Context dependent non canonical WNT signaling mediates activation of fibroblasts by transforming growth factor-beta

Actions of transforming growth factor-beta are largely context dependent. For instance, TGF-beta is growth inhibitory to epithelial cells and many tumor cell-lines while it stimulates the growth of mesenchymal cells. TGF-beta also activates fibroblast cells to a myofibroblastic phenotype. In order to understand how the responsiveness of fibroblasts to TGF-beta would change in the context of transformation, we have compared the differential gene regulation by TGF-beta in immortal fibroblasts (hFhTERT), transformed fibroblasts (hFhTERT-LTgRAS) and a human fibrosarcoma cell-line (HT1080). The analysis revealed regulation of 6735, 4163, and 3478 probe-sets by TGF-beta in hFhTERT, hFhTERT-LTgRAS and HT1080 cells respectively. Intriguingly, 5291 probe-sets were found to be either regulated in hFhTERT or hFhTERT-LTgRAS cells while 2274 probe-sets were regulated either in hFhTERT or HT1080 cells suggesting that the response of immortal hFhTERT cells to TGF-beta is vastly different compared to the response of both the transformed cells hFhTERT-LTgRAS and HT1080 to TGF-beta. Strikingly, WNT pathway showed enrichment in the hFhTERT cells in Gene Set Enrichment Analysis. Functional studies showed induction of WNT4 by TGF-beta in hFhTERT cells and TGF-beta conferred action of these cells was mediated by WNT4. While TGF-beta activated both canonical and non-canonical WNT pathways in hFhTERT cells, Erk1/2 and p38 Mitogen Activated Protein Kinase pathways were activated in hFhTERT-LTgRAS and HT1080 cells. This suggests that transformation of immortal hFhTERT cells by SV40 large T antigen and activated RAS caused a switch in their response to TGF-beta which matched with the response of HT1080 cells to TGF-beta. These data suggest context dependent activation of non-canonical signaling by TGF-beta. (C) 2015 Published by Elsevier Inc.

Contrasting Electronic Requirements for C-H Binding and C-H Activation in d(6) Half-Sandwich Complexes of Rhenium and Tungsten

A computational study of the interaction half-sandwich metal fragments (metal=Re/W, electron count=d(6)), containing linear nitrosyl (NO+), carbon monoxide (CO), trifluorophosphine (PF3), N-heterocyclic carbene (NHC) ligands with alkanes are conducted using density functional theory employing the hybrid meta-GGA functional (M06). Electron deficiency on the metal increases with the ligand in the order NHC < CO < PF3 < NO+. Electron-withdrawing ligands like NO+ lead to more stable alkane complexes than NHC, a strong electron donor. Energy decomposition analysis shows that stabilization is due to orbital interaction involving charge transfer from the alkane to the metal. Reactivity and dynamics of the alkane fragment are facilitated by electron donors on the metal. These results match most of the experimental results known for CO and PF3 complexes. The study suggests activation of alkane in metal complexes to be facile with strong donor ligands like NHC. (C) 2015 Wiley Periodicals, Inc.

Ru (II)-Catalyzed C-H Activation: Ketone-Directed Novel 1,4-Addition of Ortho C-H Bond to Maleimides

A 1,4-addition with the nucleophilic center generated at the ortho carbon atom of an aromatic ketone in the presence of the highly reactive alpha-C-H bond, using a directing group strategy, is presented. The reaction yields pharmaceutically useful 3-arylated succinimide derivatives. In order to gain understanding of this redox neutral reaction, despite the presence of copper acetate, and to substantiate the lack of Heck-type products, DFT calculations have been carried out.

Shock propagation in gas dynamics: explicit form of higher order compatibility conditions

With the use of tensor analysis and the method of singular surfaces, an infinite system of equations can be derived to study the propagation of curved shocks of arbitrary strength in gas dynamics. The first three of these have been explicitly given here. This system is further reduced to one involving scalars only. The choice of dependent variables in the infinite system is quite important, it leads to coefficients free from singularities for all values of the shock strength.

