TY - JOUR
AU - Frotscher, Michael
AU - Gundelfinger, Eckart
AU - Peter Jonas
AU - Neher, Erwin
AU - Seeburg, Peter
ID - 3817
IS - 2
JF - Cell and Tissue Research
TI - The most important recent advances in synapse research from my point of view--and what remains to be done
VL - 326
ER -
TY - JOUR
AB - Rigorous analysis of synaptic transmission in the central nervous system requires access to presynaptic terminals. However, cortical terminals have been largely inaccessible to presynaptic patch-clamp recording, due to their small size. Using improved patch-clamp techniques in brain slices, we recorded from mossy fiber terminals in the CA3 region of the hippocampus, which have a diameter of 2-5 microm. The major steps of improvement were the enhanced visibility provided by high-numerical aperture objectives and infrared illumination, the development of vibratomes with minimal vertical blade vibrations and the use of sucrose-based solutions for storage and cutting. Based on these improvements, we describe a protocol that allows us to routinely record from hippocampal mossy fiber boutons. Presynaptic recordings can be obtained in slices from both rats and mice. Presynaptic recordings can be also obtained in slices from transgenic mice in which terminals are labeled with enhanced green fluorescent protein.
AU - Bischofberger, Josef
AU - Engel, Dominique
AU - Li, Liyi
AU - Geiger, Jörg R
AU - Peter Jonas
ID - 3818
IS - 4
JF - Nature Protocols
TI - Patch-clamp recording from mossy fiber terminals in hippocampal slices
VL - 1
ER -
TY - CONF
AB - A stochastic graph game is played by two players on a game graph with probabilistic transitions. We consider stochastic graph games with omega-regular winning conditions specified as Rabin or Streett objectives. These games are NP-complete and coNP-complete, respectively. The value of the game for a player at a state s given an objective Phi is the maximal probability with which the player can guarantee the satisfaction of Phi from s. We present a strategy-improvement algorithm to compute values in stochastic Rabin games, where an improvement step involves solving Markov decision processes (MDPs) and nonstochastic Rabin games. The algorithm also computes values for stochastic Streett games but does not directly yield an optimal strategy for Streett objectives. We then show how to obtain an optimal strategy for Streett objectives by solving certain nonstochastic Streett games.
AU - Krishnendu Chatterjee
AU - Thomas Henzinger
ID - 3888
TI - Strategy improvement for stochastic Rabin and Streett games
VL - 4137
ER -
TY - CONF
AB - We study observation-based strategies for two-player turn-based games on graphs with omega-regular objectives. An observation-based strategy relies on imperfect information about the history of a play, namely, on the past sequence of observations. Such games occur in the synthesis of a controller that does not see the private state of the plant. Our main results are twofold. First, we give a fixed-point algorithm for computing the set of states from which a player can win with a deterministic observation-based strategy for any omega-regular objective. The fixed point is computed in the lattice of antichains of state sets. This algorithm has the advantages of being directed by the objective and of avoiding an explicit subset construction on the game graph. Second, we give an algorithm for computing the set of states from which a player can win with probability 1 with a randomized observation-based strategy for a Buchi objective. This set is of interest because in the absence of perfect information, randomized strategies are more powerful than deterministic ones. We show that our algorithms are optimal by proving matching lower bounds.
AU - Krishnendu Chatterjee
AU - Doyen, Laurent
AU - Thomas Henzinger
AU - Raskin, Jean-François
ID - 3889
TI - Algorithms for omega-regular games with imperfect information
VL - 4207
ER -
TY - CONF
AB - We consider two-player infinite games played on graphs. The games are concurrent, in that at each state the players choose their moves simultaneously and independently, and stochastic, in that the moves determine a probability distribution for the successor state. The value of a game is the maximal probability with which a player can guarantee the satisfaction of her objective. We show that the values of concurrent games with w-regular objectives expressed as parity conditions can be decided in NP boolean AND coNP. This result substantially improves the best known previous bound of 3EXPTIME. It also shows that the full class of concurrent parity games is no harder than the special case of turn-based stochastic reachability games, for which NP boolean AND coNP is the best known bound. While the previous, more restricted NP boolean AND coNP results for graph games relied on the existence of particularly simple (pure memoryless) optimal strategies, in concurrent games with parity objectives optimal strategies may not exist, and epsilon-optimal strategies (which achieve the value of the game within a parameter epsilon > 0) require in general both randomization and infinite memory. Hence our proof must rely on a more detailed analysis of strategies and, in addition to the main result, yields two results that are interesting on their own. First, we show that there exist epsilon-optimal strategies that in the limit coincide with memoryless strategies; this parallels the celebrated result of Mertens-Neyman for concurrent games with limit-average objectives. Second, we complete the characterization of the memory requirements for epsilon-optimal strategies for concurrent games with parity conditions, by showing that memoryless strategies suffice for epsilon-optimality for coBachi conditions.
AU - Krishnendu Chatterjee
AU - de Alfaro, Luca
AU - Thomas Henzinger
ID - 3890
TI - The complexity of quantitative concurrent parity games
ER -
TY - CONF
AB - We study infinite stochastic games played by two-players over a finite state space, with objectives specified by sets of infinite traces. The games are concurrent (players make moves simultaneously and independently), stochastic (the next state is determined by a probability distribution that depends on the current state and chosen moves of the players) and infinite (proceeds for infinite number of rounds). The analysis of concurrent stochastic games can be classified into: quantitative analysis, analyzing the optimum value of the game; and qualitative analysis, analyzing the set of states with optimum value 1. We consider concurrent games with tail objectives, i.e., objectives that are independent of the finite-prefix of traces, and show that the class of tail objectives are strictly richer than the omega-regular objectives. We develop new proof techniques to extend several properties of concurrent games with omega-regular objectives to concurrent games with tail objectives. We prove the positive limit-one property for tail objectives, that states for all concurrent games if the optimum value for a player is positive for a tail objective Phi at some state, then there is a state where the optimum value is 1 for Phi, for the player. We also show that the optimum values of zero-sum (strictly conflicting objectives) games with tail objectives can be related to equilibrium values of nonzero-sum (not strictly conflicting objectives) games with simpler reachability objectives. A consequence of our analysis presents a polynomial time reduction of the quantitative analysis of tail objectives to the qualitative analysis for the sub-class of one-player stochastic games (Markov decision processes).
