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  • Open Access English
    Authors: 
    Adrián A. Davín; Eric Tannier; Tom A. Williams; Bastien Boussau; Daubin; Gergely J. Szöllősi;
    Publisher: Cold Spring Harbor Laboratory
    Project: EC | GENECLOCKS (714774)

    Biodiversity has always been predominantly microbial and the scarcity of fossils from bacteria, archaea and microbial eukaryotes has prevented a comprehensive dating of the tree of life. Here we show that patterns of lateral gene transfer deduced from the analysis of modern genomes encode a novel and abundant source of information about the temporal coexistence of lineages throughout the history of life. We use new phylogenetic methods to reconstruct the history of thousands of gene families and demonstrate that dates implied by gene transfers are consistent with estimates from relaxed molecular clocks in Bacteria, Archaea and Eukaryotes. An inspection of discrepancies between transfers and clocks and a comparison with mammal fossils show that gene transfer in microbes is potentially as informative for dating the tree of life as the geological record in macroorganisms.

  • Open Access
    Authors: 
    John Michael; Luke McEllin; Annalena Felber;
    Publisher: Elsevier BV
    Project: EC | Sense of Commitment (679092)

    A wealth of research in recent decades has investigated the effects of various forms of coordination upon prosocial attitudes and behavior. To structure and constrain this research, we provide a framework within which to distinguish and interrelate different hypotheses about the psychological mechanisms underpinning various prosocial effects of various forms of coordination. To this end, we introduce a set of definitions and distinctions that can be used to tease apart various forms of prosociality and coordination. We then identify a range of psychological mechanisms that may underpin the effects of coordination upon prosociality. We show that different hypotheses about the underlying psychological mechanisms motivate different predictions about the effects of various forms of coordination in different circumstances.

  • Open Access
    Authors: 
    Éva Rajnavölgyi; Renáta Laczik; Viktor Kun; Lajos Szente; Éva Fenyvesi;
    Publisher: Beilstein Institut
    Country: Hungary
    Project: EC | TORNADO (222720)

    The n−3 fatty acids are not produced by mammals, although they are essential for hormone synthesis and maintenance of cell membrane structure and integrity. They have recently been shown to inhibit inflammatory reactions and also emerged as potential treatment options for inflammatory diseases, such as rheumatoid arthritis, asthma and inflammatory bowel diseases. Dendritic cells (DC) play a central role in the regulation of both innate and adaptive immunity and upon inflammatory signals they produce various soluble factors among them cytokines and chemokines that act as inflammatory or regulatory mediators. In this study we monitored the effects of α-linoleic acid, eicosapentaenoic acid and docosahexaenoic acid solubilized in a dimethyl sulfoxide (DMSO)/ethanol 1:1 mixture or as complexed by randomly methylated α-cyclodextrin (RAMEA) on the inflammatory response of human monocyte-derived dendritic cells (moDC). The use of RAMEA for enhancing aqueous solubility of n−3 fatty acids has the unambiguous advantage over applying RAMEB (the β-cyclodextrin analog), since there is no interaction with cell membrane cholesterol. In vitro differentiated moDC were left untreated or were stimulated by bacterial lipopolysaccharide and polyinosinic:polycytidylic acid, mimicking bacterial and viral infections, respectively. The response of unstimulated and activated moDC to n−3 fatty acid treatment was tested by measuring the cell surface expression of CD1a used as a phenotypic and CD83 as an activation marker of inflammatory moDC differentiation and activation by using flow cytometry. Monocyte-derived DC activation was also monitored by the secretion level of the pro- and anti-inflammatory cytokines IL-1β, TNF-α, IL-6, IL-10 and IL-12, respectively. We found that RAMEA-complexed n−3 fatty acids reduced the expression of CD1a protein in both LPS and Poly(I:C) stimulated moDC significantly, but most efficiently by eicosapentaenic acid, while no significant change in the expression of CD83 protein was observed. The production of IL-6 by LPS-activated moDC was also reduced significantly when eicosapentaenic acid was added as a RAMEA complex as compared to its DMSO-solubilized form or to the other two n−3 fatty acids either complexed or not. Based on these results n−3 fatty acids solubilized by RAMEA provide with a new tool for optimizing the anti-inflammatory effects of n−3 fatty acids exerted on human moDC and mediated through the GP120 receptor without interfering with the cell membrane structure.

