SEARCH · PubMed Health

Results for “Process optimization”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 379 records · Page 21Linked to original sources

PubMed1997

Tandem repeats of T helper epitopes enhance immunogenicity of fusion proteins by promoting processing and presentation.

Empirical findings have shown that recombinant chimeric proteins may be made more immunogenic if T helper epitopes are incorporated as tandem repeats. In the present study we investigated the mechanisms responsible for the enhanced immunogenicity of fusion proteins composed of the heat-stable enterotoxin of enterotoxigenic E. coli (STa) linked to multiple copies of the ovalbumin323-339 T helper epitope (ova) and a connecting dimer of an Ig-binding region of Staphylococcus aureus protein A (ZZ), which were previously shown to stimulate strong anti-STa titres in mice. We used B cell and macrophage cell lines as APC and IL-2 production by ova-specific T cells as our read-out system. Fusion proteins containing four repeated T helper epitopes were found to be the most immunogenic and resulted in 50-fold higher IL-2 production than constructs with a single T helper epitope. Under limiting APC conditions the construct with four epitopes was the best inducer of IL-2, indicating that this construct was most effectively processed by the APC. Analysis of IL-2R alpha expression by flow cytometry confirmed that four copies gave the highest frequency of activated T cells in culture, indicating a direct correlation between ability to activate T cells and IL-2 production in culture. Also in vivo, the fusion protein with four epitopes exhibited the strongest T cell priming effect. Moreover, both in vitro and in vivo, the ZZ construct was found to serve as an efficient means for targeting of the fusion proteins to B cells, thereby allowing access to the Ig receptor uptake pathway for Ag. The present study provides direct evidence that fusion proteins can be constructed to optimize processing in the individual APC and enhance activation of clonal T cells.

Animals↗

PubMed2003

Method development in high-performance liquid chromatography for high-throughput profiling and metabonomic studies of biofluid samples.

"Metabonomics" has in the past decade demonstrated enormous potential in furthering the understanding of, for example, disease processes, toxicological mechanisms, and biomarker discovery. The same principles can also provide a systematic and comprehensive approach to the study of food ingredient impact on consumer health. However, "metabonomic" methodology requires the development of rapid, advanced analytical tools to comprehensively profile biofluid metabolites within consumers. Until now, NMR spectroscopy has been used for this purpose almost exclusively. Chromatographic techniques and in particular HPLC, have not been exploited accordingly. The main drawbacks of chromatography are the long analysis time, instabilities in the sample fingerprint and the rigorous sample preparation required. This contribution addresses these problems in the quest to develop generic methods for high-throughput profiling using HPLC. After a careful optimization process, stable fingerprints of biofluid samples can be obtained using standard HPLC equipment. A method using a short monolithic column and a rapid gradient with a high flow-rate has been developed that allowed rapid and detailed profiling of larger numbers of urine samples. The method can be easily translated into a slow, shallow-gradient high-resolution method for identification of interesting peaks by LC-MS/NMR. A similar approach has been applied for cell culture media samples. Due to the much higher protein content of such samples non-porous polymer-based small particle columns yielded the best results. The study clearly shows that HPLC can be used in metabonomic fingerprinting studies.

Body Fluids↗

PubMed1995

N-acyl-2-substituted-1,3-thiazolidines, a new class of non-narcotic antitussive agents: studies leading to the discovery of ethyl 2-[(2-methoxyphenoxy)methyl]-beta-oxothiazolidine-3-propanoate.

