81 research outputs found

    Crecimiento, fabricación y caracterización de diodos electroluminiscentes basados en pozos cuánticos de InGaN

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    Teniendo en cuenta la energía del gap de los binarios que forman el temario InGaN (GaN, 3.4 eV; InN, 0.9 eV), es fácil ver que con este material se puede abarcar todo el espectro visible. El objetivo de esta Tesis es estudiar el crecimiento por MBE y las propiedades del InGaN, con la finalidad de fabricar un diodo electroluminiscente eficiente con capa activa compuesta por pozos cuánticos de InGaN con barreras de GaN. La fabricación del LED conlleva también el estudio del dopaje tipo p en el GaN, empleando Magnesio. El crecimiento de capas gruesas de InGaN se ha estudiado como paso previo al de pozos cuánticos. Se ha determinado una temperatura de inicio de evaporación del Indio de la superficie de crecimiento en tomo a 560*C, obteniéndose las mejores capas para temperaturas de substrato ligeramente superiores a ésta y con relación III/V ligeramente superior a la unidad. En el apartado óptico, se ha observado que la amplitud de las fluctuaciones locales en el contenido de Indio en las muestras aumenta cuando se incrementa el contenido promedio de éste. En el crecimiento de pozos cuánticos de InGaN con barreras de GaN, se obtiene los mejores resultados cuando se mantiene fijo el flujo de Galio durante pozo y barrera y se favorece la formación de una capa de Indio segregada a la superficie durante el crecimiento del pozo. A partir de las propiedades de la emisión en cada caso se establece un mayor dominio sobre la energía de la misma de los campos piezoeléctricos en pozos de espesor mayor de 4 nm y de las fluctuaciones de Indio en pozos con éste menor de 3 nm. Con la técnica de crecimiento de pozos cuánticos desarrollada, y empleando cinco pozos de InxGa(1-x)N(-2 nm)/GaN (-5 nm) como capa activa, se han crecido y fabricado dispositivos emitiendo desde el ultravioleta cercano (3.4 eV) hasta el verde (2.4 eV) variando el contenido de Indio de los pozos desde 0 hasta 25 por ciento de Indio. Como método de mejora de los dispositivos se ha estudiado la incorporación del LED a una cavidad resonante centrada en el verde (5 10 nm), realizada con un espejo superior de Aluminio y un reflector de Bragg de AlGaN/GaN como espejo inferior. La potencia de emisión obtenida de este modo es 7 uW a 20 mA, con una intensidad 10 veces mayor que la del LED convencional de la misma longitud de onda. Otro de los métodos de mejora estudiados es la optimización del dopaje de GaN empleando Mg, en el que se ha realizado un estudio en función de la temperatura de célula de Mg, fijando la temperatura de substrato en 690* C. El intervalo útil de temperaturas de la primera queda delimitado por el extremo inferior (-375 *C) por la concentración residual que posean las capas, que ha de ser vencida por el dopaje. El extremo superior (-450' C) queda definido por la generación de defectos en las muestras, lo que puede llevar a un cambio de la polaridad de la capa, produciendo una caída en la incorporación del Mg. Las condiciones óptimas de dopaje se alcanzan para Tmg= 435* C, con una concentración de huecos de 3E 17 cm-3

    Structural Characterization of Al0.37In0.63N/AlN/p-Si (111) Heterojunctions Grown by RF Sputtering for Solar Cell Applications

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    Compact Al0.37In0.63N layers were grown by radiofrequency sputtering on bare and 15 nm-thick AlN-buffered Si (111) substrates. The crystalline quality of the AlInN layers was studied by high-resolution X-ray diffraction measurements and transmission electron microscopy. Both techniques show an improvement of the structural properties when the AlInN layer is grown on a 15 nm-thick AlN buffer. The layer grown on bare silicon exhibits a thin amorphous interfacial layer between the substrate and the AlInN, which is not present in the layer grown on the AlN buffer layer. A reduction of the density of defects is also observed in the layer grown on the AlN buffer

