Stable silencing of SNAP-25 in PC12 cells by RNA interference

BACKGROUND: SNAP-25 is a synaptic protein known to be involved in exocytosis of synaptic vesicles in neurons and of large dense-core vesicles in neuroendocrine cells. Its role in exocytosis has been studied in SNAP-25 knockout mice, in lysed synaptosomes lacking functional SNAP-25 and in cells after treatment with botulinum toxins A or E that specifically cleave SNAP-25. These studies have shown that SNAP-25 appears to be required for most but not all evoked secretion. In order to further study the role of SNAP-25 in catecholamine secretion from PC12 cells we have used the recently developed technique of RNA interference to generate PC12 cell lines with virtually undetectable levels of SNAP-25. RNA interference is the sequence-specific silencing or knockdown of gene expression triggered by the introduction of double-stranded RNA into a cell. RNA interference can be elicited in mammalian cells in a number of ways, one of which is by the expression of small hairpin RNAs from a transfected plasmid. Selection of stably transfected cell lines expressing a small hairpin RNA allows one-time characterization of the degree and specificity of gene silencing and affords a continuing source of well-characterized knockdown cells for experimentation. RESULTS: A PC12 cell line stably transfected with a plasmid expressing an shRNA targeting SNAP-25 has been established. This SNAP-25 knockdown cell line has barely detectable levels of SNAP-25, but normal levels of other synaptic proteins. Catecholamine secretion elicited by depolarization of the SNAP-25 knockdown cells was reduced to 37% of control. CONCLUSION: Knockdown of SNAP-25 in PC12 cells reduces but does not eliminate evoked secretion of catecholamines. Transient expression of human SNAP-25 in the knockdown cells rescues the deficit in catecholamine secretion

On the Geometry of Surface Stress

We present a fully general derivation of the Laplace--Young formula and discuss the interplay between the intrinsic surface geometry and the extrinsic one ensuing from the immersion of the surface in the ordinary euclidean three-dimensional space. We prove that the (reversible) work done in a general surface deformation can be expressed in terms of the surface stress tensor and the variation of the intrinsic surface metric

Ferromagnetism in the Infinite-U Hubbard Model

We have studied the stability of the ferromagnetic state in the infinite-U Hubbard model on a square lattice by approximate diagonalization of finite lattices using the density matrix renormalization group technique. By studying lattices with up to 5X20 sites, we have found the ferromagnetic state to be stable below the hole density of 22 percent. Beyond 22 percent of hole doping, the total spin of the ground state decreased gradually to zero with increasing hole density.Comment: 13 pages, RevteX 3.0, seven figures appended in uuencoded form, correcting problems with uuencoded figure

Characteristics of a Mixed Thorium-Uranium Dioxide High-Burnup Fuel

Future nuclear fuels must satisfy three sets of requirements: longer times between refueling; concerns for weapons proliferation; and development of a spent fuel form more suitable for direct geologic disposal. This project has investigated a fuel consisting of mixed thorium and uranium dioxide to satisfy these requirements. Results using the SCALE 4.3 code system indicated that the mixed Th-U fuel could be burned to 72 MWD/kg or 100 MWD/kg using 25% of 35% UO2 respectively. The uranium remained below 20% total fissile fraction throughout the cycle, making it unusable for weapons. Total plutonium production per MWD was a factor of 4.5 less in the Th-U fuel than in the conventional fuel; Pu-239 production per MWD was a factor of 6.5 less; and the plutonium produced was high in Pu-238, leading to a decay heat 5 times greater than that from plutonium derived from conventional fuel and 40 times greater than weapons grade plutonium. High decay heat would require active cooling of any crude weapon, lest the components surrounding the plutonium be melted. Spontaneous neutron production for plutonium from Th-U fuel was 2.3 times greater than that from conventional fuel and 15 times greater than that from weapons grade plutonium. High spontaneous neutron production drastically limits the probable yield of a crude weapon. Because ThO2 is the highest oxide of thorium, while UO2 can be oxidized further to U3O8, ThO2-UO2 fuel may be a superior wasteform if the spent fuel is ever to be exposed to oxygenated water. Even if the cost of fabricating the mixed Th-U fuel is $100/kg greater, the cost of the Th-U fuel is 13% to 15% less than that of the fuels using uranium only

