@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{4586, abstract = {Fairness is a mathematical abstraction: in a multiprogramming environment, fairness abstracts the details of admissible (“fair”) schedulers; in a distributed environment, fairness abstracts the speeds of independent processors. We argue that the standard definition of fairness often is unnecessarily weak and can be replaced by the stronger, yet still abstract, notion of finitary fairness. While standard weak fairness requires that no enabled transition is postponed forever, finitary weak fairness requires that for every run of a system there is an unknown bound k such that no enabled transition is postponed more than k consecutive times. In general, the finitary restriction fin(F) of any given fairness assumption F is the union of all w-regular safety properties that are contained in F. The adequacy of the proposed abstraction is demonstrated in two ways. Suppose that we prove a program property under the assumption of finitary fairness. In a multiprogramming environment, the program then satisfies the property for all fair finite-state schedulers. In a distributed environment, the program then satisfies the property for all choices of lower and upper bounds on the speeds (or timings) of processors}, author = {Alur, Rajeev and Henzinger, Thomas A}, booktitle = {Proceedings 9th Annual IEEE Symposium on Logic in Computer Science}, issn = {0018-9162}, location = {Paris, France}, pages = {52 -- 61}, publisher = {IEEE}, title = {{Finitary fairness}}, doi = {10.1109/LICS.1994.316087 }, year = {1994}, } @inbook{4590, abstract = {We introduce a temporal logic for the specification of real-time systems. Our logic, TPTL, employs a novel quantifier construct for referencing time: the "freeze" quantifier binds a variable to the time of the local temporal context. TPTL is both a natural language for specification and a suitable formalism for verification. We present a tableau-based decision procedure and a model-checking algorithm for TPTL. Several generalizations of TPTL are shown to be highly undecidable.}, author = {Alur, Rajeev and Henzinger, Thomas A}, booktitle = {Theories and Experiences for Real-Time System Development}, editor = {Rus, Teodor and Rattray, Charles}, isbn = { 9789810219239}, keywords = {real-time systems, clock variables}, pages = {1 -- 29}, publisher = {World Scientific Publishing}, title = {{Real-time system = discrete system + clock variables}}, doi = {10.1142/9789812831583_0001}, volume = {2}, year = {1994}, } @article{4591, abstract = {We introduce a temporal logic for the specification of real-time systems. Our logic, TPTL, employs a novel quantifier construct for referencing time: the freeze quantifier binds a variable to the time of the local temporal context. TPTL is both a natural language for specification and a suitable formalism for verification. We present a tableau-based decision procedure and a model-checking algorithm for TPTL. Several generalizations of TPTL are shown to be highly undecidable.}, author = {Alur, Rajeev and Henzinger, Thomas A}, issn = {0004-5411}, journal = {Journal of the ACM}, number = {1}, pages = {181 -- 204}, publisher = {ACM}, title = {{A really temporal logic}}, doi = {10.1145/174644.174651}, volume = {41}, year = {1994}, } @inproceedings{4614, abstract = {We develop a theory of equivalences for timed systems. Two systems are equivalent iff external observers cannot observe differences in their behavior. The notion of equivalence depends, therefore, on the distinguishing power of the observers. The power of an observer to measure time results in untimed, clock, and timed equivalences: an untimed observer cannot measure the time difference between events; a clock observer uses a clock to measure time differences with finite precision; a timed observer is able to measure time differences with arbitrary precision. We show that the distinguishing power of clock observers grows with the number of observers, and approaches, in the limit, the distinguishing power of a timed observer. More precisely, given any equivalence for untimed systems, two timed systems are k-clock congruent, for a nonnegative integer k, iff their compositions with every environment that uses k clocks are untimed equivalent. Both k-clock bisimulation congruence and k-clock trace congruence form strict decidable hierarchies that converge towards the corresponding timed equivalences. Moreover, k-clock bisimulation congruence and k-clock trace congruence provide an adequate and abstract semantics for branching-time and linear-time logics with k clocks. Our results impact on the verification of timed systems in two ways. First, our decision procedure for k-clock bisimulation congruence leads to a new, symbolic, decision procedure for timed bisimilarity. Second, timed trace equivalence is known to be undecidable. If the number of environment clocks is bounded, however, then our decision procedure for k-clock trace congruence allows the verification of timed systems in a trace model.