Environmental and geometrical effects on the mechanics of bonded composite joints in aerospace structures

Application of highly efficient bonded composite joints to flight critical aerospace structures is currently limited in use, and is generally applied to secondary structures where component failure is not detrimental to overall safety. Less efficient and more traditional fastened joints may be utilised as the behaviour is well understood and characterised thoroughly in literature. The limited use of bonded composite joints to primary components is partly due to the lack of damage tolerant assessment, particularly as a result from either adverse operational environments or defects in the bondline. It is currently problematic to evaluate the damage tolerant performance of bonded composite joints to an acceptable level due to the complexity of damage mechanisms and challenges in detection or monitoring of failure. The progression of damage is inherently difficult to appreciate because of different failure modes interacting and greatly influencing each other. These interactions can also be drastically affected by several features including changes in geometrical, material, boundary, and environmental conditions. Understanding the various failure modes under typical aerospace operational circumstances, with regards to types of bondline faults, is essential to analysing damage tolerance of bonded composite scarf joints in primary structural application. From thorough review of the literature, a comprehensive test program was conducted to investigate the quasi-static structural performance of bonded composite scarf joints under a vast array of geometrical and environmental conditions, representative of aerospace structures, which include the effects of pre-flawed bondlines. The identification of several critical failure mechanisms was highlighted, in both the adhesive layer and bonded adherends, where failure phenomena were captured through a variety of advanced imaging techniques including Scanning Electron Microscopy (SEM), optical microscopy, and micro Computed Tomography (μCT). The results of this program have highlighted the significance of not only the type of failure that occur for various joint conditions, but also the severity of each damage mechanism. Because of this work, the overall performance was directly compared to corresponding failure mechanisms, providing new insight towards damage tolerant assessment of bonded composite scarf joints. Extending from the knowledge gained in experimental test program, an extensive benchmark study was conducted to assess the “current-state-of-the-art” analysis of progressive damage modelling, towards bonded composite scarf joints, using the commercially available Abaqus CAE package. The results showed that current methods can provide great insight into the general performance and damage progression of bonded composite joints provided, however in certain aspects provided mixed results in terms of accurate strength predations, and the ability to represent failure mechanisms observed from experimental results. A new analysis methodology has been developed to overcome previous modelling limitations, which includes the combined effects of intralaminar adherend damage, interlaminar delamination, composite based debonding, inelastic bondline deformation and bulk failure of the adhesive layer. Using inbuilt Abaqus functions, Continuum Damage Mechanics (CDM) and Cohesive Zone Modelling (CZM) were used to describe the nature of damage progression in the current study. The use of CDM can be broken down further into the Abaqus fibre reinforce and ductile material failure models. CZM was used to simulate both interlaminar delamination and debonding at the adhesive adherend interface. To capture the simultaneous combination of all these non-linear failure methods, an explicit Finite Element (FE) integration scheme was used. Validation of the new methodology highlighted the requirement for simulating all failure mechanisms observed from experimental findings, to have a high-fidelity failure model which can accurately predict the behaviour of bonded composite scarf joints, over various geometrical and environmental conditions. For the first time, it can be seen how various geometries and environments have a significant effect on the development of damage, which causes overall failure in bonded composite scarf joints. For the conditions investigated in the experimental test program, significant insight has been provided into not only when and where critical damage initiation regions are located, but also the interactions of failure progression which lead to a loss in performance. This critical assessment of failure mechanisms has lead to the development of simple design guidelines which will aid in the critical analysis of bonded composite joints towards flight critical structures. These guidelines focus on critical areas where damage will initiate and progress, to provide joint design allowables which will not cause significant irreversible deformation, or minimise the effects of critical damage progression. The research presented within this thesis is significant to the development of future bonded composite scarf joints, towards application in flight critical structures, in terms of both aircraft safety and structural efficiency

The PRIDE database and related tools and resources in 2019: improving support for quantification data

The PRoteomics IDEntifications (PRIDE) database (https://www.ebi.ac.uk/pride/) is the world's largest data repository of mass spectrometry-based proteomics data, and is one of the founding members of the global ProteomeXchange (PX) consortium. In this manuscript, we summarize the developments in PRIDE resources and related tools since the previous update manuscript was published in Nucleic Acids Research in 2016. In the last 3years, public data sharing through PRIDE (as part of PX) has definitely become the norm in the field. In parallel, data re-use of public proteomics data has increased enormously, with multiple applications. We first describe the new architecture of PRIDE Archive, the archival component of PRIDE. PRIDE Archive and the related data submission framework have been further developed to support the increase in submitted data volumes and additional data types. A new scalable and fault tolerant storage backend, Application Programming Interface and web interface have been implemented, as a part of an ongoing process. Additionally, we emphasize the improved support for quantitative proteomics data through the mzTab format. At last, we outline key statistics on the current data contents and volume of downloads, and how PRIDE data are starting to be disseminated to added-value resources including Ensembl, UniProt and Expression Atlas

The PRoteomics IDEntification (PRIDE) Converter 2 Framework: An Improved Suite of Tools to Facilitate Data Submission to the PRIDE Database and the ProteomeXchange Consortium

