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.     

Room temperature R-curve and stable crack growth behaviour of ZrB2–SiC ceramic composites

ABSTRACT

R-curve and controlled stable crack growth behaviour of ZrB₂–17vol.-%SiC and ZrB₂–45vol.-%SiC ceramic composites was studied on V-notched samples using four-point bending at room temperature. The rising K_1R behaviour was determined as a function of the crack extension Δa with a crack bridging mechanism being dominant in such behaviour. Significant differences in crack growth rates were found within the same composition of ceramics simply as the crack length varied during crack growth processes. These differences are indicative of the significant influence of microstructural parameters of the ceramics on crack propagation. The peculiarities of stress intensity factor K₁ and the crack growth-specific behaviour in ZrB₂–SiC particulate ceramic composites are discussed.     

Production of the Carboxylate Reductase from Nocardia otitidiscaviarum in a Soluble,Active Form for in vitro Applications

Accessing aldehydes from carboxylate moieties is often a challenging task. In this regard, carboxylate reductases (CARs) are promising catalysts provided by nature that are able to accomplish this task in just one step, avoiding over-reduction to the alcohol product. However, the heterologous expression of CARs can be quite difficult due to the excessive formation of insoluble protein, thus hindering further characterization and application of the enzyme. Here, the heterologous production of the carboxylate reductase from Nocardia otitidiscaviarum (NoCAR) was optimized by a combination of i) optimized cultivation conditions, ii) post-translational modification with a phosphopantetheinyl transferase and iii) selection of an appropriate expression strain. Especially, the selection of Escherichia coli tuner cells as host had a strong effect on the final 110-fold increase in the specific activity of NoCAR. This highly active NoCAR was used to reduce sodium benzoate to benzaldehyde, and it was successfully assembled with an in vitro regeneration of ATP and NADPH, being capable of reducing about 30 mM sodium benzoate with high selectivity in only 2 h of reaction.     

Robust Fitting in Computer Vision: Easy or Hard?

International Journal of Computer Vision - Robust model fitting plays a vital role in computer vision, and research into algorithms for robust fitting continues to be active. Arguably the most...     

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.