Dihydro-β-agarofurans from the Australian rainforest plant Denhamia celastroides that inhibit leucine transport in prostate cancer cells

Four new dihydro-β-agarofurans, denhaminols K–N ( 4 – 7 ), along with three known secondary metabolites, denhaminols A–C ( 1 – 3 ) were obtained from the large-scale isolation studies of the leaves of the Australian endemic rainforest plant, Denhamia celastroides. The structures of the previously undescribed compounds were determined by detailed 1D and 2D nuclear magnetic resonance spectroscopy, mass spectrometry, ultraviolet, and infrared data analysis. All compounds were found to inhibit the activity of leucine transport in a human prostate cancer cell line with IC₅₀ values ranging from 5.1–74.9 μM. Dihydro-β-agarofurans 1 – 7 showed better potency than the L-type amino acid transporter family inhibitor, 2-aminobicyclo[2.2.1]-heptane-2-carboxylic acid (BCH).     

Generalized thermoelastic Lamb waves in a plate bordered with layers of inviscid liquid

The propagation of thermoelastic waves in a homogeneous isotropic, thermally conducting plate bordered with layers of inviscid liquid or half-space of inviscid liquid on both sides is investigated in the context of generalized theories of thermoelasticity. Secular equations for the plate in closed form and isolated mathematical conditions for symmetric and antisymmetric wave modes in completely separate terms are derived. The results for coupled and uncoupled theories of thermoelasticity have been obtained as particular cases. The different regions of secular equations are obtained and special cases, such as Lame modes, thin plate waves and short wavelength waves of the secular equations are also discussed. The secular equations for thermoelastic leaky Lamb waves are also obtained and deduced. The amplitudes of displacement components and temperature change have also been computed and studied. Finally, the numerical solution is carried out for an aluminum-epoxy composite and aluminum materials plate bordered with water. The dispersion curves for symmetric and antisymmetric thermoelastic wave modes and amplitudes of displacement and temperature change in case of fundamental symmetric (S₀) and skew symmetric (A₀) modes are presented in order to illustrate and compare the theoretical results. The theory and numerical computations are found to be in close agreement. The results have been deduced and compared with the relevant publications available in the literature at the relevant stages of the work.     

Design considerations for a two-dimensional rapid scanning fluorimeter

The design or a two-dimensional rapid scanning fluorimeter which eliminates much unneeded transfer optics is described. The advantages and disadvantages of commercially available optical systems are discussed with regard to preservation of image quality and relative cost. The combination of holographic polychromators and conventional lenses in the recommended design produces spectra as accurate as those obtained on most conventional fluorimeters.     

A note on completeness and strongly clean rings

Many authors have investigated the behavior of strong cleanness under certain ring extensions. In this note, we investigate the classical problem of lifting idempotents, in order to consolidate and extend these results. Our main result is that if R$R$ is a ring which is complete with respect to an ideal I$I$ and if x$x$ is an element of R$R$ whose image in R/I$R/I$ is strongly π$\pi$-regular, then x$x$ is strongly clean in R$R$. This generalizes Theorem 2.1 of Chen and Zhou (2007)  [9].     

Equations in simple matrix groups: algebra, geometry, arithmetic, dynamics

We present a survey of results on word equations in simple groups, as well as their analogues and generalizations, which were obtained over the past decade using various methods: group-theoretic and coming from algebraic and arithmetic geometry, number theory, dynamical systems and computer algebra. Our focus is on interrelations of these machineries which led to numerous spectacular achievements, including solutions of several long-standing problems.     

High performance liquid chromatography/video fluorometry. Part II: Applications

A video fluorometer is used as a detector for HPLC to characterize highly complex samples. Data selection and evaluation techniques are discussed so as to speed the spectral identification process. Several well-known polynuclear aromatic hydrocarbons are found in the samples.     

A novel liquid chromatography/tandem mass spectrometry based depletion method for measuring red blood cell partitioning of pharmaceutical compounds in drug discovery

A novel liquid chromatography/tandem mass spectrometry (LC/MS/MS)-based depletion method for measuring compound partitioning between human plasma and red blood cells (RBC) in a drug discovery environment is presented. Conventionally, RBC partitioning is determined by separate measurements of drug concentrations in equilibrating plasma and whole blood or RBC using separate standards prepared in their respective matrices, i.e., in plasma and whole blood or RBC lysates. The process is very tedious, labor-intensive, and difficult to automate. In addition, interferences from the heme and other highly abundant cellular composites make the measurement of the drug concentration in whole blood or RBC inevitably variable even with a highly specific LC/MS/MS method. Therefore, there is an imminent need to develop a straightforward and fast method to assess the partitioning of drug-like compounds in RBC.This work describes an LC/MS/MS-based depletion assay that measures the compound concentration in plasma that has been equilibrating with RBC. Compounds were spiked into fresh human whole blood and plasma respectively to a final concentration of 500 nM. Both the spiked whole blood and plasma control were incubated at 37 degrees C for up to 60 min. During the time course, aliquots of plasma and whole blood from both incubation mixtures were sampled at 10 and 60 min. The whole blood samples were centrifuged to yield the plasma. The plasma samples from both incubations were extracted using a protein precipitation method, and analyzed using LC/MS/MS under the multiple-reaction monitoring (MRM) mode. The RBC partitioning ratio was calculated using the analyte peak area responses of the plasma samples through an equation deduced in this work.The method was first tested using two commercial compounds, phenoprobamate and acetazolamide, to determine the optimal incubation conditions and the concentration dependency of the assay. The assay reproducibility was also assessed by three inter-day assays for phenoprobamate. This method was further evaluated using 20 commercial compounds of different classes with a wide range of RBC partitioning coefficients and the results were compared with those reported in the literature. Excellent correlation (R2=0.9396) was found between the measured and literature values. In addition, several proprietary compounds were assayed using both the new and traditional methods and the measured partitioning ratios from the two methods are equivalent. The experiments in this work demonstrate that the LC/MS/MS-based depletion method can provide direct and accurate measurement of RBC partitioning for compounds in drug discovery.