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PubMed1980

[Principles for optimizing and gauging certain processes in vaccine production technology. V. Complex approach to gauging processes involved in assuring aseptic conditions in incubators].

The contamination of the cultivator with the extraneous microflora in the process of growing microorganisms in various apparatus has been shown to have the probabilistic character. The index of aseptic effectiveness is recommended for the comparative evaluation of the effectiveness of the processes which ensure the achievement and maintenance of aseptic conditions in the process of the cultivation of microorganisms in the laboratory and industrial equipment, as well as for changing the scale of the process.

Antisepsis↗
PubMed1995

[Optimization of scanning and processing parameters for the three-dimensional reconstruction in computerized tomography of the facial bones].

The evolution of computer technology has significantly improved the performances of three-dimensional reconstructions from Computed Tomographic images. The authors discuss the examination technique and the modalities of three-dimensional reconstruction based upon a new advanced workstation. This unit is based on a Sun Sparkstation linked with the main computer of the CT scanner. The workstation is extremely fast, the processing time for a high resolution three-dimensional image of the maxillofacial region being about 3 minutes. The scanning parameters, image reconstruction and visualization were investigated on cases of maxillofacial (mainly posttraumatic) conditions. The most important scanning parameters are slice thickness, table incrementation, dose, scan plane. Slice thickness and table incrementation are the parameters bearing the greatest influence on the quality of the three-dimensional images. Dose is also important but bears no influence on image quality: therefore it can be kept as low as possible to reduce patient exposure. The scanning plane has some minor effect; coronal images have some advantages over axial images but in many cases only axial images can be acquired. The reconstruction parameters are the threshold and the matrix. The threshold may range 70 to 300 HU but in most cases ranges 120 to 200 HU. An advantage offered by this system is that it allows threshold values to be changed after the reconstruction has been completed, without performing a new reconstruction. The visualization parameters include four rendering methods, i.e. the surface mode, the integral mode, the maximum intensity projection and the ray sum. The surface mode is the one yielding the best results for bones while the others are used for the reconstruction of soft tissues and vessels. The workstation enables the three-dimensional images to be processed with shading parameters, and to be modified with cut planes, disarticulation methods and other interactive methods.

Bone Diseases↗
PubMed1986

Effect of tissue processing on the immunostaining of inflammatory cell surface epitopes identified by monoclonal antibodies.

Optimal tissue processing conditions were defined for the immunohistochemical detection of inflammatory cell surface epitopes identified by OKT3, OKT4, OKT6, OKT8, OKIa1, OKM1, Leu7 and pan B cell antibodies. Snap-freezing in isopentan was superior to liquid nitrogen in preservation of morphology. Embedding of the tissues in Tissue-Tek II O.C.T. Compound diminished the intensity of immunostaining with all antibodies studied; however, the embedded tissues tolerated longer storage without drying. Optimal fixation with satisfactory preservation of morphology and immunogenicity was achieved with fixation of the frozen sections in acetone at 4 degrees C for 5 min. Blocking of the endogenous peroxidase with methanol-H2O2 treatment destroyed all epitopes studied except those identified with OKIa1, OKT6 and Leu7.

Antibodies, Monoclonal↗
PubMed2001

Replicative response, immunophenotype, and functional activity of monocyte-derived versus CD34(+)-derived dendritic cells following exposure to various expansion and maturational stimuli.

Dendritic cells (DCs), generated ex vivo from blood mononuclear cells (PBMC) or CD34(+) stem cells, are being used to develop novel immunotherapies. To establish optimal DC generation, a direct comparison of the optimal cell source, culture conditions, and maturation stimuli was performed, utilizing phenotypic and functional assays as end points. Plastic adherent monocytes from PBMC were expanded in a serum-free medium (X-Vivo 10) for 7 days using GM-CSF/IL-4; CD34(+) cells were expanded for 14 days using GM-CSF/IL-4/ Flt3L, in either X-Vivo 10 alone or with albumin or autologous plasma. Expanded DC from both cell sources were matured for 7 days with CD40L or IFN-alpha/TNF-alpha. Starting from 2 x 10(7) monocytes, the optimal expansion/maturation process yielded 1.73 +/- 0.52 x 10(6) CD86(+) DC. Optimal expansion of CD34(+) cells (83.9 +/- 25.0-fold) was achieved using X-Vivo 10 with 5% plasma, matured with CD40L, and yielded 10.68 +/- 2.72 x 10(6) CD86(+) DC from 1 x 10(6) CD34(+) cells. Mature DC from PBMC or CD34(+) cells had similar enhanced expression of MHC class II HLA-DR, CD80, CD83, and CD86 and were potent stimulators of mixed lymphocyte reactions. Prior to maturation, all groups of DC actively phagocytosed apoptotic melanoma cells (approximately 50% of HLA-DR(+)). CD34(+) DC matured with CD40L or IFN-alpha/TNF-alpha had reduced phagocytic capability (34 and 31% of HLA-DR(+) DC, respectively). Similar expansion and functional activity was found using cryopreserved DC precursors, cultured in gas permeable bags. We conclude that both cell lineages produce potent mature DC, permitting exploration of the optimal clinical strategy to trigger anti-tumor immune responses in patients with malignancies.

