[The creative process as a search for optimal control].
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Adaptation, Physiological↗
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Results for “Process optimization”
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[Cultivation of Bordetella pertussis in liquid semisynthetic nutrient media with ion-exchange resins].
The possibility of optimizing the processes of B. pertussis cultivation carried out in liquid semisynthetic culture media with strong-base anion-exchange resins is shown. The use of strong-base ionites enhances the reproducibility of cultivation processes, increases the activity of microbial populations and the concentration of microorganisms. B. pertussis cultures grown in the media with anion-exchange resins are characterized by pronounced biological activity.
Animals↗
[Effect of metabolism-oriented substrate administration on energy and protein metabolism in polytraumatized artificial respiration patients].
An adequate "individually tailored" infusion and nutritional therapy is one of the essential prerequisites for an optimal healing process - especially in ventilated, polytraumatized patients with reduced compensatory capacities. There are nevertheless practically no publications dealing with the effect of substrate application adjusted to the measured metabolic rate on the energy and protein metabolism of the critically ill. In order to clarify this situation a prospective study was carried out on a group of 40 polytraumatized, ventilated patients, who were randomized into four groups, each receiving different infusion and nutritional regimen. The O2-consumption, energy expenditure, nitrogen balance and substrate concentrations in plasma and urine were determined, and the urea production rate and substrate turnover of all patients calculated. In the groups given nutritional support carbohydrate application adjusted to O2-consumption - lead to blood glucose concentrations which were persistently high. However, median values did not exceed 10 mmol/l and insulin application was never necessary. Energy expenditure - calculated from O2-consumption - averaged about 3000 kcal/day and was clearly below values previously reported in the literature for patients comparable to those studied in this investigation. There was no difference in energy expenditure between the patients treated with various infusion regimen. In none of the groups the median plasma urea concentration did exceed reference range. Despite an apparent improvement in nitrogen retention rate - through an increased amino-acid intake and a balanced energy input - an increased urea production rate resulted. When a balanced delivery of energy-yielding substrates is given, 2 g amino-acids/kg/day seems to be the upper limit of nitrogen support in the critically ill. 3-methylhistidine excretion in urine was parallel to urea production rate, indicating that the amino-acid sparing effect of carbohydrates is mainly derived from amino-acid conservation in muscle. These results seem to indicate that even in the early posttraumatic period a substrate application, adjusted to the measured turnover is possible without leading to a disturbance in homeostasis.
Adolescent↗
Interactions among enzyme, antibody, drug, and time in enzyme immunoassays for drugs of abuse.
Published information on the major interactive variables of enzymic immunoassays for drugs, whether in urine or serum, is scanty. Using the Syva EMIT-dau Barbiturates assay as an example, we examined the following interactive variables with respect to test response: concentrations of enzyme, antibody, and drug; urine matrix; and time. The results suggest a process for optimizing this type of enzyme immunoassay. Transformation of the data gives indirect evidence of heterogeneous antibody reactions that are drug-concentration dependent.
Antibodies↗
Perceived orientation of dot patterns: influence of the number of dots and the overall form of the pattern.
Sixty subjects were tested to assign orientation to 10 dot patterns differing in their overall form and the number of dots in the pattern. The patterns were presented in four different positions in the visual field and two ways of estimation of the orientation were used. It was demonstrated that the assignment of orientation to the patterns did not depend on their position in the visual field, as well as on the method of estimation used. A quantitative measure for the elongation of a dot pattern has been proposed, which correlates with the degree of unambiguity in the estimation of the orientation of the pattern: the greater the elongation the smaller the standard deviation of the estimates given by the subjects. The same holds true for the dependence of the standard deviation on the dot number for dot patterns with equal elongations. The data obtained support the hypothesis that the assignment of orientation to dot patterns results from a process of optimization that takes place in the visual system.
