@article{2643, abstract = {Metabotropic γ-aminobutyric acid receptors (GABAB) are involved in pre- and postsynaptic inhibitory effects upon auditory neurons and have been implicated in different aspects of acoustic information processing. To understand better the mechanisms by which GABAB receptors mediate their inhibitory effects, we used pre-embedding immunocytochemical techniques combined with quantification of immunogold particles to reveal the precise subcellular distribution of the GABAB1 subunit in the rat dorsal cochlear nucleus. At the light microscopic level, GABAB1 was detected in all divisions of the cochlear complex. The most intense immunoreactivity for GABAB1 was found in the dorsal cochlear nucleus, whereas immunoreactivity in the anteroventral and posteroventral cochlear nuclei was very low. In the dorsal cochlear nucleus, a punctate labeling was observed in the superficial (molecular and fusiform cell) layers. At the electron microscopic level, GABAB1 was found at both post- and presynaptic locations. Postsynaptically, GABAB1 was localized mainly in the dendritic spines of presumed fusiform cells. Quantitative immunogold immunocytochemistry revealed that the highest concentration of GABA B1 in the plasma membrane was in dendritic spines, followed by dendritic shafts and somata. Thus, the most intense immunoreactivity for GABAB1 was observed in dendritic spines with a high density of immunogold particles at extrasynaptic sites, peaking around 300 nm from glutamatergic synapses. This is in contrast to GABAergic synapses, in which GABAB1 was only occasionally found. Presynaptically, receptor immunoreactivity was detected primarily in axospinous endings, probably from granule cells, in both the active zone and extrasynaptic sites. The localization of GABAB1 relative to synaptic sites in the DCN suggests a role for the receptor in the regulation of dendritic excitability and excitatory inputs.}, author = {Luján, Rafael and Ryuichi Shigemoto and Kulik, Ákos and Juíz, José M}, journal = {Journal of Comparative Neurology}, number = {1}, pages = {36 -- 46}, publisher = {Wiley-Blackwell}, title = {{Localization of the GABAB receptor 1a/b subunit relative to glutamatergic synapses in the dorsal cochlear nucleus of the rat}}, doi = {10.1002/cne.20160}, volume = {475}, year = {2004}, } @article{2638, abstract = {Among various types of low- and high-threshold calcium channels, the high voltage-activated P/Q-type channel is the most abundant in the cerebellum. These P/Q-type channels are involved in the regulation of neurotransmitter release and in the integration of dendritic inputs. We used an antibody specific for the α1A subunit of the P/Q-type channel in quantitative pre-embedding immunogold labelling combined with three-dimensional reconstruction to reveal the subcellular distribution of pre- and postsynaptic P/Q-type channels in the rat cerebellum. At the light microscopic level, immunoreactivity for the α1A protein was prevalent in the molecular layer, whereas immunostaining was moderate in the somata of Purkinje cells and weak in the granule cell layer. At the electron microscopic level, the most intense Immunoreactivity for the α1A subunit was found in the presynaptic active zone of parallel fibre varicosities. The dendritic spines of Purkinje cells were also strongly labelled with the highest density of immunoparticles detected within 180 nm from the edge of the asymmetrical parallel fibre-Purkinje cell synapses. By contrast, the immunolabelling was sparse in climbing fibre varicosities and axon terminals of GABAergic cells, and weak and diffuse in dendritic shafts of Purkinje cells. The association of the α1A subunit with the glutamatergic parallel fibre-Purkinje cell synapses suggests that presynaptic channels have a major role in the mediation of excitatory neurotransmission, whereas postsynaptic channels are likely to be involved in depolarization-induced generation of local calcium transients in Purkinje cells.}, author = {Kulik, Ákos and Nakadate, Kazuhiko and Hagiwara, Akari and Fukazawa, Yugo and Luján, Rafael and Saito, Hiromitsu and Suzuki, Noboru and Futatsugi, Akira and Mikoshiba, Katsuhiko and Frotscher, Michael and Ryuichi Shigemoto}, journal = {European Journal of Neuroscience}, number = {8}, pages = {2169 -- 2178}, publisher = {Wiley-Blackwell}, title = {{Immunocytochemical localization of the α1A subunit of the P/Q-type calcium channel in the rat cerebellum}}, doi = {10.1111/j.0953-816X.2004.03319.x}, volume = {19}, year = {2004}, } @article{2640, abstract = {Hyperpolarization-activated cation currents (Ih) contribute to various physiological properties and functions in the brain, including neuronal pacemaker activity, setting of resting membrane potential, and dendritic integration of synaptic input. Four subunits of the Hyperpolarization-activated and Cyclic-Nucleotide-gated nonselective cation channels (HCN1-4), which generate Ih, have been cloned recently. To better understand the functional diversity of Ih in the brain, we examined precise immunohistochemical localization of four HCNs in the rat brain. Immunoreactivity for HCN1 showed predominantly cortical distribution, being intense in the neocortex, hippocampus, superior colliculus, and cerebellum, whereas those for HCN3 and HCN4 exhibited subcortical distribution mainly concentrated in the hypothalamus and thalamus, respectively. Immunoreactivity for HCN2 had a widespread distribution throughout the brain. Double immunofluorescence revealed colocalization of immunoreactivity for HCN1 and HCN2 in distal dendrites of pyramidal cells in the hippocampus and neocortex. At the electron microscopic level, immunogold particles for HCN1 and HCN2 had similar distribution patterns along plasma membrane of dendritic shafts in layer I of the neocortex and stratum lacunosum moleculare of the hippocampal CA1 area, suggesting that these subunits could form heteromeric channels. Our results further indicate that HCNs are localized not only in somato-dendritic compartments but also in axonal compartments of neurons. Immunoreactivity for HCNs often occurred in preterminal rather than terminal portions of axons and in specific populations of myelinated axons. We also found HCN2-immunopositive oligodendrocytes including perineuronal oligodendrocytes throughout the brain. These results support previous electrophysiological findings and further suggest unexpected roles of Ih channels in the brain.}, author = {Notomi, Takuya and Ryuichi Shigemoto}, journal = {Journal of Comparative Neurology}, number = {3}, pages = {241 -- 276}, publisher = {Wiley-Blackwell}, title = {{Immunohistochemical localization of Ih channel subunits, HCN1-4, in the rat brain}}, doi = {10.1002/cne.11039}, volume = {471}, year = {2004}, } @article{2641, abstract = {The Na+-K+ pump current (Ip) and the h-current (Ih) flowing through hyperpolarization-activated channels (h-channels) participate in generating the resting potential. These two currents are thought to be produced independently. We show here bidirectional interactions between Na+-K+ pumps and h-channels in mesencephalic trigeminal neurons. Activation of Ih leads to the generation of two types of ouabain-sensitive Ip with temporal profiles similar to those of instantaneous and slow components of I h, presumably reflecting Na+ transients in a restricted cellular space. Moreover, the Ip activated by instantaneous I h can facilitate the subsequent activation of slow Ih. Such counteractive and cooperative interactions were also disclosed by replacing extracellular Na+ with Li+, which is permeant through h-channels but does not stimulate the Na+-K+ pump as strongly as Na+ ions. These observations indicate that the interactions are bidirectional and mediated by Na+ ions. Also after substitution of extracellular Na+ with Li+, the tail Ih was reduced markedly despite an enhancement of Ih itself, attributable to a negative shift of the reversal potential for I h presumably caused by intracellular accumulation of Li+ ions. This suggests the presence of a microdomain where the interactions can take place. Thus, the bidirectional interactions between Na+-K + pumps and h-channels are likely to be mediated by Na+ microdomain. Consistent with these findings, hyperpolarization-activated and cyclic nucleotide-modulated subunits (HCN1/2) and the Na+-K + pump α3 isoform were colocalized in plasma membrane of mesencephalic trigeminal neurons having numerous spines.