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Results for “Process optimization”

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At least 397 records · Page 22Linked to original sources

PubMed1997

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↗

PubMed2005

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↗

PubMedDate not supplied

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↗

PubMed2003

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↗

PubMed2004

Implementation of ALARA radiation protection on the ISS through polyethylene shielding augmentation of the Service Module Crew Quarters.

With 5-7 month long duration missions at 51.6 degrees inclination in Low Earth Orbit, the ionizing radiation levels to which International Space Station (ISS) crewmembers are exposed will be the highest planned occupational exposures in the world. Even with the expectation that regulatory dose limits will not be exceeded during a single tour of duty aboard the ISS, the "as low as reasonably achievable" (ALARA) precept requires that radiological risks be minimized when possible through a dose optimization process. Judicious placement of efficient shielding materials in locations where crewmembers sleep, rest, or work is an important means for implementing ALARA for spaceflight. Polyethylene (CnHn) is a relatively inexpensive, stable, and, with a low atomic number, an effective shielding material that has been certified for use aboard the ISS. Several designs for placement of slabs or walls of polyethylene have been evaluated for radiation exposure reduction in the Crew Quarters (CQ) of the Zvezda (Star) Service Module. Optimization of shield designs relies on accurate characterization of the expected primary and secondary particle environment and modeling of the predicted radiobiological responses of critical organs and tissues. Results of the studies shown herein indicate that 20% or more reduction in equivalent dose to the CQ occupant is achievable. These results suggest that shielding design and risk analysis are necessary measures for reducing long-term radiological risks to ISS inhabitants and for meeting legal ALARA requirements. Verification of shield concepts requires results from specific designs to be compared with onboard dosimetry.

Astronauts↗

PubMed1998

MTD-ADJ: a multiconformational minimal topologic difference for determining bioactive conformers using adjusted biological activities.

The active conformation is part of a conformational mixture with experimental activity Yexp, and is used in QSAR studies to extract more information regarding the ligand-receptor interaction. To reflect the relative amount (alpha) of the active conformation, we adjust Yexp: Yadj = Yexp - log alpha. We establish a quantitative structure-activity relationship (QSAR) between Yadj and 3D conformational characteristics for the acetylcholinesterase (AChE) hydrolysis rates of 25 acetic esters. The 3D-QSAR model was obtained using the adjusted multiconformational minimal steric/topologic difference (MTD-ADJ) method, optimizing the receptor map based on Yadj for each conformer. Yadj was updated during each step of the optimization process. alpha and Yadj are based on the Boltzmann distribution calculated using AMI (MOPAC 6.0) relative energies of the COSMIC 90 derived conformers. The MTD-ADJ results are: (i) the 3D-QSAR models obtained by this procedure have significant statistical parameters and are similar to the unadjusted (MTD-MC, using Yexp) models; (ii) the selected bioactive conformations are extended, occupy cavity vertices and, for the same structures, have the same MTD value; and (iii) the optimized conformational map of the neutral ligands obtained from the MTD-ADJ model fits well in the active site of the crystallographic structure of AChE (from Torpedo californica). We propose a neutral ligands binding site model for AChE. Our results show that MTD-ADJ, which can be implemented in any 3D-QSAR method, is capable of providing additional information regarding the active conformations, and can be used to gain further insight into the ligand-receptor models for which no structural data are available.

Acetylcholinesterase↗

PubMed2002

Study of different off-line sample processing procedures and the measurement of antibiotic and antiviral levels in human serum by high-performance liquid chromatography.

We attempted to devise a preparation method for clinical samples that could be used for all antibiotics and antivirals. We studied thirteen antibiotics, including five penicillins, four cephalosporins, metronidazole, ofloxacin, and sulfamethoxazole and four protease inhibitors including indinavir, retonavir, nelfinavir, and sequinavir. We compared four sample preparation techniques including solvent precipitation, filtration and resin column. We employ HPLC methods based on a minimal number of columns and mobile phases. We were unable to find one sample preparation method that could be used for all antibiotics and antivirals. But, we did develop an algorithm for determining optimal processing procedures for all drugs.

