19684 research outputs found
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Pharmaceutical Analysis of Protein–Peptide Coformulations and the Influence of Polysorbates
No full textCoformulation is an approach to formulating multiple biopharmaceutical therapeutics in a single formulation, promising the benefits of both therapies in one dose. However, as molecular stability is a key consideration in traditional biopharmaceutical formulations, stability of coformulations will require extensive investigation. This study evaluated the effects of traditional formulation stabilizers, specifically surfactants, at different grades, namely, regular grade (RG) Tween 20 and Tween 80 and Super-refined Polysorbate 20 and 80. Their effects were assessed through their interactions with human serum albumin (HSA) and a glucagon-like peptide-1 (GLP-1) receptor agonist (MEDI7219). Isothermal titration calorimetry (ITC) and differential scanning calorimetry (DSC) were implemented to determine the strength of the binding interactions and thermal stability of the tertiary system. ITC confirmed that upon titration of MEDI7219 into a solution of HSA and RG, Tween 20 the binding affinity of the peptide was reduced, resulting in negatively cooperative binding. However, when the peptide was titrated into a solution of HSA and both grades of Tween 80, the binding affinity increased with positive cooperative binding. DSC established that MEDI7219 increased the thermal stability of HSA to a similar extent to the polysorbates. Combining peptide and polysorbate did not further increase the thermal stability of HSA; however, it did reduce the unfolding of HSA molecules in the absence of heat. Overall, the unique findings in this study have demonstrated that the order of addition in a ternary coformulation affects the final composition which is an important consideration for pharmaceutical development
Novel Investigation of Influence of Torsional Load on Unbalance Fault Indicators for Induction Motors
No full textThis paper investigates how the torsional load affects two vibration-based unbalance fault indicators. This investigation is important for unbalance fault diagnosis in multiple constant load conditions, which are unavoidable for many rotating machines. Coupled flexural–torsional dynamics of an unbalanced disc–shaft system, as the representative of an induction motor, is investigated via a continuous shaft–beam model. Numerical investigations reveal that the fundamental rotating intensity of the transversal acceleration is independent of the torsional load. So, the novel speed-invariant version of this indicator, which is obtained by normalizing the fundamental rotating intensity by the fourth power of the rotational speed, is also load-independent. The comprehensive experimental trials confirm load-independency of the considered two unbalance fault indicators. The important novel outcome is that, by conducting numerical analysis and comprehensive experimental trials with a belt conveyor system under various constant loading conditions, the load-independency of the fundamental rotating harmonic intensity as well as novel speed-invariant unbalance feature are justified.</p
Multiple Impacts on Adolescent Well-Being During COVID-19 School Closures:Insights From Professionals for Future Policy Using a Conceptual Framework
No full textPurpose: This study explores the impacts of school closures during the COVID-19 pandemic on the domains of adolescent well-being from the UN H6+ framework, reported by health and educational professionals worldwide. Methods: Semistructured individual online interviews were conducted in six languages during the second wave of the COVID-19 pandemic (March–December 2021) with health and education professionals who volunteered for follow-up after participating in an anonymous online survey. The UN H6+ 5-domain conceptual framework of adolescent well-being was used as a framework for the directed content analysis of the combined interview dataset. Results: A total of 60 interviews—translated into English—were analyzed from 38 education and 22 health professionals in 28 countries/territories. Participant reports showed impacts on all five adolescent well-being domains, but mainly domain 1 (good health and nutrition), domain 3 (safety and a supportive environment) and domain 4 (learning, competence, education, skills, and employability). Reflections of 2-connectedness and 5-agency were also present. Their reports included mainly negative impacts, but also some positive insights to take forward. Discussion: Policymakers must recognize impacts of school closures during the pandemic on multiple domains of adolescent well-being and the potential for widening inequalities. Schools play a critical mitigating role that goes beyond education. The call to action for the adolescent health community is to recognize and address ongoing potential long-term impacts on well-being and inequalities in their everyday practice. It is also important to advocate locally, nationally, and globally for careful consideration of the consequences of school closures in future health crises.</p
Hydrogen-based trains, trucks, and buses:techno-socio-economic challenges and perspective
No full textMaking transportation sustainable and resilient in terms of environmental, social, and economic perspectives is the key consideration for the future passenger and freight transportation systems. Due to the urgent need to reduce carbon footprints by countries, followed by the government’s investments and initiatives, the fuel cell electric vehicles (FCEVs) market is estimated to have a significant gross in the coming years. Hydrogen is the only type of fuel for this process, so when referring to FCEVs, it implies the fuel is hydrogen. The potential impact of fuel cell electric (FCE) freight and passenger transportation is not only limited to the environmental benefits but countries developing FCEVs have created new jobs and economic opportunities. To this end, this chapter provides a comprehensive overview of the techno-socio-economic challenges and opportunities regarding FCE heavy vehicles, that is, trains, trucks, and buses. It concludes that FCEVs are reasonable alternatives to petrol- and diesel-powered vehicles in meeting sustainable goals with environmental, social, and long-term economic benefits. Meanwhile, infrastructure upgradation regarding refueling and control systems, public awareness, and safety concerns require more investments and stakeholder collaborations to meet the challenges and targets
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