Antigens, CD↗
PubMed2002

Continuous twin screw extrusion for the wet granulation of lactose.

The suitability of continuous twin screw extrusion for the wet granulation of alpha-lactose monohydrate was studied and compared with conventional high shear granulation. The influence of process parameters (screw speed and total input rate) and formulation variables (water and polyvinylpyrrolidone (PVP) concentration) on the properties of granules (yield, particle size distribution, friability and compressibility) and tablets (tablet tensile strength, friability and disintegration time) was investigated. Variation of the formulation and process parameters had a major effect on the process feasibility. Optimization of these parameters is required to allow continuous processing and to ensure a high yield. Total input rate, screw speed and water concentration had a minor influence on the granule and the tablet properties. The addition of PVP had no major influence on the granule properties, but significantly affected the tablet characteristics. For granules formulated with and without PVP a yield above 50%, a friability below 30% and a compressibility below 15% was obtained. Tablets without PVP showed a tensile strength below 0.6 MPa, a friability above 1% and a disintegration time below 3 min, whereas tablets with PVP showed a tensile strength above 0.6 MPa, a friability below 1% and a disintegration time ranging from 8 to 15 min. High shear granulation was only possible when PVP was added and it required a higher amount of water. It was concluded that wet granulation of alpha-lactose monohydrate using continuous twin screw extrusion is a robust process and might offer a suitable alternative for high shear granulation in the pharmaceutical industry.

Algorithms↗
PubMed1997

An open medical imaging workstation architecture for platform-independent 3-D medical image processing and visualization.

A need for an entirely new medical workstation design was identified to increase the deployment of 3-D medical imaging and multimedia communication. Recent wide acceptance of the Word Wide Web (WWW) as a general communication service within the global network has shown how big the impact of standards and open systems can be. Information is shared among heterogeneous systems and diverse applications on various hardware platforms only by agreeing on a common format for information distribution. For medical image communications, the Digital Imaging and Communication in Medicine (DICOM) standard is possibly anticipating such a role. Logically, the next step is open software: platform-independent tools, which can as easily be transferred and used on multiple platforms. Application of the platform-independent programming language Java enables creation of plug-in tools, which can easily extend the basic system. Performance problems inherent to all interpreter systems can be circumvented by using a hybrid approach. Computationally intensive functions like image processing functions can be integrated into a natively implemented optimized image processing kernel. Plug-in tools implemented in Java can utilize the kernel functions via a Java-wrapper library. This approach is comparable to the implementation of computationally intensive operations in hardware.

Computer Communication Networks↗
PubMed2005

Do common mechanisms of adaptation mediate color discrimination and appearance? Uniform backgrounds.

Color vision is useful for detecting surface boundaries and identifying objects. Are the signals used to perform these two functions processed by common mechanisms, or has the visual system optimized its processing separately for each task? We measured the effect of mean chromaticity and luminance on color discriminability and on color appearance under well-matched stimulus conditions. In the discrimination experiments, a pedestal spot was presented in one interval and a pedestal + test in a second. Observers indicated which interval contained the test. In the appearance experiments, observers matched the appearance of test spots across a change in background. We analyzed the data using a variant of Fechner's proposal, that the rate of apparent stimulus change is proportional to visual sensitivity. We found that saturating visual response functions together with a model of adaptation that included multiplicative gain control and a subtractive term accounted for data from both tasks. This result suggests that effects of the contexts we studied on color appearance and discriminability are controlled by the same underlying mechanism.

Adaptation, Ocular↗
PubMed2003

[Determination and QSPR study on the electrochemical reduction characteristics of chlorinated aromatic compounds].

The relationship between the reduction characteristics and molecular structure of 87 chlorinated aromatics including naphthalenes, biphenyls, benzenes and phenols was studied by using quantitative structure-property relationship technique. The result indicated that there was significant correlation between reduction potential and the energy of the lowest unoccupied molecular orbital and the number of chlorine atoms in molecule. The study threw more light on the nature of reduction process, and provided valuable basic data for designing and optimizing treatment process.

