Cyclic Stretch Induces Inducible Nitric Oxide Synthase and Soluble Guanylate Cyclase in Pulmonary Artery Smooth Muscle Cells

In the pulmonary vasculature, mechanical forces such as cyclic stretch induce changes in vascular signaling, tone and remodeling. Nitric oxide is a potent regulator of soluble guanylate cyclase (sGC), which drives cGMP production, causing vasorelaxation. Pulmonary artery smooth muscle cells (PASMCs) express inducible nitric oxide synthase (iNOS), and while iNOS expression increases during late gestation, little is known about how cyclic stretch impacts this pathway. In this study, PASMC were subjected to cyclic stretch of 20% amplitude and frequency of 1 Hz for 24 h and compared to control cells maintained under static conditions. Cyclic stretch significantly increased cytosolic oxidative stress as compared to static cells (62.9 ± 5.9% vs. 33.3 ± 5.7% maximal oxidation), as measured by the intracellular redox sensor roGFP. Cyclic stretch also increased sGCβ protein expression (2.5 ± 0.9-fold), sGC activity (1.5 ± 0.2-fold) and cGMP levels (1.8 ± 0.2-fold), as well as iNOS mRNA and protein expression (3.0 ± 0.9 and 2.6 ± 0.7-fold, respectively) relative to control cells. An antioxidant, recombinant human superoxide dismutase (rhSOD), significantly decreased stretch-induced cytosolic oxidative stress, but did not block stretch-induced sGC activity. Inhibition of iNOS with 1400 W or an iNOS-specific siRNA inhibited stretch-induced sGC activity by 30% and 68% respectively vs. static controls. In conclusion, cyclic stretch increases sGC expression and activity in an iNOS-dependent manner in PASMC from fetal lambs. The mechanism that produces iNOS and sGC upregulation is not yet known, but we speculate these effects represent an early compensatory mechanism to counteract the effects of stretch-induced oxidative stress. A better understanding of the interplay between these two distinct pathways could provide key insights into future avenues to treat infants with pulmonary hypertension.     

The Cellular and Molecular Carcinogenic Effects of Radon Exposure: A Review

Radon-222 is a naturally occurring radioactive gas that is responsible for approximately half of the human annual background radiation exposure globally. Chronic exposure to radon and its decay products is estimated to be the second leading cause of lung cancer behind smoking, and links to other forms of neoplasms have been postulated. Ionizing radiation emitted during the radioactive decay of radon and its progeny can induce a variety of cytogenetic effects that can be biologically damaging and result in an increased risk of carcinogenesis. Suggested effects produced as a result of alpha particle exposure from radon include mutations, chromosome aberrations, generation of reactive oxygen species, modification of the cell cycle, up or down regulation of cytokines and the increased production of proteins associated with cell-cycle regulation and carcinogenesis. A number of potential biomarkers of exposure, including translocations at codon 249 of TP53 in addition to HPRT mutations, have been suggested although, in conclusion, the evidence for such hotspots is insufficient. There is also substantial evidence of bystander effects, which may provide complications when calculating risk estimates as a result of exposure, particularly at low doses where cellular responses often appear to deviate from the linear, no-threshold hypothesis. At low doses, effects may also be dependent on cellular conditions as opposed to dose. The cellular and molecular carcinogenic effects of radon exposure have been observed to be both numerous and complex and the elevated chronic exposure of man may therefore pose a significant public health risk that may extend beyond the association with lung carcinogenesis.     

A Semi‐Batch Process for Nitroxide Mediated Radical Polymerization

Summary: A semi‐batch process using nitroxide mediated polymerization, was explored for the design of low molecular weight solvent‐borne coatings, typical of those used in the automotive industry. While living radical polymerization (LRP) offers many advantages in the control of polymer chain microstructure that may confer important physical and chemical property benefits to coatings, adapting LRP to a semi‐batch process poses significant challenges in the design and operation of the process. Using styrene monomer, various two‐component initiating systems (free radical initiator, 4‐hydroxy‐TEMPO) were studied to understand the effects of different initiators on the course of polymerization. In addition, an alkoxyamine was synthesized and used as the initiating source. The initiators Luperox 7M75 and Luperox 231 give higher polymerization rates and reasonable control over polymerization, while benzoyl peroxide (BPO), Vazo 67, and the alkoxyamine are less effective. The number of polymer chains in the final product is always less than the theoretical value, reflecting poor initiation efficiency, probably resulting from undesirable termination reactions that become important due to the nature of the semi‐batch process. Adding camphorsulfonic acid (CSA) or charging initiator concurrently with monomer during semi‐batch feed, can increase the polymerization rate while maintaining the living character of the polymerization. The copolymerization of styrene and butyl acrylate is also shown to exhibit living character.

