI. Conversely, the hilus of the dentate gyrus, anterodorsal thalamic nucleus, central nucleus of the inferior colliculus, and dorsal tegmental nucleus showed intense to moderate SPR-LI but contained few axons with SP-LI. These findings confirmed the presence of the 'mismatch' problem between SP and SPR localizations. However, the distribution of SPR- LI was quite consistent with that of the SP-binding activity, which has been studied via autoradiography. This indicates that the sites of SPR-LI revealed in the present study represent most, if not all, sites of SP-binding activity.}, author = {Nakaya, Yoshifumi and Kaneko, Takeshi and Shigemoto, Ryuichi and Nakanishi, Shigetada and Mizuno, Noboru}, issn = {0021-9967}, journal = {Journal of Comparative Neurology}, number = {2}, pages = {249 -- 274}, publisher = {Wiley-Blackwell}, title = {{Immunohistochemical localization of substance P receptor in the central nervous system of the adult rat}}, doi = {10.1002/cne.903470208}, volume = {347}, year = {1994}, } @article{2550, abstract = {A cDNA clone for a new rat metabotropic glutamate receptor termed mGluR7 was isolated through polymerase chain reaction-mediated DNA amplification by using primer sequences conserved among the metabotropic receptor (mGluR) family and by the subsequent screening of a rat forebrain cDNA library. The cloned mGluR7 subtype consists of 915 amino acid residues and exhibits a structural architecture common to the mGluR family with a large extracellular domain preceding the seven putative membrane-spanning domains. mGluR7 shows the highest sequence similarity to mGluR4 and mGluR6 among the members of the mGluR family. Similar to mGluR4 and mGluR6, mGluR7 inhibits forskolin- stimulated cyclic AMP accumulation in response to agonist interaction and potently reacts with L-2-amino-4-phosphonobutyrate and L-serine-O-phosphate in Chinese hamster ovary cells transfected with the cloned cDNA. RNA blot and in situ hybridization analyses of mGluR7 mRNA indicated that it is widely expressed in many neuronal cells of the central nervous system and is thus different from the more limitedly expressed mGluR4 or mGluR6 mRNA. mGluR7 together with mGluR4 thus corresponds to the putative L-2-amino-4- phosphonobutyrate receptor which plays an important role in modulation of glutamate transmission in the central nervous system.}, author = {Okamoto, Naoyuki and Hori, Seiji and Akazawa, Chihiro and Hayashi, Yasunori and Shigemoto, Ryuichi and Mizuno, Noboru and Nakanishi, Shigetada}, journal = {Journal of Biological Chemistry}, number = {2}, pages = {1231 -- 1236}, publisher = {American Society for Biochemistry and Molecular Biology}, title = {{Molecular characterization of a new metabotropic glutamate receptor mGluR7 coupled to inhibitory cyclic AMP signal transduction}}, doi = {10.1016/S0021-9258(17)42247-2}, volume = {269}, year = {1994}, } @article{2551, abstract = {Expression patterns of mRNAs of l-AP4-sensitive metabotropic glutamate receptors (mGluR4, mGluR6, mGluR7) in the rat retina were examined by northern blot analysis and in situ hybridization histochemistry. Expression patterns of mGluR4 and mGluR7 mRNAs were quite different from that of mGluR6 mRNA which was expressed at the outer part of the inner nuclear layer. The mGluR4 mRNA was expressed on the cell bodies of the ganglion cells, but not in the inner or outer nuclear layer. The expression of mGluR7 mRNA was observed throughout the entire region of the inner nuclear layer and on the cell bodies of the ganglion cells.}, author = {Akazawa, Chihiro and Ohishi, Hitoshi and Nakajima, Yoshiaki and Okamoto, Naoyuki and Shigemoto, Ryuichi and Nakanishi, Shigetada and Mizuno, Noboru}, issn = {0304-3940}, journal = {Neuroscience Letters}, number = {1-2}, pages = {52 -- 54}, publisher = {Elsevier}, title = {{Expression of mRNAs of l-AP4-sensitive metabotropic glutamate receptors (mGluR4, mGluR6, mGluR7) in the rat retina}}, doi = {10.1016/0304-3940(94)90602-5}, volume = {171}, year = {1994}, } @article{2552, abstract = {The superficial layers of the superior colliculus (SC) have been known to contain many axons showing substance P-like immunoreactivity (SP-LI). We, therefore, immunohistochemically examined the distribution of SP receptor (SPR) in the superficial layers of the SC in the rat by using a specific antibody against SPR. The majority of SC neurons with SPR-LI were distributed in the zonal and the superficial gray layers, the rest of them were in the optic layer. Electron microscopy revealed that SPR-immunoreaction products in SC neurons were distributed not only in postsynaptic sites, but also in non-synaptic regions of perikaryal and dendritic profiles.