Effect of Freezer Programs on Real-Time Storage Results of Dissolution Profiles

Carstensen and Rhodes¹ have suggested that when, in stability programs, assays cannot be performed immediately after the protocol-designated storage time, then freezing them until such a time when assays can be performed would be a reasonable manner to retain the protocol schedule. They caution, however, that such a procedure may not be valid for dissolution data. The article to follow deals with real-time data showing that such a process is feasible for Nalidixic Acid tablets (and presumably for other tablets as well), and that, furthermore, the dissolution pattern would seem to be “frozen” as well.     

Long range peak demand forecasting under conditions of high growth

An extended logistic model with a varying asymptotic upper bound for long-range peak demand forecasting is described. The model has been applied to a typical fast growing system, the Saudi Consolidated Electric Company. The forecasts are compared with actual demands and with those obtained from classical forecasting methods. The model gave relatively accurate peak demand forecasts compared with other classical methods. The model with a single load observation is capable of producing several peak demand forecasts corresponding to different levels of maximum temperature and various levels of social activity. The forecasts produced by the model were also stable irrespective of the length of the ex-post simulation period     

Displacement control crack-growth instability in an elastic-softening material

The criterion for crack growth instability in an elastic-softening material that is subjected to displacement control loading conditions is examined. A theoretical analysis of the model of a solid containing two symmetrically situated deep cracks and with tensile loading of the remaining ligament, defines the criterion for crack growth instability. The criterion is expressed in terms of the material's softening characteristics and the solid's geometrical parameters. The analysis covers the complete spectrum of material behaviour from the case where the softening zone is very small to the case where instability does not occur until the softening zone traverses the ligament between the crack tips.     

Insertional re-activation of a chloramphenicol acetyltransferase misfolding mutant protein

The deletion of nine residues from the C-terminus of the bacterialchloramphenicol acetyltransferase (CAT) results in depositionof the mutant protein in cytoplasmic inclusion bodies and lossof chloramphenicol resistance in Escherichia coli. This foldingdefect is relieved by C-terminal fusion of the polypeptide withas few as two residues. Based on these observations, efficientpositive selection for the cloning of DNA fragments has beendemonstrated. The cloning vector encodes a C-terminally truncatedCAT protein. Restriction sites in front of the stop codon allowthe insertion of target DNA, resulting in the production ofproperly folded CAT fusion proteins and regained chloramphenicolresistance. The positive selection of recombinants is accomplishedby growth of transformants on chloramphenicol-containing agarplates. The method appears particularly convenient for the cloningof DNA fragments amplified by the PCR because minimal informationto restore CAT folding can be included in the primers. The cloningof random sequences shows that the folding defect can be relievedby fusion to a wide variety of peptides, providing great flexibilityto the positive selection system. This vector may also contributeto the determination of the role of the C-terminus in CAT folding.     

Characterization of allergoids from ovalbumin in vitro and in vivo

Several in vivo and in vitro methods for monitoring immunological properties of two allergoids obtained by formaldehyde treatment of ovalbumin (OA) were developed. The calculated molecular weight of allergoids was 80 kD (OA-F1) and 165 kD (OA-F2), respectively. The allergenic activity in vitro of allergoids in mast-cell histamine release assay was 1000 times lower than of OA. Both allergoids showed reduced ability to induce passive cutaneous anaphylaxis in the Sprague-Dawley rats or systemic anaphylaxis in Dunkin-Harley guinea-pigs. The ability of OA and allergoids to bind to the OA-specific IgE antibodies was measured in vivo by the inhibition of passive cutaneous anaphylaxis (PCA-inhibition). Allergoid binding to IgE was 51-66% lower than the native allergen. Moreover, the avidity of OA-specific IgG antibodies, measured by ELISA-inhibition, for allergoids and allergen was of the same order. Allergoids induced a different pattern of humoral immune response from that, induced by the native allergen. Thus, after immunization of BALB/c mouse, both allergoids induced a higher production of IgG and a lower production of IgE than OA, only OA-F2 induced a lower production of IgG1. The differences in the IgA response to the immunogens was not significant. Delayed hypersensitivity studies in the BALB/c mouse showed that allergoids were 5- to 12-times less effective in inducing a cell-mediated immune response than OA. The present study provides a battery of immunological methods for preclinical testing of modified allergens.     

Polymer networks based on α,ω-methacrylate-terminated poly(1,3-dioxolane)

α,ω-Methacrylate-terminated poly(1,3-dioxolane)s (polyDXL) were synthesized by cationic ring-opening polymerization of DXL in the presence of methylene-bis(oxyethylmethacrylate) as transfer agent. If the initiator concentration is small compared with the transfer agent concentration, the molecular weights of the polymers are governed by the ratio of the reacted monomer to the reacted transfer agent. The α,ω-methacrylate-terminated polyDXLs obtained undergo free radical polymerization with formation of polyacetal networks. The properties of the networks as function of the molecular weight of the corresponding prepolymers are reported.     

