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Multiple Peaks (multiple + peak)
Selected AbstractsPharmacokinetics of E-6087, a new anti-inflammatory agent, in rats and dogsBIOPHARMACEUTICS AND DRUG DISPOSITION, Issue 6 2001Raquel F. Reinoso Abstract The pharmacokinetics of E-6087, a newly developed cyclooxygenase-2 inhibitor, was studied in rats and dogs after single oral and intravenous doses. In both animal species, E-6087 was characterized by a long elimination half-life (20,35 h), a low plasma clearance (0.10,0.22 l h,1 kg,1) and a relatively large volume of distribution (2,6 l kg,1). Oral bioavailability was lower in dogs than in rats whereas a faster elimination was found in rats. Multiple peaks were present regardless of administration route and animal species, suggesting the existence of enterohepatic circulation. Gender effect on the pharmacokinetics of E-6087 was only found in rats, with greater exposure and longer elimination in females than in males. Food intake reduced the bioavailability (,22%) with no apparent changes in the absorption rate. After oral dosing of 1, 5 and 25 mg kg,1 to rats, linearity was lost at the highest dose due to the low aqueous solubility of E-6087. Drug absorption was improved by micronization. E-6087 and E-6132, (a pharmacologically active metabolite), showed different pharmacokinetics. The higher percentage of E-6087 at early times suggests that E-6087 is the main compound responsible for in vivo activity, although E-6132 would contribute to the activity at later times. Copyright © 2001 John Wiley & Sons, Ltd. [source] RAPID EVOLUTIONARY ESCAPE BY LARGE POPULATIONS FROM LOCAL FITNESS PEAKS IS LIKELY IN NATUREEVOLUTION, Issue 6 2005Daniel M. Weinreich Abstract Fitness interactions between loci in the genome, or epistasis, can result in mutations that are individually deleterious but jointly beneficial. Such epistasis gives rise to multiple peaks on the genotypic fitness landscape. The problem of evolutionary escape from such local peaks has been a central problem of evolutionary genetics for at least 75 years. Much attention has focused on models of small populations, in which the sequential fixation of valley genotypes carrying individually deleterious mutations operates most quickly owing to genetic drift. However, valley genotypes can also be subject to mutation while transiently segregating, giving rise to copies of the high fitness escape genotype carrying the jointly beneficial mutations. In the absence of genetic recombination, these mutations may then fix simultaneously. The time for this process declines sharply with increasing population size, and it eventually comes to dominate evolutionary behavior. Here we develop an analytic expression for Ncrit, the critical population size that defines the boundary between these regimes, which shows that both are likely to operate in nature. Frequent recombination may disrupt high-fitness escape genotypes produced in populations larger than Ncrit before they reach fixation, defining a third regime whose rate again slows with increasing population size. We develop a novel expression for this critical recombination rate, which shows that in large populations the simultaneous fixation of mutations that are beneficial only jointly is unlikely to be disrupted by genetic recombination if their map distance is on the order of the size of single genes. Thus, counterintuitively, mass selection alone offers a biologically realistic resolution to the problem of evolutionary escape from local fitness peaks in natural populations. [source] Analyzing Bank Filtration by Deconvoluting Time Series of Electric ConductivityGROUND WATER, Issue 3 2007Olaf A. Cirpka Knowing the travel-time distributions from infiltrating rivers to pumping wells is important in the management of alluvial aquifers. Commonly, travel-time distributions are determined by releasing a tracer pulse into the river and measuring the breakthrough curve in the wells. As an alternative, one may measure signals of a time-varying natural tracer in the river and in adjacent wells and infer the travel-time distributions by deconvolution. Traditionally this is done by fitting a parametric function such as the solution of the one-dimensional advection-dispersion equation to the data. By choosing a certain parameterization, it is impossible to determine features of the travel-time distribution that do not follow the general shape of the parameterization, i.e., multiple peaks. We present a method to determine travel-time distributions by nonparametric deconvolution of electric-conductivity time series. Smoothness of the inferred transfer function is achieved by a geostatistical approach, in which the transfer function is assumed as a second-order intrinsic random time variable. Nonnegativity is enforced by the method of Lagrange multipliers. We present an approach to directly compute the best nonnegative estimate and to generate sets of plausible solutions. We show how the smoothness of the transfer function can be estimated from the data. The approach is applied to electric-conductivity measurements taken at River Thur, Switzerland, and five wells in the adjacent aquifer, but the method can also be applied to other time-varying natural tracers such as temperature. At our field site, electric-conductivity fluctuations appear to be an excellent natural tracer. [source] Cyst Distribution and Hatching Pattern of Chirocephalus ruffoi (Crustacea, Anostraca) in an Experimental Undisturbed PoolINTERNATIONAL REVIEW OF HYDROBIOLOGY, Issue 3 2005Graziella Mura Abstract The pattern of cyst distribution in the absence of turbation and their hatching