Adult↗
[Principles of optimization and scaling of certain processes in the technology of vaccine production. IV. Typical problems of scaling certain processes in the technology of vaccine production].
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Technology, Pharmaceutical↗
Thickness of the air-blood barriers in vertebrate lungs.
The thickness of the air-blood barriers in the lungs of a series of mammals, reptiles and amphibians was estimated using stereological methods. There was considerable variation in the measurements, the thickest barrier being that of the crested newt (2.81 micrometer) and the thinnest that of the mouse (1.27 micrometer). The arithmetic mean thickness of the barriers was related to body weight in mammals but not in reptiles or amphibians. There were no significant differences between the minimum thickness of the barriers nor in the volume proportions of their constituent layers in the three orders of animals. The ratio of the arithmetic mean thickness to the harmonic mean thickness of the barriers was highest in mammals. These data indicate that the process of optimization of lung architecture for gas exchange is most marked in mammals.
Air↗
Discordant expression of CD28 ligands, BB-1, and B7 on keratinocytes in vitro and psoriatic cells in vivo.
The process for optimal T-cell activation requires not only engagement of the T-cell receptor/CD3 complex, but also the delivery of additional co-stimulatory signals that synergize with the primary response mediated through the T-cell receptor. Thus, the regulated expression of ligands for such co-stimulatory molecules can be critical in determining whether a cell can effectively activate T cells following the presentation of a foreign antigen. The CD28 antigen has recently been shown to mediate such co-stimulatory signals by interacting with the B7/BB-1 molecule expressed on activated B cells and monocytes. We show in this study that activated keratinocytes, both in vitro and in vivo display a discordance in expression between B7 and BB-1 based on differential monoclonal antibody (MAb) reactivity. Activated keratinocytes in vitro, as well as psoriatic keratinocytes and epithelial cells in the thymus, are reactive with the BB-1 MAb but not anti-B7 MAbs. These BB-1 positive cells fail to express detectable B7 messenger RNA by Northern blot analysis. Furthermore, keratinocytes bind specifically to CD28-transfected COS7 cells, and this binding is inhibited by anti-CD28 and anti-BB-1 but not B7 MAbs. These studies suggest: 1) that the MAb against BB-1 binds a functional epitope on a molecule distinct from B7 as detected on activated keratinocytes in vitro and in vivo and 2) that keratinocytes in skin and epithelial cells in thymus can express cell-surface molecules that might mediate T-cell co-stimulation via CD28.
Antibodies, Monoclonal↗
Relation of follicular dendritic reticulum cells to Reed-Sternberg cells of Hodgkin's disease with emphasis on the expression of CD21 antigen.
Based on observations of 66 cases, in which tissues were specially processed to optimize the simultaneous preservation of cell membrane antigens and morphology, we provide evidence in favor of a relationship between follicular dendritic reticulum cells (FDRC) and Reed-Sternberg (RS) cells of Hodgkin's disease (HD) other than the lymphocyte predominance subtype. RS cells were intimately related to the FDRC network (75% of cases), and the expression of CD21 antigen was frequent (41% of cases). Exclusive expression of CD21 antigen was found in 11 cases of HD, while the expression of other B-cell-associated markers (CD19, CD20, CD22) was both variable and inconsistent. The expression of T-cell antigens (CD3, CD4, CD8) was rare. Null phenotype of RS cells was observed in 27 of 66 cases (41%). Epstein-Barr virus (EBV) nucleic acids were found in 34 of 66 (51.5%) cases. Double labeling techniques showed the presence of EBV-positive RS cells within the FDRC network. A non-B-cell origin of RS cells was supported by the differential expression of EBV latent antigens in HD (latent membrane protein+, EB nuclear antigen 2-), which is unusual in EBV-driven lymphoblastoid cell lines and EBV-positive B-cell lymphomas. FDRC and RS cells are known to share morphological traits (binucleated cells), and both cell types possess Fc receptor for IgG. The hypothesis is further backed by the findings of CD15 antigen expression by occasional RS-like dysplastic FDRC in Castleman's disease (five cases), which is characterized by hyperplasia of FDRC. Whether FDRC might be the only cells involved in the conversion to RS cells by the loss or gain of antigens remains to be determined.
