TY - JOUR AB - About 20% of the world's population uses the Web, and a large majority thereof uses Web search engines to find information. As a result, many Web researchers are devoting much effort to improving the speed and capability of search technology. AU - Henzinger, Monika H ID - 11884 IS - 5837 JF - Science SN - 0036-8075 TI - Search technologies for the internet VL - 317 ER - TY - CONF AB - How much can smart combinatorial algorithms improve web search engines? To address this question we will describe three algorithms that have had a positive impact on web search engines: The PageRank algorithm, algorithms for finding near-duplicate web pages, and algorithms for index server loadbalancing. AU - Henzinger, Monika H ID - 11924 SN - 9780898716245 T2 - 18th Annual ACM-SIAM Symposium on Discrete Algorithms TI - Combinatorial algorithms for web search engines: three success stories ER - TY - JOUR AB - A 671 nm diode laser with a mode-hop-free tuning range of 40 GHz is described. This long tuning range is achieved by simultaneously ramping the external cavity length with the laser injection current. The laser output pointing remains fixed, independent of its frequency because of the cover slip cavity design. This system is simple, economical, robust, and easy to use for spectroscopy, as we demonstrate with lithium vapor and lithium atom beam experiments. AU - Carr, Adra AU - Serchest, Yancey AU - Waitukaitis, Scott R AU - Perreault, John AU - Lonij, Vincent AU - Cronin, Alexander ID - 128 IS - 10 JF - Review of Scientific Instruments TI - Cover slip external cavity diode laser VL - 78 ER - TY - JOUR AB - In flies, the large tangential cells of the lobula plate represent an important processing center for visual navigation based on optic flow. Although the visual response properties of these cells have been well studied in blowflies, information on their synaptic organization is mostly lacking. Here we study the distribution of presynaptic release and postsynaptic inhibitory sites in the same set of cells in Drosophila melanogaster. By making use of transgenic tools and immunohistochemistry, our results suggest that HS and VS cells of Drosophila express γ-aminobutyric acid (GABA) receptors in their dendritic region within the lobula plate, thus being postsynaptic to inhibitory input there. At their axon terminals in the protocerebrum, both cell types express synaptobrevin, suggesting the presence of presynaptic specializations there. HS- and VS-cell terminals additionally show evidence for postsynaptic GABAergic input, superimposed on this synaptic polarity. Our findings are in line with the general circuit for visual motion detection and receptive field properties as postulated from electrophysiological and optical recordings in blowflies, suggesting a similar functional organization of lobula plate tangential cells in the two species. AU - Raghu, Shamprasad V AU - Maximilian Jösch AU - Borst, Alexander AU - Reiff, Dierk F ID - 1297 IS - 4 JF - Journal of Comparative Neurology TI - Synaptic organization of lobula plate tangential cells in Drosophila: γ-aminobutyric acid receptors and chemical release sites VL - 502 ER - TY - CHAP AB - This book contains research articles on Diophantine Geometry, written by participants of a research program held at the Ennio De Giorgi Mathematical Research Center in Pisa, Italy, during the period April – July 2005. The authors are eminent experts in the field. Several subfields of the main topic are presented; the volume thus is particularly useful to get a broad overview of recent research developments. AU - Browning, Timothy D AU - Heath Brown, Roger ED - Zannier, Umberto ID - 167 T2 - Diophantine Geometry TI - Simultaneous equal sums of three powers VL - 4 ER - TY - JOUR AB - The authors investigate the composition profile of SiGe islands after capping with Si to form quantum dots, using a two step etching procedure and atomic force microscopy. Initially, the Si capping layers are removed by etching selectively Si over Ge and then the composition of the disclosed islands is addressed by selectively etching Ge over Si. For samples grown at 580 °C the authors show that even when overgrowth leads to a flat Si surface and the islands undergo strong morphological changes, a Ge-rich core region is still preserved in the dot. At high growth and overgrowth temperatures (740 °C), the experiments show that the newly formed base of the buried islands is more Si rich than their top. Furthermore, the authors find that for the growth conditions used, no lateral motion takes place during capping. AU - Georgios Katsaros AU - Stoffel, Mathieu AU - Rastelli, Armando AU - Schmidt, Oliver G AU - Kern, Klaus AU - Tersoff, Jerry ID - 1750 IS - 1 JF - Applied Physics Letters TI - Three-dimensional isocompositional profiles of buried SiGeSi (001) islands VL - 91 ER - TY - JOUR AB - In quantum information science, the phase of a wave function plays an important role in encoding information. Although most experiments in this field rely on dynamic effects to manipulate this information, an alternative approach is to use geometric phase, which has been argued to have potential fault tolerance. We demonstrated the controlled accumulation of a geometric phase, Berry's phase, in a superconducting qubit; we manipulated the qubit geometrically by means of microwave radiation and observed the accumulated phase in an interference experiment. We found excellent agreement with Berry's predictions and also observed a geometry-dependent contribution to dephasing. AU - Leek, Peter J AU - Johannes Fink AU - Blais, Alexandre AU - Bianchetti, R AU - Göppl, M AU - Gambetta, Jay M AU - Schuster, David I AU - Frunzio, Luigi AU - Schoelkopf, Robert J AU - Wallraff, Andreas ID - 1762 IS - 5858 JF - Science TI - Observation of Berry's phase in a solid-state qubit VL - 318 ER - TY - JOUR AB - Intrinsically photosensitive melanopsin-containing retinal ganglion cells (ipRGCs) control important physiological processes, including the circadian rhythm, the pupillary reflex, and the suppression of locomotor behavior (reviewed in [1]). ipRGCs are also activated by classical photoreceptors, the rods and cones, through local retinal circuits [2, 3]. ipRGCs can be transsynaptically labeled through the pupillary-reflex circuit with the derivatives of the Bartha strain of the alphaherpesvirus pseudorabies virus(PRV) [4, 5] that express GFP [6-12]. Bartha-strain derivatives spread only in the retrograde direction [13]. There is evidence that infected cells function normally for a while during GFP expression [7]. Here we combine transsynaptic PRV labeling, two-photon laser microscopy, and electrophysiological techniques to trace the local circuit of different ipRGC subtypes in the mouse retina and record light-evoked activity from the transsynaptically labeled ganglion cells. First, we show that ipRGCs are connected by monostratified amacrine cells that provide strong inhibition from classical-photoreceptor-driven circuits. Second, we show evidence that dopaminergic interplexiform cells are synaptically connected to ipRGCs. The latter finding provides a circuitry link between light-dark adaptation and ipRGC function. AU - Viney, Tim J AU - Bálint, Kamill AU - Hillier, Dániel AU - Sandra Siegert AU - Boldogköi, Zsolt S AU - Enquist, Lynn W AU - Meister, Markus AU - Cepko, Constance L AU - Roska, Botond M ID - 1797 IS - 11 JF - Current Biology TI - Local retinal circuits of melanopsin-containing ganglion cells identified by transsynaptic viral tracing VL - 17 ER - TY - JOUR AB - Respiratory complex I (NADH:ubiquinone oxidoreductase) is an L-shaped multisubunit protein assembly consisting of a hydrophobic membrane arm and a hydrophilic peripheral arm. It catalyses the transfer of two electrons from NADH to quinone coupled to the translocation of four protons across the membrane. Although we have solved recently the crystal structure of the peripheral arm, the structure of the complete enzyme and the coupling mechanism are not yet known. The membrane domain of Escherichia coli complex I consists of seven different subunits with total molecular mass of 258 kDa. It is significantly more stable than the whole enzyme, which allowed us to obtain well-ordered two-dimensional crystals of the domain, belonging to the space group p22121. Comparison of the projection map of negatively stained crystals with previously published low-resolution structures indicated that the characteristic curved shape of the membrane domain is remarkably well conserved between bacterial and mitochondrial enzymes, helping us to interpret projection maps in the context of the intact complex. Two pronounced stain-excluding densities at the distal end of the membrane domain are likely to represent the two large antiporter-like subunits NuoL and NuoM. Cryo-electron microscopy on frozen-hydrated crystals allowed us to calculate a projection map at 8 Å resolution. About 60 transmembrane α-helices, both perpendicular to the membrane plane and tilted, are present within one membrane domain, which is consistent with secondary structure predictions. A possible binding site and access channel for quinone are found at the interface with the peripheral arm. Tentative assignment of individual subunits to the features of the map has been made. The location of subunits NuoL and NuoM at substantial distance from the peripheral arm, which contains all the redox centres of the complex, indicates that conformational changes are likely to play a role in the mechanism of coupling between electron transfer and proton pumping. AU - Baranova, Ekaterina A AU - Holt, Peter J AU - Leonid Sazanov ID - 1965 IS - 1 JF - Journal of Molecular Biology TI - Projection structure of the membrane domain of Escherichia coli respiratory Complex I at 8 Å resolution VL - 366 ER - TY - JOUR AB - Respiratory complex I catalyses the transfer of electrons from NADH to quinone coupled to the translocation of protons across the membrane. The mechanism of coupling and the structure of the complete enzyme are not known. The membrane domain of the complex contains three similar antiporter-like subunits NuoL/M/N, probably involved in proton pumping. We have previously shown that subunits NuoL/M can be removed from the rest of the complex, suggesting their location at the distal end of the membrane domain. Here, using electron microscopy and single particle analysis, we show that subunits NuoL and M jointly occupy a distal half of the membrane domain, separated by about 10 nm from the interface with the peripheral arm. This indicates that coupling mechanism of complex I is likely to involve long range conformational changes. AU - Baranova, Ekaterina A AU - Morgan, David J AU - Leonid Sazanov ID - 1969 IS - 2 SPEC. ISS. JF - Journal of Structural Biology TI - Single particle analysis confirms distal location of subunits NuoL and NuoM in Escherichia coli complex I VL - 159 ER - TY - JOUR AB - Complex I of respiratory chains plays a central role in cellular energy production. Mutations in its subunits lead to many human neurodegenerative diseases. Recently, a first atomic structure of the hydrophilic domain of complex I from Thermus thermophilus was determined. This domain represents a catalytic core of the enzyme. It consists of eight different subunits, contains all the redox centers, and comprises more than half of the entire complex. In this review, novel mechanistic implications of the structure are discussed, and the effects of many known mutations of complex I subunits are interpreted in a structural context. AU - Leonid Sazanov ID - 1964 IS - 9 JF - Biochemistry TI - Respiratory complex I: Mechanistic and structural insights provided by the crystal structure of the hydrophilic domain VL - 46 ER - TY - CONF AB - We present a novel multi-scale representation and acquisition method for the animation of high-resolution facial geometry and wrinkles. We first acquire a static scan of the face including reflectance data at the highest possible quality. We then augment a traditional marker-based facial motion-capture system by two synchronized video cameras to track expression wrinkles. The resulting model consists of high-resolution geometry, motion-capture data, and expression wrinkles in 2D parametric form. This combination represents the facial shape and its salient features at multiple scales. During motion synthesis the motion-capture data deforms the high-resolution geometry using a linear shell-based mesh-deformation method. The wrinkle geometry is added to the facial base mesh using nonlinear energy optimization. We present the results of our approach for performance replay as well as for wrinkle editing. AU - Bernd Bickel AU - Botsch, Mario AU - Angst, Roland AU - Matusik, Wojciech AU - Otaduy, Miguel A AU - Pfister, Hanspeter AU - Groß, Markus S ID - 2091 TI - Multi scale capture of facial geometry and motion ER - TY - JOUR AB - We present a novel multi-scale representation and acquisition method for the animation of high-resolution facial geometry and wrinkles. We first acquire a static scan of the face including reflectance data at the highest possible quality. We then augment a traditional marker-based facial motion-capture system by two synchronized video cameras to track expression wrinkles. The resulting model consists of high-resolution geometry, motion-capture data, and expression wrinkles in 2D parametric form. This combination represents the facial shape and its salient features at multiple scales. During motion synthesis the motion-capture data deforms the high-resolution geometry using a linear shell-based mesh-deformation method. The wrinkle geometry is added to the facial base mesh using nonlinear energy optimization. We present the results of our approach for performance replay as well as for wrinkle editing. AU - Bernd Bickel AU - Botsch, Mario AU - Angst, Roland AU - Matusik, Wojciech AU - Otaduy, Miguel A AU - Pfister, Hanspeter AU - Groß, Markus S ID - 2093 IS - 3 