Servicio de comunicación causal bidirecciional sin contención.

Las arquitecturas jerárquicas de comunicación causal se presentan como una alternativa habitual para reducir el elevado tamaño de la información de control causal a enviar en cada mensaje, cuando la comunicación se realiza entre un subconjunto de procesos que pertenecen a un grupo muy numeroso. Sin embargo, en estas arquitecturas, los nodos intermedios de la jerarquía padecen un efecto indeseable denominado efecto convoy. Estos nodos intermedios tienden a generar ráfagas de envíos que sobrecargan tanto a los nodos de los niveles inferiores de la jerarquía como a la red, provocando pérdidas de mensajes y periodos entre ráfagas de infrautilización de la red. Este artículo presenta un servicio causal bidireccional sin contención que, aplicado a los nodos intermedios de la jerarquía, soluciona el efecto convoy. Este servicio causal sin contención entrega a la capa de aplicación y envía al sistema un mensaje sin esperar la entrega o el envío previo de mensajes que constituyen la historia causal del primero, por lo que evita las ráfagas de entrega y de envío de mensajes. La entrega de un mensaje va acompañada de un identificador causal, que es un número natural que indica el número de orden de ese mensaje en la secuencia causal total. El envío de un mensaje supone construir un vector causal válido a partir de un identiificador causal, que permita ordenar dicho mensaje en orden causal en el proceso receptor

Automatic Abdominal Aortic Aneurysm segmentation in MR images

Abdominal Aortic Aneurism is a disease related to a weakening in the aortic wall that can cause a break in the aorta and the death. The detection of an unusual dilatation of a section of the aorta is an indicative of this disease. However, it is difficult to diagnose because it is necessary image diagnosis using computed tomography or magnetic resonance. An automatic diagnosis system would allow to analyze abdominal magnetic resonance images and to warn doctors if any anomaly is detected. We focus our research in magnetic resonance images because of the absence of ionizing radiation. Although there are proposals to identify this disease in magnetic resonance images, they need an intervention from clinicians to be precise and some of them are computationally hard. In this paper we develop a novel approach to analyze magnetic resonance abdominal images and detect the lumen and the aortic wall. The method combines different algorithms in two stages to improve the detection and the segmentation so it can be applied to similar problems with other type of images or structures. In a first stage, we use a spatial fuzzy C-means algorithm with morphological image analysis to detect and segment the lumen; and subsequently, in a second stage, we apply a graph cut algorithm to segment the aortic wall. The obtained results in the analyzed images are pretty successful obtaining an average of 79% of overlapping between the automatic segmentation provided by our method and the aortic wall identified by a medical specialist. The main impact of the proposed method is that it works in a completely automatic way with a low computational cost, which is of great significance for any expert and intelligent system

IL-1R and inflammasomes mediate early pulmonary protective mechanisms in respiratory brucella abortus infection

Brucella spp. infection is frequently acquired through contaminated aerosols. The role of interleukin-1 beta (IL-1β) in the early pulmonary response to respiratory Brucella infection is unknown. As shown here, IL-1β levels in lung homogenates and bronchoalveolar lavage fluid (BALF) of mice intratracheally inoculated with B. abortus were increased at 3 and 7 days p.i. At 7 days p.i., pulmonary CFU numbers were higher in IL-1 receptor (IL-1R) knockout (KO) mice than in wild type (WT) mice. At different times p.i. CFU in lungs and BALF were higher in mice lacking some inflammasome components (caspase-1, AIM2, NLRP3) than in WT mice. At 2 days p.i. pulmonary levels of IL-1b and CXCL1 (neutrophils chemoattractant) were lower in caspase-1/11 KO mice. At day 3 p.i., neutrophils counts in BALF were lower in caspase-1/11 KO mice than in WT mice. During in vitro infections, IL-1β secretion was lower in alveolar macrophages from caspase-1/11, NLRP3 or AIM2 KO mice than in WT controls. Similarly, IL-1β production by B. abortus-infected alveolar epithelial cells was reduced by pretreatment with a specific caspase-1 inhibitor. This study shows that IL-1R, probably through IL-1β action, and the NLRP3 and AIM2 inflammasomes are involved in pulmonary innate immune protective mechanisms against respiratory B. abortus infection.Fil: Hielpos, María Soledad. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Estudios de la Inmunidad Humoral Prof. Ricardo A. Margni. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Estudios de la Inmunidad Humoral Prof. Ricardo A. Margni; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; ArgentinaFil: Fernandez, Andrea Giselle. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Estudios de la Inmunidad Humoral Prof. Ricardo A. Margni. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Estudios de la Inmunidad Humoral Prof. Ricardo A. Margni; ArgentinaFil: Falivene, Juliana. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Estudios de la Inmunidad Humoral Prof. Ricardo A. Margni. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Estudios de la Inmunidad Humoral Prof. Ricardo A. Margni; ArgentinaFil: Alonso Paiva, Iván Mathias. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Estudios de la Inmunidad Humoral Prof. Ricardo A. Margni. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Estudios de la Inmunidad Humoral Prof. Ricardo A. Margni; ArgentinaFil: Muñoz González, Florencia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Estudios de la Inmunidad Humoral Prof. Ricardo A. Margni. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Estudios de la Inmunidad Humoral Prof. Ricardo A. Margni; ArgentinaFil: Ferrero, Mariana Cristina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Estudios de la Inmunidad Humoral Prof. Ricardo A. Margni. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Estudios de la Inmunidad Humoral Prof. Ricardo A. Margni; ArgentinaFil: Campos, Priscila C.. Universidade Federal de Minas Gerais; BrasilFil: Vieira, Angelica T.. Universidade Federal de Minas Gerais; BrasilFil: Oliveira, Sergio Costa. Universidade Federal de Minas Gerais; BrasilFil: Baldi, Pablo Cesar. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Estudios de la Inmunidad Humoral Prof. Ricardo A. Margni. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Estudios de la Inmunidad Humoral Prof. Ricardo A. Margni; Argentin

