Targeting Cancer Gene Therapy with Magnetic Nanoparticles

Recent advances in cancer genomics have opened up unlimited potential for treating cancer by directly targeting culprit genes. However, novel delivery methods are needed in order for this potential to be translated into clinically viable treatments for patients. Magnetic nanoparticle technology offers the potential to achieve selective and efficient delivery of therapeutic genes by using external magnetic fields, and also allows simultaneous imaging to monitor the delivery in vivo. Compared to conventional gene delivery strategies, this technique has been shown to significantly increase gene delivery to human xenograft tumors models, as well as various internal organs (e.g. liver, kidney) and the central nervous system. Magnetic nanoparticle technology, therefore, has the potential to turn the challenge of gene therapy in vivo into a new frontier for cancer treatment

Hydrogen contamination in Ge-doped SiO[sub 2] thin films prepared by helicon activated reactive evaporation

Germanium-doped silicon oxidethin films were deposited at low temperature by using an improved helicon plasma assisted reactive evaporation technique. The origins of hydrogen contamination in the film were investigated, and were found to be H incorporation during deposition and postdeposition water absorption. The H incorporation during deposition was avoided by using an effective method to eliminate the residual hydrogen present in the depositionsystem. The microstructure, chemical bonds, chemical etch rate, and optical index of the films were studied as a function of the deposition conditions. Granular microstructures were observed in low-density films, and were found to be the cause of postdeposition water absorption. The granular microstructure was eliminated and the film was densified by increasing the helicon plasma power and substrate bias during deposition. A high-density film was shown to have no postdeposition water absorption and no OH detected by using a Fourier-transform infrared spectrometer

Ab Initio Study of Phase Stability in Doped TiO2

Ab-initio density functional theory (DFT) calculations of the relative stability of anatase and rutile polymorphs of TiO2 were carried using all-electron atomic orbitals methods with local density approximation (LDA). The rutile phase exhibited a moderate margin of stability of ~ 3 meV relative to the anatase phase in pristine material. From computational analysis of the formation energies of Si, Al, Fe and F dopants of various charge states across different Fermi level energies in anatase and in rutile, it was found that the cationic dopants are most stable in Ti substitutional lattice positions while formation energy is minimised for F- doping in interstitial positions. All dopants were found to considerably stabilise anatase relative to the rutile phase, suggesting the anatase to rutile phase transformation is inhibited in such systems with the dopants ranked F>Si>Fe>Al in order of anatase stabilisation strength. Al and Fe dopants were found to act as shallow acceptors with charge compensation achieved through the formation of mobile carriers rather than the formation of anion vacancies

Three-Dimensional Spin-Orbit Coupling in a Trap

We investigate the properties of an atom under the influence of a synthetic three-dimensional spin-orbit coupling (Weyl coupling) in the presence of a harmonic trap. The conservation of total angular momentum provides a numerically efficient scheme for finding the spectrum and eigenfunctions of the system. We show that at large spin-orbit coupling the system undergoes dimensional reduction from three to one dimension at low energies, and the spectrum is approximately Landau level-like. At high energies, the spectrum is approximately given by the three-dimensional isotropic harmonic oscillator. We explore the properties of the ground state in both position and momentum space. We find the ground state has spin textures with oscillations set by the spin-orbit length scale

Activation of Extracellular-signal Regulated Kinase (ERK1/2) by Fluid Shear is Ca\u3csup\u3e2+\u3c/sup\u3e- and ATP-dependent in MC3T3-E1 Osteoblasts

To determine the role of Ca2+ signaling in activation of the Mitogen-Activated Protein Kinase (MAPK) pathway, we subjected MC3T3-E1 pre-osteoblastic cells to inhibitors of Ca2+ signaling during application of fluid shear stress (FSS). FSS only activated ERK1/2, rapidly inducing phosphorylation within 5 min of the onset of shear. Phosphorylation of ERK1/2 (pERK1/2) was significantly reduced when Cai2+ was chelated with BAPTA or when Ca2+ was removed from the flow media. Inhibition of both the L-type voltage-sensitive Ca2+ channel and the mechanosensitive cation-selective channel blocked FSS-induced pERK1/2. Inhibition of phospholipase C with U73122 significantly reduced pERK1/2. This inhibition did not result from blockage of intracellular Ca2+ release, but a loss of PKC activation. Recent data suggests a role of ATP release and purinergic receptor activation in mechanotransduction. Apyrase-mediated hydrolysis of extracellular ATP completely blocked FSS-induced phosphorylation of ERK1/2, while the addition of exogenous ATP to static cells mimicked the effects of FSS on pERK1/2. Two P2 receptors, P2Y2 and P2X7, have been associated with the anabolic responses of bone to mechanical loading. Using both iRNA techniques and primary osteoblasts isolated from P2X7 knockout mice, we found that the P2X7, but not the P2Y2, purinergic receptor was involved in ERK1/2 activation under FSS. These data suggest that FSS-induced ERK1/2 phosphorylation requires Ca2+-dependent ATP release, however both increased Cai2+ and PKC activation are needed for complete activation. Further, this ATP-dependent ERK1/2 phosphorylation is mediated through P2X7, but not P2Y2, purinergic receptors