Polysorbate identity and quantity dictate the extensional flow properties of protein-excipient solutions

While protein medications are promising for treatment of cancer and autoimmune diseases, challenges persist in terms of development and injection stability of high-concentration formulations. Here, the extensional flow properties of protein-excipient solutions are examined via dripping-onto-substrate extensional rheology, using a model ovalbumin (OVA) protein and biocompatible excipients polysorbate 20 (PS20) and 80 (PS80). Despite similar PS structures, differences in extensional flow are observed based on PS identity in two regimes: at moderate total concentrations where surface tension differences drive changes in extensional flow behavior, and at small PS:OVA ratios, which impact the onset of weakly elastic flow behavior. Undesirable elasticity is observed in ultra-concentrated formulations, independent of PS identity; higher PS contents are required to observe these effects than in analogous polymeric excipient solutions. These studies reveal novel extensional flow behaviors in protein-excipient solutions, and provide a straightforward methodology for assessing the extensional flow stability of new protein-excipient formulations.     

Multiple Chemical Features Impact Biological Performance Diversity of a Highly Active Natural Product-Inspired Library

A systematic, diversity-oriented synthesis approach was employed to access a natural product-inspired flavonoid library with diverse chemical features, including chemical properties, scaffold, stereochemistry, and appendages. Using Cell Painting, the effects of these diversity elements were evaluated, and multiple chemical features that predict biological performance diversity were identified. Scaffold identity appears to be the dominant predictor of performance diversity, but stereochemistry and appendages also contribute to a lesser degree. In addition, the diversity of chemical properties contributed to performance diversity, and the driving chemical property was dependent on the scaffold. These results highlight the importance of key chemical features that may inform the creation of small-molecule, performance-diverse libraries to improve the efficiency and success of high-throughput screening campaigns.     

A parametric investigation on seat/occupant contact forces and their relationship with initially perceived discomfort using a configurable seat

The present work investigates the contact forces between sitters and seat as well as their correlations with perceived discomfort. Twelve different economy class aeroplane seat configurations were simulated using a multi-adjustable experimental seat by varying seat pan and backrest angles, as well as seat pan compressed surface. Eighteen males and 18 females, selected by their body mass index and stature, tested these configurations for two sitting postures. Perceived discomfort was significantly affected by seat parameters and posture and correlated both with normal force distribution on the seat-pan surface and with normal forces at the lumbar and head supports. Lower discomfort ratings were obtained for more evenly distributed normal forces on the seat pan. Shear force at the seat pan surface was at its lowest when sitters were allowed to self-select their seat-pan angle, supporting that a shear force should be reduced but not zeroed to improve seating comfort.

Practitioner Summary: The effects of seat-pan and backrest angle, anthropometric dimensions and sitting posture on contact forces and perceived discomfort were investigated using a multi-adjustable experimental seat. In addition to preferred seat profile parameters, the present work provides quantitative guidelines on contact force requirement for improving seating comfort.     

The perceived risk of the Line 5 Pipeline and spills under ice

Using the psychometric paradigm of risk in conjunction with surveys of the Michigan public (n = 638) and a regional planning organization (n = 65), we examine the perceived risk and concerns associated with underwater oil pipelines, the Enbridge Line 5 pipeline in particular, and oil spills under ice. The fate of Line 5 is heavily debated in Michigan, specifically the portion that traverses the Straits of Mackinac, which can be ice-covered for months. Scant literature examines how individuals perceive the risk associated with Line 5, its alternatives, or potential spills in open water or under ice. Here we identify considerable concern regarding both the pipeline and the potential for spills under ice on behalf of the public, and increased concern about spills under ice on behalf of the planning organization. Organization members' concerns are significantly predicted by beliefs about the difficulty in remediating spills, however not by beliefs about spills' likelihood, difficulty in detection, noticeability, or consequences. Our results identify the need to better examine and communicate the risks associated with underwater pipelines and spills, both in open water and under ice, as well as options for remediating oil captured under ice. Furthermore, we recommend the adoption of decision-making and risk governance processes that explicitly expand analysis of the social, economic and environmental tradeoffs of underwater pipelines such as Line 5.     