Tyrosine kinases and calcium dependent activation of endothelial cell phospholipase D by diperoxovanadate

Reactive oxygen species (ROS) mediated modulation of signal transduction pathways represent an important mechanism of cell injury and barrier dysfunction leading to the development of vascular disorders. Towards understanding the role of ROS in vascular dysfunction, we investigated the effect of diperoxovanadate (DPV), derived from mixing hydrogen peroxide and vanadate, on the activation of phospholipase D (PLD) in bovine pulmonary artery endothelial cells (BPAECs). Addition of DPV to BPAECs in the presence of .05% butanol resulted in an accumulation of [P-32] phosphatidylbutanol (PBt) in a dose- and time-dependent manner. DPV also caused an increase in tyrosine phosphorylation of several protein bands (Mr 20-200 kD), as determined by Western blot analysis with antiphosphotyrosine antibodies. The DPV-induced [P-32] PBt-accumulation was inhibited by putative tyrosine kinase inhibitors such as genistein, herbimycin, tyrphostin and by chelation of Ca2+ with either EGTA or BAPTA, however, pretreatment of BPAECs with the inhibitor PKC bisindolylmaleimide showed minimal inhibition. Also down-regulation of PKC alpha and epsilon, the major isotypes of PKC in BPAECs, by TPA (100 nM, 18 h) did not attenuate the DPV-induced PLD activation. The effects of putative tyrosine kinase and PKC inhibitors were specific as determined by comparing [P-32] PBt formation between DPV and TPA. In addition to tyrosine kinase inhibitors, antioxidants such as N-acetylcysteine and pyrrolidine dithiocarbamate also attenuated DPV-induced protein tyrosine phosphorylation and PLD stimulation. These results suggest that oxidation, prevented by reduction with thiol compounds, is involved in DPV-dependent protein tyrosine phosphorylation and PLD activation.

Determination of diffusion parameters and activation energy of diffusion in V3Si phase with A15 crystal structure

Diffusion such is the integrated diffusion coefficient of the phase, the tracer diffusion coefficient of species at different temperatures and the activation energy for diffusion, are determined in V3Si phase with A15 crystal structure. The tracer diffusion coefficient of Si Was found to be negligible compared to the tracer diffusion coefficient of V. The calculated diffusion parameters will help to validate the theoretical analysis of defect structure of the phase, which plays an important role in the superconductivity.

Maximal regularity for second order non-autonomous Cauchy problems

We consider some non-autonomous second order Cauchy problems of the form u + B(t)(u) over dot + A(t)u = f (t is an element of [0, T]), u(0) = (u) over dot(0) = 0. We assume that the first order problem (u) over dot + B(t)u = f (t is an element of [0, T]), u(0) = 0, has L-p-maximal regularity. Then we establish L-p-maximal regularity of the second order problem in situations when the domains of B(t(1)) and A(t(2)) always coincide, or when A(t) = kappa B(t).

Higher-Order Nonlinearity In Accretion Disks: Quasi-Periodic Oscillations Of Black Hole And Neutron Star Sources And Their Spin

We propose a unified model to explain Quasi-Periodic Oscillation (QPO), particularly of high frequency, observed from black hole and neutron star systems globally. We consider accreting systems to be damped harmonic oscillators exhibiting epicyclic oscillations with higher-order nonlinear resonance to explain QPO. The resonance is expected to be driven by the disturbance from the compact object at its spin frequency. The model explains various properties parallelly for both types of the compact object. It describes QPOs successfully for ten different compact sources. Based on this, we predict the spin frequency of the neutron star Sco X-1 and specific angular momentum of black holes GRO J1655–40, XTE J1550–564, H1743–322, and GRS 1915+105.

