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PubMedDate not supplied

[Optimization of immobilization conditions for acid proteinase from Aspergillus awamori].

To optimize the immobilization conditions for acid proteinase from Aspergillus awamori by covalent binding through glutaraldehyde, experiments were carried out using the Box-Wilson method. The optimization process was assessed on the basis of absolute activity A, coefficient of activity retention gamma and their product A gamma. The following conditions can be recommended: glutaraldehyde concentration 50--60 mg/g, enzyme concentration not less than 40 mg/g, time of glutaraldehyde treatment 2--2.5 hrs, immobilization time 2 hrs, pH about 4.0, and temperature 35--40 degrees C. Under these conditions A=220--230 U/g, gamma = 23--24% Agamma = 5,000--6,000.

Aspergillus↗
PubMed1995

The macroheterogeneity of recombinant human interferon-gamma produced by Chinese-hamster ovary cells is affected by the protein and lipid content of the culture medium.

The culture environment exerts a major effect on the glycosylation pattern of recombinant human interferon-gamma (IFN-gamma) produced by Chinese-hamster ovary (CHO) cells. The recombinant IFN-gamma is heterogeneous and consists of a mixture of fully (2N), partially (1N) and non-glycosylated (0N) glycoforms, and throughout batch cultures there is a decline in the proportion of fully glycosylated IFN-gamma. Glucose and glutamine, nutrients that are depleted early in such cultures, were prima facie candidates for causing such a shift in glycoform profile. Batch feeding of these nutrients did not prevent the decline in 2N glycoform, but the glycosylation pattern of IFN-gamma was affected by the initial glutamine concentration in the culture. Under different serum-free environments the extent of IFN-gamma glycosylation was affected by (1) the concentration of BSA, (2) the quality of BSA, (3) the lipid composition of the culture medium and (4) the presence of surfactants. Moreover, the inclusion of serum in cultures caused changes in the molecular masses of the major glycoforms, that was indicative of cleavage of the core polypeptide. The results reported emphasize the necessity of considering the effects of culture media on product quality as well as on product quantity during process optimization.

Animals↗
PubMed1994

[Quantitative evaluation of myocardial perfusion with ultrafast magnetic resonance tomography].

With the advent of ultrafast Magnetic Resonance Imaging (MRI), it is now possible to produce images with high temporal resolution. This gives the opportunity to record the passage of the paramagnetic contrast material Gadolinium-DTPA through the tissue of the heart muscle, yielding information on regional myocardial perfusion. We assessed the accuracy of MRI to detect and quantify reductions in coronary flow secondary to stenosis in dogs and patients. Regional blood flow was measured in dogs by left atrial injection of microspheres labeled with different radioactive isotopes. Signal intensity (SI) curves were generated in regions of interest over the myocardium and the cavum of the left ventricle. A newly developed two-compartment model based on the indicator-dilution method was used for interpretation of the SI-curves. In an optimization process the free parameters of the model equation were fitted to the measured SI-curves. The following flow parameters were determined: model parameter Q*, time to peak intensity (T), maximum signal intensity (SImax) and mean transit time (MTT) as calculated from a gamma variate fit. Absolute blood flow values were calculated for the parameters MTT and Q* assuming that the intravascular volume represents 10% of the total myocardial tissue volume. Measurements were performed on a 1.5 T Magnetom SP (Siemens AG, Erlangen) using a Turbo Flash sequence (TR = 6.5 ms, TE = 3 ms, TI = 100 ms, Flip Winkel = 9 degrees). Endsystolic images (voxel size = 1.8, 2.7, 15 mm3) were taken with an 18-cm Helmholtz surface coil in the short-axis view. A Gd-DTPA bolus (0.05 mmol/kg) was injected into the left atrium of 3 anesthetized closed-chest dogs. From the myocardial SI-curves the different parameters of myocardial perfusion were compared with flow assessed by microsphere injection over a wide range of myocardial blood flows (from 0.04 ml/min/g to 7.6 ml/min/g). A third-order polynominal fit showed a good correlation for the parameter Q* and MTT, whereas T and SImax were found to have a poor correlation. The linear regression analysis for a limited range of < 2 ml/min/g showed a superior estimation of myocardial perfusion for the parameter Q* than MTT. Blood flow > 2 ml/min/g was significantly underestimated by the MRT-measurements, but the parameter Q* showed the smallest amount of the divergent changes.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗
PubMedDate not supplied

[Selection and mutation from the theoretical information point of view--limits of the preservation of genetic information].

