Dendrimer Conjugation Enhances Tumor Penetration and Cell Kill of Doxorubicin in 3D Coculture Lung Cancer Models

Background: Doxorubicin (DOX) is a potent chemotherapeutic widely used for solid tumors (1). Despite high efficacy in 2D cell culture, DOX efficacy does not translate to in vivo lung cancer models (2). Major side effects such as cardiotoxicity may be alleviated with nano-based drug delivery systems (nanoDDS). However, tumor penetration of DOX and DOX-nanoDDS is largely unknown and is an additional barrier to effective clinical therapy (3). Here we describe a nanoDDS capable of enhancing the penetration of DOX. Methods: DOX was conjugated to generation 4 poly(amido-amine) dendrimers through (GFLG) tumor- liable bond. G4SA-GFLG-DOX was synthesized/characterized. spheroids were formed of (A549) lung adenocarcinoma cells and (3T3) fibroblasts. Spheroids were characterized for ECM components with immunohistochemistry. Confocal microscopy was used to evaluate the penetration, internalization, and colocalization of DOX and G4SA-GFLG-DOX. MTT assay and Caspase 3/7 to assess 2D and 3D cytotoxicity. Flow cytometry to determine cells uptake. Results: DOX conjugation to dendrimer resulted in G4SA-GFLG-DOX with ~5.5 DOX, 10±1 nm hydrodynamic diameter, and a -17±3 mV zeta-potential. Spheroids of (A549:3T3) were ECM- rich, developed ECM containing collagen-I, hyaluronan, laminin, and fibronectin. While DOX and G4SA-GFLG-DOX had similar toxicities in 2D model, G4SA-GFLG-DOX demonstrated a 3.1-fold greater penetration into spheroids compared to DOX and correlated to a greater efficacy as measured by caspase 3/7 activity. Also, flow cytometry showed higher uptake of G4SA- GFLG-DOX in cancer cells compared to fibroblasts. Conclusion: The work demonstrates enhanced penetration of DOX, via dendrimer conjugation, into an ECM- rich 3D lung cancer model. The enhanced penetration of G4SA-GFLG-DOX correlated with greater antitumor efficacy. Acknowledgements: We acknowledge partial financial support from the Center for Pharmaceutical Engineering and Sciences - School of Pharmacy at VCU. This study was supported by VCU Quest for Distinction and NSF (DRM #1508363). Microscopy was performed at the VCU Microscopy Facility, supported, in part, by funding from NIH-NCI Cancer Center Support Grant P30 CA016059. RA would like to acknowledge King Faisal University (KFU) and Saudi Arabian Cultural Mission (SACM) for a scholarship.https://scholarscompass.vcu.edu/gradposters/1091/thumbnail.jp

Line and Continuum Variability in Active Galaxies

We compared optical spectroscopic and photometric data for 18 AGN galaxies over 2 to 3 epochs, with time intervals of typically 5 to 10 years. We used the Multi-Object Double Spectrograph (MODS) at the Large Binocular Telescope (LBT) and compared the spectra to data taken from the SDSS database and the literature. We find variations in the forbidden oxygen lines as well as in the hydrogen recombination lines of these sources. For 4 of the sources we find that, within the calibration uncertainties, the variations in continuum and line spectra of the sources are very small. We argue that it is mainly the difference in black hole mass between the samples that is responsible for the different degree of continuum variability. In addition we find that for an otherwise constant accretion rate the total line variability (dominated by the narrow line contributions) reverberates the continuum variability with a dependency $\Delta L_{line} \propto (\Delta L_{cont.})^{\frac{3}{2}}$. Since this dependency is prominently expressed in the narrow line emission it implies that the luminosity dominating part of the narrow line region must be very compact with a size of the order of at least 10 light years. A comparison to literature data shows that these findings describe the variability characteristics of a total of 61 broad and narrow line sources.Comment: 30 pages including the appendix, 18 figures including the appendix. Accepted 2015 September 3. Received 2015 August 24; in original form 2015 July 3 in Monthly Notices of the Royal Astronomical Societ

Some diophantine quadruples in the ring Z[√-2]

A complex diophantine quadruple with the property D,$(z)$, where $z in$ Z$[sqrt {-2}]$, is a subset of Z$[sqrt {-2}]$ of four elements such that the product of its any two distinct elements increased by $z$ is a perfect square in Z$[sqrt{-2}]$. In the present paper we prove that if $b$ is an odd integer, then there does not exist a diophantine quadruple with the property D$(a + bsqrt{-2})$. For $z=a+bsqrt{-2}$, where $b$ is even, we prove that there exist at least two distinct complex diophantine quadruples if $a$ and $b$ satisfy some congruence conditions

Optimum Functions for Radial Wires of Monopole Antennas with Arbitrary Elevation Angles

Monopole antennas on the earth usually use ground screen with simple radial wires to improve their radiation performance. The number of radials,N, is usually considered a constant in the screen. This paper studies the effect of changing N and considering it as a function of distance, ρ, from the monopole using a simple and yet a fast method. The function N(ρ) is optimized for different beam angles of an HF monopoleantenna. The theoretical functions are converted to practical functions to be formed using meandered lines. Practicable calculated results are validated bymethod of moments. Furthermore it is shown that for low angle radiation aconstant N(ρ) with optimized radius of the ground screen is the best choice. The results can be used for higher frequencies, i.e. VHF and UHF frequency bands as well

Magnetically geared induction machines

A wound-rotor induction machine is artfully coupled to a magnetic gear to achieve a high-torque-density drive system called magnetically geared induction machine (MaGIM). The high-speed rotor of MaGIM is common to both the machine and gear sides. A rotating diode rectifier electrically links the machine's wound rotor and a dc boost winding on the gear side to increase the torque-transmission capabilities of the overall system. The first investigations on a 100 kW-120 r/min MaGIM are promising, since an increase in torque of ∼ 15% could be obtained by inserting the diode rectifier. For fixed speed applications, this induction-machine-based system can be directly supplied from the main