Modelo de gobierno de datos para una entidad tributaria peruana

El objetivo de esta tesis es determinar un modelo de gobierno de datos para la administraci?n tributaria peruana, la importancia percibida sobre su relaci?n con la calidad de datos y el valor. La necesidad de un modelo se da en un contexto en que las administraciones tributarias est?n utilizando t?cnicas anal?ticas avanzadas para mejorar el cumplimiento tributario, y se hace necesario ver sus datos como activos organizacionales. Un modelo de gobierno de datos permitir? identificar brechas, proponer acciones para su implementaci?n. Se revisan los conceptos te?ricos, se exploran modelos propuestos por diferentes autores e instituciones, se obtiene un modelo de gobierno de datos con los elementos derivados de la revisi?n bibliogr?fica. Se realiza el an?lisis contextual sobre otras entidades de gobierno en el mundo, sobre los hallazgos de una encuesta realizada en 55 pa?ses por el FTA de la OECD, y los planes estrat?gicos de administraciones tributarias de Argentina, Chile y Bolivia determinando las tendencias y modelo. Se analiza el ecosistema tributario en Per?, el plan estrat?gico de la entidad tributaria identificando la relaci?n con los elementos del modelo, esto permite determinar el modelo de gobierno de datos propuesto para la entidad tributaria peruana que incluye propuestas detalladas de implementaci?n

AGT haplotype in ITGA4 gene is related to antibody-mediated rejection in heart transplant patients

[Abstract] Introduction. One of the main problems involved in heart transplantation (HT) is antibody-mediated rejection (AMR). Many aspects of AMR are still unresolved, including its etiology, diagnosis and treatment. In this project, we hypothesize that variants in genes involved in B-cell biology in HT patients can yield diagnostic and prognostic information about AMR. Methods. Genetic variants in 61 genes related to B-cell biology were analyzed by next generation sequencing in 46 HT patients, 23 with and 23 without AMR. Results. We identified 3 single nucleotide polymorphisms in ITGA4 gene (c.1845G>A, c.2633A>G, and c.2883C>T) that conformed the haplotype AGT-ITGA4. This haplotype is associated with the development of AMR. Moreover, AMR patients with the haplotype AGT-ITGA4 present lower levels of integrin α-4 in serum samples compared to the reference GAC haplotype in control patients. Conclusion. We can conclude that polymorphisms in genes related to the biology of B-cells could have an important role in the development of AMR. In fact, the AGT haplotype in ITGA4 gene could potentially increase the risk of AMR.Instituto de Salud Carlos III; PI13/0217

La elaboración de la Ordenanza de Montes de Marina, de 31 de enero de 1748, base de la política oceánica de la monarquía española durante el siglo XVIII

The aim of this study is to analyze, from a legal and institutional perspective, the several preparatory work done by the Spanish monarchy in order to create, in 1748, a forest Ordinance for naval construction that competed with the needs of the rural populations who saw how their daily raw material, extracted from the trees.Este estudio pretende analizar, desde una perspectiva jurídico-institucional, los diversos trabajos preparatorios que abordó la Monarquía española con objeto de crear, en 1748, una Ordenanza forestal para fomento naval, que compitió con las necesidades de las poblaciones rurales que veían cómo les era despojada su materia prima cotidiana, extraída de los árboles

The nation of the persecuted scholars, episcopaliam, heresy and historical memory in the Courts of Cadiz

RESUMEN: Estudio el debate sobre la Inquisición en las Cortes de Cádiz, teniendo en cuenta la influencia de los libros de Llorente o Puigblanch y la definición del concepto de herejía que se hizo por la Comisión de Constitución. Esto es lo que marcó la nueva visión del pasado español por parte de los diputados liberales. Fueron muy críticos con la Inquisición por sus procedimientos, pero mantuvieron el delito de herejía. De ese pasado quedaron excluidos los descendientes de «judíos» y «moros». Los nuevos «mártires» habían sido los teólogos, biblistas y escritores del XVI perseguidos por la Inquisición. Criticaron el proceso inquisitorial contra el arzobispo Carranza como ataque a la jurisdicción episcopal, poniéndole como ejemplo de prelado sabio y evangélico. Más que en principios liberales, el decreto de abolición de 22 de febrero de 1813 se inscribió en la lógica de propuestas radicales del reformismo del reformismo borbónico.ABSTRACT: I study the debate on the Inquisition in the Cortes of Cadiz, taking into account the influence of Llorente or Puigblanch books and the definition of the concept of heresy that was made by the Committee on Constitution. This is what marked the new vision of the Spanish past by Liberal members. They were very critical of the Inquisition because of their procedures, but they kept the crime of heresy. The descendants of «Jews» and «moros» were excluded from that past. The new «martyrs» were theologians, Biblical scholars and writers of the 16th persecuted by the Inquisition. They criticized the Inquisition against Archbishop Carranza as attack the episcopal jurisdiction, putting him as an example of wise and Evangelical prelate. More on liberal principles, Decree of abolition of February 22, 1813 he joined the logic of radical proposals for the reformism of the Bourbon reformism.Este trabajo se ha realizado en el marco del proyecto de investigación HAR 2015-6894-C3-1-P. “De reinos a naciones. Las transformaciones del sistema cortesano (Siglos XVIII-XIX)”

Voltage Gated Calcium Channels Negatively Regulate Protective Immunity to Mycobacterium tuberculosis

