Estimation de diversité à grande échelle par inférence de l'origine des noms de famille

International audienceThe study of surnames as both linguistic and geographical markers of the past has proven valuable in several research fields spanning from biology and genetics to demography and social mobility. This article builds upon the existing literature to conceive and develop a surname origin classifier based on a data-driven typology. This enables us to explore a methodology to describe large-scale estimates of the relative diversity of social groups, especially when such data is scarcely available. We subsequently analyze the representativeness of surname origins for 15 socio-professional groups in France.L’étude des noms de famille comme marqueurs linguistique et géographique du passé s’est avérée pertinente dans des contextes variés allant de la biologie et la génétique, à la démographie et la mobilité sociale. Cet article construit à partir d’éléments de la littérature existante un classifieur des origines des noms de famille basé sur une typologie issue des données. Cela nous permet d’explorer une méthodologie pour estimer à grande échelle la diversité relative des groupes sociaux, en particulier lorsque de telles données sont difficilement accessibles. Enfin, nous analysons la représentativité des origines de noms de famille de 15 groupes socio-professionnels en France

Assessing the macroeconomic impact of Brexit through trade and migration channels

Este trabajo conjunto de Bundesbank, Banque de France y Banco de España analiza en detalle algunos de los numerosos canales a través de los cuales el brexit afectará a la economía del Reino Unido y a la de sus socios comerciales. En particular, se centra en los canales comercial y migratorio, haciendo una evaluación más general de los costes de la salida de la UE utilizando un modelo de gravedad. El canal comercial por sí solo puede reducir el PIB del Reino Unido un 2 % a medio plazo si el Reino Unido vuelve a las reglas de la OMC, mientras que un modelo de gravedad más general apuntaría a que el PIB del Reino Unido se reduciría casi un 6 % en comparación con el escenario de no salida. Por lo tanto, de acuerdo con nuestro análisis, el «coste de estar fuera de Europa» (como se estableció originalmente en el trabajo seminal de Cecchini en 1988) se encuentra entre el 2 % y el 6 % en términos de pérdidas del PIB real para el Reino Unido. Este impacto es en gran medida asimétrico, ya que el PIB de la zona del euro no se ve prácticamente afectado por este evento, al situarse menos de un 1 % por debajo del escenario de no salida en 2023. El estudio también pone de manifiesto cómo los resultados son sensibles a la reacción de las políticas económicas. En general, las políticas monetarias y fiscales pueden actuar para amortiguar el shock del brexitsin embargo, su efectividad depende de la fuente subyacente de la perturbaciónThis joint work by the Bundesbank, the Banque de France and the Banco de España highlights some of the numerous channels through which Brexit will affect the UK economy and its economic partners. In particular, it focuses on trade and migration channels, adding a more general assessment of exiting the EU through the use of a gravity model. The trade channel alone may cut UK GDP by 2% over the medium term if the UK reverts to WTO rules, while a more general gravity model would point to UK GDP falling by almost 6% compared to baseline. According to our analysis, the ‘cost of non-Europe’ (such as originally stated by Cecchini’s seminal work in 1988) lies therefore between 2% and 6% in terms of real GDP losses for the UK. With the shock being largely asymmetric, the EA remains relatively unscathed by the UK’s exit, with GDP less than 1% lower than baseline by 2023. The study also shows that results are sensitive to the envisaged policy response. In general, monetary and fiscal policies may act to cushion a Brexit-related shockhowever, the potency of the policy response depends on the underlying source of the shoc

Best Available Techniques (BAT) Reference Document for Waste treatment Industrial Emissions Directive 2010/75/EU (Integrated Pollution Prevention and Control)

