Gene deficiency in activating Fcγ receptors influences the macrophage phenotypic balance and reduces atherosclerosis in mice

Immunity contributes to arterial inflammation during atherosclerosis. Oxidized low-density lipoproteins induce an autoimmune response characterized by specific antibodies and immune complexes in atherosclerotic patients. We hypothesize that specific Fcγ receptors for IgG constant region participate in atherogenesis by regulating the inflammatory state of lesional macrophages. In vivo we examined the role of activating Fcγ receptors in atherosclerosis progression using bone marrow transplantation from mice deficient in γ-chain (the common signaling subunit of activating Fcγ receptors) to hyperlipidemic mice. Hematopoietic deficiency of Fcγ receptors significantly reduced atherosclerotic lesion size, which was associated with decreased number of macrophages and T lymphocytes, and increased T regulatory cell function. Lesions of Fcγ receptor deficient mice exhibited increased plaque stability, as evidenced by higher collagen and smooth muscle cell content and decreased apoptosis. These effects were independent of changes in serum lipids and antibody response to oxidized low-density lipoproteins. Activating Fcγ receptor deficiency reduced pro-inflammatory gene expression, nuclear factor-κB activity, and M1 macrophages at the lesion site, while increasing anti-inflammatory genes and M2 macrophages. The decreased inflammation in the lesions was mirrored by a reduced number of classical inflammatory monocytes in blood. In vitro, lack of activating Fcγ receptors attenuated foam cell formation, oxidative stress and pro-inflammatory gene expression, and increased M2-associated genes in murine macrophages. Our study demonstrates that activating Fcγ receptors influence the macrophage phenotypic balance in the artery wall of atherosclerotic mice and suggests that modulation of Fcγ receptor-mediated inflammatory responses could effectively suppress atherosclerosis

Neonatal spontaneous biliary perforation: Case report

AbstractObjectiveSpontaneous biliary perforation in neonates is rare. The etiology of this pathology is idiopathic and various management strategies ranging from non-operative treatment to complex operations, such as biliary-enteric reconstruction, are performed, with few reported outcomes.Case reportA 3-week-old female, born at term, presented fever, abdominal distension, and acholic stool. An ultrasound was performed, which revealed generalized ascites and a poorly-defined collection. An emergency laparotomy confirmed perforation in the distal common bile duct and a biliary-enteric-anastomosis was performed.DiscussionWide drainage has been reported as the best initial management strategy for spontaneous biliary perforation, although it depends on the patient's clinical status and intraoperative findings.ConclusionsSpontaneous infantile biliary perforation is rare. Main management is wide drainage with, most perforations being resolved in 2 weeks

Valle del Cauca - Competitividad Sectorial Internacional. Sector: Fabricación de papel y productos de papel ; Imprentas y Editoriales

This paper presents the results of research in international competitiveness of papermaking and paper products: Printing and Publishing for both Colombia and the Cauca Valley between 2000 and 2007. A comparison between Valle, Antioquia and Bogota, regions that form the backbone of most dynamic sector, which in turn was regarded as one of the key priority production of the domestic agenda of competitiveness and productivity of Valle del Cauca, to address challenges of national and international markets. Measurements are made regarding the United States, Venezuela, Ecuador, Peru, Bolivia, Mexico, Costa Rica, Guatemala, Brazil and Chile. The results of the indicators used suggest that the department of Valle del Cauca must develop a strategy to widen participation has won the Central American markets to market sector products, which will convert these alternative markets for expansion export. And most notably for recovery in the share of production in both pulp, paper and cardboard, such as printers and publishers, from mid 1990 onwards, have fallen significantly.El presente escrito muestra los resultados de la investigación en competitividad internacional del sector de fabricación de papel y productos de papel: Imprentas y editoriales, tanto para Colombia como para el Valle del Cauca entre los años 2000 y 2007. Hace una comparación entre Valle, Antioquia y Bogotá, regiones que conforman el eje de mayor dinamismo del sector, que a su vez fue considerado como una de las apuestas productivas priorizadas de la Agenda Interna de Competitividad y Productividad del Valle del Cauca, para enfrentar los retos que plantean los mercados nacionales e internacionales. Las mediciones se hacen con respecto de los Estados Unidos, Venezuela, Ecuador, Perú, Bolivia, México, Costa Rica, Guatemala, Brasil y Chile. Los resultados de los indicadores aplicados sugieren que el departamento del Valle del Cauca debe desarrollar una estrategia para ampliar la participación que ha ganado en los mercados centroamericanos para la comercialización de los productos del sector, lo que permitirá convertir estos mercados en alternativa para su expansión exportadora. Y, muy principalmente para recuperarse en la participación de la producción tanto en pulpa, papel y cartón, como imprentas y editoriales que, desde mediados de la década de 1990, en adelante, presentan una caída significativa

Extended WKB method, resonances and supersymmetric radial barriers

Semiclassical approximations are implemented in the calculation of position and width of low energy resonances for radial barriers. The numerical integrations are delimited by t/T<<8, with t the period of a classical particle in the barrier trap and T the resonance lifetime. These energies are used in the construction of `haired' short range potentials as the supersymmetric partners of a given radial barrier. The new potentials could be useful in the study of the transient phenomena which give rise to the Moshinsky's diffraction in time.Comment: 12 pages, 4 figures, 3 table

Implementation of Sliding Mode Control in a Semi Bridgeless Boost Converter with Power Factor Correction