Monitoring systems and determination of actual fatigue usage

At GKN, fatigue monitoring of important components has been conducted since 1979. The monitoring methods depend on the mechanisms of damage; quasi-static loads are regarded as well as dynamic loads. The components were selected for monitoring on the basis of a system analysis. The data resulting from monitoring are used to optimise operation mode steadily. Experience shows that the use of monitoring data as input for fatigue assessment is the most realistic and cost-effective way. This fatigue assessment uses global and local sensitivity studies to evaluate the load-stress relation for each component. These relations can be programmed to produce stress vs. time curves. These are processed according to ASME rules to give a realistic fatigue usage.     

A new monitoring system for piping systems in fossil fired power plants

A CEC-funded project has been performed to tackle the problem of producing an advanced Life Monitoring System (LMS) which would calculate the creep and fatigue damage experienced by high temperature pipework components. Four areas were identified where existing Life Monitoring System technology could be improved:

1. 1. the inclusion of creep relaxation

2. 2. the inclusion of external loads on components

3. 3. a more accurate method of calculating thermal stresses due to temperature transients

4. 4. the inclusion of high cycle fatigue terms.

The creep relaxation problem was solved using stress reduction factors in an analytical in-elastic stress calculation. The stress reduction factors were produced for a number of common geometries and materials by means of non-linear finite element analysis. External loads were catered for by producing influence coefficients from in-elastic analysis of the particular piping system and using them to calculate bending moments at critical positions on the pipework from load and displacement measurements made at the convenient points at the pipework. The thermal stress problem was solved by producing a completely new solution based on Green's Function and Fast Fourier transforms. This allowed the thermal stress in a complex component to be calculated from simple non-intrusive thermocouple measurements made on the outside of the component. The high-cycle fatigue problem was dealt with precalculating the fatigue damage associated with standard transients and adding this damage to cumulative total when a transient occurred.

The site testing provided good practical experience and showed up problems which would not otherwise have been detected.     

Study of photosensitive mixtures of TMAE and helium, hydrocarbon or CF4-based carrier gases

Among the photocathodes used for particle identification based on the Cherenkov Ring Imaging technique, the TMAE molecule is still the best in terms of quantum efficiency. Despite the fact that TMAE gaseous photocathodes have already been used in a number of large experiments, one still seeks answers to many detailed questions. We present a systematic study of gaseous photocathodes based on TMAE mixed with helium, hydrocarbon and CF₄-based gases at normal pressure. The study includes a measurement of the electron drift velocity, gas quenching properties, single electron pulse height spectra and anode wire aging. The paper makes recommendations for carrier gas mixtures to obtain the best quenching, and suggests how to manage TMAE wire aging. This study was motivated by a specific particle identification detector proposal, the Fast Drift CRID proposed for the B-factory at SLAC.     

Nitric oxide reduction and carbon monoxide oxidation over carbon-supported copper-chromium catalysts

Carbon supported copper-chromium catalysts are shown to be very active for both the reduction of nitric oxide with carbon monoxide and the oxidation of carbon monoxide with oxygen. Mixed copper-chromium oxide active phases have good activity in the simultaneous removal of nitric oxide and carbon monoxide from exhaust gases. The influence of several catalyst variables has been investigated. The activity per volume of catalyst increases with increasing loading, while the intrinsic activity shows a maximum around C/M=100−50. An optimum catalyst for nitric oxide reduction and carbon monoxide oxidation has a copper/chromium ratio of 2/1. The apparent activation energy for the carbon monoxide oxidation over carbon supported copper-chromium catalysts is 77 kJ/mol, suggesting that the Cu---O bond rupture is the rate-limiting process. The reduction of nitric oxide takes place at higher temperatures. Since all catalysts have a low selectivity for molecular nitrogen formation at lower temperatures, the dissociation of nitric oxide is probably rate determining, resulting in a slightly reduced catalyst system. In an excess of carbon monoxide the reaction is first-order in nitric oxide and zero-order in carbon monoxide. Moisture inhibits the reaction by reversible competitive adsorption, whereas carbon dioxide does not. Oxygen completely inhibits the reduction of nitric oxide due to the more rapid reoxidation of the catalytic sites compared to nitric oxide. Therefore, the reduction of nitric oxide takes place only when all oxygen has been converted and, hence, is shifted to higher temperatures. As a possible consequence, the production of nitrous oxide is reduced. Nitric oxide and molecular oxygen react preferentially with carbon monoxide, so, in an excess of oxidizing component, gasification of the carbon support occurs at higher temperatures after carbon monoxide has been completely consumed.