Anti-Bacterial Agents↗

PubMed1993

Cardiovascular applications of the ALOPEX optimization technique.

ALOPEX is a general optimization process incorporating a cost function containing a large number of parameters which may be simultaneously adjusted until the cost function reaches an optimum (maximum or minimum); local extremes are avoided by introducing random noise into the procedure. In this paper, ALOPEX is incorporated into a simple haemodynamic study in which an electric analogue model of the left ventricle is used to develop equations of myocardial stroke work. Pilot experiments were undertaken in rabbits (n = 5) to gauge the effectiveness of this optimizing technique. In the control state, calculated stroke work for the rabbit was determined to be 50 +/- 7 mmHg ml, while ALOPEX predicted a stroke work of 51 +/- 7 mmHg ml. ALOPEX is capable of following changing cardiovascular states when pharmacological agents are introduced. For example, after nitroprusside treatment, stroke work was reduced by 38 +/- 6% (P < 0.05) while ALOPEX predicted a 42 +/- 4% reduction from baseline (P < 0.05). Methoxamine treatment increased stroke work by 74 +/- 34%, while ALOPEX predicted a 73 +/- 43% increase above control values. There were no statistical differences between calculated and ALOPEX predicted values. Individual model parameters such as maximum left ventricular elastance (Emax) and left ventricular end diastolic volume (EDV) were also predicted correctly by ALOPEX. We have found that the ALOPEX optimization technique is useful in predicting components of multi-parametric functions. In particular, we have shown it to be adaptable to a simple haemodynamic model.

Algorithms↗

PubMed2005

Online LC-MS-MS process monitoring for optimization of biological treatment of wastewater containing azo dye concentrates.

A biological high-performance treatment process comprising two 40-L reactor compartments has been developed for purification and decoloration of concentrated textile wastewater containing up to 15 g L(-1) reactive dyestuff. The decoloration rate of 95% meets the requirements of German legislation for textile wastewater treatment. Successful process development and optimization was achieved by use of high-performance liquid chromatography, with diode-array and electrospray tandem mass spectrometric (LC-ESI-MS-MS) detection, coupled with inline microfiltration membrane-sampling devices, applied online to bioreactors as a process analytical tool for the first time. The optimum process performance was found by correlation of dye and decoloration product-specific concentrations with summary properties such as redox potential and dissolved oxygen content. Details of the degradation and decoloration mechanism for the azo dye reactive black 5 was revealed by using mass spectrometry for structure elucidation.

Azo Compounds↗

PubMed2005

Sustained delivery of growth factors from methylidene malonate 2.1.2-based polymers.

The incorporation of growth factors into new methylidene malonate 2.1.2-based biocompatible polymeric blends of oligomers and polymers to improve their stability and controlled release was investigated. Five growth factors were used in this study: FGF2, PDGF, TGF-beta, NGF and GM-CSF. Formulation in poly(methylidene malonate 2.1.2) blends was achieved by a four-step optimized process, using different oligomers/polymers ratios. Once dried, formulations could be subsequently stored at 4 or 20 degrees C or immediately subjected to degradation in conditioned cell culture medium. Toxicity of blends and their degradation products were evaluated in several cell lines with MTT. Bioactivity and biospecificity of the formulated growth factors were investigated using MTT and immunohistochemical staining. Combined ELISA and crystal violet colorimetric assays were performed to analyze growth factors release. Limited toxicities were observed for unloaded poly(methylidene malonate 2.1.2) blends. Once optimized, growth factors formulations did not reveal lower bioactivities or loss of biospecificity. Moreover, a sustained release over a 21-day period with more than 90% of preserved bioactivity was reached. To conclude, dual growth factor delivery was made possible by the mean of poly(methylidene malonate 2.1.2) blends. These studies demonstrate the ability of methylidene malonate 2.1.2-based polymeric blends for the delivery of growth factors.

Animals↗

PubMed2005

Direct electrochemistry of hemoglobin immobilized on gold electrode by Langmuir-Blodgett technique.