JF - ACM Transactions on Graphics TI - Multi scale capture of facial geometry and motion VL - 26 ER - TY - JOUR AB - We introduce a new appearance-modeling paradigm for synthesizing the internal structure of a 3D model from photographs of a few cross-sections of a real object. When the internal surfaces of the 3D model are revealed as it is cut, carved, or simply clipped, we synthesize their texture from the input photographs. Our texture synthesis algorithm is best classified as a morphing technique, which efficiently outputs the texture attributes of each surface point on demand. For determining source points and their weights in the morphing algorithm, we propose an interpolation domain based on BSP trees that naturally resembles planar splitting of real objects. In the context of the interpolation domain, we define efficient warping and morphing operations that allow for real-time synthesis of textures. Overall, our modeling paradigm, together with its realization through our texture morphing algorithm, allow users to author 3D models that reveal highly realistic internal surfaces in a variety of artistic flavors. AU - Pietroni, Nico AU - Otaduy, Miguel A AU - Bernd Bickel AU - Ganovelli, Fabio AU - Groß, Markus S ID - 2092 IS - 3 JF - Computer Graphics Forum TI - Texturing internal surfaces from a few cross-sections VL - 26 ER - TY - JOUR AB - We extend to infinite dimensions an explicit formula of Chill, Fašangová, Metafune, and Pallara for the optimal angle of analyticity of analytic Ornstein-Uhlenbeck semigroups. The main ingredient is an abstract representation of the Ornstein-Uhlenbeck operator in divergence form. AU - Jan Maas AU - van Neerven, Jan M ID - 2118 IS - 3 JF - Archiv der Mathematik TI - On analytic Ornstein-Uhlenbeck semigroups in infinite dimensions VL - 89 ER - TY - JOUR AB - We use the x-ray absorption fine structure spectroscopy at Nb K edge to reveal the local atomic structure of KxNa1−xNbO3 (PSN) solid solutions. The study is performed over the temperature range 10–1023K for six different x values. We show that only the combined analysis of extended x-ray absorption fine structure and preedge fine structure provides complete and reliable information about the local structure of NbO6 octahedra. Such extensive treatment of the experimental data shows that the local structure of PSN could be described within the spherical model proposed earlier as a hypothesis for perovskite-type ferroelectric zirconates. We reveal that the Nb atoms are localized near their average positions on the sphere surfaces for all temperatures and x values. With regard to previous results we point out the features of microscopic structure common for PSN and perovskite-type zirconates. AU - Mikhail Lemeshko AU - Nazarenko, Elena S AU - Gonchar, A.A AU - Reznichenko, Larisa A AU - Nedoseykina, Tatiana I AU - Novakovich, Alexander A AU - Mathon, Olivier AU - Joly, Yves AU - Vedrinskiǐ, Rostislav V ID - 2135 JF - Physical Review B - Condensed Matter and Materials Physics TI - EXAFS studies of the local atomic structure of the lead-free piezoelectric ceramics KxNa1−xNbO3 over the temperature range 10–1023K VL - 76 ER - TY - JOUR AB - Local atomic structure of the piezoelectric ceramics KxNa 1-xNbO3 (x≤0.00, 0.05, 0.30, 0.40, 0.50 and 0.65) is studied in all phase regions (10 K-1023 K) using Nb K-edge extended X-ray absorption fine-structure (EXAFS) spectroscopy. We have shown the validity of a new spherical model for phase transitions on the basis of both fitting of EXAFS signal in the R-space and differential EXAFS analysis. Within this model the Nb atoms are located on the surfaces of small spheres of constant radii surrounding centers of NbO6 octahedrons in all phases. The distribution of the Nb atom on this surface changes during phase transitions. Besides, the analysis of local structure reveals that the geometry of NbO6 octahedra does not depend on the x value at each temperature, whereas the octahedra rotation angles do. AU - Mikhail Lemeshko AU - Nazarenko, Elena S AU - Gonchar, Anastasia A AU - Reznichenko, Larisa A AU - Mathon, Olivier AU - Joly, Yves AU - Vedrinskiǐ, Rostislav V ID - 2143 IS - 2 JF - EPL TI - Phase transitions in lead-free piezoelectric ceramics: Study of local atomic structure VL - 77 ER - TY - JOUR AB - We use the x-ray absorption fine structure spectroscopy at Nb K edge to reveal the local atomic structure of Kx Na1-x Nb O3 (PSN) solid solutions. The study is performed over the temperature range 10-1023 K for six different x values. We show that only the combined analysis of extended x-ray absorption fine structure and preedge fine structure provides complete and reliable information about the local structure of Nb O6 octahedra. Such extensive treatment of the experimental data shows that the local structure of PSN could be described within the spherical model proposed earlier as a hypothesis for perovskite-type ferroelectric zirconates. We reveal that the Nb atoms are localized near their average positions on the sphere surfaces for all temperatures and x values. With regard to previous results we point out the features of microscopic structure common for PSN and perovskite-type zirconates. AU - Mikhail Lemeshko AU - Nazarenko, Elena S AU - Gonchar, Anastasia A AU - Reznichenko, Larisa A AU - Nedoseykina, Tatiana I AU - Novakovich, Alexander A AU - Mathon, Olivier AU - Joly, Yves AU - Vedrinskiǐ, Rostislav V ID - 2145 IS - 13 JF - Physical Review B - Condensed Matter and Materials Physics TI - EXAFS studies of the local atomic structure of the lead free piezoelectric ceramics Kx Na1-x Nb O3 over the temperature range 10-1023 K VL - 76 ER - TY - JOUR AB - This paper contains a proof of the Manin conjecture for the singular cubic surface S ⊂ P3 that is defined by the equation x1 x22 + x2 x02 + x33 = 0. In fact if U ⊂ S is the Zariski open subset obtained by deleting the unique line from S, and H is the usual exponential height on P3 (Q), then the height zeta function ∑x ∈ U (Q) H (x)- s is analytically continued to the half-plane R e (s) > 9 / 10. AU - De La Bretèche, Régis AU - Browning, Timothy D AU - Derenthal, Ulrich ID - 219 IS - 1 JF - Annales Scientifiques de l'Ecole Normale Superieure TI - On Manin's conjecture for a certain singular cubic surface VL - 40 ER - TY - JOUR AB - Let X ⊂ ℙN be a geometrically integral cubic hypersurface defined over ℚ, with singular locus of dimension at most dim X - 4. The main result in this paper is a proof of the fact that X(ℚ) contains OεX,(BdimX+ε) points of height at most B. AU - Timothy Browning ID - 220 IS - 1-2 JF - Mathematika TI - Counting rational points on cubic hypersurfaces VL - 54 ER - TY - JOUR AU - De La Bretèche, Régis AU - Browning, Timothy D ID - 221 IS - 1 JF - Michigan Mathematical Journal TI - On Manin's conjecture for singular del Pezzo surfaces of degree four, I VL - 55 ER - TY - JOUR AB - Acknowledgements. The authors are grateful to Ulrich Derenthal and Brendan Hassett for several useful conversations relating to universal torsors for singular del Pezzo surfaces. Special thanks are due to Roger Heath–Brown whose ideas led us to the proof of Lemma 6. The paper was finalised while the first author was at the École Normale Supérieure, and the second author was at Oxford University supported by EPSRC grant number GR/R93155/01. The hospitality and financial support of these institutions is gratefully acknowledged. Finally, the authors would like to thank the anonymous referee for his careful reading of the manuscript and numerous useful suggestions. AU - de la Bretèche, Régis AU - Timothy Browning ID - 222 IS - 3 JF - Mathematical Proceedings of the Cambridge Philosophical Society TI - On Manin's conjecture for singular del Pezzo surfaces of degree four, II VL - 143 ER - TY - JOUR AB - Let Q be a non-singular diagonal quadratic form in at least four variables. We provide upper bounds for the number of integer solutions to the equation Q = 0, which lie in a box with sides of length 2B, as B → ∞. The estimates obtained are completely uniform in the coefficients of the form, and become sharper as they grow larger in modulus. AU - Timothy Browning ID - 223 IS - 1 JF - Monatshefte fur Mathematik TI - Density of integer solutions to diagonal quadratic forms VL - 152 ER - TY - JOUR AB - It was recently shown by Hansen that the Wigner-Yanase entropy is, for general states of quantum systems, not subadditive with respect to decomposition into two subsystems, although this property is known to hold for pure states. We investigate the question whether the weaker property of subadditivity for pure states with respect to decomposition into more than two subsystems holds. This property would have interesting applications in quantum chemistry. We show, however, that it does not hold in general, and provide a counterexample. AU - Robert Seiringer ID - 2367 IS - 3 JF - Letters in Mathematical Physics TI - On the failure of subadditivity of the Wigner-Yanase entropy VL - 80 ER - TY - JOUR AB - The increasing interest in the Müller density-matrix-functional theory has led us to a systematic mathematical investigation of its properties. This functional is similar to the Hartree-Fock (HF) functional, but with a modified exchange term in which the square of the density matrix γ(x, x′) is replaced by the square of γ1 2 (x, x′). After an extensive introductory discussion of density-matrix-functional theory we show, among other things, that this functional is convex (unlike the HF functional) and that energy minimizing γ 's have unique densities ρ(r), which is a physically desirable property often absent in HF theory. We show that minimizers exist if N≤Z, and derive various properties of the minimal energy and the corresponding minimizers. We also give a precise statement about the equation for the orbitals of γ, which is more complex than for HF theory. We state some open mathematical questions about the theory together with conjectured solutions. AU - Frank, Rupert L AU - Lieb, Élliott H AU - Robert Seiringer AU - Siedentop, Heinz K ID - 2372 IS - 5 JF - Physical Review A - Atomic, Molecular, and Optical Physics TI - Müller's exchange-correlation energy in density-matrix-functional theory VL - 76 ER - TY - JOUR AB - After recalling briefly the connection between spontaneous symmetry breaking and off-diagonal long-range order for models of magnets a general proof of spontaneous breaking of gauge symmetry as a consequence of Bose-Einstein condensation is presented. The proof is based on a rigorous validation of Bogoliubov's c-number substitution for the k = 0 mode operator α0. AU - Lieb, Élliott H AU - Robert Seiringer AU - Yngvason, Jakob ID - 2370 IS - 3 JF - Reports on Mathematical Physics TI - Bose-Einstein condensation and spontaneous symmetry breaking VL - 59 ER - TY - JOUR AB - We give a Cwikel-Lieb-Rozenblum type bound on the number of bound states of Schrödinger operators with matrix-valued potentials using the functional integral method of Lieb. This significantly improves the constant in this inequality obtained earlier by Hundertmark. AU - Frank, Rupert L AU - Lieb, Élliott H AU - Robert Seiringer ID - 2375 IS - 2-3 JF - Letters in Mathematical Physics TI - Number of bound states of Schrödinger operators with matrix-valued potentials VL - 82 ER - TY - JOUR AB - For the BCS equation with local two-body interaction λV(x), we give a rigorous analysis of the asymptotic behavior of the critical temperature as γ"0. We derive necessary and sufficient conditions onV(x) for the existence of a nontrivial solution for all values of γ>0. AU - Frank, Rupert L AU - Hainzl, Christian AU - Naboko, Serguei N AU - Robert Seiringer ID - 2373 IS - 4 JF - Journal of Geometric Analysis TI - The critical temperature for the BCS equation at weak coupling VL - 17 ER - TY - JOUR AB - We give a proof of stability of relativistic matter with magnetic fields all the way up to the critical value of the nuclear charge Zα = 2/π. AU - Frank, Rupert L AU - Lieb, Élliott H AU - Robert Seiringer ID - 2371 IS - 2 JF - Communications in Mathematical Physics TI - Stability of relativistic matter with magnetic fields for nuclear charges up to the critical value VL - 275 ER - TY - JOUR AB - Signal molecules known as phytohormones play a decisive role in processing signals coming to plants from the surrounding environment. They include auxin — a simple compound with a large range of effects. Auxin is irregularly deposited in plant tissues, it accumulates in certain cellules and through activation of a signal cascade it causes changes in the development programme of these cellules. This article forms a part of the series prepared in honour of the anniversary of the important plant physiologist — Bohumil Němec. AU - Friml, Jirí ID - 2451 JF - Živa TI - Auxin - Universal development signal in plant life VL - 1 ER - TY - JOUR AU - Michniewicz, Marta AU - Brewer, Philip B AU - Jirí Friml ID - 2462 JF - The Arabidopsis Book TI - Polar auxin transport and asymmetric auxin distribution VL - 5 ER - TY - JOUR AB - Metabotropic glutamate receptor 4 (mGluR4) is localized mainly to presynaptic membranes in the brain. Rat neostriatum has been reported to contain two types of mGluR4-immunoreactive axon varicosities: small, weakly immunoreactive varicosities that were distributed randomly (type 1) and large, intensely immunoreactive ones that were often aligned linearly (type 2). In the present study, most type 1 terminals formed asymmetric synapses on dendritic spines, whereas type 2 terminals made symmetric synapses on dendritic shafts, showing immunoreactivity for GABAergic markers. After depletion of neostriatal neurons, type 2 but not type 1 varicosities were largely decreased in the damaged region. When medium-sized spiny neurons (MSNs) were labeled with Sindbis virus expressing membrane-targeted green fluorescent protein, mGluR4 immunoreactivity was observed on some varicosities of their axon collaterals in immunofluorescence and immunoelectron