@article{3481, abstract = {1. The influence of intracellular factors on current rectification of different subtypes of native α-amino-3-hydroxy-5-methyl-4-isoxazolepropionate receptors (AMPARs) was studied in rat brain slices by combining fast application of glutamate with patch pipette perfusion. 2. The peak current-voltage (I-V) relation of the AMPARs expressed in Bergmann glial cells of cerebellum and dentate gyrus (DG) basket cells of hippocampus was weakly rectifying in outside-out patches and nystatin-perforated vesicles, but showed a doubly rectifying shape with a region of reduced slope between 0 and +40 mV in nucleated patches. The I-V relation of AMPARs expressed in hippocampal CA3 pyramidal neurones was linear in all recording configurations. 3. Intracellular application of 2.5 μM spermine, a naturally occurring polyamine, blocked outward currents in outside-oat patches from Bergmann glial cells and DG basket cells in a voltage-dependent manner, generating I-V relations with a doubly rectifying shape which were similar to those recorded in nucleated patches. AMPARs in CA3 pyramidal cell patches were unaffected by 25 μM spermine. 4. The half-maximal blocking concentration of spermine at +40 mV was 0.3 μM in Bergmann glial cell patches and 1.5 μM in DG basket cell patches, whereas it was much higher (≥ 100 μM) for CA3 pyramidal. cell patches. Spermidine also affected current rectification, but with lower affinity. The block of outward current by polyamines following voltage jumps developed within < 0.5 ms. 5. We conclude that current rectification, rather than being an intrinsic property of the Ca2+ permeable AMPAR channel, is generated by polyamine block.}, author = {Koh, Duk and Burnashev, Nail and Jonas, Peter M}, issn = {0022-3751}, journal = {Journal of Physiology}, number = {Pt 2}, pages = {305 -- 312}, publisher = {Wiley-Blackwell}, title = {{Block of native Ca(2+)-permeable AMPA receptors in rat brain by intracellular polyamines generates double rectification}}, doi = {10.1113/jphysiol.1995.sp020813}, volume = {486}, year = {1995}, } @article{3480, abstract = {Recording of glutamate-activated currents in membrane patches was combine with RT-PCR-mediated AMPA receptor (AMPAR) subunit mRNA analysis in single identified cells of rat brain slices. Analysis of AMPARs in principal neurons end interneurons of hippocampus and neocortex and in auditory relay neurons and Bergmann glial cells indicates that the GluR-B subunit in its flip version determines formation of receptors with relatively slow gating, whereas the GluR-D subunit promotes assembly of more rapidly gated receptors. The relation between Ca 2+ permeability of AMPAR channels and the relative GluR-B mRNA abundance is consistent with the dominance of this subunit in determining the Ca 2+ permeability of native receptors. The results suggest that differential expression of GluR-B and GluR-D subunit genes, as well as splicing end editing of their mRNAs, account for the differences in gating and Ca 2+ permeability of native AMPAR channels.}, author = {Geiger, Jörg and Melcher, Thorsten and Koh, Duk and Sakmann, Bert and Seeburg, Peter and Jonas, Peter M and Monyer, Hannah}, issn = {0896-6273}, journal = {Neuron}, number = {1}, pages = {193 -- 204}, publisher = {Elsevier}, title = {{Relative abundance of subunit mRNAs determines gating and Ca(2+) permeability of AMPA receptors in principal neurons and interneurons in rat CNS}}, doi = {10.1016/0896-6273(95)90076-4}, volume = {15}, year = {1995}, } @misc{3597, author = {Kirkpatrick, Mark and Barton, Nicholas H}, booktitle = {Nature}, issn = {0028-0836}, pages = {388 -- 389}, publisher = {Nature Publishing Group}, title = {{Déjà vu all over again}}, doi = {10.1038/377388a0}, volume = {377}, year = {1995}, } @article{3640, abstract = {The probability of fixation of a favorable mutation is reduced if selection at other loci causes inherited variation in fitness. A general method for calculating the fixation probability of an allele that can find itself in a variety of genetic backgrounds is applied to find the effect of substitutions, fluctuating polymorphisms, and deleterious mutations in a large population. With loose linkage, r, the effects depend on the additive genetic variance in relative fitness, var(W), and act by reducing effective population size by (N/Ne) = 1 + var(W)/2r2. However, tightly linked loci can have a substantial effect not predictable from Ne. Linked deleterious mutations reduce the fixation probability of weakly favored alleles by exp (-2U/R), where U is the total mutation rate and R is the map length in Morgans. Substitutions can cause a greater reduction: an allele with advantage s < scrit = (pi 2/6) loge (S/s) [var(W)/R] is very unlikely to be fixed. (S is the advantage of the substitution impeding fixation.) Fluctuating polymorphisms at many (n) linked loci can also have a substantial effect, reducing fixation probability by exp [square root of 2Kn var(W)/R] [K = -1/E((u-u)2/uv) depending on the frequencies (u,v) at the selected polymorphisms]. Hitchhiking due to all three kinds of selection may substantially impede adaptation that depends on weakly favored alleles.