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  • Publication . Article . Other literature type . Preprint . 2016
    Open Access English
    Authors: 
    Eyal Elyashiv; Shmuel Sattath; Tina T. Hu; Alon Strutsovsky; Graham McVicker; Peter Andolfatto; Graham Coop; Guy Sella;
    Publisher: Public Library of Science (PLoS)
    Country: United States
    Project: NSF | Collaborative Research: A... (1262645)

    © 2016 Elyashiv et al. Natural selection at one site shapes patterns of genetic variation at linked sites. Quantifying the effects of “linked selection” on levels of genetic diversity is key to making reliable inference about demography, building a null model in scans for targets of adaptation, and learning about the dynamics of natural selection. Here, we introduce the first method that jointly infers parameters of distinct modes of linked selection, notably background selection and selective sweeps, from genome-wide diversity data, functional annotations and genetic maps. The central idea is to calculate the probability that a neutral site is polymorphic given local annotations, substitution patterns, and recombination rates. Information is then combined across sites and samples using composite likelihood in order to estimate genome-wide parameters of distinct modes of selection. In addition to parameter estimation, this approach yields a map of the expected neutral diversity levels along the genome. To illustrate the utility of our approach, we apply it to genome-wide resequencing data from 125 lines in Drosophila melanogaster and reliably predict diversity levels at the 1Mb scale. Our results corroborate estimates of a high fraction of beneficial substitutions in proteins and untranslated regions (UTR). They allow us to distinguish between the contribution of sweeps and other modes of selection around amino acid substitutions and to uncover evidence for pervasive sweeps in untranslated regions (UTRs). Our inference further suggests a substantial effect of other modes of linked selection and of adaptation in particular. More generally, we demonstrate that linked selection has had a larger effect in reducing diversity levels and increasing their variance in D. melanogaster than previously appreciated.

  • Publication . Conference object . Article . Preprint . 2019 . Embargo End Date: 01 Jan 2019
    Open Access
    Authors: 
    Fedor Vladimirovich Borisyuk; Albert Gordo; Viswanath Sivakumar;
    Publisher: arXiv

    In this paper we present a deployed, scalable optical character recognition (OCR) system, which we call Rosetta, designed to process images uploaded daily at Facebook scale. Sharing of image content has become one of the primary ways to communicate information among internet users within social networks such as Facebook and Instagram, and the understanding of such media, including its textual information, is of paramount importance to facilitate search and recommendation applications. We present modeling techniques for efficient detection and recognition of text in images and describe Rosetta's system architecture. We perform extensive evaluation of presented technologies, explain useful practical approaches to build an OCR system at scale, and provide insightful intuitions as to why and how certain components work based on the lessons learnt during the development and deployment of the system. Comment: Proceedings of the 24th ACM SIGKDD International Conference on Knowledge Discovery & Data Mining (KDD) 2018, London, United Kingdom

  • Open Access
    Authors: 
    Moshe Goldsmith; Barad S; Knafo M; Alon Savidor; Shifra Ben-Dor; Alexander Brandis; Tevie Mehlman; Yoav Peleg; Shira Albeck; Orly Dym; +2 more
    Publisher: Cold Spring Harbor Laboratory

    AbstractGrass pea (Lathyrus sativus L.) is a grain legume commonly grown in parts of Asia and Africa for food and forage. While being a highly nutritious and robust crop, able to survive both drought and floods, it produces a neurotoxic compound, β-N-oxalyl-L-α,β-diaminopropionic acid (β-ODAP), which can cause a severe neurological disorder if consumed as a main diet component. So far, the enzyme that catalyzes the formation of β-ODAP has not been identified. By combining protein purification and enzymatic assays with transcriptomic and proteomic analyses, we were able to identify the enzyme β-ODAP synthetase (BOS) from grass pea. We show that BOS is an HXXXD-type acyltransferase of the BAHD superfamily and that its crystal structure is highly similar to that of plant hydroxycinnamoyl transferases. The identification of BOS, more than 50 years after it was proposed, paves the way towards the generation of non-toxic grass pea cultivars safe for human and animal consumption.