}, author = {Kang, Youngnam and Notomi, Takuya and Saito, Mitsuru and Zhang, Wei and Ryuichi Shigemoto}, journal = {Journal of Neuroscience}, number = {14}, pages = {3694 -- 3702}, publisher = {Society for Neuroscience}, title = {{Bidirectional interactions between H-channels and Na+-K + pumps in mesencephalic trigeminal neurons}}, doi = {10.1523/JNEUROSCI.5641-03.2004}, volume = {24}, year = {2004}, } @misc{2636, author = {Momiyama, Akiko and Ryuichi Shigemoto}, booktitle = {Tanpakushitsu kakusan koso Protein nucleic acid enzyme}, number = {3 Suppl}, pages = {287 -- 294}, publisher = {Kyoritsu Shuppan}, title = {{Function and distribution of glutamate receptors in the central synapses}}, volume = {49}, year = {2004}, } @article{2645, abstract = {The globus pallidus (GP) is a critical component of the basal ganglia circuitry controlling motor behavior. Dysregulation of GP activity has been implicated in a number of psychomotor disorders, including Parkinson's disease (PD), in which a cardinal feature of the pathophysiology is an alteration in the pattern and synchrony of discharge in GP neurons. Yet the determinants of this activity in GP neurons are poorly understood. To help fill this gap, electrophysiological, molecular, and computational approaches were used to identify and characterize GABAergic GP neurons in tissue slices from rodents. In vitro, GABAergic GP neurons generate a regular, autonomous, single-spike pacemaker activity. Hyperpolarization-activated, cyclic nucleotide-gated cation (HCN) channels make an important contribution to this process: their blockade with ZD7288 significantly slowed discharge rate and decreased its regularity. HCN currents evoked by somatic voltage clamp had fast and slow components. Single-cell RT-PCR and immunohistochemical approaches revealed robust expression of HCN2 subunits as well as significant levels of HCN1 subunits in GABAergic GP neurons. Transient activation of striatal GABAergic input to GP neurons led to a resetting of rhythmic discharge that was dependent on HCN currents. Simulations suggested that the ability of transient striatal GABAergic input to reset pacemaking was dependent on dendritic HCN2/HCN1 channels. Together, these studies show that HCN channels in GABAergic GP neurons are key determinants of the regularity and rate of pacemaking as well as striatal resetting of this activity, implicating HCN channels in the emergence of synchrony in PD.}, author = {Chan, Savio and Ryuichi Shigemoto and Mercer, Jeff N and Surmeier, James D}, journal = {Journal of Neuroscience}, number = {44}, pages = {9921 -- 9932}, publisher = {Society for Neuroscience}, title = {{HCN2 and HCN1 channels govern the regularity of autonomous pacemaking and synaptic resetting in globus pallidus neurons}}, doi = {10.1523/JNEUROSCI.2162-04.2004}, volume = {24}, year = {2004}, } @article{2644, abstract = {The release of GABA in synapses is modulated by presynaptic metabotropic glutamate receptors (mGluRs). We tested whether GABA release to identified hippocampal neurons is influenced by group III mGluR activation using the agonist L-(+)-2-amino-4-phosphonobutyric acid (L-AP4) on inhibitory postsynaptic currents (IPSCs) evoked in CA1 interneurons and pyramidal cells. In interneurons, characterized with biocytin and immunolabelling for somatostatin, evoked IPSCs were depressed by 50 μM L-AP4 (activating mGluR4 and 8) to 68±6% of control, but they were rarely depressed in pyramidal cells (96±4% of control). At 300-500 μM concentration (activating mGluR4, 7 and 8), L-AP4 depressed IPSCs in both interneurons (to 70±6%) and pyramidal cells (to 67±4%). The change in trial-to-trial variability and in paired-pulse depression indicated a presynaptic action. In interneurons, the degree of IPSC depression was variable (to 9-87%), and a third of IPSCs were not affected by L-AP4. The L-AP4-evoked IPSC depression was blocked by LY341495. The depression of IPSCs was similar in O-LM cells and other interneurons. The lack of cell-type selectivity and the similar efficacy of different concentrations of L-AP4 suggest that several group III mGluRs are involved in the depression of IPSCs. Electron microscopic immunocytochemistry confirmed that mGluR4, mGluR7a and mGluR8a occur in the presynaptic active zone of GABAergic terminals on interneurons, but not on those innervating pyramidal cells. The high variability of L-AP4-evoked IPSC suppression is in line with the selective expression of presynaptic mGluRs by several distinct types of GABAergic neuron innervating each interneuron type.}, author = {Kogo, Naoki and Dalezios, Yannis and Capogna,Marco and Ferraguti, Francesco and Ryuichi Shigemoto and Somogyi, Péter}, journal = {European Journal of Neuroscience}, number = {10}, pages = {2727 -- 2740}, publisher = {Wiley-Blackwell}, title = {{Depression of GABAergic input to identified hippocampal neurons by group III metabotropic glutamate receptors in the rat}}, doi = {10.1111/j.0953-816X.2004.03394.x}, volume = {19}, year = {2004}, } @article{2646, abstract = {Metabotropic γ-aminobutyric acid receptors (GABAB) play modulatory roles in central synaptic transmission and are involved in controlling neuronal migration during development. We used immunohistochemical methods to elucidate the expression pattern as well as the cellular and the precise subcellular localization of the GABAB1a/b and GABAB2 subunits in the rat hippocampus during prenatal and postnatal development. At the light microscopic level, both GABABB1a/b and GABAB2 were expressed in the hippocampal primordium from embryonic day E14. During postnatal development, immunoreactivity for GABAB1a/b and GABAB2 was distributed mainly in pyramidal cells, with discrete GABABB1a/b-immunopositive cell bodies of interneurons present throughout the hippocampus. Using double immunofluorescence, we demonstrated that during the second week of postnatal development, GABAB1a/b but not GABAB2 was expressed in glial cells throughout the hippocampal formation. At the electron microscopic level, GABAB1a/b and GABAB2 showed a similar distribution pattern during postnatal development. Thus, at all ages the two receptor subunits were located postsynaptically in dendritic spines and shafts at extrasynaptic and perisynaptic sites in both pyramidal and nonpyramidal cells. We further demonstrated that the two subunits were localized presynaptically along the extrasynaptic plasma membrane of axon terminals and along the presynaptic active zone in both asymmetrical and, to a lesser extent, symmetrical synapses. These results suggest that GABAB receptors are widely expressed in the hippocampus throughout development and that GABABB1a/b and GABAB2 form both pre- and postsynaptic receptors.}, author = {López-Bendito, Guillermina and Ryuichi Shigemoto and Kulik, Ákos and Vida, Imre and Fairén, Alfonso and Luján, Rafael}, journal = {Hippocampus}, number = {7}, pages = {836 -- 848}, publisher = {Wiley-Blackwell}, title = {{ Distribution of metabotropic GABA receptor subunits GABAB1a/b and GABAB2 in the rat hippocampus during prenatal and postnatal development}}, doi = {10.1002/hipo.10221}, volume = {14}, year = {2004}, } @article{2706, abstract = {The Pauli operator describes the energy of a nonrelativistic quantum particle with spin in a magnetic field and an external potential. Bounds on the sum of the negative eigenvalues are called magnetic Lieb-Thirring (MLT) inequalities. The purpose of this paper is twofold. First, we prove a new MLT inequality in a simple way. Second, we give a short summary of our recent proof of a more refined MLT inequality(8) and we explain the differences between the two results and methods. The main feature of both estimates, compared to earlier results, is that in the large field regime they grow with the optimal (first) power of the strength of the magnetic field. As a byproduct of the method, we also obtain optimal upper bounds on the pointwise density of zero energy eigenfunctions of the Dirac operator.}, author = {László Erdös and Solovej, Jan P}, journal = {Journal of Statistical Physics}, number = {1-4}, pages = {475 -- 506}, publisher = {Springer}, title = {{Magnetic Lieb-Thirring inequalities with optimal dependence on the field strength}}, doi = {10.1023/B:JOSS.0000037216.45270.1d}, volume = {116}, year = {2004}, } @article{2707, abstract = {We give a nonrigorous derivation of the nonlinear Boltzmann equation from the Schrödinger evolution of interacting fermions. The argument is based mainly on the assumption that a quasifree initial state satisfies a property called restricted quasifreeness in the weak coupling limit at any later time. By definition, a state is called restricted quasifree if the four-point and the eight-point functions of the state factorize in the same manner as in a quasifree state.}, author = {László Erdös and Salmhofer, Manfred and Yau, Horng-Tzer}, journal = {Journal of Statistical Physics}, number = {1-4}, pages = {367 -- 380}, publisher = {Springer}, title = {{On the quantum Boltzmann equation}}, doi = {10.1023/B:JOSS.0000037224.56191.ed}, volume = {116}, year = {2004}, } @article{2741, abstract = {The Pauli operator describes the energy of a nonrelativistic quantum particle with spin 1/2 in a magnetic field and an external potential. A new Lieb-Thirring type inequality on the sum of the negative eigenvalues is presented. The main feature compared to earlier results is that in the large field regime the present estimate grows with the optimal (first) power of the strength of the magnetic field. As a byproduct of the method, we also obtain an optimal upper bound on the pointwise density of zero energy eigenfunctions of the Dirac operator. The main technical tools are: (i) a new localization scheme for the square of the resolvent of a general class of second order elliptic operators; (ii) a geometric construction of a Dirac operator with a constant magnetic field that approximates the original Dirac operator in a tubular neighborhood of a fixed field line. The errors may depend on the regularity of the magnetic field but they are uniform in the field strength.