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 1,153 records · Page 64Linked to original sources

PubMed1986

Pyridoxal 5'-phosphate-dependent histidine decarboxylase. Inactivation by alpha-fluoromethylhistidine and comparative sequences at the inhibitor- and coenzyme-binding sites.

Pyridoxal phosphate-dependent histidine decarboxylase from Morganella morganii AM-15 was inactivated by (S)-alpha-fluoromethylhistidine by a pseudo first-order reaction, with KI and k inact values of 0.1 mM and 32.2 min-1, respectively, and was most efficient at pH 6.5-7.0. Both L-histidine and the competitive inhibitor, L-histidine methyl ester, protected against inactivation. The apoenzyme was not inactivated. These findings indicate that inhibition is a mechanism-based process. Under optimal conditions a single molecule of alpha-fluoromethylhistidine inactivates one enzyme subunit, indicating that no escaping side reaction occurs during the inactivation process. The bound inactivator is not released by dialysis of the native protein but is released upon denaturation by heat or urea. This released product was not fully characterized, but it contains the tritium of ring-labeled alpha-fluoromethyl-[3H]histidine, exhibits the spectral properties of a 3-hydroxypyridine derivative, and does not yield any amino acids on hydrolysis. The label was much more stable following borohydride reduction of the inactivated protein, and a tryptic peptide containing the modified residue was isolated. Sequencing of this peptide and the corresponding peptide from the native enzyme revealed that the inactivator binds to a serine residue of the holoenzyme. Two P-pyridoxyl peptides from tryptic or CNBr digests of the NaBH4-reduced enzyme were also isolated. Sequence and compositional data obtained with these peptides showed that the serine residue to which the inhibitor binds is not near the lysine residue that binds pyridoxal-P in the primary sequence of the protein, although the two residues must be near one another in the three-dimensional structure to account for these results. A speculative mechanism for inactivation, consistent with the experimental findings, is presented.

Amino Acid Sequence↗

PubMed2003

Development pharmaceutics of microbicide formulations. Part II: formulation, evaluation, and challenges.

In recent years, AIDS and sexually transmitted diseases (STDs) have become a burgeoning problem and are spreading at an alarming rate. Microbicides are being developed as a new therapeutic category for prevention of transmission of sexually transmitted infections (STIs) and HIV. Many of the microbicide formulations (MF) may fail to elicit a protective response either because of a lack of efficacy or inadequate formulation. Manufacturing a stable, efficacious, safe, and optimal product is the main objective of formulation development programs. Preformulation parameters (PP), as discussed in Part I of this series, influence formulation development significantly and should be considered carefully before designing a formulation strategy. Initially, based on PP and market research, a target product profile (TPP) is generated, which defines product attributes that can be normally classified as "essential" and "desirable." A complex and dynamic process begins thereafter that takes into consideration myriad factors starting from selection of delivery system, selection of excipients, compatibility study, prototype composition, selection of process and optimization, stability testing, scale up, manufacturing under good manufacturing practices (GMP), and packaging development. Prototype formulations are evaluated for several performance characteristics (e.g., dispersion behavior, bioadhesion, retention, spreading, rheology). These compositions are also subjected to biologic evaluation by various in vitro and in vivo models. Such a well-planned, well-coordinated, and well-implemented formulation development program not only accelerates overall development but also minimizes failures in subsequent clinical development studies. The objective of this review is to highlight the importance of formulation science, outline the steps involved in this process, and explore how these can be exploited for achieving optimal MF.

Administration, Intravaginal↗

PubMed2004

Process implementation aspects for biocatalytic hydrocarbon oxyfunctionalization.

