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Results for “Process optimization”

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PubMed1994

Glutathione disulfide variability in normal human blood.

A prevailing opinion is that glutathione disulfide (GSSG) levels in human blood are very low, but many studies have reported variable results. Therefore, our objective was to determine valid processing conditions for GSSG measurement and apply them to normal human blood samples. Reproducibility and stability of GSSG were demonstrated in acid extracts of a single sample of fresh whole blood by repetitive measurements during a 6-h period in which the %CVs were < 10. In contrast, in normal subjects tested repeatedly over several years, GSSG values ranging from < 2 to 166 nmol per 10(10) red blood cells were obtained and the overall %CV was 46. Lower GSSG values were obtained in hemolysates and ultrafiltrates. Thus, these results indicate that blood GSSG concentrations differ due to biological variation using optimal processing conditions.

Adult↗

PubMed2006

e-Care integration: To meet the demographic challenge.

Current multi-agency models of care will be wholly unsustainable when faced with the forecast doubling of over 65s in the developed and developing nations to around 40% of their populations of the next decades. The resulting imbalance between demand and skilled resources is beginning to force radical change towards a fully "joined up" cross-disciplinary, cross-agency service that spans the wide spectrum of medical and social care. This paper offers a basis for a radically revised model that combines end-to-end service processes optimization; the use of integrated assistive technology systems to help the elderly maintain an independent lifestyle; personal risk reduction through medical and status monitoring; extended care-watch and service co-ordination. It then develops an IPTV based approach to provide the necessary infrastructure to underpin provision of these facilities both at home and in the community. These substantial benefits are reviewed and weighed against the inherent loss of privacy that can result from the pervasive computing aspects of the care watch approach, together with the trust building and change management aspects that are inevitably involved in the rationalisation process.

Activities of Daily Living↗

PubMed2001

[Cornea bank of Lyon: from quality diagnosis to ISO 9001 certification].

The tissue and cell bank of the HCL (Hospices Civils de Lyon) has, since 10 June 1999, consisted of two sections with related activities: cell culture for the Skin Substitutes Laboratory (Laboratoire des Substituts Cutanés, LSC) and preservation of corneas at 31 degrees C for the Cornea Bank. As the LSC had been ISO 9001 certified since March 1997 our aim, since merger, was to raise the Cornea Bank to the same level of quality as the LSC, so as to coincide with the renewal of the LSC certificate in February 2000. The methods we used (project, quality control, analysis and process optimization) led us to receive official certification only nine months after the merger. The procedure started with a program of quality control at the Cornea Bank from February 1999 onwards, in order to list the work and equipment required, evaluate its documentation system and what was needed to incorporate this new activity into the existing system of quality assurance at the LSC. On the 7th March 2000, the Tissue and Cell Bank of the HCL obtained an ISO 9001 certificate for its combined functions. As well as achieving our objectives and the strong points highlighted by the auditor during the renewal process, this quality assessment revealed many advantages: improvements in the conservation of corneas, economies in staff replacement and reductions in both the cost of maintaining quality, the cost of the corneas themselves, etc. The decree 'Banque' no. 99-741 of 30th August 1999, which put in place the system of authorization of tissue banks in France, demands quality control. Our application for certification which started in early 1999 had anticipated this regulation. This helped us enormously when compiling the dossier accompanying the official request and was an essential element in obtaining the favourable response of the ASSAPS on 21 June 2000.

Certification↗

PubMed2002

Optimization of the isoelectric precipitation method to obtain protein isolates from amaranth (Amaranthus cruentus) seeds.

This research was conducted to evaluate the effect of extraction pH (7.8-9.2) and precipitation pH (4.3-5.7) on four selected quality attributes of protein isolates from amaranth seeds (Amaranthus cruentus) such as protein content (PC), whiteness index (WI), enthalpy of transition (EN), and denaturation temperature (DT). Ten different treatments involving extraction and precipitation pH combinations were analyzed by a central composite design; the experimental data were fitted by a second-order model using a least-squares method for each one of the four dependent variables. Response surface methodology was used for the optimization process; in addition, a common optimum value for the four dependent variables was obtained utilizing the desirability method. A confirmatory test showed that the generated regression equations could adequately predict performance of this isoelectric precipitation method. The results indicate that extraction pH and precipitation pH showed an important effect on PC, WI, and EN. However, the different combinations did not significantly affect the DT. Values of 9.2 and 8.0 for extraction pH and 5.7 for precipitation pH produced the best overall result for all responses. Finally, the results have shown that it is possible to obtain protein isolates from A. cruentus seeds at optimized values of extraction pH and precipitation pH, which presented a high protein content and good physicochemical properties.

