3,948 research outputs found

    Morphoproteomic profiling of the mammalian target of rapamycin (mTOR) signaling pathway in desmoplastic small round cell tumor (EWS/WT1), Ewing's sarcoma (EWS/FLI1) and Wilms' tumor(WT1).

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    BackgroundDesmoplastic small round cell tumor (DSRCT) is a rare sarcoma in adolescents and young adults. The hallmark of this disease is a EWS-WT1 translocation resulting from apposition of the Ewing's sarcoma (EWS) gene with the Wilms' tumor (WT1) gene. We performed morphoproteomic profiling of DSRCT (EWS-WT1), Ewing's sarcoma (EWS-FLI1) and Wilms' tumor (WT1) to better understand the signaling pathways for selecting future targeted therapies.MethodologyThis pilot study assessed patients with DSRCT, Wilms' tumor and Ewing's sarcoma. Morphoproteomics and immunohistochemical probes were applied to detect: p-mTOR (Ser2448); p-Akt (Ser473); p-ERK1/2 (Thr202/Tyr204); p-STAT3 (Tyr 705); and cell cycle-related analytes along with their negative controls.Principal findingsIn DSRCT the PI3K/Akt/mTOR pathway is constitutively activated by p-Akt (Ser 473) expression in the nuclear compartment of the tumor cells and p-mTOR phosphorylated on Ser 2448, suggesting mTORC2 (rictor+mTOR) as the dominant form. Ewing's sarcoma had upregulated p-Akt and p-mTOR, predominantly mTORC2. In Wilm's tumor, the mTOR pathway is also activated with most tumor cells moderately expressing p-mTOR (Ser 2448) in plasmalemmal and cytoplasmic compartments. This coincides with the constitutive activation of one of the downstream effectors of the mTORC1 signaling pathway, namely p-p70S6K (Thr 389). There was constitutive activation of the Ras/Raf/ERK pathway p-ERK 1/2 (Thr202/Tyr204) expression in the Wilms tumor and metastatic Ewing's sarcoma, but not in the DSRCT.ConclusionMORPHOPROTEOMIC TUMOR ANALYSES REVEALED CONSTITUTIVE ACTIVATION OF THE MTOR PATHWAY AS EVIDENCED BY: (a) expression of phosphorylated (p)-mTOR, p-p70S6K; (b) mTORC 2 in EWS and DSRCT; (c) ERK signaling was seen in the advanced setting indicating these as resistance pathways to IGF1R related therapies. This is the first morphoproteomic study of such pathways in these rare malignancies and may have potential therapeutic implications. Further study using morphoproteomic assessments of these tumors are warranted

    Unusual Digital Patterns in EPS: Evidence On the Association Between Earnings Management and Company Characteristics

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    Prior studies (Thomas, 1989; Das and Zhang, 2003) provide evidence of earnings manipulation to achieve cognitive reference points in EPS. The current study extends this line of research by examining the relation between unusual digital patterns in the right EPS position and specific firm characteristics. Results suggest that the propensity to manage earnings to effect desired EPS results is particularly associated with company size and to a lesser degree with operating performance and the level of debt leverage employed

    Aqueous route for the synthesis of platinum, ruthenium and ceria nanoparticles on multi-walled carbon nanotubes for the electrooxidation of methanol and ethanol

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    The electrochemical oxidation of methanol and ethanol in acidic media was studied using electrodes composed of multi-walled carbon nanotubes (MWCNTs) decorated with Pt, Ru and ceria nanoparticles. Polystyrene sulfonate (PSS) was used to disperse the MWCNTs in water and provide nucleation sites for the growth of catalyst nanoparticles. Composite electrodes were characterized for structural and electrochemical properties and all electrodes modified with Ru displayed greater catalytic ability for alcohol oxidation than those without Ru. In addition, the inclusion of ceria seemed to increase the catalytic ability in every sample suggesting a synergistic effect between Pt, Ru and ceria for the oxidation of methanol and ethanol. The catalytic effect of Pt and Ru concentration was studied by holding Ru concentrations constant and increasing the concentration of Pt. The same concentration of ceria was used for all modified electrodes. The results of this study show that the electrode prepared from 3:1 Pt:Ru solutions with ceria showed the highest peak current density for methanol oxidation (at 0.6 V vs. Ag/AgCl/Cl-) which was nearly 20 times greater than that for an unmodified Pt electrode. Similar results were seen for ethanol oxidation on the same electrode which resulted in peak current densities greater than 20 times those for the unmodified Pt electrode at 0.8 V versus Ag/AgCl/Cl-