microscopies. Furthermore, type 2 varicosities were often positive for substance P but mostly negative for striatal interneuron markers and preproenkephalin. Thus, striatonigral/striato- entopeduncular MSNs are likely to be the largest source of type 2 mGluR4-immunopositive axon terminals in the neostriatum. Next, in the double-immunofluorescence study, almost all choline acetyltransferase (ChAT)-immunopositive and 41% of NK1 receptor-positive dendrites were heavily associated with type 2 mGluR4-immunoreactive varicosities. Neuronal nitric oxide synthase (nNOS)-positive dendrites, in contrast, seemed associated with only a few type 2 varicosities. Conversely, almost all type 2 varicosities were closely apposed to NK1 receptor-positive dendrites that were known to be derived from cholinergic and nNOS-producing interneurons. These findings indicate that the mGluR4-positive terminals of MSN axon collaterals selectively form synapses with neostriatal cholinergic interneurons. AU - Kuramoto, Eriko AU - Fujiyama, Fumino AU - Unzai, Tomo AU - Nakamura, Kouichi AU - Hioki, Hiroyuki AU - Furuta, Takahiro AU - Ryuichi Shigemoto AU - Ferraguti, Francesco AU - Kaneko, Takeshi ID - 2495 IS - 5 JF - Journal of Comparative Neurology TI - Metabotropic glutamate receptor 4-immunopositive terminals of medium-sized spiny neurons selectively form synapses with cholinergic interneurons in the rat neostriatum VL - 500 ER - TY - JOUR AB - Glutamate is one candidate for the neurotransmitters and/or neuromodulators involved in taste signaling in taste buds. Group II metabotropic glutamate receptors (mGluRs: mGluR2 and mGluR3) are known to function as presynaptic receptors that regulate the release of glutamate and/or other neurotransmitters in the central nervous system. Group II mGluRs are negatively linked to adenylyl cyclase through Gαi subunits and thereby reduce the turnover of cAMP. In rat taste tissues, a subset of adenylyl-cyclase-8-expressing taste cells coexpress the Gαi subunits gustducin and Gαi2. However, the expression patterns of group II mGluRs in rat taste tissues have not yet been elucidated. We have therefore examined the expression patterns of mGluR2, mGluR3, and gustducin in rat gustatory tissues. Reverse transcription/polymerase chain reaction assays have revealed that mGluR2 and mGluR3 mRNAs are expressed in the circumvallate papillae. In situ hybridization analyses have detected positive signals for mGluR2 and mGluR3 mRNAs only in the circumvallate taste buds. Among the fungiform, foliate, and circumvallate papillae, an antibody against mGluR2/3 labels a subset of taste bud cells and nerve fibers immediately beneath the taste lingual epithelium. Double-labeling experiments have demonstrated that mGluR2/3-positive cells coexpress gustducin. These results indicate that mGluR2 and mGluR3 are coupled to Gαi subunits and play roles in glutamate-mediated signaling in taste transductions. AU - Toyono, Takashi AU - Kataoka, Shinji AU - Seta, Yuji AU - Ryuichi Shigemoto AU - Toyoshima, Kuniaki ID - 2496 IS - 1 JF - Cell and Tissue Research TI - Expression of group II metabotropic glutamate receptors in rat gustatory papillae VL - 328 ER - TY - JOUR AB - Substance P (SP) is known to be a peptide that facilitates epileptic activity of principal cells in the hippocampus. Paradoxically, in other models, it was found to be protective against seizures by activating substance P receptor (SPR)-expressing interneurons. Thus, these cells appear to play an important role in the generation and regulation of epileptic seizures. The number, distribution, morphological features and input characteristics of SPR-immunoreactive cells were analyzed in surgically removed hippocampi of 28 temporal lobe epileptic patients and eight control hippocampi in order to examine their changes in epileptic tissues. SPR is expressed in a subset of inhibitory cells in the control human hippocampus, they are multipolar interneurons with smooth dendrites, present in all hippocampal subfields. This cell population is considerably different from SPR-positive cells of the rat hippocampus. The CA1 (cornu Ammonis subfield 1) region was chosen for the detailed morphological analysis of the SPR-immunoreactive cells because of its extreme vulnerability in epilepsy. The presence of various neurochemical markers identifies functionally distinct interneuron types, such as those responsible for perisomatic, dendritic or interneuron-selective inhibition. We found considerable colocalization of SPR with calbindin but not with parvalbumin, calretinin, cholecystokinin and somatostatin, therefore we suppose that SPR-positive cells participate mainly in dendritic inhibition. In the non-sclerotic CA1 region they are mainly preserved, whereas their number is decreased in the sclerotic cases. In the epileptic samples their morphology is considerably altered, they possessed more dendritic branches, which often became beaded. Analyses of synaptic coverage revealed that the ratio of symmetric synaptic input of SPR-immunoreactive cells has increased in epileptic samples. Our results suggest that SPR-positive cells are preserved while principal cells are present in the CA1 region, but show reactive changes in epilepsy including intense branching and growth of their dendritic arborization. AU - Tóth, Kinga AU - Wittner, Lucia AU - Urbán, Z AU - Doyle, Werner K AU - Buzsáki, György AU - Ryuichi Shigemoto AU - Freund, Tamás F AU - Maglóczky, Zsófia ID - 2665 IS - 2 JF - Neuroscience TI - Morphology and synaptic input of substance P receptor-immunoreactive interneurons in control and epileptic human hippocampus VL - 144 ER - TY - JOUR AB - GABAB receptors (GABABRs) are involved in early events during neuronal development. The presence of GABABRs in developing oligodendrocytes has not been established. Using immunofluorescent co-localization, we have identified GABABR proteins in O4 marker-positive oligodendrocyte precursor cells (OPCs) in 4-day-old mouse brain periventricular white matter. In culture, OPCs, differentiated oligodendrocytes (DOs) and type 2 astrocytes (ASTs) express both the GABAB1abcdf and GABAB2 subunits of the GABABR. Using semiquantitative PCR analysis with GABABR isoform-selective primers we found that the expression level of GABAB1abd was substantially higher in OPCs or ASTs than in DOs. In contrast, the GABAB2 isoform showed a similar level of expression in OPCs and DOs, and a significantly higher level in ASTs. This indicates that the expression of GABAB1 and GABAB2 subunits are under independent control during oligodendroglial development. Activation of GABABRs using the selective agonist baclofen demonstrated that these receptors are functionally active and negatively coupled to adenylyl cyclase. Manipulation of GABABR activity had no effect on OPC migration in a conventional agarose drop assay, whereas baclofen significantly increased OPC migration in a more sensitive transwell microchamber-based assay. Exposure of cultured OPCs to baclofen increased their proliferation, providing evidence for a functional role of GABABRs in oligodendrocyte development. The presence of GABABRs in developing oligodendrocytes provides a new mechanism for neuronal-glial interactions during development and may offer a novel target for promoting remyelination following white matter injury. AU - Luyt, Karen AU - Slade, Timothy P AU - Dorward, Jienchi J AU - Durant, Claire F AU - Wu, Yue AU - Ryuichi Shigemoto AU - Mundell, Stuart J AU - Váradi, Anikó AU - Molnár, Elek ID - 2666 IS - 3 JF - Journal of Neurochemistry TI - Developing oligodendrocytes express functional GABAB receptors that stimulate cell proliferation and migration VL - 100 ER - TY - JOUR AB - Hyperpolarization-activated, cyclic nucleotide-gated cation (HCN) channels are expressed postsynaptically in the rodent globus pallidus (GP), where they play several important roles in controlling GP neuronal activity. To further elucidate the role of HCN channels in the GP, immunocytochemical and electrophysiological approaches were used to test the hypothesis that HCN channels are also expressed presynaptically on the local axon collaterals of GP neurons. At the electron microscopic level, immunoperoxidase labelling for HCN1 and HCN2 was localized in GP somata and dendritic processes, myelinated and unmyelinated axons, and axon terminals. One population of labelled terminals formed symmetric synapses with somata and proximal dendrites and were immunoreactive for parvalbumin, consistent with the axon collaterals of GABAergic GP projection neurons. In addition, labelling for HCN2 and, to a lesser degree, HCN1 was observed in axon terminals that formed asymmetric synapses and were immunoreactive for the vesicular glutamate transporter 2. Immunogold labelling demonstrated that HCN1 and HCN2 were located predominantly at extrasynaptic sites along the plasma membrane of both types of terminal. To determine the function of presynaptic HCN channels in the GP, we performed whole-cell recordings from GP neurons in vitro. Bath application of the HCN channel blocker ZD7288 resulted in an increase in the frequency of mIPSCs but had no effect on their amplitude, implying that HCN channels tonically regulate the release of GABA. Their presence, and predicted role in modulating transmitter release, represents a hitherto unidentified mechanism whereby HCN channels influence the activity of GP neurons. AU - Boyes, Justin AU - Bolam, John P AU - Ryuichi Shigemoto AU - Stanford, Ian M ID - 2668 IS - 7 JF - European Journal of Neuroscience TI - Functional presynaptic HCN channels in the rat globus pallidus VL - 25 ER - TY - JOUR AB - The number of AMPA receptor (AMPAR) is the major determinant of synaptic strength at glutamatergic synapses, but little is known about the absolute number and density of AMPARs in individual synapses. Using SDS-digested freeze-fracture replica labeling, which has high detection efficiency comparable with electrophysiological noise analysis for functional AMPAR, we analyzed three kinds of excitatory synapses in the molecular layer of the adult rat cerebellum. In parallel fiber (PF)-Purkinje cell (PC) synapses, we found large variability in the number (38.1 ± 34.4 particles per synapse, mean ± SD; range, 2-178 particles per synapse) and density (437 ± 277 particles/μm2; range, 48-1210 particles/μm2) of immunogold-labeled AMPARs. Two-dimensional view and high sensitivity of this method revealed irregular-shaped small AMPAR clusters within synapses. Climbing fiber (CF)-PC synapses had higher number of AMPAR labeling (68.6 ± 34.5 particles per synapse) than PF-PC and PF-interneuron synapses (36.8 ± 14.4 particles per synapse). Furthermore, AMPAR density at CF-PC and PF-interneuron synapses was approximately five times higher and more uniform than that at PF-PC synapses. These results suggest input- and target-dependent regulation of AMPAR-mediated synaptic strength. AU - Masugi-Tokita, Miwako AU - Tarusawa, Etsuko AU - Watanabe, Masahiko AU - Molnár, Elek AU - Fujimoto, Kazushi AU - Ryuichi Shigemoto ID - 2667 IS - 8 JF - Journal of Neuroscience TI - Number and density of AMPA receptors in individual synapses in the rat cerebellum as revealed by SDS-digested freeze-fracture replica labeling VL - 27 ER - TY - JOUR AB - The properties of the hyperpolarization-activated current (Ih) and its roles in hippocampal network function evolve radically during development. Because Ih is conducted by the hyperpolarization- activated cyclic nucleotide-gated (HCN) cation channels, we tested the hypothesis that understanding the quantitative developmental profiles of HCN1, HCN2, and HCN4 expression, and the isoform- and age-specific progression of their subcellular distribution, should shed light on the established modifications of the properties of Ih throughout development. Combined quantitative in situ hybridization, regional western blots, and high-resolution, dual-label immunocytochemistry revealed striking and novel information about the expression and distribution of the HCN channel isoforms in the developing hippocampal formation. In cornus ammon 1 (CA) pyramidal cell layer, a robust increase of HCN1 mRNA and protein expression occurred with age, with reciprocal reduction of HCN4 and relatively stable HCN2 levels. These distinct expression patterns raised the contribution of HCN1 to the total HCN channel pool from 33% to 65% consonant with acceleration and reduced cyclic adenosine mono phosphate (cAMP) sensitivity of Ih in this region with age. In CA3, strong expression of HCN1 already neonatally supports the recently established role of this conductance in neonatal, age-specific, hippocampal oscillations (giant depolarizing potentials). Notably, HCN1 channels were present and probably transported to dendritic compartments already on postnatal day (P) 2, whereas HCN2 channel protein was not evident in dendrites for the first 2 weeks of life. HCN2 mRNA and protein expression remained fairly constant subsequent to the first week of life in all hippocampal subfields examined, whereas HCN4 mRNA and protein expression declined after maximal neonatal expression, so that the contribution of this isoform to the total HCN channel pool dropped from 43% (CA1) and 34% (CA3) on P11 to 8% (CA1) and 19% (CA3) on P90. Interneuronal expression of all HCN channel isoforms in stratum pyramidale was robust in parvalbumin-but not in cholecystokinin-expressing populations and with a subunit-specific subcellular distribution. Taken together, these data suggest that early in life, HCN4 may contribute significantly to the functions of Ih in specific hippocampal regions. In addition, these evolving, differential quantitative, and subcellular expression patterns of the HCN channel isoforms support age-specific properties and functions of Ih within the developing hippocampal formation. AU - Brewster, Amy L AU - Chen, Yuncai AU - Bender, Roland A AU - Yeh, Amy AU - Ryuichi Shigemoto AU - Baram, Tallie Z ID - 2669 IS - 3 JF - Cerebral Cortex TI - Quantitative analysis and subcellular distribution of mRNA and protein expression of the hyperpolarization-activated cyclic nucleotide-gated channels throughout development in rat hippocampus VL - 17 ER - TY - JOUR AB - Excitatory synaptic transmission is inhibited by G protein coupled receptors, including the adenosine A1, GABAB, and metabotropic glutamate receptor 7. These receptors are present in nerve terminals where they reduce the release of glutamate through activating signaling pathways negatively coupled to Ca2+ channels and adenylyl cyclase. However, it is not clear whether these receptors operate in distinct subpopulations of nerve terminals or if they are co-expressed in the same nerve terminals, despite the functional consequences that such distributions may have on synaptic transmission. Applying Ca2+ imaging and immunocytochemistry, we show that these three G protein coupled receptors coexist in a subpopulation of cerebrocortical nerve terminals. The three receptors share an intracellular signaling pathway through which their inhibitory responses are integrated and coactivation of these receptors produced an integrated response. Indeed, this response was highly variable, from a synergistic response at subthreshold agonist concentrations to an occluded response at high agonist concentrations. The presence of multiple receptors in a nerve terminal could be responsible for the physiological effects of neurotransmitter spillover from neighboring synapses or alternatively, the co-release of transmitters by the same nerve terminal. AU - Ladera, Carolina AU - Godino, María D AU - Martín, Ricardo J AU - Luján, Rafael AU - Ryuichi Shigemoto AU - Ciruela, Francisco AU - Torres, Magdalena AU - Sánchez-Prieto, José ID - 2673 IS - 6 JF - Journal of Neurochemistry TI - The coexistence of multiple receptors in a single nerve terminal provides evidence for pre-synaptic integration VL - 103 ER - TY - JOUR AB - Increasing evidence supports roles for the current mediated by hyperpolarization-activated cyclic nucleotide-gated (HCN) channels, I h, in hippocampal maturation and specifically in the evolving changes of intrinsic properties as well as network responses of hippocampal neurons. Here, we describe a novel developmental plasticity of HCN channel expression in axonal and presynaptic compartments: HCN1 channels were localized to axon terminals of the perforant path (the major hippocampal afferent pathway) of immature rats, where they modulated synaptic efficacy. However, presynaptic expression and functions of the channels disappeared with maturation. This was a result of altered channel transport to the axons, because HCN1 mRNA and protein levels in entorhinal cortex neurons, where the perforant path axons originate, were stable through adulthood. Blocking action potential firing in vitro increased presynaptic expression of HCN1 channels in the perforant path, suggesting that network activity contributed to regulating this expression. These findings support a novel developmentally regulated axonal transport of functional ion channels and suggest a role for HCN1 channel-mediated presynaptic I h in hippocampal maturation. AU - Bender, Roland A AU - Kirschstein, Timo AU - Kretz, Oliver AU - Brewster, Amy L AU - Richichi, Cristina AU - Rüschenschmidt, Christiane AU - Ryuichi Shigemoto AU - Beck,Heinz AU - Frotscher, Michael AU - Baram, Tallie Z ID - 2671 IS - 17 JF - Journal of Neuroscience TI - Localization of HCN1 channels to presynaptic compartments: Novel plasticity that may contribute to hippocampal maturation VL - 27 ER - TY - JOUR AB - Hyperpolarization-activated cyclic nucleotide-modulated (HCN) "pacemaker" channel subunits are integral membrane proteins that assemble as tetramers to form channels in cardiac conduction tissue and nerve cells. Previous studies have suggested that the HCN2 and HCN4 channel isoforms physically interact when overexpressed in mammalian cells, but whether they are able to co-assemble and form functional channels remains unclear. The extent to which co-assembly occurs over self-assembly and whether HCN2-HCN4 heteromeric channels are formed in native tissue are not known. In this study, we show co-assembly of HCN2 and HCN4 in live Chinese hamster ovary cells using bioluminescence resonance energy transfer (BRET2), a novel approach for studying tetramerization of ion channel subunits. Together with results from electrophysiological and imaging approaches, the BRET2 data show that HCN2 and HCN4 subunits self-assemble and co-assemble with equal preference. We also demonstrate colocalization of HCN2 and HCN4 and a positive correlation of their intensities in the embryonic mouse heart using immunohistochemistry, as well as physical interactions between these isoforms in the rat thalamus by coimmunoprecipitation. Together, these data support the formation of HCN2-HCN4 heteromeric channels in native tissue. AU - Whitaker, Gina M AU - Angoli, Damiano AU - Nazzari, Hamed AU - Ryuichi Shigemoto AU - Accili, Eric A ID - 2672 IS - 31 JF - Journal of Biological Chemistry TI - HCN2 and HCN4 isoforms self-assemble and co-assemble with equal preference to form functional pacemaker channels VL - 282 ER - TY - GEN AB - Glutamate and GABA are the main transmitters in the central nervous system and their effects are mediated by ionotropic and metabotropic receptors. Immunogold electron microscopy has revealed the quantitative localization of these receptors at 20-30 nm resolution. SDS-digested freeze-fracture replica labeling (SDS-FRL), a newly developed immunogold method, provides an accurate estimate of molecule numbers. Here, we summarize the recent advances in quantitative receptor localization, including use of SDS-FRL analyses to determine numbers of AMPA-type glutamate receptors in the cerebellum. The two-dimensional view and high sensitivity of SDS-FRL have revealed small, irregularly shaped AMPA receptor clusters within cerebellar synapses. AU - Masugi-Tokita, Miwako AU - Ryuichi Shigemoto ID - 2670 IS - 3 T2 - Current Opinion in Neurobiology TI - High-resolution quantitative visualization of glutamate and GABA receptors at central synapses VL - 17 ER - TY - CHAP AU - László Erdös ED - Gesztesy, Fritz ED - Deift, Percy ED - Galvez, Percy ED - Perry, Peter ED - Schlag, Wilhelm ID - 2705 T2 - Spectral Theory and Mathematical Physics: a Festschrift in Honor of Barry Simon's 60th Birthday TI - Recent developments in quantum mechanics with magnetic fields VL - 76 ER - TY - JOUR AB - We consider random Schrödinger equations on ℝd for d ≥ 3 with a homogeneous Anderson-Poisson type random potential. Denote by λ the coupling constant and ψt the solution with initial data ψ0. The space and time variables scale as χ ≃λ-2-κ/2, t ≃λ-2-κ with 0 < kappa; < kappa;0(d). We prove that, in the limit λ → 0, the expectation of the Wigner distribution of ψt converges weakly to the solution of a heat equation in the space variable x for arbitrary L2 initial data. The proof is based on a rigorous analysis of Feynman diagrams. In the companion paper [10] the analysis of the non-repetition diagrams was presented. In this paper we complete the proof by estimating the recollision diagrams and showing that the main terms, i.e. the ladder diagrams with renormalized propagator, converge to the heat equation. AU - László Erdös AU - Salmhofer, Manfred AU - Yau, Horng-Tzer ID - 2750 IS - 1 JF - Communications in Mathematical Physics TI - Quantum diffusion of the random Schrödinger evolution in the scaling limit II. The recollision diagrams VL - 271 ER - TY - JOUR AB - We consider random Schrödinger equations on ℤd for d ≥ 3 with identically distributed random potential. Denote by λ the coupling constant and ψ t the solution with initial data ψ 0. The space and time variables scale as x ∼ λ -2-κ/2,t ∼ λ-2-κ with 0 < κ < κ0(d). We prove that, in the limit λ → 0, the expectation of the Wigner distribution of ψ t converges weakly to a solution of a heat equation in the space variable x for arbitrary L 2 initial data. The diffusion coefficient is uniquely determined by the kinetic energy associated to the momentum υ. This work is an extension to the lattice case of our previous result in the continuum [8,9]. Due to the non-convexity of the level surfaces of the dispersion relation, the estimates of several Feynman graphs are more involved. AU - László Erdös AU - Salmhofer, Manfred AU - Yau, Horng-Tzer ID - 2751 IS - 4 JF - Annales Henri Poincare TI - Quantum diffusion for the Anderson model in the scaling limit VL - 8 ER - TY - JOUR AB - We prove L p -bounds on the Fourier transform of measures μ supported on two dimensional surfaces. Our method allows to consider surfaces whose Gauss curvature vanishes on a one-dimensional submanifold. Under a certain non-degeneracy condition, we prove that μ ∧ ε L 4+β, β > 0, and we give a logarithmically divergent bound on the L 4-norm. We use this latter bound to estimate almost singular integrals involving the dispersion relation, e(p)= ∑13 [1-\cos p_j]} , of the discrete Laplace operator on the cubic lattice. We briefly explain our motivation for this bound originating in the theory of random Schrödinger operators. AU - László Erdös AU - Salmhofer, Manfred ID - 2752 IS - 2 JF - Mathematische Zeitschrift TI - Decay of the Fourier transform of surfaces with vanishing curvature VL - 257 ER - TY - GEN AB - We prove rigorously that the one-particle density matrix of three dimensional interacting Bose systems with a short-scale repulsive pair interaction converges to the solution of the cubic non-linear Schrödinger equation in a suitable scaling limit. The result is extended to k-particle density matrices for all positive integer k. AU - László Erdös AU - Schlein, Benjamin AU - Yau, Horng-Tzer ID - 2749 IS - 3 T2 - Inventiones Mathematicae TI - Derivation of the cubic non linear Schrödinger equation from quantum dynamics of many body systems VL - 167 ER - TY - JOUR AB - The time-dependent Gross-Pitaevskii equation describes the dynamics of initially trapped Bose-Einstein condensates. We present a rigorous proof of this fact starting from a many-body bosonic Schrödinger equation with a short-scale repulsive interaction in the dilute limit. Our proof shows the persistence of an explicit short-scale correlation structure in the condensate. AU - László Erdös AU - Schlein, Benjamin AU - Yau, Horng-Tzer ID - 2748 IS - 4 JF - Physical Review Letters TI - Rigorous derivation of the Gross-Pitaevskii equation VL - 98 ER - TY - GEN AB - Pipe flow is a prominent example among the shear flows that undergo transition to turbulence without mediation by a linear instability of the laminar profile. Experiments on pipe flow, as well as plane Couette and plane Poiseuille flow, show that triggering turbulence depends sensitively on initial conditions, that between the laminar and the turbulent states there exists no intermediate state with simple spatial or temporal characteristics, and that turbulence is not persistent, i.e., it can decay again, if the observation time is long enough. All these features can consistently be explained on the assumption that the turbulent state corresponds to a chaotic saddle in state space. The goal of this review is to explain this concept, summarize the numerical and experimental evidence for pipe flow, and outline the consequences for related flows. AU - Eckhardt, Bruno AU - Schneider, Tobias M AU - Björn Hof AU - Westerweel, Jerry ID - 2793 T2 - Annual Review of Fluid Mechanics TI - Turbulence transition in pipe flow VL - 39 ER - TY - CONF AU - Björn Hof AU - Tax, Wilco AU - Westerweel, Jerry ID - 2794 TI - Lifetime of turbulence in pipe flow VL - 117 ER - TY - JOUR AB - Summary: Regulatory CD4+ T cells, enriched in the CD25 pool of healthy individuals, mediate natural tolerance and prevent autoimmune diseases. Despite their fundamental and potential clinical significance, regulatory T (TR) cells have not yet been incorporated in a coherent theory of the immune system. This article reviews experimental evidence and theoretical arguments supporting a model of TR cell dynamics, uncovering some of its most relevant biological implications. According to this model, the persistence and expansion of TR cell populations depend strictly on specific interactions they make with antigen-presenting cells (APCs) and conventional effector T (TE) cells. This three-partner crossregulation imposes that TR cells feed on the specific autoimmune activities they suppress, with implications ranging from their interactions with other cells to their repertoire selection in the periphery and in the thymus, and to the relationship between these cells and the innate immune system. These implications stem from the basic prediction that the peripheral dynamics sort the CD4+ T-cell repertoire into two subsets: a less diverse set of small clones of autoreactive effector and regulatory cells that regulate each other’s growth, and a more diverse set of barely autoreactive TE cell clones, whose expansion is limited only by APC availability. It is argued that such partitioning of the repertoire sets the ground for self–non-self discrimination. AU - Carneiro, Jorge AU - Leon, Kalet AU - Caramalho, Íris AU - Van Den Dool, Carline AU - Gardner, Rui AU - Oliveira, Vanessa AU - Bergman, Marie L AU - Sepúlveda, Nuno AU - Tiago Paixao AU - Faro, Jose AU - Demengeot, Jocelyne ID - 2893 IS - 1 JF - Immunological Reviews TI - When three is not a crowd a Crossregulation Model of the dynamics and repertoire selection of regulatory CD4 T cells VL - 216 ER - TY - JOUR AB - Gene expression from both parental alleles is beneficial by masking the effects of deleterious recessive mutations and by reducing the noise in gene expression in diploid organisms. However, a class of genes are expressed preferentially or strictly from a single allele. The selective advantage of avoiding biallelic expression is clear for allelic-excluded antigen receptor and odorant receptor genes, genes undergoing X-chromosome