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At least 433 records · Page 24Linked to original sources

Microwave-assisted solvent extraction and gas chromatography ion trap mass spectrometry procedure for the determination of persistent organochlorine pesticides (POPs) in marine sediment.

Microwave-assisted solvent extraction of persistent organochlorine pesticides (POPs) in marine sediment was developed and optimized by means of two-level factorial designs. Six variables (microwave power, extraction time and temperature, amount of sample, solvent volume, and sample moisture) were considered as factors in the optimization process. The results show that the amount of sample to be extracted and solvent volume are statistically significant for the overall recovery of the studied pesticides, although compromise conditions have to be established with the object of avoiding overpressure in closed vessels. After extraction, a clean up step including the use of a silica cartridge was performed prior to chromatographic determination in order to remove interferences. The optimized procedure was compared to conventional Soxhlet extraction. The MS-MS ion preparation mode was applied to improve the sensitivity and selectivity of the chromatographic technique.

Gas Chromatography-Mass Spectrometry↗

Disinfection and dewatering of wastewater solids by interstitial vapor generation.

Disinfection of wastewater solids (waste activated solids [WAS]) by interstitial vapor generation was investigated. In addition to the magnitude of disinfection, the amount of water removed and cost relative to traditional residuals disinfection processes was also examined. The process of interstitial vapor generation occurs as a result of the rapid heating of liquid in the interstices of the solid-liquid array. Intense heating causes boiling of the slurry liquid, resulting in an expanding vapor front that simultaneously dewaters the wastewater solids and contributes to the destruction of viable pathogenic microorganisms. Objectives of the study were threefold: (1) to validate disinfection of WAS using the interstitial vapor technique; (2) establish the degree of possible drying of the residuals using the techniques; and (3) establish the key operating variables for the process. Results showed a significant reduction in the most probable number of total coliforms and Escherichia coli (E. coli). Specifically, greater than four-log unit reductions were produced for both total coliform and E. coli bacteria. In addition to quantifying the reduction in bacteria, the percent solids were increased from an initial amount of 7.6% (mass basis) to a final solids content greater than 90% using optimal processing conditions. Cost comparisons were also conducted and shown to be quite favorable when compared with traditional disinfection methods such as lime addition. Because of the high level of E. coli reduction achieved, the process of interstitial vapor generation is shown to be capable of converting a class B biosolids into a class A pathogen reduced product. For example, an initial most probable number (MPN) of 1.2 x 10(6) E. coli bacteria were reduced to 19 at the extreme conditions of the process, well below the requirement of an MPN of 1000 for fecal coliform bacteria. Given its ability to disinfect and dewater wastewater solids, the interstitial vapor generation process was found to be a robust and beneficial technique to produce an environmental and publicly acceptable recyclable biosolids resource.

Bacteria↗

Proteomic investigation of metabolic shift in mammalian cell culture.

Mammalian cells, under typical cultivation conditions, produce large quantities of lactate and ammonia that affect cell growth adversely and result in low cell concentration. Controlled nutrient feeding to maintain low concentrations of glucose and glutamine reduces metabolite production drastically, altering the metabolism of the cells. This metabolic shift results in higher cell concentration in continuous cultures and does not affect the specific productivity of the cells. We have taken a proteomics approach to investigate the differential protein expression with metabolic shift. Using two-dimensional gel electrophoresis (2-DE) and mass spectrometry (MS), we have found at least eight differentially expressed spots; two proteins were down-regulated, and the others were up-regulated with metabolic shift. These included metabolic enzymes, the brain form of phosphoglycerate mutase, which was down-regulated, and the precursor of the 23 kDa subunit of NADH-ubiquinone oxidoreductase, which was up-regulated. Another enzyme, the L1 isozyme of ubiquitin carboxyl-terminal hydrolase, which is involved in protein turnover and degradation, was also up-regulated in the metabolically altered cells. The remaining down-regulated spot had been identified as two isoforms of cytoplasmic actins, while three of the up-regulated spots were viral GAG polyproteins from various murine viruses. An unidentified protein was also up-regulated in the cells with altered metabolic state. This study shows the potential of using a proteomics approach in deciphering the intracellular changes in cells with physiological changes such as metabolism shift. The new insight into cell metabolism afforded by this analysis will greatly facilitate process optimization of continuous cell cultures.

