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Purpose: This study will use Monte Carlo to simulate the Cyberknife system, and intend to develop the third-party tool to evaluate the dose verification of specific patient plans in TPS. Methods: By simulating the treatment head using the BEAMnrc and DOSXYZnrc software, the comparison between the calculated and measured data will be done to determine the beam parameters. The dose distribution calculated in the Raytracing, Monte Carlo algorithms of TPS (Multiplan Ver4.0.2) and in-house Monte Carlo simulation method for 30 patient plans, which included 10 head, lung and liver cases in each, were analyzed. The γ analysis with the combined 3mm/3% criteria would be introduced to quantitatively evaluate the difference of the accuracy between three algorithms. Results: More than 90% of the global error points were less than 2% for the comparison of the PDD and OAR curves after determining the mean energy and FWHM.The relative ideal Monte Carlo beam model had been established. Based on the quantitative evaluation of dose accuracy for three algorithms, the results of γ analysis shows that the passing rates (84.88±9.67% for head,98.83±1.05% for liver,98.26±1.87% for lung) of PTV in 30 plans between Monte Carlo simulation and TPS Monte Carlo algorithms were good. And the passing rates (95.93±3.12%,99.84±0.33% in each) of PTV in head and liver plans between Monte Carlo simulation and TPS Ray-tracing algorithms were also good. But the difference of DVHs in lung plans between Monte Carlo simulation and Ray-tracing algorithms was obvious, and the passing rate (51.263±38.964%) of γ criteria was not good. It is feasible that Monte Carlo simulation was used for verifying the dose distribution of patient plans. Conclusion: Monte Carlo simulation algorithm developed in the CyberKnife system of this study can be used as a reference tool for the third-party tool, which plays an important role in dose verification of patient plans. This work was supported in part by the grant from Chinese Natural Science Foundation (Grant No. 11275105). Thanks for the support from Accuray Corp.

We report the characterization of 12 polymorphic microsatellite markers in the biotrophic fungus Puccinia triticina , the causal agent of leaf rust on wheat. An enrichment protocol was used to isolate microsatellite loci and polymorphism was explored with 15 European isolates. Significant level of cross-amplification (44% of the loci) was found in P. striiformis .

We report the characterization of 12 microsatellite markers in the biotrophic fungus Puccinia striiformis f.sp. tritici , responsible for yellow rust on wheat. An enrichment protocol was used to isolate microsatellite loci, and polymorphism was explored with 96 isolates from natural populations collected from several French and Chinese locations. Eight primers (67%) showed cross-amplification when tested with eight isolates of P. triticina .

GIS system of forest fire alarm” whose basic units are the fire detectors dispersedly installed in the forest communicates wirelessly, and sends the forest fire alarm to command center through the Internet, and the core of the command center is the electronic map and its controlling strategy design. Combining with system functions, this paper introduced detector encoding, information format and related transmission, discussed the structure, elements, data of the electronic map and its drawing algorithm, and the simulation of the electronic map is realized.

Objectives Ketoconazole is extensively used as an index inhibitor of cytochrome P450-3A (CYP3A) activity in vitro and in vivo, but the mechanism of ketoconazole inhibition of CYP3A still is not clearly established. Methods Inhibition of metabolite formation by ketoconazole (seven concentrations from 0.01 to 1.0 µm) was studied in human liver microsomes (n = 4) at six to seven substrate concentrations for triazolam, midazolam, and testosterone, and at two substrate concentrations for nifedipine. Key findings Analysis of multiple data points per liver sample based on a mixed competitive–noncompetitive model yielded mean inhibition constant Ki values in the range of 0.011 to 0.045 µm. Ketoconazole IC50 increased at higher substrate concentrations, thereby excluding pure noncompetitive inhibition. For triazolam, testosterone, and midazolam α-hydroxylation, mean values of α (indicating the ‘mix’ of competitive and noncompetitive inhibition) ranged from 2.1 to 6.3. However, inhibition of midazolam 4-hydroxylation was consistent with a competitive process. Determination of Ki and α based on the relation between 50% inhibitory concentration values and substrate concentration yielded similar values. Pre-incubation of ketoconazole with microsomes before addition of substrate did not enhance inhibition, whereas inhibition by troleandomycin was significantly enhanced by pre-incubation. Conclusions Ketoconazole inhibition of triazolam α- and 4-hydroxylation, midazolam α-hydroxylation, testosterone 6β-hydroxylation, and nifedipine oxidation appeared to be a mixed competitive–noncompetitive process, with the noncompetitive component being dominant but not exclusive. Quantitative estimates of Ki were in the low nanomolar range for all four substrates.