  • Open Access
    Authors: 
    Müller, Márta;
    Publisher: ELTE Germanistisches Institut
    Country: Hungary
    Project: EC | COLLMOT (227878)
  • Publication . Other literature type . Article . Research . Preprint . 2021
    Open Access English
    Authors: 
    Fruehwirth, Rudolf; Wulz, Claudia-Elisabeth; Melo da Costa, Eliza; Brandao Malbouisson, Helena; Tomei, Thiago; de Moraes Gregores, Eduardo; de Souza Lemos, Dener; Garcia Fuentes, Francisco Ignacio; Agram, Jean-Laurent; Brom, Jean-Marie; +279 more
    Publisher: Elsevier
    Countries: Italy, Germany, Belgium, Italy, Turkey, Croatia, United States, Spain, Turkey, Italy ...
    Project: EC | LHCTOPVLQ (752730), EC | INSIGHTS (765710), EC | AMVA4NewPhysics (675440)

    Measurements of the second Fourier harmonic coefficient (v2) of the azimuthal distributions of prompt and nonprompt D0 mesons produced in pp and pPb collisions are presented. Nonprompt D0 mesons come from beauty hadron decays. The data samples are collected by the CMS experiment at nucleon-nucleon center-of-mass energies of 13 and 8.16 TeV, respectively. In high multiplicity pp collisions, v2 signals for prompt charm hadrons are reported for the first time, and are found to be comparable to those for light-flavor hadron species over a transverse momentum (pT) range of 2–6 GeV. Compared at similar event multiplicities, the prompt D0 meson v2 values in pp and pPb collisions are similar in magnitude. The v2 values for open beauty hadrons are extracted for the first time via nonprompt D0 mesons in pPb collisions. For pT in the range of 2–5 GeV, the results suggest that v2 for nonprompt D0 mesons is smaller than that for prompt D0 mesons. These new measurements indicate a positive charm hadron v2 in pp collisions and suggest a mass dependence in v2 between charm and beauty hadrons in the pPb system. These results provide insights into the origin of heavy-flavor quark collectivity in small systems. Individuals have received support from the Marie-Curie program and the European Research Council and Horizon 2020 Grant, contract Nos. 675440, 752730, and 765710 (European Union); CERN; the Programa Estatal de Fomento de la Investigación Científica y Técnica de Excelencia María de Maeztu, grant MDM-2015-0509 and the Programa Severo Ochoa del Principado de Asturias. CMS Collaboration: et al. Funded by SCOAP3. Peer reviewed

  • Open Access
    Authors: 
    Teruel, María; Barturen, Guillermo; Martínez Bueno, Manuel; Castellini Pérez, Olivia; Barroso Gil, Miguel; Povedano, Elena; Kerick, Martin; Català Moll, Francesc; Makowska, Zuzanna; Buttgereit, Anne; +100 more
    Publisher: Springer Science and Business Media LLC
    Countries: Spain, Spain, Hungary
    Project: EC | NECESSITY (806975)