Antibodies↗
Synergistic cooperation between T cell lymphokines for induction of the nitric oxide synthase gene in murine peritoneal macrophages.
The ability of T cell-derived cytokines to induce the expression of the nitric oxide synthase (NOS) gene in murine peritoneal macrophages was examined. IL-2 or TNF-alpha alone had no effect either on gene expression or enzyme activity, whereas IFN-gamma had only modest activity. When IL-2 or TNF-alpha were used in combination with IFN-gamma, there was a marked cooperative induction of both mRNA and enzyme activity. The cooperative effects were truly synergistic, as the consequences of combined cytokine treatment were many times greater than was seen with any of the agents acting independently. The expression of NOS mRNA and enzyme activity in response to combined lymphokine treatments was a continuous process reaching optimal levels between 24 and 48 h after stimulation. Concentration dependency for both IL-2 and TNF-alpha suggested that their effects were mediated through interaction with the corresponding defined cell surface receptors. Human rTNF-alpha was as effective a stimulus as murine TNF-alpha; because human TNF-alpha is recognized only by the p55 Type II TNF receptor, this structure appears to mediate the response to TNF-alpha. When IL-2 and TNF-alpha were added at saturating doses in the presence of IFN-gamma, there was an additive effect on NOS mRNA expression suggesting that IL-2 and TNF-alpha cooperate with IFN-gamma through at least partially distinct intracellular signaling pathways. Expression of NOS mRNA in response to IFN-gamma/IL-2 or IFN-gamma/TNF-alpha treatment required protein synthesis, suggesting that cooperative cytokine induction of NOS involves the intermediate expression of new gene products. Such molecular controls for regulation of inducible macrophage gene expression can be contrasted with regulatory control of other inflammatory genes such as IP-10 and TNF-alpha.
Amino Acid Oxidoreductases↗
[Optimization of a protocol for automatic solid phase synthesis of peptides using a variable volume flow reactor].
The protocol for solid phase peptide synthesis using automatic synthesizers MilliGen/Biosearch 9500 and 9600 with built-in variable volume flow-reactors has been elaborated. The data of swellographic monitoring were used for optimization of process parameters. The peptides involving from 10 to 21 amino acid residues were synthesized using developed protocol. Significant economy of reagents and solvents has been demonstrated for synthesis of good quality peptides.
Amino Acid Sequence↗
[Solution kinetics of magnesium oxide containing granules produced by laboratory scale fluidization].
In practice of manufacturing industrial pharmaceutical products, the technique of fluidization has been used extensively in the past decades. The authors studied the magnesium oxide-containing granulates made by fluidization granulation in laboratory, to optimize the process, to determine the neutralization kinetic parameters of granulates, to establish the connections between the method of granulation and the release of active substances. According to our findings, the pharmaceutical product's characteristics in the aspects of physics, chemistry, stability and bioavailability may remarkably change without fixing the border conditions of parameters within limits.
Kinetics↗
[Current methods in rapid diagnosis of tuberculosis].
The field of mycobacteriology has significantly advanced during the past 10 years. Optimized specimen processing, fluorescence microscopy, radiometric mycobacterial detection system, and use of nucleic acid probes for identification provide more rapid and more sensitive detection of tuberculous mycobacteria. Nevertheless, the diagnosis of tuberculosis is often a long and tedious process which can take up to several weeks. Recently, several new and rapid diagnostic tests have been developed. Despite major advances, the serodiagnosis of tuberculosis remains an investigational method requiring further development and prospective evaluation. Detection of tuberculostearic acid in cerebrospinal fluid by use of gas chromatography-mass spectrometry has proven to be a very rapid, sensitive, and specific test for tuberculous meningitis. The most recent development is the use of polymerase chain reaction (PCR) for the detection of Mycobacterium tuberculosis directly in clinical specimens. PCR is an extremely sensitive and rapid method based on in vitro amplification of specific DNA sequences. However, before using this method for clinical practice, further efforts to develop simple routine procedures that are safe from cross-contamination are warranted. Furthermore, large-scale trials are needed to determine the clinical value of diagnostic PCR assay for diagnosis of tuberculosis in different patient populations.
