A copper chaperone-mimetic polytherapy for SOD1-associated amyotrophic lateral sclerosis

Amyotrophic lateral sclerosis (ALS)-associated mutations in Cu/Zn superoxide dismutase (SOD1) reduce folding stability, resulting in misfolding, aggregation, and ultimately cellular toxicity. A great deal of effort has focused on preventing the misfolding and aggregation of SOD1 as a potential therapy for ALS, however, the results have been mixed. Here, we utilise a small-molecule polytherapy of CuATSM and ebselen to mimic the metal delivery and disulfide bond promoting activity of SOD1’s cellular chaperone, the ‘copper chaperone for SOD1’ (CCS). We find that polytherapy using CuATSM and ebselen is highly effective at reducing inclusion formation in a cell model of SOD1 aggregation, reduces mutant SOD1-associated cell death, and promotes effective maturation of SOD1 beyond either compound alone. Our data suggest that a polytherapy of CuATSM and ebselen may be an effective method of treating SOD1-associated ALS.

Toxic Metals in Liquid and Aerosol from Pod-Type Electronic Cigarettes

High-quality, accurate data on liquid contents and aerosol emissions from electronic nicotine delivery systems (ENDS, e.g., e-cigarettes) are crucial to address potential health concerns as these devices evolve and mature. Metals are an important class of ENDS constituents that merit attention as they have various health implications. Proper sampling, handling and aerosol trapping materials are essential to generate accurate quantitative metal data and to reduce the likelihood of inaccurate results originating from inappropriate collection vessels and materials that contribute to high background levels. Published methods that meet these criteria were applied to the analyses of chromium, nickel, copper, zinc, cadmium, tin and lead in liquid and aerosol from mint/menthol and tobacco flavors of currently popular pod-based devices from three manufacturers. Metal concentrations from pods that had not been used for generating aerosol ranged from below our lowest reportable level to 0.164 µg/g for Cr, 61.3 µg/g for Ni, 927 µg/g for Cu, 14.9 µg/g for Zn, 58.2 µg/g for Sn and 2.56 µg/g for Pb. Cadmium was included in our analyte panel and was not present above detection limits in liquid or aerosol. Aerosol metal concentrations (using a 55-mL puff) ranged from below our lowest reportable level to 29.9 ng/10 puffs for Cr, 373 ng/10 puffs for Ni, 209 ng/10 puffs for Cu, 4,580 ng/10 puffs for Zn, 127 ng/10 puffs for Sn and 463 ng/10 puffs for Pb. Our results showed some metal delivery from all the products examined and highly variable metal levels between manufacturer, brand and package.

About this title - Archean Granitoids of India: Windows into Early Earth Tectonics

Granitoids form the bulk of the Archean continental crust and preserve key information on early Earth evolution. India hosts five main Archean cratonic blocks (Aravalli, Bundelkhand, Singhbhum, Bastar and Dharwar). This book summarizes the available information on Archean granitoids of Indian cratons. The chapters cover a broad spectrum of themes related to granitoid typology, emplacement mechanism, petrogenesis, phase-equilibria modelling, temporal distribution, tectonic setting, and their roles in fluid evolution, metal delivery and mineralizations. The book presents a broader picture incorporating regional- to cratons-scale comparisons, implications for Archean geodynamic processes, and temporal changes thereof. This synthesis work, integrating modern concepts on granite petrology and crustal evolution, offers an irreplaceable body of reference information for any geologist interested in Archean Indian granitoids.

Increasing Hot Rolling Mass of Steel Sheet Products

The article exposes contemporary materials and structures for metallurgy. Feasible increase of dynamic forces on the rolling machinery during rolling of billets with masses up to 20 t (Stand No.1 of CWM 1700 HR, «U.S. Steel Košice», Košice, Slovakia, and PJSC «Illich MMPP», Mariupol, Ukraine) is discussed. It is proved that weight of billet, velocities of metal delivery to working rolls and rolling significantly influence the dynamic loads during metal biting. The technical solutions are suggested which would allow the steady rolling process of billets with masses up to 20 t and prevent accidental failures of frame parts, chocks and main lines.

Review on Vertical Twin-Roll Strip Casting: A Key Technology for Quality Strips

Nowadays near-net-shape casting technology is an important area of research in the iron and steel industry. Among different kinds of near-net-shape casting process, twin-roll casting process has received much attention among researchers. Twin-roll casting (TRC) has been the subject of extensive research, not only to develop the technology but also to achieve an understanding of microstructural evolution and to produce quality strips. The main issues concerning the design and operation of twin-roll casters are metal-mold heat transfer, metal delivery system, and their possible effects on the solid shell formation and characteristics of the strips. The present review gives an idea about the process aspect, modeling, and quality issues in vertical twin-roll strip casting process and helps to improve the design of twin-roll strip caster.

Magnetic Damping of Liquid Steel Flows in Horizontal Single Belt Casting (HSBC)

A preliminary computational fluid flow model has been developed to simulate the magnetic braking of liquid steel on a water-cooled, rapidly moving, horizontal belt. The liquid steel issuing from the proposed vertical slot-nozzle should ideally move isokinetically with the belt during freezing. In this study, ANSYS Fluent 14.5 software was used to model the 3-D turbulent flow of liquid steel. A 288 core High Performance Computer cluster located at the McGill Metals Processing Centre was used for high-speed computation. The standard k–ε model was used to simulate the turbulence. Similarly, the magnetic induction method was used to calculate the induced heterogeneous magnetic field, from which the current density and electromagnetic forces produced were computed. The behavior of the proposed magnetic flow control was first validated against previous experimental work and was then applied to predict the performance of the proposed slot nozzle. The predicted results show that by applying a DC Magnetic brake to the proposed metal delivery system, near isokinetic conditions can be rapidly established.