Fitting stochastic epidemic models to gene genealogies using linear noise approximation

Phylodynamics is a set of population genetics tools that aim at reconstructing demographic history of a population based on molecular sequences of individuals sampled from the population of interest. One important task in phylodynamics is to estimate changes in (effective) population size. When applied to infectious disease sequences such estimation of population size trajectories can provide information about changes in the number of infections. To model changes in the number of infected individuals, current phylodynamic methods use non-parametric approaches, parametric approaches, and stochastic modeling in conjunction with likelihood-free Bayesian methods. The first class of methods yields results that are hard-to-interpret epidemiologically. The second class of methods provides estimates of important epidemiological parameters, such as infection and removal/recovery rates, but ignores variation in the dynamics of infectious disease spread. The third class of methods is the most advantageous statistically, but relies on computationally intensive particle filtering techniques that limits its applications. We propose a Bayesian model that combines phylodynamic inference and stochastic epidemic models, and achieves computational tractability by using a linear noise approximation (LNA) --- a technique that allows us to approximate probability densities of stochastic epidemic model trajectories. LNA opens the door for using modern Markov chain Monte Carlo tools to approximate the joint posterior distribution of the disease transmission parameters and of high dimensional vectors describing unobserved changes in the stochastic epidemic model compartment sizes (e.g., numbers of infectious and susceptible individuals). We apply our estimation technique to Ebola genealogies estimated using viral genetic data from the 2014 epidemic in Sierra Leone and Liberia.Comment: 43 pages, 6 figures in the main tex

Quantifying evolutionary constraints on B cell affinity maturation

The antibody repertoire of each individual is continuously updated by the evolutionary process of B cell receptor mutation and selection. It has recently become possible to gain detailed information concerning this process through high-throughput sequencing. Here, we develop modern statistical molecular evolution methods for the analysis of B cell sequence data, and then apply them to a very deep short-read data set of B cell receptors. We find that the substitution process is conserved across individuals but varies significantly across gene segments. We investigate selection on B cell receptors using a novel method that side-steps the difficulties encountered by previous work in differentiating between selection and motif-driven mutation; this is done through stochastic mapping and empirical Bayes estimators that compare the evolution of in-frame and out-of-frame rearrangements. We use this new method to derive a per-residue map of selection, which provides a more nuanced view of the constraints on framework and variable regions.Comment: Previously entitled "Substitution and site-specific selection driving B cell affinity maturation is consistent across individuals

Identifying entanglement using quantum "ghost" interference and imaging

We report a quantum interference and imaging experiment which quantitatively demonstrates that Einstein-Podolsky-Rosen (EPR) type entangled two-photon states exhibit both momentum-momentum and position-position correlations, stronger than any classical correlation. The measurements show indeed that the uncertainties in the sum of momenta and in the difference of positions of the entangled two-photon satisfy both EPR inequalities D(k1+k2)<min(D(k1),D(k2)) and D(x1-x2)<min(D(x1),D(x2)). These two inequalities, together, represent a non-classicality condition. Our measurements provide a direct way to distinguish between quantum entanglement and classical correlation in continuous variables for two-photons/two photons systems.Comment: We have changed Eq.(2) from one inequality to two inequalities. The two expressions are actually consistent with each other, but the new one represents a more stringent condition for entanglement and, in our opinion, better explains the original idea of EPR. We have clarified this point in the paper. 4 pages; submitted to PR

Adding flavour to twistor strings

Twistor string theory is known to describe a wide variety of field theories at tree-level and has proved extremely useful in making substantial progress in perturbative gauge theory. We explore the twistor dual description of a class of N=2 UV-finite super-Yang-Mills theories with fundamental flavour by adding 'flavour' branes to the topological B-model on super-twistor space and comment on the appearance of these objects. Evidence for the correspondence is provided by matching amplitudes on both sides.Comment: 6 pages; contribution to the proceedings for the European Physical Society conference on High Energy Physics in Manchester, 19-25 July 2007. v3: Typos correcte

