An experimental study of hydrogen sorption and permeation in high-performance polyamides

Semicrystalline polyamides (PAs) are optimal materials to develop high-pressure resistant liners for type IV hydrogen storage tanks due to a favorable combination of barrier performance, mechanical resistance, and lightness. However, experimental data on hydrogen transport in PAs are incomplete or inconsistent, and usually do not report separately the contributions of solubility and diffusivity, hence limiting a deep understanding of the permeation mechanism and its dependence on the material structure. Moreover, recent developments have led to the design of modified polyamides which could better serve the high-pressure storage applications. In this work, the hydrogen barrier performance of Polyamide 6 (PA6), Polyamide 11 (PA11) and an impact-modified PA 6 (PA6-I), was evaluated and the results obtained with different techniques and on different samples compared. Permeation measurements were performed in constant-volume and constant-pressure apparatuses at different temperatures and pressures, on different samples of each material. Sorption measurements were carried out into a differential sorption system. Results from the permeation and sorption devices were compared against each other and with literature data, allowing to understand the effect of various factors. The H2 2 solubility in PA is mostly affected by density, as a lower free volume of the amorphous phase leads to a lower gas uptake. On the other hand, diffusivity and, consequently, permeability, are also strongly affected by the morphology of the crystal phase, which depends on the production protocol. In most of the cases inspected, the discrepancy between data from different experimental techniques or literature works can be explained by the different crystal morphology of the samples used in the test. Temperature enhances diffusivity, permeability and solubility, while the pressure reduces the permeability, as it lowers the free volume, and increases the activation energy of permeation. An estimation of the minimum thickness required to meet high-pressure storage technical guidelines was provided for the case of PA6-I

Immunomodulation of Myocardial Fibrosis

Immunotherapy is a potential cornerstone in the treatment of myocardial fibrosis. During a myocardial insult or heart failure, danger signals stimulate innate immune cells to produce chemokines and profibrotic cytokines, which initiate self-escalating inflammatory processes by attracting and stimulating adaptive immune cells. Stimulation of fibroblasts by inflammatory processes and the need to replace damaged cardiomyocytes fosters reshaping of the cardiac fibroblast landscape. In this review, we discuss new immunomodulatory strategies that manipulate and direct cardiac fibroblast activation and differentiation. In particular, we highlight immunomodulatory strategies that target fibroblasts such as chimeric antigen receptor T cells, interleukin-11, and invariant natural killer T-cells. Moreover, we discuss the potential of manipulating both innate and adaptive immune system components for the translation into clinical validation. Clearly, multiple pathways should be considered to develop innovative approaches to ameliorate myocardial fibrosis and hence to reduce the risk of heart failure

Genetic and Phenotypic Characterization of Nexilin (NEXN)-Related Cardiomyopathy : Results From a Multicentric Study

Nexilin (NEXN)-related cardiomyopathies (CMPs) are largely unexplored.This study investigated the causative role of NEXN in CMPs, examining its phenotypic expression and prognostic profile.Twelve referral centers collected phenotypic/genotypic data of patients with NEXN variants. Variant rarity was determined according to gnomAD allele frequency in CMPs. Burden enrichment tested rare NEXN variants in hypertrophic (HCM) and dilated cardiomyopathy (DCM)/nondilated left ventricular cardiomyopathy (NDLVC) CMPs against gnomAD non-Finnish Europeans (NFE). Outcomes of validated variants were detailed, with prognostic comparisons to Titin (TTN)- and Filamin C (FLNC)-related CMP cohorts.Involving 60 NEXN carriers with rare, protein-altering variants, a significant enrichment of NEXN-truncating variants (tvs) was found in the DCM/NDLVC cohort (0.39% vs 0.09% in gnomAD NFE; P = 0.0001), whereas no association was observed with HCM. Patients with DCM/NDLVC with NEXNtv (n = 17; median age: 45 years [Q1-Q3: 36-55 years], 88% probands, 53% male) showed mild left ventricular dilatation (indexed end-diastolic volume 69 mL [Q1-Q3: 46-87 mL]), mildly reduced left ventricular ejection fraction (44% [Q1-Q3: 31%-53%]), and myocardial fibrosis (64%). NYHA functional class I was common (71%). During a 45-month median follow-up (Q1-Q3: 11-130 months), 53% of patients were implanted with an implantable cardioverter-defibrillator and 25% had malignant ventricular arrhythmias (MVAs). Compared with TTN-CMP, NEXN-CMP exhibited earlier and more frequent MVAs at higher ejection fractions, and no significant differences were found against FLNC-CMP.NEXNtvs were significantly associated with DCM/NDLVC, characterized by mild cardiac abnormalities, infrequent heart failure, common fibrosis, and arrhythmias. This largest NEXN variant carrier cohort to date contributes to defining the causative role of this rare genotype and its associated phenotype

Development of a quantitative theory of polycondensation

This review presents the first systematic treatment of the voluminous literature on the theory of polycondensation. Processes for obtaining homo- and copolymers with linear and branched macromolecules are considered. Emphasis is on a thorough discussion of various polycondensation models, and the methods of their solution for the calculation of the statistical characteristics of the chemical structure of polymers. The effects on these characteristics of the process modes for thermodynamically and kinetically controlled regimes of a polycondensation are analyzed in detail