behaviour were studied in an outdoor artificial pool, where just differentiated adults of the anostracan Chirocephalus ruffoi (sex ratio 1:3) lived until it dried up. The horizontal and vertical distributions of cysts in the pool bed were determined. The comparison between cyst bank estimate (Mura, 2004) and the actual number of cysts counted in the pool bed revealed an estimate error of 20.9%. Resting eggs occurred only in the upper 2.5 cm thick soil sections and decreased within this section as depth increased. Peripheral areas of the pool contained significantly larger numbers of cysts than the central area. Multiway analysis on the results recorded in hatching success (nested ANOVA) revealed that the differences were significantly affected by initial soil conditions, treatment and vertical distribution of cysts. Among these factors, vertical distribution (sections nested in cores) was the most influential. Hatching success was significantly inversely related to depth. Differences in the timing of hatching depending on the above considered factors were also noted. A nearly synchronous hatching pattern was observed only for cysts from initially dry sediment of the uppermost layers. In all successively deeper layers, hatching showed multiple peaks and was increasingly delayed and erratic (already mentioned). ANCOVA within each of the experimental conditions revealed significant differences in hatching frequencies (time as covariate) depending on sediment depth. Within any given layer, ANCOVA revealed a significant influence of initial sediment conditions and treatment on the timing of hatching. (© 2005 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim) [source] Implications of mitochondrial DNA polyphyly in two ecologically undifferentiated but morphologically distinct migratory birds, the masked and white-browed woodswallows Artamus spp. of inland AustraliaJOURNAL OF AVIAN BIOLOGY, Issue 6 2006Leo Joseph The white-browed woodswallow Artamus superciliosus and masked woodswallow A. personatus (Passeriformes: Artamidae) are members of Australia's diverse arid- and semi-arid zone avifauna. Widely sympatric and among Australia's relatively few obligate long-distance temperate-tropical migrants, the two are well differentiated morphologically but not ecologically and vocally. They are pair breeders unlike other Artamus species, which are at least facultative cooperative breeders. For these reasons they are an excellent case in which to use molecular data in integrative study of their evolution from ecological and biogeographical perspectives. We used mitochondrial DNA (mtDNA) to test whether they are each other's closest relatives, whether they evolved migration independently, whether they have molecular signatures of population expansions like some other Australian arid zone birds, and to estimate the timing of any inferred population expansions. Their mtDNAs are monophyletic with respect to other species of Artamus but polyphyletic with respect to each other. The two species appear not to have evolved migration independently of each other but their morphological and mtDNA evolution have been strongly decoupled. Some level of hybridization and introgression cannot be dismissed outright as being involved in their mtDNA polyphyly but incomplete sorting of their most recent common ancestor's mtDNA is a simpler explanation consistent with their ecology. Bayesian phylogenetic inference and analyses of diversity within the two species (n=77) with conventional diversity statistics, statistical parsimony, and tests for population expansion vs stability (Tajima's D, Fu's Fs and Ramos-Onsin and Rozas's R2) all favour recent population increases. However, a non-starlike network suggests expansion(s) relatively early in the Pleistocene. Repeated population bottlenecks corresponding with multiple peaks of Pleistocene aridity could explain our findings, which add a new dimension to accruing data on the effects of Pleistocene aridity on the Australian biota. [source] Dynamics of experimental production of Thelohanellus hovorkai (Myxozoa: Myxosporea) in fish and oligochaete alternate hostsJOURNAL OF FISH DISEASES, Issue 10 2003Y S Liyanage Abstract The dynamics of development and production of Thelohanellus hovorkai (Myxozoa) were examined to investigate factors inducing haemorrhagic thelohanellosis in carp, Cyprinus carpio L. Fresh actinospores of T. hovorkai were harvested from the oligochaete alternate host, Branchiura sowerbyi, and used for infection experiments with myxosporean-free carp. Visualization of actinospores by fluorescent labelling revealed that sporoplasms penetrated the gill filaments of carp immersed in an actinospore suspension as early as 30 min post-exposure (PE). Plasmodia of T. hovorkai developed in the connective tissues of various organs and matured 3,5 weeks PE; dispersion of myxospores from degenerate plasmodia occurred 5,7 weeks PE. Challenges with a high dose of actinospores (4.5 × 106 spores per fish) resulted in the onset of disease, which was more easily achieved by the oral intubation of actinospores than by immersion in an actinospore suspension. Actinosporean-free B. sowerbyi were exposed to different densities of myxospores (104,106 spores per oligochaete) and subsequently reared at different temperatures (15, 20, 25 °C). At 20 and 25 °C, actinospore releases were first detected 40,43 days PE, with multiple peaks of release (max. 7 × 105 actinospores day,1) during the next 60 days. We concluded that the developmental cycle of T. hovorkai was completed within 3,5 months at 20,25 °C, and that the ingestion of large numbers of actinospores orally, possibly by