Dynamical Transition of Water in the Grooves of DNA Duplex at Low Temperature

At low temperature (below its freezing/melting temperature), liquid water under confinement is known to exhibit anomalous dynamical features. Here we study structure and dynamics of water in the grooves of a long DNA duplex using molecular dynamics simulations with TIP5P potential at low temperature. We find signatures of a dynamical transition in both translational and orientational dynamics of water molecules in both the major and the minor grooves of a DNA duplex. The transition occurs at a slightly higher temperature (TGL ≈ 255 K) than the temperature at which the bulk water is found to undergo a dynamical transition, which for the TIP5P potential is at 247 K. Groove water, however, exhibits markedly different temperature dependence of its properties from the bulk. Entropy calculations reveal that the minor groove water is ordered even at room temperature, and the transition at T ≈ 255 K can be characterized as a strong-to-strong dynamical transition. Confinement of water in the grooves of DNA favors the formation of a low density four-coordinated state (as a consequence of enthalpy−entropy balance) that makes the liquid−liquid transition stronger. The low temperature water is characterized by pronounced tetrahedral order, as manifested in the sharp rise near 109° in the O−O−O angle distribution. We find that the Adams−Gibbs relation between configurational entropy and translational diffusion holds quite well when the two quantities are plotted together in a master plot for different region of aqueous DNA duplex (bulk, major, and minor grooves) at different temperatures. The activation energy for the transfer of water molecules between different regions of DNA is found to be weakly dependent on temperature.

On the short-range order in Al-Mn quasicrystals during low-temperature ageing

We report the evolution of diffuse intensity during the low-temperature ageing of Al-Mn quasicrystals. This is taken as evidence of short-range order in the icosahedral phase prior to its decomposition. The implication of these diffuse intensities is discussed.

Compressible second-order boundary layers for three-dimensional stagnation point flows with mass transfer

All the second-order boundary-layer effects have been studied for the steady laminar compressible 3-dimensional stagnation-point flows with variable properties and mass transfer for both saddle and nodal point regions. The governing equations have been solved numerically using an implicit finite-difference scheme. Results for the heat transfer and skin friction have been obtained for several values of the mass-transfer rate, wall temperature, and also for several values of parameters characterizing the nature of stagnation point and variable gas properties. The second-order effects on the heat transfer and skin friction at the wall are found to be significant and at large injection rates, they dominate over the results of the first-order boundary layer, but the effect of large suction is just the opposite. In general, the second-order effects are more pronounced in the saddle-point region than in the nodal-point region. The overall heat-transfer rate for the 3-dimensional flows is found to be more than that of the 2-dimensional flows.

New temperature fluctuation method for direct determination of thermal activation energy of deep levels in semiconductors

A new method is suggested where the thermal activation energy is measured directly and not as a slope of an Arrhenius plot. The sample temperature T is allowed to fluctuate about a temperature T0. The reverse-biased sample diode is repeatedly pulsed towards zero bias and the transient capacitance C1 at time t1 is measured The activation energy is obtained by monitoring the fluctuations in C1 and T. The method has been used to measure the activation energy of the gold acceptor level in silicon.

Graphical method to include temperature variation of activation energy in Hall data analysis

A graphical method is presented for Hall data analysis, including the temperature variation of activation energy due to screening. This method removes the discrepancies noted in the analysis of recently reported Hall data on Si(In).

Unsteady laminar incompressible second-order boundary-layer flow at a three-dimensional stagnation point

The unsteadely laminar incompressible second-order boundary-layer flow at the stagnation point of a three-dimensional body has been studied for both nodal and saddle point regions. The effects of mass transfer and Prandtl number have been taken into account. The equations governing the flow have been solved numerically using an implicit finite-difference scheme. It has been found that the parameter characterizing the unsteadiness in the velocity of the free stream, the nature of the stagnation point, the mass transfer and Prandtl number strongly affect the second-order skin friction and heat transfer. The overall skin friction becomes less due to second-order effects but the heat transfer has the opposite behaviour. For large injection, the second-order skin-friction and heat-transfer results prevail over the first-order boundary layer results whereas for the case of large suction the behaviour is just the opposite.

Testing approximate theories of first-order phase transitions on the two-dimensional Potts model

The two-dimensional,q-state (q>4) Potts model is used as a testing ground for approximate theories of first-order phase transitions. In particular, the predictions of a theory analogous to the Ramakrishnan-Yussouff theory of freezing are compared with those of ordinary mean-field (Curie-Wiess) theory. It is found that the Curie-Weiss theory is a better approximation than the Ramakrishnan-Yussouff theory, even though the former neglects all fluctuations. It is shown that the Ramakrishnan-Yussouff theory overestimates the effects of fluctuations in this system. The reasons behind the failure of the Ramakrishnan-Yussouff approximation and the suitability of using the two-dimensional Potts model as a testing ground for these theories are discussed.