The Critical Role of Passive Permeability in Designing Successful Drugs

Passive permeability is a key property in drug disposition and delivery. It is critical for gastrointestinal absorption, brain penetration, renal reabsorption, defining clearance mechanisms and drug-drug interactions. Passive diffusion rate is translatable across tissues and animal species, while the extent of absorption is dependent on drug properties, as well as in vivo physiology/pathophysiology. Design principles have been developed to guide medicinal chemistry to enhance absorption, which combine the balance of aqueous solubility, permeability and the sometimes unfavorable compound characteristic demanded by the target. Permeability assays have been implemented that enable rapid development of structure-permeability relationships for absorption improvement. Future advances in assay development to reduce nonspecific binding and improve mass balance will enable more accurately measurement of passive permeability. Design principles that integrate potency, selectivity, passive permeability and other ADMET properties facilitate rapid advancement of successful drug candidates to patients.     

Synthesis and Application of Novel Nano Fe-BTC/GO Composites as Highly Efficient Photocatalysts in the Dye Degradation

Topics in Catalysis - Nano Fe-BTC/graphene oxide (GO) composites were successfully synthesized by hydrothermal treatment with a microwave-assisted method. Samples were characterized by X-ray...     

CuInS2/SiNWs/Si composite material for application as potential photoelectrode for photoelectrochemical hydrogen generation

This work aims at developing a new composite material based on nanosized semiconducting CuInS₂ (CIS) particles combined with silicon nanowires grown on a silicon substrate (SiNWs/Si) for photoelectrochemical (PEC)-splitting of water. The CIS particles were prepared via a colloidal method using N-methylimidazole (NMI) as the solvent and an annealing treatment. The SiNWs were obtained by chemical etching of silicon (100) substrates assisted by a metal. The CIS/SiNWs/Si composite material was obtained by deposition of an aliquot of a suspension of CIS particles onto the SiNWs/Si substrate, using spin coating followed by a drying step. The XRD pattern demonstrated that CuInS₂ grows in the tetragonal/chalcopyrite phase, while SiNWs/Si presents a cubic structure. The SEM images show semi-spherical particles (～10 nm) distributed on the surface of silicon nanowires (～10 μm). The EIS measurements reveal n-type conductivity for CIS, SiNWs/Si and CIS/SiNWs/Si materials, which could favour the oxidation reaction of water molecules.     

Molten salt synthesis of MAX phases in the Ti-Al-C system

The molten salt method was used to synthesise the MAX phase compounds Ti₂AlC and Ti₃AlC₂ from elemental powders. Between 900–1000?°C, Ti₂AlC was formed alongside ancillary phases TiC and TiAl, which decreased in abundance with increasing synthesis temperature. Changing the stoichiometry and increasing the synthesis temperature to 1300?°C resulted in formation of Ti₃AlC₂ alongside Ti₂AlC and TiC. The type of salt flux used had little effect on the product formation. The reaction pathway for Ti₂AlC was determined to be the initial formation of TiC_1-x templating on the graphite and titanium aluminides.     

Performance Analysis of Pulse Generators on Residual Stress of Machined Silicon Steel Using the EDM Process

The cracks in the workpiece specimens can reduce the fatigue life of any machine components. Since the residual stress has a considerable amount of influence on determining crack formation over the machined surface, it is very essential to analyze the residual stress developed in any machining process. However, it is a very tedious process to compute the residual stress over the machined surface. In the present study, an endeavor has been made to measure and analyze the residual stress of machined silicon steel as a workpiece using the EDM process with different energy distribution. The nano-indentation method was used to compute the residual stress produced over the machined surface. From the experimental results, it was found that the uniform energy distribution has produced higher compressive residual stress owing to the tiny and uniform spark energy distribution. It has also been observed that the tool electrode has a considerable amount of influence on determining development of residual stress in the EDM process.     

Alloy optimisation of bainitic steel for large plastic mould

Based on the phase transformation theories, especially the T₀ concept of bainite transformation, alloy optimisation of bainitic steel with carbides has been carried out aiming at the produce of plastic mould with large cross-section. The effect of manganese and silicon on proeutectoid ferrite and bainite transformation is explored by dilatometric analysis, XRD and different microscopy techniques. The results show that after the alloy optimisation, the transformation of proeutectoid ferrite is suppressed and when the cooling rate is lower than 0·1°C?s^??1, the new lower bainite transformation appears by decreasing carbon capacity of austenite and promoting carbide precipitation. Industrial production proves that the optimised alloy SDP1 can meet the demand for the plastic mould with the thickness of 1050?mm.     

Prediction of rock mass P wave velocity using blasthole drilling information

In this paper, the development of the models for the prediction of rock mass P wave velocity is presented. For model development, the database of 53 cases including widely used and recorded drilling parameters and P wave velocity was constructed from the field studies conducted in 13 open pit lignite mines. Both conventional linear, non-linear multiple regression and Adaptive Neuro Fuzzy Inference System (ANFIS) were used for model development. Prediction performance indicators showed that ANFIS model presented the best performance and it can successfully be used for the preliminary prediction of P wave velocities of rock masses.     

Preparation of highly crystalline titanium-based ceramic microfibers from polymer precursor blend by needle-less electrospinning

The aim of the present contribution is to study the influence of the post-spinning heat - treatment of single TiO₂/PVP precursor fibers on the properties and morphology of the final titanium-based microfibers. The post-spinning treatment conditions were: calcination in air at 450–600?°C and pyrolysis in argon at 1000–1700?°C. Calcination resulted in a production of anatase-rich and pure rutile fibers. The use of an alternative sintering method, the low-temperature plasma treatment, led to the crystallization of the composite Magnéli phases/polymer fibers. As a result of the same one precursor, pyrolysis at 1000?°C, the Carbon/TiO₂ composite fibers were obtained. Rising the treatment temperature in inert atmosphere led to the formation of the titanium carbide fibers. The formation process and all the obtained products were characterized by differential scanning calorimetry accompanied with thermogravimetric analysis (DSC/TGA), scanning and transmission electron microscopy (SEM, TEM), X-ray diffraction (XRD), and image analysis techniques.     

Antitumor Effects of Vitamin D Analogs on Hamster and Mouse Melanoma Cell Lines in Relation to Melanin Pigmentation

Deregulated melanogenesis is involved in melanomagenesis and melanoma progression and resistance to therapy. Vitamin D analogs have anti-melanoma activity. While the hypercalcaemic effect of the active form of Vitamin D (1,25(OH)₂D₃) limits its therapeutic use, novel Vitamin D analogs with a modified side chain demonstrate low calcaemic activity. We therefore examined the effect of secosteroidal analogs, both classic (1,25(OH)₂D₃ and 25(OH)D₃), and novel relatively non-calcemic ones (20(OH)D₃, calcipotriol, 21(OH)pD, pD and 20(OH)pL), on proliferation, colony formation in monolayer and soft-agar, and mRNA and protein expression by melanoma cells. Murine B16-F10 and hamster Bomirski Ab cell lines were shown to be effective models to study how melanogenesis affects anti-melanoma treatment. Novel Vitamin D analogs with a short side-chain and lumisterol-like 20(OH)pL efficiently inhibited rodent melanoma growth. Moderate pigmentation sensitized rodent melanoma cells towards Vitamin D analogs, and altered expression of key genes involved in Vitamin D signaling, which was opposite to the effect on heavily pigmented cells. Interestingly, melanogenesis inhibited ligand-induced Vitamin D receptor translocation and ligand-induced expression of VDR and CYP24A1 genes. These findings indicate that melanogenesis can affect the anti-melanoma activity of Vitamin D analogs in a complex manner.