The Best Available Techniques (BAT) Reference Document for Waste Treatment is the result of the information exchange since the kick-off meeting which was held from 25 to 28 November 2013. The information collection took place in 2014 and 2015 and the final meeting took place in March 2017. The document includes information on the following waste treatment processes: - Mechanical treatment in shredders of metal waste - Mechanical treatment of VFCs and VHCs containing equipment - Mechanical treatment of waste with calorific value - Aerobic treatment of waste - Anaerobic treatment of waste - Mechanical-Biological treatment of waste (MBT) - Physico-chemical treatment of solid and pasty waste - Re-refining of waste oil - Physico-chemical treatment of waste with calorific value - Regeneration of spent solvents - Physico-chemical and/or biological treatment of water-based liquid waste - Regeneration / recovery of pollution abatement components / Flue-Gas Treatment (FGT) of waste - Recovery of components from spent catalysts - Treatment of excavated contaminated soil - Treatment of POPs-containing waste - Treatment of mercury-containing wasteJRC.B.5-Circular Economy and Industrial Leadershi

Mechanism of membrane fusion induced by vesicular stomatitis virus G protein

The glycoproteins (G proteins) of vesicular stomatitis virus (VSV) and related rhabdoviruses (e.g., rabies virus) mediate both cell attachment and membrane fusion. The reversibility of their fusogenic conformational transitions differentiates them from many other low-pH-induced viral fusion proteins. We report single-virion fusion experiments, using methods developed in previous publications to probe fusion of influenza and West Nile viruses. We show that a three-stage model fits VSV single-particle fusion kinetics: (i) reversible, pH-dependent, G-protein conformational change from the known prefusion conformation to an extended, monomeric intermediate; (ii) reversible trimerization and clustering of the G-protein fusion loops, leading to an extended intermediate that inserts the fusion loops into the target-cell membrane; and (iii) folding back of a cluster of extended trimers into their postfusion conformations, bringing together the viral and cellular membranes. From simulations of the kinetic data, we conclude that the critical number of G-protein trimers required to overcome membrane resistance is 3 to 5, within a contact zone between the virus and the target membrane of 30 to 50 trimers. This sequence of conformational events is similar to those shown to describe fusion by influenza virus hemagglutinin (a “class I” fusogen) and West Nile virus envelope protein (“class II”). Our study of VSV now extends this description to “class III” viral fusion proteins, showing that reversibility of the low-pH-induced transition and architectural differences in the fusion proteins themselves do not change the basic mechanism by which they catalyze membrane fusion

DAMP Signaling is a Key Pathway Inducing Immune Modulation after Brain Injury

Acute brain lesions induce profound alterations of the peripheral immune response comprising the opposing phenomena of early immune activation and subsequent immunosuppression. The mechanisms underlying this brain-immune signaling are largely unknown. We used animal models for experimental brain ischemia as a paradigm of acute brain lesions and additionally investigated a large cohort of stroke patients. We investigated the inflammatory potency of HMGB1 and its signaling pathways by immunological in vivo and in vitro techniques. Features of the complex behavioral sickness behavior syndrome were characterized by homecage behavior analysis. HMGB1 downstream signaling, particularly with RAGE, was studied in various transgenic animal models and by pharmacological blockade. Our results indicate that HMGB1 was released from the ischemic brain in the hyperacute phase of stroke in mice and patients. Cytokines secreted in the periphery in response to brain injury induced sickness behavior, which could be abrogated by inhibition of the HMGB1-RAGE pathway or direct cytokine neutralization. Subsequently, HMGB1-release induced bone marrow egress and splenic proliferation of bone marrow-derived suppressor cells, inhibiting the adaptive immune responses in vivo and vitro. Furthermore, HMGB1-RAGE signaling resulted in functional exhaustion of mature monocytes and lymphopenia, the hallmarks of immune suppression after extensive ischemia. This study introduces the HMGB1-RAGE-mediated pathway as a key mechanism explaining the complex postischemic brain-immune interactions