AU - Krishnendu Chatterjee
ID - 3891
TI - Concurrent games with tail objectives
VL - 4207
ER -
TY - JOUR
AB - Wnt11 is a key signal, determining cell polarization and migration during vertebrate gastrulation. It is known that Wnt11 functionally interacts with several signaling components, the homologues of which control planar cell polarity in Drosophila melanogaster. Although in D. melanogaster these components are thought to polarize cells by asymmetrically localizing at the plasma membrane, it is not yet clear whether their subcellular localization plays a similarly important role in vertebrates. We show that in zebrafish embryonic cells, Wnt11 locally functions at the plasma membrane by accumulating its receptor, Frizzled 7, on adjacent sites of cell contacts. Wnt11-induced Frizzled 7 accumulations recruit the intracellular Wnt signaling mediator Dishevelled, as well as Wnt11 itself, and locally increase cell contact persistence. This increase in cell contact persistence is mediated by the local interaction of Wnt11, Frizzled 7, and the atypical cadherin Flamingo at the plasma membrane, and it does not require the activity of further downstream effectors of Wnt11 signaling, such as RhoA and Rok2. We propose that Wnt11, by interacting with Frizzled 7 and Flamingo, modulates local cell contact persistence to coordinate cell movements during gastrulation.
AU - Witzel, Sabine
AU - Zimyanin, Vitaly
AU - Carreira Barbosa, Filipa
AU - Tada, Masazumi
AU - Heisenberg, Carl-Philipp J
ID - 4140
IS - 5
JF - Journal of Cell Biology
TI - Wnt11 controls cell contact persistence by local accumulation of Frizzled 7 at the plasma membrane
VL - 175
ER -
TY - JOUR
AB - Systems of three interacting particles are notorious for their complex physical behaviour. A landmark theoretical result in few-body quantum physics is Efimov\'s prediction1,2 of a universal set of bound trimer states appearing for three identical bosons with a resonant two-body interaction. Counterintuitively, these states even exist in the absence of a corresponding two-body bound state. Since the formulation of Efimov\'s problem in the context of nuclear physics 35 years ago, it has attracted great interest in many areas of physics3-8. However, the observation of Efimov quantum states has remained an elusive goal3,5. Here we report the observation of an Efimov resonance in an ultracold gas of caesium atoms. The resonance occurs in the range of large negative two-body scattering lengths, arising from the coupling of three free atoms to an Efimov trimer. Experimentally, we observe its signature as a giant three-body recombination loss9,10 when the strength of the two-body interaction is varied. We also detect a minimum 9,11,12 in the recombination loss for positive scattering lengths, indicating destructive interference of decay pathways. Our results confirm central theoretical predictions of Efimov physics and represent a starting point with which to explore the universal properties of resonantly interacting few-body systems7. While Feshbach resonances13,14 have provided the key to control quantum-mechanical interactions on the two-body level, Efimov resonances connect ultracold matter15 to the world of few-body quantum phenomena.
AU - Kraemer, Tobias
AU - Mark, Michael
AU - Waldburger, Philipp
AU - Danzl, Johann G
AU - Chin, Cheng
AU - Engeser, Bastian
AU - Lange, Adam
AU - Pilch, Karl
AU - Jaakkola, Antti
AU - Nägerl, Hanns
AU - Grimm, Rudolf
ID - 1033
IS - 7082
JF - Nature
TI - Evidence for Efimov quantum states in an ultracold gas of caesium atoms
VL - 440
ER -
TY - CONF
AB - Three interacting particles form a system which is well known for its complex physical behavior. A landmark theoretical result in few-body quantum physics is Efimov\'s prediction of a universal set of weakly bound trimer states appearing for three identical bosons with a resonant two-body interaction [1, 2]. Surprisingly, these states even exist in the absence of a corresponding two-body bound state and their precise nature is largely independent of the particular type of the two-body interaction potential. Efimov\'s scenario has attracted great interest in many areas of physics; an experimental test however has not been achieved. We report the observation of an Efimov resonance in an ultracold thermal gas of cesium atoms [3]. The resonance occurs in the range of large negative two-body scattering lengths and arises from the coupling of three free atoms to an Efimov trimer. We observe its signature as a giant three-body recombination loss when the strength of the two-body interaction is varied near a Feshbach resonance. This resonance develops into a continuum resonance at non-zero collision energies, and we observe a shift of the resonance position as a function of temperature. We also report on a minimum in the recombination loss for positive scattering lengths, indicating destructive interference of decay pathways. Our results confirm central theoretical predictions of Efimov physics and represent a starting point from which to explore the universal properties of resonantly interacting few-body systems.
AU - Nägerl, Hanns
AU - Kraemer, Tobias
AU - Mark, Michael
AU - Waldburger, Philipp
AU - Danzl, Johann G
AU - Engeser, Bastian
AU - Lange, Adam
AU - Pilch, Karl
AU - Jaakkola, Antti
AU - Chin, Cheng
AU - Grimm, Rudolf
ID - 1034
TI - Experimental evidence for Efimov quantum states
VL - 869
ER -
TY - CONF
AB - Control of physical simulation has become a popular topic in the field of computer graphics. Keyframe control has been applied to simulations of rigid bodies, smoke, liquid, flocks, and finite element-based elastic bodies. In this paper, we create a framework for controlling systems of interacting particles -- paying special attention to simulations of cloth and flocking behavior. We introduce a novel integrator-swapping approximation in order to apply the adjoint method to linearized implicit schemes appropriate for cloth simulation. This allows the control of cloth while avoiding computationally infeasible derivative calculations. Meanwhile, flocking control using the adjoint method is significantly more efficient than currently-used methods for constraining group behaviors, allowing the controlled simulation of greater numbers of agents in fewer optimization iterations.
AU - Wojtan, Christopher J
AU - Mucha, Peter
AU - Turk, Greg
ID - 3758
TI - Keyframe control of complex particle systems using the adjoint method
ER -
TY - JOUR
AB - The detection of microRNAs (miRNAs) at single-cell resolution is important for studying the role of these posttranscriptional regulators. Here, we use a dual-fluorescent green fluorescent protein (GFP)-reporter/monomeric red fluorescent protein (mRFP)-sensor (DFRS) plasmid, injected into zebrafish blastomeres or electroporated into defined tissues of mouse embryos in utero or ex utero, to monitor the dynamics of specific miRNAs in individual live cells. This approach reveals, for example, that in the developing mouse central nervous system,, miR-124a is expressed not only in postmitotic neurons but also in neuronal progenitor cells. Collectively, our results demonstrate that acute administration of DFRS plasmids.offers an alternative to previous in situ hybridization and transgenic approaches and allows the monitoring of miRNA appearance and disappearance in defined cell lineages during vertebrate development.
