The Cysteine Protease Giardipain-1 from Giardia duodenalis Contributes to a Disruption of Intestinal Homeostasis

In giardiasis, diarrhoea, dehydration, malabsorption, weight loss and/or chronic inflammation are indicative of epithelial barrier dysfunction. However, the pathogenesis of giardiasis is still enigmatic in many aspects. Here, we show evidence that a cysteine protease of Giardia duodenalis called giardipain-1, contributes to the pathogenesis of giardiasis induced by trophozoites of the WB strain. In an experimental system, we demonstrate that purified giardipain-1 induces apoptosis and extrusion of epithelial cells at the tips of the villi in infected jirds (Meriones unguiculatus). Moreover, jird infection with trophozoites expressing giardipain-1 resulted in intestinal epithelial damage, cellular infiltration, crypt hyperplasia, goblet cell hypertrophy and oedema. Pathological alterations were more pronounced when jirds were infected intragastrically with Giardia trophozoites that stably overexpress giardipain-1. Furthermore, Giardia colonization in jirds results in a chronic inflammation that could relate to the dysbiosis triggered by the protist. Taken together, these results reveal that giardipain-1 plays a key role in the pathogenesis of giardiasis.     

Self-Amplifying RNA Approach for Protein Replacement Therapy

Messenger RNA (mRNA) technology has already been successfully tested preclinically and there are ongoing clinical trials for protein replacement purposes; however, more effort has been put into the development of prevention strategies against infectious diseases. Apparently, mRNA vaccine approval against coronavirus disease 2019 (COVID-19) is a landmark for opening new opportunities for managing diverse health disorders based on this approach. Indeed, apart from infectious diseases, it has also been widely tested in numerous directions including cancer prevention and the treatment of inherited disorders. Interestingly, self-amplifying RNA (saRNA)-based technology is believed to display more developed RNA therapy compared with conventional mRNA technique in terms of its lower dosage requirements, relatively fewer side effects, and possessing long-lasting effects. Nevertheless, some challenges still exist that need to be overcome in order to achieve saRNA-based drug approval in clinics. Hence, the current review discusses the feasibility of saRNA utility for protein replacement therapy on various health disorders including rare hereditary diseases and also provides a detailed overview of saRNA advantages, its molecular structure, mechanism of action, and relevant delivery platforms.     

Comparison of contact resistance between accumulation-mode and inversion-mode multigate FETs

The performances of accumulation-mode and inversion-mode multigate FETs are compared. The influence of gate underlap on the electrical properties is analyzed. Both simulation results and experimental data show that in a device with gate underlap, accumulation-mode devices have a higher current drive, lower source and drain resistance and less process variability than inversion-mode FETs.     

Hydrodynamics of fluidization in a semicircular bed with a jet

A hydrodynamic model of fluidization was developed that computes void fractions, pressure and solid and gas velocities in cylindrical fluidized beds. Cmputed time-averaged gas velocity distributions of a jet compared well with Westinghouse experimental data without the use of any fitted parameters. The main empirical input was a drag correlation from the literature.     

Designing mechanical components to a specified reliability and confidence level

A methodology for determining the lower one-sided confidence limit on the reliability, R_L1, of mechanical components and structural members is presented. To accomplish this, charts for R_L1 values at 50%, 60%, 70%, 80%, 90%, 95%, 99% and 99.9% confidence levels are given. A methodology for designing components and structural members to a desired reliability with greater than 50% assurance is proposed. All of these methodologies are illustrated by examples.     

Solutions of the two-dimensional Navier-Stokes equations by Chebyshev expansion methods

The steady two-dimensional Navier-Stokes equations in both the vorticity-stream function and the vorticity-velocity formulation are solved by Chebyshev expansion methods. Numerical experiments for the driven flow in a rectangular cavity and the developing flow in a circular tube at low Reynolds numbers are described.     

A review of the sponge iron process for the storage and transmission of remotely generated marine energy

The UK's vast marine energy resource is mostly located in remote areas west and north of Scotland, and transmission of this energy to the mainland will be required. This may be achieved by using this ‘stranded’ power to generate hydrogen electrolytically, which may in turn be stored or transported using sponge iron technology. This paper reviews the technology and research needed to bring such a process on stream. We propose utilising techniques that have been developed for the oxygen carriers used in chemical looping, and also those used in early processes for hydrogen generation in the chemical industry. We briefly outline the design requirements for an energy efficient sponge iron plant. It is shown that the iron sponge system presents better energy efficiencies than alternative forms of bulk storage such as liquid hydrogen, magnesium hydride slurry, some at least of the metal hydrides, or methylcyclohexane–toluene–hydrogen, provided that requirements can be met for particle durability and reactivity.