Effects of the Anti-Tumorigenic Agent AT101 on Human Glioblastoma Cells in the Microenvironmental Glioma Stem Cell Niche

Glioblastoma (GBM) is a barely treatable disease due to its profound chemoresistance. A distinct inter- and intratumoral heterogeneity reflected by specialized microenvironmental niches and different tumor cell subpopulations allows GBMs to evade therapy regimens. Thus, there is an urgent need to develop alternative treatment strategies. A promising candidate for the treatment of GBMs is AT101, the R(-) enantiomer of gossypol. The present study evaluates the effects of AT101, alone or in combination with temozolomide (TMZ), in a microenvironmental glioma stem cell niche model of two GBM cell lines (U251MG and U87MG). AT101 was found to induce strong cytotoxic effects on U251MG and U87MG stem-like cells in comparison to the respective native cells. Moreover, a higher sensitivity against treatment with AT101 was observed upon incubation of native cells with a stem-like cell-conditioned medium. This higher sensitivity was reflected by a specific inhibitory influence on the p-p42/44 signaling pathway. Further, the expression of CXCR7 and the interleukin-6 receptor was significantly regulated upon these stimulatory conditions. Since tumor stem-like cells are known to mediate the development of tumor recurrences and were observed to strongly respond to the AT101 treatment, this might represent a promising approach to prevent the development of GBM recurrences.     

Fabrication, assembly, and characterization of molecular electronic components

One of the ultimate miniaturizations in nanotechnology is molecular electronics, where devices will consist of individual molecules. There are many complications associated with the use of molecules in electronic devices, such as the electronic perturbations in the molecule associated with being bonded to an electrode, how electrons traverse the metal-molecule junction, and the difficulty of macroscopically addressing single to very few molecules. Whether fabricating a test structure or a usable device, the use of self-assembly is fundamental to the fabrication of molecular electronic devices. We will discuss how to fabricate self-assembled monolayers into test assemblies and how to use intermolecular interactions to direct molecules into desired positions to create nanostructures and to connect functional molecules to the outside world. These assemblies serve as test structures for measurements on single or bundled molecules. The development of several experimental techniques, including various scanning probes, mercury drop junctions, break junctions, nanopores, crossed wires, and other techniques using nanoparticles have enabled the ability to test these structures and make reproducible measurements on single molecules. Many of these methods have been developed to test molecules with potential for integration into devices such as oligo (phenylene-ethynylene) molecules and other /spl pi/-conjugated molecules, in ensemble or single-molecule measurements.     

HRTEM observation of the monoclinic-to-tetragonal m-t) phase transition in nanocrystalline ZrO2

The orientation relations m(100) || t(001), m[001] || t[110]; m(011) || t(100), m[100] || t[001]; m(100) || t(110), m[001] || t[001]; m(013) || t(116), m[001] || t[001] (indices for the primitive tetragonal cell) have been found between the tetragonal (t) and monoclinic (m) domains during the electron irradiation-induced m-t phase transition observed in-situ with HREM within isolated zirconia nanoparticles. Geometric models of the m-t interfaces are proposed.     

Representation of shift-invariant operators onL 2 byH ∞ transfer functions: An elementary proof,a generalization toL p,and a counterexample forL ∞

We give an elementary proof of the well-known fact that shift-invariant operators onL ²[0, ∞) are represented by transfer functions which are bounded and analytic on the right open half-plane. We prove a generalization to Banach space-valuedL ^p -functions, where 1≤p<∞. We show that the result no longer holds forp=∞. This research was supported partially by the Weizmann Fellowship, and partially by the Air Force Office of Scientific Research under Contract F49620-86-C-0111.     