MD-2 is required for disulfide HMGB1-dependent TLR4 signaling

Innate immune receptors for pathogen- and damage-associated molecular patterns (PAMPs and DAMPs) orchestrate inflammatory responses to infection and injury. Secreted by activated immune cells or passively released by damaged cells, HMGB1 is subjected to redox modification that distinctly influences its extracellular functions. Previously, it was unknown how the TLR4 signalosome distinguished between HMGB1 isoforms. Here we demonstrate that the extracellular TLR4 adaptor, myeloid differentiation factor 2 (MD-2), binds specifically to the cytokine-inducing disulfide isoform of HMGB1, to the exclusion of other isoforms. Using MD-2–deficient mice, as well as MD-2 silencing in macrophages, we show a requirement for HMGB1-dependent TLR4 signaling. By screening HMGB1 peptide libraries, we identified a tetramer (FSSE, designated P5779) as a specific MD-2 antagonist preventing MD-2–HMGB1 interaction and TLR4 signaling. P5779 does not interfere with lipopolysaccharide-induced cytokine/chemokine production, thus preserving PAMP-mediated TLR4–MD-2 responses. Furthermore, P5779 can protect mice against hepatic ischemia/reperfusion injury, chemical toxicity, and sepsis. These findings reveal a novel mechanism by which innate systems selectively recognize specific HMGB1 isoforms. The results may direct toward strategies aimed at attenuating DAMP-mediated inflammation while preserving antimicrobial immune responsiveness

Identification of CD163 as an antiinflammatory receptor for HMGB1-haptoglobin complexes

Secreted by activated cells or passively released by damaged cells, extracellular HMGB1 is a prototypical damage-associated molecular pattern (DAMP) inflammatory mediator. During the course of developing extracorporeal approaches to treating injury and infection, we inadvertently discovered that haptoglobin, the acute phase protein that binds extracellular hemoglobin and targets cellular uptake through CD163, also binds HMGB1. Haptoglobin-HMGB1 complexes elicit the production of antiinflammatory enzymes (heme oxygenase-1) and cytokines (e.g., IL-10) in WT but not in CD163-deficient macrophages. Genetic disruption of haptoglobin or CD163 expression significantly enhances mortality rates in standardized models of intra-abdominal sepsis in mice. Administration of haptoglobin to WT and to haptoglobin gene-deficient animals confers significant protection. These findings reveal a mechanism for haptoglobin modulation of the inflammatory action of HMGB1, with significant implications for developing experimental strategies targeting HMGB1-dependent inflammatory diseases

Novel role of PKR in inflammasome activation and HMGB1 release

The inflammasome regulates release of caspase activation-dependent cytokines, including IL-1β, IL-18, and high-mobility group box 1 (HMGB1)1-5. During the course of studying HMGB1 release mechanisms, we discovered an important role of double-stranded RNA dependent protein kinase (PKR) in inflammasome activation. Exposure of macrophages to inflammasome agonists induced PKR autophosphorylation. PKR inactivation by genetic deletion or pharmacological inhibition severely impaired inflammasome activation in response to double-stranded RNA, ATP, monosodium urate, adjuvant aluminum, rotenone, live E. coli, anthrax lethal toxin, DNA transfection, and S. Typhimurium infection. PKR deficiency significantly inhibited the secretion of IL-1beta, IL-18 and HMGB1 in E. coli-induced peritonitis. PKR physically interacts with multiple inflammasome components, including NLR family pyrin domain-containing 3 (NLRP3), NLR family pyrin domain-containing 1 (NLRP1), NLR family CARD domain-containing protein 4 (NLRC4), Absent in melanoma 2 (AIM2), and broadly regulates inflammasome activation. PKR autophosphorylation in a cell free system with recombinant NLRP3, ASC and pro-casapse-1 reconstitutes inflammasome activity. These results reveal a critical role of PKR in inflammasome activation, and indicate that it should be possible to pharmacologically target this molecule to treat inflammation

Three Modern Roles for Logic in AI

We consider three modern roles for logic in artificial intelligence, which are based on the theory of tractable Boolean circuits: (1) logic as a basis for computation, (2) logic for learning from a combination of data and knowledge, and (3) logic for reasoning about the behavior of machine learning systems.Comment: To be published in PODS 202