The response of the ionospheric F region to the large solar flare that occurred near 1500 UT on August 7, 1972, has been monitored by means of Faraday rotation measurements made at 17 stations in North America, Europe, and Africa. With observations spanning more than 10 hours in local time and more than 70 deg in latitude, the first truly global morphology of a flare‐induced F region event was obtained. The sizes of the individual sudden increases in the total electron content (Sitec) ranged from 1.8 to 8.6 × 1016 el/m²; on a percentage basis, all the Sitec fell within the 15 to 30% range. No obvious relationship was found between the sizes of the increases and the solar zenith angles at the various subionospheric points, nor between the observed Sitec and the sudden flare effects (SFE) seen on nearby magnetometer recordings. The latitudinal behavior provided the only simple ordering parameter found in the data, the lower latitudes having larger observed increases than the higher latitudes. Millstone Hill incoherent scatter data showed that nearly 40% of the total content enhancement observed at that site came from heights above 300 km. All the Sitec had a rise time of about 10 min, during which the Tec rate of change showed an excellent correlation with the time development of the solar radio burst monitored at 35,000 MHz.
RO5263397 [(S)-4-(3-fluoro-2-methyl-phenyl)-4,5-dihydro-oxazol-2-ylamine], a new compound that showed promising results in animal models of schizophrenia, is mainly metabolized in humans by N-glucuronidation. Enzyme studies, using the (then) available commercial uridine 59-diphosphate-glucuronosyltransferases (UGTs), suggested that UGT1A4 is responsible for its conjugation. In the first clinical trial, in which RO5263397 was administered orally to healthy human volunteers, a 136-fold above-average systemic exposure to the parent compound was found in one of the participants. Further administration in this trial identified two more such poor metabolizers, all three of African origin. Additional in vitro studies with recombinant UGTs showed that the contribution of UGT2B10 to RO5263397 glucuronidation is much higher than UGT1A4 at clinically relevant concentrations. DNA sequencing in all of these poor metabolizers identified a previously uncharacterized splice site mutation that prevents assembly of full-length UGT2B10 mRNA and thus functional UGT2B10 protein expression. Further DNA database analyses revealed the UGT2B10 splice site mutation to be highly frequent in individuals of African origin (45%), moderately frequent in Asians (8%) and almost unrepresented in Caucasians (,1%). A prospective study using hepatocytes from 20 individual African donors demonstrated a .100-fold lower intrinsic clearance of RO5263397 in cells homozygous for the splice site variant allele. Our results highlight the need to include UGT2B10 when screening the human UGTs for the enzymes involved in the glucuronidation of a new compound, particularly when there is a possibility of N-glucuronidation. Moreover, this study demonstrates the importance of considering different ethnicities during drug development.
The relationship between rainfall characteristics and urbanization over the eastern United States was examined by analyzing four datasets: daily rainfall in 4593 surface stations over the last 50 years (1958–2008), a high-resolution gridded rainfall product, reanalysis wind data, and a proxy for urban land use (gridded human population data). Results indicate that summer monthly rainfall amounts show an increasing trend in urbanized regions. The frequency of heavy rainfall events has a potential positive bias toward urbanized regions. Most notably, consistent with case studies for individual cities, the climatology of rainfall amounts downwind of urban–rural boundaries shows a significant increasing trend. Analysis of heavy (90th percentile) and extreme (99.5th percentile) rainfall events indicated decreasing trends of heavy rainfall events and a possible increasing trend for extreme rainfall event frequency over urban areas. Results indicate that the urbanization impact was more pronounced in the northeastern and midwestern United States with an increase in rainfall amounts. In contrast, the southeastern United States showed a slight decrease in rainfall amounts and heavy rainfall event frequencies. Results suggest that the urbanization signature is becoming detectable in rainfall climatology as an anthropogenic influence affecting regional precipitation; however, extracting this signature is not straightforward and requires eliminating other dynamical confounding feedbacks.
The problem of the water table in equilibrium with the rainfall on sloping land is analyzed by solving Boussinesq's equation. It is assumed that the hillside is drained by parallel ditches which are founded in the impermeable layer. A nomegram is presented for calculating the ditch spacing as a function of rate of replenishment, soil hydraulic conductivity, and maximum height of the water table above the impermeable layer.
[1] This study investigates how increasing city size affects local weather modification potential using an innovative new method: the real atmosphere, idealized land-surface (RAIL) method. The RAIL method simplifies the land surface by making a flat, homogeneous land surface for a control simulation. Using the Regional Atmospheric Modeling System, an instance of weak linear convection was simulated over three nested grids with a minimum grid spacing of 0.75 km. Using the RAIL method, cities of radius 5 to 40 km were placed in the path of the simulated precipitation to study the impact. For the weak-convection case, the urban area effects showed urban heat island and urban moisture depression effects and produced regions of both precipitation suppression and invigoration downwind of the city. Modification increased up to a radius of 20 km and more slowly after indicating a threshold city size for urban modification on thunderstorms.
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