Oxidoreductases catalyze a large variety of regio-, stereo-, and chemoselective hydrocarbon oxyfunctionalizations, reactions, which are important in industrial organic synthesis but difficult to achieve by chemical means. This review summarizes process implementation aspects for the in vivo application of the especially versatile enzyme class of oxygenases, capable of specifically introducing oxygen from molecular oxygen into a large range of organic molecules. Critical issues such as reaching high enzyme activity and specificity, product degradation, cofactor recycling, reactant toxicity, and substrate and oxygen mass transfer can be overcome by biochemical process engineering and biocatalyst engineering. Both strategies provide a growing toolset to facilitate process implementation, optimization, and scale-up. Major advances were achieved via heterologous overexpression of oxygenase genes, directed evolution, metabolic engineering, and in situ product removal. Process examples from industry and academia show that the combined use of different concepts enables efficient oxygenase-based whole-cell catalysis of various commercially interesting reactions such as the biosynthesis of chiral compounds, the specific oxyfunctionalization of complex molecules, and also the synthesis of medium-priced chemicals. Better understanding of the cell metabolism and future developments in both biocatalyst and bioprocess engineering are expected to promote the implementation of many and various industrial biooxidation processes.

Biotechnology↗

PubMedDate not supplied

[Optimization of the local thermocoagulation process as applied to stereotaxic neurosurgery].

A mathematic model was set up to find the thermal response of tissues to thermocoagulation. This model was studied by means of an analogue computer so as to establish optimal operating parameters for high-resistance heating probes. The smallest size of the layer of incomplete necrosis was used as criteria for optimization. The results suggest that the best performance characteristics in thermal coagulation can be achieved by using controlled temperatures from 77 to 87 degrees C (applied intermittently or continually).

Computers, Analog↗

PubMed2006

Optimization of a pilot-scale process for producing lupin protein isolates with valuable technological properties and minimum thermal damage.

This paper describes a pilot process for obtaining protein isolates from white lupin seed with improved water solubility and technofunctional properties as well as reduced thermal damage. After a careful optimization of the process parameters, two valuable food ingredients were prepared: lupin protein isolate type E, with a useful emulsifying capacity, and lupin protein isolate type F, with a high capability of foam formation and stabilization. The spray-drying process was particularly critical for inducing some thermal damage, but a careful selection of the conditions permitted ingredients having only marginally impaired lysine bioavailability to be obtained. The reproducibility of the protein extraction process was tested on two different lupin varieties.

Chemical Phenomena↗

PubMed1999

Diamond-like carbon coatings for orthopaedic applications: an evaluation of tribological performance.

A detailed investigation of the tribological behaviour of vacuum arc diamond-like carbon coated Ti-6Al-4V against a medical grade ultra-high molecular weight polyethylene is conducted in this work in order to investigate the potential use of diamond-like carbon coatings for orthopaedic appplications. Lubricated and non-lubricated wear experiments are performed using a standard pin-on-disc wear tester. The coefficient of friction is monitored continuously during testing and wear rate calculations are performed using surface profilometry measurements of worn disc surfaces. Sliding wear tests show the existence of two distinct friction and wear regimes distinguished by physically different mechanisms. In the first stages of wear, adhesion and abrasion are the dominant mechanisms of wear while fatigue processes are activated later in the tests. The effects of diamond-like carbon coating structure, surface roughness and lubrication on tribological behaviour are presented. Optimal process-structure-property design for vacuum arc plasma deposition is utilized in order to obtain strong adhesion to the titanium alloy substrate. Diamond-like carbon coatings significantly improve the friction and wear performance of the orthopaedic bearing pair and show exceptional promise for biomedical applications.

Journal Article↗

PubMed2004

Selection of beam orientations in intensity-modulated radiation therapy using single-beam indices and integer programming.

