Filtering for bilinear systems with a lipschitz nonlinearity using LPV approach

This paper deals with the H _?? filtering problem for a class of nonlinear systems. This class of nonlinear systems is composed of a bilinear part and of a lipschitzian one. The use of an unbiasedness condition for the bilinear part (called quasi unbiasedness condition) permits to parameterize the filter matrices through a single gain. Two LPV (Linear Parameter Varying) extensions of the bounded real lemma are used to solve the filtering problem. This approach reduces the conservatism inherent to the boundedness of the inputs. Then the filtering solution is expressed in terms of LMI (Linear Matrix Inequality) to be verified at the vertices of a polytope. A numerical example is finally given to illustrate our approach.     

Energy Metabolites as Biomarkers in Ischemic and Dilated Cardiomyopathy

With more than 25 million people affected, heart failure (HF) is a global threat. As energy production pathways are known to play a pivotal role in HF, we sought here to identify key metabolic changes in ischemic- and non-ischemic HF by using a multi-OMICS approach. Serum metabolites and mRNAseq and epigenetic DNA methylation profiles were analyzed from blood and left ventricular heart biopsy specimens of the same individuals. In total we collected serum from n = 82 patients with Dilated Cardiomyopathy (DCM) and n = 51 controls in the screening stage. We identified several metabolites involved in glycolysis and citric acid cycle to be elevated up to 5.7-fold in DCM (p = 1.7 × 10⁻⁶). Interestingly, cardiac mRNA and epigenetic changes of genes encoding rate-limiting enzymes of these pathways could also be found and validated in our second stage of metabolite assessment in n = 52 DCM, n = 39 ischemic HF and n = 57 controls. In conclusion, we identified a new set of metabolomic biomarkers for HF. We were able to identify underlying biological cascades that potentially represent suitable intervention targets.     

Ivabradine Induces Cardiac Protection against Myocardial Infarction by Preventing Cyclophilin-A Secretion in Pigs under Coronary Ischemia/Reperfusion

In response to cardiac ischemia/reperfusion, proteolysis mediated by extracellular matrix metalloproteinase inducer (EMMPRIN) and its secreted ligand cyclophilin-A (CyPA) significantly contributes to cardiac injury and necrosis. Here, we aimed to investigate if, in addition to the effect on the funny current (I(f)), Ivabradine may also play a role against cardiac necrosis by reducing EMMPRIN/CyPA-mediated cardiac inflammation. In a porcine model of cardiac ischemia/reperfusion (IR), we found that administration of 0.3 mg/kg Ivabradine significantly improved cardiac function and reduced cardiac necrosis by day 7 after IR, detecting a significant increase in cardiac CyPA in the necrotic compared to the risk areas, which was inversely correlated with the levels of circulating CyPA detected in plasma samples from the same subjects. In testing whether Ivabradine may regulate the levels of CyPA, no changes in tissue CyPA were found in healthy pigs treated with 0.3 mg/kg Ivabradine, but interestingly, when analyzing the complex EMMPRIN/CyPA, rather high glycosylated EMMPRIN, which is required for EMMPRIN-mediated matrix metalloproteinase (MMP) activation and increased CyPA bonding to low-glycosylated forms of EMMPRIN were detected by day 7 after IR in pigs treated with Ivabradine. To study the mechanism by which Ivabradine may prevent secretion of CyPA, we first found that Ivabradine was time-dependent in inhibiting co-localization of CyPA with the granule exocytosis marker vesicle-associated membrane protein 1 (VAMP1). However, Ivabradine had no effect on mRNA expression nor in the proteasome and lysosome degradation of CyPA. In conclusion, our results point toward CyPA, its ligand EMMPRIN, and the complex CyPA/EMMPRIN as important targets of Ivabradine in cardiac protection against IR.     

Electrolytic cell engineering and device optimization for electrosynthesis of e-biofuels via co-valorisation of bio-feedstocks and captured CO2

Utilizing CO₂ in an electro-chemical process and synthesizing value-added chemicals are amongst the few viable and scalable pathways in carbon capture and utilization technologies.CO₂ electro-reduction is also counted as one of the main options entailing less fossil fuel consumption and as a future electrical energy storage strategy.The current study aims at developing a new electrochemical platform to produce low-carbon e-biofuel through multifunctional electrosynthesis and integrated co-valorisation of biomass feedstocks with captured CO₂.In this approach,CO₂ is reduced at the cathode to produce drop-in fuels(e.g.,methanol)while value-added chemicals(e.g.,selective oxidation of alcohols,aldehydes,carboxylic acids and amines/amides)are produced at the anode.In this work,a numerical model of a continuous-flow design considering various anodic and cathodic reactions was built to determine the most techno-economically feasible configurations from the aspects of energy efficiency,environment impact and economical values.The reactor design was then optimized via parametric analysis.     