Alkylation↗

Design of experiments for capillary electrophoretic enantioresolution of salbutamol using dermatan sulfate.

Statistical experimental design was used for the optimization and for robustness evaluation of a capillary electrophoretic method developed for the enantioresolution of salbutamol. Dermatan sulfate was used as chiral selector. The goal of the study was to obtain an efficient and fast separation. An eight-run Plackett-Burman matrix was used during the optimization process for the screening of the factors and to adjust the experimental domain under study. Response surface methodology was adopted after the screening phase to obtain information about how the factors percentage of chiral selector, pH and voltage affected the considered responses resolution and analysis time. The Derringer desirability function, which makes it possible to combine results obtained for properties measured on different scales, was used to simultaneously optimize the two responses. Robustness testing was carried out using a Plackett-Burman matrix. The method was found robust as regards the response resolution while voltage and chiral selector were found to be critical factors for the robustness of analysis time response. The proposed CE method permitted the complete enantioseparation of racemic salbutamol and was applied to its chiral resolution in spiked urine samples.

Adrenergic beta-Agonists↗

Microinjection of DNA into the nuclei of human vascular smooth muscle cells.

BACKGROUND: It is challenging to successfully transfect human vascular cells by conventional techniques. We evaluated the efficiency of transfection of human smooth muscle cells (SMC) using a method of direct nuclear microinjection of DNA constructs. MATERIALS AND METHODS: The nuclei of explanted human saphenous vein SMC were microinjected with the plasmid pCMVbeta, containing the lacZ gene for beta-galactosidase (beta-gal). Efficiency of injection and expression were assessed by histochemical staining for beta-gal. Injected SMC were subjected to standard assays of viability and migration. RESULTS: Parameters affecting the conditions of injection were systematically analyzed to achieve optimal transfection efficiency. A vertical injection resulted in a twofold increase in expression of beta-gal compared to a horizontal approach. A DNA concentration of 100 ng/microl (390 copies/injection) provided a maximal rate of expression. No further increase in expression was evident at higher concentrations. Maximal expression was achieved with a time of injection of 200-500 ms, an injection pressure of 5-10 psi, and a pipette tip size of 0.6 microm, resulting in an injection volume of 0.03 pl. Cytoplasmic injection did not result in gene expression. The ability of SMC to migrate under videomicroscopy was not altered by the injection process. Optimizing all injection parameters resulted in cell viability >95% and efficiency of injection of 59%. CONCLUSION: DNA encoding a variety of intracellular proteins can be efficiently microinjected into human vascular SMC. Coupled with the use of videomicroscopy, this technique can allow for the evaluation of genes that might modulate important cellular processes such as proliferation and migration.

Cell Movement↗

Aqueous ethylcellulose dispersion of ethylcellulose. I. Evaluation of coating process variables.

Formulation and process variables play an important role in the film-forming properties of coating polymers. Three selected independent coating process variables, namely, percent solids content in the coating polymeric dispersion, inlet-air temperature, and spray rate of the polymeric dispersion, were investigated in this study to determine their effect on the performance characteristics of tablets coated with a plasticized aqueous ethylcellulose dispersion (Sure-lease) in a fluid-bed equipment. Response surface methodology (RSM) was utilized to study the complex relationship between these process variables and selected response variables. Three response variables were considered, namely, rate of drug release from the "untreated" coated tablets and the "thermal-treated" coated tablets and microindentation hardness of the untreated coated tablets. A 12-point factorial experimental design was utilized, and three-dimensional (3-D) response surface plots were generated using a second-order polynomial model. The model provided information needed to predict optimal process conditions. Drug release from the coated tablets followed zero-order kinetics. Inlet-air temperature was found to be the most critical process variable for all the three response variables studied. A correlation was observed between the drug release rate and the microindentation hardness of the applied polymeric coat in the case of untreated coated tablets. The 3-D response surface plots indicated that lower rates of drug release from the coated tablets may be obtained by using high inlet-air temperature and low spray rate of the polymeric dispersion during coating.

