Development of a simulation platform of all-electric aircraft on-board systems for energy management studies

This paper deals with the development of a simulation platform for the dynamic analysis of systems characterised by different physical domains. The research has been carried out in the context of the EC-funded Clean Sky Joint Technology Initiative (Green Regional Aircraft/All-Electric Aircraft domain). In particular, the objective of the research is focused on the on-board systems of new All-Electric Aircraft, where a crucial design point is related to the electrical energy management. In the “all-electric” concept, where pneumatic and hydraulic power systems are eliminated to improve aviation costs and environmental impact, the dynamics of electrical power absorptions is to be characterised and managed to avoid excessive peaks with respect to generators capabilities. The paper describes the architecture of a Matlab/Simulink simulation platform developed in order to design and validate of the electrical energy management logics, which lead up to 32% reduction of the maximum power request for the case study considered. Thanks to an approach based on a mixing of cosimulation and S-function compiling, the platform integrates models coming from different environments (AMESim, Dymola/Modelica), and developed by various partners/specialists

VEGF188 promotes corneal reinnervation after injury

Vascular endothelial growth factor A (VEGF) induces angiogenesis and vascular hyperpermeability in ocular tissues and is therefore a key therapeutic target for eye conditions in which these processes are dysregulated. In contrast, the therapeutic potential of VEGF's neurotrophic roles in the eye has remained unexploited. In particular, it is not known whether modulating levels of any of the 3 major alternatively spliced VEGF isoforms might provide a therapeutic approach to promote neural health in the eye without inducing vascular pathology. Here, we have used a variety of mouse models to demonstrate differences in overall VEGF levels and VEGF isoform ratios across tissues in the healthy eye. We further show that VEGF isoform expression was differentially regulated in retinal versus corneal disease models. Among the 3 major isoforms - termed VEGF120, VEGF164, and VEGF188 - VEGF188 was upregulated to the greatest extent in injured cornea, where it was both necessary and sufficient for corneal nerve regeneration. Moreover, topical VEGF188 application further promoted corneal nerve regeneration without inducing pathological neovascularization. VEGF isoform modulation should therefore be explored further for its potential in promoting neural health in the eye

A Study on the Use of XCT and FEA to Predict the Elastic Behavior of Additively Manufactured Parts of Cylindrical Geometry

Defining general criteria for the acceptability of defects within industrial components is often complicated, since the specific load conditions and the criticality of the given application should be considered individually. In order to minimize the risk of failure, high safety factors are commonly adopted during quality control. However this practice is likely to cause the rejection of components whose defects would be instead acceptable if a more sound knowledge of the component behaviour were achieved. Parts produced by additive manufacturing (AM) may suffer from various defects, including micro- or macro-holes, delamination and microstructural discontinuities. Such processes, which are specially suitable for one-off components, require robust and reliable inspection before a part is accepted or rejected, since the refusal of even a single part at the end of the production process represents a significant loss. For this reason, it would be very useful to simulate in a reliable way whether a certain defect is truly detrimental to the proper working of the part during operation or whether the component can still be used, despite the presence of a defect. To this purpose, the paper highlights the benefits of a synergistic interaction between Industrial X-ray computed tomography (XCT) and finite element analysis (FEA). Internal defects of additively manufactured parts can be identified in a non-destructive way by means of XCT. Then FEA can be performed on the XCT-based virtual model of the real component, rather than on the ideal CAD geometry. A proof of concept of this approach is proposed here for a reference construct produced in an Aluminium alloy by AM. Numerical results of the proposed combined XCT–FEA procedure are contrasted with experimental data from tensile tests. The findings sustain the reliability of the method and allow to assess its full provisional accuracy for parts of cylindrical geometry designed to operate in the elastic field. The paper moves a step beyond the present application limits of tomography as it is currently employed for AM parts and it evidences instead the possibility of extending the usage of tomography to acceptance testing and prediction of operative behaviour

Data segmentation based on the local intrinsic dimension

One of the founding paradigms of machine learning is that a small number of variables is often sufficient to describe high-dimensional data. The minimum number of variables required is called the intrinsic dimension (ID) of the data. Contrary to common intuition, there are cases where the ID varies within the same data set. This fact has been highlighted in technical discussions, but seldom exploited to analyze large data sets and obtain insight into their structure. Here we develop a robust approach to discriminate regions with different local IDs and segment the points accordingly. Our approach is computationally efficient and can be proficiently used even on large data sets. We find that many real-world data sets contain regions with widely heterogeneous dimensions. These regions host points differing in core properties: folded versus unfolded configurations in a protein molecular dynamics trajectory, active versus non-active regions in brain imaging data, and firms with different financial risk in company balance sheets. A simple topological feature, the local ID, is thus sufficient to achieve an unsupervised segmentation of high-dimensional data, complementary to the one given by clustering algorithms

Antigen Retrieval and Its Effect on the MALDI-MSI of Lipids in Formalin-Fixed Paraffin-Embedded Tissue