In this research, we reported a novel method of forming hemoglobin (Hb)-linoleic acid (LA) Langmuir-Blodgett (LB) monolayer by spreading Hb solution directly onto the subphase covered with a layer of LA. This method is suitable for preparing electrochemical devices with protein-lipid LB film because almost no protein adsorbed on electrode surface before protein-lipid film transferred from air-water interface to electrode, which ensured better electrode activity. The compressibility of Hb-LA monolayer was used to character the phase transition during compression process. Optimal experimental conditions were obtained by analyzing pressure-time, pressure-area and pressure-compressibility curves. The direct electrochemistry of Hb, which was immobilized on Au electrode surface incorporated with LA layer by LB method, was investigated using cyclic voltammetry for the first time. The electrode modified with Hb-LA LB film holds high electrochemical activity and shows a fast direct electron transfer of Hb. Redox peak currents increased linearly with the increase of scan rate, indicating a surface-controlled electrode process. The electron transfer rate constant was 2.68+/-0.45 s-1. As a target of this research, this work provides a new way to prepare biomimetic film and biosensor.

Biosensing Techniques↗

PubMed1993

Intrinsic nature of the three-dimensional structure of proteins as determined by distance geometry with good sampling properties.

A protocol for distance geometry calculation is shown to have excellent sampling properties in the determination of three-dimensional structures of proteins from nuclear magnetic resonance (NMR) data. This protocol uses a simulated annealing optimization employing mass-weighted molecular dynamics in four-dimensional space (Havel, T.F. (1991) Prog. Biophys. Mol. Biol., 56, 43-78). It attains an extremely large radius of convergence, allowing a random coil conformation to be used as the initial estimate for the succeeding optimization process. Computations are performed with four systems of simulated distance data as tests of the protocol, using an unconstrained L-alanine 30mer and three different types of proteins, bovine pancreatic trypsin inhibitor, the alpha-amylase inhibitor Tendamistat, and the N-terminal domain of the 434-repressor. The test of the unconstrained polypeptide confirms that the sampled conformational space is that of the statistical random coil. In the larger and more complicated systems of the three proteins, the protocol gives complete convergence of the optimization without any trace of initial structure dependence. As a result of an exhaustive conformational sampling by the protocol, the intrinsic nature of the structures generated with distance restraints derived from NMR data has been revealed. When the sampled structures are compared with the corresponding X-ray structures, we find that the averages of the sampled structures always show a certain pattern of discrepancy from the X-ray structure. This discrepancy is due to the short distance nature of the distance restraints, and correlates with the characteristic shape of the protein molecule.

Animals↗

PubMed2000

Novel inhibitors of DNA gyrase: 3D structure based biased needle screening, hit validation by biophysical methods, and 3D guided optimization. A promising alternative to random screening.

Random screening provided no suitable lead structures in a search for novel inhibitors of the bacterial enzyme DNA gyrase. Therefore, an alternative approach had to be developed. Relying on the detailed 3D structural information of the targeted ATP binding site, our approach combines as key techniques (1) an in silico screening for potential low molecular weight inhibitors, (2) a biased high throughput DNA gyrase screen, (3) validation of the screening hits by biophysical methods, and (4) a 3D guided optimization process. When the in silico screening was performed, the initial data set containing 350 000 compounds could be reduced to 3000 molecules. Testing these 3000 selected compounds in the DNA gyrase assay provided 150 hits clustered in 14 classes. Seven classes could be validated as true, novel DNA gyrase inhibitors that act by binding to the ATP binding site located on subunit B: phenols, 2-amino-triazines, 4-amino-pyrimidines, 2-amino-pyrimidines, pyrrolopyrimidines, indazoles, and 2-hydroxymethyl-indoles. The 3D guided optimization provided highly potent DNA gyrase inhibitors, e. g., the 3,4-disubstituted indazole 23 being a 10 times more potent DNA gyrase inhibitor than novobiocin (3).

Anti-Infective Agents↗

PubMed1999

Optimal stoichiometric designs of ATP-producing systems as determined by an evolutionary algorithm.

