Paper 4: Instabilities in downslope propagating gravity currents

In this paper, the stability of a gravity current propagating down an inclined channel is explored. The gravity current is generated through a partial lock release. A local analysis of the flow about the lock is conducted using classical methodologies in two-layer shallow water theory, which is here developed to allow for drag and an angled channel. A global analysis of the flow is done by exploring the long-time forced steady state, using non-linear simulations solving the full three-dimensional Navier-Stokes equations. A steady state is forced through the inclusion of a so-called mask function. For sufficiently large slope angles, wave-like instabilities are observed on the density interface (pycnocline) of the generated gravity current. Spectral Proper-Orthogonal Decomposition of the time-series data provides evidence that instability arises via the interaction of two asymmetric vorticity waves, occurring on either side of a critical layer, akin to a spatially evolving Kelvin-Helmholtz instability. The work in this paper is exploratory in nature and motivates further investigation

Dose, exposure time, and resolution in Serial X-ray Crystallography

The resolution of X-ray diffraction microscopy is limited by the maximum dose that can be delivered prior to sample damage. In the proposed Serial Crystallography method, the damage problem is addressed by distributing the total dose over many identical hydrated macromolecules running continuously in a single-file train across a continuous X-ray beam, and resolution is then limited only by the available molecular and X-ray fluxes and molecular alignment. Orientation of the diffracting molecules is achieved by laser alignment. We evaluate the incident X-ray fluence (energy/area) required to obtain a given resolution from (1) an analytical model, giving the count rate at the maximum scattering angle for a model protein, (2) explicit simulation of diffraction patterns for a GroEL-GroES protein complex, and (3) the frequency cut off of the transfer function following iterative solution of the phase problem, and reconstruction of an electron density map in the projection approximation. These calculations include counting shot noise and multiple starts of the phasing algorithm. The results indicate counting time and the number of proteins needed within the beam at any instant for a given resolution and X-ray flux. We confirm an inverse fourth power dependence of exposure time on resolution, with important implications for all coherent X-ray imaging. We find that multiple single-file protein beams will be needed for sub-nanometer resolution on current third generation synchrotrons, but not on fourth generation designs, where reconstruction of secondary protein structure at a resolution of 0.7 nm should be possible with short exposures.Comment: 19 pages, 7 figures, 1 tabl

Early p53 mutations in nondysplastic Barrett's tissue detected by the restriction site mutation (RSM) methodology

Barrett's oesophagus is a premalignant condition whose incidence is rising dramatically. Molecular markers are urgently needed to identify Barrett's patients at the highest risk of cancer progression. To this end, we have used a rapid molecular technique, restriction site mutation (RSM), to detect low-frequency mutations in the p53 tumour suppressor gene in premalignant Barrett's tissues of cancer-free patients. In total, 38 endoscopically diagnosed Barrett's patients with a range of histological stages of Barrett's progression, plus four control patients without Barrett's oesophagus, were analysed for early p53 mutations. Tissue samples taken from these patients (93 samples in total) were analysed for the presence of low-frequency p53 mutations at hotspot codons: 175, 213, 248, 249, 282. In total, 13 of the 38 Barrett's patients were shown to possess a p53 mutation in at least one sample (no mutations in the four control patients). Although no statistically significant associations were found, p53 mutations reflected histological progression in Barrett's patients with p53 mutations found in 30% of metaplasia patients (P=0.4) and low-grade dysplasia patients (P=0.33) and 45% of high-grade dysplasia patients (P=0.15). Detected p53 mutations were mainly GC to AT transitions at CpG sites

Temperature dependent surface relaxations of Ag(111)

The temperature dependent surface relaxation of Ag(111) is calculated by density-functional theory. At a given temperature, the equilibrium geometry is determined by minimizing the Helmholtz free energy within the quasiharmonic approximation. To this end, phonon dispersions all over the Brillouin zone are determined from density-functional perturbation theory. We find that the top-layer relaxation of Ag(111) changes from an inward contraction (-0.8 %) to an outward expansion (+6.3%) as the temperature increases from T=0 K to 1150 K, in agreement with experimental findings. Also the calculated surface phonon dispersion curves at room temperature are in good agreement with helium scattering measurements. The mechanism driving this surface expansion is analyzed.Comment: 6 pages, 7 figures, submitted to Phys. Rev. B (May 1998). Other related publications can be found at http://www.rz-berlin.mpg.de/th/paper.htm

