@article{2864,
  abstract     = {Using an electrospray tandem mass spectrometer as a concentration-sensitive detector, a method has been developed to quantify femtomole amounts of plant growth regulators (i.e. isoprenoid type cytokinins, zeatin, dihydrozeatin, isopentenyladenine and their respective riboside and glucoside analogues) and the second messenger adenosine 3':5'-cyclic monophosphate (3':5'-cAMP). Miniaturisation of the chromatographic setup using capillary high performance liquid chromatographic (HPLC) ion spray mass spectrometry increased the sensitivity to the low femtomole region. Application of automated capillary column switching allowed the introduction of large injection volumes into the HPLC system. Aliquots (25 μL) were injected into one dimension of the HPLC set-up and stacked onto a micro pre-column. By means of mobile phase switching the pre-column was back-flushed to introduce the analytes onto the analytical column. For cytokinin analysis positive electrospray ionisation was used and resulted in 2.5-25 fmol detection limits. Cyclic nucleotides were separated under ion-pair conditions using tetrabutyl ammonium bromide as ion-pair reagent and were detected under negative electrospray ionisation conditions. Here a 25 fmol detection limit was determined. Following this approach, cytokinins and 3':5'-cAMP extracted from only mg amounts of apical shoot meristem and chloroplasts obtained from Nicotiana tabacum cv. Petit Havana SR1 were identified and quantified.},
  author       = {Witters, Erwin and Vanhoutte, Koen and Dewitte, Walter and Macháčková, Ivana and Benková, Eva and Van Dongen, Walter and Esmans, Eddy and Van Onckelen, Henri},
  issn         = {0958-0344},
  journal      = {Phytochemical Analysis},
  number       = {3},
  pages        = {143 -- 151},
  publisher    = {Wiley-Blackwell},
  title        = {{Analysis of cyclic nucleotides and cytokinins in minute plant samples using phase system switching capillary electrospray liquid chromatography tandem mass spectrometry}},
  doi          = {10.1002/(SICI)1099-1565(199905/06)10:3&lt;143::AID-PCA441&gt;3.0.CO;2-G},
  volume       = {10},
  year         = {1999},
}

@article{2865,
  abstract     = {Although cytokinins (CKs) affect a number of processes connected with chloroplasts, it has never been rigorously proven that chloroplasts contain CKs. We isolated intact chloroplasts from tobacco (Nicotiana tabacum L. cv SR1) and wheat (Triticum aestivum L. cv Ritmo) leaves and determined their CKs by liquid chromatography/tandem mass spectroscopy. Chloroplasts from both species contained a whole spectrum of CKs, including free bases (zeatin and isopentenyladenine), ribosides (zeatin riboside, and isopentenyladenosine), ribotides (isopentenyladenosine-5′-monophosphate, zeatin riboside-5′-monophosphate, and dihydrozeatin riboside-5′-monophosphate), and N-glucosides (zeatin-N 9-glucoside, dihydrozeatin-N 9-glucoside, zeatin-N 7-glucoside, and isopentenyladenine-N-glucosides). In chloroplasts there was a moderately higher relative amount of bases, ribosides, and ribotides than in leaves, and a significantly increased level ofN 9-glucosides of zeatin and dihydrozeatin. Tobacco and wheat chloroplasts were prepared from leaves at the end of either a dark or light period. After a dark period, chloroplasts accumulated more CKs than after a light period. The differences were moderate for free bases and ribosides, but highly significant for glucosides. Tobacco chloroplasts from dark-treated leaves contained zeatin riboside-O-glucoside and dihydrozeatin riboside-O-glucoside, as well as a relatively high CK oxidase activity. These data show that chloroplasts contain a whole spectrum of CKs and the enzymatic activity necessary for their metabolism. },
  author       = {Benková, Eva and Witters, Erwin and Van Dongen, Walter and Kolář, Jan and Motyka, Václav and Brzobohatý, Břetislav and Van Onckelen, Henri and Macháčková, Ivana},
  issn         = {0032-0889},
  journal      = {Plant Physiology},
  number       = {1},
  pages        = {245 -- 251},
  publisher    = {American Society of Plant Biologists},
  title        = {{Cytokinins in tobacco and wheat chloroplasts. Occurrence and changes due to light/dark treatment}},
  doi          = {10.1104/pp.121.1.245},
  volume       = {121},
  year         = {1999},
}

