8,270 research outputs found

    Ruthenium arene complexes as anticancer agents: an XAS study

    Get PDF
    Two Ru(III) complexes that have already entered clinical trials, [ImH]trans-[RuCl4(dmso)(Im)] (NAMI-A, Im = imidazole) and [InH]trans-[RuCl4(Ind)2] (KP1019, Ind = indazole), are potential alternatives to Pt chemotherapeutic drugs since they are effective against cancers untreatable by cisplatin. These compounds have been proposed to operate by an “activation by reduction” process, with a reduction of Ru(III) to the more active Ru(II) species in vivo, which has thus generated an interest towards organometallic Ru(II) arene complexes. The leading complexes of this field would be the RAPTA-C pioneered by Dyson and co-workers which showed anti-metastatic activity akin to NAMI-A and the [Ru(p-cymene)(en)]Cl pioneered by Sadler and co-workers which displayed cytotoxicity in vitro. These compounds show great promise due to the versatility in systematically modifying them in order to exhibit desirable physical, chemical and biological properties, mainly by changing the nature of the arene ligand and introducing different chelating ligands that may enhance selectivity towards tumour cells. Traditional anticancer drugs were designed to target DNA but in recent years, serum proteins have been found to be more relevant for the field of Ru anticancer drugs. In order to improve drug efficacy, an understanding of the mechanisms and speciation of these complexes in biological medium is needed. X-ray absorption spectroscopy (EXAFS, XANES) and X-ray fluorescence mapping (XFM) have been used according to previous methods to study the speciation in biological fluids, extracellular matrix and cells to provide insights into the biological activities of various Ru arene complexes. The compounds were first analysed using UV-Vis for their kinetics but this technique was not sensitive enough to differentiate the speciation products. A library of Ru(II) arene model complexes containing biologically relevant ligands (N/O and S-donors) were synthesized and their structures confirmed using multiple scattering (MS). The Ru compounds reacted under various biological conditions were then analysed using multiple linear regression, and the speciation products formed either by aquation or ligand-exchange were able to be identified. In particular, the results of RAPTA-C in rat blood cells were interesting where large changes in the XAS spectra was observed when red blood cells were present in the samples, which indicates extensive metabolism of Ru in whole blood. XFM was useful in analysing the speciation of the Ru-bound proteins in electrophoresis gels and the preliminary results of NAMI-A, KP1019 and RAPTA-C provided good insights on the different serum protein binding affinity of these complexes, and how it might affect their anticancer properties

    Ruthenium arene complexes as anticancer agents: an XAS study

    Get PDF
    Two Ru(III) complexes that have already entered clinical trials, [ImH]trans-[RuCl4(dmso)(Im)] (NAMI-A, Im = imidazole) and [InH]trans-[RuCl4(Ind)2] (KP1019, Ind = indazole), are potential alternatives to Pt chemotherapeutic drugs since they are effective against cancers untreatable by cisplatin. These compounds have been proposed to operate by an “activation by reduction” process, with a reduction of Ru(III) to the more active Ru(II) species in vivo, which has thus generated an interest towards organometallic Ru(II) arene complexes. The leading complexes of this field would be the RAPTA-C pioneered by Dyson and co-workers which showed anti-metastatic activity akin to NAMI-A and the [Ru(p-cymene)(en)]Cl pioneered by Sadler and co-workers which displayed cytotoxicity in vitro. These compounds show great promise due to the versatility in systematically modifying them in order to exhibit desirable physical, chemical and biological properties, mainly by changing the nature of the arene ligand and introducing different chelating ligands that may enhance selectivity towards tumour cells. Traditional anticancer drugs were designed to target DNA but in recent years, serum proteins have been found to be more relevant for the field of Ru anticancer drugs. In order to improve drug efficacy, an understanding of the mechanisms and speciation of these complexes in biological medium is needed. X-ray absorption spectroscopy (EXAFS, XANES) and X-ray fluorescence mapping (XFM) have been used according to previous methods to study the speciation in biological fluids, extracellular matrix and cells to provide insights into the biological activities of various Ru arene complexes. The compounds were first analysed using UV-Vis for their kinetics but this technique was not sensitive enough to differentiate the speciation products. A library of Ru(II) arene model complexes containing biologically relevant ligands (N/O and S-donors) were synthesized and their structures confirmed using multiple scattering (MS). The Ru compounds reacted under various biological conditions were then analysed using multiple linear regression, and the speciation products formed either by aquation or ligand-exchange were able to be identified. In particular, the results of RAPTA-C in rat blood cells were interesting where large changes in the XAS spectra was observed when red blood cells were present in the samples, which indicates extensive metabolism of Ru in whole blood. XFM was useful in analysing the speciation of the Ru-bound proteins in electrophoresis gels and the preliminary results of NAMI-A, KP1019 and RAPTA-C provided good insights on the different serum protein binding affinity of these complexes, and how it might affect their anticancer properties

