Inhibition of Human α‐Methylacyl CoA Racemase (AMACR): a Target for Prostate Cancer

The enzyme α‐methylacyl CoA racemase (AMACR) is involved in the metabolism of branched‐chain fatty acids and has been identified as a promising therapeutic target for prostate cancer. By using the recently available human AMACR from HEK293 kidney cell cultures, we tested a series of new rationally designed inhibitors to determine the structural requirements in the acyl component. An N‐methylthiocarbamate (K_i=98 nM ), designed to mimic the proposed enzyme‐bound enolate, was found to be the most potent AMACR inhibitor reported to date.     

Anthraquinone Losses During Alkaline Pulping

Extensive loss of anthraquinone (AQ) or the active catalyst anthrahydroquinone (AHQ) from the AQ –- AHQ catalytic cycle has been explained in part by side reactions leading to the reaction product anthrone (anthracen-9-one), followed by subsequent formation of adducts with lignin quinone methides. Degradation of an adduct between anthrone and the quinone methide of guaiacylglycerol-β-guaiacyl ether, under soda pulping conditions, resulted in a complex mixture of products. The mixture included 3-guaiacylbenzanthrone, bianthronyl, bianthrone, guaiacol, AQ, trans-coniferyl alcohol, trans-coniferylaldehyde, cis- and trans-1-(3-methoxy-4-hydroxyphenyl)-2-(2-methoxyphenoxy)ethene, vanillin, and 2-methoxy-4-vinylphenol. C-13 NMR studies of lignins isolated from soda/AQ spent liquors indicated the presence of residual anthrone adducts and a significant content of chemically attached AQ.     

Transport of surface-modified nanoparticles through cell monolayers

We synthesized three peptides, a D-polyarginyl peptide (r8(FITC)), a Tat peptide (Tat(FITC)), and a control peptide (Cp(FITC)) and attached each to amino-CLIO, a nanoparticle 30 nm in diameter. We then examined the effective permeability, Peff, of all six materials through CaCo-2 monolayers. The transport of peptide-nanoparticles was characterized by a lag phase (0-8 h) and a steady-state phase (9-27 h). The steady-state Peff values for peptides were in the order r8(FITC)>Tat(FITC)=Cp(FITC). When r8(FITC) and Tat(FITC) peptides were attached to the nanoparticle, they conferred their propensity to traverse cell monolayers onto the nanoparticle, whereas Cp(FITC) did not. Thus, when the r8(FITC) peptide was attached to the amino-CLIO nanoparticle, the resulting peptide-nanoparticle had a Peff similar to that of this poly-D-arginyl peptide alone. The Peff of r8(FITC)-CLIO (MW approximately 1000 kDa) was similar to that of mannitol (MW=182 Da), a poorly transported reference substance, with a far lower molecular weight. These results are the first to indicate that the modification of nanoparticles by attachment of membrane-translocating sequence-based peptides can alter nanoparticle transport through monolayers. This suggests that the surface modification of nanoparticles might be a general strategy for enhancing the permeability of drugs and that high-permeability nanoparticle-based therapeutics can be useful in selected pharmaceutical applications.     

Desulfurization of commercial fuels by π-complexation: Monolayer CuCl/γ-Al2O3

Monolayer CuCl/γ-Al₂O₃ sorbent was studied for desulfurization of a commercial jet fuel (364.3 ppmw S) and a commercial diesel (140 ppmw S). The sorbent was prepared by means of spontaneous monolayer dispersion methods. Deep desulfurization (sulfur levels of <1 ppmw) was accomplished with this sorbent using a fixed-bed adsorber. The CuCl/γ-Al₂O₃ sorbent was capable of removing 6.4 and 11.2 mg of sulfur per gram for jet fuel at breakthrough (at <1 ppmw S) and saturation, respectively. The same sorbent was capable of removing 0.94 and 1.8 mg of sulfur per gram for BP diesel at breakthrough and saturation, respectively. The difference in sulfur capacities for jet fuel and diesel was apparently caused by the difference in concentrations of strongly binding compounds, such as nitrogen heterocycles, heavy (polynuclear) aromatics and fuel additives. In comparison with CuCl/γ-Al₂O₃, Cu(I)Y zeolite has higher sulfur capacities but is less stable and can be easily oxidized to Cu(II)Y by fuel additives (such as oxygenates) and moisture and consequently loses π-complexation ability. However, all these cuprous π-complexation sorbents selectively adsorb thiophenic compounds over aromatics and olefins (as predicted by the high separation factors), which resulted in the observed desulfurization capability. A feasibility study is shown for efficient regeneration of CuCl/γ-Al₂O₃ using ultrasound at ambient temperature. Possible problems associated with desulfurization using π-complexation sorbents for commercial fuels are discussed.     

