TY - JOUR
AB - A class of valued constraint satisfaction problems (VCSPs) is characterised by a valued constraint language, a fixed set of cost functions on a finite domain. Finite-valued constraint languages contain functions that take on rational costs and general-valued constraint languages contain functions that take on rational or infinite costs. An instance of the problem is specified by a sum of functions from the language with the goal to minimise the sum. This framework includes and generalises well-studied constraint satisfaction problems (CSPs) and maximum constraint satisfaction problems (Max-CSPs).
Our main result is a precise algebraic characterisation of valued constraint languages whose instances can be solved exactly by the basic linear programming relaxation (BLP). For a general-valued constraint language Γ, BLP is a decision procedure for Γ if and only if Γ admits a symmetric fractional polymorphism of every arity. For a finite-valued constraint language Γ, BLP is a decision procedure if and only if Γ admits a symmetric fractional polymorphism of some arity, or equivalently, if Γ admits a symmetric fractional polymorphism of arity 2.
Using these results, we obtain tractability of several novel and previously widely-open classes of VCSPs, including problems over valued constraint languages that are: (1) submodular on arbitrary lattices; (2) bisubmodular (also known as k-submodular) on arbitrary finite domains; (3) weakly (and hence strongly) tree-submodular on arbitrary trees.
AU - Kolmogorov, Vladimir
AU - Thapper, Johan
AU - Živný, Stanislav
ID - 2271
IS - 1
JF - SIAM Journal on Computing
TI - The power of linear programming for general-valued CSPs
VL - 44
ER -
TY - JOUR
AB - We show that a non-singular integral form of degree d is soluble over the integers if and only if it is soluble over ℝ and over ℚp for all primes p, provided that the form has at least (d - 1/2 √d)2d variables. This improves on a longstanding result of Birch.
AU - Timothy Browning
AU - Prendiville, Sean M
ID - 256
IS - 731
JF - Journal fur die Reine und Angewandte Mathematik
TI - Improvements in Birch's theorem on forms in many variables
VL - 2017
ER -
TY - JOUR
AB - For suitable pairs of diagonal quadratic forms in eight variables we use the circle method to investigate the density of simultaneous integer solutions and relate this to the problem of estimating linear correlations among sums of two squares.
AU - Timothy Browning
AU - Munshi, Ritabrata
ID - 257
IS - 4
JF - Forum Mathematicum
TI - Pairs of diagonal quadratic forms and linear correlations among sums of two squares
VL - 27
ER -
TY - CHAP
AB - Given a number field k and a projective algebraic variety X defined over k, the question of whether X contains a k-rational point is both very natural and very difficult. In the event that the set X(k) of k-rational points is not empty, one can also ask how the points of X(k) are distributed. Are they dense in X under the Zariski topology? Are they dense in the set.
AU - Browning, Timothy D
ID - 258
T2 - Arithmetic and Geometry
TI - A survey of applications of the circle method to rational points
ER -
TY - JOUR
AB - The Hasse principle and weak approximation is established for non-singular cubic hypersurfaces X over the function field
AU - Timothy Browning
AU - Vishe, Pankaj
ID - 259
IS - 3
JF - Geometric and Functional Analysis
TI - Rational points on cubic hypersurfaces over F_q(t)
VL - 25
ER -
TY - JOUR
AU - Timothy Browning
AU - Dietmann, Rainer
AU - Heath-Brown, Roger
ID - 260
IS - 4
JF - Journal of the Institute of Mathematics of Jussieu
TI - Erratum Rational points on intersections of cubic and quadric hypersurfaces
VL - 14
ER -
TY - JOUR
AB - Glycoinositolphosphoceramides (GIPCs) are complex sphingolipids present at the plasma membrane of various eukaryotes with the important exception of mammals. In fungi, these glycosphingolipids commonly contain an alpha-mannose residue (Man) linked at position 2 of the inositol. However, several pathogenic fungi additionally synthesize zwitterionic GIPCs carrying an alpha-glucosamine residue (GlcN) at this position. In the human pathogen Aspergillus fumigatus, the GlcNalpha1,2IPC core (where IPC is inositolphosphoceramide) is elongated to Manalpha1,3Manalpha1,6GlcNalpha1,2IPC, which is the most abundant GIPC synthesized by this fungus. In this study, we identified an A. fumigatus N-acetylglucosaminyltransferase, named GntA, and demonstrate its involvement in the initiation of zwitterionic GIPC biosynthesis. Targeted deletion of the gene encoding GntA in A. fumigatus resulted in complete absence of zwitterionic GIPC; a phenotype that could be reverted by episomal expression of GntA in the mutant. The N-acetylhexosaminyltransferase activity of GntA was substantiated by production of N-acetylhexosamine-IPC in the yeast Saccharomyces cerevisiae upon GntA expression. Using an in vitro assay, GntA was furthermore shown to use UDP-N-acetylglucosamine as donor substrate to generate a glycolipid product resistant to saponification and to digestion by phosphatidylinositol-phospholipase C as expected for GlcNAcalpha1,2IPC. Finally, as the enzymes involved in mannosylation of IPC, GntA was localized to the Golgi apparatus, the site of IPC synthesis.