Low Temperature Acoustic Properties of Poly-Crystalline Aluminium

As in other structurally disordered solids, the low temperature acoustic properties of poly-crystalline aluminium are governed by atomic two-level tunneling systems. The particular temperature variation of sound velocity and internal friction depends on the dynamical behaviour of these tunneling systems, which is expected to be determined by interaction with thermal phonons and conduction electrons as in metallic glasses. In earlier measurements on aluminium-wires no significant difference was found whether the sample was superconducting or kept in the normal state by a sufficiently high magnetic field and the concluding claim was ‘absence of electron-assisted relaxation for tunneling systems in poly-crystalline metals’. In this report, vibrating reed measurements are presented of pure poly-crystalline Al with a special sample shape that reduces the influence of the clamping. We in fact find significant differences between the sample being normal conducting or superconducting. The overall behaviour indeed resembles very closely that of metallic glasses and clearly demonstrates that also in Al tunneling systems couple to conduction electrons as expected. As a quantitative result we may state that the density of states of tunneling systems in poly-crystalline Al is considerably smaller than in metallic glasses. PACS numbers: 61.43.-j, 62.65.+k, 63.50.+x     

Relationship between the genomic organization and the overlapping embryonic expression patterns of the zebrafish dlx genes

To understand the relationship between the expression and the genomic organization of the zebrafish dlx genes, we have determined the genomic structure of the dlx2 and dlx4 loci. This led to the identification of the zebrafish dlx1 and dlx6 genes, which are closely linked to dlx2 and dlx4, respectively. Therefore, the inverted convergent configuration of Dlx genes is conserved among vertebrates. Analysis of the expression patterns of dlx1 and dlx6 showed striking similarities to those of dlx2 and dlx4, respectively, the genes to which they are linked. Furthermore, the expression patterns of dlx3 and dlx7, which likely constitute a third pair of convergently transcribed genes, are indistinguishable. Thus, the overlapping expression patterns of linked Dlx genes during embryonic development suggest that they share cis-acting sequences that control their spatiotemporal expression. The evolutionary conservation of the genomic organization and combinatorial expression of Dlx genes in distantly related vertebrates suggest tight control mechanisms that are essential for their function during development.     

Decomposition of electromagnetic boundary conditions at planarinterfaces with applications to TE and TM field solutions

Electromagnetic fields in homogeneous source-free regions can be decomposed into fields that are TE and TM with respect to a particular reference direction (e.g., the z direction). If transverse sources exist, both TE and TM fields may be excited simultaneously. This paper considers the case of two infinite regions having a common planar interface and prescribed sources (surface currents) on the interface. The source currents are decomposed in a manner consistent with the decomposition of the fields. Accordingly, a procedure is established for describing the boundary conditions at the interface in terms of the longitudinal field components E_z, H_z and the surface currents J¯_s. The development is unique in that the continuity of the transverse field components at the boundary are not explicitly considered but interpreted in terms of z-directed fields. This boundary condition approach is shown to give results consistent with those obtained by matching the tangential fields at the interface using vector transforms. A simple example illustrating the procedure using a ring of current in free-space is presented     

Online monitoring by dynamically refining imprecise models

Model-based monitoring determines faults in a supervised system by comparing the available system's measurements with a priori information represented by the system's mathematical model. Especially in technical environments, a monitoring system must be able to reason with incomplete knowledge about the supervised system, to process noisy and erroneous observations and to react within a limited time. We present MOSES, a model-based monitoring system which is based on imprecise models where the structure is known and the parameters may be imprecisely specified by numerical intervals. As a consequence, only bounds on the trajectories can be derived with imprecise models. These bounds are computed using traditional numerical integration techniques starting from individual points on the external surface of the model's uncertainty space. When new measurements from the supervised system become available, MOSES checks the consistency of this new information with the model's prediction and refutes inconsistent parts from the uncertainty space of the model. A fault in the supervised system is detected when the complete model's uncertainty space has been refuted. MOSES bridges and extends methodologies from the FDI and DX communities by refining the model's uncertainty space conservatively through refutation, by applying standard numerical techniques for deriving the trajectories of imprecise models and by exploiting the measurements as soon as possible for online monitoring. The performance of MOSES is evaluated based on examples and by online monitoring a complex heating system.