Automation and validation of micronucleus detection in the 3D EpiDerm™ human reconstructed skin assay and correl

Recent restrictions on the testing of cosmetic ingredients in animals have resulted in the need to test the genotoxic potential of chemicals exclusively in vitro prior to licensing. However, as current in vitro tests produce some misleading positive results, sole reliance on such tests could prevent some chemicals with safe or beneficial exposure levels from being marketed. The 3D human reconstructed skin micronucleus (RSMN) assay is a promising new in vitro approach designed to assess genotoxicity of dermally applied compounds. The assay utilises a highly differentiated in vitro model of the human epidermis. For the first time, we have applied automated micronucleus detection to this assay using MetaSystems Metafer Slide Scanning Platform (Metafer), demonstrating concordance with manual scoring. The RSMN assay's fixation protocol was found to be compatible with the Metafer, providing a considerably shorter alternative to the recommended Metafer protocol. Lowest observed genotoxic effect levels (LOGELs) were observed for mitomycin-C at 4.8 μg/ ml and methyl methanesulfonate (MMS) at 1750 μg/ml when applied topically to the skin surface. In-medium dosing with MMS produced a LOGEL of 20 μg/ml, which was very similar to the topical LOGEL when considering the total mass of MMS added. Comparisons between 3D medium and 2D LOGELs resulted in a 7-fold difference in total mass of MMS applied to each system, suggesting a protective function of the 3D microarchitecture. Interestingly, hydrogen peroxide (H2O 2), a positive clastogen in 2D systems, tested negative in this assay. A non-genotoxic carcinogen, methyl carbamate, produced negative results, as expected. We also demonstrated expression of the DNA repair protein N-methylpurine-DNA glycosylase in EpiDerm™. Our preliminary validation here demonstrates that the RSMN assay may be a valuable followup to the current in vitro test battery, and together with its automation, could contribute to minimising unnecessary in vivo tests by reducing in vitro misleading positives. © The Author 2014

An ellipsoidal mirror for focusing neutral atomic and molecular beams

Manipulation of atomic and molecular beams is essential to atom optics applications including atom lasers, atom lithography, atom interferometry and neutral atom microscopy. The manipulation of charge-neutral beams of limited polarizability, spin or excitation states remains problematic, but may be overcome by the development of novel diffractive or reflective optical elements. In this paper, we present the first experimental demonstration of atom focusing using an ellipsoidal mirror. The ellipsoidal mirror enables stigmatic off-axis focusing for the first time and we demonstrate focusing of a beam of neutral, ground-state helium atoms down to an approximately circular spot, (26.8±0.5) μm×(31.4±0.8) μm in size. The spot area is two orders of magnitude smaller than previous reflective focusing of atomic beams and is a critical milestone towards the construction of a high-intensity scanning helium microscope

An ellipsoidal mirror for focusing neutral atomic and molecular beams

Manipulation of atomic and molecular beams is essential to atom optics applications including atom lasers, atom lithography, atom interferometry and neutral atom microscopy. The manipulation of charge-neutral beams of limited polarizability, spin or excitation states remains problematic, but may be overcome by the development of novel diffractive or reflective optical elements. In this paper, we present the first experimental demonstration of atom focusing using an ellipsoidal mirror. The ellipsoidal mirror enables stigmatic off-axis focusing for the first time and we demonstrate focusing of a beam of neutral, ground-state helium atoms down to an approximately circular spot, (26.8±0.5) μm×(31.4±0.8) μm in size. The spot area is two orders of magnitude smaller than previous reflective focusing of atomic beams and is a critical milestone towards the construction of a high-intensity scanning helium microscope