While the process of IMRT planning involves optimization of the dose distribution, the procedure for selecting the beam inputs for this process continues to be largely trial-and-error. We have developed an integer programming (IP) optimization method to optimize beam orientation using mean organ-at-risk (MOD) data from single-beam plans. Two test cases were selected in which one organ-at-risk (OAR) and four OARs were simulated, respectively, along with a PTV. Beam orientation space was discretized in 10 degrees increments. For each beam orientation, a single-beam plan without intensity modulation and without constraints on OAR dose was generated and normalized to yield a mean PTV dose of 2 Gy and the corresponding MOD was calculated. The degree of OAR sparing was related to the average OAR MODs resulting from the beam orientations utilized with improvements of up to 10% at some dose levels. On the other hand, OAR DVHs in the IMRT plans were insensitive to beam numbers (in the 6-9 range) for similar average single-beam MODs. These MOD data were input to an IP optimization process, which then selected specified numbers of beam angles as inputs to a treatment planning system. Our results show that sets of beam angles with lower average single-beam MODs produce IMRT plans with better OAR sparing than manually selected beam angles. To optimize beam orientations, weights were assigned to each OAR following MOD input to the IP which was subsequently solved using the branch-and-cut algorithm. Seven-beam orientations obtained from solving the IP were applied to the test case with four OARs and the resulting plan with a dose prescription of 63 Gy was compared with an equi-spaced beam plan. The IP selected beams produced dose-volume improvements of up to 40% for OARs proximal to the PTV. Further improvement in the DVH can be obtained by increasing the weights assigned to these OARs but at the expense of the remaining OARs.

Abdomen↗

PubMed2005

Improvement of image quality in chest MDCT using nonlinear wavelet shrinkage with trimmed-thresholding.

Multidetector-row computed tomography (MDCT) has dramatically increased the speed of scanning, and allows high-resolution imaging compared with conventional single detector-row CT (SDCT). However, the use MDCT makes use of an increase in volume scanning, and causes a simultaneous increase in radiation dose to the patient. Thus, the radiation dose from the X-ray CT has become a problem in recent years. In this study, nonlinear wavelet-based edge preservation de-noising using trimmed-thresholding was applied to reconstructed low-dose chest MDCT images, and optimal wavelet processing including wavelet functions and thresholding methods was examined. Moreover, the usefulness of the de-noising for reducing radiation dose was examined. As a result of optimized edge preservation de-noising, noise reduction was achieved with little deterioration in image quality, and the wavelet function used at that time was Coiflet's with shorter support. As a result, almost the same quality of reconstructed image of the chest phantom was obtained for conventional scanning and low-dose scanning with the wavelet de-noising method using trimmed- thresholding. That is, the radiation dose from MDCT could be reduced using this wavelet-based de-noising method.

Humans↗

PubMedDate not supplied

The remedial year in the general surgery board certification process: how effective is it?

BACKGROUND: The American Board of Surgery (ABS) intends to assure high standards for knowledge and experience in every graduate from an approved general surgery program. They have gone to great lengths to devise an optimal remediation process for every candidate failing to reach these standards. But what is the effectiveness of the remediation process? METHODS: ABS data outlined the history and development of the remediation process up to its current form. A core component of this process is a specifically structured additional year of training at selected institutions. Ten institutions, which were classified as outstanding by the ABS, received a standardized confidential questionnaire to collect data that included the institution's impetus to administer a remedial year (RY), organization of their RY, specific emphasis points, role of advisors, funding, and choice of RY candidates. Each institution was asked to mail a letter to their RY graduates, asking for their participation in a follow-up study aimed at characterizing the failing candidate. RESULTS: ABS data have been available since 1980. Pass rates for the qualifying written examination (QE) improved steadily from about 63% in 1985 to 78% in 2003. Pass rates for the certifying oral examination (CE) have been consistently around 75% since 1985 with improvement to just above 80% within the last 4 years. In 1995, a new ABS policy was announced requiring an additional year of structured training with specific elements. For the QE, the general pool pass rates continued their steady improvement. Although the results for RY candidates did reveal a 20% improved pass rate, they were still 30 percentage points lower when compared with the general pass rates. No improvement was noted in the CE results. In 2003, ABS enacted the latest policy change, which consists of an alternative pathway for QE. The initial experience for 2003 is disappointing. Less than 10 candidates have taken advantage of this alternative, and pass rates have not improved. The policy for CE was changed to allow 5 attempts (up from 3 attempts) in 5 years, and currently it is too early to determine the impact of this change. Nine of 10 institutions agreed to participate in our study. They identified the essential elements of a successful RY. They also emphasized that CE remediation has to go beyond correction of simple knowledge deficits. And they characterized the ideal candidate for remediation. No RY graduates agreed to participate in the planned follow-up study to characterize the failing candidate. CONCLUSION: The RY process seems to have a valid potential if specific conditions are met. We do believe that differentiation is needed between the QE and the CE remedial year programs. Because the CE incorporates rhetorical skills, an emphasis should be placed on public speaking and presentation skills in a remedial year for the CE. We recommend several possible avenues for consideration: identifying the resident at risk and intervening during residency, incorporating the RY process into the ongoing practice routine of the individual candidate, and actively recruiting participation of candidates in a needs assessment study.

