Molecular Strategies to Distinguish Key Subphenotypes in Sarcoidosis

Sarcoidosis is a multisystemic disease of unknown etiology and unpredictable course, characterized by histopathological conglomerates of inflammatory cells defined as granulomas. These lesions however are non-pathognomonic, and in the absence of an identifiable etiologic agent, there are not specific diagnostic test for sarcoidosis. Despite the variable course of sarcoidosis, the lungs are affected in 90 percent of the cases. Approximately 25-30% of sarcoidosis patients progress to a complicated phenotype with progressive disease, leading to pulmonary fibrosis and organ dysfunction with increased mortality. These cases are in desperate need for biomarkers, conventional sarcoidosis biomarkers have proven to be insufficiently sensitive for implementation in routine clinical care. In this dissertation, I focused on the use of alternate strategies for biomarkers development utilizing genomic base approaches based on high-throughput molecular assays to characterize genotype, gene expression, and epigenetics that define sarcoidosis subphenotypes. Our results demonstrated that the integration of expression quantitative loci (eQTL) studies increase the power of Genome-wide association studies (GWAS). We identified SNPs that were associated to complicated sarcoidosis in African Americans (AA) and in European Americans (EA), and then we validated these SNPs by Massarray. Furthermore, at the transcript level, we identified the Peripheral Mononuclear Cells (PBMCs) responses to TNF-α exposure, a cytokine involved in the initiation of granulomas and progression of fibrosis in sarcoidosis and identified a differential dysregulation in pathways unique to complicated sarcoidosis. At the transcriptome level, we profiled microdisected granulomas from lung and lymph nodes, and identified a hub of genes that were dysregulated only in sarcoidosis in both compartments. Additionally, we compared the genomic profile of these granulomas in Sarcoidosis vs Tuberculosis (TB) and Coccidioidomycosis. We corroborated that some genes previously suggested as potential sarcoidosis markers were also present in fungal or mycobacterium granulomas, pointing to a common mechanistic origin. We also demonstrated a strong similarity at the transcriptional level between Sarcoidosis and TB. The contribution of the epigenetic mechanisms to the clinical presentation of sarcoidosis was assessed through DNA methylation analysis, complicated sarcoidosis reveled a hypo-methylated pattern in genes within HLA complex while the miRNA analysis derived a molecular signature consisting of 17 protein-coding genes, potentially regulated by 8 miRNAs dysregulated in complicated sarcoidosis

Investigation of the effect of contact pattern design on the mechanical and thermal behaviors of plastic-steel helical gear drives

This article describes an investigation that has been conducted to assess the effects of the contact pattern design on the mechanical and thermal behaviors of plastic-steel helical gear drives. The maximum contact pressure, frictional power loss, transmission error function and operating temperature are determined for different designs of the pinion tooth surfaces. Several numerical examples based on loaded tooth contact analyses and steady-state heat transfer analyses are carried out considering different types of micro-geometry modifications of the involute tooth surfaces. The obtained results show that an appropriate design of the pinion tooth surfaces can help reducing the maximum contact pressure and the maximum operating temperature, increasing the durability of the transmission. The frictional power loss and the peak-to-peak transmission error can be diminished, improving the performance of the transmission and increasing its efficiency. Also, it has been shown that the design of the pinion tooth surfaces can provide some capability to the transmission to absorb angular misalignments.Funding for open access charge: CRUE-Universitat Jaume

Sistema de predicción de kilometraje y servicios automotrices

Actualmente en el Perú, muchas empresas concesionarias o talleres automotrices, no cuentan con sistemas ERP o sistemas que realicen predicciones sobre los servicios que brindan, generando una disminución de ingresos a por la pérdida de clientes y falta o sobre stock de repuestos. Debido a este problema se realizó la investigación y desarrollo de un sistema de predicción de futuros servicios de mantenimiento de vehículos, utilización de recursos y análisis de clientes, lo cual podrá aumentar la rentabilidad y calidad de servicio, de los concesionarios y talleres automotrices. En este primer producto mínimo viable, se desarrolló un software de escritorio por medio del cual los clientes podrán ingresar su base de datos de servicios de mantenimiento realizados en formato Excel, luego se podrá añadir nuevos datos y actualizar el proceso en el que se encuentra el servicio, también se podrá exportar esta base de datos actualizada. Finalmente, el valor agregado de este producto mínimo viable será la predicción de servicios de mantenimiento según vehículo, modelo de vehículo, predicción de utilización de recursos y análisis de los clientes, toda esta información se mostrará con sus porcentajes de exactitud. Concluyendo con las pruebas realizadas para las predicciones de servicios de mantenimiento excluyendo los outliers, el 63% de las predicciones tuvo un error de entre -2000 y 2000 kilómetros, y el 47% de las predicciones tuvo un error de entre -1000 y 1000 kilómetros.Currently in Peru, many dealerships or automotive workshops do not have ERP systems or systems that make predictions about the services they provide, generating a decrease in revenue due to loss of customers and lack or overstock of spare parts. Due to this problem, the research and development of a predictive system for future vehicle maintenance services, resource utilization and customer analysis was carried out, which will increase the profitability and quality of service of automotive dealerships and workshops. In this first minimum viable product, a desktop software was developed through which customers can enter their database of maintenance services performed in Excel format, then they can add new data and update the process in which the service is, and can also export this updated database. Finally, the added value of this minimum viable product will be the prediction of maintenance services according to vehicle, vehicle model, resource utilization prediction and customer analysis, all this information will be displayed with their accuracy percentages. Concluding with the tests performed for the predictions of maintenance services excluding outliers, 63% of the predictions had an error between -2000 and 2000 kilometers, and 47% of the predictions had an error between -1000 and 1000 kilometers

Radiowave Propagation Prediction in a Wind Farm Enviroment and Wind Turbine Scattering Model

One of the environmental effects of wind farms is the electromagnetic interference due to the scattering produced by the wind turbines on the electromagnetic waves of different radio communication services propagating through them. A previous work [4] is updated here and the scattering models for the nacelle and the wind turbine are shown and validated. Radio wave propagation losses are estimated more precisely through a parabolic equation approach. Finally, a comparison between theoretical and measured values for the Power Delay Profile (PDP) of the multipath channel through a wind farm is showed

Interferencias de los parques eólicos en el servicio de TV

This paper analyzes the problematic of the interferences created by wind farms. Wind turbines may cause interferences to television and microwave signals due to reflections and diffractions of those signals from both the tower (stationary) and the blades (non-stationary). The ITU Radiocommunication Assembly, on the BT 805 [1], specifies a simplified model of impairment caused to television reception by a single wind turbine considering only free space propagation. This paper shows the extensions to a multiple turbine case, the inclusion of other propagation models (plain earth and ITU-R P.1546) and presents more accurate models to obtain the scattering produced by a wind turbine, as well as their implementation on friendly-use softwar