Collaborative Engineering: An Airbus Case Study

AbstractThis document introduces the main concepts of Collaborative Engineering as a new methodology, procedures and tools to design and develop an aircraft, as Airbus Military is implementing.Airbus designs and industrializes aircrafts under Concurrent Engineering techniques since decades with success. The introduction of new PLM methodologies, procedures and tools, mainly in the industrialization areas, and the need to reduce time-to-market conducted Airbus Military to push the engineering teams to do things in a different way.Traditional Engineering works sequentially, Concurrent Engineering basically overlaps tasks between teams using maturity states and taking assuming risks. Collaborative Engineering promotes a single team to develop product, processes and resources from the conceptual phase to the start of the serial production. The deliverable of the team is an iDMU (industrial DMU), a complete definition and verification of the virtual manufacturing of the product

AGN Black Hole Masses and Bolometric Luminosities

Black hole mass, along with mass accretion rate, is a fundamental property of active galactic nuclei. Black hole mass sets an approximate upper limit to AGN energetics via the Eddington limit. We collect and compare all AGN black hole mass estimates from the literature; these 177 masses are mostly based on the virial assumption for the broad emission lines, with the broad-line region size determined from either reverberation mapping or optical luminosity. We introduce 200 additional black hole mass estimates based on properties of the host galaxy bulges, using either the observed stellar velocity dispersion or using the fundamental plane relation to infer $\sigma$; these methods assume that AGN hosts are normal galaxies. We compare 36 cases for which black hole mass has been generated by different methods and find, for individual objects, a scatter as high as a couple of orders of magnitude. The less direct the method, the larger the discrepancy with other estimates, probably due to the large scatter in the underlying correlations assumed. Using published fluxes, we calculate bolometric luminosities for 234 AGNs and investigate the relation between black hole mass and luminosity. In contrast to other studies, we find no significant correlation of black hole mass with luminosity, other than those induced by circular reasoning in the estimation of black hole mass. The Eddington limit defines an approximate upper envelope to the distribution of luminosities, but the lower envelope depends entirely on the sample of AGN included. For any given black hole mass, there is a range in Eddington ratio of up to three orders of magnitude.Comment: 43 pages with 10 figures. Accepted for publication in Ap

Therapeutic intranasal vaccine HB-ATV-8 prevents atherogenesis and non-alcoholic fatty liver disease in a pig model of atherosclerosis

BACKGROUND AND AIMS: Atherosclerosis as an inflammatory disease involved in the etiology of cardiovascular disease worldwide, in our days demands an array of different therapeutic approaches in order to soon be able to visualize an effective prevention. Based on an immunotherapeutic approach, we designed a non-invasive vaccine (HB-ATV-8), contained in a micellar nanoparticle composed of lipids and a peptide segment derived from the C-terminus of the cholesterol-ester transfer protein (CETP). Now we extend our successful proof of concept from the rabbit to a porcine model and investigated its effect in an attempt to undoubtedly establish the efficacy of vaccination in a model closer to the human. METHODS: A preclinical trial was designed to study the efficacy of vaccine HB-ATV-8 in pigs (Large White × Landrace). Male experimental animals were fed with standard diet (control), high fat diet (HFD) or the same HFD but treated with HB-ATV-8 (HFD + Vaccine) applied nasally for up to 7 months. All biochemical and enzymatic analyses were performed in peripheral venous blood and thoracic aorta and liver samples examined using conventional, two-photon excitation and second harmonic generation microscopy to identify atherosclerotic and hepatic lesions. mRNA concentrations for KLF2, ACTA2, SOD1, COL1A1 genes and protein levels for PPARα and ABCA1 were quantified in aorta and liver respectively using qPCR and Western blot analysis. RESULTS: The administration of vaccine HB-ATV-8 induced anti-CETP IgG antibodies and reduced atherosclerotic and hepatic lesions promoted by the high fat diet. In addition, plasma triglyceride levels of vaccine treated pigs fed the HFD were similar to those of control group, in contrast to high concentrations reached with animals exclusively fed with HFD. Moreover, HFD promotes a tendency to decreased hepatic PPARα levels and increase in aorta gene expression of KLF2, ACTA2, SOD1 and COL1A1, while vaccine application promotes recovery close to control values. CONCLUSIONS: Vaccine HB-ATV-8 administration constitutes a promissory preventive approach useful in the control of atherogenesis and fatty liver disease. The positive results obtained, the non-invasive characteristics of the vaccine, the simple design employed in its conception and its low production cost, support the novelty of this therapeutic strategy designed to prevent the process of atherogenesis and control the development of fatty liver disease

Tumor-Associated Microbiome: Where Do We Stand?

