Moserkusk0309

In our previous study, we observed that androgen deprivation therapy (ADT) may induce a compensatory increase in MAPK or JNK signaling. Here, we tested the effects of the MEK inhibitors PD0325901 and GSK1120212, ERK1/2 inhibitor GDC-0994, and the JNK inhibitor AS602801 alone and in combination with the AR inhibitor enzalutamide (ENZ) in androgen-sensitive LNCaP cells and androgen-resistant C4-2 and 22Rv1 cells. Enzalutamide combined with AS602801 synergistically killed LNCaP, C4-2, and 22Rv1 cells, and decreased migration and invasion of LNCaP and C4-2 cells. We studied the combination of enzalutamide with AS602801 in vivo using luciferase labeled LNCaP xenografts, and observed that combination of ENZ with AS602801 significantly suppressed tumor growth compared with either drug alone. Importantly, combination therapy resulted in dramatic loss of AR mRNA and protein. Surprisingly, mechanistic studies and Nanostring data suggest that AS602801 likely activates JNK signaling to induce apoptosis. Since AS602801 had sufficient safety and toxicity profile to advance from Phase I to Phase II in clinical trials, repurposing of this compound may represent an opportunity for rapid translation for clinical therapy of CRPC patients. HYPOTHESIS Mechanistic understanding of particle-flocculant interactions and its link to the resulting floc structure is essential for developing tailings treatments with enhanced consolidation rates. A noninvasive, in-situ visualization of the floc formation and the consequent sediment microstructure via tri-dimensional laser scanning confocal microscopy (LSCM) can enable establishing the quantitative link between the flocculation conditions and bulk properties of the resulting sediment structures. EXPERIMENTS A dual fluorescence/reflectance confocal imaging protocol is developed to non-invasively detect morphological changes in dense oil sands tailings during flocculation with an anionic polymer and the subsequent sediment compaction stages for three different polymer dosages. The image reconstruction is developed to quantify the organics/clay volume fractions in the sediment and the floc network characteristics through the pseudo fractal dimension which are related to the bulk rheological properties following a 5-day densification period. FINDINGS In-situ imaging of the flocculation process gives insights into the variable floc density and size at different stages of mixing. The acquired 3D images of the flocculated sediment reveal that bitumen remains within the flocs. The increase in the polymer dosage results in the reduction of the sediment fractality and strength attributed to the possible formation of more swelled floc structures. Clay reflectance detection is validated using a model kaolinite clay dispersion. The developed methodology may ultimately be used as a guiding tool for standard screening of the new flocculants and flocculation protocols for various mineral tailings systems. The electrochromic (EC) properties of inorganic-organic hybrids of tungsten oxide/reduced graphene oxide (WO3/rGO) thin films were examined. Using hydrothermal method WO3 nanorods were deposited on a conducting Indium-doped tin oxide (ITO) glass substrate. In succession, the reduced graphene oxide thin film was coated on WO3 thin film using improved Hummers method. The structural, morphological, optical, and electrochromic responses of WO3, rGO, and WO3/rGO films are illustrated. Compared with pure WO3 film, WO3/rGO composite film demonstrates improved EC performance because of enhanced double insertion/extraction of ions and electrons. It realizes a large optical modulation (58.8% at 633 nm) with a significant increase in Coloration Efficiency (CE) and EC stability. The preferred spatial orientation of single-wall carbon nanotubes (SWCNTs) in their interaction with enzymes determines their behavior either as nano-supports or as inhibitors. α -chymotrypsin (α-CT) is considered a serine protease model for studying nanomaterial/proteases interactions. The interaction of α-CT with pristine single-wall carbon nanotubes is still unknown. Here α-CT/SWCNT hybrids are synthesized and characterized. Spectroscopic, microscopic and kinetic measurements, coupled to molecular dynamics simulations, provide a detailed description of the interaction between α-CT and SWCNTs. selleck chemical The SWCNT binding pocket was unambiguously identified. A perfect match is observed with the crevice structure of the α-CT substrate binding pocket. The activity of α-CT, upon SWCNT binding, is dramatically reduced, as expected by the interaction of the SWCNT in the active site of the protein. π-π stacking between aromatic residues and the conjugated surface of SWCNT governs α-CT/SWCNT interactions. An important role in the bonding appears also for purely hydrophobic residues and with residues able to establish surfactant-like interactions. The secondary structure of α-CT and the catalytic triad structure are not perturbed by the complex formation, on the contrary the volume of the substrate binding pocket is strongly reduced by SWCNT binding because SWCNT occupies the α-CT substrate binding site, clogging the active site. HYPOTHESIS Although capillary imbibition of solid foams is involved in many industrial applications, general theory for capillary imbibition has never been proved to apply for this specific class of porous materials. EXPERIMENTS In order to compare accurately experiment and theory we produce solid foam samples with monodisperse pore size distributions and tunable pore volume fraction, and we measure their permeability (Darcy), their capillary pressure and their imbibition rate. FINDINGS Our findings reveal that the imbibition velocity is qualitatively compatible with the Washburn theory but it is one order of magnitude smaller than the predicted value. This deviation is attributed to the excess time spent by the liquid-gas interface through connections between pores, for which an empirical expression is provided as a function of pore size and solid volume fraction. Our results provide the first step to understand deeply the imbibition process in foams and to predict imbibition rates for various foamed materials.