The Proteasomal Deubiquitinating Enzyme PSMD14 Regulates Macroautophagy by Controlling Golgi-to-ER Retrograde Transport

Ubiquitination regulates several biological processes, however the role of specific members of the ubiquitinome on intracellular membrane trafficking is not yet fully understood. Here, we search for ubiquitin-related genes implicated in protein membrane trafficking performing a High-Content siRNA Screening including 1187 genes of the human “ubiquitinome” using amyloid precursor protein (APP) as a reporter. We identified the deubiquitinating enzyme PSMD14, a subunit of the 19S regulatory particle of the proteasome, specific for K63-Ub chains in cells, as a novel regulator of Golgi-to-endoplasmic reticulum (ER) retrograde transport. Silencing or pharmacological inhibition of PSMD14 with Capzimin (CZM) caused a robust increase in APP levels at the Golgi apparatus and the swelling of this organelle. We showed that this phenotype is the result of rapid inhibition of Golgi-to-ER retrograde transport, a pathway implicated in the early steps of the autophagosomal formation. Indeed, we observed that inhibition of PSMD14 with CZM acts as a potent blocker of macroautophagy by a mechanism related to the retention of Atg9A and Rab1A at the Golgi apparatus. As pharmacological inhibition of the proteolytic core of the 20S proteasome did not recapitulate these effects, we concluded that PSMD14, and the K63-Ub chains, act as a crucial regulatory factor for macroautophagy by controlling Golgi-to-ER retrograde transport

Epigenetic Modulation of Gremlin-1/NOTCH Pathway in Experimental Crescentic Immune-Mediated Glomerulonephritis

Crescentic glomerulonephritis is a devastating autoimmune disease that without early and properly treatment may rapidly progress to end-stage renal disease and death. Current immunosuppressive treatment provides limited efficacy and an important burden of adverse events. Epigenetic drugs are a source of novel therapeutic tools. Among them, bromodomain and extraterminal domain (BET) inhibitors (iBETs) block the interaction between bromodomains and acetylated proteins, including histones and transcription factors. iBETs have demonstrated protective effects on malignancy, inflammatory disorders and experimental kidney disease. Recently, Gremlin-1 was proposed as a urinary biomarker of disease progression in human anti-neutrophil cytoplasmic antibody (ANCA)-associated crescentic glomerulonephritis. We have now evaluated whether iBETs could regulate Gremlin-1 in experimental anti-glomerular basement membrane nephritis induced by nephrotoxic serum (NTS) in mice, a model resembling human crescentic glomerulonephritis. In NTS-injected mice, the iBET JQ1 inhibited renal Gremlin-1 overexpression and diminished glomerular damage, restoring podocyte numbers. Chromatin immunoprecipitation assay demonstrated BRD4 enrichment of the Grem-1 gene promoter in injured kidneys, consistent with Gremlin-1 epigenetic regulation. Moreover, JQ1 blocked BRD4 binding and inhibited Grem-1 gene transcription. The beneficial effect of iBETs was also mediated by modulation of NOTCH pathway. JQ1 inhibited the gene expression of the NOTCH effectors Hes-1 and Hey-1 in NTS-injured kidneys. Our results further support the role for epigenetic drugs, such as iBETs, in the treatment of rapidly progressive crescentic glomerulonephritis

