Factorial experimental design intended for the optimization of the alumina purification conditions

NASA Astrophysics Data System (ADS)

Brahmi, Mounaouer; Ba, Mohamedou; Hidri, Yassine; Hassen, Abdennaceur

2018-04-01

The objective of this study was to determine the optimal conditions by using the experimental design methodology for the removal of some impurities associated with the alumina. So, three alumina qualities of different origins were investigated under the same conditions. The application of full-factorial designs on the samples of different qualities of alumina has followed the removal rates of the sodium oxide. However, a factorial experimental design was developed to describe the elimination of sodium oxide associated with the alumina. The experimental results showed that chemical analyze followed by XRF prior treatment of the samples, provided a primary idea concerning these prevailing impurities. Therefore, it appeared that the sodium oxide constituted the largest amount among all impurities. After the application of experimental design, analysis of the effectors different factors and their interactions showed that to have a better result, we should reduce the alumina quantity investigated and by against increase the stirring time for the first two samples, whereas, it was necessary to increase the alumina quantity in the case of the third sample. To expand and improve this research, we should take into account all existing impurities, since we found during this investigation that the levels of partial impurities increased after the treatment.

Effect of experimental design on the prediction performance of calibration models based on near-infrared spectroscopy for pharmaceutical applications.

PubMed

Bondi, Robert W; Igne, Benoît; Drennen, James K; Anderson, Carl A

2012-12-01

Near-infrared spectroscopy (NIRS) is a valuable tool in the pharmaceutical industry, presenting opportunities for online analyses to achieve real-time assessment of intermediates and finished dosage forms. The purpose of this work was to investigate the effect of experimental designs on prediction performance of quantitative models based on NIRS using a five-component formulation as a model system. The following experimental designs were evaluated: five-level, full factorial (5-L FF); three-level, full factorial (3-L FF); central composite; I-optimal; and D-optimal. The factors for all designs were acetaminophen content and the ratio of microcrystalline cellulose to lactose monohydrate. Other constituents included croscarmellose sodium and magnesium stearate (content remained constant). Partial least squares-based models were generated using data from individual experimental designs that related acetaminophen content to spectral data. The effect of each experimental design was evaluated by determining the statistical significance of the difference in bias and standard error of the prediction for that model's prediction performance. The calibration model derived from the I-optimal design had similar prediction performance as did the model derived from the 5-L FF design, despite containing 16 fewer design points. It also outperformed all other models estimated from designs with similar or fewer numbers of samples. This suggested that experimental-design selection for calibration-model development is critical, and optimum performance can be achieved with efficient experimental designs (i.e., optimal designs).

D-OPTIMAL EXPERIMENTAL DESIGNS TO TEST FOR DEPARTURE FROM ADDITIVITY IN A FIXED-RATIO MIXTURE RAY.

EPA Science Inventory

Traditional factorial designs for evaluating interactions among chemicals in a mixture are prohibitive when the number of chemicals is large. However, recent advances in statistically-based experimental design have made it easier to evaluate interactions involving many chemicals...

Optimization of thiamethoxam adsorption parameters using multi-walled carbon nanotubes by means of fractional factorial design.

PubMed

Panić, Sanja; Rakić, Dušan; Guzsvány, Valéria; Kiss, Erne; Boskovic, Goran; Kónya, Zoltán; Kukovecz, Ákos

2015-12-01

The aim of this work was to evaluate significant factors affecting the thiamethoxam adsorption efficiency using oxidized multi-walled carbon nanotubes (MWCNTs) as adsorbents. Five factors (initial solution concentration of thiamethoxam in water, temperature, solution pH, MWCNTs weight and contact time) were investigated using 2V(5-1) fractional factorial design. The obtained linear model was statistically tested using analysis of variance (ANOVA) and the analysis of residuals was used to investigate the model validity. It was observed that the factors and their second-order interactions affecting the thiamethoxam removal can be divided into three groups: very important, moderately important and insignificant ones. The initial solution concentration was found to be the most influencing parameter on thiamethoxam adsorption from water. Optimization of the factors levels was carried out by minimizing those parameters which are usually critical in real life: the temperature (energy), contact time (money) and weight of MWCNTs (potential health hazard), in order to maximize the adsorbed amount of the pollutant. The results of maximal adsorbed thiamethoxam amount in both real and optimized experiments indicate that among minimized parameters the adsorption time is one that makes the largest difference. The results of this study indicate that fractional factorial design is very useful tool for screening the higher number of parameters and reducing the number of adsorption experiments. Copyright © 2015 Elsevier Ltd. All rights reserved.

In Silico Constraint-Based Strain Optimization Methods: the Quest for Optimal Cell Factories

PubMed Central

Maia, Paulo; Rocha, Miguel

2015-01-01

SUMMARY Shifting from chemical to biotechnological processes is one of the cornerstones of 21st century industry. The production of a great range of chemicals via biotechnological means is a key challenge on the way toward a bio-based economy. However, this shift is occurring at a pace slower than initially expected. The development of efficient cell factories that allow for competitive production yields is of paramount importance for this leap to happen. Constraint-based models of metabolism, together with in silico strain design algorithms, promise to reveal insights into the best genetic design strategies, a step further toward achieving that goal. In this work, a thorough analysis of the main in silico constraint-based strain design strategies and algorithms is presented, their application in real-world case studies is analyzed, and a path for the future is discussed. PMID:26609052

An examination of effect estimation in factorial and standardly-tailored designs

PubMed Central

Allore, Heather G; Murphy, Terrence E

2012-01-01

Background Many clinical trials are designed to test an intervention arm against a control arm wherein all subjects are equally eligible for all interventional components. Factorial designs have extended this to test multiple intervention components and their interactions. A newer design referred to as a ‘standardly-tailored’ design, is a multicomponent interventional trial that applies individual interventional components to modify risk factors identified a priori and tests whether health outcomes differ between treatment arms. Standardly-tailored designs do not require that all subjects be eligible for every interventional component. Although standardly-tailored designs yield an estimate for the net effect of the multicomponent intervention, it has not yet been shown if they permit separate, unbiased estimation of individual component effects. The ability to estimate the most potent interventional components has direct bearing on conducting second stage translational research. Purpose We present statistical issues related to the estimation of individual component effects in trials of geriatric conditions using factorial and standardly-tailored designs. The medical community is interested in second stage translational research involving the transfer of results from a randomized clinical trial to a community setting. Before such research is undertaken, main effects and synergistic and or antagonistic interactions between them should be identified. Knowledge of the relative strength and direction of the effects of the individual components and their interactions facilitates the successful transfer of clinically significant findings and may potentially reduce the number of interventional components needed. Therefore the current inability of the standardly-tailored design to provide unbiased estimates of individual interventional components is a serious limitation in their applicability to second stage translational research. Methods We discuss estimation of individual component effects from the family of factorial designs and this limitation for standardly-tailored designs. We use the phrase ‘factorial designs’ to describe full-factorial designs and their derivatives including the fractional factorial, partial factorial, incomplete factorial and modified reciprocal designs. We suggest two potential directions for designing multicomponent interventions to facilitate unbiased estimates of individual interventional components. Results Full factorial designs and their variants are the most common multicomponent trial design described in the literature and differ meaningfully from standardly-tailored designs. Factorial and standardly-tailored designs result in similar estimates of net effect with different levels of precision. Unbiased estimation of individual component effects from a standardly-tailored design will require new methodology. Limitations Although clinically relevant in geriatrics, previous applications of standardly-tailored designs have not provided unbiased estimates of the effects of individual interventional components. Discussion Future directions to estimate individual component effects from standardly-tailored designs include applying D-optimal designs and creating independent linear combinations of risk factors analogous to factor analysis. Conclusion Methods are needed to extract unbiased estimates of the effects of individual interventional components from standardly-tailored designs. PMID:18375650

Actinobacteria consortium as an efficient biotechnological tool for mixed polluted soil reclamation: Experimental factorial design for bioremediation process optimization.

PubMed

Aparicio, Juan Daniel; Raimondo, Enzo Emanuel; Gil, Raúl Andrés; Benimeli, Claudia Susana; Polti, Marta Alejandra

2018-01-15

The objective of the present work was to establish optimal biological and physicochemical parameters in order to remove simultaneously lindane and Cr(VI) at high and/or low pollutants concentrations from the soil by an actinobacteria consortium formed by Streptomyces sp. M7, MC1, A5, and Amycolatopsis tucumanensis AB0. Also, the final aim was to treat real soils contaminated with Cr(VI) and/or lindane from the Northwest of Argentina employing the optimal biological and physicochemical conditions. In this sense, after determining the optimal inoculum concentration (2gkg -1 ), an experimental design model with four factors (temperature, moisture, initial concentration of Cr(VI) and lindane) was employed for predicting the system behavior during bioremediation process. According to response optimizer, the optimal moisture level was 30% for all bioremediation processes. However, the optimal temperature was different for each situation: for low initial concentrations of both pollutants, the optimal temperature was 25°C; for low initial concentrations of Cr(VI) and high initial concentrations of lindane, the optimal temperature was 30°C; and for high initial concentrations of Cr(VI), the optimal temperature was 35°C. In order to confirm the model adequacy and the validity of the optimization procedure, experiments were performed in six real contaminated soils samples. The defined actinobacteria consortium reduced the contaminants concentrations in five of the six samples, by working at laboratory scale and employing the optimal conditions obtained through the factorial design. Copyright © 2017 Elsevier B.V. All rights reserved.

The Operator Guide: An Ambient Persuasive Interface in the Factory

NASA Astrophysics Data System (ADS)

Meschtscherjakov, Alexander; Reitberger, Wolfgang; Pöhr, Florian; Tscheligi, Manfred

In this paper we introduce the context of a semiconductor factory as a promising area for the application of innovative interaction approaches. In order to increase efficiency ambient persuasive interfaces, which influence the operators' behaviour to perform in an optimized way, could constitute a potential strategy. We present insights gained from qualitative studies conducted in a specific semiconductor factory and provide a description of typical work processes and already deployed interfaces in this context. These findings informed the design of a prototype of an ambient persuasive interface within this realm - the "Operator Guide". Its overall aim is to improve work efficiency, while still maintaining a minimal error rate. We provide a detailed description of the Operator Guide along with an outlook of the next steps within a user-centered design approach.

Gearing up to the factory of the future

NASA Astrophysics Data System (ADS)

Godfrey, D. E.

1985-01-01

The features of factories and manufacturing techniques and tools of the near future are discussed. The spur to incorporate new technologies on the factory floor will originate in management, who must guide the interfacing of computer-enhanced equipment with traditional manpower, materials and machines. Electronic control with responsiveness and flexibility will be the key concept in an integrated approach to processing materials. Microprocessor controlled laser and fluid cutters add accuracy to cutting operations. Unattended operation will become feasible when automated inspection is added to a work station through developments in robot vision. Optimum shop management will be achieved through AI programming of parts manufacturing, optimized work flows, and cost accounting. The automation enhancements will allow designers to affect directly parts being produced on the factory floor.

A new efficient mixture screening design for optimization of media.

PubMed

Rispoli, Fred; Shah, Vishal

2009-01-01

Screening ingredients for the optimization of media is an important first step to reduce the many potential ingredients down to the vital few components. In this study, we propose a new method of screening for mixture experiments called the centroid screening design. Comparison of the proposed design with Plackett-Burman, fractional factorial, simplex lattice design, and modified mixture design shows that the centroid screening design is the most efficient of all the designs in terms of the small number of experimental runs needed and for detecting high-order interaction among ingredients. (c) 2009 American Institute of Chemical Engineers Biotechnol. Prog., 2009.

Novel Starch-PVA Polymer for Microparticle Preparation and Optimization Using Factorial Design Study

PubMed Central

Chattopadhyay, Helen; De, Amit Kumar; Datta, Sriparna

2015-01-01

The aim of our present work was to optimize the ratio of a very novel polymer, starch-polyvinyl alcohol (PVA), for controlled delivery of Ornidazole. Polymer-coated drug microparticles were prepared by emulsion method. Microscopic study, scanning electron microscopic study, and atomic force microscopic study revealed that the microparticles were within 10 micrometers of size with smooth spherical shape. The Fourier transform infrared spectroscopy showed absence of drug polymer interaction. A statistical 32 full factorial design was used to study the effect of different concentration of starch and PVA on the drug release profile. The three-dimensional plots gave us an idea about the contribution of each factor on the release kinetics. Hence this novel polymer of starch and polyvinyl alcohol can be utilized for control release of the drug from a targeted delivery device. PMID:27347511

D-OPTIMAL EXPERIMENTAL DESIGNS TO TEST FOR DEPARTURE FROM ADDITIVITY IN A FIXED-RATIO MIXTURE RAY.

EPA Science Inventory

Humans are exposed to mixtures of environmental compounds. A regulatory assumption is that the mixtures of chemicals act in an additive manner. However, this assumption requires experimental validation. Traditional experimental designs (full factorial) require a large number of e...

Experimental design methods for bioengineering applications.

PubMed

Keskin Gündoğdu, Tuğba; Deniz, İrem; Çalışkan, Gülizar; Şahin, Erdem Sefa; Azbar, Nuri

2016-01-01

Experimental design is a form of process analysis in which certain factors are selected to obtain the desired responses of interest. It may also be used for the determination of the effects of various independent factors on a dependent factor. The bioengineering discipline includes many different areas of scientific interest, and each study area is affected and governed by many different factors. Briefly analyzing the important factors and selecting an experimental design for optimization are very effective tools for the design of any bioprocess under question. This review summarizes experimental design methods that can be used to investigate various factors relating to bioengineering processes. The experimental methods generally used in bioengineering are as follows: full factorial design, fractional factorial design, Plackett-Burman design, Taguchi design, Box-Behnken design and central composite design. These design methods are briefly introduced, and then the application of these design methods to study different bioengineering processes is analyzed.

Factorial experimental design for the culture of human embryonic stem cells as aggregates in stirred suspension bioreactors reveals the potential for interaction effects between bioprocess parameters.

PubMed

Hunt, Megan M; Meng, Guoliang; Rancourt, Derrick E; Gates, Ian D; Kallos, Michael S

2014-01-01

Traditional optimization of culture parameters for the large-scale culture of human embryonic stem cells (ESCs) as aggregates is carried out in a stepwise manner whereby the effect of varying each culture parameter is investigated individually. However, as evidenced by the wide range of published protocols and culture performance indicators (growth rates, pluripotency marker expression, etc.), there is a lack of systematic investigation into the true effect of varying culture parameters especially with respect to potential interactions between culture variables. Here we describe the design and execution of a two-parameter, three-level (3(2)) factorial experiment resulting in nine conditions that were run in duplicate 125-mL stirred suspension bioreactors. The two parameters investigated here were inoculation density and agitation rate, which are easily controlled, but currently, poorly characterized. Cell readouts analyzed included fold expansion, maximum density, and exponential growth rate. Our results reveal that the choice of best case culture parameters was dependent on which cell property was chosen as the primary output variable. Subsequent statistical analyses via two-way analysis of variance indicated significant interaction effects between inoculation density and agitation rate specifically in the case of exponential growth rates. Results indicate that stepwise optimization has the potential to miss out on the true optimal case. In addition, choosing an optimum condition for a culture output of interest from the factorial design yielded similar results when repeated with the same cell line indicating reproducibility. We finally validated that human ESCs remain pluripotent in suspension culture as aggregates under our optimal conditions and maintain their differentiation capabilities as well as a stable karyotype and strong expression levels of specific human ESC markers over several passages in suspension bioreactors.

Applications of Chemiluminescence in the Teaching of Experimental Design

ERIC Educational Resources Information Center

Krawczyk, Tomasz; Slupska, Roksana; Baj, Stefan

2015-01-01

This work describes a single-session laboratory experiment devoted to teaching the principles of factorial experimental design. Students undertook the rational optimization of a luminol oxidation reaction, using a two-level experiment that aimed to create a long-lasting bright emission. During the session students used only simple glassware and…

Optimization of permeability for quality improvement by using factorial design

NASA Astrophysics Data System (ADS)

Said, Rahaini Mohd; Miswan, Nor Hamizah; Juan, Ng Shu; Hussin, Nor Hafizah; Ahmad, Aminah; Kamal, Mohamad Ridzuan Mohamad

2017-05-01

Sand castings are used worldwide by the manufacturing process in Metal Casting Industry, whereby the green sand are the commonly used sand mould type in the industry of sand casting. The defects on the surface of casting product is one of the problems in the industry of sand casting. The problems that relates to the defect composition of green sand are such as blowholes, pinholes shrinkage and porosity. Our objective is to optimize the best composition of green sand in order to minimize the occurrence of defects. Sand specimen of difference parameters (Bentonite, Green Sand, Cold dust and water) were design and prepared to undergo permeability test. The 24 factorial design experiment with four factors at difference composition were runs, and the total of 16 runs experiment were conducted. The developed models based on the experimental design necessary models were obtained. The model with a high coefficient of determination (R2=0.9841) and model for predicted and actual fitted well with the experimental data. Using the Analysis of Design Expert software, we identified that bentonite and water are the main interaction effect in the experiments. The optimal settings for green sand composition are 100g silica sand, 21g bentonite, 6.5 g water and 6g coal dust. This composition gives an effect of permeability number 598.3GP.

The roles of xylan and lignin in oxalic acid pretreated corncob during separate enzymatic hydrolysis and ethanol fermentation

Treesearch

Jae-Won Lee; Rita C.L.B. Rodrigues; Hyun Joo Kim; In-Gyu Choi; Thomas W. Jeffries

2010-01-01

High yields of hemicellulosic and cellulosic sugars are critical in obtaining economical conversion of agricultural residues to ethanol. To optimize pretreatment conditions, we evaluated oxalic acid loading rates, treatment temperatures and times in a 23 full factorial design. Response-surface analysis revealed an optimal oxalic acid pretreatment...

Optimization of antibacterial activity by Gold-Thread (Coptidis Rhizoma Franch) against Streptococcus mutans using evolutionary operation-factorial design technique.

PubMed

Choi, Ung-Kyu; Kim, Mi-Hyang; Lee, Nan-Hee

2007-11-01

This study was conducted to find the optimum extraction condition of Gold-Thread for antibacterial activity against Streptococcus mutans using The evolutionary operation-factorial design technique. Higher antibacterial activity was achieved in a higher extraction temperature (R2 = -0.79) and in a longer extraction time (R2 = -0.71). Antibacterial activity was not affected by differentiation of the ethanol concentration in the extraction solvent (R2 = -0.12). The maximum antibacterial activity of clove against S. mutans determined by the EVOP-factorial technique was obtained at 80 degrees C extraction temperature, 26 h extraction time, and 50% ethanol concentration. The population of S. mutans decreased from 6.110 logCFU/ml in the initial set to 4.125 logCFU/ml in the third set.

Experimental Investigation of the Application of Microramp Flow Control to an Oblique Shock Interaction

NASA Technical Reports Server (NTRS)

Hirt, Stefanie M.; Anderson, Bernhard H.

2009-01-01

The effectiveness of microramp flow control devices in controlling an oblique shock interaction was tested in the 15- by 15-Centimeter Supersonic Wind Tunnel at NASA Glenn Research Center. Fifteen microramp geometries were tested varying the height, chord length, and spacing between ramps. Measurements of the boundary layer properties downstream of the shock reflection were analyzed using design of experiments methods. Results from main effects, D-optimal, full factorial, and central composite designs were compared. The designs provided consistent results for a single variable optimization.

In-situ implant containing PCL-curcumin nanoparticles developed using design of experiments.

PubMed

Kasinathan, Narayanan; Amirthalingam, Muthukumar; Reddy, Neetinkumar D; Jagani, Hitesh V; Volety, Subrahmanyam M; Rao, Josyula Venkata

2016-01-01

Polymeric delivery system is useful in reducing pharmacokinetic limitations viz., poor absorption and rapid elimination associated with clinical use of curcumin. Design of experiment is a precise and cost effective tool useful in analyzing the effect of independent variables and their interaction on the product attributes. To evaluate the effect of process variables involved in preparation of curcumin-loaded polycaprolactone (PCL) nanoparticles (CPN). In the present experiment, CPNs were prepared by emulsification solvent evaporation technique. The effect of independent variables on the dependent variable was analyzed using design of experiments. Anticancer activity of CPN was studied using Ehrlich ascites carcinoma (EAC) model. In-situ implant was developed using PLGA as polymer. The effect of independent variables was studied in two stages. First, the effect of drug-polymer ratio, homogenization speed and surfactant concentration on size was studied using factorial design. The interaction of homogenization speed with homogenization time on mean particle size of CPN was then evaluated using central composite design. In the second stage, the effect of these variables (under the conditions optimized for producing particles <500 nm) on percentage drug encapsulation was evaluated using factorial design. CPN prepared under optimized conditions were able to control the development of EAC in Swiss albino mice and enhanced their survival time. PLGA based in-situ implant containing CPN prepared under optimized conditions showed sustained drug release. This implant could be further evaluated for pharmacological activities.

Optimization of Soluble Expression and Purification of Recombinant Human Rhinovirus Type-14 3C Protease Using Statistically Designed Experiments: Isolation and Characterization of the Enzyme.

PubMed

Antoniou, Georgia; Papakyriacou, Irineos; Papaneophytou, Christos

2017-10-01

Human rhinovirus (HRV) 3C protease is widely used in recombinant protein production for various applications such as biochemical characterization and structural biology projects to separate recombinant fusion proteins from their affinity tags in order to prevent interference between these tags and the target proteins. Herein, we report the optimization of expression and purification conditions of glutathione S-transferase (GST)-tagged HRV 3C protease by statistically designed experiments. Soluble expression of GST-HRV 3C protease was initially optimized by response surface methodology (RSM), and a 5.5-fold increase in enzyme yield was achieved. Subsequently, we developed a new incomplete factorial (IF) design that examines four variables (bacterial strain, expression temperature, induction time, and inducer concentration) in a single experiment. The new design called Incomplete Factorial-Strain/Temperature/Time/Inducer (IF-STTI) was validated using three GST-tagged proteins. In all cases, IF-STTI resulted in only 10% lower expression yields than those obtained by RSM. Purification of GST-HRV 3C was optimized by an IF design that examines simultaneously the effect of the amount of resin, incubation time of cell lysate with resin, and glycerol and DTT concentration in buffers, and a further 15% increase in protease recovery was achieved. Purified GST-HRV 3C protease was active at both 4 and 25 °C in a variety of buffers.

Optimization of the Ion Source-Mass Spectrometry Parameters in Non-Steroidal Anti-Inflammatory and Analgesic Pharmaceuticals Analysis by a Design of Experiments Approach

NASA Astrophysics Data System (ADS)

Paíga, Paula; Silva, Luís M. S.; Delerue-Matos, Cristina

2016-10-01

The flow rates of drying and nebulizing gas, heat block and desolvation line temperatures and interface voltage are potential electrospray ionization parameters as they may enhance sensitivity of the mass spectrometer. The conditions that give higher sensitivity of 13 pharmaceuticals were explored. First, Plackett-Burman design was implemented to screen significant factors, and it was concluded that interface voltage and nebulizing gas flow were the only factors that influence the intensity signal for all pharmaceuticals. This fractionated factorial design was projected to set a full 22 factorial design with center points. The lack-of-fit test proved to be significant. Then, a central composite face-centered design was conducted. Finally, a stepwise multiple linear regression and subsequently an optimization problem solving were carried out. Two main drug clusters were found concerning the signal intensities of all runs of the augmented factorial design. p-Aminophenol, salicylic acid, and nimesulide constitute one cluster as a result of showing much higher sensitivity than the remaining drugs. The other cluster is more homogeneous with some sub-clusters comprising one pharmaceutical and its respective metabolite. It was observed that instrumental signal increased when both significant factors increased with maximum signal occurring when both codified factors are set at level +1. It was also found that, for most of the pharmaceuticals, interface voltage influences the intensity of the instrument more than the nebulizing gas flowrate. The only exceptions refer to nimesulide where the relative importance of the factors is reversed and still salicylic acid where both factors equally influence the instrumental signal.

Teaching fractional factorial experiments via course delegate designed experiments.

PubMed

Coleman, S; Antony, J

1999-01-01

Industrial experiments are fundamental in enhancing the understanding and knowledge of a process and product behavior. Designed industrial experiments assist people in understanding, investigating, and improving their processes. The purpose of a designed experiment is to understand which factors might influence the process output and then to determine those factor settings that optimize the process output. Teaching "design of experiments" using textbook examples does not fully shed light on how to identify and formulate the problem, identify factors, and determine the performance of the physical experiment. Presented here is an example of how to teach fractional factorial experiments in a course on designed experiments. Also presented is a practical, hands-on experiment that has been found to be extremely successful in instilling confidence and motivation in course delegates. The experiment provides a great stimulus to the delegates for the application of experimental design in their own work environment.

Custom fractional factorial designs to develop atorvastatin self-nanoemulsifying and nanosuspension delivery systems--enhancement of oral bioavailability.

PubMed

Hashem, Fahima M; Al-Sawahli, Majid M; Nasr, Mohamed; Ahmed, Osama A A

2015-01-01

Poor water solubility of a drug is a major challenge in drug delivery research and a main cause for limited bioavailability and pharmacokinetic parameters. This work aims to utilize custom fractional factorial design to assess the development of self-nanoemulsifying drug delivery systems (SNEDDS) and solid nanosuspensions (NS) in order to enhance the oral delivery of atorvastatin (ATR). According to the design, 14 experimental runs of ATR SNEDDS were formulated utilizing the highly ATR solubilizing SNEDDS components: oleic acid, Tween 80, and propylene glycol. In addition, 12 runs of NS were formulated by the antisolvent precipitation-ultrasonication method. Optimized formulations of SNEDDS and solid NS, deduced from the design, were characterized. Optimized SNEDDS formula exhibited mean globule size of 73.5 nm, zeta potential magnitude of -24.1 mV, and 13.5 μs/cm of electrical conductivity. Optimized solid NS formula exhibited mean particle size of 260.3 nm, 7.4 mV of zeta potential, and 93.2% of yield percentage. Transmission electron microscopy showed SNEDDS droplets formula as discrete spheres. The solid NS morphology showed flaky nanoparticles with irregular shapes using scanning electron microscopy. The release behavior of the optimized SNEDDS formula showed 56.78% of cumulative ATR release after 10 minutes. Solid NS formula showed lower rate of release in the first 30 minutes. Bioavailability estimation in Wistar albino rats revealed an augmentation in ATR bioavailability, relative to ATR suspension and the commercial tablets, from optimized ATR SNEDDS and NS formulations by 193.81% and 155.31%, respectively. The findings of this work showed that the optimized nanocarriers enhance the oral delivery and pharmacokinetic profile of ATR.

Study of the effect of temperature, irradiance and salinity on growth and yessotoxin production by the dinoflagellate Protoceratium reticulatum in culture by using a kinetic and factorial approach.

PubMed

Paz, Beatriz; Vázquez, José A; Riobó, Pilar; Franco, José M

2006-10-01

A complete first order orthogonal plan was used to optimize the growth and the production of yessotoxin (YTX) by the dinoflagellate Protoceratium reticulatum in culture by controlling salinity, temperature and irradiance. Initially, an approach to the kinetic data of cellular density and YTX production for each one of the experimental design conditions was performed. The P. reticulatum growth and YTX production were fitted to logistical equations and to a first-order kinetic model, respectively. The parameters obtained from this adjustment were used as dependent variables for the formulation of the empirical equations of the factorial design tested. The results showed that in practically all the cases for both, P. reticulatum growth and YTX production, irradiance is the primary independent variable and has a positive effect in the range 50-90 micromol photons m(-2) s(-1). Additionally, in certain specific cases, temperature reveals significant positive effects when maintained between 15 and 23 degrees C and salinity in the range of 20-34 displays negative effects. Despite the narrow ranges used in the work, results showed the suitability of factorial analysis to evaluate the optimal conditions for growth and yessotoxin production by the dinoflagellate P. reticulatum.

Influence of the Formulation Parameters on the Particle Size and Encapsulation Efficiency of Resveratrol in PLA and PLA-PEG Blend Nanoparticles: A Factorial Design.

PubMed

Lindner, Gabriela da Rocha; Dalmolin, Luciana Facco; Khalil, Najeh Maissar; Mainardes, Rubiana Mara

2015-12-01

Polymeric nanoparticles are colloidal systems that promote protection and modification of physicochemical characteristics of a drug and that also ensure controlled and extended drug release. This paper reports a 2(3) factorial design study to optimize poly(lactide) (PLA) and poly(lactide)-polyethylene glycol (PLA-PEG) blend nanoparticles containing resveratrol (RVT) for prolonged release. The independent variables analyzed were solvent composition, surfactant concentration and ratio of aqueous to organic phase (two levels each factor). Mean particle size and RVT encapsulation efficiency were set as the dependent variables. The selected optimized parameters were set as organic phase comprised of a mixture of dichloromethane and ethyl acetate, 1% of surfactant polyvinyl alcohol and a 3:1 ratio of aqueous to organic phase, for both PLA and PLA-PEG blend nanoparticles. This formulation originated nanoparticles with size of 228 ± 10 nm and 185 ± 70 nm and RVT encapsulation efficiency of 82 ± 10% and 76 ± 7% for PLA and PLA-PEG blend nanoparticles, respectively. The in vitro release study showed a biphasic pattern with prolonged RVT release and PEG did not influence the RVT release. The in vitro release data were in favor of Higuchi-diffusion kinetics for both nanoformulations and the Kossmeyer-Peppas coefficient indicated that anomalous transport was the main release mechanism of RVT. PLA and PLA-PEG blend nanoparticles produced with single emulsion-solvent evaporation technology were found to be a promising approach for the incorporation of RVT and promoted its controlled release. The factorial design is a tool of great value in choosing formulations with optimized parameters.

Novel Solid Lipid Nanocarrier Of Glibenclamide: A Factorial Design Approach With Response Surface Methodology.

PubMed

Pandey, Sonia; Patel, Payal; Gupta, Arti

2018-05-21

In the present investigation a factorial design approach attempt was applied to develop the solid lipid nanoparticles (SLN) of Glibenclamide (GLB) a poorly water-soluble drug (BCS -II) used in the treatment of type 2 diabetes. Prime objectives of this experiment are to optimize the SLN formulation of Glibenclamide and improve the therapeutic effectiveness of the developed formulation. Glibenclamide loaded SLNs (GLB-SLN) were fabricated by High speed homogenization technique. A 32-factorial design approach has been employed to assess the influence of two independent variables, namely amount of Poloxamer 188 and Glyceryl Monostearate on entrapment efficiency (% EE) (Y1), Particle Size (nm) (Y2), % drug release at 8hr Q8 (Y3) and 24 hr Q24 (Y4) of prepared SLNs. Differential scanning calorimetry analysis revealed the compatibility of the drug into lipid matrix with surfactant, while Transmission electron and Scanning electron microscopy studies indicated the size and shape of SLN. The entrapment efficiency, particle size, Q8 and Q24 of the optimized SLNs were 88.93%, 125 nm, 31.12±0.951% and 86.07±1.291% respectively. Optimized GLB-SLN formula was derived from an overlay plot. Three dimensional response surface plots and regression equations confirmed the corresponding influence of selected independent variables on measured responses. In vivo testing of the GLB-SLN in diabetic albino rats demonstrated significant antidiabetic effect of GLB-SLN. The hypoglycemic effect obtained by GLB-SLN remained significantly higher than that given by drug alone and marketed formulation, further confirming the higher therapeutic effectiveness of the GLB-SLN formulation. Our findings suggested the feasibility of investigated system for oral administration of Glibenclamide. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Optimization of the Ion Source-Mass Spectrometry Parameters in Non-Steroidal Anti-Inflammatory and Analgesic Pharmaceuticals Analysis by a Design of Experiments Approach.

PubMed

Paíga, Paula; Silva, Luís M S; Delerue-Matos, Cristina

2016-10-01

The flow rates of drying and nebulizing gas, heat block and desolvation line temperatures and interface voltage are potential electrospray ionization parameters as they may enhance sensitivity of the mass spectrometer. The conditions that give higher sensitivity of 13 pharmaceuticals were explored. First, Plackett-Burman design was implemented to screen significant factors, and it was concluded that interface voltage and nebulizing gas flow were the only factors that influence the intensity signal for all pharmaceuticals. This fractionated factorial design was projected to set a full 2(2) factorial design with center points. The lack-of-fit test proved to be significant. Then, a central composite face-centered design was conducted. Finally, a stepwise multiple linear regression and subsequently an optimization problem solving were carried out. Two main drug clusters were found concerning the signal intensities of all runs of the augmented factorial design. p-Aminophenol, salicylic acid, and nimesulide constitute one cluster as a result of showing much higher sensitivity than the remaining drugs. The other cluster is more homogeneous with some sub-clusters comprising one pharmaceutical and its respective metabolite. It was observed that instrumental signal increased when both significant factors increased with maximum signal occurring when both codified factors are set at level +1. It was also found that, for most of the pharmaceuticals, interface voltage influences the intensity of the instrument more than the nebulizing gas flowrate. The only exceptions refer to nimesulide where the relative importance of the factors is reversed and still salicylic acid where both factors equally influence the instrumental signal. Graphical Abstract ᅟ.

An intelligent factory-wide optimal operation system for continuous production process

NASA Astrophysics Data System (ADS)

Ding, Jinliang; Chai, Tianyou; Wang, Hongfeng; Wang, Junwei; Zheng, Xiuping

2016-03-01

In this study, a novel intelligent factory-wide operation system for a continuous production process is designed to optimise the entire production process, which consists of multiple units; furthermore, this system is developed using process operational data to avoid the complexity of mathematical modelling of the continuous production process. The data-driven approach aims to specify the structure of the optimal operation system; in particular, the operational data of the process are used to formulate each part of the system. In this context, the domain knowledge of process engineers is utilised, and a closed-loop dynamic optimisation strategy, which combines feedback, performance prediction, feed-forward, and dynamic tuning schemes into a framework, is employed. The effectiveness of the proposed system has been verified using industrial experimental results.

Algorithm for designing smart factory Industry 4.0

NASA Astrophysics Data System (ADS)

Gurjanov, A. V.; Zakoldaev, D. A.; Shukalov, A. V.; Zharinov, I. O.

2018-03-01

The designing task of production division of the Industry 4.0 item designing company is being studied. The authors proposed an algorithm, which is based on the modified V L Volkovich method. This algorithm allows generating options how to arrange the production with robotized technological equipment functioning in the automatic mode. The optimization solution of the multi-criteria task for some additive criteria is the base of the algorithm.

Optimization and influence of parameter affecting the compressive strength of geopolymer concrete containing recycled concrete aggregate: using full factorial design approach

NASA Astrophysics Data System (ADS)

Krishnan, Thulasirajan; Purushothaman, Revathi

2017-07-01

There are several parameters that influence the properties of geopolymer concrete, which contains recycled concrete aggregate as the coarse aggregate. In the present study, the vital parameters affecting the compressive strength of geopolymer concrete containing recycled concrete aggregate are analyzedby varying four parameters with two levels using full factorial design in statistical software Minitab® 17. The objective of the present work is to gain an idea on the optimization, main parameter effects, their interactions and the predicted response of the model generated using factorial design. The parameters such as molarity of sodium hydroxide (8M and 12M), curing time (6hrs and 24 hrs), curing temperature (60°C and 90°C) and percentage of recycled concrete aggregate (0% and 100%) are considered. The results show that the curing time, molarity of sodium hydroxide and curing temperature were the orderly significant parameters and the percentage of Recycled concrete aggregate (RCA) was statistically insignificant in the production of geopolymer concrete. Thus, it may be noticeable that the RCA content had negligible effect on the compressive strength of geopolymer concrete. The expected responses from the generated model showed a satisfactory and rational agreement to the experimental data with the R2 value of 97.70%. Thus, geopolymer concrete comprising recycled concrete aggregate can solve the major social and environmental concerns such as the depletion of the naturally available aggregate sources and disposal of construction and demolition waste into the landfill.

A factorial design experiment as a pilot study for noninvasive genetic sampling.

PubMed

Renan, Sharon; Speyer, Edith; Shahar, Naama; Gueta, Tomer; Templeton, Alan R; Bar-David, Shirli

2012-11-01

Noninvasive genetic sampling has increasingly been used in ecological and conservation studies during the last decade. A major part of the noninvasive genetic literature is dedicated to the search for optimal protocols, by comparing different methods of collection, preservation and extraction of DNA from noninvasive materials. However, the lack of quantitative comparisons among these studies and the possibility that different methods are optimal for different systems make it difficult to decide which protocol to use. Moreover, most studies that have compared different methods focused on a single factor - collection, preservation or extraction - while there could be interactions between these factors. We designed a factorial experiment, as a pilot study, aimed at exploring the effect of several collection, preservation and extraction methods, and the interactions between them, on the quality and amplification success of DNA obtained from Asiatic wild ass (Equus hemionus) faeces in Israel. The amplification success rates of one mitochondrial DNA and four microsatellite markers differed substantially as a function of collection, preservation and extraction methods and their interactions. The most efficient combination for our system integrated the use of swabs as a collection method with preservation at -20 °C and with the Qiagen DNA Stool Kit with modifications as the DNA extraction method. The significant interaction found between the collection, preservation methods and the extraction methods reinforces the importance of conducting a factorial design experiment, rather than examining each factor separately, as a pilot study before initiating a full-scale noninvasive research project. © 2012 Blackwell Publishing Ltd.

Factorial Design Approach in Proportioning Prestressed Self-Compacting Concrete.

PubMed

Long, Wu-Jian; Khayat, Kamal Henri; Lemieux, Guillaume; Xing, Feng; Wang, Wei-Lun

2015-03-13

In order to model the effect of mixture parameters and material properties on the hardened properties of, prestressed self-compacting concrete (SCC), and also to investigate the extensions of the statistical models, a factorial design was employed to identify the relative significance of these primary parameters and their interactions in terms of the mechanical and visco-elastic properties of SCC. In addition to the 16 fractional factorial mixtures evaluated in the modeled region of -1 to +1, eight axial mixtures were prepared at extreme values of -2 and +2 with the other variables maintained at the central points. Four replicate central mixtures were also evaluated. The effects of five mixture parameters, including binder type, binder content, dosage of viscosity-modifying admixture (VMA), water-cementitious material ratio (w/cm), and sand-to-total aggregate ratio (S/A) on compressive strength, modulus of elasticity, as well as autogenous and drying shrinkage are discussed. The applications of the models to better understand trade-offs between mixture parameters and carry out comparisons among various responses are also highlighted. A logical design approach would be to use the existing model to predict the optimal design, and then run selected tests to quantify the influence of the new binder on the model.

Kinetic models in industrial biotechnology - Improving cell factory performance.

PubMed

Almquist, Joachim; Cvijovic, Marija; Hatzimanikatis, Vassily; Nielsen, Jens; Jirstrand, Mats

2014-07-01

An increasing number of industrial bioprocesses capitalize on living cells by using them as cell factories that convert sugars into chemicals. These processes range from the production of bulk chemicals in yeasts and bacteria to the synthesis of therapeutic proteins in mammalian cell lines. One of the tools in the continuous search for improved performance of such production systems is the development and application of mathematical models. To be of value for industrial biotechnology, mathematical models should be able to assist in the rational design of cell factory properties or in the production processes in which they are utilized. Kinetic models are particularly suitable towards this end because they are capable of representing the complex biochemistry of cells in a more complete way compared to most other types of models. They can, at least in principle, be used to in detail understand, predict, and evaluate the effects of adding, removing, or modifying molecular components of a cell factory and for supporting the design of the bioreactor or fermentation process. However, several challenges still remain before kinetic modeling will reach the degree of maturity required for routine application in industry. Here we review the current status of kinetic cell factory modeling. Emphasis is on modeling methodology concepts, including model network structure, kinetic rate expressions, parameter estimation, optimization methods, identifiability analysis, model reduction, and model validation, but several applications of kinetic models for the improvement of cell factories are also discussed. Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

Optimization of factors to obtain cassava starch films with improved mechanical properties

NASA Astrophysics Data System (ADS)

Monteiro, Mayra; Oliveira, Victor; Santos, Francisco; Barros Neto, Eduardo; Silva, Karyn; Silva, Rayane; Henrique, João; Chibério, Abimaelle

2017-08-01

In this study, was investigated the optimization of the factors that significantly influenced the mechanical property improvement of cassava starch films through complete factorial design 23. The factors to be analyzed were cassava starch, glycerol and modified clay contents. A regression model was proposed by the factorial analysis, aiming to estimate the condition of the individual factors investigated in the optimum state of the mechanical properties of the biofilm, using the following statistical tool: desirability function and response surface. The response variable that delimits the improvement of the mechanical property of the biofilm is the tensile strength, such improvement is obtained by maximizing the response variable. The factorial analysis showed that the best combination of factor configurations to reach the best response was found to be: with 5g of cassava starch, 10% of glycerol and 5% of modified clay, both percentages in relation to the dry mass of starch used. In addition, the starch biofilm showing the lowest response contained 2g of cassava starch, 0% of modified clay and 30% of glycerol, and was consequently considered the worst biofilm.

Cameo: A Python Library for Computer Aided Metabolic Engineering and Optimization of Cell Factories.

PubMed

Cardoso, João G R; Jensen, Kristian; Lieven, Christian; Lærke Hansen, Anne Sofie; Galkina, Svetlana; Beber, Moritz; Özdemir, Emre; Herrgård, Markus J; Redestig, Henning; Sonnenschein, Nikolaus

2018-04-20

Computational systems biology methods enable rational design of cell factories on a genome-scale and thus accelerate the engineering of cells for the production of valuable chemicals and proteins. Unfortunately, the majority of these methods' implementations are either not published, rely on proprietary software, or do not provide documented interfaces, which has precluded their mainstream adoption in the field. In this work we present cameo, a platform-independent software that enables in silico design of cell factories and targets both experienced modelers as well as users new to the field. It is written in Python and implements state-of-the-art methods for enumerating and prioritizing knockout, knock-in, overexpression, and down-regulation strategies and combinations thereof. Cameo is an open source software project and is freely available under the Apache License 2.0. A dedicated Web site including documentation, examples, and installation instructions can be found at http://cameo.bio . Users can also give cameo a try at http://try.cameo.bio .

Statistical optimization of the growth factors for Chaetoceros neogracile using fractional factorial design and central composite design.

PubMed

Jeong, Sung-Eun; Park, Jae-Kweon; Kim, Jeong-Dong; Chang, In-Jeong; Hong, Seong-Joo; Kang, Sung-Ho; Lee, Choul-Gyun

2008-12-01

Statistical experimental designs; involving (i) a fractional factorial design (FFD) and (ii) a central composite design (CCD) were applied to optimize the culture medium constituents for production of a unique antifreeze protein by the Antartic microalgae Chaetoceros neogracile. The results of the FFD suggested that NaCl, KCl, MgCl2, and Na2SiO3 were significant variables that highly influenced the growth rate and biomass production. The optimum culture medium for the production of an antifreeze protein from C. neogracile was found to be Kalleampersandrsquor;s artificial seawater, pH of 7.0ampersandplusmn;0.5, consisting of 28.566 g/l of NaCl, 3.887 g/l of MgCl2, 1.787 g/l of MgSO4, 1.308 g/l of CaSO4, 0.832 g/l of K2SO4, 0.124 g/l of CaCO3, 0.103 g/l of KBr, 0.0288 g/l of SrSO4, and 0.0282 g/l of H3BO3. The antifreeze activity significantly increased after cells were treated with cold shock (at -5oC) for 14 h. To the best of our knowledge, this is the first report demonstrating an antifreeze-like protein of C. neogracile.

Determination of the clean-up efficiency of the solid-phase extraction of rosemary extracts: Application of full-factorial design in hyphenation with Gaussian peak fit function.

PubMed

Meischl, Florian; Kirchler, Christian Günter; Jäger, Michael Andreas; Huck, Christian Wolfgang; Rainer, Matthias

2018-02-01

We present a novel method for the quantitative determination of the clean-up efficiency to provide a calculated parameter for peak purity through iterative fitting in conjunction with design of experiments. Rosemary extracts were used and analyzed before and after solid-phase extraction using a self-fabricated mixed-mode sorbent based on poly(N-vinylimidazole/ethylene glycol dimethacrylate). Optimization was performed by variation of washing steps using a full three-level factorial design and response surface methodology. Separation efficiency of rosmarinic acid from interfering compounds was calculated using an iterative fit of Gaussian-like signals and quantifications were performed by the separate integration of the two interfering peak areas. Results and recoveries were analyzed using Design-Expert® software and revealed significant differences between the washing steps. Optimized parameters were considered and used for all further experiments. Furthermore, the solid-phase extraction procedure was tested and compared with commercial available sorbents. In contrast to generic protocols of the manufacturers, the optimized procedure showed excellent recoveries and clean-up rates for the polymer with ion exchange properties. Finally, rosemary extracts from different manufacturing areas and application types were studied to verify the developed method for its applicability. The cleaned-up extracts were analyzed by liquid chromatography with tandem mass spectrometry for detailed compound evaluation to exclude any interference from coeluting molecules. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Formulation optimization of gentamicin loaded Eudragit RS100 microspheres using factorial design study.

PubMed

Singh, Deependra; Saraf, Swarnlata; Dixit, Vinod Kumar; Saraf, Shailendra

2008-04-01

Gentamicin-Eudragit RS100 microspheres were prepared by modified double emulsion method. A 3(2) full factorial experiment was designed to study the effects of the composition of outer aqueous phase in terms of amount of glycerol (viscosity effect) and sodium chloride (osmotic pressure gradient effect) on the entrapment efficiency and % yield and microsphere size. The results of analysis of variance test for responses measured indicated that the test is significant (p>0.05). The contribution of sodium chloride concentration was found to be higher on entrapment efficiency and % yield, whereas glycerol produced significant effect on the mean diameter of microspheres. Microspheres demonstrated spherical particles in the size range of 33.24-60.43 microm. In vitro release profile of optimized formulation demonstrated sustained release for 24 h following Higuchi kinetics. Finally, drug bioactivity was found to remain intact after microencapsulation. Response surface graphs are presented to examine the effects of independent variables on the responses studied. Thus, by formulation design important parameters affecting formulation characteristics of gentamicin loaded Eudragit RS100 microspheres can be identified for controlled delivery with desirable characters in terms of maximum entrapment and yield.

Enhancement of the bioavailability of an antihypertensive drug by transdermal protransfersomal system: formulation and in vivo study.

PubMed

Morsi, Nadia M; Aboelwafa, Ahmed A; Dawoud, Marwa H S

2018-06-01

Timolol Maleate (TiM), a nonselective β-adrenergic blocker, is a potent highly effective agent for management of hypertension. The drug suffers from poor oral bioavailability (50%) due to its first pass effect and a short elimination half-life of 4 h; resulting in its frequent administration. Transdermal formulation may circumvent these problems in the form of protransfersomes. The aim of this study is to develop and optimize transdermal protransfersomal system of Timolol Maleate by film deposition on carrier method where protransfersomes were converted to transfersomes upon skin hydration following transdermal application under occlusive conditions. Two 2 3 full factorial designs were employed to investigate the influence of three formulation variables which were; phosphatidyl choline: surfactant molar ratio, carrier: mixture and the type of SAA each on particle size, drug entrapment efficiency and release rate. The optimized formulation was evaluated regarding permeation through hairless rat skin and compared with oral administration of aqueous solution on male Wistar rats. Optimized protransfersomal system had excellent permeation rate through shaved rat skin (780.69 μg/cm 2 /h) and showed six times increase in relative bioavailability with prolonged plasma profile up to 72 h. A potential protransfresomal transdermal system was successfully developed and factorial design was found to be a smart tool in its optimization.

Toward precision smoking cessation treatment I: Moderator results from a factorial experiment.

PubMed

Piper, Megan E; Schlam, Tanya R; Cook, Jessica W; Smith, Stevens S; Bolt, Daniel M; Loh, Wei-Yin; Mermelstein, Robin; Collins, Linda M; Fiore, Michael C; Baker, Timothy B

2017-02-01

The development of tobacco use treatments that are effective for all smokers is critical to improving clinical and public health. The Multiphase Optimization Strategy (MOST) uses highly efficient factorial experiments to evaluate multiple intervention components for possible inclusion in an optimized tobacco use treatment. Factorial experiments permit analyses of the influence of patient characteristics on main and interaction effects of multiple, relatively discrete, intervention components. This study examined whether person-factor and smoking characteristics moderated the main or interactive effects of intervention components on 26-week self-reported abstinence rates. This fractional factorial experiment evaluated six smoking cessation intervention components among primary care patients (N=637): Prequit Nicotine Patch vs. None, Prequit Nicotine Gum vs. None, Preparation Counseling vs. None, Intensive Cessation In-Person Counseling vs. Minimal, Intensive Cessation Telephone Counseling vs. Minimal, and 16 vs. 8 Weeks of Combination Nicotine Replacement Therapy (NRT; nicotine patch+nicotine gum). Both psychiatric history and smoking heaviness moderated intervention component effects. In comparison with participants with no self-reported history of a psychiatric disorder, those with a positive history showed better response to 16- vs. 8-weeks of combination NRT, but a poorer response to counseling interventions. Also, in contrast to light smokers, heavier smokers showed a poorer response to counseling interventions. Heavy smokers and those with psychiatric histories demonstrated a differential response to intervention components. This research illustrates the use of factorial designs to examine the interactions between person characteristics and relatively discrete intervention components. Future research is needed to replicate these findings. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Study of Montmorillonite Clay for the Removal of Copper (II) by Adsorption: Full Factorial Design Approach and Cascade Forward Neural Network

PubMed Central

Turan, Nurdan Gamze; Ozgonenel, Okan

2013-01-01

An intensive study has been made of the removal efficiency of Cu(II) from industrial leachate by biosorption of montmorillonite. A 24 factorial design and cascade forward neural network (CFNN) were used to display the significant levels of the analyzed factors on the removal efficiency. The obtained model based on 24 factorial design was statistically tested using the well-known methods. The statistical analysis proves that the main effects of analyzed parameters were significant by an obtained linear model within a 95% confidence interval. The proposed CFNN model requires less experimental data and minimum calculations. Moreover, it is found to be cost-effective due to inherent advantages of its network structure. Optimization of the levels of the analyzed factors was achieved by minimizing adsorbent dosage and contact time, which were costly, and maximizing Cu(II) removal efficiency. The suggested optimum conditions are initial pH at 6, adsorbent dosage at 10 mg/L, and contact time at 10 min using raw montmorillonite with the Cu(II) removal of 80.7%. At the optimum values, removal efficiency was increased to 88.91% if the modified montmorillonite was used. PMID:24453833

Application of factorial designs to study factors involved in the determination of aldehydes present in beer by on-fiber derivatization in combination with gas chromatography and mass spectrometry.

PubMed

Carrillo, Génesis; Bravo, Adriana; Zufall, Carsten

2011-05-11

With the aim of studying the factors involved in on-fiber derivatization of Strecker aldehydes, furfural, and (E)-2-nonenal with O-(2,3,4,5,6-pentafluorobenzyl)hydroxylamine in beer, factorial designs were applied. The effect of the temperature, time, and NaCl addition on the analytes' derivatization/extraction efficiency was studied through a factorial 2(3) randomized-block design; all of the factors and their interactions were significant at the 95% confidence level for most of the analytes. The effect of temperature and its interactions separated the analytes in two groups. However, a single sampling condition was selected that optimized response for most aldehydes. The resulting method, combining on-fiber derivatization with gas chromatography-mass spectrometry, was validated. Limits of detections were between 0.015 and 1.60 μg/L, and relative standard deviations were between 1.1 and 12.2%. The efficacy of the internal standardization method was confirmed by recovery percentage (73-117%). The method was applied to the determination of aldehydes in fresh beer and after storage at 28 °C.

Optimization of the SPME parameters and its online coupling with HPLC for the analysis of tricyclic antidepressants in plasma samples.

PubMed

Alves, Claudete; Fernandes, Christian; Dos Santos Neto, Alvaro José; Rodrigues, José Carlos; Costa Queiroz, Maria Eugênia; Lanças, Fernando Mauro

2006-07-01

Solid-phase microextraction (SPME)-liquid chromatography (LC) is used to analyze tricyclic antidepressant drugs desipramine, imipramine, nortriptyline, amitriptyline, and clomipramine (internal standard) in plasma samples. Extraction conditions are optimized using a 2(3) factorial design plus a central point to evaluate the influence of the time, temperature, and matrix pH. A Polydimethylsiloxane-divinylbenzene (60-mum film thickness) fiber is selected after the assessment of different types of coating. The chromatographic separation is realized using a C(18) column (150 x 4.6 mm, 5-microm particles), ammonium acetate buffer (0.05 mol/L, pH 5.50)-acetonitrile (55:45 v/v) with 0.1% of triethylamine as mobile phase and UV-vis detection at 214 nm. Among the factorial design conditions evaluated, the best results are obtained at a pH 11.0, temperature of 30 degrees C, and extraction time of 45 min. The proposed method, using a lab-made SPME-LC interface, allowed the determination of tricyclic antidepressants in in plasma at therapeutic concentration levels.

Pediatric Diabetic Ketoacidosis, Fluid Therapy and Cerebral Injury: The Design of a Factorial Randomized Controlled Trial

PubMed Central

Glaser, Nicole S.; Ghetti, Simona; Casper, T. Charles; Dean, J. Michael; Kuppermann, Nathan

2013-01-01

Treatment protocols for pediatric diabetic ketoacidosis (DKA) vary considerably among centers in the United States and worldwide. The optimal protocol for intravenous fluid administration is an area of particular controversy, mainly in regard to possible associations between rates of intravenous fluid infusion and the development of cerebral edema, the most common and most feared complication of DKA in children. Theoretical concerns about associations between osmotic fluid shifts and cerebral edema have prompted recommendations for conservative fluid infusion during DKA. However, recent data suggest that cerebral hypoperfusion may play a role in cerebral injury associated with DKA. Currently there are no existing data from prospective clinical trials to determine the optimal fluid treatment protocol for pediatric DKA. The Pediatric Emergency Care Applied Research Network FLUID (Fluid Therapies Under Investigation in DKA) Study is the first prospective randomized trial to evaluate fluid regimens for pediatric DKA. This 13-center nationwide factorial-design study will evaluate the effects of rehydration rate and fluid sodium content on neurological status during DKA treatment, the frequency of clinically-overt CE, and long-term neurocognitive outcomes following DKA. PMID:23490311

Factorial Design Approach in Proportioning Prestressed Self-Compacting Concrete

PubMed Central

Long, Wu-Jian; Khayat, Kamal Henri; Lemieux, Guillaume; Xing, Feng; Wang, Wei-Lun

2015-01-01

In order to model the effect of mixture parameters and material properties on the hardened properties of, prestressed self-compacting concrete (SCC), and also to investigate the extensions of the statistical models, a factorial design was employed to identify the relative significance of these primary parameters and their interactions in terms of the mechanical and visco-elastic properties of SCC. In addition to the 16 fractional factorial mixtures evaluated in the modeled region of −1 to +1, eight axial mixtures were prepared at extreme values of −2 and +2 with the other variables maintained at the central points. Four replicate central mixtures were also evaluated. The effects of five mixture parameters, including binder type, binder content, dosage of viscosity-modifying admixture (VMA), water-cementitious material ratio (w/cm), and sand-to-total aggregate ratio (S/A) on compressive strength, modulus of elasticity, as well as autogenous and drying shrinkage are discussed. The applications of the models to better understand trade-offs between mixture parameters and carry out comparisons among various responses are also highlighted. A logical design approach would be to use the existing model to predict the optimal design, and then run selected tests to quantify the influence of the new binder on the model. PMID:28787990

Engineering plant metabolism into microbes: from systems biology to synthetic biology.

PubMed

Xu, Peng; Bhan, Namita; Koffas, Mattheos A G

2013-04-01

Plant metabolism represents an enormous repository of compounds that are of pharmaceutical and biotechnological importance. Engineering plant metabolism into microbes will provide sustainable solutions to produce pharmaceutical and fuel molecules that could one day replace substantial portions of the current fossil-fuel based economy. Metabolic engineering entails targeted manipulation of biosynthetic pathways to maximize yields of desired products. Recent advances in Systems Biology and the emergence of Synthetic Biology have accelerated our ability to design, construct and optimize cell factories for metabolic engineering applications. Progress in predicting and modeling genome-scale metabolic networks, versatile gene assembly platforms and delicate synthetic pathway optimization strategies has provided us exciting opportunities to exploit the full potential of cell metabolism. In this review, we will discuss how systems and synthetic biology tools can be integrated to create tailor-made cell factories for efficient production of natural products and fuel molecules in microorganisms. Copyright © 2012 Elsevier Ltd. All rights reserved.

Quantitative and qualitative optimization of allergen extraction from peanut and selected tree nuts. Part 2. Optimization of buffer and ionic strength using a full factorial experimental design.

PubMed

L'Hocine, Lamia; Pitre, Mélanie

2016-03-01

A full factorial design was used to assess the single and interactive effects of three non-denaturing aqueous (phosphate, borate, and carbonate) buffers at various ionic strengths (I) on allergen extractability from and immunoglobulin E (IgE) immunoreactivity of peanut, almond, hazelnut, and pistachio. The results indicated that the type and ionic strength of the buffer had different effects on protein recovery from the nuts under study. Substantial differences in protein profiles, abundance, and IgE-binding intensity with different combinations of pH and ionic strength were found. A significant interaction between pH and ionic strength was observed for pistachio and almond. The optimal buffer system conditions, which maximized the IgE-binding efficiency of allergens and provided satisfactory to superior protein recovery yield and profiles, were carbonate buffer at an ionic strength of I=0.075 for peanut, carbonate buffer at I=0.15 for almond, phosphate buffer at I=0.5 for hazelnut, and borate at I=0.15 for pistachio. The buffer type and its ionic strength could be manipulated to achieve the selective solubility of desired allergens. Crown Copyright © 2015. Published by Elsevier Ltd. All rights reserved.

Solenoid Fringe Field Effects for the Neutrino Factory Linac - MAD-X Investigation

DOE Office of Scientific and Technical Information (OSTI.GOV)

M. Aslaninejad,C. Bontoiu,J. Pasternak,J. Pozimski,Alex Bogacz

2010-05-01

International Design Study for the Neutrino Factory (IDS-NF) assumes the first stage of muon acceleration (up to 900 MeV) to be implemented with a solenoid based Linac. The Linac consists of three styles of cryo-modules, containing focusing solenoids and varying number of SRF cavities for acceleration. Fringe fields of the solenoids and the focusing effects in the SRF cavities have significant impact on the transverse beam dynamics. Using an analytical formula, the effects of fringe fields are studied in MAD-X. The resulting betatron functions are compared with the results of beam dynamics simulations using OptiM code.

Optimization and Technological Development Strategies of an Antimicrobial Extract from Achyrocline alata Assisted by Statistical Design

PubMed Central

Demarque, Daniel P.; Fitts, Sonia Maria F.; Boaretto, Amanda G.; da Silva, Júlio César Leite; Vieira, Maria C.; Franco, Vanessa N. P.; Teixeira, Caroline B.; Toffoli-Kadri, Mônica C.; Carollo, Carlos A.

2015-01-01

Achyrocline alata, known as Jateí-ka-há, is traditionally used to treat several health problems, including inflammations and infections. This study aimed to optimize an active extract against Streptococcus mutans, the main bacteria that causes caries. The extract was developed using an accelerated solvent extraction and chemometric calculations. Factorial design and response surface methodologies were used to determine the most important variables, such as active compound selectivity. The standardized extraction recovered 99% of the four main compounds, gnaphaliin, helipyrone, obtusifolin and lepidissipyrone, which represent 44% of the extract. The optimized extract of A. alata has a MIC of 62.5 μg/mL against S. mutans and could be used in mouth care products. PMID:25710523

Mechanistic analysis of Zein nanoparticles/PLGA triblock in situ forming implants for glimepiride.

PubMed

Ahmed, Osama Abdelhakim Aly; Zidan, Ahmed Samir; Khayat, Maan

2016-01-01

The study aims at applying pharmaceutical nanotechnology and D-optimal fractional factorial design to screen and optimize the high-risk variables affecting the performance of a complex drug delivery system consisting of glimepiride-Zein nanoparticles and inclusion of the optimized formula with thermoresponsive triblock copolymers in in situ gel. Sixteen nanoparticle formulations were prepared by liquid-liquid phase separation method according to the D-optimal fractional factorial design encompassing five variables at two levels. The responses investigated were glimepiride entrapment capacity (EC), particle size and size distribution, zeta potential, and in vitro drug release from the prepared nanoparticles. Furthermore, the feasibility of embedding the optimized Zein-based glimepiride nanoparticles within thermoresponsive triblock copolymers poly(lactide-co-glycolide)-block-poly(ethylene glycol)-block-poly(lactide-co-glycolide) in in situ gel was evaluated for controlling glimepiride release rate. Through the systematic optimization phase, improvement of glimepiride EC of 33.6%, nanoparticle size of 120.9 nm with a skewness value of 0.2, zeta potential of 11.1 mV, and sustained release features of 3.3% and 17.3% drug released after 2 and 24 hours, respectively, were obtained. These desirability functions were obtained at Zein and glimepiride loadings of 50 and 75 mg, respectively, utilizing didodecyldimethylammonium bromide as a stabilizer at 0.1% and 90% ethanol as a common solvent. Moreover, incorporating this optimized formulation in triblock copolymers-based in situ gel demonstrated pseudoplastic behavior with reduction of drug release rate as the concentration of polymer increased. This approach to control the release of glimepiride using Zein nanoparticles/triblock copolymers-based in situ gel forming intramuscular implants could be useful for improving diabetes treatment effectiveness.

Design, Optimization and Application of Small Molecule Biosensor in Metabolic Engineering.

PubMed

Liu, Yang; Liu, Ye; Wang, Meng

2017-01-01

The development of synthetic biology and metabolic engineering has painted a great future for the bio-based economy, including fuels, chemicals, and drugs produced from renewable feedstocks. With the rapid advance of genome-scale modeling, pathway assembling and genome engineering/editing, our ability to design and generate microbial cell factories with various phenotype becomes almost limitless. However, our lack of ability to measure and exert precise control over metabolite concentration related phenotypes becomes a bottleneck in metabolic engineering. Genetically encoded small molecule biosensors, which provide the means to couple metabolite concentration to measurable or actionable outputs, are highly promising solutions to the bottleneck. Here we review recent advances in the design, optimization and application of small molecule biosensor in metabolic engineering, with particular focus on optimization strategies for transcription factor (TF) based biosensors.

Design, Optimization and Application of Small Molecule Biosensor in Metabolic Engineering

PubMed Central

Liu, Yang; Liu, Ye; Wang, Meng

2017-01-01

The development of synthetic biology and metabolic engineering has painted a great future for the bio-based economy, including fuels, chemicals, and drugs produced from renewable feedstocks. With the rapid advance of genome-scale modeling, pathway assembling and genome engineering/editing, our ability to design and generate microbial cell factories with various phenotype becomes almost limitless. However, our lack of ability to measure and exert precise control over metabolite concentration related phenotypes becomes a bottleneck in metabolic engineering. Genetically encoded small molecule biosensors, which provide the means to couple metabolite concentration to measurable or actionable outputs, are highly promising solutions to the bottleneck. Here we review recent advances in the design, optimization and application of small molecule biosensor in metabolic engineering, with particular focus on optimization strategies for transcription factor (TF) based biosensors. PMID:29089935

Chapter 9: 30 Years of Living in a Solar House in Colorado

DOE Office of Scientific and Technical Information (OSTI.GOV)

Emery, Keith A; Emery, Pat

2016-12-03

Having met in 1980 while working at the National Renewable Energy Laboratory, we were inspired by the vision of a renewable energy future to raise our family in a passive solar home. A basic, factory-cut, trilevel house design was selected in 1985 and intentionally sited and modified according to passive solar design principles to optimize conservation and solar gain, with a plan to add photovoltaics as soon as feasible.

Medium Optimization for the Production of Fibrinolytic Enzyme by Paenibacillus sp. IND8 Using Response Surface Methodology

PubMed Central

Prakash Vincent, Samuel Gnana

2014-01-01

Production of fibrinolytic enzyme by a newly isolated Paenibacillus sp. IND8 was optimized using wheat bran in solid state fermentation. A 25 full factorial design (first-order model) was applied to elucidate the key factors as moisture, pH, sucrose, yeast extract, and sodium dihydrogen phosphate. Statistical analysis of the results has shown that moisture, sucrose, and sodium dihydrogen phosphate have the most significant effects on fibrinolytic enzymes production (P < 0.05). Central composite design (CCD) was used to determine the optimal concentrations of these three components and the experimental results were fitted with a second-order polynomial model at 95% level (P < 0.05). Overall, 4.5-fold increase in fibrinolytic enzyme production was achieved in the optimized medium as compared with the unoptimized medium. PMID:24523635

Virtual Factory Framework for Supporting Production Planning and Control.

PubMed

Kibira, Deogratias; Shao, Guodong

2017-01-01

Developing optimal production plans for smart manufacturing systems is challenging because shop floor events change dynamically. A virtual factory incorporating engineering tools, simulation, and optimization generates and communicates performance data to guide wise decision making for different control levels. This paper describes such a platform specifically for production planning. We also discuss verification and validation of the constituent models. A case study of a machine shop is used to demonstrate data generation for production planning in a virtual factory.

