New Quinoxaline Derivatives as Dual Pim-1/2 Kinase Inhibitors: Design,Synthesis and Biological Evaluation

Proviral integration site for Moloney murine leukemia virus (Pim)-1/2 kinase overexpression has been identified in a variety of hematologic (e.g., multiple myeloma or acute myeloid leukemia (AML)) and solid (e.g., colorectal carcinoma) tumors, playing a key role in cancer progression, metastasis, and drug resistance, and is linked to poor prognosis. These kinases are thus considered interesting targets in oncology. We report herein the design, synthesis, structure–activity relationships (SAR) and in vitro evaluations of new quinoxaline derivatives, acting as dual Pim1/2 inhibitors. Two lead compounds (5c and 5e) were then identified, as potent submicromolar Pim-1 and Pim-2 inhibitors. These molecules were also able to inhibit the growth of the two human cell lines, MV4-11 (AML) and HCT-116 (colorectal carcinoma), expressing high endogenous levels of Pim-1/2 kinases.     

The effect of functionalization on structure and electrical conductivity of multi-walled carbon nanotubes

Nanosized powders of Ti-Nb oxide core-shell nanocrystals with atomic ratios of Nb/Ti = 0.11, 0.25, and 0.38 have been prepared by two preparation routes. The first route was co-precipitation, followed by␣annealing, using NbCl₅ as a source of Nb. The second route was coating of pure TiO₂ nanocrystals by Nb-isopropoxide in liquid medium, followed by impregnation of the Nb into the nanoparticles by annealing. Both methods yielded anatase nanocrystals with a Nb-rich shell and a core, which had much lower Nb loadings. The anatase structure solid solution (with Nb incorporated) was stable under annealing up to 760°C. The particle size remained within the nanometric scale (<50 nm) under heat-treatment up to 760°C. It has been shown that the fabricated powders can be redispersed in aqueous media by simple ultrasound treatment, resulting in nanosized dispersions. Using a variety of analytical techniques, including depth profiling of single nanocrystallites by AES combined with sputtering by Ar ions, the mechanism of the core-shell structure creation was studied. It is proposed that the formation of the core-shell structure is governed by solubility limitations in the co-precipitation route and by solubility and diffusion limitations in the coating-incorporation route.     

Surjectivity for Hamiltonian loop group spaces

Let G be a compact Lie group, and let LG denote the corresponding loop group. Let (X,) be a weakly symplectic Banach manifold. Consider a Hamiltonian action of LG on (X,), and assume that the moment map :XL ^* is proper. We consider the function ||²:X, and use a version of Morse theory to show that the inclusion map j:^-1(0)X induces a surjection j ^*:H _G ^*(X)H _G ^*(^-1(0)), in analogy with Kirwans surjectivity theorem in the finite-dimensional case. We also prove a version of this surjectivity theorem for quasi-Hamiltonian G-spaces.     

Solid‐state NMR as a tool to describe and quantify the morphology of photoactive layers used in plastic solar cells

The optimization and control of the nanomorphology of thin films used as active layer in bulk heterojunction (BHJ) plastic solar cells is of key importance for a better understanding of the photovoltaic mechanisms and for increasing the device performances. Hereto, solid‐state NMR relaxation experiments have been evaluated to describe the film morphology of one of the “work‐horse” systems poly(2‐methoxy‐5‐(3′,7′‐dimethyloctyloxy)‐1,4‐phenylene‐vinylene)/[6, 6]‐phenyl‐C₆₁butyric acid methyl ester (MDMO‐PPV/PCBM) in a quantitative way. Attention is focused on the influence of the processing solvent (toluene vs. chlorobenzene), the blend composition, and the casting technique, that is, spin coating versus doctor blading. It is demonstrated that independently of the solvent and casting technique, part of the PCBM becomes phase separated from the mixed phase. Whereas casting from toluene results in the development of well‐defined PCBM crystallites, casting from chlorobenzene leads to the formation of PCBM‐rich domains that contain substructures of weakly organized PCBM nanoclusters. The amount and physico‐chemical state of the phase separated PCBM is quantified by solid‐state NMR relaxation times experiments. © 2011 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2011     

Dispersion and attenuation of the eigenwaves for light propagation in heiicoidal liquid crystals

The dispersion curves and attenuation factors of the Bloch eigenwaves in heiicoidal liquid crystals (chiral smectic C and cholesterics) are calculated using the 4 × 4 characteristic matrix method. Four possible types of eigenmodes are seen to exist in the medium. The reflection peaks, which correspond to odd parts of the full pitch, are total reflection peaks, while those corresponding to even parts of the full pitch are composed of three branches at high incidence angles, where the outer branches are selective reflection and the central one is a total reflection peak. Selective reflection regions occur only at the edges of the Brillouin zones, while total reflections can occur anywhere inside the zones. The former are interpreted according to the coupled mode theory as resonant Bragg reflections, with the latter as exchange Bragg reflections. When the tilt direction exceeds the propagation direction, the central branch of the even sequence of peaks starts to be due to resonant Bragg reflections. The first order peak for cholesterics becomes strongly structured at large incidence angles.     

Ermittelung metallischer Gifte

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