Discovery of Novel Symmetrical 1,4-Dihydropyridines as Inhibitors of Multidrug-Resistant Protein (MRP4) Efflux Pump for Anticancer Therapy

Despite the development of targeted therapies in cancer, the problem of multidrug resistance (MDR) is still unsolved. Most patients with metastatic cancer die from MDR. Transmembrane efflux pumps as the main cause of MDR have been addressed by developed inhibitors, but early inhibitors of the most prominent and longest known efflux pump P-glycoprotein (P-gp) were disappointing. Those inhibitors have been used without knowledge about the expression of P-gp by the treated tumor. Therefore the use of inhibitors of transmembrane efflux pumps in clinical settings is reconsidered as a promising strategy in the case of the respective efflux pump expression. We discovered novel symmetric inhibitors of the symmetric efflux pump MRP4 encoded by the ABCC4 gene. MRP4 is involved in many kinds of cancer with resistance to anticancer drugs. All compounds showed better activities than the best known MRP4 inhibitor MK571 in an MRP4-overexpressing cell line assay, and the activities could be related to the various substitution patterns of aromatic residues within the symmetric molecular framework. One of the best compounds was demonstrated to overcome the MRP4-mediated resistance in the cell line model to restore the anticancer drug sensitivity as a proof of concept.     

Synthesis of diisocyanides with phenolic groups and their polymerization to helically chiral poly(quinoxaline‐2,3‐diyl)s

The development of synthetic routes which lead to five new diisocyanide monomers with one or two phenolic groups is described. Their polymerization behavior is studied with Pd‐ and Ni‐based initiators, as well as under microwave irradiation. The polymerizability is mainly dominated by steric effects as is concluded from experiments using different protecting groups. Chiroptical properties of these new polymers are studied by CD‐spectroscopy. After deprotection, helically chiral poly(quinoxalin‐2,3‐diyl)s are obtained which display a Brønsted function attached to a stereolabile biaryl axis whose configuration should be influenced by the chiral polymer backbone. © 2015 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2015 , 53, 1320–1329     

Finite Element Solution of Conical Diffraction Problems

This paper is devoted to the numerical study of diffraction by periodic structures of plane waves under oblique incidence. For this situation Maxwell's equations can be reduced to a system of two Helmholtz equations in R ² coupled via quasiperiodic transmission conditions on the piecewise smooth interfaces between different materials. The numerical analysis is based on a strongly elliptic variational formulation of the differential problem in a bounded periodic cell involving nonlocal boundary operators. We obtain existence and uniqueness results for discrete solutions and provide the corresponding error analysis.     

Expressive equivalence of least and inflationary fixed-point logic

We study the relationship between least and inflationary fixed-point logic. In 1986, Gurevich and Shelah proved that in the restriction to finite structures, the two logics have the same expressive power. On infinite structures however, the question whether there is a formula in IFP not equivalent to any LFP-formula was left open.

In this paper, we answer the question negatively, i.e. we show that the two logics are equally expressive on arbitrary structures. We give a syntactic translation of IFP-formulae to LFP-formulae such that the two formulae are equivalent on all structures.

As a consequence of the proof we establish a close correspondence between the LFP-alternation hierarchy and the IFP-nesting depth hierarchy. We also show that the alternation hierarchy for IFP collapses to the first level, i.e. the complement of any inflationary fixed point is itself an inflationary fixed point.     

A Bicriterial Optimization Problem of Antenna Design

In this paper we consider a special optimization problem withtwo objectives which arises in antenna theory. It is shown that thisabstract bicriterial optimization problem has at least one solution.Discretized versions of this problem are also discussed, and therelationships between these finite dimensional problems and the infinitedimensional problem are investigated. Moreover, we presentnumerical results for special parameters using a multiobjectiveoptimization method.     

Detailed nuclear structure studies far from stability

State-of-the-art spectroscopy of nuclei far from stability has achieved an extraordinary level of sophistication and detail in the last ten years. In principle, if a state can be populated, it can be characterized by its energy, spin, parity, and major decay paths. Sometimes its lifetime can be measured. In practice, one is confronted with enormous complexity. To convert raw spectroscopic data into nuclear structure data involves a complex process of disentangling gamma rays and conversion electrons into decay schemes. Specifically, coincidence techniques, especially coincidence intensities, play a crucial role in this process. Recent examples and methods from work done at UNISOR are presented.     

Soft X-ray resonant magnetic scattering studies on Fe/CoO exchange bias system

We have used soft X-ray resonant magnetic scattering (XRMS) to search for the presence of an effective ferromagnetic moment belonging to the antiferromagnetic (AF) layer which is in close contact with a ferromagnetic (F) layer. Taking advantage of the element specificity of the XRMS technique, we have measured hysteresis loops of both Fe and CoO layers of a CoO(40 Å)/Fe (150 Å) exchange bias bilayer. From these measurements we have concluded that the proximity of the F layer induces a magnetic moment in the AF layer. The F moment of the AF layer has two components: one is frozen and does not follow the applied magnetic field and the other one follows in phase the ferromagnetic magnetization of the F layer. The temperature dependence of the F components belonging to the AF layer is shown and discussed.