ABSTRACT: This paper proposes a new sliding surface for controlling a Semi-Bridgeless Boost Converter (SBBC) which simultaneously includes Power Factor Correction (PFC) and DC bus regulation. The proposed sliding surface is composed of three terms: First, a normalized DC voltage error term for controlling DC bus and rejecting DC voltage disturbances, normalization was performed for increasing system robustness during start-up and large disturbances. Second, an AC current error term for implementing a PFC scheme and guarantying fast current stabilization during disturbances. Third, an integral of AC current error term for increasing the stability of the overall system. Also, an Adaptive Hysteresis Band (AHB) is implemented for keeping constant the switching frequency and reducing the THDi. The proposed sliding surface was validated by means of sliding mode conditions and Lyapunov stability criteria. Simulations for comparing performance were performed between: a cascade PI control, a hybrid PI-Sliding Mode Control (PI-SMC), and Sliding Mode Control (SMC) with the proposed surface; additionally, it is presented an stability analysis for the proposed surface in start-up and under large perturbations. It is also presented experimental results for PI-SMC and SMC implemented in a SBBC prototype. The proposed surface implemented in the SMC presents the best dynamic behavior removing DC over voltages and responding faster under DC voltage changes or DC load current perturbations

A beam-beam monitoring detector for the MPD experiment at NICA

The Multi-Purpose Detector (MPD) is to be installed at the Nuclotron Ion Collider fAcility (NICA) of the Joint Institute for Nuclear Research (JINR). Its main goal is to study the phase diagram of the strongly interacting matter produced in heavy-ion collisions. These studies, while providing insight into the physics of heavy-ion collisions, are relevant for improving our understanding of the evolution of the early Universe and the formation of neutron stars. In order to extend the MPD trigger capabilities, we propose to include a high granularity beam-beam monitoring detector (BE-BE) to provide a level-0 trigger signal with an expected time resolution of 30 ps. This new detector will improve the determination of the reaction plane by the MPD experiment, a key measurement for flow studies that provides physics insight into the early stages of the reaction. In this work, we use simulated Au+Au collisions at NICA energies to show the potential of such a detector to determine the event plane resolution, providing further redundancy to the detectors originally considered for this purpose namely, the Fast Forward Detector (FFD) and the Hadron Calorimeter (HCAL). We also show our results for the time resolution studies of two prototype cells carried out at the T10 beam line at the CERN PS complex.Comment: 16 pages, 12 figures. Updated to published version with added comments and correction

Biological aspects of little tunny Euthynnus alletteratus from Spanish and Portuguese waters.

This study provides information on some biological aspects of Euthynnus alletteratus from the western Mediterranean (Spanish coast) and in the Atlantic Ocean (south of Iberian Peninsula). A total of 1266 individuals were measured between 2003 and 2017. The L-W relationship was calculated with W equal to 0.01242 FL3.058 . Histological analysis of the ovaries and the monthly variation of the gonadosomatic index for both sexes suggested that the spawning season for Euthynnus alletteratus in the western Mediterranean Sea takes place from June to August. The lengths at first maturity (L50) were estimated to be 50.1 cm and 43.4 cm FL for female and male, respectively. Age at first maturity (A50) was calculated

Live imaging of neolymphangiogenesis identifies acute antimetastatic roles of dsRNA mimics.

Long-range communication between tumor cells and the lymphatic vasculature defines competency for metastasis in different cancer types, particularly in melanoma. Nevertheless, the discovery of selective blockers of lymphovascular niches has been compromised by the paucity of experimental systems for whole-body analyses of tumor progression. Here, we exploit immunocompetent and immunodeficient mouse models for live imaging of Vegfr3-driven neolymphangiogenesis, as a versatile platform for drug screening in vivo. Spatiotemporal analyses of autochthonous melanomas and patient-derived xenografts identified double-stranded RNA mimics (dsRNA nanoplexes) as potent inhibitors of neolymphangiogenesis, metastasis, and post-surgical disease relapse. Mechanistically, dsRNA nanoplexes were found to exert a rapid dual action in tumor cells and in their associated lymphatic vasculature, involving the transcriptional repression of the lymphatic drivers Midkine and Vegfr3, respectively. This suppressive function was mediated by a cell-autonomous type I interferon signaling and was not shared by FDA-approved antimelanoma treatments. These results reveal an alternative strategy for targeting the tumor cell-lymphatic crosstalk and underscore the power of Vegfr3-lymphoreporters for pharmacological testing in otherwise aggressive cancers.The authors thank previous and present colleagues in the CNIO Melanoma Group, particularly Damia Tormo and Lisa Osterloh for help and support at the initial stages of this study; Jose A Esteban (CSIC-UAM) for critical reading of this manuscript; Lionel Larue (INSERM; France) and Martin McMahon (Hunstman Cancer Center, USA) for the Tyr:CreERT2 and BrafCA mouse strains, respectively; and Ignacio Melero at Hospital Clinico, Pamplona, Spain, for Ifnar1-deficient mice. The authors thank Isabel Blanco, Soraya Ruiz, and Virginia Granda (CNIO-Animal Facility Unit), Diego Megias (CNIO-Confocal Unit), and Eduardo Jose Caleiras and Patricia Gonzalez (CNIO-Histopathology Unit) for technical assistance. M.S.S. is funded by grants from the Spanish Ministry of Economy and Innovation (SAF2017-89533-R), the Asociacion Espanola Contra el Cancer (AECC), Fundacion La Caixa, and an Established Investigator Award by the Melanoma Research Alliance (MRA). D.O. is funded by grants from the Spanish Ministry of Health (AES-PIS PI18/1057) and "Beca Leonardo a Investigadores y Creadores Culturales 2018 de la Fundacion BBVA". The CNIO Proteomics Unit belongs to ProteoRed, PRB3-ISCIII, supported by grant PT17/0019. S.O. is also supported by a grant from the Spanish Ministry of Economy, Industry and Competitiveness (BFU2015-71376-R).S