}, author = {László Erdös and Solovej, Jan P}, journal = {Annales Henri Poincare}, number = {4}, pages = {671 -- 741}, publisher = {Birkhäuser}, title = {{Uniform Lieb-Thirring inequality for the three-dimensional Pauli operator with a strong non-homogeneous magnetic field}}, doi = {10.1007/s00023-004-0180-x}, volume = {5}, year = {2004}, } @article{2742, abstract = {We consider a system of N weakly interacting fermions with a real analytic pair interaction. We prove that for a general class of initial data there exists a fixed time T such that the difference between the one particle density matrix of this system and the solution of the nonlinear Hartree equation is of order N−1 for any time t⩽T.}, author = {Elgart, Alexander and László Erdös and Schlein, Benjamin and Yau, Horng-Tzer}, journal = {Journal de Mathématiques Pures et Appliquées}, number = {10}, pages = {1241 -- 1273}, publisher = {Elsevier}, title = {{Nonlinear Hartree equation as the mean field limit of weakly coupled fermions}}, doi = {10.1016/j.matpur.2004.03.006}, volume = {83}, year = {2004}, } @article{2787, abstract = {The results of experimental and numerical investigations of the onset of oscillatory convection in a sidewall heated rectangular cavity of molten gallium are reported. Detailed comparisons are made between experimental observations and calculations from numerical simulations of a three-dimensional Boussinesq model. The onset of time-dependence takes place through supercritical Hopf bifurcations and the loci of critical points in the (Gr, Pr)-plane are qualitatively similar with excellent agreement between the frequencies of the oscillatory motion. This provides a severe test of the control of the experiment since the mode of oscillation is extremely sensitive to imperfections. Detailed numerical investigations reveal that there are a pair of Hopf bifurcations which exist on two asymmetric states which themselves arise at a subcritical pitchfork from the symmetric state. There is no evidence for this in the experiment and this qualitative difference is attributed to non-Boussinesq perturbations which increase with Gr. However, the antisymmetric spatial structure of the oscillatory state is robust and is present in both the experiment and the numerical model. Moreover, the detailed analysis of the numerical results reveals the origins of the oscillatory instability.}, author = {Björn Hof and Juel, Anne and Zhao, Li and Henry, Daniel and Ben Hadid, Hamda and Mullin, Tom P}, journal = {Journal of Fluid Mechanics}, pages = {391 -- 413}, publisher = {Cambridge University Press}, title = {{On the onset of oscillatory convection in molten gallium}}, doi = {10.1017/S0022112004000527}, volume = {515}, year = {2004}, } @article{2786, abstract = {Transition to turbulence in pipe flow is one of the most fundamental and longest- standing problems in fluid dynamics. Stability theory suggests that the flow remains laminar for all flow rates, but in practice pipe flow becomes turbulent even at moderate speeds. This transition drastically affects the transport efficiency of mass, momentum, and heat. On the basis of the recent discovery of unstable traveling waves in computational studies of the Navier-Stokes equations and ideas from dynamical systems theory, a model for the transition process has been suggested. We report experimental observation of these traveling waves in pipe flow, confirming the proposed transition scenario and suggesting that the dynamics associated with these unstable states may indeed capture the nature of fluid turbulence.}, author = {Björn Hof and van Doorne, Casimir W and Westerweel, Jerry and Nieuwstadt, Frans T and Faisst, Holger and Eckhardt, Bruno and Wedin, Håkan and Kersweli, Richard R and Waleffe, Fabian}, journal = {Science}, number = {5690}, pages = {1594 -- 1598}, publisher = {American Association for the Advancement of Science}, title = {{Experimental observation of nonlinear traveling waves in turbulent pipe flow}}, doi = {10.1126/science.1100393}, volume = {305}, year = {2004}, } @article{2998, abstract = {The packaging of the genomic DNA into chromatin in the cell nucleus requires machineries that facilitate DNA-dependent processes such as transcription in the presence of repressive chromatin structures. Using co-immunoprecipitation we have identified in Arabidopsis thaliana cells the FAcilitates Chromatin Transcription (FACT) complex, consisting of the 120-kDa Spt16 and the 71-kDa SSRP1 proteins. Indirect immunofluorecence analyses revealed that both FACT subunits co-localize to nuclei of the majority of cell types in embryos, shoots and roots, whereas FACT is not present in terminally differentiated cells such as mature trichoblasts or cells of the root cap. In the nucleus, Spt16 and SSRP1 are found in the cytologically defined euchromatin of interphase cells independent of the status of DNA replication, but the proteins are not associated with heterochromatic chromocentres and condensed mitotic chromosomes. FACT can be detected by chromatin immunoprecipitation over the entire transcribed region (5′-UTR, coding sequence, 3′-UTR) of actively transcribed genes, whereas it does not occur at transcriptionally inactive heterochromatic regions and intergenic regions. FACT localizes to inducible genes only after induction of transcription, and the association of the complex with the genes correlates with the level of transcription. Collectively, these results indicate that FACT assists transcription elongation through plant chromatin.}, author = {Duroux, Meg and Houben, Andreas and Růžička, Kamil and Jirí Friml and Grasser, Klaus D}, journal = {Plant Journal}, number = {5}, pages = {660 -- 671}, publisher = {Wiley-Blackwell}, title = {{The chromatin remodelling complex FACT associates with actively transcribed regions of the Arabidopsis genome}}, doi = {10.1111/j.1365-313X.2004.02242.x}, volume = {40}, year = {2004}, } @article{2997, abstract = {Polar transport-dependent local accumulation of auxin provides positional cues for multiple plant patterning processes. This directional auxin flow depends on the polar subcellular localization of the PIN auxin efflux regulators. Overexpression of the PINOID protein kinase induces a basal-to-apical shift in PIN localization, resulting in the loss of auxin gradients and strong defects in embryo and seedling roots. Conversely, pid loss of function induces an apical-to-basal shift in PIN1 polar targeting at the inflorescence apex, accompanied by defective organogenesis. Our results show that a PINOID-dependent binary switch controls PIN polarity and mediates changes in auxin flow to create local gradients for patterning processes.}, author = {Jirí Friml and Yang, Xiong and Michniewicz, Marta and Weijers, Dolf and Quint, Ab and Tietz, Olaf and Benjamins, René and Ouwerkerk, Pieter B and Ljung, Karin and Sandberg, Göran and Hooykaas, Paul J and Palme, Klaus and Offringa, Remko}, journal = {Science}, number = {5697}, pages = {862 -- 865}, publisher = {American Association for the Advancement of Science}, title = {{A PINOID-dependent binary switch in apical-basal PIN polar targeting directs auxin efflux}}, doi = {10.1126/science.1100618}, volume = {306}, year = {2004}, } @article{2999, abstract = {Embryogenesis of flowering plants establishes a basic body plan with apical-basal, radial and bilateral patterns from the single-celled zygote. Arabidopsis embryogenesis exhibits a nearly invariant cell division pattern and therefore is an ideal system for studies of early plant development. However, plant embryos are difficult to access for experimental manipulation, as they develop deeply inside maternal tissues. Here we present a method for the culture of zygotic Arabidopsis embryos in vitro. The technique omits excision of the embryo by culturing the entire ovule, thus greatly facilitating the time and effort involved. It enables external manipulation of embryo development and culture from the earliest developmental stages up to maturity. Administration of various chemical treatments as well as the use of different molecular markers is demonstrated together with standard techniques for visualizing gene expression and protein localization in in vitro cultivated embryos. The presented set of techniques allows for so far unavailable molecular physiology approaches in the study of early plant development.