    AlxIn1−xN on Si (100) Solar Cells (x = 0–0.56) Deposited by RF Sputtering

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    We investigate the photovoltaic performance of solar cells based on n-AlxIn1−xN (x = 0–0.56) on p-Si (100) hetero-junctions deposited by radio frequency sputtering. The AlxIn1−xN layers own an optical bandgap absorption edge tuneable from 1.73 eV to 2.56 eV within the Al content range. This increase of Al content results in more resistive layers (≈10−4–1 Ω·cm) while the residual carrier concentration drops from ~1021 to ~1019 cm−3 . As a result, the top n-contact resistance varies from ≈10−1 to 1 MΩ for InN to Al0.56In0.44N-based devices, respectively. Best results are obtained for devices with 28% Al that exhibit a broad external quantum efficiency covering the full solar spectrum with a maximum of 80% at 750 nm, an open-circuit voltage of 0.39 V, a short-circuit current density of 17.1 mA/cm2 and a conversion efficiency of 2.12% under air mass 1.5 global (AM1.5G) illumination (1 sun), rendering them promising for novel low-cost III-nitride on Si photovoltaic devices. For Al contents above 28%, the electrical performance of the structures lessens due to the high top-contact resistivityThis research was funded by the national projects from the Ministry of Research and Innovation TEC2017-84378-R and NERA (RTI2018-101037-B-I00); the projects from the Comunidad de Madrid SINFOTON2-CM (P2018/NMT-4326), MADRID-PV2 (P-2018/EMT-4308) and SOLA (CM/JIN/2019-013); the projects from the University of Alcalá ANIS (CCG2018/EXP-042) and PISA (CCG19/IA-005); and by the FEDER program. R. Blasco acknowledges the financial support of his contract associated with the Ramon y Cajal Fellowship RYC-2013-1408

    How to play with the spectral sensitivity of interferometers using slow light concepts and how to do it practically

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    We describe some interesting features that arise when slow and fast light structures are introduced in interferometers. With different configurations, one can obtain a spectral sensitivity enhancement of the interferometer or an enhanced robustness to laser frequency drifts. Furthermore, we describe simple practical ways to implement slow and fast light media in practical interferometers. We believe that these ideas may have interesting implications in optical sensing

    Estudio experimental de un proceso de inyección continua de vapor en el equipo de desplazamiento radial

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    El objetivo de este artículo es presentar una metodología que permita reproducir a escala de laboratorio el proceso de recobro térmico denominado inyección continua de vapor utilizando el equipo de desplazamiento radial E.D.R Para el desarrollo de este proyecto se llevaron a cabo 4 fases de experimentación que integradas contribuyeron al desarrollo de la prueba de inyección continua de vapor a escala de laboratorio. En la primera parte de este trabajo se procedió a la construcción de plugs sintéticos para el análisis y determinación de las variables más infuyentes para su construcción y la posterior determinación de las propiedades petrofísicas básicas. Posteriormente se desarrollaron una serie de pruebas preliminares de inyección de vapor utilizando los plugs construidos con el fn de identifcar y seleccionar los parámetros operacionales óptimos del equipo generador de vapor.Posteriormente se procedió con la construcción del medio poroso homogéneo el cual representa un cuarto de patrón de yacimiento y constituye el modelo físico en el que se realizará la prueba de desplazamiento utilizando vapor, también se añade un procedimiento técnico para la ejecución de pruebas de inyección continua de vapor utilizando el equipo de desplazamiento radial (E.D.R.) y se incluyen los resultados fnales de la prueba realizada. Finalmente se presenta el  desarrollo del modelo analítico utilizado para representar el proceso de inyección continua de vapor y posteriormente la construcción y ejecución del modelo de simulación numérica a condiciones de laboratorio. De la misma manera se incluye la comparación y el análisis de los resultados de los tres modelos utilizados para el desarrollo de este proyecto.  The objective of this article is to present a methodology to reproduce the thermal enhanced oil recovery process called steamfooding, at laboratory scale, using the radial displacement equipment. For the development of this project were conducted four stages of experimentation; all of them integrated contributed to the design of the steamfooding test at laboratory scale. The frst stage of the process consist on the construction of synthetic plugs for analyzing and determining the most important variables in the process and the basic petro physical properties. Subsequently, were developed a series of preliminary steamfooding tests with the plugs previously built, with the purpose of determining the optimum operational parameters of the steam generator equipment.  Later, the homogeneous porous media was buildt; it represents the fourth part of a reservoir pattern, this constitute he physical model in which the displacement test with steam will be done, it is also presented the technical procedure for the steamfooding tests using the Radial Displacement Equipment (E.D.R) and the fnal results of the est developed. Finally is presented the development of the analytical model used for predicting and representing a steamfooding process and the subsequent execution of the numerical simulation model at laboratory conditions. Alike is included the results analysis and comparison between the three models used for the development of this project

