Studies on the blood precursors of milk protein

Publication authorized February 5, 1939.Digitized 2007 AES.Includes bibliographical references (pages 19-20)

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

Degenerate flag varieties: moment graphs and Schr\"oder numbers

We study geometric and combinatorial properties of the degenerate flag varieties of type A. These varieties are acted upon by the automorphism group of a certain representation of a type A quiver, containing a maximal torus T. Using the group action, we describe the moment graphs, encoding the zero- and one-dimensional T-orbits. We also study the smooth and singular loci of the degenerate flag varieties. We show that the Euler characteristic of the smooth locus is equal to the large Schr\"oder number and the Poincar\'e polynomial is given by a natural statistics counting the number of diagonal steps in a Schr\"oder path. As an application we obtain a new combinatorial description of the large and small Schr\"oder numbers and their q-analogues.Comment: 25 page

The relation of the route of administration of thyroxine, thyroprotein, and intermediate products upon their utilization by ruminants

Publication authorized February 2, 1946.Digitized 2007 AES.Includes bibliographical references (pages 19-20)

A study of the involution of the mammary gland of the goat

Publication authorized February 28, 1936."Submitted by the junior author to the Department of Dairy Husbandry in partial fulfillment of the requirements for the degree of Master of Arts, 1936"--P. [5].Digitized 2007 AES.Includes bibliographical references (page 23)

Renal phenotype of Et-1 transgenic mice is modulated by androgens

<p>Abstract</p> <p>Introduction</p> <p>Activation of the endothelin (ET) system promotes inflammation and fibrosis in various tissues including the kidney. Male ET-1 transgenic mice are characterized by chronic kidney inflammation and renal scarring. We hypothesized that this renal phenotype might be modulated by androgens. Thus the aim of our study was to elucidate the impact of gonadectomy in ET-1 transgenic mice on kidney function and morphology.</p> <p>Methods</p> <p>Male ET-1 transgenic mice at the age of 10 weeks were randomly allocated to the following groups: normal ET transgenic mice (ET; n = 17) and ET transgenic mice that underwent castration (ET+cas; n = 12). Study duration was 9 months. Creatinine clearance and protein excretion was monitored. At study end animals were sacrificed and kidneys were harvested for histology/immunhistochemistry.</p> <p>Results</p> <p>Castration significantly ameliorated glomerulosclerosis in ET-1 transgenic mice (ET glomerulosclerosis-score: 3.0 ± 0.17 vs ET+cas: 2.4 ± 0.17; p < 0.05) as well as renal perivascular fibrosis (ET fibrosis-score: 3.0 ± 0.14 vs ET+cas: 2.2 ± 0.14; p < 0.05). However, interstitial fibrosis and media/lumenratio of renal arteries remained unaffected by castration. Regarding inflammation, castration significantly reduced the number of CD4-positive cells in renal tissue of ET-1 transgenic mice (ET CD4-positive cells/10000 cells: 355 ± 72 vs ET+cas: 147 ± 28; p < 0.05). Renal tissue contents of CD8 positive cells as well as of macrophages were not affected by castration. Regarding kidney function castration significantly reduced proteinuria in ET-1 transgenic mice whereas creatinine clearance did not differ between study groups.</p> <p>Conclusion</p> <p>Our study demonstrates that the renal histopathological phenotype in male ET-1 transgenic mice with regard to glomerulosclerosis, proteinuria, perivascular fibrosis and immune cell immigration is ameliorated by castration. We thus conclude that the effects of ET-1 overexpression on renal tissue injury are modulated by androgens.</p

Viologen-immobilized 2D polymer film enabling highly efficient electrochromic device for solar-powered smart window

Electrochromic devices (ECDs) have emerged as a unique class of optoelectronic devices for the development of smart windows. However, current ECDs typically suffer from low coloration efficiency (CE) and high energy consumption, which have thus hindered their practical applications, especially as components in solar-powered EC windows. Here, the high-performance ECDs with a fully crystalline viologen-immobilized 2D polymer (V2DP) thin film as the color-switching layer is demonstrated. The high density of vertically oriented pore channels (pore size approximate to 4.5 nm; pore density approximate to 5.8 x 1016 m-2) in the synthetic V2DP film enables high utilization of redox-active viologen moieties and benefits for Li+ ion diffusion/transport. As a result, the as-fabricated ECDs achieve a rapid switching speed (coloration, 2.8 s; bleaching, 1.2 s), and a high CE (989 cm2 C-1, and low energy consumption (21.1 µW cm-2). Moreover, it is managed to fabricate transmission-tunable, self-sustainable EC window prototypes by vertically integrating the V2DP ECDs with transparent solar cells. This work sheds light on designing electroactive 2D polymers with molecular precision for optoelectronics and paves a practical route toward developing self-powered EC windows to offset the electricity consumption of buildings