There is no doubt that evolution can only operate in accordance with the laws of thermodynamics. To transform this simple perception into a statement that can be quantified it is necessary to examine how the entropy (or the information content) changes by means of the two main factors of evolution: selection and mutation. In the present paper this aim was reached by using the methods of information theory. That evolution becomes possible the change of information by mutation and selection must not be negative in the long run. Consequently an upper limit for the information content of the genome must be assumed. If the evolution as a self-optimizing process gains this upper limit it reaches a dynamic equilibrium at which the increase of entropy by mutation balances the decrease of entropy by selection. In particular it was examined under which circumstances of dynamic equilibrium master-genotypes (genotypes that can preserve their specific sequence over a long time) can exist.

Biological Evolution↗
PubMed1994

Methods and strategies available for the process control and optimization of monoclonal antibody production.

The objective of this paper is to explore the range of methods and strategies available for the process control and optimization of monoclonal antibody production by hybridoma cell culture. Emphasis will be placed on the choice of the level of complexity incorporated into the process control and optimisation procedure. It will be shown that the behaviour of hybridomas in culture is influenced by sophisticated cellular metabolic activities and various interactive environmental factors and that the understanding and modelling of the way hybridomas grow in the bioreactor should enable optimisation of bioreactor operating conditions to achieve maximum monoclonal antibody formation. However, due to the lack of on-line instrumentation of important biological variables and the incomplete knowledge of hybridoma cultivation process, there exist many limitations and challenges to the advent of applications of process control and optimisation in this field. To solve the problem, introduction of industrially practical biological measurements and development of new control concepts are inevitable. At the end of this paper, we shall discuss possible schemes for the control of the physiological state of cells in order that balanced cell growth and maximum monoclonal antibody synthesis may be achieved.

Animals↗
PubMedDate not supplied

[Optimization of the process of larval development in the housefly as a utilizer of organic wastes in a human biological life support system].

The development of Musca domestica L. larvae as utilizers of organic wastes in the biological life support system was investigated by methods of mathematical planning. The optimization of the process under study is based on the reduction to the canonical form of regression models set by second order polynomials. This approach was tested when determining optimal conditions for larval development and substrate utilization with respect to 5 factors. On the basis of optimization results the following parameters were selected to ensure effective utilization of the substrate by larvae: the amount of substrate--150 g, its height--2.0 cm, temperature--34-35 degrees, humidity--77%, larval density--10 larvae per g wet substrate.

Animals↗
PubMed1994

Optimal protocol for processing high-volume and Peds Plus blood cultures by the BACTEC NR860.

The optimal incubation period for blood cultures collected in high-volume (Plus 26) and anaerobic (NR7A) media or Peds Plus medium and processed by the BACTEC NR860 was evaluated during a 12-month period. Organisms were recovered from 9% (1528 of 16,870) of blood culture vials (14% [1302 of 9118] of sets). Ninety-eight percent of positive vials were detected by day 5. Thirty-three vials (Plus 26 or NR7A) became positive on day 6 or 7; all positive Peds Plus vials were detected by day 5. Therapy did not change in response to detection of the organisms (26 "occasional" pathogens, 9 "usual" pathogens) in these vials. One usual pathogen had potential clinical significance, but the patient from whom the culture was collected died before it became positive. In the author's institution, the 5-day protocol for processing blood cultures could be adopted without compromising patient care.

Bacteremia↗
PubMedDate not supplied

Optimal temperature control policy for a two-stage recombinant fermentation process.

The optimal temperature control policy to be followed in the operation of a two-stage fermentation system in which gene expression is induced by a temperature-sensitive gene switching system was studied. A genetically structured model was used to describe product formation, and kinetic equations based on experimental data were used to quantify the specific gene expression rate and parameters that affect plasmid instability. A constant temperature control policy and temperature profiling control policy including temperature cycling were studied and compared. Maximum average production rate was obtained from a temperature control policy in which the second stage was operated initially at about 40.5 degrees C and the temperature decreased slightly to a constant value at 40.0 degrees C. The maximum average production rate, which corresponds to the optimal temperature control policy, for an operation of 180 h was 29.7 units of protein (mg of cells)-1 h-1.