No Effect of Omega-3 Fatty Acid Supplementation on Cognition and Mood in Individuals with Cognitive Impairment and Probable Alzheimer’s Disease: A Randomised Controlled Trial

Findings from epidemiological and observational studies have indicated that diets high in omega-3 polyunsaturated fatty acids (PUFAs) such as docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) may reduce the risk of cognitive decline and Alzheimer’s disease (AD). To determine if increasing intake of DHA and EPA through supplementation is beneficial to cognition and mood in individuals with cognitive impairment no dementia (CIND) or Alzheimer’s disease (AD) a four month, randomised, double-blind, placebo controlled study was conducted. Fifty-seven participants with CIND and nineteen with AD were randomised to receive either omega-3 PUFAs (600 mg EPA and 625 mg DHA per day) or placebo (olive oil) over a four month period. Elevating depleted levels of EPA and DHA through supplementation in individuals with CIND or AD was found to have negligible beneficial effect on their cognition or mood. These findings confirm an overall negligible benefit of omega-3 PUFA supplementation for those with cognitive impairment and dementia. More intervention studies need to be undertaken with longer study durations and larger sample sizes. It may prove fruitful to examine effects of different doses as well as effects in other dementia subtypes.     

Facile Proton Transport in Ammonium Borosulfate—An Unhumidified Solid Acid Polyelectrolyte for Intermediate Temperatures

High proton conductivity is reported for unhumidified ammonium borosulfate, NH₄[B(SO₄)₂], a solid acid coordination polymer that contains 1D, hydrogen-bonded NH₄⁺···¹_∞[B(SO₄)_4/2]⁻ chains. NH₄[B(SO₄)₂] is thermally stable to 320 °C and is amenable to sintering into monolithic, polycrystalline discs at 200 °C and about 300 MPa of uniaxial pressure. Impedance spectroscopy measurements reveal ionic conductivities for sintered ammonium borosulfate of 0.1 mS cm⁻¹ at 25 °C and up to 10 mS cm⁻¹ at 180 °C in ambient air. No superprotonic transition is observed in the temperature range of 25–180 °C. Ab initio molecular dynamics simulations show these high conductivities are aided by free rotation of the NH₄⁺ units and significant gyrational mobility of the SO₄ tetrahedra, which, in turn, provide facile pathways for proton locomotion. High conductivities, a wide operational temperature window, and tolerance to both ambient and anhydrous conditions make NH₄[B(SO₄)]₂ an attractive candidate electrolyte for intermediate-temperature hydrogen fuel cells that may enable operation at temperatures as high as 300 °C without active humidification.     

Preparation,thermal and mechanical properties of poly (ether-imide) composite reinforced with carbon nanotube buckypaper

Vacuum filtration technique was employed in order to prepare multiwalled carbon nanotube buckypapers (MWCNT-BP) through a well-dispersed suspension of MWCNT/H₂O with the aid of Triton X-100 surfactant. The obtained BP (buckypaper) was then infiltrated with a solution of poly (ether-imide) (PEI) under vacuum conditions. The visual inspection demonstrated the importance of the centrifugation procedure before the vacuum filtration of the suspension, revealing a smooth surface of the as-prepared buckypaper. Thermogravimetric experiments (TGA) and scanning electron microscopy analyses have demonstrated the role of isopropyl alcohol in the removal of Triton X-100 from the nanotube network. SEM observations of the cross-section view of the samples revealed a porous network of the fabricated BP, and an impregnated structure of the PEI/BP composite, suggesting a good interfacial bonding between MWCNT and PEI. Moreover, significant improvements were achieved in mechanical and thermal properties of PEI matrix by the incorporation of BP, as the increase of both the storage modulus (42%) and the T _g (11 °C) for the PEI/BP composite. TGA have shown a significant increase in the onset decomposition temperature of the polymer by the incorporation of the BP. © 2019 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2020 , 137, 48330.     

Development and optimisation of a defined high cell density yeast medium

Saccharomyces cerevisiae cells grown in a small volume of chemically defined media neither reach the desired cell density nor grow at a fast enough rate to scale down the volume and increase the sample number of classical biochemical assays, as the detection limit of the readout often requires a high number of cells as an input. To ameliorate this problem, we developed and optimised a new high cell density (HCD) medium for S. cerevisiae. Starting from a widely used synthetic medium composition, we systematically varied the concentrations of all components without the addition of other compounds. We used response surface methodology to develop and optimise the five components of the medium: glucose, yeast nitrogen base, amino acids, monosodium glutamate, and inositol. We monitored growth, cell number, and cell size to ensure that the optimisation was towards a greater density of cells rather than just towards an increase in biomass (i.e., larger cells). Cells grown in the final medium, HCD, exhibit growth more similar to the complex medium yeast extract peptone dextrose (YPD) than to the synthetic defined (SD) medium. Whereas the final cell density of HCD prior to the diauxic shift is increased compared with YPD and SD about threefold and tenfold, respectively. We found normal cell-cycle behaviour throughout the growth phases by monitoring DNA content and protein expression using fluorescent reporters. We also ensured that HCD media could be used with a variety of strains and that they allow selection for all common yeast auxotrophic markers.