}, author = {Alur, Rajeev and Courcoubetis, Costas and Henzinger, Thomas A}, booktitle = {5th International Conference on Concurrency Theory}, isbn = {3540583297}, location = {Uppsala, Sweden}, pages = {162 -- 177}, publisher = {Schloss Dagstuhl - Leibniz-Zentrum für Informatik}, title = {{The observational power of clocks}}, doi = {10.1007/BFb0015008}, volume = {836}, year = {1994}, } @inproceedings{4615, abstract = {We introduce the class of event- recording timed automata (ERA). An event-recording automaton contains, for every event a, a clock that records the time of the last occurrence of a. The class ERA is, on one hand, expressive enough to model (finite) timed transition systems and, on the other hand, determinizable and closed under all boolean operations. As a result, the language inclusion problem is decidable for event-recording automata. We present a translation from timed transition systems to event-recording automata, which leads to an algorithm for checking if two timed transition systems have the same set of timed behaviors. We also consider event-predicting timed automata (EPA), which contain clocks that predict the time of the next occurrence of an event. The class of event-clock automata (ECA), which contain both event-recording and event-predicting clocks, is a suitable specification language for real-time properties. We provide an algorithm for checking if a timed automaton meets a specification that is given as an event-clock automaton.}, author = {Alur, Rajeev and Fix, Limor and Henzinger, Thomas A}, booktitle = {International Conference on Computer Aided Verification}, isbn = {9783540484691}, location = {Stanford, CA, United States of America}, pages = {1 -- 13}, publisher = {Springer}, title = {{A determinizable class of timed automata}}, doi = {10.1007/3-540-58179-0_39}, volume = {818}, year = {1994}, } @inproceedings{4617, abstract = {We extend the timed-automaton model for real-time systems [AD90] to a formal model for hybrid systems: while the continuous variables of a timed automaton are clocks that measure time, the continuous variables of a hybrid system are governed by arbitrary differential equations. We then adopt the verification methodology for timed automata [ACD90, ACD+92, HNSY92] to analyze hybrid systems: while the verification problem is decidable for timed automata, we obtain semidecision procedures for the class of hybrid systems whose continuous variables change in a piecewise linear fashion. }, author = {Alur, Rajeev and Courcoubetis, Costas and Henzinger, Thomas A and Ho, Pei and Nicollin, Xavier and Olivero, Alfredo and Sifakis, Joseph and Yovine, Sergio}, booktitle = {11th International Conference on Analysis and Optimization of Systems Discrete Event Systems}, isbn = {978-3-540-19896-3}, location = {Sophia-Antipolis, France}, pages = {331 -- 351}, publisher = {Springer}, title = {{The algorithmic analysis of hybrid systems}}, doi = {10.1007/BFb0033565}, volume = {199}, year = {1994}, } @article{6167, abstract = {The tra-1 gene is the terminal regulator in the sex determination pathway in C. elegans, directing all aspects of somatic sexual differentiation. Recessive loss-of-function (lf) mutations in tra-1 masculinize XX animals (normally somatically female), while dominant gain-of-function mutations feminize XO animals (normally male). Most tra-1 (lf) mutations can be fitted into a simple allelic series of somatic masculinization, but a small number of lf alleles do not fit into this series. Here we show that three of these mutations are associated with DNA rearrangements 5' to the coding region. One allele is an inversion that may be subject to a position effect. We also report the isolation of a new class of tra-1 alleles that are responsive to mutations in the smg system of RNA surveillance. We show that two of these express RNAs of aberrant size. We suggest that the smg-sensitive mutations may identify a carboxy-terminal domain required for negative regulation of tra-1 activity.