The synthesis of a novel class of antitussive agents is described. The compounds were examined for antitussive activity in guinea pig after cough induction by electrical or chemical stimulation. Ethyl 2-[(2-methoxyphenoxy)methyl]-beta-oxothiazolidine-3-propanoate (BBR 2173, moguisteine, 7) and other structurally related compounds showed a significant level of activity, comparable to that of codeine and dextromethorphan. The compounds presented in this paper are characterized by the N-acyl-2-substituted-1,3-thiazolidine moiety, which is a novel entry in the field of antitussive agents. The serendipitous discovery of the role played by the thiazolidine moiety in determining the antitussive effect promoted extensive investigations on these structures. This optimization process on N-acyl-2-substituted-1,3-thiazolidines led to the initial identification of 2-[(2-methoxypheoxy)methyl]-3-[2-(acetylthio)acetyl]- 1,3-thiazolidine (18a) as an interesting lead compound. The careful study of the rapid and very complicated metabolism of 18a provided further insights for the design of newer related derivatives. The observation that the metabolic oxidation on the lateral chain's sulfur of 18a to sulfoxide maintained the antitussive properties suggested the introduction of isosteric functional groups with respect to the sulfoxide moiety. Subsequent structural modifications showed that hydrolyzable malonic residues in the 3-position of the thiazolidine ring were able to assure high antitussive activity. This optimization ultimately led to the selection of moguisteine (7) as the most effective and safest representative of the series. Moguisteine is completely devoid of unwanted side effects (such as sedation and addiction), and its activity was demonstrated also in clinical studies.

Animals↗

PubMed1996

Evaluating sol-gel ceramic thin films for metal implant applications. I. Processing and structure of zirconia films on Ti-6AI-4V.

Thin ceramic films or coatings over metallic bone-interfacing implant surfaces have the potential to improve implant performance with respect to implant fixation, wear, or corrosion. In this study, zirconia (ZrO2) thin films formed on Ti-6AI-4V using a polymeric alkoxide-based solgel process were investigated. ZrO2 films of uniform thickness on the order of 100 nm were obtained by dip coating Ti-6AI-4V samples into a zirconium propoxide containing solution using a substrate withdrawal speed ranging from 2 to 8 cm/min and a sol of nominal viscosity approximately 6 cps. These films were essentially free of surface macrodefects but had random submicron "pinholes." X-ray diffraction studies suggested that the films were at least partially crystalline, with some "metastable" cubic and/or tetragonal phases after annealing for 1 h at 500 degrees C. The demonstrated reproducibility of this approach for producing good quality ZrO2 films on Ti-6AI-4V warrants further studies to optimize processing conditions for implant applications.

Alloys↗

PubMed2002

Sulfur polymer solidification/stabilization of elemental mercury waste.

Elemental mercury, contaminated with radionuclides, presents a waste disposal problem throughout the Department of Energy complex. In this paper we describe a new process to immobilize elemental mercury wastes, including those contaminated with radionuclides, in a form that is non-dispersible, will meet EPA leaching criteria, and has low mercury vapor pressure. In this stabilization and solidification process, elemental mercury is combined with an excess of powdered sulfur polymer cement (SPC) and sulfide additives in a mixing vessel and heated to approximately 40 degrees C for several hours, until all of the mercury is converted into mercuric sulfide (HgS). Additional SPC is then added and the temperature of the mixture raised to 135 degrees C, resulting in a molten liquid which is poured into a mold where it cools and solidifies. The final treated waste was characterized by powder X-ray diffraction and found to be a mixture of the hexagonal and orthorhombic forms of mercuric sulfide. The Toxicity Characteristic Leaching Procedure was used to assess mercury releases, which for the optimized process averaged 25.8 microg/l, with some samples being well below the new EPA Universal Treatment Standard of 25 microg/l. Longer term leach tests were also conducted, indicating that the leaching process was dominated by diffusion. Values for the effective diffusion coefficient averaged 7.6x10(-18) cm2/s. Concentrations of mercury vapor from treated waste in equilibrium static headspace tests averaged 0.6 mg/m3.

Diffusion↗

PubMed2001

The contribution of combinatorial chemistry to lead generation: an interim analysis.