    Primary Sjögren’s syndrome (SS) is a systemic autoimmune disease characterized by lymphocytic infiltration and damage of exocrine salivary and lacrimal glands. The etiology of SS is complex with environmental triggers and genetic factors involved. By conducting an integrated multi-omics study, we confirmed a vast coordinated hypomethylation and overexpression effects in IFN-related genes, what is known as the IFN signature. Stratified and conditional analyses suggest a strong interaction between SS-associated HLA genetic variation and the presence of Anti-Ro/SSA autoantibodies in driving the IFN epigenetic signature and determining SS. We report a novel epigenetic signature characterized by increased DNA methylation levels in a large number of genes enriched in pathways such as collagen metabolism and extracellular matrix organization. We identified potential new genetic variants associated with SS that might mediate their risk by altering DNA methylation or gene expression patterns, as well as disease-interacting genetic variants that exhibit regulatory function only in the SS population. Our study sheds new light on the interaction between genetics, autoantibody profiles, DNA methylation and gene expression in SS, and contributes to elucidate the genetic architecture of gene regulation in an autoimmune population. Funding for the preparation of this manuscript has received support from the Innovative Medicines Initiative Joint Undertaking under grant agreement no 115,565, resources composed of the financial contribution from the European Union's Seventh Framework Program (FP7/2007-2013) and the EFPIA companies' in kind contribution. MT is supported by a Spanish grant from Health Department, Junta de Andalucia (PI/0017/2016) and through the Innovative Medicines Initiative 2 Joint Undertaking under grant agreement No 806975. This Joint Undertaking receives support from the European Union's Horizon 2020 research and innovation programme and EFPIA. EC-M was funded by the Postdoctoral Training Subprogramme Juan de la Cierva-Ministry of Economy and Competitiveness (FJCI_2014_20652). We thank Ralf Lesche for the production of RNASeq data and Marc Torres Ciuro for design support. Innovative Medicines Initiative Joint Undertaking from the European Union's Seventh Framework Program (FP7/2007-2013) 115,565 Innovative Medicines Initiative 2 Joint Undertaking 806975 European Union's Horizon 2020 research and innovation programme Postdoctoral Training Subprogramme Juan de la Cierva-Ministry of Economy and Competitiveness FJCI_2014_20652 Junta de Andalucia PI/0017/2016 EFPIA companies EFPIA

  • Publication . Article . Preprint . 2019
    Open Access English
    Authors: 
    Itai Benjamini; Ádám Timár;
    Project: EC | NOISE (772466)

    Consider an ergodic unimodular random one-ended planar graph $\G$ of finite expected degree. We prove that it has an isometry-invariant locally finite embedding in the Euclidean plane if and only if it is invariantly amenable. By "locally finite" we mean that any bounded open set intersects finitely many embedded edges. In particular, there exist invariant embeddings in the Euclidean plane for the Uniform Infinite Planar Triangulation and for the critical Augmented Galton-Watson Tree conditioned to survive. Roughly speaking, a unimodular embedding of $\G$ is one that is jointly unimodular with $\G$ when viewed as a decoration. We show that $\G$ has a unimodular embedding in the hyperbolic plane if it is invariantly nonamenable, and it has a unimodular embedding in the Euclidean plane if and only if it is invariantly amenable. Similar claims hold for representations by tilings instead of embeddings. 24 pages, 4 figures

  • Open Access English
    Authors: 
    Fergus J. Couch; Kyriaki Michailidou; Gustavo Mendoza-Fandiño; Janna Lilyquist; Emily Hallberg; Simona Agata; Christine B. Ambrosone; Irene L. Andrulis; Hoda Anton-Culver; Volker Arndt; +194 more
    Publisher: Uppsala universitet, Institutionen för immunologi, genetik och patologi
    Countries: Norway, Spain, Finland, China (People's Republic of), United Kingdom, United States, United Kingdom, Denmark, Spain, United Kingdom ...
    Project: NWO | Secure and gentle grip of... (11477), WT , NIH | Discovery Expansion and R... (5U19CA148065-04), NIH | Follow-up of Ovarian Canc... (3U19CA148112-04S1), EC | COGS (223175), CIHR , NIH | A genome-wide association... (5R01CA128978-02), NIH | Elucidating Loci Involved... (5U19CA148537-02)