Cellulose↗

Impact of nonlinear heat transfer on temperature control in regional hyperthermia.

We describe an optimization process specially designed for regional hyperthermia of deep-seated tumors in order to achieve desired steady-state temperature distributions. A nonlinear three-dimensional heat transfer model based on temperature-dependent blood perfusion is applied to predict the temperature. Using linearly implicit methods in time and adaptive multilevel finite elements in space, we are able to integrate efficiently the instationary nonlinear heat equation with high accuracy. Optimal heating is obtained by minimizing an integral objective function which measures the distance between desired and model predicted temperatures. A sequence of minima is calculated from successively improved constant-rate perfusion models employing a damped Newton method in an inner iteration. We compare temperature distributions for two individual patients calculated on coarse and fine spatial grids and present numerical results of optimizations for a Sigma 60 Applicator of the BSD 2000 Hyperthermia System.

Algorithms↗

Optimization of road networks using evolutionary strategies

A road network usually has to fulfill two requirements: (i) it should as far as possible provide direct connections between nodes to avoid large detours; and (ii) the costs for road construction and maintenance, which are assumed proportional to the total length of the roads, should be low. The optimal solution is a compromise between these contradictory demands, which in our model can be weighted by a parameter. The road optimization problem belongs to the class of frustrated optimization problems. In this paper, a special class of evolutionary strategies, such as the Boltzmann and Darwin and mixed strategies, are applied to find differently optimized solutions (graphs of varying density) for the road network, depending on the degree of frustration. We show that the optimization process occurs on two different time scales. In the asymptotic limit, a fixed relation between the mean connection distance (detour) and the total length (costs) of the network exists that defines a range of possible compromises. Furthermore, we investigate the density of states, which describes the number of solutions with a certain fitness value in the stationary regime. We find that the network problem belongs to a class of optimization problems in which more effort in optimization certainly yields better solutions. An analytical approximation for the relation between effort and improvement is derived.

Journal Article↗

Optimal design of non-Newtonian, micro-scale viscous pumps for biomedical devices.

The present paper addresses the numerical optimization of geometrical parameters of non-Newtonian micro-scale viscous pumps for biomedical devices. The objective is to maximize the mass flow rate per unit of shaft power consumed by the rotor when an external pressure load is applied along the channel that houses the rotor. Two geometric parameters are considered in the optimization process: (i) the height of the channel that houses the rotor (H) and (ii), the eccentricity (epsilon) of the rotor. Three different micro-scale viscous pump configurations were tested: a straight-housed pump (I-shaped housing) and two curved housed pumps (L- and U-shaped housings). The stress-strain constitutive law is modeled by a power-law relation. The results show that the geometric optimization of micro-scale viscous pumps is critical since the mass flow rate propelled by the rotor is highly dependent on epsilon and H. Numerical simulations indicate that mass flow rate is maximized when epsilon approximately 0, namely when the rotor is placed at a distance of 0.05 radii from the lower wall. The results also show that micro-scale viscous pumps with curved housing provide higher mass flow rate per unit of shaft power consumed when compared with straight-housed pumps. The results are presented in terms optimized dimensions of all three configurations (i.e., H(opt) and epsilon(opt)) and for values of the power-law index varying between 0.5 (shear thinning fluids) and 1.5 (shear-thickening fluids).

Biomedical Engineering↗

Optimal design of connectivity in neural network training.

Many authors consider neural network (NN) supervised training as an optimization process during which the weights are iteratively adjusted in order to minimise an error (cost) function, which represents the difference between the obtained and the aimed output. The error function surface is usually nonconvex, can be highly convoluted, with many plateaux and long narrow troughs, and can encounter many saddle and local minima (LM) points. Because backpropagation (BP), which is widely used method for supervised learning, uses local methods for optimization, it can get stuck in LM. This can make learning very difficult and sometimes its convergence to optimal solution--not possible. In this paper we propose a stochastic method for global optimization (GO), which make use of a uniformly distributed LP tau sequence of points. The developed technique is tested with common benchmark problems and used for neural network supervised learning. The conducted tests show that the proposed method can be successfully used for an optimal supervised training of small size NN.