AU - Engel, Jakob
AU - Schmalhorst, Philipp S
AU - Kruger, Anke
AU - Muller, Christina
AU - Buettner, Falk
AU - Routier, Françoise
ID - 802
IS - 12
JF - Glycobiology
TI - Characterization of an N-acetylglucosaminyltransferase involved in Aspergillus fumigatus zwitterionic glycoinositolphosphoceramide biosynthesis
VL - 25
ER -
TY - JOUR
AB - Human immunodeficiency virus type 1 (HIV-1) assembly proceeds in two stages. First, the 55 kilodalton viral Gag polyprotein assembles into a hexameric protein lattice at the plasma membrane of the infected cell, inducing budding and release of an immature particle. Second, Gag is cleaved by the viral protease, leading to internal rearrangement of the virus into the mature, infectious form. Immature and mature HIV-1 particles are heterogeneous in size and morphology, preventing high-resolution analysis of their protein arrangement in situ by conventional structural biology methods. Here we apply cryo-electron tomography and sub-tomogram averaging methods to resolve the structure of the capsid lattice within intact immature HIV-1 particles at subnanometre resolution, allowing unambiguous positioning of all Î±-helices. The resulting model reveals tertiary and quaternary structural interactions that mediate HIV-1 assembly. Strikingly, these interactions differ from those predicted by the current model based on in vitro-assembled arrays of Gag-derived proteins from Mason-Pfizer monkey virus. To validate this difference, we solve the structure of the capsid lattice within intact immature Mason-Pfizer monkey virus particles. Comparison with the immature HIV-1 structure reveals that retroviral capsid proteins, while having conserved tertiary structures, adopt different quaternary arrangements during virus assembly. The approach demonstrated here should be applicable to determine structures of other proteins at subnanometre resolution within heterogeneous environments.
AU - Florian Schur
AU - Hagen, Wim J
AU - Rumlová, Michaela
AU - Ruml, Tomáš
AU - Müller B
AU - Kraüsslich, Hans Georg
AU - Briggs, John A
ID - 814
IS - 7535
JF - Nature
TI - Structure of the immature HIV-1 capsid in intact virus particles at 8.8 Å resolution
VL - 517
ER -
TY - JOUR
AB - The polyprotein Gag is the primary structural component of retroviruses. Gag consists of independently folded domains connected by flexible linkers. Interactions between the conserved capsid (CA) domains of Gag mediate formation of hexameric protein lattices that drive assembly of immature virus particles. Proteolytic cleavage of Gag by the viral protease (PR) is required for maturation of retroviruses from an immature form into an infectious form. Within the assembled Gag lattices of HIV-1 and Mason- Pfizer monkey virus (M-PMV), the C-terminal domain of CA adopts similar quaternary arrangements, while the N-terminal domain of CA is packed in very different manners. Here, we have used cryo-electron tomography and subtomogram averaging to study in vitro-assembled, immature virus-like Rous sarcoma virus (RSV) Gag particles and have determined the structure of CA and the surrounding regions to a resolution of ~8 Å. We found that the C-terminal domain of RSV CA is arranged similarly to HIV-1 and M-PMV, whereas the N-terminal domain of CA adopts a novel arrangement in which the upstream p10 domain folds back into the CA lattice. In this position the cleavage site between CA and p10 appears to be inaccessible to PR. Below CA, an extended density is consistent with the presence of a six-helix bundle formed by the spacer-peptide region. We have also assessed the affect of lattice assembly on proteolytic processing by exogenous PR. The cleavage between p10 and CA is indeed inhibited in the assembled lattice, a finding consistent with structural regulation of proteolytic maturation.