Certification↗

PubMedDate not supplied

Optimization of microencapsulation of acrylic adhesives.

The preparation of microcapsules of an acrylic adhesive in a solvent medium with reticulated walls of melamine-formaldehyde was studied. In order to obtain the best experimental conditions for this process, the methodology of factorial design was used. It was found that, among the 11 tested parameters, four had an important effect on the microencapsulation: amount of wall polymer, amount and nature of the copolymer, GANTREZ, and amount of adhesive in the core. The process was optimized using a surface response methodology. A layer of microcapsules deposited on paper gave, after manual breakage, very good adhesive properties.

Acrylates↗

PubMed2003

Intensity-modulated stereotactic radiotherapy vs. stereotactic conformal radiotherapy for the treatment of meningioma located predominantly in the skull base.

PURPOSE: This study evaluates a possible advantage of intensity-modulated stereotactic radiotherapy (IMSRT) over stereotactic conformal radiotherapy (SCRT) in the treatment of lesions in the base of the skull. METHODS AND MATERIALS: Ten patients (7 with a skull base meningioma) planned for routine SCRT were replanned for IMSRT. The criteria for comparison were the same for both methods: optimal dose to the planning target volume (PTV) and optimal sparing of the organs at risk (OAR). For SCRT, sparing of OAR was achieved by conformal avoidance using 5-6 fields. The IMSRT inverse planning process used optimized OAR sparing through user-defined dose constraints. Dose to the PTV and OAR were assessed by dose-volume histograms, maximum dose, 2 conformity indices, and volumes of relevant isodoses. RESULTS: The conformity index is consistently higher for IMSRT, the largest improvement being for the multifocal and irregular cases. Volumes of the 90% and 80% isodoses were smaller for IMSRT, whereas the volume of the 30% isodose was larger for IMSRT in 6 cases. The maximum dose was consistently higher for IMSRT (mean values 102% and 108% for SCRT and IMSRT, respectively). Sparing of OAR was better with IMSRT, especially for those OARs situated in or near a concave PTV. CONCLUSIONS: In terms of PTV coverage, there is an advantage in using IMSRT for all target shapes, but especially for irregular and concave targets. The dose to OAR is lower with IMSRT, although the volume of normal tissue receiving a low dose can be larger than for SCRT.

Aged↗

PubMed1996

The review process used by US health care plans to evaluate new medical technology for coverage.

OBJECTIVE: To examine the process and information used by medical directors (MDs) of private health plans to make medical coverage determinations for new medical technologies, and to assess the influence of plan characteristics on the process. DESIGN: Cross-sectional national survey. PARTICIPANTS: Two hundred thirty-one MDs at private health plans representing 66% and 72% of the US population covered by HMOs and indemnity plans, respectively. MEASUREMENTS: Actual and optimal review process, final decision authority, sources, and evidence used for technology coverage decisions. RESULTS: In 96% of plans, MDs take part in the medical policy review process for new technology. However, MDs have final authority over coverage decisions in only 27% of plans. Indemnity plans are more likely to assert that MDs should be responsible for final decisions, odds ration (OR) = 3.3 (95% confidence interval [95% CI] 1.4, 10). Optimal sources of information of new technology were journals, medical society statements or practice guidelines, and opinions of national experts. Actual sources of information used differed from optimal ones; local experts were used more often than is considered optimal (p < .001). For-profit plans were more likely than nonprofit plans to use national experts, OR 2.5 (95% CI 1.3, 5.0), and practice guidelines, OR 5.0 (95% CI 2.5, 10). Randomized trials (94% of MDs) meta-analyses (61%), and reviews (42%) were considered the best evidence for making coverage decisions. Barriers to making optimal decisions were lack of timely evidence on effectiveness and cost-effectiveness, not legal or regulatory issues; HMO, small, and nonprofit plans were two or three times more likely to list lack of cost-effectiveness data than their counterparts (p < .05). CONCLUSIONS: Although MDs are nearly always involved in the technology evaluation process, a minority of MDs retain final authority over coverage decisions. Evidence from strong scientific research designs is the most frequently cited basis for decisions, but there is need for more timely, rigorous scientific evidence on medical interventions. How a health plan evaluates a new medical technology for coverage varies with identifiable plan characteristics.