The reduction of l-cystine hydrochloride at stationary and rotating disc mercury electrodes

The kinetics of l-cystine hydrochloride reduction have been studied at a mercury-plated copper rotating disc electrode (RDE) and at a stationary mercury disc electrode (SMDE) in 0.1 mol dm⁻³ HCl at 298 K. The reduction of the disulphide is irreversible and hydrogen evolution is the major side reaction. In contrast to steady state electrode kinetic studies at a mercury drop electrode (which shows a well-defined limiting current), the mercury-plated Cu RDE shows overlap between disulphide reduction and hydrogen evolution. These effects are attributable to strong reactant adsorption with a calculated surface coverage close to 100%. A Tafel slope of −185 mV per decade is found with a cathodic transfer coefficient of 0.32 and a formal rate constant of 6.7 × 10⁻⁹ m s⁻¹. The relative merits of steady state voltammetry at a mercury-plated copper RDE and linear sweep voltammetry at the SMDE are discussed, as is the mechanism of l-cysteine hydrochloride formation.     

Color constancy from invariant wavelength ratios: An algorithm to simplify the chromatic adaptation model

In a recent article on color constancy, the chromatic adaptation model was of a novel type comprising three components separately calculated—hue, chromaticness, and lightness. The constant hue component was a simple calculation of predicted wavelength but the other two components were less direct. This article provides an algorithm to simplify the model's calculation. Calculation is far simpler and more intuitive than conventional models using complex 3 × 3 matrix transforms with their various and contentious adaptation primaries and potential disadvantages (e.g., in brightness and color gamut). The model is shown to be at least as accurate as six other (conventional) models and does not require high math skill. © 2015 Wiley Periodicals, Inc. Col Res Appl, 41, 468–476, 2016     

The Exception That Proves the Rule: How Sodium Chelation Can Alter the Charge-Cell Binding Correlation of Fluorescein-Based Multimodal Imaging Agents

In the present study we describe and explain an aberrant behavior in terms of receptor binding profile of a fluorescein-based multimodal imaging agent for gastrin releasing peptide receptor (GRPR) visualization by elucidating a chelating mechanism on sodium ions of its fluorescent dye moiety. This hypothesis is supported by both biological results and spectroscopic analyses of different fluorescein-carrying conjugates and an equally charged set of analogous tartrazine-based GRPR-binding imaging agents. Fluorescein interacts with sodium which reduces the overall negative charge of the dye molecule by one. This reduction in apparent total net charge explains the exceptional behavior found for the fluorescein-based multimodal bioconjugate in the context of the charge-cell binding correlation hypothesis.     

Synthesis and biological investigation of novel tricyclic benzodiazepinedione-based RGD analogues

Integrins, a widely expressed family of heterodimeric cell surface adhesion proteins, are expressed in a variety of cell types. They play a decisive role in cell-cell adhesion or cell to extracellular matrix adhesion events. Antagonists of alpha(v)beta(3) or alpha(IIb)beta(3) integrin may have a potential use in suppression of pathological processes. We present the synthesis of novel tricyclic benzodiazepinedione-based RGD analogues, which were subsequently tested in a solid-phase receptor assay in order to investigate their binding affinities towards alpha(v)beta(3) and alpha(IIb)beta(3) integrin.     

Processing and Mechanical Properties of Al2O3/Ni3Al Composites with Interpenetrating Network Microstructure

Composites with microstructures of interpenetrating networks were manufactured by gas pressure infiltration of Ni₃Al into porous preforms of aluminum oxide. Composites with Ni₃Al contents of between 15% and 30% by volume were made and evaluated mechanically at temperatures between room temperature and 1000°C. The fracture strength, the fracture toughness, Young's modulus, and the thermal expansion coefficient were measured for each composite and test condition and were correlated with the microstructures of the composites. Composites with low Ni₃Al contents had strengths below 400 MPa, presumably due to microcracking along the interface between the Ni₃Al and the Al₂O₃. The composite with the highest content of Ni₃Al, 30 vol%, had a mean fracture strength of 675 ± 16 MPa, a Weibull modulus of 23.9, and a room-temperature toughness of 9.2 ± 0.5 MPa·m^1/2.     

High-Thermal-Conductivity Aluminum Nitride Ceramics: The Effect of Thermodynamic, Kinetic, and Microstructural Factors

Improvement in the thermal conductivity of aluminum nitride (AlN) can be realized by additives that have a high thermodynamic affinity toward alumina (Al₂O₃), as is clearly demonstrated in the aluminum nitride-yttria (AlN-Y₂O₃) system. A wide variety of lanthanide dopants are compared at equimolar lanthanide oxide:alumina (Ln₂O₃: Al₂O₃, where Ln is a lanthanide element) ratios, with samaria (Sm₂O₃) and lutetia (Lu₂O₃) being the dopants that give the highest- and lowest-thermal-conductivity AlN composites, respectively. The choice of the sintering aid and the dopant level is much more important than the microstructure that evolves during sintering. A contiguous AlN phase provides rapid heat conduction paths, even at short sintering times. AlN contiguity decreases slightly as the annealing times increase in the range of 1–1000 min at 1850°C. However, a substantial increase in thermal conductivity results, because of purification of AlN grains by dissolution-reprecipitation and bulk diffusion. Removal of grain-boundary phases, with a concurrent increase in AlN contiguity, occurs at high annealing temperatures or at long times and is a natural consequence of high dihedral angles (poor wetting) in liquidphase-sintered AlN ceramics.