Promoter analysis of RPE65, the gene encoding a 61-kDa retinal pigment epithelium-specific protein

OBJECTIVES: This study compared the long-term effects of complete atrioventricular junction (AVJ) ablation with those of AVJ modification in patients with medically refractory atrial fibrillation (AF). BACKGROUND: Comparisons between the long-term effects of AVJ ablation with those of AVJ modification in patients with medically refractory AF have not been systematically studied. METHODS: Sixty patients with medically refractory AF were randomly assigned to receive complete AVJ ablation with permanent pacing or AVJ modification. Subjective perception of quality of life (QOL) was assessed by a semiquantitative questionnaire before and 1 and 6 months after ablation. Cardiac performance was evaluated by echocardiography and radionuclide angiography within 24 h (baseline) and at 1 and 6 months after ablation. RESULTS: Both methods were associated with significant improvement in general QOL and a significant reduction in the frequency of major symptoms and symptoms during attacks. The frequency of hospital admission and emergency room visits and antiarrhythmic drug trials significantly decreased after ablation in both groups. However, patients after complete AVJ ablation had a significantly greater improvement in general QOL and a significantly reduced frequency of major symptoms and symptoms during attacks (including palpitation, dizziness, chest oppression, blurred vision and syncope). Left ventricular (LV) systolic function and the ability to perform activities of daily life significantly improved after ablation in patients with depressed LV function in both groups. All improvements after ablation or modification were maintained over the 6-month follow-up period. CONCLUSIONS: AVJ ablation with permanent pacing, as compared with AVJ modification, had a significantly greater ability to decrease the frequency of attacks and the extent of symptoms of AF, and the patients who received this procedure were more satisfied with their general well-being.     

(Pheo)melanin photosensitizes UVA-induced DNA damage in cultured human melanocytes

The question of whether melanins are photoprotecting and/or photosensitizing in human skin cells continues to be debated. To evaluate the role of melanin upon UVA irradiation, DNA single-strand breaks (ssb) were measured in human melanocytes differing only in the amount of pigment produced by culturing at two different concentrations, basic (0.01 mM) or high (0.2 mM), of L-tyrosine, the main precursor of melanin. In parallel, pheo- and total melanin contents of the cells were determined. Identical experiments were performed with two melanocyte cultures derived from a skin type I and a skin type VI individual. For the first time the correlation between UVA-induced genotoxicity and pheo-/total melanin content has been investigated. We observed that cultured in basic medium, the skin type VI melanocytes contained 10 times more total melanin and about seven times more pheomelanin than the skin type I melanocytes. Elevation of tyrosine level in the culture medium resulted in an increase of both pheo- and total melanin levels in both melanocyte cultures; however, the melanin composition of skin type I melanocytes became more pheomelanogenic, whereas that of skin type VI melanocytes remained the same. The skin type VI melanocytes cultured in basic medium demonstrated a very high sensitivity (1.18 ssb per 10(10) Da per kJ per m2) toward UVA that is probably related to their high pheo- and total melanin content. Their UVA sensitivity, however, did not change after increasing their melanin content by culturing at high tyrosine concentration. In contrast, the skin type I melanocytes demonstrated a low sensitivity (0.04 ssb per 10(10) Da per kJ per m2) toward UVA when cultured in basic medium, but increasing their melanin content resulted in a 3-fold increase in their UVA sensitivity (0.13 ssb per 10(10) Da per kJ per m2). These results demonstrate that UVA-irradiated cultured human melanocytes are photosensitized by their own synthesized chromophores, most likely pheomelanin and/or melanin intermediates.     

Proton magnetic resonance imaging of lipid in pecan embryos

Magnetic resonance images of plant tissues typically are manifestations of water protons in tissues. Within oilseeds, however, lipids contain a major portion of the mobile protons, which should enable specific imaging of lipids. In this study, experiments were done to demonstrate spin-echo imaging (SEI) and chemical-shift imaging (CSI) of lipid within nonimbibed and imbibed embryos of pecan (Carya illinoensis), a high-lipid seed. Magnetic resonance spectra of airdry embryos contained a single major peak for lipid, whereas those of imbibed embryos contained separate peaks for water and lipid. This separation of spectral peaks enabled CSI of distributions of either lipids or water in imbibed embryos. A longer spin-spin relaxation time of lipid protons than of water protons in imbibed embryos allowed selective SEI of lipids in those embryos. SEI of normal, dry embryos revealed fairly uniform distribution of lipids across tissues. Similar images of embryos damaged by the fungusPhoma exocarpina or the insectZerara viridula were less intense than those of a normal embryo, reflecting the lower oil contents of the damaged embryos. Magnetic resonance imaging should provide a useful technology for studying lipid distribution and metabolism within oil seeds.     

