Sounding Out Pharmaceutical Processes

High-resolution ultrasonic spectroscopy is a novel technique with enormous potential for analysis of a wide range of samples and processes. This technique is based on precision measurements of velocity and attenuation of acoustical waves at high frequencies propagating through materials. It allows fast at/on line measurements analysis of formulation consistency (composition, structure) of raw materials, ingredients and intermediates, process impurity analysis, particle sizing, batch to batch variation, stability assessment etc in pharmaceutical industry. The technology can be used for static fingerprint measurements or for dynamic analysis of systems. Optical transparency is not required as ultrasonic waves propagate through opaque samples. The analysis is fast and non-destructive. High-resolution ultrasonic spectrometers were developed, patented and brought to the market by Ultrasonic Scientific Ltd. and recognised with various international awards. These instruments require small sample volumes, down to 0.03 ml, and give excellent resolution. They can be used for the analysis of composition, aggregation, particle sizing, gelation, micellisation, crystallisation, sedimentation, enzymatic activity, conformational transitions in polymers, biopolymer-ligand binding and antigen-antibody interactions, etc. This article describes main features of High-Resolution Ultrasonic Spectroscopy and area of applications of new high-resolution HR-US series of ultrasonic spectrometers. Several applications are illustrated including the monitoring of denaturation and aggregation of proteins in antibody solution, the measurements of the particle size in emulsions, precipitation in synthetic blood substitutes and crystallisation     

Application of adsorptive voltammetry to assess the stability of modified alanine aminotransferases

Alanine aminotransferase has been stabilized by using chemical modification with both bis(imidates) (of varying length) and succinic anhydride. The voltammetric behavior of the native enzyme and its various modified forms has been studied by using both cyclic voltammetry and differential pulse adsorptive voltammetry. A distinctive accumulation pattern was found for each of the stabilized enzymes at the static mercury drop electrode with respect to the native alanine aminotransferase. Adsorptive voltammetry was demonstrated to be a useful technique to assess the extent of chemical modification of this enzyme, which is indirectly related to their stability for use in biotechnological processes. The sue of differential pulse adsorptive voltammetry, after a preconcentration of the enzyme for 300 s at the electrode surface, has yielded a detection limit of 1.0 x 10(-9) M.     

Long-term validated simulation of a building integrated photovoltaic system

Electrical and thermal simulations of a building integrated photovoltaic system were undertaken with a transient system simulation program using real field input weather data. Predicted results were compared with actual measured data. A site dependent global-diffuse correlation is proposed. The best-tilted surface radiation model for estimating insolation on the inclined surface was selected by statistical tests. To predict the module temperature, a linear correlation equation is developed which relates the temperature difference between module and ambient to insolation. Different combinations of tilted surface radiation model, global-diffuse correlation model and predicted module temperature were used to carry out the simulation and corresponding simulated results compared with the measured data to determine the best combination which gave the least error. Results show that modification of global-diffuse correlation and module temperature prediction improved the overall accuracy of the simulation model. The monthly error between measured and predicted PV output was lied below 16%. Over the period of simulation, the monthly average error between measured and predicted PV output was estimated to be 6.79% whereas, the monthly average error between measured and predicted inverter output was 4.74%.     

Nonstationary response of nonlinear systems using equivalent linearization with a compact analytical form of the excitation process

A new method based on equivalent linearization approaches is presented for estimating the nonstationary response of a class of nonlinear multi-degree-of-freedom systems subjected to nonstationary excitations. The highly efficient method is based on creating a compact analytical approximation of measured nonstationary excitation process data through use of a two-stage decomposition procedure. The analytic data condensation of the excitation process is performed in two stages; (1) by performing the Karhunen–Loeve spectral decomposition on the covariance matrix of the input random process to obtain the dominant eigenvectors, and (2) by fitting these eigenvectors with orthogonal polynomials to produce a truncated series of analytically approximated eigenvectors. The efficiency and accuracy of the method is demonstrated through simulation with synthetically generated excitation data as well as measured data from a real-world physical process. Although the decomposition procedure used can characterize very general input processes, because the equivalent linearization technique requires the Gaussian assumption of the response process, the constraint on applying this approach is similar to the constraints on all other equivalent linearization techniques. However, the additional freedom gained from being able to work with data-based nonstationary random processes is a significant addition to this area of research.     