    Common variants in 94 loci have been associated with breast cancer including 15 loci with genome-wide significant associations (P<5 × 10(-8)) with oestrogen receptor (ER)-negative breast cancer and BRCA1-associated breast cancer risk. In this study, to identify new ER-negative susceptibility loci, we performed a meta-analysis of 11 genome-wide association studies (GWAS) consisting of 4,939 ER-negative cases and 14,352 controls, combined with 7,333 ER-negative cases and 42,468 controls and 15,252 BRCA1 mutation carriers genotyped on the iCOGS array. We identify four previously unidentified loci including two loci at 13q22 near KLF5, a 2p23.2 locus near WDR43 and a 2q33 locus near PPIL3 that display genome-wide significant associations with ER-negative breast cancer. In addition, 19 known breast cancer risk loci have genome-wide significant associations and 40 had moderate associations (P<0.05) with ER-negative disease. Using functional and eQTL studies we implicate TRMT61B and WDR43 at 2p23.2 and PPIL3 at 2q33 in ER-negative breast cancer aetiology. All ER-negative loci combined account for ∼11% of familial relative risk for ER-negative disease and may contribute to improved ER-negative and BRCA1 breast cancer risk prediction. B.C.A.C. was funded through a European Community Seventh Framework Programme under grant agreement no 223175 (HEALTH-F2-2009-223175; COGS); Cancer Research UK (C1287/A10118, C1287/A10710, C12292/A11174, C1281/A12014, C5047/A8384, C5047/A15007, C5047/A10692); the National Institutes of Health Specialized Program of Research Excellence (SPORE) in Breast Cancer (CA116201), R01 grants (CA128978, CA176785, CA192393), and Post-Cancer GWAS initiative (1U19 CA148537, 1U19 CA148065 and 1U19 CA148112 - the GAME-ON initiative); the Canadian Institutes of Health Research (CIHR) for the CIHR Team in Familial Risks of Breast Cancer, the Breast Cancer Res. Foundation, and the Ovarian Cancer Research Fund. CIMBA genotyping was supported by National Institutes of Health grant (CA128978); the Department of Defence (W81XWH-10-1-0341); and the Breast Cancer Res. Foundation. CIMBA data management and data analysis were supported by Cancer Research UK grants C12292/A11174 and C1287/A10118. This is the final version of the article. It first appeared from Nature Publishing Group via http://dx.doi.org/10.1038/ncomms11375

  • Open Access English
    Authors: 
    Fragione, Giacomo; Ginsburg, Idan; Bence Kocsis;
    Publisher: Zenodo
    Project: EC | GalNUC (638435)

    The recent discovery of gravitational waves has opened new horizons for physics. Current and upcoming missions, such as LIGO, VIRGO, KAGRA, and LISA, promise to shed light on black holes of every size from stellar mass (SBH) sizes up to supermassive black holes which reside in galactic nuclei. The intermediate mass black hole (IMBH) family has not been detected beyond any reasonable doubt neither directly nor indirectly. Recent analyses suggest observational evidence for the presence of IMBHs in the centers of two Galactic globular clusters. In this paper, we investigate the possibility that globular clusters were born with a central IMBH, which undergo repeated merger events with SBHs in the cluster core. By means of a semi-analytical method, we follow the evolution of the primordial cluster population in the galactic potential and the Gravitational Wave (GW) mergers of the binary IMBH-SBH systems. Our models predict ≈1000 IMBHs within 1 kpc from the Galactic Center. Our results show that the IMBH-SBH merger rate density changes from \(\mathcal{R} \approx 1000\,\mathrm{Gpc}^{-3}\mathrm{yr}^{-1}\) beyond \(z\approx 2\) to \(\mathcal{R} \approx 1-10\,\mathrm{Gpc}^{-3}\mathrm{yr}^{-1}\) at \(z\approx 0\). The rates at low redshifts may be significantly higher if young massive star clusters host IMBHs. The merger rates are dominated by IMBHs with masses between \(10^3-10^4\,\mathrm{M}_{\odot}\). Currently there are no LIGO/VIRGO upper limits for GW sources in this mass range, but our results show that at design sensitivity these instruments may detect these IMBH-SBH mergers in the coming years. LISA and the Einstein Telescope will be best suited to detect these GW events. The inspirals of IMBH-SBH systems may also generate an unresolved GW background.

  • Open Access English
    Authors: 
    Péter Bálint; Ian Melbourne;
    Publisher: Springer New York LLC
    Country: United Kingdom
    Project: EC | STOCHEXTHOMOG (320977)

    For geometric Lorenz attractors (including the classical Lorenz attractor) we obtain a greatly simplified proof of the central limit theorem which applies also to the more general class of codimension two singular hyperbolic attractors. We also obtain the functional central limit theorem and moment estimates, as well as iterated versions of these results. A consequence is deterministic homogenisation (convergence to a stochastic differential equation) for fast-slow dynamical systems whenever the fast dynamics is singularly hyperbolic of codimension two. Comment: Minor corrections. Published online in J. Stat. Phys