Simultaneous saccharification and ethanol fermentation of oxalic acid pretreated corncob assessed with response surface methodology

Treesearch

Jae-Won Lee; Rita C.L.B. Rodrigues; Thomas W. Jeffries

2009-01-01

Response surface methodology was used to evaluate optimal time, temperature and oxalic acid concentration for simultaneous saccharification and fermentation (SSF) of corncob particles by Pichia stipitis CBS 6054. Fifteen different conditions for pretreatment were examined in a 23 full factorial design with six axial points. Temperatures ranged from 132 to 180º...

Factorial design optimization of experimental variables in the on-line separation/preconcentration of copper in water samples using solid phase extraction and ICP-OES determination.

PubMed

Escudero, Luis A; Cerutti, S; Olsina, R A; Salonia, J A; Gasquez, J A

2010-11-15

An on-line preconcentration procedure using solid phase extraction (SPE) for the determination of copper in different water samples by inductively coupled plasma optical emission spectrometry (ICP-OES) is proposed. The copper was retained on a minicolumn filled with ethyl vinyl acetate (EVA) at pH 8.0 without using any complexing reagent. The experimental optimization step was performed using a two-level full factorial design. The results showed that pH, sample loading flow rate, and their interaction (at the tested levels) were statistically significant. In order to determine the best conditions for preconcentration and determination of copper, a final optimization of the significant factors was carried out using a central composite design (CCD). The calibration graph was linear with a regression coefficient of 0.995 at levels near the detection limit up to at least 300 μg L(-1). An enrichment factor (EF) of 54 with a preconcentration time of 187.5 s was obtained. The limit of detection (3σ) was 0.26 μg L(-1). The sampling frequency for the developed methodology was about 15 samples/h. The relative standard deviation (RSD) for six replicates containing 50 μg L(-1) of copper was 3.76%. The methodology was successfully applied to the determination of Cu in tap, mineral, river water samples, and in a certified VKI standard reference material. Copyright © 2010 Elsevier B.V. All rights reserved.

Development of a factory/refinery method to measure total, soluble, and insoluble starch in sugar products

USDA-ARS?s Scientific Manuscript database

An easy, rapid, and inexpensive method was developed to measure total, soluble, and insoluble starch in products at the factory and refinery, using microwave-assisted neutralization chemistry. The method was optimized using the previously developed USDA Starch Research method as a reference. Optimal...

D-optimal experimental designs to test for departure from additivity in a fixed-ratio mixture ray.

PubMed

Coffey, Todd; Gennings, Chris; Simmons, Jane Ellen; Herr, David W

2005-12-01

Traditional factorial designs for evaluating interactions among chemicals in a mixture may be prohibitive when the number of chemicals is large. Using a mixture of chemicals with a fixed ratio (mixture ray) results in an economical design that allows estimation of additivity or nonadditive interaction for a mixture of interest. This methodology is extended easily to a mixture with a large number of chemicals. Optimal experimental conditions can be chosen that result in increased power to detect departures from additivity. Although these designs are used widely for linear models, optimal designs for nonlinear threshold models are less well known. In the present work, the use of D-optimal designs is demonstrated for nonlinear threshold models applied to a fixed-ratio mixture ray. For a fixed sample size, this design criterion selects the experimental doses and number of subjects per dose level that result in minimum variance of the model parameters and thus increased power to detect departures from additivity. An optimal design is illustrated for a 2:1 ratio (chlorpyrifos:carbaryl) mixture experiment. For this example, and in general, the optimal designs for the nonlinear threshold model depend on prior specification of the slope and dose threshold parameters. Use of a D-optimal criterion produces experimental designs with increased power, whereas standard nonoptimal designs with equally spaced dose groups may result in low power if the active range or threshold is missed.

Development and validation of LC-MS/MS method for the quantification of oxcarbazepine in human plasma using an experimental design.

PubMed

Srinubabu, Gedela; Ratnam, Bandaru Veera Venkata; Rao, Allam Appa; Rao, Medicherla Narasimha

2008-01-01

A rapid tandem mass spectrometric (MS-MS) method for the quantification of Oxcarbazepine (OXB) in human plasma using imipramine as an internal standard (IS) has been developed and validated. Chromatographic separation was achieved isocratically on a C18 reversed-phase column within 3.0 min, using a mobile phase of acetonitrile-10 mM ammonium formate (90 : 10 v/v) at a flow rate of 0.3 ml/min. Quantitation was achieved using multiple reaction monitoring (MRM) scan at MRM transitions m/z 253>208 and m/z 281>86 for OXB and the IS respectively. Calibration curves were linear over the concentration range of 0.2-16 mug/ml (r>0.999) with a limit of quantification of 0.2 mug/ml. Analytical recoveries of OXB from spiked human plasma were in the range of 74.9 to 76.3%. Plackett-Burman design was applied for screening of chromatographic and mass spectrometric factors; factorial design was applied for optimization of essential factors for the robustness study. A linear model was postulated and a 2(3) full factorial design was employed to estimate the model coefficients for intermediate precision. More specifically, experimental design helps the researcher to verify if changes in factor values produce a statistically significant variation of the observed response. The strategy is most effective if statistical design is used in most or all stages of the screening and optimizing process for future method validation of pharmacokinetic and bioequivalence studies.

Polymeric nanoparticles loaded with the 3,5,3'-triiodothyroacetic acid (Triac), a thyroid hormone: factorial design, characterization, and release kinetics.

PubMed

Dos Santos, Karen C; da Silva, Maria Fatima Gf; Pereira-Filho, Edenir R; Fernandes, Joao B; Polikarpov, Igor; Forim, Moacir R

2012-01-01

This present investigation deals with the development and optimization of polymeric nanoparticle systems loaded with 3,5,3'-triiodothyroacetic acid (Triac). A 2(11-6) fractional factorial design and another 2(2) factorial design were used to study the contrasts on particle size distribution, morphology, surface charge, drug content, entrapment efficiency, and in vitro drug release profiles. The independent variables were the concentration of Triac, type and quantity of both polymer and oil, quantity of Span™ 60 and Tween® 80, volume of solvent and water, and velocity of both magnetic stirring and the transfer of the organic phase into the aqueous solution. The results of optimized formulations showed a narrow size distribution with a polydispersity index lower than 0.200. The particle sizes were on average 159.6 nm and 285.6 nm for nanospheres and nanocapsules, respectively. The zeta potential was higher than 20 mV (in module) and the entrapment efficiency was nearly 100%. A high-performance liquid chromatography method was developed, validated, and efficiently applied to Triac quantification in colloidal suspension. The main independent variables were the type and quantity of the polymer and oil. In vitro drug release profile depicted several features to sustain Triac release. Different formulations showed various release rates indicating an interaction between Triac and other formulation compounds such as polymer and/or oil quantity. Two different models were identified (biexponential and monoexponential) that allowed the control of both the release rate and Triac concentration. Thus, the prepared nanoparticles described here may be of clinical importance in delivering Triac for thyroid treatment.

Removing lead from metallic mixture of waste printed circuit boards by vacuum distillation: factorial design and removal mechanism.

PubMed

Li, Xingang; Gao, Yujie; Ding, Hui

2013-10-01

The lead removal from the metallic mixture of waste printed circuit boards by vacuum distillation was optimized using experimental design, and a mathematical model was established to elucidate the removal mechanism. The variables studied in lead evaporation consisted of the chamber pressure, heating temperature, heating time, particle size and initial mass. The low-level chamber pressure was fixed at 0.1 Pa as the operation pressure. The application of two-level factorial design generated a first-order polynomial that agreed well with the data for evaporation efficiency of lead. The heating temperature and heating time exhibited significant effects on the efficiency, which was validated by means of the copper-lead mixture experiments. The optimized operating conditions within the region studied were the chamber pressure of 0.1 Pa, heating temperature of 1023 K and heating time of 120 min. After the conditions were employed to remove lead from the metallic mixture of waste printed circuit boards, the efficiency was 99.97%. The mechanism of the effects was elucidated by mathematical modeling that deals with evaporation, mass transfer and condensation, and can be applied to a wider range of metal removal by vacuum distillation. Copyright © 2013 Elsevier Ltd. All rights reserved.

Factorial design studies of antiretroviral drug-loaded stealth liposomal injectable: PEGylation, lyophilization and pharmacokinetic studies

NASA Astrophysics Data System (ADS)

Sudhakar, Beeravelli; Krishna, Mylangam Chaitanya; Murthy, Kolapalli Venkata Ramana

2016-01-01

The aim of the present study was to formulate and evaluate the ritonavir-loaded stealth liposomes by using 32 factorial design and intended to delivered by parenteral delivery. Liposomes were prepared by ethanol injection method using 32 factorial designs and characterized for various physicochemical parameters such as drug content, size, zeta potential, entrapment efficiency and in vitro drug release. The optimization process was carried out using desirability and overlay plots. The selected formulation was subjected to PEGylation using 10 % PEG-10000 solution. Stealth liposomes were characterized for the above-mentioned parameters along with surface morphology, Fourier transform infrared spectrophotometer, differential scanning calorimeter, stability and in vivo pharmacokinetic studies in rats. Stealth liposomes showed better result compared to conventional liposomes due to effect of PEG-10000. The in vivo studies revealed that stealth liposomes showed better residence time compared to conventional liposomes and pure drug solution. The conventional liposomes and pure drug showed dose-dependent pharmacokinetics, whereas stealth liposomes showed long circulation half-life compared to conventional liposomes and pure ritonavir solution. The results of statistical analysis showed significance difference as the p value is (<0.05) by one-way ANOVA. The result of the present study revealed that stealth liposomes are promising tool in antiretroviral therapy.

Formulation of wax oxybenzone microparticles using a factorial approach.

PubMed

Gomaa, Y A; Darwish, I A; Boraei, N A; El-Khordagui, L K

2010-01-01

Oxybenzone wax microparticles (MPs) were prepared by the hydrophobic congealable disperse phase method. The formulation of oxybenzone-loaded MPs was optimized using a 2⁴ experimental design. Factorial analysis indicated that the main MP characteristics were influenced by initial drug loading, emulsification speed, emulsifier concentration and hydrophilic-lipophilic balance. MPs were spherical with 50.5–88.1 μm size range, 17.8–38.9 drug content in mg/100 mg MPs and 33.1–87.2% oxybenzone release in 1 h. A wide range of sunscreen delivery systems suitable for different formulation purposes were generated which may contribute to the advanced formulation of sunscreen products with improved performance.

Production optimization of invertase by Lactobacillus brevis Mm-6 and its immobilization on alginate beads.

PubMed

Awad, Ghada E A; Amer, Hassan; El-Gammal, Eman W; Helmy, Wafaa A; Esawy, Mona A; Elnashar, Magdy M M

2013-04-02

A sequential optimization strategy, based on statistical experimental designs, was employed to enhance the production of invertase by Lactobacillus brevis Mm-6 isolated from breast milk. First, a 2-level Plackett-Burman design was applied to screen the bioprocess parameters that significantly influence the invertase production. The second optimization step was performed using fractional factorial design in order to optimize the amounts of variables have the highest positive significant effect on the invertase production. A maximal enzyme activity of 1399U/ml was more than five folds the activity obtained using the basal medium. Invertase was immobilized onto grafted alginate beads to improve the enzyme's stability. Immobilization process increased the operational temperature from 30 to 60°C compared to the free enzyme. The reusability test proved the durability of the grafted alginate beads for 15 cycles with retention of 100% of the immobilized enzyme activity to be more convenient for industrial uses. Copyright © 2013 Elsevier Ltd. All rights reserved.

Development and Optimization of Dispersible Tablet of Bacopa monnieri with Improved Functionality for Memory Enhancement.

PubMed

Thakkar, Vaishali Tejas; Deshmukh, Amol; Hingorani, Lal; Juneja, Payal; Baldaniya, Lalji; Patel, Asha; Pandya, Tosha; Gohel, Mukesh

2017-01-01

The Bacopa monnieri is traditional Ayurvedic medicine, and reported for memory-enhancing effects. The Bacoside is poorly soluble, bitter in taste and responsible for the memory enhancement action. Memory enhancer is commonly prescribed for children or elder people. Poor solubility, patient compliance and bitterness were a major driving force to develop taste masked β-cyclodextrin complex and dispersible tablets. The inclusion complex of Bacopa monnieri and β-cyclodextrin was prepared in different molar ratios of Bacopa monnieri by Co-precipitation method. Phase solubility study was conducted to evaluate the effect of β-cyclodextrin on aqueous solubility of Bacoside A. The characterization was determined by Fourier transformation infrared spectroscopy (FTIR),Differential scanning calorimetry (DSC) and X-ray diffraction study (XRD).Crospovidone and croscarmallose sodium were used as super disintigrant. The 3 2 full factorial design was adopted to investigate the influence of two superdisintegrants on the wetting time and disntegration time of the tablets. The result revels that molar ratio (1:4) of inclusion complex enhance 3-fold solubility. Full factorial design was successfully employed for the optimization of dispersible tablet of B. monnieri . The short-term accelerated stability study confirmed that high stability of B. monnieri in inclusion complex.

Pediatric diabetic ketoacidosis, fluid therapy, and cerebral injury: the design of a factorial randomized controlled trial.

PubMed

Glaser, Nicole S; Ghetti, Simona; Casper, T Charles; Dean, J Michael; Kuppermann, Nathan

2013-09-01

Treatment protocols for pediatric diabetic ketoacidosis (DKA) vary considerably among centers in the USA and worldwide. The optimal protocol for intravenous (IV) fluid administration is an area of particular controversy, mainly in regard to possible associations between rates of IV fluid infusion and the development of cerebral edema (CE), the most common and the most feared complication of DKA in children. Theoretical concerns about associations between osmotic fluid shifts and CE have prompted recommendations for conservative fluid infusion during DKA. However, recent data suggest that cerebral hypoperfusion may play a role in cerebral injury associated with DKA. Currently, there are no existing data from prospective clinical trials to determine the optimal fluid treatment protocol for pediatric DKA. The Pediatric Emergency Care Applied Research Network FLUID (FLuid therapies Under Investigation in DKA) study is the first prospective randomized trial to evaluate fluid regimens for pediatric DKA. This 13-center nationwide factorial design study will evaluate the effects of rehydration rate and fluid sodium content on neurological status during DKA treatment, the frequency of clinically overt CE and long-term neurocognitive outcomes following DKA. © 2013 John Wiley & Sons A/S.

Optimization of acidic extraction of astaxanthin from Phaffia rhodozyma *

PubMed Central

Ni, Hui; Chen, Qi-he; He, Guo-qing; Wu, Guang-bin; Yang, Yuan-fan

2008-01-01

Optimization of a process for extracting astaxanthin from Phaffia rhodozyma by acidic method was investigated, regarding several extraction factors such as acids, organic solvents, temperature and time. Fractional factorial design, central composite design and response surface methodology were used to derive a statistically optimal model, which corresponded to the following optimal condition: concentration of lactic acid at 5.55 mol/L, ratio of ethanol to yeast dry weight at 20.25 ml/g, temperature for cell-disruption at 30 °C, and extraction time for 3 min. Under this condition, astaxanthin and the total carotenoids could be extracted in amounts of 1294.7 μg/g and 1516.0 μg/g, respectively. This acidic method has advantages such as high extraction efficiency, low chemical toxicity and no special requirement of instruments. Therefore, it might be a more feasible and practical method for industrial practice. PMID:18196613

Formulation, optimization, and evaluation of self-emulsifying drug delivery systems of nevirapine

PubMed Central

Chintalapudi, Ramprasad; Murthy, T. E. G. K.; Lakshmi, K. Rajya; Manohar, G. Ganesh

2015-01-01

Background: The aim of the present study was to formulate and optimize the self-emulsifying drug delivery systems (SEDDS) of nevirapine (NVP) by use of 22 factorial designs to enhance the oral absorption of NVP by improving its solubility, dissolution rate, and diffusion profile. SEDDS are the isotropic mixtures of oil, surfactant, co-surfactant and drug that form oil in water microemulsion when introduced into the aqueous phase under gentle agitation. Materials and Methods: Solubility of NVP in different oils, surfactants, and co-surfactants was determined for the screening of excipients. Pseudo-ternary phase diagrams were constructed by the aqueous titration method, and formulations were developed based on the optimum excipient combinations with the help of data obtained through the maximum micro emulsion region containing combinations of oil, surfactant, and co-surfactant. The formulations of SEDDS were optimized by 22 factorial designs. Results: The optimum formulation of SEDDS contains 32.5% oleic acid, 44.16% tween 20, and 11.9% polyethylene glycol 600 as oil, surfactant, and co-surfactant respectively. The SEDDS was evaluated for the following drug content, self-emulsification time, rheological properties, zeta potential, in vitro diffusion studies, thermodynamic stability studies, and in vitro dissolution studies. An increase in dissolution was achieved by SEDDS compared to pure form of NVP. Conclusion: Overall, this study suggests that the dissolution and oral bioavailability of NVP could be improved by SEDDS technology. PMID:26682191

Optimization of headspace solid-phase microextraction by means of an experimental design for the determination of methyl tert.-butyl ether in water by gas chromatography-flame ionization detection.

PubMed

Dron, Julien; Garcia, Rosa; Millán, Esmeralda

2002-07-19

A procedure for determination of methyl tert.-butyl ether (MTBE) in water by headspace solid-phase microextraction (HS-SPME) has been developed. The analysis was carried out by gas chromatography with flame ionization detection. The extraction procedure, using a 65-microm poly(dimethylsiloxane)-divinylbenzene SPME fiber, was optimized following experimental design. A fractional factorial design for screening and a central composite design for optimizing the significant variables were applied. Extraction temperature and sodium chloride concentration were significant variables, and 20 degrees C and 300 g/l were, respectively chosen for the best extraction response. With these conditions, an extraction time of 5 min was sufficient to extract MTBE. The calibration linear range for MTBE was 5-500 microg/l and the detection limit 0.45 microg/l. The relative standard deviation, for seven replicates of 250 microg/l MTBE in water, was 6.3%.

The International Design Study for the Neutrino Factory

DOE Office of Scientific and Technical Information (OSTI.GOV)

Long, K.

2008-02-21

The International Design Study for a future Neutrino Factory and super-beam facility (the ISS) established the physics case for a high-precision programme of long-baseline neutrino-oscillation measurements. The ISS also identified baseline specifications for the Neutrino Factory accelerator complex and the neutrino detector systems. This paper summarises the objectives of the International Design Study for the Neutrino Factory (the IDS-NF). The IDS-NF will build on the work of the ISS to deliver a Reference Design Report for the Neutrino Factory by 2012/13 and an Interim Design Report by 2010/11.

Screening of Actinomycetes from mangrove ecosystem for L-asparaginase activity and optimization by response surface methodology.

PubMed

Usha, Rajamanickam; Mala, Krishnaswami Kanjana; Venil, Chidambaram Kulandaisamy; Palaniswamy, Muthusamy

2011-01-01

Marine actinomycetes were isolated from sediment samples collected from Pitchavaram mangrove ecosystem situated along the southeast coast of India. Maximum actinomycete population was noted in rhizosphere region. About 38% of the isolates produced L-asparaginase. One potential strain KUA106 produced higher level of enzyme using tryptone glucose yeast extract medium. Based on the studied phenotypic characteristics, strain KUA106 was identified as Streptomyces parvulus KUA106. The optimization method that combines the Plackett-Burman design, a factorial design and the response surface method, which were used to optimize the medium for the production of L-asparaginase by Streptomycetes parvulus. Four medium factors were screened from eleven medium factors by Plackett-Burman design experiments and subsequent optimization process to find out the optimum values of the selected parameters using central composite design was performed. Asparagine, tryptone, d) extrose and NaCl components were found to be the best medium for the L-asparaginase production. The combined optimization method described here is the effective method for screening medium factors as well as determining their optimum level for the production of L-asparaginase by Streptomycetes parvulus KUAP106.

Application of Response Surface Methodology for Optimization of Extracellular Glucoamylase Production by Candida guilliermondii.

PubMed

Mohamed, Lagzouli; Kettani, Youssfi El; Ali, Aitounejjar; Mohamed, Elyachioui; Mohamed, Jadal

2017-01-01

Glucoamylase is among the most important enzymes in biotechnology. The present study aims to determine better conditions for growth and glucoamylase production by Candida guilliermondii and to reduce the overall cost of the medium using Box-Behnken design with one central point and response surface methodology. Box-Behnken factorial design based on three levels was carried out to obtain optimal medium combination of five independent variables such as initial pH, soluble starch, CH4N2O, yeast extract and MgSO4. Forty one randomized mediums were incubated in flask on a rotary shaker at 105 rpm for 72 h at 30°C. The production of biomass was found to be pH and starch dependent, maximum production when the starch concentration was 8 g L-1 and the initial pH was 6, while maximum glucoamylase production was found at 6.5 of initial pH, 4 g L-1 yeast extract and 6 g L-1 starch, whereas yeast extract and urea were highly significant, but interacted negatively. Box-Behnken factorial design used for the analysis of treatment combinations gave a second-order polynomial regression model with R2 = 0.976 for Biomass and R2 = 0.981 for glucoamylase. The final biomass and glucoamylase activity obtained was very close to the calculated parameters according to the p-values (p<0.001), the predicted optimal parameters were confirmed and provides a basis for further studies in baking additives and in the valuation of starch waste products.

Application study of evolutionary operation methods in optimization of process parameters for mosquito coils industry

NASA Astrophysics Data System (ADS)

Ginting, E.; Tambunanand, M. M.; Syahputri, K.

2018-02-01

Evolutionary Operation Methods (EVOP) is a method that is designed used in the process of running or operating routinely in the company to enables high productivity. Quality is one of the critical factors for a company to win the competition. Because of these conditions, the research for products quality has been done by gathering the production data of the company and make a direct observation to the factory floor especially the drying department to identify the problem which is the high water content in the mosquito incense coil. PT.X which is producing mosquito coils attempted to reduce product defects caused by the inaccuracy of operating conditions. One of the parameters of good quality insect repellent that is water content, that if the moisture content is too high then the product easy to mold and broken, and vice versa if it is too low the products are easily broken and burn shorter hours. Three factors that affect the value of the optimal water content, the stirring time, drying temperature and drying time. To obtain the required conditions Evolutionary Operation (EVOP) methods is used. Evolutionary Operation (EVOP) is used as an efficient technique for optimization of two or three variable experimental parameters using two-level factorial designs with center point. Optimal operating conditions in the experiment are stirring time performed for 20 minutes, drying temperature at 65°C, and drying time for 130 minutes. The results of the analysis based on the method of Evolutionary Operation (EVOP) value is the optimum water content of 6.90%, which indicates the value has approached the optimal in a production plant that is 7%.

On optimal control problem for conservation law modelling one class of highly re-entrant production systems

NASA Astrophysics Data System (ADS)

D'Apice, Ciro; Kogut, Peter I.

2017-07-01

We discuss the optimal control problem stated as the minimization in the L2-sense of the mismatch between the actual out-flux and a demand forecast for a hyperbolic conservation law that models a highly re-entrant production system. The output of the factory is described as a function of the work in progress and the position of the so-called push-pull point (PPP) where we separate the beginning of the factory employing a push policy from the end of the factory, which uses a pull policy.

Particle flow oriented electromagnetic calorimeter optimization for the circular electron positron collider

NASA Astrophysics Data System (ADS)

Zhao, H.; Fu, C.; Yu, D.; Wang, Z.; Hu, T.; Ruan, M.

2018-03-01

The design and optimization of the Electromagnetic Calorimeter (ECAL) are crucial for the Circular Electron Positron Collider (CEPC) project, a proposed future Higgs/Z factory. Following the reference design of the International Large Detector (ILD), a set of silicon-tungsten sampling ECAL geometries are implemented into the Geant4 simulation, whose performance is then scanned using Arbor algorithm. The photon energy response at different ECAL longitudinal structures is analyzed, and the separation performance between nearby photon showers with different ECAL transverse cell sizes is investigated and parametrized. The overall performance is characterized by a set of physics benchmarks, including νν H events where Higgs boson decays into a pair of photons (EM objects) or gluons (jets) and Z→τ+τ- events. Based on these results, we propose an optimized ECAL geometry for the CEPC project.

Optimization of the Neutrino Factory, revisited

NASA Astrophysics Data System (ADS)

Agarwalla, Sanjib K.; Huber, Patrick; Tang, Jian; Winter, Walter

2011-01-01

We perform the baseline and energy optimization of the Neutrino Factory including the latest simulation results on the magnetized iron detector (MIND). We also consider the impact of τ decays, generated by νμ → ντ or ν e → ντ appearance, on the mass hierarchy, CP violation, and θ 13 discovery reaches, which we find to be negligible for the considered detector. For the baseline-energy optimization for small sin2 2 θ 13, we qualitatively recover the results with earlier simulations of the MIND detector. We find optimal baselines of about 2500km to 5000km for the CP violation measurement, where now values of E μ as low as about 12 GeV may be possible. However, for large sin2 2 θ 13, we demonstrate that the lower threshold and the backgrounds reconstructed at lower energies allow in fact for muon energies as low as 5 GeV at considerably shorter baselines, such as FNAL-Homestake. This implies that with the latest MIND analysis, low-and high-energy versions of the Neutrino Factory are just two different versions of the same experiment optimized for different parts of the parameter space. Apart from a green-field study of the updated detector performance, we discuss specific implementations for the two-baseline Neutrino Factory, where the considered detector sites are taken to be currently discussed underground laboratories. We find that reasonable setups can be found for the Neutrino Factory source in Asia, Europe, and North America, and that a triangular-shaped storage ring is possible in all cases based on geometrical arguments only.

Design of Experiments with Multiple Independent Variables: A Resource Management Perspective on Complete and Reduced Factorial Designs

PubMed Central

Collins, Linda M.; Dziak, John J.; Li, Runze

2009-01-01

An investigator who plans to conduct experiments with multiple independent variables must decide whether to use a complete or reduced factorial design. This article advocates a resource management perspective on making this decision, in which the investigator seeks a strategic balance between service to scientific objectives and economy. Considerations in making design decisions include whether research questions are framed as main effects or simple effects; whether and which effects are aliased (confounded) in a particular design; the number of experimental conditions that must be implemented in a particular design and the number of experimental subjects the design requires to maintain the desired level of statistical power; and the costs associated with implementing experimental conditions and obtaining experimental subjects. In this article four design options are compared: complete factorial, individual experiments, single factor, and fractional factorial designs. Complete and fractional factorial designs and single factor designs are generally more economical than conducting individual experiments on each factor. Although relatively unfamiliar to behavioral scientists, fractional factorial designs merit serious consideration because of their economy and versatility. PMID:19719358

Optimization of Maghemite (γ-Fe2O3) Nano-Powder Mixed micro-EDM of CoCrMo with Multiple Responses Using Gray Relational Analysis (GRA)

NASA Astrophysics Data System (ADS)

Mejid Elsiti, Nagwa; Noordin, M. Y.; Idris, Ani; Saed Majeed, Faraj

2017-10-01

This paper presents an optimization of process parameters of Micro-Electrical Discharge Machining (EDM) process with (γ-Fe2O3) nano-powder mixed dielectric using multi-response optimization Grey Relational Analysis (GRA) method instead of single response optimization. These parameters were optimized based on 2-Level factorial design combined with Grey Relational Analysis. The machining parameters such as peak current, gap voltage, and pulse on time were chosen for experimentation. The performance characteristics chosen for this study are material removal rate (MRR), tool wear rate (TWR), Taper and Overcut. Experiments were conducted using electrolyte copper as the tool and CoCrMo as the workpiece. Experimental results have been improved through this approach.

Systems metabolic engineering of Corynebacterium glutamicum for production of the chemical chaperone ectoine.

PubMed

Becker, Judith; Schäfer, Rudolf; Kohlstedt, Michael; Harder, Björn J; Borchert, Nicole S; Stöveken, Nadine; Bremer, Erhard; Wittmann, Christoph

2013-11-15

The stabilizing and function-preserving effects of ectoines have attracted considerable biotechnological interest up to industrial scale processes for their production. These rely on the release of ectoines from high-salinity-cultivated microbial producer cells upon an osmotic down-shock in rather complex processor configurations. There is growing interest in uncoupling the production of ectoines from the typical conditions required for their synthesis, and instead design strains that naturally release ectoines into the medium without the need for osmotic changes, since the use of high-salinity media in the fermentation process imposes notable constraints on the costs, design, and durability of fermenter systems. Here, we used a Corynebacterium glutamicum strain as a cellular chassis to establish a microbial cell factory for the biotechnological production of ectoines. The implementation of a mutant aspartokinase enzyme ensured efficient supply of L-aspartate-beta-semialdehyde, the precursor for ectoine biosynthesis. We further engineered the genome of the basic C. glutamicum strain by integrating a codon-optimized synthetic ectABCD gene cluster under expressional control of the strong and constitutive C. glutamicum tuf promoter. The resulting recombinant strain produced ectoine and excreted it into the medium; however, lysine was still found as a by-product. Subsequent inactivation of the L-lysine exporter prevented the undesired excretion of lysine while ectoine was still exported. Using the streamlined cell factory, a fed-batch process was established that allowed the production of ectoine with an overall productivity of 6.7 g L(-1) day(-1) under growth conditions that did not rely on the use of high-salinity media. The present study describes the construction of a stable microbial cell factory for recombinant production of ectoine. We successfully applied metabolic engineering strategies to optimize its synthetic production in the industrial workhorse C. glutamicum and thereby paved the way for further improvements in ectoine yield and biotechnological process optimization.

A practical limit to trials needed in one-person randomized controlled experiments.

PubMed

Alemi, Roshan; Alemi, Farrokh

2007-01-01

Recently in this journal, J. Olsson and colleagues suggested the use of factorial experimental designs to guide a patient's efforts to choose among multiple interventions. These authors argue that factorial design, where every possible combination of the interventions is tried, is superior to sequential trial and errors. Factorial design is efficient in identifying the effectiveness of interventions (factor effect). Most patients care only about feeling better and not why their conditions are improving. If the goal of the patient is to get better and not to estimate the factor effect, then no control groups are needed. In this article, we show a modification in the factorial design of experiments proposed by Olsson and colleagues where a full-factorial design is planned, but experimentation is stopped when the patient's condition improves. With this modification, the number of trials is radically fewer than those needed by factorial design. For example, a patient trying out 4 different interventions with a median probability of success of .50 is expected to need 2 trials before stopping the experimentation in comparison with 32 in a full-factorial design.

Optimization of pectinase immobilization on grafted alginate-agar gel beads by 24 full factorial CCD and thermodynamic profiling for evaluating of operational covalent immobilization.

PubMed

Abdel Wahab, Walaa A; Karam, Eman A; Hassan, Mohamed E; Kansoh, Amany L; Esawy, Mona A; Awad, Ghada E A

2018-07-01

Pectinase produced by a honey derived from the fungus Aspergillus awamori KX943614 was covalently immobilized onto gel beads made of alginate and agar. Polyethyleneimine, glutaraldehyde, loading time and enzyme's units were optimized by 2 4 full factorial central composite design (CCD). The immobilization process increased the optimal working pH for the free pectinase from 5 to a broader range of pH4.5-5.5 and the optimum operational temperature from 55°C to a higher temperature, of 60°C, which is favored to reduce the enzyme's microbial contamination. The thermodynamics studies showed a thermal stability enhancement against high temperature for the immobilized formula. Moreover, an increase in half-lives and D-values was achieved. The thermodynamic studies proved that immobilization of pectinase made a remarkable increase in enthalpy and free energy because of enzyme stability enhancement. The reusability test revealed that 60% of pectinase's original activity was retained after 8 successive cycles. This gel formula may be convenient for immobilization of other industrial enzymes. Copyright © 2018 Elsevier B.V. All rights reserved.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Adey, D.; Appleby, R. B.; Bayes, R.

Neutrino beams produced from the decay of muons in a racetrack-like decay ring (the so called Neutrino Factory) provide a powerful way to study neutrino oscillation physics and, in addition, provide unique beams for neutrino interaction studies. The Neutrinos from STORed Muons (nuSTORM) facility uses a neutrino factory-like design. Due to the particular nature of nuSTORM, it can also provide an intense, very pure, muon neutrino beam from pion decay. This so-called 'Neo-conventional' muon-neutrino beam from nuSTORM makes nuSTORM a hybrid neutrino factory. Here in this paper we describe the facility and give a detailed description of the neutrino beamsmore » that are available and the precision to which they can be characterized. We then show its potential for a neutrino interaction physics program and present sensitivity plots that indicate how well the facility can perform for short-baseline oscillation searches. Lastly, we comment on the performance potential of a 'Neo-conventional' muon neutrino beam optimized for long-baseline neutrino-oscillation physics.« less

Design, Characterization, and Optimization of Controlled Drug Delivery System Containing Antibiotic Drug/s

PubMed Central

Shelate, Pragna; Dave, Divyang

2016-01-01

The objective of this work was design, characterization, and optimization of controlled drug delivery system containing antibiotic drug/s. Osmotic drug delivery system was chosen as controlled drug delivery system. The porous osmotic pump tablets were designed using Plackett-Burman and Box-Behnken factorial design to find out the best formulation. For screening of three categories of polymers, six independent variables were chosen for Plackett-Burman design. Osmotic agent sodium chloride and microcrystalline cellulose, pore forming agent sodium lauryl sulphate and sucrose, and coating agent ethyl cellulose and cellulose acetate were chosen as independent variables. Optimization of osmotic tablets was done by Box-Behnken design by selecting three independent variables. Osmotic agent sodium chloride, pore forming agent sodium lauryl sulphate, and coating agent cellulose acetate were chosen as independent variables. The result of Plackett-Burman and Box-Behnken design and ANOVA studies revealed that osmotic agent and pore former had significant effect on the drug release up to 12 hr. The observed independent variables were found to be very close to predicted values of most satisfactory formulation which demonstrates the feasibility of the optimization procedure in successful development of porous osmotic pump tablets containing antibiotic drug/s by using sodium chloride, sodium lauryl sulphate, and cellulose acetate as key excipients. PMID:27610247

Implementing Clinical Research Using Factorial Designs: A Primer.

PubMed

Baker, Timothy B; Smith, Stevens S; Bolt, Daniel M; Loh, Wei-Yin; Mermelstein, Robin; Fiore, Michael C; Piper, Megan E; Collins, Linda M

2017-07-01

Factorial experiments have rarely been used in the development or evaluation of clinical interventions. However, factorial designs offer advantages over randomized controlled trial designs, the latter being much more frequently used in such research. Factorial designs are highly efficient (permitting evaluation of multiple intervention components with good statistical power) and present the opportunity to detect interactions amongst intervention components. Such advantages have led methodologists to advocate for the greater use of factorial designs in research on clinical interventions (Collins, Dziak, & Li, 2009). However, researchers considering the use of such designs in clinical research face a series of choices that have consequential implications for the interpretability and value of the experimental results. These choices include: whether to use a factorial design, selection of the number and type of factors to include, how to address the compatibility of the different factors included, whether and how to avoid confounds between the type and number of interventions a participant receives, and how to interpret interactions. The use of factorial designs in clinical intervention research poses choices that differ from those typically considered in randomized clinical trial designs. However, the great information yield of the former encourages clinical researchers' increased and careful execution of such designs. Copyright © 2017. Published by Elsevier Ltd.

Dual controlled release, in situ gelling periodontal sol of metronidazole benzoate and serratiopeptidase: statistical optimization and mechanistic evaluation.

PubMed

Kumari, Neeraj; Pathak, Kamla

2012-01-01

In situ gelling syringeable periodontal sol capable of dual controlled delivery of metronidazole benzoate and serratiopeptidase was designed based on 2(3) factorial design with drug, poloxamer 407 and aerosil as independent variables and sol gel transition characteristics, %CDR(48h) and palatability as responses. The sols had agreeable taste, were mucoadhesive, syringeable and inverted into gels at periodontal cavity temperature. F8 with optimal drug release was identified as the best formulation. The dispersion characteristics of poloxamer significantly affected the pharmacotechnical properties of the in situ gelling systems. Extra design checkpoint generated using Design Expert software 8.02 (Stat-Ease, USA) validated the experimental design. Thus a thermoreversible, in situ gelling and syringeable periodontal sol with acceptable taste characteristics that offered controlled release of metronidazole benzoate and serratiopeptidase was developed for application into the periodontal pocket. The developed optimized sol was satisfactory in terms of taste, syringeability, palatability and incorporation of serratiopeptidase as anti-inflammatory agent, has the potential of developing a therapeutically efficacious system for treatment of periodontal inflammatory anaerobic infections.

Optimization of segmented thermoelectric generator using Taguchi and ANOVA techniques.

PubMed

Kishore, Ravi Anant; Sanghadasa, Mohan; Priya, Shashank

2017-12-01

Recent studies have demonstrated that segmented thermoelectric generators (TEGs) can operate over large thermal gradient and thus provide better performance (reported efficiency up to 11%) as compared to traditional TEGs, comprising of single thermoelectric (TE) material. However, segmented TEGs are still in early stages of development due to the inherent complexity in their design optimization and manufacturability. In this study, we demonstrate physics based numerical techniques along with Analysis of variance (ANOVA) and Taguchi optimization method for optimizing the performance of segmented TEGs. We have considered comprehensive set of design parameters, such as geometrical dimensions of p-n legs, height of segmentation, hot-side temperature, and load resistance, in order to optimize output power and efficiency of segmented TEGs. Using the state-of-the-art TE material properties and appropriate statistical tools, we provide near-optimum TEG configuration with only 25 experiments as compared to 3125 experiments needed by the conventional optimization methods. The effect of environmental factors on the optimization of segmented TEGs is also studied. Taguchi results are validated against the results obtained using traditional full factorial optimization technique and a TEG configuration for simultaneous optimization of power and efficiency is obtained.

On the use of metabolic control analysis in the optimization of cyanobacterial biosolar cell factories.

PubMed

Angermayr, S Andreas; Hellingwerf, Klaas J

2013-09-26

Oxygenic photosynthesis will have a key role in a sustainable future. It is therefore significant that this process can be engineered in organisms such as cyanobacteria to construct cell factories that catalyze the (sun)light-driven conversion of CO2 and water into products like ethanol, butanol, or other biofuels or lactic acid, a bioplastic precursor, and oxygen as a byproduct. It is of key importance to optimize such cell factories to maximal efficiency. This holds for their light-harvesting capabilities under, for example, circadian illumination in large-scale photobioreactors. However, this also holds for the "dark" reactions of photosynthesis, that is, the conversion of CO2, NADPH, and ATP into a product. Here, we present an analysis, based on metabolic control theory, to estimate the optimal capacity for product formation with which such cyanobacterial cell factories have to be equipped. Engineered l-lactic acid producing Synechocystis sp. PCC6803 strains are used to identify the relation between production rate and enzymatic capacity. The analysis shows that the engineered cell factories for l-lactic acid are fully limited by the metabolic capacity of the product-forming pathway. We attribute this to the fact that currently available promoter systems in cyanobacteria lack the genetic capacity to a provide sufficient expression in single-gene doses.

Design and synthesis of a novel multifunctional stabilizer for highly stable uc(dl)-tetrahydropalmatine nanosuspensions and in vitro study

NASA Astrophysics Data System (ADS)

Yan, Beibei; Wang, Yancai; Wang, Lulu; Zhou, Yuqi; Shang, Xueyun; Zhao, Juan; Liu, Yangyang; Du, Juan

2018-05-01

The present study aimed to prepare stable uc(dl)-tetrahydropalmatine (uc(dl)-THP) nanosuspensions of optimized formulation with PEGylated chitosan as a multifunctional stabilizer using the antisolvent precipitation method. A central composite design project of three factors and five-level full factorial (53) was applied to design the experimental program, and response surface methodology analysis was used to optimize the experimental conditions. The effects of critical influencing factors such as PEGylated chitosan concentration, operational temperature, and ultrasonic energy on particle size and zeta potential were investigated. Under the optimization nanosuspension formulation, the particle size was 269 nm and zeta potential was at 37.4 mV. Also, the uc(dl)-THP nanosuspensions maintained good physical stability after 2 months, indicating the potential ability of the multifunctional stabilizer for stable nanosuspension formulation. Hence, the present findings indicated that PEGylated chitosan could be used as the ideal stabilizer to form a physically stable nanosuspension formulation.

Development and Optimization of Dispersible Tablet of Bacopa monnieri with Improved Functionality for Memory Enhancement

PubMed Central

Thakkar, Vaishali Tejas; Deshmukh, Amol; Hingorani, Lal; Juneja, Payal; Baldaniya, Lalji; Patel, Asha; Pandya, Tosha; Gohel, Mukesh

2017-01-01

Introduction: The Bacopa monnieri is traditional Ayurvedic medicine, and reported for memory-enhancing effects. The Bacoside is poorly soluble, bitter in taste and responsible for the memory enhancement action. Memory enhancer is commonly prescribed for children or elder people. Objective: Poor solubility, patient compliance and bitterness were a major driving force to develop taste masked β-cyclodextrin complex and dispersible tablets. Materials and Methods: The inclusion complex of Bacopa monnieri and β-cyclodextrin was prepared in different molar ratios of Bacopa monnieri by Co-precipitation method. Phase solubility study was conducted to evaluate the effect of β-cyclodextrin on aqueous solubility of Bacoside A. The characterization was determined by Fourier transformation infrared spectroscopy (FTIR),Differential scanning calorimetry (DSC) and X-ray diffraction study (XRD).Crospovidone and croscarmallose sodium were used as super disintigrant. The 32 full factorial design was adopted to investigate the influence of two superdisintegrants on the wetting time and disntegration time of the tablets. Conclusion: The result revels that molar ratio (1:4) of inclusion complex enhance 3-fold solubility. Full factorial design was successfully employed for the optimization of dispersible tablet of B. monnieri. The short-term accelerated stability study confirmed that high stability of B. monnieri in inclusion complex. PMID:28979076

Synthesis and factorial design applied to a novel chitosan/sodium polyphosphate nanoparticles via ionotropic gelation as an RGD delivery system.

PubMed

Kiilll, Charlene Priscila; Barud, Hernane da Silva; Santagneli, Sílvia Helena; Ribeiro, Sidney José Lima; Silva, Amélia M; Tercjak, Agnieszka; Gutierrez, Junkal; Pironi, Andressa Maria; Gremião, Maria Palmira Daflon

2017-02-10

Chitosan nanoparticles have been extensively studied for both drug and protein/peptide delivery. The aim of this study was to develop an optimized chitosan nanoparticle, by ionotropic gelation method, using 3 2 full factorial design with a novel polyanion, sodium polyphosphate, well known under the trade name Graham salt. The effects of these parameters on the particle size, zeta potential, and morphology and association efficiency were investigated. The optimized nanoparticles showed an estimated size of 166.20±1.95nm, a zeta potential of 38.7±1.2mV and an efficacy of association of 97.0±2.4%. The Atomic Force Microscopy (AFM) and Scanning Electronic Microscopy (SEM) revealed spherical nanoparticles with uniform size. Molecular interactions among the components of the nanoparticles and peptide were evaluated by Fourier Transform Infrared Spectra (FTIR) and Differential Scanning Calorimetry (DSC). The obtained results indicated that, the developed nanoparticles demonstrated high biocompatible, revealing no or low toxicity in the human cancer cell line (Caco-2). In conclusion, this work provides parameters that contribute to production of chitosan nanoparticles and sodium polyphosphate with desirable size, biocompatible and enabling successful use for protein/peptides delivery. Copyright © 2016 Elsevier Ltd. All rights reserved.

Product modular design incorporating preventive maintenance issues

NASA Astrophysics Data System (ADS)

Gao, Yicong; Feng, Yixiong; Tan, Jianrong

2016-03-01

Traditional modular design methods lead to product maintenance problems, because the module form of a system is created according to either the function requirements or the manufacturing considerations. For solving these problems, a new modular design method is proposed with the considerations of not only the traditional function related attributes, but also the maintenance related ones. First, modularity parameters and modularity scenarios for product modularity are defined. Then the reliability and economic assessment models of product modularity strategies are formulated with the introduction of the effective working age of modules. A mathematical model used to evaluate the difference among the modules of the product so that the optimal module of the product can be established. After that, a multi-objective optimization problem based on metrics for preventive maintenance interval different degrees and preventive maintenance economics is formulated for modular optimization. Multi-objective GA is utilized to rapidly approximate the Pareto set of optimal modularity strategy trade-offs between preventive maintenance cost and preventive maintenance interval difference degree. Finally, a coordinate CNC boring machine is adopted to depict the process of product modularity. In addition, two factorial design experiments based on the modularity parameters are constructed and analyzed. These experiments investigate the impacts of these parameters on the optimal modularity strategies and the structure of module. The research proposes a new modular design method, which may help to improve the maintainability of product in modular design.

Development and experimental design of a novel controlled-release matrix tablet formulation for indapamide hemihydrate.

PubMed

Antovska, Packa; Ugarkovic, Sonja; Petruševski, Gjorgji; Stefanova, Bosilka; Manchevska, Blagica; Petkovska, Rumenka; Makreski, Petre

2017-11-01

Development, experimental design and in vitro in vivo correlation (IVIVC) of controlled-release matrix formulation. Development of novel oral controlled delivery system for indapamide hemihydrate, optimization of the formulation by experimental design and evaluation regarding IVIVC on a pilot scale batch as a confirmation of a well-established formulation. In vitro dissolution profiles of controlled-release tablets of indapamide hemihydrate from four different matrices had been evaluated in comparison to the originator's product Natrilix (Servier) as a direction for further development and optimization of a hydroxyethylcellulose-based matrix controlled-release formulation. A central composite factorial design had been applied for the optimization of a chosen controlled-release tablet formulation. The controlled-release tablets with appropriate physical and technological properties had been obtained with a matrix: binder concentration variations in the range: 20-40w/w% for the matrix and 1-3w/w% for the binder. The experimental design had defined the design space for the formulation and was prerequisite for extraction of a particular formulation that would be a subject for transfer on pilot scale and IVIV correlation. The release model of the optimized formulation has shown best fit to the zero order kinetics depicted with the Hixson-Crowell erosion-dependent mechanism of release. Level A correlation was obtained.

Statistical Modeling Studies of Iron Recovery from Red Mud Using Thermal Plasma

NASA Astrophysics Data System (ADS)

Swagat, S. Rath; Archana, Pany; Jayasankar, K.; Ajit, K. Mitra; C. Satish, Kumar; Partha, S. Mukherjee; Barada, K. Mishra

2013-05-01

Optimization studies of plasma smelting of red mud were carried out. Reduction of the dried red mud fines was done in an extended arc plasma reactor to recover the pig iron. Lime grit and low ash metallurgical (LAM) coke were used as the flux and reductant, respectively. 2-level factorial design was used to study the influence of all parameters on the responses. Response surface modeling was done with the data obtained from statistically designed experiments. Metal recovery at optimum parameters was found to be 79.52%.

Chemometric optimization of the robustness of the near infrared spectroscopic method in wheat quality control.

PubMed

Pojić, Milica; Rakić, Dušan; Lazić, Zivorad

2015-01-01

A chemometric approach was applied for the optimization of the robustness of the NIRS method for wheat quality control. Due to the high number of experimental (n=6) and response variables to be studied (n=7) the optimization experiment was divided into two stages: screening stage in order to evaluate which of the considered variables were significant, and optimization stage to optimize the identified factors in the previously selected experimental domain. The significant variables were identified by using fractional factorial experimental design, whilst Box-Wilson rotatable central composite design (CCRD) was run to obtain the optimal values for the significant variables. The measured responses included: moisture, protein and wet gluten content, Zeleny sedimentation value and deformation energy. In order to achieve the minimal variation in responses, the optimal factor settings were found by minimizing the propagation of error (POE). The simultaneous optimization of factors was conducted by desirability function. The highest desirability of 87.63% was accomplished by setting up experimental conditions as follows: 19.9°C for sample temperature, 19.3°C for ambient temperature and 240V for instrument voltage. Copyright © 2014 Elsevier B.V. All rights reserved.

Chitosan Nanoparticles of Gamma-Oryzanol: Formulation, Optimization, and In vivo Evaluation of Anti-hyperlipidemic Activity.

PubMed

Rawal, Tejal; Mishra, Neha; Jha, Abhishek; Bhatt, Apurva; Tyagi, Rajeev K; Panchal, Shital; Butani, Shital

2018-05-01

The elevated blood levels of cholesterol and low-density lipoproteins result in hyperlipidemia. The available expensive prophylactic treatments are kindred with severe side effects. Therefore, we fabricated the polymeric nanoparticles of gamma-oryzanol to achieving the improved efficacy of drug. The nanoparticles were prepared by ionic gelation method and optimized using 2 3 full factorial design taking drug/polymer ratio (X 1 ), polymer/cross linking agent ratio (X 2 ), and stirring speed (X 3 ) as independent variables. The average particle size, percentage entrapment efficiency, and in vitro drug release at 2, 12, and 24 h were selected as response parameters. The factorial batches were statistically analyzed and optimized. The optimized nanoparticles were characterized with respect to particle size (141 nm) and zeta potential (+ 6.45 mV). Results obtained with the prepared and characterized formulation showed 83% mucoadhesion towards the intestinal mucosa. The in vitro findings were complemented well by in vivo anti-hyperlipidemic activity of developed formulation carried out in Swiss albino mouse model. The in vivo studies showed improved atherogenic index, malondialdehyde, and superoxide dismutase levels in poloxamer-407-induced hyperlipidemic animals when treated with oryzanol and gamma-oryzanol nanoformulation. Based on our findings, we believe that chitosan-mediated delivery of gamma-oryzanol nanoparticles might prove better in terms of anti-hyperlipidemic therapeutics.

A statistical approach to optimizing concrete mixture design.

PubMed

Ahmad, Shamsad; Alghamdi, Saeid A

2014-01-01

A step-by-step statistical approach is proposed to obtain optimum proportioning of concrete mixtures using the data obtained through a statistically planned experimental program. The utility of the proposed approach for optimizing the design of concrete mixture is illustrated considering a typical case in which trial mixtures were considered according to a full factorial experiment design involving three factors and their three levels (3(3)). A total of 27 concrete mixtures with three replicates (81 specimens) were considered by varying the levels of key factors affecting compressive strength of concrete, namely, water/cementitious materials ratio (0.38, 0.43, and 0.48), cementitious materials content (350, 375, and 400 kg/m(3)), and fine/total aggregate ratio (0.35, 0.40, and 0.45). The experimental data were utilized to carry out analysis of variance (ANOVA) and to develop a polynomial regression model for compressive strength in terms of the three design factors considered in this study. The developed statistical model was used to show how optimization of concrete mixtures can be carried out with different possible options.

A Statistical Approach to Optimizing Concrete Mixture Design

PubMed Central

Alghamdi, Saeid A.

2014-01-01

A step-by-step statistical approach is proposed to obtain optimum proportioning of concrete mixtures using the data obtained through a statistically planned experimental program. The utility of the proposed approach for optimizing the design of concrete mixture is illustrated considering a typical case in which trial mixtures were considered according to a full factorial experiment design involving three factors and their three levels (33). A total of 27 concrete mixtures with three replicates (81 specimens) were considered by varying the levels of key factors affecting compressive strength of concrete, namely, water/cementitious materials ratio (0.38, 0.43, and 0.48), cementitious materials content (350, 375, and 400 kg/m3), and fine/total aggregate ratio (0.35, 0.40, and 0.45). The experimental data were utilized to carry out analysis of variance (ANOVA) and to develop a polynomial regression model for compressive strength in terms of the three design factors considered in this study. The developed statistical model was used to show how optimization of concrete mixtures can be carried out with different possible options. PMID:24688405

Optimization of culture medium for novel cell-associated tannase production from Bacillus massiliensis using response surface methodology.

PubMed

Belur, Prasanna D; Goud, Rakesh; Goudar, Dinesh C

2012-02-01

Naturally immobilized tannase (tannin acyl hydrolase, E.C. 3.1.1.20) has many advantages, as it avoids the expensive and laborious operation of isolation, purification, and immobilization, plus it is highly stable in adverse pH and temperature. However, in the case of cell-associated enzymes, since the enzyme is associated with the biomass, separation of the pure biomass is necessary. However, tannic acid, a known inducer of tannase, forms insoluble complexes with media proteins, making it difficult to separate pure biomass. Therefore, this study optimizes the production of cell-associated tannase using a "protein-tannin complex" free media. An exploratory study was first conducted in shake-flasks to select the inducer, carbon source, and nitrogen sources. As a result it was found that gallic acid induces tannase synthesis, a tryptose broth gives higher biomass, and lactose supplementation is beneficial. The medium was then optimized using response surface methodology based on the full factorial central composite design in a 3 l bioreactor. A 2(3) factorial design augmented by 7 axial points (alpha = 1.682) and 2 replicates at the center point was implemented in 17 experiments. A mathematical model was also developed to show the effect of each medium component and their interactions on the production of cell-associated tannase. The validity of the proposed model was verified, and the optimized medium was shown to produce maximum cell-associated tannase activity of 9.65 U/l, which is 93.8% higher than the activity in the basal medium, after 12 h at pH 5.0, 30 degrees C. The optimum medium consists of 38 g/l lactose, 50 g/l tryptose, and 2.8 g/l gallic acid.

Optimization and Evaluation of Gastroretentive Ranitidine HCl Microspheres by Using Factorial Design with Improved Bioavailability and Mucosal Integrity in Ulcer Model.

PubMed

Khattab, Abeer; Zaki, Nashwah

2017-05-01

The purpose of our investigation was to develop and optimize the drug entrapment efficiency and bioadhesion properties of mucoadhesive chitosan microspheres containing ranitidine HCl prepared by an ionotropic gelation method as a gastroretentive delivery system; thus, we improved their protective and therapeutic gastric effects in an ulcer model. A 3 × 2 2 full factorial design was adopted to study the effect of three different factors, i.e., the type of polymer at three levels (chitosan, chitosan/hydroxypropylmethylcellulose, and chitosan/methylcellulose), the type of solvent at two levels (acetic acid and lactic acid), and the type of chitosan at two levels (low molecular weight (LMW) and high molecular weight (HMW)). The studied responses were particle size, swelling index, drug entrapment efficiency, bioadhesion (as determined by wash-off and rinsing tests), and T 80% of drug release. Studies of the in vivo mucoadhesion and in vivo protective and healing effects of the optimized formula against gastric ulcers were carried out using albino rats (with induced gastric ulceration) and were compared to the effects of free ranitidine powder. A pharmacokinetic study in rabbits showed a significant, 2.1-fold increase in theAUC 0-24 of the ranitidine microspheres compared to free ranitidine after oral administration. The optimized formula showed higher drug entrapment efficiency and mucoadhesion properties and had more protective and healing effects on induced gastric ulcers in rats than ranitidine powder. In conclusion, the prolonged gastrointestinal residence time and the stability of the mucoadhesive microspheres of ranitidine as well as the synergistic healing effect of chitosan could contribute to increasing the potential of its anti-gastric ulcer activity.

Multi-disciplinary optimization of railway wheels

NASA Astrophysics Data System (ADS)

Nielsen, J. C. O.; Fredö, C. R.

2006-06-01

A numerical procedure for multi-disciplinary optimization of railway wheels, based on Design of Experiments (DOE) methodology and automated design, is presented. The target is a wheel design that meets the requirements for fatigue strength, while minimizing the unsprung mass and rolling noise. A 3-level full factorial (3LFF) DOE is used to collect data points required to set up Response Surface Models (RSM) relating design and response variables in the design space. Computationally efficient simulations are thereafter performed using the RSM to identify the solution that best fits the design target. A demonstration example, including four geometric design variables in a parametric finite element (FE) model, is presented. The design variables are wheel radius, web thickness, lateral offset between rim and hub, and radii at the transitions rim/web and hub/web, but more variables (including material properties) can be added if needed. To improve further the performance of the wheel design, a constrained layer damping (CLD) treatment is applied on the web. For a given load case, compared to a reference wheel design without CLD, a combination of wheel shape and damping optimization leads to the conclusion that a reduction in the wheel component of A-weighted rolling noise of 11 dB can be achieved if a simultaneous increase in wheel mass of 14 kg is accepted.

Family context assessment in a public health study.

PubMed

Velasco, David; Sánchez de Miguel, Manuel; Egurza, Maitane; Arranz, Enrique; Aranbarri, Aritz; Fano, Eduardo; Ibarluzea, Jesús

2014-01-01

To analyze the factorial structure of a new instrument to assess the quality of the family context (Etxadi-Gangoiti Scale) in a sample from the Gipuzkoa cohort of the Environment and Childhood (Infancia y Medio Ambiente [INMA]) study. Families in a sample of 433 two-year-old children were assessed in a home visit with subsequent analysis of the factorial structure and psychometric properties of the data. An exploratory factorial analysis (principal axis factoring and varimax rotation) and a confirmatory factorial analysis were carried out; partial confirmation of the original factorial structure of the instrument was obtained, which revealed the following factorial structures. Subscale (1): promotion of cognitive and linguistic development, social skills, psychomotor skills, and pretend play and imitation; subscale (2): promotion of independence and self-esteem, provision of optimal frustration, social and emotional quality of the relationship, and absence of physical punishment; subscale (3): paternal involvement, low exposure to family conflict, low frequency of family conflict, relationship with the extended family, social support, diversity of experiences, low frequency of stressful events, and low parental perception of stress. The structure of the original instrument structure was partially confirmed, which was attributed to the characteristics of the sample. We stress the importance of the variability obtained in the evaluation of the families, as well as of adequate indicators of reliability in such evaluation. The new instrument could be used in public health to identify deficient family contexts and to design preventive interventions focused on parenting skills. Copyright © 2013 SESPAS. Published by Elsevier Espana. All rights reserved.

Application of synthetic biology for production of chemicals in yeast Saccharomyces cerevisiae.

PubMed

Li, Mingji; Borodina, Irina

2015-02-01

Synthetic biology and metabolic engineering enable generation of novel cell factories that efficiently convert renewable feedstocks into biofuels, bulk, and fine chemicals, thus creating the basis for biosustainable economy independent on fossil resources. While over a hundred proof-of-concept chemicals have been made in yeast, only a very small fraction of those has reached commercial-scale production so far. The limiting factor is the high research cost associated with the development of a robust cell factory that can produce the desired chemical at high titer, rate, and yield. Synthetic biology has the potential to bring down this cost by improving our ability to predictably engineer biological systems. This review highlights synthetic biology applications for design, assembly, and optimization of non-native biochemical pathways in baker's yeast Saccharomyces cerevisiae We describe computational tools for the prediction of biochemical pathways, molecular biology methods for assembly of DNA parts into pathways, and for introducing the pathways into the host, and finally approaches for optimizing performance of the introduced pathways. © FEMS 2015. All rights reserved. For permissions, please e-mail: journals.permission@oup.com.

Enhanced α-amylase production by a marine protist, Ulkenia sp. using response surface methodology and genetic algorithm.

PubMed

Shirodkar, Priyanka V; Muraleedharan, Usha Devi

2017-11-26

Amylases are a group of enzymes with a wide variety of industrial applications. Enhancement of α-amylase production from the marine protists, thraustochytrids has been attempted for the first time by applying statistical-based experimental designs using response surface methodology (RSM) and genetic algorithm (GA) for optimization of the most influencing process variables. A full factorial central composite experimental design was used to study the cumulative interactive effect of nutritional components viz., glucose, corn starch, and yeast extract. RSM was performed on two objectives, that is, growth of Ulkenia sp. AH-2 (ATCC® PRA-296) and α-amylase activity. When GA was conducted for maximization of the enzyme activity, the optimal α-amylase activity was found to be 71.20 U/mL which was close to that obtained by RSM (71.93 U/mL), both of which were in agreement with the predicted value of 72.37 U/mL. Optimal growth at the optimized process variables was found to be 1.89A 660nm . The optimized medium increased α-amylase production by 1.2-fold.

Polymeric behavior evaluation of PVP K30-poloxamer binary carrier for solid dispersed nisoldipine by experimental design.

PubMed

Kyaw Oo, May; Mandal, Uttam K; Chatterjee, Bappaditya

2017-02-01

High melting point polymeric carrier without plasticizer is unacceptable for solid dispersion (SD) by melting method. Combined polymer-plasticizer carrier significantly affects drug solubility and tableting property of SD. To evaluate and optimize the combined effect of a binary carrier consisting PVP K30 and poloxamer 188, on nisoldipine solubility and tensile strength of amorphous SD compact (SD compact ) by experimental design. SD of nisoldpine (SD nisol ) was prepared by melt mixing with different PVP K30 and poloxamer amount. A 3 2 factorial design was employed using nisoldipine solubility and tensile strength of SD compact as response variables. Statistical optimization by design expert software, and SD nisol characterization using ATR FTIR, DSC and microscopy were done. PVP K30:poloxamer, at a ratio of 3.73:6.63, was selected as the optimized combination of binary polymeric carrier resulting nisoldipine solubility of 115 μg/mL and tensile strength of 1.19 N/m 2 . PVP K30 had significant positive effect on both responses. Increase in poloxamer concentration after a certain level decreased nisoldipine solubility and tensile strength of SD compact . An optimized PVP K30-poloxamer binary composition for SD carrier was developed. Tensile strength of SD compact can be considered as a response for experimental design to optimize SD.

Resolution V fractional factorial design for screening of factors affecting weakly basic drugs liposomal systems.

PubMed

Nageeb El-Helaly, Sara; Habib, Basant A; Abd El-Rahman, Mohamed K

2018-07-01

This study aims to investigate factors affecting weakly basic drugs liposomal systems. Resolution V fractional factorial design (2 V 5-1 ) is used as an example of screening designs that would better be used as a wise step before proceeding with detailed factors effects or optimization studies. Five factors probable to affect liposomal systems of weakly basic drugs were investigated using Amisulpride as a model drug. Factors studied were; A: Preparation technique B: Phosphatidyl choline (PhC) amount (mg) C: Cholesterol: PhC molar ratio, D: Hydration volume (ml) and E: Sonication type. Levels investigated were; Ammonium sulphate-pH gradient technique or Transmembrane zinc chelation-pH gradient technique, 200 or 400 mg, 0 or 0.5, 10 or 20 ml and bath or probe sonication for A, B, C, D and E respectively. Responses measured were Particle size (PS) (nm), Zeta potential (ZP) (mV) and Entrapment efficiency percent (EE%). Ion selective electrode was used as a novel method for measuring unentrapped drug concentration and calculating entrapment efficiency without the need for liposomal separation. Factors mainly affecting the studied responses were Cholesterol: PhC ratio and hydration volume for PS, preparation technique for ZP and preparation technique and hydration volume for EE%. The applied 2 V 5-1 design enabled the use of only 16 trial combinations for screening the influence of five factors on weakly basic drugs liposomal systems. This clarifies the value of the use of screening experiments before extensive investigation of certain factors in detailed optimization studies. Copyright © 2018 Elsevier B.V. All rights reserved.

Informing the Uninformed: Optimizing the Consent Message Using a Fractional Factorial Design

PubMed Central

Tait, Alan R.; Voepel-Lewis, Terri; Nair, Vijayan N.; Narisetty, Naveen N.; Fagerlin, Angela

2013-01-01

Objective Research information should be presented in a manner that promotes understanding. However, many parents and research subjects have difficulty understanding and making informed decisions. This study was designed to examine the effect of different communication strategies on parental understanding of research information. Participants 640 parents of children scheduled for elective surgery Design Observational study using a fractional factorial design Setting Large tertiary care children's hospital Interventions Parents were randomized to receive information about a hypothetical pain trial presented in one of 16 consent documents containing different combinations of 5 selected communication strategies (i.e., length, readability, processability [formatting], graphical display, and supplemental verbal disclosure). Main outcome measures Parents were interviewed to determine their understanding of the study elements (e.g., protocol, alternatives etc.) and their gist (main point) and verbatim (actual) understanding of the risks and benefits. Results Main effects for understanding were found for processability, readability, message length, use of graphics, and verbal discussion. Consent documents with high processability, 8th grade reading level, and graphics resulted in significantly greater gist and verbatim understanding compared with forms without these attributes (mean difference, 95% CI = 0.57, 0.26–0.88, correct responses out of 7 and 0.54, 0.20–0.88 correct responses out of 4 for gist and verbatim, respectively). Conclusions Results identified several communication strategy combinations that improved parents' understanding of research information. Adoption of these active strategies by investigators, clinicians, IRBs, and study sponsors represents a simple, practical, and inexpensive means to optimize the consent message and enhance parental, participant, and patient understanding. PMID:23700028

Estimation and Optimization of the Parameters Preserving the Lustre of the Fabrics

NASA Astrophysics Data System (ADS)

Prodanova, Krasimira

2009-11-01

The paper discusses the optimization of the continuance of the Damp-Heating Process of a steaming iron press machine, and the preserving of the lustre of the fabrics. In order to be obtained high qualitative damp-heating processing, it is necessary to monitor parameters such as temperature, damp, and pressure during the process. The purpose of the present paper is a mathematical model to be constructed that adequately describes the technological process using multivariate data analysis. It was established that the full factorial design of type 23 is not adequate. The research has proceeded with central rotatable design of experiment. The obtained model adequately describes the technological process of damp-heating treatment in the defined factor space. The present investigation is helpful to the technological improvement and modernization in sewing companies.

