@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}, } @article{4033, abstract = {A collection of geometric selection lemmas is proved, such as the following: For any set P of n points in three-dimensional space and any set S of m spheres, where each sphere passes through a distinct point pair in P. there exists a point x, not necessarily in P, that is enclosed by Ω(m2/(n2 log6 n2/m)) of the spheres in S. Similar results apply in arbitrary fixed dimensions, and for geometric bodies other than spheres. The results have applications in reducing the size of geometric structures, such as three-dimensional Delaunay triangulations and Gabriel graphs, by adding extra points to their defining sets.}, author = {Chazelle, Bernard and Edelsbrunner, Herbert and Guibas, Leonidas and Hershberger, John and Seidel, Raimund and Sharir, Micha}, issn = {0097-5397}, journal = {SIAM Journal on Computing}, number = {6}, pages = {1138 -- 1151}, publisher = {SIAM}, title = {{Selecting heavily covered points}}, doi = {10.1137/S0097539790179919 }, volume = {23}, year = {1994}, } @article{4037, abstract = {Frequently, data in scientific computing is in its abstract form a finite point set in space, and it is sometimes useful or required to compute what one might call the `'shape” of the set. For that purpose, this article introduces the formal notion of the family of alpha-shapes of a finite point set in R3. Each shape is a well-defined polytope, derived from the Delaunay triangulation of the point set, with a parameter alpha is-an-element-of R controlling the desired level of detail. An algorithm is presented that constructs the entire family of shapes for a given set of size n in time O(n2), worst case. A robust implementation of the algorithm is discussed, and several applications in the area of scientific computing are mentioned.}, author = {Edelsbrunner, Herbert and Mücke, Ernst}, journal = {ACM Transactions on Graphics}, number = {1}, pages = {43 -- 72}, publisher = {ACM}, title = {{Three-dimensional alpha shapes}}, doi = {10.1145/174462.156635}, volume = {13}, year = {1994}, } @article{4038, abstract = {We consider a variety of problems on the interaction between two sets of line segments in two and three dimensions. These problems range from counting the number of intersecting pairs between m blue segments and n red segments in the plane (assuming that two line segments are disjoint if they have the same color) to finding the smallest vertical distance between two nonintersecting polyhedral terrains in three-dimensional space. We solve these problems efficiently by using a variant of the segment tree. For the three-dimensional problems we also apply a variety of recent combinatorial and algorithmic techniques involving arrangements of lines in three-dimensional space, as developed in a companion paper.}, author = {Chazelle, Bernard and Edelsbrunner, Herbert and Guibas, Leonidas and Sharir, Micha}, issn = {0178-4617}, journal = {Algorithmica}, number = {2}, pages = {116 -- 132}, publisher = {Springer}, title = {{Algorithms for bichromatic line-segment problems and polyhedral terrains}}, doi = {10.1007/BF01182771}, volume = {11}, year = {1994}, } @article{4039, abstract = {Let P be a simple polygon with n vertices. We present a simple decomposition scheme that partitions the interior of P into O(n) so-called geodesic triangles, so that any line segment interior to P crosses at most 2 log n of these triangles. This decomposition can be used to preprocess P in a very simple manner, so that any ray-shooting query can be answered in time O(log n). The data structure requires O(n) storage and O(n log n) preprocessing time. By using more sophisticated techniques, we can reduce the preprocessing time to O(n). We also extend our general technique to the case of ray shooting amidst k polygonal obstacles with a total of n edges, so that a query can be answered in O(√ log n) time.}, author = {Chazelle, Bernard and Edelsbrunner, Herbert and Grigni, Michelangelo and Guibas, Leonidas and Hershberger, John and Sharir, Micha and Snoeyink, Jack}, issn = {0178-4617}, journal = {Algorithmica}, number = {1}, pages = {54 -- 68}, publisher = {Springer}, title = {{Ray shooting in polygons using geodesic triangulations}}, doi = {10.1007/BF01377183}, volume = {12}, year = {1994}, } @article{4179, abstract = {Neurotrophin-3 (NT-3) is a member of the neurotrophin gene family and is highly expressed in the developing rat cerebellum. Here we show that brain-derived neurotrophic factor (BDNF) increased by approximately 10-fold the NT-3 mRNA levels in cultured cerebellar granule neurons isolated from postnatal rats, whereas nerve growth factor (NGF) and NT-3 itself had no effect. The effect of BDNF was additive to that of triiodothyronine (T3), which also increased NT-3 mRNA in these neurons. The drug K252a inhibited the BDNF-mediated stimulation of NT-3 expression, suggesting an involvement of trkB receptors. Nuclear run-on experiments showed that BDNF enhanced NT-3 transcription, whereas the stability of NT-3 mRNA remained unchanged. The data presented are the first demonstration that one neurotrophin regulates the expression of another and provide evidence that NT-3 production in granule neurons is regulated by both BDNF and T3.}, author = {Leingärtner, Axel and Heisenberg, Carl-Philipp J and Kolbeck, Roland and Thoenen, Hans and Lindholm, Dan}, issn = {1083-351X}, journal = {Journal of Biological Chemistry}, number = {2}, pages = {828 -- 830}, publisher = {American Society for Biochemistry and Molecular Biology}, title = {{Brain-derived neurotrophic factor increases neurotrophin-3 expression in cerebellar granule neurons}}, doi = {10.1016/s0021-9258(17)42186-7}, volume = {269}, year = {1994}, } @article{4202, abstract = {NERVE growth factor (NGF) injected into the otherwise unlesioned adult rat septum induced sprouting of presumptive cholinergic fibres positive for p75(NGFR) and acetylcholinesterase (AChE). These fibres did not stain for tyrosine hydroxylase and therefore did not represent sympathetic ingrowth. Neurofilament staining on adjacent sections revealed fibres with similar morphology, suggesting new outgrowth in the form of sprouting rather than the upregulation of p75(NGFR) and AChE in pre-existing fibres. Simultaneous injections of subneurotoxic doses of N-methyl-D-aspartate (NMDA) significantly potentiated the effect of NGF on cholinergic fibre sprouting and caused pronounced glial fibrillary acidic protein (GFAP)positive astrocytosis. Application of NMDA alone did not elicit sprouting of this type. These findings indicate that NGF can induce the sprouting of uninjured adult rat septal cholinergic fibres in vivo and suggest that reactive astrocytes are not inhibitory to cholinergic axonal outgrowth, and might serve as a substrate for growing axons in the presence of NGF.}, author = {Heisenberg, Carl-Philipp J and Cooper, John and Berke, J and Sofroniew, Michael}, issn = {0959-4965}, journal = {Neuroreport}, number = {4}, pages = {413 -- 416}, publisher = {Lippincott, Williams & Wilkins}, title = {{NMDA potentiates NGF-induced sprouting of septal cholinergic fibres}}, doi = {10.1097/00001756-199401120-00010 }, volume = {5}, 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}, }