DNA, Recombinant↗
PubMedDate not supplied

Effects of optimization and image processing in digital chest radiography: an ROC study with an anthropomorphic phantom.

A digital system for chest radiography based on a large image intensifier was compared to a conventional film-screen system. The digital system was optimized with regard to spatial and contrast resolution and dose. The images were digitally processed for contrast and edge enhancement. A simulated pneumothorax and two simulated nodules were positioned over the lungs and the mediastinum of an anthropomorphic phantom. Observer performance was evaluated with ROC analysis. Five observers assessed the processed digital images and the conventional full-size radiographs. The time spent viewing the full-size radiographs and the digital images was recorded. For the simulated pneumothorax, the results showed perfect performance for the full-size radiographs and detectability was high also for the processed digital images. No significant difference in the detectability of the simulated nodules was seen between the two imaging systems. The results for the digital images showed a significantly improved detectability for the nodules in the mediastinum as compared to a previous ROC study where no optimization and image processing was available. No significant difference in detectability was seen between the former and the present ROC study for small nodules in the lung. No difference was seen in the time spent assessing the conventional full-size radiographs and the digital images. The study indicates that processed digital images produced by a large image intensifier are equal in image quality to conventional full-size radiographs for low-contrast objects such as nodules.

Evaluation Studies as Topic↗
PubMed1993

[The optimization of the process of instrumental learning with a low intensity of the conditioned stimulus].

The influence of the intensity of conditional stimulation on the speed of instrumental teaching of rats at different probabilities of casual fulfillment of the reaction under development (VSPR) was investigated. The VSPR value significantly affects the number of positive and negative confirmations in the early period of teaching and, finally, the informational individuum-environment interaction. Therefore, with the existing choice of VSPR values the dependence of the speed of teaching upon different unfavourable factors lessens, which may be used for optimization of the process of instrumental teaching at a low intensity of the conditional signal.

Acoustic Stimulation↗
PubMed1993

Toward a theory of optimal hearing aid processing.

An ideal hearing aid for a peripheral hearing loss would process the incoming signal in order to give a perfect match between the cochlear outputs of the impaired ear and a reference normal ear. As a first step toward this objective, a model of the normal and impaired peripheral auditory system was used to derive the optimal hearing-aid processing filter based on a minimum mean-squared error criterion. The auditory model includes the compression and suppression effects of the cochlear mechanics and the sensitivity of the neural transduction process. Simplifying assumptions were then incorporated into the processing to yield a practical frequency-dependent adaptive gain system. Processing examples of several individual speech sounds are presented for a flat hearing loss, and the results indicate that a three-channel compression system with adjustable gains and band edges will be close to the optimal solution for this case.

Adaptation, Physiological↗
PubMed1977

[Principles for optimizing and guaging several processes in the technology of vaccine production. I. Several problems in guaging and optimizing thermal sterilization of fluids].

Thermal sterilization of fluids--one of the widespread operations in microbiological laboratories and in vaccine production--solves two tasks: provides sterility and maximal preservation of biological value of the sterilized fluid. A possibility and expediency of using some indices for the quantitative assessment of the efficacy of the sterilization regimens, including measurement of the sterilization processes is considered in this work. A possible way of the regimen optimization on the basis of known values of the activation energies of the processes of decomposition of thermolabile components and inactivation of foreign microbial flora is assessed.

Hot Temperature↗
PubMed1992

Optimization of a process for the production of (R)-2-hydroxy-4-phenylbutyric acid--an intermediate for inhibitors of angiotensin converting enzyme.

