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• This study reveals, for the first time, the micro-mechanism of deformation of γ″ strengthened superalloys using neutron diffraction. • Inconel 718 samples with different γ″ variant distributions were prepared by different stress ageing heat treatments. • The γ″ variant-sensitive deformation behavior was studied by interpreting the stress-lattice strain curves. • Compressive-aged sample shows larger yield strength compared to the tensile-aged sample • The difference in strengthening arises from the interactions between dislocations and different γ″ variants. Strengthening in Inconel 718 superalloy is derived from dislocation interaction with γ″ precipitates, which exist in disk-shaped three possible orientation variants with their {100} habit plane normal to each other. The interactions between dislocations and γ″ precipitates vary according to the γ″ orientation variants, which makes the deformation behaviour complicated and difficult to reveal experimentally. In this work, γ″ variant distributions of Inconel 718 samples were tailored by ageing heat treatment under either tensile or compressive stress. The γ″ variant-sensitive deformation behaviours were then studied by in situ tensile tests via neutron diffraction at room temperature. It is demonstrated that yielding first takes place in grains oriented with <110> parallel to the loading direction. An identical lattice strain response to applied stress of both the γ matrix and the γ″ precipitates was observed during yielding, suggesting that dislocations shearing through the γ″ precipitates is predominant at this stage. Variations in yield strength for samples with different γ″ variant distributions were observed, which can be attributed to different strengthening that arises from interactions between dislocation and different γ″ variants. [ABSTRACT FROM AUTHOR]

This study was undertaken with the objective to demonstrate clinical equivalence of a standard 400 μg/d dose of inhaled beclomethasone dipropionate (BDP) given via a new HFA-134a propellant (Chiesi Farmaceutici S.p.A., Parma, Italy), in two dose-units of 50 μg and 100 μg or with the conventional chlorofluorocarbon (CFC) (Becotide™, 50 μg unit dose, Allen & Hanburys, U.K.). A total of 218 children, ages 6-16, with mild to moderate persistent asthma in a stable phase, entered a 2-week run-in period and were then assigned to a 12-week treatment with one of the three treatment tests, following a double-blind, double-dummy (100 μg-dose strength as open arm), multicenter, parallel groups design. Two hundred seven patients entered the intent-to-treat (ITT) analysis and 181 completed the study period. The following efficacy variables were daily recorded by children on a diary card: morning and evening PEFR, number of daytime and nighttime asthma attacks, number of nocturnal awakenings because of asthma, symptoms' scores and intake of salbutamol. Pulmonary function tests (forced expiratory volume in 1 second [FEV₁], forced vital capacity [FVC], peak expiratory flow rate [PEFR], forced expiratory flow between 25%-75% of vital capacity [FEV_25-75], midexpiratory flow [MEF₅₀], forced expiratory flow at 25% of vital capacity [FEF₂₅] were measured at the clinic visits at -2, 0, 2, 4, 8 and 12 weeks of treatment. A blood sample for the measurement of morning cortisol was taken between 8:00 AM and 10:00 AM at the start and at the end of the treatment. Equivalence between the three treatment groups was demonstrated for the primary outcome measure morning PEFR as well as for the evening PEFR. No significant differences among the groups were observed for the other efficacy variables, except for FEV₁ and FVC (significantly higher increase in the two HFA groups than in the CFC group) and for the intake of salbutamol (non-significantly higher decrease of consumption in the CFC group). The three treatments also gave comparable results in terms of adverse drug reactions and of mean values of morning serum cortisol. No signs of marked cortisol decrease were reported in any of the three groups. The results of the present study therefore show that the new HFA-134a propellant can represent an alternative to the traditional CFCs in the delivery of 400 μg/d BDP in mild to moderate asthmatic children.

This study was undertaken with the objective to demonstrate clinical equivalence of a standard 400 μg/d dose of inhaled beclomethasone dipropionate (BDP) given via a new HFA-134a propellant (Chiesi Farmaceutici S.p.A., Parma, Italy), in two dose-units of 50 μg and 100 μg or with the conventional chlorofluorocarbon (CFC) (Becotide™, 50 μg unit dose, Allen & Hanburys, U.K.). A total of 218 children, ages 6-16, with mild to moderate persistent asthma in a stable phase, entered a 2-week run-in period and were then assigned to a 12-week treatment with one of the three treatment tests, following a double-blind, double-dummy (100 μg-dose strength as open arm), multicenter, parallel groups design. Two hundred seven patients entered the intent-to-treat (ITT) analysis and 181 completed the study period. The following efficacy variables were daily recorded by children on a diary card: morning and evening PEFR, number of daytime and nighttime asthma attacks, number of nocturnal awakenings because of asthma, symptoms' scores and intake of salbutamol. Pulmonary function tests (forced expiratory volume in 1 second [FEV1], forced vital capacity [FVC], peak expiratory flow rate [PEFR], forced expiratory flow between 25%-75% of vital capacity [FEV25-75], midexpiratory flow [MEF50], forced expiratory flow at 25% of vital capacity [FEF25] were measured at the clinic visits at -2, 0, 2, 4, 8 and 12 weeks of treatment. A blood sample for the measurement of morning cortisol was taken between 8:00 AM and 10:00 AM at the start and at the end of the treatment. Equivalence between the three treatment groups was demonstrated for the primary outcome measure morning PEFR as well as for the evening PEFR. No significant differences among the groups were observed for the other efficacy variables, except for FEV1and FVC (significantly higher increase in the two HFA groups than in the CFC group) and for the intake of salbutamol (non-significantly higher decrease of consumption in the CFC group). The three treatments also gave comparable results in terms of adverse drug reactions and of mean values of morning serum cortisol. No signs of marked cortisol decrease were reported in any of the three groups. The results of the present study therefore show that the new HFA-134a propellant can represent an alternative to the traditional CFCs in the delivery of 400 μg/d BDP in mild to moderate asthmatic children.

