Inhibition of nuclear factor-kappa B differentially affects thyroid cancer cell growth, apoptosis, and invasion

<p>Abstract</p> <p>Background</p> <p>Nuclear factor-κB (NF-κB) is constitutively activated in many cancers and plays a key role in promoting cell proliferation, survival, and invasion. Our understanding of NF-κB signaling in thyroid cancer, however, is limited. In this study, we have investigated the role of NF-κB signaling in thyroid cancer cell proliferation, invasion, and apoptosis using selective genetic inhibition of NF-κB in advanced thyroid cancer cell lines.</p> <p>Results</p> <p>Three pharmacologic inhibitors of NF-κB differentially inhibited growth in a panel of advanced thyroid cancer cell lines, suggesting that these NF-κB inhibitors may have off-target effects. We therefore used a selective genetic approach to inhibit NF-κB signaling by overexpression of a dominant-negative IκBα (mIκBα). These studies revealed decreased cell growth in only one of five thyroid cancer cell lines (8505C), which occurred through a block in the S-G2/M transition. Resistance to TNFα-induced apoptosis was observed in all cell lines, likely through an NF-κB-dependent mechanism. Inhibition of NF-κB by mIκBα sensitized a subset of cell lines to TNFα-induced apoptosis. Sensitive cell lines displayed sustained activation of the stress-activated protein kinase/c-Jun NH2-terminal kinase (SAPK/JNK) pathway, defining a potential mechanism of response. Finally, NF-κB inhibition by mIκBα expression differentially reduced thyroid cancer cell invasion in these thyroid cancer cell lines. Sensitive cell lines demonstrated approximately a two-fold decrease in invasion, which was associated with differential expression of MMP-13. MMP-9 was reduced by mIκBα expression in all cell lines tested.</p> <p>Conclusions</p> <p>These data indicate that selective inhibition of NF-κB represents an attractive therapeutic target for the treatment of advanced thyroid. However, it is apparent that global regulation of thyroid cancer cell growth and invasion is not achieved by NF-κB signaling alone. Instead, our findings suggest that other important molecular processes play a critical role in defining the extent of NF-κB function within cancer cells.</p

Investigation of superconducting interactions and amorphous semiconductors

Research papers on superconducting interactions and properties and on amorphous materials are presented. The search for new superconductors with improved properties was largely concentrated on the study of properties of thin films. An experimental investigation of interaction mechanisms revealed no new superconductivity mechanism. The properties of high transition temperature, type 2 materials prepared in thin film form were studied. A pulsed field solenoid capable of providing fields in excess of 300 k0e was developed. Preliminary X-ray measurements were made of V3Si to determine the behavior of cell constant deformation versus pressure up to 98 kilobars. The electrical properties of amorphous semiconducting materials and bulk and thin film devices, and of amorphous magnetic materials were investigated for developing radiation hard, inexpensive switches and memory elements

Effect of varying material anisotropy on critical current anisotropy in vicinal YBa2Cu3O7-delta thin films

The high $T_{c}$ cuprate superconductors are noted for their anisotropic layered structure, certain of these materials indeed tend toward the limit of a Lawrence-Doniach superconductor. However, YBa$_2$Cu$_3$O$_{7-\delta}$ has a smaller anisotropy than would be expected from its interlayer spacing. This is due to the cuprate chains in the structure. To investigate the influence of the chain oxygen on transport properties critical current versus applied field angle measurements were performed on fully oxygenated and de-oxygenated YBa$_2$Cu$_3$O$_{7-\delta}$ thin films and optimally oxygenated Y$_{0.75}$Ca$_{0.2}$Ba$_2$Cu$_3$O$_{7-\delta}$ thin films. The films were grown on 10$^{\circ}$ mis-cut SrTiO$_3$ substrates to enable the intrinsic vortex channelling effect to be observed. The form of the vortex channelling minimum observed in field angle dependent critical current studies on the films was seen to depend on film oxygenation. The vortex channelling effect is dependent on a angular dependent cross-over to a string-pancake flux line lattice. The results obtained appear to be consistent with the prediction of Blatter et al. [Rev. Mod. Phys., 66 (4): 1125 (1994)] that increased superconducting anisotropy leads to the kinked string-pancake lattice existing over a smaller angular range.EPSR

Zurek-Kibble domain structures: The Dynamics of Spontaneous Vortex formation in Annular Josephson Tunnel Junctions

Phase transitions executed in a finite time show a domain structure with defects, that has been argued by Zurek and Kibble to depend in a characteristic way on the quench rate. In this letter we present an experiment to measure the Zurek-Kibble scaling exponent sigma. Using symmetric and long Josephson Tunnel Junctions, for which the predicted index is sigma = 0.25, we find sigma = 0.27 +/- 0.05. Further, there is agreement with the ZK prediction for the overall normalisation.Comment: To be published in Phys. Rev. Lett