Cross-Sectional Studies↗

PubMed2006

Polyhedral organelles compartmenting bacterial metabolic processes.

Bacterial polyhedral organelles are extremely large macromolecular complexes consisting of metabolic enzymes encased within a multiprotein shell that is somewhat reminiscent of a viral capsid. Recent investigations suggest that polyhedral organelles are widely used by bacteria for optimizing metabolic processes. The distribution and diversity of these unique structures has been underestimated because many are not formed during growth on standard laboratory media and because electron microscopy is required for their observation. However, recent physiological studies and genomic analyses tentatively indicate seven functionally distinct organelles distributed among over 40 genera of bacteria. Functional studies conducted thus far are consistent with the idea that polyhedral organelles act as microcompartments that enhance metabolic processes by selectively concentrating specific metabolites. Relatively little is known about how this is achieved at the molecular level. Possible mechanisms include regulation of enzyme activity or efficiency, substrate channeling, a selectively permeable protein shell, and/or differential solubility of metabolites within the organelle. Given their complexity and distinctive structure, it would not be surprising if aspects of their biochemical mechanism are unique. Therefore, the unusual structure of polyhedral organelles raises intriguing questions about their assembly, turnover, and molecular evolution, very little of which is understood.

Bacteria↗

PubMedDate not supplied

Design and optimization of hot-filling pasteurization conditions: Cupuaçu (Theobroma grandiflorum) fruit pulp case study.

Cupuaçu (Theobroma grandiflorum) is an Amazonian tropical fruit with a great economic potential. Pasteurization, by a hot-filling technique, was suggested for the preservation of this fruit pulp at room temperature. The process was implemented with local communities in Brazil. The process was modeled, and a computer program was written in Turbo Pascal. The relative importance among the pasteurization process variables (initial product temperature, heating rate, holding temperature and time, container volume and shape, cooling medium type and temperature) on the microbial target and quality was investigated, by performing simulations according to a screening factorial design. Afterward, simulations of the different processing conditions were carried out. The holding temperature (T(F)) and time (t(hold)) affected pasteurization value (P), and the container volume (V) influenced largely the quality parameters. The process was optimized for retail (1 L) and industrial (100 L) size containers, by maximizing volume average quality in terms of color lightness and sensory "fresh notes" and minimizing volume average total color difference and sensory "cooked notes". Equivalent processes were designed and simulated (P(91)( degrees )(C) = 4.6 min on Alicyclobacillus acidoterrestris spores) and final quality (color, flavor, and aroma attributes) was evaluated. Color was slightly affected by the pasteurization processes, and few differences were observed between the six equivalent treatments designed (T(F) between 80 and 97 degrees C). T(F) >/= 91 degrees C minimized "cooked notes" and maximized "fresh notes" of cupuaçu pulp aroma and flavor for 1 L container. Concerning the 100 L size, the "cooked notes" development can be minimized with T(F) >/= 91 degrees C, but overall the quality was greatly degraded as a result of the long cooling times. A more efficient method to speed up the cooling phase was recommended, especially for the industrial size of containers.

Bacillus↗

PubMed1995

Pro: early extubation after cardiac surgery decreases intensive care unit stay and cost.

