Pharmacokinetics of sifuvirtide, a novel anti-HIV-1 peptide, in monkeys and its inhibitory concentration in vitro

Aim: To study the pharmacokinetics of sifuvirtide, a novel anti-human immunodeficiency virus (HIV) peptide, in monkeys and to compare the inhibitory concentrations of sifuvirtide and enfuvirtide on HIV-1-infected-cell fusion. Methods: Monkeys received 1.2 mg/kg iv or sc of sifuvirtide. An on-line solid-phase extraction procedure combined with liquid chromatography tandem mass spectrometry (SPELC/MS/MS) was established and applied to determine the concentration of sifuvirtide in monkey plasma. A four-I-127 iodinated peptide was used as an internal standard. Fifty percent inhibitory concentration (IC50) of sifuvirtide on cell fusion was determined by co-cultivation assay. Results: The assay was validated with good precision and accuracy. The calibration curve for sifuvirtide in plasma was linear over a range of 4.88-5000 mu g/L, with correlation coefficients above 0.9923. After iv or sc administration, the observed peak concentrations of sifuvirtide were 10626 +/- 2886 mu g/L and 528 +/- 191 mu g/L, and the terminal elimination half-lives (T,12) were 6.3 +/- 0.9 h and 5.5 +/- 1.0 h, respectively. After sc, T-max was 0.25-2 h, and the absolute bioavailability was 49% +/- 13%. Sifuvirtide inhibited the syncytium formation between HIV-1 chronically infected cells and uninfected cells with an IC50 of 0.33 mu g/L. Conclusion: An on-line SPE-LC/MS/MS approach was established for peptide pharmacokinetic studies. Sifuvirtide was rapidly absorbed subcutaneously into the blood circulation. The T-1/2 of sifuvirtide was remarkably longer than that of its analog, enfuvirtide, reported in healthy monkeys and it conferred a long-term plasma concentration level which was higher than its IC50 in vitro.

Effects of irradiation on formaldehyde concentration and nutritional changes of formalin treated fish, Pampus chinensis

Formaldehyde is a very reactive compound capable of interacting with many functional groups of proteins including intermolecular and intramolecular cross-links of the molecules. The formation of cross-linking bonds may induce conformational change in proteins that favor further interaction of functional and hydrophobic groups. Formaldehyde which has been using illegally as a chemical preservative by some fish traders in our country. A study was carried out to determine the effects of irradiation (1.5 KGy) on formaldehyde concentration and nutritional (protein and lipid) changes of formalin (37% formaldehyde) treated fish (fresh) samples and found that the concentration of formaldehyde both in treated samples (0.37% formalin and 0.37% formalin with 1.5 KGy irradiation) were 37.0 µg/gm and 36.75 µg/gm. On the other hand, the amount of protein and lipid in treated samples before radiation (14.56% and 3.49%) and after radiation (14.15% and 3.25%). That means, radiation has no effect on the change of protein, lipid and formaldehyde.

Natural selection on EPAS1 (HIF2 alpha) associated with low hemoglobin concentration in Tibetan highlanders

By impairing both function and survival, the severe reduction in oxygen availability associated with high-altitude environments is likely to act as an agent of natural selection. We used genomic and candidate gene approaches to search for evidence of such genetic selection. First, a genome-wide allelic differentiation scan (GWADS) comparing indigenous highlanders of the Tibetan Plateau (3,200 3,500 m) with closely related lowland Han revealed a genome-wide significant divergence across eight SNPs located near EPAS1. This gene encodes the transcription factor HIF2 alpha, which stimulates production of red blood cells and thus increases the concentration of hemoglobin in blood. Second, in a separate cohort of Tibetans residing at 4,200 m, we identified 31 EPAS1 SNPs in high linkage disequilibrium that correlated significantly with hemoglobin concentration. The sex-adjusted hemoglobin concentration was, on average, 0.8 g/dL lower in the major allele homozygotes compared with the heterozygotes. These findings were replicated in a third cohort of Tibetans residing at 4,300 m. The alleles associating with lower hemoglobin concentrations were correlated with the signal from the GWADS study and were observed at greatly elevated frequencies in the Tibetan cohorts compared with the Han. High hemoglobin concentrations are a cardinal feature of chronic mountain sickness offering one plausible mechanism for selection. Alternatively, as EPAS1 is pleiotropic in its effects, selection may have operated on some other aspect of the phenotype. Whichever of these explanations is correct, the evidence for genetic selection at the EPAS1 locus from the GWADS study is supported by the replicated studies associating function with the allelic variants.