AU - Tonelli, Davide
AU - Calegari, Frederico
AU - Fei, Ji
AU - Nomura, Tadashi
AU - Osumi, Noriko
AU - Heisenberg, Carl-Philipp J
AU - Huttner, Wieland
ID - 4145
IS - 6
JF - Biotechniques
TI - Single-cell detection of microRNAs in developing vertebrate embryos after acute administration of a dual-fluorescence reporter/sensor plasmid
VL - 41
ER -
TY - JOUR
AB - During vertebrate gastrulation, a well-orchestrated series of morphogenetic changes leads to the formation of the three germ layers: the ectoderm, mesoderm and endoderm. The analysis of gene expression patterns during gastrulation has been central to the identification of genes involved in germ layer formation. However, many proteins are regulated on a translational or post-translational level and are thus undetectable by gene expression analysis. Therefore, we developed a 2D-gel-based comparative proteomic approach to target proteins involved in germ layer morphogenesis during zebrafish gastrulation. Proteomes of ectodermal and mesendodermal progenitor cells were compared and 35 significantly regulated proteins were identified by mass spectrometry, including several proteins with predicted functions in cytoskeletal organization. A comparison of our proteomic results with data obtained in an accompanying microarray-based gene expression analysis revealed no significant overlap, confirming the complementary nature of proteomics and transcriptomics. The regulation of ezrin2, which was identified based on a reduction in spot intensity in mesendodermal cells, was independently validated. Furthermore, we show that ezrin2 is activated by phosphorylation in mesendodermal cells and is required for proper germ layer morphogenesis. We demonstrate the feasibility of proteomics in zebrafish, concluding that proteomics is a valuable tool for analysis of early development.
AU - Link, Vinzenz
AU - Carvalho, Lara
AU - Castanon, Irinka
AU - Stockinger, Petra
AU - Shevchenko, Andrej
AU - Heisenberg, Carl-Philipp J
ID - 4176
IS - 10
JF - Journal of Cell Science
TI - Identification of regulators of germ layer morphogenesis using proteomics in zebrafish
VL - 119
ER -
TY - JOUR
AB - Background: Zebrafish (D. rerio) has become a powerful and widely used model system for the analysis of vertebrate embryogenesis and organ development. While genetic methods are readily available in zebrafish, protocols for two dimensional (2D) gel electrophoresis and proteomics have yet to be developed. Results: As a prerequisite to carry out proteomic experiments with early zebrafish embryos, we developed a method to efficiently remove the yolk from large batches of embryos. This method enabled high resolution 2D gel electrophoresis and improved Western blotting considerably. Here, we provide detailed protocols for proteomics in zebrafish from sample preparation to mass spectrometry (MS), including a comparison of databases for MS identification of zebrafish proteins. Conclusion: The provided protocols for proteomic analysis of early embryos enable research to be taken in novel directions in embryogenesis.
AU - Link, Vinzenz
AU - Shevchenko, Andrej
AU - Heisenberg, Carl-Philipp J
ID - 4173
JF - BMC Developmental Biology
TI - Proteomics of early zebrafish embryos
VL - 6
ER -
TY - JOUR
AB - Detailed reconstruction of the spatiotemporal history of embryonic cells is key to understanding tissue formation processes but is often complicated by the large number of cells involved, particularly so in vertebrates. Through a combination of high-resolution time-lapse lineage tracing and antibody staining, we have analyzed the movement of mesencephalic and metencephalic cell populations in the early zebrafish embryo. To facilitate the analysis of our cell tracking data, we have created TracePilot, a software tool that allows interactive manipulation and visualization of tracking data. We demonstrate its utility by showing novel visualizations of cell movement in the developing zebrafish brain. TracePilot (http://www.mpi-cbg.de/tracepilot) is Java-based, available free of charge, and has a program structure that allows the incorporation of additional analysis tools.
AU - Langenberg, Tobias
AU - Dracz, Tadeusz
AU - Oates, Andrew
AU - Heisenberg, Carl-Philipp J
AU - Brand, Michael
ID - 4178
IS - 4
JF - Developmental Dynamics
TI - Analysis and visualization of cell movement in the developing zebrafish brain
VL - 235
ER -
TY - JOUR
AB - Epithelial morphogenesis depends on coordinated changes in cell shape, a process that is still poorly understood. During zebrafish epiboly and Drosophila dorsal closure, cell-shape changes at the epithelial margin are of critical importance. Here evidence is provided for a conserved mechanism of local actin and myosin 2 recruitment during theses events. It was found that during epiboly of the zebrafish embryo, the movement of the outer epithelium (enveloping layer) over the yolk cell surface involves the constriction of marginal cells. This process depends on the recruitment of actin and myosin 2 within the yolk cytoplasm along the margin of the enveloping layer. Actin and myosin 2 recruitment within the yolk cytoplasm requires the Ste20-like kinase Msn1, an orthologue of Drosophila Misshapen. Similarly, in Drosophila, actin and myosin 2 localization and cell constriction at the margin of the epidermis mediate dorsal closure and are controlled by Misshapen. Thus, this study has characterized a conserved mechanism underlying coordinated cell-shape changes during epithelial morphogenesis.
AU - Köppen, Mathias
AU - Fernández, Beatriz
AU - Carvalho, Lara
AU - Jacinto, António
AU - Heisenberg, Carl-Philipp J
ID - 4184
IS - 14
JF - Development
TI - Coordinated cell-shape changes control epithelial movement in zebrafish and Drosophila
VL - 133
ER -
TY - JOUR
AB - The molecular and cellular mechanisms governing cell motility and directed migration in response to the chemokine SDF-1 are largely unknown. Here, we demonstrate that zebrafish primordial germ cells whose migration is guided by SDF-1 generate bleb-like protrusions that are powered by cytoplasmic flow. Protrusions are formed at sites of higher levels of free calcium where activation of myosin contraction occurs. Separation of the acto-myosin cortex from the plasma membrane at these sites is followed by a flow of cytoplasm into the forming bleb. We propose that polarized activation of the receptor CXCR4 leads to a rise in free calcium that in turn activates myosin contraction in the part of the cell responding to higher levels of the ligand SDF-1. The biased formation of new protrusions in a particular region of the cell in response to SDF-1 defines the leading edge and the direction of cell migration.