Cultura, política, subjetividad. Un estudio de caso

En este trabajo presentamos una apretada síntesis del proyecto de investigación Cultura, política subjetividad. Un estudio de caso. De algún modo también, constituye el punto de llegada en una línea de estudios iniciados en 19941, que va desde los problemas de la configuración del espacio público hasta la producción de subjetividad. En efecto, el proyecto inmediato anterior estuvo dedicado a la conceptualización del espacio público como lugar (comunicacionalmente constituido) de despliegue de las relaciones propiamente políticas de los distintos “actores sociales” con los institutos especializados de gobierno del estado, así como –en el otro caso– en la indagación en las formas de distanciamiento/desconocimiento que los nuevos actores erigen respecto de lo que estos institutos emblematizan. En éste, hemos trabajado sobre la constitución de los sujetos de la política, aventurando algunas conjeturas que intentamos precisar a través de un trabajo de campo, a saber, y de modo central, que la constitución y la intervención política de los sujetos resultan de procesos guiados antes por identificaciones afectivas, imaginarias, que a su vez encuentran su argamasa en el tejido cultural de una presunta comunidad, que por itinerarios de la racionalidad. Dicho en breve, este aspecto es el que nos propusimos rastrear esta vez, mediante entrevistas en profundidad, tomando como referencia algunos procesos recientes como el conflicto de 2008, marcado por el significante “campo”, que fue tema excluyente de la agenda política durante 126 días

The RNA Polymerase II Factor RPAP1 Is Critical for Mediator-Driven Transcription and Cell Identity

The RNA polymerase II-associated protein 1 (RPAP1) is conserved across metazoa and required for stem cell differentiation in plants; however, very little is known about its mechanism of action or its role in mammalian cells. Here, we report that RPAP1 is essential for the expression of cell identity genes and for cell viability. Depletion of RPAP1 triggers cell de-differentiation, facilitates reprogramming toward pluripotency, and impairs differentiation. Mechanistically, we show that RPAP1 is essential for the interaction between RNA polymerase II (RNA Pol II) and Mediator, as well as for the recruitment of important regulators, such as the Mediator-specific RNA Pol II factor Gdown1 and the C-terminal domain (CTD) phosphatase RPAP2. In agreement, depletion of RPAP1 diminishes the loading of total and Ser5-phosphorylated RNA Pol II on many genes, with super-enhancer-driven genes among the most significantly downregulated. We conclude that Mediator/RPAP1/RNA Pol II is an ancient module, conserved from plants to mammals, critical for establishing and maintaining cell identity.We are grateful to Elisa Varela for assistance with morula and blastocyst fixa- tion. Work in the laboratory of M.S. is funded by the CNIO and the IRB and by grants from the Spanish Ministry of Economy co-funded by the European Regional Development Fund (ERDF) (SAF2013-48256-R), the European Research Co uncil (ERC-2014-AdG/66 9622), the Region al Government of Ma- drid co-funded by the Euro pean Social Fund (ReCaRe project), the Euro pean Union (RISK-IR project), the Botin Foundation and Banco Santander (Santander Universities Glo bal Division), the Ramon Areces Found ation, and the AXA Foundation. S.R. was funded by a contract from the Ramon y Cajal Program(RYC-2011-09242) and by the Spanish Ministry of Economy co- funded by the ERDF (SAF2013-49147- P and SAF2016-80874-PS

¿Es suficiente la protección otorgada por gafas plomadas en cardiología intervencionista?

Background: It is not known whether leaded glass goggles with 0.25 mm Pb equivalency, used in interventional cardiology procedures, attenuate radiation below the levels established by the latest recommendation of the International Commission on Radiological Protection (ICRP). Aim: To assess ifthe degree of attenuation of the secondary ionizing radiation achieved by the use of 0.25 mm Pb leaded glass goggles, in occupationally exposed workers in interventional cardiology procedures, meets the latest ICRP recommendations. Material and Methods: A prospective investigation was carried out to compare the eye exposure to secondary ionizing radiation received by occupationally exposed personnel in a 9 months period. A set of two thermo luminescent dosimeters was arranged in the front and back of leaded glass goggles in a cohort ofseven members of an interventional cardiology service, exposed to 1057 consecutive procedures. Results: The monthly dose equivalent measurement performed in front ofthe goggles ranged between 1.1 and 6.5 mSv, for paramedics and interventional cardiologists. The radiation measured in the back of the glass varied between 0.66 and 2.75 mSv, respectively. The degree of attenuation of the dose at eye level ranged from 40% to 57.7%, respectively. The projected annual exposure would reach 33 mSvfor the interventional cardiologist. Conclusions: With a similar load ofwork and wearing 0.25 mm Pb equivalent glass goggles, interventional cardiologists will exceed the crystalline equivalent dose limit recommended by the ICRP (20 mSv/year averaged over the past 5 years)