The successful double cryopreservation of rabbit (Oryctolagus cuniculus) semen in large volume using the directional freezing technique with reduced concentration of cryoprotectant

Using directional freezing, Our objective was to cryopreserve rabbit semen and achieve fertility that was equal or higher than that achieved with conventional freezing. The working hypothesis was that controlling the ice-front propagation would allow redu

Effect of bend orientation on life and puncture point location due to solid particle erosion of a high concentration flow in pneumatic conveyors

An investigation into predicting failure of pneumatic conveyor pipe bends due to hard solid particle impact erosion has been carried out on an industrial scale test rig. The bend puncture point locations may vary with many factors. However, bend orientation was suspected of being a main factor due to the biased particle distribution pattern of a high concentration flow. In this paper, puncture point locations have been studied with different pipe bend orientations and geometry (a solids loading ratio of 10 being used for the high concentration flow). Test results confirmed that the puncture point location is indeed most significantly influenced by the bend orientation (especially for a high concentration flow) due to the biased particle distribution and biased particle flux distribution. © 2004 Elsevier B.V. All rights reserved.

Effect of particle concentration on erosion rate of mild steel bends in a pneumatic conveyor

Particle concentration is known as a main factor that affects erosion rate of pipe bends in pneumatic conveyors. With consideration of different bend radii, the effect of particle concentration on weight loss of mild steel bends has been investigated in an industrial scale test rig. Experimental results show that there was a significant reduction of the specific erosion rate for high particle concentrations. This reduction was considered to be as a result of the shielding effect during the particle impacts. An empirical model is given. Also a theoretical study of scaling on the shielding effect, and comparisons with some existing models, are presented. It is found that the reduction in specific erosion rate (relative to particle concentration) has a stronger relationship in conveying pipelines than has been found in the erosion tester. © 2004 Elsevier B.V. All rights reserved.

The distribution and concentration levels of trace metals in water and sediments of Lake Victoria, Kenya

The water and bottom sediments of Lake Victoria (Kenya) were analysed for A1, Fe, Mn, Zn, Pb, Cu, Cr and Cd. The total metal concentrations were determined and their mean variations and distributions discussed. The bottom lake waters showed higher concentration levels than the surface waters. The range of values (in mg/l) in the bottom and surface lake waters were as follows: Surface Waters: A1(0.08 - 3.98), Fe(0.09 - 4.01), Mn(0.02 - 0.10). Zn(0.01 -0.07), Pb(0.001- 0.007), Cu(not detected - 0.006), Cr(not detected - 0.004). Bottom Waters: A1(0.1 0 - 6.59), Fe(0.23 - 9.64), Mn(0.04 - 0.39), Zn(0.01- 0.08), Pb(0.002 - 0.009), Cu(not detected - 0.03). Cr(not detected -0.002). River mouths and shallow areas in the lake showed higher total metal concentrations than offshore deeper areas. Apart from natural metal levels, varied urban activities and wastes greatly contribute to the lake metal pollution as shown by high Pb and Zn levels in sediments, around Kisumu and Homa Bay areas. Other comparatively high values and variations could be attributed to the varied geological characteristics of the lake and its sediments. Compared to the established W.H.O (1984) drinking water standards manganese, aluminium and iron levels were above these limits whereas zinc, lead, chromium, copper and cadmium were below.

Experimental investigation of turbine stator well rim seal, reingestion and interstage seal flows using gas concentration techniques and displacement measurements

Gas turbine engine performance requires effective and reliable internal cooling over the duty cycle of the engine. Life predictions for rotating components subject to the main gas path temperatures are vital. This demands increased precision in the specification of the internal air system flows which provide turbine stator well cooling and sealing. This in turn requires detailed knowledge of the flow rates through rim seals and interstage labyrinth seals. Knowledge of seal movement and clearances at operating temperatures is of great importance when prescribing these flows. A test facility has been developed at the University of Sussex, incorporating a two stage turbine rated at 400 kW with an individual stage pressure ratio of 1.7:1. The mechanical design of the test facility allows internal cooling geometry to be rapidly re-configured, while cooling flow rates of between 0.71 CW, ENT and 1.46 C W, ENT, may be set to allow ingress or egress dominated cavity flows. The main annulus and cavity conditions correspond to in cavity rotational Reynolds numbers of 1.71×106< Reφ <1.93×106. Displacement sensors have been used to establish hot running seal clearances over a range of stator well flow conditions, allowing realistic flow rates to be calculated. Additionally, gas seeding techniques have been developed, where stator well and main annulus flow interactions are evaluated by measuring changes in gas concentration. Experiments have been performed which allow rim seal and re-ingestion flows to be quantified. It will be shown that this work develops the measurement of stator well cooling flows and provides data suitable for the validation of improved thermo-mechanical and CFD codes, beneficial to the engine design process. Copyright © 2011 by Rolls-Royce plc.