}, author = {Zarkower, David and de Bono, Mario and Aronoff, Rachel and Hodgkin, Jonathan}, issn = {0192-253X}, journal = {Developmental Genetics}, number = {3}, pages = {240--250}, publisher = {Wiley}, title = {{Regulatory rearrangements and smg-sensitive allels of the C. elegans sex-determining gene tra-1}}, doi = {10.1002/dvg.1020150306}, volume = {15}, year = {1994}, } @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}, } @misc{3453, author = {Von Kitzing, Eberhard and Jonas, Peter M and Sakmann, Bert}, booktitle = {Molecular and cellular mechanisms of neurotransmitter release}, isbn = {0781702208}, pages = {235 -- 260}, publisher = {Raven Press}, title = {{Quantal analysis of excitatory postsynaptic currents at the hippocampal mossy fiber-CA3 pyramidal cell synapse}}, doi = {10.1016/0166-2236(95)90088-8}, volume = {29}, year = {1994}, } @article{3460, abstract = {Excitatory postsynaptic currents in neurones of the central nervous system have a dual-component time course that results from the co-activation of AMPA/kainate-type and NMDA-type glutamate receptors. New approaches in electrophysiology and molecular biology have provided a better understanding of the factors that determine the kinectics of excitatory postsynaptic currents. Recent studies suggest that the time course of neurotransmitter concentration in the synaptic cleft, the gating properties of the native channels, and the glutamate receptor subunit composition all appear to be important factors.}, author = {Jonas, Peter M and Spruston, Nelson}, issn = {0959-4388}, journal = {Current Opinion in Neurobiology}, number = {3}, pages = {366 -- 372}, publisher = {Elsevier}, title = {{Mechanisms shaping glutamate-mediated excitatory postsynaptic currents in the CNS}}, doi = {10.1016/0959-4388(94)90098-1}, volume = {4}, year = {1994}, } @article{3475, abstract = {1. A potassium channel activated by internal Na+ ions (K+Na channel) was identified in peripheral myelinated axons of Xenopus laevis using the cell-attached and excised configurations of the patch clamp technique. 2. The single-channel conductance for the main open state was 88 pS with [K+]o = 105 mM and pS with [K+]o = 2.5 mM ([K+]i = 105 mM). The channel was selectively permeable to K+ over Na+ ions. A characteristic feature of the K+Na channel was the frequent occurrence of subconductance states. 3. The open probability of the channel was strongly dependent on the concentration of Na+ ions at the inner side of the membrane. The half-maximal activating Na+ concentration and the Hill coefficient were 33 mM and 2.9, respectively. The open probability of the channel showed only weak potential dependence. 4. The K+Na channel was relatively insensitive to external tetraethylammonium (TEA+) in comparison with voltage-dependent axonal K+ channels; the half-maximal inhibitory concentration (IC50) was 21.3 mM (at -90 mV). In contrast, the channel was blocked by low concentrations of external Ba2+ and Cs+ ions, with IC50 values of 0.7 and 1.1 mM, respectively (at -90 mV). The block by Ba2+ and Cs+ was more pronounced at negative than at positive membrane potentials. 5. A comparison of the number of K+Na channels in nodal and paranodal patches from the same axon revealed that the channel density was about 10-fold higher at the node of Ranvier than at the paranode. Moreover, a correlation between the number of K+Na channels and voltage-dependent Na+ channels in the same patches was found, suggesting co-localization of both channel types. 6. As weakly potential-dependent ('leakage') channels, axonal K+Na channels may be involved in setting the resting potential of vertebrate axons. Simulations of Na+ ion diffusion suggest two possible mechanisms of activation of K+Na channels: the local increase of Na+ concentration in a cluster of Na+ channels during a single action potential or the accumulation in the intracellular axonal compartment during a train of action potentials.