AU - Blaser, Heiko
AU - Reichman Fried, Michal
AU - Castanon, Irinka
AU - Dumstrei, Karin
AU - Marlow, Florence
AU - Kawakami, Koichi
AU - Solnica Krezel, Lilianna
AU - Heisenberg, Carl-Philipp J
AU - Raz, Erez
ID - 4218
IS - 5
JF - Developmental Cell
TI - Migration of zebrafish primordial germ cells: A role for myosin contraction and cytoplasmic flow
VL - 11
ER -
TY - JOUR
AB - The growth function of populations is central in biomathematics. The main dogma is the existence of density-dependence mechanisms, which can be modelled with distinct functional forms that depend on the size of the Population. One important class of regulatory functions is the theta-logistic, which generalizes the logistic equation. Using this model as a motivation, this paper introduces a simple dynamical reformulation that generalizes many growth functions. The reformulation consists of two equations, one for population size, and one for the growth rate. Furthermore, the model shows that although population is density-dependent, the dynamics of the growth rate does not depend either on population size, nor on the carrying capacity. Actually, the growth equation is uncoupled from the population size equation, and the model has only two parameters, a Malthusian parameter rho and a competition coefficient theta. Distinct sign combinations of these parameters reproduce not only the family of theta-logistics, but also the van Bertalanffy, Gompertz and Potential Growth equations, among other possibilities. It is also shown that, except for two critical points, there is a general size-scaling relation that includes those appearing in the most important allometric theories, including the recently proposed Metabolic Theory of Ecology. With this model, several issues of general interest are discussed such as the growth of animal population, extinctions, cell growth and allometry, and the effect of environment over a population. (c) 2005 Elsevier Ltd. All rights reserved.
AU - de Vladar, Harold
ID - 4237
IS - 2
JF - Journal of Theoretical Biology
TI - Density-dependence as a size-independent regulatory mechanism
VL - 238
ER -
TY - JOUR
AB - We study the extent to which the Hausdorff dimension of a compact subset of an infinite-dimensional Banach space is affected by a typical mapping into a finite-dimensional space. It is possible that the dimension drops under all such mappings, but the amount by which it typically drops is controlled by the ‘thickness exponent’ of the set, which was defined by Hunt and Kaloshin (Nonlinearity12 (1999), 1263–1275). More precisely, let $X$ be a compact subset of a Banach space $B$ with thickness exponent $\tau$ and Hausdorff dimension $d$. Let $M$ be any subspace of the (locally) Lipschitz functions from $B$ to $\mathbb{R}^{m}$ that contains the space of bounded linear functions. We prove that for almost every (in the sense of prevalence) function $f \in M$, the Hausdorff dimension of $f(X)$ is at least $\min\{ m, d / (1 + \tau) \}$. We also prove an analogous result for a certain part of the dimension spectra of Borel probability measures supported on $X$. The factor $1 / (1 + \tau)$ can be improved to $1 / (1 + \tau / 2)$ if $B$ is a Hilbert space. Since dimension cannot increase under a (locally) Lipschitz function, these theorems become dimension preservation results when $\tau = 0$. We conjecture that many of the attractors associated with the evolution equations of mathematical physics have thickness exponent zero. We also discuss the sharpness of our results in the case $\tau > 0$.
AU - OTT, WILLIAM
AU - HUNT, BRIAN
AU - Kaloshin, Vadim
ID - 8514
IS - 3
JF - Ergodic Theory and Dynamical Systems
SN - 0143-3857
TI - The effect of projections on fractal sets and measures in Banach spaces
VL - 26
ER -
TY - CONF
AB - We consider the evolution of a set carried by a space periodic incompressible stochastic flow in a Euclidean space. We
report on three main results obtained in [8, 9, 10] concerning long time behaviour for a typical realization of the stochastic flow. First, at time t most of the particles are at a distance of order √t away from the origin. Moreover, we prove a Central Limit Theorem for the evolution of a measure carried by the flow, which holds for almost every realization of the flow. Second, we show the existence of a zero measure full Hausdorff dimension set of points, which
escape to infinity at a linear rate. Third, in the 2-dimensional case, we study the set of points visited by the original set by time t. Such a set, when scaled down by the factor of t, has a limiting non random shape.
AU - Kaloshin, Vadim
AU - DOLGOPYAT, D.
AU - KORALOV, L.
ID - 8515
SN - 9789812562012
T2 - XIVth International Congress on Mathematical Physics
TI - Long time behaviour of periodic stochastic flows
ER -
TY - JOUR
AU - Kaloshin, Vadim
AU - Saprykina, Maria
ID - 8513
IS - 2
JF - Discrete & Continuous Dynamical Systems - A
SN - 1553-5231
TI - Generic 3-dimensional volume-preserving diffeomorphisms with superexponential growth of number of periodic orbits
VL - 15
ER -
TY - JOUR
AB - We demonstrate the feasibility of recording 1H–15N correlation spectra of proteins in only one second of acquisition time. The experiment combines recently proposed SOFAST-HMQC with Hadamard-type 15N frequency encoding. This allows site-resolved real-time NMR studies of kinetic processes in proteins with an increased time resolution. The sensitivity of the experiment is sufficient to be applicable to a wide range of molecular systems available at millimolar concentration on a high magnetic field spectrometer.
AU - Schanda, Paul
AU - Brutscher, Bernhard
ID - 8490
IS - 2
JF - Journal of Magnetic Resonance
KW - Nuclear and High Energy Physics
KW - Biophysics
KW - Biochemistry
KW - Condensed Matter Physics
SN - 1090-7807
TI - Hadamard frequency-encoded SOFAST-HMQC for ultrafast two-dimensional protein NMR
VL - 178
ER -
TY - JOUR
AB - Structure elucidation of proteins by either NMR or X‐ray crystallography often requires the screening of a large number of samples for promising protein constructs and optimum solution conditions. For large‐scale screening of protein samples in solution, robust methods are needed that allow a rapid assessment of the folding of a polypeptide under diverse sample conditions. Here we present HET‐SOFAST NMR, a highly sensitive new method for semi‐quantitative characterization of the structural compactness and heterogeneity of polypeptide chains in solution. On the basis of one‐dimensional 1H HET‐SOFAST NMR data, obtained on well‐folded, molten globular, partially‐ and completely unfolded proteins, we define empirical thresholds that can be used as quantitative benchmarks for protein compactness. For 15N‐enriched protein samples, two‐dimensional 1H‐15N HET‐SOFAST correlation spectra provide site‐specific information about the structural heterogeneity along the polypeptide chain.
AU - Schanda, Paul
AU - Forge, Vincent
AU - Brutscher, Bernhard
ID - 8489
IS - S1
JF - Magnetic Resonance in Chemistry
SN - 0749-1581
TI - HET-SOFAST NMR for fast detection of structural compactness and heterogeneity along polypeptide chains
VL - 44
ER -
TY - JOUR
AB - We demonstrate for different protein samples that three-dimensional HNCO and HNCA correlation spectra may be recorded in a few minutes acquisition time using the band-selective excitation short-transient sequences presented here. This opens new perspectives for the NMR structural investigation of unstable protein samples and real-time site-resolved studies of protein kinetics.