}, author = {Sauer, Michael and Jirí Friml}, journal = {Plant Journal}, number = {5}, pages = {835 -- 843}, publisher = {Wiley-Blackwell}, title = {{In vitro culture of Arabidopsis embryos within their ovules}}, doi = {10.1111/j.1365-313X.2004.02248.x}, volume = {40}, year = {2004}, } @inproceedings{3208, abstract = {A new technique for proving the adaptive indistinguishability of two systems, each composed of some component systems, is presented, using only the fact that corresponding component systems are non-adaptively indistinguishable. The main tool is the definition of a special monotone condition for a random system F, relative to another random system G, whose probability of occurring for a given distinguisher D is closely related to the distinguishing advantage ε of D for F and G, namely it is lower and upper bounded by ε and (1+ln1), respectively. A concrete instantiation of this result shows that the cascade of two random permutations (with the second one inverted) is indistinguishable from a uniform random permutation by adaptive distinguishers which may query the system from both sides, assuming the components’ security only against non-adaptive one-sided distinguishers. As applications we provide some results in various fields as almost k-wise independent probability spaces, decorrelation theory and computational indistinguishability (i.e., pseudo-randomness).}, author = {Maurer, Ueli M and Krzysztof Pietrzak}, pages = {410 -- 427}, publisher = {Springer}, title = {{Composition of random systems: When two weak make one strong}}, doi = {10.1007/978-3-540-24638-1_23}, volume = {2951}, year = {2004}, } @inbook{3587, author = {Ulrich, Florian and Heisenberg, Carl-Philipp J}, booktitle = {Fish development and genetics : the zebrafish and medaka models}, editor = {Korzh, Vladimir and Gong, Zhiyuan}, pages = {39 -- 86}, publisher = {World Scientific Publishing}, title = {{Gastrulation in zebrafish}}, volume = {2}, year = {2004}, } @article{3617, abstract = {The coalescent process can describe the effects of selection at linked loci only if selection is so strong that genotype frequencies evolve deterministically. Here, we develop methods proposed by Kaplan, Darden, and Hudson to find the effects of weak selection. We show that the overall effect is given by an extension to Price's equation: the change in properties such as moments of coalescence times is equal to the covariance between those properties and the fitness of the sample of genes. The distribution of coalescence times differs substantially between allelic classes, even in the absence of selection. However, the average coalescence time between randomly chosen genes is insensitive to the current allele frequency and is affected significantly by purifying selection only if deleterious mutations are common and selection is strong (i.e., the product of population size and selection coefficient, Ns > 3). Balancing selection increases mean coalescence times, but the effect becomes large only when mutation rates between allelic classes are low and when selection is extremely strong. Our analysis supports previous simulations that show that selection has surprisingly little effect on genealogies. Moreover, small fluctuations in allele frequency due to random drift can greatly reduce any such effects. This will make it difficult to detect the action of selection from neutral variation alone.}, author = {Nicholas Barton and Etheridge, Alison M}, journal = {Genetics}, number = {2}, pages = {1115 -- 1131}, publisher = {Genetics Society of America}, title = {{The effect of selection on genealogies}}, doi = {10.1534/genetics.166.2.1115}, volume = {166}, year = {2004}, } @misc{3616, author = {Nicholas Barton}, booktitle = {Current Biology}, number = {15}, pages = {R603 -- R604}, publisher = {Cell Press}, title = {{Speciation: Why, how, where and when?}}, doi = {10.1016/j.cub.2004.07.037}, volume = {14}, year = {2004}, } @inproceedings{3688, abstract = {Capturing images of documents using handheld digital cameras has a variety of applications in academia, research, knowledge management, retail, and office settings. The ultimate goal of such systems is to achieve image quality comparable to that currently achieved with flatbed scanners even for curved, warped, or curled pages. This can be achieved by high-accuracy 3D modeling of the page surface, followed by a "flattening" of the surface. A number of previous systems have either assumed only perspective distortions, or used techniques like structured lighting, shading, or side-imaging for obtaining 3D shape. This paper describes a system for handheld camera-based document capture using general purpose stereo vision methods followed by a new document dewarping technique. Examples of shape modeling and dewarping of book images is shown.}, author = {Ulges, Adrian and Christoph Lampert and Breuel,Thomas M}, pages = {198 -- 200}, publisher = {ACM}, title = {{Document capture using stereo vision}}, doi = {10.1145/1030397.1030434}, year = {2004}, } @article{3810, abstract = {Voltage-gated potassium (Kv) channels control action potential repolarization, interspike membrane potential, and action potential frequency in excitable cells. It is thought that the combinatorial association between distinct alpha and beta subunits determines whether Kv channels function as non-inactivating delayed rectifiers or as rapidly inactivating A-type channels. We show that membrane lipids can convert A-type channels into delayed rectifiers and vice versa. Phosphoinositides remove N-type inactivation from A-type channels by immobilizing the inactivation domains. Conversely, arachidonic acid and its amide anandamide endow delayed rectifiers with rapid voltage-dependent inactivation. The bidirectional control of Kv channel gating by lipids may provide a mechanism for the dynamic regulation of electrical signaling in the nervous system.}, author = {Oliver, Dominik and Lien, Cheng-Chang and Soom, Malle and Baukrowitz, Thomas and Peter Jonas and Fakler, Bernd}, journal = {Science}, number = {5668}, pages = {265 -- 70}, publisher = {American Association for the Advancement of Science}, title = {{Functional conversion between A-type and delayed rectifier K+ channels by membrane lipids}}, doi = {10.1126/science.1094113}, volume = {304}, year = {2004}, } @inproceedings{3894, abstract = {We study infinite stochastic games played by n-players on a finite graph with goals given by sets of infinite traces. The games are stochastic (each player simultaneously and independently chooses an action at each round, and the next state is determined by a probability distribution depending on the current state and the chosen actions), infinite (the game continues for an infinite number of rounds), nonzero sum (the players' goals are not necessarily conflicting), and undiscounted. We show that if each player has a reachability objective, that is, if the goal for each player i is to visit some subset R-i of the states, then there exists an epsilon-Nash equilibrium in memoryless strategies, for every epsilon > 0. However, exact Nash equilibria need not exist. We study the complexity of finding such Nash equilibria, and show that the payoff of some epsilon-Nash equilibrium in memoryless strategies can be epsilon-approximated in NP. We study the important subclass of n-player turn-based probabilistic games, where at each state at most one player has a nontrivial choice of moves. For turn-based probabilistic games, we show the existence of epsilon-Nash equilibria in pure strategies for games where the objective of player i is a Borel set B-i of infinite traces. However, exact Nash equilibria may not exist. For the special case of omega-regular objectives, we show exact Nash equilibria exist, and can be computed in NP when the omega-regular objectives are expressed as parity objectives.}, author = {Krishnendu Chatterjee and Majumdar, Ritankar S and Jurdziński, Marcin}, pages = {26 -- 40}, publisher = {Springer}, title = {{On Nash equilibria in stochastic games}}, doi = {10.1007/978-3-540-30124-0_6}, volume = {3210}, year = {2004}, } @inproceedings{3895, abstract = {In 2-player non-zero-sum games, Nash equilibria capture the options for rational behavior if each player attempts to maximize her payoff. In contrast to classical game theory, we consider lexicographic objectives: first, each player tries to maximize her own payoff, and then, the player tries to minimize the opponent's payoff. Such objectives arise naturally in the verification of systems with multiple components. There, instead of proving that each component satisfies its specification no matter how the other components behave, it often suffices to prove that each component satisfies its specification provided that the other components satisfy their specifications. We say that a Nash equilibrium is secure if it is an equilibrium with respect to the lexicographic objectives of both players. We prove that in graph games with Borel objectives, which include the games that arise in verification, there may be several Nash equilibria, but there is always a unique maximal payoff profile of secure equilibria. We show how this equilibrium can be computed in the case of omega-regular objectives, and we characterize the memory requirements of strategies that achieve the equilibrium.