Symmetry Breaking in Linearly Coupled Dynamical Lattices

We examine one- and two-dimensional (1D and 2D) models of linearly coupled lattices of the discrete-nonlinear-Schr{\"{o}}dinger type. Analyzing ground states of the systems with equal powers in the two components, we find a symmetry-breaking phenomenon beyond a critical value of the squared $l^2$-norm. Asymmetric states, with unequal powers in their components, emerge through a subcritical pitchfork bifurcation, which, for very weakly coupled lattices, changes into a supercritical one. We identify the stability of various solution branches. Dynamical manifestations of the symmetry breaking are studied by simulating the evolution of the unstable branches. The results present the first example of spontaneous symmetry breaking in 2D lattice solitons. This feature has no counterpart in the continuum limit, because of the collapse instability in the latter case.Comment: 9 pages, 9 figures, submitted to Phys. Rev. E, Apr, 200

Theory of transverse spin dynamics in a polarized Fermi liquid and an itinerant ferromagnet

The linear equations for transverse spin dynamics in a weakly polarized degenerate Fermi liquid with arbitrary relationship between temperature and polarization are derived from Landau-Silin phenomenological kinetic equation with general form of two-particle collision integral. Unlike the previous treatment where Fermi velocity and density of states have been taken as constants independent of polarization here we made derivation free from this assumption. The obtained equations are applicable for description of spin dynamics in paramagnetic Fermi liquid with finite polarization as well in an itinerant ferromagnet. In both cases transverse spin wave frequency is found to be proportional to the square of the wave vector with complex constant of proportionality (diffusion coefficient) such that the damping has a finite value at T=0. The polarization dependence of the diffusion coefficient is found to be different for a polarized Fermi liquid and for an itinerant ferromagnet. These conclusions are confirmed by derivation of transverse spin wave dispersion law in frame of field theoretical methods from the integral equation for the vortex function. It is shown that similar derivation taking into consideration the divergency of static transverse susceptibility also leads to the same attenuating spin wave spectrum.Comment: 7 pages, no figure

Self Consistent Expansion for the Molecular Beam Epitaxy Equation

Motivated by a controversy over the correct results derived from the dynamic renormalization group (DRG) analysis of the non linear molecular beam epitaxy (MBE) equation, a self-consistent expansion (SCE) for the non linear MBE theory is considered. The scaling exponents are obtained for spatially correlated noise of the general form $D({\vec r - \vec r',t - t'}) = 2D_0 | {\vec r - \vec r'} |^{2\rho - d} \delta ({t - t'})$. I find a lower critical dimension $d_c (\rho) = 4 + 2\rho$, above, which the linear MBE solution appears. Below the lower critical dimension a r-dependent strong-coupling solution is found. These results help to resolve the controversy over the correct exponents that describe non linear MBE, using a reliable method that proved itself in the past by predicting reasonable results for the Kardar-Parisi-Zhang (KPZ) system, where DRG failed to do so.Comment: 16 page

Comparison of CDMS [100] and [111] oriented germanium detectors

The Cryogenic Dark Matter Search (CDMS) utilizes large mass, 3" diameter $\times$ 1" thick target masses as particle detectors. The target is instrumented with both phonon and ionization sensors and comparison of energy in each channel provides event-by-event classification of electron and nuclear recoils. Fiducial volume is determined by the ability to obtain good phonon and ionization signal at a particular location. Due to electronic band structure in germanium, electron mass is described by an anisotropic tensor with heavy mass aligned along the symmetry axis defined by the [111] Miller index (L valley), resulting in large lateral component to the transport. The spatial distribution of electrons varies significantly for detectors which have their longitudinal axis orientations described by either the [100] or [111] Miller indices. Electric fields with large fringing component at high detector radius also affect the spatial distribution of electrons and holes. Both effects are studied in a 3 dimensional Monte Carlo and the impact on fiducial volume is discussed.Comment: Low Temperature Detector 14 conference proceedings to be published in the Journal of Low Temperature Physic

Macroscopic Quantum Tunneling of a Domain Wall in a Ferromagnetic Metal

The macroscopic quantum tunneling of a planar domain wall in a ferromagnetic metal is studied based on the Hubbard model. It is found that the ohmic dissipation is present even at zero temperature due to the gapless Stoner excitation, which is the crucial difference from the case of the insulating magnet. The dissipative effect is calculated as a function of width of the wall and is shown to be effective in a thin wall and in a weak ferromagnet. The results are discussed in the light of recent experiments on ferromagnets with strong anisotropy. PACS numbers:75.60.Ch, 03.65.Sq, 75.10.LpComment: 13page