Evaporation of a packet of quantized vorticity

A recent experiment has confirmed the existence of quantized turbulence in superfluid He3-B and suggested that turbulence is inhomogenous and spreads away from the region around the vibrating wire where it is created. To interpret the experiment we study numerically the diffusion of a packet of quantized vortex lines which is initially confined inside a small region of space. We find that reconnections fragment the packet into a gas of small vortex loops which fly away. We determine the time scale of the process and find that it is in order of magnitude agreement with the experiment.Comment: figure 1a,b,c and d, figure2, figure

Dynamics of ripple formation on silicon surfaces by ultrashort laser pulses in sub-ablation conditions

An investigation of ultrashort pulsed laser induced surface modification due to conditions that result in a superheated melted liquid layer and material evaporation are considered. To describe the surface modification occurring after cooling and resolidification of the melted layer and understand the underlying physical fundamental mechanisms, a unified model is presented to account for crater and subwavelength ripple formation based on a synergy of electron excitation and capillary waves solidification. The proposed theoretical framework aims to address the laser-material interaction in sub-ablation conditions and thus minimal mass removal in combination with a hydrodynamics-based scenario of the crater creation and ripple formation following surface irradiation with single and multiple pulses, respectively. The development of the periodic structures is attributed to the interference of the incident wave with a surface plasmon wave. Details of the surface morphology attained are elaborated as a function of the imposed conditions and results are tested against experimental data

Seasonal changes of whole root system conductance by a drought-tolerant grape root system

The role of root systems in drought tolerance is a subject of very limited information compared with above-ground responses. Adjustments to the ability of roots to supply water relative to shoot transpiration demand is proposed as a major means for woody perennial plants to tolerate drought, and is often expressed as changes in the ratios of leaf to root area (AL:AR). Seasonal root proliferation in a directed manner could increase the water supply function of roots independent of total root area (AR) and represents a mechanism whereby water supply to demand could be increased. To address this issue, seasonal root proliferation, stomatal conductance (gs) and whole root system hydraulic conductance (kr) were investigated for a drought-tolerant grape root system (Vitis berlandieri×V. rupestris cv. 1103P) and a non-drought-tolerant root system (Vitis riparia×V. rupestris cv. 101-14Mgt), upon which had been grafted the same drought-sensitive clone of Vitis vinifera cv. Merlot. Leaf water potentials (ψL) for Merlot grafted onto the 1103P root system (–0.91±0.02 MPa) were +0.15 MPa higher than Merlot on 101-14Mgt (–1.06±0.03 MPa) during spring, but dropped by approximately –0.4 MPa from spring to autumn, and were significantly lower by –0.15 MPa (–1.43±0.02 MPa) than for Merlot on 101-14Mgt (at –1.28±0.02 MPa). Surprisingly, gs of Merlot on the drought-tolerant root system (1103P) was less down-regulated and canopies maintained evaporative fluxes ranging from 35–20 mmol vine−1 s−1 during the diurnal peak from spring to autumn, respectively, three times greater than those measured for Merlot on the drought-sensitive rootstock 101-14Mgt. The drought-tolerant root system grew more roots at depth during the warm summer dry period, and the whole root system conductance (kr) increased from 0.004 to 0.009 kg MPa−1 s−1 during that same time period. The changes in kr could not be explained by xylem anatomy or conductivity changes of individual root segments. Thus, the manner in which drought tolerance was conveyed to the drought-sensitive clone appeared to arise from deep root proliferation during the hottest and driest part of the season, rather than through changes in xylem structure, xylem density or stomatal regulation. This information can be useful to growers on a site-specific basis in selecting rootstocks for grape clonal material (scions) grafted to them

High Temperature Photochemistry in the Atmosphere of HD189733b

Recent infrared spectroscopy of hot exoplanets is beginning to reveal their atmospheric composition. Deep with in the planetary atmosphere, the composition is controlled by thermochemical equilibrium. Photochemistry becomes important higher in the atmosphere, at levels above ~1 bar. These two chemistries compete between ~1-10 bars in hot Jupiter-like atmospheres, depending on the strength of the eddy mixing and temperature. HD189733b provides an excellent laboratory in which to study the consequences of chemistry of hot atmospheres. The recent spectra of HD189733b and HD209458b contain signatures of CH4, CO2, CO and H2O. Here we identify the primary chemical pathways that govern the abundances of CH4, CO2, CO and H2O in the cases of thermochemical equilibrium chemistry, photochemistry, and their combination. Our results suggest that the abundance of these species can be photochemically enhanced above or below the thermochemical equilibrium value, so some caution must be taken when assuming that an atmosphere is in strict thermochemical equilibrium

Slow 4He^{4}He Quenches Produce Fuzzy, Transient Vortices

We examine the Zurek scenario for the production of vortices in quenches of liquid $^{4}He$ in the light of recent experiments. Extending our previous results to later times, we argue that short wavelength thermal fluctuations make vortices poorly defined until after the transition has occurred. Further, if and when vortices appear, it is plausible that that they will decay faster than anticipated from turbulence experiments, irrespective of quench rates.Comment: 4 pages, Revtex file, no figures Apart from a more appropriate title, this paper differs from its predecessor by including temperature, as well as pressure, quenche