662 research outputs found

    Synergistic antitumor activity of camptothecin-doxorubicin combinations and their conjugates with hyaluronic acid

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    Combinations of topoisomerase inhibitors I and II have been found to synergistically inhibit cancer cell growth in vitro, yet clinical studies of these types of combinations have not progressed beyond phase II trials. The results of clinical combinations of topoisomerase (top) I and II inhibitors typically fall within one of two categories: little to no improvement in therapeutic efficacy, or augmented toxicity compared to the single drug counterparts. Hence, despite the promising activity of top I and II inhibitor combinations in vitro, their clinical applicability has not been realized. Here, we report the use of polymer-drug conjugates as a means to co-deliver synergistic doses of top I and II inhibitors camptothecin (CPT) and doxorubicin (DOX) to tumors in vivo in a 4T1 breast cancer model. At specific molar ratios, DOX and CPT were found to be among the most synergistic combinations reported to date, with combination indices between 0.01 and 0.1. The identified optimal ratios were controllably conjugated to hyaluronic acid, and elicited significant tumor reduction of murine 4T1 breast cancer model when administered intravenously. This study elucidates a method to identify synergistic drug combinations and translate them to in vivo by preserving the synergistic ratio via conjugation to a carrier polymer, thus opening a promising approach to translate drug combinations to clinically viable treatment regimens

    Long range absorption in the scattering of 6He on 208Pb and 197Au at 27 MeV

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    Quasi-elastic scattering of 6He at E_lab=27 MeV from 197Au has been measured in the angular range of 6-72 degrees in the laboratory system employing LEDA and LAMP detection systems. These data, along with previously analysed data of 6He + 208Pb at the same energy, are analyzed using Optical Model calculations. The role of Coulomb dipole polarizability has been investigated. Large imaginary diffuseness parameters are required to fit the data. This result is an evidence for long range absorption mechanisms in 6He induced reactions.Comment: 10 pages, 10 figures, minor corrections. To appear in Nucl. Phys.

    Stratification strength and light climate explain variation in chlorophyll a at the continental scale in a European multilake survey in a heatwave summer.

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    To determine the drivers of phytoplankton biomass, we collected standardized morphometric, physical, and biological data in 230 lakes across the Mediterranean, Continental, and Boreal climatic zones of the European continent. Multilinear regression models tested on this snapshot of mostly eutrophic lakes (median total phosphorus [TP] = 0.06 and total nitrogen [TN] = 0.7 mg L 1), and its subsets (2 depth types and 3 climatic zones), show that light climate and stratification strength were the most significant explanatory variables for chlorophyll a (Chl a) variance. TN was a significant predictor for phytoplankton biomass for shallow and continental lakes, while TP never appeared as an explanatory variable, suggesting that under high TP, light, which partially controls stratification strength, becomes limiting for phytoplankton development. Mediterranean lakes were the warmest yet most weakly stratified and had significantly less Chl a than Boreal lakes, where the temperature anomaly from the long-term average, during a summer heatwave was the highest (+4 C) and showed a significant, exponential relationship with stratification strength. This European survey represents a summer snapshot of phytoplankton biomass and its drivers, and lends support that light and stratification metrics, which are both affected by climate change, are better predictors for phytoplankton biomass in nutrient-rich lakes than nutrient concentrations and surface temperature

    Coupled influences of particle shape, surface property and flow hydrodynamics on rod-shaped colloid transport in porous media

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    Hypothesis: Natural or engineered colloidal particles are often non-spherical in shape. In contrast to the widely-used “homogeneous sphere” assumption, the non-spherical particle shape is expected to alter particle–fluid-surface interactions, which in turn affect particle transport and retention. Experiments and Simulations: Polystyrene microspheres were stretched to rod-shaped particles of two aspect ratios (2:1, 6:1). The transport and retention behaviors of rods versus spheres were investigated in packed quartz sand columns and impinging jet systems. In parallel, a 3D trajectory model was employed to simulate particle translation and rotation, and to elucidate the role and underlying mechanisms of particle shape impact on transport. Findings: Rods were observed to undergo rotating and tumbling motions in response to fluid shear from experiments and simulations. However, no distinct retention trends between rods and spheres were observed from column studies, despite BSA-coating on particles, Fe-coating on sand or velocity change. This was primarily due to the super-hydrophobic nature of colloid surfaces acquired from stretching process, which in hydrophilic sand columns, dominated particle–surface charge interactions. Simulations using colloids with randomly distributed charge patches qualitatively produced the observed insensitivity in retention respecting aspect ratio under low charge coverage (<30%). Hence, particle shape influences were strongly coupled with colloid surface properties and flow hydrodynamics