In the process of finding new drug candidates medicinal chemists nowadays have a variety of options to choose from, one is to apply combinatorial chemistry techniques. Since the early 1990's synthetic and analytical methods as well as new technologies have been growing rapidly in the area of combinatorial chemistry. Applying these techniques have resulted in the production of large numbers of compounds. A trend is observed towards smaller libraries of compounds with more drug-like properties. An analysis is made to establish the contribution of combinatorial chemistry in providing new lead candidates for (pre)clinical development towards new pharmaceutical products. Ten representative examples are given to describe the impact of ombinatorial chemistry on different levels of the lead discovery and optimization process. Furthermore, reports on combinatorial chemistry products that are already in (pre)clinical development were traced back to their source. The interim analysis showed only limited success of combinatorial chemistry approaches in terms of delivering leads. Second generation libraries appear more drug-like and focussed and may result in more compounds entering clinical studies in the future.

Combinatorial Chemistry Techniques↗

PubMed1980

[Correlative neuropsychology & neurobiology by evoked potentials in central nervous aging process (author's transl)].

Evoked potentials (VEP, SEP) in 40 elderly patients, who were in different states of vitality and aged from 71 to 95, were recorded and analysed. Specific neuronal activity of the cortex on the one hand and neuropsychological and clinical parameters on the other hand should be correlated. No correlation between SEP and the results of neuropsychological assessment had been suggested, and there was not any. Regular VEP correlate significantly with both, prompt time of reaction and a good psychological performance in the reduced Wechsler Adult Intelligence Scale (WAIS). The results do not provide a neurophysiological parameter of intellectual faculties. Regular VEP and SEP, however, mean that the visual and somatosensory cortex and subcortex has not been impaired to any extent. In other words normal VEP and SEP suggest normal mental and motor ability. This, "state of vitality" and neurobiological items as "mental flexibility" and "sensomotor flexibility" operationalised and defined may be related to recorded function of the neuron, respectively. Basically, the results seem to confirm that a specific optimated process, which has been succeeded in a human ecological relation between "activity and performance", and intact neuronal function does appear, even if the primary spectrum of adaption that is caused by aging might be narrowed and easy to be disturbed altogether.

Aged↗

PubMed1993

Concepts of optimality and efficiency in biology and medicine from the viewpoint of philosophy of science.

If everything happens strictly according to the natural laws, which meet extremum principles, in what way can the possibility for life be characterised, so that the optimization processes of evolution can take place? Is it legitimate to "enlarge" the natural laws by certain laws of conservation? The question then arises of which are the new conservation quantities that are introduced by life itself? The concept of genidentity, which must not be confused with the biological concept of genes, is introduced and used to characterise the interface between animate and inanimate systems by the principle of conservation of genidentity. It thus becomes clear that animate systems can differ in the way and in how reliably they achieve their goal of self-preservation. The abundance of possibilities to be or not to be able to reach this goal offers the necessary scope in which the notion of a postulated assumed optimization in the theory of evolution is conceivable. The conservation principle of genidentical systems creates the possibility of evolutionary optimization by ranking these systems. An optimal lifespan of an individual genidentical system refers to the conservation principle of genidentical systems on a second supra-individual level (species). The optimization of the growth of a species needs the conservation of a genidentical system on a third level (symbiotic systems). The ranking of genidentical systems onto ever higher levels--so that the higher conservation principles always impose restrictions on the ones below--would come to an end when the minimization of raw materials and energy consumption limits all possible and available resources. Since the spectrum extending between opposite goals lies within the range of possible means of optimization, supposedly evolutionary goals of optimization are always attributed to nature by the observer.

Biological Evolution↗

PubMed1995

Processing of visual motion direction in the fronto-parallel plane in the stationary or moving observer.

To examine the effect of concurrent self-motion on the perception of the direction of object-motion, random-dot kinematograms were employed in which the strength of the directional signal was manipulated by varying the percentage of coherently moving pixels. The subject's task was to indicate the motion direction of briefly presented displays while undergoing whole body rotations with angular accelerations of 0, 5, 15, or 45 degrees/s2. The perception of the direction of visual motion in the horizontal plane was impaired only when visual and vestibular motion directions were incongruous. The impairment increases with both increasing angular acceleration and decreasing percentage of coherently moving pixels. For object-motion in the vertical plane, an impairment was found for both congruous and incongruous combination of visual and vestibular stimulation, although not as pronounced for the latter (i.e., visual upward, vestibular downward stimulation, and vice versa). These results are discussed in terms of postnatal development and neurophysiological optimization processes resulting from intersensory 'updating' through every-day experience of object-motion during self-motion.