AU - Schanda, Paul
AU - Van Melckebeke, Hélène
AU - Brutscher, Bernhard
ID - 8488
IS - 28
JF - Journal of the American Chemical Society
KW - Colloid and Surface Chemistry
KW - Biochemistry
KW - General Chemistry
KW - Catalysis
SN - 0002-7863
TI - Speeding up three-dimensional protein NMR experiments to a few minutes
VL - 128
ER -
TY - BOOK
AB - Harold Davenport was one of the truly great mathematicians of the twentieth century. Based on lectures he gave at the University of Michigan in the early 1960s, this book is concerned with the use of analytic methods in the study of integer solutions to Diophantine equations and Diophantine inequalities. It provides an excellent introduction to a timeless area of number theory that is still as widely researched today as it was when the book originally appeared. The three main themes of the book are Waring's problem and the representation of integers by diagonal forms, the solubility in integers of systems of forms in many variables, and the solubility in integers of diagonal inequalities. For the second edition of the book a comprehensive foreword has been added in which three prominent authorities describe the modern context and recent developments. A thorough bibliography has also been added.
AU - Davenport, Harold
AU - Timothy Browning
ID - 210
T2 - Analytic methods for diophantine equations and diophantine inequalities
TI - Analytic methods for diophantine equations and diophantine inequalities
ER -
TY - JOUR
AB - Let f ∈ ℤ[x] be a polynomial of degree d. The paucity of non-trivial positive integer solutions to the equation f(x1)+f(x 2)=f(x3)+f(x4) is established, provided that d ≤ 7$. Also the corresponding situation is investigated for equal sums of three like polynomials.
AU - Timothy Browning
ID - 211
IS - 6
JF - Bulletin of the London Mathematical Society
TI - Equal sums of like polynomials
VL - 37
ER -
TY - JOUR
AB - For any n ≧ 2, let F ∈ ℤ [ x 1, … , xn ] be a form of degree d≧ 2, which produces a geometrically irreducible hypersurface in ℙn–1. This paper is concerned with the number N(F;B) of rational points on F = 0 which have height at most B. For any ε > 0 we establish the estimate N(F; B) = O(B n− 2+ ε ), whenever either n ≦ 5 or the hypersurface is not a union of lines. Here the implied constant depends at most upon d, n and ε.
AU - Timothy Browning
AU - Heath-Brown, Roger
ID - 212
IS - 584
JF - Journal fur die Reine und Angewandte Mathematik
TI - Counting rational points on hypersurfaces
ER -
TY - JOUR
AB - Given an absolutely irreducible ternary form F, the purpose of this paper is to produce better upper bounds for the number of integer solutions to the equation F=0, that are restricted to lie in very lopsided boxes. As an application of the main result, a new paucity estimate is obtained for equal sums of two like powers.
AU - Timothy Browning
AU - Heath-Brown, Roger
ID - 214
IS - 2
JF - Mathematische Zeitschrift
TI - Plane curves in boxes and equal sums of two powers
VL - 251
ER -
TY - JOUR
AB - We show that the number of nontrivial rational points of height at most B, which lie on the cubic surface x1 x2 x3 = x4 (x1 + x2 + x3)2, has order of magnitude B (log B)6. This agrees with Manin's conjecture.
AU - Timothy Browning
ID - 217
IS - 2
JF - Journal of Number Theory
TI - The density of rational points on a certain singular cubic surface
VL - 119
ER -
TY - JOUR
AB - The human norepinephrine (NE) transporter (hNET) attenuates neuronal signaling by rapid NE clearance from the synaptic cleft, and NET is a target for cocaine and amphetamines as well as therapeutics for depression, obsessive-compulsive disorder, and post-traumatic stress disorder. In spite of its central importance in the nervous system, little is known about how NET substrates, such as NE, 1-methyl-4-tetrahydropyridinium (MPP+), or amphetamine, interact with NET at the molecular level. Nor do we understand the mechanisms behind the transport rate. Previously we introduced a fluorescent substrate similar to MPP+, which allowed separate and simultaneous binding and transport measurement (Schwartz, J. W., Blakely, R. D., and DeFelice, L. J. (2003) J. Biol. Chem. 278, 9768-9777). Here we use this substrate, 4-(4-(dimethylamino)styrl)-N-methyl-pyridinium (ASP+), in combination with green fluorescent protein-tagged hNETs to measure substrate-transporter stoichiometry and substrate binding kinetics. Calibrated confocal microscopy and fluorescence correlation spectroscopy reveal that hNETs, which are homo-multimers, bind one substrate molecule per transporter subunit. Substrate residence at the transporter, obtained from rapid on-off kinetics revealed in fluorescence correlation spectroscopy, is 526 μs. Substrate residence obtained by infinite dilution is 1000 times slower. This novel examination of substrate-transporter kinetics indicates that a single ASP + molecule binds and unbinds thousands of times before being transported or ultimately dissociated from hNET. Calibrated fluorescent images combined with mass spectroscopy give a transport rate of 0.06 ASP +/hNET-protein/s, thus 36,000 on-off binding events (and 36 actual departures) occur for one transport event. Therefore binding has a low probability of resulting in transport. We interpret these data to mean that inefficient binding could contribute to slow transport rates.
AU - Schwartz, Joel W
AU - Gaia Novarino
AU - Piston, David W
AU - DeFelice, Louis J
ID - 2307
IS - 19
JF - Journal of Biological Chemistry
TI - Substrate binding stoichiometry and kinetics of the norepinephrine transporter
VL - 280
ER -
TY - BOOK
AB - This book contains a unique survey of the mathematically rigorous results about the quantum-mechanical many-body problem that have been obtained by the authors in the past seven years. It addresses a topic that is not only rich mathematically, using a large variety of techniques in mathematical analysis, but is also one with strong ties to current experiments on ultra-cold Bose gases and Bose-Einstein condensation. The book provides a pedagogical entry into an active area of ongoing research for both graduate students and researchers. It is an outgrowth of a course given by the authors for graduate students and post-doctoral researchers at the Oberwolfach Research Institute in 2004. The book also provides a coherent summary of the field and a reference for mathematicians and physicists active in research on quantum mechanics.