Neural Networks, Computer↗

Multiple microfermentor battery: a versatile tool for use with automated parallel cultures of microorganisms producing recombinant proteins and for optimization of cultivation protocols.

A multiple microfermentor battery was designed for high-throughput recombinant protein production in Escherichia coli. This novel system comprises eight aerated glass reactors with a working volume of 80 ml and a moving external optical sensor for measuring optical densities at 600 nm (OD600) ranging from 0.05 to 100 online. Each reactor can be fitted with miniature probes to monitor temperature, dissolved oxygen (DO), and pH. Independent temperature regulation for each vessel is obtained with heating/cooling Peltier devices. Data from pH, DO, and turbidity sensors are collected on a FieldPoint (National Instruments) I/O interface and are processed and recorded by a LabVIEW program on a personal computer, which enables feedback control of the culture parameters. A high-density medium formulation was designed, which enabled us to grow E. coli to OD600 up to 100 in batch cultures with oxygen-enriched aeration. Accordingly, the biomass and the amount of recombinant protein produced in a 70-ml culture were at least equivalent to the biomass and the amount of recombinant protein obtained in a Fernbach flask with 1 liter of conventional medium. Thus, the microfermentor battery appears to be well suited for automated parallel cultures and process optimization, such as that needed for structural genomics projects.

Automation↗

Clinical treatment planning optimization by Powell's method for gamma unit treatment system.

PURPOSE: This article presents a new optimization method for stereotactic radiosurgery treatment planning for gamma unit treatment system. METHODS AND MATERIALS: The gamma unit has been utilized in stereotactic radiosurgery for about 30 years, but the usual procedure for a physician-physicist team to design a treatment plan is a trial-and-error approach. Isodose curves are viewed on two-dimensional computed tomography (CT) or magnetic resonance (MR) image planes, which is not only time consuming but also seldom achieves the optimal treatment plan, especially when the isocenter weights are regarded. We developed a treatment-planning system on a computer workstation in which Powell's optimization method is realized. The optimization process starts with the initial parameters (the number of isocenters as well as corresponding 3D isocenters' coordinates, collimator sizes, and weight factors) roughly determined by the physician-physicist team. The objective function can be changed to consider protection of sensitive tissues. RESULTS: We use the plan parameters given by a well-trained physician-physicist team, or ones that the author give roughly as the initial parameters for the optimization procedure. Dosimetric results of optimization show a better high dose-volume conformation to the target volume compared to the doctor's plan. CONCLUSION: This method converges quickly and is not sensitive to the initial parameters. It achieves an excellent conformation of the estimated isodose curves with the contours of the target volume. If the initial parameters are varied, there will be a little difference in parameters' configuration, but the dosimetric results proved almost to be the same.

Algorithms↗

Analytical anion-exchange HPLC of recombinant type-5 adenoviral particles.

The expanding use of adenoviral vectors for gene therapy has brought about the need for new analytical tools. We have developed an anion-exchange high-performance liquid chromatography method to analyze recombinant adenovirus serotype 5 samples. Before this assay, available analytical methods consisted of either long-term biological assays or required highly purified test articles. These methods were inadequate for optimizing adenovirus production and purification. This assay can quantitate viral particles in either crude lysates or highly pure samples. It can be used to assess particles in both dilute and concentrated samples over a wide dynamic range. Moreover, the population of viral particles eluted in the peak contains most of the infectious virions. This assay is a sensitive technique that overcomes the limitations of previous methods. It provides an essential tool to accomplish process optimization.

Adenoviridae↗

Resolution of recombinant human interleukin 10 from variants by recycling free flow focusing.

Recombinant human interleukin 10 (rhIL-10) is a potential human therapeutic agent for treating inflammatory bowel diseases and rheumatoid arthritis. The rhIL-10 molecule derived from Escherichia coli including bodies consists of two identical subunits forming a noncovalent dimer. Since the ability to separate rhIL-10 from closely related impurities was highly desirable, recycling free flow focusing (RFFF) was utilized for the purification process development of rhIL-10. Under nondenaturing conditions, RFFF was able to separate rhIL-10 from fractions enriched in rhIL-10 variants. Three major monomeric variants (A, B, and C) can be identified and quantitated by reversed phase HPLC. The isoelectric point (pI) of rhIL-10 was empirically determined to be 8.2 while that for the three variant populations were in the range 7.3-7.5. Knowledge of these pI's would potentially facilitate the optimization process for ion-exchange chromatography. Furthermore, the technique provided a mild and fast preparation procedure for obtaining the recombinant protein and its variants for further characterization, as evidenced in the separation of rhIL-1- from variant C by successive RFFF treatments.