    On the magnetic structure of the solar transition region

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    We examine the hypothesis that ``cool loops'' dominate emission from solar transition region plasma below temperatures of 2×1052\times10^5K. We compare published VAULT images of H Lα\alpha, a lower transition region line, with near-contemporaneous magnetograms from Kitt Peak, obtained during the second flight (VAULT-2) on 14 June 2002. The measured surface fields and potential extrapolations suggest that there are too few short loops, and that Lα\alpha emission is associated with the base regions of longer, coronal loops. VAULT-2 data of network boundaries have an asymmetry on scales larger than supergranules, also indicating an association with long loops. We complement the Kitt Peak data with very sensitive vector polarimetric data from the Spectro-Polarimeter on board Hinode, to determine the influence of very small magnetic concentrations on our analysis. From these data two classes of behavior are found: within the cores of strong magnetic flux concentrations (>5×1018> 5\times10^{18} Mx) associated with active network and plage, small-scale mixed fields are absent and any short loops can connect just the peripheries of the flux to cell interiors. Core fields return to the surface via longer, most likely coronal, loops. In weaker concentrations, short loops can connect between concentrations and produce mixed fields within network boundaries as suggested by Dowdy and colleagues. The VAULT-2 data which we examined are associated with strong concentrations. We conclude that the cool loop model applies only to a small fraction of the VAULT-2 emission, but we cannot discount a significant role for cool loops in quieter regions. We suggest a physical picture for how network Lα\alpha emission may occur through the cross-field diffusion of neutral atoms from chromospheric into coronal plasma.Comment: Accepted by ApJ, 9 May 200

    Chemical and physical properties of bulk aerosols within four sectors observed during TRACE-P

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    Chemical and physical aerosol data collected on the DC-8 during TRACE-P were grouped into four sectors based on back trajectories. The four sectors represent long-range transport from the west (WSW), regional circulation over the western Pacific and Southeast Asia (SE Asia), polluted transport from northern Asia with substantial sea salt at low altitudes (NNW) and a substantial amount of dust (Channel). WSW has generally low mixing ratios at both middle and high altitudes, with the bulk of the aerosol mass due to non-sea-salt water-soluble inorganic species. Low altitude SE Asia also has low mean mixing ratios in general, with the majority of the aerosol mass comprised of non-sea-salts, however, soot is also relatively important in this region. NNW had the highest mean sea salt mixing ratios, with the aerosol mass at low altitudes (\u3c2 km) evenly divided between sea salts, non-sea-salts, and dust. The highest mean mixing ratios of water-soluble ions and soot were observed at the lowest altitudes (\u3c2 km) in the Channel sector. The bulk of the aerosol mass exported from Asia emanates from Channel at both low and midaltitudes, due to the prevalence of dust compared to other sectors. Number densities show enhanced fine particles for Channel and NNW, while their volume distributions are enhanced due to sea salt and dust. Low-altitude Channel exhibits the highest condensation nuclei (CN) number densities along with enhanced scattering coefficients, compared to the other sectors. At midaltitudes (2–7 km), low mean CN number densities coupled with a high proportion of nonvolatile particles (≥65%) observed in polluted sectors (Channel and NNW) are attributed to wet scavenging which removes hygroscopic CN particles. Low single scatter albedo in SE Asia reflects enhanced soot