Treatment of methyl halodifluoroacetates, XCF2CO2Me (X = Cl, Br, I), with organic halidesRY in the presence of KF and CuI at an appropriate temperature in DMF gave thecorresponding trifluoromethylated derivatives, RCF3, in moderate to high yields. A processinvolving difluorocarbene and trifluoromethide intermediates is suggested.

The mass accommodation coefficient (α) for acetone on water has been measured as a function of temperature in the range 260-285 K. The experimental method employs a monodispersed train of fast-moving droplets (80-230 μm in diameter) in a low-pressure flow reactor. Droplet-trace gas interaction times are on the order of a few milliseconds. The mass accommodation coefficient has a negative temperature dependence and decreases from 0.066 to 0.013 over the above range. As with the previously studied alcohols, α can be expressed in terms of an observed Gibbs free energy as α/(1-α)=exp(-ΔG o bs /RT), with ΔH obs =-12.7 kcal/mol and ΔS obs =-53.6 eu

CF3l was synthesized in high yields by treatment of XCF2CO2Me(X = Cl or Br) with iodine in the presence of potassium fluoride and copper iodide; if Kl was used instead of KF under similar conditions, CF2l2 was obtained in moderate yields.

Treatment of aryl chlorides containing electron-withdrawing groups with methyl fluorosulfonyl difluoroacetate or methyl halodifluoroacetate in the presence of potassium fluoride and copper iodide gave the corresponding trifluoromethyl derivatives in moderate to high yields.

Treatment of methyl halodifluoroacetates, XCF2CO2Me (X = Cl, Br, I), with organic halidesRY in the presence of KF and CuI at an appropriate temperature in DMF gave thecorresponding trifluoromethylated derivatives, RCF3, in moderate to high yields. A processinvolving difluorocarbene and trifluoromethide intermediates is suggested.

Graphene nanoribbon (GNR) is a quasi one-dimensional film, in which a bandgap exists through the quantum confinement and/or localization effect. Compared to bulk graphene, GNR has high potential in achieving high I on /I off ratio. The carrier mobility of GNR, however, exhibits strong degradation because of the uncontrollable edge roughness and/or states. Most reported GNR-FETs are patterned using ebeam-lithography processes, where the spot size of the electron beam limits the edge smoothness1. In this work, we present a GNR fabrication method based on a nanowire-mask, where the edge roughness is determined by the surface roughness of the nanowire ( hole ∼1180cm2/(Vs), I on /I off >7 and low frequency noise figure A∼10−6 at 300K. Moreover, short-channel SLR (∼250nm) shows conductance quantization at 77K3, and confirms that the quasi-ballistic transport properties can be achieved through this method.

International audience; Puccinia striiformis f.sp. tritici (PST), a basidiomycota responsible for wheat yellow rust, has a strict clonal behavior and a low genetic diversity in European and Australian populations. On the other hand high diversity has been reported in Chinese populations. Moreover it is thought that in China yellow rust epidemics start recurrently from the western highlands where over-summering occurs. To compare PST genetic diversity in this area to the one described in France seven AFLP primer combinations were used to analyze a sample of 160 isolates collected in 2001 in five counties of Gansu Province. The AFLP data revealed 40 polymorphic bands, discriminating 139 AFLP genotypes. Linkage disequilibrium and phylogeographic analyses support the hypothesis of a reproductive mode that is not strictly clonal. In this regard Chinese isolates from Gansu strongly contrast with the European studies using the same markers. Genetic diversity of this 1 y sampling in Gansu is found to be seven times higher than the one observed in France over 20 y and exhibits lower linkage disequilibrium. The effective population size of the French sample was estimated to be 1000 times smaller than the Gansu population. These results support the hypothesis of large population size as well as the occurrence of genetic recombination, while the importance of Gansu as a main over-summering area requires assessment through larger scale studies.