}, author = {Krishnendu Chatterjee and Thomas Henzinger and Jurdziński, Marcin}, pages = {160 -- 169}, publisher = {IEEE}, title = {{Games with secure equilibria}}, doi = {10.1109/LICS.2004.1319610}, year = {2004}, } @article{3931, abstract = {Hyaluronan is an unsulfated glycosaminoglycan (GAG) that is ubiquitously expressed in the extracellular matrix (ECM) of all vertebrates, where hyaluronan rich matrices constitute a particular permissive environment for the development of complex biological structures and also for tumor progression. Because of its conserved structure and ubiquitous expression, antibodies for its histochemical detection cannot be produced. We have engineered a fusion protein, neurocan-GFP, and expressed it as a secreted molecule in mammalian cells. Neurocan-GFP fusion protein specifically binds to hyaluronan and directly visualizes hyaluronan on tissue sections, revealing a very detailed picture of hyaluronan distribution. The fluorescent fusion protein can be used in combination with antibodies and nuclear markers for double or triple staining. In addition, it is suitable to visualize hyaluronan on living cells by time-lapse video microscopy. The successful production and application of the neurocan-GFP fusion protein opens up new perspectives for using GFP fusion proteins as detection tools in histological and cytological studies complementing conventional antibody and biotin/avidin techniques.}, author = {Zhang, Hui and Baader, Stephan L and Michael Sixt and Kappler, Joachim and Rauch, Uwe}, journal = {Journal of Histochemistry and Cytochemistry}, number = {7}, pages = {915 -- 922}, publisher = {Histochemical Society}, title = {{Neurocan-GFP fusion protein: a new approach to detect hyaluronan on tissue sections and living cells}}, doi = {10.1369/jhc.3A6221.2004}, volume = {52}, year = {2004}, } @article{3929, abstract = {The Nef protein of human and simian immunodeficiency virus (HIV/SIV) is believed to interfere with T cell activation signals by forming a signaling complex at the plasma membrane. Composition and function of the complex are not fully understood. Here we report that Nef recruits the Polycomb Group (PcG) protein Eed, so far known as a nuclear factor and repressor of transcription, to the membrane of cells. The Nef-induced translocation of Eed led to a potent stimulation of Tat-dependent HIV transcription, implying that Eed removal from the nucleus is required for optimal Tat function. Similar to Nef action, activation of integrin receptors recruited Eed to the plasma membrane, also leading to enhanced Tat/Nef-mediated transcription. Our results suggest a link between membrane-associated activation processes and transcriptional derepression and demonstrate how HIV exploits this mechanism.}, author = {Witte, Vanessa and Laffert, Bernd and Rosorius, Olaf and Lischka, Peter and Blume, Katja and Galler, Gunther and Stilper, Andrea and Willbold, Dieter and D'Aloja, Paola and Michael Sixt and Kolanus, Johanna and Ott, Melanie and Kolanus, Waldemar and Schuler, Gerold and Baur, Andreas S}, journal = {Molecular Cell}, number = {2}, pages = {179 -- 190}, publisher = {Cell Press}, title = {{HIV-1 Nef mimics an integrin receptor signal that recruits the polycomb group protein Eed to the plasma membrane}}, doi = {10.1016/S1097-2765(04)00004-8}, volume = {13}, year = {2004}, } @article{3990, abstract = {The writhing number measures the global geometry of a closed space curve or knot. We show that this measure is related to the average winding number of its Gauss map. Using this relationship, we give an algorithm for computing the writhing number for a polygonal knot with n edges in time roughly proportional to n(1.6). We also implement a different, simple algorithm and provide experimental evidence for its practical efficiency.}, author = {Agarwal, Pankaj K and Herbert Edelsbrunner and Wang, Yusu}, journal = {Discrete & Computational Geometry}, number = {1}, pages = {37 -- 53}, publisher = {Springer}, title = {{Computing the writhing number of a polygonal knot}}, doi = {10.1007/s00454-004-2864-x}, volume = {32}, year = {2004}, } @article{4224, abstract = {Developing cells acquire positional information by reading the graded distribution of morphogens. In Drosophila, the Dpp morphogen forms a long-range concentration gradient by spreading from a restricted source in the developing wing. It has been assumed that Dpp spreads by extracellular diffusion. Under this assumption, the main role of endocytosis in gradient formation is to downregulate receptors at the cell surface. These surface receptors bind to the ligand and thereby interfere with its long-range movement. Recent experiments indicate that Dpp spreading is mediated by Dynamin-dependent endocytosis in the target tissue, suggesting that extracellular diffusion alone cannot account for Dpp dispersal. Here, we perform a theoretical study of a model for morphogen spreading based on extracellular diffusion, which takes into account receptor binding and trafficking. We compare profiles of ligand and surface receptors obtained in this model with experimental data. To this end, we monitored directly the pool of surface receptors and extracellular Dpp with specific antibodies. We conclude that current models considering pure extracellular diffusion cannot explain the observed role of endocytosis during Dpp long-range movement.}, author = {Kruse, Karsten and Pantazis, Periklis and Bollenbach, Mark Tobias and Julicher, Frank and Gonzalez Gaitan, Marcos}, journal = {Development}, number = {19}, pages = {4843 -- 4856}, publisher = {Company of Biologists}, title = {{Dpp gradient formation by dynamin-dependent endocytosis: receptor trafficking and the diffusion model}}, doi = {10.1242/dev.01335}, volume = {131}, year = {2004}, } @inbook{4239, author = {Harold Vladar and Cipriani, Roberto and Scharifker, Benjamin and Bubis, Jose}, booktitle = {Life in the Universe From the Miller Experiment to the Search for Life on Other Worlds}, editor = {Seckbach,J. and Chela-Flores,J. and Owen,T. and Raulin,F.}, pages = {83 -- 87}, publisher = {Springer}, title = {{A Mechanism for the Prebiotic Emergence of Proteins}}, doi = {3807}, volume = {7}, year = {2004}, } @article{4253, abstract = {We consider a single genetic locus which carries two alleles, labelled P and Q. This locus experiences selection and mutation. It is linked to a second neutral locus with recombination rate r. If r = 0, this reduces to the study of a single selected locus. Assuming a Moran model for the population dynamics, we pass to a diffusion approximation and, assuming that the allele frequencies at the selected locus have reached stationarity, establish the joint generating function for the genealogy of a sample from the population and the frequency of the P allele. In essence this is the joint generating function for a coalescent and the random background in which it evolves. We use this to characterize, for the diffusion approximation, the probability of identity in state at the neutral locus of a sample of two individuals (whose type at the selected locus is known) as solutions to a system of ordinary differential equations. The only subtlety is to find the boundary conditions for this system. Finally, numerical examples are presented that illustrate the accuracy and predictions of the diffusion approximation. In particular, a comparison is made between this approach and one in which the frequencies at the selected locus are estimated by their value in the absence of fluctuations and a classical structured coalescent model is used.}, author = {Nicholas Barton and Etheridge, Alison M and Sturm, Anja K}, journal = {Annals of Applied Probability}, number = {2}, pages = {754 -- 785}, publisher = {Institute of Mathematical Statistics}, title = {{Coalescence in a Random Background}}, volume = {14}, year = {2004}, } @misc{3142, abstract = {Assembly of neuronal circuits is controlled by the sequential acquisition of neuronal subpopulation-specific identities at progressive developmental steps. Whereas neuronal features involved in initial phases of differentiation are already established at cell-cycle exit, recent findings, based mainly on work in the peripheral nervous system, suggest that the timely integration of signals encountered en route to targets and from the target region itself is essential to control late steps in connectivity. As neurons project towards their targets they require target-derived signals to establish mature axonal projections and acquire neuronal traits such as the expression of distinct combinations of neurotransmitters. Recent evidence presented in this review shows that this principle, of a signaling interplay between target-derived signals and neuronal cell bodies, is often mediated through transcriptional events and is evolutionarily conserved.