    Numerical Jordan-Wigner approach for two dimensional spin systems

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    We present a numerical self consistent variational approach based on the Jordan-Wigner transformation for two dimensional spin systems. We apply it to the study of the well known quantum (S=1/2) antiferromagnetic XXZ system as a function of the easy-axis anisotropy \Delta on a periodic square lattice. For the SU(2) case the method converges to a N\'eel ordered ground state irrespectively of the input density profile used and in accordance with other studies. This shows the potential utility of the proposed method to investigate more complicated situations like frustrated or disordered systems.Comment: Revtex, 8 pages, 4 figure

    Effect of cosmological evolution on Solar System constraints and on the scalarization of neutron stars in massless scalar-tensor theories

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    Certain scalar-tensor theories of gravity that generalize Jordan-Fierz-Brans-Dicke theory are known to predict nontrivial phenomenology for neutron stars. In these theories, first proposed by Damour and Esposito-Farese, the scalar field has a standard kinetic term and couples conformally to the matter fields. The weak equivalence principle is therefore satisfied, but scalar effects may arise in strong-field regimes, e.g., allowing for violations of the strong equivalence principle in neutron stars ("spontaneous scalarization") or in sufficiently tight binary neutron-star systems ("dynamical/induced scalarization"). The original scalar-tensor theory proposed by Damour and Esposito-Farese is in tension with Solar System constraints (for couplings that lead to scalarization), if one accounts for cosmological evolution of the scalar field and no mass term is included in the action. We extend here the conformal coupling of that theory, in order to ascertain if, in this way, Solar System tests can be passed, while retaining a nontrivial phenomenology for neutron stars. We find that, even with this generalized conformal coupling, it is impossible to construct a theory that passes both big bang nucleosynthesis and Solar System constraints, while simultaneously allowing for scalarization in isolated/binary neutron stars

    Single and Many Particle Correlation Functions and Uniform Phase Bases for Strongly Correlated Systems

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    The need for suitable many or infinite fermion correlation functions to describe some low dimensional strongly correlated systems is discussed. This is linked to the need for a correlated basis, in which the ground state may be postive definite, and in which single particle correlations may suffice. A particular trial basis is proposed, and applied to a certain quasi-1D model. The model is a strip of the 2D square lattice wrapped around a cylinder, and is related to the ladder geometries, but with periodic instead of open boundary conditions along the edges. Analysis involves a novel mean-field approach and exact diagonalisation. The model has a paramagnetic region and a Nagaoka ferromagnetic region. The proposed basis is well suited to the model, and single particle correlations in it have power law decay for the paramagnet, where the charge motion is qualitatively hard core bosonic. The mean field also leads to a BCS-type model with single particle long range order.Comment: 23 pages, in plain tex, 12 Postscript figures included. Accepted for publication in J.Physics : Condensed Matte

    Orbital and physical parameters of eclipsing binaries from the ASAS catalogue - IX. Spotted pairs with red giants

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    We present spectroscopic and photometric solutions for three spotted systems with red giant components. Absolute physical and orbital parameters for these double-lined detached eclipsing binary stars are presented for the first time. These were derived from the V-, and I-band ASAS and WASP photometry, and new radial velocities calculated from high quality optical spectra we obtained with a wide range of spectrographs and using the two-dimensional cross-correlation technique (TODCOR). All of the investigated systems (ASAS J184949-1518.7, BQ Aqr, and V1207 Cen) show the differential evolutionary phase of their components consisting of a main-sequence star or a subgiant and a red giant, and thus constitute very informative objects in terms of testing stellar evolution models. Additionally, the systems show significant chromospheric activity of both components. They can be also classified as classical RS CVn-type stars. Besides the standard analysis of radial velocities and photometry, we applied spectral disentangling to obtain separate spectra for both components of each analysed system which allowed for a more detailed spectroscopic study. We also compared the properties of red giant stars in binaries that show spots, with those that do not, and found that the activity phenomenon is substantially suppressed for stars with Rossby number higher than ∼1 and radii larger than ∼20 R⊙
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