A series of uptake studies have been completed for the gas phase carbonyl halides CCl2O and CF2O and the haloacetyl halides CCl3CClO, CF3CFO and CF3CClO which are oxidation intermediates of volatile fluorocarbon, chlorocarbon and hydrofluorocarbon (HCFC) species in the atmosphere. The experimental apparatus in these studies employs a fast moving monodispersed train of droplets (50 to 200 μm in diameter) passed through a low pressure flow reactor. Experiments were done as a function of droplet pH and gas/droplet interaction time. The measured uptake coefficients (γ) for all these molecules are less than our experimental detection limit of 5 × 10−4 for pH 7 droplets at 300 K. From the results of the measurements and other available data, the uptake coefficients for these species are estimated to be 10−6 < γ < 10−4. The lower limit is sufficiently large so that the tropospheric removal rate of the species is not expected to affect the ozone depletion potential values of the HCFC parent species for CF2O, CF3CFO and CF3CClO. However with such uncertainty it is not possible to determine the partitioning of the ocean/land deposition of the species.

The uptake of gas-phase formaldehyde and acetaldehyde by water droplets was measured along with mass accomodation coefficients. Formaldehyde uptake is predictable, but that of acetaldehyde as short gas-droplet contact times is greater than predicted due to a chemisorbed surface complex at the gas-water interface that may explain the high measured concentration of acetaldehyde in clouds relative to formaldehyde. The small uptake coefficients suggest that this may be the limiting factor in aldehyde uptake into clouds. 36 refs., 10 figs., 3 tabs.

Cowpea (Vigna unguiculata [L.] Walp. ‘California Blackeye') plants were grown at seven rates of phosphorus (P) fertilization: 0.0 to 3.6 mM P provided weekly. When plants were eight weeks old, stomatal conductance (Cs) was measured before and after lowering soil water potential to ‐1.0 MPa with a sorbitol solution. Prestress Cs was between 4 and 5 mm/s in 0.0 to 2.4 P plants and varied between 5 and 7 mm/s in 3.0 and 3.6 P plants. Declines in Cs were similar after lowering of soil water potential in plants of all treatments except 0.6 P, which tended to have lower Cs.

In optical burst switching (OBS) networks, the data channel scheduling algorithm is one of the most important issues, which have a great impact on network performances. Currently, there are various data channel scheduling algorithms. Among them, the rescheduling algorithm is more attractive because it could adaptively reallocate the data channels even when they have been occupied by some data bursts (DB), and release some channel resource for the latter DB in most situations. However when the traffic load is heavy, it is not effective any more, and would worsen network performance. Therefore, this paper proposes a new rescheduling algorithm, namely VB-Rescheduling algorithm. According to the state of the data channels, it reschedules data blocks on demand by three granularities (i.e., virtual burst, child-burst cluster and normal burst). Compared with other rescheduling algorithms, it has some advantages as follows. Firstly, it could keep the same sequence of the arriving data bursts at a node as the corresponding control packets. Secondly, it is more flexible to reschedule data blocks. Finally, simulation results show that it can greatly improve OBS network performance in terms of the overall packet loss probability and the link utilization, compared with traditional OBS rescheduling algorithm (whose rescheduling granularity is normal burst) and the native virtual burst scheduling scheme.

A model for the nonreactive uptake of gas molecules by liquids is described. The model uses the concept that the interface is a narrow region of a dense gaslike state within which nucleation is continually occurring. In this region, clusters that are formed in a critical size grow by condensation and merge with the nearby bulk liquid. The incoming gas molecule participates in this nucleation process. If this molecule becomes part of a critical-sized cluster, then it will be incorporated into the bulk liquid via condensation growth. A quantitative formulation of this model leads to an expression for the mass accommodation coefficient on water that is in agreement with experimental measurements.