}, author = {Ogawa Meguro, Reiko and Shigemoto, Ryuichi and Itoh, Kazuo and Konishi, Akira and Mizuno, Noboru}, issn = {0304-3940}, journal = {Neuroscience Letters}, number = {2}, pages = {135 -- 138}, publisher = {Elsevier}, title = {{Immunohistochemical localization of substance P receptor in the superior colliculus. A light and electron microscope study in the rat}}, doi = {10.1016/0304-3940(94)90469-3}, volume = {166}, year = {1994}, } @article{2553, abstract = {Distribution of the mRNAs for three subtypes of prostaglandin E (PGE) receptors in the mouse kidney was investigated by in situ hybridization. The mRNA for EP1 subtype, which is coupled to Ca2+ mobilization, was specifically localized to the collecting ducts from the cortex to the papilla. The mRNA for EP2 subtype, which is linked to stimulation of adenylate cyclase, was localized to the glomeruli. The mRNA for EP3 subtype, which is coupled to inhibition of adenylate cyclase, was located densely in the tubules in the outer medulla and in the distal tubules in the cortex. These results exhibit distinct cellular localization of three subtypes of PGE receptor in the kidney and suggest that PGE2 exerts multiple functions via these subtypes expressed in different segments of the nephron.}, author = {Sugimoto, Yukihiko and Namba, Tsunehisa and Shigemoto, Ryuichi and Negishi, Manabu and Ichikawa, Atsushi and Narumiya, Shuh}, issn = {0363-6127}, journal = {American Journal of Physiology}, number = {5}, pages = {F823 -- F828}, publisher = {American Physiological Society}, title = {{Distinct cellular localization of mRNAs for three subtypes of prostaglandin E receptor in kidney}}, doi = {10.1152/ajprenal.1994.266.5.F823}, volume = {266}, year = {1994}, } @article{2554, abstract = {The retinal bipolar cell receiving glutamate transmission from photoreceptors mediates a key process in segregating visual signals into ON center and OFF center pathways. This transmission involves a G protein- coupled metabotropic glutamate receptor (mGluR). Immunocytochemical and immunoelectron microscopic studies indicate the restricted localization of a specific mGluR subtype, mGluR6, at the postsynaptic site of the rat rod bipolar cell. This specialization is developmentally regulated: mGluR6 is initially distributed in both the soma and dendrites and is finally concentrated on the postsynaptic site. The mGluR6 localization is reversed when photoreceptors degenerate in the mutant rat with retinal dystrophy. Evidence is thus presented indicating specialized, developmentally regulated receptor distribution in the central nervous system and the crucial role of mGluR6 in photoreceptor-bipolar cell synaptic transmission.}, author = {Nomura, Akinori and Shigemoto, Ryuichi and Nakamura, Yasuhisa and Okamoto, Naoyuki and Mizuno, Noboru and Nakanishi, Shigetada}, issn = {0092-8674}, journal = {Cell}, number = {3}, pages = {361 -- 369}, publisher = {Cell Press}, title = {{Developmentally regulated postsynaptic localization of a metabotropic glutamate receptor in rat rod bipolar cells}}, doi = {10.1016/0092-8674(94)90151-1}, volume = {77}, year = {1994}, } @article{2555, abstract = {Antibodies were raised against two distinct extracellular sequences of the rat mGluR1 metabotropic glutamate receptor expressed as bacterial fusion proteins. Both antibodies specifically reacted with mGluR1 in the rat cerebellum and inhibited the mGluR1 activity as assessed by the analysis of glutamate-stimulated inositol phosphate formation in CHO cells expressing mGluR1. Using these antibodies, we examined the role of mGluR1 in the induction of long-term depression in cultured Purkinje cells. In voltage- clamped Purkinje cells, current induced by iontophoretically applied glutamate was persistently depressed by depolarization of the Purkinje cells in conjunction with the glutamate application. The mGluR1 antibodies completely blocked the depression of glutamate-induced current. The results indicate that activation of mGluR1 is necessary for the induction of cerebellar long-term depression and that these mGluR1 antibodies can be used as selective antagonists.