  • Publication . Article . Preprint . 2014
    Open Access English
    Authors: 
    Kerner, Dmitry;
    Project: EC | DURFEE (334347)

    Consider rectangular matrices over a local ring R. In the previous work we have obtained criteria for block-diagonalization of such matrices, i.e. U A V=A_1\oplus A_2, where U,V are invertible matrices over R. In this short note we extend the criteria to the decomposability of quiver representations over R. Preliminary brief announcement

  • Open Access English
    Authors: 
    Biskup, Marek; Louidor, Oren;
    Project: EC | MOTTPROXIMITY (276923), NSF | Large Scale Phenomena in ... (1407558)

    We study the extremal process associated with the Discrete Gaussian Free Field on the square lattice and elucidate how the conformal symmetries manifest themselves in the scaling limit. Specifically, we prove that the joint process of spatial positions ($x$) and centered values ($h$) of the extreme local maxima in lattice versions of a bounded domain $D\subset\mathbb C$ converges, as the lattice spacing tends to zero, to a Poisson point process with intensity measure $Z^D(dx)\otimes e^{-\alpha h}d h$, where $\alpha$ is a constant and $Z^D$ is a random a.s.-finite measure on $D$. The random measures $\{Z^D\}$ are naturally interrelated; restrictions to subdomains are governed by a Gibbs-Markov property and images under analytic bijections $f$ by the transformation rule $(Z^{f(D)}\circ f)(d x)\overset{\text{law}}=|f'(x)|^4\, Z^D(d x)$. Conditions are given that determine the laws of these measures uniquely. These identify $Z^D$ with the critical Liouville Quantum Gravity associated with the Continuum Gaussian Free Field. Comment: 58 pages, 4 figs, version to appear in Commun. Math. Phys

  • Open Access
    Authors: 
    Spencer Bastani; Tomer Blumkin; Luca Micheletto;

    In this paper we highlight a novel role played by the non-linear income tax in the presence of adverse selection in the labor market due to asymmetric information between workers and firms. Relying on the Rothschild and Stiglitz equilibrium concept, we show that an appropriate choice of the tax schedule enables the government to affect the wage distribution by controlling the transmission of information in the labor market. This represents an additional channel through which the government can foster the pursuit of its redistributive goals.

  • Publication . Preprint . Conference object . Article . 2015
    Open Access
    Authors: 
    Haim Avron; Alex Druinsky; Anshul Gupta;
    Publisher: Association for Computing Machinery (ACM)

    Asynchronous methods for solving systems of linear equations have been researched since Chazan and Miranker's [1969] pioneering paper on chaotic relaxation. The underlying idea of asynchronous methods is to avoid processor idle time by allowing the processors to continue to make progress even if not all progress made by other processors has been communicated to them. Historically, the applicability of asynchronous methods for solving linear equations has been limited to certain restricted classes of matrices, such as diagonally dominant matrices. Furthermore, analysis of these methods focused on proving convergence in the limit. Comparison of the asynchronous convergence rate with its synchronous counterpart and its scaling with the number of processors have seldom been studied and are still not well understood. In this article, we propose a randomized shared-memory asynchronous method for general symmetric positive definite matrices. We rigorously analyze the convergence rate and prove that it is linear and is close to that of the method's synchronous counterpart if the processor count is not excessive relative to the size and sparsity of the matrix. We also present an algorithm for unsymmetric systems and overdetermined least-squares. Our work presents a significant improvement in the applicability of asynchronous linear solvers as well as in their convergence analysis, and suggests randomization as a key paradigm to serve as a foundation for asynchronous methods.

  • Publication . Article . Other literature type . Preprint . 2022
    Open Access English
    Authors: 
    Laura Sberna; Stanislav Babak; Sylvain Marsat; Andrea Caputo; Giulia Cusin; Alexandre Toubiana; Enrico Barausse; Chiara Caprini; Tito Dal Canton; Alberto Sesana; +1 more
    Project: EC | GRU (101007855), EC | LDMThExp (682676), EC | GRAMS (815673), EC | B Massive (818691)

    Binaries of relatively massive black holes like GW190521 have been proposed to form in dense gas environments, such as the disks of Active Galactic Nuclei (AGNs), and they might be associated with transient electromagnetic counterparts. The interactions of this putative environment with the binary could leave a significant imprint at the low gravitational wave frequencies observable with the Laser Interferometer Space Antenna (LISA). We show that LISA will be able to detect up to ten GW190521-like black hole binaries, with sky position errors $\lesssim1$ deg$^2$. Moreover, it will measure directly various effects due to the orbital motion around the supermassive black hole at the center of the AGN, especially the Doppler modulation and the Shapiro time delay. Thanks to a careful treatment of their frequency domain signal, we were able to perform the full parameter estimation of Doppler and Shapiro-modulated binaries as seen by LISA. We find that the Doppler and Shapiro effects will allow for measuring the AGN parameters (radius and inclination of the orbit around the AGN, central black hole mass) with up to percent-level precision. Properly modeling these low-frequency environmental effects is crucial to determine the binary formation history, as well as to avoid biases in the reconstruction of the source parameters and in tests of general relativity with gravitational waves. 13+4 pages, 7+1 figures v3: corrected typo in Fig 5