Pharmacologic Control of CAR T Cells

Chimeric antigen receptor (CAR) therapy is a promising modality for the treatment of advanced cancers that are otherwise incurable. During the last decade, different centers worldwide have tested the anti-CD19 CAR T cells and shown clinical benefits in the treatment of B cell tumors. However, despite these encouraging results, CAR treatment has also been found to lead to serious side effects and capricious response profiles in patients. In addition, the CD19 CAR success has been difficult to reproduce for other types of malignancy. The appearance of resistant tumor variants, the lack of antigen specificity, and the occurrence of severe adverse effects due to over-stimulation of the therapeutic cells have been identified as the major impediments. This has motivated a growing interest in developing strategies to overcome these hurdles through CAR control. Among them, the combination of small molecules and approved drugs with CAR T cells has been investigated. These have been exploited to induce a synergistic anti-cancer effect but also to control the presence of the CAR T cells or tune the therapeutic activity. In the present review, we discuss opportunistic and rational approaches involving drugs featuring anti-cancer efficacy and CAR-adjustable effect.     

The Prominin-1-Derived Peptide Improves Cardiac Function Following Ischemia

Myocardial infarction (MI) remains the leading cause of death in the western world. Despite advancements in interventional revascularization technologies, many patients are not candidates for them due to comorbidities or lack of local resources. Non-invasive approaches to accelerate revascularization within ischemic tissues through angiogenesis by providing Vascular Endothelial Growth Factor (VEGF) in protein or gene form has been effective in animal models but not in humans likely due to its short half-life and systemic toxicity. Here, we tested the hypothesis that PR1P, a small VEGF binding peptide that we developed, which stabilizes and upregulates endogenous VEGF, could be used to improve outcome from MI in rodents. To test this hypothesis, we induced MI in mice and rats via left coronary artery ligation and then treated animals with every other day intraperitoneal PR1P or scrambled peptide for 14 days. Hemodynamic monitoring and echocardiography in mice and echocardiography in rats at 14 days showed PR1P significantly improved multiple functional markers of heart function, including stroke volume and cardiac output. Furthermore, molecular biology and histological analyses of tissue samples showed that systemic PR1P targeted, stabilized and upregulated endogenous VEGF within ischemic myocardium. We conclude that PR1P is a potential non-invasive candidate therapeutic for MI.     

Processing,microstructure, and mechanical properties of hot-pressed ZrB2 ceramics with a complex Zr/Si/O-based additive

Densification behavior, microstructure, and mechanical properties of zirconium diboride (ZrB₂) ceramics modified with a complex Zr/Si/O-based additive were studied. ZrB₂ ceramics with 5–20 vol.% additions of Zr/Si/O-based additive were densified to >95% relative density at temperatures as low as 1400°C by hot-pressing. Improved densification behavior of ZrB₂ was observed with increasing additive content. The most effective additive amount for densification was 20 vol.%, hot-pressed at 1400°C (∼98% relative density). Microstructural analysis revealed up to 7 vol.% of residual second phases in the final ceramics. Improved densification behavior was attributed to ductility of the silicide phase, liquid phase formation at the hot-pressing temperatures, silicon wetting of ZrB₂ particles, and reactions of surface oxides. Room temperature strength ranged from 390 to 750 MPa and elastic modulus ranged from 440 to 490 GPa. Vickers hardness ranged from 15 to 16 GPa, and indentation fracture toughness was between 4.0 and 4.3 MPa·m^1/2. The most effective additive amount was 7.5 vol.%, which resulted in high relative density after hot-pressing at 1600°C and the best combination of mechanical properties.     

Correction to: An Updated Index Including Toughness for Hot-Cracking Susceptibility

Metallurgical and Materials Transactions A -     

An Updated Index Including Toughness for Hot-Cracking Susceptibility

Metallurgical and Materials Transactions A - Hot cracking is one of the major defects that can occur in laser-based additive manufacturing. During the terminal stage of solidification, hot cracking...