AU - Lieb, Élliott H
AU - Robert Seiringer
AU - Solovej, Jan P
AU - Yngvason, Jakob
ID - 2335
T2 - The mathematics of the Bose gas and its condensation
TI - The mathematics of the Bose gas and its condensation
VL - 34
ER -
TY - CHAP
AB -
Now that the low temperature properties of quantum-mechanical many-body systems (bosons) at low density, ρ, can be examined experimentally it is appropriate to revisit some of the formulas deduced by many authors 4–5 decades ago, and to explore new regimes not treated before. For systems with repulsive (i.e. positive) interaction potentials the experimental low temperature state and the ground state are effectively synonymous — and this fact is used in all modeling. In such cases, the leading term in the energy/particle is 2πħ2 aρ/m where a is the scattering length of the two-body potential. Owing to the delicate and peculiar nature of bosonic correlations (such as the strange N 7/5 law for charged bosons), four decades of research failed to establish this plausible formula rigorously. The only previous lower bound for the energy was found by Dyson in 1957, but it was 14 times too small. The correct asymptotic formula has been obtained by us and this work will be presented. The reason behind the mathematical difficulties will be emphasized. A different formula, postulated as late as 1971 by Schick, holds in two dimensions and this, too, will be shown to be correct. With the aid of the methodology developed to prove the lower bound for the homogeneous gas, several other problems have been successfully addressed. One is the proof by us that the Gross-Pitaevskii equation correctly describes the ground state in the ‘traps’ actually used in the experiments. For this system it is also possible to prove complete Bose condensation and superfluidity as we have shown. On the frontier of experimental developments is the possibility that a dilute gas in an elongated trap will behave like a one-dimensional system; we have proved this mathematically. Another topic is a proof that Foldy’s 1961 theory of a high density Bose gas of charged particles correctly describes its ground state energy; using this we can also prove the N 7/5 formula for the ground state energy of the two-component charged Bose gas proposed by Dyson in 1967. All of this is quite recent work and it is hoped that the mathematical methodology might be useful, ultimately, to solve more complex problems connected with these interesting systems.
AU - Lieb, Élliott H
AU - Robert Seiringer
AU - Solovej, Jan P
AU - Yngvason, Jakob
ED - Benedicks, Michael
ED - Jones, Peter W
ED - Smirnov, Stanislav
ED - Winckler, Björn
ID - 2336
T2 - Perspectives in Analysis
TI - The quantum-mechanical many-body problem: The Bose gas
VL - 27
ER -
TY - JOUR
AB - The validity of substituting a c-number z for the k = 0 mode operator a0 is established rigorously in full generality, thereby verifying one aspect of Bogoliubov's 1947 theory. This substitution not only yields the correct value of thermodynamic quantities such as the pressure or ground state energy, but also the value of |z|2 that maximizes the partition function equals the true amount of condensation in the presence of a gauge-symmetry-breaking term. This point had previously been elusive.
AU - Lieb, Élliott H
AU - Robert Seiringer
AU - Yngvason, Jakob
ID - 2359
IS - 8
JF - Physical Review Letters
TI - Justification of c-number substitutions in bosonic hamiltonians
VL - 94
ER -
TY - JOUR
AB - The strong subadditivity of entropy plays a key role in several areas of physics and mathematics. It states that the entropy S[±]=- Tr(Ï±lnÏ±) of a density matrix Ï±123 on the product of three Hilbert spaces satisfies S[Ï±123]- S[Ï±12]≤S[Ï±23]-S[Ï±2]. We strengthen this to S[Ï±123]-S[Ï±12] ≤αnα(S[Ï±23α]-S[Ï±2α]), where the nα are weights and the Ï±23α are partitions of Ï±23. Correspondingly, there is a strengthening of the theorem that the map A|Trexp[L+lnA] is concave. As applications we prove some monotonicity and convexity properties of the Wehrl coherent state entropy and entropy inequalities for quantum gases.
AU - Lieb, Élliott H
AU - Robert Seiringer
ID - 2361
IS - 6
JF - Physical Review A - Atomic, Molecular, and Optical Physics
TI - Stronger subadditivity of entropy
VL - 71
ER -
TY - JOUR
AB - Recent developments in the physics of low-density trapped gases make it worthwhile to verify old, well-known results that, while plausible, were based on perturbation theory and assumptions about pseudopotentials. We use and extend recently developed techniques to give a rigorous derivation of the asymptotic formula for the ground-state energy of a dilute gas of N fermions interacting with a short-range, positive potential of scattering length a. For spin-12 fermions, this is E∼E0+(22m)2πNa, where E0 is the energy of the noninteracting system and is the density. A similar formula holds in two dimensions (2D), with a replaced by ln(a2). Obviously this 2D energy is not the expectation value of a density-independent pseudopotential.
AU - Lieb, Élliott H
AU - Robert Seiringer
AU - Solovej, Jan P
ID - 2362
IS - 5
JF - Physical Review A - Atomic, Molecular, and Optical Physics
TI - Ground state energy of the low density Fermi gas
VL - 71
ER -
TY - JOUR
AB - Intersection graphs of disks and of line segments, respectively, have been well studied, because of both practical applications and theoretically interesting properties of these graphs. Despite partial results, the complexity status of the Clique problem for these two graph classes is still open. Here, we consider the Clique problem for intersection graphs of ellipses, which, in a sense, interpolate between disks and line segments, and show that the problem is APX-hard in that case. Moreover, this holds even if for all ellipses, the ratio of the larger over the smaller radius is some prescribed number. Furthermore, the reduction immediately carries over to intersection graphs of triangles. To our knowledge, this is the first hardness result for the Clique problem in intersection graphs of convex objects with finite description complexity. We also describe a simple approximation algorithm for the case of ellipses for which the ratio of radii is bounded.
AU - Ambühl, Christoph
AU - Uli Wagner
ID - 2427
IS - 3
JF - Theory of Computing Systems
TI - The Clique problem in intersection graphs of ellipses and triangles
VL - 38
ER -
TY - CONF
AB - We consider an online version of the conflict-free coloring of a set of points on the line, where each newly inserted point must be assigned a color upon insertion, and at all times the coloring has to be conflict-free, in the sense that in every interval I there is a color that appears exactly once in I. We present several deterministic and randomized algorithms for achieving this goal, and analyze their performance, that is, the maximum number of colors that they need to use, as a function of the number n of inserted points. We first show that a natural and simple (deterministic) approach may perform rather poorly, requiring Ω(√n) colors in the worst case. We then modify this approach, to obtain an efficient deterministic algorithm that uses a maximum of Θ(log 2 n) colors. Next, we present two randomized solutions. The first algorithm requires an expected number of at most O(log 2 n) colors, and produces a coloring which is valid with high probability, and the second one, which is a variant of our efficient deterministic algorithm, requires an expected number of at most O(log n log log n) colors but always produces a valid coloring. We also analyze the performance of the simplest proposed algorithm when the points are inserted in a random order, and present an incomplete analysis that indicates that, with high probability, it uses only O(log n) colors. Finally, we show that in the extension of this problem to two dimensions, where the relevant ranges are disks, n colors may be required in the worst case. The average-case behavior for disks, and cases involving other planar ranges, are still open.