Experimental Design For Photoresist Characterization

NASA Astrophysics Data System (ADS)

Luckock, Larry

1987-04-01

In processing a semiconductor product (from discrete devices up to the most complex products produced) we find more photolithographic steps in wafer fabrication than any other kind of process step. Thus, the success of a semiconductor manufacturer hinges on the optimization of their photolithographic processes. Yet, we find few companies that have taken the time to properly characterize this critical operation; they are sitting in the "passenger's seat", waiting to see what will come out, hoping that the yields will improve someday. There is no "black magic" involved in setting up a process at its optimum conditions (i.e. minimum sensitivity to all variables at the same time). This paper gives an example of a real world situation for optimizing a photolithographic process by the use of a properly designed experiment, followed by adequate multidimensional analysis of the data. Basic SPC practices like plotting control charts will not, by themselves, improve yields; the control charts are, however, among the necessary tools used in the determination of the process capability and in the formulation of the problems to be addressed. The example we shall consider is the twofold objective of shifting the process average, while tightening the variance, of polysilicon line widths. This goal was identified from a Pareto analysis of yield-limiting mechanisms, plus inspection of the control charts. A key issue in a characterization of this type of process is the number of interactions between variables; this example rules out two-level full factorial and three-level fractional factorial designs (which cannot detect all of the interactions). We arrive at an experiment with five factors at five levels each. A full factorial design for five factors at three levels would require 3125 wafers. Instead, we will use a design that allows us to run this experiment with only 25 wafers, for a significant reduction in time, materials and manufacturing interruption in order to complete the experiment. An optimum solution is then determined via response surface analysis and a series of 3-D and contour plots are shown. The offset between the mask dimensions and poly CD at the optimum operating conditions is discussed with respect to yield, profits and return-on-investment. The expert system used for process optimization covers all types of process steps, producing the best custom designed experiment based on the actual equipment used. The knowledge base contains parameter lists, by machine make and model, ranked by sensitivity and controllability. One option allows 3-D spatial characterization of equipment. For the purpose of this presentation, we will assume that we want to optimize a photo-lithographic process used for polysilicon pattern definition and that we have determined minimum and maximum line widths, based on electrical yield requirements of the product. For this MOS process, the minimum critical dimension (CD) for the poly gate was determined by punchthrough voltage, threshold voltage, etc., while the maximum CD was determined from other performance factors like access time. We will start with the product engineer's analysis.

Recirculating linacs for a neutrino factory - Arc optics design and optimization

DOE Office of Scientific and Technical Information (OSTI.GOV)

Alex Bogacz; Valeri Lebedev

2001-10-21

A conceptual lattice design for a muon accelerator based on recirculating linacs (Nucl. Instr. and Meth. A 472 (2001) 499, these proceedings) is presented here. The challenge of accelerating and transporting a large phase space of short-lived muons is answered here by presenting a proof-of-principle lattice design for a recirculating linac accelerator. It is the centerpiece of a chain of accelerators consisting of a 3GeV linac and two consecutive recirculating linear accelerators, which facilitates acceleration starting after ionization cooling at 190MeV/c and proceeding to 50GeV. Beam transport issues for large-momentum-spread beams are accommodated by appropriate lattice design choices. The resultingmore » arc optics is further optimized with a sextupole correction to suppress chromatic effects contributing to the emittance dilution. The presented proof-of-principle design of the arc optics with horizontal separation of multi-pass beams can be extended to all passes in both recirculating linacs.« less

Spatially organizing biochemistry: choosing a strategy to translate synthetic biology to the factory.

PubMed

Jakobson, Christopher M; Tullman-Ercek, Danielle; Mangan, Niall M

2018-05-29

Natural biochemical systems are ubiquitously organized both in space and time. Engineering the spatial organization of biochemistry has emerged as a key theme of synthetic biology, with numerous technologies promising improved biosynthetic pathway performance. One strategy, however, may produce disparate results for different biosynthetic pathways. We use a spatially resolved kinetic model to explore this fundamental design choice in systems and synthetic biology. We predict that two example biosynthetic pathways have distinct optimal organization strategies that vary based on pathway-dependent and cell-extrinsic factors. Moreover, we demonstrate that the optimal design varies as a function of kinetic and biophysical properties, as well as culture conditions. Our results suggest that organizing biosynthesis has the potential to substantially improve performance, but that choosing the appropriate strategy is key. The flexible design-space analysis we propose can be adapted to diverse biosynthetic pathways, and lays a foundation to rationally choose organization strategies for biosynthesis.

Synthetic biology: tools to design microbes for the production of chemicals and fuels.

PubMed

Seo, Sang Woo; Yang, Jina; Min, Byung Eun; Jang, Sungho; Lim, Jae Hyung; Lim, Hyun Gyu; Kim, Seong Cheol; Kim, Se Yeon; Jeong, Jun Hong; Jung, Gyoo Yeol

2013-11-01

The engineering of biological systems to achieve specific purposes requires design tools that function in a predictable and quantitative manner. Recent advances in the field of synthetic biology, particularly in the programmable control of gene expression at multiple levels of regulation, have increased our ability to efficiently design and optimize biological systems to perform designed tasks. Furthermore, implementation of these designs in biological systems highlights the potential of using these tools to build microbial cell factories for the production of chemicals and fuels. In this paper, we review current developments in the design of tools for controlling gene expression at transcriptional, post-transcriptional and post-translational levels, and consider potential applications of these tools. Copyright © 2013 Elsevier Inc. All rights reserved.

Interim Design Report for the International Design Study for a Neutrino Factory

DOE Office of Scientific and Technical Information (OSTI.GOV)

Choubey, S.; Gandhi, R.; Goswami, S.

2011-10-01

The starting point for the International Design Study for the Neutrino Factory (the IDS-NF) was the output of the earlier International Scoping Study for a future Neutrino Factory and super-beam facility (the ISS). The accelerator facility described in section 2 incorporates the improvements that have been derived from the substantial amount of work carried out within the Accelerator Working Group. Highlights of these improvements include: (1) Initial concepts for the implementation of the proton driver at each of the three example sites, CERN, FNAL, and RAL; (2) Detailed studies of the energy deposition in the target area; (3) A reductionmore » in the length of the muon beam phase-rotation and bunching systems; (4) Detailed analyses of the impact of the risk that stray magnetic field in the accelerating cavities in the ionization cooling channel will reduce the maximum operating gradient. Several alternative ionization-cooling lattices have been developed as fallback options to mitigate this technical risk; (5) Studies of particle loss in the muon front-end and the development of strategies to mitigate the deleterious effects of such losses; (6) The development of more complete designs for the muon linac and re-circulating linacs; (7) The development of a design for the muon FFAG that incorporates insertions for injection and extraction; and (8) Detailed studies of diagnostics in the decay ring. Other sub-systems have undergone a more 'incremental' evolution; an indication that the design of the Neutrino Factory has achieved a degree of maturity. The design of the neutrino detectors described in section 3 has been optimized and the Detector Working Group has made substantial improvements to the simulation and analysis of the Magnetized Iron Neutrino Detector (MIND) resulting in an improvement in the overall neutrino-detection efficiency and a reduction in the neutrino-energy threshold. In addition, initial consideration of the engineering of the MIND has generated a design that is feasible and a finite element analysis of the toroidal magnetic field to produce a realistic field map has been carried out. Section 3 also contains, for the first time, a specification for the near-detector systems and a demonstration that the neutrino flux can be determined with a precision of 1% through measurements of inverse muon decay at the near detector. The performance of the facility, the work of the Physics and Performance Evaluation Group, is described in section 1. The effect of the improved MIND performance is to deliver a discovery reach for CP-invariance violation in the lepton sector, the determination of the mass hierarchy, and of {theta}{sub 13} that extends down to values of sin{sup 2} 2{theta}{sub 13} {approx} 5 x 10{sup -5} and is robust against systematic uncertainties. In addition, the improved neutrino-energy threshold has allowed an indicative analysis of the kind of re-optimization of the facility that could be carried out should {theta}{sub 13} be found close to the current upper bound. The results presented in section 1 demonstrate that the discovery reach as well as the precision with which the oscillation parameters can be measured at the baseline Neutrino Factory is superior to that of other proposed facilities for all possible values of sin{sup 2} 2{theta}{sub 13}.« less

Parameters optimization defined by statistical analysis for cysteine-dextran radiolabeling with technetium tricarbonyl core.

PubMed

Núñez, Eutimio Gustavo Fernández; Faintuch, Bluma Linkowski; Teodoro, Rodrigo; Wiecek, Danielle Pereira; da Silva, Natanael Gomes; Papadopoulos, Minas; Pelecanou, Maria; Pirmettis, Ioannis; de Oliveira Filho, Renato Santos; Duatti, Adriano; Pasqualini, Roberto

2011-04-01

The objective of this study was the development of a statistical approach for radiolabeling optimization of cysteine-dextran conjugates with Tc-99m tricarbonyl core. This strategy has been applied to the labeling of 2-propylene-S-cysteine-dextran in the attempt to prepare a new class of tracers for sentinel lymph node detection, and can be extended to other radiopharmaceuticals for different targets. The statistical routine was based on three-level factorial design. Best labeling conditions were achieved. The specific activity reached was 5 MBq/μg. Crown Copyright © 2011. Published by Elsevier Ltd. All rights reserved.

A Market-Based Approach to Multi-factory Scheduling

NASA Astrophysics Data System (ADS)

Vytelingum, Perukrishnen; Rogers, Alex; MacBeth, Douglas K.; Dutta, Partha; Stranjak, Armin; Jennings, Nicholas R.

In this paper, we report on the design of a novel market-based approach for decentralised scheduling across multiple factories. Specifically, because of the limitations of scheduling in a centralised manner - which requires a center to have complete and perfect information for optimality and the truthful revelation of potentially commercially private preferences to that center - we advocate an informationally decentralised approach that is both agile and dynamic. In particular, this work adopts a market-based approach for decentralised scheduling by considering the different stakeholders representing different factories as self-interested, profit-motivated economic agents that trade resources for the scheduling of jobs. The overall schedule of these jobs is then an emergent behaviour of the strategic interaction of these trading agents bidding for resources in a market based on limited information and their own preferences. Using a simple (zero-intelligence) bidding strategy, we empirically demonstrate that our market-based approach achieves a lower bound efficiency of 84%. This represents a trade-off between a reasonable level of efficiency (compared to a centralised approach) and the desirable benefits of a decentralised solution.

Status of the nuSTORM Facility and a Possible Extension for Long-Baseline $$\

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bross, Alan D.; Liu, Ao; Lagrange, Jean-Baptiste

2015-11-03

Neutrino beams produced from the decay of muons in a racetrack-like decay ring (the so called Neutrino Factory) provide a powerful way to study neutrino oscillation physics and, in addition, provide unique beams for neutrino interaction studies. The Neutrinos from STORed Muons (nuSTORM) facility uses a neutrino factory-like design. Due to the particular nature of nuSTORM, it can also provide an intense, very pure, muon neutrino beam from pion decay. This so-called “Neo-conventional" muon neutrino beam from nuSTORM makes nuSTORM a hybrid neutrino factory. In this paper we describe the facility and give a detailed description of the neutrino beammore » fluxes that are available and the precision to which these fluxes can be determined. We then present sensitivity plots that indicated how well the facility can perform for short-baseline oscillation searches and show its potential for a neutrino interaction physics program. Finally, we comment on the performance potential of the "Neo-conventional" muon neutrino beam optimized for long- baseline neutrino-oscillation physics.« less

Engineering Translation in Mammalian Cell Factories to Increase Protein Yield: The Unexpected Use of Long Non-Coding SINEUP RNAs.

PubMed

Zucchelli, Silvia; Patrucco, Laura; Persichetti, Francesca; Gustincich, Stefano; Cotella, Diego

2016-01-01

Mammalian cells are an indispensable tool for the production of recombinant proteins in contexts where function depends on post-translational modifications. Among them, Chinese Hamster Ovary (CHO) cells are the primary factories for the production of therapeutic proteins, including monoclonal antibodies (MAbs). To improve expression and stability, several methodologies have been adopted, including methods based on media formulation, selective pressure and cell- or vector engineering. This review presents current approaches aimed at improving mammalian cell factories that are based on the enhancement of translation. Among well-established techniques (codon optimization and improvement of mRNA secondary structure), we describe SINEUPs, a family of antisense long non-coding RNAs that are able to increase translation of partially overlapping protein-coding mRNAs. By exploiting their modular structure, SINEUP molecules can be designed to target virtually any mRNA of interest, and thus to increase the production of secreted proteins. Thus, synthetic SINEUPs represent a new versatile tool to improve the production of secreted proteins in biomanufacturing processes.

Overview of the Neutrinos from Stored Muons Facility - nuSTORM

DOE PAGES

Adey, D.; Appleby, R. B.; Bayes, R.; ...

2017-07-19

Neutrino beams produced from the decay of muons in a racetrack-like decay ring (the so called Neutrino Factory) provide a powerful way to study neutrino oscillation physics and, in addition, provide unique beams for neutrino interaction studies. The Neutrinos from STORed Muons (nuSTORM) facility uses a neutrino factory-like design. Due to the particular nature of nuSTORM, it can also provide an intense, very pure, muon neutrino beam from pion decay. This so-called 'Neo-conventional' muon-neutrino beam from nuSTORM makes nuSTORM a hybrid neutrino factory. Here in this paper we describe the facility and give a detailed description of the neutrino beamsmore » that are available and the precision to which they can be characterized. We then show its potential for a neutrino interaction physics program and present sensitivity plots that indicate how well the facility can perform for short-baseline oscillation searches. Lastly, we comment on the performance potential of a 'Neo-conventional' muon neutrino beam optimized for long-baseline neutrino-oscillation physics.« less

Design, analysis and presentation of factorial randomised controlled trials

PubMed Central

Montgomery, Alan A; Peters, Tim J; Little, Paul

2003-01-01

Background The evaluation of more than one intervention in the same randomised controlled trial can be achieved using a parallel group design. However this requires increased sample size and can be inefficient, especially if there is also interest in considering combinations of the interventions. An alternative may be a factorial trial, where for two interventions participants are allocated to receive neither intervention, one or the other, or both. Factorial trials require special considerations, however, particularly at the design and analysis stages. Discussion Using a 2 × 2 factorial trial as an example, we present a number of issues that should be considered when planning a factorial trial. The main design issue is that of sample size. Factorial trials are most often powered to detect the main effects of interventions, since adequate power to detect plausible interactions requires greatly increased sample sizes. The main analytical issues relate to the investigation of main effects and the interaction between the interventions in appropriate regression models. Presentation of results should reflect the analytical strategy with an emphasis on the principal research questions. We also give an example of how baseline and follow-up data should be presented. Lastly, we discuss the implications of the design, analytical and presentational issues covered. Summary Difficulties in interpreting the results of factorial trials if an influential interaction is observed is the cost of the potential for efficient, simultaneous consideration of two or more interventions. Factorial trials can in principle be designed to have adequate power to detect realistic interactions, and in any case they are the only design that allows such effects to be investigated. PMID:14633287

Microwave-assisted of dispersive liquid-liquid microextraction and spectrophotometric determination of uranium after optimization based on Box-Behnken design and chemometrics methods.

PubMed

Niazi, Ali; Khorshidi, Neda; Ghaemmaghami, Pegah

2015-01-25

In this study an analytical procedure based on microwave-assisted dispersive liquid-liquid microextraction (MA-DLLME) and spectrophotometric coupled with chemometrics methods is proposed to determine uranium. In the proposed method, 4-(2-pyridylazo) resorcinol (PAR) is used as a chelating agent, and chloroform and ethanol are selected as extraction and dispersive solvent. The optimization strategy is carried out by using two level full factorial designs. Results of the two level full factorial design (2(4)) based on an analysis of variance demonstrated that the pH, concentration of PAR, amount of dispersive and extraction solvents are statistically significant. Optimal condition for three variables: pH, concentration of PAR, amount of dispersive and extraction solvents are obtained by using Box-Behnken design. Under the optimum conditions, the calibration graphs are linear in the range of 20.0-350.0 ng mL(-1) with detection limit of 6.7 ng mL(-1) (3δB/slope) and the enrichment factor of this method for uranium reached at 135. The relative standard deviation (R.S.D.) is 1.64% (n=7, c=50 ng mL(-1)). The partial least squares (PLS) modeling was used for multivariate calibration of the spectrophotometric data. The orthogonal signal correction (OSC) was used for preprocessing of data matrices and the prediction results of model, with and without using OSC, were statistically compared. MA-DLLME-OSC-PLS method was presented for the first time in this study. The root mean squares error of prediction (RMSEP) for uranium determination using PLS and OSC-PLS models were 4.63 and 0.98, respectively. This procedure allows the determination of uranium synthesis and real samples such as waste water with good reliability of the determination. Copyright © 2014. Published by Elsevier B.V.

Multivariate optimization of an analytical method for the analysis of dog and cat foods by ICP OES.

PubMed

da Costa, Silvânio Silvério Lopes; Pereira, Ana Cristina Lima; Passos, Elisangela Andrade; Alves, José do Patrocínio Hora; Garcia, Carlos Alexandre Borges; Araujo, Rennan Geovanny Oliveira

2013-04-15

Experimental design methodology was used to optimize an analytical method for determination of the mineral element composition (Al, Ca, Cd, Cr, Cu, Ba, Fe, K, Mg, Mn, P, S, Sr and Zn) of dog and cat foods. Two-level full factorial design was applied to define the optimal proportions of the reagents used for microwave-assisted sample digestion (2.0 mol L(-1) HNO3 and 6% m/v H2O2). A three-level factorial design for two variables was used to optimize the operational conditions of the inductively coupled plasma optical emission spectrometer, employed for analysis of the extracts. A radiofrequency power of 1.2 kW and a nebulizer argon flow of 1.0 L min(-1) were selected. The limits of quantification (LOQ) were between 0.03 μg g(-1) (Cr, 267.716 nm) and 87 μg g(-1) (Ca, 373.690 nm). The trueness of the optimized method was evaluated by analysis of five certified reference materials (CRMs): wheat flour (NIST 1567a), bovine liver (NIST 1577), peach leaves (NIST 1547), oyster tissue (NIST 1566b), and fish protein (DORM-3). The recovery values obtained for the CRMs were between 80 ± 4% (Cr) and 117 ± 5% (Cd), with relative standard deviations (RSDs) better than 5%, demonstrating that the proposed method offered good trueness and precision. Ten samples of pet food (five each of cat and dog food) were acquired at supermarkets in Aracaju city (Sergipe State, Brazil). Concentrations in the dog food ranged between 7.1 mg kg(-1) (Ba) and 2.7 g kg(-1) (Ca), while for cat food the values were between 3.7 mg kg(-1) (Ba) and 3.0 g kg(-1) (Ca). The concentrations of Ca, K, Mg, P, Cu, Fe, Mn, and Zn in the food were compared with the guidelines of the United States' Association of American Feed Control Officials (AAFCO) and the Brazilian Ministry of Agriculture, Livestock, and Food Supply (Ministério da Agricultura, Pecuária e Abastecimento-MAPA). Copyright © 2013 Elsevier B.V. All rights reserved.

Optimization of Medium Composition for the Production of Neomycin by Streptomyces fradiae NCIM 2418 in Solid State Fermentation

PubMed Central

Vastrad, B. M.; Neelagund, S. E.

2014-01-01

Neomycin production of Streptomyces fradiae NCIM 2418 was optimized by using response surface methodology (RSM), which is powerful mathematical approach comprehensively applied in the optimization of solid state fermentation processes. In the first step of optimization, with Placket-Burman design, ammonium chloride, sodium nitrate, L-histidine, and ammonium nitrate were established to be the crucial nutritional factors affecting neomycin production significantly. In the second step, a 24 full factorial central composite design and RSM were applied to determine the optimal concentration of significant variable. A second-order polynomial was determined by the multiple regression analysis of the experimental data. The optimum values for the important nutrients for the maximum were obtained as follows: ammonium chloride 2.00%, sodium nitrate 1.50%, L-histidine 0.250%, and ammonium nitrate 0.250% with a predicted value of maximum neomycin production of 20,000 g kg−1 dry coconut oil cake. Under the optimal condition, the practical neomycin production was 19,642 g kg−1 dry coconut oil cake. The determination coefficient (R 2) was 0.9232, which ensures an acceptable admissibility of the model. PMID:25009746

Optimization of process parameters for a quasi-continuous tablet coating system using design of experiments.

PubMed

Cahyadi, Christine; Heng, Paul Wan Sia; Chan, Lai Wah

2011-03-01

The aim of this study was to identify and optimize the critical process parameters of the newly developed Supercell quasi-continuous coater for optimal tablet coat quality. Design of experiments, aided by multivariate analysis techniques, was used to quantify the effects of various coating process conditions and their interactions on the quality of film-coated tablets. The process parameters varied included batch size, inlet temperature, atomizing pressure, plenum pressure, spray rate and coating level. An initial screening stage was carried out using a 2(6-1(IV)) fractional factorial design. Following these preliminary experiments, optimization study was carried out using the Box-Behnken design. Main response variables measured included drug-loading efficiency, coat thickness variation, and the extent of tablet damage. Apparent optimum conditions were determined by using response surface plots. The process parameters exerted various effects on the different response variables. Hence, trade-offs between individual optima were necessary to obtain the best compromised set of conditions. The adequacy of the optimized process conditions in meeting the combined goals for all responses was indicated by the composite desirability value. By using response surface methodology and optimization, coating conditions which produced coated tablets of high drug-loading efficiency, low incidences of tablet damage and low coat thickness variation were defined. Optimal conditions were found to vary over a large spectrum when different responses were considered. Changes in processing parameters across the design space did not result in drastic changes to coat quality, thereby demonstrating robustness in the Supercell coating process. © 2010 American Association of Pharmaceutical Scientists

Novel non-ionic surfactant proniosomes for transdermal delivery of lacidipine: optimization using 2(3) factorial design and in vivo evaluation in rabbits.

PubMed

Soliman, Sara M; Abdelmalak, Nevine S; El-Gazayerly, Omaima N; Abdelaziz, Nabaweya

2016-06-01

Proniosomes offer a versatile vesicle drug delivery concept with potential for delivery of drugs via transdermal route. To develop proniosomal gel using cremophor RH 40 as non-ionic surfactant containing the antihypertensive drug lacidipine for transdermal delivery so as to avoid its extensive first pass metabolism and to improve its permeation through the skin. Proniosomes containing 1% lacidipine were prepared by the coacervation phase separation method, characterized, and optimized using a 2(3) full factorial design to define the optimum conditions to produce proniosomes with high entrapment efficiency, minimal vesicle size, and high-percentage release efficiency. The amount of cholesterol (X1), the amount of soya lecithin (X2), and the amount of cremophor RH 40 (X3) were selected as three independent variables. The system F4 was found to fulfill the maximum requisite of an optimum system because it had minimum vesicle size, maximum EE, maximum release efficiency, and maximum desirability. The optimized system (F4) was then converted to proniosomal gel using carbopol 940 (1% w/w). In vitro permeation through excised rabbit skin study revealed higher flux (6.48 ± 0.45) for lacidipine from the optimized proniosomal gel when compared with the corresponding emulgel (3.04 ± 0.13) mg/cm(2)/h. The optimized formulation was evaluated for its bioavailability compared with commercial product. Statistical analysis revealed significant increase in AUC (0 - α) 464.17 ± 113.15 ng h/ml compared with 209.02 ± 47.35 ng h/ml for commercial tablet. Skin irritancy and histopathological investigation of rat skin revealed its safety. Cremophor RH 40 proniosomal gel could be considered as very promising nanocarriers for transdermal delivery of lacidipine.

Application of Optimization Techniques to Spectrally Modulated, Spectrally Encoded Waveform Design

DTIC Science & Technology

2008-09-01

means y1 and y2 do indeed differ [22]. 43 To compare means for more than two populations, the Least Significant Difference ( LSD ) test may be used...case, the LSD test for a full-factorial design is given by LSD = tα 2 ,Ne−a √ 2 eTe n(Ne − a) , (2.41) where α is the significance level and ν = Ne − a...rejected if the means differ by more than the LSD [22]. 44 III. Methodology In many respects, the goal of this dissertation is to develop and

Optimisation of resolution in micellar electrokinetic chromatography by multivariate evaluation of electrolytes.

PubMed

Mikaeli, S; Thorsén, G; Karlberg, B

2001-01-12

A novel approach to multivariate evaluation of separation electrolytes for micellar electrokinetic chromatography is presented. An initial screening of the experimental parameters is performed using a Plackett-Burman design. Significant parameters are further evaluated using full factorial designs. The total resolution of the separation is calculated and used as response. The proposed scheme has been applied to the optimisation of the separation of phenols and the chiral separation of (+)-1-(9-anthryl)-2-propyl chloroformate-derivatized amino acids. A total of eight experimental parameters were evaluated and optimal conditions found in less than 48 experiments.

Studies on a novel doughnut-shaped minitablet for intraocular drug delivery.

PubMed

Choonara, Yahya E; Pillay, Viness; Carmichael, Trevor; Danckwerts, Michael P

2007-12-28

The objective of this study was to evaluate the effect of 2 independent formulation variables on the drug release from a novel doughnut-shaped minitablet (DSMT) in order to optimize formulations for intraocular drug delivery. Formulations were based on a 3(2) full-factorial design. The 2 independent variables were the concentration of Resomer (% wt/wt) and the type of Resomer grade (RG502, RG503, and RG504), respectively. The evaluated response was the drug release rate constant computed from a referenced marketed product and in vitro drug release data obtained at pH 7.4 in simulated vitreous humor. DSMT devices were prepared containing either of 2 model drugs, ganciclovir or foscarnet, using a Manesty F3 tableting press fitted with a novel central-rod, punch, and die setup. Dissolution data revealed biphasic drug release behavior with 55% to 60% drug released over 120 days. The inherent viscosity of the various Resomer grades and the concentration were significant to achieve optimum release rate constants. Using the resultant statistical relationships with the release rate constant as a response, the optimum formulation predicted for devices formulated with foscarnet was 70% wt/wt of Resomer RG504, while 92% wt/wt of Resomer RG503 was ideal for devices formulated with ganciclovir. The results of this study revealed that the full-factorial design was a suitable tool to predict an optimized formulation for prolonged intraocular drug delivery.

Selection and optimization of Bacillus atrophaeus inoculum medium and its effect on spore yield and thermal resistance.

PubMed

Sella, Sandra Regina B R; Dlugokenski, Regina Elizabete F; Guizelini, Belquis P; Vandenberghe, Luciana P S; Medeiros, Adriane B P; Pandey, Ashok; Soccol, Carlos Ricardo

2008-12-01

Bacillus atrophaeus's spores are used as biological indicators to monitor sterilization processes and as a Bacillus anthracis surrogate in the development and validation of biosafety methods. The regular use of biological indicators to evaluate the efficiency of sterilization processes is a legal requirement for health services. However, its high cost hinders its widespread use. Aiming at developing a cost-effective inoculum medium, soybean molasses and nutrient-supplemented vinasse were evaluated for their effectiveness in solid-state fermentation (SSF). In biomass production, the results demonstrated that all tested compositions favor growth by providing the nutritional demands of the microorganism. Optimum casein peptone and soybean molasses concentration (1.0%, 2.5%, or 4.0%) was determined by a 2((2-0)) factorial experimental design. The results have showed a positive influence of peptone on biomass production. In order to define peptone final concentration (4.0% or 6.0%), a 2(2) factorial experimental design was used. An optimized medium containing 4.0% soybean molasses and 4.0% casein peptone was similar in performance to a synthetic control medium (tryptone soy broth) in dry-heat thermal-resistant spore production by SSF. An experiment performed under optimum SSF conditions resulted in 1.9 x 10(10) CFU g(-1) dry matter with D (160 degrees C) = 5.2 +/- 0.2 min.

Enhanced diesel fuel fraction from waste high-density polyethylene and heavy gas oil pyrolysis using factorial design methodology.

PubMed

Joppert, Ney; da Silva, Alexsandro Araujo; da Costa Marques, Mônica Regina

2015-02-01

Factorial Design Methodology (FDM) was developed to enhance diesel fuel fraction (C9-C23) from waste high-density polyethylene (HDPE) and Heavy Gas Oil (HGO) through co-pyrolysis. FDM was used for optimization of the following reaction parameters: temperature, catalyst and HDPE amounts. The HGO amount was constant (2.00 g) in all experiments. The model optimum conditions were determined to be temperature of 550 °C, HDPE = 0.20 g and no FCC catalyst. Under such conditions, 94% of pyrolytic oil was recovered, of which diesel fuel fraction was 93% (87% diesel fuel fraction yield), no residue was produced and 6% of noncondensable gaseous/volatile fraction was obtained. Seeking to reduce the cost due to high process temperatures, the impact of using higher catalyst content (25%) with a lower temperature (500 °C) was investigated. Under these conditions, 88% of pyrolytic oil was recovered (diesel fuel fraction yield was also 87%) as well as 12% of the noncondensable gaseous/volatile fraction. No waste was produced in these conditions, being an environmentally friendly approach for recycling the waste plastic. This paper demonstrated the usefulness of using FDM to predict and to optimize diesel fuel fraction yield with a great reduction in the number of experiments. Copyright © 2014 Elsevier Ltd. All rights reserved.

Factorial design applied to the optimization of lipid composition of topical antiherpetic nanoemulsions containing isoflavone genistein

PubMed Central

Argenta, Débora Fretes; de Mattos, Cristiane Bastos; Misturini, Fabíola Dallarosa; Koester, Leticia Scherer; Bassani, Valquiria Linck; Simões, Cláudia Maria Oliveira; Teixeira, Helder Ferreira

2014-01-01

The aim of this study was to optimize topical nanoemulsions containing genistein, by means of a 23 full factorial design based on physicochemical properties and skin retention. The experimental arrangement was constructed using oil type (isopropyl myristate or castor oil), phospholipid type (distearoylphosphatidylcholine [DSPC] or dioleylphosphaditylcholine [DOPC]), and ionic cosurfactant type (oleic acid or oleylamine) as independent variables. The analysis of variance showed effect of third order for particle size, polydispersity index, and skin retention of genistein. Nanoemulsions composed of isopropyl myristate/DOPC/oleylamine showed the smallest diameter and highest genistein amount in porcine ear skin whereas the formulation composed of isopropyl myristate/DSPC/oleylamine exhibited the lowest polydispersity index. Thus, these two formulations were selected for further studies. The formulations presented positive ζ potential values (>25 mV) and genistein content close to 100% (at 1 mg/mL). The incorporation of genistein in nanoemulsions significantly increased the retention of this isoflavone in epidermis and dermis, especially when the formulation composed by isopropyl myristate/DOPC/oleylamine was used. These results were supported by confocal images. Such formulations exhibited antiherpetic activity in vitro against herpes simplex virus 1 (strain KOS) and herpes simplex virus 22 (strain 333). Taken together, the results show that the genistein-loaded nanoemulsions developed in this study are promising options in herpes treatment. PMID:25336951

Factorial Experiments: Efficient Tools for Evaluation of Intervention Components

PubMed Central

Collins, Linda M.; Dziak, John J.; Kugler, Kari C.; Trail, Jessica B.

2014-01-01

Background An understanding of the individual and combined effects of a set of intervention components is important for moving the science of preventive medicine interventions forward. This understanding can often be achieved in an efficient and economical way via a factorial experiment, in which two or more independent variables are manipulated. The factorial experiment is a complement to the randomized controlled trial (RCT); the two designs address different research questions. Purpose This article offers an introduction to factorial experiments aimed at investigators trained primarily in the RCT. Method The factorial experiment is compared and contrasted with other experimental designs used commonly in intervention science to highlight where each is most efficient and appropriate. Results Several points are made: factorial experiments make very efficient use of experimental subjects when the data are properly analyzed; a factorial experiment can have excellent statistical power even if it has relatively few subjects per experimental condition; and when conducting research to select components for inclusion in a multicomponent intervention, interactions should be studied rather than avoided. Conclusions Investigators in preventive medicine and related areas should begin considering factorial experiments alongside other approaches. Experimental designs should be chosen from a resource management perspective, which states that the best experimental design is the one that provides the greatest scientific benefit without exceeding available resources. PMID:25092122

Composite fuselage crown panel manufacturing technology

NASA Technical Reports Server (NTRS)

Willden, Kurtis; Metschan, S.; Grant, C.; Brown, T.

1992-01-01

Commercial fuselage structures contain significant challenges in attempting to save manufacturing costs with advanced composite technology. Assembly issues, materials costs, and fabrication of elements with complex geometry are each expected to drive the cost of composite fuselage structure. Key technologies, such as large crown panel fabrication, were pursued for low cost. An intricate bond panel design and manufacturing concept were selected based on the efforts of the Design Build Team. The manufacturing processes selected for the intricate bond design include multiple large panel fabrication with Advanced Tow Placement (ATP) process, innovative cure tooling concepts, resin transfer molding of long fuselage frames, and use of low cost materials forms. The process optimization for final design/manufacturing configuration included factory simulations and hardware demonstrations. These efforts and other optimization tasks were instrumental in reducing costs by 18 pct. and weight by 45 pct. relative to an aluminum baseline. The qualitative and quantitative results of the manufacturing demonstrations were used to assess manufacturing risks and technology readiness.

Recirculating linacs for a neutrino factory - Arc optics design and optimization

DOE Office of Scientific and Technical Information (OSTI.GOV)

Valeri Lebedev; S. Bogacz

2001-10-25

A conceptual lattice design for a muon accelerator based on recirculating linacs (Nucl. Instr. and Meth. A 472 (2001) 499, these proceedings) is presented here. The challenge of accelerating and transporting a large phase space of short-lived muons is answered here by presenting a proof-of-principle lattice design for a recirculating linac accelerator. It is the centerpiece of a chain of accelerators consisting of a 3 GeV linac and two consecutive recirculating linear accelerators, which facilitates acceleration starting after ionization cooling at 190 MeV/c and proceeding to 50 GeV. Beam transport issues for large-momentum-spread beams are accommodated by appropriate lattice designmore » choices. The resulting arc optics is further optimized with a sextupole correction to suppress chromatic effects contributing to the emittance dilution. The presented proof-of-principle design of the arc optics with horizontal separation of multi-pass beams can be extended to all passes in both recirculating linacs.« less

Composite fuselage crown panel manufacturing technology

NASA Technical Reports Server (NTRS)

Willden, Kurtis; Metschan, S.; Grant, C.; Brown, T.

1992-01-01

Commercial fuselage structures contain significant challenges in attempting to save manufacturing costs with advanced composite technology. Assembly issues, material costs, and fabrication of elements with complex geometry are each expected to drive the cost of composite fuselage structures. Boeing's efforts under the NASA ACT program have pursued key technologies for low-cost, large crown panel fabrication. An intricate bond panel design and manufacturing concepts were selected based on the efforts of the Design Build Team (DBT). The manufacturing processes selected for the intricate bond design include multiple large panel fabrication with the Advanced Tow Placement (ATP) process, innovative cure tooling concepts, resin transfer molding of long fuselage frames, and utilization of low-cost material forms. The process optimization for final design/manufacturing configuration included factory simulations and hardware demonstrations. These efforts and other optimization tasks were instrumental in reducing cost by 18 percent and weight by 45 percent relative to an aluminum baseline. The qualitative and quantitative results of the manufacturing demonstrations were used to assess manufacturing risks and technology readiness.

Synthesis and acid digestion of biomorphic ceramics: determination of alkaline and alkaline earth ions.

PubMed

Bosch Ojeda, Catalina; Sánchez Rojas, Fuensanta; Cano Pavón, José Manuel

2007-09-01

Ceramic and glass are some of the more recent engineering materials and those that are most resistant to environmental conditions. They belong to advanced materials in that they are being developed for the aerospace and electronics industries. In the last decade, a new class of ceramic materials has been the focus of particular attention. The materials were produced with natural, renewable resources (wood or wood-based products). In this work, we have synthesised a new biomorphic ceramic material from oak wood and Si infiltration. After the material characterization, we have optimized the dissolution of the sample by acid attack in an oven under microwave irradiation. Experimental designs were used as a multivariate strategy for the evaluation of the effects of varying several variables at the same time. The optimization was performed in two steps using factorial design for preliminary evaluation and a Draper-Lin design for determination of the critical experimental conditions. Five variables (time, power, volume of HNO3, volume H2SO4 and volume of HF) were considered as factors and as a response the concentration of different metal ions in the optimization process. Interactions between analytical factors and their optimal levels were investigated using a Draper-Lin design.

Simulation study to determine the impact of different design features on design efficiency in discrete choice experiments

PubMed Central

Vanniyasingam, Thuva; Cunningham, Charles E; Foster, Gary; Thabane, Lehana

2016-01-01

Objectives Discrete choice experiments (DCEs) are routinely used to elicit patient preferences to improve health outcomes and healthcare services. While many fractional factorial designs can be created, some are more statistically optimal than others. The objective of this simulation study was to investigate how varying the number of (1) attributes, (2) levels within attributes, (3) alternatives and (4) choice tasks per survey will improve or compromise the statistical efficiency of an experimental design. Design and methods A total of 3204 DCE designs were created to assess how relative design efficiency (d-efficiency) is influenced by varying the number of choice tasks (2–20), alternatives (2–5), attributes (2–20) and attribute levels (2–5) of a design. Choice tasks were created by randomly allocating attribute and attribute level combinations into alternatives. Outcome Relative d-efficiency was used to measure the optimality of each DCE design. Results DCE design complexity influenced statistical efficiency. Across all designs, relative d-efficiency decreased as the number of attributes and attribute levels increased. It increased for designs with more alternatives. Lastly, relative d-efficiency converges as the number of choice tasks increases, where convergence may not be at 100% statistical optimality. Conclusions Achieving 100% d-efficiency is heavily dependent on the number of attributes, attribute levels, choice tasks and alternatives. Further exploration of overlaps and block sizes are needed. This study's results are widely applicable for researchers interested in creating optimal DCE designs to elicit individual preferences on health services, programmes, policies and products. PMID:27436671

Nano-transfersomes as a novel carrier for transdermal delivery.

PubMed

Chaudhary, Hema; Kohli, Kanchan; Kumar, Vikash

2013-09-15

The aim of this study was to design and optimize a nano-transfersomes of Diclofenac diethylamine (DDEA) and Curcumin (CRM). A 3(3) factorial design (Box-Behnken) was used to derive a polynomial equation (second order) to construct 2-D (contour) and 3-D (Response Surface) plots for prediction of responses. The ratio of lipid to surfactant (X1), weight of lipid to surfactant (X2) and sonication time (X3) (independent variables) and dependent variables [entrapment efficiency of DDEA (Y1), entrapment efficiency of CRM (Y2), effect on particle size (Y3), flux of DDEA (Y4), and flux of CRM (Y5)] were studied. The 2-D and 3-D plots were drawn and a statistical validity of the polynomials was established to find the compositions of optimized formulation. The design established the role of the derived polynomial equation, 2-D and 3-D plots in predicting the values of dependent variables for the preparation and optimization of nano-transfersomes for transdermal drug release. Copyright © 2013 Elsevier B.V. All rights reserved.

Application of response surface methodology for optimization of polygalacturonase production by Aspergillus niger.

PubMed

Yadav, Kaushlesh K; Garg, Neelima; Kumar, Devendra; Kumar, Sanjay; Singh, Achal; Muthukumar, M

2015-01-01

Polygalacturonase (PG) degrades pectin into D-galacturonic acid monomers and is used widely in food industry especially for juice clarification. In the present study,. fermentation conditions for polygalacturonase production by Asgergillus niger NAIMCCF-02958, using mango peel as substrate, were optimized using the 2(3) factorial design with central composite rotatable experimental design (CCRD) of response surface methodology (RSM). The maximum PG activity 723.66 U g(-1) was achieved under pH 4.0, temperature 30 degrees C and 2% inoculum by response surface curve. The experimental value of PG activity wkas higher 607.65 U g(-1) than the predicted value 511.75 U g(-1). Under the proposed optimized conditions, the determination coefficient (R2) was equal to 0.66 indicating that the model could explain 66% of the total variation as well as establish the relationship between the variables and the responses. ANOVA analysis and the three dimensional plots also confirmed interactions among the parameters.

A quality-by-design approach to risk reduction and optimization for human embryonic stem cell cryopreservation processes.

PubMed

Mitchell, Peter D; Ratcliffe, Elizabeth; Hourd, Paul; Williams, David J; Thomas, Robert J

2014-12-01

It is well documented that cryopreservation and resuscitation of human embryonic stem cells (hESCs) is complex and ill-defined, and often suffers poor cell recovery and increased levels of undesirable cell differentiation. In this study we have applied Quality-by-Design (QbD) concepts to the critical processes of slow-freeze cryopreservation and resuscitation of hESC colony cultures. Optimized subprocesses were linked together to deliver a controlled complete process. We have demonstrated a rapid, high-throughput, and stable system for measurement of cell adherence and viability as robust markers of in-process and postrecovery cell state. We observed that measurement of adherence and viability of adhered cells at 1 h postseeding was predictive of cell proliferative ability up to 96 h in this system. Application of factorial design defined the operating spaces for cryopreservation and resuscitation, critically linking the performance of these two processes. Optimization of both processes resulted in enhanced reattachment and post-thaw viability, resulting in substantially greater recovery of cryopreserved, pluripotent cell colonies. This study demonstrates the importance of QbD concepts and tools for rapid, robust, and low-risk process design that can inform manufacturing controls and logistics.

Research on the Decision Method of Maintenance Materials Direct Supply

NASA Astrophysics Data System (ADS)

Zhu, Qian; Shi, Xiaopei; Liu, Shenyang; Luo, Guangxu; Zhu, Chen

2018-05-01

With the further development of civil military integration, more and more maintenance materials will be supplied by the factory directly. Aiming at the mode condition of maintenance materials factory direct supply, maintenance materials needs equipment support in the process of facing a number of direct supply manufacturers how to decision problems, using AHP, considering many factors optimization of direct supply manufacturers involved, and gives the weights of the evaluation indexes of the direct supply manufacturers to evaluate optimal. Finally, with 4 straights for the manufacturer as an example, considering the various evaluation indexes to carry out evaluation and drawing the correct evaluation of direct supply manufacturers, the best manufacturers direct supply is selected. An example shows that, AHP can provide scientific and theoretical basis to materials factory direct supply security.

Design and Optimization of Floating Drug Delivery System of Acyclovir

PubMed Central

Kharia, A. A.; Hiremath, S. N.; Singhai, A. K.; Omray, L. K.; Jain, S. K.

2010-01-01

The purpose of the present work was to design and optimize floating drug delivery systems of acyclovir using psyllium husk and hydroxypropylmethylcellulose K4M as the polymers and sodium bicarbonate as a gas generating agent. The tablets were prepared by wet granulation method. A 32 full factorial design was used for optimization of drug release profile. The amount of psyllium husk (X1) and hydroxypropylmethylcellulose K4M (X2) were selected as independent variables. The times required for 50% (t50%) and 70% (t70%) drug dissolution were selected as dependent variables. All the designed nine batches of formulations were evaluated for hardness, friability, weight variation, drug content uniformity, swelling index, in vitro buoyancy, and in vitro drug release profile. All formulations had floating lag time below 3 min and constantly floated on dissolution medium for more than 24 h. Validity of the developed polynomial equation was verified by designing two check point formulations (C1 and C2). The closeness of predicted and observed values for t50% and t70% indicates validity of derived equations for the dependent variables. These studies indicated that the proper balance between psyllium husk and hydroxypropylmethylcellulose K4M can produce a drug dissolution profile similar to the predicted dissolution profile. The optimized formulations followed Higuchi's kinetics while the drug release mechanism was found to be anomalous type, controlled by diffusion through the swollen matrix. PMID:21694992

Design and optimization of floating drug delivery system of acyclovir.

PubMed

Kharia, A A; Hiremath, S N; Singhai, A K; Omray, L K; Jain, S K

2010-09-01

The purpose of the present work was to design and optimize floating drug delivery systems of acyclovir using psyllium husk and hydroxypropylmethylcellulose K4M as the polymers and sodium bicarbonate as a gas generating agent. The tablets were prepared by wet granulation method. A 3(2) full factorial design was used for optimization of drug release profile. The amount of psyllium husk (X1) and hydroxypropylmethylcellulose K4M (X2) were selected as independent variables. The times required for 50% (t(50%)) and 70% (t(70%)) drug dissolution were selected as dependent variables. All the designed nine batches of formulations were evaluated for hardness, friability, weight variation, drug content uniformity, swelling index, in vitro buoyancy, and in vitro drug release profile. All formulations had floating lag time below 3 min and constantly floated on dissolution medium for more than 24 h. Validity of the developed polynomial equation was verified by designing two check point formulations (C1 and C2). The closeness of predicted and observed values for t(50%) and t(70%) indicates validity of derived equations for the dependent variables. These studies indicated that the proper balance between psyllium husk and hydroxypropylmethylcellulose K4M can produce a drug dissolution profile similar to the predicted dissolution profile. The optimized formulations followed Higuchi's kinetics while the drug release mechanism was found to be anomalous type, controlled by diffusion through the swollen matrix.

A Randomized Longitudinal Factorial Design to Assess Malaria Vector Control and Disease Management Interventions in Rural Tanzania

PubMed Central

Kramer, Randall A.; Mboera, Leonard E. G.; Senkoro, Kesheni; Lesser, Adriane; Shayo, Elizabeth H.; Paul, Christopher J.; Miranda, Marie Lynn

2014-01-01

The optimization of malaria control strategies is complicated by constraints posed by local health systems, infrastructure, limited resources, and the complex interactions between infection, disease, and treatment. The purpose of this paper is to describe the protocol of a randomized factorial study designed to address this research gap. This project will evaluate two malaria control interventions in Mvomero District, Tanzania: (1) a disease management strategy involving early detection and treatment by community health workers using rapid diagnostic technology; and (2) vector control through community-supported larviciding. Six study villages were assigned to each of four groups (control, early detection and treatment, larviciding, and early detection and treatment plus larviciding). The primary endpoint of interest was change in malaria infection prevalence across the intervention groups measured during annual longitudinal cross-sectional surveys. Recurring entomological surveying, household surveying, and focus group discussions will provide additional valuable insights. At baseline, 962 households across all 24 villages participated in a household survey; 2,884 members from 720 of these households participated in subsequent malariometric surveying. The study design will allow us to estimate the effect sizes of different intervention mixtures. Careful documentation of our study protocol may also serve other researchers designing field-based intervention trials. PMID:24840349

A randomized longitudinal factorial design to assess malaria vector control and disease management interventions in rural Tanzania.

PubMed

Kramer, Randall A; Mboera, Leonard E G; Senkoro, Kesheni; Lesser, Adriane; Shayo, Elizabeth H; Paul, Christopher J; Miranda, Marie Lynn

2014-05-16

The optimization of malaria control strategies is complicated by constraints posed by local health systems, infrastructure, limited resources, and the complex interactions between infection, disease, and treatment. The purpose of this paper is to describe the protocol of a randomized factorial study designed to address this research gap. This project will evaluate two malaria control interventions in Mvomero District, Tanzania: (1) a disease management strategy involving early detection and treatment by community health workers using rapid diagnostic technology; and (2) vector control through community-supported larviciding. Six study villages were assigned to each of four groups (control, early detection and treatment, larviciding, and early detection and treatment plus larviciding). The primary endpoint of interest was change in malaria infection prevalence across the intervention groups measured during annual longitudinal cross-sectional surveys. Recurring entomological surveying, household surveying, and focus group discussions will provide additional valuable insights. At baseline, 962 households across all 24 villages participated in a household survey; 2,884 members from 720 of these households participated in subsequent malariometric surveying. The study design will allow us to estimate the effect sizes of different intervention mixtures. Careful documentation of our study protocol may also serve other researchers designing field-based intervention trials.

Factorial experiments: efficient tools for evaluation of intervention components.

PubMed

Collins, Linda M; Dziak, John J; Kugler, Kari C; Trail, Jessica B

2014-10-01

An understanding of the individual and combined effects of a set of intervention components is important for moving the science of preventive medicine interventions forward. This understanding can often be achieved in an efficient and economical way via a factorial experiment, in which two or more independent variables are manipulated. The factorial experiment is a complement to the RCT; the two designs address different research questions. To offer an introduction to factorial experiments aimed at investigators trained primarily in the RCT. The factorial experiment is compared and contrasted with other experimental designs used commonly in intervention science to highlight where each is most efficient and appropriate. Several points are made: factorial experiments make very efficient use of experimental subjects when the data are properly analyzed; a factorial experiment can have excellent statistical power even if it has relatively few subjects per experimental condition; and when conducting research to select components for inclusion in a multicomponent intervention, interactions should be studied rather than avoided. Investigators in preventive medicine and related areas should begin considering factorial experiments alongside other approaches. Experimental designs should be chosen from a resource management perspective, which states that the best experimental design is the one that provides the greatest scientific benefit without exceeding available resources. Copyright © 2014 American Journal of Preventive Medicine. Published by Elsevier Inc. All rights reserved.

An approach to optimize sample preparation for MALDI imaging MS of FFPE sections using fractional factorial design of experiments.

PubMed

Oetjen, Janina; Lachmund, Delf; Palmer, Andrew; Alexandrov, Theodore; Becker, Michael; Boskamp, Tobias; Maass, Peter

2016-09-01

A standardized workflow for matrix-assisted laser desorption/ionization imaging mass spectrometry (MALDI imaging MS) is a prerequisite for the routine use of this promising technology in clinical applications. We present an approach to develop standard operating procedures for MALDI imaging MS sample preparation of formalin-fixed and paraffin-embedded (FFPE) tissue sections based on a novel quantitative measure of dataset quality. To cover many parts of the complex workflow and simultaneously test several parameters, experiments were planned according to a fractional factorial design of experiments (DoE). The effect of ten different experiment parameters was investigated in two distinct DoE sets, each consisting of eight experiments. FFPE rat brain sections were used as standard material because of low biological variance. The mean peak intensity and a recently proposed spatial complexity measure were calculated for a list of 26 predefined peptides obtained by in silico digestion of five different proteins and served as quality criteria. A five-way analysis of variance (ANOVA) was applied on the final scores to retrieve a ranking of experiment parameters with increasing impact on data variance. Graphical abstract MALDI imaging experiments were planned according to fractional factorial design of experiments for the parameters under study. Selected peptide images were evaluated by the chosen quality metric (structure and intensity for a given peak list), and the calculated values were used as an input for the ANOVA. The parameters with the highest impact on the quality were deduced and SOPs recommended.

Formulation and evaluation of floating tablet of H2-receptor antagonist.

PubMed

Kesarla, Rajesh S; Vora, Pratik Ashwinbhai; Sridhar, B K; Patel, Gunvant; Omri, Abdelwahab

2015-01-01

Conventional sustained dosage form of ranitidine hydrochloride (HCl) does not prevent frequent administration due to its degradation in colonic media and limited absorption in the upper part of GIT. Ranitidine HCl floating tablet was formulated with sublimation method to overcome the stated problem. Compatibility study for screening potential excipients was carried out using Fourier transform infrared spectroscopy (FT-IR) and differential scanning chromatography (DSC). Selected excipients were further evaluated for optimizing the formulation. Preliminary screening of binder, polymer and sublimating material was based on hardness and drug release, drug release with release kinetics and floating lag time with total floatation time, respectively. Selected excipients were subjected to 3(2) factorial design with polymer and sublimating material as independent factors. Matrix tablets were obtained by using 16/32" flat-faced beveled edges punches followed by sublimation. FT-IR and DSC indicated no significant incompatibility with selected excipients. Klucel-LF, POLYOX WSR N 60 K and l-menthol were selected as binder, polymer and sublimating material, respectively, for factorial design batches after preliminary screening. From the factorial design batches, optimum concentration to release the drug within 12 h was found to be 420 mg of POLYOX and 40 mg of l-menthol. Stability studies indicated the formulation as stable. Ranitidine HCl matrix floating tablets were formulated to release 90% of drug in stomach within 12 h. Hence, release of the drug could be sustained within narrow absorption site. Moreover, the dosage form was found to be floating within a fraction of second independent of the pH of media ensuring a robust formulation.

Optimization strategies for radiation induced grafting of 4-vinylpyridine onto poly(ethylene-co-tetraflouroethene) film using Box-Behnken design

NASA Astrophysics Data System (ADS)

Mahmoud Nasef, Mohamed; Shamsaei, Ezzatollah; Ghassemi, Payman; Ahmed Aly, Amgad; Hamid Yahaya, Abdul

2012-04-01

The radiation induced grafting of 4-vinylpyridine (4-VP) onto poly(ethylene-co-tetrafluoroethene) (ETFE) was optimized using the Box-Behnken factorial design available in the response surface method (RSM). The optimized grafting parameters; absorbed dose, monomer concentration, grafting time and reaction temperature were varied in four levels to quantify their effect on the grafting yield (GY). The validity of the statistical model was supported by the small deviation between the predicted (GY=61%) and experimental (GY=57%) values. The optimum conditions for enhancing GY were determined at the following values: monomer concentration of 48 vol%, absorbed dose of 64 kGy, reaction time of 4 h and temperature of 68 °C. A comparison was made between the optimization model developed for the present grafting system and that for grafting of 1-vinylimidazole (1-VIm) onto ETFE to confirm the validly and reliability of the Box-Behnken for the optimization of various radiation induced grafting reactions. Fourier transform infrared (FTIR), thermogravimetric analysis (TGA) and X-ray diffraction (XRD) were used to investigate the properties of the obtained films and provide evidence for grafting.

Surface Roughness Optimization of Polyamide-6/Nanoclay Nanocomposites Using Artificial Neural Network: Genetic Algorithm Approach

PubMed Central

Moghri, Mehdi; Omidi, Mostafa; Farahnakian, Masoud

2014-01-01

During the past decade, polymer nanocomposites attracted considerable investment in research and development worldwide. One of the key factors that affect the quality of polymer nanocomposite products in machining is surface roughness. To obtain high quality products and reduce machining costs it is very important to determine the optimal machining conditions so as to achieve enhanced machining performance. The objective of this paper is to develop a predictive model using a combined design of experiments and artificial intelligence approach for optimization of surface roughness in milling of polyamide-6 (PA-6) nanocomposites. A surface roughness predictive model was developed in terms of milling parameters (spindle speed and feed rate) and nanoclay (NC) content using artificial neural network (ANN). As the present study deals with relatively small number of data obtained from full factorial design, application of genetic algorithm (GA) for ANN training is thought to be an appropriate approach for the purpose of developing accurate and robust ANN model. In the optimization phase, a GA is considered in conjunction with the explicit nonlinear function derived from the ANN to determine the optimal milling parameters for minimization of surface roughness for each PA-6 nanocomposite. PMID:24578636

Advances and prospects of Bacillus subtilis cellular factories: From rational design to industrial applications.

PubMed

Gu, Yang; Xu, Xianhao; Wu, Yaokang; Niu, Tengfei; Liu, Yanfeng; Li, Jianghua; Du, Guocheng; Liu, Long

2018-05-15

Bacillus subtilis is the most characterized gram-positive bacterium that has significant attributes, such as growing well on cheap carbon sources, possessing clear inherited backgrounds, having mature genetic manipulation methods, and exhibiting robustness in large-scale fermentations. Till date, B. subtilis has been identified as attractive hosts for the production of recombinant proteins and chemicals. By applying various systems and synthetic biology tools, the productivity features of B. subtilis can be thoroughly analyzed and further optimized via metabolic engineering. In the present review, we discussed why B. subtilis is the primary organisms used for metabolic engineering and industrial applications. Additionally, we summarized the recent advances in systems and synthetic biology, engineering strategies for improving cellular performances, and metabolic engineering applications of B. subtilis. In particular, we proposed emerging opportunities and essential strategies to enable the successful development of B. subtilis as microbial cell factories. Copyright © 2018. Published by Elsevier Inc.

Enhancing the Effectiveness of Smoking Treatment Research: Conceptual Bases and Progress

PubMed Central

Baker, Timothy B.; Collins, Linda M.; Mermelstein, Robin; Piper, Megan E.; Schlam, Tanya R.; Cook, Jessica W.; Bolt, Daniel M.; Smith, Stevens S.; Jorenby, Douglas E.; Fraser, David; Loh, Wei-Yin; Theobald, Wendy E.; Fiore, Michael C.

2015-01-01

Background and aims A chronic care strategy could potentially enhance the reach and effectiveness of smoking treatment by providing effective interventions for all smokers, including those who are initially unwilling to quit. This paper describes the conceptual bases of a National Cancer Institute-funded research program designed to develop an optimized, comprehensive, chronic care smoking treatment. Methods This research is grounded in three methodological approaches: 1) the Phase-Based Model, which guides the selection of intervention components to be experimentally evaluated for the different phases of smoking treatment (motivation, preparation, cessation, and maintenance); 2) the Multiphase Optimization Strategy (MOST), which guides the screening of intervention components via efficient experimental designs and, ultimately, the assembly of promising components into an optimized treatment package; and 3) pragmatic research methods, such as electronic health record recruitment, that facilitate the efficient translation of research findings into clinical practice. Using this foundation and working in primary care clinics, we conducted three factorial experiments (reported in three accompanying articles) to screen 15 motivation, preparation, cessation, and maintenance phase intervention components for possible inclusion in a chronic care smoking treatment program. Results This research identified intervention components with relatively strong evidence of effectiveness at particular phases of smoking treatment and it demonstrated the efficiency of the MOST approach in terms both of the number of intervention components tested and of the richness of the information yielded. Conclusions A new, synthesized research approach efficiently evaluates multiple intervention components to identify promising components for every phase of smoking treatment. Many intervention components interact with one another, supporting the use of factorial experiments in smoking treatment development. PMID:26581974

Conceptuation, formulation and evaluation of sustained release floating tablets of captopril compression coated with gastric dispersible hydrochlorothiazide using 23 factorial design

PubMed Central

Sirisha, Pathuri Lakshmi; Babu, Govada Kishore; Babu, Puttagunta Srinivasa

2014-01-01

Ambulatory blood pressure monitoring is regarded as the gold standard for hypertensive therapy in non-dipping hypertension patients. A novel compression coated formulation of captopril and hydrochlorothiazide (HCTZ) was developed in order to improve the efficacy of antihypertensive therapy considering the half-life of both drugs. The synergistic action using combination therapy can be effectively achieved by sustained release captopril (t1/2= 2.5 h) and fast releasing HCTZ (average t1/2= 9.5 h). The sustained release floating tablets of captopril were prepared by using 23 factorial design by employing three polymers i.e., ethyl cellulose (EC), carbopol and xanthan gum at two levels. The formulations (CF1-CF8) were optimized using analysis of variance for two response variables, buoyancy and T50%. Among the three polymers employed, the coefficients and P values for the response variable buoyancy and T50% using EC were found to be 3.824, 0.028 and 0.0196, 0.046 respectively. From the coefficients and P values for the two response variables, formulation CF2 was optimized, which contains EC polymer alone at a high level. The CF2 formulation was further compression coated with optimized gastric dispersible HCTZ layer (HF9). The compression coated tablet was further evaluated using drug release kinetics. The Q value of HCTZ layer is achieved within 20 min following first order release whereas the Q value of captopril was obtained at 6.5 h following Higuchi model, from which it is proved that rapid release HCTZ and slow release of captopril is achieved. The mechanism of drug release was analyzed using Peppas equation, which showed an n >0.90 confirming case II transportation mechanism for drug release. PMID:25006552

Tuning Parameters in Heuristics by Using Design of Experiments Methods

NASA Technical Reports Server (NTRS)

Arin, Arif; Rabadi, Ghaith; Unal, Resit

2010-01-01

With the growing complexity of today's large scale problems, it has become more difficult to find optimal solutions by using exact mathematical methods. The need to find near-optimal solutions in an acceptable time frame requires heuristic approaches. In many cases, however, most heuristics have several parameters that need to be "tuned" before they can reach good results. The problem then turns into "finding best parameter setting" for the heuristics to solve the problems efficiently and timely. One-Factor-At-a-Time (OFAT) approach for parameter tuning neglects the interactions between parameters. Design of Experiments (DOE) tools can be instead employed to tune the parameters more effectively. In this paper, we seek the best parameter setting for a Genetic Algorithm (GA) to solve the single machine total weighted tardiness problem in which n jobs must be scheduled on a single machine without preemption, and the objective is to minimize the total weighted tardiness. Benchmark instances for the problem are available in the literature. To fine tune the GA parameters in the most efficient way, we compare multiple DOE models including 2-level (2k ) full factorial design, orthogonal array design, central composite design, D-optimal design and signal-to-noise (SIN) ratios. In each DOE method, a mathematical model is created using regression analysis, and solved to obtain the best parameter setting. After verification runs using the tuned parameter setting, the preliminary results for optimal solutions of multiple instances were found efficiently.

Determination of tailored filter sets to create rayfiles including spatial and angular resolved spectral information.

PubMed

Rotscholl, Ingo; Trampert, Klaus; Krüger, Udo; Perner, Martin; Schmidt, Franz; Neumann, Cornelius

2015-11-16

To simulate and optimize optical designs regarding perceived color and homogeneity in commercial ray tracing software, realistic light source models are needed. Spectral rayfiles provide angular and spatial varying spectral information. We propose a spectral reconstruction method with a minimum of time consuming goniophotometric near field measurements with optical filters for the purpose of creating spectral rayfiles. Our discussion focuses on the selection of the ideal optical filter combination for any arbitrary spectrum out of a given filter set by considering measurement uncertainties with Monte Carlo simulations. We minimize the simulation time by a preselection of all filter combinations, which bases on factorial design.

Statistical analysis of the factors that influenced the mechanical properties improvement of cassava starch films

NASA Astrophysics Data System (ADS)

Monteiro, Mayra; Oliveira, Victor; Santos, Francisco; Barros Neto, Eduardo; Silva, Karyn; Silva, Rayane; Henrique, João; Chibério, Abimaelle

2017-08-01

In order to obtain cassava starch films with improved mechanical properties in relation to the synthetic polymer in the packaging production, a complete factorial design 23 was carried out in order to investigate which factor significantly influences the tensile strength of the biofilm. The factors to be investigated were cassava starch, glycerol and modified clay contents. Modified bentonite clay was used as a filling material of the biofilm. Glycerol was the plasticizer used to thermoplastify cassava starch. The factorial analysis suggested a regression model capable of predicting the optimal mechanical property of the cassava starch film from the maximization of the tensile strength. The reliability of the regression model was tested by the correlation established with the experimental data through the following statistical analyse: Pareto graph. The modified clay was the factor of greater statistical significance on the observed response variable, being the factor that contributed most to the improvement of the mechanical property of the starch film. The factorial experiments showed that the interaction of glycerol with both modified clay and cassava starch was significant for the reduction of biofilm ductility. Modified clay and cassava starch contributed to the maximization of biofilm ductility, while glycerol contributed to the minimization.

Use of fractional factorial design for optimization of digestion procedures followed by multi-element determination of essential and non-essential elements in nuts using ICP-OES technique.

PubMed

Momen, Awad A; Zachariadis, George A; Anthemidis, Aristidis N; Stratis, John A

2007-01-15

Two digestion procedures have been tested on nut samples for application in the determination of essential (Cr, Cu, Fe, Mg, Mn, Zn) and non-essential (Al, Ba, Cd, Pb) elements by inductively coupled plasma-optical emission spectrometry (ICP-OES). These included wet digestions with HNO(3)/H(2)SO(4) and HNO(3)/H(2)SO(4)/H(2)O(2). The later one is recommended for better analytes recoveries (relative error<11%). Two calibrations (aqueous standard and standard addition) procedures were studied and proved that standard addition was preferable for all analytes. Experimental designs for seven factors (HNO(3), H(2)SO(4) and H(2)O(2) volumes, digestion time, pre-digestion time, temperature of the hot plate and sample weight) were used for optimization of sample digestion procedures. For this purpose Plackett-Burman fractional factorial design, which involve eight experiments was adopted. The factors HNO(3) and H(2)O(2) volume, and the digestion time were found to be the most important parameters. The instrumental conditions were also optimized (using peanut matrix rather than aqueous standard solutions) considering radio-frequency (rf) incident power, nebulizer argon gas flow rate and sample uptake flow rate. The analytical performance, such as limits of detection (LOD<0.74mugg(-1)), precision of the overall procedures (relative standard deviation between 2.0 and 8.2%) and accuracy (relative errors between 0.4 and 11%) were assessed statistically to evaluate the developed analytical procedures. The good agreement between measured and certified values for all analytes (relative error <11%) with respect to IAEA-331 (spinach leaves) and IAEA-359 (cabbage) indicates that the developed analytical method is well suited for further studies on the fate of major elements in nuts and possibly similar matrices.

Formulation, optimization, and in vitro/in vivo evaluation of furosemide nanosuspension for enhancement of its oral bioavailability

NASA Astrophysics Data System (ADS)

Sahu, Bhanu P.; Das, Malay K.

