Basse Jackson (pillowclam02)

Through gel electrophoretic studies, we identified that, at a feed ratio of DNA to AX of 115, AX is capable of forming polyplexes with DNA in the form of nanoparticles with an average hydrodynamic diameter of ∼100 nm and surface charge of -1.40 ± 0.91 mV. We envision that chemically modified AX, originally sourced from agricultural waste materials and not from food products, can be used as functional nanomaterials for gene delivery in the agrochemical sector thus catalyzing the circular approach of sustainability.The natural products combretastatin A-1 (CA1) and combretastatin A-4 (CA4) function as potent inhibitors of tubulin polymerization and as selective vascular disrupting agents (VDAs) in tumors. Bioreductively activatable prodrug conjugates (BAPCs) can enhance selectivity by serving as substrates for reductase enzymes specifically in hypoxic regions of tumors. A series of CA1-BAPCs incorporating nor-methyl, mono-methyl, and gem-dimethyl nitrothiophene triggers were synthesized together with corresponding CA4-BAPCs, previously reported by Davis (Mol. Cancer Ther. 2006, 5 (11), 2886), for comparison. The CA4-gem-dimethylnitrothiophene BAPC 45 proved exemplary in comparison to its nor-methyl 43 and mono-methyl 44 congeners. It was stable in phosphate buffer (pH 7.4, 24 h), was cleaved (25%, 90 min) by NADPH-cytochrome P450 oxidoreductase (POR), was inactive (desirable prodrug attribute) as an inhibitor of tubulin polymerization (IC50 > 20 μM), and demonstrated hypoxia-selective activation in the A549 cell line [hypoxia cytotoxicity ratio (HCR) = 41.5]. The related CA1-gem-dimethylnitrothiophene BAPC 41 was also promising (HCR = 12.5) with complete cleavage (90 min) upon treatment with POR. In a preliminary in vivo dynamic bioluminescence imaging study, BAPC 45 (180 mg/kg, ip) induced a decrease (within 4 h) in light emission in a 4T1 syngeneic mouse breast tumor model, implying activation and vascular disruption.A simple imaging add-on utilizing the combination of a relay lens and an optical grating to a nulling ellipsometer for the purpose of imaging and correcting angular distortion is designed, built, and tested. Image contrast is achieved on a standardized silicon wafer, graphene transferred on silicon wafer, a self-assembled monolayer of 1-octadecanethiol on gold, and a 11 mixture of dilauroylphosphatidylcholine / distearoylphosphatidylcholine (DLPC/DSPC) on copper. The configuration used in this paper corrects the angular distortion and depth of focus with a spatial resolution of 4.38 μm in the laser's incident direction and 7.81 μm in the direction that is perpendicular to the incident plane together with 3 Å of normal resolution while still maintaining a large field of view of at least 720 μm × 550 μm in focus without executing any line scanning, post-image reconstruction, or specially customized objective method. Better resolution is possibly attained with higher NA optics.Understanding the conformational characteristics of protein complexes in solution is crucial for a deeper insight in their biological function. Molecular dynamics simulations performed on high performance computing plants and with modern simulation techniques can be used to obtain large data sets that contain conformational and thermodynamic information about biomolecular systems. While this can in principle give a detailed picture of protein-protein interactions in solution and therefore complement experimental data, it also raises the challenge of processing exceedingly large high-dimensional data sets with several million samples. Here we present a novel method for the characterization of protein-protein interactions, which combines a neural network based dimensionality reduction technique to obtain a two-dimensional representation of the conformational space with a density based clustering algorithm for state detection and a metric which assesses the (dis)similarity between different conformational spaces. This method is highly scalable