    Effect of different buffer layers on the quality of InGaN layers grown on Si

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    This work studies the effect of four different types of buffer layers on the structural and optical properties of InGaN layers grown on Si(111) substrates and their correlation with electrical characteristics. The vertical electrical conduction of n-InGaN/buffer-layer/p-Si heterostructures, with In composition near 46%, which theoretically produces an alignment of the bands, is analyzed. Droplet elimination by radical-beam irradiation was successfully applied to grow high quality InGaN films on Si substrates for the first time. Among several buffer choices, an AlN buffer layer with a thickness above 24 nm improves the structural and optical quality of the InGaN epilayer while keeping a top to bottom ohmic behavior. These results will allow fabricating double-junction InGaN/Si solar cells without the need of tunnel junctions between the two sub-cells, therefore simplifying the device design

    Feline Leukemia Virus and Other Pathogens as Important Threats to the Survival of the Critically Endangered Iberian Lynx (Lynx pardinus)

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    BACKGROUND: The Iberian lynx (Lynx pardinus) is considered the most endangered felid species in the world. In order to save this species, the Spanish authorities implemented a captive breeding program recruiting lynxes from the wild. In this context, a retrospective survey on prevalence of selected feline pathogens in free-ranging lynxes was initiated. METHODOLOGY/ PRINCIPAL FINDINGS: We systematically analyzed the prevalence and importance of seven viral, one protozoan (Cytauxzoon felis), and several bacterial (e.g., hemotropic mycoplasma) infections in 77 of approximately 200 remaining free-ranging Iberian lynxes of the Doñana and Sierra Morena areas, in Southern Spain, between 2003 and 2007. With the exception of feline immunodeficiency virus (FIV), evidence of infection by all tested feline pathogens was found in Iberian lynxes. Fourteen lynxes were feline leukemia virus (FeLV) provirus-positive; eleven of these were antigenemic (FeLV p27 positive). All 14 animals tested negative for other viral infections. During a six-month period in 2007, six of the provirus-positive antigenemic lynxes died. Infection with FeLV but not with other infectious agents was associated with mortality (p<0.001). Sequencing of the FeLV surface glycoprotein gene revealed a common origin for ten of the eleven samples. The ten sequences were closely related to FeLV-A/61E, originally isolated from cats in the USA. Endogenous FeLV sequences were not detected. CONCLUSIONS/SIGNIFICANCE: It was concluded that the FeLV infection most likely originated from domestic cats invading the lynx's habitats. Data available regarding the time frame, co-infections, and outcome of FeLV-infections suggest that, in contrast to the domestic cat, the FeLV strain affecting the lynxes in 2007 is highly virulent to this species. Our data argue strongly for vaccination of lynxes and domestic cats in and around lynx's habitats in order to prevent further spread of the virus as well as reduction the domestic cat population if the lynx population is to be maintained

    Syphilis at the Crossroad of Phylogenetics and Paleopathology

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    The origin of syphilis is still controversial. Different research avenues explore its fascinating history. Here we employed a new integrative approach, where paleopathology and molecular analyses are combined. As an exercise to test the validity of this approach we examined different hypotheses on the origin of syphilis and other human diseases caused by treponemes (treponematoses). Initially, we constructed a worldwide map containing all accessible reports on palaeopathological evidences of treponematoses before Columbus's return to Europe. Then, we selected the oldest ones to calibrate the time of the most recent common ancestor of Treponema pallidum subsp. pallidum, T. pallidum subsp. endemicum and T. pallidum subsp. pertenue in phylogenetic analyses with 21 genetic regions of different T. pallidum strains previously reported. Finally, we estimated the treponemes' evolutionary rate to test three scenarios: A) if treponematoses accompanied human evolution since Homo erectus; B) if venereal syphilis arose very recently from less virulent strains caught in the New World about 500 years ago, and C) if it emerged in the Americas between 16,500 and 5,000 years ago. Two of the resulting evolutionary rates were unlikely and do not explain the existent osseous evidence. Thus, treponematoses, as we know them today, did not emerge with H. erectus, nor did venereal syphilis appear only five centuries ago. However, considering 16,500 years before present (yBP) as the time of the first colonization of the Americas, and approximately 5,000 yBP as the oldest probable evidence of venereal syphilis in the world, we could not entirely reject hypothesis C. We confirm that syphilis seems to have emerged in this time span, since the resulting evolutionary rate is compatible with those observed in other bacteria. In contrast, if the claims of precolumbian venereal syphilis outside the Americas are taken into account, the place of origin remains unsolved. Finally, the endeavor of joining paleopathology and phylogenetics proved to be a fruitful and promising approach for the study of infectious diseases