2014-04-01

Furosemide is a poorly soluble diuretic used for treatment of hypertension and edema. It has very poor or variable oral bioavailability due to its reduced solubility in gastric fluid and reduced permeability in intestinal fluid. The aim of this study was to prepare nanosuspension of furosemide to enhance its oral bioavailability by increasing its dissolution in stomach where it has better permeability. Full factorial design was used for a systematic approach of formulation and optimization. The nanosuspensions were prepared by precipitation with ultrasonication method. Polyvinyl acetate was used for sterically stabilizing the nanosuspensions. The diffusing drug concentration and stabilizer were used as the factors and the particle size, polydispersity index, and drug release were selected as dependent variables and characterized. The effect of nanoprecipitation on enhancement of oral bioavailability of furosemide nanosuspension was studied by in vitro dissolution and in vivo absorption studies in rats and compared to pure drug. Quality by design using full factorial design provided a systematic approach in optimizing nanosuspensions to produce products with desired quality. Stable nanosuspension were obtained with average size range of the precipitated nanoparticles between 150 and 300 nm and were found to be homogenous showing a narrow polydispersity index of 0.3 ± 0.1. The in vivo studies on rats revealed a significant increase in the oral absorbtion of furosemide in the nanosuspension compared to pure drug. The AUC0→24 and C max values of nanosuspension were approximately 1.38- and 1.68-fold greater than that of pure drug, respectively. Furosemide nanosuspension showed 20.06 ± 0.02 % decrease in systolic blood pressure compared to 13.37 + 0.02 % in plain furosemide suspension, respectively. The improved oral bioavailability and pharmacodynamic effect of furosemide may be due to the improved dissolution of furosemide in simulated gastric fluid which results in enhanced oral systemic absorption of furosemide from stomach region where it has better permeability.

Optimization studies on compression coated floating-pulsatile drug delivery of bisoprolol.

PubMed

Jagdale, Swati C; Bari, Nilesh A; Kuchekar, Bhanudas S; Chabukswar, Aniruddha R

2013-01-01

The purpose of the present work was to design and optimize compression coated floating pulsatile drug delivery systems of bisoprolol. Floating pulsatile concept was applied to increase the gastric residence of the dosage form having lag phase followed by a burst release. The prepared system consisted of two parts: a core tablet containing the active ingredient and an erodible outer shell with gas generating agent. The rapid release core tablet (RRCT) was prepared by using superdisintegrants with active ingredient. Press coating of optimized RRCT was done by polymer. A 3² full factorial design was used for optimization. The amount of Polyox WSR205 and Polyox WSR N12K was selected as independent variables. Lag period, drug release, and swelling index were selected as dependent variables. Floating pulsatile release formulation (FPRT) F13 at level 0 (55 mg) for Polyox WSR205 and level +1 (65 mg) for Polyox WSR N12K showed lag time of 4 h with >90% drug release. The data were statistically analyzed using ANOVA, and P < 0.05 was statistically significant. Release kinetics of the optimized formulation best fitted the zero order model. In vivo study confirms burst effect at 4 h in indicating the optimization of the dosage form.

Optimization Studies on Compression Coated Floating-Pulsatile Drug Delivery of Bisoprolol

PubMed Central

Jagdale, Swati C.; Bari, Nilesh A.; Kuchekar, Bhanudas S.; Chabukswar, Aniruddha R.

2013-01-01

The purpose of the present work was to design and optimize compression coated floating pulsatile drug delivery systems of bisoprolol. Floating pulsatile concept was applied to increase the gastric residence of the dosage form having lag phase followed by a burst release. The prepared system consisted of two parts: a core tablet containing the active ingredient and an erodible outer shell with gas generating agent. The rapid release core tablet (RRCT) was prepared by using superdisintegrants with active ingredient. Press coating of optimized RRCT was done by polymer. A 32 full factorial design was used for optimization. The amount of Polyox WSR205 and Polyox WSR N12K was selected as independent variables. Lag period, drug release, and swelling index were selected as dependent variables. Floating pulsatile release formulation (FPRT) F13 at level 0 (55 mg) for Polyox WSR205 and level +1 (65 mg) for Polyox WSR N12K showed lag time of 4 h with >90% drug release. The data were statistically analyzed using ANOVA, and P < 0.05 was statistically significant. Release kinetics of the optimized formulation best fitted the zero order model. In vivo study confirms burst effect at 4 h in indicating the optimization of the dosage form. PMID:24367788

Development of a fast, lean and agile direct pelletization process using experimental design techniques.

PubMed

Politis, Stavros N; Rekkas, Dimitrios M

2017-04-01

A novel hot melt direct pelletization method was developed, characterized and optimized, using statistical thinking and experimental design tools. Mixtures of carnauba wax (CW) and HPMC K100M were spheronized using melted gelucire 50-13 as a binding material (BM). Experimentation was performed sequentially; a fractional factorial design was set up initially to screen the factors affecting the process, namely spray rate, quantity of BM, rotor speed, type of rotor disk, lubricant-glidant presence, additional spheronization time, powder feeding rate and quantity. From the eight factors assessed, three were further studied during process optimization (spray rate, quantity of BM and powder feeding rate), at different ratios of the solid mixture of CW and HPMC K100M. The study demonstrated that the novel hot melt process is fast, efficient, reproducible and predictable. Therefore, it can be adopted in a lean and agile manufacturing setting for the production of flexible pellet dosage forms with various release rates easily customized between immediate and modified delivery.

Statistical optimization of process parameters for the production of tannase by Aspergillus flavus under submerged fermentation.

PubMed

Mohan, S K; Viruthagiri, T; Arunkumar, C

2014-04-01

Production of tannase by Aspergillus flavus (MTCC 3783) using tamarind seed powder as substrate was studied in submerged fermentation. Plackett-Burman design was applied for the screening of 12 medium nutrients. From the results, the significant nutrients were identified as tannic acid, magnesium sulfate, ferrous sulfate and ammonium sulfate. Further the optimization of process parameters was carried out using response surface methodology (RSM). RSM has been applied for designing of experiments to evaluate the interactive effects through a full 31 factorial design. The optimum conditions were tannic acid concentration, 3.22 %; fermentation period, 96 h; temperature, 35.1 °C; and pH 5.4. Higher value of the regression coefficient (R 2  = 0.9638) indicates excellent evaluation of experimental data by second-order polynomial regression model. The RSM revealed that a maximum tannase production of 139.3 U/ml was obtained at the optimum conditions.

Data related to the experimental design for powder bed binder jetting additive manufacturing of silicone.

PubMed

Liravi, Farzad; Vlasea, Mihaela

2018-06-01

The data included in this article provides additional supporting information on our recent publication (Liravi et al., 2018 [1]) on a novel hybrid additive manufacturing (AM) method for fabrication of three-dimensional (3D) structures from silicone powder. A design of experiments (DoE) study has been carried out to optimize the geometrical fidelity of AM-made parts. This manuscript includes the details of a multi-level factorial DOE and the response optimization results. The variation in the temperature of powder-bed when exposed to heat is plotted as well. Furthermore, the effect of blending ratio of two parts of silicone binder on its curing speed was investigated by conducting DSC tests on a silicone binder with 100:2 precursor to curing agent ratio. The hardness of parts fabricated with non-optimum printing conditions are included and compared.

Design of experiments with four-factors for a PEM fuel cell optimization

NASA Astrophysics Data System (ADS)

Olteanu, V.; Pǎtularu, L.; Popescu, C. L.; Popescu, M. O.; Crǎciunescu, A.

2017-07-01

Nowadays, many research efforts are allocated for the development of fuel cells, since they constitute a carbon-free electrical energy generator which can be used for stationary, mobile and portable applications. The maximum value of the delivered power of a fuel cell depends on many factors as: the height of plates' channels, the stoichiometry level of the air flow, the air pressure for the cathode, and of the actual operating electric current density. In this paper, two levels, full four-factors factorial experiment has been designed in order to obtain the appropriate response surface which approximates the maximum delivered power dependence of the above-mentioned factors. The optimum set of the fuel-cell factors which determine the maximum value of the delivered power was determined and a comparison between simulated and measured optimal Power versus Current Density characteristics is given.

Engineering tolerance to industrially relevant stress factors in yeast cell factories.

PubMed

Deparis, Quinten; Claes, Arne; Foulquié-Moreno, Maria R; Thevelein, Johan M

2017-06-01

The main focus in development of yeast cell factories has generally been on establishing optimal activity of heterologous pathways and further metabolic engineering of the host strain to maximize product yield and titer. Adequate stress tolerance of the host strain has turned out to be another major challenge for obtaining economically viable performance in industrial production. Although general robustness is a universal requirement for industrial microorganisms, production of novel compounds using artificial metabolic pathways presents additional challenges. Many of the bio-based compounds desirable for production by cell factories are highly toxic to the host cells in the titers required for economic viability. Artificial metabolic pathways also turn out to be much more sensitive to stress factors than endogenous pathways, likely because regulation of the latter has been optimized in evolution in myriads of environmental conditions. We discuss different environmental and metabolic stress factors with high relevance for industrial utilization of yeast cell factories and the experimental approaches used to engineer higher stress tolerance. Improving stress tolerance in a predictable manner in yeast cell factories should facilitate their widespread utilization in the bio-based economy and extend the range of products successfully produced in large scale in a sustainable and economically profitable way. © FEMS 2017.

Engineering tolerance to industrially relevant stress factors in yeast cell factories

PubMed Central

Deparis, Quinten; Claes, Arne; Foulquié-Moreno, Maria R.

2017-01-01

Abstract The main focus in development of yeast cell factories has generally been on establishing optimal activity of heterologous pathways and further metabolic engineering of the host strain to maximize product yield and titer. Adequate stress tolerance of the host strain has turned out to be another major challenge for obtaining economically viable performance in industrial production. Although general robustness is a universal requirement for industrial microorganisms, production of novel compounds using artificial metabolic pathways presents additional challenges. Many of the bio-based compounds desirable for production by cell factories are highly toxic to the host cells in the titers required for economic viability. Artificial metabolic pathways also turn out to be much more sensitive to stress factors than endogenous pathways, likely because regulation of the latter has been optimized in evolution in myriads of environmental conditions. We discuss different environmental and metabolic stress factors with high relevance for industrial utilization of yeast cell factories and the experimental approaches used to engineer higher stress tolerance. Improving stress tolerance in a predictable manner in yeast cell factories should facilitate their widespread utilization in the bio-based economy and extend the range of products successfully produced in large scale in a sustainable and economically profitable way. PMID:28586408

Simulation study to determine the impact of different design features on design efficiency in discrete choice experiments.

PubMed

Vanniyasingam, Thuva; Cunningham, Charles E; Foster, Gary; Thabane, Lehana

2016-07-19

Discrete choice experiments (DCEs) are routinely used to elicit patient preferences to improve health outcomes and healthcare services. While many fractional factorial designs can be created, some are more statistically optimal than others. The objective of this simulation study was to investigate how varying the number of (1) attributes, (2) levels within attributes, (3) alternatives and (4) choice tasks per survey will improve or compromise the statistical efficiency of an experimental design. A total of 3204 DCE designs were created to assess how relative design efficiency (d-efficiency) is influenced by varying the number of choice tasks (2-20), alternatives (2-5), attributes (2-20) and attribute levels (2-5) of a design. Choice tasks were created by randomly allocating attribute and attribute level combinations into alternatives. Relative d-efficiency was used to measure the optimality of each DCE design. DCE design complexity influenced statistical efficiency. Across all designs, relative d-efficiency decreased as the number of attributes and attribute levels increased. It increased for designs with more alternatives. Lastly, relative d-efficiency converges as the number of choice tasks increases, where convergence may not be at 100% statistical optimality. Achieving 100% d-efficiency is heavily dependent on the number of attributes, attribute levels, choice tasks and alternatives. Further exploration of overlaps and block sizes are needed. This study's results are widely applicable for researchers interested in creating optimal DCE designs to elicit individual preferences on health services, programmes, policies and products. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Inactivation disinfection property of Moringa Oleifera seed extract: optimization and kinetic studies

NASA Astrophysics Data System (ADS)

Idris, M. A.; Jami, M. S.; Hammed, A. M.

2017-05-01

This paper presents the statistical optimization study of disinfection inactivation parameters of defatted Moringa oleifera seed extract on Pseudomonas aeruginosa bacterial cells. Three level factorial design was used to estimate the optimum range and the kinetics of the inactivation process was also carried. The inactivation process involved comparing different disinfection models of Chicks-Watson, Collins-Selleck and Homs models. The results from analysis of variance (ANOVA) of the statistical optimization process revealed that only contact time was significant. The optimum disinfection range of the seed extract was 125 mg/L, 30 minutes and 120rpm agitation. At the optimum dose, the inactivation kinetics followed the Collin-Selleck model with coefficient of determination (R2) of 0.6320. This study is the first of its kind in determining the inactivation kinetics of pseudomonas aeruginosa using the defatted seed extract.

Optimized and validated flow-injection spectrophotometric analysis of topiramate, piracetam and levetiracetam in pharmaceutical formulations.

PubMed

Hadad, Ghada M; Abdel-Salam, Randa A; Emara, Samy

2011-12-01

Application of a sensitive and rapid flow injection analysis (FIA) method for determination of topiramate, piracetam, and levetiracetam in pharmaceutical formulations has been investigated. The method is based on the reaction with ortho-phtalaldehyde and 2-mercaptoethanol in a basic buffer and measurement of absorbance at 295 nm under flow conditions. Variables affecting the determination such as sample injection volume, pH, ionic strength, reagent concentrations, flow rate of reagent and other FIA parameters were optimized to produce the most sensitive and reproducible results using a quarter-fraction factorial design, for five factors at two levels. Also, the method has been optimized and fully validated in terms of linearity and range, limit of detection and quantitation, precision, selectivity and accuracy. The method was successfully applied to the analysis of pharmaceutical preparations.

Optimization and analysis of large chemical kinetic mechanisms using the solution mapping method - Combustion of methane

NASA Technical Reports Server (NTRS)

Frenklach, Michael; Wang, Hai; Rabinowitz, Martin J.

1992-01-01

A method of systematic optimization, solution mapping, as applied to a large-scale dynamic model is presented. The basis of the technique is parameterization of model responses in terms of model parameters by simple algebraic expressions. These expressions are obtained by computer experiments arranged in a factorial design. The developed parameterized responses are then used in a joint multiparameter multidata-set optimization. A brief review of the mathematical background of the technique is given. The concept of active parameters is discussed. The technique is applied to determine an optimum set of parameters for a methane combustion mechanism. Five independent responses - comprising ignition delay times, pre-ignition methyl radical concentration profiles, and laminar premixed flame velocities - were optimized with respect to thirteen reaction rate parameters. The numerical predictions of the optimized model are compared to those computed with several recent literature mechanisms. The utility of the solution mapping technique in situations where the optimum is not unique is also demonstrated.

Improvement of biomass production and glucoamylase activity by Candida famata using factorial design.

PubMed

Mosbah, Habib; Aissa, Imen; Hassad, Nahla; Farh, Dhaker; Bakhrouf, Amina; Achour, Sami

2016-07-01

To improve biomass production and glucoamylase activity (GA) by Candida famata, culture conditions were optimized. A 2(3) full factorial design (FFD) with a response surface model was used to evaluate the effects and interactions of pH (X1 ), time of cultivation (X2 ), and starch concentration (X3 ) on the biomass production and enzyme activity. A total of 16 experiments were conducted toward the construction of an empiric model and a first-order equation. It was found that all factors (X1 , X2 , and X3 ) and their interactions were significant at a certain confidence level (P < 0.05). Using this methodology, the optimum values of the three tested parameters were obtained as follows: pH 6; time of cultivation 24 H and starch concentration 7 g/L, respectively. Our results showed that the starch concentration (X3) has significantly influenced both dependent variables, biomass production and GA of C. famata. Under this optimized medium, the experimental biomass production and GA obtained were 1.8 ± 0.54 g/L and 0.078 ± 0.012 µmol/L/Min, about 1.5- and 1.8-fold, respectively, higher than those in basal medium. The (R(2) ) coefficients obtained were 0.997 and 0.990, indicating an adequate degree of reliability in the model. Approximately 99% of validity of the predicted value was achieved. © 2015 International Union of Biochemistry and Molecular Biology, Inc.

Factorial Design Based Multivariate Modeling and Optimization of Tunable Bioresponsive Arginine Grafted Poly(cystaminebis(acrylamide)-diaminohexane) Polymeric Matrix Based Nanocarriers.

PubMed

Yang, Rongbing; Nam, Kihoon; Kim, Sung Wan; Turkson, James; Zou, Ye; Zuo, Yi Y; Haware, Rahul V; Chougule, Mahavir B

2017-01-03

Desired characteristics of nanocarriers are crucial to explore its therapeutic potential. This investigation aimed to develop tunable bioresponsive newly synthesized unique arginine grafted poly(cystaminebis(acrylamide)-diaminohexane) [ABP] polymeric matrix based nanocarriers by using L9 Taguchi factorial design, desirability function, and multivariate method. The selected formulation and process parameters were ABP concentration, acetone concentration, the volume ratio of acetone to ABP solution, and drug concentration. The measured nanocarrier characteristics were particle size, polydispersity index, zeta potential, and percentage drug loading. Experimental validation of nanocarrier characteristics computed from initially developed predictive model showed nonsignificant differences (p > 0.05). The multivariate modeling based optimized cationic nanocarrier formulation of <100 nm loaded with hydrophilic acetaminophen was readapted for a hydrophobic etoposide loading without significant changes (p > 0.05) except for improved loading percentage. This is the first study focusing on ABP polymeric matrix based nanocarrier development. Nanocarrier particle size was stable in PBS 7.4 for 48 h. The increase of zeta potential at lower pH 6.4, compared to the physiological pH, showed possible endosomal escape capability. The glutathione triggered release at the physiological conditions indicated the competence of cytosolic targeting delivery of the loaded drug from bioresponsive nanocarriers. In conclusion, this unique systematic approach provides rational evaluation and prediction of a tunable bioresponsive ABP based matrix nanocarrier, which was built on selected limited number of smart experimentation.

Numerical verification of two-component dental implant in the context of fatigue life for various load cases.

PubMed

Szajek, Krzysztof; Wierszycki, Marcin

2016-01-01

Dental implant designing is a complex process which considers many limitations both biological and mechanical in nature. In earlier studies, a complete procedure for improvement of two-component dental implant was proposed. However, the optimization tasks carried out required assumption on representative load case, which raised doubts on optimality for the other load cases. This paper deals with verification of the optimal design in context of fatigue life and its main goal is to answer the question if the assumed load scenario (solely horizontal occlusal load) leads to the design which is also "safe" for oblique occlussal loads regardless the angle from an implant axis. The verification is carried out with series of finite element analyses for wide spectrum of physiologically justified loads. The design of experiment methodology with full factorial technique is utilized. All computations are done in Abaqus suite. The maximal Mises stress and normalized effective stress amplitude for various load cases are discussed and compared with the assumed "safe" limit (equivalent of fatigue life for 5e6 cycles). The obtained results proof that coronial-appical load component should be taken into consideration in the two component dental implant when fatigue life is optimized. However, its influence in the analyzed case is small and does not change the fact that the fatigue life improvement is observed for all components within whole range of analyzed loads.

Design of experiments utilization to map the processing capabilities of a micro-spray dryer: particle design and throughput optimization in support of drug discovery.

PubMed

Ormes, James D; Zhang, Dan; Chen, Alex M; Hou, Shirley; Krueger, Davida; Nelson, Todd; Templeton, Allen

2013-02-01

There has been a growing interest in amorphous solid dispersions for bioavailability enhancement in drug discovery. Spray drying, as shown in this study, is well suited to produce prototype amorphous dispersions in the Candidate Selection stage where drug supply is limited. This investigation mapped the processing window of a micro-spray dryer to achieve desired particle characteristics and optimize throughput/yield. Effects of processing variables on the properties of hypromellose acetate succinate were evaluated by a fractional factorial design of experiments. Parameters studied include solid loading, atomization, nozzle size, and spray rate. Response variables include particle size, morphology and yield. Unlike most other commercial small-scale spray dryers, the ProCepT was capable of producing particles with a relatively wide mean particle size, ca. 2-35 µm, allowing material properties to be tailored to support various applications. In addition, an optimized throughput of 35 g/hour with a yield of 75-95% was achieved, which affords to support studies from Lead-identification/Lead-optimization to early safety studies. A regression model was constructed to quantify the relationship between processing parameters and the response variables. The response surface curves provide a useful tool to design processing conditions, leading to a reduction in development time and drug usage to support drug discovery.

Modeling and optimization of ultrasound-assisted extraction of polyphenolic compounds from Aronia melanocarpa by-products from filter-tea factory.

PubMed

Ramić, Milica; Vidović, Senka; Zeković, Zoran; Vladić, Jelena; Cvejin, Aleksandra; Pavlić, Branimir

2015-03-01

Aronia melanocarpa by-product from filter-tea factory was used for the preparation of extracts with high content of bioactive compounds. Extraction process was accelerated using sonication. Three level, three variable face-centered cubic experimental design (FCD) with response surface methodology (RSM) was used for optimization of extraction in terms of maximized yields for total phenolics (TP), flavonoids (TF), anthocyanins (MA) and proanthocyanidins (TPA) contents. Ultrasonic power (X₁: 72-216 W), temperature (X₂: 30-70 °C) and extraction time (X₃: 30-90 min) were investigated as independent variables. Experimental results were fitted to a second-order polynomial model where multiple regression analysis and analysis of variance were used to determine fitness of the model and optimal conditions for investigated responses. Three-dimensional surface plots were generated from the mathematical models. The optimal conditions for ultrasound-assisted extraction of TP, TF, MA and TPA were: X₁=206.64 W, X₂=70 °C, X₃=80.1 min; X₁=210.24 W, X₂=70 °C, X₃=75 min; X₁=216 W, X₂=70 °C, X₃=45.6 min and X₁=199.44 W, X₂=70 °C, X₃=89.7 min, respectively. Generated model predicted values of the TP, TF, MA and TPA to be 15.41 mg GAE/ml, 9.86 mg CE/ml, 2.26 mg C3G/ml and 20.67 mg CE/ml, respectively. Experimental validation was performed and close agreement between experimental and predicted values was found (within 95% confidence interval). Copyright © 2014 Elsevier B.V. All rights reserved.

Optimization of flask culture medium and conditions for hyaluronic acid production by a Streptococcus equisimilis mutant nc2168.

PubMed

Chen, Yong-Hao; Li, Jun; Liu, Li; Liu, Hong-Zhi; Wang, Qiang

2012-10-01

A mutant designated NC2168, which was selected from wild-type Streptococcus equisimilis CVCC55116 by ultraviolet ray combined with(60)Co-γ ray treatment and does not produce streptolysin, was employed to produce hyaluronic acid (HA). In order to increase the output of HA in a flask, the culture medium and conditions for NC2168 were optimized in this study. The influence of culture medium ingredients including carbon sources, nitrogen sources and metal ions on HA production was evaluated using factional factorial design. The mathematical model, which represented the effect of each medium component and their interaction on the yield of HA, was established by the quadratic rotary combination design and response surface method. The model estimated that, a maximal yield of HA could be obtained when the concentrations of yeast extract, peptone, glucose, and MgSO4 were set at 3 g/100 mL, 2 g/100 mL, 0.5 g/100 mL and 0.15 g/100 mL, respectively. Compared with the values obtained by other runs in the experimental design, the optimized medium resulted in a remarkable increase in the output of HA and the maximum of the predicted HA production was 174.76 mg/L. The model developed was accurate and reliable for predicting the production of HA by NC2168.Cultivation conditions were optimized by an orthogonal experimental design and the optimal conditions were as follows: temperature 33°C, pH 7.8, agitation speed 200 rpm, medium volume 20 mL.

Assessing the applicability of the Taguchi design method to an interrill erosion study

NASA Astrophysics Data System (ADS)

Zhang, F. B.; Wang, Z. L.; Yang, M. Y.

2015-02-01

Full-factorial experimental designs have been used in soil erosion studies, but are time, cost and labor intensive, and sometimes they are impossible to conduct due to the increasing number of factors and their levels to consider. The Taguchi design is a simple, economical and efficient statistical tool that only uses a portion of the total possible factorial combinations to obtain the results of a study. Soil erosion studies that use the Taguchi design are scarce and no comparisons with full-factorial designs have been made. In this paper, a series of simulated rainfall experiments using a full-factorial design of five slope lengths (0.4, 0.8, 1.2, 1.6, and 2 m), five slope gradients (18%, 27%, 36%, 48%, and 58%), and five rainfall intensities (48, 62.4, 102, 149, and 170 mm h-1) were conducted. Validation of the applicability of a Taguchi design to interrill erosion experiments was achieved by extracting data from the full dataset according to a theoretical Taguchi design. The statistical parameters for the mean quasi-steady state erosion and runoff rates of each test, the optimum conditions for producing maximum erosion and runoff, and the main effect and percentage contribution of each factor obtained from the full-factorial and Taguchi designs were compared. Both designs generated almost identical results. Using the experimental data from the Taguchi design, it was possible to accurately predict the erosion and runoff rates under the conditions that had been excluded from the Taguchi design. All of the results obtained from analyzing the experimental data for both designs indicated that the Taguchi design could be applied to interrill erosion studies and could replace full-factorial designs. This would save time, labor and costs by generally reducing the number of tests to be conducted. Further work should test the applicability of the Taguchi design to a wider range of conditions.

MapFactory - Towards a mapping design pattern for big geospatial data

NASA Astrophysics Data System (ADS)

Rautenbach, Victoria; Coetzee, Serena

2018-05-01

With big geospatial data emerging, cartographers and geographic information scientists have to find new ways of dealing with the volume, variety, velocity, and veracity (4Vs) of the data. This requires the development of tools that allow processing, filtering, analysing, and visualising of big data through multidisciplinary collaboration. In this paper, we present the MapFactory design pattern that will be used for the creation of different maps according to the (input) design specification for big geospatial data. The design specification is based on elements from ISO19115-1:2014 Geographic information - Metadata - Part 1: Fundamentals that would guide the design and development of the map or set of maps to be produced. The results of the exploratory research suggest that the MapFactory design pattern will help with software reuse and communication. The MapFactory design pattern will aid software developers to build the tools that are required to automate map making with big geospatial data. The resulting maps would assist cartographers and others to make sense of big geospatial data.

Design Optimization and In Vitro-In Vivo Evaluation of Orally Dissolving Strips of Clobazam

PubMed Central

Bala, Rajni; Khanna, Sushil; Pawar, Pravin

2014-01-01

Clobazam orally dissolving strips were prepared by solvent casting method. A full 32 factorial design was applied for optimization using different concentration of film forming polymer and disintegrating agent as independent variable and disintegration time, % cumulative drug release, and tensile strength as dependent variable. In addition the prepared films were also evaluated for surface pH, folding endurance, and content uniformity. The optimized film formulation showing the maximum in vitro drug release, satisfactory in vitro disintegration time, and tensile strength was selected for bioavailability study and compared with a reference marketed product (frisium5 tablets) in rabbits. Formulation (F6) was selected by the Design-expert software which exhibited DT (24 sec), TS (2.85 N/cm2), and in vitro drug release (96.6%). Statistical evaluation revealed no significant difference between the bioavailability parameters of the test film (F6) and the reference product. The mean ratio values (test/reference) of C max (95.87%), t max (71.42%), AUC0−t (98.125%), and AUC0−∞ (99.213%) indicated that the two formulae exhibited comparable plasma level-time profiles. PMID:25328709

Manganese ore tailing: optimization of acid leaching conditions and recovery of soluble manganese.

PubMed

Santos, Olívia de Souza Heleno; Carvalho, Cornélio de Freitas; Silva, Gilmare Antônia da; Santos, Cláudio Gouvêa Dos

2015-01-01

Manganese recovery from industrial ore processing waste by means of leaching with sulfuric acid was the objective of this study. Experimental conditions were optimized by multivariate experimental design approaches. In order to study the factors affecting leaching, a screening step was used involving a full factorial design with central point for three variables in two levels (2(3)). The three variables studied were leaching time, concentration of sulfuric acid and sample amount. The three factors screened were shown to be relevant and therefore a Doehlert design was applied to determine the best working conditions for leaching and to build the response surface. By applying the best leaching conditions, the concentrations of 12.80 and 13.64 %w/w of manganese for the global sample and for the fraction -44 + 37 μm, respectively, were found. Microbeads of chitosan were tested for removal of leachate acidity and recovering of soluble manganese. Manganese recovery from the leachate was 95.4%. Upon drying the leachate, a solid containing mostly manganese sulfate was obtained, showing that the proposed optimized method is efficient for manganese recovery from ore tailings. Copyright © 2014 Elsevier Ltd. All rights reserved.

Optimization of photocatalytic degradation of palm oil mill effluent in UV/ZnO system based on response surface methodology.

PubMed

Ng, Kim Hoong; Cheng, Yoke Wang; Khan, Maksudur R; Cheng, Chin Kui

2016-12-15

This paper reports on the optimization of palm oil mill effluent (POME) degradation in a UV-activated-ZnO system based on central composite design (CCD) in response surface methodology (RSM). Three potential factors, viz. O 2 flowrate (A), ZnO loading (B) and initial concentration of POME (C) were evaluated for the significance analysis using a 2 3 full factorial design before the optimization process. It is found that all the three main factors were significant, with contributions of 58.27% (A), 15.96% (B) and 13.85% (C), respectively, to the POME degradation. In addition, the interactions between the factors AB, AC and BC also have contributed 4.02%, 3.12% and 1.01% to the POME degradation. Subsequently, all the three factors were subjected to statistical central composite design (CCD) analysis. Quadratic models were developed and rigorously checked. A 3D-response surface was subsequently generated. Two successive validation experiments were carried out and the degradation achieved were 55.25 and 55.33%, contrasted with 52.45% for predicted degradation value. Copyright © 2016 Elsevier Ltd. All rights reserved.

User-oriented design strategies for a Lunar base

NASA Astrophysics Data System (ADS)

Jukola, Paivi

'Form follows function can be translated, among other, to communicate a desire to prioritize functional objectives for a particular design task. Thus it is less likely that a design program for a multi-functional habitat, for an all-purpose vehicle, or for a general community, will lead to most optimal, cost-effective and sustainable solutions. A power plant, a factory, a farm and a research center have over centuries had different logistical and functional requirements, despite of the local culture on various parts around the planet Earth. 'The same size fits all' concept is likely to lead to less user-friendly solutions. The paper proposes to rethink and to investigate alternative strategies to formulate objectives for a Lunar base. Diverse scientific experiments and potential future research programs for the Moon have a number of functional requirements that differ from each other. A crew of 4-6 may not be optimal for the most innovative research. The discussion is based on research of Human Factors and Design for visiting professor lectures for a Lunar base project with Howard University and NASA Marshall Space Center 2009-2010.

Multilevel Factorial Experiments for Developing Behavioral Interventions: Power, Sample Size, and Resource Considerations†

PubMed Central

Dziak, John J.; Nahum-Shani, Inbal; Collins, Linda M.

2012-01-01

Factorial experimental designs have many potential advantages for behavioral scientists. For example, such designs may be useful in building more potent interventions, by helping investigators to screen several candidate intervention components simultaneously and decide which are likely to offer greater benefit before evaluating the intervention as a whole. However, sample size and power considerations may challenge investigators attempting to apply such designs, especially when the population of interest is multilevel (e.g., when students are nested within schools, or employees within organizations). In this article we examine the feasibility of factorial experimental designs with multiple factors in a multilevel, clustered setting (i.e., of multilevel multifactor experiments). We conduct Monte Carlo simulations to demonstrate how design elements such as the number of clusters, the number of lower-level units, and the intraclass correlation affect power. Our results suggest that multilevel, multifactor experiments are feasible for factor-screening purposes, because of the economical properties of complete and fractional factorial experimental designs. We also discuss resources for sample size planning and power estimation for multilevel factorial experiments. These results are discussed from a resource management perspective, in which the goal is to choose a design that maximizes the scientific benefit using the resources available for an investigation. PMID:22309956

Multilevel factorial experiments for developing behavioral interventions: power, sample size, and resource considerations.

PubMed

Dziak, John J; Nahum-Shani, Inbal; Collins, Linda M

2012-06-01

Factorial experimental designs have many potential advantages for behavioral scientists. For example, such designs may be useful in building more potent interventions by helping investigators to screen several candidate intervention components simultaneously and to decide which are likely to offer greater benefit before evaluating the intervention as a whole. However, sample size and power considerations may challenge investigators attempting to apply such designs, especially when the population of interest is multilevel (e.g., when students are nested within schools, or when employees are nested within organizations). In this article, we examine the feasibility of factorial experimental designs with multiple factors in a multilevel, clustered setting (i.e., of multilevel, multifactor experiments). We conduct Monte Carlo simulations to demonstrate how design elements-such as the number of clusters, the number of lower-level units, and the intraclass correlation-affect power. Our results suggest that multilevel, multifactor experiments are feasible for factor-screening purposes because of the economical properties of complete and fractional factorial experimental designs. We also discuss resources for sample size planning and power estimation for multilevel factorial experiments. These results are discussed from a resource management perspective, in which the goal is to choose a design that maximizes the scientific benefit using the resources available for an investigation. (c) 2012 APA, all rights reserved

Improved optimization of polycyclic aromatic hydrocarbons (PAHs) mixtures resolution in reversed-phase high-performance liquid chromatography by using factorial design and response surface methodology.

PubMed

Andrade-Eiroa, Auréa; Diévart, Pascal; Dagaut, Philippe

2010-04-15

A new procedure for optimizing PAHs separation in very complex mixtures by reverse phase high performance (RPLC) is proposed. It is based on changing gradually the experimental conditions all along the chromatographic procedure as a function of the physical properties of the compounds eluted. The temperature and speed flow gradients allowed obtaining the optimum resolution in large chromatographic determinations where PAHs with very different medium polarizability have to be separated. Whereas optimization procedures of RPLC methodologies had always been accomplished regardless of the physico-chemical properties of the target analytes, we found that resolution is highly dependent on the physico-chemical properties of the target analytes. Based on resolution criterion, optimization process for a 16 EPA PAHs mixture was performed on three sets of difficult-to-separate PAHs pairs: acenaphthene-fluorene (for the optimization procedure in the first part of the chromatogram where light PAHs elute), benzo[g,h,i]perylene-dibenzo[a,h]anthracene and benzo[g,h,i]perylene-indeno[1,2,3-cd]pyrene (for the optimization procedure of the second part of the chromatogram where the heavier PAHs elute). Two-level full factorial designs were applied to detect interactions among variables to be optimized: speed flow, temperature of column oven and mobile-phase gradient in the two parts of the studied chromatogram. Experimental data were fitted by multivariate nonlinear regression models and optimum values of speed flow and temperature were obtained through mathematical analysis of the constructed models. An HPLC system equipped with a reversed phase 5 microm C18, 250 mm x 4.6mm column (with acetonitrile/water mobile phase), a column oven, a binary pump, a photodiode array detector (PDA), and a fluorimetric detector were used in this work. Optimum resolution was achieved operating at 1.0 mL/min in the first part of the chromatogram (until 45 min) and 0.5 mL/min in the second one (from 45 min to the end) and by applying programmed temperature gradient (15 degrees C until 30 min and progressively increasing temperature until reaching 40 degrees C at 45 min). (c) 2009 Elsevier B.V. All rights reserved.

Single element injector cold flow testing for STME swirl coaxial injector element design

NASA Technical Reports Server (NTRS)

Hulka, J.; Schneider, J. A.

1993-01-01

An oxidizer-swirled coaxial element injector is being investigated for application in the Space Transportation Main Engine (STME). Single element cold flow experiments were conducted to provide characterization of the STME injector element for future analysis, design, and optimization. All tests were conducted to quiescent, ambient backpressure conditions. Spray angle, circumferential spray uniformity, dropsize, and dropsize distribution were measured in water-only and water/nitrogen flows. Rupe mixing efficiency was measured using water/sucrose solution flows with a large grid patternator for simple comparative evaluation of mixing. Factorial designs of experiment were used for statistical evaluation of injector geometrical design features and propellant flow conditions on mixing and atomization. Increasing the free swirl angle of the liquid oxidizer had the greatest influence on increasing the mixing efficiency. The addition of gas assistance had the most significant effect on reducing oxidizer droplet size parameters and increasing droplet size distribution. Increasing the oxidizer injection velocity had the greatest influence for reducing oxidizer droplet size parameters and increasing size distribution for non-gas assisted flows. Single element and multi-element subscale hot fire testing are recommended to verify optimized designs before committing to the STME design.

Nanoemulsions containing a synthetic chalcone as an alternative for treating cutaneous leshmaniasis: optimization using a full factorial design

PubMed Central

de Mattos, Cristiane Bastos; Argenta, Débora Fretes; Melchiades, Gabriela de Lima; Sechini Cordeiro, Marlon Norberto; Tonini, Maiko Luis; Moraes, Milene Hoehr; Weber, Tanara Beatriz; Roman, Silvane Souza; Nunes, Ricardo José; Teixeira, Helder Ferreira; Steindel, Mário; Koester, Letícia Scherer

2015-01-01

Nanoemulsions are drug delivery systems that may increase the penetration of lipophilic compounds through the skin, enhancing their topical effect. Chalcones are compounds of low water solubility that have been described as promising molecules for the treatment of cutaneous leishmaniasis (CL). In this context, the aim of this work was to optimize the development of a nanoemulsion containing a synthetic chalcone for CL treatment using a 22 full factorial design. The formulations were prepared by spontaneous emulsification and the experimental design studied the influence of two independent variables (type of surfactant – soybean lecithin or sorbitan monooleate and type of co-surfactants – polysorbate 20 or polysorbate 80) on the physicochemical characteristics of the nanoemulsions, as well as on the skin permeation/retention of the synthetic chalcone in porcine skin. In order to evaluate the stability of the systems, the antileishmanial assay was performed against Leishmania amazonensis 24 hours and 60 days after the preparation of the nanoemulsions. The formulation composed of soybean lecithin and polysorbate 20 presented suitable physicochemical characteristics (droplet size 171.9 nm; polydispersity index 0.14; zeta potential −39.43 mV; pH 5.16; and viscosity 2.00 cP), drug content (91.09%) and the highest retention in dermis (3.03 µg·g−1) – the main response of interest – confirmed by confocal microscopy. This formulation also presented better stability of leishmanicidal activity in vitro against L. amazonensis amastigote forms (half maximal inhibitory concentration value 0.32±0.05 µM), which confirmed the potential of the nanoemulsion soybean lecithin and polysorbate 20 for CL treatment. PMID:26366075

Nanoemulsions containing a synthetic chalcone as an alternative for treating cutaneous leshmaniasis: optimization using a full factorial design.

PubMed

de Mattos, Cristiane Bastos; Argenta, Débora Fretes; Melchiades, Gabriela de Lima; Cordeiro, Marlon Norberto Sechini; Tonini, Maiko Luis; Moraes, Milene Hoehr; Weber, Tanara Beatriz; Roman, Silvane Souza; Nunes, Ricardo José; Teixeira, Helder Ferreira; Steindel, Mário; Koester, Letícia Scherer

2015-01-01

Nanoemulsions are drug delivery systems that may increase the penetration of lipophilic compounds through the skin, enhancing their topical effect. Chalcones are compounds of low water solubility that have been described as promising molecules for the treatment of cutaneous leishmaniasis (CL). In this context, the aim of this work was to optimize the development of a nanoemulsion containing a synthetic chalcone for CL treatment using a 2(2) full factorial design. The formulations were prepared by spontaneous emulsification and the experimental design studied the influence of two independent variables (type of surfactant - soybean lecithin or sorbitan monooleate and type of co-surfactants - polysorbate 20 or polysorbate 80) on the physicochemical characteristics of the nanoemulsions, as well as on the skin permeation/retention of the synthetic chalcone in porcine skin. In order to evaluate the stability of the systems, the antileishmanial assay was performed against Leishmania amazonensis 24 hours and 60 days after the preparation of the nanoemulsions. The formulation composed of soybean lecithin and polysorbate 20 presented suitable physicochemical characteristics (droplet size 171.9 nm; polydispersity index 0.14; zeta potential -39.43 mV; pH 5.16; and viscosity 2.00 cP), drug content (91.09%) and the highest retention in dermis (3.03 µg·g(-1)) - the main response of interest - confirmed by confocal microscopy. This formulation also presented better stability of leishmanicidal activity in vitro against L. amazonensis amastigote forms (half maximal inhibitory concentration value 0.32±0.05 µM), which confirmed the potential of the nanoemulsion soybean lecithin and polysorbate 20 for CL treatment.

Asymmetric flow field flow fractionation with light scattering detection - an orthogonal sensitivity analysis.

PubMed

Galyean, Anne A; Filliben, James J; Holbrook, R David; Vreeland, Wyatt N; Weinberg, Howard S

2016-11-18

Asymmetric flow field flow fractionation (AF 4 ) has several instrumental factors that may have a direct effect on separation performance. A sensitivity analysis was applied to ascertain the relative importance of AF 4 primary instrument factor settings for the separation of a complex environmental sample. The analysis evaluated the impact of instrumental factors namely, cross flow, ramp time, focus flow, injection volume, and run buffer concentration on the multi-angle light scattering measurement of natural organic matter (NOM) molar mass (MM). A 2 (5-1) orthogonal fractional factorial design was used to minimize analysis time while preserving the accuracy and robustness in the determination of the main effects and interactions between any two instrumental factors. By assuming that separations resulting in smaller MM measurements would be more accurate, the analysis produced a ranked list of effects estimates for factors and interactions of factors based on their relative importance in minimizing the MM. The most important and statistically significant AF 4 instrumental factors were buffer concentration and cross flow. The least important was ramp time. A parallel 2 (5-2) orthogonal fractional factorial design was also employed on five environmental factors for synthetic natural water samples containing silver nanoparticles (NPs), namely: NP concentration, NP size, NOM concentration, specific conductance, and pH. None of the water quality characteristic effects or interactions were found to be significant in minimizing the measured MM; however, the interaction between NP concentration and NP size was an important effect when considering NOM recovery. This work presents a structured approach for the rigorous assessment of AF 4 instrument factors and optimal settings for the separation of complex samples utilizing efficient orthogonal factional factorial design and appropriate graphical analysis. Copyright © 2016 Elsevier B.V. All rights reserved.

Statistical optimization and fabrication of a press coated pulsatile dosage form to treat nocturnal acid breakthrough.

PubMed

Agarwal, Vaibhav; Bansal, Mayank

2013-08-01

Present work focuses on the use of mimosa seed gum to develop a drug delivery system making combined use of floating and pulsatile principles, for the chrono-prevention of nocturnal acid breakthrough. The desired aim was achieved by fabricating a floating delivery system bearing time - lagged coating of Mimosa pudica seed polymer for the programmed release of Famotidine. Response Surface Methodology was the statistical tool that was employed for experiment designing, mathematical model generation and optimization study. A 3(2) full factorial design was used in designing the experiment.% weight ratio of mimosa gum to hydroxy propyl methyl cellulose in the coating combination and the coating weight were the independent variables, whereas the lag time and the cumulative % drug release in 360 minutes were the observed responses. Results revealed that both the coating composition and the coating weight significantly affected the release of drug from the dosage form. The optimized formulation prepared according to the computer generated software, Design-Expert(®) deciphered response which were in close proximity with the experimental responses, thus confirming the robustness as well as accuracy of the predicted model for the utilization of natural polymer like mimosa seed gum for the chronotherapeutic treatment of nocturnal acid breakthrough.

Effects of N source concentration and NH4(+)/NO3(-) ratio on phenylethanoid glycoside pattern in tissue cultures of Plantago lanceolata L.: a metabolomics driven full-factorial experiment with LC-ESI-MS(3.).

PubMed

Gonda, Sándor; Kiss-Szikszai, Attila; Szűcs, Zsolt; Máthé, Csaba; Vasas, Gábor

2014-10-01

Tissue cultures of a medicinal plant, Plantago lanceolata L. were screened for phenylethanoid glycosides (PGs) and other natural products (NPs) with LC-ESI-MS(3). The effects of N source concentration and NH4(+)/NO3(-) ratio were evaluated in a full-factorial (FF) experiment. N concentrations of 10, 20, 40 and 60mM, and NH4(+)/NO3(-) ratios of 0, 0.11, 0.20 and 0.33 (ratio of NH4(+) in total N source) were tested. Several peaks could be identified as PGs, of which, 16 could be putatively identified from the MS/MS/MS spectra. N source concentration and NH4(+)/NO3(-) ratio had significant effects on the metabolome, their effects on individual PGs were different despite these metabolites were of the same biosynthethic class. Chief PGs were plantamajoside and acteoside (verbascoside), their highest concentrations were 3.54±0.83% and 1.30±0.40% of dry weight, on media 10(0.33) and 40(0.33), respectively. NH4(+)/NO3(-) ratio and N source concentration effects were examined on a set of 89 NPs. For most NPs, high increases in abundance were observed compared to Murashige-Skoog medium. Abundances of 42 and 10 NPs were significantly influenced by the N source concentration and the NH4(+)/NO3(-) ratio, respectively. Optimal media for production of different NP clusters were 10(0), 10(0.11) and 40(0.33). Interaction was observed between NH4(+)/NO3(-) ratio and N source concentration for many NPs. It was shown in simulated experiments, that one-factor at a time (OFAT) experimental designs lead to sub-optimal media compositions for production of many NPs, and alternative experimental designs (e.g. FF) should be preferred when optimizing medium N source for optimal yield of NPs. If using OFAT, the N source concentration is to be optimized first, followed by NH4(+)/NO3(-) ratio, as this reduces the likeliness of suboptimal yield results. Copyright © 2014 Elsevier Ltd. All rights reserved.

Designing optimal cell factories: integer programming couples elementary mode analysis with regulation

PubMed Central

2012-01-01

Background Elementary mode (EM) analysis is ideally suited for metabolic engineering as it allows for an unbiased decomposition of metabolic networks in biologically meaningful pathways. Recently, constrained minimal cut sets (cMCS) have been introduced to derive optimal design strategies for strain improvement by using the full potential of EM analysis. However, this approach does not allow for the inclusion of regulatory information. Results Here we present an alternative, novel and simple method for the prediction of cMCS, which allows to account for boolean transcriptional regulation. We use binary linear programming and show that the design of a regulated, optimal metabolic network of minimal functionality can be formulated as a standard optimization problem, where EM and regulation show up as constraints. We validated our tool by optimizing ethanol production in E. coli. Our study showed that up to 70% of the predicted cMCS contained non-enzymatic, non-annotated reactions, which are difficult to engineer. These cMCS are automatically excluded by our approach utilizing simple weight functions. Finally, due to efficient preprocessing, the binary program remains computationally feasible. Conclusions We used integer programming to predict efficient deletion strategies to metabolically engineer a production organism. Our formulation utilizes the full potential of cMCS but adds additional flexibility to the design process. In particular our method allows to integrate regulatory information into the metabolic design process and explicitly favors experimentally feasible deletions. Our method remains manageable even if millions or potentially billions of EM enter the analysis. We demonstrated that our approach is able to correctly predict the most efficient designs for ethanol production in E. coli. PMID:22898474

Increasing Optimism Protects Against Pain-Induced Impairment in Task-Shifting Performance.

PubMed

Boselie, Jantine J L M; Vancleef, Linda M G; Peters, Madelon L

2017-04-01

Persistent pain can lead to difficulties in executive task performance. Three core executive functions that are often postulated are inhibition, updating, and shifting. Optimism, the tendency to expect that good things happen in the future, has been shown to protect against pain-induced performance deterioration in executive function updating. This study tested whether this protective effect of a temporary optimistic state by means of a writing and visualization exercise extended to executive function shifting. A 2 (optimism: optimism vs no optimism) × 2 (pain: pain vs no pain) mixed factorial design was conducted. Participants (N = 61) completed a shifting task once with and once without concurrent painful heat stimulation after an optimism or neutral manipulation. Results showed that shifting performance was impaired when experimental heat pain was applied during task execution, and that optimism counteracted pain-induced deterioration in task-shifting performance. Experimentally-induced heat pain impairs shifting task performance and manipulated optimism or induced optimism counteracted this pain-induced performance deterioration. Identifying psychological factors that may diminish the negative effect of persistent pain on the ability to function in daily life is imperative. Copyright © 2016 American Pain Society. Published by Elsevier Inc. All rights reserved.

Manufacturing engineering: Principles for optimization

NASA Astrophysics Data System (ADS)

Koenig, Daniel T.

Various subjects in the area of manufacturing engineering are addressed. The topics considered include: manufacturing engineering organization concepts and management techniques, factory capacity and loading techniques, capital equipment programs, machine tool and equipment selection and implementation, producibility engineering, methods, planning and work management, and process control engineering in job shops. Also discussed are: maintenance engineering, numerical control of machine tools, fundamentals of computer-aided design/computer-aided manufacture, computer-aided process planning and data collection, group technology basis for plant layout, environmental control and safety, and the Integrated Productivity Improvement Program.

Factorial Design: An Eight Factor Experiment Using Paper Helicopters

NASA Technical Reports Server (NTRS)

Kozma, Michael

1996-01-01

The goal of this paper is to present the analysis of the multi-factor experiment (factorial design) conducted in EG490, Junior Design at Loyola College in Maryland. The discussion of this paper concludes the experimental analysis and ties the individual class papers together.

Application of response surface methodology (RSM) for the removal of methylene blue dye from water by nano zero-valent iron (NZVI).

PubMed

Khosravi, Morteza; Arabi, Simin

In this study, iron zero-valent nanoparticles were synthesized, characterized and studied for removal of methylene blue dye in water solution. The reactions were mathematically described as the function of parameters such as nano zero-valent iron (NZVI) dose, pH, contact time and initial dye concentration, and were modeled by the use of response surface methodology. These experiments were carried out as a central composite design consisting of 30 experiments determined by the 2(4) full factorial designs with eight axial points and six center points. The results revealed that the optimal conditions for dye removal were NZVI dose 0.1-0.9 g/L, pH 3-11, contact time 20-100 s, and initial dye concentration 10-50 mg/L, respectively. Under these optimal values of process parameters, the dye removal efficiency of 92.87% was observed, which very close to the experimental value (92.21%) in batch experiment. In the optimization, R(2) and R(2)adj correlation coefficients for the model were evaluated as 0.96 and 0.93, respectively.

Comparison of empirical strategies to maximize GENEHUNTER lod scores.

PubMed

Chen, C H; Finch, S J; Mendell, N R; Gordon, D

1999-01-01

We compare four strategies for finding the settings of genetic parameters that maximize the lod scores reported in GENEHUNTER 1.2. The four strategies are iterated complete factorial designs, iterated orthogonal Latin hypercubes, evolutionary operation, and numerical optimization. The genetic parameters that are set are the phenocopy rate, penetrance, and disease allele frequency; both recessive and dominant models are considered. We selected the optimization of a recessive model on the Collaborative Study on the Genetics of Alcoholism (COGA) data of chromosome 1 for complete analysis. Convergence to a setting producing a local maximum required the evaluation of over 100 settings (for a time budget of 800 minutes on a Pentium II 300 MHz PC). Two notable local maxima were detected, suggesting the need for a more extensive search before claiming that a global maximum had been found. The orthogonal Latin hypercube design was the best strategy for finding areas that produced high lod scores with small numbers of evaluations. Numerical optimization starting from a region producing high lod scores was the strategy that found the highest maximum observed.

A simple, rapid and novel method based on salting-out assisted liquid-liquid extraction for ochratoxin A determination in beer samples prior to ultra-high performance liquid chromatography coupled to tandem mass spectrometry.

PubMed

Mariño-Repizo, Leonardo; Goicoechea, Hector; Raba, Julio; Cerutti, Soledad

2018-06-07

A novel, simple, easy and cheap sample treatment strategy based on salting-out assisted liquid-liquid extraction (SALLE) for ochratoxin A (OTA) ultra-trace analysis in beer samples using ultra-high performance liquid chromatography-tandem mass spectrometry determination was developed. The factors involved in the efficiency of pretreatment were studied employing factorial design in the screening phase and the optimal conditions of the significant variables on the analytical response were evaluated using a central composite face-centred design (CCF). Consequently, the amount of salt ((NH 4 ) 2 SO 4 ), together with the volumes of sample, hydrophilic (acetone) and nonpolar (toluene) solvents, and times of vortexing and centrifugation were optimized. Under optimized conditions, the limits of detection (LOD) and quantification (LOQ) were 0.02 µg l -1 and 0.08 µg l -1 respectively. OTA extraction recovery by SALLE was approximately 90% (0.2 µg l -1 ). Furthermore, the methodology was in agreement with EU Directive requirements and was successfully applied for analysis of beer samples.

Evaluation and simultaneous optimization of bio-hydrogen production using 3 2 factorial design and the desirability function

NASA Astrophysics Data System (ADS)

Cuetos, M. J.; Gómez, X.; Escapa, A.; Morán, A.

Various mixtures incorporating a simulated organic fraction of municipal solid wastes and blood from a poultry slaughterhouse were used as substrate in a dark fermentation process for the production of hydrogen. The individual and interactive effects of hydraulic retention time (HRT), solid content in the feed (%TS) and proportion of residues (%Blood) on bio-hydrogen production were studied in this work. A central composite design and response surface methodology were employed to determine the optimum conditions for the hydrogen production process. Experimental results were approximated to a second-order model with the principal effects of the three factors considered being statistically significant (P < 0.05). The production of hydrogen obtained from the experimental point at conditions close to best operability was 0.97 L Lr -1 day -1. Moreover, a desirability function was employed in order to optimize the process when a second, methanogenic, phase is coupled with it. In this last case, the optimum conditions lead to a reduction in the production of hydrogen when the optimization process involves the maximization of intermediary products.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cai, Yunhai

Similar to a super B-factory, a circular Higgs factory will require strong focusing systems near the interaction points and a low-emittance lattice in arcs to achieve a factory luminosity. At electron beam energy of 120 GeV, beamstrahlung effects during the collision pose an additional challenge to the collider design. In particular, a large momentum acceptance at 2 percent level is necessary to retain an adequate beam lifetime. This turns out to be the most challenging aspect in the design of circular Higgs factory. In this paper, an example will be provided to illustrate the beam dynamics in circular Higgs factory,more » emphasizing on the chromatic optics. Basic optical modules and advanced analysis will be presented. Most important, we will show that 2% momentum aperture is achievable« less

Evaluation of various parameters of calcium-alginate immobilization method for enhanced alkaline protease production by Bacillus licheniformis NCIM-2042 using statistical methods.

PubMed

Potumarthi, Ravichandra; Subhakar, Ch; Pavani, A; Jetty, Annapurna

2008-04-01

Calcium-alginate immobilization method for the production of alkaline protease by Bacillus licheniformis NCIM-2042 was optimized statistically. Four variables, such as sodium-alginate concentration, calcium chloride concentration, inoculum size and agitation speed were optimized by 2(4) full factorial central composite design and subsequent analysis and model validation by a second-order regression equation. Eleven carbon, 11 organic nitrogen and seven inorganic nitrogen sources were screened by two-level Plackett-Burman design for maximum alkaline protease production by using optimized immobilized conditions. The levels of four variables, such as Na-alginate 2.78%; CaCl(2), 2.15%; inoculum size, 8.10% and agitation, 139 rpm were found to be optimum for maximal production of protease. Glucose, soybean meal and ammonium sulfate were resulted in maximum protease production at 644 U/ml, 720 U/ml, and 806 U/ml when screened for carbon, organic nitrogen and inorganic nitrogen sources, respectively, using optimized immobilization conditions. Repeated fed batch mode of operation, using optimized immobilized conditions, resulted in continuous operation for 12 cycles without disintegration of beads. Cross-sectional scanning electron microscope images have shown the growth pattern of B. licheniformis in Ca-alginate immobilized beads.

Gaming in the Classroom: An Innovative Way to Teach Factorial Designs

ERIC Educational Resources Information Center

Stansbury, Jessica A.; Munro, Geoffrey D.

2013-01-01

This study tested the effectiveness of video game use for instruction of factorial designs in a research methods course. Students designed and conducted a mini study, playing "Dance, Dance, Revolution", using video game scores as the dependent variable. A mixed-design analysis of variance revealed a significantly greater increase from pretest to…

Experimental designs for modeling retention patterns and separation efficiency in analysis of fatty acid methyl esters by gas chromatography-mass spectrometry.

PubMed

Skartland, Liv Kjersti; Mjøs, Svein A; Grung, Bjørn

2011-09-23

The retention behavior of components analyzed by chromatography varies with instrumental settings. Being able to predict how changes in these settings alter the elution pattern is useful, both with regards to component identification, as well as with regards to optimization of the chromatographic system. In this work, it is shown how experimental designs can be used for this purpose. Different experimental designs for response surface modeling of the separation of fatty acid methyl esters (FAME) as function of chromatographic conditions in GC have been evaluated. Full factorial, central composite, Doehlert and Box-Behnken designs were applied. A mixture of 38 FAMEs was separated on a polar cyanopropyl substituted polysilphenylene-siloxane phase capillary column. The temperature gradient, the start temperature of the gradient, and the carrier gas velocity were varied in the experiments. The modeled responses, as functions of chromatographic conditions, were retention time, retention indices, peak widths, separation efficiency and resolution between selected peak pairs. The designs that allowed inclusion of quadratic terms among the predictors performed significantly better than factorial design. Box-Behnken design provided the best results for prediction of retention, but the differences between the central composite, Doehlert and Box-Behnken designs were small. Retention indices could be modeled with much better accuracy than retention times. However, because the errors of predicted tR of closely eluting peaks were highly correlated, models of resolution (Rs) that were based on retention time had errors in the same range as corresponding models based on ECL. Copyright © 2011 Elsevier B.V. All rights reserved.

Engineering cytosolic acetyl-coenzyme A supply in Saccharomyces cerevisiae: Pathway stoichiometry, free-energy conservation and redox-cofactor balancing.

PubMed

van Rossum, Harmen M; Kozak, Barbara U; Pronk, Jack T; van Maris, Antonius J A

2016-07-01

Saccharomyces cerevisiae is an important industrial cell factory and an attractive experimental model for evaluating novel metabolic engineering strategies. Many current and potential products of this yeast require acetyl coenzyme A (acetyl-CoA) as a precursor and pathways towards these products are generally expressed in its cytosol. The native S. cerevisiae pathway for production of cytosolic acetyl-CoA consumes 2 ATP equivalents in the acetyl-CoA synthetase reaction. Catabolism of additional sugar substrate, which may be required to generate this ATP, negatively affects product yields. Here, we review alternative pathways that can be engineered into yeast to optimize supply of cytosolic acetyl-CoA as a precursor for product formation. Particular attention is paid to reaction stoichiometry, free-energy conservation and redox-cofactor balancing of alternative pathways for acetyl-CoA synthesis from glucose. A theoretical analysis of maximally attainable yields on glucose of four compounds (n-butanol, citric acid, palmitic acid and farnesene) showed a strong product dependency of the optimal pathway configuration for acetyl-CoA synthesis. Moreover, this analysis showed that combination of different acetyl-CoA production pathways may be required to achieve optimal product yields. This review underlines that an integral analysis of energy coupling and redox-cofactor balancing in precursor-supply and product-formation pathways is crucial for the design of efficient cell factories. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Purification optimization for a recombinant single-chain variable fragment against type 1 insulin-like growth factor receptor (IGF-1R) by using design of experiment (DoE).

PubMed

Song, Yong-Hong; Sun, Xue-Wen; Jiang, Bo; Liu, Ji-En; Su, Xian-Hui

2015-12-01

Design of experiment (DoE) is a statistics-based technique for experimental design that could overcome the shortcomings of traditional one-factor-at-a-time (OFAT) approach for protein purification optimization. In this study, a DoE approach was applied for optimizing purification of a recombinant single-chain variable fragment (scFv) against type 1 insulin-like growth factor receptor (IGF-1R) expressed in Escherichia coli. In first capture step using Capto L, a 2-level fractional factorial analysis and successively a central composite circumscribed (CCC) design were used to identify the optimal elution conditions. Two main effects, pH and trehalose, were identified, and high recovery (above 95%) and low aggregates ratio (below 10%) were achieved at the pH range from 2.9 to 3.0 with 32-35% (w/v) trehalose added. In the second step using cation exchange chromatography, an initial screening of media and elution pH and a following CCC design were performed, whereby the optimal selectivity of the scFv was obtained on Capto S at pH near 6.0, and the optimal conditions for fulfilling high DBC and purity were identified as pH range of 5.9-6.1 and loading conductivity range of 5-12.5 mS/cm. Upon a further gel filtration, the final purified scFv with a purity of 98% was obtained. Finally, the optimized conditions were verified by a 20-fold scale-up experiment. The purities and yields of intermediate and final products all fell within the regions predicted by DoE approach, suggesting the robustness of the optimized conditions. We proposed that the DoE approach described here is also applicable in production of other recombinant antibody constructs. Copyright © 2015 Elsevier Inc. All rights reserved.

Optimization of headspace solid phase micro-extraction of volatile compounds from papaya fruit assisted by GC-olfactometry.

PubMed

da Rocha, Renier Felinto Julião; da Silva Araújo, Ídila Maria; de Freitas, Sílvia Maria; Dos Santos Garruti, Deborah

2017-11-01

Optimization of the extraction conditions to investigate the volatile composition of papaya fruit involving headspace solid phase micro-extraction was carried out using multivariate strategies such as factorial design and response surface methodology. The performance of different combinations of time for reaching the equilibrium in the headspace and time for maximum extraction of volatiles was evaluated by GC-olfactometry of the extract (intensity of papaya characteristic aroma), number of peaks and total area in the chromatogram. Thirty-two compounds were identified by GC-MS under the optimized extraction conditions, the majority of which were aldehydes, both in number of compounds and area. Major compounds were δ-octalactone, β-citral, benzaldehyde, heptanal, benzyl isothiocyanate, isoamyl acetate, γ-octalactone, (E)-linalool oxide and benzyl alcohol. Seven aldehydes and two other compounds are reported for the first time in papaya's volatile profile.

Enhancement of L-asparaginase production by isolated Bacillus circulans (MTCC 8574) using response surface methodology.

PubMed

Hymavathi, M; Sathish, T; Subba Rao, Ch; Prakasham, R S

2009-10-01

L-asparaginase production was optimized using isolated Bacillus circulans (MTCC 8574) under solid-state fermentation (SSF) using locally available agricultural waste materials. Among different agricultural materials (red gram husk, bengal gram husk, coconut, and groundnut cake), red gram husk gave the maximum enzyme production. A wide range of SSF parameters were optimized for maximize the production of L-asparaginase. Preliminary studies revealed that incubation temperature, moisture content, inoculum level, glucose, and L-asparagine play a vital role in enzyme yield. The interactive behavior of each of these parameters along with their significance on enzyme yield was analyzed using fractional factorial central composite design (FFCCD). The observed correlation coefficient (R(2)) was 0.9714. Only L-asparagine and incubation temperature, were significant in linear and quadratic terms. L-asparaginase yield improved from 780 to 2,322 U/gds which is more than 300% using FFCCD as a means of optimizing conditions.

Optimization and Prediction of Angular Distortion and Weldment Characteristics of TIG Square Butt Joints

NASA Astrophysics Data System (ADS)

Narang, H. K.; Mahapatra, M. M.; Jha, P. K.; Biswas, P.

2014-05-01

Autogenous arc welds with minimum upper weld bead depression and lower weld bead bulging are desired as such welds do not require a second welding pass for filling up the upper bead depressions (UBDs) and characterized with minimum angular distortion. The present paper describes optimization and prediction of angular distortion and weldment characteristics such as upper weld bead depression and lower weld bead bulging of TIG-welded structural steel square butt joints. Full factorial design of experiment was utilized for selecting the combinations of welding process parameter to produce the square butts. A mathematical model was developed to establish the relationship between TIG welding process parameters and responses such as upper bead width, lower bead width, UBD, lower bead height (bulging), weld cross-sectional area, and angular distortions. The optimal welding condition to minimize UBD and lower bead bulging of the TIG butt joints was identified.

Ultrasound-assisted extraction for total sulphur measurement in mine tailings.

PubMed

Khan, Adnan Hossain; Shang, Julie Q; Alam, Raquibul

2012-10-15

A sample preparation method for percentage recovery of total sulphur (%S) in reactive mine tailings based on ultrasound-assisted digestion (USAD) and inductively coupled plasma-optical emission spectroscopy (ICP-OES) was developed. The influence of various methodological factors was screened by employing a two-level and three-factor (2(3)) full factorial design and using KZK-1, a sericite schist certified reference material (CRM), to find the optimal combination of studied factors and %S. Factors such as the sonication time, temperature and acid combination were studied, with the best result identified as 20 min of sonication, 80°C temperature and 1 ml of HNO(3):1 ml of HCl, which can achieve 100% recovery for the selected CRM. Subsequently a fraction of the 2(3) full factorial design was applied to mine tailings. The percentage relative standard deviation (%RSD) for the ultrasound method is less than 3.0% for CRM and less than 6% for the mine tailings. The investigated method was verified by X-ray diffraction analysis. The USAD method compared favorably with existing methods such as hot plate assisted digestion method, X-ray fluorescence and LECO™-CNS method. Copyright © 2012 Elsevier B.V. All rights reserved.

Microencapsulation of Theobroma cacao L. waste extract: optimization using response surface methodology.