The design of metabolic pathways is thought to be the result of an optimization process such that the structure of contemporary metabolic routes maximizes a particular objective function. Recently, it has been shown that some essential stoichiometric properties of glycolysis can be explained on the basis of the requirement for a high ATP production rate. Because the number of stoichiometrically feasible designs increases strongly with the number of reactions involved, a systematic analysis of all the possibilities turns out to be inaccessible beyond a certain system size. We present, therefore, an alternative approach to compute in a more efficient way the optimal design of glycolysis interacting with an external ATP-consuming reaction. The algorithm is based on the laws of evolution by natural selection, and may be viewed as a particular version of evolutionary algorithms. The following conclusions are derived: (a) evolutionary algorithms are very useful search strategies in determining optimal stoichiometries of metabolic pathways. (b) Essential topological features of the glycolytic network may be explained on the basis of flux optimization. (c) There is a strong interrelation between the optimal stoichiometries and the thermodynamic and kinetic properties of the participating reactions. (d) Some subsequences of reactions in optimal pathways are strongly conserved at variation of system parameters, which may be understood by applying principles of metabolic control analysis.

Adenosine Triphosphatases↗

PubMed1995

Optimization of intensity-modulated 3D conformal treatment plans based on biological indices.

To overcome the limitations of the intensity modulation optimization techniques based on dose criteria, we introduce a method for optimizing intensity distributions in which we employ an objective function based on biological indices. The objective function also includes constraints on dose and dose-volume combinations to ensure that the results are consistent with the physician's judgement. We apply a variant of the steepest-descent method to optimize the objective function. The method is three-dimensional and incorporates scattered radiation in the optimization process using an iterative scheme employing the pencil beam convolution method. Previously we had shown that the inverse technique of obtaining optimum intensity distributions, for which the objectives are defined in terms of a desired uniform dose to the target volume and desired upper limits of dose to normal organs, produces satisfactory approximations of the desired dose distributions for prostate plans. However, for lung, the performance of this technique was considerably inferior. Our conclusion was that, in general, it is not sufficient to specify the objectives of optimization purely in terms of a desired pattern of dose and that the objectives should also incorporate biology, perhaps in the form of biological indices. We demonstrate that the biology-based approach produces lung plans that are superior to those produced when only dose-based objectives are used. For the treatment of prostate, the two methods produce comparable dose distributions.

Adenocarcinoma↗

PubMed2005

Ca(2+)-independent phospholipase A2 participates in the vesicular transport of milk proteins.

Changes in the lipid composition of intracellular membranes are believed to take part in the molecular processes that sustain traffic between organelles of the endocytic and exocytic transport pathways. Here, we investigated the participation of the calcium-independent phospholipase A2 in the secretory pathway of mammary epithelial cells. Treatment with bromoenol lactone, a suicide substrate which interferes with the production of lysophospholipids by the calcium-independent phospholipase A2, resulted in the reduction of milk proteins secretion. The inhibitor slowed down transport of the caseins from the endoplasmic reticulum to the Golgi apparatus and affected the distribution of p58 and p23, indicating that the optimal process of transport of these proteins between the endoplasmic reticulum, the endoplasmic reticulum/Golgi intermediate compartment and/or the cis-side of the Golgi was dependent upon the production of lysolipids. Moreover, bromoenol lactone was found to delay the rate of protein transport from the trans-Golgi network to the plasma membrane. Concomitantly, membrane-bound structures containing casein accumulated in the juxtanuclear Golgi region. We concluded from these results that efficient formation of post-Golgi carriers also requires the phospholipase activity. These data further support the participation of calcium-independent phospholipase A2 in membrane trafficking and shed a new light on the tubulo/vesicular transport of milk protein through the secretory pathway.

Animals↗

PubMed2004

Tamoxifen in topical liposomes: development, characterization and in-vitro evaluation.