AU - Schur, Florian
AU - Dick, Robert
AU - Hagen, Wim
AU - Vogt, Volker
AU - Briggs, John
ID - 815
IS - 20
JF - Journal of Virology
TI - The structure of immature virus like Rous sarcoma virus gag particles reveals a structural role for the p10 domain in assembly
VL - 89
ER -
TY - JOUR
AU - Einhorn, Lukas
AU - Fazekas, Judit
AU - Muhr, Martina
AU - Schoos, Alexandra
AU - Oida, Kumiko
AU - Singer, Josef
AU - Panakova, Lucia
AU - Manzano-Szalai, Krisztina
AU - Jensen-Jarolim, Erika
ID - 8242
IS - 2
JF - Journal of Allergy and Clinical Immunology
SN - 0091-6749
TI - Generation of recombinant FcεRIα of dog, cat and horse for component-resolved allergy diagnosis in veterinary patients
VL - 135
ER -
TY - JOUR
AB - Plants maintain capacity to form new organs such as leaves, flowers, lateral shoots and roots throughout their postembryonic lifetime. Lateral roots (LRs) originate from a few pericycle cells that acquire attributes of founder cells (FCs), undergo series of anticlinal divisions, and give rise to a few short initial cells. After initiation, coordinated cell division and differentiation occur, giving rise to lateral root primordia (LRP). Primordia continue to grow, emerge through the cortex and epidermal layers of the primary root, and finally a new apical meristem is established taking over the responsibility for growth of mature lateral roots [for detailed description of the individual stages of lateral root organogenesis see Malamy and Benfey (1997)]. To examine this highly dynamic developmental process and to investigate a role of various hormonal, genetic and environmental factors in the regulation of lateral root organogenesis, the real time imaging based analyses represent extremely powerful tools (Laskowski et al., 2008; De Smet et al., 2012; Marhavy et al., 2013 and 2014). Herein, we describe a protocol for real time lateral root primordia (LRP) analysis, which enables the monitoring of an onset of the specific gene expression and subcellular protein localization during primordia organogenesis, as well as the evaluation of the impact of genetic and environmental perturbations on LRP organogenesis.
AU - Peter Marhavy
AU - Eva Benková
ID - 832
IS - 8
JF - Bio-protocol
TI - Real time analysis of lateral root organogenesis in arabidopsis
VL - 5
ER -
TY - JOUR
AB - The large majority of three-dimensional structures of biological macromolecules have been determined by X-ray diffraction of crystalline samples. High-resolution structure determination crucially depends on the homogeneity of the protein crystal. Overall ‘rocking’ motion of molecules in the crystal is expected to influence diffraction quality, and such motion may therefore affect the process of solving crystal structures. Yet, so far overall molecular motion has not directly been observed in protein crystals, and the timescale of such dynamics remains unclear. Here we use solid-state NMR, X-ray diffraction methods and μs-long molecular dynamics simulations to directly characterize the rigid-body motion of a protein in different crystal forms. For ubiquitin crystals investigated in this study we determine the range of possible correlation times of rocking motion, 0.1–100 μs. The amplitude of rocking varies from one crystal form to another and is correlated with the resolution obtainable in X-ray diffraction experiments.
AU - Ma, Peixiang
AU - Xue, Yi
AU - Coquelle, Nicolas
AU - Haller, Jens D.
AU - Yuwen, Tairan
AU - Ayala, Isabel
AU - Mikhailovskii, Oleg
AU - Willbold, Dieter
AU - Colletier, Jacques-Philippe
AU - Skrynnikov, Nikolai R.
AU - Schanda, Paul
ID - 8456
JF - Nature Communications
KW - General Biochemistry
KW - Genetics and Molecular Biology
KW - General Physics and Astronomy
KW - General Chemistry
SN - 2041-1723
TI - Observing the overall rocking motion of a protein in a crystal
VL - 6
ER -
TY - JOUR
AB - We review recent advances in methodologies to study microseconds‐to‐milliseconds exchange processes in biological molecules using magic‐angle spinning solid‐state nuclear magnetic resonance (MAS ssNMR) spectroscopy. The particularities of MAS ssNMR, as compared to solution‐state NMR, are elucidated using numerical simulations and experimental data. These simulations reveal the potential of MAS NMR to provide detailed insight into short‐lived conformations of biological molecules. Recent studies of conformational exchange dynamics in microcrystalline ubiquitin are discussed.