}, author = {Simon Hippenmeyer and Kramer, Ina and Arber, Silvia}, booktitle = {Trends in Neurosciences}, number = {8}, pages = {482 -- 488}, publisher = {Elsevier}, title = {{Control of neuronal phenotype: What targets tell the cell bodies}}, doi = {10.1016/j.tins.2004.05.012}, volume = {27}, year = {2004}, } @article{3178, abstract = {Minimum cut/maximum flow algorithms on graphs have emerged as an increasingly useful tool for exactor approximate energy minimization in low-level vision. The combinatorial optimization literature provides many min-cut/max-flow algorithms with different polynomial time complexity. Their practical efficiency, however, has to date been studied mainly outside the scope of computer vision. The goal of this paper is to provide an experimental comparison of the efficiency of min-cut/max flow algorithms for applications in vision. We compare the running times of several standard algorithms, as well as a new algorithm that we have recently developed. The algorithms we study include both Goldberg-Tarjan style "push -relabel" methods and algorithms based on Ford-Fulkerson style "augmenting paths." We benchmark these algorithms on a number of typical graphs in the contexts of image restoration, stereo, and segmentation. In many cases, our new algorithm works several times faster than any of the other methods, making near real-time performance possible. An implementation of our max-flow/min-cut algorithm is available upon request for research purposes.}, author = {Boykov, Yuri and Vladimir Kolmogorov}, journal = {IEEE Transactions on Pattern Analysis and Machine Intelligence}, number = {9}, pages = {1124 -- 1137}, publisher = {IEEE}, title = {{An experimental comparison of min-cut/max-flow algorithms for energy minimization in vision}}, doi = {10.1109/TPAMI.2004.60}, volume = {26}, year = {2004}, } @article{3173, abstract = {In the last few years, several new algorithms based on graph cuts have been developed to solve energy minimization problems in computer vision. Each of these techniques constructs a graph such that the minimum cut on the graph also minimizes the energy. Yet, because these graph constructions are complex and highly specific to a particular energy function, graph cuts have seen limited application to date. In this paper, we give a characterization of the energy functions that can be minimized by graph cuts. Our results are restricted to functions of binary variables. However, our work generalizes many previous constructions and is easily applicable to vision problems that involve large numbers of labels, such as stereo, motion, image restoration, and scene reconstruction. We give a precise characterization of what energy functions can be minimized using graph cuts, among the energy functions that can be written as a sum of terms containing three or fewer binary variables. We also provide a general-purpose construction to minimize such an energy function. Finally, we give a necessary condition for any energy function of binary variables to be minimized by graph cuts. Researchers who are considering the use of graph cuts to optimize a particular energy function can use our results to determine if this is possible and then follow our construction to create the appropriate graph. A software implementation is freely available.}, author = {Vladimir Kolmogorov and Zabih, Ramin}, journal = {IEEE Transactions on Pattern Analysis and Machine Intelligence}, number = {2}, pages = {147 -- 159}, publisher = {IEEE}, title = {{What energy functions can be minimized via graph cuts? }}, doi = {10.1109/TPAMI.2004.1262177}, volume = {26}, year = {2004}, } @article{3172, abstract = {The simultaneous multiple volume (SMV) approach in navigator-gated MRI allows the use of the whole motion range or the entire scan time for the reconstruction of final images by simultaneously acquiring different image volumes at different motion states. The motion tolerance range for each volume is kept small, thus SMV substantially increases the scan efficiency of navigator methods while maintaining the effectiveness of motion suppression. This article reports a general implementation of the SMV approach using a multiprocessor scheduling algorithm. Each motion state is regarded as a processor and each volume is regarded as a job. An efficient scheduling that completes all jobs in minimal time is maintained even when the motion pattern changes. Initial experiments demonstrated that SMV significantly increased the scan efficiency of navigatorgated MRI.}, author = {Vladimir Kolmogorov and Nguyen, Thành D and Nuval, Anthony and Spincemaille, Pascal and Prince, Martin R and Zabih, Ramin and Wang, Yusu}, journal = {Magnetic Resonance in Medicine}, number = {2}, pages = {362 -- 367}, publisher = {Wiley-Blackwell}, title = {{Multiprocessor scheduling implementation of the simultaneous multiple volume SMV navigator method}}, doi = {10.1002/mrm.20162}, volume = {52}, year = {2004}, } @inproceedings{3177, abstract = {Feature space clustering is a popular approach to image segmentation, in which a feature vector of local properties (such as intensity, texture or motion) is computed at each pixel. The feature space is then clustered, and each pixel is labeled with the cluster that contains its feature vector. A major limitation of this approach is that feature space clusters generally lack spatial coherence (i.e., they do not correspond to a compact grouping of pixels). In this paper, we propose a segmentation algorithm that operates simultaneously in feature space and in image space. We define an energy function over both a set of clusters and a labeling of pixels with clusters. In our framework, a pixel is labeled with a single cluster (rather than, for example, a distribution over clusters). Our energy function penalizes clusters that are a poor fit to the data in feature space, and also penalizes clusters whose pixels lack spatial coherence. The energy function can be efficiently minimized using graph cuts. Our algorithm can incorporate both parametric and non-parametric clustering methods. It can be applied to many optimization-based clustering methods, including k-means and k-medians, and can handle models which are very close in feature space. Preliminary results are presented on segmenting real and synthetic images, using both parametric and non-parametric clustering.}, author = {Zabih, Ramin and Vladimir Kolmogorov}, pages = {437 -- 444}, publisher = {IEEE}, title = {{Spatially coherent clustering using graph cuts}}, doi = {10.1109/CVPR.2004.1315196}, volume = {2}, year = {2004}, } @inproceedings{3179, abstract = {The problem of efficient, interactive foreground/background segmentation in still images is of great practical importance in image editing. Classical image segmentation tools use either texture (colour) information, e.g. Magic Wand, or edge (contrast) information, e.g. Intelligent Scissors. Recently, an approach based on optimization by graph-cut has been developed which successfully combines both types of information. In this paper we extend the graph-cut approach in three respects. First, we have developed a more powerful, iterative version of the optimisation. Secondly, the power of the iterative algorithm is used to simplify substantially the user interaction needed for a given quality of result. Thirdly, a robust algorithm for "border matting" has been developed to estimate simultaneously the alpha-matte around an object boundary and the colours of foreground pixels. We show that for moderately difficult examples the proposed method outperforms competitive tools.}, author = {Rother, Carsten and Vladimir Kolmogorov and Blake, Andrew}, number = {3}, pages = {309 -- 314}, publisher = {ACM}, title = {{"GrabCut" - Interactive foreground extraction using iterated graph cuts }}, doi = {10.1145/1015706.1015720}, volume = {23}, year = {2004}, } @article{3420, abstract = {Single-molecule force-spectroscopy was employed to unfold and refold single sodium-proton antiporters (NhaA) of Escherichia coli from membrane patches. Although transmembrane α-helices and extracellular polypeptide loops exhibited sufficient stability to individually establish potential barriers against unfolding, two helices predominantly unfolded pairwise, thereby acting as one structural unit. Many of the potential barriers were detected unfolding NhaA either from the C-terminal or the N-terminal end. It was found that some molecular interactions stabilizing secondary structural elements were directional, while others were not. Additionally, some interactions appeared to occur between the secondary structural elements. After unfolding ten of the 12 helices, the extracted polypeptide was allowed to refold back into the membrane. After five seconds, the refolded polypeptide established all secondary structure elements of the native protein. One helical pair showed a characteristic spring like “snap in” into its folded conformation, while the refolding process of other helices was not detected in particular. Additionally, individual helices required characteristic periods of time to fold. Correlating these results with the primary structure of NhaA allowed us to obtain the first insights into how potential barriers establish and determine the folding kinetics of the secondary structure elements.