}, author = {Shigemoto, Ryuichi and Abe, Takaaki and Nomura, Sakashi and Nakanishi, Shigetada and Hirano, Tomoo}, issn = {0896-6273}, journal = {Neuron}, number = {6}, pages = {1245 -- 1255}, publisher = {Elsevier}, title = {{Antibodies inactivating mGluR1 metabotropic glutamate receptor block long-term depression in cultured Purkinje cells}}, doi = {10.1016/0896-6273(94)90441-3}, volume = {12}, year = {1994}, } @article{2557, abstract = {The distribution of the metabotropic glutamate receptors mGluR2 and mGluR3 was immunohistochemically examined in the rat cerebellar cortex at both light and electron microscope levels. An antibody was raised against a fusion protein containing a C-terminal portion of mGluR2. On immunoblot, the antibody reacted with both mGluR2 and mGluR3 in rat brain. mGluR2/3 immunoreactivity was expressed in cell bodies, dendrites, and axon terminals of Golgi cells, as well as in presumed glial processes. Golgi axon terminals with mGluR2/3 immunoreactivity were often encountered in the vicinity of glutamatergic mossy fiber terminals. The results suggest that transmitter glutamate may exert control influences upon Golgi cells not only through dendritic mGluR2/3, but also through axonal mGluR2/3.}, author = {Ohishi, Hitoshi and Ogawa Meguro, Reiko and Shigemoto, Ryuichi and Kaneko, Takeshi and Nakanishi, Shigetada and Mizuno, Noboru}, issn = {0896-6273}, journal = {Neuron}, number = {1}, pages = {55 -- 66}, publisher = {Elsevier}, title = {{Immunohistochemical localization of metabotropic glutamate receptors, mGluR2 and mGluR3, in rat cerebellar cortex}}, doi = {10.1016/0896-6273(94)90459-6}, volume = {13}, year = {1994}, } @article{2713, author = {Erdös, László}, issn = {0012-7094}, journal = {Duke Mathematical Journal}, number = {2}, pages = {541 -- 566}, publisher = {Duke University Press}, title = {{Estimates on stochastic oscillatory integrals and on the heat kernel of the magnetic Schrödinger operator}}, doi = {10.1215/S0012-7094-94-07619-9}, volume = {76}, year = {1994}, } @article{1949, abstract = {H+-transhydrogenase (H+-Thase) and NADP-linked isocitrate dehydrogenase (NADP-ICDH) are very active in animal mitochondria but their physiological function is only poorly understood. This is especially so in the case of the heart and muscle, where there are no major consumers of NADPH. We propose here that H+-Thase and NADP-ICDH have a combined function in the fine regulation of the activity of the tricarboxylic acid (TCA) cycle, providing enhanced sensitivy to changes in energy demand. This is achieved through cycling of substrates by NAD-linked ICDH, NADP-linked ICDH and H+-Thase. It is proposed that NAD-ICDH operates in the forward direction of the TCA cycle, but NADP-ICDH is driven in reverse by elevated levels of NADPH resulting from the action of the transmembrane proton electrochemical potential gradient (Δp) on H+-Thase. This has the effect of increasing the sensitivity to allosteric modifiers of NAD-ICDH (NADH, ADP, ATP, Ca2+ etc), potentially giving rise to large changes in the net flux from iso-citrate to α-ketoglutarate. Furthermore, changes in the level of Δp resulting from changes in the demand for ATP would, via H+-Thase, shift the redox state of the NADP pool and this, in turn, would lead to a change in the rate of the reaction catalysed by NADP-ICDH and hence to an additional and complementary effect on the net metabolic flux from isocitrate to α-ketoglutarate. Other consequences of this substrate cycle are, (i) the production of heat at the expense of Δp, which may contribute to thermoregulation in the animal, and (ii) an increased rate of dissipation of Δp (leak).}, author = {Sazanov, Leonid A and Jackson, Julie}, issn = {0014-5793}, journal = {FEBS Letters}, number = {2-3}, pages = {109 -- 116}, publisher = {Elsevier}, title = {{Proton translocating transhydrogenase and NAD- and NADP-linked isocitrate dehydrogenases operate in a substrate cycle which contributes to fine regulation of the tricarboxylic acid cycle activity in mitochondria}}, doi = {10.1016/0014-5793(94)00370-X}, volume = {344}, year = {1994}, } @article{1953, abstract = {The respiratory burst induced by phorbol myristate acetate in mouse macrophages was inhibited by ultra-low doses (10-15 -10-13 M) of an opioid peptide [d-Ala2] methionine enkephalinamide. The effect disappeared at concentrations above and below this range. The inhibition approached 50% and was statistically significant (P < 0.001). Increasing the time of the opioid incubation with cells brought about a shift in the maximal effect to lower concentrations of the opioid (from 10-13 to 5 · 10-15 M) and led to a decrease in the value of the effect, fully in accord with the previously proposed adaptation mechanism of the action of ultra-low doses.