AU - Fiat, Amos
AU - Levy, Meital B
AU - Matoušek, Jiří
AU - Pach, Elchanan M
AU - Sharir, Micha
AU - Smorodinsky, Shakhar
AU - Uli Wagner
AU - Welzl, Emo
ID - 2428
TI - Online conflict-free coloring for intervals
ER -
TY - JOUR
AB - Local accumulation of the plant growth regulator auxin mediates pattern formation in Arabidopsis roots and influences outgrowth and development of lateral root- and shoot-derived primordia. However, it has remained unclear how auxin can simultaneously regulate patterning and organ outgrowth and how its distribution is stabilized in a primordium-specif ic manner. Here we show that five PIN genes collectively control auxin distribution to regulate cell division and cell expansion in the primary root. Furthermore, the joint action of these genes has an important role in pattern formation by focusing the auxin maximum and restricting the expression domain of PLETHORA (PLT) genes, major determinants for root stem cell specification. In turn, PLT genes are required for PIN gene transcription to stabilize the auxin maximum at the distal root tip. Our data reveal an interaction network of auxin transport facilitators and root fate determinants that control patterning and growth of the root primordium.
AU - Billou, Ikram
AU - Xu, Jian
AU - Wildwater, Marjolein
AU - Willemsen, Viola
AU - Paponov, Ivan A
AU - Jirí Friml
AU - Heldstra, Renze
AU - Aida, Mitsuhiro
AU - Palme, Klaus J
AU - Scheres, Ben
ID - 2455
IS - 7021
JF - Nature
TI - The PIN auxin efflux facilitator network controls growth and patterning in Arabidopsis roots
VL - 433
ER -
TY - CHAP
AU - Dubová, J
AU - Hejátko, Jan
AU - Jirí Friml
ED - Meyers, Robert A
ID - 2463
T2 - Encyclopedia of Molecular Cell Biology and Molecular Medicine
TI - Reproduction, plants
VL - 12
ER -
TY - CHAP
AU - Jirí Friml
AU - Wiśniewska, Justyna
ED - Fleming, Andrew J.
ID - 2464
T2 - Intercellular Communication in Plants
TI - Auxin as an intercellular signal
VL - 16
ER -
TY - JOUR
AB - In the ant Cardiocondyla obscurior, wingless males compete with nestmate males for access to female mating
partners, leading to local mate competition (LMC). Queen number varies between colonies, resulting in
variation in the strength of LMC. Cremer & Heinze (2002, Proceedings of the Royal Society of London, Series B,
269, 417–422) showed that colonies responded to increasing queen number by producing a less femalebiased
sex ratio, as predicted by LMC theory. However, the proximate mechanisms responsible for this
variation in the sex ratio could not be determined because the study was restricted to adult sex ratios.With
LMC, the primary sex ratio (proportion of haploid eggs laid by the queen) is expected to be female biased,
which lowers the conflict between queens and workers over sex allocation. We compared the primary sex
ratios laid by queens in monogynous and in polygynous experimental colonies of C. obscurior. The
proportion of haploid eggs laid by queens was significantly lower in single-queen than in multiple-queen
colonies. Furthermore, queens rapidly adjusted their primary sex ratios to changes in colony queen
number. This is the first report of an adaptive adjustment of the primary sex ratio in response to LMC by
ant queens.
AU - De Menten, Ludivine
AU - Cremer, Sylvia
AU - Heinze, Jürgen
AU - Aron, Serge
ID - 3915
IS - 5
JF - Animal Behaviour
TI - Primary sex ratio adjustment by ant queens in response to local mate competition
VL - 69
ER -
TY - JOUR
AB - Divergent reproductive interests of males and females often cause sexual conflict [1] and [2]. Males of many species manipulate females by transferring seminal fluids that boost female short-term fecundity while decreasing their life expectancy and future reproductivity [3] and [4]. The life history of ants, however, is expected to reduce sexual conflict; whereas most insect females show repeated phases of mating and reproduction, antqueens mate only during a short period early in life and undergo a lifelong commitment to their mates by storing sperm [5]. Furthermore, sexual offspring can only be reared after a sterile worker force has been built up [5]. Therefore, the males should also profit from a long female lifespan. In the antCardiocondyla obscurior, mating indeed has a positive effect on the lifetime reproductive success of queens. Queens that mated to either one fertile or one sterilized male lived considerably longer and started laying eggs earlier than virgin queens. Only queens that received viable sperm from fertile males showed increased fecundity. The lack of a trade-off between fecundity and longevity is unexpected, given evolutionary theories of aging [6]. Our data instead reveal the existence of sexual cooperation in ants.
AU - Schrempf, Alexandra
AU - Heinze, Jürgen
AU - Cremer, Sylvia
ID - 3916
IS - 3
JF - Current Biology
TI - Sexual cooperation: mating increases longevity in ant queens
VL - 15
ER -
TY - JOUR
AB - Resident dendritic cells (DC) within the T cell area of the lymph node take up soluble antigens that enter via the afferent lymphatics before antigen carrying DC arrive from the periphery. The reticular network within the lymph node is a conduit system forming the infrastructure for the fast delivery of soluble substances from the afferent lymph to the lumen of high endothelial venules (HEVs). Using high-resolution light microscopy and 3D reconstruction, we show here that these conduits are unique basement membrane-like structures ensheathed by fibroblastic reticular cells with occasional resident DC embedded within this cell layer. Conduit-associated DC are capable of taking up and processing soluble antigens transported within the conduits, whereas immigrated mature DC occur remote from the reticular fibers. The conduit system is, therefore, not a closed compartment that shuttles substances through the lymph node but represents the morphological equivalent to the filtering function of the lymph node.
AU - Sixt, Michael K
AU - Kanazawa, Nobuo
AU - Selg, Manuel
AU - Samson, Thomas
AU - Roos, Gunnel
AU - Reinhardt, Dieter
AU - Pabst, Reinhard
AU - Lutz, Manfred
AU - Sorokin, Lydia
ID - 3933
IS - 1
JF - Immunity
TI - The conduit system transports soluble antigens from the afferent lymph to resident dendritic cells in the T cell area of the lymph node
VL - 22
ER -
TY - CONF
AB - We present an efficient algorithm for generating a small set of coarse alignments between interacting proteins using meaningful features on their surfaces. The proteins are treated as rigid bodies, but the results are more generally useful as the produced configurations can serve as input to local improvement algorithms that allow for protein flexibility. We apply our algorithm to a diverse set of protein complexes from the Protein Data Bank, demonstrating the effectivity of our algorithm, both for bound and for unbound protein docking problems.