Characterization of constitutional liquid film migration in nickel-base alloy 718

When multiphase alloys are rapidly heated, it is possible to cause melting of the interface between phases. This is called constitutional liquation if, during melting, the bulk composition is in a nonliquid region of the phase diagram but the tie-line between the liquating phases passes through a liquid region. The liquid produced during constitutional liquation can spread along grain boundaries and promote liquid film migration (LFM). This is known as constitutional liquid film migration (CLFM), which is thermodynamically similar to liquid film migration; however, mechanistically there are significant differences. Nickel-base alloy 718 has been studied to show the features of migration that are unique to CLFM. Experimentation consisted of heat-treating rods of alloy 718 to promote the trapping of niobium carbide particles on the grain boundaries. These samples were then subjected to isothermal treatments above their constitutional-liquation temperature, which produced CLFM of the grain boundaries. The movement of the liquid films away from their centers of curvature, the formation of a new solid solution behind the migrated liquid films, and the reversals of curvature of the migrated liquid films confirmed that CLFM was the phenomenon observed. The concentration of niobium behind the migrated liquid films for isothermal treatments below the solidus temperature was shown to be greater than the niobium concentration in the matrix. Above the solidus temperature, there was no increase in niobium concentration. The validity of the coherency strain hypothesis as the driving force for CLFM in alloy 718 is discussed.     

Potentially reactive cyclic carbamate metabolite of the antiepileptic drug felbamate produced by human liver tissue in vitro

To gain insights into the different forms of modified amyloid beta peptides (A beta) in the Alzheimer disease (AD) and Down syndrome (DS) brain, we used two-site ELISAs with antibodies specific for isomerized (i.e. A beta with L-isoaspartate at positions 1 and 7) and pyroglutamate-modified (i.e. A beta beginning with pyroglutamate at position 3) forms of A beta to quantitate the levels of these different A beta peptides in formic acid extracts of AD and DS frontal cortex. Despite variations in the proportions of distinct forms of A beta in AD and DS frontal cortex, the major species of A beta in these samples were A betaN3(pyroGlu)-42 as well as A beta x-42 (where x is a residue at position 2 or less in A beta), whereas isomerized A beta was a minor species. Further, the levels of isomerized and pyroglutamate-modified forms of A beta terminating at amino acid 42 were higher than those ending at amino acid 40. The abundance of the distinct forms of A beta reported here in formic acid extracts of AD and DS frontal cortex suggests that these A beta species could play important roles in the deposition of A beta in AD and DS brains.     

Electromagnetic fast firing for ultrashallow junction formation

The creation of low resistivity, ultrashallow source/drain regions in MOS device structures requires rapid thermal processing (RTP) techniques that restrict diffusion and activate a significant percentage of the implanted dopant species. While current heating techniques depend upon illumination based heating, a new technology, electromagnetic induction heating (EMIH), achieves a rapid heating of the silicon by coupling electromagnetic radiation directly into the silicon wafer. Heating rates of 125/spl deg/C/s to temperatures in excess of 1050/spl deg/C have been achieved for 75- and 100-mm-diameter wafers at input powers of 1000 and 1300 W, respectively. These ramp rates are suitable for ultrashallow junction formation, and junctions shallower than 30 nm with sheet resistances lower than 600 /spl Omega//square have been achieved. This paper details the application of electromagnetic heating using radiation in the microwave, 2450 MHz, frequency regime. Experimental results, comparing microwave annealed implants to the well documented SEMATECH requirements, and simulations, utilizing a coupled electromagnetic-thermal computer model, of the heating process are discussed.     

Influences of changes in mechanical properties of an overcored sample on the far-field stress calculation

The concentration factors for the determination of far-field stresses have been calculated based on three-dimensional FLAC^3D simulated results. FLAC^3D is an explicit finite difference computer program. Three-dimensional numerical simulations have been conducted using FLAC^3D to determine the influence of altered overcored sample parameters on the far-field stress calculation. Both Young's modulus and Poisson's ratio are known to change during overcoring in highly stressed rock as a result of stress-relief damage. Modification factors have been proposed to take into account the influence of the reduction in Young's modulus on the far-field stress calculation. The influence of change in Poisson's ratio has also been analyzed. A method of determining a Young's modulus value suitable for use in the far-field stress calculation is described and the influence of reduction in Young's modulus of an overcored sample on the determination of the stress ratio (SR) in the RPR method is analyzed. Using the proposed modification, the in situ stresses for the Atomic Energy of Canada Limited's Underground Research Laboratory are re-calculated based on 21 deep doorstopper measurements. The re-calculation shows an increase in the trend of stress magnitudes versus depth in the URL.     

Sample-sort simulated annealing.

A simulated annealing (SA) algorithm called Sample-Sort that is artificially extended across an array of samplers is proposed. The sequence of temperatures for a serial SA algorithm is replaced with an array of samplers operating at static temperatures and the single stochastic sampler is replaced with a set of samplers. The set of samplers uses a biased generator to sample the same distribution of a serial SA algorithm to maintain the same convergence property. Sample-Sort was compared to SA by applying both to a set of global optimization problems and found to be comparable if the number of iterations per sampler was sufficient. If the evaluation phase dominates the computational requirements, Sample-Sort could take advantage of parallel processing.