@book{3137,
  abstract     = {This volume provides an overview of glutamate receptors and their role in excitatory neurotransmission. It focusses on three aspects. First, it describes the functional, molecular, and pharmacological properties of glutamate receptors (AMPA, NMDA, and kainate receptors). Second, it gives a survey how these receptors are involved in synaptic transmission at different glutamatergic synapses in the mammalian CNS. Finally, it adresses how overactivation of glutamate receptors can lead to excitotoxic cell death, and emphasizes the importance of glutamate receptors as potential therapeutical targets. The chapters, written by leading scientists, give accurate summaries of facets that have emerged recently in this field. The book demonstrates the strength of a multidisciplinary approach involving physiology, pharmacology, and molecular biology. It will be useful for other scientists in and outside the field, lecturers and students at different educational levels.},
  editor       = {Jonas, Peter M and Monyer, Hannah},
  isbn         = {978-3-642-08539-0},
  issn         = {1865-0325},
  pages        = {XXII, 535},
  publisher    = {Springer},
  title        = {{Ionotropic Glutamate Receptors in the CNS}},
  doi          = {10.1007/978-3-662-08022-1},
  volume       = {141},
  year         = {1999},
}

@article{3148,
  abstract     = {Accurate proteolytic processing of neuropeptide and peptide hormone precursors by members of the kexin/furin family of proteases is key to determining both the identities and activities of signaling peptides. Here we identify amontillado (amon), the Drosophila melanogaster homolog of the mammalian neuropeptide processing protease PC2, and show that in contrast to vertebrate PC2, amontillado expression undergoes extensive regulation in the nervous system during development. In situ hybridization reveals that expression of amontillado is restricted to the final stages of embryogenesis when it is found in anterior sensory structures and in only 168 cells in the brain and ventral nerve cord. After larvae hatch from their egg shells, the sensory structures and most cells in the CNS turn off or substantially reduce amontillado expression, suggesting that amontillado plays a specific role late in embryogenesis. Larvae lacking the chromosomal region containing amontillado show no gross anatomical defects and respond to touch. However, such larvae show a greatly reduced frequency of a hatching behavior of wild- type Drosophila in which larvae swing their heads, scraping through the eggshell with their mouth hooks. Ubiquitous expression of amontillado can restore near wild-type levels of this behavior, whereas expression of amontillado with an alanine substitution for the catalytic histidine cannot. These results suggest that amontillado expression is regulated as part of a programmed modulation of neural signaling that controls hatching behavior by producing specific neuropeptides in particular neurons at an appropriate developmental time.},
  author       = {Siekhaus, Daria E and Fuller, Robert},
  issn         = {0270-6474},
  journal      = {Journal of Neuroscience},
  number       = {16},
  pages        = {6942 -- 6954},
  publisher    = {Society for Neuroscience},
  title        = {{A role for amontillado the Drosophila homolog of the neuropeptide precursor processing protease PC2 in triggering hatching behavior}},
  doi          = {10.1523/jneurosci.19-16-06942.1999},
  volume       = {19},
  year         = {1999},
}