Formalin-fixed paraffin-embedded (FFPE) tissue represents the primary source of clinical tissue and is routinely used in MALDI-MSI studies. However, it is not particularly suitable for lipidomics imaging given that many species are depleted during tissue processing. Irrespective, a number of solvent-resistant lipids remain, but their extraction may be hindered by the cross-link between proteins. Therefore, an antigen retrieval step could enable the extraction of a greater number of lipids and may provide information that is complementary to that which can be obtained from other biomolecules, such as proteins. In this short communication, we aim to address the effect of performing antigen retrieval prior to MALDI-MSI of lipids in FFPE tissue. As a result, an increased number of lipid signals could be detected and may have derived from lipid species that are known to be implicated in the lipid-protein cross-linking that is formed as a result of formalin fixation. Human renal cancer tissue was used as a proof of concept to determine whether using these detected lipid signals were also able to highlight the histopathological regions that were present. These preliminary findings may highlight the potential to enhance the clinical relevance of the lipidomic information obtained from FFPE tissue

In-Depth Mapping of the Urinary N-Glycoproteome: Distinct Signatures of ccRCC-related Progression

Protein N-glycosylation is one of the most important post-translational modifications and is involved in many biological processes, with aberrant changes in protein N-glycosylation patterns being closely associated with several diseases, including the progression and spreading of tumours. In light of this, identifying these aberrant protein glycoforms in tumours could be useful for understanding the molecular mechanism of this multifactorial disease, developing specific biomarkers and finding novel therapeutic targets. We investigated the urinary N-glycoproteome of clear cell renal cell carcinoma (ccRCC) patients at different stages (n = 15 at pT1 and n = 15 at pT3), and of non-ccRCC subjects (n = 15), using an N-glyco-FASP-based method. Using label-free nLC-ESI MS/MS, we identified and quantified several N-glycoproteins with altered expression and abnormal changes affecting the occupancy of the glycosylation site in the urine of RCC patients compared to control. In particular, nine of them had a specific trend that was directly related to the stage progression: CD97, COCH and P3IP1 were up-expressed whilst APOB, FINC, CERU, CFAH, HPT and PLTP were down-expressed in ccRCC patients. Overall, these results expand our knowledge related to the role of this post-translational modification in ccRCC and translation of this information into pre-clinical studies could have a significant impact on the discovery of novel biomarkers and therapeutic target in kidney cancer

Concentration-dependent antagonism and culture conversion in pulmonary tuberculosis

Background There is scant evidence to support target drug exposures for optimal tuberculosis outcomes. We therefore assessed whether pharmacokinetic/pharmacodynamic (PK/PD) parameters could predict 2-month culture conversion. Methods One hundred patients with pulmonary tuberculosis (65% HIV-co-infected) were intensively sampled to determine rifampicin, isoniazid and pyrazinamide plasma concentrations after 7-8 weeks of therapy, and pharmacokinetic parameters determined using non-linear-mixed-effects models. Detailed clinical data and sputum for culture were collected at baseline, 2 and 5-6 months. Minimum inhibitory concentrations (MIC) were determined on baseline isolates. Multivariate logistic regression and the assumption-free multivariate adaptive regression splines (MARS) were used to identify clinical and PK/PD predictors of 2-month culture conversion. Potential PK/PD predictors included 24-hour-area-under-the-curve (AUC0-24), peak concentration (Cmax), AUC0-24/MIC, Cmax/MIC and % time that concentrations persisted above MIC (%TMIC). Results 26% of patients had Cmax (mg/L) of rifampicin4.6 mg/L, higher isoniazid exposures were associated with improved rates of culture conversion. Conclusions PK/PD analyses using MARS identified isoniazid Cmax and rifampicin Cmax/MIC thresholds below which there is concentration-dependent antagonism that reduces 2-month sputum culture conversion

Manufacturing of PAV-ONE, a Permeator against Vacuum Mock-Up with Niobium Membrane

The Permeator Against Vacuum (PAV) is one of the proposed technologies for the Tritium Extraction System of the WCLL BB (Water-Cooled Lithium-Lead Breeding Blanket) of the EU DEMO reactor. In this paper, the manufacturing of the first PAV mock-up with a niobium membrane with a cylindrical configuration is presented. This work aimed to demonstrate the possibility of manufacturing a relevant-size PAV to be later tested in the TRIEX-II facility. The adopted prototypical solutions are described in detail, starting with the methodology developed to join the Nb tubes with a 10CrMo9-10 (A182 F22) plate. Dedicated manufacturing and welding procedures, based on vacuum brazing with a nickel-based brazing alloy, were developed to solve the problem. This new kind of brazing was first analyzed to check the morphology of the joint and then tested to check its capability to withstand the TRIEX-II operative conditions. In parallel, the compatibility with a lithium-lead environment was analyzed by exposing samples of niobium and 10CrMo9-10 (A335 P22) to a flow of the eutectic alloy at 500 °C up to 4000 h. Finally, the PAV mock-up was installed in the TRIEX-II facility

211 * CLINICAL AND ANATOMICAL PREDICTORS OF MITRACLIP THERAPY FAILURE FOR FUNCTIONAL MITRAL REGURGITATION

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