Benzene↗
PubMed1990

[A computerized method for optimization of radioimmunoassays].

The authors have developed a one step quantitative method for radioimmunoassay optimization. The method is rapid and necessitates only to perform a series of saturation curves with different titres of the antiserum. After calculating the saturation point at several antiserum titres using the Scatchard plot, the authors have produced a table that predicts the main characteristics of the standard curve (Bo/T, Bo and T) that will prevail for any combination of antiserum titre and percentage of sites saturation. The authors have developed a microcomputer program able to interpolate all the data needed to produce such a table from the results of the saturation curves. This computer program permits also to predict the sensitivity of the assay at any experimental conditions if the antibody does not discriminate between the labeled and the non labeled antigen. The authors have tested the accuracy of this optimization table with two in house RIA systems: 17-beta-estradiol, and hLH. The results obtained experimentally, including sensitivity determinations, were concordant with those predicted from the optimization table. This method accelerates and improves greatly the process of optimization of radioimmunoassays.

Humans↗
PubMed2001

Smoothing intensity-modulated beam profiles to improve the efficiency of delivery.

Intensity-modulated beam profiles are generated by an inverse planning or optimization algorithm, a process that, being computationally complex and intensive, is inherently susceptible to noise and numerical artifacts. These artifacts make delivery of the beams more difficult, oftentimes for little, if any, observable improvement in the dose distributions. In this work we examine two approaches for smoothing the beam profiles. The first approach is to smooth the beam profiles subsequent to each iteration in the optimization process (method A). The second approach is to include a term within the objective function that specifies the smoothness of the profiles as an optimization criterion (method B). The two methods were applied to a phantom study as well as three clinical sites: paraspinal, nasopharynx, and prostate. For the paraspinal and nasopharynx cases, which have critical organs with low tolerance doses in close proximity, method B produced sharper dose gradients, better target dose homogeneity, and more critical organ sparing. In the less demanding prostate case, the two methods give similar results. In addition, method B is more efficient during optimization, requiring fewer iterations, but less efficient during DMLC delivery, requiring a longer beam-on time.

Algorithms↗
PubMed2005

Reducing CO2 emissions and energy consumption of heat-integrated distillation systems.

Distillation systems are energy and power intensive processes and contribute significantly to the greenhouse gases emissions (e.g. carbon dioxide). Reducing CO2 emissions is an absolute necessity and expensive challenge to the chemical process industries in orderto meetthe environmental targets as agreed in the Kyoto Protocol. A simple model for the calculation of CO2 emissions from heat-integrated distillation systems is introduced, considering typical process industry utility devices such as boilers, furnaces, and turbines. Furnaces and turbines consume large quantities of fuels to provide electricity and process heats. As a result, they produce considerable amounts of CO2 gas to the atmosphere. Boilers are necessary to supply steam for heating purposes; besides, they are also significant emissions contributors. The model is used in an optimization-based approach to optimize the process conditions of an existing crude oil atmospheric tower in order to reduce its CO2 emissions and energy demands. It is also applied to generate design options to reduce the emissions from a novel internally heat-integrated distillation column (HIDiC). A gas turbine can be integrated with these distillation systems for larger emissions reduction and further energy savings. Results show that existing crude oil installations can save up to 21% in energy and 22% in emissions, when the process conditions are optimized. Additionally, by integrating a gas turbine, the total emissions can be reduced further by 48%. Internal heat-integrated columns can be a good alternative to conventional heat pump and other energy intensive close boiling mixtures separations. Energy savings can reach up to 100% with respect to reboiler heat requirements. Emissions of these configurations are cut down by up to 83%, compared to conventional units, and by 36%, with respect to heat pump alternatives. Importantly, cost savings and more profit are gained in parallel to emissions minimization.

Air Pollution↗
PubMed2004

Optimizing the hit-to-lead process using SPR analysis.

Secondary screening and lead optimization, where a large number of "hit" compounds are refined to a viable set of "lead" drug candidates, are considered to be bottlenecks to the drug discovery process and are targets for streamlining. Surface plasmon resonance (SPR) is a nonlabel technology that can generate kinetic data on biomolecular interactions. This allows researchers to quantitate the binding characteristics of lead compounds with their targets in terms of affinity, specificity, and association/dissociation rates in parallel. The latest generation of SPR biosensors integrate the hit-to-lead process and generate a greater depth of information, providing answers that cannot be addressed by traditional end-point assays. This allows users to make more informed choices on the selection of candidate molecules prior to preclinical development. A number of studies have used SPR biosensors in secondary screening, lead optimization, quantitative structure-activity relationship analysis, and predictive adsorption, distribution, metabolism, excretion, and/or toxicity evaluations.

