Selective Delivery of Doxorubicin to EGFR+ Cancer Cells by Cetuximab–DNA Conjugates

Doxorubicin is a hydrophobic anticancer drug that has poor selectivity, due to the lack of active targeting capability. Here, learning lessons from the success of antibody–drug conjugates, we have designed a new doxorubicin delivery system without conjugating doxorubicin to antibody directly. In this setup, cetuximab, an antibody that targets the epidermal growth factor receptor (EGFR) in cancer cells, was conjugated to a single-stranded DNA with a carefully designed sequence in a site-selective manner by using the DNA-templated protein conjugation (DTPC) method. The DNA duplex in the conjugates serves as a carrier of doxorubicin through noncovalent intercalation, and cetuximab functions as the targeting agent; this could drastically decrease systemic toxicity and potentially avoid under- or overdosing. The size of conjugates loaded with doxorubicin was about 8.77 or 16.61 nm when characterized by dynamic light scattering and atomic force microscopy, respectively. In vitro cytotoxicity and selective cancer cell killing was investigated against two EGFR⁺ cell lines (KB and MDA-MB-231) and one EGFR⁻ cell line (NIH-3T3). Cytotoxicity and flow cytometry data showed that doxorubicin loaded in cetuximab–DNA conjugates was more potent in terms of cell cytotoxicity than free doxorubicin in EGFR-overexpressed cell lines, thus suggesting that the conjugates were more selectively and easily taken up into cells, followed by rapid release of doxorubicin from the system into the cytoplasm from endosomes.     

The effect of Al2O3 on the friction performance of automotive brake friction materials

This study consists of two stages. In the first stage, bronze-based break linings were produced and friction-wear properties of them were investigated. In the second stage, 0.5%, 1%, 2% and 4% alumina (Al₂O₃) powders were added to the bronze-based powders and Al₂O₃ reinforced bronze-based break linings were produced. Friction–wear properties of the Al₂O₃ reinforced samples were aslo investigated and compared to those of plain bronze-based ones. For this purpose, friction coefficient and wear behaviour of the samples were tested on the grey cast iron disc. The hardness and density of the samples were also determined. Microstructures of the samples before and after the sintering and the worn surfaces of the wear specimens were examined using a scanning electron microscope (SEM). The sample compacted at 350 MPa and sintered at 820 °C exhibited the optimum friction–wear behaviour. With increase in friction surface temperature, a reduction in the friction coefficient of the samples was observed. The lowest reduction in the friction coefficient with increasing temperature was for the 2% and 4% Al₂O₃ reinforced samples. The SEM images of the sample indicated that increase in Al₂O₃ content resulted in adhesive wear. With increase in Al₂O₃ content, a reduction in mass loss of the samples was also observed. Overall, the samples reinforced with 2% and 4% Al₂O₃ exhibited the best results.     

Increasing profit by improving gas handling systems

The availability of a smelter’s gas handling systems is crucial to the profitability of the plant. In new projects, the best technical and economic result is achieved if the gas handling systems are integrated into the process. This integration requires close cooperation between the smelter process designer and the gas handling designer. In modernization projects, environmentally, economically, and technically feasible solutions can be found, and smelter productivity can be increased when imagination and new technology are applied.     

Transformation of the EFQM approach from business towards operations excellence

The purpose of this paper is to provide an enabler-based approach for a supervised self-assessment of operations excellence (OsE). Based on the latest approaches of excellence in operations from the literature as well as on the philosophy of the EFQM model, an OsE working definition was developed. In contrast to operational excellence (OE), which deals exclusively with the optimization of result driven processes, OsE promotes the enhancement of operation-specific enablers and linked results. The evaluation of crucial cause–effect relationships of relevant enabler and result criteria supports the determination of a company’s capability to achieve sustainability and excellence in terms of its operations. To foster a methodical integration of OsE in organizations, a phase model for a systematic assessment process was designed and verified with 24 companies in the Austrian machinery and metalware industries.