The combination of FLT3 and DNA methyltransferase inhibition is synergistically cytotoxic to FLT3/ITD acute myeloid leukemia cells

Effective treatment regimens for elderly acute myeloid leukemia (AML) patients harboring internal tandem duplication mutations in the FMS-like tyrosine kinase-3 (FLT3) gene (FLT3/ITD) are lacking and represent a significant unmet need. Recent data on the effects of FLT3 tyrosine kinase inhibitors on FLT3/ITD+ AML showed promising clinical activity, including in elderly patients. DNA methyltransferase (DNMT) inhibitors such as decitabine (5-aza-2-deoxycytidine, DEC) and 5-azacitidine (AZA) demonstrated clinical benefit in AML, are well tolerated and are associated with minimal increases in FLT3 ligand, which can represent a potential resistance mechanism to FLT3 inhibitors. In addition, both FLT3 and DNMT inhibition are associated with the induction of terminal differentiation of myeloid blasts. Consequently, there is a strong theoretical rationale for combining FLT3 and DNMT inhibition for FLT3/ITD+ AML. We therefore sought to study the anti-leukemic effects of DEC, AZA and FLT3 inhibitors, either as single agents or in combination, on AML cell lines and primary cells derived from newly diagnosed and relapsed AML patients. Our studies indicate that combined treatment using FLT3 inhibition and hypomethylation confers synergistic anti-leukemic effects, including apoptosis, growth inhibition and differentiation. The simultaneous administration of AZA and FLT3 inhibition appears to be the most efficacious combination in this regard. These drugs may provide a novel therapeutic approach for FLT3/ITD+ AML, in particular for older patients

Evaluation of aircraft microwave data for locating zones for well stimulation and enhanced gas recovery

Imaging radar was evaluated as an adjunct to conventional petroleum exploration techniques, especially linear mapping. Linear features were mapped from several remote sensor data sources including stereo photography, enhanced LANDSAT imagery, SLAR radar imagery, enhanced SAR radar imagery, and SAR radar/LANDSAT combinations. Linear feature maps were compared with surface joint data, subsurface and geophysical data, and gas production in the Arkansas part of the Arkoma basin. The best LANDSAT enhanced product for linear detection was found to be a winter scene, band 7, uniform distribution stretch. Of the individual SAR data products, the VH (cross polarized) SAR radar mosaic provides for detection of most linears; however, none of the SAR enhancements is significantly better than the others. Radar/LANDSAT merges may provide better linear detection than a single sensor mapping mode, but because of operator variability, the results are inconclusive. Radar/LANDSAT combinations appear promising as an optimum linear mapping technique, if the advantages and disadvantages of each remote sensor are considered

Thermal Re-emission Model

Starting from a continuum description, we study the non-equilibrium roughening of a thermal re-emission model for etching in one and two spatial dimensions. Using standard analytical techniques, we map our problem to a generalized version of an earlier non-local KPZ (Kardar-Parisi-Zhang) model. In 2+1 dimensions, the values of the roughness and the dynamic exponents calculated from our theory go like $\alpha \approx z \approx 1$ and in 1+1 dimensions, the exponents resemble the KPZ values for low vapor pressure, supporting experimental results. Interestingly, Galilean invariance is maintained althrough.Comment: 4 pages, minor textual corrections and typos, accepted in Physical Review B (rapid

Wavefunction topology of two-dimensional time-reversal symmetric superconductors

We discuss the topology of the wavefunctions of two-dimensional time-reversal symmetric superconductors. We consider (a) the planar state, (b) a system with broken up-down reflection symmetry, and (c) a system with general spin-orbit interaction. We show explicitly how the relative sign of the order parameter on the two Fermi surfaces affects this topology, and clarify the meaning of the $Z_2$ classification for these topological states.Comment: only the Introduction has been modified from v