@article{3444,
  abstract     = {This study examined intermittent, high-frequency (100-200 Hz) oscillatory patterns in the CA1 region of the hippocampus in the absence of theta activity, i.e., during and in between sharp wave (SPW) bursts. Pyramidal and interneuronal activity was phase-locked not only to large amplitude (&gt;7 SD from baseline) oscillatory events, which are present mainly during SPWs, but to smaller amplitude (&lt;4 SD) patterns, as well. Large-amplitude events were in the 140-200 Hz, &quot;ripple&quot; frequency range. Lower-amplitude events, however, contained slower, 100-130 Hz (&quot;slow&quot;) oscillatory patterns. Fast ripple waves reversed just below the CA1 pyramidal layer, whereas slow oscillatory potentials reversed in the stratum radiatum and/or in the stratum oriens. Parallel CA1-CA3 recordings revealed correlated CA3 field and unit activity to the slow CA1 waves but not to fast ripple waves. These findings suggest that fast ripples emerge in the CA1 region, whereas slow (100-130 Hz) oscillatory patterns are generated in the CA3 region and transferred to the CA1 field.},
  author       = {Csicsvari, Jozsef L and Hirase, Hajima and Czurkó, András and Mamiya, Akira and Buzsáki, György},
  issn         = {0270-6474},
  journal      = {Journal of Neuroscience},
  number       = {16},
  publisher    = {Society for Neuroscience},
  title        = {{Fast  network  oscillations  in the  hippocampal  CA1 region of the behaving rat}},
  doi          = {10.1523/JNEUROSCI.19-16-j0001.1999},
  volume       = {19},
  year         = {1999},
}

@article{3445,
  abstract     = {The medial septal region and the hippocampus are connected reciprocally via GABAergic neurons, but the physiological role of this loop is still not well understood. In an attempt to reveal the physiological effects of the hippocamposeptal GABAergic projection, we cross-correlated hippocampal sharp wave (SPW) ripples or theta activity and extracellular units recorded in the medial septum and diagonal band of Broca (MSDB) in freely moving rats. The majority of single MSDB cells (60%) were significantly suppressed during SPWs. Most cells inhibited during SPW (80%) fired rhythmically and phase-locked to the negative peak of the CA1 pyramidal layer theta waves. Because both SPW and the negative peak of local theta waves correspond to the maximum discharge probability of CA1 pyramidal cells and interneuron classes, the findings indicate that the activity of medial septal neurons can be negatively (during SPW) or positively (during theta waves) correlated with the activity of hippocampal interneurons. We hypothesize that the functional coupling between medial septal neurons and hippocampal interneurons varies in a state-dependent manner.},
  author       = {Dragoi, George and Carpi, Daniel and Recce, Michael and Csicsvari, Jozsef L and Buzsáki, György},
  issn         = {0270-6474},
  journal      = {Journal of Neuroscience},
  number       = {14},
  pages        = {6191 -- 6199},
  publisher    = {Society for Neuroscience},
  title        = {{Interactions between hippocampus and medial septum during sharp waves and theta oscillation in the behaving rat}},
  doi          = {10.1523/JNEUROSCI.19-14-06191.1999},
  volume       = {19},
  year         = {1999},
}

@inbook{3456,
  abstract     = {L-a-amino-3-hydroxy-5-methyl-4-isoxazolepropionate receptors (AMPARs) and N-methyl-D-aspartate receptors (NMDARs) are the two major types of postsynaptic glutamate receptors (GluRs) that mediate excitatory synaptic transmission in the mammalian central nervous system (CNS). Both AMPARs and NMDARs are multimeric proteins, probably tetramers, formed by a variety of molecularly distinct subunits. AMPARs can be assembled from four types of subunits, termed GIuR-A, -B, -C, and -D (or, in an alternative nomenclature, G1uR1, G1uR2, GluR3, and G1uR4). Additional molecular diversity of AMPARs is generated by alternative splicing of the flip-flop module and RNA editing at the Q/R and R/G site. NMDARs are heteromers primarily assembled from NR1 subunits and NR2A, B, C, or D subunits. Various splice variants have been identified for the NR1 subunit, and a new NR3 subunit has been discovered recently. Considering all combinatorial possibilities, the molecular diversity of glutamate-receptor channels is considerable (HOLLMANN, this volume).},
  author       = {Monyer, Hannah and Jonas, Peter M and Rossier, Jean},
  booktitle    = {Ionotropic Glutamate Receptors in the CNS},
  editor       = {Jonas, Peter M and Monyer, Hannah},
  isbn         = {9783642085390},
  pages        = {309 -- 339},
  publisher    = {Springer},
  title        = {{Molecular determinants controlling functional properties of AMPARs and NMDARs in the mammalian CNS}},
  doi          = {10.1007/978-3-662-08022-1_9},
  volume       = {141},
  year         = {1999},
}