Advanced search in
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6,139 Research products, page 1 of 614
  • Open Access English
    Authors: 
    Adrián A. Davín; Eric Tannier; Tom A. Williams; Bastien Boussau; Daubin; Gergely J. Szöllősi;
    Publisher: Cold Spring Harbor Laboratory
    Project: EC | GENECLOCKS (714774)

    Biodiversity has always been predominantly microbial and the scarcity of fossils from bacteria, archaea and microbial eukaryotes has prevented a comprehensive dating of the tree of life. Here we show that patterns of lateral gene transfer deduced from the analysis of modern genomes encode a novel and abundant source of information about the temporal coexistence of lineages throughout the history of life. We use new phylogenetic methods to reconstruct the history of thousands of gene families and demonstrate that dates implied by gene transfers are consistent with estimates from relaxed molecular clocks in Bacteria, Archaea and Eukaryotes. An inspection of discrepancies between transfers and clocks and a comparison with mammal fossils show that gene transfer in microbes is potentially as informative for dating the tree of life as the geological record in macroorganisms.

  • Open Access
    Authors: 
    John Michael; Luke McEllin; Annalena Felber;
    Publisher: Elsevier BV
    Project: EC | Sense of Commitment (679092)

    A wealth of research in recent decades has investigated the effects of various forms of coordination upon prosocial attitudes and behavior. To structure and constrain this research, we provide a framework within which to distinguish and interrelate different hypotheses about the psychological mechanisms underpinning various prosocial effects of various forms of coordination. To this end, we introduce a set of definitions and distinctions that can be used to tease apart various forms of prosociality and coordination. We then identify a range of psychological mechanisms that may underpin the effects of coordination upon prosociality. We show that different hypotheses about the underlying psychological mechanisms motivate different predictions about the effects of various forms of coordination in different circumstances.

  • Open Access
    Authors: 
    Éva Rajnavölgyi; Renáta Laczik; Viktor Kun; Lajos Szente; Éva Fenyvesi;
    Publisher: Beilstein Institut
    Country: Hungary
    Project: EC | TORNADO (222720)

    The n−3 fatty acids are not produced by mammals, although they are essential for hormone synthesis and maintenance of cell membrane structure and integrity. They have recently been shown to inhibit inflammatory reactions and also emerged as potential treatment options for inflammatory diseases, such as rheumatoid arthritis, asthma and inflammatory bowel diseases. Dendritic cells (DC) play a central role in the regulation of both innate and adaptive immunity and upon inflammatory signals they produce various soluble factors among them cytokines and chemokines that act as inflammatory or regulatory mediators. In this study we monitored the effects of α-linoleic acid, eicosapentaenoic acid and docosahexaenoic acid solubilized in a dimethyl sulfoxide (DMSO)/ethanol 1:1 mixture or as complexed by randomly methylated α-cyclodextrin (RAMEA) on the inflammatory response of human monocyte-derived dendritic cells (moDC). The use of RAMEA for enhancing aqueous solubility of n−3 fatty acids has the unambiguous advantage over applying RAMEB (the β-cyclodextrin analog), since there is no interaction with cell membrane cholesterol. In vitro differentiated moDC were left untreated or were stimulated by bacterial lipopolysaccharide and polyinosinic:polycytidylic acid, mimicking bacterial and viral infections, respectively. The response of unstimulated and activated moDC to n−3 fatty acid treatment was tested by measuring the cell surface expression of CD1a used as a phenotypic and CD83 as an activation marker of inflammatory moDC differentiation and activation by using flow cytometry. Monocyte-derived DC activation was also monitored by the secretion level of the pro- and anti-inflammatory cytokines IL-1β, TNF-α, IL-6, IL-10 and IL-12, respectively. We found that RAMEA-complexed n−3 fatty acids reduced the expression of CD1a protein in both LPS and Poly(I:C) stimulated moDC significantly, but most efficiently by eicosapentaenic acid, while no significant change in the expression of CD83 protein was observed. The production of IL-6 by LPS-activated moDC was also reduced significantly when eicosapentaenic acid was added as a RAMEA complex as compared to its DMSO-solubilized form or to the other two n−3 fatty acids either complexed or not. Based on these results n−3 fatty acids solubilized by RAMEA provide with a new tool for optimizing the anti-inflammatory effects of n−3 fatty acids exerted on human moDC and mediated through the GP120 receptor without interfering with the cell membrane structure.