Guía de práctica clínica para el tratamiento del cáncer de próstata metastásico hormonosensible en el Seguro Social del Perú (EsSalud)

Introduction: This article summarizes the clinical practice guideline (CPG) for the treatment of metastatic hormone-sensitive prostate cancer in the Social Security of Peru (EsSalud). Objective: To provide evidence-based clinical recommendations for the treatment of adults with hormone-sensitive metastatic adenocarcinoma of the prostate with de novo or recurrent presentation and high or low metastatic volume in EsSalud. Methods: A guideline development group (GDG) was formed, which included specialist physicians and methodologists, who formulated clinical questions. Systematic searches were conducted for systematic reviews and - when deemed relevant - primary studies in PubMed during 2022. Evidence was selected to answer each of the clinical questions posed. The certainty of evidence was assessed using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) methodology. In periodic working meetings, the GEG used the GRADE methodology to review the evidence and formulate recommendations. The CPG was reviewed by external experts before its approval. Results: The CPG addressed 6 clinical questions, divided into 2 main topics: considerations on androgen deprivation therapy (ADT) and ADT combined with other therapies. Based on these questions, 10 recommendations were formulated (4 strong and 6 conditional), and 6 points of good clinical practice. Conclusion: Evidence-based recommendations were issued for the management of patients with this pathology.Introducción: Este artículo resume la guía de práctica clínica (GPC) para el tratamiento del cáncer de próstata metastásico hormonosensible en el Seguro Social del Perú (EsSalud). Objetivo: Proveer recomendaciones clínicas basadas en evidencia para el tratamiento de adultos con adenocarcinoma de próstata metastásico hormonosensible con presentación de novo o recurrente y de alto o bajo volumen metastásico en EsSalud. Métodos: Se conformó un grupo elaborador de la guía (GEG) que incluyó médicos especialistas y metodólogos, el cual formuló preguntas clínicas. Se realizaron búsquedas sistemáticas de revisiones sistemáticas y –cuando fue considerado pertinente– estudios primarios en PubMed durante el 2022. Se seleccionó la evidencia para responder cada una de las preguntas clínicas planteadas. Se evaluó la certeza de evidencia usando la metodología Grading of Recommendations Assessment, Development, and Evaluation (GRADE). En reuniones de trabajo periódicas, el GEG usó la metodología GRADE para revisar la evidencia y formular las recomendaciones. La GPC fue revisada por expertos externos antes de su aprobación. Resultados: La GPC abordó 6 preguntas clínicas, divididas en 2 temas principales: consideraciones sobre la terapia de deprivación androgénica (TDA) y TDA combinada con otras terapias. En base a dichas preguntas se formularon 10 recomendaciones (4 fuertes y 6 condicionales) y 6 puntos de buena práctica clínica. Conclusión: Se emitieron recomendaciones basadas en evidencia para el manejo de pacientes con esta patología

The Fourteenth Data Release of the Sloan Digital Sky Survey: First Spectroscopic Data from the extended Baryon Oscillation Spectroscopic Survey and from the second phase of the Apache Point Observatory Galactic Evolution Experiment

The fourth generation of the Sloan Digital Sky Survey (SDSS-IV) has been in operation since July 2014. This paper describes the second data release from this phase, and the fourteenth from SDSS overall (making this, Data Release Fourteen or DR14). This release makes public data taken by SDSS-IV in its first two years of operation (July 2014-2016). Like all previous SDSS releases, DR14 is cumulative, including the most recent reductions and calibrations of all data taken by SDSS since the first phase began operations in 2000. New in DR14 is the first public release of data from the extended Baryon Oscillation Spectroscopic Survey (eBOSS); the first data from the second phase of the Apache Point Observatory (APO) Galactic Evolution Experiment (APOGEE-2), including stellar parameter estimates from an innovative data driven machine learning algorithm known as "The Cannon"; and almost twice as many data cubes from the Mapping Nearby Galaxies at APO (MaNGA) survey as were in the previous release (N = 2812 in total). This paper describes the location and format of the publicly available data from SDSS-IV surveys. We provide references to the important technical papers describing how these data have been taken (both targeting and observation details) and processed for scientific use. The SDSS website (www.sdss.org) has been updated for this release, and provides links to data downloads, as well as tutorials and examples of data use. SDSS-IV is planning to continue to collect astronomical data until 2020, and will be followed by SDSS-V.Comment: SDSS-IV collaboration alphabetical author data release paper. DR14 happened on 31st July 2017. 19 pages, 5 figures. Accepted by ApJS on 28th Nov 2017 (this is the "post-print" and "post-proofs" version; minor corrections only from v1, and most of errors found in proofs corrected