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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.

  • Open Access English
    Authors: 
    M. Adinolfi; A. Aloisio; F. Ambrosino; A. Andryakov; A. Antonelli; M. Antonelli; F. Anulli; C. Bacci; A. Bankamp; G. Barbiellini; +132 more
    Country: Italy

    Abstract The main aim of the KLOE experiment at DAΦNE, the Frascati φ-factory, is to study CP violation in the K0– K 0 system. Requirements on shower detection are very stringent. An hermetic, lead-scintillating fiber sampling calorimeter has been chosen and built. A review of the methods used to calibrate and reconstruct energy and timing is reported in this paper. Emphasis is given to the calibration procedures developed using the 2.4 pb−1 collected in 1999. An energy resolution of 5.7%/ E/ GeV is achieved together with a linearity in energy response better than 1% above 50 MeV. A time resolution of ∼54 ps / E/ GeV is also measured on samples of radiative Bhabha and Φ decays.

  • Open Access English
    Authors: 
    Amit Tirosh; Electron Kebebew;
    Publisher: Future Medicine Ltd

    Neuroendocrine tumors (NETs) are rare neoplasms that emerge mainly from the GI tract, pancreas and respiratory tract. The incidence of NETs has increased more than sixfold in the last decades. NETs typically express somatostatin receptors on their cell surface, which can be targeted by ‘cold’ somatostatin analogs for therapy or by ‘hot’ radiolabeled somatostatin analogs for tumor localization and treatment. 68-Gallium-DOTA peptides (DOTATATE, DOTATOC, DOTANOC) positron emission tomography/computed tomography is a highly accurate imaging modality for NETs that has been found to be more sensitive for NET detection than other imaging modalities. In the current review, we will discuss the clinical utility of 68-Gallium-DOTATATE positron emission tomography/computed tomography for the diagnosis and management of patients with NETs.

  • 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

  • Closed Access English
    Authors: 
    Luke F. Gockowski; Neil D. Dolinski; Roberto Chavez; Noy Cohen; Fabian Eisenreich; Stefan Hecht; Robert M. McMeeking; Craig J. Hawker; Megan T. Valentine;
    Country: Netherlands

    Multimaterial additive manufacturing is an enabling tool for exploring difficult to access structure-property relationships. In this work, a recently developed multimaterial printing approach, solution mask liquid lithography, is used to produce porous polymer-polymer composites inspired by tough, hierarchical structures found in nature. The results demonstrate that varying the size and packing of pores in the core structure leads to significant enhancement in crack deflection. Finite element analysis reveals that this enhancement is linked to geometry-dependent stress distribution.

  • Open Access English
    Authors: 
    Omid Amini; David Peleg; Stéphane Pérennes; Ignasi Sau; Saket Saurabh;
    Publisher: HAL CCSD
    Country: France

    International audience; In this article we provide hardness results and approximation algorithms for the following three natural degree-constrained subgraph problems, which take as input an undirected graph G=(V,E). Let d>=2 be a fixed integer. The Maximumd-degree-bounded Connected Subgraph (MDBCS"d) problem takes as additional input a weight function @w:E->R^+, and asks for a subset E^'@?E such that the subgraph induced by E^' is connected, has maximum degree at most d, and @?"e"@?"E"^"'@w(e) is maximized. The Minimum Subgraph of Minimum Degree>=d (MSMD"d) problem involves finding a smallest subgraph of G with minimum degree at least d. Finally, the Dual Degree-densek-Subgraph (DDDkS) problem consists in finding a subgraph H of G such that |V(H)|@?k and the minimum degree in H is maximized.

  • 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: 
    David Kimhy; Susan Harlap; Shmuel Fennig; L. Deutsch; Benjamin Draiman; Cheryl Corcoran; Deborah Goetz; Daniella Nahon; Dolores Malaspina;

    Background Animal models of schizophrenia suggest a link between maternal crowding during pregnancy and increased risk of the offspring to develop physiological, developmental, and behavioral abnormalities that are comparable to those observed in schizophrenia. We tested the hypothesis that a similar link is present in humans.

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