    Growth at infinity and index of polynomial maps

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    Let F: Kn→Kn be a polynomial map such that F−1(0) is compact, where View the MathML source. Then we give a condition implying that there is a uniform bound for the Łojasiewicz exponent at infinity in certain deformations of F. This fact gives a result about the invariance of the global index of FThe first author was partially supported by DGICYT Grant MTM2012-33073. The second author was partially supported by FAPESP-BEPE 2012/22365-8.Bivià-Ausina, C.; Huarcaya, JAC. (2015). Growth at infinity and index of polynomial maps. Journal of Mathematical Analysis and Applications. 422(2):1414-1433. https://doi.org/10.1016/j.jmaa.2014.09.062S14141433422

    Effect of bending test on the performance of CdTe solar cells on flexible ultra-thin glass produced by MOCVD

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    The development of lightweight and flexible solar modules is highly desirable for high specific power applications, building integrated photovoltaics, unmanned aerial vehicles and space. Flexible metallic and polyimide foils are frequently used, but in this work an alternative substrate with attractive properties, ultra-thin glass (UTG) has been employed. CdTe solar cells with average efficiency reaching 14.7% AM1.5G efficiency have been produced on UTG of 100 μm thickness. Little has been reported on the effects on PV performance when flexed, so we investigated the effects on J-V parameters when the measurements were performed in 40 mm and 32 mm bend radius, and in a planar state before and after the bend curvature was applied. The flat J-V measurements after 32 mm bending test showed some improvement in efficiency, Voc and FF, with values higher than the first measurement in a planar state. In addition, two CdTe solar cells with identical initial performance were subjected to 32 mm static bending test for 168 hours, the results showed excellent uniformity and stability and no significant variation on J-V parameters was observed. External quantum efficiency and capacitance voltage measurements were performed and showed no significant change in spectral response or carrier concentration. Residual stress analysis showed that no additional strain was induced within the film after the bending test and that the overall strain was low. This has demonstrated the feasibility of using CdTe solar cells on UTG in new applications, when a curved module is required without compromising performance

    Search for composite and exotic fermions at LEP 2

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    A search for unstable heavy fermions with the DELPHI detector at LEP is reported. Sequential and non-canonical leptons, as well as excited leptons and quarks, are considered. The data analysed correspond to an integrated luminosity of about 48 pb^{-1} at an e^+e^- centre-of-mass energy of 183 GeV and about 20 pb^{-1} equally shared between the centre-of-mass energies of 172 GeV and 161 GeV. The search for pair-produced new leptons establishes 95% confidence level mass limits in the region between 70 GeV/c^2 and 90 GeV/c^2, depending on the channel. The search for singly produced excited leptons and quarks establishes upper limits on the ratio of the coupling of the excited fermio

    Search for lightest neutralino and stau pair production in light gravitino scenarios with stau NLSP

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    Promptly decaying lightest neutralinos and long-lived staus are searched for in the context of light gravitino scenarios. It is assumed that the stau is the next to lightest supersymmetric particle (NLSP) and that the lightest neutralino is the next to NLSP (NNLSP). Data collected with the Delphi detector at centre-of-mass energies from 161 to 183 \GeV are analysed. No evidence of the production of these particles is found. Hence, lower mass limits for both kinds of particles are set at 95% C.L.. The mass of gaugino-like neutralinos is found to be greater than 71.5 GeV/c^2. In the search for long-lived stau, masses less than 70.0 to 77.5 \GeVcc are excluded for gravitino masses from 10 to 150 \eVcc . Combining this search with the searches for stable heavy leptons and Minimal Supersymmetric Standard Model staus a lower limit of 68.5 \GeVcc may be set for the stau mas

    Search for direct production of charginos and neutralinos in events with three leptons and missing transverse momentum in √s = 7 TeV pp collisions with the ATLAS detector

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    A search for the direct production of charginos and neutralinos in final states with three electrons or muons and missing transverse momentum is presented. The analysis is based on 4.7 fb−1 of proton–proton collision data delivered by the Large Hadron Collider and recorded with the ATLAS detector. Observations are consistent with Standard Model expectations in three signal regions that are either depleted or enriched in Z-boson decays. Upper limits at 95% confidence level are set in R-parity conserving phenomenological minimal supersymmetric models and in simplified models, significantly extending previous results
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