    First Latin American clinical practice guidelines for the treatment of systemic lupus erythematosus: Latin American Group for the Study of Lupus (GLADEL, Grupo Latino Americano de Estudio del Lupus)-Pan-American League of Associations of Rheumatology (PANLAR)

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    Systemic lupus erythematosus (SLE), a complex and heterogeneous autoimmune disease, represents a significant challenge for both diagnosis and treatment. Patients with SLE in Latin America face special problems that should be considered when therapeutic guidelines are developed. The objective of the study is to develop clinical practice guidelines for Latin American patients with lupus. Two independent teams (rheumatologists with experience in lupus management and methodologists) had an initial meeting in Panama City, Panama, in April 2016. They selected a list of questions for the clinical problems most commonly seen in Latin American patients with SLE. These were addressed with the best available evidence and summarised in a standardised format following the Grading of Recommendations Assessment, Development and Evaluation approach. All preliminary findings were discussed in a second face-to-face meeting in Washington, DC, in November 2016. As a result, nine organ/system sections are presented with the main findings; an 'overarching' treatment approach was added. Special emphasis was made on regional implementation issues. Best pharmacologic options were examined for musculoskeletal, mucocutaneous, kidney, cardiac, pulmonary, neuropsychiatric, haematological manifestations and the antiphospholipid syndrome. The roles of main therapeutic options (ie, glucocorticoids, antimalarials, immunosuppressant agents, therapeutic plasma exchange, belimumab, rituximab, abatacept, low-dose aspirin and anticoagulants) were summarised in each section. In all cases, benefits and harms, certainty of the evidence, values and preferences, feasibility, acceptability and equity issues were considered to produce a recommendation with special focus on ethnic and socioeconomic aspects. Guidelines for Latin American patients with lupus have been developed and could be used in similar settings.Fil: Pons Estel, Bernardo A.. Centro Regional de Enfermedades Autoinmunes y Reumáticas; ArgentinaFil: Bonfa, Eloisa. Universidade de Sao Paulo; BrasilFil: Soriano, Enrique R.. Instituto Universitario Hospital Italiano de Buenos Aires. Rectorado.; ArgentinaFil: Cardiel, Mario H.. Centro de Investigación Clínica de Morelia; MéxicoFil: Izcovich, Ariel. Hospital Alemán; ArgentinaFil: Popoff, Federico. Hospital Aleman; ArgentinaFil: Criniti, Juan M.. Hospital Alemán; ArgentinaFil: Vásquez, Gloria. Universidad de Antioquia; ColombiaFil: Massardo, Loreto. Universidad San Sebastián; ChileFil: Duarte, Margarita. Hospital de Clínicas; ParaguayFil: Barile Fabris, Leonor A.. Hospital Angeles del Pedregal; MéxicoFil: García, Mercedes A.. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín; ArgentinaFil: Amigo, Mary Carmen. Centro Médico Abc; MéxicoFil: Espada, Graciela. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños "Ricardo Gutiérrez"; ArgentinaFil: Catoggio, Luis J.. Hospital Italiano. Instituto Universitario. Escuela de Medicina; ArgentinaFil: Sato, Emilia Inoue. Universidade Federal de Sao Paulo; BrasilFil: Levy, Roger A.. Universidade do Estado de Rio do Janeiro; BrasilFil: Acevedo Vásquez, Eduardo M.. Universidad Nacional Mayor de San Marcos; PerúFil: Chacón Díaz, Rosa. Policlínica Méndez Gimón; VenezuelaFil: Galarza Maldonado, Claudio M.. Corporación Médica Monte Sinaí; EcuadorFil: Iglesias Gamarra, Antonio J.. Universidad Nacional de Colombia; ColombiaFil: Molina, José Fernando. Centro Integral de Reumatología; ColombiaFil: Neira, Oscar. Universidad de Chile; ChileFil: Silva, Clóvis A.. Universidade de Sao Paulo; BrasilFil: Vargas Peña, Andrea. Hospital Pasteur Montevideo; UruguayFil: Gómez Puerta, José A.. Hospital Clinic Barcelona; EspañaFil: Scolnik, Marina. Instituto Universitario Hospital Italiano de Buenos Aires. Rectorado.; ArgentinaFil: Pons Estel, Guillermo J.. Centro Regional de Enfermedades Autoinmunes y Reumáticas; Argentina. Hospital Provincial de Rosario; ArgentinaFil: Ugolini Lopes, Michelle R.. Universidade de Sao Paulo; BrasilFil: Savio, Verónica. Instituto Universitario Hospital Italiano de Buenos Aires. Rectorado.; ArgentinaFil: Drenkard, Cristina. University of Emory; Estados UnidosFil: Alvarellos, Alejandro J.. Hospital Privado Universitario de Córdoba; ArgentinaFil: Ugarte Gil, Manuel F.. Universidad Cientifica del Sur; Perú. Hospital Nacional Guillermo Almenara Irigoyen; PerúFil: Babini, Alejandra. Instituto Universitario Hospital Italiano de Buenos Aires. Rectorado.; ArgentinaFil: Cavalcanti, André. Universidade Federal de Pernambuco; BrasilFil: Cardoso Linhares, Fernanda Athayde. Hospital Pasteur Montevideo; UruguayFil: Haye Salinas, Maria Jezabel. Hospital Privado Universitario de