Modified Epidermal Growth Factor Receptor (EGFR)-Bearing Liposomes (MRBLs) Are Sensitive to EGF in Solution

Cancers often overexpress EGF and other growth factors to promote cell replication and migration. Previous work has not produced targeted drug carriers sensitive to abnormal amounts of growth factors. This work demonstrates that liposomes bearing EGF receptors covalently crosslinked to p-toluic acid or methyl-PEO4-NHS ester (or, in short, MRBLs) exhibit an increased rate of release of encapsulated drug compounds when EGF is present in solution. Furthermore, the modified EGF receptors retain the abilities to form dimers in the presence of EGF and bind specifically to EGF. These results demonstrate that MRBLs are sensitive to EGF in solution and indicate that MRBL-reconstituted modified EGF receptors, in the presence of EGF in solution, form dimers which increase MRBL permeability to encapsulated compounds

Effect of disorder on topological charge pumping in the Rice-Mele model

Recent experiments with ultracold quantum gases have successfully realized integer-quantized topological charge pumping in optical lattices. Motivated by this progress, we study the effects of static disorder on topological Thouless charge pumping. We focus on the half-filled Rice-Mele model of free spinless fermions and consider random diagonal disorder. In the instantaneous basis, we compute the polarization, the entanglement spectrum, and the local Chern marker. As a first main result, we conclude that the space-integrated local Chern marker is best suited for a quantitative determination of topological transitions in a disordered system. In the time-dependent simulations, we use the time-integrated current to obtain the pumped charge in slowly periodically driven systems. As a second main result, we observe and characterize a disorder-driven breakdown of the quantized charge pump. There is an excellent agreement between the static and the time-dependent ways of computing the pumped charge. The topological transition occurs well in the regime where all states are localized on the given system sizes and is therefore not tied to a delocalization-localization transition of Hamiltonian eigenstates. For individual disorder realizations, the breakdown of the quantized pumping occurs for parameters where the spectral bulk gap inherited from the band gap of the clean system closes, leading to a globally gapless spectrum. As a third main result and with respect to the analysis of finite-size systems, we show that the disorder average of the bulk gap severely overestimates the stability of quantized pumping. A much better estimate is the typical value of the distribution of energy gaps, also called mode of the distribution

Pharmaceutical quality of antibiotics in Small Island Nations in the Western Pacific region: a pilot survey

Background: Australia’s closest neighbours in the Western Pacific face many procurement, distribution and regulatory challenges providing patients with quality pharmaceuticals on limited budgets. This study tested the hypothesis that some antibiotics being used within the healthcare systems of Papua New Guinea, Vanuatu and the Solomon Islands were substandard, and through this pilot project explored challenges and constraints around collaborative regional pharmaceutical quality testing opportunities.Methods: A list of 11 commonly used and ‘essential’ acute care intravenous and oral antibiotic products was compiled. A purposive sample of 20 units of each listed medicine was collected at the earliest possible point of the supply chain within the three participating nations. These samples were transported to Australia for analysis.Results: All oral and intravenous product samples complied with uniformity of mass standards, except for oral amoxicillin from Country 3. Most antibiotics showed uniformity of content except for cloxacillin.Conclusion: Most samples met quality standards, except for cloxacillin, which failed dramatically and this may indicate increased susceptibility to degradation in tropical settings. Although the results are reassuring compared with recent studies of pharmaceutical quality in this region, products of substandard quality were identified. The issues encountered in the timely testing of samples demonstrate the need for innovative solutions to promote pharmaceutical quality assurance, particularly in resource-limited settings. Strategic regional cooperation could greatly increase testing capability for Small Island Nations, benefiting the most vulnerable populations and strengthening antibiotic stewardship across the region