feeding on infected oligochaetes, resulted in a disease condition in carp. [source] Variability in red supergiant stars: pulsations, long secondary periods and convection noiseMONTHLY NOTICES OF THE ROYAL ASTRONOMICAL SOCIETY, Issue 4 2006L. L. Kiss ABSTRACT We study the brightness variations of galactic red supergiant stars using long-term visual light curves collected by the American Association of Variable Star Observers over the last century. The full sample contains 48 red semiregular or irregular variable stars, with a mean time-span of observations of 61 yr. We determine periods and period variability from analyses of power density spectra and time,frequency distributions. We find two significant periods in 18 stars. Most of these periods fall into two distinct groups, ranging from a few hundred to a few thousand days. Theoretical models imply fundamental, first and possibly second overtone mode pulsations for the shorter periods. Periods greater than 1000 d form a parallel period,luminosity relation that is similar to the long secondary periods of the asymptotic giant branch stars. A number of individual power spectra shows a single mode resolved into multiple peaks under a Lorentzian envelope, which we interpret as evidence for stochastic oscillations, presumably caused by the interplay of convection and pulsations. We find a strong 1/f noise component in the power spectra that is remarkably similar in almost all stars of the sample. This behaviour fits the picture of irregular photometric variability caused by large convection cells, analogous to the granulation background seen in the Sun. [source] Optical gravitational lensing experiment: OGLE-1999-BUL-19 , the first multipeak parallax eventMONTHLY NOTICES OF THE ROYAL ASTRONOMICAL SOCIETY, Issue 2 2002Martin C. Smith Abstract We describe a highly unusual microlensing event, OGLE-1999-BUL-19. Unlike most standard microlensing events, this event exhibits multiple peaks in its light curve. The Einstein radius crossing time for this event is approximately 1 yr, which is unusually long. We show that the additional peaks in the light curve can be caused by the very small value for the relative transverse velocity of the lens projected on to the observer plane (). Since this value is significantly less than the speed of the orbit of the Earth around the Sun (v,, 30km s,1), the motion of the Earth induces these multiple peaks in the light curve. This value for is the lowest velocity so far published and we believe that this is the first multiple-peak parallax event ever observed. We also found that the event can be somewhat better fitted by a rotating binary-source model, although this is to be expected since every parallax microlensing event can be exactly reproduced by a suitable binary-source model. A face-on rotating binary-lens model was also identified, but this provides a significantly worse fit. We conclude that the most likely cause for this multipeak behaviour is parallax microlensing rather than microlensing by a binary source. However, this event may be exhibiting a slight binary-source signature in addition to these parallax-induced multiple peaks. With spectroscopic observations it is possible to test this ,parallax plus binary-source' hypothesis and (in the instance that the hypothesis turns out to be correct) to simultaneously fit both models and obtain a measurement of the lens mass. Furthermore, spectroscopic observations could also supply information regarding the lens properties, possibly providing another avenue for determining the lens mass. We also investigated the nature of the blending for this event, and found that the majority of the I -band blending is contributed by a source roughly aligned with the lensed source. This implies that most of the I -band blending is caused by light from the lens or a binary companion to the source. However, in the V band, there appears to be a second blended source 0.35 arcsec away from the lensed source. Hubble Space Telescope observations will be very useful for understanding the nature of the blends. We also suggest that a radial velocity survey of all parallax events will be very useful for further constraining the lensing kinematics and understanding the origins of these events and the excess of long events toward the bulge. [source] Solid-phase synthesis and characterization of N -methyl-rich peptidesCHEMICAL BIOLOGY & DRUG DESIGN, Issue 2 2005M. Teixidó Abstract:, A library of peptides required for a project investigating the factors relevant for blood,brain barrier transport was synthesized on solid phase. As a result of the high N -methylamino acid content in the peptides, their syntheses were challenging and form the basis of the work presented here. The coupling of protected N -methylamino acids with N -methylamino acids generally occurs in low yield. (7-azabenzotriazol-1-yloxy)-tris(pyrrolidino)phosphonium hexafluorophosphate (PyAOP) or PyBOP/1-hydroxy-7-azabenzotriazole (HOAt), are the most promising coupling reagents for these couplings. When a peptide contains an acetylated N -methylamino acid at the N-terminal position, loss of Ac- N -methylamino acid occurs during trifluoroacetic acid (TFA) cleavage of the peptide from the resin. Other side reactions resulting from acidic cleavage are described here, including fragmentation between consecutive N -methylamino acids and formation of diketopiperazines (DKPs). The time of cleavage is shown to greatly influence synthetic results. Finally, high-performance liquid chromatography (HPLC) profiles of N -methyl-rich peptides show multiple peaks because of slow conversion between conformers. [source] | ||||||||||