PURPOSE: Tamoxifen, an anti-estrogen compound, has recently been figured as a useful agent in the treatment of certain skin specific disorders. This recent found application has generated an interest in its topical formulation in order to avoid the side effects associated with oral administration, while parenteral administration is restricted due to its limited aqueous solubility. Liposomal carriers, well known for their potential in topical drug delivery, have been chosen to help transport tamoxifen molecules in the skin layers. These vesicles are also expected to provide lipid enriched hydrating conditions to help retain the drug molecules within the dermal layers, at or near to the site of action. With this objective, tamoxifen loaded liposomal systems have been prepared and their topical performance has been compared with non-liposomal systems containing tamoxifen. METHOD: Multilamellar liposomes of tamoxifen were prepared by thin film hydration method. Various formulation ( viz. lipid composition, drug-lipid ratio, amount and type of surface charge imparting agent etc.) and process parameters (hydration temperature, hydration time etc.) were studied to obtain liposomes with desired attributes. Prepared liposomes were characterized for morphological and micromeritic attributes, employing Malvern mastersizer and optical microscopy. Stability of the liposomes in terms of their drug holding capacity was assessed for a period of 5 weeks, on storage under defined conditions. Liposomal formulations of tamoxifen were evaluated for in-vitro skin permeation, using mice skin. The results thus obtained were compared with that of aqueous solution and Carbopol gel, containing tamoxifen in equal amounts. RESULTS: Optimized process and formulation parameters resulted in multilameller, homogenous population of liposomes in the size range of 1 to 13 mm (mean vesicle diameter 5.3 microm), exhibiting normal size distribution. Maximum loading of tamoxifen was noted to be 57.5% (38.3 mu g of drug per mg of lipids), for liposomes composed of hydrogenated phosphatidylcholine and cholesterol, employing 66.6 microg drug per mg of lipids during preparation. Incorporation of dicetylphosphate or stearylamine as charge imparting agent did not influence the vesicular entrapment of TAM in a favorable manner. Amongst different storage conditions, the liposomes stored at 2 to 8 degrees C were found to be most stable, with only 5% drug loss over the storage period of 5 weeks. Significantly higher skin permeation of tamoxifen from liposomal formulations (flux values 63.67 microg/cm2/h and 59.87 microg/cm2/h for liposomal suspension and liposomal gel) has been achieved, as compared to solution (21.65 microg/cm2/h) and Carbopol gel (24.55 microg/cm2/h) containing tamoxifen. Higher magnitude of tamoxifen retention in the skin layers was noted with liposomal formulations vis-à-vis non-liposomal formulations of the drug. CONCLUSION: Tamoxifen molecules could be successfully entrapped in the liposomes with reasonable drug-loading and desired vesicle specific characters. Higher rate of drug transfer across the skin with liposomal formulations of tamoxifen, suggests that the drug in its lipo-solubilised state might have found facilitated entry into the tough barrier consisting of stratum corneum. The phospholipid enriched amphiphillic nature of the vesicles can be held responsible for modifying the properties of the keratinised layer. Integration of phospholipid molecules with the skin lipids might have served further, to help retain the drug molecules within the skin, thus leading to prolonged presence of drug molecules at the receptor site. These findings have been seen to support the improved and localized drug action in the skin, thus providing a better option to deal with skin-cited problems.

Administration, Cutaneous↗

PubMed2003

A two-stage interval-stochastic programming model for waste management under uncertainty.

This study introduces a two-stage interval-stochastic programming (TISP) model for the planning of solid-waste management systems under uncertainty. The model is derived by incorporating the concept of two-stage stochastic programming within an interval-parameter optimization framework. The approach has the advantage that policy determined by the authorities, and uncertain information expressed as intervals and probability distributions, can be effectively communicated into the optimization processes and resulting solutions. In the modeling formulation, penalties are imposed when policies expressed as allowable waste-loading levels are violated. In its solution algorithm, the TISP model is converted into two deterministic submodels, which correspond to the lower and upper bounds for the desired objective-function value. Interval solutions, which are stable in the given decision space with associated levels of system-failure risk, can then be obtained by solving the two submodels sequentially. Two special characteristics of the proposed approach make it unique compared with other optimization techniques that deal with uncertainties. First, the TISP model provides a linkage to predefined policies determined by authorities that have to be respected when a modeling effort is undertaken; second, it furnishes the reflection of uncertainties presented as both probabilities and intervals. The developed model is applied to a hypothetical case study of regional solid-waste management. The results indicate that reasonable solutions have been generated. They provide desired waste-flow patterns with minimized system costs and maximized system feasibility. The solutions present as stable interval solutions with different risk levels in violating the waste-loading criterion and can be used for generating decision alternatives.

Environment↗