Acceleration↗

PubMed2003

Development of an automated extraction procedure for detection of human papillomavirus DNA in liquid based cytology samples.

Liquid based cytology samples are being used increasingly to improve cervical screening and have the advantage that residual cell suspension is available for other tests such as human papillomavirus (HPV) detection. However, as the transport medium is optimised for downstream cytology, problems can be experienced during extraction of nucleic acid. This study aimed to develop a robust protocol for automated extraction of HPV DNA from cervical, liquid based cytology samples using a high throughput robotic system. Considerable modification of existing clinical extraction protocols for swab specimens, together with optimisation of required sample input volume was required to reduce sample blockage during the extraction to acceptable levels. The blockage rate and optimal processing volume was assessed by extracting a fixed volume (1/4) of re-suspended material from the centrifuged pellets of 10, 5 and 1 ml aliquots of 200 specimens. Analysis revealed 17.5% blockage with specimens originating from 10 ml aliquots; 3% with 5 ml and no blockage with 1 ml aliquots of the same samples. A 3% blockage level is acceptable for an automatic well clearance procedure to be followed. HPV testing of the extracts by real-time PCR showed a 1.5% loss of sensitivity in extracts originating from 1 ml aliquots as compared with 5 ml aliquots with a consequent loss of detectable HPV genotypes after reverse hybridisation. In short, 5 ml of liquid based cytology specimen is recommended for nucleic acid extraction, to allow optimal detection of HPV types in clinical samples while retaining maximum efficiency of the robotic extraction procedure.

DNA, Viral↗

PubMed1992

Deficiency of acylpeptide hydrolase in small-cell lung carcinoma cell lines.

During protein biosynthesis, processing of the N terminus of many proteins may occur through acetylation and deacetylation. The enzyme acylpeptide hydrolase is likely involved in deacetylation of nascent peptide chains or of bioactive peptides. The related enzyme, acylase, hydrolyzes the acetyl amino acid product of the acylpeptide hydrolase reaction to acetate and a free amino acid. There is a reciprocal relationship between the substrates for these enzymes (i.e., substrates for one enzyme are competitive inhibitors for the other). In several cultured cell lines, including normal and malignant cells, the ratio of acylpeptide hydrolase to acylase enzyme activities appears to be coordinated and characteristic for a given cell type. Thus, in normal cultured lung cells, hamster ovary cells, hepatoma cells, and lymphocyte cells, nearly equal amounts of these enzymes are expressed, conducive to optimal processing of acetylated N-terminal residues. Four lines of erythroleukemic cell lines were found to express nearly twice as much acylase as acylpeptide hydrolase activity. In the Ehrlich ascites tumor cell line, where 80% of the proteins have been reported to remain acetylated at their N terminus, acylpeptide hydrolase is hardly expressed but acylase activity is not reduced. The 3p21 region of human chromosome 3, which contains the DNF15S2 locus that encodes acylpeptide hydrolase (Jones et al., Proc Natl Acad Sci USA 1991;88:2194), undergoes deletion in some carcinoma cells; the gene that encodes for the acylase is also present on region 3p of the same chromosome. We found that both acylpeptide hydrolase and acylase activities are practically absent in six small-cell lung carcinoma cell lines tested.(ABSTRACT TRUNCATED AT 250 WORDS)

Amidohydrolases↗

PubMed1993

Multiple coding and the evolutionary properties of RNA secondary structure.