PubMed

Gabbay Alves, Taís Vanessa; Silva da Costa, Russany; Aliakbarian, Bahar; Casazza, Alessandro Alberto; Perego, Patrizia; Carréra Silva Júnior, José Otávio; Ribeiro Costa, Roseane Maria; Converti, Attilio

2017-03-01

The cocoa extract (Theobroma cacao L.) has a significant amount of polyphenols (TP) with potent antioxidant activity (AA). This study aims to optimise microencapsulation of the extract of cocoa waste using chitosan and maltodextrin. Microencapsulation tests were performed according to a Box-Behnken factorial design, and the results were evaluated by response surface methodology with temperature, maltodextrin concentration (MD) and extract flowrate (EF) as independent variables, and the fraction of encapsulated TP, TP encapsulation yield, AA, yield of drying and solubility index as responses. The optimum conditions were: inlet temperature of 170 °C, MD of 5% and EF of 2.5 mL/min. HPLC analysis identified epicatechin as the major component of both the extract and microparticles. TP release was faster at pH 3.5 than in water. These results as a whole suggest that microencapsulation was successful and the final product can be used as a nutrient source for aquatic animal feed. Highlights Microencapsulation is optimised according to a factorial design of the Box-Behnken type. Epicatechin is the major component of both the extract and microcapsules. The release of polyphenols from microcapsules is faster at pH 3.5 than in water.

Optimization of Shea (Vitellaria paradoxa) butter quality using screw expeller extraction.

PubMed

Gezahegn, Yonas A; Emire, Shimelis A; Asfaw, Sisay F

2016-11-01

The quality of Shea butter is highly affected by processing factors. Hence, the aim of this work was to evaluate the effects of conditioning duration (CD), moisture content (MC), and die temperature (DT) of screw expeller on Shea butter quality. A combination of 3 3 full factorial design and response surface methodology was used for this investigation. Response variables were refractive index, acid value, and peroxide value. The model enabled to identify the optimum operating settings (CD = 28-30 min, MC = 3-5 g/100 g, and DT = 65-70°C) for maximize refractive index and minimum acid value. For minimum peroxide value 0 min CD, 10 g/100 g MC, and 30°C were discovered. In all-over optimization, optimal values of 30 min CD, 9.7 g/100 g MC, and 70°C DT were found. Hence, the processing factors must be at their optimal values to achieve high butter quality and consistence.

Mathematical model for dynamic cell formation in fast fashion apparel manufacturing stage

NASA Astrophysics Data System (ADS)

Perera, Gayathri; Ratnayake, Vijitha

2018-05-01

This paper presents a mathematical programming model for dynamic cell formation to minimize changeover-related costs (i.e., machine relocation costs and machine setup cost) and inter-cell material handling cost to cope with the volatile production environments in apparel manufacturing industry. The model is formulated through findings of a comprehensive literature review. Developed model is validated based on data collected from three different factories in apparel industry, manufacturing fast fashion products. A program code is developed using Lingo 16.0 software package to generate optimal cells for developed model and to determine the possible cost-saving percentage when the existing layouts used in three factories are replaced by generated optimal cells. The optimal cells generated by developed mathematical model result in significant cost saving when compared with existing product layouts used in production/assembly department of selected factories in apparel industry. The developed model can be considered as effective in minimizing the considered cost terms in dynamic production environment of fast fashion apparel manufacturing industry. Findings of this paper can be used for further researches on minimizing the changeover-related costs in fast fashion apparel production stage.

Characterization and optimization of cell seeding in scaffolds by factorial design: quality by design approach for skeletal tissue engineering.

PubMed

Chen, Yantian; Bloemen, Veerle; Impens, Saartje; Moesen, Maarten; Luyten, Frank P; Schrooten, Jan

2011-12-01

Cell seeding into scaffolds plays a crucial role in the development of efficient bone tissue engineering constructs. Hence, it becomes imperative to identify the key factors that quantitatively predict reproducible and efficient seeding protocols. In this study, the optimization of a cell seeding process was investigated using design of experiments (DOE) statistical methods. Five seeding factors (cell type, scaffold type, seeding volume, seeding density, and seeding time) were selected and investigated by means of two response parameters, critically related to the cell seeding process: cell seeding efficiency (CSE) and cell-specific viability (CSV). In addition, cell spatial distribution (CSD) was analyzed by Live/Dead staining assays. Analysis identified a number of statistically significant main factor effects and interactions. Among the five seeding factors, only seeding volume and seeding time significantly affected CSE and CSV. Also, cell and scaffold type were involved in the interactions with other seeding factors. Within the investigated ranges, optimal conditions in terms of CSV and CSD were obtained when seeding cells in a regular scaffold with an excess of medium. The results of this case study contribute to a better understanding and definition of optimal process parameters for cell seeding. A DOE strategy can identify and optimize critical process variables to reduce the variability and assists in determining which variables should be carefully controlled during good manufacturing practice production to enable a clinically relevant implant.

Removal of copper in leachate from mining residues using electrochemical technology.

PubMed

Lambert, Andréa; Drogui, Patrick; Daghrir, Rimeh; Zaviska, François; Benzaazoua, Mostafa

2014-01-15

This research is related to a laboratory study on the performance of a successive mining residues leaching and electrochemical copper recovery process. To clearly define the experimental region for response surface methodology (RSM), a preliminary study was performed by applying a current intensity varying from 0.5 A to 4.0 A for 60 min. By decreasing the current intensity from 4.0 A to 0.5 A, a good adhesion and a very smooth and continuous interface of copper was formed and deposited on the cathode electrode. However, the removal rate of Cu decreased from 83.7% to 37.9% when the current intensity passed from 4.0 A to 0.5 A, respectively. Subsequently, the factorial design and central composite design methodologies were successively employed to define the optimal operating conditions for copper removal in the mining residues leachate. Using a 2(3) factorial matrix, the best performance for copper removal (97.7%) was obtained at a current intensity of 2.0 A during 100 min. The current intensity and electrolysis time were found to be the most influent parameters. The contribution of current intensity and electrolysis time was around 65.8% and 33.9%, respectively. The treatment using copper electrode and current intensity of 1.3 A during 80 min was found to be the optimal conditions in terms of cost/effectiveness. Under these conditions, 86% of copper can be recovered for a total cost of 0.56 $ per cubic meter of treated mining residues leachate. Copyright © 2013 Elsevier Ltd. All rights reserved.

An algorithm for generating all possible 2(p-q) fractional factorial designs and its use in scientific experimentation

NASA Technical Reports Server (NTRS)

Sidik, S. M.

1973-01-01

An algorithm and computer program are presented for generating all the distinct 2(p-q) fractional factorial designs. Some applications of this algorithm to the construction of tables of designs and of designs for nonstandard situations and its use in Bayesian design are discussed. An appendix includes a discussion of an actual experiment whose design was facilitated by the algorithm.

The effects of experimental pain and induced optimism on working memory task performance.

PubMed

Boselie, Jantine J L M; Vancleef, Linda M G; Peters, Madelon L

2016-07-01

Pain can interrupt and deteriorate executive task performance. We have previously shown that experimentally induced optimism can diminish the deteriorating effect of cold pressor pain on a subsequent working memory task (i.e., operation span task). In two successive experiments we sought further evidence for the protective role of optimism on pain-induced working memory impairments. We used another working memory task (i.e., 2-back task) that was performed either after or during pain induction. Study 1 employed a 2 (optimism vs. no-optimism)×2 (pain vs. no-pain)×2 (pre-score vs. post-score) mixed factorial design. In half of the participants optimism was induced by the Best Possible Self (BPS) manipulation, which required them to write and visualize about a life in the future where everything turned out for the best. In the control condition, participants wrote and visualized a typical day in their life (TD). Next, participants completed either the cold pressor task (CPT) or a warm water control task (WWCT). Before (baseline) and after the CPT or WWCT participants working memory performance was measured with the 2-back task. The 2-back task measures the ability to monitor and update working memory representation by asking participants to indicate whether the current stimulus corresponds to the stimulus that was presented 2 stimuli ago. Study 2 had a 2 (optimism vs. no-optimism)×2 (pain vs. no-pain) mixed factorial design. After receiving the BPS or control manipulation, participants completed the 2-back task twice: once with painful heat stimulation, and once without any stimulation (counter-balanced order). Continuous heat stimulation was used with temperatures oscillating around 1°C above and 1°C below the individual pain threshold. In study 1, the results did not show an effect of cold pressor pain on subsequent 2-back task performance. Results of study 2 indicated that heat pain impaired concurrent 2-back task performance. However, no evidence was found that optimism protected against this pain-induced performance deterioration. Experimentally induced pain impairs concurrent but not subsequent working memory task performance. Manipulated optimism did not counteract pain-induced deterioration of 2-back performance. It is important to explore factors that may diminish the negative impact of pain on the ability to function in daily life, as pain itself often cannot be remediated. We are planning to conduct future studies that should shed further light on the conditions, contexts and executive operations for which optimism can act as a protective factor. Copyright © 2016 Scandinavian Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.

The application and use of chemical space mapping to interpret crystallization screening results

PubMed Central

Snell, Edward H.; Nagel, Ray M.; Wojtaszcyk, Ann; O’Neill, Hugh; Wolfley, Jennifer L.; Luft, Joseph R.

2008-01-01

Macromolecular crystallization screening is an empirical process. It often begins by setting up experiments with a number of chemically diverse cocktails designed to sample chemical space known to promote crystallization. Where a potential crystal is seen a refined screen is set up, optimizing around that condition. By using an incomplete factorial sampling of chemical space to formulate the cocktails and presenting the results graphically, it is possible to readily identify trends relevant to crystallization, coarsely sample the phase diagram and help guide the optimization process. In this paper, chemical space mapping is applied to both single macromolecules and to a diverse set of macromolecules in order to illustrate how visual information is more readily understood and assimilated than the same information presented textually. PMID:19018100

The application and use of chemical space mapping to interpret crystallization screening results.

PubMed

Snell, Edward H; Nagel, Ray M; Wojtaszcyk, Ann; O'Neill, Hugh; Wolfley, Jennifer L; Luft, Joseph R

2008-12-01

Macromolecular crystallization screening is an empirical process. It often begins by setting up experiments with a number of chemically diverse cocktails designed to sample chemical space known to promote crystallization. Where a potential crystal is seen a refined screen is set up, optimizing around that condition. By using an incomplete factorial sampling of chemical space to formulate the cocktails and presenting the results graphically, it is possible to readily identify trends relevant to crystallization, coarsely sample the phase diagram and help guide the optimization process. In this paper, chemical space mapping is applied to both single macromolecules and to a diverse set of macromolecules in order to illustrate how visual information is more readily understood and assimilated than the same information presented textually.

Development, optimization and validation of gas chromatographic fingerprinting of Brazilian commercial diesel fuel for quality control.

PubMed

dos Santos, Bruno César Diniz Brito; Flumignan, Danilo Luiz; de Oliveira, José Eduardo

2012-10-01

A three-step development, optimization and validation strategy is described for gas chromatography (GC) fingerprints of Brazilian commercial diesel fuel. A suitable GC-flame ionization detection (FID) system was selected to assay a complex matrix such as diesel. The next step was to improve acceptable chromatographic resolution with reduced analysis time, which is recommended for routine applications. Full three-level factorial designs were performed to improve flow rate, oven ramps, injection volume and split ratio in the GC system. Finally, several validation parameters were performed. The GC fingerprinting can be coupled with pattern recognition and multivariate regressions analyses to determine fuel quality and fuel physicochemical parameters. This strategy can also be applied to develop fingerprints for quality control of other fuel types.

A Sino-Finnish Initiative for Experimental Teaching Practices Using the Design Factory Pedagogical Platform

ERIC Educational Resources Information Center

Björklund, Tua A.; Nordström, Katrina M.; Clavert, Maria

2013-01-01

The paper presents a Sino-Finnish teaching initiative, including the design and experiences of a series of pedagogical workshops implemented at the Aalto-Tongji Design Factory (DF), Shanghai, China, and the experimentation plans collected from the 54 attending professors and teachers. The workshops aimed to encourage trying out interdisciplinary…

Cyber and physical equipment digital control system in Industry 4.0 item designing company

NASA Astrophysics Data System (ADS)

Gurjanov, A. V.; Zakoldaev, D. A.; Shukalov, A. V.; Zharinov, I. O.

2018-05-01

The problem of organization of digital control of the item designing company equipped with cyber and physical systems is being studied. A scheme of cyber and physical systems and personnel interaction in the Industry 4.0 smart factory company is presented. A scheme of assembly units transportation in the Industry 4.0 smart factory company is provided. A scheme of digital control system in the Industry 4.0 smart factory company is given.

Bioretention Systems: Partial Factorial Designs for Nitrate Removal

EPA Science Inventory

Changes in nutrient loadings are monitored by introducing captured stormwater runoff into eight outdoor rain gardens at EPA’s Urban Water Research Facility in Edison, New Jersey scaled for residential and urban landscapes. The partial factorial design includes non-vegetated meso...

Response surface optimization of medium components for naringinase production from Staphylococcus xylosus MAK2.

PubMed

Puri, Munish; Kaur, Aneet; Singh, Ram Sarup; Singh, Anubhav

2010-09-01

Response surface methodology was used to optimize the fermentation medium for enhancing naringinase production by Staphylococcus xylosus. The first step of this process involved the individual adjustment and optimization of various medium components at shake flask level. Sources of carbon (sucrose) and nitrogen (sodium nitrate), as well as an inducer (naringin) and pH levels were all found to be the important factors significantly affecting naringinase production. In the second step, a 22 full factorial central composite design was applied to determine the optimal levels of each of the significant variables. A second-order polynomial was derived by multiple regression analysis on the experimental data. Using this methodology, the optimum values for the critical components were obtained as follows: sucrose, 10.0%; sodium nitrate, 10.0%; pH 5.6; biomass concentration, 1.58%; and naringin, 0.50% (w/v), respectively. Under optimal conditions, the experimental naringinase production was 8.45 U/mL. The determination coefficients (R(2)) were 0.9908 and 0.9950 for naringinase activity and biomass production, respectively, indicating an adequate degree of reliability in the model.

Formulation optimization and evaluation of jackfruit seed starch-alginate mucoadhesive beads of metformin HCl.

PubMed

Nayak, Amit Kumar; Pal, Dilipkumar

2013-08-01

The present study deals with the formulation optimization of jackfruit (Artocarpus heterophyllus Lam., family: Moraceae) seed starch (JFSS)-alginate mucoadhesive beads containing metformin HCl through ionotropic gelation using 3(2) factorial design. The effect of sodium alginate to JFSS ratio and CaCl2 concentration on the drug encapsulation efficiency (DEE, %), and cumulative drug release at 10h (R10h, %) was optimized. The optimized beads containing metformin HCl showed DEE of 97.48±3.92%, R10h of 65.70±2.22%, and mean diameter of 1.16±0.11mm. The in vitro drug release from these beads was followed controlled-release (zero-order) pattern with super case-II transport mechanism. The beads were also characterized by SEM and FTIR. The swelling and degradation of these beads were influenced by pH of the test medium. The optimized beads also exhibited good mucoadhesivity and significant hypoglycemic effect in alloxan-induced diabetic rats over prolonged period after oral administration. Copyright © 2013 Elsevier B.V. All rights reserved.

SWITCH: a dynamic CRISPR tool for genome engineering and metabolic pathway control for cell factory construction in Saccharomyces cerevisiae.

PubMed

Vanegas, Katherina García; Lehka, Beata Joanna; Mortensen, Uffe Hasbro

2017-02-08

The yeast Saccharomyces cerevisiae is increasingly used as a cell factory. However, cell factory construction time is a major obstacle towards using yeast for bio-production. Hence, tools to speed up cell factory construction are desirable. In this study, we have developed a new Cas9/dCas9 based system, SWITCH, which allows Saccharomyces cerevisiae strains to iteratively alternate between a genetic engineering state and a pathway control state. Since Cas9 induced recombination events are crucial for SWITCH efficiency, we first developed a technique TAPE, which we have successfully used to address protospacer efficiency. As proof of concept of the use of SWITCH in cell factory construction, we have exploited the genetic engineering state of a SWITCH strain to insert the five genes necessary for naringenin production. Next, the naringenin cell factory was switched to the pathway control state where production was optimized by downregulating an essential gene TSC13, hence, reducing formation of a byproduct. We have successfully integrated two CRISPR tools, one for genetic engineering and one for pathway control, into one system and successfully used it for cell factory construction.

Improved conventional and microwave-assisted silylation protocols for simultaneous gas chromatographic determination of tocopherols and sterols: Method development and multi-response optimization.

PubMed

Poojary, Mahesha M; Passamonti, Paolo

2016-12-09

This paper reports on improved conventional thermal silylation (CTS) and microwave-assisted silylation (MAS) methods for simultaneous determination of tocopherols and sterols by gas chromatography. Reaction parameters in each of the methods developed were systematically optimized using a full factorial design followed by a central composite design. Initially, experimental conditions for CTS were optimized using a block heater. Further, a rapid MAS was developed and optimized. To understand microwave heating mechanisms, MAS was optimized by two distinct modes of microwave heating: temperature-controlled MAS and power-controlled MAS, using dedicated instruments where reaction temperature and microwave power level were controlled and monitored online. Developed methods: were compared with routine overnight derivatization. On a comprehensive level, while both CTS and MAS were found to be efficient derivatization techniques, MAS significantly reduced the reaction time. The optimal derivatization temperature and time for CTS found to be 55°C and 54min, while it was 87°C and 1.2min for temperature-controlled MAS. Further, a microwave power of 300W and a derivatization time 0.5min found to be optimal for power-controlled MAS. The use of an appropriate derivatization solvent, such as pyridine, was found to be critical for the successful determination. Catalysts, like potassium acetate and 4-dimethylaminopyridine, enhanced the efficiency slightly. The developed methods showed excellent analytical performance in terms of linearity, accuracy and precision. Copyright © 2016 Elsevier B.V. All rights reserved.

Midlands Teaching Factory, LTD.

ERIC Educational Resources Information Center

Midlands Technical Coll., Columbia, SC.

In 1987, Midlands Technical College (MTC), in Columbia, South Carolina, initiated a Computer Integrated Manufacturing (CIM) project, the Midlands Teaching Factory, LTD, which integrated various college departments with the goal of manufacturing a high quality, saleable product. The faculty developed a teaching factory model which was designed to…

Application of response surface methodology for the optimization of supercritical fluid extraction of essential oil from pomegranate (Punica granatum L.) peel.

PubMed

Ara, Katayoun Mahdavi; Raofie, Farhad

2016-07-01

Essential oils and volatile components of pomegranate ( Punica granatum L.) peel of the Malas variety from Meybod, Iran, were extracted using supercritical fluid extraction (SFE) and hydro-distillation methods. The experimental parameters of SFE that is pressure, temperature, extraction time, and modifier (methanol) volume were optimized using a central composite design after a (2 4-1 ) fractional factorial design. Detailed chemical composition of the essential oils and volatile components obtained by hydro-distillation and optimum condition of the supercritical CO 2 extraction were analyzed by GC-MS, and seventy-three and forty-six compounds were identified according to their retention indices and mass spectra, respectively. The optimum SFE conditions were 350 atm pressure, 55 °C temperature, 30 min extraction time, and 150 µL methanol. Results showed that oleic acid, palmitic acid and (-)-Borneol were major compounds in both extracts. The optimum extraction yield was 1.18 % (w/w) for SFE and 0.21 % (v/w) for hydro-distillation.

Multi-response optimization of Artemia hatching process using split-split-plot design based response surface methodology

PubMed Central

Arun, V. V.; Saharan, Neelam; Ramasubramanian, V.; Babitha Rani, A. M.; Salin, K. R.; Sontakke, Ravindra; Haridas, Harsha; Pazhayamadom, Deepak George

2017-01-01

A novel method, BBD-SSPD is proposed by the combination of Box-Behnken Design (BBD) and Split-Split Plot Design (SSPD) which would ensure minimum number of experimental runs, leading to economical utilization in multi- factorial experiments. The brine shrimp Artemia was tested to study the combined effects of photoperiod, temperature and salinity, each with three levels, on the hatching percentage and hatching time of their cysts. The BBD was employed to select 13 treatment combinations out of the 27 possible combinations that were grouped in an SSPD arrangement. Multiple responses were optimized simultaneously using Derringer’s desirability function. Photoperiod and temperature as well as temperature-salinity interaction were found to significantly affect the hatching percentage of Artemia, while the hatching time was significantly influenced by photoperiod and temperature, and their interaction. The optimum conditions were 23 h photoperiod, 29 °C temperature and 28 ppt salinity resulting in 96.8% hatching in 18.94 h. In order to verify the results obtained from BBD-SSPD experiment, the experiment was repeated preserving the same set up. Results of verification experiment were found to be similar to experiment originally conducted. It is expected that this method would be suitable to optimize the hatching process of animal eggs. PMID:28091611

Use of response surface methodology in a fed-batch process for optimization of tricarboxylic acid cycle intermediates to achieve high levels of canthaxanthin from Dietzia natronolimnaea HS-1.

PubMed

Nasri Nasrabadi, Mohammad Reza; Razavi, Seyed Hadi

2010-04-01

In this work, we applied statistical experimental design to a fed-batch process for optimization of tricarboxylic acid cycle (TCA) intermediates in order to achieve high-level production of canthaxanthin from Dietzia natronolimnaea HS-1 cultured in beet molasses. A fractional factorial design (screening test) was first conducted on five TCA cycle intermediates. Out of the five TCA cycle intermediates investigated via screening tests, alfaketoglutarate, oxaloacetate and succinate were selected based on their statistically significant (P<0.05) and positive effects on canthaxanthin production. These significant factors were optimized by means of response surface methodology (RSM) in order to achieve high-level production of canthaxanthin. The experimental results of the RSM were fitted with a second-order polynomial equation by means of a multiple regression technique to identify the relationship between canthaxanthin production and the three TCA cycle intermediates. By means of this statistical design under a fed-batch process, the optimum conditions required to achieve the highest level of canthaxanthin (13172 + or - 25 microg l(-1)) were determined as follows: alfaketoglutarate, 9.69 mM; oxaloacetate, 8.68 mM; succinate, 8.51 mM. Copyright 2009 The Society for Biotechnology, Japan. Published by Elsevier B.V. All rights reserved.

Development and Validation of a Stability-Indicating HPLC Method for Imidapril and Its Degradation Products Using a Design of Experiment (DoE) Approach.

PubMed

Arumugam, Abiramasundari; Joshi, Amita; Vasu, Kamala K

2017-11-01

The present work focused on the application of design of experiment (DoE) principles to the development and optimization of a stability-indicating method (SIM) for the drug imidapril hydrochloride and its degradation products (DPs). The resolution of peaks for the DPs and their drug in a SIM can be influenced by many factors. The factors studied here were pH, gradient time, organic modifier, flow rate, molar concentration of the buffer, and wavelength, with the aid of a Plackett-Burman design. Results from the Plackett-Burman study conspicuously showed influence of two factors, pH and gradient time, on the analyzed response, particularly, the resolution of the closely eluting DPs (DP-5 and DP-6) and the retention time of the last peak. Optimization of the multiresponse processes was achieved through Derringer's desirability function with the assistance of a full factorial design. Separation was achieved using a C18 Phenomenex Luna column (250 × 4.6 mm id, 5 µm particle size) at a flow rate of 0.8 mL/min at 210 nm. The optimized mobile phase composition was ammonium-acetate buffer (pH 5) in pump A and acetonitrile-methanol (in equal ratio) in pump B with a run time of 40 min using a gradient method.

Cr(VI) transport via a supported ionic liquid membrane containing CYPHOS IL101 as carrier: system analysis and optimization through experimental design strategies.

PubMed

Rodríguez de San Miguel, Eduardo; Vital, Xóchitl; de Gyves, Josefina

2014-05-30

Chromium(VI) transport through a supported liquid membrane (SLM) system containing the commercial ionic liquid CYPHOS IL101 as carrier was studied. A reducing stripping phase was used as a mean to increase recovery and to simultaneously transform Cr(VI) into a less toxic residue for disposal or reuse. General functions which describe the time-depending evolution of the metal fractions in the cell compartments were defined and used in data evaluation. An experimental design strategy, using factorial and central-composite design matrices, was applied to assess the influence of the extractant, NaOH and citrate concentrations in the different phases, while a desirability function scheme allowed the synchronized optimization of depletion and recovery of the analyte. The mechanism for chromium permeation was analyzed and discussed to contribute to the understanding of the transfer process. The influence of metal concentration was evaluated as well. The presence of different interfering ions (Ca(2+), Al(3+), NO3(-), SO4(2-), and Cl(-)) at several Cr(VI): interfering ion ratios was studied through the use of a Plackett and Burman experimental design matrix. Under optimized conditions 90% of recovery was obtained from a feed solution containing 7mgL(-1) of Cr(VI) in 0.01moldm(-3) HCl medium after 5h of pertraction. Copyright © 2014 Elsevier B.V. All rights reserved.

The Factorial Survey: Design Selection and its Impact on Reliability and Internal Validity

ERIC Educational Resources Information Center

Dülmer, Hermann

2016-01-01

The factorial survey is an experimental design consisting of varying situations (vignettes) that have to be judged by respondents. For more complex research questions, it quickly becomes impossible for an individual respondent to judge all vignettes. To overcome this problem, random designs are recommended most of the time, whereas quota designs…

CO2 adsorption on diatomaceous earth modified with cetyltrimethylammonium bromide and functionalized with tetraethylenepentamine: Optimization and kinetics.

PubMed

Pornaroonthama, Phuwadej; Thouchprasitchai, Nutthavich; Pongstabodee, Sangobtip

2015-07-01

The carbon dioxide (CO2) adsorbent diatomaceous earth (DE) was modified with cetyltrimethylammonium bromide (CTAB) and functionalized with varying levels of tetraethylenepentamine (TEPA). The CO2 absorption at atmospheric pressure was optimized by varying the TEPA-loading level (0-40% (w/w)), operating temperature (40-80 °C) and water vapor concentration (0-16% (v/v)) in a 10% (v/v) CO2 feed stream in helium balance using a full 2(3) factorial design. The TEPA/CTAB-DE adsorbents were characterized by X-ray diffractometry, Fourier transform infrared spectrometry and thermogravimetric analyses. The CO2 adsorption capacity increased as each of these three factors increased. The TEPA loading level-water concentration interaction had a positive influence on the CO2 adsorption while the operating temperature-water concentration interaction was antagonistic. The optimal condition for CO2 adsorption on 40%TEPA/CTAB-DE, evaluated via a factorial design response surface method (RSM), was a temperature of 58-68 °C and a water vapor concentration of 9.5-14% (v/v), with a maximum CO2 adsorption capacity of 149.4 mg g(-1) at 63.5 °C and 12% (v/v) water vapor concentration in the feed. Validation and sensitivity tests revealed that the estimated CO2 adsorption capacity was within ±4% of the experimental values, suggesting that the RSM model was satisfied and acceptable. From three kinetic models (pseudo-first-order, pseudo-second-order model and Avrami's equation), assessed using an error function (Err) and the coefficient of determination (R(2)), Avrami's equation was the most appropriate to describe the kinetics of CO2 adsorption on the 40%TEPA/CTAB-DE adsorbent and suggested that more than one reaction pathway occurred in the CO2 adsorption. Copyright © 2015 Elsevier Ltd. All rights reserved.

Preconcentration and determination of ceftazidime in real samples using dispersive liquid-liquid microextraction and high-performance liquid chromatography with the aid of experimental design.

PubMed

Razmi, Rasoul; Shahpari, Behrouz; Pourbasheer, Eslam; Boustanifar, Mohammad Hasan; Azari, Zhila; Ebadi, Amin

2016-11-01

A rapid and simple method for the extraction and preconcentration of ceftazidime in aqueous samples has been developed using dispersive liquid-liquid microextraction followed by high-performance liquid chromatography analysis. The extraction parameters, such as the volume of extraction solvent and disperser solvent, salt effect, sample volume, centrifuge rate, centrifuge time, extraction time, and temperature in the dispersive liquid-liquid microextraction process, were studied and optimized with the experimental design methods. Firstly, for the preliminary screening of the parameters the taguchi design was used and then, the fractional factorial design was used for significant factors optimization. At the optimum conditions, the calibration curves for ceftazidime indicated good linearity over the range of 0.001-10 μg/mL with correlation coefficients higher than the 0.98, and the limits of detection were 0.13 and 0.17 ng/mL, for water and urine samples, respectively. The proposed method successfully employed to determine ceftazidime in water and urine samples and good agreement between the experimental data and predictive values has been achieved. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Design Expert Supported Mathematical Optimization and Predictability Study of Buccoadhesive Pharmaceutical Wafers of Loratadine

PubMed Central

Dey, Surajit; Parcha, Versha; Bhattacharya, Shiv Sankar; Ghosh, Amitava

2013-01-01

Objective. The objective of this work encompasses the application of the response surface approach in the development of buccoadhesive pharmaceutical wafers of Loratadine (LOR). Methods. Experiments were performed according to a 32 factorial design to evaluate the effects of buccoadhesive polymer, sodium alginate (A), and lactose monohydrate as ingredient, of hydrophilic matrix former (B) on the bioadhesive force, disintegration time, percent (%) swelling index, and time taken for 70% drug release (t 70%). The effect of the two independent variables on the response variables was studied by response surface plots and contour plots generated by the Design-Expert software. The desirability function was used to optimize the response variables. Results. The compatibility between LOR and the wafer excipients was confirmed by differential scanning calorimetry, FTIR spectroscopy, and X-ray diffraction (XRD) analysis. Bioadhesion force, measured with TAXT2i texture analyzer, showed that the wafers had a good bioadhesive property which could be advantageous for retaining the drug into the buccal cavity. Conclusion. The observed responses taken were in agreement with the experimental values, and Loratadine wafers were produced with less experimental trials, and a patient compliant product was achieved with the concept of formulation by design. PMID:23781498

Feed additive production by fermentation of herb Polygonum hydropiper L. and cassava pulp with simultaneous flavonoid dissolution.

PubMed

Song, Zhen-Tao; Zhu, Ming-Jun

2017-03-01

Fermentation of herb Polygonum hydropiper L. (PHL) and cassava pulp (CP) for feed additive production with simultaneous flavonoid dissolution was investigated, and a two-stage response surface methodology (RSM) based on Plackett-Burman factorial design (PB design) was used to optimize the flavonoid dissolution and protein content. Using the screening function of PB design, four different significant factors for the two response variables were acquired: factors A (CP) and B (PHL) for the flavonoid dissolution versus factors G (inoculum size) and H (fermentation time) for protein content. Then, two RSMs were used sequentially to improve the values of the two response variables separately. The mutual corroboration of the experimental results in the present study confirmed the validity of the associated experimental design. The validation experiment showed a flavonoid dissolution rate of 94.00%, and a protein content of 18.20%, gaining an increase in 21.20% and 199.10% over the control, respectively. The present study confirms the feasibility of feed additive production by Saccharomyces cerevisiae with CP and PHL and simultaneous optimization of flavonoid dissolution and protein content using a two-stage RSM. © 2016 International Union of Biochemistry and Molecular Biology, Inc.

Design and ocular tolerance of flurbiprofen loaded ultrasound-engineered NLC.

PubMed

Gonzalez-Mira, E; Egea, M A; Garcia, M L; Souto, E B

2010-12-01

Packaging small drug molecules, such as non-steroidal anti-inflammatory drugs (NSAIDs) into nanoparticulate systems has been reported as a promising approach to improve the drug's bioavailability, biocompatibility and safety profiles. In the last 20 years, lipid nanoparticles (lipid dispersions) entered the nanoparticulate library as novel carrier systems due to their great potential as an alternative to other systems such as polymeric nanoparticles and liposomes for several administration routes. For ocular instillation nanoparticulate carriers are required to have a low mean particle size, with the lowest polydispersity as possible. The purpose of this work was to study the combined influence of 2-level, 4-factor variables on the formulation of flurbiprofen (FB), a lipophilic NSAID, in lipid carriers currently named as nanostructured lipid carriers (NLC). NLC were produced with stearic acid (SA) and castor oil (CO) stabilized by Tween® 80 (non-ionic surfactant) in aqueous dispersion. A 2(4) full factorial design based on 4 independent variables was used to plan the experiments, namely, the percentage of SA with regard to the total lipid, the FB concentration, the stabilizer concentration, and the storage conditions (i.e., storage temperature). The effects of these parameters on the mean particle size, polydispersity index (PI) and zeta potential (ZP) were investigated as dependent variables. The optimization process was achieved and the best formulation corresponded to the NLC formulation composed of 0.05 (wt%) FB, 1.6 (wt%) Tween® 80 and a 50:50 ratio of SA to CO, with an average diameter of 288 nm, PI 0.245 of and ZP of -29 mV. This factorial design study has proven to be a useful tool in optimizing FB-loaded NLC formulations. Stability of the optimized NLC was predicted using a TurbiScanLab® and the ocular tolerance was assessed in vitro and in vivo by the Eytex® and Draize test, respectively. The developed systems were shown physico-chemically stable with high tolerance for eye instillation. Copyright © 2010 Elsevier B.V. All rights reserved.

Hollow fiber-based liquid phase microextraction with factorial design optimization and gas chromatography-tandem mass spectrometry for determination of cannabinoids in human hair.

PubMed

Emídio, Elissandro Soares; de Menezes Prata, Vanessa; de Santana, Fernando José Malagueño; Dórea, Haroldo Silveira

2010-08-15

A new method, based on hollow fiber liquid-phase microextraction (HF-LPME) and gas chromatography-tandem mass spectrometry (GC-MSMS), was developed for determination of Delta(9)-tetrahydrocannabinol (THC), cannabidiol (CBD) and cannabinol (CBN) in samples of human hair. Since hair is a solid matrix, the samples were subjected to alkaline digestion using NaOH. The aqueous solutions obtained were extracted using a 6cm polypropylene fiber (600microm i.d., 200microm wall thickness, 0.2microm pore size) for each extraction. A 2(5-1) fractional factorial design for screening, and a central composite design for optimization of significant variables, was applied during development of the extraction method. The variables evaluated were the type of extraction solvent, pH, stirring speed, extraction time, and acceptor phase volume. The optimized conditions for the proposed extraction procedure were 10mg of hair sample; 20microL of butyl acetate; aqueous (pH 14) donor phase containing 6.8% NaCl; 600rpm stirring speed; 20min extraction time. A linear response was obtained in the ranges 1-500pgmg(-1) (CBD and CBN) and 20-500pgmg(-1) (THC), with regression coefficients >0.99. Precision, determined as the relative standard deviation, was 3.3-8.9% (intra-day) and 4.4-13.7% (inter-day). Absolute recoveries varied in the ranges 4.4-4.8% (CBD), 7.6-8.9% (THC) and 7.7-8.2% (CBN). Limits of detection (LOD, S/N=3) and quantification (LOQ, S/N=10) were 0.5-15pgmg(-1) and 1-20pgmg(-1), respectively. The method was successfully used to determine CBD, THC and CBN in hair samples from patients in a drug dependency rehabilitation center. Concentrations varied in the ranges 1-18pgmg(-1) (CBD), 20-232pgmg(-1) (THC) and 9-107pgmg(-1) (CBN), confirming the suitability of the method for monitoring studies. Copyright 2010 Elsevier B.V. All rights reserved.

Development, Optimization, and Validation of a Microplate Bioassay for Relative Potency Determination of Linezolid Using a Design Space Concept, and its Measurement Uncertainty.

PubMed

Saviano, Alessandro Morais; Francisco, Fabiane Lacerda; Ostronoff, Celina Silva; Lourenço, Felipe Rebello

2015-01-01

The aim of this study was to develop, optimize, and validate a microplate bioassay for relative potency determination of linezolid in pharmaceutical samples using quality-by-design and design space approaches. In addition, a procedure is described for estimating relative potency uncertainty based on microbiological response variability. The influence of culture media composition was studied using a factorial design and a central composite design was adopted to study the influence of inoculum proportion and triphenyltetrazolium chloride in microbial growth. The microplate bioassay was optimized regarding the responses of low, medium, and high doses of linezolid, negative and positive controls, and the slope, intercept, and correlation coefficient of dose-response curves. According to optimization results, design space ranges were established using: (a) low (1.0 μg/mL), medium (2.0 μg/mL), and high (4.0 μg/mL) doses of pharmaceutical samples and linezolid chemical reference substance; (b) Staphylococcus aureus ATCC 653 in an inoculum proportion of 10%; (c) antibiotic No. 3 culture medium pH 7.0±0.1; (d) 6 h incubation at 37.0±0.1ºC; and (e) addition of 50 μL of 0.5% (w/v) triphenyltetrazolium chloride solution. The microplate bioassay was linear (r2=0.992), specific, precise (repeatability RSD=2.3% and intermediate precision RSD=4.3%), accurate (mean recovery=101.4%), and robust. The overall measurement uncertainty was reasonable considering the increased variability inherent in microbiological response. Final uncertainty was comparable with those obtained with other microbiological assays, as well as chemical methods.

Research on a new fiber-optic axial pressure sensor of transformer winding based on fiber Bragg grating

NASA Astrophysics Data System (ADS)

Liu, Yuan; Li, Lianqing; Zhao, Lin; Wang, Jiqiang; Liu, Tongyu

2017-12-01

Based on the principle of the fiber Bragg grating, a new type of fiber-optic pressure sensor for axial force measurement of transformer winding is designed, which is designed with the structure of bending plate beam, the optimization of the packaging process, and material of the sensor. Through the calibration experiment to calibrate the sensor, the field test results of the Taikai transformer factory show that the sensitivity of the sensor is 0.133 pm/kPa and the repeatability error is 2.7% FS. The data of the fiber-optic pressure sensor in different positions maintain consistent and repeatable, which can meet the requirement of the real-time monitoring of the axial force of transformer winding.

Design and statistical optimization of glipizide loaded lipospheres using response surface methodology.

PubMed

Shivakumar, Hagalavadi Nanjappa; Patel, Pragnesh Bharat; Desai, Bapusaheb Gangadhar; Ashok, Purnima; Arulmozhi, Sinnathambi

2007-09-01

A 32 factorial design was employed to produce glipizide lipospheres by the emulsification phase separation technique using paraffin wax and stearic acid as retardants. The effect of critical formulation variables, namely levels of paraffin wax (X1) and proportion of stearic acid in the wax (X2) on geometric mean diameter (dg), percent encapsulation efficiency (% EE), release at the end of 12 h (rel12) and time taken for 50% of drug release (t50), were evaluated using the F-test. Mathematical models containing only the significant terms were generated for each response parameter using the multiple linear regression analysis (MLRA) and analysis of variance (ANOVA). Both formulation variables studied exerted a significant influence (p < 0.05) on the response parameters. Numerical optimization using the desirability approach was employed to develop an optimized formulation by setting constraints on the dependent and independent variables. The experimental values of dg, % EE, rel12 and t50 values for the optimized formulation were found to be 57.54 +/- 1.38 mum, 86.28 +/- 1.32%, 77.23 +/- 2.78% and 5.60 +/- 0.32 h, respectively, which were in close agreement with those predicted by the mathematical models. The drug release from lipospheres followed first-order kinetics and was characterized by the Higuchi diffusion model. The optimized liposphere formulation developed was found to produce sustained anti-diabetic activity following oral administration in rats.

Rapidly absorbed orodispersible tablet containing molecularly dispersed felodipine for management of hypertensive crisis: development, optimization and in vitro/in vivo studies.

PubMed

Basalious, Emad B; El-Sebaie, Wessam; El-Gazayerly, Omaima

2013-01-01

A liquisolid orodispersible tablet of felodipine, a BCS Class II drug, was developed to improve drug dissolution and absorption through the buccal mucosa for management of hypertensive crisis. A 24 full-factorial design was applied to optimize felodipine liquisolid systems (FLSs) having acceptable flow properties and possessing enhanced drug dissolution rates. Four formulation variables; The liquid type, X1 (PG or PEG), drug concentration, X2 (10% and 20%), type of coat, X3 (Aerosil® and Aeroperl®) and excipients ratio, X4 (10 and 20) were included in the design. The systems were assessed for dissolution and flow properties. Following optimization, the formulation components (X1, X2, X3 and X4) were PEG, 10%, Aerosil® and 20, respectively. The optimized FLS was compressed into felodipine liquisolid orodispersible tablet using Prosolv® as carrier material (FLODT-2). The in vitro and in vivo disintegration times of FLODT-2 were 9 and 7 s, respectively. The in vivo pharmacokinetic study using human volunteers showed a significant increase in dissolution and absorption rates of the formulation of FLODT-2 compared to soft gelatin capsules filled with felodipine solution in PEG under the same conditions. Our results proposed that the optimized FLODT formulation could be promising to manage hypertensive crisis.

Optimization strategies based on sequential quadratic programming applied for a fermentation process for butanol production.

PubMed

Pinto Mariano, Adriano; Bastos Borba Costa, Caliane; de Franceschi de Angelis, Dejanira; Maugeri Filho, Francisco; Pires Atala, Daniel Ibraim; Wolf Maciel, Maria Regina; Maciel Filho, Rubens

2009-11-01

In this work, the mathematical optimization of a continuous flash fermentation process for the production of biobutanol was studied. The process consists of three interconnected units, as follows: fermentor, cell-retention system (tangential microfiltration), and vacuum flash vessel (responsible for the continuous recovery of butanol from the broth). The objective of the optimization was to maximize butanol productivity for a desired substrate conversion. Two strategies were compared for the optimization of the process. In one of them, the process was represented by a deterministic model with kinetic parameters determined experimentally and, in the other, by a statistical model obtained using the factorial design technique combined with simulation. For both strategies, the problem was written as a nonlinear programming problem and was solved with the sequential quadratic programming technique. The results showed that despite the very similar solutions obtained with both strategies, the problems found with the strategy using the deterministic model, such as lack of convergence and high computational time, make the use of the optimization strategy with the statistical model, which showed to be robust and fast, more suitable for the flash fermentation process, being recommended for real-time applications coupling optimization and control.

Optimization of clean extraction methods to isolate carotenoids from the microalga Neochloris oleoabundans and subsequent chemical characterization using liquid chromatography tandem mass spectrometry.

PubMed

Castro-Puyana, María; Herrero, Miguel; Urreta, Iratxe; Mendiola, Jose A; Cifuentes, Alejandro; Ibáñez, Elena; Suárez-Alvarez, Sonia

2013-05-01

A novel experimental design was used to optimize the extraction of carotenoids from Neochloris oleoabundans using pressurized liquid extraction with food-grade solvents such as ethanol and limonene. Experimental factors, including the extraction temperature and the solvent composition, were optimized using a three-level factorial design. The response variables extraction yield and total amount of carotenoids were assessed. The statistical analysis of the results provided mathematical models to predict the behavior of the responses as a function of the factors involved in the process. The optimum conditions predicted by the model developed in this study were 112 °C as the extraction temperature and 100% ethanol as the extraction solvent. Chemical characterization of the extracts obtained was performed by means of high-performance liquid chromatography-tandem mass spectrometry. The results obtained demonstrated that, under certain growth conditions (photoautotrophically cultured in a medium supplemented with 0.3 g L(-1) KNO3), N. oleoabundans accumulated significant total amounts of the carotenoids (from 57.4 to 120.2 mg carotenoids per gram of extract depending on the extraction conditions), mainly lutein, cantaxanthin, zeaxanthin, and astaxanthin monoesters and diesters.

Improved cellulase production by Botryosphaeria rhodina from OPEFB at low level moisture condition through statistical optimization.

PubMed

Bahrin, E K; Ibrahim, M F; Abd Razak, M N; Abd-Aziz, S; Shah, U K Md; Alitheen, N; Salleh, M Md

2012-01-01

The response surface method was applied in this study to improve cellulase production from oil palm empty fruit bunch (OPEFB) by Botryosphaeria rhodina. An experimental design based on a two-level factorial was employed to screen the significant environmental factors for cellulase production. The locally isolated fungus Botryosphaeria rhodina was cultivated on OPEFB under solid-state fermentation (SSF). From the analysis of variance (ANOVA), the initial moisture content, amount of substrate, and initial pH of nutrient supplied in the SSF system significantly influenced cellulase production. Then the optimization of the variables was done using the response surface method according to central composite design (CCD). Botryosphaeria rhodina exhibited its best performance with a high predicted value of FPase enzyme production (17.95 U/g) when the initial moisture content was at 24.32%, initial pH of nutrient was 5.96, and 3.98 g of substrate was present. The statistical optimization from actual experiment resulted in a significant increment of FPase production from 3.26 to 17.91 U/g (5.49-fold). High cellulase production at low moisture content is a very rare condition for fungi cultured in solid-state fermentation.

Design, Development and Optimization of S (-) Atenolol Floating Sustained Release Matrix Tablets Using Surface Response Methodology

PubMed Central

Gunjal, P. T.; Shinde, M. B.; Gharge, V. S.; Pimple, S. V.; Gurjar, M. K.; Shah, M. N.

2015-01-01

The objective of this present investigation was to develop and formulate floating sustained release matrix tablets of s (-) atenolol, by using different polymer combinations and filler, to optimize by using surface response methodology for different drug release variables and to evaluate the drug release pattern of the optimized product. Floating sustained release matrix tablets of various combinations were prepared with cellulose-based polymers: Hydroxypropyl methylcellulose, sodium bicarbonate as a gas generating agent, polyvinyl pyrrolidone as a binder and lactose monohydrate as filler. The 32 full factorial design was employed to investigate the effect of formulation variables on different properties of tablets applicable to floating lag time, buoyancy time, % drug release in 1 and 6 h (D1 h,D6 h) and time required to 90% drug release (t90%). Significance of result was analyzed using analysis of non variance and P < 0.05 was considered statistically significant. S (-) atenolol floating sustained release matrix tablets followed the Higuchi drug release kinetics that indicates the release of drug follows anomalous (non-Fickian) diffusion mechanism. The developed floating sustained release matrix tablet of improved efficacy can perform therapeutically better than a conventional tablet. PMID:26798171

Design, Development and Optimization of S (-) Atenolol Floating Sustained Release Matrix Tablets Using Surface Response Methodology.

PubMed

Gunjal, P T; Shinde, M B; Gharge, V S; Pimple, S V; Gurjar, M K; Shah, M N

2015-01-01

The objective of this present investigation was to develop and formulate floating sustained release matrix tablets of s (-) atenolol, by using different polymer combinations and filler, to optimize by using surface response methodology for different drug release variables and to evaluate the drug release pattern of the optimized product. Floating sustained release matrix tablets of various combinations were prepared with cellulose-based polymers: Hydroxypropyl methylcellulose, sodium bicarbonate as a gas generating agent, polyvinyl pyrrolidone as a binder and lactose monohydrate as filler. The 3(2) full factorial design was employed to investigate the effect of formulation variables on different properties of tablets applicable to floating lag time, buoyancy time, % drug release in 1 and 6 h (D1 h,D6 h) and time required to 90% drug release (t90%). Significance of result was analyzed using analysis of non variance and P < 0.05 was considered statistically significant. S (-) atenolol floating sustained release matrix tablets followed the Higuchi drug release kinetics that indicates the release of drug follows anomalous (non-Fickian) diffusion mechanism. The developed floating sustained release matrix tablet of improved efficacy can perform therapeutically better than a conventional tablet.

An Analysis of Fixed Wing Tactical Airlifter Characteristics Using an Intra-Theater Airlift Computer Model

DTIC Science & Technology

1991-09-01

an Experimental Design ...... 31 Selection of Variables .................... ... 34 Defining Measures of Effectiveness ....... 37 Specification of...Required Number of Replications 44 Modification of Scenario Files ......... ... 46 Analysis of the Main Effects of a Two Level Factorial Design ...48 Analysis of the Interaction Effects of a *Two Level Factorial Design .. ............. ... 49 Yate’s Algorithm ......... ................ 50

Cost Effectiveness Analysis of Quasi-In-Motion Wireless Power Transfer for Plug-In Hybrid Electric Transit Buses from Fleet Perspective

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wang, Lijuan; Gonder, Jeff; Brooker, Aaron

This study evaluated the costs and benefits associated with the use of stationary-wireless-power-transfer-enabled plug-in hybrid electric buses and determined the cost effectiveness relative to conventional buses and hybrid electric buses. A factorial design was performed over a number of different battery sizes, charging power levels, and f bus stop charging stations. The net present costs were calculated for each vehicle design and provided the basis for design evaluation. In all cases, given the assumed economic conditions, the conventional bus achieved the lowest net present cost while the optimal plug-in hybrid electric bus scenario beat out the hybrid electric comparison scenario.more » The parameter sensitivity was also investigated under favorable and unfavorable market penetration assumptions.« less

The Effect of Framing on Surrogate Optimism Bias: A Simulation Study

PubMed Central

Patel, Dev; Cohen, Elan D.; Barnato, Amber E.

2016-01-01

Purpose To explore the effect of emotion priming and physician communication behaviors on optimism bias. Materials and Methods We conducted a 5 × 2 between-subject randomized factorial experiment using a web-based interactive video designed to simulate a family meeting for a critically ill spouse/parent. Eligibility included age ≥ 35 and self-identifying as the surrogate for a spouse/parent. The primary outcome was the surrogate's election of code status. We defined optimism bias as the surrogate's estimate of prognosis with CPR > their recollection of the physician's estimate. Results 256/373 respondents (69%) logged-in and were randomized and 220 (86%) had non-missing data for prognosis. 67/220 (30%) overall, and 56/173 (32%) of those with an accurate recollection of the physician's estimate had optimism bias. Optimism bias correlated with choosing CPR (p<.001). Emotion priming (p=.397), physician attention to emotion (p=.537), and framing of CPR as the social norm (p=.884) did not affect optimism bias. Framing the decision as the patient's vs. the surrogate's (25% vs. 36%, p=.066) and describing the alternative to CPR as “allow natural death” instead of “do not resuscitate” (25% vs. 37%, p =.035) decreased optimism bias. Conclusions Framing of CPR choice during code status conversations may influence surrogates’ optimism bias. PMID:26796950

Optimization of lipids production by Cryptococcus laurentii 11 using cheese whey with molasses.

PubMed

Castanha, Rodrigo Fernandes; Mariano, Adriano Pinto; de Morais, Lilia Aparecida Salgado; Scramin, Shirlei; Monteiro, Regina Teresa Rosim

2014-01-01

This study aimed the optimization of culture condition and composition for production of Cryptococcus laurentii 11 biomass and lipids in cheese whey medium supplemented with sugarcane molasses. The optimization of pH, fermentation time, and molasses concentration according to a full factorial statistical experimental design was followed by a Plackett-Burman experimental design, which was used to determine whether the supplementation of the culture medium by yeast extract and inorganic salts could provide a further enhancement of lipids production. The following conditions and composition of the culture medium were found to optimize biomass and lipids production: 360 h fermentation, 6.5 pH and supplementation of (g L(-1)): 50 molasses, 0.5 yeast extract, 4 KH2PO4, 1 Na2HPO4, 0.75 MgSO4 · 7H2O and 0.002 ZnSO4 · H2O. Additional supplementation with inorganic salts and yeast extract was essential to optimize the production, in terms of product concentration and productivity, of neutral lipids by C. laurentii 11. Under this optimized condition, the production of total lipids increased by 133% in relation to control experiment (from 1.27 to 2.96 g L(-1)). The total lipids indicated a predominant (86%) presence of neutral lipids with high content of 16- and 18-carbon-chain saturated and monosaturated fatty acids. This class of lipids is considered especially suitable for the production of biodiesel.

Optimization of multiwalled carbon nanotubes reinforced hollow-fiber solid-liquid-phase microextraction for the determination of polycyclic aromatic hydrocarbons in environmental water samples using experimental design.

PubMed

Hamedi, Raheleh; Hadjmohammadi, Mohammad Reza

2017-09-01

A novel design of hollow-fiber liquid-phase microextraction containing multiwalled carbon nanotubes as a solid sorbent, which is immobilized in the pore and lumen of hollow fiber by the sol-gel technique, was developed for the pre-concentration and determination of polycyclic aromatic hydrocarbons in environmental water samples. The proposed method utilized both solid- and liquid-phase microextraction media. Parameters that affect the extraction of polycyclic aromatic hydrocarbons were optimized in two successive steps as follows. Firstly, a methodology based on a quarter factorial design was used to choose the significant variables. Then, these significant factors were optimized utilizing central composite design. Under the optimized condition (extraction time = 25 min, amount of multiwalled carbon nanotubes = 78 mg, sample volume = 8 mL, and desorption time = 5 min), the calibration curves showed high linearity (R 2  = 0.99) in the range of 0.01-500 ng/mL and the limits of detection were in the range of 0.007-1.47 ng/mL. The obtained extraction recoveries for 10 ng/mL of polycyclic aromatic hydrocarbons standard solution were in the range of 85-92%. Replicating the experiment under these conditions five times gave relative standard deviations lower than 6%. Finally, the method was successfully applied for pre-concentration and determination of polycyclic aromatic hydrocarbons in environmental water samples. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Exploring metabolic engineering design principles for the photosynthetic production of lactic acid by Synechocystis sp. PCC6803

PubMed Central

2014-01-01

Background Molecular engineering of the intermediary physiology of cyanobacteria has become important for the sustainable production of biofuels and commodity compounds from CO2 and sunlight by “designer microbes.” The chemical commodity product L-lactic acid can be synthesized in one step from a key intermediary metabolite of these organisms, pyruvate, catalyzed by a lactate dehydrogenase. Synthetic biology engineering to make “designer microbes” includes the introduction and overexpression of the product-forming biochemical pathway. For further optimization of product formation, modifications in the surrounding biochemical network of intermediary metabolism have to be made. Results To improve light-driven L-lactic acid production from CO2, we explored several metabolic engineering design principles, using a previously engineered L-lactic acid producing mutant strain of Synechocystis sp. PCC6803 as the benchmark. These strategies included: (i) increasing the expression level of the relevant product-forming enzyme, lactate dehydrogenase (LDH), for example, via expression from a replicative plasmid; (ii) co-expression of a heterologous pyruvate kinase to increase the flux towards pyruvate; and (iii) knockdown of phosphoenolpyruvate carboxylase to decrease the flux through a competing pathway (from phosphoenolpyruvate to oxaloacetate). In addition, we tested selected lactate dehydrogenases, some of which were further optimized through site-directed mutagenesis to improve the enzyme’s affinity for the co-factor nicotinamide adenine dinucleotide phosphate (NADPH). The carbon partitioning between biomass and lactic acid was increased from about 5% to over 50% by strain optimization. Conclusion An efficient photosynthetic microbial cell factory will display a high rate and extent of conversion of substrate (CO2) into product (here: L-lactic acid). In the existing CO2-based cyanobacterial cell factories that have been described in the literature, by far most of the control over product formation resides in the genetically introduced fermentative pathway. Here we show that a strong promoter, in combination with increased gene expression, can take away a significant part of the control of this step in lactic acid production from CO2. Under these premises, modulation of the intracellular precursor, pyruvate, can significantly increase productivity. Additionally, production enhancement is achieved by protein engineering to increase co-factor specificity of the heterologously expressed LDH. PMID:24991233

Optimizing conditions for the extraction of pigments in cochineals (Dactylopius coccus Costa) using response surface methodology.

PubMed

González, Mónica; Méndez, Jesús; Carnero, Aurelio; Lobo, M Gloria; Afonso, Ana

2002-11-20

A simple method was developed for the extraction and determination of color pigments in cochineals (Dactylopius coccus Costa). The procedure was based on the solvent extraction of pigments in insect samples using methanol:water (65:35, v:v) as extractant. Two-level factorial design was used in order to optimize the solvent extraction parameters: temperature, time, methanol concentration in the extractant mixture, and the number of extractions. The results suggest that the number of extractions is statistically the most significant factor. The separation and determination of the pigments was carried out by high-performance liquid chromatography with UV-visible detection. Because the absorption spectra of different pigments are different in the visible region, it is convenient to use a diode array detector to obtain chromatographic profiles that allow for the characterization of the extracted pigments.

Fractional Factorial Design Study on the Performance of GAC-Enhanced Electrocoagulation Process Involved in Color Removal from Dye Solutions.

PubMed

Secula, Marius Sebastian; Cretescu, Igor; Cagnon, Benoit; Manea, Liliana Rozemarie; Stan, Corneliu Sergiu; Breaban, Iuliana Gabriela

2013-07-10

The aim of this study was to determine the effects of main factors and interactions on the color removal performance from dye solutions using the electrocoagulation process enhanced by adsorption on Granular Activated Carbon (GAC). In this study, a mathematical approach was conducted using a two-level fractional factorial design ( FFD ) for a given dye solution. Three textile dyes: Acid Blue 74, Basic Red 1, and Reactive Black 5 were used. Experimental factors used and their respective levels were: current density (2.73 or 27.32 A/m²), initial pH of aqueous dye solution (3 or 9), electrocoagulation time (20 or 180 min), GAC dose (0.1 or 0.5 g/L), support electrolyte (2 or 50 mM), initial dye concentration (0.05 or 0.25 g/L) and current type (Direct Current- DC or Alternative Pulsed Current- APC ). GAC-enhanced electrocoagulation performance was analyzed statistically in terms of removal efficiency, electrical energy, and electrode material consumptions, using modeling polynomial equations. The statistical significance of GAC dose level on the performance of GAC enhanced electrocoagulation and the experimental conditions that favor the process operation of electrocoagulation in APC regime were determined. The local optimal experimental conditions were established using a multi-objective desirability function method.

Improvement of Storage Medium for Cultured Human Retinal Pigment Epithelial Cells Using Factorial Design.

PubMed

Pasovic, L; Utheim, T P; Reppe, S; Khan, A Z; Jackson, C J; Thiede, B; Berg, J P; Messelt, E B; Eidet, J R

2018-04-09

Storage of human retinal pigment epithelium (hRPE) can contribute to the advancement of cell-based RPE replacement therapies. The present study aimed to improve the quality of stored hRPE cultures by identifying storage medium additives that, alone or in combination, contribute to enhancing cell viability while preserving morphology and phenotype. hRPE cells were cultured in the presence of the silk protein sericin until pigmentation. Cells were then stored for 10 days in storage medium plus sericin and either one of 46 different additives. Individual effects of each additive on cell viability were assessed using epifluorescence microscopy. Factorial design identified promising additive combinations by extrapolating their individual effects. Supplementing the storage medium with sericin combined with adenosine, L-ascorbic acid and allopurinol resulted in the highest cell viability (98.6 ± 0.5%) after storage for three days, as measured by epifluorescence microscopy. Flow cytometry validated the findings. Proteomics identified 61 upregulated and 65 downregulated proteins in this storage group compared to the unstored control. Transmission electron microscopy demonstrated the presence of melanosomes after storage in the optimized medium. We conclude that the combination of adenosine, L-ascorbic acid, allopurinol and sericin in minimal essential medium preserves RPE pigmentation while maintaining cell viability during storage.

Fractional Factorial Design Study on the Performance of GAC-Enhanced Electrocoagulation Process Involved in Color Removal from Dye Solutions

PubMed Central

Secula, Marius Sebastian; Cretescu, Igor; Cagnon, Benoit; Manea, Liliana Rozemarie; Stan, Corneliu Sergiu; Breaban, Iuliana Gabriela

2013-01-01

The aim of this study was to determine the effects of main factors and interactions on the color removal performance from dye solutions using the electrocoagulation process enhanced by adsorption on Granular Activated Carbon (GAC). In this study, a mathematical approach was conducted using a two-level fractional factorial design (FFD) for a given dye solution. Three textile dyes: Acid Blue 74, Basic Red 1, and Reactive Black 5 were used. Experimental factors used and their respective levels were: current density (2.73 or 27.32 A/m2), initial pH of aqueous dye solution (3 or 9), electrocoagulation time (20 or 180 min), GAC dose (0.1 or 0.5 g/L), support electrolyte (2 or 50 mM), initial dye concentration (0.05 or 0.25 g/L) and current type (Direct Current—DC or Alternative Pulsed Current—APC). GAC-enhanced electrocoagulation performance was analyzed statistically in terms of removal efficiency, electrical energy, and electrode material consumptions, using modeling polynomial equations. The statistical significance of GAC dose level on the performance of GAC enhanced electrocoagulation and the experimental conditions that favor the process operation of electrocoagulation in APC regime were determined. The local optimal experimental conditions were established using a multi-objective desirability function method. PMID:28811405

Sorption of water alkalinity and hardness from high-strength wastewater on bifunctional activated carbon: process optimization, kinetics and equilibrium studies.

PubMed

Amosa, Mutiu K

2016-08-01

Sorption optimization and mechanism of hardness and alkalinity on bifunctional empty fruit bunch-based powdered activation carbon (PAC) were studied. The PAC possessed both high surface area and ion-exchange properties, and it was utilized in the treatment of biotreated palm oil mill effluent. Batch adsorption experiments designed with Design Expert(®) were conducted in correlating the singular and interactive effects of the three adsorption parameters: PAC dosage, agitation speed and contact time. The sorption trends of the two contaminants were sequentially assessed through a full factorial design with three factor interaction models and a central composite design with polynomial models of quadratic order. Analysis of variance revealed the significant factors on each design response with very high R(2) values indicating good agreement between model and experimental values. The optimum operating conditions of the two contaminants differed due to their different regions of operating interests, thus necessitating the utility of desirability factor to get consolidated optimum operation conditions. The equilibrium data for alkalinity and hardness sorption were better represented by the Langmuir isotherm, while the pseudo-second-order kinetic model described the adsorption rates and behavior better. It was concluded that chemisorption contributed majorly to the adsorption process.

A Classroom of Polymer Factories.

ERIC Educational Resources Information Center

Harris, Mary E.; Van Natta, Sandra

1998-01-01

Provides an activity in which students create small classroom factories and investigate several aspects of production including design, engineering, quality control, waste management, packaging, shipment, and communication. (DDR)

Effect of medium components and culture conditions in Bacillus subtilis EA-CB0575 spore production.

PubMed

Posada-Uribe, Luisa F; Romero-Tabarez, Magally; Villegas-Escobar, Valeska

2015-10-01

Bacillus subtilis spores have important biotechnological applications; however, achieving both, high spore cell densities and sporulation efficiencies in fermentation, is poorly reported. In this study, medium components and culture conditions were optimized with different statistical methods to increase spore production of the plant growth promoting rhizobacteria B. subtilis EA-CB0575. Key medium components were determined with Plackett-Burman (PB) design, and the optimum concentration levels of two components (glucose, MgSO4·7H2O) were optimized with a full factorial and central composite design, achieving 1.37 × 10(9) CFU/mL of spore cell density and 93.5 % of sporulation efficiency in shake flask. The optimized medium was used to determine the effect of culture conditions on spore production at bioreactor level, finding that maintaining pH control did not affect significantly spore production, while the interaction of agitation and aeration rates had a significant effect on spore cell density. The overall optimization generated a 17.2-fold increase in spore cell density (8.78 × 10(9) CFU/mL) and 1.9-fold increase in sporulation efficiency (94.2 %) compared to that of PB design. These results indicate the potential of B. subtilis EA-CB0575 to produce both, high spore cell densities and sporulation efficiencies, with very low nutrient requirements and short incubation period which can represent savings of process production.

Design of experiments for the development of poly( d, l-lactide- co-glycolide) nanoparticles loaded with Uncaria tomentosa

NASA Astrophysics Data System (ADS)

Ribeiro, Ana Ferreira; Ferreira, Carina Torres Garruth; dos Santos, Juliana Fernandes; Cabral, Lúcio Mendes; de Sousa, Valéria Pereira

2015-02-01

Polymeric nanoparticles have been shown to be effective carriers for natural substances that possess anticancer properties. Incorporation of these natural substances into polymeric nanoparticles increases targeting of these drugs, thus reducing side effects. Uncaria tomentosa (UT) is a Peruvian Amazon plant (existing in the Brazilian Amazon rainforest) that possesses promising anti-tumor activity. This paper describes the development of poly( d, l-lactide- co-glycolide) (PLGA) nanoparticles loaded with UT extract. The emulsion solvent evaporation method was utilized and the initial conditions were determined for the organic phase (OP) and the aqueous phase (AP). The influence of surfactant (type and concentration), PLGA concentration and AP volume on nanoparticle size, polydispersity index (PI), and entrapment efficiency (EE) was determined using a fractional factorial design (FFD). In addition, the formulation was optimized using a Box-Behnken design. After the conditions were optimized, UT nanoparticles were obtained using an OP composed of an ethyl acetate:acetone (3:2) mixture which contained the UT alkaloids and PLGA, and an AP composed of a buffered solution of Poloxamer 188 (pH 7.5). The optimized formulation produced an EE of 64.6 %, a particle size of 107.4 nm and a PI of 0.163. The preliminary experiments provided important information regarding the behavior of the nanoparticulate system and the FFD used in this study greatly facilitated the selection of the most optimal conditions for formulation development.

A new multiresponse optimization approach in combination with a D-Optimal experimental design for the determination of biogenic amines in fish by HPLC-FLD.

