TY - JOUR AB - We give a cohomological interpretation of both the Kac polynomial and the refined Donaldson-Thomas-invariants of quivers. This interpretation yields a proof of a conjecture of Kac from 1982 and gives a new perspective on recent work of Kontsevich-Soibelman. Thisis achieved by computing, via an arithmetic Fourier transform, the dimensions of the isotypical components of the cohomology of associated Nakajima quiver varieties under the action of a Weyl group. The generating function of the corresponding Poincare polynomials is an extension of Hua's formula for Kac polynomials of quivers involving Hall-Littlewood symmetric functions. The resulting formulae contain a wide range of information on the geometry of the quiver varieties. AU - Tamas Hausel AU - Letellier, Emmanuel AU - Rodríguez Villegas, Fernando ID - 1442 IS - 3 JF - Annals of Mathematics TI - Positivity for Kac polynomials and DT-invariants of quivers VL - 177 ER - TY - CHAP AB - Here we survey several results and conjectures on the cohomology of the total space of the Hitchin system: the moduli space of semi-stable rank n and degree d Higgs bundles on a complex algebraic curve C. The picture emerging is a dynamic mixture of ideas originating in theoretical physics such as gauge theory and mirror symmetry, Weil conjectures in arithmetic algebraic geometry, representation theory of finite groups of Lie type and Langlands duality in number theory. AU - Tamas Hausel ID - 1443 T2 - Handbook of Moduli: Volume II TI - Global topology of the Hitchin system VL - 25 ER - TY - JOUR AB - We study connections between the topology of generic character varieties of fundamental groups of punctured Riemann surfaces, Macdonald polynomials, quiver representations, Hilbert schemes on Cx × Cx, modular forms and multiplicities in tensor products of irreducible characters of finite general linear groups. AU - Tamas Hausel AU - Letellier, Emmanuel AU - Rodríguez Villegas, Fernando ID - 1469 JF - Advances in Mathematics TI - Arithmetic harmonic analysis on character and quiver varieties II VL - 234 ER - TY - JOUR AB - We show that a natural isomorphism between the rational cohomology groups of the two zero-dimensional Hilbert schemes of n-points of two surfaces, the affine plane minus the axes and the cotangent bundle of an elliptic curve, exchanges the weight filtration on the first set of cohomology groups with the perverse Leray filtration associated with a natural fibration on the second set of cohomology groups. We discuss some associated hard Lefschetz phenomena. AU - De Cataldo, Mark A AU - Tamas Hausel AU - Migliorini, Luca ID - 1470 JF - Journal of Singularities TI - Exchange between perverse and weight filtration for the Hilbert schemes of points of two surfaces VL - 7 ER - TY - JOUR AU - Aceto, Luca AU - Henzinger, Monika H AU - Sgall, Jiří ID - 11758 IS - 1 JF - Information and Computation SN - 0890-5401 TI - 38th International Colloquium on Automata, Languages and Programming VL - 222 ER - TY - JOUR AB - The development of a functional tissue requires coordination of the amplification of progenitors and their differentiation into specific cell types. The molecular basis for this coordination during myotome ontogeny is not well understood. Dermomytome progenitors that colonize the myotome first acquire myocyte identity and subsequently proliferate as Pax7-expressing progenitors before undergoing terminal differentiation. We show that the dynamics of sonic hedgehog (Shh) signaling is crucial for this transition in both avian and mouse embryos. Initially, Shh ligand emanating from notochord/floor plate reaches the dermomyotome, where it both maintains the proliferation of dermomyotome cells and promotes myogenic differentiation of progenitors that colonized the myotome. Interfering with Shh signaling at this stage produces small myotomes and accumulation of Pax7-expressing progenitors. An in vivo reporter of Shh activity combined with mouse genetics revealed the existence of both activator and repressor Shh activities operating on distinct subsets of cells during the epaxial myotomal maturation. In contrast to observations in mice, in avians Shh promotes the differentiation of both epaxial and hypaxial myotome domains. Subsequently, myogenic progenitors become refractory to Shh; this is likely to occur at the level of, or upstream of, smoothened signaling. The end of responsiveness to Shh coincides with, and is thus likely to enable, the transition into the growth phase of the myotome. AU - Kahane, Nitza AU - Ribes, Vanessa AU - Anna Kicheva AU - Briscoe, James AU - Kalcheim, Chaya ID - 1726 IS - 8 JF - Development TI - The transition from differentiation to growth during dermomyotome-derived myogenesis depends on