@inbook{3457,
  abstract     = {Principal neurons and interneurons are the two main classes of cells in cortical neuronal networks. Principal neurons (granule cells or pyramidal neurons) have transregional axonal projections and release glutamate onto their postsynaptic target cells. In contrast, interneurons have local, but often extensive, axonal arborizations and use γ-aminobutyric acid (GABA) as a transmitter. Although interneurons represent only approximately 10% of the neuronal population, they control the electrical activity of the entire network (FREUND and BUZSÁKI 1996). Interneurons forming inhibitory synapses on the somata or axon initial segments of their postsynaptic target cells are thought to set the threshold of action potential initiation (MILES et al. 1996) and can synchronize the collective activities of large principal neuron ensembles (COBB et al. 1995). In contrast, interneurons establishing inhibitory synapses mainly on dendrites could suppress dendritic Na+ or Ca2+ spikes (BUZSÁKI et al. 1996; MILES et al. 1996) and, thus, regulate plasticity at glutamatergic synapses in the cortex (DAVIES et al.1991).},
  author       = {Geiger, Jörg and Roth, Arnd and Taskin, Birol and Jonas, Peter M},
  booktitle    = {Ionotropic Glutamate Receptors in the CNS},
  editor       = {Monyer, Hannah and Jonas, Peter M},
  isbn         = {9783642085390},
  pages        = {363 -- 398},
  publisher    = {Springer},
  title        = {{Glutamate-mediated synaptic excitation of cortical interneurons}},
  doi          = {10.1007/978-3-662-08022-1_11},
  volume       = {141},
  year         = {1999},
}

@article{3515,
  abstract     = {Oscillations in neuronal networks are assumed to serve various physiological functions, from coordination of motor patterns to perceptual binding of sensory information. Here, we describe an ultra-slow oscillation (0.025 Hz) in the hippocampus. Extracellular and intracellular activity was recorded from the CA1 and subicular regions in rats of the Wistar and Sprague-Dawley strains. anesthetized with urethane. in a subgroup of Wistar rats (23%), spontaneous afterdischarges (4.7 +/- 1.6 s) occurred regularly at 40.8 +/- 15.7 s. The afterdischarge was initiated by a fast increase of population synchrony (100-250 Hz oscillation; “tonic” phase), followed by large-amplitude rhythmic waves and associated action potentials at gamma and beta frequency (15-50 Hz; “clonic” phase). The afterdischarges were bilaterally synchronous and terminated relatively abruptly without post-ictal depression. Single-pulse stimulation of the commissural input could trigger afterdischarges, but only at times when they were about to occur. Commissural stimulation evoked inhibitory postsynaptic potentials in pyramidal cells. However, when the stimulus triggered an afterdischarge, the inhibitory postsynaptic potential was absent and the cells remained depolarized during most of the afterdischarge. Afterdischarges were not observed in the Sprague-Dawley rats. Long-term analysis of interneuronal activity in intact, drug-free rats also revealed periodic excitability changes in the hippocampal network at 0.025 Hz. These findings indicate the presence of an ultra-slow oscillation in the hippocampal formation. The ultra-slow clock induced afterdischarges in susceptible animals. We hypothesize that a transient failure of GABAergic inhibition in a subset of Wistar rats is responsible for the emergence of epileptiform patterns. (C) 1999 IBRO. Published by Elsevier Science Ltd.},
  author       = {Penttonen, Markku and Nurminen, Nina and Miettinen, Riitta and Sirviö, Jouni and Henze, Darrell and Csicsvari, Jozsef L and Buzsáki, György},
  issn         = {0306-4522},
  journal      = {Neuroscience},
  number       = {3},
  pages        = {735 -- 743},
  publisher    = {Elsevier},
  title        = {{Ultra-slow oscillation (0.025 Hz) triggers hippocampal afterdischarges in Wistar rats}},
  doi          = {10.1016/S0306-4522(99)00367-X},
  volume       = {94},
  year         = {1999},
}