Immunomodulation of Myocardial Fibrosis

Immunotherapy is a potential cornerstone in the treatment of myocardial fibrosis. During a myocardial insult or heart failure, danger signals stimulate innate immune cells to produce chemokines and profibrotic cytokines, which initiate self-escalating inflammatory processes by attracting and stimulating adaptive immune cells. Stimulation of fibroblasts by inflammatory processes and the need to replace damaged cardiomyocytes fosters reshaping of the cardiac fibroblast landscape. In this review, we discuss new immunomodulatory strategies that manipulate and direct cardiac fibroblast activation and differentiation. In particular, we highlight immunomodulatory strategies that target fibroblasts such as chimeric antigen receptor T cells, interleukin-11, and invariant natural killer T-cells. Moreover, we discuss the potential of manipulating both innate and adaptive immune system components for the translation into clinical validation. Clearly, multiple pathways should be considered to develop innovative approaches to ameliorate myocardial fibrosis and hence to reduce the risk of heart failure

Novel imprinting techniques for fabrication of multilevel flexible electronics

We report a novel method to selectively deposit materials from solution into imprinted micro-capillaries. Dewetting of the solvent just outside the capillaries is balanced to evaporation inside the capillaries. In this way conductive u-wires can be self-assembled and self-aligned on flexible substrates opening the route to faster and cheaper plastic electronics

Roll-to-roll UV imprint lithography for flexible electronics

We propose a roll-to-roll UV imprint lithography tool as a way to pattern flexible PET foil with µm-resolution. As a way to overcome dimensional instability of the foil and its effect on overlay, a self-align approach was investigated, that permits to make several layers in a single lithography step. Flexible Ni-stamps were used, with a single level and with 2 levels. The stamps were fabricated on wafers using conventional optical lithography and Si etching. Thin Ni replica, both single and multilevel, were obtained by electroplating using a thickness of 50 µm. The flexible Ni stamps were attached on the main drum that is placed on a conventional roll-to-roll machine. Resist was dispensed drop by drop by valve-jet nozzle using solvent-free UV resist. The imprint speed was of 0.35 m/min, using a UV illumination of 2 W. Fifty imprints were made in a row, equivalent to 20 m foil length. High imprint quality was observed with good reproducibility. All features type were replicated, from 500 µm contact pads to 800 nm wide trenches and 1 µm wide lines. A resolution of 800 nm in 1 µm thick resist was obtained for single level imprint. Multi-level imprints (2 levels) show the same quality in replication with a resolution of 1 µm. © 2011 Elsevier B.V. All rights reserved

Clonal Hematopoiesis of Indeterminate Potential From a Heart Failure Specialist's Point of View

ABSTRACT Clonal hematopoiesis of indeterminate potential (CHIP) is a common bone marrow abnormality induced by age‐related DNA mutations, which give rise to proinflammatory immune cells. These immune cells exacerbate atherosclerotic cardiovascular disease and may induce or accelerate heart failure. The mechanisms involved are complex but point toward a central role for proinflammatory macrophages and an inflammasome‐dependent immune response (IL‐1 [interleukin‐1] and IL‐6 [interleukin‐6]) in the atherosclerotic plaque or directly in the myocardium. Intracardiac inflammation may decrease cardiac function and induce cardiac fibrosis, even in the absence of atherosclerotic cardiovascular disease. The pathophysiology and consequences of CHIP may differ among implicated genes as well as subgroups of patients with heart failure, based on cause (ischemic versus nonischemic) and ejection fraction (reduced ejection fraction versus preserved ejection fraction). Evidence is accumulating that CHIP is associated with cardiovascular mortality in ischemic and nonischemic heart failure with reduced ejection fraction and involved in the development of heart failure with preserved ejection fraction. CHIP and corresponding inflammatory pathways provide a highly potent therapeutic target. Randomized controlled trials in patients with well‐phenotyped heart failure, where readily available anti‐inflammatory therapies are used to intervene with clonal hematopoiesis, may pave the way for a new area of heart failure treatment. The first clinical trials that target CHIP are already registered

Clinical impact of re-evaluating genes and variants implicated in dilated cardiomyopathy

Purpose Accurate interpretation of variants detected in dilated cardiomyopathy (DCM) is crucial for patient care but has proven challenging. We applied a set of proposed refined American College of Medical Genetics and Genomics/Association for Molecular Pathology (ACMG/AMP) criteria for DCM, reclassified all detected variants in robust genes, and associated these results to patients' phenotype. Methods The study included 902 DCM probands from the Maastricht Cardiomyopathy Registry who underwent genetic testing. Two gene panel sizes (extended n = 48; and robust panel n = 14) and two standards of variant classification (standard versus the proposed refined ACMG/AMP criteria) were applied to compare genetic yield. Results A pathogenic or likely pathogenic (P/LP) variant was found in 17.8% of patients, and a variant of uncertain significance (VUS) was found in 32.8% of patients when using method 1 (extended panel (n = 48) + standard ACMG/AMP), compared to respectively 16.9% and 12.9% when using method 2 (robust panel (n = 14) + standard ACMG/AMP), and respectively 14% and 14.5% using method 3 (robust panel (n = 14) + refined ACMG/AMP). Patients with P/LP variants had significantly lower event-free survival compared to genotype-negative DCM patients. Conclusion Stringent gene selection for DCM genetic testing reduced the number of VUS while retaining ability to detect similar P/LP variants. The number of genes on diagnostic panels should be limited to genes that have the highest signal to noise ratio