}, author = {Barton, Nicholas H}, issn = {0016-6731}, journal = {Genetics}, number = {2}, pages = {821 -- 841}, publisher = {Genetics Society of America}, title = {{Linkage and the limits to natural selection}}, doi = {http://www.genetics.org/content/140/2/821.long}, volume = {140}, year = {1995}, } @article{4028, abstract = {Efficient algorithms are described for computing topological, combinatorial, and metric properties of the union of finitely many spherical balls in R(d) These algorithms are based on a simplicial complex dual to a decomposition of the union of balls using Voronoi cells, and on short inclusion-exclusion formulas derived from this complex. The algorithms are most relevant in R(3) where unions of finitely many balls are commonly used as models of molecules.}, author = {Edelsbrunner, Herbert}, issn = {0179-5376}, journal = {Discrete & Computational Geometry}, number = {1}, pages = {415 -- 440}, publisher = {Springer}, title = {{The union of balls and its dual shape}}, doi = {10.1007/BF02574053}, volume = {13}, year = {1995}, } @article{4029, abstract = {A general and direct method for computing the Betti numbers of a finite simplicial complex in Bd is given. This method is complete for d less than or equal to 3, where versions of this method run in time O(n alpha(n)) and O(n), n the number of simplices. An implementation of the algorithm is applied to alpha shapes, which is a novel geometric modeling tool.}, author = {Delfinado, Cecil and Edelsbrunner, Herbert}, issn = {0167-8396}, journal = {Computer Aided Geometric Design}, number = {7}, pages = {771 -- 784}, publisher = {Elsevier}, title = {{An incremental algorithm for Betti numbers of simplicial complexes on the 3-sphere}}, doi = {10.1016/0167-8396(95)00016-Y}, volume = {12}, year = {1995}, } @article{4297, abstract = {The F5 (2n = 34) and FM2 (2n = 44-46) chromosome races of the Sceloporus grammicus complex form a parapatric hybrid zone in the Mexican state of Hidalgo, characterized by steep concordant clines among three diagnostic chromosome markers across a straight-line distance of about 2 km. Here, we show that this zone is actually structured into local patches in which hybridization extends over an extremely irregular front. The distribution of hybrid-index (HI) scores across the transect reveals some hybridization at almost all localities mapped in a central 7 km x 3 km area. Pooling the central samples produces both a strong heterozygote deficit for all diagnostic markers and strong linkage disequilibria between all pairwise combinations of these (unlinked) markers. Moreover, a highly significant association exists between the habitat on which each individual was caught and its karyotype (F5 chromosomes are more likely to be found on oak). Analysis of genotype frequencies over a range of spatial scales shows that there is no significant heterozygote deficit or habitat association within local areas of less than about 200 m; however, there is significant linkage disequilibrium over the smallest scales (R = D (pquv)1/2 = 0.29, support limits, 0.18-0.36) over 100 m. These patterns suggest that lizards mate and choose habitats randomly within local patches. This conclusion is supported by mark-recapture estimates of dispersal (≈ 80 m in a generation) and by inference of matings from embryo and maternal karyotypes. Closer examination of the two-dimensional pattern reveals a convoluted cline for all three markers, with a width of 830 m (support limits 770 m-930 m). This cline width, combined with the strength of local linkage disequilibrium, implies a dispersal rate of σ = 160 m in a generation and an effective selection pressure of 30% on each chromosome marker. The proportion of inviable embryos is greater in females from the center of the hybrid zone; this is caused by effects associated with both karyotype and location. The hybrid zone is likely to be maintained by selection against chromosomal heterozygotes, by other kinds of selection against hybrids, and by selection adapting the chromosome races to different habitats. The structure of the contact may be caused by both random drift and by selection in relation to habitat.