PubMed

Herrero, A; Sanllorente, S; Reguera, C; Ortiz, M C; Sarabia, L A

2016-11-16

A new strategy to approach multiresponse optimization in conjunction to a D-optimal design for simultaneously optimizing a large number of experimental factors is proposed. The procedure is applied to the determination of biogenic amines (histamine, putrescine, cadaverine, tyramine, tryptamine, 2-phenylethylamine, spermine and spermidine) in swordfish by HPLC-FLD after extraction with an acid and subsequent derivatization with dansyl chloride. Firstly, the extraction from a solid matrix and the derivatization of the extract are optimized. Ten experimental factors involved in both stages are studied, seven of them at two levels and the remaining at three levels; the use of a D-optimal design leads to optimize the ten experimental variables, significantly reducing by a factor of 67 the experimental effort needed but guaranteeing the quality of the estimates. A model with 19 coefficients, which includes those corresponding to the main effects and two possible interactions, is fitted to the peak area of each amine. Then, the validated models are used to predict the response (peak area) of the 3456 experiments of the complete factorial design. The variability among peak areas ranges from 13.5 for 2-phenylethylamine to 122.5 for spermine, which shows, to a certain extent, the high and different effect of the pretreatment on the responses. Then the percentiles are calculated from the peak areas of each amine. As the experimental conditions are in conflict, the optimal solution for the multiresponse optimization is chosen from among those which have all the responses greater than a certain percentile for all the amines. The developed procedure reaches decision limits down to 2.5 μg L -1 for cadaverine or 497 μg L -1 for histamine in solvent and 0.07 mg kg -1 and 14.81 mg kg -1 in fish (probability of false positive equal to 0.05), respectively. Copyright © 2016 Elsevier B.V. All rights reserved.

Integrating PCLIPS into ULowell's Lincoln Logs: Factory of the future

NASA Technical Reports Server (NTRS)

Mcgee, Brenda J.; Miller, Mark D.; Krolak, Patrick; Barr, Stanley J.

1990-01-01

We are attempting to show how independent but cooperating expert systems, executing within a parallel production system (PCLIPS), can operate and control a completely automated, fault tolerant prototype of a factory of the future (The Lincoln Logs Factory of the Future). The factory consists of a CAD system for designing the Lincoln Log Houses, two workcells, and a materials handling system. A workcell consists of two robots, part feeders, and a frame mounted vision system.

Using Blocked Fractional Factorial Designs to Construct Discrete Choice Experiments for Health Care Studies

PubMed Central

Jaynes, Jessica; Wong, Weng Kee; Xu, Hongquan

2016-01-01

Discrete choice experiments (DCEs) are increasingly used for studying and quantifying subjects preferences in a wide variety of health care applications. They provide a rich source of data to assess real-life decision making processes, which involve trade-offs between desirable characteristics pertaining to health and health care, and identification of key attributes affecting health care. The choice of the design for a DCE is critical because it determines which attributes’ effects and their interactions are identifiable. We apply blocked fractional factorial designs to construct DCEs and address some identification issues by utilizing the known structure of blocked fractional factorial designs. Our design techniques can be applied to several situations including DCEs where attributes have different number of levels. We demonstrate our design methodology using two health care studies to evaluate (1) asthma patients’ preferences for symptom-based outcome measures, and (2) patient preference for breast screening services. PMID:26823156

Evaluation of chromatographic columns packed with semi- and fully porous particles for benzimidazoles separation.

PubMed

Gonzalo-Lumbreras, Raquel; Sanz-Landaluze, Jon; Cámara, Carmen

2015-07-01

The behavior of 15 benzimidazoles, including their main metabolites, using several C18 columns with standard or narrow-bore diameters and different particle size and type were evaluated. These commercial columns were selected because their differences could affect separation of benzimidazoles, and so they can be used as alternative columns. A simple screening method for the analysis of benzimidazole residues and their main metabolites was developed. First, the separation of benzimidazoles was optimized using a Kinetex C18 column; later, analytical performances of other columns using the above optimized conditions were compared and then individually re-optimized. Critical pairs resolution, analysis run time, column type and characteristics, and selectivity were considered for chromatographic columns comparison. Kinetex XB was selected because it provides the shortest analysis time and the best resolution of critical pairs. Using this column, the separation conditions were re-optimized using a factorial design. Separations obtained with the different columns tested can be applied to the analysis of specific benzimidazoles residues or other applications. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Evaluation of polyvinyl alcohols as mucoadhesive polymers for mucoadhesive buccal tablets prepared by direct compression.

PubMed

Ikeuchi-Takahashi, Yuri; Ishihara, Chizuko; Onishi, Hiraku

2017-09-01

The purpose of the present work was to evaluate polyvinyl alcohols (PVAs) as a mucoadhesive polymer for mucoadhesive buccal tablets prepared by direct compression. Various polymerization degree and particle diameter PVAs were investigated for their usability. The tensile strength, in vitro adhesive force, and water absorption properties of the tablets were determined to compare the various PVAs. The highest values of the tensile strength and the in vitro adhesive force were observed for PVAs with a medium viscosity and small particle size. The optimal PVA was identified by a factorial design analysis. Mucoadhesive tablets containing the optimal PVA were compared with carboxyvinyl polymer and hydroxypropyl cellulose formulations. The optimal PVA gives a high adhesive force, has a low viscosity, and resulted in relatively rapid drug release. Formulations containing carboxyvinyl polymer had high tensile strengths but short disintegration times. Higher hydroxypropyl cellulose concentration formulations had good adhesion forces and very long disintegration times. We identified the optimal characteristics of PVA, and the usefulness of mucoadhesive buccal tablets containing this PVA was suggested from their formulation properties.

Optimization of Penicillium aurantiogriseum protease immobilization on magnetic nanoparticles for antioxidant peptides' obtainment.

PubMed

Duarte Neto, José Manoel Wanderley; Maciel, Jackeline da Costa; Campos, Júlia Furtado; Carvalho Junior, Luiz Bezerra de; Marques, Daniela Araújo Viana; Lima, Carolina de Albuquerque; Porto, Ana Lúcia Figueiredo

2017-08-09

This work reports an optimization of protease from Penicillium aurantiogriseum immobilization on polyaniline-coated magnetic nanoparticles for antioxidant peptides' obtainment derived from bovine casein. Immobilization process was optimized using a full two-level factorial design (2 4 ) followed by a response surface methodology. Using the derivative, casein was hydrolyzed uncovering its peptides that were sequenced and had antioxidant properties tested through (2,2'-Azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) diammonium salt) (ABTS) radical scavenging and hydrogen peroxide scavenging assays. Optimal conditions for immobilization were 2 hr of immobilization, offered protein amount of 200 µg/mL, immobilization pH of 6.3 and 7.3 hr of activation. Derivative keeps over 74% of its original activity after reused five times. Free and immobilized enzyme casein hydrolysates presented similar peptide mass fingerprints, and prevalent peptides could be sequenced. Hydrolysates presented more than 2.5× higher ROS scavenging activity than nonhydrolyzed casein, which validates the immobilized protease capacity to develop casein-derived natural ingredients with potential for functional foods.

Optimization of elutriation device for filtration of microplastic particles from sediment.

PubMed

Zhu, X

2015-03-15

The increasing presence of plastic pollution in marine ecosystems has become a major concern. In the environment, plastics break down into smaller and smaller pieces of microplastics. Methods of microplastic recovery are needed to reduce the dangers they can pose to a variety of organisms. An elutriation device was manufactured and optimized to achieve maximum microplastic recovery. The parameters flow rate and diameter of elutriation column were varied and their domain of variation was determined. A composite factorial experimental design was generated using MODDE 10.1 and was undergone. The optimal values of flow rate and column diameter were determined to be 385 L h(-1) and 5.06 cm respectively, under constraints, to achieve a maximum feasible microplastics recovery percentage of 50.2%. The elutriation process can be improved through further testing, and can be tested in the field to compare its efficiency to that of manual microplastics filtration. Copyright © 2015 Elsevier Ltd. All rights reserved.

Blends of jackfruit seed starch-pectin in the development of mucoadhesive beads containing metformin HCl.

PubMed

Nayak, Amit Kumar; Pal, Dilipkumar

2013-11-01

In this work, calcium pectinate-jackfruit (Artocarpus heterophyllus Lam.) seed starch (JFSS) mucoadhesive beads containing metformin HCl were developed through ionotropic-gelation. Effects of pectin and JFSS amounts on drug encapsulation efficiency (DEE), and cumulative drug release after 10 h (R10 h) were optimized using 3(2) factorial design. The optimized calcium pectinate-JFSS beads containing metformin HCl showed DEE of 94.11 ± 3.92%, R10 h of 48.88 ± 2.02%, and mean diameter of 2.06 ± 0.20 mm. The in vitro drug release from these beads was followed controlled-release (zero-order) pattern with super case-II transport mechanism. The beads were also characterized by SEM and FTIR. The pH of test mediums was found critical for swelling and mucoadhesion of these beads. The optimized calcium pectinate-JFSS beads also exhibited good mucoadhesivity and significant hypoglycemic effect in alloxan-induced diabetic rats over prolonged period after oral administration. Copyright © 2013 Elsevier B.V. All rights reserved.

Factorial Based Response Surface Modeling with Confidence Intervals for Optimizing Thermal Optical Transmission Analysis of Atmospheric Black Carbon

EPA Science Inventory

We demonstrate how thermal-optical transmission analysis (TOT) for refractory light-absorbing carbon in atmospheric particulate matter was optimized with empirical response surface modeling. TOT employs pyrolysis to distinguish the mass of black carbon (BC) from organic carbon (...

Transdermal film-loaded finasteride microplates to enhance drug skin permeation: Two-step optimization study.

PubMed

Ahmed, Tarek A; El-Say, Khalid M

2016-06-10

The goal was to develop an optimized transdermal finasteride (FNS) film loaded with drug microplates (MIC), utilizing two-step optimization, to decrease the dosing schedule and inconsistency in gastrointestinal absorption. First; 3-level factorial design was implemented to prepare optimized FNS-MIC of minimum particle size. Second; Box-Behnken design matrix was used to develop optimized transdermal FNS-MIC film. Interaction among MIC components was studied using physicochemical characterization tools. Film components namely; hydroxypropyl methyl cellulose (X1), dimethyl sulfoxide (X2) and propylene glycol (X3) were optimized for their effects on the film thickness (Y1) and elongation percent (Y2), and for FNS steady state flux (Y3), permeability coefficient (Y4), and diffusion coefficient (Y5) following ex-vivo permeation through the rat skin. Morphological study of the optimized MIC and transdermal film was also investigated. Results revealed that stabilizer concentration and anti-solvent percent were significantly affecting MIC formulation. Optimized FNS-MIC of particle size 0.93μm was successfully prepared in which there was no interaction observed among their components. An enhancement in the aqueous solubility of FNS-MIC by more than 23% was achieved. All the studied variables, most of their interaction and quadratic effects were significantly affecting the studied variables (Y1-Y5). Morphological observation illustrated non-spherical, short rods, flakes like small plates that were homogeneously distributed in the optimized transdermal film. Ex-vivo study showed enhanced FNS permeation from film loaded MIC when compared to that contains pure drug. So, MIC is a successful technique to enhance aqueous solubility and skin permeation of poor water soluble drug especially when loaded into transdermal films. Copyright © 2016 Elsevier B.V. All rights reserved.

Quasi-isochronous muon collection channels

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ankenbrandt, Charles M.; Neuffer, David; Johnson, Rolland P.

2015-04-26

Intense muon beams have many potential commercial and scientific applications, ranging from low-energy investigations of the basic properties of matter using spin resonance to large energy-frontier muon colliders. However, muons originate from a tertiary process that produces a diffuse swarm. To make useful beams, the swarm must be rapidly captured and cooled before the muons decay. In this STTR project a promising new concept for the collection and cooling of muon beams to increase their intensity and reduce their emittances was investigated, namely, the use of a nearly isochronous helical cooling channel (HCC) to facilitate capture of the muons intomore » RF bunches. The muon beam can then be cooled quickly and coalesced efficiently to optimize the luminosity of a muon collider, or could provide compressed muon beams for other applications. Optimal ways to integrate such a subsystem into the rest of a muon collection and cooling system, for collider and other applications, were developed by analysis and simulation. The application of quasi-isochronous helical cooling channels (QIHCC) for RF capture of muon beams was developed. Innovative design concepts for a channel incorporating straight solenoids, a matching section, and an HCC, including RF and absorber, were developed, and its subsystems were simulated. Additionally, a procedure that uses an HCC to combine bunches for a muon collider was invented and simulated. Difficult design aspects such as matching sections between subsystems and intensity-dependent effects were addressed. The bunch recombination procedure was developed into a complete design with 3-D simulations. Bright muon beams are needed for many commercial and scientific reasons. Potential commercial applications include low-dose radiography, muon catalyzed fusion, and the use of muon beams to screen cargo containers for homeland security. Scientific uses include low energy beams for rare process searches, muon spin resonance applications, muon beams for neutrino factories, and muon colliders as Higgs factories or energy-frontier discovery machines.« less

A distribution-free multi-factorial profiler for harvesting information from high-density screenings.

PubMed

Besseris, George J

2013-01-01

Data screening is an indispensable phase in initiating the scientific discovery process. Fractional factorial designs offer quick and economical options for engineering highly-dense structured datasets. Maximum information content is harvested when a selected fractional factorial scheme is driven to saturation while data gathering is suppressed to no replication. A novel multi-factorial profiler is presented that allows screening of saturated-unreplicated designs by decomposing the examined response to its constituent contributions. Partial effects are sliced off systematically from the investigated response to form individual contrasts using simple robust measures. By isolating each time the disturbance attributed solely to a single controlling factor, the Wilcoxon-Mann-Whitney rank stochastics are employed to assign significance. We demonstrate that the proposed profiler possesses its own self-checking mechanism for detecting a potential influence due to fluctuations attributed to the remaining unexplainable error. Main benefits of the method are: 1) easy to grasp, 2) well-explained test-power properties, 3) distribution-free, 4) sparsity-free, 5) calibration-free, 6) simulation-free, 7) easy to implement, and 8) expanded usability to any type and size of multi-factorial screening designs. The method is elucidated with a benchmarked profiling effort for a water filtration process.

A Distribution-Free Multi-Factorial Profiler for Harvesting Information from High-Density Screenings

PubMed Central

Besseris, George J.

2013-01-01

Data screening is an indispensable phase in initiating the scientific discovery process. Fractional factorial designs offer quick and economical options for engineering highly-dense structured datasets. Maximum information content is harvested when a selected fractional factorial scheme is driven to saturation while data gathering is suppressed to no replication. A novel multi-factorial profiler is presented that allows screening of saturated-unreplicated designs by decomposing the examined response to its constituent contributions. Partial effects are sliced off systematically from the investigated response to form individual contrasts using simple robust measures. By isolating each time the disturbance attributed solely to a single controlling factor, the Wilcoxon-Mann-Whitney rank stochastics are employed to assign significance. We demonstrate that the proposed profiler possesses its own self-checking mechanism for detecting a potential influence due to fluctuations attributed to the remaining unexplainable error. Main benefits of the method are: 1) easy to grasp, 2) well-explained test-power properties, 3) distribution-free, 4) sparsity-free, 5) calibration-free, 6) simulation-free, 7) easy to implement, and 8) expanded usability to any type and size of multi-factorial screening designs. The method is elucidated with a benchmarked profiling effort for a water filtration process. PMID:24009744

The combination of simulation and response methodology and its application in an aggregate production plan

NASA Astrophysics Data System (ADS)

Chen, Zhiming; Feng, Yuncheng

1988-08-01

This paper describes an algorithmic structure for combining simulation and optimization techniques both in theory and practice. Response surface methodology is used to optimize the decision variables in the simulation environment. A simulation-optimization software has been developed and successfully implemented, and its application to an aggregate production planning simulation-optimization model is reported. The model's objective is to minimize the production cost and to generate an optimal production plan and inventory control strategy for an aircraft factory.

Factorial study of rain garden design for nitrogen removal

EPA Science Inventory

Abstract Nitrate (〖NO〗_3^--N ) removal studies in bioretention systems showed great variability in removal rates and in some cases 〖NO〗_3^--N was exported. A 3-way factorial design (2 x 2 x 4) was devised for eight outdoor un-vegetated rain gardens to evaluate the effects of ...

More Powerful Tests of Simple Interaction Contrasts in the Two-Way Factorial Design

ERIC Educational Resources Information Center

Hancock, Gregory R.; McNeish, Daniel M.

2017-01-01

For the two-way factorial design in analysis of variance, the current article explicates and compares three methods for controlling the Type I error rate for all possible simple interaction contrasts following a statistically significant interaction, including a proposed modification to the Bonferroni procedure that increases the power of…

Optimization and mechanisms for biodecoloration of a mixture of dyes by Trichosporon akiyoshidainum HP 2023.

PubMed

Martorell, María M; Rosales Soro, María Del M; Pajot, Hipólito F; de Figueroa, Lucía I C

2017-09-16

Trichosporon akiyoshidainum HP2023 is a basidiomycetous yeast isolated from Las Yungas rainforest (Tucumán, Argentina) and selected based on its outstanding textile-dye-decolorizing ability. In this work, the decolorization process was optimized using Reactive Black 5 as dye model. Lactose and urea were chosen as carbon and nitrogen sources through a one-at-time approach. Afterwards, factorial designs were employed for medium optimization, leading to the formulation of a simpler optimized medium which contains in g L -1 : lactose 10, yeast extract 1, urea 0.5, KH 2 PO 4 1 and MgSO 4 1. Temperature and agitation conditions were also optimized. The optimized medium and incubation conditions for dye removal were extrapolated to other dyes individually and a mixture of them. Dye removal process happened through both biosorption and biodegradation mechanisms, depending primarily on the dye structure. A positive relation between initial inoculum and dye removal rate and a negative relation between initial dye concentration and final dye removal percentages were found. Under optimized conditions, T. akiyoshidainum HP2023 was able to completely remove a mixture of dyes up to a concentration of 300 mg L -1 , a concentration much higher than those expected in real effluents.

Expression in Escherichia coli, refolding and crystallization of Aspergillus niger feruloyl esterase A using a serial factorial approach.

PubMed

Benoit, Isabelle; Coutard, Bruno; Oubelaid, Rachid; Asther, Marcel; Bignon, Christophe

2007-09-01

Hydrolysis of plant biomass is achieved by the combined action of enzymes secreted by microorganisms and directed against the backbone and the side chains of plant cell wall polysaccharides. Among side chains degrading enzymes, the feruloyl esterase A (FAEA) specifically removes feruloyl residues. Thus, FAEA has potential applications in a wide range of industrial processes such as paper bleaching or bio-ethanol production. To gain insight into FAEA hydrolysis activity, we solved its crystal structure. In this paper, we report how the use of four consecutive factorial approaches (two incomplete factorials, one sparse matrix, and one full factorial) allowed expressing in Escherichia coli, refolding and then crystallizing Aspergillus niger FAEA in 6 weeks. Culture conditions providing the highest expression level were determined using an incomplete factorial approach made of 12 combinations of four E. coli strains, three culture media and three temperatures (full factorial: 36 combinations). Aspergillus niger FAEA was expressed in the form of inclusion bodies. These were dissolved using a chaotropic agent, and the protein was purified by affinity chromatography on Ni column under denaturing conditions. A suitable buffer for refolding the protein eluted from the Ni column was found using a second incomplete factorial approach made of 96 buffers (full factorial: 3840 combinations). After refolding, the enzyme was further purified by gel filtration, and then crystallized following a standard protocol: initial crystallization conditions were found using commercial crystallization screens based on a sparse matrix. Crystals were then optimized using a full factorial screen.

Formulation and evaluation of flurbiprofen microemulsion.

PubMed

Ambade, K W; Jadhav, S L; Gambhire, M N; Kurmi, S D; Kadam, V J; Jadhav, K R

2008-01-01

The purpose of the present study was to investigate the microemulsion formulations for topical delivery of Flurbiprofen (FP) in order to by pass its gastrointestinal adverse effects. The pseudoternary phase diagrams were developed and various microemulsion formulations were prepared using Isopropyl Myristate (IPM), Ethyl Oleate (EO) as oils, Aerosol OT as surfactant and Sorbitan Monooleate as cosurfactant. The transdermal permeability of flurbiprofen from microemulsions containing IPM and EO as two different oil phases was analyzed using Keshary-Chien diffusion cell through excised rat skin. Flurbiprofen showed higher in vitro permeation from IPM as compared to that of from EO microemulsion. Thus microemulsion containing IPM as oil phase were selected for optimization. The optimization was carried out using 2(3) factorial design. The optimized formula was then subjected to in vivo anti-inflammatory study and the performance of flurbiprofen from optimized formulation was compared with that of gel cream. Flurbiprofen from optimized microemulsion formulation was found to be more effective as compared to gel cream in inhibiting the carrageenan induced rat paw edema at all time intervals. Histopathological investigation of rat skin revealed the safety of microemulsion formulation for topical use. Thus the present study indicates that, microemulsion can be a promising vehicle for the topical delivery of flurbiprofen.

Preparation and characterization of sustained-release rotigotine film-forming gel.

PubMed

Li, Xiang; Zhang, Renyu; Liang, Rongcai; Liu, Wei; Wang, Chenhui; Su, Zhengxing; Sun, Fengying; Li, Youxin

2014-01-02

The aim of this study was to develop a film-forming gel formulation of rotigotine with hydroxypropyl cellulose (HPC) and Carbomer 934. To optimize this formulation, we applied the Response Surface Analysis technique and evaluated the gel's pharmacokinetic properties. The factors chosen for factorial design were the concentration of rotigotine, the proportion of HPC and Carbomer 934, and the concentration of ST-Elastomer 10. Each factor was varied over three levels: low, medium and high. The gel formulation was evaluated and optimized according to its accumulated permeation rate (Flux) through Franz-type diffusion. A pharmacokinetic study of rotigotine gel was performed with rabbits. The Flux of the optimized formulation reached the maximum (199.17 μg/cm(2)), which was 3% rotigotine and 7% ST-Elastomer 10 with optimal composition of HPC: Carbomer 934 (5:1). The bioavailability of the optimized formulation compared with intravenous administration was approximately 20%. A film-forming gel of rotigotine was successfully developed using the response surface analysis technique. The results of this study may be helpful in finding an optimum formulation for transdermal delivery of a drug. The product may improve patients' compliance and provide better efficacy. Copyright © 2013 Elsevier B.V. All rights reserved.

Toward the lowest energy consumption and emission in biofuel production: combination of ideal reactors and robust hosts.

PubMed

Xu, Ke; Lv, Bo; Huo, Yi-Xin; Li, Chun

2018-04-01

Rising feedstock costs, low crude oil prices, and other macroeconomic factors have threatened biofuel fermentation industries. Energy-efficient reactors, which provide controllable and stable biological environment, are important for the large-scale production of renewable and sustainable biofuels, and their optimization focus on the reduction of energy consumption and waste gas emission. The bioreactors could either be aerobic or anaerobic, and photobioreactors were developed for the culture of algae or microalgae. Due to the cost of producing large-volume bioreactors, various modeling strategies were developed for bioreactor design. The achievement of ideal biofuel reactor relies on not only the breakthrough of reactor design, but also the creation of super microbial factories with highest productivity and metabolic pathway flux. Copyright © 2017 Elsevier Ltd. All rights reserved.

Design and optimize of 3-axis filament winding machine

NASA Astrophysics Data System (ADS)

Quanjin, Ma; Rejab, M. R. M.; Idris, M. S.; Bachtiar, B.; Siregar, J. P.; Harith, M. N.

2017-10-01

Filament winding technique is developed as the primary process for composite cylindrical structures fabrication at low cost. Fibres are wound on a rotating mandrel by a filament winding machine where resin impregnated fibres pass through a pay-out eye. This paper aims to develop and optimize a 3-axis, lightweight, practical, efficient, portable filament winding machine to satisfy the customer demand, which can fabricate pipes and round shape cylinders with resins. There are 3 main units on the 3-axis filament winding machine, which are the rotary unit, the delivery unit and control system unit. Comparison with previous existing filament winding machines in the factory, it has 3 degrees of freedom and can fabricate more complex shape specimens based on the mandrel shape and particular control system. The machine has been designed and fabricated on 3 axes movements with control system. The x-axis is for movement of the carriage, the y-axis is the rotation of mandrel and the z-axis is the movement of the pay-out eye. Cylindrical specimens with different dimensions and winding angles were produced. 3-axis automated filament winding machine has been successfully designed with simple control system.

The Design and Implementation of Adsorptive Removal of Cu(II) from Leachate Using ANFIS

PubMed Central

Turan, Nurdan Gamze; Ozgonenel, Okan

2013-01-01

Clinoptilolite was investigated for the removal of Cu(II) ions from industrial leachate. Adaptive neural fuzzy interface system (ANFIS) was used for modeling the batch experimental system and predicting the optimal input values, that is, initial pH, adsorbent dosage, and contact time. Experiments were studied under laboratory batch and fixed bed conditions. The outcomes of suggested ANFIS modeling were then compared to a full factorial experimental design (23), which was utilized to assess the effect of three factors on the adsorption of Cu(II) ions in aqueous leachate of industrial waste. It was observed that the optimized parameters are almost close to each other. The highest removal efficiency was found as about 93.65% at pH 6, adsorbent dosage 11.4 g/L, and contact time 33 min for batch conditions of 23 experimental design and about 90.43% at pH 5, adsorbent dosage 15 g/L and contact time 35 min for batch conditions of ANFIS. The results show that clinoptilolite is an efficient sorbent and ANFIS, which is easy to implement and is able to model the batch experimental system. PMID:23844405

Response Surface Modeling of Combined-Cycle Propulsion Components using Computational Fluid Dynamics

NASA Technical Reports Server (NTRS)

Steffen, C. J., Jr.

2002-01-01

Three examples of response surface modeling with CFD are presented for combined cycle propulsion components. The examples include a mixed-compression-inlet during hypersonic flight, a hydrogen-fueled scramjet combustor during hypersonic flight, and a ducted-rocket nozzle during all-rocket flight. Three different experimental strategies were examined, including full factorial, fractionated central-composite, and D-optimal with embedded Plackett-Burman designs. The response variables have been confined to integral data extracted from multidimensional CFD results. Careful attention to uncertainty assessment and modeling bias has been addressed. The importance of automating experimental setup and effectively communicating statistical results are emphasized.

Formulation design of a highly hygroscopic drug (pyridostigmine bromide) for its hygroscopic character improvement and investigation of in vitro/in vivo dissolution properties.

PubMed

Huang, Yuh-Tyng; Tsai, Tong-Rong; Cheng, Chun-Jen; Cham, Thau-Ming; Lai, Tsun-Fwu; Chuo, Wen-Ho

2007-04-01

Pyridostigmine bromide (PB) sustained-release (SR) pellets were developed by extrusion-spheronization and fluid-bed methods using Taguchi experimental and 2(3) full factorial design. In vitro studies, the 2(3) full factorial design was utilized to search for the optimal SR pellets with specific release rate at different time intervals (release percent of 2, 6, 12, and 24 hr were 6.24, 33.48, 75.18, and 95.26%, respectively) which followed a zero-order mechanism (n=0.93). The results of moisture absorption by Karl Fischer has shown the optimum SR pellets at 25 degrees C/60% RH, 30 degrees C/65% RH, and 40 degrees C/75% RH chambers from 1 hr-4 weeks, attributing that the moisture absorption was not significantly increased. In the in vivo study, the results of the bioavailability data showed the Tmax (from 0.65+/-0.082 hr-4.82+/-2.12 hr) and AUC0-30 hr (from 734.88+/-230.68 ng/mL.hr-1454.86+/-319.28 ng/mL.hr) were prolonged and increased, as well as Cmax (from 251.87+/-27.51 ng/mL-115.08+/-14.87 ng/mL) was decreased for optimum SR-PB pellets when compared with commercial immediate-release (IR) tablets. Furthermore, a good linear regression relationship (r=0.9943) was observed between the fraction dissolution and fraction absorption for the optimum SR pellets. In this study, the formulation design not only improved the hygroscopic character of PB but also achieved the SR effect.

Torsemide Fast Dissolving Tablets: Development, Optimization Using Box-Bhenken Design and Response Surface Methodology, In Vitro Characterization, and Pharmacokinetic Assessment.

PubMed

El-Shenawy, Ahmed A; Ahmed, Mahmoud M; Mansour, Heba F; Abd El Rasoul, Saleh

2017-08-01

The present study planed to develop new fast dissolving tablets (FDTs) of torsemide. Solid dispersions (SDs) of torsemide and sorbitol (3:1) or polyvinylpyrrolidone (PVP) k25 were prepared. The prepared SDs were evaluated for in-vitro dissolution. Fourier transform infrared spectroscopy and differential scanning calorimetry for SDs revealed no drug/excipient interactions and transformation of torsemide to the amorphous form. Torsemide/sorbitol SD was selected for formulation of torsemide FDTs by direct compression method. Box-Bhenken factorial design was employed to design 15 formulations using croscarmellose sodium and crospovidone at different concentrations. The response surface methodology was used to analyze the effect of changing these concentrations (independent variables) on disintegration time (Y 1 ), percentage friability (Y 2 ), and amount torsemide released at 10 min. The physical mixtures of torsemide and the used excipients were evaluated for angle of repose, Hausner's ratio, and Carr's index. The prepared FDTs tablets were evaluated for wetting and disintegration time, weight variation, drug content, percentage friability, thickness, hardness, and in vitro release. Based on the in-vitro results and factorial design characterization, F10 and F7 were selected for bioavailability studies following administration to Albino New Zealand rabbits. They showed significantly higher C max and (AUC 0-12 ) and shorter T max than those obtained after administration of the corresponding ordinary commercial Torseretic ® tablets. Stability study was conducted for F10 that showed good stability upon storage at 30°C/75% RH and 40°C/75% RH for 3 months.

Taguchi method of experimental design in materials education

NASA Technical Reports Server (NTRS)

Weiser, Martin W.

1993-01-01

Some of the advantages and disadvantages of the Taguchi Method of experimental design as applied to Materials Science will be discussed. This is a fractional factorial method that employs the minimum number of experimental trials for the information obtained. The analysis is also very simple to use and teach, which is quite advantageous in the classroom. In addition, the Taguchi loss function can be easily incorporated to emphasize that improvements in reproducibility are often at least as important as optimization of the response. The disadvantages of the Taguchi Method include the fact that factor interactions are normally not accounted for, there are zero degrees of freedom if all of the possible factors are used, and randomization is normally not used to prevent environmental biasing. In spite of these disadvantages it is felt that the Taguchi Method is extremely useful for both teaching experimental design and as a research tool, as will be shown with a number of brief examples.

The Skateboard Factory: Curriculum by Design--Oasis Skateboard Factory Q&A with Craig Morrison

ERIC Educational Resources Information Center

Pearson, George

2012-01-01

Since its opening three years ago, Oasis Skateboard Factory (OSF), founded by teacher Craig Morrison, has attracted considerable media exposure and received a Ken Spencer Award from the CEA for its innovative program. OSF is one of three programs offered by Oasis Alternative Secondary School, one of 22 alternative secondary schools of the Toronto…

Clustering Words to Match Conditions: An Algorithm for Stimuli Selection in Factorial Designs

ERIC Educational Resources Information Center

Guasch, Marc; Haro, Juan; Boada, Roger

2017-01-01

With the increasing refinement of language processing models and the new discoveries about which variables can modulate these processes, stimuli selection for experiments with a factorial design is becoming a tough task. Selecting sets of words that differ in one variable, while matching these same words into dozens of other confounding variables…

A Methodology for the Assessment of Experiential Learning Lean: The Lean Experience Factory Study

ERIC Educational Resources Information Center

De Zan, Giovanni; De Toni, Alberto Felice; Fornasier, Andrea; Battistella, Cinzia

2015-01-01

Purpose: The purpose of this paper is to present a methodology to assess the experiential learning processes of learning lean in an innovative learning environment: the lean model factories. Design/methodology/approach: A literature review on learning and lean management literatures was carried out to design the methodology. Then, a case study…

Performing Contrast Analysis in Factorial Designs: From NHST to Confidence Intervals and Beyond

ERIC Educational Resources Information Center

Wiens, Stefan; Nilsson, Mats E.

2017-01-01

Because of the continuing debates about statistics, many researchers may feel confused about how to analyze and interpret data. Current guidelines in psychology advocate the use of effect sizes and confidence intervals (CIs). However, researchers may be unsure about how to extract effect sizes from factorial designs. Contrast analysis is helpful…

Organization of project works in Industry 4.0 digital item designing companies

NASA Astrophysics Data System (ADS)

Gurjanov, A. V.; Zakoldaev, D. A.; Shukalov, A. V.; Zharinov, I. O.

2018-05-01

The task of the project works organization in the Industry 4.0 item designing digital factories is being studied. There is a scheme of the item designing component life cycle. There is also a scheme how to develop and confirm the quality of the item designing component documentation using the mathematical modelling. There is a description of the self-organization principles for the cyber and physical technological equipment in the Industry 4.0 «smart factory» company during the manufacturing process.

Optimal Site Characterization and Selection Criteria for Oyster Restoration using Multicolinear Factorial Water Quality Approach

NASA Astrophysics Data System (ADS)

Yoon, J.

2015-12-01

Elevated levels of nutrient loadings have enriched the Chesapeake Bay estuaries and coastal waters via point and nonpoint sources and the atmosphere. Restoring oyster beds is considered a Best Management Practice (BMP) to improve the water quality as well as provide physical aquatic habitat and a healthier estuarine system. Efforts include declaring sanctuaries for brood-stocks, supplementing hard substrate on the bottom and aiding natural populations with the addition of hatchery-reared and disease-resistant stocks. An economic assessment suggests that restoring the ecological functions will improve water quality, stabilize shorelines, and establish a habitat for breeding grounds that outweighs the value of harvestable oyster production. Parametric factorial models were developed to investigate multicolinearities among in situ water quality and oyster restoration activities to evaluate posterior success rates upon multiple substrates, and physical, chemical, hydrological and biological site characteristics to systematically identify significant factors. Findings were then further utilized to identify the optimal sites for successful oyster restoration augmentable with Total Maximum Daily Loads (TMDLs) and BMPs. Factorial models evaluate the relationship among the dependent variable, oyster biomass, and treatments of temperature, salinity, total suspended solids, E. coli/Enterococci counts, depth, dissolved oxygen, chlorophyll a, nitrogen and phosphorus, and blocks consist of alternative substrates (oyster shells versus riprap, granite, cement, cinder blocks, limestone marl or combinations). Factorial model results were then compared to identify which combination of variables produces the highest posterior biomass of oysters. Developed Factorial model can facilitate maximizing the likelihood of successful oyster reef restoration in an effort to establish a healthier ecosystem and to improve overall estuarine water quality in the Chesapeake Bay estuaries.

Solid-substrate bioprocessing of cow dung for the production of carboxymethyl cellulase by Bacillus halodurans IND18.

PubMed

Vijayaraghavan, P; Prakash Vincent, S G; Dhillon, G S

2016-02-01

The production of carboxymethyl cellulase (CMCase) by Bacillus halodurans IND18 under solid substrate fermentation (SSF) using cow dung was optimized through two level full factorial design and second order response surface methodology (RSM). The central composite design (CCD) was employed to optimize the vital fermentation parameters, such as pH of the substrate, concentration of nitrogen source (peptone) and ion (sodium dihydrogen phosphate) sources in medium for achieving higher enzyme production. The optimum medium composition was found to be 1.46% (w/w) peptone, 0.095% (w/w) sodium dihydrogen phosphate and pH 8.0. The model prediction of 4210IU/g enzyme activity at optimum conditions was verified experimentally as 4140IU/g. The enzyme was active over a broad temperature range (40-60±1°C) and pH (7.0-9.0) with maximal activity at 60±1°C and pH 8.0. This study demonstrated the potential of cow dung as novel substrate for CMCase production. Copyright © 2015 Elsevier Ltd. All rights reserved.

Design and Implementation of a Wireless Sensor and Actuator Network to Support the Intelligent Control of Efficient Energy Usage.

PubMed

Blanco, Jesús; García, Andrés; Morenas, Javier de Las

2018-06-09

Energy saving has become a major concern for the developed society of our days. This paper presents a Wireless Sensor and Actuator Network (WSAN) designed to provide support to an automatic intelligent system, based on the Internet of Things (IoT), which enables a responsible consumption of energy. The proposed overall system performs an efficient energetic management of devices, machines and processes, optimizing their operation to achieve a reduction in their overall energy usage at any given time. For this purpose, relevant data is collected from intelligent sensors, which are in-stalled at the required locations, as well as from the energy market through the Internet. This information is analysed to provide knowledge about energy utilization, and to improve efficiency. The system takes autonomous decisions automatically, based on the available information and the specific requirements in each case. The proposed system has been implanted and tested in a food factory. Results show a great optimization of energy efficiency and a substantial improvement on energy and costs savings.

Design and characterization of sustained release ketoprofen entrapped carnauba wax microparticles.

PubMed

Oliveira, Rodinelli B; Nascimento, Thais L; Lima, Eliana M

2012-01-01

Ketoprofen is a non-steroid anti-inflammatory drug (NSAID) used in the treatment of rheumatic diseases and in mild to moderate pain. Ketoprofen has a short biological half-life and the commercially available conventional release formulations require dosages to be administered at least 2-3 times a day. Due to these characteristics, ketoprofen is a good candidate for the preparation of controlled release formulations. In this work, a multiparticulate-sustained release dosage form containing ketoprofen in a carnauba wax matrix was developed. Particles were prepared by an emulsion congealing technique. System variables were optimized using fractional factorial and response surface experimental design. Characterization of the particles included size and morphology, flow rate, drug loading and in vitro drug release. Spherical particles were obtained with high drug load and sustained drug release profile. The optimized particles had an average diameter of approximately 200 µm, 50% (w/w) drug load, good flow properties and prolonged ketoprofen release for more than 24 h. Carnauba wax microspheres prepared in this work represent a new multiparticulate-sustained release system for the NSAID ketoprofen, exhibiting good potential for application in further pharmaceutical processes.

Determination of total arsenic and arsenic(III) in phosphate fertilizers by hydride generation atomic absorption spectrometry after ultrasound-assisted extraction based on a control acid media.

PubMed

Rezende, Helen Cristine; Coelho, Nivia Maria Melo

2014-01-01

An ultrasound-assisted extraction procedure was developed for determination of inorganic arsenic (As) in phosphate fertilizer by hydride generation atomic absorption spectrometry. The variables that affect the hydride generation step were optimized, including the reducer, acid, sample flow rate, and concentrations of the acid and reducer. The determination of As(lll) was performed through the simple control of solution pH with a 0.5 M citric acid-sodium citrate buffer solution at pH 4.5, and total As was determined after a pre-reduction reaction with 1.0% (w/v) thiourea. Ultrasound-assisted acid extraction was performed, and the parameters sonication time and acid and Triton X-114 concentrations were optimized using a 23 factorial design and central composite design. LODs for As(lll) and total As were 0.029 and 0.022 microg/L, respectively. The accuracy of the method was confirmed with certified reference materials. The method was successfully applied in the determination of inorganic As in phosphate fertilizer samples.

Optimization and Prediction of Ultimate Tensile Strength in Metal Active Gas Welding.

PubMed

Ampaiboon, Anusit; Lasunon, On-Uma; Bubphachot, Bopit

2015-01-01

We investigated the effect of welding parameters on ultimate tensile strength of structural steel, ST37-2, welded by Metal Active Gas welding. A fractional factorial design was used for determining the significance of six parameters: wire feed rate, welding voltage, welding speed, travel angle, tip-to-work distance, and shielded gas flow rate. A regression model to predict ultimate tensile strength was developed. Finally, we verified optimization of the process parameters experimentally. We achieved an optimum tensile strength (558 MPa) and wire feed rate, 19 m/min, had the greatest effect, followed by tip-to-work distance, 7 mm, welding speed, 200 mm/min, welding voltage, 30 V, and travel angle, 60°. Shield gas flow rate, 10 L/min, was slightly better but had little effect in the 10-20 L/min range. Tests showed that our regression model was able to predict the ultimate tensile strength within 4%.

Use of maize wastewater for the cultivation of the Pleurotus spp. mushroom and optimization of its biological efficiency.

PubMed

Loss, Edenes; Royer, Andrea Rafaela; Barreto-Rodrigues, Marcio; Barana, Ana Claudia

2009-07-30

This study evaluated the Pleurotus spp. mushroom production process using an effluent from the maize agroindustrial process as a carbon and nitrogen source and as a wetting agent. A complete experimental design based on factorial planning was used to optimize the biological efficiency and evaluate the effect of the concentration of effluent, pH and species of Pleurotus. The results indicated that the effluent affects the biological efficiency for the production of both species of mushrooms at all pH values studied. The maximum biological efficiency predicted by the model (81.36%) corresponded to the point defined by the effluent contents (X(1)=1), pH (X(2)=-1) and fungus species (X(3)=1), specifically 50%, 5.0 and P. floridae, respectively. The results demonstrated that the effluent is a good alternative for the production of Pleurotus mushrooms.

An optimized formulation of a thermostable spray dried virus-like particles vaccine against human papillomavirus

PubMed Central

Saboo, Sugandha; Tumban, Ebenezer; Peabody, Julianne; Wafula, Denis; Peabody, David S.; Chackerian, Bryce; Muttil, Pavan

2016-01-01

Existing vaccines against human papillomavirus (HPV) require continuous cold-chain storage. Previously, we developed a bacteriophage virus-like particle (VLP) based vaccine for Human Papillomavirus (HPV) infection, which elicits broadly neutralizing antibodies against diverse HPV types. Here, we formulated these VLPs into a thermostable dry powder using a multi-component excipient system and by optimizing the spray drying parameters using a half-factorial design approach. Dry powder VLPs were stable after spray drying and after long-term storage at elevated temperatures. Immunization of mice with a single dose of reconstituted dry powder VLPs that were stored at 37°C for more than a year elicited high anti-L2 IgG antibody titers. Spray dried thermostable, broadly protective L2 bacteriophage VLPs vaccine could be accessible to remote regions of the world (where ~84% of cervical cancer patients reside) by eliminating the cold-chain requirement during transportation and storage. PMID:27019231

Sample size requirements for separating out the effects of combination treatments: randomised controlled trials of combination therapy vs. standard treatment compared to factorial designs for patients with tuberculous meningitis.

PubMed

Wolbers, Marcel; Heemskerk, Dorothee; Chau, Tran Thi Hong; Yen, Nguyen Thi Bich; Caws, Maxine; Farrar, Jeremy; Day, Jeremy

2011-02-02

In certain diseases clinical experts may judge that the intervention with the best prospects is the addition of two treatments to the standard of care. This can either be tested with a simple randomized trial of combination versus standard treatment or with a 2 x 2 factorial design. We compared the two approaches using the design of a new trial in tuberculous meningitis as an example. In that trial the combination of 2 drugs added to standard treatment is assumed to reduce the hazard of death by 30% and the sample size of the combination trial to achieve 80% power is 750 patients. We calculated the power of corresponding factorial designs with one- to sixteen-fold the sample size of the combination trial depending on the contribution of each individual drug to the combination treatment effect and the strength of an interaction between the two. In the absence of an interaction, an eight-fold increase in sample size for the factorial design as compared to the combination trial is required to get 80% power to jointly detect effects of both drugs if the contribution of the less potent treatment to the total effect is at least 35%. An eight-fold sample size increase also provides a power of 76% to detect a qualitative interaction at the one-sided 10% significance level if the individual effects of both drugs are equal. Factorial designs with a lower sample size have a high chance to be underpowered, to show significance of only one drug even if both are equally effective, and to miss important interactions. Pragmatic combination trials of multiple interventions versus standard therapy are valuable in diseases with a limited patient pool if all interventions test the same treatment concept, it is considered likely that either both or none of the individual interventions are effective, and only moderate drug interactions are suspected. An adequately powered 2 x 2 factorial design to detect effects of individual drugs would require at least 8-fold the sample size of the combination trial. Current Controlled Trials ISRCTN61649292.

Tracing Staphylococcus aureus in small and medium-sized food-processing factories on the basis of molecular sub-species typing.

PubMed

Koreňová, Janka; Rešková, Zuzana; Véghová, Adriana; Kuchta, Tomáš

2015-01-01

Contamination by Staphylococcus aureus of the production environment of three small or medium-sized food-processing factories in Slovakia was investigated on the basis of sub-species molecular identification by multiple locus variable number of tandem repeats analysis (MLVA). On the basis of MLVA profiling, bacterial isolates were assigned to 31 groups. Data from repeated samplings over a period of 3 years facilitated to draw spatial and temporal maps of the contamination routes for individual factories, as well as identification of potential persistent strains. Information obtained by MLVA typing allowed to identify sources and routes of contamination and, subsequently, will allow to optimize the technical and sanitation measures to ensure hygiene.

Optimization of biotransformation from phytosterol to androstenedione by a mutant Mycobacterium neoaurum ZJUVN-08.

PubMed

Zhang, Xiao-yan; Peng, Yong; Su, Zhong-rui; Chen, Qi-he; Ruan, Hui; He, Guo-qing

2013-02-01

Biotransformation of phytosterol (PS) by a newly isolated mutant Mycobacterium neoaurum ZJUVN-08 to produce androstenedione has been investigated in this paper. The parameters of the biotransformation process were optimized using fractional factorial design and response surface methodology. Androstenedione was the sole product in the fermentation broth catalyzed by the mutant M. neoaurum ZJUVN-08 strain. Results showed that molar ratio of hydroxypropyl-β-cyclodextrin (HP-β-CD) to PS and substrate concentrations were the two most significant factors affecting androstenedione production. By analyzing the statistical model of three-dimensional surface plot, the optimal process conditions were observed at 0.1 g/L inducer, pH 7.0, molar ratio of HP-β-CD to PS 1.92:1, 8.98 g/L PS, and at 120 h of incubation time. Under these conditions, the maximum androstenedione yield was 5.96 g/L and nearly the same with the non-optimized (5.99 g/L), while the maximum PS conversion rate was 94.69% which increased by 10.66% compared with the non-optimized (84.03%). The predicted optimum conditions from the mathematical model were in agreement with the verification experimental results. It is considered that response surface methodology was a powerful and efficient method to optimize the parameters of PS biotransformation process.

Optimization of biotransformation from phytosterol to androstenedione by a mutant Mycobacterium neoaurum ZJUVN-08*

PubMed Central

Zhang, Xiao-yan; Peng, Yong; Su, Zhong-rui; Chen, Qi-he; Ruan, Hui; He, Guo-qing

2013-01-01

Biotransformation of phytosterol (PS) by a newly isolated mutant Mycobacterium neoaurum ZJUVN-08 to produce androstenedione has been investigated in this paper. The parameters of the biotransformation process were optimized using fractional factorial design and response surface methodology. Androstenedione was the sole product in the fermentation broth catalyzed by the mutant M. neoaurum ZJUVN-08 strain. Results showed that molar ratio of hydroxypropyl-β-cyclodextrin (HP-β-CD) to PS and substrate concentrations were the two most significant factors affecting androstenedione production. By analyzing the statistical model of three-dimensional surface plot, the optimal process conditions were observed at 0.1 g/L inducer, pH 7.0, molar ratio of HP-β-CD to PS 1.92:1, 8.98 g/L PS, and at 120 h of incubation time. Under these conditions, the maximum androstenedione yield was 5.96 g/L and nearly the same with the non-optimized (5.99 g/L), while the maximum PS conversion rate was 94.69% which increased by 10.66% compared with the non-optimized (84.03%). The predicted optimum conditions from the mathematical model were in agreement with the verification experimental results. It is considered that response surface methodology was a powerful and efficient method to optimize the parameters of PS biotransformation process. PMID:23365012

Promoting contraceptive use among unmarried female migrants in one factory in Shanghai: a pilot workplace intervention.

PubMed

Qian, Xu; Smith, Helen; Huang, Wenyuan; Zhang, Jie; Huang, Ying; Garner, Paul

2007-05-31

In urban China, more single women are becoming pregnant and resorting to induced abortion, despite the wide availability of temporary methods of contraception. We developed and piloted a workplace-based intervention to promote contraceptive use in unmarried female migrants working in privately owned factories. Quasi-experimental design. In consultation with clients, we developed a workplace based intervention to promote contraception use in unmarried female migrants in a privately owned factory. We then implemented this in one factory, using a controlled before-and-after design. The intervention included lectures, bespoke information leaflets, and support to the factory doctors in providing a contraceptive service. 598 women participated: most were under 25, migrants to the city, with high school education. Twenty percent were lost when staff were made redundant, and implementation was logistically complicated. All women attended the initial lecture, and just over half the second lecture. Most reported reading the educational material provided (73%), but very few women reported using the free family planning services offered at the factory clinic (5%) or the Family Planning Institute (3%). At baseline, 90% (N = 539) stated that contraceptives were required if having sex before marriage; of those reporting sex in the last three months, the majority reporting using contraceptives (78%, 62/79) but condom use was low (44%, 35/79). Qualitative data showed that the reading material seemed to be popular and young women expressed a need for more specific reproductive health information, particularly on HIV/AIDS. Women wanted services with some privacy and anonymity, and views on the factory service were mixed. Implementing a complex intervention with a hard to reach population through a factory in China, using a quasi-experimental design, is not easy. Further research should focus on the specific needs and service preferences of this population and these should be considered in any policy reform so that contraceptive use may be encouraged among young urban migrant workers.

Hydrophilic interaction liquid chromatography in analysis of granisetron HCl and its related substances. Retention mechanisms and method development.

PubMed

Maksić, Jelena; Tumpa, Anja; Stajić, Ana; Jovanović, Marko; Rakić, Tijana; Jančić-Stojanović, Biljana

2016-05-10

In this paper separation of granisetron and its two related substances in HILIC mode is presented. Separation was done on silica column derivatized with sulfoalkylbetaine groups (ZIC-HILIC). Firstly, retention mechanisms were assessed whereby retention factors of substances were followed in wide range of acetonitrile content (80-97%), at constant concentration of aqueous buffer (10mM) as well as at constant pH value of 3.0. Further, in order to developed optimal HILIC method, Design of Experiments (DoE) methodology was applied. For optimization full factorial design 3(2) was employed. Influence of acetonitrile content and ammonium acetate concentration were investigated while pH of the water phase was kept at 3.3. Adequacy of obtained mathematical models was confirmed by ANOVA. Optimization goals (α>1.15 and minimal run time) were accomplished with 94.7% of acetonitrile in mobile phase and 70 mM of ammonium acetate in water phase. Optimal point was in the middle of defined Design Space. In the next phase, robustness was experimetally tested by Rechtschaffen design. The investigated factors and their levels were: acetonitrile content (±1%), ammonium acetate molarity in water phase (±2 mM), pH value of water phase (±0.2) and column temperature (±4 °C). The validation scope included selectivity, linearity, accuracy and precision as well as determination of limit of detection (LOD) and limit of quantification (LOQ) for the related substances. Additionally, the validation acceptance criteria were met in all cases. Finally, the proposed method could be successfully utilized for estimation of granisetron HCl and its related substances in tablets and parenteral dosage forms, as well as for monitoring degradation under various stress conditions. Copyright © 2016 Elsevier B.V. All rights reserved.

Design of experiments for amino acid extraction from tobacco leaves and their subsequent determination by capillary zone electrophoresis.

PubMed

Hodek, Ondřej; Křížek, Tomáš; Coufal, Pavel; Ryšlavá, Helena

2017-03-01

In this study, we optimized a method for the determination of free amino acids in Nicotiana tabacum leaves. Capillary electrophoresis with contactless conductivity detector was used for the separation of 20 proteinogenic amino acids in acidic background electrolyte. Subsequently, the conditions of extraction with HCl were optimized for the highest extraction yield of the amino acids because sample treatment of plant materials brings some specific challenges. Central composite face-centered design with fractional factorial design was used in order to evaluate the significance of selected factors (HCl volume, HCl concentration, sonication, shaking) on the extraction process. In addition, the composite design helped us to find the optimal values for each factor using the response surface method. The limits of detection and limits of quantification for the 20 proteinogenic amino acids were found to be in the order of 10 -5 and 10 -4  mol l -1 , respectively. Addition of acetonitrile to the sample was tested as a method commonly used to decrease limits of detection. Ambiguous results of this experiment pointed out some features of plant extract samples, which often required specific approaches. Suitability of the method for metabolomic studies was tested by analysis of a real sample, in which all amino acids, except for L-methionine and L-cysteine, were successfully detected. The optimized extraction process together with the capillary electrophoresis method can be used for the determination of proteinogenic amino acids in plant materials. The resulting inexpensive, simple, and robust method is well suited for various metabolomic studies in plants. As such, the method represents a valuable tool for research and practical application in the fields of biology, biochemistry, and agriculture.

The effect of framing on surrogate optimism bias: A simulation study.

PubMed

Patel, Dev; Cohen, Elan D; Barnato, Amber E

2016-04-01

To explore the effect of emotion priming and physician communication behaviors on optimism bias. We conducted a 5 × 2 between-subject randomized factorial experiment using a Web-based interactive video designed to simulate a family meeting for a critically ill spouse/parent. Eligibility included age at least 35 years and self-identifying as the surrogate for a spouse/parent. The primary outcome was the surrogate's election of code status. We defined optimism bias as the surrogate's estimate of prognosis with cardiopulmonary resuscitation (CPR) > their recollection of the physician's estimate. Of 373 respondents, 256 (69%) logged in and were randomized and 220 (86%) had nonmissing data for prognosis. Sixty-seven (30%) of 220 overall and 56 of (32%) 173 with an accurate recollection of the physician's estimate had optimism bias. Optimism bias correlated with choosing CPR (P < .001). Emotion priming (P = .397), physician attention to emotion (P = .537), and framing of CPR as the social norm (P = .884) did not affect optimism bias. Framing the decision as the patient's vs the surrogate's (25% vs 36%, P = .066) and describing the alternative to CPR as "allow natural death" instead of "do not resuscitate" (25% vs 37%, P = .035) decreased optimism bias. Framing of CPR choice during code status conversations may influence surrogates' optimism bias. Copyright © 2015 Elsevier Inc. All rights reserved.

Quality-by-design-based ultra high performance liquid chromatography related substances method development by establishing the proficient design space for sumatriptan and naproxen combination.

PubMed

Patel, Prinesh N; Karakam, Vijaya Saradhi; Samanthula, Gananadhamu; Ragampeta, Srinivas

2015-10-01

Quality-by-design-based methods hold greater level of confidence for variations and greater success in method transfer. A quality-by-design-based ultra high performance liquid chromatography method was developed for the simultaneous assay of sumatriptan and naproxen along with their related substances. The first screening was performed by fractional factorial design comprising 44 experiments for reversed-phase stationary phases, pH, and organic modifiers. The results of screening design experiments suggested phenyl hexyl column and acetonitrile were the best combination. The method was further optimized for flow rate, temperature, and gradient time by experimental design of 20 experiments and the knowledge space was generated for effect of variable on response (number of peaks ≥ 1.50 - resolution). Proficient design space was generated from knowledge space by applying Monte Carlo simulation to successfully integrate quantitative robustness metrics during optimization stage itself. The final method provided the robust performance which was verified and validated. Final conditions comprised Waters® Acquity phenyl hexyl column with gradient elution using ammonium acetate (pH 4.12, 0.02 M) buffer and acetonitrile at 0.355 mL/min flow rate and 30°C. The developed method separates all 13 analytes within a 15 min run time with fewer experiments compared to the traditional quality-by-testing approach. ©2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Exobiopolymer production of Ophiocordyceps dipterigena BCC 2073: optimization, production in bioreactor and characterization

PubMed Central

2010-01-01

Background Biopolymers have various applications in medicine, food and petroleum industries. The ascomycetous fungus Ophiocordyceps dipterigena BCC 2073 produces an exobiopolymer, a (1→3)-β-D-glucan, in low quantity under screening conditions. Optimization of O. dipterigena BCC 2073 exobiopolymer production using experimental designs, a scale-up in 5 liter bioreactor, analysis of molecular weight at different cultivation times, and levels of induction of interleukin-8 synthesis are described in this study. Results In order to improve and certify the productivity of this strain, a sequential approach of 4 steps was followed. The first step was the qualitative selection of the most appropriate carbon and nitrogen sources (general factorial design) and the second step was quantitative optimization of 5 physiological factors (fractional factorial design). The best carbon and nitrogen source was glucose and malt extract respectively. From an initial production of 2.53 g·L-1, over 13 g·L-1 could be obtained in flasks under the improved conditions (5-fold increase). The third step was cultivation in a 5 L bioreactor, which produced a specific growth rate, biomass yield, exobiopolymer yield and exobiopolymer production rate of 0.014 h-1, 0.32 g·g-1 glucose, 2.95 g·g biomass-1 (1.31 g·g-1 sugar), and 0.65 g.(L·d)-1, respectively. A maximum yield of 41.2 g·L-1 was obtained after 377 h, a dramatic improvement in comparison to the initial production. In the last step, the basic characteristics of the biopolymer were determined. The molecular weight of the polymer was in the range of 6.3 × 105 - 7.7 × 105 Da. The exobiopolymer, at 50 and 100. μg·mL-1, induced synthesis in normal dermal human fibroblasts of 2227 and 3363 pg·mL-1 interleukin-8 respectively. Conclusions High exobiopolymer yield produced by O. dipterigena BCC 2073 after optimization by qualitative and quantitative methods is attractive for various applications. It induced high IL-8 production by normal dermal fibroblasts, which makes it promising for application as wound healing material. However, there are still other possible applications for this biopolymer, such as an alternative source of biopolymer substitute for hyaluronic acid, which is costly, as a thickening agent in the cosmetic industry due to its high viscosity property, as a moisturizer, and in encapsulation. PMID:20624309

Strategic Investment Plan Fiscal Year 1993.

DTIC Science & Technology

1993-09-01

Groundwater ........................ 283 Heavy Metals in Soils, Sludges, Sediments and Water .................... 321 Energetics in Soils and Groundwater...technologies and tools to achieve a design for reconfiguring existing PEP production facilities into agile factories which will reduce total life cycle wastes...facilities. When use of existing facilities is not practical, a special demonstration testbed may be built. The factory design will then be developed

Performing Contrast Analysis in Factorial Designs: From NHST to Confidence Intervals and Beyond

PubMed Central

Wiens, Stefan; Nilsson, Mats E.

2016-01-01

Because of the continuing debates about statistics, many researchers may feel confused about how to analyze and interpret data. Current guidelines in psychology advocate the use of effect sizes and confidence intervals (CIs). However, researchers may be unsure about how to extract effect sizes from factorial designs. Contrast analysis is helpful because it can be used to test specific questions of central interest in studies with factorial designs. It weighs several means and combines them into one or two sets that can be tested with t tests. The effect size produced by a contrast analysis is simply the difference between means. The CI of the effect size informs directly about direction, hypothesis exclusion, and the relevance of the effects of interest. However, any interpretation in terms of precision or likelihood requires the use of likelihood intervals or credible intervals (Bayesian). These various intervals and even a Bayesian t test can be obtained easily with free software. This tutorial reviews these methods to guide researchers in answering the following questions: When I analyze mean differences in factorial designs, where can I find the effects of central interest, and what can I learn about their effect sizes? PMID:29805179

Multivariate study of parameters in the determination of pesticide residues in apple by headspace solid phase microextraction coupled to gas chromatography-mass spectrometry using experimental factorial design.

PubMed

Abdulra'uf, Lukman Bola; Tan, Guan Huat

2013-12-15

Solid-phase microextraction (SPME) is a solvent-less sample preparation method which combines sample preparation, isolation, concentration and enrichment into one step. In this study, multivariate strategy was used to determine the significance of the factors affecting the solid phase microextraction of pesticide residues (fenobucarb, diazinon, chlorothalonil and chlorpyrifos) using a randomised factorial design. The interactions and effects of temperature, time and salt addition on the efficiency of the extraction of the pesticide residues were evaluated using 2(3) factorial designs. The analytes were extracted with 100 μm PDMS fibres according to the factorial design matrix and desorbed into a gas chromatography-mass spectrometry detector. The developed method was applied for the analysis of apple samples and the limits of detection were between 0.01 and 0.2 μg kg(-)(1), which were lower than the MRLs for apples. The relative standard deviations (RSD) were between 0.1% and 13.37% with average recovery of 80-105%. The linearity ranges from 0.5-50 μg kg(-)(1) with correlation coefficient greater than 0.99. Copyright © 2013 Elsevier Ltd. All rights reserved.

Design of a Conceptual Bumper Energy Absorber Coupling Pedestrian Safety and Low-Speed Impact Requirements

PubMed Central

Mo, Fuhao; Zhao, Siqi; Yu, Chuanhui; Duan, Shuyong

2018-01-01

The car front bumper system needs to meet the requirements of both pedestrian safety and low-speed impact which are somewhat contradicting. This study aims to design a new kind of modular self-adaptive energy absorber of the front bumper system which can balance the two performances. The X-shaped energy-absorbing structure was proposed which can enhance the energy absorption capacity during impact by changing its deformation mode based on the amount of external collision energy. Then, finite element simulations with a realistic vehicle bumper system are performed to demonstrate its crashworthiness in comparison with the traditional foam energy absorber, which presents a significant improvement of the two performances. Furthermore, the structural parameters of the X-shaped energy-absorbing structure including thickness (t u), side arc radius (R), and clamping boost beam thickness (t b) are analyzed using a full factorial method, and a multiobjective optimization is implemented regarding evaluation indexes of both pedestrian safety and low-speed impact. The optimal parameters are then verified, and the feasibility of the optimal results is confirmed. In conclusion, the new X-shaped energy absorber can meet both pedestrian safety and low-speed impact requirements well by altering the main deformation modes according to different impact energy levels. PMID:29581728

Design of a Conceptual Bumper Energy Absorber Coupling Pedestrian Safety and Low-Speed Impact Requirements.

PubMed

Mo, Fuhao; Zhao, Siqi; Yu, Chuanhui; Xiao, Zhi; Duan, Shuyong

2018-01-01

The car front bumper system needs to meet the requirements of both pedestrian safety and low-speed impact which are somewhat contradicting. This study aims to design a new kind of modular self-adaptive energy absorber of the front bumper system which can balance the two performances. The X-shaped energy-absorbing structure was proposed which can enhance the energy absorption capacity during impact by changing its deformation mode based on the amount of external collision energy. Then, finite element simulations with a realistic vehicle bumper system are performed to demonstrate its crashworthiness in comparison with the traditional foam energy absorber, which presents a significant improvement of the two performances. Furthermore, the structural parameters of the X-shaped energy-absorbing structure including thickness ( t u ), side arc radius ( R ), and clamping boost beam thickness ( t b ) are analyzed using a full factorial method, and a multiobjective optimization is implemented regarding evaluation indexes of both pedestrian safety and low-speed impact. The optimal parameters are then verified, and the feasibility of the optimal results is confirmed. In conclusion, the new X-shaped energy absorber can meet both pedestrian safety and low-speed impact requirements well by altering the main deformation modes according to different impact energy levels.

CEC-atmospheric pressure ionization MS of pesticides using a surfactant-bound monolithic column.

PubMed

Gu, Congying; Shamsi, Shahab A

2010-04-01

A surfactant bound poly (11-acrylaminoundecanoic acid-ethylene dimethacrylate) monolithic column was simply prepared by in situ co-polymerization of 11-acrylaminoundecanoic acid and ethylene dimethacrylate with 1-propanol, 1,4-butanediol and water as porogens in 100 microm id fused-silica capillary in one step. This column was used in CEC-atmospheric pressure photoionization (APPI)-MS system for separation and detection of N-methylcarbamates pesticides. Numerous parameters are optimized for CEC-APPI-MS. After evaluation of the mobile phase composition, sheath liquid composition and the monolithic capillary outlet position, a fractional factorial design was selected as a screening procedure to identify factors of ionization source parameters, such as sheath liquid flow rate, drying gas flow rate, drying gas temperature, nebulizing gas pressure, vaporizer temperature and capillary voltage, which significantly influence APPI-MS sensitivity. A face-centered central composite design was further utilized to optimize the most significant parameters and predict the best sensitivity. Under optimized conditions, S/Ns around 78 were achieved for an injection of 100 ng/mL of each pesticide. Finally, this CEC-APPI-MS method was successfully applied to the analysis of nine N-methylcarbamates in spiked apple juice sample after solid phase extraction with recoveries in the range of 65-109%.

Optimization of microbial detoxification for an aquatic mercury-contaminated environment.

PubMed

Figueiredo, Neusa L; Canário, João; Serralheiro, Maria Luísa; Carvalho, Cristina

2017-01-01

Mercury (Hg) reduction performed by microorganisms is well recognized as a biological means for remediation of contaminated environment. Recently, studies demonstrated that Hg-resistant microorganisms of Tagus Estuary are involved in metal reduction processes. In the present study, aerobic microbial community isolated from a highly Hg-contaminated area of Tagus Estuary was used to determine the optimization of the reduction process in conditions such as the contaminated ecosystem. Factorial design methodology was employed to examine the influence of glucose, sulfate, iron, and chloride on Hg reduction. In the presence of several concentrations of these elements, microbial community reduced Hg in a range of 37-61% of the initial 0.1 mg/ml Hg 2+ levels. The response prediction through central composite design showed that the increase of sulfate concentration led to an optimal response in Hg reduction by microbial community, while the rise in chloride levels markedly decreased metal reduction. Iron may exert antagonistic effects depending upon the media composition. These results are useful in understanding the persistence of Hg contamination in Tagus Estuary after inactivation of critical industrial units, as well as data might also be beneficial for development of new bioremediation strategies either in Tagus Estuary and/or in other Hg-contaminated aquatic environments.