Biosensing Techniques↗
PubMed2004

Development and optimization of an adenovirus production process.

Adenoviral vectors have a number of advantages such as their ability to infect post-mitotic tissues. They are produced at high titers and are currently used in 28% of clinical protocols targeting mainly cancer diseases through different strategies. The major disadvantages of the first generation of recombinant adenoviruses are addressed by developing new recombinant adenovirus vectors with improved capacity and safety and reduced inflammatory response. To meet increasing needs of adenovirus vectors for gene therapy programs, parallel development of efficient, scalable and reproducible production processes is required. HEK-293 complementing cell line physiology, metabolism and viral infection kinetics were studied at small scale to identify optimal culture conditions. Batch, fed-batch and perfusion culture modes were evaluated. Development of new monitoring tools (in situ GFP probe) and quantification techniques (HPLC determination of total viral particles) contributed to acceleration of process development. On-line monitoring of physiological parameters such as respiration and biovolume of the culture allowed real-time supervision and control of critical phases of the process. Use of column chromatographic steps instead of CsCl gradient purification greatly eased process scale-up. The implementation of the findings at large scale led to the development of an optimized and robust integrated process for adenovirus production using HEK-293 cells cultured in suspension and serum-free medium. The two-step column-chromatography purification was optimized targeting compliance with clinical material specifications. The complete process is routinely operated at a 20-L scale and has been scaled-up to 100 L. Scale-up of adenoviral vector production in suspension and serum-free medium, and purification according to regulatory requirements, are achievable. To overcome metabolic limitations at high cell densities, use of perfusion mode with low-shear cell retention devices is now a common trend in adenovirus manufacturing. Further process improvements will rely on better understanding of the mechanisms of virus replication and maturation in complementing host cells.

Adenoviridae↗
PubMed2001

Application of laser measuring, numerical simulation and rapid prototyping to titanium dental castings.

OBJECTIVES: This paper describes a method of making titanium dental crowns by means of integrating laser measuring, numerical simulation and rapid prototype (RP) manufacture of wax patterns for the investment casting process. METHODS: Four real tooth crowns (FDI No. 24, 25, 26, 27) were measured by means of 3D laser scanning. The laser digitized geometry of the crowns was processed and converted into standard CAD models in STL format, which is used by RP systems and numerical simulation software. Commercial software (MAGMASOFT) was used to simulate the casting process and optimize the runner and gating system (sprue) design. RP crowns were 'printed' directly on a ModelMaker II 3D Plotting System. A silicone negative mold (soft tool) was made from the RP crowns, then more than hundreds wax crowns were duplicated. The duplicated crowns were joined to the optimized runner and gating system. By using the investment casting process 20-25 replicas of each crown were made on a centrifugal casting machine. All castings were examined for porosity by X-ray radiographs. RESULTS: By using the integrated scanning, simulation, RP pattern and casting procedure, cast crowns, free of porosity, with excellent functional contour and a smooth surface finish, were obtained from the first casting trial. SIGNIFICANCE: The coupling of laser digitizing and RP indicates a potential to replace the traditional 'impression taking and waxing' procedure in dental laboratory, with the quality of the cast titanium prostheses also being improved by using the numerically optimized runner and gating system design.

Calcium Sulfate↗
PubMed1996

Dynamical control of the dialysis process. Part II: An improved algorithm for the solution of a tracking problem.

An efficient algorithm for the optimization of process parameters during dialysis has been developed. By solving a tracking-problem for prescribed time courses of distinguished variables, it is possible to compute optimal concentrations of electrolytes in dialysate as well as an optimal rate of ultrafiltration. These variables are indirectly influencing the status of the patient and can be directly modelled. They are describing the important exchange processes between blood and dialysate as well as between the different distribution spaces within the patient during dialysis. Their time courses are determined by an individually identifiable patient model. The tracking problem was treated as a dynamic optimization problem, and a continuous descent procedure which is usually employed for solving unconstrained static optimization problems has been adapted in such a manner that it is applicable for the solution of this problem. The used method is characterized by its simple mode of application, short solution time and moderate storage need. Especially in cases of contradictional requirements for desired time courses of model outputs the used optimization method performs well.

Algorithms↗