Schematic representation of the exchange reaction to produce N‐TEMPO capped polymer chains.     

Ca-based sorbent looping combustion for CO2 capture in pilot-scale dual fluidized beds

To demonstrate process feasibility of in situ CO₂ capture from combustion of fossil fuels using Ca-based sorbent looping technology, a flexible atmospheric dual fluidized bed combustion system has been constructed. Both reactors have an ID of 100 mm and can be operated at up to 1000 °C at atmospheric pressure. This paper presents preliminary results for a variety of operating conditions, including sorbent looping rate, flue gas stream volume, CaO/CO₂ ratio and combustion mode for supplying heat to the sorbent regenerator, including oxy-fuel combustion of biomass and coal with flue gas recirculation to achieve high-concentration CO₂ in the off-gas. It is the authors' belief that this study is the first demonstration of this technology using a pilot-scale dual fluidized bed system, with continuous sorbent looping for in situ CO₂ capture, albeit at atmospheric pressure. A multi-cycle test was conducted and a high CO₂ capture efficiency (> 90%) was achieved for the first several cycles, which decreased to a still acceptable level (> 75%) even after more than 25 cycles. The cyclic sorbent was sampled on-line and showed general agreement with the features observed using a lab-scale thermogravimetric analysis (TGA) apparatus. CO₂ capture efficiency decreased with increasing number of sorbent looping cycles as expected, and sorbent attrition was found to be another significant factor to be limiting sorbent performance.     

Remaining Fatigue Life Assessment of Plasma Sprayed Thermal Barrier Coatings

Ceramic functional coatings are frequently applied to structural materials, covering a wide range of thermomechanical and electrochemical applications. The main limiting feature is their reliability when subjected to cyclic transient thermal stresses. The study described in this article is a continuation of earlier research study focused on acoustic emission (AE) monitoring of the thermomechanical aging effects in ceramic coatings. Here, emphasis is placed on the usefulness of combining AE short-term monitoring with finite element modeling (FEM) to predict the performance of such coatings when subjected to cyclic thermal loads. The FEM study presented in this article is based on a three-dimensional, time-dependent approach, of the stress fields that developed within the coatings during the post-deposition cooling step and the thermal cycling. Experiments were conducted using yttrium-stabilized zirconia (YSZ) and Alumina (Al₂O₃) ceramic coatings combined with a NiCr-based intermetallic bond coat.     

An integrated dimensionality reduction and surrogate optimization approach for plant-wide chemical process operation

With liquefied natural gas becoming increasingly prevalent as a flexible source of energy, the design and optimization of industrial refrigeration cycles becomes even more important. In this article, we propose an integrated surrogate modeling and optimization framework to model and optimize the complex CryoMan Cascade refrigeration cycle. Dimensionality reduction techniques are used to reduce the large number of process decision variables which are subsequently supplied to an array of Gaussian processes, modeling both the process objective as well as feasibility constraints. Through iterative resampling of the rigorous model, this data-driven surrogate is continually refined and subsequently optimized. This approach was not only able to improve on the results of directly optimizing the process flow sheet but also located the set of optimal operating conditions in only 2 h as opposed to the original 3 weeks, facilitating its use in the operational optimization and enhanced process design of large-scale industrial chemical systems.     