It is now recognized that many important atmospheric reactions occur inside aqueous droplets of clouds and fogs. Recognition of the importance of these heterogeneous processes has stimulated an increasing amount of research in this area and a growing understanding about the nature of heterogeneous processes. Mass accommodation coefficients ({alpha}) have been measured as a function of temperature in the range 260-291 K for methanol, ethanol, 1-propanol, 2-propanol, 2-methyl-2-propanol, ethylene glycol, chloroethanol, bromoethanol, iodoethanol, formic acid, and acetic acid. The experimental method employs a monodispersed train of droplets ({le}230 {mu}m in diameter) in a low-pressure flow reactor. Droplet-trace gas interaction times are in the range (2-10) x 10{sup {minus}3} s. All mass accommodation coefficients show a negative temperature dependence and can be well expressed in terms of an observed Gibbs free energy as {alpha}/(1{minus}{alpha}) = exp({minus}{Delta}G{sub obs}/RT). Of the species studied, iodoethanol has the largest mass accommodation coefficient; for this molecule {alpha} ranges from about 0.04 at 290 K to 0.2 at 260 K. 1-Propanol has the smallest {alpha}; it ranges from about 0.01 at 290 K to 0.07 at 260 K. The results show systematic trends. Most notably, when {Delta}G{sub obs} is expressed as {Delta}G{sub obs} = {Delta}H{sub obs} {minus}more » T{Delta}S{sub obs}, is observed that the magnitudes of both {Delta}H{sub obs} and {Delta}S{sub obs} correlate and increase in the sequence diols < acids < haloethanols < alkyl alcohols. The results have led to the development of a model for the uptake of gas-phase molecules by liquids.« less

Human serum albumin, HSA, was immobilized onto the surface of silica-based magnetic beads. The beads were used to isolate known HSA ligands from a mixture containing ligands and nonligands. The separation was accomplished manually and was also automated. The results indicate that an automated "ligand-fishing" technique can be developed using magnetic beads containing an immobilized protein.

This paper reviews current status of silicon microphotonics and the recent prototype of on-chip optical interconnection. Si microphotonics pursues complementary metal oxide semiconductor (CMOS)-compatibility of photonic devices to reduce the materials diversity eventually to integrate on Si chips. Fractal optical H-trees have been implemented on a chip and found to be a technology breakthrough beyond metal interconnection. It has shown that large RC time constants associated with metal can be eliminated at least long distant data communication on a chip, and eventually improve yield and power issues. This has become the world's first electronic and photonic integrated circuits (EPICs) and the possibility of at least 10 GHz clocking for personal computers has been demonstrated.

To summarize the radiological and clinical features of radiation-induced external auditory canal carcinomas (RIEACCs) in patients with nasopharyngeal carcinomas (NPCs) after radiation therapy.CT, MRI and clinical features in 16 patients with histologically proven RIEACCs were retrospectively reviewed. There were 2 females and 14 males, with a median age of 52.5 years at the time of diagnosis of RIEACC. Imaging parameters including lesion extent, size, margin, shape, bone destruction, adjacent structure invasion, density/signal intensity, and pattern and degree of enhancement were assessed. Clinical features including clinical staging, histological type, treatment and radiation dose (RD) of primary NPC as well as the histological type, staging of radiation-induced tumour and the latent period between NPC and RIT were recorded.All patients had a single RIEACC. The lesions had a size of 3.5 ± 1.4 cm and were localized (n = 7) or extensive (n = 9). Most of the lesions were partially or ill defined with an irregular shape and had an intermediate density/signal pattern and moderate homogeneous enhancement. The latent period of RIEACCs ranged from 10 to 20 years in nine patients with a RD of 68-70 Gy; from 2 to 10 years in five patients with a RD of 68-74 Gy; and more than 20 years in two patients with a RD of 70 or 72 Gy.An external auditory canal (EAC) mass with homogeneous, intermediate CT density or signal intensity in patients with NPC after radiotherapy is highly suggestive of RIEACC, which should be included in the routine surveillance for patients with NPC after radiotherapy.RIEACCs could occur as short as 2 years after radiotherapy in patients with NPC and have distinct features from otitis media and sarcomas. This EAC malignancy should be included in routine surveillance for patients with NPC after radiotherapy.