@article{3518,
  abstract     = {Information in neuronal networks may be represented by the spatiotemporal patterns of spikes. Here we examined the temporal coordination of pyramidal cell spikes in the rat hippocampus during slow-wave sleep. In addition, rats were trained to run in a defined position in space (running wheel) to activate a selected group of pyramidal cells. A template-matching method and a joint probability map method were used for sequence search. Repeating spike sequences in excess of chance occurrence were examined by comparing the number of repeating sequences in the original spike trains and in surrogate trains after Monte Carlo shuffling of the spikes. Four different shuffling procedures were used to control for the population dynamics of hippocampal neurons. Repeating spike sequences in the recorded cell assemblies were present in both the awake and sleeping animal in excess of what might be predicted by random variations. Spike sequences observed during wheel running were “replayed” at a faster timescale during single sharp-wave bursts of slow-wave sleep. We hypothesize that the endogenously expressed spike sequences during sleep reflect reactivation of the circuitry modified by previous experience. Reactivation of acquired sequences may serve to consolidate information.},
  author       = {Nádasdy, Zoltán and Hirase, Hajima and Czurkó, András and Csicsvari, Jozsef L and Buzsáki, György},
  issn         = {0270-6474},
  journal      = {Journal of Neuroscience},
  number       = {21},
  pages        = {9497 -- 9507},
  publisher    = {Society for Neuroscience},
  title        = {{Replay and time compression of recurring spike sequences in the hippocampus}},
  doi          = {10.1523/JNEUROSCI.19-21-09497.1999},
  volume       = {19},
  year         = {1999},
}

@article{3519,
  abstract     = {In contrast to sensory cortical areas of the brain, the relevant physiological inputs to the hippocampus, leading to selective activation of pyramidal cells, are largely unknown. Pyramidal cells are thought to be phasically activated by spatial cues and a variety of sensory and motor stimuli. Here, we used a behavioural `space clamp' method, which involved the confinement of the actively running animal in a defined position in space (running wheel) and kept sensory inputs constant. Twelve percent of the recorded CA1 pyramidal cells were selectively active while the rat was running in the wheel. Cell firing was specific to the direction of running and disappeared after rotating the recording apparatus. The discharge frequency of pyramidal cells and interneurons was sustained as long as the rat ran continuously in the wheel. Furthermore, the discharge frequency of pyramidal cells and interneurons increased with increasing running velocity, even though the frequency of hippocampal theta waves remained constant. The discharge frequency of some `wheel-related' pyramidal cells could increase more than 10-fold between 10 and 100 cm/s, whereas the firing rate of `non-wheel' cells remained constantly low. We hypothesize that: (i) a necessary condition for place-specific discharge of hippocampal pyramidal cells is the presence of theta oscillation; and (ii) relevant stimuli can tonically and selectively activate hippocampal pyramidal cells as long as theta activity is present.},
  author       = {Czurkó, András and Hirase, Hajima and Csicsvari, Jozsef L and Buzsáki, György},
  issn         = {0953-816X},
  journal      = {European Journal of Neuroscience},
  number       = {1},
  pages        = {344 -- 352},
  publisher    = {Wiley-Blackwell},
  title        = {{Sustained activation of hippocampal pyramidal cells by ‘space clamping' in a running wheel}},
  doi          = {10.1046/j.1460-9568.1999.00446.x},
  volume       = {11},
  year         = {1999},
}