temporally restricted hedgehog signaling VL - 140 ER - TY - JOUR AB - Cells at different positions in a developing tissue receive different concentrations of signaling molecules, called morphogens, and this influences their cell fate. Morphogen concentration gradients have been proposed to control patterning as well as growth in many developing tissues. Some outstanding questions about tissue patterning by morphogen gradients are the following: What are the mechanisms that regulate gradient formation and shape? Is the positional information encoded in the gradient sufficiently precise to determine the positions of target gene domain boundaries? What are the temporal dynamics of gradients and how do they relate to patterning and growth? These questions are inherently quantitative in nature and addressing them requires measuring morphogen concentrations in cells, levels of downstream signaling activity, and kinetics of morphogen transport. Here we first present methods for quantifying morphogen gradient shape in which the measurements can be calibrated to reflect actual morphogen concentrations. We then discuss using fluorescence recovery after photobleaching to study the kinetics of morphogen transport at the tissue level. Finally, we present particle tracking as a method to study morphogen intracellular trafficking. AU - Anna Kicheva AU - Holtzer, Laurent AU - Wartlick, Ortrud AU - Schmidt, Thomas S AU - González-Gaitán, Marcos A ID - 1727 IS - 5 JF - Cold Spring Harbor Protocols TI - Quantitative imaging of morphogen gradients in drosophila imaginal discs VL - 8 ER - TY - JOUR AB - We report on hole g-factor measurements in three terminal SiGe self-assembled quantum dot devices with a top gate electrode positioned very close to the nanostructure. Measurements of both the perpendicular as well as the parallel g-factor reveal significant changes for a small modulation of the top gate voltage. From the observed modulations, we estimate that, for realistic experimental conditions, hole spins can be electrically manipulated with Rabi frequencies in the order of 100 MHz. This work emphasises the potential of hole-based nano-devices for efficient spin manipulation by means of the g-tensor modulation technique. AU - Ares, Natalia AU - Georgios Katsaros AU - Golovach, Vitaly N AU - Zhang, Jianjun AU - Prager, Aaron A AU - Glazman, Leonid I AU - Schmidt, Oliver G AU - De Franceschi, Silvano ID - 1760 IS - 26 JF - Applied Physics Letters TI - SiGe quantum dots for fast hole spin Rabi oscillations VL - 103 ER - TY - JOUR AB - We report an electric-field-induced giant modulation of the hole g factor in SiGe nanocrystals. The observed effect is ascribed to a so-far overlooked contribution to the g factor that stems from the mixing between heavy- and light-hole wave functions. We show that the relative displacement between the confined heavy- and light-hole states, occurring upon application of the electric field, alters their mixing strength leading to a strong nonmonotonic modulation of the g factor. AU - Ares, Natalia AU - Golovach, Vitaly N AU - Georgios Katsaros AU - Stoffel, Mathieu AU - Fournel, Frank AU - Glazman, Leonid I AU - Schmidt, Oliver G AU - De Franceschi, Silvano ID - 1759 IS - 4 JF - Physical Review Letters TI - Nature of tunable hole g factors in quantum dots VL - 110 ER - TY - JOUR AB - The geometric aspects of quantum mechanics are emphasized most prominently by the concept of geometric phases, which are acquired whenever a quantum system evolves along a path in Hilbert space, that is, the space of quantum states of the system. The geometric phase is determined only by the shape of this path and is, in its simplest form, a real number. However, if the system has degenerate energy levels, then matrix-valued geometric state transformations, known as non-Abelian holonomies-the effect of which depends on the order of two consecutive paths-can be obtained. They are important, for example, for the creation of synthetic gauge fields in cold atomic gases or the description of non-Abelian anyon statistics. Moreover, there are proposals to exploit non-Abelian holonomic gates for the purposes of noise-resilient quantum computation. In contrast to Abelian geometric operations, non-Abelian ones have been observed only in nuclear quadrupole resonance experiments with a large number of spins, and without full characterization of the geometric process and its non-commutative nature. Here we realize non-Abelian non-adiabatic holonomic quantum operations on a single, superconducting, artificial three-level atom by applying a well-controlled, two-tone microwave drive. Using quantum process tomography, we determine fidelities of the resulting non-commuting gates that exceed 95 per cent. We