This article evaluates evolutionary properties of the transition from RNA primary sequence to RNA secondary structure. It focuses on the restrictions that the conservation of a protein code in an RNA sequence puts on its potential to evolve towards a specific secondary structure. Restricting the mutations to those that do not affect the coding for a protein restricts both the accessibility and the connectivity of the sequence space. The accessibility is restricted because only certain point mutations are allowed. The connectivity is restricted because no insertions and deletions are allowed. Simulating an evolutionary search process for a specific secondary structure shows that (i) the reduction of allowable point mutations allows for adaptation to some large-scale topology, but strongly reduces the possibility of small-scale adaptations, (ii) the abolition of insertions and deletions has very little effect on the results of the search process. During the evolutionary search process for a secondary structure with a specific topology and a high frequency of base-pairing the quasispecies moves into a subspace in which the similarity between secondary structures of neighboring sequences is relatively high. Increased similarity between second structures of neighboring sequences is also found in the Rev responsive element (RRE) in the lentiviruses Caprine arthritis-encephalitis virus and Visna virus. In these viruses a biased nucleotide frequency in the RRE region suggests that selection for the RRE RNA secondary structure affects the amino acid sequence of the env gene. Our results show a variation in the ruggedness of fitness landscapes which are based on a high degree of epistatic interactions. Fitness landscapes play an essential role, not only in biotic evolution, but also in all kinds of optimization processes (Hill Climbing, Simulated Annealing, Genetic Algorithms, etc). Variation in their ruggedness should therefore be taken into account in the analysis of these processes.

Amino Acid Sequence↗

PubMed1991

Observations on maximum entropy processing of MR images.

A maximum entropy (MAXENT) criteria for MR image processing optimizations has previously shown poor performance, but this note observes that there are two entirely different kinds of "data transmission" applications which appear to have been intermixed. In the two cases, "image entropy" actually refers to different kinds of data variables. The previous literature formulations are for transfer of data in which pixel-locations are the transmitted variable, and these pixels may be neither uniform nor constant. The second application concerns the MRI data set for display. Its data variables are image pixel-values of magnetization intensity, and the data transfer mode has the sense of visual display. When MAXENT criteria are modified to address an array of pixel-value intensities, and use a pixel-value information entropy rather than pixel-locations entropy, then successful data processing results. Restoring display visualization from highly nonuniform surface coils for lumbar spine scans are demonstrated, as an example of MAXENT usefulness.

Image Processing, Computer-Assisted↗

PubMed2005

Evaluation of the performance of mechanisms for noise attenuation in a single-gene expression.

Experiments of synthetic gene regulatory modules and theoretical studies have clarified the stochastic nature of gene expression. The establishment of methods to control the fluctuation in gene expression is an indispensable step to the synthesis of robust and reliable genetic modules. In this study, we evaluate the performances of several major mechanisms to attenuate the fluctuation in a single-gene expression; noise attenuation through the control of the ratio of the transcription rate to the translation one, the interaction between synthesized proteins and background molecules, and an autoregulatory negative feedback. We analytically derive the dependence of the noise intensity on the parameter values related to elementary reaction processes, optimal conditions to attenuate the noise, and the limitation of the attenuation for those mechanisms. Our results can be an important basis for selecting the most efficient combination of the components in the design and synthesis of robust and reliable genetic modules. Furthermore, the knowledge on the performances that we obtain can also play a role in understanding the design principle of the intracellular gene regulatory networks.

Computational Biology↗

PubMed1979

[Nutritional optimization of thermal processing of canned food].

The model developed by Barreiro, Salas and Herrera (7) for the prediction of nutrient losses during the thermal processing of conduction heated foods was used in this work to optimize the thermal processing, maximizing nutrient retention in processes with equivalent sterilization values. The processes were stimulated in a digital computer (taking pea purée canned in cans 307 x 409 as the product analyzed). Aall of the processes had equivalent sterilization values with respect to Clostridium botulinum. The thiamine retention associated with each process was calculated by the model of Barreiro, Salas and Herrera (7). The maximum fraction of thiamine retained was of 0.688 for a process at 114.2 degrees C (237.5 degrees F) for 95 minutes. Also, the possibility of the existence of a can with optimum dimensions for maximum thiamine retention, with the same sterilization values, was studied. It was found that this optimum, with the same does not exist; on the contrary, the retention was at a minimum when the diameter approaches infinite and the height zero, and viceversa. For this reason, from the nutrient retention point of view, it is better to process the product in flat or slender cans for a given sterilization value.