@article{3524,
  abstract     = {We examined whether excitation and inhibition are balanced in hippocampal cortical networks. Extracellular field and single-unit activity were recorded by multiple tetrodes and multisite silicon probes to reveal the timing of the activity of hippocampal CAI pyramidal cells and classes of interneurons during theta waves and sharp wave burst (SPW)-associated field ripples. The somatic and dendritic inhibition of pyramidal cells was deduced from the activity of interneurons in the pyramidal layer [int(p)] and in the alveus and st. oriens [int(a/o)], respectively. int(p) and int(a/o) discharged an average of 60 and 20 degrees before the population discharge of pyramidal cells during the theta cycle, respectively. SPW ripples were associated with a 2.5-fold net increase of excitation. The discharge frequency of int(a/o) increased, decreased (”anti-SPW” cells), or did not change (”SPW-independent” cells) during SPW suggesting that not all interneurons are innervated by pyramidal cells. Int(p) either fired together with (unimodal cells) or both before and after (bimodal cells) the pyramidal cell burst. During fast-ripple oscillation, the activity of interneurons in both the int(p) and int(a/o) groups lagged the maximum discharge probability of pyramidal neurons by 1-2 msec. Network state changes, as reflected by field activity, covaried with changes in the spike train dynamics of single cells and their interactions. Summed activity of parallel-recorded interneurons, but not of pyramidal cells, reliably predicted theta cycles, whereas the reverse was true for the ripple cycles of SPWs. We suggest that network-driven excitability changes provide temporal windows of opportunity for single pyramidal cells to suppress, enable, or facilitate selective synaptic inputs.},
  author       = {Csicsvari, Jozsef L and Hirase, Hajima and Czurkó, András and Mamiya, Akira and Buzsáki, György},
  issn         = {0270-6474},
  journal      = {Journal of Neuroscience},
  number       = {1},
  pages        = {274 -- 287},
  publisher    = {Society for Neuroscience},
  title        = {{Oscillatory coupling of hippocampal pyramidal cells and interneurons in the behaving rat}},
  doi          = {10.1523/JNEUROSCI.19-01-00274.1999},
  volume       = {19},
  year         = {1999},
}

@article{3539,
  abstract     = {In the hippocampus, spatial representation of the environment has been suggested to be coded by either the firing rate of pyramidal cell assemblies or the relative timing of the action potentials during the theta EEG cycle. Here, we used a behavioural `space clamp' method, which involved the confinement of the actively running animal in a defined position in space (running wheel) to examine how `spatial' and other inputs affect firing rate and timing of hippocampal CA1 pyramidal cells and interneurons. Nineteen per cent of the recorded CA1 pyramidal cells were selectively active while the rat was running in the wheel in a given direction ('wheel' cells). Spatial rotation of the apparatus showed that selective discharge of pyramidal cells in the wheel was under the combined influence of distal and apparatus cues. During steady running, both discharge rate and theta phase were constant. Rotation of the wheel apparatus resulted in a shift of both firing rate and preferred theta phase. The discharge frequency of `wheel' cells increased threefold (on average) with increasing running velocity. In contrast, change in running speed had relatively little effect on the theta phase-related discharge of `wheel' cells. Our findings indicate that mechanisms that regulate rate and phase of spikes are overlapping but not necessarily identical.},
  author       = {Hirase, Hajima and Czurkó, András and Csicsvari, Jozsef L and Buzsáki, György},
  issn         = {0953-816X},
  journal      = {European Journal of Neuroscience},
  number       = {12},
  pages        = {4373 -- 4380},
  publisher    = {Wiley-Blackwell},
  title        = {{Firing rate and theta-phase coding by hippocampal pyramidal neurons during ‘space clamping’}},
  doi          = {10.1046/j.1460-9568.1999.00853.x},
  volume       = {11},
  year         = {1999},
}