The original PRIDE Converter tool greatly simplified the process of submitting mass spectrometry (MS)-based proteomics data to the PRIDE database. However, after much user feedback, it was noted that the tool had some limitations and could not handle several user requirements that were now becoming commonplace. This prompted us to design and implement a whole new suite of tools that would build on the successes of the original PRIDE Converter and allow users to generate submission-ready, well-annotated PRIDE XML files. The PRIDE Converter 2 tool suite allows users to convert search result files into PRIDE XML (the format needed for performing submissions to the PRIDE database), generate mzTab skeleton files that can be used as a basis to submit quantitative and gel-based MS data, and post-process PRIDE XML files by filtering out contaminants and empty spectra, or by merging several PRIDE XML files together. All the tools have both a graphical user interface that provides a dialog-based, user-friendly way to convert and prepare files for submission, as well as a command-line interface that can be used to integrate the tools into existing or novel pipelines, for batch processing and power users. The PRIDE Converter 2 tool suite will thus become a cornerstone in the submission process to PRIDE and, by extension, to the ProteomeXchange consortium of MS-proteomics data repositories.publishedVersio

Application of BRET to monitor ligand binding to GPCRs

Bioluminescence resonance energy transfer (BRET) is a well-established method for investigating protein-protein interactions. Here we present a BRET approach to monitor ligand binding to G protein–coupled receptors (GPCRs) on the surface of living cells made possible by the use of fluorescent ligands in combination with a bioluminescent protein (NanoLuc) that can be readily expressed on the N terminus of GPCRs

Building ProteomeTools based on a complete synthetic human proteome.

We describe ProteomeTools, a project building molecular and digital tools from the human proteome to facilitate biomedical research. Here we report the generation and multimodal liquid chromatography-tandem mass spectrometry analysis of \u3e330,000 synthetic tryptic peptides representing essentially all canonical human gene products, and we exemplify the utility of these data in several applications. The resource (available at http://www.proteometools.org) will be extended to \u3e1 million peptides, and all data will be shared with the community via ProteomicsDB and ProteomeXchange

Itaconate Links Inhibition of Succinate Dehydrogenase with Macrophage Metabolic Remodeling and Regulation of Inflammation

Remodeling of the tricarboxylic acid (TCA) cycle is a metabolic adaptation accompanying inflammatory macrophage activation. During this process, endogenous metabolites can adopt regulatory roles that govern specific aspects of inflammatory response, as recently shown for succinate, which regulates the pro-inflammatory IL-1β-HIF-1α axis. Itaconate is one of the most highly induced metabolites in activated macrophages, yet its functional significance remains unknown. Here, we show that itaconate modulates macrophage metabolism and effector functions by inhibiting succinate dehydrogenase-mediated oxidation of succinate. Through this action, itaconate exerts anti-inflammatory effects when administered in vitro and in vivo during macrophage activation and ischemia-reperfusion injury. Using newly generated Irg1(−/−) mice, which lack the ability to produce itaconate, we show that endogenous itaconate regulates succinate levels and function, mitochondrial respiration, and inflammatory cytokine production during macrophage activation. These studies highlight itaconate as a major physiological regulator of the global metabolic rewiring and effector functions of inflammatory macrophages

Minería de datos para el descubrimiento de patrones en enfermedades respiratorias en Bogotá, Colombia

Trabajo de InvestigaciónEl presente proyecto se basa en la aplicación de minería de datos mediante el algoritmo de clustering K- means que permita la generación de un modelo descriptivo con el análisis de los datos y con el objetivo de identificar posibles comportamientos en enfermedades respiratorias en la ciudad de Bogotá. El conjunto de clústeres generados por la herramienta RapidMiner es la recopilación de datos de un periodo de cinco años de 2012 a 2016, en donde se contemplan el número de casos asociados a 184 diagnósticos de enfermedades respiratorias y la edad de los pacientes corresponde de 0 a 5 años.Trabajo de Investigación1. GENERALIDADES 2. OBJETIVOS 3. JUSTIFICACIÓN 4. DELIMITACIÓN 5. MARCO REFERENCIAL 6. METODOLOGÍA 7. FUENTES DE EXTRACCIÓN Y SUS VARIABLES 8. DISEÑO 9. SELECCIÓN DE ALGORITMOS DE CLUSTERING 10. RECONOCER PATRONES A PARTIR DE LA INFORMACIÓN RECOPILADA 11. CONCLUSIONES 12. TRABAJOS FUTUROS 13. REFERENCIAS BIBLIOGRÁFICAS 14. ANEXOSPregradoIngeniero de Sistema

Inducing cancer indolence by targeting mitochondrial Complex I is potentiated by blocking macrophage-mediated adaptive responses

Converting carcinomas in benign oncocytomas has been suggested as a potential anti-cancerstrategy. One of the oncocytoma hallmarks is the lack of respiratory complex I (CI). Herewe use genetic ablation of this enzyme to induce indolence in two cancer types, andshow this is reversed by allowing the stabilization of Hypoxia Inducible Factor-1 alpha(HIF-1α). We further show that on the long run CI-deficient tumors re-adapt to their inabilityto respond to hypoxia, concordantly with the persistence of human oncocytomas. Wedemonstrate that CI-deficient tumors survive and carry out angiogenesis, despite theirinability to stabilize HIF-1α. Such adaptive response is mediated by tumor associated mac-rophages, whose blockage improves the effect of CI ablation. Additionally, the simultaneouspharmacological inhibition of CI function through metformin and macrophage infiltrationthrough PLX-3397 impairs tumor growth in vivo in a synergistic manner, setting the basisfor an efficient combinatorial adjuvant therapy in clinical trials