The production of interleukin-1 alpha immunoreactivity by human oviductal cells in a coculture system

PURPOSE: The aim of this study was to determine the concentration of interleukin-1 alpha in human embryo culture medium with or without oviductal cell coculture and to correlate the interleukin-1 alpha levels with pregnancy. METHODS: Culture media from 32 in vitro fertilization and embryo transfer cycles were assayed for interleukin-1 alpha by immunoassay technique. Human embryos were cultured in Earles' balanced salt solution supplemented with 15% preovulatory serum (sEBSS) in 16 of these cycles, while embryos in the rest of the cycles were cocultured with human oviductal cells in sEBSS. RESULTS: Both sEBSS and spent sEBSS after embryo culture contained low or undetectable levels of interleukin-1 alpha in the pregnant and nonpregnant cycles. On the other hand, oviductal cells significantly increased the amount of interleukin-1 alpha immunoreactivity in the conventional culture medium or coculture medium (P < 0.001, Mann-Whitney rank sum test). The concentrations of interleukin-1 alpha in the spent sEBSS after oviductal cell culture and after coculture with human embryos were 1.5 +/- 1.0 and 1.3 +/- 0.9 pg/ml, respectively. There was no difference in the interleukin-1 alpha concentration between the pregnant and the nonpregnant coculture cycles. CONCLUSIONS: These data showed that human oviductal cells produced interleukin-1 alpha immunoreactivity in a coculture system. However, this production could not be used as a marker for successful embryo implantation.     

Intermediate-grade lymphomas treated with cyclophosphamide-doxorubicin- vincristine-prednisone-bleomycin alternated with cyclophosphamide-methotrexate-etoposide-dexamethasone. Application of prognostic models to data analysis

BACKGROUND: Numerous treatment strategies have been tried with the aim of improving results for patients with intermediate-grade lymphomas (IGL) over those achieved with cyclophosphamide, doxorubicin, vincristine, prednisone, and bleomycin (CHOP-Bleo), and numerous prognostic models have been developed to identify and separate risk groups. This study reports on a new protocol for Ann Arbor Stages II-IV IGL that consists of CHOP-Bleo alternated with a new regimen of cyclophosphamide, methotrexate, etoposide, and dexamethasone (CMED) and radiation therapy and demonstrates the usefulness of prognostic models for identifying risk groups and comparing treatment programs. METHODS: One hundred seventy patients with Ann Arbor Stages II-IV IGL were treated with alternating cycles of CHOP-Bleo and CMED for a total of 12 cycles. Involved field radiation therapy was interspersed with courses of chemotherapy for patients with Stage II and Stage III disease. Results were analyzed and compared with those of the authors' previous study of CHOP-Bleo and radiation therapy using the Ann Arbor staging system, their earlier prognostic model, and the recently published International Index. RESULTS: A complete remission occurred in 78% of the patients. The overall 5-year survival rate was 67%. Survival was better for patients with Ann Arbor Stage II disease (80%) than for those with Stage III or Stage IV (67% and 58%, respectively). High tumor burden, above-normal levels of serum lactic dehydrogenase, serum beta 2-microglobulin, and Ann Arbor Stage IV disease were adverse factors. The International Index and the authors' earlier prognostic model separated four prognostic groups. CHOP-Bleo/CMED was generally well tolerated. Neutropenic fever was the major complication that occurred in 25 patients during treatment. Six of these patients died of sepsis. CONCLUSIONS: This study demonstrated that CHOP-Bleo/CMED is a well-tolerated regimen that produced better results than those reported for a former study that used CHOP-Bleo alone. Further, results for CHOP-Bleo/CMED compared favorably with those of other second- and third-generation regimens. The study also validated the usefulness of prognostic models and, in particular, the new International Index for identifying risk groups.     

Murine thymic lymphoma is associated with a species-specific hematopoietic progenitor cell subpopulation

Many strains of laboratory mouse are uniquely susceptible to the development of T cell lymphoma/leukemia, either spontaneously or as a result of chemical or radiation exposure. In contrast, T cell leukemias or lymphomas which are relatively uncommon in human populations, are not easily induced by radiation, and are not generally associated with chemotherapy or chemical exposure. Evidence is presented to suggest that differences in the susceptibility to the development of these malignancies is related to subtle but important variations in the regulation of hematopoietic stem cell differentiation between these two species.