Post-critical set and non existence of preserved meromorphic two-forms

We present a family of birational transformations in $CP_2$ depending on two, or three, parameters which does not, generically, preserve meromorphic two-forms. With the introduction of the orbit of the critical set (vanishing condition of the Jacobian), also called ``post-critical set'', we get some new structures, some "non-analytic" two-form which reduce to meromorphic two-forms for particular subvarieties in the parameter space. On these subvarieties, the iterates of the critical set have a polynomial growth in the \emph{degrees of the parameters}, while one has an exponential growth out of these subspaces. The analysis of our birational transformation in $CP_2$ is first carried out using Diller-Favre criterion in order to find the complexity reduction of the mapping. The integrable cases are found. The identification between the complexity growth and the topological entropy is, one more time, verified. We perform plots of the post-critical set, as well as calculations of Lyapunov exponents for many orbits, confirming that generically no meromorphic two-form can be preserved for this mapping. These birational transformations in $CP_2$, which, generically, do not preserve any meromorphic two-form, are extremely similar to other birational transformations we previously studied, which do preserve meromorphic two-forms. We note that these two sets of birational transformations exhibit totally similar results as far as topological complexity is concerned, but drastically different results as far as a more ``probabilistic'' approach of dynamical systems is concerned (Lyapunov exponents). With these examples we see that the existence of a preserved meromorphic two-form explains most of the (numerical) discrepancy between the topological and probabilistic approach of dynamical systems.Comment: 34 pages, 7 figure

Convergence and multiplicities for the Lempert function

Given a domain $\Omega \subset \mathbb C$, the Lempert function is a functional on the space Hol (\D,\Omega) of analytic disks with values in $\Omega$, depending on a set of poles in $\Omega$. We generalize its definition to the case where poles have multiplicities given by local indicators (in the sense of Rashkovskii's work) to obtain a function which still dominates the corresponding Green function, behaves relatively well under limits, and is monotonic with respect to the indicators. In particular, this is an improvement over the previous generalization used by the same authors to find an example of a set of poles in the bidisk so that the (usual) Green and Lempert functions differ.Comment: 24 pages; many typos corrected thanks to the referee of Arkiv for Matemati

Nowhere minimal CR submanifolds and Levi-flat hypersurfaces

A local uniqueness property of holomorphic functions on real-analytic nowhere minimal CR submanifolds of higher codimension is investigated. A sufficient condition called almost minimality is given and studied. A weaker necessary condition, being contained a possibly singular real-analytic Levi-flat hypersurface is studied and characterized. This question is completely resolved for algebraic submanifolds of codimension 2 and a sufficient condition for noncontainment is given for non algebraic submanifolds. As a consequence, an example of a submanifold of codimension 2, not biholomorphically equivalent to an algebraic one, is given. We also investigate the structure of singularities of Levi-flat hypersurfaces.Comment: 21 pages; conjecture 2.8 was removed in proof; to appear in J. Geom. Ana

Consistency Conditions on S-Matrix of Spin 1 Massless Particles

Motivated by new techniques in the computation of scattering amplitudes of massless particles in four dimensions, like BCFW recursion relations, the question of how much structure of the S-matrix can be determined from purely S-matrix arguments has received new attention. The BCFW recursion relations for massless particles of spin 1 and 2 imply that the whole tree-level S-matrix can be determined in terms of three-particle amplitudes (evaluated at complex momenta). However, the known proofs of the validity of the relations rely on the Lagrangian of the theory, either by using Feynman diagrams explicitly or by studying the effective theory at large complex momenta. This means that a purely S-matrix theoretic proof of the relations is still missing. The aim of this paper is to provide such a proof for spin 1 particles by extending the four-particle test introduced by P. Benincasa and F. Cachazo in arXiv:0705.4305[hep-th] to all particles. We show how n-particle tests imply that the rational function built from the BCFW recursion relations possesses all the correct factorization channels including holomorphic and anti-holomorphic collinear limits. This in turn implies that they give the correct S-matrix of the theory.Comment: 24 pages, 4 figure