Mycobacterium tuberculosis modulates levels and activity of key intracellular second messengers to evade protective immune responses. Calcium release from voltage gated calcium channels (VGCC) regulates immune responses to pathogens. In this study, we investigated the roles of VGCC in regulating protective immunity to mycobacteria in vitro and in vivo. Inhibiting L-type or R-type VGCC in dendritic cells (DCs) either using antibodies or by siRNA increased calcium influx in an inositol 1,4,5-phosphate and calcium release calcium activated channel dependent mechanism that resulted in increased expression of genes favoring pro-inflammatory responses. Further, VGCC-blocked DCs activated T cells that in turn mediated killing of M. tuberculosis inside macrophages. Likewise, inhibiting VGCC in infected macrophages and PBMCs induced calcium influx, upregulated the expression of pro-inflammatory genes and resulted in enhanced killing of intracellular M. tuberculosis. Importantly, compared to healthy controls, PBMCs of tuberculosis patients expressed higher levels of both VGCC, which were significantly reduced following chemotherapy. Finally, blocking VGCC in vivo in M. tuberculosis infected mice using specific antibodies increased intracellular calcium and significantly reduced bacterial loads. These results indicate that L-type and R-type VGCC play a negative role in M. tuberculosis infection by regulating calcium mobilization in cells that determine protective immunity

Discovering Conformational Sub-States Relevant to Protein Function

Background: Internal motions enable proteins to explore a range of conformations, even in the vicinity of native state. The role of conformational fluctuations in the designated function of a protein is widely debated. Emerging evidence suggests that sub-groups within the range of conformations (or sub-states) contain properties that may be functionally relevant. However, low populations in these sub-states and the transient nature of conformational transitions between these substates present significant challenges for their identification and characterization. Methods and Findings: To overcome these challenges we have developed a new computational technique, quasianharmonic analysis (QAA). QAA utilizes higher-order statistics of protein motions to identify sub-states in the conformational landscape. Further, the focus on anharmonicity allows identification of conformational fluctuations that enable transitions between sub-states. QAA applied to equilibrium simulations of human ubiquitin and T4 lysozyme reveals functionally relevant sub-states and protein motions involved in molecular recognition. In combination with a reaction pathway sampling method, QAA characterizes conformational sub-states associated with cis/trans peptidyl-prolyl isomerization catalyzed by the enzyme cyclophilin A. In these three proteins, QAA allows identification of conformational sub-states, with critical structural and dynamical features relevant to protein function. Conclusions: Overall, QAA provides a novel framework to intuitively understand the biophysical basis of conformational diversity and its relevance to protein function. © 2011 Ramanathan et al

Hepcidin Is Involved in Iron Regulation in the Ischemic Brain

Oxidative stress plays an important role in neuronal injuries caused by cerebral ischemia. It is well established that free iron increases significantly during ischemia and is responsible for oxidative damage in the brain. However, the mechanism of this ischemia-induced increase in iron is not completely understood. In this report, the middle cerebral artery occlusion (MCAO) rat model was performed and the mechanism of iron accumulation in cerebral ischemia-reperfusion was studied. The expression of L-ferritin was significantly increased in the cerebral cortex, hippocampus, and striatum on the ischemic side, whereas H-ferritin was reduced in the striatum and increased in the cerebral cortex and hippocampus. The expression level of the iron-export protein ferroportin1 (FPN1) significantly decreased, while the expression of transferrin receptor 1 (TfR1) was increased. In order to elucidate the mechanisms of FPN1 regulation, we studied the expression of the key regulator of FPN1, hepcidin. We observed that the hepcidin level was significantly elevated in the ischemic side of the brain. Knockdown hepcidin repressed the increasing of L-ferritin and decreasing of FPN1 invoked by ischemia-reperfusion. The results indicate that hepcidin is an important contributor to iron overload in cerebral ischemia. Furthermore, our results demonstrated that the levels of hypoxia-inducible factor-1α (HIF-1α) were significantly higher in the cerebral cortex, hippocampus and striatum on the ischemic side; therefore, the HIF-1α-mediated TfR1 expression may be another contributor to the iron overload in the ischemia-reperfusion brain

Anti-tumour necrosis factor discontinuation in inflammatory bowel disease patients in remission: study protocol of a prospective, multicentre, randomized clinical trial

Background: Patients with inflammatory bowel disease who achieve remission with anti-tumour necrosis factor (anti-TNF) drugs may have treatment withdrawn due to safety concerns and cost considerations, but there is a lack of prospective, controlled data investigating this strategy. The primary study aim is to compare the rates of clinical remission at 1?year in patients who discontinue anti-TNF treatment versus those who continue treatment. Methods: This is an ongoing, prospective, double-blind, multicentre, randomized, placebo-controlled study in patients with Crohn?s disease or ulcerative colitis who have achieved clinical remission for ?6?months with an anti-TNF treatment and an immunosuppressant. Patients are being randomized 1:1 to discontinue anti-TNF therapy or continue therapy. Randomization stratifies patients by the type of inflammatory bowel disease and drug (infliximab versus adalimumab) at study inclusion. The primary endpoint of the study is sustained clinical remission at 1?year. Other endpoints include endoscopic and radiological activity, patient-reported outcomes (quality of life, work productivity), safety and predictive factors for relapse. The required sample size is 194 patients. In addition to the main analysis (discontinuation versus continuation), subanalyses will include stratification by type of inflammatory bowel disease, phenotype and previous treatment. Biological samples will be obtained to identify factors predictive of relapse after treatment withdrawal. Results: Enrolment began in 2016, and the study is expected to end in 2020. Conclusions: This study will contribute prospective, controlled data on outcomes and predictors of relapse in patients with inflammatory bowel disease after withdrawal of anti-TNF agents following achievement of clinical remission. Clinical trial reference number: EudraCT 2015-001410-1