  • Open Access English
    Authors: 
    Irene Jiménez Guerrero; Francisco Pérez-Montaño; Gustavo Mateus da Silva; Naama Wagner; Dafna Shkedy; Mei Zhao; Lorena Pizarro; Maya Bar; Ron Walcott; Guido Sessa; +2 more
    Publisher: Cold Spring Harbor Laboratory

    AbstractMany Gram-negative plant and animal pathogenic bacteria employ a type III secretion system (T3SS) to secrete protein effectors into the cells of their hosts and promote disease. The plant pathogen Acidovorax citrulli requires a functional T3SS for pathogenicity. As with Xanthomonas and Ralstonia spp., an AraC-type transcriptional regulator, HrpX, regulates expression of genes encoding T3SS components and type III-secreted effectors (T3Es) in A. citrulli. A previous study reported eleven T3E genes in this pathogen, based on the annotation of a sequenced strain. We hypothesized that this was an underestimation. Guided by this hypothesis, we aimed at uncovering the T3E arsenal of the A. citrulli model strain, M6. We carried out a thorough sequence analysis searching for similarity to known T3Es from other bacteria. This analysis revealed 51 A. citrulli genes whose products are similar to known T3Es. Further, we combined machine learning and transcriptomics to identify novel T3Es. The machine learning approach ranked all A. citrulli M6 genes according to their propensity to encode T3Es. RNA-Seq revealed differential gene expression between wild-type M6 and a mutant defective in HrpX. Data combined from these approaches led to the identification of seven novel T3E candidates, that were further validated using a T3SS-dependent translocation assay. These T3E genes encode hypothetical proteins, do not show any similarity to known effectors from other bacteria, and seem to be restricted to plant pathogenic Acidovorax species. Transient expression in Nicotiana benthamiana revealed that two of these T3Es localize to the cell nucleus and one interacts with the endoplasmic reticulum. This study not only uncovered the arsenal of T3Es of an important pathogen, but it also places A. citrulli among the “richest” bacterial pathogens in terms of T3E cargo. It also revealed novel T3Es that appear to be involved in the pathoadaptive evolution of plant pathogenic Acidovorax species.Author summaryAcidovorax citrulli is a Gram-negative bacterium that causes bacterial fruit blotch (BFB) disease of cucurbits. This disease represents a serious threat to cucurbit crop production worldwide. Despite the agricultural importance of BFB, the knowledge about basic aspects of A. citrulli-plant interactions is rather limited. As many Gram-negative plant and animal pathogenic bacteria, A. citrulli employs a complex secretion system, named type III secretion system, to deliver protein virulence effectors into the host cells. In this work we aimed at uncovering the arsenal of type III-secreted effectors (T3Es) of this pathogen by combination of bioinformatics and experimental approaches. We found that this bacterium possesses at least 51 genes that are similar to T3E genes from other pathogenic bacteria. In addition, our study revealed seven novel T3Es that seem to occur only in A. citrulli strains and in other plant pathogenic Acidovorax species. We found that two of these T3Es localize to the plant cell nucleus while one partially interacts with the endoplasmic reticulum. Further characterization of the novel T3Es identified in this study may uncover new host targets of pathogen effectors and new mechanisms by which pathogenic bacteria manipulate their hosts.

  • Open Access English
    Authors: 
    Eyal Buks; Chunqing Deng; Jean-Luc F. X. Orgazzi; Martin Otto; Adrian Lupascu;
    Project: NSERC

    We study a system consisting of a superconducting flux qubit strongly coupled to a microwave cavity. The fundamental cavity mode is externally driven and the response is investigated in the weak nonlinear regime. We find that near the crossing point, at which the resonance frequencies of the cavity mode and qubit coincide, the sign of the Kerr coefficient changes, and consequently the type of nonlinear response changes from softening to hardening. Furthermore, the cavity response exhibits superharmonic resonances when the ratio between the qubit frequency and the cavity fundamental mode frequency is tuned close to an integer value. The nonlinear response is characterized by the method of intermodulation and both signal and idler gains are measured. The experimental results are compared with theoretical predictions and good qualitative agreement is obtained. The superharmonic resonances have potential for applications in quantum amplification and generation of entangled states of light.

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