The recurrent or new trends of early extubation after cardiac surgery are here to stay in the 1990s. The preoperative status does not necessarily predict the postoperative course and prolonged mechanical ventilation following cardiac surgery should not be uncritically considered as routine. All patients should be assessed for tracheal extubation at the earliest opportunity when the criteria are met in the ICU. Early extubation post-cardiac surgery does reduce ICU and hospital length of stay and costs. It also allows early ICU discharge and reduces case cancellations without any increase in postoperative complications and readmission. These studies have emphasized that the change in the process of care to early extubation can affect patient outcome as well as costs in cardiac patient care. The substantial difference in cost savings per cardiac case between "criteria discharge" and "actual discharge" points out the importance of the organization of the process of care being delivered. To achieve maximum cost benefit from early extubation in cardiac patients, the organization of the perioperative management of these patients must be optimized. This process of care includes intraoperative anesthetic modification; organization of ICU and staff expertise; postoperative early extubation and management; acute pain service; ICU discharge policy; utilization of step-down unit and surgical ward; and communication among cardiac patient management teams (cardiovascular surgeon, cardiac anesthesiologist, ICU staff, nurses, respiratory therapists, physiotherapists, and social workers), which are all vital to the success of such a program.

Cardiac Surgical Procedures↗

PubMed1999

A process economic approach to develop a dilute-acid cellulose hydrolysis process to produce ethanol from biomass.

Successful deployment of a bioethanol process depends on the integration of technologies that can be economically commercialized. Pretreatment and fermentation operations of the traditional enzymatic bioethanol-production process constitute the largest portion of the capital and operating costs. Cost reduction in these areas, through improved reactions and reduced capital, will improve the economic feasibility of a large-scale plant. A technoeconomic model was developed using the ASPEN Plus modeling software package. This model included a two-stage pretreatment operation with a co-current first stage and countercurrent second stage, a lignin adsorption unit, and a cofermentation unit. Data from kinetic modeling of the pretreatment reactions, verified by bench-scale experiments, were used to create the ASPEN Plus base model. Results from the initial pretreatment and fermentation yields of the two-stage system correlated well to the performance targets established by the model. The ASPEN Plus model determined mass and energy-balance information, which was supplied to an economic module to determine the required selling price of the ethanol. Several pretreatment process variables such as glucose yield, liquid: solid ratio, additional pretreatment stages, and lignin adsorption were varied to determine which parameters had the greatest effect on the process economics. Optimized values for these key variables became target values for the bench-scale research, either to achieve or identify as potential obstacles in the future commercialization process. Results from this modeling and experimentation sequence have led to the design of an advanced two-stage engineering- scale reactor for a dilute-acid hydrolysis process.

Journal Article↗

PubMed2004

A stochastic model simulating the capture of pathogenic micro-organisms by superparamagnetic particles in an isodynamic magnetic field.

The method of immunomagnetic separation (IMS) has become an established technique to concentrate and separate animal cells, biologically active compounds and pathogenic micro-organisms from clinical, food and environmental matrices. One drawback of this technique is that the analysis is only possible for small sample volumes. We have developed a stochastic model that involves numerical simulations to optimize the process of concentration of pathogenic micro-organisms onto superparamagnetic carrier particles (SCPs) in a gradient magnetic field. Within the range of the system parameters varied in the simulations, optimal conditions favour larger particles with higher magnetite concentrations. The dependence on magnetic field intensity and gradient together with concentration of particles and micro-organisms was found to be less important for larger SCPs but these parameters can influence the values of the collision time for small particles. These results will be useful in aiding the design of apparatus for immunomagnetic separation from large volume samples.

Anisotropy↗

PubMed1986

In vivo experiments with the excimer laser--technical parameters and healing processes.

In vivo experiments on rabbit corneae with the excimer laser (lambda = 193 nm) are presented. A new delivery system using total-reflecting prisms is described. For corneal surgery a repetition rate of about 50 Hz seems to be optimal. Healing processes of the cornea are demonstrated. It is supposed that the corneal incisions by excimer laser have not to be as deep as those induced by knives to change corneal curvature.

Animals↗