Córdoba; ArgentinaFil: Fuentes Silva, Yurilis J.. Universidad de Oriente - Núcleo Bolívar; VenezuelaFil: Montandon De Oliveira E Silva, Ana Carolina. Universidade Federal de Goiás; BrasilFil: Eraso Garnica, Ruth M.. Universidad de Antioquia; ColombiaFil: Herrera Uribe, Sebastián. Hospital General de Medellin Luz Castro de Gutiérrez; ColombiaFil: Gómez Martín, DIana. Instituto Nacional de la Nutrición Salvador Zubiran; MéxicoFil: Robaina Sevrini, Ricardo. Universidad de la República; UruguayFil: Quintana, Rosana M.. Hospital Provincial de Rosario; Argentina. Centro Regional de Enfermedades Autoinmunes y Reumáticas; ArgentinaFil: Gordon, Sergio. Hospital Interzonal General de Agudos Dr Oscar Alende. Unidad de Reumatología y Enfermedades Autoinmunes Sistémicas; ArgentinaFil: Fragoso Loyo, Hilda. Instituto Nacional de la Nutrición Salvador Zubiran; MéxicoFil: Rosario, Violeta. Hospital Docente Padre Billini; República DominicanaFil: Saurit, Verónica. Hospital Privado Universitario de Córdoba; ArgentinaFil: Appenzeller, Simone. Universidade Estadual de Campinas; BrasilFil: Dos Reis Neto, Edgard Torres. Universidade Federal de Sao Paulo; BrasilFil: Cieza, Jorge. Hospital Nacional Edgardo Rebagliati Martins; PerúFil: González Naranjo, Luis A.. Universidad de Antioquia; ColombiaFil: González Bello, Yelitza C.. Ceibac; MéxicoFil: Collado, María Victoria. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Médicas; ArgentinaFil: Sarano, Judith. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Médicas; ArgentinaFil: Retamozo, Maria Soledad. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones en Ciencias de la Salud. Universidad Nacional de Córdoba. Instituto de Investigaciones en Ciencias de la Salud; ArgentinaFil: Sattler, María E.. Provincia de Buenos Aires. Ministerio de Salud. Hospital Interzonal de Agudos "Eva Perón"; ArgentinaFil: Gamboa Cárdenas, Rocio V.. Hospital Nacional Guillermo Almenara Irigoyen; PerúFil: Cairoli, Ernesto. Universidad de la República; UruguayFil: Conti, Silvana M.. Hospital Provincial de Rosario; ArgentinaFil: Amezcua Guerra, Luis M.. Instituto Nacional de Cardiologia Ignacio Chavez; MéxicoFil: Silveira, Luis H.. Instituto Nacional de Cardiologia Ignacio Chavez; MéxicoFil: Borba, Eduardo F.. Universidade de Sao Paulo; BrasilFil: Pera, Mariana A.. Hospital Interzonal General de Agudos General San Martín; ArgentinaFil: Alba Moreyra, Paula B.. Universidad Nacional de Córdoba. Facultad de Medicina; ArgentinaFil: Arturi, Valeria. Hospital Interzonal General de Agudos General San Martín; ArgentinaFil: Berbotto, Guillermo A.. Provincia de Buenos Aires. Ministerio de Salud. Hospital Interzonal de Agudos "Eva Perón"; ArgentinaFil: Gerling, Cristian. Hospital Interzonal General de Agudos Dr Oscar Alende. Unidad de Reumatología y Enfermedades Autoinmunes Sistémicas; ArgentinaFil: Gobbi, Carla Andrea. Universidad Nacional de Córdoba. Facultad de Medicina; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Gervasoni, Viviana L.. Hospital Provincial de Rosario; ArgentinaFil: Scherbarth, Hugo R.. Hospital Interzonal General de Agudos Dr Oscar Alende. Unidad de Reumatología y Enfermedades Autoinmunes Sistémicas; ArgentinaFil: Brenol, João C. Tavares. Hospital de Clinicas de Porto Alegre; BrasilFil: Cavalcanti, Fernando. Universidade Federal de Pernambuco; BrasilFil: Costallat, Lilian T. Lavras. Universidade Estadual de Campinas; BrasilFil: Da Silva, Nilzio A.. Universidade Federal de Goiás; BrasilFil: Monticielo, Odirlei A.. Hospital de Clinicas de Porto Alegre; BrasilFil: Seguro, Luciana Parente Costa. Universidade de Sao Paulo; BrasilFil: Xavier, Ricardo M.. Hospital de Clinicas de Porto Alegre; BrasilFil: Llanos, Carolina. Universidad Católica de Chile; ChileFil: Montúfar Guardado, Rubén A.. Instituto Salvadoreño de la Seguridad Social; El SalvadorFil: Garcia De La Torre, Ignacio. Hospital General de Occidente; MéxicoFil: Pineda, Carlos. Instituto Nacional de Rehabilitación; MéxicoFil: Portela Hernández, Margarita. Umae Hospital de Especialidades Centro Medico Nacional Siglo Xxi; MéxicoFil: Danza, Alvaro. Hospital Pasteur Montevideo; UruguayFil: Guibert Toledano, Marlene. Medical-surgical Research Center; CubaFil: Reyes, Gil Llerena. Medical-surgical Research Center; CubaFil: Acosta Colman, Maria Isabel. Hospital de Clínicas; ParaguayFil: Aquino, Alicia M.. Hospital de Clínicas; ParaguayFil: Mora Trujillo, Claudia S.. Hospital Nacional Edgardo Rebagliati Martins; PerúFil: Muñoz Louis, Roberto. Hospital Docente Padre Billini; República DominicanaFil: García Valladares, Ignacio. Centro de Estudios de Investigación Básica y Clínica; MéxicoFil: Orozco, María Celeste. Instituto de Rehabilitación Psicofísica; ArgentinaFil: Burgos, Paula I.. Pontificia Universidad Católica de Chile; ChileFil: Betancur, Graciela V.. Instituto de Rehabilitación Psicofísica; ArgentinaFil: Alarcón, Graciela S.. Universidad Peruana Cayetano Heredia; Perú. University of Alabama at Birmingahm; Estados Unido

