This paper outlines strategies in alignment with ICH M7 for systematically assessing the potential risk posed by mutagenic degradants in active pharmaceutical ingredients (API) and formulated products. A mutagen risk assessment (MRA) process that involves degradation should include results from focused drug substance and drug product stress testing experiments (e.g., at elevated temperature, a ...

Stress response mechanisms that modulate the dynamics of tRNA degradation and accumulation from the cytoplasm to the nucleus have been studied in yeast, the rat hepatoma and human cells. In the current study, we investigated tRNA degradation and accumulation in HeLa cells under various forms of stress. We found that initiator tRNA(Met) (tRNA(iMet)) was specifically degraded under heat stress. T...

The failure and degradation mechanisms of gate-all-around silicon nanowire FET subjected to electrostatic discharge (ESD) are investigated through device modeling. Transmission line pulse stress test is simulated and device degradation physics is modeled. The device degradation level, interface state concentration and hard breakdown are shown and analyzed. From the model, we found that ESD stre...

AIMS Atrial fibrillation (AF), a common tachyarrhythmia in clinical practice, is associated with increased oxidative stress. Structural remodelling in atrial myocytes, including myofibril degradation, is an important characteristic of AF. However, the mechanism underlying AF-induced cellular structural remodelling remains unclear. The aim of this study was to investigate the role of oxidative s...

Microbial consortia consisting of cooperational strains exhibit biodegradation performance superior to that of single microbial strains and improved remediation efficiency by relieving the environmental stress. Tetrahydrofuran (THF), a universal solvent widely used in chemical and pharmaceutical synthesis, significantly affects the environment. As a refractory pollutant, THF can be degraded by ...

Reactivity to traumatic stress varies between individuals and only a minority of those exposed to trauma develops stress-induced psychopathologies. Currently extensive effort is made to unravel the specific mechanisms predisposing to vulnerability vs. resilience to stress. We investigated in rats the role of β-endorphin metabolism in vulnerability to acute traumatic stress. Responders (showing ...

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Accelerated Degradation tests (ADTs) are widely used to assess the lifetime information of highly reliable products possessing quality characteristics that both degrade over time and can be related to reliability. Hence, how to design an efficient ADT plan for assessing product’s lifetime information at normal-use stress (especially for the optimal sample-size allocation to higher test-stress l...

Poly lactic acid (PLA) is widely used for the manufacture of biodegradable stents (BDSs). It was observed and investigated that tensile loads can significantly affect the degradation rate of PLA in our previous study. Additionally, non-uniform degradation can arise from complicated stress distributions in implanted stents under long-term and pulsatile tensile loading. The objective of this work...