AU - Wang, Yusu
AU - Agarwal, Pankaj K
AU - Brown, Paul
AU - Herbert Edelsbrunner
AU - Rudolph, Johannes
ID - 3982
TI - Coarse and reliable geometric alignment for protein docking
ER -
TY - JOUR
AB - Cdc25 phosphatases are key activators of the eukaryotic cell cycle and compelling anticancer targets because their overexpression has been associated with numerous cancers. However, drug discovery targeting these phosphatases has been hampered by the lack of structural information about how Cdc25s interact with their native protein substrates, the cyclin-dependent kinases. Herein, we predict a docked orientation for Cdc25B with its Cdk2-pTpY-CycA protein substrate by a rigid-body docking method and refine the docked models with full-scale molecular dynamics simulations and minimization. We validate the stable ensemble structure experimentally by a variety of in vitro and in vivo techniques. Specifically, we compare our model with a crystal structure of the substrate-trapping mutant of Cdc25B. We identify and validate in vivo a novel hot-spot residue on Cdc25B (Arg492) that plays a central role in protein substrate recognition. We identify a hot-spot residue on the Substrate Cdk2 (Asp206) and confirm its interaction with hot-spot residues on Cdc25 using hot-spot swapping and double mutant cycles to derive interaction energies. Our experimentally validated model is consistent with previous studies of Cdk2 and its interaction partners and initiates the opportunity for drug discovery of inhibitors that target the remote binding sites of this protein-protein interaction.
AU - Sohn, Jungsan
AU - Parks, Jerry M
AU - Buhrman, Gregory
AU - Brown, Paul
AU - Kristjánsdóttir, Kolbrun
AU - Safi, Alexias
AU - Herbert Edelsbrunner
AU - Yang, Weitao T
AU - Rudolph, Johannes
ID - 3983
IS - 50
JF - Biochemistry
TI - Experimental validation of the docking orientation of Cdc25 with its Cdk2-CycA protein substrate
VL - 44
ER -
TY - JOUR
AB - Adaptive dynamics describes the evolution of an asexual population through the successive substitution of mutations of small effect. Waxman & Gavrilets (2005) give an excellent overview of the method and its applications. In this note, we focus on the plausibility of the key assumption that mutations have small effects, and the consequences of relaxing that assumption. We argue that: (i) successful mutations often have large effects; (ii) such mutations generate a qualitatively different evolutionary pattern, which is inherently stochastic; and (iii) in models of competition for a continuous resource, selection becomes very weak once several phenotypes are established. This makes the effects of introducing new mutations unpredictable using the methods of adaptive dynamics.
We should make clear at the outset that our criticism is of methods that rely on local analysis of fitness gradients (eqn 2 of Waxman & Gavrilets, 2005), and not of the broader idea that evolution can be understood by examining the invasion of successive mutations. We use the term ‘adaptive dynamics’ to refer to the former technique, and contrast it with a more general population genetic analysis of probabilities of invasion.
AU - Nicholas Barton
AU - Jitka Polechova
ID - 4138
IS - 5
JF - Journal of Evolutionary Biology
TI - The limitations of adaptive dynamics as a model of evolution
VL - 18
ER -
TY - JOUR
AB - We examined causes of speciation in asexual populations in both sympatry and parapatry, providing an alternative explanation for the speciation patterns reported by Dieckmann and Doebeli (1999) and Doebeli and Dieckmann (2003). Both in sympatry and parapatry, they find that speciation occurs relatively easily. We reveal that in the sympatric clonal model, the equilibrium distribution is continuous and the disruptive selection driving evolution of discrete clusters is only transient. Hence, if discrete phenotypes are to remain stable in the sympatric sexual model, there should be some source of nontransient disruptive selection that will drive evolution of assortment. We analyze sexually reproducing populations using the Bulmer’s infinitesimal model and show that cost-free assortment alone leads to speciation and disruptive selection only arises when the optimal distribution cannot be matched—in this example, because the phenotypic range is limited. In addition, Doebeli and Dieckmann’s analyses assumed a high genetic variance and a high mutation rate. Thus, these theoretical models do not support the conclusion that sympatric speciation is a likely outcome of competition for resources. In their parapatric model (Doebeli and Dieckmann 2003), clustering into distinct phenotypes is driven by edge effects, rather than by frequency-dependent competition.
AU - Jitka Polechova
AU - Nicholas Barton
ID - 4249
IS - 6
JF - Evolution; International Journal of Organic Evolution
TI - Speciation through competition: A critical review
VL - 59
ER -
TY - JOUR
AB - In finite populations subject to selection, genetic drift generates negative linkage disequilibrium, on average, even if selection acts independently (i.e. multiplicatively) upon all loci. Negative disequilibrium reduces the variance in fitness and hence, by FISHER's Fundamental Theorem (1930), slows the rate of increase in mean fitness. Modifiers that increase recombination eliminate the negative disequilibria that impede selection and consequently increase in frequency by 'hitch-hiking'. In addition, recombinant progeny are more fit on average than non-recombinant progeny when there is negative linkage disequilibrium and loci interact multiplicatively. For both these reasons, stochastic fluctuations in linkage disequilibrium in finite populations favor the evolution of increased rates of recombination, even in the absence of epistatic interactions among loci and even when disequilibrium is initially absent. The method developed within this paper quantifies the strength of selection on a modifier allele that increases recombination due to stochastically generated linkage disequilibria. The analysis indicates that, in a population subject to multiplicative selection, genetic associations generated by drift do select for increased recombination, a result that is confirmed by Monte Carlo simulations. Selection for a modifier that increases recombination is highest when linkage among all loci is tight, when beneficial alleles rise from low to high frequency, and when the population size is small.
AU - Nicholas Barton
AU - Otto, Sarah P
ID - 4251
IS - 4
JF - Genetics
TI - Evolution of recombination due to random drift
VL - 169
ER -
TY - JOUR
AB - Empirical studies of quantitative genetic variation have revealed robust patterns that are observed both across traits and across species. However, these patterns have no compelling explanation, and some of the observations even appear to be mutually incompatible. We review and extend a major class of theoretical models, ‘mutation–selection models’, that have been proposed to explain quantitative genetic variation. We also briefly review an alternative class of ‘balancing selection models’. We consider to what extent the models are compatible with the general observations, and argue that a key issue is understanding and modelling pleiotropy. We discuss some
AU - Johnson, Toby
AU - Nicholas Barton
ID - 4252
IS - 1459
JF - Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences
TI - Theoretical models of selection and mutationon quantitative traits
VL - 360
ER -
TY - CONF
AU - Podelski,Andreas
AU - Thomas Wies
ID - 4367
TI - Boolean Heaps
ER -
TY - CONF
AU - Alur, Rajeev
AU - Pavol Cerny
AU - Madhusudan,P.
AU - Nam,Wonhong
ID - 4404
TI - Synthesis of interface specifications for Java classes
ER -