(R)-2-Hydroxy-4-phenylbutyric acid, an intermediate in the manufacture of inhibitors of angiotensin converting enzyme, can be produced continuously in an enzyme membrane reactor by enzymatic reduction of its corresponding alpha-keto acid. D-Lactate dehydrogenase (D-LDH) from Staphylococcus epidermidis was chosen as the most appropriate enzyme to carry out the NADH-dependent reduction. Formate dehydrogenase (FDH) was used for NADH regeneration. Detailed kinetic measurements and a mathematical model for the coupled enzyme reactions were applied to calculate the optimal conditions for continuous production of the alpha-hydroxy acid. A mass of 1 kg [corrected] (R)-2-hydroxy-4-phenylbutyric acid was synthesized in a 220 ml enzyme membrane reactor over a period of 4 weeks. A mean space-time-yield of 165 g l-1 d-1 was achieved at low enzyme consumptions of 150 U kg-1 alpha-hydroxy acid for FDH and D-LDH.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1993

Optimizing the biolistic process for different biological applications.

The biolistic process is still rapidly evolving. We do not anticipate further major improvements in biolistic apparatus. There will probably still be further major improvements in particles, DNA coating, and vectors, as well as significant further advances in understanding of biological determinants of cell penetration and survival. The technology has currently reached the point at which it can be readily and reliably used for a wide range of applications. Given the information presented in this chapter, new applications can be optimized fairly readily.

Animals↗
PubMed1993

Cytologic evaluation of serous effusions. Processing techniques and optimal number of smears for routine preparation.

A double-blind retrospective review of 90 pleural and ascitic fluids was performed to determine the optimal number of smears necessary to produce an accurate evaluation, and to analyze the utility of different preparation techniques. Each case had four Papanicolaou-stained smears (two alcohol fixed and two Saccomanno fixed) and one Diff-Quik-stained, air-dried smear. Forty cases originally were reported as positive (37 adenocarcinoma, 1 lymphoma, and 2 Pneumocystis carinii) and 50 were reported as negative. The results showed that the diagnostic yield of evaluating five smears compared with three (one of each preparation) is identical. Air-dried smears were the most sensitive in identifying malignant cells and infectious organisms. It is concluded that (1) the diagnostic accuracy is enhanced by the use of several preparation techniques to include air-dried smears and (2) when variable processing methods are used, the evaluation of more than three smears does not increase the diagnostic yield.

Adenocarcinoma↗
PubMed1984

Model aided dynamic process analysis and optimization for the nourseothricin fermentation.

The relation between product formation and growth kinetics could be characterized by two facts: the specific product formation rate depends on the ageing of the population and on the specific growth rate. These relation was formulated and quantified by a mathematical model, which was fitted to experimental data of a representative fermentation run und used to predict an optimal fermentation mode. In the result of this discussion cyclic fed batch fermentation was found to be optimal.

Anti-Bacterial Agents↗
PubMed1979

The role of glucocorticoid hormones as biological amplifiers.

Recent research in hormone action has been aimed at studying single effects in well-defined systems. As exemplified in several chapters of this book, it has been possible to deduce a general mechanism of action of the glucocorticoids using this approach. Most hormones, and the glucocorticoids in particular, do not act as independent agents in the intact animal. Although the best known example of how glucocorticoids interact with other hormones is the amplification of the effect of those whose action is mediated by cAMP, these steroids also augment the effects of a variety of other hormones and effectors. Such interactions are of interest in clinical medicine as well, since glucocorticoid hormones are used in combination with other drugs in a number of conditions, including the treatment of asthma, allergies, and certain kinds of shock and cancer. Neither the biochemical nor the pharmacologic basis for the effects of the glucocorticoids is known. In some cases the actions of other hormones are not observed unless the tissue has first been exposed to glucocorticoids. In these instances the glucocorticoids are said to exert a "permissive effect," since they allow a process to proceed at a maximal rate even though the steroid itself has no effect on this process. There is no doubt that such examples exist, as documented above: thus the concept of a "permissive effect" does have utility. The term fails to describe the more general role the glucocorticoids play, since in many instances the steroid also has a direct effect on the process itself, or optimizes a process in which the primary effector is not as yet known. Because of these cases, and because the historically more general usage first proposed by INGLE [1] seems to have been forgotten, use of the term "permissive effect" has been avoided in this chapter. An ultimate goal in glucocorticoid hormone research is to identify the mechanisms involved in the amplification effect these hormones exert. Now that the actions of these hormones and of the hormones they interact with are being defined, such work is within the realm of feasibility.

Animals↗