Bacteriological Techniques↗
A central pseudoknotted three-way junction imposes tRNA-like mimicry and the orientation of three 5' upstream pseudoknots in the 3' terminus of tobacco mosaic virus RNA.
A three-dimensional model of the histidylable 3'-terminal tRNA-like domain of tobacco mosaic virus RNA is proposed on the basis of a comparative structural analysis, chemical and enzymatic probing, combined with graphical modeling of three RNA constructs of increasing size (38, 108, and 182 nt) derived from the 3'-terminal viral RNA sequence. The comparison between the probing patterns of the three RNAs allowed the determination of the relative orientation of these structural domains in the full-length viral tRNA-like structure. Modeling data indicate that only one of the two possible isomers of the three-way junction located at a central position of the tRNA-like domain is in agreement with structural data. Interestingly, this isomer gives rise to a molecule bearing a structural mimicry with the L-shape of canonical tRNAs. A pseudoknotted acceptor branch containing a T-like loop is located perpendicularly to an anticodon-like branch. Moreover, a single-stranded RNA stretch belonging to the pseudoknotted central core mimics a D-like loop and it is proposed that it interacts via two conserved guanosines with nucleotides of the T-like loop as found in canonical tRNAs. This model is valid for the 3' noncoding regions of tobamoviral RNAs as well as for the tRNA-like domain of the satellite tobacco mosaic virus RNA. All three molecules are substrates for yeast HisRS; however, whereas the complete viral genome is required for optimal histidylation capacities, both charging levels and affinity constants are decreased for the three RNA transcripts, suggesting that additional contacts located outside the tRNA-like domain are needed for an optimal aminoacylation process.
Base Sequence↗
A formal model of family medicine.
BACKGROUND: The American Board of Family Practice is developing a computer-based recertification process. An optimal implementation requires a formal model of family medicine, which will become the basis for a knowledge base. DESIGN: The proposed model of family medicine contains six entities: Population, Record, Agents of Change, Health States, Findings, and Courses of Action. The model illustrates 15 important relations between entities. For instance: Health States Lead to Health States, and Findings Associate with Health States. These two relations describe natural history, manifestations of disease, and the effects of medical interventions and risk factors. Because time is such an important aspect of primary care, nearly all numeric data are represented as graphs of possible values over time, called Patterns, which include details about periodicity. Patterns and other aspects of the model provide a means of describing covariance between observations, such as the influence of height on weight. RESULTS: The model reflects many family practice activities and suggests some formal descriptions of family practice. For instance, diagnostic activities focus largely on classifying early or short segments of Patterns in Findings. Most medical interventions attempt to alter either the probability distributions in a Lead-to relation or the impact of a Finding. CONCLUSION: The proposed model of family medicine could find uses in many applications, including computer-based tests, medical records, reference systems, and decision support tools.
Family Practice↗
Mouse bone marrow-derived mast cells undergo exocytosis, prostanoid generation, and cytokine expression in response to G protein-activating polybasic compounds after coculture with fibroblasts in the presence of c-kit ligand.