Clostridium botulinum↗

PubMed2002

Scaling-up of a lactose wet granulation process in Mi-Pro high shear mixers.

The high shear wet granulation upscaling possibilities of a Pro-C-epT Mi-Pro 250 ml with a batch size of 40 g were investigated by down-scaling an alpha-lactose monohydrate wet granulation process from a Collette Gral 10 (8 l batch size) to a Pro-C-epT Mi-Pro with different bowl volumes of 5 l, and 1900, 900 and 250 ml. The wet granulation process was optimised in the Gral 10, next an octagonal design was build around the central point. Two process parameters, the impeller tip speed and the water content, were varied at three levels, which resulted in a two-factor three-level experimental design. alpha-Lactose monohydrate 200 M was granulated using a polyvinylpyrollidone K 30 (2.5% on dry material) binder solution. The granules were dried at 25 degrees C for 24 h, sieved and characterised. The granules were compressed to tablets. In all mixer volumes the used impeller tip speed range did not influence the granule or tablet properties. In all bowl volumes the influence of water concentration on actual yield, particle size distribution and granule friability was similar. All batch sizes resulted in tablets of similar quality. For the selected formulation the lab scale Mi-Pro high shear mixers with different bowl volumes could be used to determine the optimal process parameters and to scale up to the Collette Gral 10 pilot scale.

Lactose↗

PubMed2002

A photoacoustic technique for depth-resolved in situ monitoring of biofilms.

Biofilms occur in natural and engineered water systems. Biofouling in technical processes lowers the water quality and increases the frictional resistance in tubes. In wastewater treatment plants, biofilms are used for removal of organic an inorganic pollutants. For improvement of antifouling strategies and for process optimization in wastewater treatments plants, an analytical technique for online monitoring of biofilms is needed. In this article, a new setup for in situ monitoring of biofilms by photoacoustic spectroscopy is presented. To produce a biofilm, a mixture of microorganisms was grown in a nutrient solution inside a tube reactor. The content of the tube reactor was pumped through a flow channel, and biofilms were generated at the inner surfaces. Three photoacoustic sensor heads were integrated at different positions into the base plate of the flow channel. By photoacoustic spectroscopy, growth, thickness, and detachment of biofilms can be monitored on-line and nondestructively. Experiments presented in this article showed that the flow conditions influence the structure and thickness of biofilms. By changing the pH value, electrostatic interactions inside the biofilm matrix were influenced, and the subsequent detachment processes were observed online. The interaction of iron(III) oxide particles with biofilms led to particle adsorption on the outer and inner surfaces of the biofilm. Afterwards, biofilm flocs were sloughed off from the base biofilm.

Acoustics↗

PubMedDate not supplied

A triage system for processing fine needle aspiration cytology specimens.

Fine needle aspiration (FNA) cytology is increasingly used in the operating room, in radiology suites and in physicians' offices. A major cause of nondiagnostic FNA specimens is poor preparation techniques. To avoid this problem, we have developed a triage system for handling and preparing FNA specimens. (1) For aspirations performed without a cytotechnologist present, the aspirate is rinsed into 50% ethanol; Cytospin slides are then prepared and stained by the Papanicolaou method. Clinicians are disposed toward this indirect method since no special slide preparation techniques are necessary. The results are equal to those of direct smear preparations, and material so prepared may also be used for immunocytochemistry. (2) When a cytotechnologist is present, both direct and indirect preparations are made. (3) When an immediate interpretation is desired, to ensure adequacy and/or to make a diagnosis, alcohol-fixed direct smears are stained with a modified toluidine blue-eosin stain and read by the cytopathologist. This offers the advantage of a quick diagnosis, which may be made in less than 90 seconds, but with nuclear detail equal to that of the Papanicolaou stain and with good background staining. In summary, our three-tiered approach offers optimal processing for aspirates collected in various settings in our institution.

Biopsy, Needle↗