    Calibration of Distributionally Robust Empirical Optimization Models

    Full text link
    We study the out-of-sample properties of robust empirical optimization problems with smooth ϕ\phi-divergence penalties and smooth concave objective functions, and develop a theory for data-driven calibration of the non-negative "robustness parameter" δ\delta that controls the size of the deviations from the nominal model. Building on the intuition that robust optimization reduces the sensitivity of the expected reward to errors in the model by controlling the spread of the reward distribution, we show that the first-order benefit of ``little bit of robustness" (i.e., δ\delta small, positive) is a significant reduction in the variance of the out-of-sample reward while the corresponding impact on the mean is almost an order of magnitude smaller. One implication is that substantial variance (sensitivity) reduction is possible at little cost if the robustness parameter is properly calibrated. To this end, we introduce the notion of a robust mean-variance frontier to select the robustness parameter and show that it can be approximated using resampling methods like the bootstrap. Our examples show that robust solutions resulting from "open loop" calibration methods (e.g., selecting a 90%90\% confidence level regardless of the data and objective function) can be very conservative out-of-sample, while those corresponding to the robustness parameter that optimizes an estimate of the out-of-sample expected reward (e.g., via the bootstrap) with no regard for the variance are often insufficiently robust.Comment: 51 page

    Surface-Modified Membrane as A Separator for Lithium-Ion Polymer Battery

    Get PDF
    This paper describes the fabrication of novel modified polyethylene (PE) membranes using plasma technology to create high-performance and cost-effective separator membranes for practical applications in lithium-ion polymer batteries. The modified PE membrane via plasma modification process plays a critical role in improving wettability and electrolyte retention, interfacial adhesion between separators and electrodes, and cycle performance of lithium-ion polymer batteries. This paper suggests that the performance of lithium-ion polymer batteries can be greatly enhanced by the plasma modification of commercial separators with proper functional materials for targeted application

    Efficient Coupling Between Photonic and Dielectric-Loaded Surface Plasmon Polariton Waveguides With the Same Core Material

    Get PDF
    We theoretically investigate how to efficiently couple a photonic waveguide to a dielectric-loaded surface plasmon polariton (DLSPP) waveguide when they are based on a common core material. The DLSPP waveguide is tapered and butt coupled to the photonic waveguide. First, we propose the use of a dielectric with a higher refractive index than the dielectrics of previous DLSPP waveguides. The photonic and DLSPP waveguides are designed to reduce the loss and tapering region length of the coupling, and the tapering region is optimized. We achieve the coupling between the photonic and DLSPP waveguides based on a dielectric of refractive index of 1.57 with a coupling loss of 2.3 dB through a 3-mu m-long coupling region. The coupling loss is further reduced by modifying the DLSPP waveguide into a double-DLSPP ((DLSPP)-L-2) waveguide. The (DLSPP)-L-2 waveguide has an additional low-index dielectric between its high-index dielectric and metal layer. Designed appropriately, the (DLSPP)-L-2 waveguide can be coupled to the photonic waveguide with a coupling loss of 1.1 dB through a 4-mu m-long coupling region. Since the photonic and DLSPP or (DLSPP)-L-2 waveguides investigated in this paper can be simultaneously fabricated, they may constitute an easily realizable hybrid planar lightwave circuit with a relatively low loss.open

    Harms Of Loot Boxes And Approaching Regulation In Singapore

    Get PDF
    ‘Loot boxes’ are a type of videogame monetization model that contains randomized rewards of varying rarities which emerged in recent years. The element of chance seeks to entice players into buying loot boxes in hopes of receiving a rare and desirable reward. The design of loot boxes has been identified to be addictive and to entice players to spend more money than they estimate they would. With links to addiction and gambling behaviours, loot boxes may cause social harm if unregulated. Singapore is not new to the videogaming scene and may seek to regulate loot boxes should it emerge as a social problem amongst Singaporeans. By acknowledging existing approaches towards regulating loot boxes and situating loot boxes in Singapore’s social context, this paper explores Lessig’s four modalities of constraint as a framework to hypothesize regulatory options for Singapore

    Healthcare Database and Research at Biostatistics Core Facility of John A. Burns School of Medicine

    Get PDF
    The Department of Quantitative Health Science at John A. Burns School of Medicine operates a Biostatistics Core Facility, which employs extensive healthcare databases to advance health-related research and enhance our understanding of healthcare. The Core Facility is dedicated to offering biostatistical research assistance to basic science, clinical, and translational researchers. Its expertise lies in the areas of study design, data management and analysis, grant proposal development, methodology research, and education in biostatistics and related fields

    Mildly explosive autoregression with anti-persistent errors

    Get PDF
    Ministry of Education, Singapore under its Academic Research Funding Tier
    corecore