inactivation in females and parental genomic imprinted genes. In contrast, there is no clear biological rationale for the predominant and stochastic monoallelic expression of cytokine genes in the immune system, and the underlying mechanism is elusive and controversial. A clarification of the mechanism of predominant monoallelic expression would be instrumental in better understanding its eventual biological functional. This prompted the development of a quantitative framework that could describe the dynamics of the pattern of allele expression of the IL-10 gene, from which general quantitative insights could be gained. We report that the experimental observations on these patterns of allelic expression cannot be easily reconciled with a simple model of stochastic transcriptional activation, in which the two alleles are, at any time, equally competent for transcription. Instead, these observations call into action a general model of eukaryotic transcriptional regulation according to which the locus competence for transcription is dynamic, involving multiple, cooperative and stochastic modification steps. In this model, the probability that an allele becomes transcriptionally active is a function of the number of chromatin modifications that it accumulated. On the basis of the properties of this model, we argue that predominant monoallelic expression might have had no adaptive role, and may have evolved under indirect selection for low frequency of expressing cells. AU - Tiago Paixao AU - Carvalho, Tiago P AU - Calado, Dinis P AU - Carneiro, Jorge ID - 2896 IS - 4 JF - Immunology and Cell Biology TI - Quantitative insights into stochastic monoallelic expression of cytokine genes VL - 85 ER - TY - CONF AU - Kumar, M Pawan AU - Vladimir Kolmogorov AU - Torr, Philip H ID - 2933 TI - An Analysis of Convex Relaxations for MAP Estimation ER - TY - JOUR AB - Directional transport of the phytohormone auxin is established primarily at the point of cellular afflux and is required for the establishment and maintenance of plant polarity. Studies in whole plants and heterologous systems indicate that PIN-FORMED (PIN) and P-glycoprotein (PGP) transport proteins mediate the cellular efflux of natural and synthetic auxins. However, aromatic anion transport resulting from PGP and PIN expression in nonplant systems was also found to lack tha high level of substrate specificity seen in planta. Furthermore, previous reports that PGP19 stabilizes PIN1 on the plasma membrane suggested that PIN-PGP interactions might regulate polar auxin efflux. Hare, we show that PGP1 and PGP19 colocalized with PIN1 in the shoot apax in Arabidopsis thaliana and with PIN1 and PIN2 in root tissues. Specific PGP-PIN interactions were seen in yeast two-hybrid and colmmunoprecipitation assays. PIN-PGP interactions appeared to enhance transport activity and, to a greater extent, substrate/inhibitor specificities when coexpressed in heterologous systems. By contrast, no interactions between PGPs and the AUXIN1 influx carrier were observed. Phenotypes of pin and pgp mutants suggest discrete functional roles in auxin transport, but pin pgp mutants exhibited phenotypes that are both additive and synergistic. These results suggest that PINs and PGPs characterize coordinated, Independent auxin transport mechanisms but also function interactively in a tissue-specific manner. AU - Blakeslee, Joshua AU - Bandyopadhyay, Anindita AU - Ok, Ran Lee AU - Mravec, Jozef AU - Titapiwatanakun, Boosaree AU - Sauer, Michael AU - Makam, Srinivas N AU - Cheng, Yan AU - Bouchard, Rodolphe AU - Adamec, Jiří AU - Geisler, Markus AU - Nagashima, Akitomo AU - Sakai, Tatsuya AU - Martinoia, Enrico AU - Jirí Friml AU - Peer, Wendy A AU - Murphy, Angus S ID - 3019 IS - 1 JF - Plant Cell TI - Interactions among PIN FORMED and P glycoprotein auxin transporters in Arabidopsis VL - 19 ER - TY - JOUR AB - Cytokinesis ensures proper partitioning of the nucleocytoplasmic contents into two daughter cells. It has generally been thought that cytokinesis is accomplished differently in animals and plants because of the differences in the preparatory phases, into the centrosomal or acentrosomal nature of the process, the presence or absence of rigid cell walls, and on the basis of ‘outside‐in’ or ‘inside‐out’ mechanism. However, this long‐standing paradigm needs further reevaluation based on new findings. Recent advances reveal that plant cells, similarly to animal cells, possess astral microtubules that regulate the cell division plane. Furthermore, endocytosis has been found to be important for cytokinesis in animal and plant cells: vesicles containing endocytosed cargo provide material for the cell plate formation in plants and for closure of the midbody channel in animals. Thus, although the preparatory phases of the cell division process differ between plant and animal cells, the later phases show similarities. We unify these findings in a model that suggests a conserved mode of cytokinesis. AU - Dhonukshe, Pankaj AU - Šamaj, Jozef AU - Baluška, František AU - Friml, Jirí ID - 3023 IS - 4 JF - Bioessays : News and Reviews in Molecular, Cellular and Developmental Biology TI - A unifying new model of cytokinesis for the dividing plant and animal cells VL - 29 ER - TY - CONF AB - Polarized transport of the plant hormone auxin influences multiple growth processes in plants and is regulated by plasma-membrane-localized efflux and uptake carriers. The PGP (P-glycoprotein) ABC transporters (ATP-binding-cassette transporters), PIN (pin-formed) subfamily of major facilitator proteins and members of AUX/LAX families have been shown to independently transport auxin both in planta and in heterologous systems. However, PIN- and PGP-mediated transport in heterologous systems exhibits decreased substrate specificity and inhibitor-sensitivity compared with what is seen in plants and plant cells. To determine whether PIN-PGP interactions enhance transport specificity, we analysed interactions of the representative auxin-transporting PGPs with PIN1 and AUX1 in planta and in heterologous systems. Here, we provide evidence that PINs and PGPs interact and function both independently and co-ordinately to control polar auxin transport and impart transport specificity and directionality. These interactions take place in protein complexes stabilized by PGPs in detergent-resistant microdomains. AU - Bandyopadhyay, Anindita AU - Blakeslee, Joshua AU - Lee, Ok Ran AU - Mravec, Jozef AU - Sauer, Michael AU - Titapiwatanakun, Boosaree AU - Makam, Srinivas N AU - Bouchard, Rodolphe AU - Geisler, Markus AU - Martinoia, Enrico AU - Jirí Friml AU - Peer, Wendy A AU - Murphy, Angus S ID - 3021 IS - 1 TI - Interactions of PIN and PGP auxin transport mechanisms VL - 35 ER - TY - JOUR AB - In Arabidopsis thaliana, lateral roots are formed from root pericycle cells adjacent to the xylem poles. Lateral root development is regulated antagonistically by the plant hormones auxin and cytokinin. While a great deal is known about how auxin promotes lateral root development, the mechanism of cytokinin repression is still unclear. Elevating cytokinin levels was observed to disrupt lateral root initiation and the regular pattern of divisions that characterizes lateral root development in Arabidopsis. To identify the stage of lateral root development that is sensitive to cytokinins, we targeted the expression of the Agrobacterium tumefaciens cytokinin biosynthesis enzyme isopentenyltransferase to either xylem-pole pericycle cells or young lateral root primordia using GAL4-GFP enhancer trap lines. Transactivation experiments revealed that xylem-pole pericycle cells are sensitive to cytokinins, whereas young lateral root primordia are not. This effect is physiologically significant because transactivation of the Arabidopsis cytokinin degrading enzyme cytokinin oxidase 1 in lateral root founder cells results in increased lateral root formation. We observed that cytokinins perturb the expression of PIN genes in lateral root founder cells and prevent the formation of an auxin gradient that is required to pattern lateral root primordia. AU - Laplaze, Laurent AU - Eva Benková AU - Casimiro, Ilda AU - Maes, Lies AU - Vanneste, Steffen AU - Swarup, Ranjan AU - Weijers, Dolf AU - Calvo, Vanessa AU - Parizot, Boris AU - Herrera-Rodriguez, Maria Begoña AU - Offringa, Remko AU - Graham, Neil AU - Doumas, Patrick AU - Jirí Friml AU - Bogusz, Didier AU - Beeckman, Tom AU - Bennett, Malcolm ID - 3029 IS - 12 JF - Plant Cell TI - Cytokinins act directly on lateral root founder cells to inhibit root initiation VL - 19 ER - TY - JOUR AB - In plants, each developmental process integrates a network of signaling events that are regulated by different phytohormones, and interactions among hormonal pathways are essential to modulate their effect. Continuous growth of roots results from the postembryonic activity of cells within the root meristem that is controlled by the coordinated action of several phytohormones, including auxin and ethylene. Although their interaction has been studied intensively, the molecular and cellular mechanisms underlying this interplay are unknown. We show that the effect of ethylene on root growth is largely mediated by the regulation of the auxin biosynthesis and transport-dependent local auxin distribution. Ethylene stimulates auxin biosynthesis and basipetal auxin transport toward the elongation zone, where it activates a local auxin response leading to inhibition of cell elongation. Consistently, in mutants affected in auxin perception or basipetal auxin transport, ethylene cannot activate the auxin response nor regulate the root growth. In addition, ethylene modulates the transcription of several components of the auxin transport machinery. Thus, ethylene achieves a local activation of the auxin signaling pathway and regulates root growth by both stimulating the auxin biosynthesis and by modulating the auxin transport machinery. AU - Růžička, Kamil AU - Ljung, Karin AU - Vanneste, Steffen AU - Podhorská, Radka AU - Beeckman, Tom AU - Jirí Friml AU - Eva Benková ID - 3026 IS - 7 JF - Plant Cell TI - Ethylene regulates root growth through effects on auxin biosynthesis and transport dependent auxin distribution VL - 19 ER - TY - JOUR AB - In plants, cell polarity and tissue patterning are connected by intercellular flow of the phytohormone auxin, whose directional signaling depends on polar subcellular localization of PIN auxin transport proteins. The mechanism of polar targeting of PINs or other cargos in plants is largely unidentified, with the PINOID kinase being the only known molecular component. Here, we identify PP2A phosphatase as an important regulator of PIN apical-basal targeting and auxin distribution. Genetic analysis, localization, and phosphorylation studies demonstrate that PP2A and PINOID both partially colocalize with PINs and act antagonistically on the phosphorylation state of their central hydrophilic loop, hence mediating PIN apical-basal polar targeting. Thus, in plants, polar sorting by the reversible phosphorylation of cargos allows for their conditional delivery to specific intracellular destinations. In the case of PIN proteins, this mechanism enables switches in the direction of intercellular auxin fluxes, which mediate differential growth, tissue patterning, and organogenesis. AU - Michniewicz, Marta AU - Zago, Marcelo K AU - Abas, Lindy AU - Weijers, Dolf AU - Schweighofer, Alois AU - Meskiene, Irute AU - Heisler, Marcus G AU - Ohno, Carolyn AU - Zhang, Jing AU - Huang, Fang AU - Schwab, Rebecca AU - Weigel, Detlef AU - Meyerowitz, Elliot M AU - Luschnig, Christian AU - Offringa, Remko AU - Jirí Friml ID - 3028 IS - 6 JF - Cell TI - Antagonistic regulation of PIN phosphorylation by PP2A and PINOID directs auxin flux VL - 130 ER - TY - JOUR AB - The plant hormone auxin is frequently observed to be asymmetrically distributed across adjacent cells during crucial stages of growth and development. These auxin gradients depend on polar transport and regulate a wide variety of processes, including embryogenesis, organogenesis, vascular tissue differentiation, root meristem maintenance and tropic growth. Auxin can mediate such a perplexing array of developmental processes by acting as a general trigger for the change in developmental program in cells where it accumulates and by providing vectorial information to the tissues by its polar intercellular flow. In recent years, a wealth of molecular data on the mechanism of auxin transport and its regulation has been generated, providing significant insights into the action of this versatile coordinative signal. AU - Vieten, Anne AU - Sauer, Michael AU - Brewer, Philip AU - Friml, Jirí ID - 3024 IS - 4 JF - Trends in Plant Science TI - Molecular and cellular aspects of auxin-transport-mediated development VL - 12 ER - TY - CONF AB - Many computer vision applications rely on the efficient optimization of challenging, so-called non-submodular, binary pairwise MRFs. A promising graph cut based approach for optimizing such MRFs known as "roof duality" was recently introduced into computer vision. We study two methods which extend this approach. First, we discuss an efficient implementation of the "probing" technique introduced recently by Boros et al. [5]. It simplifies the MRF while preserving the global optimum. Our code is 400-700 faster on some graphs than the implementation of [5]. Second, we present a new technique which takes an arbitrary input labeling and tries to improve its energy. We give theoretical characterizations of local minima of this procedure. We applied both techniques to many applications, including image segmentation, new view synthesis, superresolution, diagram recognition, parameter learning, texture restoration, and image deconvolution. For several applications we see that we are able to find the global minimum very efficiently, and considerably outperform the original roof duality approach. In comparison to existing