The study of the human microbiome in oncology is a growing and rapidly evolving field. In the past few years, there has been an exponential increase in the number of studies investigating associations of microbiome and cancer, from oncogenesis and cancer progression to resistance or sensitivity to specific anticancer therapies. The gut microbiome is now known to play a significant role in antitumor immune responses and in predicting the efficacy of immune-checkpoint inhibitors in cancer patients. Beyond the gut, the tumor-associated microbiome-microbe communities located either in the tumor or within its body compartment-seems to interact with the local microenvironment and the tumor immune contexture, ultimately impacting cancer progression and treatment outcome. However, pre-clinical research focusing on causality and mechanistic pathways as well as proof-of-concept studies are still needed to fully understand the potential clinical utility of microbiome in cancer patients. Moreover, there is a need for the standardization of methodology and the implementation of quality control across microbiome studies to allow for a better interpretation and greater comparability of the results reported between them. This review summarizes the accumulating evidence in the field and discusses the current and upcoming challenges of microbiome studies

Tree-based ensembles unveil the microhabitat suitability for the invasive bleak (Alburnus alburnus L.) and pumpkinseed (Lepomis gibbosus L.): Introducing XGBoost to eco-informatics

[EN] Random Forests (RFs) and Gradient Boosting Machines (GBMs) are popular approaches for habitat suitability modelling in environmental flow assessment. However, both present some limitations theoretically solved by alternative tree-based ensemble techniques (e.g. conditional RFs or oblique RFs). Among them, eXtreme Gradient Boosting machines (XGBoost) has proven to be another promising technique that mixes subroutines developed for RFs and GBMs. To inspect the capabilities of these alternative techniques, RFs and GBMs were compared with: conditional RFs, oblique RFs and XGBoost by modelling, at the micro-scale, the habitat suitability for the invasive bleak (Alburnus alburnus L.) and pumpkinseed (Lepomis gibbosus L). XGBoost outperformed the other approaches, particularly conditional and oblique RFs, although there were no statistical differences with standard RFs and GBMs. The partial dependence plots highlighted the lacustrine origins of pumpkinseed and the preference for lentic habitats of bleak. However, the latter depicted a larger tolerance for rapid microhabitats found in run-type river segments, which is likely to hinder the management of flow regimes to control its invasion. The difference in the computational burden and, especially, the characteristics of datasets on microhabitat use (low data prevalence and high overlapping between categories) led us to conclude that, in the short term, XGBoost is not destined to replace properly optimised RFs and GBMs in the process of habitat suitability modelling at the micro-scale.This project had the support of Fundacion Biodiversidad, of Spanish Ministry for Ecological Transition. We want to thank the volunteering students of the Universitat Politecnica de Valencia, Marina de Miguel, Carlos A. Puig-Mengual, Cristina Barea, Rares Hugianu, and Pau Rodriguez. R. Munoz-Mas benefitted from a postdoctoral Juan de la Cierva fellowship from the Spanish Ministry of Science, Innovation and Universities (ref. FJCI-2016-30829). This research was supported by the Government of Catalonia (ref. 2017 SGR 548).Muñoz-Mas, R.; Gil-Martínez, E.; Oliva-Paterna, FJ.; Belda, E.; Martinez-Capel, F. (2019). Tree-based ensembles unveil the microhabitat suitability for the invasive bleak (Alburnus alburnus L.) and pumpkinseed (Lepomis gibbosus L.): Introducing XGBoost to eco-informatics. Ecological Informatics. 53:1-12. https://doi.org/10.1016/j.ecoinf.2019.100974S1125