Formulation and characterization of an apigenin-phospholipid phytosome (APLC) for improved solubility, in vivo bioavailability, and antioxidant potential.

PubMed

Telange, Darshan R; Patil, Arun T; Pethe, Anil M; Fegade, Harshal; Anand, Sridhar; Dave, Vivek S

2017-10-15

The apigenin-phospholipid phytosome (APLC) was developed to improve the aqueous solubility, dissolution, in vivo bioavailability, and antioxidant activity of apigenin. The APLC synthesis was guided by a full factorial design strategy, incorporating specific formulation and process variables to deliver an optimized product. The design-optimized formulation was assayed for aqueous solubility, in vitro dissolution, pharmacokinetics, and antioxidant activity. The pharmacological evaluation was carried out by assessing its effects on carbon tetrachloride-induced elevation of liver function marker enzymes in a rat model. The antioxidant activity was assessed by studying its effects on the liver antioxidant marker enzymes. The developed model was validated using the design-optimized levels of formulation and process variables. The physical-chemical characterization confirmed the formation of phytosomes. The optimized formulation demonstrated over 36-fold higher aqueous solubility of apigenin, compared to that of pure apigenin. The formulation also exhibited a significantly higher rate and extent of apigenin release in dissolution studies. The pharmacokinetic analysis revealed a significant enhancement in the oral bioavailability of apigenin from the prepared formulation, compared to pure apigenin. The liver function tests indicated that the prepared phytosome showed a significantly improved restoration of all carbon tetrachloride-elevated rat liver function marker enzymes. The prepared formulation also exhibited antioxidant potential by significantly increasing the levels of glutathione, superoxide dismutase, catalase, and decreasing the levels of lipid peroxidase. The study shows that phospholipid-based phytosome is a promising and viable strategy for improving the delivery of apigenin and similar phytoconstituents with low aqueous solubility. Copyright © 2016 Elsevier B.V. All rights reserved.

Optimization of parameters affecting signal intensity in an LTQ-orbitrap in negative ion mode: A design of experiments approach.

PubMed

Lemonakis, Nikolaos; Skaltsounis, Alexios-Leandros; Tsarbopoulos, Anthony; Gikas, Evagelos

2016-01-15

A multistage optimization of all the parameters affecting detection/response in an LTQ-orbitrap analyzer was performed, using a design of experiments methodology. The signal intensity, a critical issue for mass analysis, was investigated and the optimization process was completed in three successive steps, taking into account the three main regions of an orbitrap, the ion generation, the ion transmission and the ion detection regions. Oleuropein and hydroxytyrosol were selected as the model compounds. Overall, applying this methodology the sensitivity was increased more than 24%, the resolution more than 6.5%, whereas the elapsed scan time was reduced nearly to its half. A high-resolution LTQ Orbitrap Discovery mass spectrometer was used for the determination of the analytes of interest. Thus, oleuropein and hydroxytyrosol were infused via the instruments syringe pump and they were analyzed employing electrospray ionization (ESI) in the negative high-resolution full-scan ion mode. The parameters of the three main regions of the LTQ-orbitrap were independently optimized in terms of maximum sensitivity. In this context, factorial design, response surface model and Plackett-Burman experiments were performed and analysis of variance was carried out to evaluate the validity of the statistical model and to determine the most significant parameters for signal intensity. The optimum MS conditions for each analyte were summarized and the method optimum condition was achieved by maximizing the desirability function. Our observation showed good agreement between the predicted optimum response and the responses collected at the predicted optimum conditions. Copyright © 2015 Elsevier B.V. All rights reserved.

A factory concept for processing and manufacturing with lunar material

NASA Technical Reports Server (NTRS)

Driggers, G. W.

1977-01-01

A conceptual design for an orbital factory sized to process 1.5 million metric tons per year of raw lunar fines into 0.3 million metric tons of manufacturing materials is presented. A conservative approach involving application of present earth-based technology leads to a design devoid of new inventions. Earth based counterparts to the factory machinery were used to generate subsystem masses and lumped parameters for volume and mass estimates. The results are considered to be conservative since technologies more advanced than those assumed are presently available in many areas. Some attributes of potential space processing technologies applied to material refinement and component manufacture are discussed.

Using Bayesian variable selection to analyze regular resolution IV two-level fractional factorial designs

DOE PAGES

Chipman, Hugh A.; Hamada, Michael S.

2016-06-02

Regular two-level fractional factorial designs have complete aliasing in which the associated columns of multiple effects are identical. Here, we show how Bayesian variable selection can be used to analyze experiments that use such designs. In addition to sparsity and hierarchy, Bayesian variable selection naturally incorporates heredity . This prior information is used to identify the most likely combinations of active terms. We also demonstrate the method on simulated and real experiments.

Using Bayesian variable selection to analyze regular resolution IV two-level fractional factorial designs

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chipman, Hugh A.; Hamada, Michael S.

Regular two-level fractional factorial designs have complete aliasing in which the associated columns of multiple effects are identical. Here, we show how Bayesian variable selection can be used to analyze experiments that use such designs. In addition to sparsity and hierarchy, Bayesian variable selection naturally incorporates heredity . This prior information is used to identify the most likely combinations of active terms. We also demonstrate the method on simulated and real experiments.

The Efficiency of Split Panel Designs in an Analysis of Variance Model

PubMed Central

Wang, Wei-Guo; Liu, Hai-Jun

2016-01-01

We consider split panel design efficiency in analysis of variance models, that is, the determination of the cross-sections series optimal proportion in all samples, to minimize parametric best linear unbiased estimators of linear combination variances. An orthogonal matrix is constructed to obtain manageable expression of variances. On this basis, we derive a theorem for analyzing split panel design efficiency irrespective of interest and budget parameters. Additionally, relative estimator efficiency based on the split panel to an estimator based on a pure panel or a pure cross-section is present. The analysis shows that the gains from split panel can be quite substantial. We further consider the efficiency of split panel design, given a budget, and transform it to a constrained nonlinear integer programming. Specifically, an efficient algorithm is designed to solve the constrained nonlinear integer programming. Moreover, we combine one at time designs and factorial designs to illustrate the algorithm’s efficiency with an empirical example concerning monthly consumer expenditure on food in 1985, in the Netherlands, and the efficient ranges of the algorithm parameters are given to ensure a good solution. PMID:27163447

Design and optimization of a chromatographic purification process for Streptococcus pneumoniae serotype 23F capsular polysaccharide by a Design of Experiments approach.

PubMed

Ji, Yu; Tian, Yang; Ahnfelt, Mattias; Sui, Lili

2014-06-27

Multivalent pneumococcal vaccines were used worldwide to protect human beings from pneumococcal diseases. In order to eliminate the toxic organic solutions used in the traditional vaccine purification process, an alternative chromatographic process for Streptococcus pneumoniae serotype 23F capsular polysaccharide (CPS) was proposed in this study. The strategy of Design of Experiments (DoE) was introduced into the process development to solve the complicated design procedure. An initial process analysis was given to review the whole flowchart, identify the critical factors of chromatography through FMEA and chose the flowthrough mode due to the property of the feed. A resin screening study was then followed to select candidate resins. DoE was utilized to generate a resolution IV fractional factorial design to further compare candidates and narrow down the design space. After Capto Adhere was selected, the Box-Behnken DoE was executed to model the process and characterize all effects of factors on the responses. Finally, Monte Carlo simulation was used to optimize the process, test the chosen optimal conditions and define the control limit. The results of three scale-up runs at set points verified the DoE and simulation predictions. The final results were well in accordance with the EU pharmacopeia requirements: Protein/CPS (w/w) 1.08%; DNA/CPS (w/w) 0.61%; the phosphorus content 3.1%; the nitrogen 0.315% and the Methyl-pentose percentage 47.9%. Other tests of final pure CPS also met the pharmacopeia specifications. This alternative chromatographic purification process for pneumococcal vaccine without toxic organic solvents was successfully developed by the DoE approach and proved scalability, robustness and suitability for large scale manufacturing. Copyright © 2014 Elsevier B.V. All rights reserved.

Quantitative impurity analysis of monoclonal antibody size heterogeneity by CE-LIF: example of development and validation through a quality-by-design framework.

PubMed

Michels, David A; Parker, Monica; Salas-Solano, Oscar

2012-03-01

This paper describes the framework of quality by design applied to the development, optimization and validation of a sensitive capillary electrophoresis-sodium dodecyl sulfate (CE-SDS) assay for monitoring impurities that potentially impact drug efficacy or patient safety produced in the manufacture of therapeutic MAb products. Drug substance or drug product samples are derivatized with fluorogenic 3-(2-furoyl)quinoline-2-carboxaldehyde and nucleophilic cyanide before separation by CE-SDS coupled to LIF detection. Three design-of-experiments enabled critical labeling parameters to meet method requirements for detecting minor impurities while building precision and robustness into the assay during development. The screening design predicted optimal conditions to control labeling artifacts while two full factorial designs demonstrated method robustness through control of temperature and cyanide parameters within the normal operating range. Subsequent validation according to the guidelines of the International Committee of Harmonization showed the CE-SDS/LIF assay was specific, accurate, and precise (RSD ≤ 0.8%) for relative peak distribution and linear (R > 0.997) between the range of 0.5-1.5 mg/mL with LOD and LOQ of 10 ng/mL and 35 ng/mL, respectively. Validation confirmed the system suitability criteria used as a level of control to ensure reliable method performance. © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Long term growth responses of loblolly pine to optimal nutrient and water resource availability

Treesearch

Timothy J. Albaugh; H. Lee Allen; Phillip M. Dougherty; Kurt H. Johnsen

2004-01-01

A factorial combination of four treatments (control (CW), optimal growing season water availability (IW), optimum nutrient availability (FW), and combined optimum water and nutrient availability (FIW)) in four replications were initiated in an 8-year- old Pinus taeda stand growing on a droughty, nutrient-poor, sandy site in Scotland County, NC and...

Compatible validated spectrofluorimetric and spectrophotometric methods for determination of vildagliptin and saxagliptin by factorial design experiments.

PubMed

Abdel-Aziz, Omar; Ayad, Miriam F; Tadros, Mariam M

2015-04-05

Simple, selective and reproducible spectrofluorimetric and spectrophotometric methods have been developed for the determination of vildagliptin and saxagliptin in bulk and their pharmaceutical dosage forms. The first proposed spectrofluorimetric method is based on the dansylation reaction of the amino group of vildagliptin with dansyl chloride to form a highly fluorescent product. The formed product was measured spectrofluorimetrically at 455 nm after excitation at 345 nm. Beer's law was obeyed in a concentration range of 100-600 μg ml(-1). The second proposed spectrophotometric method is based on the charge transfer complex of saxagliptin with tetrachloro-1,4-benzoquinone (p-chloranil). The formed charge transfer complex was measured spectrophotometrically at 530 nm. Beer's law was obeyed in a concentration range of 100-850 μg ml(-1). The third proposed spectrophotometric method is based on the condensation reaction of the primary amino group of saxagliptin with formaldehyde and acetyl acetone to form a yellow colored product known as Hantzsch reaction, measured at 342.5 nm. Beer's law was obeyed in a concentration range of 50-300 μg ml(-1). All the variables were studied to optimize the reactions' conditions using factorial design. The developed methods were validated and proved to be specific and accurate for quality control of vildagliptin and saxagliptin in their pharmaceutical dosage forms. Copyright © 2015. Published by Elsevier B.V.

Compatible validated spectrofluorimetric and spectrophotometric methods for determination of vildagliptin and saxagliptin by factorial design experiments

NASA Astrophysics Data System (ADS)

Abdel-Aziz, Omar; Ayad, Miriam F.; Tadros, Mariam M.

2015-04-01

Simple, selective and reproducible spectrofluorimetric and spectrophotometric methods have been developed for the determination of vildagliptin and saxagliptin in bulk and their pharmaceutical dosage forms. The first proposed spectrofluorimetric method is based on the dansylation reaction of the amino group of vildagliptin with dansyl chloride to form a highly fluorescent product. The formed product was measured spectrofluorimetrically at 455 nm after excitation at 345 nm. Beer's law was obeyed in a concentration range of 100-600 μg ml-1. The second proposed spectrophotometric method is based on the charge transfer complex of saxagliptin with tetrachloro-1,4-benzoquinone (p-chloranil). The formed charge transfer complex was measured spectrophotometrically at 530 nm. Beer's law was obeyed in a concentration range of 100-850 μg ml-1. The third proposed spectrophotometric method is based on the condensation reaction of the primary amino group of saxagliptin with formaldehyde and acetyl acetone to form a yellow colored product known as Hantzsch reaction, measured at 342.5 nm. Beer's law was obeyed in a concentration range of 50-300 μg ml-1. All the variables were studied to optimize the reactions' conditions using factorial design. The developed methods were validated and proved to be specific and accurate for quality control of vildagliptin and saxagliptin in their pharmaceutical dosage forms.

Brain-targeted intranasal zaleplon solid dispersion in hydrophilic carrier system; 23 full-factorial design and in vivo determination of GABA neurotransmitter.

PubMed

Abd-Elrasheed, Eman; Nageeb El-Helaly, Sara; El-Ashmoony, Manal M; Salah, Salwa

2018-05-01

Intranasal zaleplon solid dispersion was formulated to enhance the solubility, bioavailability and deliver an effective therapy. Zaleplon belongs to Class II drugs, and undergoes extensive first-pass metabolism after oral absorption exhibiting 30% bioavailability. A 2 3 full-factorial design was chosen for the investigation of solid dispersion formulations. The effects of different variables include drug to carrier ratio (1:1 and 1:2), carrier type (polyethylene glycol 4000 and poloxamer 407), and preparation method (solvent evaporation and freeze drying) on different dissolution parameters were studied. The dependent variables determined from the in vitro characterization and their constraints were set as follows: minimum mean dissolution time, maximum dissolution efficiency and maximum percentage release. Numerical optimization was performed according to the constraints set based on the utilization of desirability functions. Differential scanning calorimetry, infrared spectroscopy, X-ray diffraction and scanning electron microscopy were performed. Ex vivo estimation of nasal cytotoxicity and assessment of the γ-aminobutyric acid level in plasma and brain 1 h after nasal SD administration in rabbits compared to the oral market product were conducted. The selected ZP-SD, with a desirability 0.9, composed of poloxamer 407 at drug to carrier ratio 1:2 successfully enhanced the bioavailability showing 44% increase in GABA concentration than the marketed tablets.

Production of highly efficient activated carbons from industrial wastes for the removal of pharmaceuticals from water-A full factorial design.

PubMed

Jaria, Guilaine; Silva, Carla Patrícia; Oliveira, João A B P; Santos, Sérgio M; Gil, María Victoria; Otero, Marta; Calisto, Vânia; Esteves, Valdemar I

2018-02-26

The wide occurrence of pharmaceuticals in aquatic environments urges the development of cost-effective solutions for their removal from water. In a circular economy context, primary paper mill sludge (PS) was used to produce activated carbon (AC) aiming the adsorptive removal of these contaminants. The use of low-cost precursors for the preparation of ACs capable of competing with commercial ACs continues to be a challenge. A full factorial design of four factors (pyrolysis temperature, residence time, precursor/activating agent ratio, and type of activating agent) at two levels was applied to the production of AC using PS as precursor. The responses analysed were the yield of production, percentage of adsorption for three pharmaceuticals (sulfamethoxazole, carbamazepine, and paroxetine), specific surface area (S BET ), and total organic carbon (TOC). Statistical analysis was performed to evaluate influencing factors in the responses and to determine the most favourable production conditions. Four ACs presented very good responses, namely on the adsorption of the pharmaceuticals under study (average adsorption percentage around 78%, which is above that of commercial AC), and S BET between 1389 and 1627 m 2  g -1 . A desirability analysis pointed out 800 °C for 60 min and a precursor/KOH ratio of 1:1 (w/w) as the optimal production conditions. Copyright © 2018 Elsevier B.V. All rights reserved.

Novel lectin-modified poly(ethylene-co-vinyl acetate) mucoadhesive nanoparticles of carvedilol: preparation and in vitro optimization using a two-level factorial design.

PubMed

Varshosaz, Jaleh; Moazen, Ellaheh

2014-08-01

Carvedilol used in cardiovascular diseases has systemic bioavailability of 25-35%. The objective of this study was production of lectin-modified poly(ethylene-co-vinyl acetate) (PEVA) as mucoadhesive nanoparticles to enhance low oral bioavailability of carvedilol. Nanoparticles were prepared by the emulsification-solvent evaporation method using a two-level factorial design. The studied variables included the vinyl acetate content of the polymer, drug and polymer content. Surface modification of PEVA nanoparticles with lectin was carried out by the adsorption method and coupling efficiency was determined using the Bradford assay. Mucoadhesion of nanoparticles was studied on mucin. The particle size, polydispersity index, zeta potential, drug loading and drug release from nanoparticles were studied. The morphology of nanoparticles and crystalline status of the entrapped drug were studied by SEM, DSC and XRD tests, respectively. Results showed the most effective factor on particle size and zeta potential was the interaction of polymer and drug content while, drug loading efficiency and mucoadhesion were more affected by the interaction of polymer type and drug content. Drug concentration was the most effective variable on the drug release rate. The drug was in amorphous state in nanoparticles. The optimum nanoparticles obtained by 45 mg of copolymer contained 12% vinyl acetate/4.3 ml of organic phase and drug concentration of 37.5 wt% of polymer.

Synergistic Effect of Hydrotrope and Surfactant on Solubility and Dissolution of Atorvastatin Calcium: Screening Factorial Design Followed by Ratio Optimization

PubMed Central

Patel, V. F.; Sarai, J.

2014-01-01

The present study was aimed at investigating the effect of hydrotrope and surfactant on poor solubility of atorvastatin calcium. Excipients screening followed by factorial design was performed to study effect of excipients and manufacturing methods on solubility of drug. Three independent factors (carrier, surfactant and manufacturing method) were evaluated at two levels using solubility as a dependant variable. Solid-state characterisation was performed using Fourier transform infrared spectroscopy and differential scanning calorimetry. Optimised complex were incorporated into orally disintegrating micro tablets and in vitro dissolution test was performed. Nicotinamide, Plasdone and sodium dodecyl sulphate were emerged as promising excipients from excipient screening. General regression analysis revealed only the type of carrier has significantly enhanced (P<0.05) the solubility of drug while other factors were found to be nonsignificant. Ratio optimisation trial revealed that drug to nicotinamide ratio is more critical in enhancing the solubility of drug (40 fold increases in solubility compared to pure drug) in comparison to drug-surfactant ratio; however the presence of surfactant deemed essential. Significantly higher rate and extent of dissolution was observed from solid dispersion complex and tablets compared to dissolution of pure drug (P<0.05). Study revealed hydrotrope and surfactant have synergistic effect on solubility and dissolution of atorvastatin calcium and this can be explored further. PMID:25593381

Formulation and optimization of coated PLGA – Zidovudine nanoparticles using factorial design and in vitro in vivo evaluations to determine brain targeting efficiency

PubMed Central

Peter Christoper, G.V.; Vijaya Raghavan, C.; Siddharth, K.; Siva Selva Kumar, M.; Hari Prasad, R.

2013-01-01

In the current study zidovudine loaded PLGA nanoparticles were prepared, coated and further investigated for its effectiveness in brain targeting. IR and DSC studies were performed to determine the interaction between excipients used and to find out the nature of drug in the formulation. Formulations were prepared by adopting 23 factorial designs to evaluate the effects of process and formulation variables. The prepared formulations were subjected for in vitro and in vivo evaluations. In vitro evaluations showed particle size below 100 nm, entrapment efficiency of formulations ranges of 28–57%, process yield of 60–76% was achieved and drug release for the formulations were in the range of 50–85%. The drug release from the formulations was found to follow Higuchi release pattern, n–value obtained after Korsemeyer plot was in the range of 0.56–0.78. In vivo evaluations were performed in mice after intraperitoneal administration of zidovudine drug solution, uncoated and coated formulation. Formulation when coated with Tween 80 achieved a higher concentration in the brain than that of the drug in solution and of the uncoated formulation. Stability studies indicated that there was no degradation of the drug in the formulation after 90 days of preparation when stored in refrigerated condition. PMID:24648825

Data Processing Factory for the Sloan Digital Sky Survey

NASA Astrophysics Data System (ADS)

Stoughton, Christopher; Adelman, Jennifer; Annis, James T.; Hendry, John; Inkmann, John; Jester, Sebastian; Kent, Steven M.; Kuropatkin, Nickolai; Lee, Brian; Lin, Huan; Peoples, John, Jr.; Sparks, Robert; Tucker, Douglas; Vanden Berk, Dan; Yanny, Brian; Yocum, Dan

2002-12-01

The Sloan Digital Sky Survey (SDSS) data handling presents two challenges: large data volume and timely production of spectroscopic plates from imaging data. A data processing factory, using technologies both old and new, handles this flow. Distribution to end users is via disk farms, to serve corrected images and calibrated spectra, and a database, to efficiently process catalog queries. For distribution of modest amounts of data from Apache Point Observatory to Fermilab, scripts use rsync to update files, while larger data transfers are accomplished by shipping magnetic tapes commercially. All data processing pipelines are wrapped in scripts to address consecutive phases: preparation, submission, checking, and quality control. We constructed the factory by chaining these pipelines together while using an operational database to hold processed imaging catalogs. The science database catalogs all imaging and spectroscopic object, with pointers to the various external files associated with them. Diverse computing systems address particular processing phases. UNIX computers handle tape reading and writing, as well as calibration steps that require access to a large amount of data with relatively modest computational demands. Commodity CPUs process steps that require access to a limited amount of data with more demanding computations requirements. Disk servers optimized for cost per Gbyte serve terabytes of processed data, while servers optimized for disk read speed run SQLServer software to process queries on the catalogs. This factory produced data for the SDSS Early Data Release in June 2001, and it is currently producing Data Release One, scheduled for January 2003.

Examining robustness of model selection with half-normal and LASSO plots for unreplicated factorial designs

DOE Office of Scientific and Technical Information (OSTI.GOV)

Jang, Dae -Heung; Anderson-Cook, Christine Michaela

When there are constraints on resources, an unreplicated factorial or fractional factorial design can allow efficient exploration of numerous factor and interaction effects. A half-normal plot is a common graphical tool used to compare the relative magnitude of effects and to identify important effects from these experiments when no estimate of error from the experiment is available. An alternative is to use a least absolute shrinkage and selection operation plot to examine the pattern of model selection terms from an experiment. We examine how both the half-normal and least absolute shrinkage and selection operation plots are impacted by the absencemore » of individual observations or an outlier, and the robustness of conclusions obtained from these 2 techniques for identifying important effects from factorial experiments. As a result, the methods are illustrated with 2 examples from the literature.« less

Examining robustness of model selection with half-normal and LASSO plots for unreplicated factorial designs

DOE PAGES

Jang, Dae -Heung; Anderson-Cook, Christine Michaela

2017-04-12

When there are constraints on resources, an unreplicated factorial or fractional factorial design can allow efficient exploration of numerous factor and interaction effects. A half-normal plot is a common graphical tool used to compare the relative magnitude of effects and to identify important effects from these experiments when no estimate of error from the experiment is available. An alternative is to use a least absolute shrinkage and selection operation plot to examine the pattern of model selection terms from an experiment. We examine how both the half-normal and least absolute shrinkage and selection operation plots are impacted by the absencemore » of individual observations or an outlier, and the robustness of conclusions obtained from these 2 techniques for identifying important effects from factorial experiments. As a result, the methods are illustrated with 2 examples from the literature.« less

Redesigning metabolism based on orthogonality principles

PubMed Central

Pandit, Aditya Vikram; Srinivasan, Shyam; Mahadevan, Radhakrishnan

2017-01-01

Modifications made during metabolic engineering for overproduction of chemicals have network-wide effects on cellular function due to ubiquitous metabolic interactions. These interactions, that make metabolic network structures robust and optimized for cell growth, act to constrain the capability of the cell factory. To overcome these challenges, we explore the idea of an orthogonal network structure that is designed to operate with minimal interaction between chemical production pathways and the components of the network that produce biomass. We show that this orthogonal pathway design approach has significant advantages over contemporary growth-coupled approaches using a case study on succinate production. We find that natural pathways, fundamentally linked to biomass synthesis, are less orthogonal in comparison to synthetic pathways. We suggest that the use of such orthogonal pathways can be highly amenable for dynamic control of metabolism and have other implications for metabolic engineering. PMID:28555623

Artocarpus heterophyllus L. seed starch-blended gellan gum mucoadhesive beads of metformin HCl.

PubMed

Nayak, Amit Kumar; Pal, Dilipkumar; Santra, Kousik

2014-04-01

Jackfruit (Artocarpus heterophyllus Lam., family: Moraceae) seed starch (JFSS)-gellan gum (GG) mucoadhesive beads containing metformin HCl were developed through ionotropic gelation technique. The effect of GG to JFSS ratio and CaCl2 concentration on the drug encapsulation efficiency (DEE, %) and cumulative drug release at 10h (R10h, %) was optimized and analyzed using response surface methodology based on 3(2) factorial design. The optimized JFSS-GG beads containing metformin HCl showed DEE of 92.67±4.46%, R10h of 61.30±2.37%, and mean diameter of 1.67±0.27 mm. The optimized beads showed pH-dependent swelling and mucoadhesivity with the goat intestinal mucosa. The in vitro drug release from all these JFSS-GG beads containing metformin HCl was followed zero-order pattern (R(2)=0.9907-0.9975) with super case-II transport mechanism over a period of 10 h. The beads were also characterized by SEM and FTIR. The optimized JFSS-GG beads containing metformin HCl exhibited significant hypoglycemic effect in alloxan-induced diabetic rats over prolonged period after oral administration. Copyright © 2014 Elsevier B.V. All rights reserved.

Biodegradability and toxicity assessment of a real textile wastewater effluent treated by an optimized electrocoagulation process.

PubMed

Manenti, Diego R; Módenes, Aparecido N; Soares, Petrick A; Boaventura, Rui A R; Palácio, Soraya M; Borba, Fernando H; Espinoza-Quiñones, Fernando R; Bergamasco, Rosângela; Vilar, Vítor J P

2015-01-01

In this work, the application of an iron electrode-based electrocoagulation (EC) process on the treatment of a real textile wastewater (RTW) was investigated. In order to perform an efficient integration of the EC process with a biological oxidation one, an enhancement in the biodegradability and low toxicity of final compounds was sought. Optimal values of EC reactor operation parameters (pH, current density and electrolysis time) were achieved by applying a full factorial 3(3) experimental design. Biodegradability and toxicity assays were performed on treated RTW samples obtained at the optimal values of: pH of the solution (7.0), current density (142.9 A m(-2)) and different electrolysis times. As response variables for the biodegradability and toxicity assessment, the Zahn-Wellens test (Dt), the ratio values of dissolved organic carbon (DOC) relative to low-molecular-weight carboxylates anions (LMCA) and lethal concentration 50 (LC50) were used. According to the Dt, the DOC/LMCA ratio and LC50, an electrolysis time of 15 min along with the optimal values of pH and current density were suggested as suitable for a next stage of treatment based on a biological oxidation process.

Minifactory: a precision assembly system adaptable to the product life cycle

NASA Astrophysics Data System (ADS)

Muir, Patrick F.; Rizzi, Alfred A.; Gowdy, Jay W.

1997-12-01

Automated product assembly systems are traditionally designed with the intent that they will be operated with few significant changes for as long as the product is being manufactured. This approach to factory design and programming has may undesirable qualities which have motivated the development of more 'flexible' systems. In an effort to improve agility, different types of flexibility have been integrated into factory designs. Specifically, automated assembly systems have been endowed with the ability to assemble differing products by means of computer-controlled robots, and to accommodate variations in parts locations and dimensions by means of sensing. The product life cycle (PLC) is a standard four-stage model of the performance of a product from the time that it is first introduced in the marketplace until the time that it is discontinued. Manufacturers can improve their return on investment by adapting the production process to the PLC. We are developing two concepts to enable manufacturers to more readily achieve this goal: the agile assembly architecture (AAA), an abstract framework for distributed modular automation; and minifactory, our physical instantation of this architecture for the assembly of precision electro-mechanical devices. By examining the requirements which each PLC stage places upon the production system, we identify characteristics of factory design and programming which are appropriate for that stage. As the product transitions from one stage to the next, the factory design and programing should also transition from one embodiment to the next in order to achieve the best return on investment. Modularity of the factory components, highly flexible product transport mechanisms, and a high level of distributed intelligence are key characteristics of minifactory that enable this adaptation.

A Quality by Experimental Design Approach to Assess the Effect of Formulation and Process Variables on the Extrusion and Spheronization of Drug-Loaded Pellets Containing Polyplasdone® XL-10.

PubMed

Saripella, Kalyan K; Loka, Nikhil C; Mallipeddi, Rama; Rane, Anuja M; Neau, Steven H

2016-04-01

Successful pellet production has been reported in literature with cross-linked poly(vinylpyrrolidone), Polyplasdone® XL-10 and INF-10. In the present study, a quality by experimental design approach was used to assess several formulation and process parameter effects on the characteristics of Polyplasdone® XL-10 pellets, including pellet size, shape, yield, usable yield, friability, and number of fines. The hypothesis is that design of experiments and appropriate data analysis allow optimization of the Polyplasdone product. High drug loading was achieved using caffeine, a moderately soluble drug to allow in vitro release studies. A five-factor, two-level, half-fractional factorial design (Resolution V) with center point batches allowed mathematical modeling of the influence of the factors and their two-factor interactions on five of the responses. The five factors were Polyplasdone® level in the powder blend, volume of water in the wet massing step, wet mixing time, spheronizer speed, and spheronization time. Each factor and/or its two-factor interaction with another factor influenced pellet characteristics. The behavior of these materials under various processing conditions and component levels during extrusion-spheronization have been assessed, discussed, and explained based on the results. Numerical optimization with a desirability of 0.974 was possible because curvature and lack of fit were not significant with any of the model equations. The values predicted by the optimization described well the observed responses. The hypothesis was thus supported.

Loteprednol Etabonate Nanoparticles: Optimization via Box-Behnken Design Response Surface Methodology and Physicochemical Characterization.

PubMed

Sah, Abhishek K; Suresh, Preeti K

2017-01-01

Abstract: The objective of the present work was to prepare and optimize the loteprednoletabonate (LE) loaded poly (D,L-lactide co-glycolide) (PLGA) polymer based nanoparticle carrier. The review on recent patents (US9006241, US20130224302A1, US2012/0028947A1) assisted in the selection of drug and polymer for designing nanoparticles for ocular delivery applications. The nanoparticles were prepared by solvent evaporation followed by high speed homogenization. Biodegradable polymer PLGA (50:50) grade was utilized to develop various formulations with different drug:polymer ratio. A Box-Behnken design with 33 factorial design was selected for the present study and 17 runs were carried out in totality. The influence of various process variables (viz., polymer concentration, homogenization speed and sonication time) on the characteristics of nanoparticles including the in vitro drug release profile were studied. The nanoparticulate formulations were evaluated for mean spherical diameter, polydispersity index (PDI), zeta potential, surface morphology, drug entrapment and in-vitro drug release profile. The entrapment efficiency, drug loading and mean particle size were found to be 96.31±1.68 %, 35.46±0.35 % and 167.6±2.1 nm respectively. The investigated process and formulation variables were found to have significant effect on the particle size, drug loading (DL), entrapment efficiency (EE), and in vitro drug release profile. A biphasic in vitro drug release profile was apparent from the optimized nanoparticles (NPs) for 24 hours. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Fabrication and Optimization of Stable, Optically Transparent, and Reusable pH-Responsive Silk Membranes

PubMed Central

Toytziaridis, Andreas; Dicko, Cedric

2016-01-01

The fabrication of silk-based membranes that are stable, optically transparent and reusable is yet to be achieved. To address this bottleneck we have developed a method to produce transparent chromogenic silk patches that are optically responsive to pH. The patches were produced by blending regenerated silk fibroin (RSF), Laponite RD (nano clay) and the organic dyes neutral red and Thionine acetate. The Laponite RD played a central role in the patch mechanical integrity and prevention of dye leaching. The process was optimized using a factorial design to maximize the patch response to pH by UV absorbance and fluorescence emission. New patches of the optimized protocol, made from solutions containing 125 μM neutral red or 250 μM of Thionine and 15 mg/mL silk, were further tested for operational stability over several cycles of pH altering. Stability, performance, and reusability were achieved over the tested cycles. The approach could be extended to other reporting molecules or enzymes able to bind to Laponite. PMID:27854303

Microwave-assisted extraction and mild saponification for determination of organochlorine pesticides in oyster samples.

PubMed

Carro, N; García, I; Ignacio, M-C; Llompart, M; Yebra, M-C; Mouteira, A

2002-10-01

A sample-preparation procedure (extraction and saponification) using microwave energy is proposed for determination of organochlorine pesticides in oyster samples. A Plackett-Burman factorial design has been used to optimize the microwave-assisted extraction and mild saponification on a freeze dried sample spiked with a mixture of aldrin, endrin, dieldrin, heptachlor, heptachorepoxide, isodrin, transnonachlor, p, p'-DDE, and p, p'-DDD. Six variables: solvent volume, extraction time, extraction temperature, amount of acetone (%) in the extractant solvent, amount of sample, and volume of NaOH solution were considered in the optimization process. The results show that the amount of sample is statistically significant for dieldrin, aldrin, p, p'-DDE, heptachlor, and transnonachlor and solvent volume for dieldrin, aldrin, and p, p'-DDE. The volume of NaOH solution is statistically significant for aldrin and p, p'-DDE only. Extraction temperature and extraction time seem to be the main factors determining the efficiency of extraction process for isodrin and p, p'-DDE, respectively. The optimized procedure was compared with conventional Soxhlet extraction.

Optimization and Validation of a Plaque Reduction Neutralization Test for the Detection of Neutralizing Antibodies to Four Serotypes of Dengue Virus Used in Support of Dengue Vaccine Development

PubMed Central

Timiryasova, Tatyana M.; Bonaparte, Matthew I.; Luo, Ping; Zedar, Rebecca; Hu, Branda T.; Hildreth, Stephen W.

2013-01-01

A dengue plaque reduction neutralization test (PRNT) to measure dengue serotype–specific neutralizing antibodies for all four virus serotypes was developed, optimized, and validated in accordance with guidelines for validation of bioanalytical test methods using human serum samples from dengue-infected persons and persons receiving a dengue vaccine candidate. Production and characterization of dengue challenge viruses used in the assay was standardized. Once virus stocks were characterized, the dengue PRNT50 for each of the four serotypes was optimized according to a factorial design of experiments approach for critical test parameters, including days of cell seeding before testing, percentage of overlay carboxymethylcellulose medium, and days of incubation post-infection to generate a robust assay. The PRNT50 was then validated and demonstrated to be suitable to detect and measure dengue serotype-specific neutralizing antibodies in human serum samples with acceptable intra-assay and inter-assay precision, accuracy/dilutability, specificity, and with a lower limit of quantitation of 10. PMID:23458954

Simultaneous determination of fumonisins B1 and B2 in different types of maize by matrix solid phase dispersion and HPLC-MS/MS.

PubMed

de Oliveira, Gabriel Barros; de Castro Gomes Vieira, Carolyne Menezes; Orlando, Ricardo Mathias; Faria, Adriana Ferreira

2017-10-15

This work involved the optimization and validation of a method, according to Directive 2002/657/EC and the Analytical Quality Assurance Manual of Ministério da Agricultura, Pecuária e Abastecimento, Brazil, for simultaneous extraction and determination of fumonisins B1 and B2 in maize. The extraction procedure was based on a matrix solid phase dispersion approach, the optimization of which employed a sequence of different factorial designs. A liquid chromatography-tandem mass spectrometry method was developed for determining these analytes using the selected reaction monitoring mode. The optimized method employed only 1g of silica gel for dispersion and elution with 70% ammonium formate aqueous buffer (50mmolL -1 , pH 9), representing a simple, cheap and chemically friendly sample preparation method. Trueness (recoveries: 86-106%), precision (RSD ≤19%), decision limits, detection capabilities and measurement uncertainties were calculated for the validated method. The method scope was expanded to popcorn kernels, white maize kernels and yellow maize grits. Copyright © 2017 Elsevier Ltd. All rights reserved.

Optimization of extraction of high purity all-trans-lycopene from tomato pulp waste.

PubMed

Poojary, Mahesha M; Passamonti, Paolo

2015-12-01

The aim of this work was to optimize the extraction of pure all-trans-lycopene from the pulp fractions of tomato processing waste. A full factorial design (FFD) consisting of four independent variables including extraction temperature (30-50 °C), time (1-60 min), percentage of acetone in n-hexane (25-75%, v/v) and solvent volume (10-30 ml) was used to investigate the effects of process variables on the extraction. The absolute amount of lycopene present in the pulp waste was found to be 0.038 mg/g. The optimal conditions for extraction were as follows: extraction temperature 20 °C, time 40 min, a solvent composition of 25% acetone in n-hexane (v/v) and solvent volume 40 ml. Under these conditions, the maximal recovery of lycopene was 94.7%. The HPLC-DAD analysis demonstrated that, lycopene was obtained in the all-trans-configuration at a very high purity grade of 98.3% while the amount of cis-isomers and other carotenoids were limited. Copyright © 2015 Elsevier Ltd. All rights reserved.

Floating capsules containing alginate-based beads of salbutamol sulfate: In vitro-in vivo evaluations.

PubMed

Malakar, Jadupati; Datta, Prabir Kumar; Purakayastha, Saikat Das; Dey, Sanjay; Nayak, Amit Kumar

2014-03-01

The present study deals with the development and evaluations of stomach-specific floating capsules containing salbutamol sulfate-loaded oil-entrapped alginate-based beads. Salbutamol sulfate-loaded oil-entrapped beads were prepared and capsulated within hard gelatin capsules (size 1). The effects of HPMC K4M and potato starch weight masses on drug encapsulation efficiency (DEE) of beads and cumulative drug release at 10h (R10 h) from capsules was analyzed by 3(2) factorial design. The optimization results indicate increasing of DEE in the oil-entrapped beads and decreasing R10 h from capsules with increment of HPMC K4M and potato starch weight masses. The optimized formulation showed DEE of 70.02 ± 3.16% and R10 h of 56.96 ± 2.92%. These capsules showed floatation over 6h and sustained drug release over 10h in gastric pH (1.2). In vivo X-ray imaging study of optimized floating capsules in rabbits showed stomach-specific gastroretention over a prolonged period. Copyright © 2013 Elsevier B.V. All rights reserved.

Hadron production experiments

NASA Astrophysics Data System (ADS)

Popov, Boris A.

2013-02-01

The HARP and NA61/SHINE hadroproduction experiments as well as their implications for neutrino physics are discussed. HARP measurements have already been used for predictions of neutrino beams in K2K and MiniBooNE/SciBooNE experiments and are also being used to improve the atmospheric neutrino flux predictions and to help in the optimization of neutrino factory and super-beam designs. First measurements released recently by the NA61/SHINE experiment are of significant importance for a precise prediction of the J-PARC neutrino beam used for the T2K experiment. Both HARP and NA61/SHINE experiments provide also a large amount of input for validation and tuning of hadron production models in Monte-Carlo generators.

Textile wastewater treatment and reuse by solar catalysis: results from a pilot plant in Tunisia.

PubMed

Bousselmi, L; Geissen, S U; Schroeder, H

2004-01-01

Based on results from bench-scale flow-film-reactors (FFR) and aerated cascade photoreactors, a solar catalytic pilot plant has been built at the site of a textile factory. This plant has an illuminated surface area of 50 m2 and is designed for the treatment of 1 m3 h(-1) of wastewater. The preliminary results are presented and compared with a bench-scale FFR using textile wastewater and dichloroacetic acid. Equivalent degradation kinetics were obtained and it was demonstrated that the solar catalytic technology is able to remove recalcitrant compounds and color. However, on-site optimization is still necessary for wastewater reuse and for an economic application.

Neutrino factory

DOE PAGES

Bogomilov, M.; Matev, R.; Tsenov, R.; ...

2014-12-08

The properties of the neutrino provide a unique window on physics beyond that described by the standard model. The study of subleading effects in neutrino oscillations, and the race to discover CP-invariance violation in the lepton sector, has begun with the recent discovery that theta(13) > 0. The measured value of theta(13) is large, emphasizing the need for a facility at which the systematic uncertainties can be reduced to the percent level. The neutrino factory, in which intense neutrino beams are produced from the decay of muons, has been shown to outperform all realistic alternatives and to be capable ofmore » making measurements of the requisite precision. Its unique discovery potential arises from the fact that only at the neutrino factory is it practical to produce high-energy electron (anti) neutrino beams of the required intensity. This paper presents the conceptual design of the neutrino factory accelerator facility developed by the European Commission Framework Programme 7 EURO nu. Design Study consortium. EURO nu coordinated the European contributions to the International Design Study for the Neutrino Factory (the IDS-NF) collaboration. The EURO nu baseline accelerator facility will provide 10(21) muon decays per year from 12.6 GeV stored muon beams serving a single neutrino detector situated at a source-detector distance of between 1 500 km and 2 500 km. A suite of near detectors will allow definitive neutrino-scattering experiments to be performed.« less

Multi-registration of software library resources

DOEpatents

Archer, Charles J [Rochester, MN; Blocksome, Michael A [Rochester, MN; Ratterman, Joseph D [Rochester, MN; Smith, Brian E [Rochester, MN

2011-04-05

Data communications, including issuing, by an application program to a high level data communications library, a request for initialization of a data communications service; issuing to a low level data communications library a request for registration of data communications functions; registering the data communications functions, including instantiating a factory object for each of the one or more data communications functions; issuing by the application program an instruction to execute a designated data communications function; issuing, to the low level data communications library, an instruction to execute the designated data communications function, including passing to the low level data communications library a call parameter that identifies a factory object; creating with the identified factory object the data communications object that implements the data communications function according to the protocol; and executing by the low level data communications library the designated data communications function.

Front End for a neutrino factory or muon collider

NASA Astrophysics Data System (ADS)

Neuffer, D.; Snopok, P.; Alexahin, Y.

2017-11-01

A neutrino factory or muon collider requires the capture and cooling of a large number of muons. Scenarios for capture, bunching, phase-energy rotation and initial cooling of μ 's produced from a proton source target have been developed, initially for neutrino factory scenarios. They require a drift section from the target, a bunching section and a varphi -δ E rotation section leading into the cooling channel. Important concerns are rf limitations within the focusing magnetic fields and large losses in the transport. The currently preferred cooling channel design is an "HFOFO Snake" configuration that cools both μ+ and μ- transversely and longitudinally. The status of the design is presented and variations are discussed.

Optimization-based Approach to Cross-layer Resource Management in Wireless Networked Control Systems

DTIC Science & Technology

2013-05-01

interest from both academia and industry [37], finding applications in un- manned robotic vehicles, automated highways and factories, smart homes and...is stable when the scaler varies slowly. The algorithm is further extended to utilize the slack resource in the network, which leads to the...model . . . . . . . . . . . . . . . . 66 Optimal sampling rate allocation formulation . . . . . 67 Price-based algorithm

B factory plans at Cornell

NASA Astrophysics Data System (ADS)

Berkelman, Karl

1989-12-01

Recent upgrade project at the Cornell Electron Storage Ring is discussed. Modification was made to make B mesons factory design possible. The CLEO detector has been rebuilt with a new superconducting magnet and a high resolution electromagnetic calorimeter made of cesium iodide scintillators.(AIP)

Sample size requirements for separating out the effects of combination treatments: Randomised controlled trials of combination therapy vs. standard treatment compared to factorial designs for patients with tuberculous meningitis

PubMed Central

2011-01-01

Background In certain diseases clinical experts may judge that the intervention with the best prospects is the addition of two treatments to the standard of care. This can either be tested with a simple randomized trial of combination versus standard treatment or with a 2 × 2 factorial design. Methods We compared the two approaches using the design of a new trial in tuberculous meningitis as an example. In that trial the combination of 2 drugs added to standard treatment is assumed to reduce the hazard of death by 30% and the sample size of the combination trial to achieve 80% power is 750 patients. We calculated the power of corresponding factorial designs with one- to sixteen-fold the sample size of the combination trial depending on the contribution of each individual drug to the combination treatment effect and the strength of an interaction between the two. Results In the absence of an interaction, an eight-fold increase in sample size for the factorial design as compared to the combination trial is required to get 80% power to jointly detect effects of both drugs if the contribution of the less potent treatment to the total effect is at least 35%. An eight-fold sample size increase also provides a power of 76% to detect a qualitative interaction at the one-sided 10% significance level if the individual effects of both drugs are equal. Factorial designs with a lower sample size have a high chance to be underpowered, to show significance of only one drug even if both are equally effective, and to miss important interactions. Conclusions Pragmatic combination trials of multiple interventions versus standard therapy are valuable in diseases with a limited patient pool if all interventions test the same treatment concept, it is considered likely that either both or none of the individual interventions are effective, and only moderate drug interactions are suspected. An adequately powered 2 × 2 factorial design to detect effects of individual drugs would require at least 8-fold the sample size of the combination trial. Trial registration Current Controlled Trials ISRCTN61649292 PMID:21288326

Multilayer perceptron architecture optimization using parallel computing techniques.

PubMed

Castro, Wilson; Oblitas, Jimy; Santa-Cruz, Roberto; Avila-George, Himer

2017-01-01

The objective of this research was to develop a methodology for optimizing multilayer-perceptron-type neural networks by evaluating the effects of three neural architecture parameters, namely, number of hidden layers (HL), neurons per hidden layer (NHL), and activation function type (AF), on the sum of squares error (SSE). The data for the study were obtained from quality parameters (physicochemical and microbiological) of milk samples. Architectures or combinations were organized in groups (G1, G2, and G3) generated upon interspersing one, two, and three layers. Within each group, the networks had three neurons in the input layer, six neurons in the output layer, three to twenty-seven NHL, and three AF (tan-sig, log-sig, and linear) types. The number of architectures was determined using three factorial-type experimental designs, which reached 63, 2 187, and 50 049 combinations for G1, G2 and G3, respectively. Using MATLAB 2015a, a logical sequence was designed and implemented for constructing, training, and evaluating multilayer-perceptron-type neural networks using parallel computing techniques. The results show that HL and NHL have a statistically relevant effect on SSE, and from two hidden layers, AF also has a significant effect; thus, both AF and NHL can be evaluated to determine the optimal combination per group. Moreover, in the three study groups, it is observed that there is an inverse relationship between the number of processors and the total optimization time.

Multilayer perceptron architecture optimization using parallel computing techniques

PubMed Central

Castro, Wilson; Oblitas, Jimy; Santa-Cruz, Roberto; Avila-George, Himer

2017-01-01

The objective of this research was to develop a methodology for optimizing multilayer-perceptron-type neural networks by evaluating the effects of three neural architecture parameters, namely, number of hidden layers (HL), neurons per hidden layer (NHL), and activation function type (AF), on the sum of squares error (SSE). The data for the study were obtained from quality parameters (physicochemical and microbiological) of milk samples. Architectures or combinations were organized in groups (G1, G2, and G3) generated upon interspersing one, two, and three layers. Within each group, the networks had three neurons in the input layer, six neurons in the output layer, three to twenty-seven NHL, and three AF (tan-sig, log-sig, and linear) types. The number of architectures was determined using three factorial-type experimental designs, which reached 63, 2 187, and 50 049 combinations for G1, G2 and G3, respectively. Using MATLAB 2015a, a logical sequence was designed and implemented for constructing, training, and evaluating multilayer-perceptron-type neural networks using parallel computing techniques. The results show that HL and NHL have a statistically relevant effect on SSE, and from two hidden layers, AF also has a significant effect; thus, both AF and NHL can be evaluated to determine the optimal combination per group. Moreover, in the three study groups, it is observed that there is an inverse relationship between the number of processors and the total optimization time. PMID:29236744

Production optimization of a heat-tolerant alkaline pectinase from Bacillus subtilis ZGL14 and its purification and characterization.

PubMed

Yu, Ping; Zhang, Yishu; Gu, Donglu

2017-09-03

Alkaline pectinase has important applications in the pretreatment of waste water from food processing and in both the fabric and paper industries. In this study, a 2-level factorial design was used to screen significant factors that affect the activity of alkaline pectinase, and the response surface methodology (RSM) with a Box-Behnken design (BBD) was used to optimize their concentrations. Starch, peptone, KH 2 PO 4 and K 2 HPO 4 ·3H 2 O were found to significantly affect the activity of alkaline pectinase. Their optimal concentrations were as follows: 4.68% starch, 1.6% peptone, 0.26% KH 2 PO 4 and 0.68% K 2 HPO 4 ·3H 2 O. Under the above conditions, the activity of alkaline pectinase was significantly improved to 734.11 U/mL. Alkaline pectinase was purified to homogeneity with a recovery rate of 9.6% and a specific activity of 52372.52 U/mg. Its optimal temperature and pH were 50°C and 8.6, respectively. The purified enzyme showed strong thermo-stability and good alkali resistance. In addition, the activity of alkaline pectinase was improved in the presence of Mg 2+ . Cu 2+ , Mn 2+ , and Co 2+ significantly inhibited its activity. This study provides an important basis for the future development and use of a heat-tolerant alkaline pectinase from B. subtilis ZGL14.

Production optimization of a heat-tolerant alkaline pectinase from Bacillus subtilis ZGL14 and its purification and characterization

PubMed Central

Yu, Ping; Zhang, Yishu; Gu, Donglu

2017-01-01

ABSTRACT Alkaline pectinase has important applications in the pretreatment of waste water from food processing and in both the fabric and paper industries. In this study, a 2-level factorial design was used to screen significant factors that affect the activity of alkaline pectinase, and the response surface methodology (RSM) with a Box-Behnken design (BBD) was used to optimize their concentrations. Starch, peptone, KH2PO4 and K2HPO4·3H2O were found to significantly affect the activity of alkaline pectinase. Their optimal concentrations were as follows: 4.68% starch, 1.6% peptone, 0.26% KH2PO4 and 0.68% K2HPO4·3H2O. Under the above conditions, the activity of alkaline pectinase was significantly improved to 734.11 U/mL. Alkaline pectinase was purified to homogeneity with a recovery rate of 9.6% and a specific activity of 52372.52 U/mg. Its optimal temperature and pH were 50°C and 8.6, respectively. The purified enzyme showed strong thermo-stability and good alkali resistance. In addition, the activity of alkaline pectinase was improved in the presence of Mg2+. Cu2+, Mn2+, and Co2+ significantly inhibited its activity. This study provides an important basis for the future development and use of a heat-tolerant alkaline pectinase from B. subtilis ZGL14. PMID:28282260

Formulation and optimization by experimental design of eco-friendly emulsions based on d-limonene.

PubMed

Pérez-Mosqueda, Luis M; Trujillo-Cayado, Luis A; Carrillo, Francisco; Ramírez, Pablo; Muñoz, José

2015-04-01

d-Limonene is a natural occurring solvent that can replace more pollutant chemicals in agrochemical formulations. In the present work, a comprehensive study of the influence of dispersed phase mass fraction, ϕ, and of the surfactant/oil ratio, R, on the emulsion stability and droplet size distribution of d-limonene-in-water emulsions stabilized by a non-ionic triblock copolymer surfactant has been carried out. An experimental full factorial design 3(2) was conducted in order to optimize the emulsion formulation. The independent variables, ϕ and R were studied in the range 10-50 wt% and 0.02-0.1, respectively. The emulsions studied were mainly destabilized by both creaming and Ostwald ripening. Therefore, initial droplet size and an overall destabilization parameter, the so-called turbiscan stability index, were used as dependent variables. The optimal formulation, comprising minimum droplet size and maximum stability was achieved at ϕ=50 wt%; R=0.062. Furthermore, the surface response methodology allowed us to obtain the formulation yielding sub-micron emulsions by using a single step rotor/stator homogenizer process instead of most commonly used two-step emulsification methods. In addition, the optimal formulation was further improved against Ostwald ripening by adding silicone oil to the dispersed phase. The combination of these experimental findings allowed us to gain a deeper insight into the stability of these emulsions, which can be applied to the rational development of new formulations with potential application in agrochemical formulations. Copyright © 2015 Elsevier B.V. All rights reserved.

Enhancement of pharmacokinetic and pharmacological behavior of ocular dorzolamide after factorial optimization of self-assembled nanostructures

PubMed Central

Afify, Enas A. M. R.; Elsayed, Ibrahim; Gad, Mary K.; Mohamed, Magdy I.

2018-01-01

Dorzolamide hydrochloride is frequently administered for the control of the intra-ocular pressure associated with glaucoma. The aim of this study is to develop and optimize self-assembled nanostructures of dorzolamide hydrochloride and L-α-Phosphatidylcholine to improve the pharmacokinetic parameters and extend the drug pharmacological action. Self-assembled nanostructures were prepared using a modified thin-film hydration technique. The formulae compositions were designed based on response surface statistical design. The prepared self-assembled nanostructures were characterized by testing their drug content, particle size, polydispersity index, zeta potential, partition coefficient, release half-life and extent. The optimized formulae having the highest drug content, zeta potential, partition coefficient, release half-life and extent with the lowest particle size and polydispersity index were subjected to further investigations including investigation of their physicochemical, morphological characteristics, in vivo pharmacokinetic and pharmacodynamic profiles. The optimized formulae were prepared at pH 8.7 (F5 and F6) and composed of L-α-Phosphatidylcholine and drug mixed in a ratio of 1:1 and 2:1 w/w, respectively. They showed significantly higher Cmax, AUC024 and AUC0∞ at the aqueous humor with extended control over the intra-ocular pressure, when compared to the marketed product; Trusopt®. The study introduced novel and promising self-assembled formulae able to permeate higher drug amount through the cornea and achieve sustained pharmacological effect at the site of action. PMID:29401498

Development and evaluation of a monolithic floating dosage form for furosemide.

PubMed

Menon, A; Ritschel, W A; Sakr, A

1994-02-01

The poor bioavailability of orally dosed furosemide (60%), a weakly acidic drug, is due to the presence of a biological window comprised of the upper gastrointestinal tract. The purpose of the present study was to develop and optimize in vitro a monolithic modified-release dosage form (MMR) for furosemide with increased gastric residence time and to evaluate the in vivo performance of the dosage form. The principle of floatation was used to restrict the MMR to the stomach. A two-factor three-level full factorial experimental design was employed for formulation development. A flow-through cell was designed to evaluate in vitro dissolution parameters. Quadratic regression models indicated the polymer viscosity and polymer:drug ratio to be significant (p < 0.05) formulation factors in determining the duration of buoyancy and the release profile. Statistical optimization using response surface methodology with certain physiological constraints relating to gastric emptying time predicted an optimal MMR. In vivo evaluation of the optimized MMR in beagle dogs resulted in a significant increase (p < 0.05) in the absolute bioavailability for the MMR dosage form (42.9%) as compared to the commercially available tablet (33.4%) and enteric product (29.5%). Significant in vitro/in vivo correlations (p < 0.05) were obtained for the MMR using deconvolution analysis normalized for bioavailability. The floating dosage form was found to be a feasible approach in delivering furosemide to the upper gastrointestinal tract to maximize drug absorption.

Optimization of the Critical Parameters of the Spherical Agglomeration Crystallization Method by the Application of the Quality by Design Approach.

PubMed

Gyulai, Orsolya; Kovács, Anita; Sovány, Tamás; Csóka, Ildikó; Aigner, Zoltán

2018-04-20

This research work presents the use of the Quality by Design (QbD) concept for optimization of the spherical agglomeration crystallization method in the case of the active agent, ambroxol hydrochloride (AMB HCl). AMB HCl spherical crystals were formulated by the spherical agglomeration method, which was applied as an antisolvent technique. Spherical crystals have good flowing properties, which makes the direct compression tableting method applicable. This means that the amount of additives used can be reduced and smaller tablets can be formed. For the risk assessment, LeanQbD Software was used. According to its results, four independent variables (mixing type and time, dT (temperature difference between solvent and antisolvent), and composition (solvent/antisolvent volume ratio)) and three dependent variables (mean particle size, aspect ratio, and roundness) were selected. Based on these, a 2⁻3 mixed-level factorial design was constructed, crystallization was accomplished, and the results were evaluated using Statistica for Windows 13 program. Product assay was performed and it was revealed that improvements in the mean particle size (from ~13 to ~200 µm), roundness (from ~2.4 to ~1.5), aspect ratio (from ~1.7 to ~1.4), and flow properties were observed while polymorphic transitions were avoided.

Microwave-assisted extraction at atmospheric pressure coupled to different clean-up methods for the determination of organophosphorus pesticides in olive and avocado oil.

PubMed

Fuentes, Edwar; Báez, María E; Díaz, Juan

2009-12-18

An effective extraction method was devised for the determination of organophosphorus pesticides (OPPs) in olive and avocado oil samples, using atmospheric pressure microwave-assisted liquid-liquid extraction (APMAE) and solid-phase extraction or low-temperature precipitation as clean-up step. A simple glass system equipped with an air-cooled condenser was designed as an extraction vessel. The pesticides were partitioned between acetonitrile and oil solution in hexane. Analytical determinations were carried out by gas chromatography-flame photometric detection and gas chromatography-tandem mass spectrometry, using a triple quadrupole mass analyzer, for confirmation purposes. Several factors influencing the extraction efficiency were investigated and optimized through fractional factorial design and Doehlert design. Under optimal conditions the recovery of pesticides from oil at 0.025 microg g(-1) ranged from 71% to 103%, except for fenthion in avocado oil, with RSDs < or = 13% (n=5). The LOQ for the entire method ranged from 0.004 to 0.015 microg g(-1). Finally, the proposed method was successfully applied to the extraction and determination of the selected pesticides in 20 commercially packed extra virgin olive oils and four commercially packed avocado oils produced in Chile. Detectable residues of different OPPs were observed in 85% of samples.

Optimizing flurbiprofen-loaded NLC by central composite factorial design for ocular delivery.

PubMed

Gonzalez-Mira, E; Egea, M A; Souto, E B; Calpena, A C; García, M L

2011-01-28

The purpose of this study was to design and optimize a new topical delivery system for ocular administration of flurbiprofen (FB), based on lipid nanoparticles. These particles, called nanostructured lipid carriers (NLC), were composed of a fatty acid (stearic acid (SA)) as the solid lipid and a mixture of Miglyol(®) 812 and castor oil (CO) as the liquid lipids, prepared by the hot high pressure homogenization method. After selecting the critical variables influencing the physicochemical characteristics of the NLC (the liquid lipid (i.e. oil) concentration with respect to the total lipid (cOil/L (wt%)), the surfactant and the flurbiprofen concentration, on particle size, polydispersity index and encapsulation efficiency), a three-factor five-level central rotatable composite design was employed to plan and perform the experiments. Morphological examination, crystallinity and stability studies were also performed to accomplish the optimization study. The results showed that increasing cOil/L (wt%) was followed by an enhanced tendency to produce smaller particles, but the liquid to solid lipid proportion should not exceed 30 wt% due to destabilization problems. Therefore, a 70:30 ratio of SA to oil (miglyol + CO) was selected to develop an optimal NLC formulation. The smaller particles obtained when increasing surfactant concentration led to the selection of 3.2 wt% of Tween(®) 80 (non-ionic surfactant). The positive effect of the increase in FB concentration on the encapsulation efficiency (EE) and its total solubilization in the lipid matrix led to the selection of 0.25 wt% of FB in the formulation. The optimal NLC showed an appropriate average size for ophthalmic administration (228.3 nm) with a narrow size distribution (0.156), negatively charged surface (-33.3 mV) and high EE (∼90%). The in vitro experiments proved that sustained release FB was achieved using NLC as drug carriers. Optimal NLC formulation did not show toxicity on ocular tissues.

Optimizing flurbiprofen-loaded NLC by central composite factorial design for ocular delivery

NASA Astrophysics Data System (ADS)

Gonzalez-Mira, E.; Egea, M. A.; Souto, E. B.; Calpena, A. C.; García, M. L.

2011-01-01

The purpose of this study was to design and optimize a new topical delivery system for ocular administration of flurbiprofen (FB), based on lipid nanoparticles. These particles, called nanostructured lipid carriers (NLC), were composed of a fatty acid (stearic acid (SA)) as the solid lipid and a mixture of Miglyol® 812 and castor oil (CO) as the liquid lipids, prepared by the hot high pressure homogenization method. After selecting the critical variables influencing the physicochemical characteristics of the NLC (the liquid lipid (i.e. oil) concentration with respect to the total lipid (cOil/L (wt%)), the surfactant and the flurbiprofen concentration, on particle size, polydispersity index and encapsulation efficiency), a three-factor five-level central rotatable composite design was employed to plan and perform the experiments. Morphological examination, crystallinity and stability studies were also performed to accomplish the optimization study. The results showed that increasing cOil/L (wt%) was followed by an enhanced tendency to produce smaller particles, but the liquid to solid lipid proportion should not exceed 30 wt% due to destabilization problems. Therefore, a 70:30 ratio of SA to oil (miglyol + CO) was selected to develop an optimal NLC formulation. The smaller particles obtained when increasing surfactant concentration led to the selection of 3.2 wt% of Tween® 80 (non-ionic surfactant). The positive effect of the increase in FB concentration on the encapsulation efficiency (EE) and its total solubilization in the lipid matrix led to the selection of 0.25 wt% of FB in the formulation. The optimal NLC showed an appropriate average size for ophthalmic administration (228.3 nm) with a narrow size distribution (0.156), negatively charged surface (-33.3 mV) and high EE (~90%). The in vitro experiments proved that sustained release FB was achieved using NLC as drug carriers. Optimal NLC formulation did not show toxicity on ocular tissues.

Formulation and in vivo assessment of terconazole-loaded polymeric mixed micelles enriched with Cremophor EL as dual functioning mediator for augmenting physical stability and skin delivery.

PubMed

Abd-Elsalam, Wessam H; El-Zahaby, Sally A; Al-Mahallawi, Abdulaziz M

2018-11-01

The aim of the current study was to formulate terconazole (TCZ) loaded polymeric mixed micelles (PMMs) incorporating Cremophor EL as a stabilizer and a penetration enhancer. A 2 3 full factorial design was performed using Design-Expert® software for the optimization of the PMMs which were formulated using Pluronic P123 and Pluronic F127 together with Cremophor EL. To confirm the role of Cremophor EL, PMMs formulation lacking Cremophor EL was prepared for the purpose of comparison. Results showed that the optimal PMMs formulation (F7, where the ratio of total Pluronics to drug was 40:1, the weight ratio of Pluronic P123 to Pluronic F127 was 4:1, and the percentage of Cremophor EL in aqueous phase was 5%) had a high micellar incorporation efficiency (92.98 ± 0.40%) and a very small micellar size (33.23 ± 8.00 nm). Transmission electron microscopy revealed that PMMs possess spherical shape and good dispersibility. The optimal PMMs exhibited superior physical stability when compared with the PMMs formulation of the same composition but lacking Cremophor EL. Ex vivo studies demonstrated that the optimal PMMs formula markedly improved the dermal TCZ delivery compared to PMMs lacking Cremophor EL and TCZ suspension. In addition, it was found that the optimal PMMs exhibited a greater extent of TCZ deposition in the rat dorsal skin relative to TCZ suspension. Moreover, histopathological studies revealed the safety of the optimal PMMs upon topical application to rats. Consequently, PMMs enriched with Cremophor EL, as a stable nano-system, could be promising for the skin delivery of TCZ.

Formulation and statistical optimization of self-microemulsifying drug delivery system of eprosartan mesylate for improvement of oral bioavailability.

PubMed

Dangre, Pankaj; Gilhotra, Ritu; Dhole, Shashikant

2016-10-01

The present investigation is aimed to design a statistically optimized self-microemulsifying drug delivery system (SMEDDS) of eprosartan mesylate (EM). Preliminary screening was carried out to find a suitable combination of various excipients for the formulation. A 3(2) full factorial design was employed to determine the effect of various independent variables on dependent (response) variables. The independent variables studied in the present work were concentration of oil (X 1) and the ratio of S mix (X 2), whereas the dependent variables were emulsification time (s), globule size (nm), polydispersity index (pdi), and zeta potential (mV), and the multiple linear regression analysis (MLRA) was employed to understand the influence of independent variables on dependent variables. Furthermore, a numerical optimization technique using the desirability function was used to develop a new optimized formulation with desired values of dependent variables. The optimized SMEDDS formulation of eprosartan mesylate (EMF-O) by the above method exhibited emulsification time, 118.45 ± 1.64 s; globule size, 196.81 ± 1.29 nm; zeta potential, -9.34 ± 1.2 mV, and polydispersity index, 0.354 ± 0.02. For the in vitro dissolution study, the optimized formulation (EMF-O) and pure drug were separately entrapped in the dialysis bag, and the study indicated higher release of the drug from EMF-O. In vivo pharmacokinetic studies in Wistar rats using PK solver software revealed 2.1-fold increment in oral bioavailability of EM from EMF-O, when compared with plain suspension of pure drug.

Optimizing the taste-masked formulation of acetaminophen using sodium caseinate and lecithin by experimental design.