Local anesthetics are useful for reducing acute pain, but their short duration precludes them from use in solely managing postoperative pain. To prolong the duration of local anesthesia, we conjugated bupivacaine to native hyaluronan (HA) and divinyl sulfone cross-linked Hylan A (Hylan B particles) using a hydrolyzable linker incorporating an imide. Bupivacaine was prepared for conjugation to HA by forming the acryl imide derivative. Separately, the carboxyl group of HA was reacted with nipsylethylamine (NEA) using carbodiimide-mediated coupling to provide HA-NEA that was subsequently reduced with tris(2-carboxyethylphosphine) hydrochloride to yield HA carrying a free sulfhydryl (HA-SH). The HA-bupivacaine conjugate was assembled by reacting HA-SH with acrylbupivacaine. Characterization of the conjugates showed 22% degree of modification by 1 mol of carboxyl. In vitro release studies comparing bupivacaine admixed in HA with bupivacaine conjugated to HA showed half-lives of 0.4 +/- 0.1 h, and 16.9 +/- 0.2 h, respectively, and the bupivacaine was released chemically unaltered as confirmed by LC-MS. In vivo studies to assess the duration of anesthetic activity were performed in a rat sciatic nerve blockade model. For these studies, bupivacaine was conjugated to Hylan B following a similar procedure, and the degree of modification obtained was 14%. Free bupivacaine (3 and 16 mg/kg) and free bupivacaine (3 mg/kg) admixed with Hylan B particles showed nerve block over 4, 9, and 6 h, respectively. Free bupivacaine (3 mg/kg) admixed with bupivacaine (13 mg/kg) conjugated to Hylan B particles showed a four to 5-fold longer impairment of motor function over the free bupivacaine formulations with a total block time of 19 h. Bupivacaine conjugated to Hylan B particles has the potential to prolong the duration of local anesthesia.

The pregnane X receptor (PXR) is a transcriptional regulator of xenobiotic metabolizing enzymes, including cytochrome P450 3A (CYP3A), and transporters. Pretreatment of mice and rats with inducers of CYP3A increases acetaminophen (APAP) hepatotoxicity. In untreated mice, the amount of hepatic CYP3A11 mRNA is 4-fold greater in PXR(-/-) mice compared to wild-type mice (Guo et al., 2003), a finding anticipated to increase APAP hepatotoxicity in PXR(-/-) mice. We investigated APAP hepatotoxicity in wild-type and PXR(-/-) mice in a C57BL/6 background, with APAP administered by gavage. Despite a 2.5-fold higher level of total hepatic CYP3A protein and a 3.6-fold higher level of CYP3A activity compared to wild-type mice, PXR(-/-) mice were less sensitive to APAP hepatotoxicity. Hepatic levels of CYP2E1 were identical in the two mouse lines, but hepatic CYP1A2 levels were 3-fold greater in wild-type mice compared to PXR(-/-) mice. Caffeine, an inhibitor of CYP1A2 activity and an enhancer of CYP3A activity, decreased APAP hepatotoxicity in wild-type mice. APAP uptake was 1.5-fold greater in wild-type mice compared to PXR(-/-) mice. No significant differences in the formation of APAP glucuronide and sulfate-conjugated metabolites were observed between wild-type and PXR(-/-) mice. Glutathione levels were similar in the two mouse lines and were transiently decreased to similar amounts after APAP administration. Our finding that APAP hepatotoxicity was decreased in PXR(-/-) mice indicates that PXR is an important modulator of APAP hepatotoxicity, through positive modulation of constitutive CYP1A2 expression and possibly through increased APAP absorption.