}, author = {Koh, Duk and Jonas, Peter M and Vogel, Werner}, issn = {0022-3751}, journal = {Journal of Physiology}, pages = {183 -- 197}, publisher = {Wiley-Blackwell}, title = {{Na+-activated K+ channels localized in the nodal region of myelinated axons of Xenopus}}, doi = {10.1113/jphysiol.1994.sp020287}, volume = {479}, year = {1994}, } @article{3476, abstract = {Tight-seal whole-cell recordings were made from cleaned somata of CA3 pyramidal cells deep in hippocampal slices from 19–21-d-old rats. The cells were filled with biocytin, and their voltage responses to short current pulses were recorded. After washout of initial sag, responses scaled linearly with injected current and were stable over time. The dendritic and axonal arbors of four cells were reconstructed and measured using light microscopy. Dendritic spines and axonal boutons were counted and the additional membrane area was incorporated into the relevant segments. The morphology of each neuron was converted into a detailed branching cable model by assuming values for specific membrane capacitance Cm and resistance Rm, and cytoplasmic resistivity Ri. These parameters were optimized for each cell by directly matching the model's response to that of the real cell by means of a modified weighted least-squares fitting procedure. By comparing the deviations between model and experimental responses to control noise recordings, approximate 95% confidence intervals were established for each parameter. If a somatic shunt was allowed, a wide range of possible Rm values produced acceptable fits. With zero shunt, Cm was 0.7–0.8 microFcm-2, Ri was 170–340 omega cm, and Rm ranged between 120 and 200 k omega cm2. The electrotonic lengths of the basal and oblique dendrites were 0.2–0.3 space constants, and those of the apical tufts were 0.4–0.7 space constants. The steady-state electrical geometry of these cells was therefore compact; average dendritic tip/soma relative synaptic efficacies were > 93% for the basal and oblique dendrites, and > 81% for the tufts. With fast transient synaptic inputs, however, the models produced a wide range of postsynaptic potential shapes and marked filtering of voltage-clamp currents.}, author = {Major, Guy and Larkman, Alan and Jonas, Peter M and Sakmann, Bert and Jack, Julian}, issn = {0270-6474}, journal = {Journal of Neuroscience}, number = {8}, pages = {4613 -- 4638}, publisher = {Society for Neuroscience}, title = {{Detailed passive cable models of whole-cell recorded CA3 pyramidal neurons in rat hippocampal slices}}, doi = {10.1523/JNEUROSCI.14-08-04613.1994}, volume = {14}, year = {1994}, } @article{3477, abstract = {Fast excitatory synaptic transmission in the CNS is mediated by AMPA-type glutamate receptor (GluR) channels. Heterologous expression suggested that the Ca2+ permeability of these receptors critically depends on the subunit composition. Using patch-clamp techniques in brain slices, we found that the Ca2+ permeability of native AMPA-type GluRs was markedly higher in nonpyramidal (P(Ca)/P(K) ≃ 0.63) than in pyramidal (P(Ca)/P(K) ≃ 0.05) neurons of rat neocortex. Analysis of mRNA in single cells indicated that the relative abundance of GluR-B-specific mRNA was significantly lower in nonpyramidal (GluR-B/GluR-non-B ≃ 0.3) than in pyramidal (GluR-B/GluR-non-B ≃ 3) cells. This suggests that differences in relative abundance of GluR-B- specific mRNA generate functional diversity of AMPA-type GluRs in neurons with respect to Ca2+ permeability.}, author = {Jonas, Peter M and Racca, Claudia and Sakmann, Bert and Seeburg, Peter and Monyer, Hannah}, issn = {0896-6273}, journal = {Neuron}, number = {6}, pages = {1281 -- 1289}, publisher = {Elsevier}, title = {{Differences in Ca(2+) permeability of AMPA-type glutamate receptor channels in neocortical neurons caused by differential GluR-B subunit expression}}, doi = {10.1016/0896-6273(94)90444-8}, volume = {12}, year = {1994}, } @inproceedings{3550, author = {Edelsbrunner, Herbert}, booktitle = {Proceedings of the 6th Canadian Conference on Computational Geometry}, location = {Saskatoon, Canada}, pages = {36 -- 44}, title = {{Modeling with simplicial complexes (topology, geometry and algorithms)}}, year = {1994}, } @article{3641, abstract = {The probability of fixation of a mutation with selective advantage s will be reduced by substitutions at other loci. The effect of a single substitution, with selective advantage S0016672300032857inline1, can be approximated as a sudden reduction in the frequency of the favourable allele, by a fraction w = 1 −(s/S)r/s (where r is the recombination rate). An expression for the effect of a given sequence of such catastrophes is derived. This also applies to the ecological prxoblem of finding the probability that a small population will survive, despite occasional disasters. It is shown that if