}, author = {Kedrov, Alexej and Ziegler, Christine and Harald Janovjak and Kühlbrandt, Werner and Mueller, Daniel J}, journal = {Journal of Molecular Biology}, number = {5}, pages = {1143 -- 1152}, publisher = {Elsevier}, title = {{Controlled unfolding and refolding of a single sodium/proton antiporter using atomic force microscopy}}, doi = {10.1016/j.jmb.2004.05.026}, volume = {340}, year = {2004}, } @article{3419, abstract = {The folding and stability of transmembrane proteins is a fundamental and unsolved biological problem. Here, single bacteriorhodopsin molecules were mechanically unfolded from native purple membranes using atomic force microscopy and force spectroscopy. The energy landscape of individual transmembrane α helices and polypeptide loops was mapped by monitoring the pulling speed dependence of the unfolding forces and applying Monte Carlo simulations. Single helices formed independently stable units stabilized by a single potential barrier. Mechanical unfolding of the helices was triggered by 3.9–7.7 Å extension, while natural unfolding rates were of the order of 10−3 s−1. Besides acting as individually stable units, helices associated pairwise, establishing a collective potential barrier. The unfolding pathways of individual proteins reflect distinct pulling speed-dependent unfolding routes in their energy landscapes. These observations support the two-stage model of membrane protein folding in which α helices insert into the membrane as stable units and then assemble into the functional protein.}, author = {Harald Janovjak and Struckmeier, Jens and Hubain, Maurice and Kessler, Max and Kedrov, Alexej and Mueller, Daniel J}, journal = {Structure}, number = {5}, pages = {871 -- 879}, publisher = {Cell Press}, title = {{Probing the energy landscape of the membrane protein bacteriorhodopsin}}, doi = {10.1016/j.str.2004.03.016}, volume = {12}, year = {2004}, } @inbook{3575, abstract = {The Jacobi set of two Morse functions defined on a common - manifold is the set of critical points of the restrictions of one func- tion to the level sets of the other function. Equivalently, it is the set of points where the gradients of the functions are parallel. For a generic pair of Morse functions, the Jacobi set is a smoothly embed- ded 1-manifold. We give a polynomial-time algorithm that com- putes the piecewise linear analog of the Jacobi set for functions specified at the vertices of a triangulation, and we generalize all results to more than two but at most Morse functions.}, author = {Herbert Edelsbrunner and Harer, John}, booktitle = {Foundations of Computational Mathematics}, pages = {37 -- 57}, publisher = {Springer}, title = {{Jacobi sets of multiple Morse functions}}, doi = {10.1017/CBO9781139106962.003}, volume = {312}, year = {2004}, } @inbook{3574, author = {Herbert Edelsbrunner}, booktitle = {Handbook of Discrete and Computational Geometry}, pages = {1395 -- 1412}, publisher = {CRC Press}, title = {{Biological applications of computational topology}}, year = {2004}, } @misc{3595, abstract = {Genome sizes vary enormously. This variation in DNA content correlates with effective population size, suggesting that deleterious additions to the genome can accumulate in small populations. On this view, the increased complexity of biological functions associated with large genomes partly reflects evolutionary degeneration.}, author = {Charlesworth, Brian and Nicholas Barton}, booktitle = {Current Biology}, number = {6}, pages = {R233 -- R235}, publisher = {Cell Press}, title = {{Genome size: Does bigger mean worse?}}, doi = {10.1016/j.cub.2004.02.054}, volume = {14}, year = {2004}, } @article{3614, abstract = {We analyze the changes in the mean and variance components of a quantitative trait caused by changes in allele frequencies, concentrating on the effects of genetic drift. We use a general representation of epistasis and dominance that allows an arbitrary relation between genotype and phenotype for any number of diallelic loci. We assume initial and final Hardy-Weinberg and linkage equilibrium in our analyses of drift-induced changes. Random drift generates transient linkage disequilibria that cause correlations between allele frequency fluctuations at different loci. However, we show that these have negligible effects, at least for interactions among small numbers of loci. Our analyses are based on diffusion approximations that summarize the effects of drift in terms of F, the inbreeding coefficient, interpreted as the expected proportional decrease in heterozygosity at each locus. For haploids, the variance of the trait mean after a population bottleneck is var(Δz̄) =inline imagewhere n is the number of loci contributing to the trait variance, VA(1)=VA is the additive genetic variance, and VA(k) is the kth-order additive epistatic variance. The expected additive genetic variance after the bottleneck, denoted (V*A), is closely related to var(Δz̄); (V*A) (1 –F)inline imageThus, epistasis inflates the expected additive variance above VA(1 –F), the expectation under additivity. For haploids (and diploids without dominance), the expected value of every variance component is inflated by the existence of higher order interactions (e.g., third-order epistasis inflates (V*AA)). This is not true in general with diploidy, because dominance alone can reduce (V*A) below VA(1 –F) (e.g., when dominant alleles are rare). Without dominance, diploidy produces simple expressions: var(Δz̄)=inline image=1 (2F) kVA(k) and (V*A) = (1 –F)inline imagek(2F)k-1VA(k) With dominance (and even without epistasis), var(Δz̄)and (V*A) no longer depend solely on the variance components in the base population. For small F, the expected additive variance simplifies to (V*A)(1 –F) VA+ 4FVAA+2FVD+2FCAD, where CAD is a sum of two terms describing covariances between additive effects and dominance and additive × dominance interactions. Whether population bottlenecks lead to expected increases in additive variance depends primarily on the ratio of nonadditive to additive genetic variance in the base population, but dominance precludes simple predictions based solely on variance components. We illustrate these results using a model in which genotypic values are drawn at random, allowing extreme and erratic epistatic interactions. Although our analyses clarify the conditions under which drift is expected to increase VA, we question the evolutionary importance of such increases.}, author = {Nicholas Barton and Turelli, Michael}, journal = {Evolution; International Journal of Organic Evolution}, number = {10}, pages = {2111 -- 2132}, publisher = {Wiley-Blackwell}, title = {{Effects of allele frequency changes on variance components under a general model of epistasis}}, doi = {10.1111/j.0014-3820.2004.tb01591.x}, volume = {58}, year = {2004}, } @article{3615, abstract = {We investigate three alternative selection-based scenarios proposed to maintain polygenic variation: pleiotropic balancing selection, G x E interactions (with spatial or temporal variation in allelic effects), and sex-dependent allelic effects. Each analysis assumes an additive polygenic trait with n diallelic loci under stabilizing selection. We allow loci to have different effects and consider equilibria at which the population mean departs from the stabilizing-selection optimum. Under weak selection, each model produces essentially identical, approximate allele-frequency dynamics. Variation is maintained under pleiotropic balancing selection only at loci for which the strength of balancing selection exceeds the effective strength of stabilizing selection. In addition, for all models, polymorphism requires that the population mean be close enough to the optimum that directional selection does not overwhelm balancing selection. This balance allows many simultaneously stable equilibria, and we explore their properties numerically. Both spatial and temporal G x E can maintain variation at loci for which the coefficient of variation (across environments) of the effect of a substitution exceeds a critical value greater than one. The critical value depends on the correlation between substitution effects at different loci. For large positive correlations (e.g., ρ2ij > 3/4), even extreme fluctuations in allelic effects cannot maintain variation. Surprisingly, this constraint on correlations implies that sex-dependent allelic effects cannot maintain polygenic variation. We present numerical results that support our analytical approximations and discuss our results in connection to relevant data and alternative variance-maintaining mechanisms.