The pregnane X receptor (PXR) is a transcriptional regulator of xenobiotic metabolizing enzymes, including cytochrome P450 3A (CYP3A), and transporters. Pretreatment of mice and rats with inducers of CYP3A increases acetaminophen (APAP) hepatotoxicity. In untreated mice, the amount of hepatic CYP3A11 mRNA is 4-fold greater in PXR(-/-) mice compared to wild-type mice (Guo et al., 2003), a finding anticipated to increase APAP hepatotoxicity in PXR(-/-) mice. We investigated APAP hepatotoxicity in wild-type and PXR(-/-) mice in a C57BL/6 background, with APAP administered by gavage. Despite a 2.5-fold higher level of total hepatic CYP3A protein and a 3.6-fold higher level of CYP3A activity compared to wild-type mice, PXR(-/-) mice were less sensitive to APAP hepatotoxicity. Hepatic levels of CYP2E1 were identical in the two mouse lines, but hepatic CYP1A2 levels were 3-fold greater in wild-type mice compared to PXR(-/-) mice. Caffeine, an inhibitor of CYP1A2 activity and an enhancer of CYP3A activity, decreased APAP hepatotoxicity in wild-type mice. APAP uptake was 1.5-fold greater in wild-type mice compared to PXR(-/-) mice. No significant differences in the formation of APAP glucuronide and sulfate-conjugated metabolites were observed between wild-type and PXR(-/-) mice. Glutathione levels were similar in the two mouse lines and were transiently decreased to similar amounts after APAP administration. Our finding that APAP hepatotoxicity was decreased in PXR(-/-) mice indicates that PXR is an important modulator of APAP hepatotoxicity, through positive modulation of constitutive CYP1A2 expression and possibly through increased APAP absorption.

Acute bronchitis is one of the most common diagnoses made by primary-care physicians. It is traditionally treated with antibiotics, (although the evidence for their effectiveness is weak and modest at best), and other even less effective treatments. Chinese medicinal herbs have been also used as treatment.This review aims to summarise the existing evidence on the comparative effectiveness and safety of Chinese medicinal herbs for treating uncomplicated acute bronchitis.We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library Issue 1, 2005), which includes the Cochrane Acute Respiratory Infections Group's specialised register; The Chinese Cochrane Centre's Controlled Trials Register (up to December 2004); MEDLINE (1966 to March Week 1, 2005); EMBASE (1988 to December 2004); and the Chinese Biomedical Database (CBM) (1980 to December 2004).Randomised controlled trials comparing Chinese medicinal herbs with placebo, antibiotics or other Western medicines for the treatment of uncomplicated acute bronchitis.At least two authors extracted data and assessed trial quality.Four trials reported the time to improvement of cough, fever, and rales associated with bronchitis and showed that patients treated with Chinese herbs had a shorter duration of signs and symptoms. Two trials reported the proportion of patients with improved signs and symptoms at follow up and showed that Chinese herbs were beneficial in terms of relief of signs and symptoms. Thirteen trials analysed the data on physician global assessment of improvement at follow up. Nine of thirteen trials showed that Chinese herbs were superior to routine treatment and the other four trials showed a similar effect to routine treatment. In general, Chinese herbs appeared beneficial. Only one trial reported on adverse effects during treatment.There is insufficient quality data to recommend the routine use of Chinese herbs for acute bronchitis. The benefit found in this systematic review could be due to publication bias and study-design limitations of the individual studies. In addition, the safety of Chinese herbs is unknown due to the lack of toxicological evidence on these Chinese herbs, though adverse events are rarely reported. Chinese herbs should be used carefully.