Concentration dependence of the Er3+ visible and infrared luminescence in Y2-x Erx O3 thin films on Si

Y2-x Erx O3 thin films, with x varying between 0 and 0.72, have been successfully grown on crystalline silicon (c-Si) substrates by radio-frequency magnetron cosputtering of Y2 O 3 and Er2 O3 targets. As-deposited films are polycrystalline, showing the body-centered cubic structure of Y2 O3, and show only a slight lattice parameter contraction when x is increased, owing to the insertion of Er ions. All the films exhibit intense Er-related optical emission at room temperature both in the visible and infrared regions. By studying the optical properties for different excitation conditions and for different Er contents, all the mechanisms (i.e., cross relaxations, up-conversions, and energy transfers to impurities) responsible for the photoluminescence (PL) emission have been identified, and the existence of two different well-defined Er concentration regimes has been demonstrated. In the low concentration regime (x up to 0.05, Er-doped regime), the visible PL emission reaches its highest intensity, owing to the influence of up-conversions, thus giving the possibility of using Y2-x Er x O3 films as an up-converting layer in the rear of silicon solar cells. However, most of the excited Er ions populate the first two excited levels 4I11/2 and 4I13/2, and above a certain excitation flux a population inversion condition between the former and the latter is achieved, opening the route for the realization of amplifiers at 2.75 μm. Instead, in the high concentration regime (Er-compound regime), an increase in the nonradiative decay rates is observed, owing to the occurrence of cross relaxations or energy transfers to impurities. As a consequence, the PL emission at 1.54 μm becomes the most intense, thus determining possible applications for Y2-x Erx O 3 as an infrared emitting material. © 2009 American Institute of Physics.

Time resolved measurement of cold start hc concentration using the fast FID

Understanding mixture formation phenomena during the first few cycles of an engine cold start is extremely important for achieving the minimum engine-out emission levels at the time when the catalytic converter is not yet operational. Of special importance is the structure of the charge (film, droplets and vapour) which enters the cylinder during this time interval as well as its concentration profile. However, direct experimental studies of the fuel behaviour in the inlet port have so far been less than fully successful due to the brevity of the process and lack of a suitable experimental technique. We present measurements of the hydrocarbon (HC) concentration in the manifold and port of a production SI engine using the Fast Response Flame Ionisation Detector (FRFID). It has been widely reported in the past few years how the FRFID can be used to study the exhaust and in-cylinder HC concentrations with a time resolution of a few degrees of crank angle, and the device has contributed significantly to the understanding of unburned HC emissions. Using the FRFID in the inlet manifold is difficult because of the presence of liquid droplets, and the low and fluctuating pressure levels, which leads to significant changes in the response time of the instrument. However, using recently developed procedures to correct for the errors caused by these effects, the concentration at the sampling point can be reconstructed to align the FRFID signal with actual events in the engine. © 1996 Society of Automotive Engineers, Inc.

Updated correlation between aircraft smoke number and black carbon concentration

Aircraft emissions of black carbon (BC) contribute to anthropogenic climate forcing and degrade air quality. The smoke number (SN) is the current regulatory measure of aircraft particulate matter emissions and quantifies exhaust plume visibility. Several correlations between SN and the exhaust mass concentration of BC (CBC) have been developed, based on measurements relevant to older aircraft engines. These form the basis of the current standard method used to estimate aircraft BC emissions (First Order Approximation version 3 [FOA3]) for the purposes of environmental impact analyses. In this study, BC with a geometric mean diameter (GMD) of 20, 30, and 60 nm and filter diameters of 19 and 35 mm are used to investigate the effect of particle size and sampling variability on SN measurements. For BC with 20 and 30 nm GMD, corresponding to BC emitted by modern aircraft engines, a smaller SN results from a given CBC than is the case for BC with 60 nm GMD, which is more typical of older engines. An updated correlation between CBC and SNthat accounts for typical size of BC emitted by modern aircraft is proposed. An uncertainty of ±25% accounts for variation in GMD in the range 20-30 nm and for the range of filter diameters. The SN-CBC correlation currently used in FOA3 underestimates by a factor of 2.5-3 for SN <15, implying that current estimates of aircraft BC emissions derived from SN are underestimated by the same factor. Copyright © American Association for Aerosol Research.