Tethered drug release from model contact lenses

Drug delivery to the eye remains a challenge due to low compliance and high amounts of drug loss resulting from anatomical barriers. Contact lens-based delivery systems offer many advantages since their increased corneal residence time can increase drug bioavailability. A releasable, sustained delivery system from a contact lens has been evaluated in the current work. Using a labile lactide spacer, comprised of poly(ethylene glycol) methacrylate, varying numbers of lactide units and succinic anhydride, a model drug, R-roscovitine, was covalently incorporated into model silicone lenses (consisting of 80 mol% N,N-dimethylacrylamide and 20 mol% of a modified silicone). This enabled a greater amount of the drug to remain in the material following extraction with isopropyl alcohol, a common purification procedure used in lens manufacturing. The incorporation of the tether and drug did not substantially alter the bulk properties of the materials, with their water content remaining between 32% and 36% and their transmittance remaining at over 90% at 600 nm. Drug release from these materials exceeded 2 weeks, with the longer lactide tethers showing greater release as expected. This demonstrates that these covalently modified materials have the potential to be used to deliver drugs in a sustained manner. © 2022 Society of Industrial Chemistry.     

Extended Scope and Understanding of Zinc-Dependent Alcohol Dehydrogenases for Reduction of Cyclic α-Diketones

Alcohol dehydrogenases (ADH) are important tools for generating chiral α-hydroxyketones. Previously, only the ADH of Thauera aromatica was known to convert cyclic α-diketones with appropriate preference. Here, we extend the spectrum of suitable enzymes by three alcohol dehydrogenases from Citrifermentans bemidjiense (CibADH), Deferrisoma camini (DecADH), and Thauera phenylacetica (ThpADH). Of these, DecADH is characterized by very high thermostability; CibADH and ThpADH convert α-halogenated cyclohexanones with increased activity. Otherwise, however, the substrate spectrum of all four ADHs is highly conserved. Structural considerations led to the conclusion that conversion of diketones requires not only the expansion of the active site into a large binding pocket, but also the circumferential modification of almost all amino acid residues that form the first shell of the binding pocket. The constellation appears to be overall highly specific for the relative positioning of the carbonyl functions and the size of the C-ring.     

Probing Defects and Spin-Phonon Coupling in CrSBr via Resonant Raman Scattering

Understanding the stability limitations and defect formation mechanisms in 2D magnets is essential for their utilization in spintronic and memory technologies. Here, defects in mono- to multilayer CrSBr are correlated with structural, vibrational, and magnetic properties. Resonant Raman scattering is used to reveal distinct vibrational defect signatures. In pristine CrSBr, it is shown that bromine atoms mediate vibrational interlayer coupling, allowing for distinguishing between surface and bulk defect modes. Environmental exposure is shown to cause drastic degradation in monolayers, with the formation of intralayer defects. This is in contrast to multilayers that predominantly show bromine surface defects. Through deliberate ion irradiation, the formation of defect modes is tuned: these are strongly polarized and resonantly enhanced, reflecting the quasi--1D electronic character of CrSBr. Strikingly, pronounced signatures of spin-phonon coupling of the intrinsic phonon modes and the ion beam-induced defect modes are observed throughout the magnetic transition temperature. Overall, defect engineering of magnetic properties is possible, with resonant Raman spectroscopy serving as a direct fingerprint of magnetic phases and defects in CrSBr.     

Cellular Disulfide Bond Formation in Bioactive Peptides and Proteins

Bioactive peptides play important roles in metabolic regulation and modulation and many are used as therapeutics. These peptides often possess disulfide bonds, which are important for their structure, function and stability. A systematic network of enzymes—a disulfide bond generating enzyme, a disulfide bond donor enzyme and a redox cofactor—that function inside the cell dictates the formation and maintenance of disulfide bonds. The main pathways that catalyze disulfide bond formation in peptides and proteins in prokaryotes and eukaryotes are remarkably similar and share several mechanistic features. This review summarizes the formation of disulfide bonds in peptides and proteins by cellular and recombinant machinery.     

Dry kiln scheduling in furniture production

In this paper, a dry kiln scheduling problem from the furniture manufacturing industry is considered. Factory-specified due dates for orders, kiln availability, kiln capacity, and travel time from the kilns to the factories are all incorporated in a model which is formulated as an integer linear program. The objective of the formulation is to minimize the maximum tardiness of orders arriving at the plants by solving a special case of scheduling n independent jobs on m non-identical parallel ciachines. Because of the computational complexity, and the fact that standard integer programming packages appear to perform very poorly on the problem, a heuristic approach is developed. Computational experience is provided which indicates that the heuristic gives very high quality solutions to problems in near real-time.     

Characterization of intermetallics in aluminum alloy 3004

The evolution of intermetallics in aluminum alloy 3004 from the casting to the thin-sheet stages is examined. Two casting types have been utilized: 650-mm-thick D.C. ingot and 12-mm-thick stationary-mold-cast strip. Size, shape, density, and area fraction of intermetallics are characterized in their matrix environment using the standard optical, scanning electron microscopy and scanning transmission electron microscopy metallographic techniques. The results are discussed in terms of a) the effect of processing parameters on the intermetallic structure and b) the impact of primary and secondary intermetallics on the microstructure development (grain size and texture) and the performance (anisotropy, bendability, metal finish, and metal transfer during forming). The strip-sourced alloy is characterized by a smaller primary intermetallic size but it affords a greater flexibility in developing a variety of primary and secondary intermetallic area fractions and size distributions. Hence it can be tailored more readily to a specific set of performance criteria.     

Poverty and disrepair: Challenging the myth of ignorance in private sector housing

As private home ownership grows in Europe, so do the problems of maintenance and repair for poorer owners. In England, it has been believed that one obstacle is the owners' apparent satisfaction with poor conditions. This paper deconstructs the questions in the English House Condition Survey 1981 on which that assumption has been based. By reference to other EHCSs and to a research methodology offering a more differentiated approach to establishing residents' views, it suggests that the problem is not ignorance at all. A more subtle understanding of the validity of housing satisfaction questionnaires is needed to develop effective policies of urban renewal.