Inhibition of Cytosolic Phospholipase A2α Induces Apoptosis in Multiple Myeloma Cells

Cytosolic phospholipase A2α (cPLA2α) is the rate-limiting enzyme in releasing arachidonic acid and biosynthesis of its derivative eicosanoids. Thus, the catalytic activity of cPLA2α plays an important role in cellular metabolism in healthy as well as cancer cells. There is mounting evidence suggesting that cPLA2α is an interesting target for cancer treatment; however, it is unclear which cancers are most relevant for further investigation. Here we report the relative expression of cPLA2α in a variety of cancers and cancer cell lines using publicly available datasets. The profiling of a panel of cancer cell lines representing different tissue origins suggests that hematological malignancies are particularly sensitive to the growth inhibitory effect of cPLA2α inhibition. Several hematological cancers and cancer cell lines overexpressed cPLA2α, including multiple myeloma. Multiple myeloma is an incurable hematological cancer of plasma cells in the bone marrow with an emerging requirement of therapeutic approaches. We show here that two cPLA2α inhibitors AVX420 and AVX002, significantly and dose-dependently reduced the viability of multiple myeloma cells and induced apoptosis in vitro. Our findings implicate cPLA2α activity in the survival of multiple myeloma cells and support further studies into cPLA2α as a potential target for treating hematological cancers, including multiple myeloma.     

Can-order policy for the periodic-review joint replenishment problem

In this paper we study the stochastic joint replenishment problem. We compare the class of periodic replenishment policies and the class of can-order policies for this problem. We present a method, based on Markov decision theory, to calculate near-optimal can-order policies for a periodic-review inventory system. Our numerical study shows that the can-order policy behaves as well as, if not better than, the periodic replenishment policies. In particular, for examples where the demand is irregular, we find cost differences up to 15% in favour of the can-order policy.     

Modelling of inextensible cable dynamics with experiments

The recognition of very stiff axial elastic motion compared to the motion in the transverse direction for cable dynamics motivates separation of the axial and transversal dynamics. For certain applications, e.g. real-time model-based control, fast calculation of the transverse motion may be of high importance, motivating the development of numerically efficient software code. Separation of axial dynamics renders possible neglection or simplification of the axial dynamics if appropriate for the system studied. A model is proposed with the assumption of axial inextensible material and negligible bending, torsion and shear stiffness in the cable. Experiments are carried out to verify the model, and the results are compared with simulations. The comparison between the experiments and numerical simulations showed good agreement up to the second frequency range with resonant behavior and the corresponding motion amplitudes.     

Inductive inference of ultimately periodic sequences

An algorithm is presented for inductive inference of ultimately periodic sequences. It can be implemented in linear time and space.Dedicated to Peter Naur on the occasion of his 60th birthday     

Degradation of blood in the human digestive tract

Samples of human faeces from patients suffering from intestinal bleeding have been studied by use of Mössbauer spectroscopy. It is shown that it is possible to follow the degradation of blood in the digestive tract.     

Ab initio calculations of electrostatic potentials and deformation densities for a series of choline ester model systems

Ab initio LCAO-MO-SCF calculations using a double zeta basis set have been performed for the methyl esters of acetic acid, carbamic acid, methylcarbonic acid, and trifluoracetic acid, in order to model the corresponding choline esters. The systems have been compared by means of population analyses, electron density differences, electrostatic potentials and potential differences. The significance of the electrostatic potential in connection with crystal structure and packing has been studied. The differences in the proton affinity of the compounds have been correlated to differences in the potentials.     

Synthesis of aryl- and heteroaryl-substituted 3-benzyloxyisothiazoles via Suzuki and Negishi cross-coupling reactions

Introduction of aryl and heteroaryl substituents into the 5-position of 3-benzyloxyisothiazole (1) using palladium-catalyzed Suzuki and Negishi cross-coupling reactions was investigated. Attempts to generate synthetically viable nucleophilic species from 1 for Suzuki- or Negishi-type cross-couplings were unsuccessful. However, using 3-benzyloxy-5-iodoisothiazole 2 as an intermediate, a range of aromatic and heteroaromatic substituents were successfully introduced under Suzuki or Negishi cross-coupling conditions in good to excellent yields.     

XANTHENE DYES AS SENSITIZERS FOR THE PHOTOREDUCTION OF WATER

Abstract— Some photochemical and photophysical properties of a group of xanthene dyes have been studied in relation to their roles as sensitizers for the photoreduction of water. New spectroscopic and kinetic measurements have been carried out with these dyes. The triplet states of the dyes undergo energy-transfer and electron-transfer, but with rate constants differing by two orders of magnitude in favour of the former pathway. The very efficient transfer of triplet energy from a group of dyes to an acceptor molecule led to the design of a greatly improved system for the photochemical production of hydrogen.