  • Open Access
    Authors: 
    Müller, Márta;
    Publisher: ELTE Germanistisches Institut
    Country: Hungary
    Project: EC | COLLMOT (227878)
  • Publication . Other literature type . Article . Research . Preprint . 2021
    Open Access English
    Authors: 
    Fruehwirth, Rudolf; Wulz, Claudia-Elisabeth; Melo da Costa, Eliza; Brandao Malbouisson, Helena; Tomei, Thiago; de Moraes Gregores, Eduardo; de Souza Lemos, Dener; Garcia Fuentes, Francisco Ignacio; Agram, Jean-Laurent; Brom, Jean-Marie; +279 more
    Publisher: Elsevier
    Countries: Italy, Germany, Belgium, Italy, Turkey, Croatia, United States, Spain, Turkey, Italy ...
    Project: EC | LHCTOPVLQ (752730), EC | INSIGHTS (765710), EC | AMVA4NewPhysics (675440)

    Measurements of the second Fourier harmonic coefficient (v2) of the azimuthal distributions of prompt and nonprompt D0 mesons produced in pp and pPb collisions are presented. Nonprompt D0 mesons come from beauty hadron decays. The data samples are collected by the CMS experiment at nucleon-nucleon center-of-mass energies of 13 and 8.16 TeV, respectively. In high multiplicity pp collisions, v2 signals for prompt charm hadrons are reported for the first time, and are found to be comparable to those for light-flavor hadron species over a transverse momentum (pT) range of 2–6 GeV. Compared at similar event multiplicities, the prompt D0 meson v2 values in pp and pPb collisions are similar in magnitude. The v2 values for open beauty hadrons are extracted for the first time via nonprompt D0 mesons in pPb collisions. For pT in the range of 2–5 GeV, the results suggest that v2 for nonprompt D0 mesons is smaller than that for prompt D0 mesons. These new measurements indicate a positive charm hadron v2 in pp collisions and suggest a mass dependence in v2 between charm and beauty hadrons in the pPb system. These results provide insights into the origin of heavy-flavor quark collectivity in small systems. Individuals have received support from the Marie-Curie program and the European Research Council and Horizon 2020 Grant, contract Nos. 675440, 752730, and 765710 (European Union); CERN; the Programa Estatal de Fomento de la Investigación Científica y Técnica de Excelencia María de Maeztu, grant MDM-2015-0509 and the Programa Severo Ochoa del Principado de Asturias. CMS Collaboration: et al. Funded by SCOAP3. Peer reviewed

  • Open Access
    Authors: 
    Teruel, María; Barturen, Guillermo; Martínez Bueno, Manuel; Castellini Pérez, Olivia; Barroso Gil, Miguel; Povedano, Elena; Kerick, Martin; Català Moll, Francesc; Makowska, Zuzanna; Buttgereit, Anne; +100 more
    Publisher: Springer Science and Business Media LLC
    Countries: Spain, Spain, Hungary
    Project: EC | NECESSITY (806975)