substitutions occur at a rate Δ, and are scattered randomly over a genetic map of length R, then an allele is unlikely to be fixed if its advantage is less than a critical value, Scrit = (π2/6)(2ΔS/(Rlog(S/s))). This threshold depends primarily on the variance in fitness per unit map length dueto substitutions, var(W)/R = 2ΔS/R. With no recombination, the fixation probability can be calculated for a finite population. If Δ > s, it is of the same order as for a neutral allele ( ≈ Δ/(2N(Δ−s))), whilst if S0016672300032857inline2, fixation probability is much higher than for a neutral allele, but much lower than in the absence of hitch-hiking S0016672300032857inline3. These results suggest that hitch-hiking may substantially impede the accumulation of weakly favoured adaptations.}, author = {Barton, Nicholas H}, issn = {0016-6723}, journal = {Genetical Research}, number = {3}, pages = {199 -- 208}, publisher = {Cambridge University Press}, title = {{The reduction in fixation probability caused by substitutions at linked loci}}, doi = {10.1017/S0016672300032857 }, volume = {64}, year = {1994}, } @article{3642, abstract = {We develop a general population genetic framework for analyzing selection on many loci, and apply it to strong truncation and disruptive selection on an additive polygenic trait. We first present statistical methods for analyzing the infinitesimal model, in which offspring breeding values are normally distributed around the mean of the parents, with fixed variance. These show that the usual assumption of a Gaussian distribution of breeding values in the population gives remarkably accurate predictions for the mean and the variance, even when disruptive selection generates substantial deviations from normality. We then set out a general genetic analysis of selection and recombination. The population is represented by multilocus cumulants describing the distribution of haploid genotypes, and selection is described by the relation between mean fitness and these cumulants. We provide exact recursions in terms of generating functions for the effects of selection on non-central moments. The effects of recombination are simply calculated as a weighted sum over all the permutations produced by meiosis. Finally, the new cumulants that describe the next generation are computed from the non-central moments. Although this scheme is applied here in detail only to selection on an additive trait, it is quite general. For arbitrary epistasis and linkage, we describe a consistent infinitesimal limit in which the short-term selection response is dominated by infinitesimal allele frequency changes and linkage disequilibria. Numerical multilocus results show that the standard Gaussian approximation gives accurate predictions for the dynamics of the mean and genetic variance in this limit. Even with intense truncation selection, linkage disequilibria of order three and higher never cause much deviation from normality. Thus, the empirical deviations frequently found between predicted and observed responses to artificial selection are not caused by linkage-disequilibrium-induced departures from normality. Disruptive selection can generate substantial four-way disequilibria, and hence kurtosis; but even then, the Gaussian assumption predicts the variance accurately. In contrast to the apparent simplicity of the infinitesimal limit, data suggest that changes in genetic variance after 10 or more generations of selection are likely to be dominated by allele frequency dynamics that depend on genetic details.}, author = {Turelli, Michael and Barton, Nicholas H}, issn = {0016-6731}, journal = {Genetics}, number = {3}, pages = {913 -- 941}, publisher = {Genetics Society of America}, title = {{Genetic and statistical analyses of strong selection on polygenic traits: What, me normal?}}, doi = {10.1093/genetics/138.3.913}, volume = {138}, year = {1994}, } @article{4032, abstract = {Every collection of t≥2 n2 triangles with a total of n vertices in ℝ3 has Ω(t4/n6) crossing pairs. This implies that one of their edges meets Ω(t3/n6) of the triangles. From this it follows that n points in ℝ3 have only O(n8/3) halving planes.}, author = {Dey, Tamal and Edelsbrunner, Herbert}, issn = {0179-5376}, journal = {Discrete & Computational Geometry}, number = {1}, pages = {281 -- 289}, publisher = {Springer}, title = {{Counting triangle crossings and halving planes}}, doi = {10.1007/BF02574381}, volume = {12}, year = {1994}, }