show that two different quantum gates, originating from two distinct paths in Hilbert space, yield non-equivalent transformations when applied in different orders. This provides evidence for the non-Abelian character of the implemented holonomic quantum operations. In combination with a non-trivial two-quantum-bit gate, our method suggests a way to universal holonomic quantum computing. AU - Abdumalikov, Abdufarrukh A AU - Johannes Fink AU - Juliusson, K AU - Pechal, M AU - Berger, Stefan T AU - Wallraff, Andreas AU - Filipp, Stefan ID - 1785 IS - 7446 JF - Nature TI - Experimental realization of non-Abelian non-adiabatic geometric gates VL - 496 ER - TY - JOUR AB - When two indistinguishable single photons impinge at the two inputs of a beam splitter they coalesce into a pair of photons appearing in either one of its two outputs. This effect is due to the bosonic nature of photons and was first experimentally observed by Hong, Ou and Mandel. Here, we present the observation of the Hong-Ou-Mandel effect with two independent single-photon sources in the microwave frequency domain. We probe the indistinguishability of single photons, created with a controllable delay, in time-resolved second-order cross- and auto-correlation function measurements. Using quadrature amplitude detection we are able to resolve different photon numbers and detect coherence in and between the output arms. This scheme allows us to fully characterize the two-mode entanglement of the spatially separated beam-splitter output modes. Our experiments constitute a first step towards using two-photon interference at microwave frequencies for quantum communication and information processing. AU - Lang, C AU - Eichler, Christopher AU - Steffen, L. Kraig AU - Johannes Fink AU - Woolley, Matthew J AU - Blais, Alexandre AU - Wallraff, Andreas ID - 1787 IS - 6 JF - Nature Physics TI - Correlations, indistinguishability and entanglement in Hong-Ou-Mandel experiments at microwave frequencies VL - 9 ER - TY - JOUR AB - We report the experimental observation and a theoretical explanation of collective suppression of linewidths for multiple superconducting qubits coupled to a good cavity. This demonstrates how strong qubit-cavity coupling can significantly modify the dephasing and dissipation processes that might be expected for individual qubits, and can potentially improve coherence times in many-body circuit QED. AU - Nissen, Felix AU - Johannes Fink AU - Mlynek, Jonas A AU - Wallraff, Andreas AU - Keeling, Jonathan M ID - 1786 IS - 20 JF - Physical Review Letters TI - Collective suppression of linewidths in circuit QED VL - 110 ER - TY - JOUR AB - In the September 12, 2013 issue of Nature, the Epi4K Consortium (. Allen etal., 2013) reported sequencing 264patient trios with epileptic encephalopathies. The Consortium focused on genes exceptionally intolerant to sequence variations and found substantial interconnections with autism and intellectual disability gene networks. AU - Gaia Novarino AU - Baek, SeungTae AU - Gleeson, Joseph G ID - 1790 IS - 1 JF - Neuron TI - The sacred disease: The puzzling genetics of epileptic disorders VL - 80 ER - TY - JOUR AB - Complex I (NADH:ubiquinone oxidoreductase) is central to cellular energy production, being the first and largest enzyme of the respiratory chain in mitochondria. It couples electron transfer from NADH to ubiquinone with proton translocation across the inner mitochondrial membrane and is involved in a wide range of human neurodegenerative disorders. Mammalian complex I is composed of 44 different subunits, whereas the 'minimal' bacterial version contains 14 highly conserved 'core' subunits. The L-shaped assembly consists of hydrophilic and membrane domains. We have determined all known atomic structures of complex I, starting from the hydrophilic domain of Thermus thermophilus enzyme (eight subunits, nine Fe-S clusters), followed by the membrane domains of the Escherichia coli (six subunits, 55 transmembrane helices) and T. thermophilus (seven subunits, 64 transmembrane helices) enzymes, and finally culminating in a recent crystal structure of the entire intact complex I from T. thermophilus (536 kDa, 16 subunits, nine Fe-S clusters, 64 transmembrane helices). The structure suggests an unusual and unique coupling mechanism via longrange conformational changes. Determination of the structure of the entire complex was possible only through this step-by-step approach, building on from smaller subcomplexes towards the entire assembly. Large membrane proteins are notoriously difficult to crystallize, and so various non-standard and sometimes counterintuitive approaches were employed in order to achieve crystal diffraction to high resolution and solve the structures. These