A semiautomated spectrophotofluorometric method for the determination of trimethoprim in blood, urine, and tissue is described. The initial extraction procedures are performed manually. The subsequent alkaline permanganate oxidation and the chloroform extraction of the fluorescent trimethoxybenzoic acid are performed by the automated system at a rate of 30 specimens/hr. The fluorescence is measured by a microflow cell in a spectrophotofluorometer. The method exhibits the same specificity and precision as the manual procedure, with a sensitivity limit in blood of 0.2 mcg./ml.

High-resolution electron microscopy of amorphous interlayers (a-interlayer) formed by solid-state diffusion between metal thin films and silicon is reviewed. In this paper, an overview of the development is presented. Pertinent data obtained on the growth kinetics and structure of a-interlayers in polycrystalline metal thin films on single-crystal silicon are reported. For the Ti/Si, Zr/Si, Hf/Si, V/Si, Nb/Si and Ta/Si systems, the growth of a-interlayer was found to follow a linear law in the initial stage. Si atoms were found to be the dominant diffusing species in the solid phase amorphization in the Ti/Si, Zr/Si, and Hf/Si systems. For the Y/Si system, the stability of amorphous interlayer depends critically on the composition of the amorphous films. Auto-correlation function analysis was utilized to determine the structure of the amorphous interlayers. HRTEM in conjunction with the fast Fourier transform were applied to determine the first nucleated crystalline phase. Simultaneous presence of multiphases was observed to occur in a number of refractory metal/Si systems. Microsc. Res. Tech. 40:136–151, 1998. © 1998 Wiley-Liss, Inc.

Clonazepam appears to be well absorbed, exhibiting peak blood levels of 6.5–13.5 ng/ml at 1–2hr after administration in human subjects receiving 2-mg single oral doses. The “apparent” half-lives of elimination ranged from 18.7 to 39hr in the subjects studied. Less than 0.5% of the dose is recoverable in the urine, suggesting complete biotransformation and/or alternative routes of excretion. Flunitrazepam in the dog is rapidly eliminated and exhibits a “first-pass” metabolism effect following oral administration, whereby the N-desmethyl metabolite is the major detectable drug component in the blood. Neither the drug nor its N-desmethyl metabolite is detected in the urine, suggesting extensive and complete biotransformation.

High‐resolution electron microscopy of amorphous interlayers (a‐interlayer) formed by solid‐state diffusion between metal thin films and silicon is reviewed. In this paper, an overview of the development is presented. Pertinent data obtained on the growth kinetics and structure of a‐interlayers in polycrystalline metal thin films on single‐crystal silicon are reported.

To learn about the effects of tension on fibroblast function, we have been studying initial cellular responses to stress-relaxation. Human foreskin fibroblasts were cultured in anchored collagen matrices for 2 days, during which time mechanical stress developed. Subsequently, the matrices were dislodged; thereby allowing stress to dissipate. Within 5 min after initiating stress-relaxation, fibroblasts retracted their pseudopodia. At this time, we observed the disappearance of cellular stress fibers and the formation of actin clusters along the cell margins. The actin was found to be located inside 200 nm diameter vesicles that were budding from the cell surface. Vesicles isolated from the matrix after stress-relaxation contained prominent 24 kDa, 36 kDa (doublet), 45 kDa, and 135 kDa polypeptides. The 45 kDa polypeptide was the major component in the Triton-insoluble vesicle fraction and appeared to be actin. The 36 kDa (doublet) polypeptide, which was found predominantly in the Triton-soluble vesicle fraction, was identified as annexin II. Vesicles also contained annexin VI and beta 1 integrin receptors but not tubulin, vimentin, vinculin or annexin I. The results suggest that stress-relaxation of fibroblasts induces a novel ectocytotic process involving transient budding of intact, plasma membrane vesicles from the cell cortex. On the basis of their morphological and biochemical features, these vesicles may be analogous to the ‘matrix vesicles’ released by chondrocytes and could play a role in extracellular matrix remodeling after wound contraction.

A six-compartment open-system model is presented to elucidate the physiological disposition of chlordiazepoxide and its two pharmacologically active biotransformation products, Ro 5-0883/1 and Ro 5-2092, in the dog following the intravenous administration of 10 mg./kg. chlordiazepoxide · HCl. The pharmaco-kinetic parameters used in the model were obtained by administering each of the three compounds separately. Excellent agreement was obtained between the plasma levels of intact drug, Ro 5-0883/1, and Ro 5-2092 found after administration of chlordiazepoxide · HCl and the calculated levels of each generated from the model. The main features of chlordiazepoxide disposition were: (a) its complete biotransformation to Ro 5-0883/1; (b) elimination of Ro 5-0883/1 almost entirely by biotransformation with up to 50% proceeding to Ro 5-2092 by oxidative deamination; and (c) elimination of Ro 5-2092 by urinary excretion and further biotransformation.