}, author = {Efanov, Alexander and Koshkin, Aleksei and Sazanov, Leonid A and Borodulina, O I and Varfolomeev, Sergei and Zaǐtsev, Sergei}, issn = {0014-5793}, journal = {FEBS Letters}, number = {2}, pages = {114 -- 116}, publisher = {Elsevier}, title = {{Inhibition of the respiratory burst in mouse macrophages by ultra-low doses of an opioid peptide is consistent with a possible adaptation mechanism}}, doi = {10.1016/0014-5793(94)01109-5}, volume = {355}, year = {1994}, } @inproceedings{4420, abstract = {We propose a methodology for the specification, verification, and design of hybrid systems. The methodology consists of the computational model of Concrete Phase Transition Systems (cptss), the specification language of Hybrid Temporal Logic (htl), the graphical system description language of Hybrid Automata, and a proof system for verifying that hybrid automata satisfy their HTL specifications. The novelty of the approach lies in the continuous-time logic, which allows specification of both point-based and interval-based properties (i.e., properties which describe changes over an interval) and provides direct references to derivatives of variables, and in the proof system that supports verification of point-based and interval-based properties. The proof rules demonstrate that sound and convenient induction rules can be established for continuous-time logics. The proof rules are illustrated on several examples.}, author = {Kapur, Arjun and Henzinger, Thomas A and Manna, Zohar and Pnueli, Amir}, booktitle = {3rd International Symposium on Formal Techniques in Real-Time and Fault-Tolerant Systems}, location = {Lübeck, Germany}, pages = {431 -- 454}, publisher = {Springer}, title = {{Proving safety properties of hybrid systems}}, doi = {10.1007/3-540-58468-4_177}, volume = {863}, year = {1994}, } @inproceedings{4440, abstract = {We present a methodology for proving temporal properties of the divergent runs of reactive systems with real-valued clocks. A run diverges if time advances beyond any bound. Since the divergent runs of a system may satisfy liveness properties that are not satisfied by some convergent runs, the standard proof rules are incomplete if only divergent runs are considered. First, we develop a sound and complete proof calculus for divergence, which is based on translating clock systems into discrete systems. Then, we show that simpler proofs can be obtained for stronger divergence assumptions, such as unknown -divergence, which requires that all delays have a minimum duration of some unknown constant . We classify all real-time systems into an infinite hierarchy, according to how well they admit the translation of eventuality properties into equivalent safety properties.}, author = {Henzinger, Thomas A and Kopke, Peter}, booktitle = {3rd International Symposium on Formal Techniques in Real-Time and Fault-Tolerant Systems}, location = {Lübeck, Gernany}, pages = {351 -- 372}, publisher = {Springer}, title = {{Verification methods for the divergent runs of clock systems}}, doi = {10.1007/3-540-58468-4_173}, volume = {863}, year = {1994}, } @article{4501, abstract = {We extend the specification language of temporal logic, the corresponding verification framework, and the underlying computational model to deal with real-;time properties of reactive systems. The abstract notion of timed transition systems generalizes traditional transition systems conservatively: qualitative fairness requirements are replaced (and superseded) by quantitative lower-bound and upper-bound timing constraints on transitions. This framework can model real-time systems that communicate either through shared variables or by message passing and real-time issues such as timeouts, process priorities (interrupts), and process scheduling. We exhibit two styles for the specification of real-time systems. While the first approach uses time-bounded versions of the temporal operators, the second approach allows explicit references to time through a special clock variable. Corresponding to the two styles of specification, we present and compare two different proof methodologies for the verification of timing requirements that are expressed in these styles. For the bounded-operator style, we provide a set of proof rules for establishing bounded-invariance and bounded-responce properties of timed transition systems. This approach generalizes the standard temporal proof rules for verifying invariance and response properties conservatively. For the explicit-clock style, we exploit the observation that every time-bounded property is a safety property and use the standard temporal proof rules for establishing safety properties.}, author = {Henzinger, Thomas A and Manna, Zohar and Pnueli, Amir}, issn = {0890-5401}, journal = {Information and Computation}, number = {2}, pages = {273 -- 337}, publisher = {Elsevier}, title = {{Temporal proof methodologies for timed transition systems}}, doi = {10.1006/inco.1994.1060}, volume = {112}, year = {1994}, }