}, author = {Turelli, Michael and Nicholas Barton}, journal = {Genetics}, number = {2}, pages = {1053 -- 1079}, publisher = {Genetics Society of America}, title = {{Polygenic variation maintained by balancing selection: pleiotropy, sex-dependent allelic effects and GxE interactions}}, doi = {10.1534/genetics.166.2.1053}, volume = {166}, year = {2004}, } @article{3807, abstract = {The time course of Mg(2+) block and unblock of NMDA receptors (NMDARs) determines the extent they are activated by depolarization. Here, we directly measure the rate of NMDAR channel opening in response to depolarizations at different times after brief (1 ms) and sustained (4.6 s) applications of glutamate to nucleated patches from neocortical pyramidal neurons. The kinetics of Mg(2+) unblock were found to be non-instantaneous and complex, consisting of a prominent fast component (time constant approximately 100 micros) and slower components (time constants 4 and approximately 300 ms), the relative amplitudes of which depended on the timing of the depolarizing pulse. Fitting a kinetic model to these data indicated that Mg(2+) not only blocks the NMDAR channel, but reduces both the open probability and affinity for glutamate, while enhancing desensitization. These effects slow the rate of NMDAR channel opening in response to depolarization in a time-dependent manner such that the slower components of Mg(2+) unblock are enhanced during depolarizations at later times after glutamate application. One physiological consequence of this is that brief depolarizations occurring earlier in time after glutamate application are better able to open NMDAR channels. This finding has important implications for spike-timing-dependent synaptic plasticity (STDP), where the precise (millisecond) timing of action potentials relative to synaptic inputs determines the magnitude and sign of changes in synaptic strength. Indeed, we find that STDP timing curves of NMDAR channel activation elicited by realistic dendritic action potential waveforms are narrower than expected assuming instantaneous Mg(2+) unblock, indicating that slow Mg(2+) unblock of NMDAR channels makes the STDP timing window more precise.}, author = {Kampa, Bjorn M and Clements, John and Peter Jonas and Stuart, Greg J}, journal = {Journal of Physiology}, number = {Pt 2}, pages = {337 -- 45}, publisher = {Wiley-Blackwell}, title = {{Kinetics of Mg(2+) unblock of NMDA receptors: implications for spike-timing dependent synaptic plasticity}}, doi = {10.1113/jphysiol.2003.058842 }, volume = {556}, year = {2004}, } @article{3809, abstract = {Neural stem cells in various regions of the vertebrate brain continuously generate neurons throughout life. In the mammalian hippocampus, a region important for spatial and episodic memory, thousands of new granule cells are produced per day, with the exact number depending on environmental conditions and physical exercise. The survival of these neurons is improved by learning and conversely learning may be promoted by neurogenesis. Although it has been suggested that newly generated neurons may have specific properties to facilitate learning, the cellular and synaptic mechanisms of plasticity in these neurons are largely unknown. Here we show that young granule cells in the adult hippocampus differ substantially from mature granule cells in both active and passive membrane properties. In young neurons, T-type Ca2+ channels can generate isolated Ca2+ spikes and boost fast Na+ action potentials, contributing to the induction of synaptic plasticity. Associative long-term potentiation can be induced more easily in young neurons than in mature neurons under identical conditions. Thus, newly generated neurons express unique mechanisms to facilitate synaptic plasticity, which may be important for the formation of new memories.}, author = {Schmidt-Hieber, Christoph and Peter Jonas and Bischofberger, Josef}, journal = {Nature}, number = {6988}, pages = {184 -- 7}, publisher = {Nature Publishing Group}, title = {{Enhanced synaptic plasticity in newly generated granule cells of the adult hippocampus}}, doi = {10.1038/nature02553}, volume = {429}, year = {2004}, } @article{3805, abstract = {The operation of neuronal networks crucially depends on a fast time course of signaling in inhibitory interneurons. Synapses that excite interneurons generate fast currents, owing to the expression of glutamate receptors of specific subunit composition. Interneurons generate brief action potentials in response to transient synaptic activation and discharge repetitively at very high frequencies during sustained stimulation. The ability to generate short-duration action potentials at high frequencies depends on the expression of specific voltage-gated K+ channels. Factors facilitating fast action potential initiation following synaptic excitation include depolarized interneuron resting potential, subthreshold conductances and active dendrites. Finally, GABA release at interneuron output synapses is rapid and highly synchronized, leading to a faster inhibition in postsynaptic interneurons than in principal cells. Thus, the expression of distinct transmitter receptors and voltage-gated ion channels ensures that interneurons operate with high speed and temporal precision.}, author = {Peter Jonas and Bischofberger, Josef and Fricker, Desdemona and Miles, Richard}, journal = {Trends in Neurosciences}, number = {1}, pages = {30 -- 40}, publisher = {Elsevier}, title = {{Interneuron Diversity series: Fast in, fast out--temporal and spatial signal processing in hippocampal interneurons}}, doi = {doi:10.1016/j.tins.2003.10.010}, volume = {27}, year = {2004}, } @article{3918, abstract = {Wingless (ergatoid) males of the tramp ant Cardiocondyla minutior attack and kill their young ergatoid rivals and thus attempt to monopolize mating with female sexuals reared in the colony. Because of the different strength of local mate competition in colonies with one or several reproductive queens, we expected the production of new ergatoid males to vary with queen number. Sex ratios were mostly female-biased, but in contrast to the sympatric species C. obscurior (Cremer and Heinze, 2002) neither the percentage of ergatoid males nor of female sexuals among the first 20 sexuals produced varied considerably with queen number. As in C. obscurior, experimental colony fragmentation led to the production of winged males, whereas in unfragmented control colonies only ergatoid males eclosed.}, author = {Heinze, Jürgen and Böttcher, A. and Cremer, Sylvia}, journal = {Insectes Sociaux}, number = {3}, pages = {275 -- 278}, publisher = {Springer}, title = {{Production of winged and wingless males in the ant, Cardiocondyla minutior}}, doi = {10.1007/s00040-004-0740-6}, volume = {51}, year = {2004}, } @inproceedings{3988, abstract = {We give an algorithm that locally improves the fit between two proteins modeled as space-filling diagrams. The algorithm defines the fit in purely geometric terms and improves by applying a rigid motion to one of the two proteins. Our implementation of the algorithm takes between three and ten seconds and converges with high likelihood to the correct docked configuration, provided it starts at a position away from the correct one by at most 18 degrees of rotation and at most 3.0Angstrom of translation. The speed and convergence radius make this an attractive algorithm to use in combination with a coarse sampling of the six-dimensional space of rigid motions.}, author = {Choi, Vicky and Agarwal, Pankaj K and Herbert Edelsbrunner and Rudolph, Johannes}, pages = {218 -- 229}, publisher = {Springer}, title = {{Local search heuristic for rigid protein docking}}, doi = {10.1007/978-3-540-30219-3_19}, volume = {3240}, year = {2004}, } @article{3986, abstract = {The motion of a biomolecule greatly depends on the engulfing solution, which is mostly water. Instead of representing individual water molecules, it is desirable to develop implicit solvent models that nevertheless accurately represent the contribution of the solvent interaction to the motion. In such models, hydrophobicity is expressed as a weighted sum of atomic surface areas. The derivatives of these weighted areas contribute to the force that drives the motion. In this paper we give formulas for the weighted and unweighted area derivatives of a molecule modeled as a space-filling diagram made up of balls in motion. Other than the radii and the centers of the balls, the formulas are given in terms of the sizes of circular arcs of the boundary and edges of the power diagram. We also give inclusion-exclusion formulas for these sizes.}, author = {Bryant, Robert and Herbert Edelsbrunner and Koehl, Patrice and Levitt, Michael}, journal = {Discrete & Computational Geometry}, number = {3}, pages = {293 -- 308}, publisher = {Springer}, title = {{The area derivative of a space-filling diagram}}, doi = {10.1007/s00454-004-1099-1}, volume = {32}, year = {2004}, }