steps, as well as the implications from the final structure, are discussed in the present review. AU - Leonid Sazanov AU - Baradaran, Rozbeh AU - Efremov, Rouslan G AU - Berrisford, John M AU - Minhas, Gurdeep S ID - 1977 IS - 5 JF - Biochemical Society Transactions TI - A long road towards the structure of respiratory complex I, a giant molecular proton pump VL - 41 ER - TY - JOUR AB - Complex I is the first and largest enzyme of the respiratory chain and has a central role in cellular energy production through the coupling of NADH:ubiquinone electron transfer to proton translocation. It is also implicated in many common human neurodegenerative diseases. Here, we report the first crystal structure of the entire, intact complex I (from Thermus thermophilus) at 3.3 Å resolution. The structure of the 536-kDa complex comprises 16 different subunits, with a total of 64 transmembrane helices and 9 iron-sulphur clusters. The core fold of subunit Nqo8 (ND1 in humans) is, unexpectedly, similar to a half-channel of the antiporter-like subunits. Small subunits nearby form a linked second half-channel, which completes the fourth proton-translocation pathway (present in addition to the channels in three antiporter-like subunits). The quinone-binding site is unusually long, narrow and enclosed. The quinone headgroup binds at the deep end of this chamber, near iron-sulphur cluster N2. Notably, the chamber is linked to the fourth channel by a 'funnel' of charged residues. The link continues over the entire membrane domain as a flexible central axis of charged and polar residues, and probably has a leading role in the propagation of conformational changes, aided by coupling elements. The structure suggests that a unique, out-of-the-membrane quinone-reaction chamber enables the redox energy to drive concerted long-range conformational changes in the four antiporter-like domains, resulting in translocation of four protons per cycle. AU - Baradaran, Rozbeh AU - Berrisford, John M AU - Minhas, Gurdeep S AU - Leonid Sazanov ID - 1978 IS - 7438 JF - Nature TI - Crystal structure of the entire respiratory complex i VL - 494 ER - TY - JOUR AB - Although transitions of sex-determination mechanisms are frequent in species with homomorphic sex chromosomes, heteromorphic sex chromosomes are thought to represent a terminal evolutionary stage owing to chromosome-specific adaptations such as dosage compensation or an accumulation of sex-specific mutations. Here we show that an autosome of Drosophila, the dot chromosome, was ancestrally a differentiated X chromosome. We analyse the whole genome of true fruitflies (Tephritidae), flesh flies (Sarcophagidae) and soldier flies (Stratiomyidae) to show that genes located on the dot chromosome of Drosophila are X-linked in outgroup species, whereas Drosophila X-linked genes are autosomal. We date this chromosomal transition to early drosophilid evolution by sequencing the genome of other Drosophilidae. Our results reveal several puzzling aspects of Drosophila dot chromosome biology to be possible remnants of its former life as a sex chromosome, such as its minor feminizing role in sex determination or its targeting by a chromosome-specific regulatory mechanism. We also show that patterns of biased gene expression of the dot chromosome during early embryogenesis, oogenesis and spermatogenesis resemble that of the current X chromosome. Thus, although sex chromosomes are not necessarily evolutionary end points and can revert back to an autosomal inheritance, the highly specialized genome architecture of this former X chromosome suggests that severe fitness costs must be overcome for such a turnover to occur. AU - Beatriz Vicoso AU - Bachtrog, Doris ID - 1991 IS - 7458 JF - Nature TI - Reversal of an ancient sex chromosome to an autosome in Drosophila VL - 499 ER - TY - JOUR AB - The rod-shaped bacterium Escherichia coli selects the cell center as site of division with the help of the proteins MinC, MinD, and MinE. This protein system collectively oscillates between the two cell poles by alternately binding to the membrane in one of the two cell halves. This dynamic behavior, which emerges from the interaction of the ATPase MinD and its activator MinE on the cell membrane, has become a paradigm for protein self-organization. Recently, it has been found that not only the binding of MinD to the membrane, but also interactions of MinE with the membrane contribute to Min-protein self-organization. Here, we show that by accounting for this finding in a computational model, we can comprehensively describe all observed Min-protein patterns in vivo and in vitro. Furthermore, by varying the system's geometry, our computations predict patterns that have not yet been reported. We