Humans↗

Electrostatic force-assisted nanoimprint lithography (EFAN).

We present and demonstrate a novel imprint method, electrostatic force-assisted nanoimprint lithography (EFAN), where a voltage applied between a mold and a substrate generates an electrostatic force that presses the mold into a resist on the substrate. We have successfully used EFAN to pattern nanostructures in a photocurable resist spin-coated on a wafer, with high fidelity and excellent uniformity over the entire substrate, in ambient atmosphere without using a vacuum chamber. In initial tests without any process optimization, 100 nm half-pitch gratings with a residual layer thickness of 22+/-5 nm were imprinted across a 100 mm diameter wafer in about 2 s. Furthermore, numerical calculations show that the field magnitude experienced by the dielectric layers on the substrate is much less than their breakdown limit. Hence, EFAN is well suited for step-and-repeat nanoimprint lithography, and its simple operation can simplify and speed up multilayer alignment process.

Crystallization↗

Genetic algorithm-assisted combinatorial search for a new green phosphor for use in tricolor white LEDs.

An evolutionary optimization process involving a genetic algorithm and combinatorial chemistry was employed for the development of green phosphors which are suitable for tricolor white-light-emitting diodes. To accomplish a high luminescent efficiency at 400 nm excitation, we screened a seven-cation oxide system including Tb, Gd, Ce, Mg, Si, Al, and B. The combination of a genetic algorithm and combinatorial chemistry enhanced the searching efficiency when applied for phosphor screening. As a result, the optimized composition was Tb(0.01)Gd(0.02)Ce(0.04)B(0.1)Si(0.83)O(delta), The luminance of this borosilicate glass was 67% that of ZnS:Cu,Al at 400-nm excitation.

Algorithms↗

Drug interactions: concerns and current approaches.

Following the recent withdrawal of several prominent drugs from US and European markets because of detrimental drug-drug interactions, metabolic drug interactions have received considerable attention in the pharmaceutical industry. In turn, the question of drug safety has received significant legal, regulatory and commercial emphasis, bringing this issue to the forefront of both industry and government drug agendas. The value of predicting the drug interactions of compounds as early as possible in the drug discovery process for all therapeutic areas cannot be underestimated. From 1964 to 1999, approximately 8% of the drugs approved by the FDA were later withdrawn from the US market. Pharmaceutical companies are facing increasing pressure to prove the long-term safety of their products, and this is complicated by the fact that animal models are not perfectly predictive of human responses, and may provide contradictory information. The failure to address safety concerns successfully during the drug optimization process may result in companies withdrawing any approved drugs from the market; drug safety issues not only present human health consequences, but also have a negative economic and public relations impact on the pharmaceutical industry. This paper discusses the significance of drug interactions, and addresses strategies to evaluate the potential of a drug candidate for drug interactions.

Animals↗

Rigorous electromagnetic design of finite-aperture diffractive optical elements by use of an iterative optimization algorithm.

We propose a rigorous electromagnetic design of two-dimensional and finite-aperture diffractive optical elements (DOEs) that employs an effective iterative optimization algorithm in conjunction with a rigorous electromagnetic computational model: the finite-difference time-domain method. The iterative optimization process, the finite-difference time-domain method, and the angular spectrum propagation method are discussed in detail. Without any approximation based on the scalar theory, the algorithm can produce rigorous design results, both numerical and graphical, with fast convergence, reasonable computational cost, and good design quality. Using our iterative algorithm, we designed a diffractive cylindrical lens and a 1-to-2-beam fanner for normal-incidence TE-mode illumination, thus showing that the optimization algorithm is valid and competent for rigorously designing diffractive optical elements. Concerning the problem of fabrication, we also evaluated the performance of the DOE when the DOE profile is discrete.

Journal Article↗