    Primary Sjögren’s syndrome (SS) is a systemic autoimmune disease characterized by lymphocytic infiltration and damage of exocrine salivary and lacrimal glands. The etiology of SS is complex with environmental triggers and genetic factors involved. By conducting an integrated multi-omics study, we confirmed a vast coordinated hypomethylation and overexpression effects in IFN-related genes, what is known as the IFN signature. Stratified and conditional analyses suggest a strong interaction between SS-associated HLA genetic variation and the presence of Anti-Ro/SSA autoantibodies in driving the IFN epigenetic signature and determining SS. We report a novel epigenetic signature characterized by increased DNA methylation levels in a large number of genes enriched in pathways such as collagen metabolism and extracellular matrix organization. We identified potential new genetic variants associated with SS that might mediate their risk by altering DNA methylation or gene expression patterns, as well as disease-interacting genetic variants that exhibit regulatory function only in the SS population. Our study sheds new light on the interaction between genetics, autoantibody profiles, DNA methylation and gene expression in SS, and contributes to elucidate the genetic architecture of gene regulation in an autoimmune population. Funding for the preparation of this manuscript has received support from the Innovative Medicines Initiative Joint Undertaking under grant agreement no 115,565, resources composed of the financial contribution from the European Union's Seventh Framework Program (FP7/2007-2013) and the EFPIA companies' in kind contribution. MT is supported by a Spanish grant from Health Department, Junta de Andalucia (PI/0017/2016) and through the Innovative Medicines Initiative 2 Joint Undertaking under grant agreement No 806975. This Joint Undertaking receives support from the European Union's Horizon 2020 research and innovation programme and EFPIA. EC-M was funded by the Postdoctoral Training Subprogramme Juan de la Cierva-Ministry of Economy and Competitiveness (FJCI_2014_20652). We thank Ralf Lesche for the production of RNASeq data and Marc Torres Ciuro for design support. Innovative Medicines Initiative Joint Undertaking from the European Union's Seventh Framework Program (FP7/2007-2013) 115,565 Innovative Medicines Initiative 2 Joint Undertaking 806975 European Union's Horizon 2020 research and innovation programme Postdoctoral Training Subprogramme Juan de la Cierva-Ministry of Economy and Competitiveness FJCI_2014_20652 Junta de Andalucia PI/0017/2016 EFPIA companies EFPIA

  • Publication . Article . Preprint . 2019
    Open Access English
    Authors: 
    Itai Benjamini; Ádám Timár;
    Project: EC | NOISE (772466)

    Consider an ergodic unimodular random one-ended planar graph $\G$ of finite expected degree. We prove that it has an isometry-invariant locally finite embedding in the Euclidean plane if and only if it is invariantly amenable. By "locally finite" we mean that any bounded open set intersects finitely many embedded edges. In particular, there exist invariant embeddings in the Euclidean plane for the Uniform Infinite Planar Triangulation and for the critical Augmented Galton-Watson Tree conditioned to survive. Roughly speaking, a unimodular embedding of $\G$ is one that is jointly unimodular with $\G$ when viewed as a decoration. We show that $\G$ has a unimodular embedding in the hyperbolic plane if it is invariantly nonamenable, and it has a unimodular embedding in the Euclidean plane if and only if it is invariantly amenable. Similar claims hold for representations by tilings instead of embeddings. 24 pages, 4 figures

  • Open Access English
    Authors: 
    Fergus J. Couch; Kyriaki Michailidou; Gustavo Mendoza-Fandiño; Janna Lilyquist; Emily Hallberg; Simona Agata; Christine B. Ambrosone; Irene L. Andrulis; Hoda Anton-Culver; Volker Arndt; +194 more
    Publisher: Uppsala universitet, Institutionen för immunologi, genetik och patologi
    Countries: Norway, Spain, Finland, China (People's Republic of), United Kingdom, United States, United Kingdom, Denmark, Spain, United Kingdom ...
    Project: NWO | Secure and gentle grip of... (11477), WT , NIH | Discovery Expansion and R... (5U19CA148065-04), NIH | Follow-up of Ovarian Canc... (3U19CA148112-04S1), EC | COGS (223175), CIHR , NIH | A genome-wide association... (5R01CA128978-02), NIH | Elucidating Loci Involved... (5U19CA148537-02)