confirm these predictions experimentally. AU - Bonny, Mike AU - Fischer-Friedrich, Elisabeth AU - Martin Loose AU - Schwille, Petra AU - Kruse, Karsten ID - 1988 IS - 12 JF - PLoS Computational Biology TI - Membrane binding of MinE allows for a comprehensive description of Min-protein pattern formation VL - 9 ER - TY - JOUR AB - Many algorithms for inferring causality rely heavily on the faithfulness assumption. The main justification for imposing this assumption is that the set of unfaithful distributions has Lebesgue measure zero, since it can be seen as a collection of hypersurfaces in a hypercube. However, due to sampling error the faithfulness condition alone is not sufficient for statistical estimation, and strong-faithfulness has been proposed and assumed to achieve uniform or high-dimensional consistency. In contrast to the plain faithfulness assumption, the set of distributions that is not strong-faithful has nonzero Lebesgue measure and in fact, can be surprisingly large as we show in this paper. We study the strong-faithfulness condition from a geometric and combinatorial point of view and give upper and lower bounds on the Lebesgue measure of strong-faithful distributions for various classes of directed acyclic graphs. Our results imply fundamental limitations for the PC-algorithm and potentially also for other algorithms based on partial correlation testing in the Gaussian case. AU - Uhler, Caroline AU - Raskutti, Garvesh AU - Bühlmann, Peter AU - Yu, Bin ID - 2010 IS - 2 JF - The Annals of Statistics TI - Geometry of the faithfulness assumption in causal inference VL - 41 ER - TY - JOUR AB - Traditional statistical methods for confidentiality protection of statistical databases do not scale well to deal with GWAS databases especially in terms of guarantees regarding protection from linkage to external information. The more recent concept of differential privacy, introduced by the cryptographic community, is an approach which provides a rigorous definition of privacy with meaningful privacy guarantees in the presence of arbitrary external information, although the guarantees may come at a serious price in terms of data utility. Building on such notions, we propose new methods to release aggregate GWAS data without compromising an individual’s privacy. We present methods for releasing differentially private minor allele frequencies, chi-square statistics and p-values. We compare these approaches on simulated data and on a GWAS study of canine hair length involving 685 dogs. We also propose a privacy-preserving method for finding genome-wide associations based on a differentially-private approach to penalized logistic regression. AU - Uhler, Caroline AU - Slavkovic, Aleksandra AU - Fienberg, Stephen ID - 2009 IS - 1 JF - Journal of Privacy and Confidentiality TI - Privacy-preserving data sharing for genome-wide association studies VL - 5 ER - TY - JOUR AB - Sex chromosomes originate from autosomes. The accumulation of sexually antagonistic mutations on protosex chromosomes selects for a loss of recombination and sets in motion the evolutionary processes generating heteromorphic sex chromosomes. Recombination suppression and differentiation are generally viewed as the default path of sex chromosome evolution, and the occurrence of old, homomorphic sex chromosomes, such as those of ratite birds, has remained a mystery. Here, we analyze the genome and transcriptome of emu (Dromaius novaehollandiae) and confirm that most genes on the sex chromosome are shared between the Z and W. Surprisingly, however, levels of gene expression are generally sex-biased for all sex-linked genes relative to autosomes, including those in the pseudoautosomal region, and the male-bias increases after gonad formation. This expression bias suggests that the emu sex chromosomes have become masculinized, even in the absence of ZW differentiation. Thus, birds may have taken different evolutionary solutions to minimize the deleterious effects imposed by sexually antagonistic mutations: some lineages eliminate recombination along the protosex chromosomes to physically restrict sexually antagonistic alleles to one sex, whereas ratites evolved sex-biased expression to confine the product of a sexually antagonistic allele to the sex it benefits. This difference in conflict resolution may explain the preservation of recombining, homomorphic sex chromosomes in other lineages and illustrates the importance of sexually antagonistic mutations driving the evolution of sex chromosomes. AU - Beatriz Vicoso AU - Kaiser, Vera B AU - Bachtrog, Doris ID - 2074 IS - 16 JF - PNAS TI - Sex biased gene expression at homomorphic sex chromosomes in emus and its implication for sex chromosome evolution VL - 110 ER -