Coordinated mm/sub-mm observations of Sagittarius A* in May 2007

At the center of the Milky Way, with a distance of ~8 kpc, the compact source Sagittarius A* (SgrA*) can be associated with a super massive black hole of ~4x10^6 solar masses. SgrA* shows strong variability from the radio to the X-ray wavelength domains. Here we report on simultaneous NIR/sub-millimeter/X-ray observations from May 2007 that involved the NACO adaptive optics (AO) instrument at the European Southern Observatory's Very Large Telescope, the Australian Telescope Compact Array (ATCA), the US mm-array CARMA, the IRAM 30m mm-telescope, and other telescopes. We concentrate on the time series of mm/sub-mm data from CARMA, ATCA, and the MAMBO bolometer at the IRAM 30m telescope.Comment: 7 pages, 3 figures, contribution for the conference "The Universe under the Microscope" (AHAR 2008), to be published in Journal of Physics: Conference Series by Institute of Physics Publishin

Composite Spin Waves, Quasi-Particles and Low Temperature resistivity in Double Exchange Systems

We make a quantum description of the electron low temperature properties of double exchange materials. In these systems there is a strong coupling between the core spin and the carriers spin. This large coupling makes the low energy spin waves to be a combination of ion and electron density spin waves. We study the form and dispersion of these composite spin wave excitations. We also analyze the spin up and down spectral functions of the temperature dependent quasi-particles of this system. Finally we obtain that the thermally activated composite spin waves renormalize the carriers effective mass and this gives rise to a low temperature resistivity scaling as T ^{5/2}.Comment: 4 pages, REVTE

A human MAP kinase interactome.

Mitogen-activated protein kinase (MAPK) pathways form the backbone of signal transduction in the mammalian cell. Here we applied a systematic experimental and computational approach to map 2,269 interactions between human MAPK-related proteins and other cellular machinery and to assemble these data into functional modules. Multiple lines of evidence including conservation with yeast supported a core network of 641 interactions. Using small interfering RNA knockdowns, we observed that approximately one-third of MAPK-interacting proteins modulated MAPK-mediated signaling. We uncovered the Na-H exchanger NHE1 as a potential MAPK scaffold, found links between HSP90 chaperones and MAPK pathways and identified MUC12 as the human analog to the yeast signaling mucin Msb2. This study makes available a large resource of MAPK interactions and clone libraries, and it illustrates a methodology for probing signaling networks based on functional refinement of experimentally derived protein-interaction maps

Ultra-low carrier concentration and surface dominant transport in Sb-doped Bi2Se3 topological insulator nanoribbons

A topological insulator is a new state of matter, possessing gapless spin-locking surface states across the bulk band gap which has created new opportunities from novel electronics to energy conversion. However, the large concentration of bulk residual carriers has been a major challenge for revealing the property of the topological surface state via electron transport measurement. Here we report surface state dominated transport in Sb-doped Bi2Se3 nanoribbons with very low bulk electron concentrations. In the nanoribbons with sub-10nm thickness protected by a ZnO layer, we demonstrate complete control of their top and bottom surfaces near the Dirac point, achieving the lowest carrier concentration of 2x10^11/cm2 reported in three-dimensional (3D) topological insulators. The Sb-doped Bi2Se3 nanostructures provide an attractive materials platform to study fundamental physics in topological insulators, as well as future applications.Comment: 5 pages, 4 figures, 1 tabl

Mott physics and band topology in materials with strong spin-orbit interaction

Recent theory and experiment have revealed that strong spin-orbit coupling can have dramatic qualitative effects on the band structure of weakly interacting solids. Indeed, it leads to a distinct phase of matter, the topological band insulator. In this paper, we consider the combined effects of spin-orbit coupling and strong electron correlation, and show that the former has both quantitative and qualitative effects upon the correlation-driven Mott transition. As a specific example we take Ir-based pyrochlores, where the subsystem of Ir 5d electrons is known to undergo a Mott transition. At weak electron-electron interaction, we predict that Ir electrons are in a metallic phase at weak spin-orbit interaction, and in a topological band insulator phase at strong spin-orbit interaction. Very generally, we show that with increasing strength of the electron-electron interaction, the effective spin-orbit coupling is enhanced, increasing the domain of the topological band insulator. Furthermore, in our model, we argue that with increasing interactions, the topological band insulator is transformed into a "topological Mott insulator" phase, which is characterized by gapless surface spin-only excitations. The full phase diagram also includes a narrow region of gapless Mott insulator with a spinon Fermi surface, and a magnetically ordered state at still larger electron-electron interaction.Comment: 10+ pages including 3+ pages of Supplementary Informatio