Enhancing Strength and Quantifying Sustainability of Building Blocks Manufactured by Geopolymerization.

Enhancing the strength of fly ash (FA)-based geopolymer by increasing the alkaline activator content is a costly and unsustainable technique. Therefore, this work was designed to reduce the activator by employing the pressured catalysis (PC) technique, coupled with the use of minerals that have filler and occupying effects. The main objective was to enhance the strength of the mix with a lower alkaline-to-precursor (A/P) ratio and create a sustainable, load-bearing building block from it. Initially, the compressive strength of the FA-based geopolymer was investigated experimentally by varying sodium silicate to sodium hydroxide and A/P ratios with ambient and hot curing. Afterward, PC was applied to the optimized proportion of constituents, and a significant increase in strength (9.6 to 20.0 Mpa) was observed at a 0.25 A/P ratio. By adding clay and dune sand (DS), the compressive strength was 19.5 and 40.4 Mpa at an A/P of 0.25 and 0.16, respectively. The strength gain mechanism was evaluated at the molecular and micro levels by conducting FTIR and SEM analyses. The environmental and economic indices and strength indicated the high sustainability of DS-based geopolymers compared to analogous blocks. The environmental and economic benefits of 23.9% reduced CO2 emissions and 24.2% less cost were provided by the DS-based block compared to the FA-clay-based block. A DS-based geopolymer obtains strength at a low A/P due to its occupying effect and results in sustainable building blocks.

Trivalent nanobody-based ligands mediate powerful activation of GPVI, CLEC-2, and PEAR1 in human platelets whereas FcγRIIA requires a tetravalent ligand.

BACKGROUND: Clustering of the receptors glycoprotein receptor VI (GPVI), C-type lectin-like receptor 2 (CLEC-2), low-affinity immunoglobulin γ Fc region receptor II-a (FcγRIIA), and platelet endothelial aggregation receptor 1 (PEAR1) leads to powerful activation of platelets through phosphorylation of tyrosine in their cytosolic tails and initiation of downstream signaling cascades. GPVI, CLEC-2, and FcγRIIA signal through YxxL motifs that activate Syk. PEAR1 signals through a YxxM motif that activates phosphoinositide 3-kinase. Current ligands for these receptors have an undefined valency and show significant batch variation and, for some, uncertain specificity. OBJECTIVES: We have raised nanobodies against each of these receptors and multimerized them to identify the minimum number of epitopes to achieve robust activation of human platelets. METHODS: Divalent and trivalent nanobodies were generated using a flexible glycine-serine linker. Tetravalent nanobodies utilize a mouse Fc domain (IgG2a, which does not bind to FcγRIIA) to dimerize the divalent nanobody. Ligand affinity measurements were determined by surface plasmon resonance. Platelet aggregation, adenosine triphosphate secretion, and protein phosphorylation were analyzed using standardized methods. RESULTS: Multimerization of the nanobodies led to a stepwise increase in affinity with divalent and higher-order nanobody oligomers having sub-nanomolar affinity. The trivalent nanobodies to GPVI, CLEC-2, and PEAR1 stimulated powerful and robust platelet aggregation, secretion, and protein phosphorylation at low nanomolar concentrations. A tetravalent nanobody was required to activate FcγRIIA with the concentration-response relationship showing a greater variability and reduced sensitivity compared with the other nanobody-based ligands, despite a sub-nanomolar binding affinity. CONCLUSION: The multivalent nanobodies represent a series of standardized, potent agonists for platelet glycoprotein receptors. They have applications as research tools and in clinical assays.

Exploring basic science knowledge retention within a cohort of undergraduate medical students in the United Kingdom: A longitudinal study.

BACKGROUND: Clinical reasoning is reliant on students having acquired a strong foundation in the basic sciences. However, there remains uncertainty regarding whether medical students are maintaining this knowledge over the span of their degrees. Therefore, this project aimed to assess long-term retention of basic science knowledge within a cohort of students from an undergraduate medical school in the United Kingdom (UK). METHODS: This longitudinal study followed a cohort of students, from their first to final year. In their final year, participants sat a bespoke formative basic science knowledge assessment that utilised 46 single-best-answer questions. To examine for long-term attainment differences, these scores were compared with those achieved in first-year assessments. RESULTS: Of the eligible students, 40% partook in the study (n = 22). Comparing assessment scores highlighted an enhancement in overall basic science knowledge between first and final year (p < 0.01). Although most basic science domains remained unchanged between both time points, anatomy and physiology scores increased (p = 0.03 and p = 0.02, respectively), whereas biochemistry scores were the only ones to decrease (p = 0.02). DISCUSSION: This project provides insight into how well students are retaining the basic sciences during their studies. Underperforming science domains were identified, alongside pedagogical explanations for their individual shortcomings; for instance, students' perceived relevance of a domain is seen as a driver for its retention. Subsequently, a group of recommendations were derived to reinforce the most affected domains. The inclusion of more questions on the underperforming sciences, in clinically focussed assessments, is one such suggestion.