techniques, such as graph cut, TRW, BP, ICM, and simulated annealing, we nearly always find a lower energy. AU - Rother, Carsten AU - Vladimir Kolmogorov AU - Lempitsky, Victor AU - Szummer, Martin ID - 3192 TI - Optimizing binary MRFs via extended roof duality ER - TY - CONF AB - The maximum flow algorithm for minimizing energy functions of binary variables has become a standard tool in computer vision. In many cases, unary costs of the energy depend linearly on parameter lambda. In this paper we study vision applications for which it is important to solve the maxflow problem for different lambda's. An example is a weighting between data and regularization terms in image segmentation or stereo: it is desirable to vary it both during training (to learn lambda from ground truth data) and testing (to select best lambda using high-knowledge constraints, e.g. user input). We review algorithmic aspects of this parametric maximum flow problem previously unknown in vision, such as the ability to compute all breakpoints of lambda and corresponding optimal configurations infinite time. These results allow, in particular, to minimize the ratio of some geometric functional, such as flux of a vector field over length (or area). Previously, such functional were tackled with shortest path techniques applicable only in 2D. We give theoretical improvements for "PDE cuts" [5]. We present experimental results for image segmentation, 3D reconstruction, and the cosegmentation problem. AU - Vladimir Kolmogorov AU - Boykov, Yuri AU - Rother, Carsten ID - 3191 TI - Applications of parametric maxflow in computer vision ER - TY - JOUR AB - Optimization techniques based on graph cuts have become a standard tool for many vision applications. These techniques allow to minimize efficiently certain energy functions corresponding to pairwise Markov Random Fields (MRFs). Currently, there is an accepted view within the computer vision community that graph cuts can only be used for optimizing a limited class of MRF energies (e.g., submodular functions). In this survey, we review some results that show that graph cuts can be applied to a much larger class of energy functions (in particular, nonsubmodular functions). While these results are well-known in the optimization community, to our knowledge they were not used in the context of computer vision and MRF optimization. We demonstrate the relevance of these results to vision on the problem of binary texture restoration. AU - Vladimir Kolmogorov AU - Rother, Carsten ID - 3193 IS - 7 JF - IEEE Transactions on Pattern Analysis and Machine Intelligence TI - Minimizing nonsubmodular functions with graph cuts - A review VL - 29 ER - TY - JOUR AB - Stereo vision has numerous applications in robotics, graphics, inspection and other areas. A prime application, one which has driven work on stereo in our laboratory, is teleconferencing in which the use of a stereo webcam already makes possible various transformations of the video stream. These include digital camera control, insertion of virtual objects, background substitution, and eye-gaze correction [9, 8]. AU - Blake, Andrew AU - Criminisi, Antonio AU - Cross, Geoffrey AU - Vladimir Kolmogorov AU - Rother, Carsten ID - 3187 JF - Springer Tracts in Advanced Robotics TI - Fusion of stereo colour and contrast VL - 28 ER - TY - CONF AB - A (k, ℓ)-robust combiner for collision-resistant hash-functions is a construction which from ℓ hash-functions constructs a hash-function which is collision-resistant if at least k of the components are collision-resistant. One trivially gets a (k, ℓ)-robust combiner by concatenating the output of any ℓ - k + 1 of the components, unfortunately this is not very practical as the length of the output of the combiner is quite large. We show that this is unavoidable as no black-box (k, ℓ)-robust combiner whose output is significantly shorter than what can be achieved by concatenation exists. This answers a question of Boneh and Boyen (Crypto'06). AU - Krzysztof Pietrzak ID - 3218 TI - Non-trivial black-box combiners for collision-resistant hash-functions don't exist VL - 4515 ER - TY - JOUR AB - The accumulation of deleterious mutations plays a major role in evolution, and key to this are the interactions between their fitness effects, known as epistasis. Whether mutations tend to interact synergistically (with multiple mutations being more deleterious than would be expected from their individual fitness effects) or antagonistically is important for a variety of evolutionary questions, particularly the evolution of sex. Unfortunately, the experimental evidence on the prevalence and strength of epistasis is mixed and inconclusive. Here we study theoretically whether synergistic or antagonistic epistasis is likely to be favored by evolution and by how much. We find that in the presence of recombination, evolution favors less synergistic or more antagonistic epistasis whenever mutations that change the epistasis in this direction are possible. This is because evolution favors increased buffering against the effects of deleterious mutations. This suggests that we should not expect synergistic epistasis to be widespread in nature and hence that the mutational deterministic hypothesis for the advantage of sex may not apply widely. AU - Desai, Michael M AU - Daniel Weissman AU - Feldman, Marcus W ID - 3305 IS - 2 JF - Genetics TI - Evolution can favor antagonistic epistasis VL - 177 ER - TY - JOUR AB - Mechanical single-molecule techniques offer exciting possibilities to investigate protein folding and stability in native environments at submolecular resolution. By applying a free-energy reconstruction procedure developed by Hummer and Szabo, which is based on a statistical theorem introduced by Jarzynski, we determined the unfolding free energy of the membrane proteins bacteriorhodopsin (BR), halorhodopsin, and the sodium-proton antiporter NhaA. The calculated energies ranged from 290.5kcal/mol for BR to 485.5kcal/mol for NhaA. For the remarkably stable BR, the equilibrium unfolding free energy was independent of pulling rate and temperature ranging between 18 and 42°C. Our experiments also revealed heterogeneous energetic properties in individual transmembrane helices. In halorhodopsin, the stabilization of a short helical segment yielded a characteristic signature in the energy profile. In NhaA, a pronounced peak was observed at a functionally important site in the protein. Since a large variety of single- and multispan membrane proteins can be tackled in mechanical unfolding experiments, our approach provides a basis for systematically elucidating energetic properties of membrane proteins with the resolution of individual secondary-structure elements. AU - Preiner, Johannes AU - Harald Janovjak AU - Rankl, Christian AU - Knaus, Helene AU - Cisneros, David A AU - Kedrov, Alexej AU - Kienberger, Ferry AU - Mueller, Daniel J AU - Hinterdorfer, Peter ID - 3411 IS - 3 JF - Biophysical Journal TI - Free energy of membrane protein unfolding derived from single-molecule force measurements VL - 93 ER - TY - GEN AB - Molecular interactions are the basic language of biological processes. They establish the forces interacting between the building blocks of proteins and other macromolecules, thus determining their functional roles. Because molecular interactions trigger virtually every biological process, approaches to decipher their language are needed. Single-molecule force spectroscopy (SMFS) has been used to detect and characterize different types of molecular interactions that occur between and within native membrane proteins. The first experiments detected and localized molecular interactions that stabilized membrane proteins, including how these interactions were established during folding of α-helical secondary structure elements into the native protein and how they changed with oligomerization, temperature, and mutations. SMFS also enables investigators to detect and locate molecular interactions established during ligand and inhibitor binding. These exciting applications provide opportunities for studying the molecular forces of life. Further developments will elucidate the origins of molecular interactions encoded in their lifetimes, interaction ranges, interplay, and dynamics characteristic of biological systems. AU - Kedrov, Alexej AU - Harald Janovjak AU - Sapra, Tanuj K AU - Mueller, Daniel J ID - 3412 T2 - Annual Review of Biophysics TI - Deciphering molecular interactions of native membrane proteins by single-molecule force spectroscopy VL - 36 ER - TY - JOUR AB - We present a general theoretical framework to discuss mechanisms of morphogen transport and gradient formation in a cell layer. Trafficking events on the cellular scale lead to transport on larger scales. We discuss in particular the case of transcytosis where morphogens undergo repeated rounds of internalization into cells and recycling. Based on a description on the cellular scale, we derive effective nonlinear transport equations in one and two dimensions which are valid on larger scales. We derive analytic expressions for the concentration dependence of the effective diffusion coefficient and the effective degradation rate. We discuss the effects of a directional bias on morphogen transport and those of the coupling of the morphogen and receptor kinetics. Furthermore, we discuss general properties of cellular transport processes such as the robustness of gradients and relate our results to recent experiments on the morphogen Decapentaplegic (Dpp) that acts in the wing disk of the fruit fly Drosophila. © 2007 The American Physical Society AU - Bollenbach, Mark Tobias AU - Kruse, Karsten AU - Pantazis, Periklis AU - Gonzalez Gaitan, Marcos AU - Julicher, Frank ID - 3427 IS - 1 JF - Physical Review E Statistical Nonlinear and Soft Matter Physics TI - Morphogen transport in epithelia VL - 75 ER - TY - JOUR AB - On the linear track, the recent firing sequences of CA1 place cells recur during sharp wave/ripple patterns (SWRs) in a reverse temporal order [Foster & Wilson (2006) Nature, 440, 680-683]. We have found similar reverse-order reactivation during SWRs in open-field exploration where the firing sequence of cells varied before each SWR. Both the onset times and the firing patterns of cells showed a tendency for reversed sequences during SWRs. These effects were observed for SWRs that occurred during exploration, but not for those during longer immobility periods. Additionally, reverse reactivation was stronger when it was preceded by higher speed (> 5 cm/s) run periods. The trend for reverse-order SWR reactivation was not significantly different in familiar and novel environments, even though SWR-associated firing rates of both pyramidal cells and interneurons were reduced in novel environments as compared with familiar. During exploration-associated SWRs (eSWR) place cells retain place-selective firing [O'Neill et al. (2006) Neuron, 49, 143-155]. Here, we have shown that each cell's firing onset was more delayed and firing probability more reduced during eSWRs the further the rat was from the middle of the cell's place field; that is, cells receiving less momentary place-related excitatory drive fired later during SWR events. However, even controlling for place field distance, the recent firing of cells was still significantly correlated with SWR reactivation sequences. We therefore propose that both place-related drive and the firing history of cells contribute to reverse reactivation during eSWRs. AU - Jozsef Csicsvari AU - Joseph O'Neill AU - Allen, Kevin AU - Senior,Timothy ID - 3523 IS - 3 JF - European Journal of Neuroscience TI - Place-selective firing contributes to the reverse-order reactivation of CA1 pyramidal cells during sharp waves in open-field exploration VL - 26 ER - TY - CONF AB - In this paper, the multiobjective optimal design of space-based reconfigurable sensor networks with novel adaptive MEMS antennas is investigated by using multiobjective evolutionary algorithms. The non-dominated sorting genetic algorithm II (NSGA-II) is employed to obtain multi-criteria Pareto-optimal solutions, which allows system designers to easily make a reasonable trade-off choice from the set of non-dominated solutions according to their preferences and system requirements. As a case study, a cluster-based satellite sensing network is simulated under multiple objectives. Most importantly, this paper also presents the application of our newly designed adaptive MEMS antennas together with the NSGA-II to the multiobjective optimal design of space-based reconfigurable sensor networks. AU - Yang, Erfu AU - Haridas, Nakul AU - El-Rayis, Ahmed O AU - Erdogan, Ahmet T AU - Arslan, Tughrul AU - Nicholas Barton ID - 3601 TI - Multiobjective optimal design of MEMS-based reconfigurable and evolvable sensor networks for space applications ER - TY - GEN AB - Recent years have seen huge advances in object recognition from images. Recognition rates beyond 95% are the rule rather than the exception on many datasets. However, most state-of-the-art methods can only decide if an object is present or not. They are not able to provide information on the object location or extent within in the image. We report on a simple yet powerful scheme that extends many existing recognition methods to also perform localization of object bounding boxes. This is achieved by maximizing the classification score over all possible subrectangles in the image. Despite the impression that this would be computationally intractable, we show that in many situations efficient algorithms exist which solve a generalized maximum subrectangle problem. We show how our method is applicable to a variety object detection frameworks and demonstrate its performance by applying it to the popular bag of visual words model, achieving competitive results on the PASCAL VOC 2006 dataset. AU - Blaschko,Matthew B AU - Hofmann,Thomas AU - Christoph Lampert ID - 3687 IS - 164 T2 - Unknown TI - Efficient subwindow search for object localization ER - TY - CONF AB - The extraction of a parametric global motion from a motion field is a task with several applications in video processing. We present two probabilistic formulations of the problem and carry out optimization using the RAST algorithm, a geometric matching method novel to motion estimation in video. RAST uses an exhaustive and adaptive search of transformation space and thus gives – in contrast to local sampling optimization techniques used in the past – a globally optimal solution. Among other applications, our framework can thus be used as a source of ground truth for benchmarking motion estimation algorithms. Our main contributions are: first, the novel combination of a state-of-the-art MAP criterion for dominant motion estimation with a search procedure that guarantees global optimality. Second, experimental results that illustrate the superior performance of our approach on synthetic flow fields as well as real-world video streams. Third, a significant speedup of the search achieved by extending the model with an additional smoothness prior. AU - Ulges, Adrian AU - Christoph Lampert AU - Keysers,Daniel AU - Breuel,Thomas M ID - 3701 TI - Optimal dominant motion estimation using adaptive search of transformation space VL - 4713 ER - TY - JOUR AB - A cell's ability to regulate gene transcription depends in large part on the energy with which transcription factors (TFs) bind their DNA regulatory sites. Obtaining accurate models of this binding energy is therefore an important goal for quantitative biology. In this article, we present a principled likelihood-based approach for inferring physical models of TF-DNA binding energy from the data produced by modern high-throughput binding assays. Central to our analysis is the ability to assess the relative likelihood of different model parameters given experimental observations. We take a unique approach to this problem and show how to compute likelihood without any explicit assumptions about the noise that inevitably corrupts such measurements. Sampling possible choices for model parameters according to this likelihood function, we can then make probabilistic predictions for the identities of binding sites and their physical binding energies. Applying this procedure to previously published data on the Saccharomyces cerevisiae TF Abf1p, we find models of TF binding whose parameters are determined with remarkable precision. Evidence for the accuracy of these models is provided by an astonishing level of phylogenetic conservation in the predicted energies of putative binding sites. Results from in vivo and in vitro experiments also provide highly consistent characterizations of Abf1p, a result that contrasts with a previous analysis of the same data. AU - Kinney,Justin B AU - Gasper Tkacik AU - Callan,Curtis G ID - 3731 IS - 2 JF - PNAS TI - Precise physical models of protein-DNA interaction from high-throughput data VL - 104 ER - TY - JOUR AB - We present an extension to Lagrangian finite element methods to allow for large plastic deformations of solid materials. These behaviors are seen in such everyday materials as shampoo, dough, and clay as well as in fantastic gooey and blobby creatures in special effects scenes. To account for plastic deformation, we explicitly update the linear basis functions defined over the finite elements during each simulation step. When these updates cause the basis functions to become ill-conditioned, we remesh the simulation domain to produce a new high-quality finite-element mesh, taking care to preserve the original boundary. We also introduce an enhanced plasticity model that preserves volume and includes creep and work hardening/softening. We demonstrate our approach with simulations of synthetic objects that squish, dent, and flow. To validate our methods, we compare simulation results to videos of real materials. AU - Bargteil, Adam AU - Wojtan, Christopher J AU - Hodgins, Jessica AU - Turk, Greg ID - 3765 IS - 3 JF - ACM Transactions on Graphics TI - A finite element method for animating large viscoplastic flow VL - 26 ER - TY - CONF AB - In this paper, we present a simple method for animating natural phenomena such as erosion, sedimentation, and acidic corrosion. We discretize the appropriate physical or chemical equations using finite differences, and we use the results to modify the shape of a solid body. We remove mass from an object by treating its surface as a level set and advecting it inward, and we deposit the chemical and physical byproducts into simulated fluid. Similarly, our technique deposits sediment onto a surface by advecting the level set outward. Our idea can be used for off-line high quality animations as well as interactive applications such as games, and we demonstrate both in this paper. AU - Wojtan, Christopher J AU - Carlson, Mark AU - Mucha, Peter AU - Turk, Greg ID - 3762 TI - Animating corrosion and erosion ER - TY - JOUR AB - Gamma frequency oscillations are thought to provide a temporal structure for information processing in the brain. They contribute to cognitive functions, such as memory formation and sensory processing, and are disturbed in some psychiatric disorders. Fast-spiking, parvalbumin-expressing, soma-inhibiting interneurons have a key role in the generation of these oscillations. Experimental analysis in the hippocampus and the neocortex reveals that synapses among these interneurons are highly specialized. Computational analysis further suggests that synaptic specialization turns interneuron networks into robust gamma frequency oscillators. AU - Bartos, Marlene AU - Vida, Imre AU - Peter Jonas ID - 3816 IS - 1 JF - Nature Reviews Neuroscience TI - Synaptic mechanisms of synchronized gamma oscillations in inhibitory interneuron networks (Review) VL - 8 ER - TY - JOUR AB - Life in a social group increases the risk of disease transmission. To counteract this threat, social insects have evolved manifold antiparasite defenses, ranging from social exclusion of infected group members to intensive care. It is generally assumed that individuals performing hygienic behaviors risk infecting themselves, suggesting a high direct cost of helping. Our work instead indicates the opposite for garden ants. Social contact with individual workers, which were experimentally exposed to a fungal parasite, provided a clear survival benefit to nontreated, naive group members upon later challenge with the same parasite. This first demonstration of contact immunity in Social Hymenoptera and complementary results from other animal groups and plants suggest its general importance in both antiparasite and antiherbivore defense. In addition to this physiological prophylaxis of adult ants, infection of the brood was prevented in our experiment by behavioral changes of treated and naive workers. Parasite-treated ants stayed away from the brood chamber, whereas their naive nestmates increased brood-care activities. Our findings reveal a direct benefit for individuals to perform hygienic behaviors toward others, and this might explain the widely observed maintenance of social cohesion under parasite attack in insect societies. AU - Ugelvig, Line V AU - Cremer, Sylvia ID - 3911 IS - 22 JF - Current Biology TI - Social prophylaxis: group interaction promotes collective immunity in ant colonies VL - 17 ER - TY - JOUR AB - Social insect colonies have evolved collective immune defences against parasites. These ‘social immune systems’ result from the cooperation of the individual group members to combat the increased risk of disease transmission that arises from sociality and group living. In this review we illustrate the pathways that parasites can take to infect a social insect colony and use these pathways as a framework to predict colony defence mechanisms and present the existing evidence. We find that the collective defences can be both prophylactic and activated on demand and consist of behavioural, physiological and organisational adaptations of the colony that prevent parasite entrance, establishment and spread. We discuss the regulation of collective immunity, which requires complex integration of information about both the parasites and the internal status of the insect colony. Our review concludes with an examination of the evolution of social immunity, which is based on the consequences of selection at both the individual and the colony level. AU - Cremer, Sylvia AU - Armitage, Sophie AU - Schmid Hempel, Paul ID - 3909 IS - 16 JF - Current Biology TI - Social immunity VL - 17 ER - TY - JOUR AU - Hughes, David AU - Cremer, Sylvia ID - 3910 IS - 5 JF - Animal Behaviour TI - Plasticity in anti-parasite behaviours and its suggested role in invasion biology VL - 74 ER - TY - JOUR AB - Herein, we study the interfaces of a set of 146 transient protein-protein interfaces in order to better understand the principles of their interactions. We define and generate the protein interface using tools from computational geometry and topology and then apply statistical analysis to its residue composition. In addition to counting individual occurrences, we evaluate pairing preferences, both across and as neighbors on one side of an interface. Likelihood correction emphasizes novel and unexpected pairs, such as the His-Cys pair found in most complexes of serine proteases with their diverse inhibitors and the Met-Met neighbor pair found in unrelated protein interfaces. We also present a visualization of the protein interface that allows for facile identification of residue-residue contacts and other biochemical properties. AU - Headd, Jeffrey J AU - Ban, Y E Andrew AU - Brown, Paul AU - Herbert Edelsbrunner AU - Vaidya, Madhuwanti AU - Rudolph, Johannes ID - 3976 IS - 7 JF - Journal of Proteome Research TI - Protein-protein interfaces: Properties, preferences, and projections VL - 6 ER - TY - CONF AB - Building on the work of Martinetz, Schulten and de Silva, Carlsson, we introduce a 2-parameter family of witness complexes and algorithms for constructing them. This family can be used to determine the gross topology of point cloud data in R-d or other metric spaces. The 2-parameter family is sensitive to differences in sampling density and thus amenable to detecting patterns within the data set. It also lends itself to theoretical analysis. For example, we can prove that in the limit, when the witnesses cover the entire domain, witness complexes in the family that share the first, scale parameter have the same homotopy type. AU - Attali, Dominique AU - Herbert Edelsbrunner AU - Harer, John AU - Mileyko, Yuriy ID - 3981 TI - Alpha-beta witness complexes VL - 4619 ER - TY - CONF AB - We study the reconstruction of a stratified space from a possibly noisy point sample. Specifically, we use the vineyard of the distance function restricted to a I-parameter family of neighborhoods of a point to assess the local homology of the stratified space at that point. We prove the correctness of this assessment under the assumption of a sufficiently dense sample. We also give an algorithm that constructs the vineyard and makes the local assessment in time at most cubic in the size of the Delaunay triangulation of the point sample. AU - Paul Bendich AU - Cohen-Steiner, David AU - Herbert Edelsbrunner AU - Harer, John AU - Morozov, Dmitriy ID - 3975 TI - Inferring local homology from sampled stratified spaces ER - TY - JOUR AB - Using inclusion-exclusion, we can write the indicator function of a union of finitely many balls as an alternating sum of indicator functions of common intersections of balls. We exhibit abstract simplicial complexes that correspond to minimal inclusion-exclusion formulas. They include the dual complex, as defined in [3], and are characterized by the independence of their simplices and by geometric realizations with the same underlying space as the dual complex. AU - Attali, Dominique AU - Herbert Edelsbrunner ID - 3977 IS - 1 JF - Discrete & Computational Geometry TI - Inclusion-exclusion formulas from independent complexes VL - 37 ER - TY - JOUR AB - Gastrulation is a morphogenetic process that results in the formation of the embryonic germ layers. Here we detail the major cell movements that occur during zebrafish gastrulation: epiboly, internalization, and convergent extension. Although gastrulation is known to be regulated by signaling pathways such as the Wnt/planar cell polarity pathway, many questions remain about the underlying molecular and cellular mechanisms. Key factors that may play a role in gastrulation cell movements are cell adhesion and cytoskeletal rearrangement. In addition, some of the driving force for gastrulation may derive from tissue interactions such as those described between the enveloping layer and the yolk syncytial layer. Future exploration of gastrulation mechanisms relies on the development of sensitive and quantitative techniques to characterize embryonic germ-layer properties. AU - Rohde, Laurel AU - Heisenberg, Carl-Philipp J ID - 4152 JF - International Review of Cytology - A Survey of Cell Biology TI - Zebrafish gastrulation: Cell movements, signals, and mechanisms VL - 261 ER - TY - JOUR AB - We are interested in the cellular and molecular mechanisms underlying tissue morphogenesis during zebrafish gastrulation. Both differential cell adhesion and contractility have been proposed to be key mechanisms by which tissues form and rearrange in development. To obtain insight into the potential roles of differential cell adhesion and contraction for germ layer morphogenesis during gastrulation, we are analyzing cell adhesion and contraction of germ layer progenitor cells using atomic force microscopy, primary tissue culture and transplantation assays. I will present and discuss data about the differential adhesiveness and contractility of germ layer progenitor cells in the context of germ layer formation during vertebrate gastrulation. AU - Krieg, Michael AU - Arboleda, Yohanna AU - Müller, Daniel