Puccinia striiformis f. sp. tritici (PST), a clonal basidiomycete causing yellow rust disease on wheat, has a long record of 'overcoming' cultivar resistance introduced by breeders. Despite the long dispersal capacity of its spores, the French population of PST presents a strong geographical structure, with the presence of a specific pathotype (array of avirulence genes) at high frequencies in the south of France. The genetic diversity underlying this differentiation was analysed by microsatellite and AFLP markers. A total of 213 French isolates belonging to 10 pathotypes collected over a 15-year period were investigated. For each of the 12 microsatellites used, polymorphism resulted from a unique allelic variant associated to the south-specific pathotype. This pathotype was characterized by 40 specific markers over the total of 63 polymorphins detected using 15 AFLP primer combinations. Phylogeographical analysis indicated a strictly clonal structure of the population, and a strong genomic divergence between the northern population and a south-specific clone. Both virulence and molecular data show that the northern French population belongs to the northwestern European population, whereas the southern clone is most likely related to a Mediterranean population, the two subpopulations resulting from the ancient divergence of two clonal lineages. While the virulence complexity in the northern population may be explained by the successive introduction of corresponding resistance genes in cultivars, the maintenance of a simple virulence type in southern France, despite gene flow between the two populations, may be explained in terms of host cultivars repartition and local adaptation to specific host or climatic conditions.

Fully depleted MOSFETs were fabricated on strained Si/strained SiGe (46% Ge)/strained Si heterostructures on insulator (HOI) for the first time, demonstrating both high electron and hole mobility enhancements while maintaining excellent subthreshold characteristics. The total thickness of the heterostructure on insulator is less than 25 nm. At an inversion charge density of 1.5/spl times/10/sup 13/ cm/sup -2/, mobility enhancements of 90% and 107% are obtained for electrons and holes respectively. The mobility increases as the cap thickness is reduced to 2 nm. HOI offers superior hole mobility than 40% strained silicon directly on insulator at all vertical fields, when the cap thickness is below 5 nm.

The effect of atazanavir on P-glycoprotein (P-gp) expression and activity, as well as its inhibitory potency against CYP3A activity, was evaluated in vitro. Induction of P-gp activity and expression was studied using LS180V cells. P-gp inhibition was studied using both LS180V cells and Caco-2 cells. P-gp activity was assessed by measuring P-gp-mediated rhodamine 123 (Rh123) transport, and P-gp expression was determined using SDS-polyacrylamide gel electrophoresis/Western blot analysis. CYP3A inhibition was tested using triazolam hydroxylation in human liver microsomes (HLM). Extended (3-day) exposure of LS180V cells to 30 microM atazanavir caused a 2.5-fold increase in immunoreactive P-gp expression as well as a concentration-dependent decrease of intracellular Rh123 to a mean 45% (S.D. 5.2%) of control. Acute exposure (2 h) of LS180V cells to atazanavir increased intracellular Rh123 concentrations up to 300% of control at 100 microM atazanavir. At 30 microM and above, acute atazanavir exposure reversed P-gp induction caused by 3-day pretreatment with 10 microM ritonavir. P-gp inhibition was also observed in Caco-2 cells, causing an effect comparable to that observed for the known P-gp inhibitor verapamil (50% of control). In HLM, atazanavir was an inhibitor of triazolam hydroxylation, with inhibitory potency greatly increased by preincubation. IC50 values with and without preincubation were 0.31 microM (S.D. 0.13) and 5.7 microM (S.D. 4.1), respectively. Thus, atazanavir is an inhibitor and inducer of P-gp as well as a potent inhibitor of CYP3A in vitro, suggesting a potential for atazanavir to cause drug-drug interactions in vivo.

The potential of the application of rapid heating to the final annealing of non-oriented steels is explored experimentally. The specific total loss and the permeability decrease with increasing final temperature. Increasing the heating rate is the only way to both reduce the loss and increase the permeability. A loss reduction of 10% and a permeability increase of 25% can be achieved when using high heating rates, without damaging the mechanical properties.

Based on the unique characteristic of spectral line center in the whole spectrum and noise threshold, a computer approach and program for the determination of spectral line position and relative intensity automatically are presented in this paper. Exploring this approach and computer program, we pre-analyzed the partially overlapped 16 line TuFIR experiment spectra of CHF3. The results of line positions and intensities for these TuFIR spectra are in excellent agreement with the results by least-square fit with heavily manual inference. The accuracy and efficiency of this method and program will ensure their wide application in complex high-resolution molecular spectrum.