Amaranthus↗

PubMed2004

Optimization of MammoSite therapy.

PURPOSE: Radiation source anisotropy causes about 10% of a spherically shaped planning target volume surrounding a MammoSite balloon to receive less than the prescribed dose. The principal dose-limiting factor for MammoSite therapy is the dose to the overlying skin. Additional limiting factors potentially include the dose to portions of the heart and lung. The goal of optimization is to deliver the prescribed dose to as much of the planning target volume as possible while avoiding toxicity to adjacent organs. METHODS AND MATERIALS: An experimental CT-based high-dose-rate brachytherapy treatment planning system was used to investigate optimization strategies for MammoSite treatment. This system implements a linear optimization of high-dose-rate dwell times on the basis of constraints assigned to points of interest and a set of potential dwell positions. RESULTS: The cylindrical symmetry of the MammoSite catheter limits the optimization process to creating spherical, ellipsoidal, or egg-shaped isodose distributions whose major axis is oriented along the catheter axis. If the dose to a limiting structure, such as skin, is not an issue, the use of multiple dwell positions can compensate for source anisotropy and create a more spherical isodose surface enclosing the planning target volume compared with a single dwell position. When skin becomes a dose-limiting factor, the catheter axis orientation, source anisotropy, dwell position, and dwell weighting can be exploited to limit the skin dose while simultaneously preserving the prescribed dose to as much of the target volume as possible. CONCLUSION: Optimization of MammoSite therapy using multiple dwell positions within the balloon is both possible and practical.

Anisotropy↗

PubMed1996

[Experimental orthopedic surgery: the practical aspects and management].

The funds to grant for a scientific research project are more and more interesting public and private administrations. A quantitative analysis of experimental research prices in all its phases is mandatory for an optimization process. The aim of this paper is to define practical and economical aspects of the experimental 'in vivo' models designed for the validation of biomaterials, with particular respect to the managerial bookkeeping of consumer goods, based on the experience of our Institute. Some tables were realized in order to quantify the resources needed to perform experimental 'in vivo' models. These tables represent a reliable tool for a continuous monitoring of managerial costs for the current year and for an accurate budget planning for the future years considering the experimental projects in progress and the planned researches. A business organization of public research facilities may lead to an optimization of costs and an easier national and international funds achievement increasing, also, the partnership with private appointers.

Animals↗

PubMed2006

Effect of processing variables on micro particulate system of aceclofenac.

Microparticulate systems of aceclofenac were prepared by modified solvent evaporation method using different variables such as polymer (cellulose acetate): drug ratios (1:9, 1:6, 1:3, and 1:1), agitation speeds (500-1,500 rpm) and stirring time (5-15 min). The effects of processing variables were evaluated by microparticle size and entrapment efficiency. The average microparticle size increases from 80.2+/-1.45 to 97.3+/-2.06 microm with increase in the polymer concentration while reduces with increase in agitation speed and stirring time; and at the higher speed gives irregular shape of particles. The highest entrapment efficiency, size uniformity, angle of repose (23.6+/-0.3 degree) and compressibility index (13.8+/-0.7%) of microparticles were found with 1:6 (polymer: drug ratio), at 1,000 rpm and 10 min stirring time among all microparticles. The in-vitro drug release study was carried out with prepared microcapsules (AC-1 to AC-4) of various polymer concentrations and optimized processing variables and compared with conventional and SR tablets. The conventional tablet and SR tablet releases maximum drug within 3 and 6h respectively while microparticulate system releases more than 12h. All formulations followed first order release kinetic and diffusion controlled drug release.

Anti-Inflammatory Agents, Non-Steroidal↗

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↗