    Rare coding variants in PLCG2, ABI3, and TREM2 implicate microglial-mediated innate immunity in Alzheimer's disease

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    We identified rare coding variants associated with Alzheimer’s disease (AD) in a 3-stage case-control study of 85,133 subjects. In stage 1, 34,174 samples were genotyped using a whole-exome microarray. In stage 2, we tested associated variants (P<1×10-4) in 35,962 independent samples using de novo genotyping and imputed genotypes. In stage 3, an additional 14,997 samples were used to test the most significant stage 2 associations (P<5×10-8) using imputed genotypes. We observed 3 novel genome-wide significant (GWS) AD associated non-synonymous variants; a protective variant in PLCG2 (rs72824905/p.P522R, P=5.38×10-10, OR=0.68, MAFcases=0.0059, MAFcontrols=0.0093), a risk variant in ABI3 (rs616338/p.S209F, P=4.56×10-10, OR=1.43, MAFcases=0.011, MAFcontrols=0.008), and a novel GWS variant in TREM2 (rs143332484/p.R62H, P=1.55×10-14, OR=1.67, MAFcases=0.0143, MAFcontrols=0.0089), a known AD susceptibility gene. These protein-coding changes are in genes highly expressed in microglia and highlight an immune-related protein-protein interaction network enriched for previously identified AD risk genes. These genetic findings provide additional evidence that the microglia-mediated innate immune response contributes directly to AD development
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