Evolutive Unification in Composite Active Galactic Nuclei

In this paper we explore an evolutionary Unified scenario involving super massive black hole and starburst with outflow, that seems capable of explaining most of the observational properties of at least part of AGNs. Our suggestion is explored inside the expectations of the Starburst model close associated with the AGN where the NLR, BLR and BAL region are produced in part by the outflow process with shells and in compact supernova remnants. The outflow process in BAL QSOs with extreme IR and Fe II emission is studied. In addition, the Fe II poblem regarding the BLR of AGN is analysed. Neither the correlations between the BAL, IR emission, FeII intensity and the intrinsic properties of the AGN are clearly understood. We suggest here that the behaviour of the BAL, IR and FeII emission in AGNs can be understood inside an evolutionary and composite model for AGNs. In our model, strong BAL systems and Fe II emission are present (and intense) in young IR objects. Orientation/ obscuration effects take the role of a second parameter providing the segregation between Sy1/Sy2 and BLRG/NLRG.Comment: 14 pages, 6 figures (submitted MNRAS

Organizational linkages for new product development: Implementation of innovation projects

Effective external and internal organization linkage characterizes new product development. Although prior research covers the external linkages to gain operational efficiencies and develop new products, the current body of scholarship on internal cross-functional linkages requires further attention. This study provides a certain level of inquiry into the antecedents of such internal linkages and presents a framework to establish the relationship between two internal functions at major fast-moving consumer goods (FMCG). The study examines the implementation of 150 innovation projects in 6 different countries over a period of three years. The objective is to study the influence of trust dimension on the perceived effectiveness of cross-functional linkage to highlight how organizational mechanisms like the amount and quality of shared communication affect trust and relationship between two functions

A Self-Organizing Algorithm for Modeling Protein Loops

Protein loops, the flexible short segments connecting two stable secondary structural units in proteins, play a critical role in protein structure and function. Constructing chemically sensible conformations of protein loops that seamlessly bridge the gap between the anchor points without introducing any steric collisions remains an open challenge. A variety of algorithms have been developed to tackle the loop closure problem, ranging from inverse kinematics to knowledge-based approaches that utilize pre-existing fragments extracted from known protein structures. However, many of these approaches focus on the generation of conformations that mainly satisfy the fixed end point condition, leaving the steric constraints to be resolved in subsequent post-processing steps. In the present work, we describe a simple solution that simultaneously satisfies not only the end point and steric conditions, but also chirality and planarity constraints. Starting from random initial atomic coordinates, each individual conformation is generated independently by using a simple alternating scheme of pairwise distance adjustments of randomly chosen atoms, followed by fast geometric matching of the conformationally rigid components of the constituent amino acids. The method is conceptually simple, numerically stable and computationally efficient. Very importantly, additional constraints, such as those derived from NMR experiments, hydrogen bonds or salt bridges, can be incorporated into the algorithm in a straightforward and inexpensive way, making the method ideal for solving more complex multi-loop problems. The remarkable performance and robustness of the algorithm are demonstrated on a set of protein loops of length 4, 8, and 12 that have been used in previous studies

Pb(II) Induces Scramblase Activation and Ceramide-Domain Generation in Red Blood Cells

The mechanisms of Pb(II) toxicity have been studied in human red blood cells using confocal microscopy, immunolabeling, fluorescence-activated cell sorting and atomic force microscopy. The process follows a sequence of events, starting with calcium entry, followed by potassium release, morphological change, generation of ceramide, lipid flip-flop and finally cell lysis. Clotrimazole blocks potassium channels and the whole process is inhibited. Immunolabeling reveals the generation of ceramide-enriched domains linked to a cell morphological change, while the use of a neutral sphingomyelinase inhibitor greatly delays the process after the morphological change, and lipid flip-flop is significantly reduced. These facts point to three major checkpoints in the process: first the upstream exchange of calcium and potassium, then ceramide domain formation, and finally the downstream scramblase activation necessary for cell lysis. In addition, partial non-cytotoxic cholesterol depletion of red blood cells accelerates the process as the morphological change occurs faster. Cholesterol could have a role in modulating the properties of the ceramide-enriched domains. This work is relevant in the context of cell death, heavy metal toxicity and sphingolipid signaling.AGA was a predoctoral student supported by the Basque Government and later by the University of the Basque Country (UPV/EHU). This work was also supported in part by grants from the Spanish Government (FEDER/MINECO BFU 2015-66306-P to F.M.G. and A.A.) and the Basque Government (IT849-13 to F.M.G. and IT838-13 to A.A.), and by the Swiss National Science Foundation