Polycationic mast cell activators, such as compound 48/80 and substance P, have been reported to activate connective tissue-type mast cells specifically by interacting directly with the Gi family of trimeric GTP-binding protein. We now demonstrate that mouse bone marrow-derived mast cells (BMMC) developed in IL-3, an immature mast cell population lacking responsiveness to the Gi-coupled polycationic mast cell activators, underwent maturation toward a connective tissue-type mast cells-like phenotype that responded to polycationic compounds after only 4 to 6 days of coculture with Swiss 3T3 fibroblasts in concert with recombinant soluble c-kit ligand (KL), whereas 3T3 or KL alone was insufficient to mediate this process. Under optimal conditions, cocultured BMMC released approximately 30% beta-hexosaminidase and generated approximately 1 ng of PGD2/10(6) cells within a few minutes in response to compound 48/80 or substance P. Furthermore, these cells expressed cytokines, such as IL-1beta and IL-6, and PG endoperoxide synthase-2 1 to 4 h after stimulation with compound 48/80 or substance P. All these responses were suppressed effectively by pertussis toxin, implicating functional Gi coupling. Regardless of the remarkable change in polycationic compound sensitivity, there was only a minimal change in the constitutive expression of Gi3 alpha after coculture. These results together with the observation that before coculture BMMC responded to thrombin through its Gi-coupled receptor suggest that the alteration in a certain step(s) distinct from the level of Gi3 alpha protein expression is important for the acquisition of responsiveness to the polycationic compounds by the synergistic action of KL and 3T3 fibroblast-derived factor. Several lines of evidence have revealed that 3T3-derived factor appears to differ from the known cytokines, prostanoids, and adhesion molecules and is a labile soluble substance.
3T3 Cells↗
Integral curves and the variational principle of intermittent normal conduction in the tachycardia-dependent right bundle branch block.
Electrocardiographic (ECG) tracings of atrial fibrillation with the tachycardia-dependent right bundle branch block (RBBB) in a patient under digitalis therapy are presented, in which supernormal phase of intraventricular conduction was well-documented. The development of long intervals terminated by a normally conducted beat was attributed to the occurrence of concealed atrio-ventricular (A-V) conduction of atrial fibrillation impulse during the supernormal phase. The ventricular interval caused by a normally conducted beat (x seconds) in the interval of 1.01-1.50 seconds (s) was transformable into from of In(x + a) + l, where parameter a = 0, 0.04, 8.08 and 0.16. The vector differential equation dy/dx = ln (x + a) + 1l which is piecewise continuous and integrable, was assumed to describe the process of optimal control. This is equivalent to the problem of finding Green's function of the region, i.e. to solving, the Dirichlet problem for the region. The solution curves given by y = (x + a) ln(x + a) + l can be interpreted as distributions. This is the first study to apply integral curves and the variational principle to mathematical modelling of normal A-V conduction in tachycardia-dependent RBBB with atrial fibrillation. Furthermore, this is the first topological study to derive some definite properties of states of the phase space of a dynamical system. There are structurally stable vector field points so-called attractors on a differential manifold or surface. The optimal control is characterized by the fixed point property. In general, mathematical modelling may be applicable to the tachycardia-dependent RBBB when the cycle lengths caused by normally conducted beats range from 1.00 to 1.50 s as a feasible region. A solution of Dirichlet problem in the region was found. It was derived from this study that the normally conducted beats appeared as period doubling of 0.38-0.59 s, i.e. the interval of supernormal phase.
Aged↗
Development of latent fingerprints using a corona discharge.
A novel technique for the development of latent fingerprints is presented. It is based on placing a fingerprint-bearing object inside a corona discharge induced plasma. The development of various real and artificial fingerprints on metallic substrates under a wide range of conditions is studied. Using the results of the development experiments and the results of X-ray photoelectron spectroscopy, it is shown that the development is based on oxidation of the fingerprint background. This is achieved by strong oxidizers generated by the discharge process, while saturated fatty-acids found in sebaceous fingerprints protect the area beneath them, resulting in a visible fingerprint. The process is optimized by minimizing the electrode gap distance and maximizing the peak discharge voltage and the pulse repetition frequency.
Dermatoglyphics↗