Discovery of ruthenium(II) metallocompound and olaparib synergy for cancer combination therapy

Synergistic drug combinations can extend the use of poly(ADP-ribose) polymerase inhibitors (PARPi) such as Olaparib to BRCA-proficient tumors and overcome acquired or de novo drug resistance. To identify new synergistic combinations for PARPi, we screened a "micro-library" comprising a mix of commercially available drugs and DNA-binding ruthenium(II) polypyridyl complexes (RPCs) for Olaparib synergy in BRCA-proficient triple-negative breast cancer cells. This identified three hits: the natural product Curcumin and two ruthenium(II)-rhenium(I) polypyridyl metallomacrocycles. All combinations identified were effective in BRCA-proficient breast cancer cells, including an Olaparib-resistant cell line, and spheroid models. Mechanistic studies indicated that synergy was achieved via DNA-damage enhancement and resultant apoptosis. Combinations showed low cytotoxicity toward non-malignant breast epithelial cells and low acute and developmental toxicity in zebrafish embryos. This work identifies RPC metallomacrocycles as a novel class of agents for cancer combination therapy and provides a proof of concept for the inclusion of metallocompounds within drug synergy screens

Analysis of Signal Propagation in an Experiment Room with Epoxy Covered Floor for Wireless Sensor Network Applications

As sensor applications combined with wireless network becoming more of an everyday applications, the optimal deployment becomes ever increasing important as that would be a key important factor in the trade-off between cost and link quality. This paper reports on the effect of epoxy covered floor on signal propagation characteristics in an experiment room. Microchip developed motes were used to measure signal propagation in an experiment room where sensors would be deployed extensively. The results show that the signal strength for 30 cm antenna height provides a significant margin with respect to signal noise floor. As for the 5 cm antenna height, there is still around 25 dB margin in average before the signal reaches noise floor. Analysis shows that the log-distance model is the best fit to the measured data. Free Space Loss model seemed to under estimate the overall performance of the signals. An important conclusion from this study is that wireless mote deployment must consider the margin between the two signals of antenna heights and the margin to noise floor to avoid link quality deterioration especially for sensitive data acquisition applications

Soliton passively mode-locked pulses generation in thulium-holmium doped fiber laser (THDFL) with molybdenum oxide saturable absorber

This work proposed and demonstrated stable passive mode-locking in a thulium-holmium doped fiber laser (THDFL) using molybdenum oxide (MoOx) deposited onto a tapered fiber as a saturable absorber (SA). The SA was fabricated using the optical deposition technique for 2.0 µm region operation. The modulation depth, saturation intensity and non-saturable loss of MoOx SA were measured to be ~24.3%, ~0.01 MW/cm2 and ~75.7%, respectively. The threshold of the mode-locking operation was obtained at a pump power of 184.3 mW with a centre wavelength of 1937.1 nm and a 3-dB bandwidth of 4 nm. It has a high signal-to-noise ratio (SNR) of ~77 dB and produces a stable pulse with a repetition rate of 11.5 MHz and a pulse width of 1.64 p

Effects of Growth Rates and Compositions on Dendrite Arm Spacings in Directionally Solidified Al-Zn Alloys

Dendritic spacing can affect microsegregation profiles and also the formation of secondary phases within interdendritic regions, which influences the mechanical properties of cast structures. To understand dendritic spacings, it is important to understand the effects of growth rate and composition on primary dendrite arm spacing (lambda(1)) and secondary dendrite arm spacing (lambda(2)). In this study, aluminum alloys with concentrations of (1, 3, and 5 wt pct) Zn were directionally solidified upwards using a Bridgman-type directional solidification apparatus under a constant temperature gradient (10.3 K/mm), resulting in a wide range of growth rates (8.3-165.0 mu m/s). Microstructural parameters, lambda(1) and lambda(2) were measured and expressed as functions of growth rate and composition using a linear regression analysis method. The values of lambda(1) and lambda(2) decreased with increasing growth rates. However, the values of lambda(1) increased with increasing concentration of Zn in the Al-Zn alloy, but the values of lambda(2) decreased systematically with an increased Zn concentration. In addition, a transition from a cellular to a dendritic structure was observed at a relatively low growth rate (16.5 mu m/s) in this study of binary alloys. The experimental results were compared with predictive theoretical models as well as experimental works for dendritic spacing. (C) The Minerals, Metals & Materials Society and ASM International 201