    Common variants in 94 loci have been associated with breast cancer including 15 loci with genome-wide significant associations (P<5 × 10(-8)) with oestrogen receptor (ER)-negative breast cancer and BRCA1-associated breast cancer risk. In this study, to identify new ER-negative susceptibility loci, we performed a meta-analysis of 11 genome-wide association studies (GWAS) consisting of 4,939 ER-negative cases and 14,352 controls, combined with 7,333 ER-negative cases and 42,468 controls and 15,252 BRCA1 mutation carriers genotyped on the iCOGS array. We identify four previously unidentified loci including two loci at 13q22 near KLF5, a 2p23.2 locus near WDR43 and a 2q33 locus near PPIL3 that display genome-wide significant associations with ER-negative breast cancer. In addition, 19 known breast cancer risk loci have genome-wide significant associations and 40 had moderate associations (P<0.05) with ER-negative disease. Using functional and eQTL studies we implicate TRMT61B and WDR43 at 2p23.2 and PPIL3 at 2q33 in ER-negative breast cancer aetiology. All ER-negative loci combined account for ∼11% of familial relative risk for ER-negative disease and may contribute to improved ER-negative and BRCA1 breast cancer risk prediction. B.C.A.C. was funded through a European Community Seventh Framework Programme under grant agreement no 223175 (HEALTH-F2-2009-223175; COGS); Cancer Research UK (C1287/A10118, C1287/A10710, C12292/A11174, C1281/A12014, C5047/A8384, C5047/A15007, C5047/A10692); the National Institutes of Health Specialized Program of Research Excellence (SPORE) in Breast Cancer (CA116201), R01 grants (CA128978, CA176785, CA192393), and Post-Cancer GWAS initiative (1U19 CA148537, 1U19 CA148065 and 1U19 CA148112 - the GAME-ON initiative); the Canadian Institutes of Health Research (CIHR) for the CIHR Team in Familial Risks of Breast Cancer, the Breast Cancer Res. Foundation, and the Ovarian Cancer Research Fund. CIMBA genotyping was supported by National Institutes of Health grant (CA128978); the Department of Defence (W81XWH-10-1-0341); and the Breast Cancer Res. Foundation. CIMBA data management and data analysis were supported by Cancer Research UK grants C12292/A11174 and C1287/A10118. This is the final version of the article. It first appeared from Nature Publishing Group via http://dx.doi.org/10.1038/ncomms11375

  • Open Access English
    Authors: 
    Fragione, Giacomo; Ginsburg, Idan; Bence Kocsis;
    Publisher: Zenodo
    Project: EC | GalNUC (638435)

    The recent discovery of gravitational waves has opened new horizons for physics. Current and upcoming missions, such as LIGO, VIRGO, KAGRA, and LISA, promise to shed light on black holes of every size from stellar mass (SBH) sizes up to supermassive black holes which reside in galactic nuclei. The intermediate mass black hole (IMBH) family has not been detected beyond any reasonable doubt neither directly nor indirectly. Recent analyses suggest observational evidence for the presence of IMBHs in the centers of two Galactic globular clusters. In this paper, we investigate the possibility that globular clusters were born with a central IMBH, which undergo repeated merger events with SBHs in the cluster core. By means of a semi-analytical method, we follow the evolution of the primordial cluster population in the galactic potential and the Gravitational Wave (GW) mergers of the binary IMBH-SBH systems. Our models predict ≈1000 IMBHs within 1 kpc from the Galactic Center. Our results show that the IMBH-SBH merger rate density changes from \(\mathcal{R} \approx 1000\,\mathrm{Gpc}^{-3}\mathrm{yr}^{-1}\) beyond \(z\approx 2\) to \(\mathcal{R} \approx 1-10\,\mathrm{Gpc}^{-3}\mathrm{yr}^{-1}\) at \(z\approx 0\). The rates at low redshifts may be significantly higher if young massive star clusters host IMBHs. The merger rates are dominated by IMBHs with masses between \(10^3-10^4\,\mathrm{M}_{\odot}\). Currently there are no LIGO/VIRGO upper limits for GW sources in this mass range, but our results show that at design sensitivity these instruments may detect these IMBH-SBH mergers in the coming years. LISA and the Einstein Telescope will be best suited to detect these GW events. The inspirals of IMBH-SBH systems may also generate an unresolved GW background.

  • Open Access English
    Authors: 
    Péter Bálint; Ian Melbourne;
    Publisher: Springer New York LLC
    Country: United Kingdom
    Project: EC | STOCHEXTHOMOG (320977)

    For geometric Lorenz attractors (including the classical Lorenz attractor) we obtain a greatly simplified proof of the central limit theorem which applies also to the more general class of codimension two singular hyperbolic attractors. We also obtain the functional central limit theorem and moment estimates, as well as iterated versions of these results. A consequence is deterministic homogenisation (convergence to a stochastic differential equation) for fast-slow dynamical systems whenever the fast dynamics is singularly hyperbolic of codimension two. Comment: Minor corrections. Published online in J. Stat. Phys

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