Effect of Boron Content on Hot Ductility and Hot Cracking Susceptibility in 316L Austenitic Stainless Steel for Welding Components

Liquation cracking may occur in the heat-affected zone during welding. Two factors influence this phenomenon: the tensile stresses generated during welding and the potential loss of ductility due to the presence of a liquid film at grain boundaries depending on their chemical composition. Gleeble hot ductility tests have been used to study the combined effect of boron content and holding time on ductility drop in the liquation temperature range of a 316L type austenitic stainless steel. It is shown that high boron contents and short holding times promote the loss of ductility in this temperature range. Secondary ion mass spectrometry has been used to correlate mechanical results to boron distribution either at grain boundaries or in the bulk. Other welding tests have been performed to confirm the influence of boron content on hot cracking sensitivity of AISI 316L stainless steels. Results indicate that cracks appear on all specimens but at different strain levels. The higher the boron content is, the more the specimen exhibits tendency to hot cracking.     

Optimisation of CO2 laser beam edge‐to‐edge welding of Al‐Mg alloy sheets

Steels applied for construction of oil and gas pipelines are analysed; examples of X70 and X80 steel pipelines are given. The mechanical properties and weldability of X70 and X80 steel as well as principles of quality inspection of pipelines performed at a building site are described. On the grounds of the literature survey and the author's own experience, both shortcomings and advantages of application of advanced high-yield-strength steels, for instance X80 steel, for construction of high-pressure pipelines are presented.     

Validation of a Gas Chromatography-Mass Spectrometry Method for the Measurement of the Redox State Metabolic Ratios Lactate/Pyruvate and β-Hydroxybutyrate/Acetoacetate in Biological Samples

The metabolic ratios lactate/pyruvate and β-hydroxybutyrate/acetoacetate are considered valuable tools to evaluate the in vivo redox cellular state by estimating the free NAD+/NADH in cytoplasm and mitochondria, respectively. The aim of the current study was to validate a gas-chromatography mass spectrometry method for simultaneous determination of the four metabolites in plasma and liver tissue. The procedure included an o-phenylenediamine microwave-assisted derivatization, followed by liquid-liquid extraction with ethyl acetate and silylation with bis(trimethylsilyl)trifluoroacetamide:trimethylchlorosilane 99:1. The calibration curves presented acceptable linearity, with a limit of quantification of 0.001 mM for pyruvate, β-hydroxybutyrate and acetoacetate and of 0.01 mM for lactate. The intra-day and inter-day accuracy and precision were within the European Medicines Agency’s Guideline specifications. No significant differences were observed in the slope coefficient of three-point standard metabolite-spiked curves in plasma or liver and water, and acceptable recoveries were obtained in the metabolite-spiked samples. Applicability of the method was tested in precision-cut liver rat slices and also in HepG2 cells incubated under different experimental conditions challenging the redox state. In conclusion, the validated method presented good sensitivity, specificity and reproducibility in the quantification of lactate/pyruvate and β-hydroxybutyrate/acetate metabolites and may be useful in the evaluation of in vivo redox states.     

PPAR-Gamma Activation May Inhibit the In Vivo Degeneration of Bioprosthetic Aortic and Aortic Valve Grafts under Diabetic Conditions

Background: We aimed to examine the anti-calcification and anti-inflammatory effects of pioglitazone as a PPAR-gamma agonist on bioprosthetic-valve-bearing aortic grafts in a rat model of diabetes mellitus (DM). Methods: DM was induced in male Wistar rats by high-fat diet with an intraperitoneal streptozotocin (STZ) injection. The experimental group received additional pioglitazone, and controls received normal chow without STZ (n = 20 each group). Cryopreserved aortic donor grafts including the aortic valve were analyzed after 4 weeks and 12 weeks in vivo for analysis of calcific bioprosthetic degeneration. Results: DM led to a significant media proliferation at 4 weeks. The additional administration of pioglitazone significantly increased circulating adiponectin levels and significantly reduced media thickness at 4 and 12 weeks, respectively (p = 0.0002 and p = 0.0107, respectively). Graft media calcification was highly significantly inhibited by pioglitazone after 12 weeks (p = 0.0079). Gene-expression analysis revealed a significant reduction in relevant chondro-osteogenic markers osteopontin and RUNX-2 by pioglitazone at 4 weeks. Conclusions: Under diabetic conditions, pioglitazone leads to elevated circulating levels of adiponectin and to an inhibition of bioprosthetic graft degeneration, including lower expression of chondro-osteogenic genes, decreased media proliferation, and inhibited graft calcification in a small-animal model of DM.