@inproceedings{3554,
  abstract     = {In computational simulation of coupled, multicomponent systems, it is frequently necessary to transfer data between meshes that may differ in resolution, structure, and discretization methodology. Typically, nodes from one mesh must be associated with elements of another mesh. In this paper, we formulate mesh association as a geometric problem and introduce two efficient mesh association algorithms. One of these algorithms requires linear time in the worst case if the meshes are well shaped and geometrically well aligned. Our formulation of the problem and our algorithms are more general than previous work and can be applied to surface meshes with curved elements.},
  author       = {Jiao, Xiangmin and Edelsbrunner, Herbert and Heath, Michael},
  booktitle    = {Proceedings of the 8th International Meshing Roundtable},
  location     = {South Lake Tahoe, CA, United States of America},
  pages        = {75 -- 82},
  publisher    = {Elsevier},
  title        = {{Mesh association: formulation and algorithms}},
  year         = {1999},
}

@inbook{3571,
  author       = {Dey, Tamal and Edelsbrunner, Herbert and Guha, Sumanta},
  booktitle    = {Advances in Discrete and Computational Geometry},
  isbn         = {9780821878149},
  pages        = {109 -- 143},
  publisher    = {American Mathematical Society},
  title        = {{Computational topology}},
  volume       = {223},
  year         = {1999},
}

@article{3582,
  abstract     = {We study edge contractions in simplicial complexes and local conditions under which they preserve the topological type. The conditions are based on a generalized notion of boundary, which lends itself to defining a nested hierarchy of triangulable spaces measuring the distance to being a manifold.},
  author       = {Dey, Tamal and Edelsbrunner, Herbert and Guha, Sumanta and Nekhayev, Dmitry},
  issn         = {0350-1302},
  journal      = {Publications de l'Institut Mathématique},
  pages        = {23 -- 45},
  publisher    = {Mathematical Institute, Serbian Academy of Sciences and Arts},
  title        = {{Topology preserving edge contraction}},
  volume       = {66},
  year         = {1999},
}

@article{3625,
  abstract     = {This article outlines theoretical models of clines in additive polygenic traits, which are maintained by stabilizing selection towards a spatially varying optimum. Clines in the trait mean can be accurately predicted, given knowledge of the genetic variance. However, predicting the variance is difficult, because it depends on genetic details. Changes in genetic variance arise from changes in allele frequency, and in linkage disequilibria. Allele frequency changes dominate when selection is weak relative to recombination, and when there are a moderate number of loci. With a continuum of alleles, gene flow inflates the genetic variance in the same way as a source of mutations of small effect. The variance can be approximated by assuming a Gaussian distribution of allelic effects; with a sufficiently steep cline, this is accurate even when mutation and selection alone are better described by the 'House of Cards' approximation. With just two alleles at each locus, the phenotype changes in a similar way: the mean remains close to the optimum, while the variance changes more slowly, and over a wider region. However, there may be substantial cryptic divergence at the underlying loci. With strong selection and many loci, linkage disequilibria are the main cause of changes in genetic variance. Even for strong selection, the infinitesimal model can be closely approximated by assuming a Gaussian distribution of breeding values. Linkage disequilibria can generate a substantial increase in genetic variance, which is concentrated at sharp gradients in trait means.},
  author       = {Barton, Nicholas H},
  issn         = {0016-6723},
  journal      = {Genetical Research},
  number       = {3},
  pages        = {223 -- 236},
  publisher    = {Cambridge University Press},
  title        = {{Clines in polygenic traits}},
  doi          = {10.1017/S001667239900422X},
  volume       = {74},
  year         = {1999},
}