AU - Ma, Peixiang
AU - Schanda, Paul
ID - 8457
IS - 3
JF - eMagRes
SN - 9780470034590
TI - Conformational exchange processes in biological systems: Detection by solid-state NMR
VL - 4
ER -
TY - JOUR
AB - The nature of factors governing the tempo and mode of protein evolution is a fundamental issue in evolutionary biology. Specifically, whether or not interactions between different sites, or epistasis, are important in directing the course of evolution became one of the central questions. Several recent reports have scrutinized patterns of long-term protein evolution claiming them to be compatible only with an epistatic fitness landscape. However, these claims have not yet been substantiated with a formal model of protein evolution. Here, we formulate a simple covarion-like model of protein evolution focusing on the rate at which the fitness impact of amino acids at a site changes with time. We then apply the model to the data on convergent and divergent protein evolution to test whether or not the incorporation of epistatic interactions is necessary to explain the data. We find that convergent evolution cannot be explained without the incorporation of epistasis and the rate at which an amino acid state switches from being acceptable at a site to being deleterious is faster than the rate of amino acid substitution. Specifically, for proteins that have persisted in modern prokaryotic organisms since the last universal common ancestor for one amino acid substitution approximately ten amino acid states switch from being accessible to being deleterious, or vice versa. Thus, molecular evolution can only be perceived in the context of rapid turnover of which amino acids are available for evolution.
AU - Usmanova, Dinara
AU - Ferretti, Luca
AU - Povolotskaya, Inna
AU - Vlasov, Peter
AU - Kondrashov, Fyodor
ID - 848
IS - 2
JF - Molecular Biology and Evolution
TI - A model of substitution trajectories in sequence space and long-term protein evolution
VL - 32
ER -
TY - JOUR
AB - In this note, we consider the dynamics associated to a perturbation of an integrable Hamiltonian system in action-angle coordinates in any number of degrees of freedom and we prove the following result of ``micro-diffusion'': under generic assumptions on $ h$ and $ f$, there exists an orbit of the system for which the drift of its action variables is at least of order $ \sqrt {\varepsilon }$, after a time of order $ \sqrt {\varepsilon }^{-1}$. The assumptions, which are essentially minimal, are that there exists a resonant point for $ h$ and that the corresponding averaged perturbation is non-constant. The conclusions, although very weak when compared to usual instability phenomena, are also essentially optimal within this setting.
AU - Bounemoura, Abed
AU - Kaloshin, Vadim
ID - 8495
IS - 4
JF - Proceedings of the American Mathematical Society
SN - 0002-9939
TI - A note on micro-instability for Hamiltonian systems close to integrable
VL - 144
ER -
TY - JOUR
AB - In the present note we announce a proof of a strong form of Arnold diffusion for smooth convex Hamiltonian systems. Let ${\mathbb T}^2$ be a 2-dimensional torus and B2 be the unit ball around the origin in ${\mathbb R}^2$ . Fix ρ > 0. Our main result says that for a 'generic' time-periodic perturbation of an integrable system of two degrees of freedom $H_0(p)+\varepsilon H_1(\theta,p,t),\quad \ \theta\in {\mathbb T}^2,\ p\in B^2,\ t\in {\mathbb T}={\mathbb R}/{\mathbb Z}$ , with a strictly convex H0, there exists a ρ-dense orbit (θε, pε, t)(t) in ${\mathbb T}^2 \times B^2 \times {\mathbb T}$ , namely, a ρ-neighborhood of the orbit contains ${\mathbb T}^2 \times B^2 \times {\mathbb T}$ .
Our proof is a combination of geometric and variational methods. The fundamental elements of the construction are the usage of crumpled normally hyperbolic invariant cylinders from [9], flower and simple normally hyperbolic invariant manifolds from [36] as well as their kissing property at a strong double resonance. This allows us to build a 'connected' net of three-dimensional normally hyperbolic invariant manifolds. To construct diffusing orbits along this net we employ a version of the Mather variational method [41] equipped with weak KAM theory [28], proposed by Bernard in [7].
AU - Kaloshin, Vadim
AU - Zhang, K
ID - 8498
IS - 8
JF - Nonlinearity
KW - Mathematical Physics
KW - General Physics and Astronomy
KW - Applied Mathematics
KW - Statistical and Nonlinear Physics
SN - 0951-7715
TI - Arnold diffusion for smooth convex systems of two and a half degrees of freedom
VL - 28
ER -
TY - JOUR
AB - We consider the cubic defocusing nonlinear Schrödinger equation in the two dimensional torus. Fix s>1. Recently Colliander, Keel, Staffilani, Tao and Takaoka proved the existence of solutions with s-Sobolev norm growing in time.
We establish the existence of solutions with polynomial time estimates. More exactly, there is c>0 such that for any K≫1 we find a solution u and a time T such that ∥u(T)∥Hs≥K∥u(0)∥Hs. Moreover, the time T satisfies the polynomial bound 0