AU - Heisenberg, Carl-Philipp J ID - 4182 IS - Supplement 1 JF - European Journal of Cell Biology TI - The role of cell adhesion and contractility for germ layer morphogenesis during zebrafish gastrulation VL - 86 ER - TY - JOUR AB - The discovery of the genetic code was one of the most important advances of modern biology. But there is more to a DNA code than protein sequence; DNA carries signals for splicing, localization, folding, and regulation that are often embedded within the protein-coding sequence. In this issue, Itzkovitz and Alon show that the specific 64-to-20 mapping found in the genetic code may have been optimized for permitting protein-coding regions to carry this extra information and suggest that this property may have evolved as a side benefit of selection to minimize the negative effects of frameshift errors. AU - Bollenbach, Mark Tobias AU - Vetsigian, Kalin AU - Kishony, Roy ID - 4225 IS - 4 JF - Genome Research TI - Evolution and multilevel optimization of the genetic code VL - 17 ER - TY - JOUR AB - In the developing fly wing, secreted morphogens such as Decapentaplegic (Dpp) and Wingless (Wg) form gradients of concentration providing positional information. Dpp forms a longer-range gradient than Wg. To understand how the range is controlled, we measured the four key kinetic parameters governing morphogen spreading: the production rate, the effective diffusion coefficient, the degradation rate, and the immobile fraction. The four parameters had different values for Dpp versus Wg. In addition, Dynamin-dependent endocytosis was required for spreading of Dpp, but not Wg. Thus, the cellular mechanisms of Dpp and Wingless spreading are different: Dpp spreading requires endocytic, intracellular trafficking. AU - Anna Kicheva AU - Pantazis, Periklis AU - Bollenbach, Tobias AU - Kalaidzidis, Yannis AU - Bittig, Thomas AU - Julicher, Frank AU - Gonzalez-Gaitan, Marcos ID - 4226 IS - 5811 JF - Science TI - Kinetics of morphogen gradient formation VL - 315 ER - TY - CONF AB - Library 2.0 and user-generated content are two terms, which are closely connected. In the presentation, I will briefly define both terms. Two example projects where user- generated content and libraries interact will be presented. The cooperation of Wikipedia and the Personennamendatei, the German cooperative name authority files is the first. The second will be Wikisource where users provide transcribed source material. Another important area of user-generated content is social tagging where users index different resources. And if the users will do so much in the future, is there still a place for librarians? But in the future user and librarians become partners and the library will provide the platform: the library 2.0. AU - Danowski, Patrick ID - 4342 TI - Library 2.0 and User-Generated Content - What can the users do for us? ER - TY - JOUR AU - Patrick Danowski AU - Pfeifer,Barbara ID - 4343 IS - 2 JF - Bibliothek - Forschung Und Praxis TI - Wikipedia und Normdateien: Wege der Vernetzung am Beispiel der Kooperation mit der Personennamendatei VL - 31 ER - TY - JOUR AU - Patrick Danowski AU - Heller,Lambert ID - 4344 IS - 2007 JF - Bibliothek - Forschung Und Praxis TI - Bibliothek 2.0 ? Wird alles anders? VL - 31 ER - TY - JOUR AB - BACKGROUND: The invention of the Genome Sequence 20 DNA Sequencing System (454 parallel sequencing platform) has enabled the rapid and high-volume production of sequence data. Until now, however, individual emulsion PCR (emPCR) reactions and subsequent sequencing runs have been unable to combine template DNA from multiple individuals, as homologous sequences cannot be subsequently assigned to their original sources. METHODOLOGY: We use conventional PCR with 5'-nucleotide tagged primers to generate homologous DNA amplification products from multiple specimens, followed by sequencing through the high-throughput Genome Sequence 20 DNA Sequencing System (GS20, Roche/454 Life Sciences). Each DNA sequence is subsequently traced back to its individual source through 5'tag-analysis. CONCLUSIONS: We demonstrate that this new approach enables the assignment of virtually all the generated DNA sequences to the correct source once sequencing anomalies are accounted for (miss-assignment rate&lt;0.4%). Therefore, the method enables accurate sequencing and assignment of homologous DNA sequences from multiple sources in single high-throughput GS20 run. We observe a bias in the distribution of the differently tagged primers that is dependent on the 5' nucleotide of the tag. In particular, primers 5' labelled with a cytosine are heavily overrepresented among the final sequences, while those 5' labelled with a thymine are strongly underrepresented. A weaker bias also exists with regards to the distribution of the sequences as sorted by the second nucleotide of the dinucleotide tags. As the results are based on a single GS20 run, the general applicability of the approach requires confirmation. However, our experiments demonstrate that 5'primer tagging is a useful method in which the sequencing power of the GS20 can be applied to PCR-based assays of multiple homologous PCR products. The new approach will be of value to a broad range of research areas, such as those of comparative genomics, complete mitochondrial analyses, population genetics, and phylogenetics. AU - Binladen, Jonas AU - Gilbert, M Thomas AU - Jonathan Bollback AU - Panitz, Frank AU - Bendixen, Christian AU - Nielsen, Rasmus AU - Willerslev, Eske ID - 4353 IS - 2 JF - PLoS One TI - The use of coded PCR primers enables high-throughput sequencing of multiple homolog amplification products by 454 parallel sequencing VL - 2 ER - TY - JOUR AB - We used a comparative genomics approach to identify genes that are under positive selection in six strains of Escherichia coli and Shigella flexneri, including five strains that are human pathogens. We find that positive selection targets a wide range of different functions in the E. coli genome, including cell surface proteins such as beta barrel porins, presumably because of the involvement of these genes in evolutionary arms races with other bacteria, phages, and/or the host immune system. Structural mapping of positively selected sites on trans-membrane beta barrel porins reveals that the residues under positive selection occur almost exclusively in the extracellular region of the proteins that are enriched with sites known to be targets of phages, colicins, or the host immune system. More surprisingly, we also find a number of other categories of genes that show very strong evidence for positive selection, such as the enigmatic rhs elements and transposases. Based on structural evidence, we hypothesize that the selection acting on transposases is related to the genomic conflict between transposable elements and the host genome. AU - Petersen, Lise AU - Jonathan Bollback AU - Dimmic, Matt AU - Hubisz, Melissa AU - Nielsen, Rasmus ID - 4356 IS - 9 JF - Genome Research TI - Genes under positive selection in Escherichia coli VL - 17 ER - TY - JOUR AB - When a beneficial mutation is fixed in a population that lacks recombination, the genetic background linked to that mutation is fixed. As a result, beneficial mutations on different backgrounds experience competition, or "clonal interference," that can cause asexual populations to evolve more slowly than their sexual counterparts. Factors such as a large population size (N) and high mutation rates (mu) increase the number of competing beneficial mutations, and hence are expected to increase the intensity of clonal interference. However, recent theory suggests that, with very large values of Nmu, the severity of clonal interference may instead decline. The reason is that, with large Nmu, genomes including both beneficial mutations are rapidly created by recurrent mutation, obviating the need for recombination. Here, we analyze data from experimentally evolved asexual populations of a bacteriophage and find that, in these nonrecombining populations with very large Nmu, recurrent mutation does appear to ameliorate this cost of asexuality. AU - Jonathan Bollback AU - Huelsenbeck, John P ID - 4355 IS - 6 JF - Molecular Biology and Evolution TI - Clonal interference is alleviated by high mutation rates in large populations VL - 24 ER - TY - JOUR AB - Homology search is one of the most ubiquitous bioinformatic tasks, yet it is unknown how effective the currently available tools are for identifying noncoding RNAs (ncRNAs). In this work, we use reliable ncRNA data sets to assess the effectiveness of methods such as BLAST, FASTA, HMMer, and Infernal. Surprisingly, the most popular homology search methods are often the least accurate. As a result, many studies have used inappropriate tools for their analyses. On the basis of our results, we suggest homology search strategies using the currently available tools and some directions for future development. AU - Freyhult, Eva K AU - Jonathan Bollback AU - Gardner, Paul P ID - 4354 IS - 1 JF - Genome Research TI - Exploring genomic dark matter: a critical assessment of the performance of homology search methods on noncoding RNA VL - 17 ER - TY - CONF AU - Maler, Oded AU - Dejan Nickovic AU - Pnueli,Amir ID - 4370 TI - On synthesizing controllers from bounded-response properties ER - TY - CONF AU - Dejan Nickovic AU - Maler, Oded ID - 4368 TI - AMT: a property-based monitoring tool for analog systems ER - TY - JOUR AB - Endocytosis is an essential process by which eukaryotic cells internalize exogenous material or regulate signaling at the cell surface [1]. Different endocytic pathways are well established in yeast and animals; prominent among them is clathrin-dependent endocytosis [2, 3]. In plants, endocytosis is poorly defined, and no molecular mechanism for cargo internalization has been demonstrated so far [4, 5], although the internalization of receptor-ligand complexes at the plant plasma membrane has recently been shown [6]. Here we demonstrate by means of a green-to-red photoconvertible fluorescent reporter, EosFP [7], the constitutive endocytosis of PIN auxin efflux carriers [8] and their recycling to the plasma membrane. Using a plant clathrin-specific antibody, we show the presence of clathrin at different stages of coated-vesicle formation at the plasma membrane in Arabidopsis. Genetic interference with clathrin function inhibits PIN internalization and endocytosis in general. Furthermore, pharmacological interference with cargo recruitment into the clathrin pathway blocks internalization of PINs and other plasma-membrane proteins. Our data demonstrate that clathrin-dependent endocytosis is operational in plants and constitutes the predominant pathway for the internalization of numerous plasma-membrane-resident proteins including PIN auxin efflux carriers. AU - Dhonukshe, Pankaj AU - Aniento, Fernando AU - Hwang, Inhwan AU - Robinson, David G AU - Mravec, Jozef AU - Stierhof, York-Dieter AU - Jirí Friml ID - 3022 IS - 6 JF - Current Biology TI - Clathrin-mediated constitutive endocytosis of PIN auxin efflux carriers in Arabidopsis VL - 17 ER - TY - JOUR AB - Polar transport of the phytohormone auxin controls numerous growth responses in plants. Molecular characterization of auxin transport in Arabidopsis thaliana has provided important insights into the mechanisms underlying the regulation of auxin distribution. In particular, the control of subcellular localization and expression of PIN-type auxin efflux components appears to be fundamental for orchestrated distribution of the growth regulator throughout the entire plant body. Here we describe the identification of two Arabidopsis loci, MOP2 and MOP3 (for MODULATOR OF PIN), that are involved in control of the steady-state levels of PIN protein. Mutations in both loci result in defects in auxin distribution and polar auxin transport, and cause phenotypes consistent with a reduction of PIN protein levels. Genetic interaction between PIN2 and both MOP loci is suggestive of functional cross-talk, which is further substantiated by findings demonstrating that ectopic PIN up-regulation is compensated in the mop background. Thus, in addition to pathways that control PIN localization and transcription, MOP2 and MOP3 appear to be involved in fine-tuning of auxin distribution via post-transcriptional regulation of PIN expression. AU - Malenica, Nenad AU - Abas, Lindy AU - Benjamins, René AU - Kitakura, Saeko AU - Sigmund, Harald F AU - Jun, Kim S AU - Hauser, Marie-Theres AU - Jirí Friml AU - Luschnig, Christian ID - 3027 IS - 4 JF - Plant Journal TI - MODULATOR of PIN genes control steady state levels of Arabidopsis PIN proteins VL - 51 ER - TY - JOUR AB - Accumulation of specific proteins at synaptic structures is essential for synapse assembly and function, but mechanisms regulating local protein enrichment remain poorly understood. At the neuromuscular junction (NMJ), subsynaptic nuclei underlie motor axon terminals within extrafusal muscle fibers and are transcriptionally distinct from neighboring nuclei. In this study, we show that expression of the ETS transcription factor Erm is highly concentrated at subsynaptic nuclei, and its mutation in mice leads to severe downregulation of many genes with normally enriched subsynaptic expression. Erm mutant mice display an expansion of the muscle central domain in which acetylcholine receptor (AChR) clusters accumulate, show gradual fragmentation of AChR clusters, and exhibit symptoms of muscle weakness mimicking congenital myasthenic syndrome (CMS). Together, our findings define Erm as an upstream regulator of a transcriptional program selective to subsynaptic nuclei at the NMJ and underscore the importance of transcriptional control of local synaptic protein accumulation. AU - Simon Hippenmeyer AU - Huber, Roland M AU - Ladle, David R AU - Murphy, Kenneth AU - Arber, Silvia ID - 3144 IS - 5 JF - Neuron TI - ETS transcription factor Erm controls subsynaptic gene expression in skeletal muscles VL - 55 ER -