}, author = {Sites, Jack and Barton, Nicholas H and Reed, Kent}, issn = {0014-3820}, journal = {Evolution}, number = {1}, pages = {9 -- 36}, publisher = {Wiley-Blackwell}, title = {{The genetic structure of a mosaic hybrid zone between two chromosome races of the Sceloporus grammicus complex (Sauria, Phrynosomatidae) in central Mexico}}, doi = {10.1111/j.1558-5646.1995.tb05955.x}, volume = {49}, year = {1995}, } @article{4296, abstract = {Three replicate lines of Drosophila melanogaster were cultured at each of two temperatures (16.5⚬C and 25⚬C) in population cages for 4 yr. The lifespans of both sexes and the fecundity and fertility of the females were then measured at both experimental temperatures. The characters showed evidence of adaptation; flies of both sexes from each selection regime showed higher longevity, and females showed higher fecundity and fertility, than flies from the other selection regime when they were tested at the experimental temperature at which they had evolved. Calculation of intrinsic rates of increase under different assumptions about the rate of population increase showed that the difference between the lines from the two selection regimes became less the higher the rate of population increase, because the lines were more similar in early adulthood than they were later. Despite the increased adaptation of the low-temperature lines to the low temperature, like the high temperature lines they produced progeny at a higher rate at the higher temperature. The lines may have independently evolved adaptations to their respective thermal regimes during the experiment, or there may have been a trade-off between adaptation to the two temperatures, or mutation pressure may have lowered adaptation to the temperature that the flies no longer encountered.}, author = {Partridge, Linda and Barrie, Brian and Barton, Nicholas H and Fowler, Kevin and French, Vernon}, issn = {0014-3820}, journal = {Evolution}, number = {3}, pages = {538 -- 544}, publisher = {Wiley-Blackwell}, title = {{Rapid laboratory evolution of adult life history traits in Drosophila melanogaster in response to temperature}}, doi = {10.1111/j.1558-5646.1995.tb02285.x}, volume = {49}, year = {1995}, } @article{4298, author = {Barton, Nicholas H}, issn = {1558-5646}, journal = {Evolution}, number = {6}, pages = {1038 -- 1045}, publisher = {Wiley}, title = {{Appendix to "A simulation study of multilocus clines" by S J E Baird}}, doi = {10.1111/j.1558-5646.1995.tb04431.x}, volume = {49}, year = {1995}, } @phdthesis{4428, abstract = {Hybrid systems are real-time systems that react to both discrete and continuous activities (such as analog signals, time, temperature, and speed). Typical examples of hybrid systems are embedded systems, timing-based communication protocols, and digital circuits at the transistor level. Due to the rapid development of microprocessor technology, hybrid systems directly control much of what we depend on in our daily lives. Consequently, the formal specification and verification of hybrid systems has become an active area of research. This dissertation presents the first general framework for the formal specification and verification of hybrid systems, as well as the first hybrid-system analysis tool--HyTech. The framework consists of a graphical finite-state-machine-like language for modeling hybrid systems, a temporal logic for modeling the requirements of hybrid systems, and a computer procedure that verifies modeled hybrid systems against modeled requirements. The tool HyTech is the implementation of the framework using C++ and Mathematica. More specifically, our hybrid-system modeling language, Hybrid Automata, is an extension of timed automata with discrete and continuous variables whose dynamics are governed by differential equations. Our requirement modeling language, ICTL, is a branching-time temporal logic, and is an extension of TCTL with stop-watch variables. Our verification procedure is a symbolic model-checking procedure that verifies linear hybrid automata against ICTL formulas. To make HyTech more efficient and effective, we use model-checking strategies and abstract operators that can expedite the verification process. To enable HyTech to verify nonlinear hybrid automata, we introduce two translations from nonlinear hybrid automata to linear hybrid automata. We have applied HyTech to analyze more than 30 hybrid-system benchmarks. In this dissertation, we present the application of HyTech to three nontrivial hybrid systems taken from the literature.}, author = {Ho, Pei}, pages = {1 -- 188}, publisher = {Cornell University}, title = {{Automatic analysis of hybrid systems}}, year = {1995}, }