@article{3626,
  abstract     = {There has recently been considerable debate over the relative importance of selection against hybrids (&quot;endogenous&quot; selection) vs. adaptation to different environments (&quot;exogenous&quot;) in maintaining stable hybrid zones and hence in speciation. Single-locus models of endogenous and exogenous viability selection generate clines of similar shape, but the comparison has not been extended to multilocus systems, which are both quantitatively and qualitatively very different from the single-locus case. Here we develop an analytical multilocus model of differential adaptation across an environmental transition and compare it to previous heterozygote disadvantage models. We show that the shape of clines generated by exogenous selection is indistinguishable from that generated by endogenous selection. A stochastic simulation model is used to test the robustness of the analytical description to the effects of drift and strong selection, and confirms the prediction that pairwise linkage disequilibria are predominantly generated by migration. However, although analytical predictions for the width of clines maintained by heterozygote disadvantage fit well with the simulation results, those for environmental adaptation are consistently too narrow; reasons for the discrepancy are discussed. There is a smooth transition between a system in which a set of loci effectively act independently of each other and one in which they act as a single nonrecombining unit.},
  author       = {Kruuk, Loeske and Baird, Stuart and Gale, Katherine and Barton, Nicholas H},
  issn         = {0016-6731},
  journal      = {Genetics},
  number       = {4},
  pages        = {1959 -- 1971},
  publisher    = {Genetics Society of America},
  title        = {{A comparison of multilocus clines maintained by environmental adaptation or by selection against hybrids}},
  doi          = {10.1093/genetics/153.4.1959},
  volume       = {153},
  year         = {1999},
}

@article{4014,
  abstract     = {A new paradigm for designing smooth surfaces is described. A finite set of points with weights specifies a closed surface in space referred to as skin. It consists of one or more components, each tangent continuous and free of self-intersections and intersections with other components. The skin varies continuously with the weights and locations of the points, and the variation includes the possibility of a topology change facilitated by the violation of tangent continuity at a single point in space and time. Applications of the skin to molecular modeling and to geometric deformation are discussed.},
  author       = {Edelsbrunner, Herbert},
  issn         = {0179-5376},
  journal      = {Discrete & Computational Geometry},
  number       = {1},
  pages        = {87 -- 115},
  publisher    = {Springer},
  title        = {{Deformable smooth surface design}},
  doi          = {10.1007/PL00009412},
  volume       = {21},
  year         = {1999},
}

@article{4204,
  abstract     = {During the development of the zebrafish nervous system both noi, a zebrafish pax2 homolog, and ace, a zebrafish fgf8 homolog, are required for development of the midbrain and cerebellum. Here we describe a dominant mutation, aussicht (aus), in which the expression of noi and ace is upregulated, In aus mutant embryos, ace is upregulated at many sites in the embryo, while Itoi expression is only upregulated in regions of the forebrain and midbrain which also express ace. Subsequent to the alterations in noi and ace expression, aus mutants exhibit defects in the differentiation of the forebrain, midbrain and eyes. Within the forebrain, the formation of the anterior and postoptic commissures is delayed and the expression of markers within the pretectal area is reduced. Within the midbrain, En and wnt1 expression is expanded. In heterozygous aus embryos, there is ectopic outgrowth of neural retina in the temporal half of the eyes, whereas in putative homozygous aus embryos, the ventral retina is reduced and the pigmented retinal epithelium is expanded towards the midline, The observation that ans mutant embryos exhibit widespread upregulation of ace raised the possibility that aus might represent an allele of the ace gene itself. However, by crossing carriers for both aus and ace, we were able to generate homozygous ace mutant embryos that also exhibited the aus phenotype, This indicated that aus is not tightly linked to ace and is unlikely to be a mutation directly affecting the ace locus. However, increased Ace activity may underly many aspects of the aus phenotype and we show that the upregulation of noi in the forebrain of aus mutants is partially dependent upon functional Ace activity. Conversely, increased ace expression in the forebrain of arcs mutants is not dependent upon functional Noi activity. We conclude that aus represents a mutation involving a locus normally required for the regulation of ace expression during embryogenesis.},
  author       = {Heisenberg, Carl-Philipp J and Brennan, Caroline and Wilson, Stephen},
  issn         = {0950-1991},
  journal      = {Development},
  number       = {10},
  pages        = {2129 -- 2140},
  publisher    = {Company of Biologists},
  title        = {{Zebrafish aussicht mutant embryos exhibit widespread overexpression of ace (fgf8) and coincident defects in CNS development}},
  doi          = {10.1242/dev.126.10.2129},
  volume       = {126},
  year         = {1999},
}