PubMed

Hoang Thi, Thanh Huong; Lemdani, Mohamed; Flament, Marie-Pierre

2013-09-10

In a previous study of ours, the association of sodium caseinate and lecithin was demonstrated to be promising for masking the bitterness of acetaminophen via drug encapsulation. The encapsulating mechanisms were suggested to be based on the segregation of multicomponent droplets occurring during spray-drying. The spray-dried particles delayed the drug release within the mouth during the early time upon administration and hence masked the bitterness. Indeed, taste-masking is achieved if, within the frame of 1-2 min, drug substance is either not released or the released amount is below the human threshold for identifying its bad taste. The aim of this work was (i) to evaluate the effect of various processing and formulation parameters on the taste-masking efficiency and (ii) to determine the optimal formulation for optimal taste-masking effect. Four investigated input variables included inlet temperature (X1), spray flow (X2), sodium caseinate amount (X3) and lecithin amount (X4). The percentage of drug release amount during the first 2 min was considered as the response variable (Y). A 2(4)-full factorial design was applied and allowed screening for the most influential variables i.e. sodium caseinate amount and lecithin amount. Optimizing these two variables was therefore conducted by a simplex approach. The SEM and DSC results of spray-dried powder prepared under optimal conditions showed that drug seemed to be well encapsulated. The drug release during the first 2 min significantly decreased, 7-fold less than the unmasked drug particles. Therefore, the optimal formulation that performed the best taste-masking effect was successfully achieved. Copyright © 2013 Elsevier B.V. All rights reserved.

Optimized zein nanospheres for improved oral bioavailability of atorvastatin

PubMed Central

Hashem, Fahima M; Al-Sawahli, Majid M; Nasr, Mohamed; Ahmed, Osama AA

2015-01-01

Background This work focuses on the development of atorvastatin utilizing zein, a natural, safe, and biocompatible polymer, as a nanosized formulation in order to overcome the poor oral bioavailability (12%) of the drug. Methods Twelve experimental runs of atorvastatin–zein nanosphere formula were formulated by a liquid–liquid phase separation method according to custom fractional factorial design to optimize the formulation variables. The factors studied were: weight % of zein to atorvastatin (X1), pH (X2), and stirring time (X3). Levels for each formulation variable were designed. The selected dependent variables were: mean particle size (Y1), zeta potential (Y2), drug loading efficiency (Y3), drug encapsulation efficiency (Y4), and yield (Y5). The optimized formulation was assayed for compatibility using an X-ray diffraction assay. In vitro diffusion of the optimized formulation was carried out. A pharmacokinetic study was also done to compare the plasma profile of the atorvastatin–zein nanosphere formulation versus atorvastatin oral suspension and the commercially available tablet. Results The optimized atorvastatin–zein formulation had a mean particle size of 183 nm, a loading efficiency of 14.86%, and an encapsulation efficiency of 29.71%. The in vitro dissolution assay displayed an initial burst effect, with a cumulative amount of atorvastatin released of 41.76% and 82.3% after 12 and 48 hours, respectively. In Wistar albino rats, the bioavailability of atorvastatin from the optimized atorvastatin–zein formulation was 3-fold greater than that from the atorvastatin suspension and the commercially available tablet. Conclusion The atorvastatin–zein nanosphere formulation improved the oral delivery and pharmacokinetic profile of atorvastatin by enhancing its oral bioavailability. PMID:26150716

Advanced continuous cultivation methods for systems microbiology.

PubMed

Adamberg, Kaarel; Valgepea, Kaspar; Vilu, Raivo

2015-09-01

Increasing the throughput of systems biology-based experimental characterization of in silico-designed strains has great potential for accelerating the development of cell factories. For this, analysis of metabolism in the steady state is essential as only this enables the unequivocal definition of the physiological state of cells, which is needed for the complete description and in silico reconstruction of their phenotypes. In this review, we show that for a systems microbiology approach, high-resolution characterization of metabolism in the steady state--growth space analysis (GSA)--can be achieved by using advanced continuous cultivation methods termed changestats. In changestats, an environmental parameter is continuously changed at a constant rate within one experiment whilst maintaining cells in the physiological steady state similar to chemostats. This increases the resolution and throughput of GSA compared with chemostats, and, moreover, enables following of the dynamics of metabolism and detection of metabolic switch-points and optimal growth conditions. We also describe the concept, challenge and necessary criteria of the systematic analysis of steady-state metabolism. Finally, we propose that such systematic characterization of the steady-state growth space of cells using changestats has value not only for fundamental studies of metabolism, but also for systems biology-based metabolic engineering of cell factories.

The Idea Factory: An Interactive Intergroup Exercise

ERIC Educational Resources Information Center

Rosh, Lisa; Leach, Evan

2011-01-01

This article outlines the Idea Factory exercise, an interactive exercise designed to help participants examine group, individual, and organizational factors that affect intergroup conflict. Specific emphasis is placed on exploring the relationship between intra- and intergroup dynamics and identifying managerial practices that foster effective…

Replicating systems concepts: Self-replicating lunar factory and demonstration

NASA Technical Reports Server (NTRS)

1982-01-01

Automation of lunar mining and manufacturing facility maintenance and repair is addressed. Designing the factory as an automated, multiproduct, remotely controlled, reprogrammable Lunar Manufacturing Facility capable of constructing duplicates of itself which would themselves be capable of further replication is proposed.

Manufacturing data analytics using a virtual factory representation.

PubMed

Jain, Sanjay; Shao, Guodong; Shin, Seung-Jun

2017-01-01

Large manufacturers have been using simulation to support decision-making for design and production. However, with the advancement of technologies and the emergence of big data, simulation can be utilised to perform and support data analytics for associated performance gains. This requires not only significant model development expertise, but also huge data collection and analysis efforts. This paper presents an approach within the frameworks of Design Science Research Methodology and prototyping to address the challenge of increasing the use of modelling, simulation and data analytics in manufacturing via reduction of the development effort. The use of manufacturing simulation models is presented as data analytics applications themselves and for supporting other data analytics applications by serving as data generators and as a tool for validation. The virtual factory concept is presented as the vehicle for manufacturing modelling and simulation. Virtual factory goes beyond traditional simulation models of factories to include multi-resolution modelling capabilities and thus allowing analysis at varying levels of detail. A path is proposed for implementation of the virtual factory concept that builds on developments in technologies and standards. A virtual machine prototype is provided as a demonstration of the use of a virtual representation for manufacturing data analytics.

Preparation, characterization and optimization of sildenafil citrate loaded PLGA nanoparticles by statistical factorial design

PubMed Central

2013-01-01

Background and the aim of the study The objective of the present study was to formulate and optimize nanoparticles (NPs) of sildenafil-loaded poly (lactic-co-glycolic acid) (PLGA) by double emulsion solvent evaporation (DESE) method. The relationship between design factors and experimental data was evaluated using response surface methodology. Method A Box-Behnken design was made considering the mass ratio of drug to polymer (D/P), the volumetric proportion of the water to oil phase (W/O) and the concentration of polyvinyl alcohol (PVA) as the independent agents. PLGA-NPs were successfully prepared and the size (nm), entrapment efficiency (EE), drug loading (DL) and cumulative release of drug from NPs post 1 and 8 hrs were assessed as the responses. Results The NPs were prepared in a spherical shape and the sizes range of 240 to 316 nm. The polydispersity index of size was lower than 0.5 and the EE (%) and DL (%) varied between 14-62% and 2-6%, respectively. The optimized formulation with a desirability factor of 0.9 was selected and characterized. This formulation demonstrated the particle size of 270 nm, EE of 55%, DL of 3.9% and cumulative drug release of 79% after 12 hrs. In vitro release studies showed a burst release at the initial stage followed by a sustained release of sildenafil from NPs up to 12 hrs. The release kinetic of the optimized formulation was fitted to Higuchi model. Conclusions Sildenafil citrate NPs with small particle size, lipophilic feature, high entrapment efficiency and good loading capacity is produced by this method. Characterization of optimum formulation, provided by an evaluation of experimental data, showed no significant difference between calculated and measured data. PMID:24355133

Optimisation of critical medium components and culture conditions for enhanced biomass and lipid production in the oleaginous diatom Navicula phyllepta: a statistical approach.

PubMed

Sabu, Sanyo; Singh, Isaac Sarojini Bright; Joseph, Valsamma

2017-12-01

Diatoms hold great promise as potential sources of biofuel production. In the present study, the biomass and lipid production in the marine diatom Navicula phyllepta, isolated from Cochin estuary, India and identified as a potential biodiesel feedstock, were optimized using Plackett-Burman (PB) statistical experimental design followed by central composite design (CCD) and response surface methodology (RSM). The growth analyses of the isolate in different nitrogen sources, salinities and five different enriched sea water media showed the best growth in the cheapest medium with minimum components using urea as nitrogen source at salinity between 25 and 40 g kg -1 . Plackett-Burman experimental analyses for screening urea, sodium metasilicate, sodium dihydrogen phosphate, ferric chloride, salinity, temperature, pH and agitation influencing lipid and biomass production showed that silicate and temperature had a positive coefficient on biomass production, and temperature had a significant positive coefficient, while urea and phosphate showed a negative coefficient on lipid content. A 2 4 factorial central composite design (FCCD) was used to optimize the concentration of the factors selected. The optimized media resulted in 1.62-fold increase (64%) in biomass (1.2 ± 0.08 g L -1 ) and 1.2-fold increase (22%) in estimated total lipid production (0.11 ± 0.003 g L -1 ) compared to original media within 12 days of culturing. A significantly higher biomass and lipid production in the optimized medium demands further development of a two-stage strategy of biomass production followed by induction of high lipid production under nutrient limitation or varying culture conditions for large-scale production of biodiesel from the marine diatom.

Optimization of Microemulsion Based Transdermal Gel of Triamcinolone.

PubMed

Jagdale, Swati; Chaudhari, Bhagyashree

2017-01-01

Triamcinolone is a long acting corticosteroid used in the treatment of arthritis, eczema, psoriasis and similar conditions which cause inflammation. Triamcinolone has half-life of 88min. Prolonged oral use is associated with gastrointestinal adverse effects as peptic ulcer, abdominal distention and ulcerative esophagitis as described in various patents. Microemulgel offers advantage of better stability, better loading capacity and controlled release especially for drug with short half life. Objective of the present study was to optimize microemulgel based transdermal delivery of triamcinolone. Saturated solubility of triamcinolone in various oils, surfactants and co-surfactants is estimated. Pseudo-ternary phase diagrams were constructed to determine the region of transparent microemulsion. Microemulsion was evaluated for globule size (FE-SEM, zetasizer), % transmittance, pH, viscosity, conductivity etc. Design of experiment was used to optimize microemulsion based gel. Carbopol 971P and HPMC K100M were used as independent variables. Microemulsion based gel was evaluated for in-vitro as well as ex-vivo parameters. Microemulsion was formulated with oleic acid, lauroglycol FCC and propylene glycol. PDI 0.197 indicated microemulsion is mono-disperse. 32 factorial design gave batch F8 as optimized. Design expert suggested drug release; gel viscosity and bio-adhesive strength were three significant dependant factors affecting the transdermal delivery. F8 showed drug release 92.62.16±1.22% through egg membrane, 95.23±1.44% through goat skin after 8hr and Korsmeyer-Peppas release model was followed. It can be concluded that a stable, effective controlled release transdermal microemulgel was optimised for triamcinolone. This would be a promising tool to deliver triamcinolone with enhanced bioavailability and reduced dosing frequency. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Mathematical Modelling of Optimization of Structures of Monolithic Coverings Based on Liquid Rubbers

NASA Astrophysics Data System (ADS)

Turgumbayeva, R. Kh; Abdikarimov, M. N.; Mussabekov, R.; Sartayev, D. T.

2018-05-01

The paper considers optimization of monolithic coatings compositions using a computer and MPE methods. The goal of the paper was to construct a mathematical model of the complete factorial experiment taking into account its plan and conditions. Several regression equations were received. Dependence between content components and parameters of rubber, as well as the quantity of a rubber crumb, was considered. An optimal composition for manufacturing the material of monolithic coatings compositions was recommended based on experimental data.

Development of biosensors and their application in metabolic engineering.

PubMed

Zhang, Jie; Jensen, Michael K; Keasling, Jay D

2015-10-01

In a sustainable bioeconomy, many commodities and high value chemicals, including pharmaceuticals, will be manufactured using microbial cell factories from renewable feedstocks. These cell factories can be efficiently generated by constructing libraries of diversified genomes followed by screening for the desired phenotypes. However, methods available for microbial genome diversification far exceed our ability to screen and select for those variants with optimal performance. Genetically encoded biosensors have shown the potential to address this gap, given their ability to respond to small molecule binding and ease of implementation with high-throughput analysis. Here we describe recent progress in biosensor development and their applications in a metabolic engineering context. We also highlight examples of how biosensors can be integrated with synthetic circuits to exert feedback regulation on the metabolism for improved performance of cell factories. Copyright © 2015 Elsevier Ltd. All rights reserved.

Constrained Response Surface Optimisation and Taguchi Methods for Precisely Atomising Spraying Process

NASA Astrophysics Data System (ADS)

Luangpaiboon, P.; Suwankham, Y.; Homrossukon, S.

2010-10-01

This research presents a development of a design of experiment technique for quality improvement in automotive manufacturing industrial. The quality of interest is the colour shade, one of the key feature and exterior appearance for the vehicles. With low percentage of first time quality, the manufacturer has spent a lot of cost for repaired works as well as the longer production time. To permanently dissolve such problem, the precisely spraying condition should be optimized. Therefore, this work will apply the full factorial design, the multiple regression, the constrained response surface optimization methods or CRSOM, and Taguchi's method to investigate the significant factors and to determine the optimum factor level in order to improve the quality of paint shop. Firstly, 2κ full factorial was employed to study the effect of five factors including the paint flow rate at robot setting, the paint levelling agent, the paint pigment, the additive slow solvent, and non volatile solid at spraying of atomizing spraying machine. The response values of colour shade at 15 and 45 degrees were measured using spectrophotometer. Then the regression models of colour shade at both degrees were developed from the significant factors affecting each response. Consequently, both regression models were placed into the form of linear programming to maximize the colour shade subjected to 3 main factors including the pigment, the additive solvent and the flow rate. Finally, Taguchi's method was applied to determine the proper level of key variable factors to achieve the mean value target of colour shade. The factor of non volatile solid was found to be one more additional factor at this stage. Consequently, the proper level of all factors from both experiment design methods were used to set a confirmation experiment. It was found that the colour shades, both visual at 15 and 45 angel of measurement degrees of spectrophotometer, were nearly closed to the target and the defective at quality gate was also reduced from 0.35 WDPV to 0.10 WDPV. This reveals that the objective of this research is met and this procedure can be used as quality improvement guidance for paint shop of automotive vehicle.

Virtual patients design and its effect on clinical reasoning and student experience: a protocol for a randomised factorial multi-centre study.

PubMed

Bateman, James; Allen, Maggie E; Kidd, Jane; Parsons, Nick; Davies, David

2012-08-01

Virtual Patients (VPs) are web-based representations of realistic clinical cases. They are proposed as being an optimal method for teaching clinical reasoning skills. International standards exist which define precisely what constitutes a VP. There are multiple design possibilities for VPs, however there is little formal evidence to support individual design features. The purpose of this trial is to explore the effect of two different potentially important design features on clinical reasoning skills and the student experience. These are the branching case pathways (present or absent) and structured clinical reasoning feedback (present or absent). This is a multi-centre randomised 2 x 2 factorial design study evaluating two independent variables of VP design, branching (present or absent), and structured clinical reasoning feedback (present or absent).The study will be carried out in medical student volunteers in one year group from three university medical schools in the United Kingdom, Warwick, Keele and Birmingham. There are four core musculoskeletal topics. Each case can be designed in four different ways, equating to 16 VPs required for the research. Students will be randomised to four groups, completing the four VP topics in the same order, but with each group exposed to a different VP design sequentially. All students will be exposed to the four designs. Primary outcomes are performance for each case design in a standardized fifteen item clinical reasoning assessment, integrated into each VP, which is identical for each topic. Additionally a 15-item self-reported evaluation is completed for each VP, based on a widely used EViP tool. Student patterns of use of the VPs will be recorded.In one centre, formative clinical and examination performance will be recorded, along with a self reported pre and post-intervention reasoning score, the DTI. Our power calculations indicate a sample size of 112 is required for both primary outcomes. This trial will provide robust evidence to support the effectiveness of different designs of virtual patients, based on student performance and evaluation. The cases and all learning materials will be open access and available on a Creative Commons Attribution-Share-Alike license.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cai, Yunhai

Similar to a super B-factory, a circular Higgs factory (CHF) will require strong focusing systems near the interaction points and a low-emittance lattice in the arcs to achieve a factory luminosity. At electron beam energy of 125 GeV, beamstrahlung effects during the collision pose an additional challenge to the collider design. In particular, a large momentum acceptance at the 2% level is necessary to retain an adequate beam lifetime. This turns out to be the most challenging aspect in the design of a CHF. In this paper, an example will be provided to illustrate the beam dynamics in a CHF,more » emphasizing the chromatic optics. Basic optical modules and advanced analysis will be presented. Most importantly, we will show that 2% momentum aperture is achievable.« less

Front End for a neutrino factory or muon collider

DOE PAGES

Neuffer, David; Snopok, Pavel; Alexahin, Yuri

2017-11-30

A neutrino factory or muon collider requires the capture and cooling of a large number of muons. Scenarios for capture, bunching, phase-energy rotation and initial cooling of μ’s produced from a proton source target have been developed, initially for neutrino factory scenarios. They require a drift section from the target, a bunching section and a Φ-δE rotation section leading into the cooling channel. Important concerns are rf limitations within the focusing magnetic fields and large losses in the transport. The currently preferred cooling channel design is an “HFOFO Snake” configuration that cools both μ + and μ - transversely andmore » longitudinally. Finally, the status of the design is presented and variations are discussed.« less

Nanoethosomes for transdermal delivery of tropisetron HCl: multi-factorial predictive modeling, characterization, and ex vivo skin permeation.

PubMed

Abdel Messih, Hanaa A; Ishak, Rania A H; Geneidi, Ahmed S; Mansour, Samar

2017-06-01

The aim of the present work is to exclusively optimize and model the effect of phospholipid type either egg phosphatidylcholine (EPC) or soybean phosphatidylcholine (SPC), together with other formulation variables, on the development of nano-ethosomal systems for transdermal delivery of a water-soluble antiemetic drug. Tropisetron HCl (TRO) is available as hard gelatin capsules and IV injections. The transdermal delivery of TRO is considered as a novel alternative route supposing to improve BAV as well as patient convenience. TRO-loaded ethanolic vesicular systems were prepared by hot technique. The effect of formulation variables were optimized through a response surface methodology using 3 × 2 2 -level full factorial design. The concentrations of both PC (A) and ethanol (B) and PC type (C) were the factors, while entrapment efficiency (Y 1 ), vesicle size (Y 2 ), polydispersity index (Y 3 ), and zeta potential (Y 4 ) were the responses. The drug permeation across rat skin from selected formulae was studied. Particle morphology, drug-excipient interactions, and vesicle stability were also investigated. The results proved the critical role of all formulation variables on ethosomal characteristics. The suggested models for all responses showed good predictability. Only the concentration of phospholipid, irrespective to PC type, had a significant effect on the transdermal flux (p < 0.01). The ethosomal vesicles were unilamellar with a nearly spherical shape. EPC-based ethosomes proved good stability. The study suggests the applicability of statistical modeling as a promising tool for prediction of ethosomal characteristics. The ethanolic vesicles were considered as novel potential nanocarriers for accentuated transdermal TRO delivery.

Fluorescent Reporter Libraries as Useful Tools for Optimizing Microbial Cell Factories: A Review of the Current Methods and Applications

PubMed Central

Delvigne, Frank; Pêcheux, Hélène; Tarayre, Cédric

2015-01-01

The use of genetically encoded fluorescent reporters allows speeding up the initial optimization steps of microbial bioprocesses. These reporters can be used for determining the expression level of a particular promoter, not only the synthesis of a specific protein but also the content of intracellular metabolites. The level of protein/metabolite is thus proportional to a fluorescence signal. By this way, mean expression profiles of protein/metabolites can be determined non-invasively at a high-throughput rate, allowing the rapid identification of the best producers. Actually, different kinds of reporter systems are available, as well as specific cultivation devices allowing the on-line recording of the fluorescent signal. Cell-to-cell variability is another important phenomenon that can be integrated into the screening procedures for the selection of more efficient microbial cell factories. PMID:26442261

Statistical optimization of medium components for avilamycin production by Streptomyces viridochromogenes Tü57-1 using response surface methodology.

PubMed

Zhu, Chuan-He; Lu, Fu-Ping; He, Ya-Nan; Zhang, Juan-Kun; Du, Lian-Xiang

2007-04-01

A fermentation medium for avilamycin production by Streptomyces viridochromogenes Tü57-1 has been optimized. Important components and their concentrations were investigated using fractional factorial design and Box-Behnken Design. The results showed that soybean flour, soluble starch, MgSO4.7H2O and CaCl2.2H2O are important for avilamycin production. A polynomial model related to medium components and avilamycin yield had been established. A high coefficient of determination (R2 = 0.92) was obtained that indicated good agreement between the experimental and predicted values of avilamycin yield. Student's T-test of each coefficient showed that all the linear and quadratic terms had significant effect (P > |T| < 0.05) on avilamycin yield. The significance of tested components was related to MgSO4.7H2O (0.37 g/L), CaCl2.2H2O (0.39 g/L), soybean flour (21.97 g/L) and soluble starch (37.22 g/L). The yield of avilamycin reached 88.33 +/- 0.94 mg/L (p < 0.05) that was 2.8-fold the initial yield.

Determination of ibuprofen enantiomers in breast milk using vortex-assisted matrix solid-phase dispersion and direct chiral liquid chromatography.

PubMed

León-González, M E; Rosales-Conrado, N

2017-09-08

A mixture of β-cyclodextrin (β-CD) and primary and secondary amine (PSA) sorbents was employed for the extraction and quantification of ibuprofen enantiomers from human breast milk, combining a vortex-assisted matrix solid-phase dispersion method (MSPD) and direct chiral liquid chromatography (CLC) with ultraviolet detection (UV). The MSPD sample preparation procedure was optimized focusing on both the type and amount of dispersion/sorption sorbents and the nature of the elution solvent, in order to obtain acceptable recoveries and avoiding enantiomer conversion. These MSPD parameters were optimized with the aid of an experimental design approach. Hence, a factorial design was used for identification of the main variables affecting the extraction process of ibuprofen enantiomers. Under optimum selected conditions, MSPD combined with direct CLC-UV was successfully applied for ibuprofen enantiomeric determination in breast milk at enantiomer levels between 0.15 and 6.0μgg -1 . The proposed analytical method also provided good repeatability, with relative standard deviations of 6.4% and 8.3% for the intra-day and inter-day precision, respectively. Copyright © 2017 Elsevier B.V. All rights reserved.

Integrated use of residues from olive mill and winery for lipase production by solid state fermentation with Aspergillus sp.

PubMed

Salgado, José Manuel; Abrunhosa, Luís; Venâncio, Armando; Domínguez, José Manuel; Belo, Isabel

2014-02-01

Two-phase olive mill waste (TPOMW) is presently the major waste produced by the olive mill industry. This waste has potential to be used as substrate for solid state fermentation (SSF) despite of its high concentration of phenolic compounds and low nitrogen content. In this work, it is demonstrated that mixtures of TPOMW with winery wastes support the production of lipase by Aspergillus spp. By agar plate screening, Aspergillus niger MUM 03.58, Aspergillus ibericus MUM 03.49, and Aspergillus uvarum MUM 08.01 were chosen for lipase production by SSF. Plackett-Burman experimental design was employed to evaluate the effect of substrate composition and time on lipase production. The highest amounts of lipase were produced by A. ibericus on a mixture of TPOMW, urea, and exhausted grape mark (EGM). Urea was found to be the most influent factor for the lipase production. Further optimization of lipase production by A. ibericus using a full factorial design (3(2)) conducted to optimal conditions of substrate composition (0.073 g urea/g and 25 % of EGM) achieve 18.67 U/g of lipolytic activity.

Parabens abatement from surface waters by electrochemical advanced oxidation with boron doped diamond anodes.

PubMed

Domínguez, Joaquín R; Muñoz-Peña, Maria J; González, Teresa; Palo, Patricia; Cuerda-Correa, Eduardo M

2016-10-01

The removal efficiency of four commonly-used parabens by electrochemical advanced oxidation with boron-doped diamond anodes in two different aqueous matrices, namely ultrapure water and surface water from the Guadiana River, has been analyzed. Response surface methodology and a factorial, composite, central, orthogonal, and rotatable (FCCOR) statistical design of experiments have been used to optimize the process. The experimental results clearly show that the initial concentration of pollutants is the factor that influences the removal efficiency in a more remarkable manner in both aqueous matrices. As a rule, as the initial concentration of parabens increases, the removal efficiency decreases. The current density also affects the removal efficiency in a statistically significant manner in both aqueous matrices. In the water river aqueous matrix, a noticeable synergistic effect on the removal efficiency has been observed, probably due to the presence of chloride ions that increase the conductivity of the solution and contribute to the generation of strong secondary oxidant species such as chlorine or HClO/ClO - . The use of a statistical design of experiments made it possible to determine the optimal conditions necessary to achieve total removal of the four parabens in ultrapure and river water aqueous matrices.

Determination of oleamide and erucamide in polyethylene films by pressurised fluid extraction and gas chromatography.

PubMed

Garrido-López, Alvaro; Esquiu, Vanesa; Tena, María Teresa

2006-08-18

A pressurized fluid extraction (PFE) and gas chromatography-flame ionization detection (GC-FID) method is proposed to determine the slip agents in polyethylene (PE) films. The study of PFE variables was performed using a fractional factorial design (FFD) for screening and a central composite design (CCD) for optimizing the main variables obtained from the Pareto charts. The variables that were studied include temperature, static time, percentage of cyclohexane and the number of extraction cycles. The final condition selected was pure isopropanol (two times) at 105 degrees C for 16min. The recovery of spiked oleamide and erucamide was around 100%. The repeatability of the method was between 9.6% for oleamide and 8% for erucamide, expressed as relative standard deviation. Finally, the method was applied to determine oleamide and erucamide in several polyethylene films and the results were statistically equal to those obtained by pyrolysis and gas-phase chemiluminescence (CL).

Combined electrocoagulation and electro-oxidation of industrial textile wastewater treatment in a continuous multi-stage reactor.

PubMed

GilPavas, Edison; Arbeláez-Castaño, Paula; Medina, José; Acosta, Diego A

2017-11-01

A combined electrocoagulation (EC) and electrochemical oxidation (EO) industrial textile wastewater treatment potential is evaluated in this work. A fractional factorial design of experiment showed that EC current density, followed by pH, were the most significant factors. Conductivity and number of electrooxidation cells did not affect chemical oxygen demand degradation (DCOD). Aluminum and iron anodes performed similarly as sacrificial anodes. Current density, pH and conductivity were chosen for a Box-Behnken design of experiment to determine optimal conditions to achieve a high DCOD minimizing operating cost (OC). The optimum to achieve a 70% DCOD with an OC of USD 1.47/m 3 was: pH of 4, a conductivity of 3.7 mS/cm and a current density of 4.1 mA/cm 2 . This study also shows the applicability of a combined EC/EO treatment process of a real complex industrial wastewater.

Process optimization for sensory characteristics of seriales (Flacourtia jangomas) ready-to-drink (RTD) beverage

NASA Astrophysics Data System (ADS)

Cimafranca, L.; Dizon, E.

2018-01-01

Seriales (Flacourtia jangomas) is an underutilized fruit in the Philippines. The processing of the fruit into a RTD beverage was standardized by statistical methods. Plackett-Burman Design (PB) was used to determine the most significant factors that affect the sensory characteristics of the product. Response surface methodology (RSM) was applied based on the factorial Central Composite Design (CCD) to determine the optimum conditions for the maximum sensory acceptability of the seriales RTD beverage. Results of the PB revealed that the most significant factors were blanching time, level of seriales and TSS level. With different levels of blanching time (0.5, 1.0, and 1.5 min.), seriales level (10, 20, 30 %) and TSS value (12, 15, 18ºBrix), the optimum region for sensory acceptability was perceived at 0.7 to 1.4 minutes blanching time, seriales level of not beyond 27 %, and TSS at any level.

R&D of the CEPC scintillator-tungsten ECAL

NASA Astrophysics Data System (ADS)

Dong, M. Y.

2018-03-01

The circular electron and positron collider (CEPC) was proposed as a future Higgs factory. To meet the physics requirements, a particle flow algorithm-oriented calorimeter system with high energy resolution and precise reconstruction is considered. A sampling calorimeter with scintillator-tungsten sandwich structure is selected as one of the electromagnetic calorimeter (ECAL) options due to its good performance and relatively low cost. We present the design, the test and the optimization of the scintillator module read out by silicon photomultiplier (SiPM), including the design and the development of the electronics. To estimate the performance of the scintillator and SiPM module for particles with different energy, the beam test of a mini detector prototype without tungsten shower material was performed at the E3 beams in Institute of High Energy Physics (IHEP). The results are consistent with the expectation. These studies provide a reference and promote the development of particle flow electromagnetic calorimeter for the CEPC.

Deep eutectic solvent-based valorization of spent coffee grounds.

PubMed

Yoo, Da Eun; Jeong, Kyung Min; Han, Se Young; Kim, Eun Mi; Jin, Yan; Lee, Jeongmi

2018-07-30

Spent coffee grounds (SCGs) are viewed as a valuable resource for useful bioactive compounds, such as chlorogenic acids and flavonoids, and we suggest an eco-friendly and efficient valorization method. A series of choline chloride-based deep eutectic solvents (DESs) were tested as green extraction solvents for use with ultrasound-assisted extraction. Extraction efficiency was evaluated based on total phenolic content (TPC), total flavonoid content, total chlorogenic acids, and/or anti-oxidant activity. A binary DES named HC-6, which was composed of 1,6-hexanediol:choline chloride (molar ratio 7:1) was designed to produce the highest efficiency. Experimental conditions were screened and optimized for maximized efficiency using a two-level fractional factorial design and a central composite design, respectively. As a result, the proposed method presented significantly enhanced TPC and anti-oxidant activity. In addition, phenolic compounds could be easily recovered from extracts at high recovery yields (>90%) by adsorption chromatography. Copyright © 2018 Elsevier Ltd. All rights reserved.

Establishing a Mathematical Equations and Improving the Production of L-tert-Leucine by Uniform Design and Regression Analysis.

PubMed

Jiang, Wei; Xu, Chao-Zhen; Jiang, Si-Zhi; Zhang, Tang-Duo; Wang, Shi-Zhen; Fang, Bai-Shan

2017-04-01

L-tert-Leucine (L-Tle) and its derivatives are extensively used as crucial building blocks for chiral auxiliaries, pharmaceutically active ingredients, and ligands. Combining with formate dehydrogenase (FDH) for regenerating the expensive coenzyme NADH, leucine dehydrogenase (LeuDH) is continually used for synthesizing L-Tle from α-keto acid. A multilevel factorial experimental design was executed for research of this system. In this work, an efficient optimization method for improving the productivity of L-Tle was developed. And the mathematical model between different fermentation conditions and L-Tle yield was also determined in the form of the equation by using uniform design and regression analysis. The multivariate regression equation was conveniently implemented in water, with a space time yield of 505.9 g L -1  day -1 and an enantiomeric excess value of >99 %. These results demonstrated that this method might become an ideal protocol for industrial production of chiral compounds and unnatural amino acids such as chiral drug intermediates.

Procedure for developing experimental designs for accelerated tests for service-life prediction. [for solar cell modules

NASA Technical Reports Server (NTRS)

Thomas, R. E.; Gaines, G. B.

1978-01-01

Recommended design procedures to reduce the complete factorial design by retaining information on anticipated important interaction effects, and by generally giving up information on unconditional main effects are discussed. A hypothetical photovoltaic module used in the test design is presented. Judgments were made of the relative importance of various environmental stresses such as UV radiation, abrasion, chemical attack, temperature, mechanical stress, relative humidity and voltage. Consideration is given to a complete factorial design and its graphical representation, elimination of selected test conditions, examination and improvement of an engineering design, and parametric study. The resulting design consists of a mix of conditional main effects and conditional interactions and represents a compromise between engineering and statistical requirements.

Improving the fermentation production of the individual key triterpene ganoderic acid me by the medicinal fungus Ganoderma lucidum in submerged culture.

PubMed

Liu, Gao-Qiang; Wang, Xiao-Ling; Han, Wen-Jun; Lin, Qin-Lu

2012-10-24

Enhanced ganoderic acid Me (GA-Me, an important anti-tumor triterpene) yield was attained with the medicinal fungus Ganoderma lucidum using response surface methodology (RSM). Interactions were studied with three variables, viz. glucose, peptone and culture time using a Central Composite Design (CCD). The CCD contains a total of 20 experiments with the first 14 experiments organized in a fractional factorial design, with the experimental trails from 15 to 20 involving the replications of the central points. A polynomial model, describing the relationships between the yield of GA-Me and the three factors in a second-order equation, was developed. The model predicted the maximum GA-Me yield of 11.9 mg·L−1 for glucose, peptone, culture time values of 44.4 g·L−1, 5.0 g·L−1, 437.1 h, respectively, and a maximum GA-Me yield of 12.4 mg·L−1 was obtained in the validation experiment, which represented a 129.6% increase in titre compared to that of the non-optimized conditions. In addition, 11.4 mg·L−1 of GA-Me was obtained in a 30-L agitated fermenter under the optimized conditions, suggesting the submerged culture conditions optimized in the present study were also suitable for GA-Me production on a large scale.

Solid formulation of a supersaturable self-microemulsifying drug delivery system for valsartan with improved dissolution and bioavailability

PubMed Central

Yeom, Dong Woo; Chae, Bo Ram; Kim, Jin Han; Chae, Jun Soo; Shin, Dong Jun; Kim, Chang Hyun; Kim, Sung Rae; Choi, Ji Ho; Song, Seh Hyon; Oh, Dongho; Sohn, Se Il; Choi, Young Wook

2017-01-01

In order to improve the dissolution and oral bioavailability of valsartan (VST), and reduce the required volume for treatment, we previously formulated a supersaturable self-microemulsifying drug delivery system (SuSMEDDS) composed of VST (80 mg), Capmul® MCM (13.2 mg), Tween® 80 (59.2 mg), Transcutol® P (59.2 mg), and Poloxamer 407 (13.2 mg). In the present study, by using Florite® PS-10 (119.1 mg) and Vivapur® 105 (105.6 mg) as solid carriers, VST-loaded solidified SuSMEDDS (S-SuSMEDDS) granules were successfully developed, which possessed good flow properties and rapid drug dissolution. By introducing croscarmellose sodium (31 mg) as a superdisintegrant, S-SuSMEDDS tablets were also successfully formulated, which showed fast disintegration and high dissolution efficiency. Preparation of granules and tablets was successfully optimized using D-optimal mixture design and 3-level factorial design, respectively, resulting in percentage prediction errors of <10%. In pharmacokinetic studies in rats, the relative bioavailability of the optimized granules was 107% and 222% of values obtained for SuSMEDDS and Diovan® powder, respectively. Therefore, we conclude that novel S-SuSMEDDS formulations offer great potential for developing solid dosage forms of a liquefied formulation such as SuSMEDDS, while improving oral absorption of drugs with poor water solubility. PMID:29212229

Solid formulation of a supersaturable self-microemulsifying drug delivery system for valsartan with improved dissolution and bioavailability.

PubMed

Yeom, Dong Woo; Chae, Bo Ram; Kim, Jin Han; Chae, Jun Soo; Shin, Dong Jun; Kim, Chang Hyun; Kim, Sung Rae; Choi, Ji Ho; Song, Seh Hyon; Oh, Dongho; Sohn, Se Il; Choi, Young Wook

2017-11-07

In order to improve the dissolution and oral bioavailability of valsartan (VST), and reduce the required volume for treatment, we previously formulated a supersaturable self-microemulsifying drug delivery system (SuSMEDDS) composed of VST (80 mg), Capmul ® MCM (13.2 mg), Tween ® 80 (59.2 mg), Transcutol ® P (59.2 mg), and Poloxamer 407 (13.2 mg). In the present study, by using Florite ® PS-10 (119.1 mg) and Vivapur ® 105 (105.6 mg) as solid carriers, VST-loaded solidified SuSMEDDS (S-SuSMEDDS) granules were successfully developed, which possessed good flow properties and rapid drug dissolution. By introducing croscarmellose sodium (31 mg) as a superdisintegrant, S-SuSMEDDS tablets were also successfully formulated, which showed fast disintegration and high dissolution efficiency. Preparation of granules and tablets was successfully optimized using D-optimal mixture design and 3-level factorial design, respectively, resulting in percentage prediction errors of <10%. In pharmacokinetic studies in rats, the relative bioavailability of the optimized granules was 107% and 222% of values obtained for SuSMEDDS and Diovan ® powder, respectively. Therefore, we conclude that novel S-SuSMEDDS formulations offer great potential for developing solid dosage forms of a liquefied formulation such as SuSMEDDS, while improving oral absorption of drugs with poor water solubility.

Design of nanosuspensions and freeze-dried PLGA nanoparticles as a novel approach for ophthalmic delivery of pranoprofen.

PubMed

Abrego, Guadalupe; Alvarado, Helen L; Egea, Maria A; Gonzalez-Mira, Elizabeth; Calpena, Ana C; Garcia, Maria L

2014-10-01

Pranoprofen (PF)-loaded poly (lactic-co-glycolic) acid (PLGA) nanoparticles (NPs) were optimized and characterized as a means of exploring novel formulations to improve the biopharmaceutical profile of this drug. These systems were prepared using the solvent displacement technique, with polyvinyl alcohol (PVA) as a stabilizer. A factorial design was applied to study the influence of several factors (the pH of the aqueous phase and the stabilizer, polymer and drug concentrations) on the physicochemical properties of the NPs. After optimization, the study was performed at two different aqueous phase pH values (4.50 and 5.50), two concentrations of PF (1.00 and 1.50 mg/mL), three of PVA (5, 10, and 25 mg/mL), and two of PLGA (9.00 and 9.50 mg/mL). These conditions produced NPs of a size appropriate particle size for ocular administration (around 350 nm) and high entrapment efficiency (80%). To improve their stability, the optimized NPs were lyophilized. X-ray, FTIR, and differential scanning calorimetry analysis confirmed the drug was dispersed inside the particles. The release profiles of PF from the primary nanosuspensions and rehydrated freeze-dried NPs were similar and exhibited a sustained drug delivery pattern. The ocular tolerance was assessed by an HET-CAM test. No signs of ocular irritancy were detected (score 0). © 2014 Wiley Periodicals, Inc. and the American Pharmacists Association.

High pressure autothermal reforming in low oxygen environments

NASA Astrophysics Data System (ADS)

Reese, Mark A.; Turn, Scott Q.; Cui, Hong

Recent interest in fuel cells has led to the conceptual design of an ocean floor, fuel cell-based, power generating station fueled by methane from natural gas seeps or from the controlled decomposition of methane hydrates. Because the dissolved oxygen concentration in deep ocean water is too low to provide adequate supplies to a fuel processor and fuel cell, oxygen must be stored onboard the generating station. A lab scale catalytic autothermal reformer capable of operating at pressures of 6-50 bar was constructed and tested. The objective of the experimental program was to maximize H 2 production per mole of O 2 supplied (H 2(out)/O 2(in)). Optimization, using oxygen-to-carbon (O 2/C) and water-to-carbon (S/C) ratios as independent variables, was conducted at three pressures using bottled O 2. Surface response methodology was employed using a 2 2 factorial design. Optimal points were validated using H 2O 2 as both a stored oxidizer and steam source. The optimal experimental conditions for maximizing the moles of H 2(out)/O 2(in) occurred at a S/C ratio of 3.00-3.35 and an O 2/C ratio of 0.44-0.48. When using H 2O 2 as the oxidizer, the moles of H 2(out)/O 2(in) increased ≤14%. An equilibrium model was also used to compare experimental and theoretical results.

Artificial neural networks as alternative tool for minimizing error predictions in manufacturing ultradeformable nanoliposome formulations.

PubMed

León Blanco, José M; González-R, Pedro L; Arroyo García, Carmen Martina; Cózar-Bernal, María José; Calle Suárez, Marcos; Canca Ortiz, David; Rabasco Álvarez, Antonio María; González Rodríguez, María Luisa

2018-01-01

This work was aimed at determining the feasibility of artificial neural networks (ANN) by implementing backpropagation algorithms with default settings to generate better predictive models than multiple linear regression (MLR) analysis. The study was hypothesized on timolol-loaded liposomes. As tutorial data for ANN, causal factors were used, which were fed into the computer program. The number of training cycles has been identified in order to optimize the performance of the ANN. The optimization was performed by minimizing the error between the predicted and real response values in the training step. The results showed that training was stopped at 10 000 training cycles with 80% of the pattern values, because at this point the ANN generalizes better. Minimum validation error was achieved at 12 hidden neurons in a single layer. MLR has great prediction ability, with errors between predicted and real values lower than 1% in some of the parameters evaluated. Thus, the performance of this model was compared to that of the MLR using a factorial design. Optimal formulations were identified by minimizing the distance among measured and theoretical parameters, by estimating the prediction errors. Results indicate that the ANN shows much better predictive ability than the MLR model. These findings demonstrate the increased efficiency of the combination of ANN and design of experiments, compared to the conventional MLR modeling techniques.

The Walking Interventions Through Texting (WalkIT) Trial: Rationale, Design, and Protocol for a Factorial Randomized Controlled Trial of Adaptive Interventions for Overweight and Obese, Inactive Adults.

PubMed

Hurley, Jane C; Hollingshead, Kevin E; Todd, Michael; Jarrett, Catherine L; Tucker, Wesley J; Angadi, Siddhartha S; Adams, Marc A

2015-09-11

Walking is a widely accepted and frequently targeted health promotion approach to increase physical activity (PA). Interventions to increase PA have produced only small improvements. Stronger and more potent behavioral intervention components are needed to increase time spent in PA, improve cardiometabolic risk markers, and optimize health. Our aim is to present the rationale and methods from the WalkIT Trial, a 4-month factorial randomized controlled trial (RCT) in inactive, overweight/obese adults. The main purpose of the study was to evaluate whether intensive adaptive components result in greater improvements to adults' PA compared to the static intervention components. Participants enrolled in a 2x2 factorial RCT and were assigned to one of four semi-automated, text message-based walking interventions. Experimental components included adaptive versus static steps/day goals, and immediate versus delayed reinforcement. Principles of percentile shaping and behavioral economics were used to operationalize experimental components. A Fitbit Zip measured the main outcome: participants' daily physical activity (steps and cadence) over the 4-month duration of the study. Secondary outcomes included self-reported PA, psychosocial outcomes, aerobic fitness, and cardiorespiratory risk factors assessed pre/post in a laboratory setting. Participants were recruited through email listservs and websites affiliated with the university campus, community businesses and local government, social groups, and social media advertising. This study has completed data collection as of December 2014, but data cleaning and preliminary analyses are still in progress. We expect to complete analysis of the main outcomes in late 2015 to early 2016. The Walking Interventions through Texting (WalkIT) Trial will further the understanding of theory-based intervention components to increase the PA of men and women who are healthy, insufficiently active and are overweight or obese. WalkIT is one of the first studies focusing on the individual components of combined goal setting and reward structures in a factorial design to increase walking. The trial is expected to produce results useful to future research interventions and perhaps industry initiatives, primarily focused on mHealth, goal setting, and those looking to promote behavior change through performance-based incentives. ClinicalTrials.gov NCT02053259; https://clinicaltrials.gov/ct2/show/NCT02053259 (Archived by WebCite at http://www.webcitation.org/6b65xLvmg).

Exploring time series retrieved from cardiac implantable devices for optimizing patient follow-up

PubMed Central

Guéguin, Marie; Roux, Emmanuel; Hernández, Alfredo I; Porée, Fabienne; Mabo, Philippe; Graindorge, Laurence; Carrault, Guy

2008-01-01

Current cardiac implantable devices (ID) are equipped with a set of sensors that can provide useful information to improve patient follow-up and to prevent health deterioration in the postoperative period. In this paper, data obtained from an ID with two such sensors (a transthoracic impedance sensor and an accelerometer) are analyzed in order to evaluate their potential application for the follow-up of patients treated with a cardiac resynchronization therapy (CRT). A methodology combining spatio-temporal fuzzy coding and multiple correspondence analysis (MCA) is applied in order to: i) reduce the dimensionality of the data and provide new synthetic indices based on the “factorial axes” obtained from MCA, ii) interpret these factorial axes in physiological terms and iii) analyze the evolution of the patient’s status by projecting the acquired data into the plane formed by the first two factorial axes named “factorial plane”. In order to classify the different evolution patterns, a new similarity measure is proposed and validated on simulated datasets, and then used to cluster observed data from 41 CRT patients. The obtained clusters are compared with the annotations on each patient’s medical record. Two areas on the factorial plane are identified, one being correlated with a health degradation of patients and the other with a stable clinical state. PMID:18838359

Comparison of Grouping Schemes for Exposure to Total Dust in Cement Factories in Korea.

PubMed

Koh, Dong-Hee; Kim, Tae-Woo; Jang, Seung Hee; Ryu, Hyang-Woo; Park, Donguk

2015-08-01

The purpose of this study was to evaluate grouping schemes for exposure to total dust in cement industry workers using non-repeated measurement data. In total, 2370 total dust measurements taken from nine Portland cement factories in 1995-2009 were analyzed. Various grouping schemes were generated based on work process, job, factory, or average exposure. To characterize variance components of each grouping scheme, we developed mixed-effects models with a B-spline time trend incorporated as fixed effects and a grouping variable incorporated as a random effect. Using the estimated variance components, elasticity was calculated. To compare the prediction performances of different grouping schemes, 10-fold cross-validation tests were conducted, and root mean squared errors and pooled correlation coefficients were calculated for each grouping scheme. The five exposure groups created a posteriori by ranking job and factory combinations according to average dust exposure showed the best prediction performance and highest elasticity among various grouping schemes. Our findings suggest a grouping method based on ranking of job, and factory combinations would be the optimal choice in this population. Our grouping method may aid exposure assessment efforts in similar occupational settings, minimizing the misclassification of exposures. © The Author 2015. Published by Oxford University Press on behalf of the British Occupational Hygiene Society.

Unit operation optimization for the manufacturing of botanical injections using a design space approach: a case study of water precipitation.

PubMed

Gong, Xingchu; Chen, Huali; Chen, Teng; Qu, Haibin

2014-01-01

Quality by design (QbD) concept is a paradigm for the improvement of botanical injection quality control. In this work, water precipitation process for the manufacturing of Xueshuantong injection, a botanical injection made from Notoginseng Radix et Rhizoma, was optimized using a design space approach as a sample. Saponin recovery and total saponin purity (TSP) in supernatant were identified as the critical quality attributes (CQAs) of water precipitation using a risk assessment for all the processes of Xueshuantong injection. An Ishikawa diagram and experiments of fractional factorial design were applied to determine critical process parameters (CPPs). Dry matter content of concentrated extract (DMCC), amount of water added (AWA), and stirring speed (SS) were identified as CPPs. Box-Behnken designed experiments were carried out to develop models between CPPs and process CQAs. Determination coefficients were higher than 0.86 for all the models. High TSP in supernatant can be obtained when DMCC is low and SS is high. Saponin recoveries decreased as DMCC increased. Incomplete collection of supernatant was the main reason for the loss of saponins. Design space was calculated using a Monte-Carlo simulation method with acceptable probability of 0.90. Recommended normal operation region are located in DMCC of 0.38-0.41 g/g, AWA of 3.7-4.9 g/g, and SS of 280-350 rpm, with a probability more than 0.919 to attain CQA criteria. Verification experiment results showed that operating DMCC, SS, and AWA within design space can attain CQA criteria with high probability.

Automation U.S.A.: Overcoming Barriers to Automation.

ERIC Educational Resources Information Center

Brody, Herb

1985-01-01

Although labor unions and inadequate technology play minor roles, the principal barrier to factory automation is "fear of change." Related problems include long-term benefits, nontechnical executives, and uncertainty of factory cost accounting. Industry support for university programs is helping to educate engineers to design, implement, and…

Engineering Robustness of Microbial Cell Factories.

PubMed

Gong, Zhiwei; Nielsen, Jens; Zhou, Yongjin J

2017-10-01

Metabolic engineering and synthetic biology offer great prospects in developing microbial cell factories capable of converting renewable feedstocks into fuels, chemicals, food ingredients, and pharmaceuticals. However, prohibitively low production rate and mass concentration remain the major hurdles in industrial processes even though the biosynthetic pathways are comprehensively optimized. These limitations are caused by a variety of factors unamenable for host cell survival, such as harsh industrial conditions, fermentation inhibitors from biomass hydrolysates, and toxic compounds including metabolic intermediates and valuable target products. Therefore, engineered microbes with robust phenotypes is essential for achieving higher yield and productivity. In this review, the recent advances in engineering robustness and tolerance of cell factories is described to cope with these issues and briefly introduce novel strategies with great potential to enhance the robustness of cell factories, including metabolic pathway balancing, transporter engineering, and adaptive laboratory evolution. This review also highlights the integration of advanced systems and synthetic biology principles toward engineering the harmony of overall cell function, more than the specific pathways or enzymes. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Visible light assisted photoelectrocatalytic degradation of sugarcane factory wastewater by sprayed CZTS thin films

NASA Astrophysics Data System (ADS)

Hunge, Y. M.; Mahadik, M. A.; Patil, V. L.; Pawar, A. R.; Gadakh, S. R.; Moholkar, A. V.; Patil, P. S.; Bhosale, C. H.

2017-12-01

Highly crystalline Cu2ZnSnS4 (CZTS) thin films have been deposited onto glass and FTO coated glass substrates by simple chemical spray-pyrolysis technique. It is an important material for solar energy conversion through the both photovoltaics and photocatalysis. The effect of substrate temperatures on the physico-chemical properties of the CZTS films is studied. The XRD study shows the formation of single phase CZTS with kesterite structure. FE-SEM analysis reveals nano flakes architecture with pin-hole and crake free surface with more adherent. The film deposited at optimized substrate temperature exhibits optical band gap energy of 1.90 eV, which lies in the visible region of the solar spectrum and useful for photocatalysis application. The photoelectrocatalytic activities of the large surface area (10 × 10 cm2) deposited CZTS thin film photocatalysts were evaluated for the degradation of sugarcane factory wastewater under visible light irradiation. The results show that the CZTS thin film photocatalyst exhibited about 90% degradation of sugar cane factory wastewater. The mineralization of sugarcane factory wastewater is studied by measuring chemical oxygen demand (COD) values.

Energy: It is life

DOE Office of Scientific and Technical Information (OSTI.GOV)

Arques, P.

1998-07-01

The relationships that seem to exist between energy and man are presented in this paper. Habitually, social coefficients are connected to the gross domestic product; some parameters with correlations are: birth rate, infant mortality rate, death rate, literacy, etc. Along with energy these define the optimal energy consumption per capita; the author presents the correlation between these parameters and energy consumed per capita. There exists a high correlation between energy consumption per capita and gross domestic product per capita. The set of parameters considered are correlated with similar values relative to these two parameters. Using data collected on a groupmore » of the different countries of the world, a table of 165 countries and 22 variables has been drawn up. From the [Country x variable] matrix, a correlation table is calculated and a factorial analysis is applied to this matrix. The first factorial plan comprises 57% of the information contained in this table. Results from this first factorial plan are presented. These parameters are analyzed: influence of a country's latitude on its inhabitants' consumption; relationship between consumed energy and gross domestic product; women's fertility rate; birth rate per 1000 population; sex ratio; life expectancy at birth; rate of literacy; death rate; population growth rate. Finally, it is difficult to define precise criteria for: an optimal distribution of population according to age, but with a power consumed of above 300 W per capita, the population becomes younger; the birth rate per 1000 population; the total fertility rate per woman; the population growth rate. The authors determine that optimal energy is approximately between 200 W and 677 W inclusive.« less

Optimization of Aqueous Extraction from Kalanchoe pinnata Leaves to Obtain the Highest Content of an Anti-inflammatory Flavonoid using a Response Surface Model.

PubMed

Dos Santos Nascimento, Luana Beatriz; de Aguiar, Paula Fernandes; Leal-Costa, Marcos Vinicius; Coutinho, Marcela Araújo Soares; Borsodi, Maria Paula Gonçalves; Rossi-Bergmann, Bartira; Tavares, Eliana Schwartz; Costa, Sônia Soares

2018-05-01

The medicinal plant Kalanchoe pinnata is a phenolic-rich species used worldwide. The reports on its pharmacological uses have increased by 70% in the last 10 years. The leaves of this plant are the main source of an unusual quercetin-diglycosyl flavonoid (QAR, quercetin arabinopyranosyl rhamnopyranoside), which can be easily extracted using water. QAR possess a strong in vivo anti-inflammatory activity. To optimize the aqueous extraction of QAR from K. pinnata leaves using a three-level full factorial design. After a previous screening design, time (x 1 ) and temperature (x 2 ) were chosen as the two independent variables for optimization. Freeze-dried leaves were extracted with water (20% w/v), at 30°C, 40°C or 50°C for 5, 18 or 30 min. QAR content (determined by HPLC-DAD) and yield of extracts were analyzed. The optimized extracts were also evaluated for cytotoxicity. The optimal heating times for extract yield and QAR content were similar in two-dimensional (2D) surface responses (between 12.8 and 30 min), but their optimal extraction temperatures were ranged between 40°C and 50°C for QAR content and 30°C and 38°C for extract yield. A compromise region for both parameters was at the mean points that were 40°C for the extraction temperature and 18 min for the total time. The optimized process is faster and spends less energy than the previous one (water; 30 min at 55°C); therefore is greener and more attractive for industrial purposes. This is the first report of extraction optimization of this bioactive flavonoid. Copyright © 2018 John Wiley & Sons, Ltd. Copyright © 2018 John Wiley & Sons, Ltd.

Process optimization for the preparation of oligomycin-loaded folate-conjugated chitosan nanoparticles as a tumor-targeted drug delivery system using a two-level factorial design method.

PubMed

Zu, Yuangang; Zhao, Qi; Zhao, Xiuhua; Zu, Shuchong; Meng, Li

2011-01-01

Oligomycin-A (Oli-A), an anticancer drug, was loaded to the folate (FA)-conjugated chitosan as a tumor-targeted drug delivery system for the purpose of overcoming the nonspecific targeting characteristics and the hydrophobicity of the compound. The two-level factorial design (2-LFD) was applied to modeling the preparation process, which was composed of five independent variables, namely FA-conjugated chitosan (FA-CS) concentration, Oli-A concentration, sodium tripolyphosphate (TPP) concentration, the mass ratio of FA-CS to TPP, and crosslinking time. The mean particle size (MPS) and the drug loading rate (DLR) of the resulting Oli-loaded FA-CS nanoparticles (FA-Oli-CSNPs) were used as response variables. The interactive effects of the five independent variables on the response variables were studied. The characteristics of the nanoparticles, such as amount of FA conjugation, drug entrapment rate (DER), DLR, surface morphology, and release kinetics properties in vitro were investigated. The FA-Oli-CSNPs with MPS of 182.6 nm, DER of 17.3%, DLR of 58.5%, and zeta potential (ZP) of 24.6 mV were obtained under optimum conditions. The amount of FA conjugation was 45.9 mg/g chitosan. The FA-Oli-CSNPs showed sustained-release characteristics for 576 hours in vitro. The results indicated that FA-Oli-CSNPs obtained as a targeted drug delivery system could be effective in the therapy of leukemia in the future.

Development and optimization of enteric coated mucoadhesive microspheres of duloxetine hydrochloride using 3(2) full factorial design.

PubMed

Setia, Anupama; Kansal, Sahil; Goyal, Naveen

2013-07-01

Microspheres constitute an important part of oral drug delivery system by virtue of their small size and efficient carrier capacity. However, the success of these microspheres is limited due to their short residence time at the site of absorption. The objective of the present study was to formulate and systematically evaluate in vitro performance of enteric coated mucoadhesive microspheres of duloxetine hydrochloride (DLX), an acid labile drug. DLX microspheres were prepared by simple emulsification phase separation technique using chitosan as carrier and glutaraldehyde as a cross-linking agent. Microspheres prepared were coated with eudragit L-100 using an oil-in-oil solvent evaporation method. Eudragit L-100was used as enteric coating polymer with the aim to release the drug in small intestine The microspheres prepared were characterized by particle size, entrapment efficiency, swelling index (SI), mucoadhesion time, in vitro drug release and surface morphology. A 3(2) full factorial design was employed to study the effect of independent variables polymer-to-drug ratio (X1) and stirring speed (X2) on dependent variables, particle size, entrapment efficiency, SI, in vitro mucoadhesion and drug release up to 24 h (t24). Microspheres formed were discrete, spherical and free flowing. The microspheres exhibited good mucoadhesive property and also showed high percentage entrapment efficiency. The microspheres were able to sustain the drug release up to 24 h. Thus, the prepared enteric coated mucoadhesive microspheres may prove to be a potential controlled release formulation of DLX for oral administration.

Analyses of multi-color plant-growth light sources in achieving maximum photosynthesis efficiencies with enhanced color qualities.

PubMed

Wu, Tingzhu; Lin, Yue; Zheng, Lili; Guo, Ziquan; Xu, Jianxing; Liang, Shijie; Liu, Zhuguagn; Lu, Yijun; Shih, Tien-Mo; Chen, Zhong

2018-02-19

An optimal design of light-emitting diode (LED) lighting that benefits both the photosynthesis performance for plants and the visional health for human eyes has drawn considerable attention. In the present study, we have developed a multi-color driving algorithm that serves as a liaison between desired spectral power distributions and pulse-width-modulation duty cycles. With the aid of this algorithm, our multi-color plant-growth light sources can optimize correlated-color temperature (CCT) and color rendering index (CRI) such that photosynthetic luminous efficacy of radiation (PLER) is maximized regardless of the number of LEDs and the type of photosynthetic action spectrum (PAS). In order to illustrate the accuracies of the proposed algorithm and the practicalities of our plant-growth light sources, we choose six color LEDs and German PAS for experiments. Finally, our study can help provide a useful guide to improve light qualities in plant factories, in which long-term co-inhabitance of plants and human beings is required.

Optimization of levulinic acid from lignocellulosic biomass using a new hybrid catalyst.

PubMed

Ya'aini, Nazlina; Amin, Nor Aishah Saidina; Asmadi, Mohd

2012-07-01

Conversion of glucose, empty fruit bunch (efb) and kenaf to levulinic acid over a new hybrid catalyst has been investigated in this study. The characterization and catalytic performance results revealed that the physico-chemical properties of the new hybrid catalyst comprised of chromium chloride and HY zeolite increased the levulinic acid production from glucose compared to the parent catalysts. Optimization of the glucose conversion process using two level full factorial designs (2(3)) with two center points reported 55.2% of levulinic acid yield at 145.2 °C, 146.7 min and 12.0% of reaction temperature, reaction time and catalyst loading, respectively. Subsequently, the potential of efb and kenaf for producing levulinic acid at the optimum conditions was established after 53.2% and 66.1% of efficiencies were reported. The observation suggests that the hybrid catalyst has a potential to be used in biomass conversion to levulinic acid. Copyright © 2012 Elsevier Ltd. All rights reserved.

Development of a chitosan based double layer-coated tablet as a platform for colon-specific drug delivery

PubMed Central

Kim, Min Soo; Yeom, Dong Woo; Kim, Sung Rae; Yoon, Ho Yub; Kim, Chang Hyun; Son, Ho Yong; Kim, Jin Han; Lee, Sangkil; Choi, Young Wook

2017-01-01

A double layer-coated colon-specific drug delivery system (DL-CDDS) was developed, which consisted of chitosan (CTN) based polymeric subcoating of the core tablet containing citric acid for microclimate acidification, followed by an enteric coating. The polymeric composition ratio of Eudragit E100 and ethyl cellulose and amount of subcoating were optimized using a two-level factorial design method. Drug-release characteristics in terms of dissolution efficiency and controlled-release duration were evaluated in various dissolution media, such as simulated colonic fluid in the presence or absence of CTNase. Microflora activation and a stepwise mechanism for drug release were postulated. Consequently, the optimized DL-CDDS showed drug release in a controlled manner by inhibiting drug release in the stomach and intestine, but releasing the drug gradually in the colon (approximately 40% at 10 hours and 92% at 24 hours in CTNase-supplemented simulated colonic fluid), indicating its feasibility as a novel platform for CDD. PMID:28053506

Optimization of Fe2+ Removal from Coal Mine Wastewater using Activated Biochar of Colocasia esculenta.

PubMed

Banerjee, Soumya; LaminKa-Ot, Augustine; Joshi, S R; Mandal, Tamal; Halder, Gopinath

2017-09-01

  The present study investigates the sorptive removal of Fe2+ from simulated coal mine waste water using steam activated biochar (SABC) developed from the roots of Colocasia esculenta. The process was optimized by response surface methodology (RSM) under the influence of pH, temperature, adsorbent dosage and contact time at a constant shaking speed of 180 rpm with an initial concentration of 3 mg/L. The uptake performance of the biosorbent was assessed following a 24 full factorial experimental matrix developed by central composite design approach. Adsorbent was characterised by SEM, EDAX, XRD and B.E.T surface area analyzer. Maximum removal of 72.96% of Fe2+ was observed at pH 7.75, temperature 37.5 °C, adsorbent dosage 1.5 g/L for a time period of 180 mins. The study suggested that SABC prepared from roots of Colocasia esculenta could be used as an efficient and cost effective sorbent for removal of Fe2+ from coal mine wastewater.

Direct liquid chromatography method for the simultaneous quantification of hydroxytyrosol and tyrosol in red wines.

PubMed

Piñeiro, Zulema; Cantos-Villar, Emma; Palma, Miguel; Puertas, Belen

2011-11-09

A validated HPLC method with fluorescence detection for the simultaneous quantification of hydroxytyrosol and tyrosol in red wines is described. Detection conditions for both compounds were optimized (excitation at 279 and 278 and emission at 631 and 598 nm for hydroxytyrosol and tyrosol, respectively). The validation of the analytical method was based on selectivity, linearity, robustness, detection and quantification limits, repeatability, and recovery. The detection and quantification limits in red wines were set at 0.023 and 0.076 mg L(-1) for hydroxytyrosol and at 0.007 and 0.024 mg L(-1) for tyrosol determination, respectively. Precision values, both within-day and between-day (n = 5), remained below 3% for both compounds. In addition, a fractional factorial experimental design was developed to analyze the influence of six different conditions on analysis. The final optimized HPLC-fluorescence method allowed the analysis of 30 nonpretreated Spanish red wines to evaluate their hydroxytyrosol and tyrosol contents.

Optimization of response surface and neural network models in conjugation with desirability function for estimation of nutritional needs of methionine, lysine, and threonine in broiler chickens.

PubMed

Mehri, Mehran

2014-07-01

The optimization algorithm of a model may have significant effects on the final optimal values of nutrient requirements in poultry enterprises. In poultry nutrition, the optimal values of dietary essential nutrients are very important for feed formulation to optimize profit through minimizing feed cost and maximizing bird performance. This study was conducted to introduce a novel multi-objective algorithm, desirability function, for optimization the bird response models based on response surface methodology (RSM) and artificial neural network (ANN). The growth databases on the central composite design (CCD) were used to construct the RSM and ANN models and optimal values for 3 essential amino acids including lysine, methionine, and threonine in broiler chicks have been reevaluated using the desirable function in both analytical approaches from 3 to 16 d of age. Multi-objective optimization results showed that the most desirable function was obtained for ANN-based model (D = 0.99) where the optimal levels of digestible lysine (dLys), digestible methionine (dMet), and digestible threonine (dThr) for maximum desirability were 13.2, 5.0, and 8.3 g/kg of diet, respectively. However, the optimal levels of dLys, dMet, and dThr in the RSM-based model were estimated at 11.2, 5.4, and 7.6 g/kg of diet, respectively. This research documented that the application of ANN in the broiler chicken model along with a multi-objective optimization algorithm such as desirability function could be a useful tool for optimization of dietary amino acids in fractional factorial experiments, in which the use of the global desirability function may be able to overcome the underestimations of dietary amino acids resulting from the RSM model. © 2014 Poultry Science Association Inc.

Muon Accelerator Program (MAP) | Neutrino Factory | Research Goals

Science.gov Websites

; Committees Research Goals Research & Development Design & Simulation Technology Development Systems Demonstrations Activities MASS Muon Cooling MuCool Test Area MICE Experiment MERIT Muon Collider Research Goals Why Muons at the Energy Frontier? How does it work? Graphics Animation Neutrino Factory Research Goals

The Old Factory

ERIC Educational Resources Information Center

Roman, Harry T.

2007-01-01

Technology education is not just about things, systems, and processes. It can also be about history, people, technological change, and impacts on society. In this design challenge, one uses technology education principles and ideas to convert an old factory into a museum and learning center. The challenge with this historical resource is to think…

Comparison of supercritical fluid extraction and ultrasound-assisted extraction of fatty acids from quince (Cydonia oblonga Miller) seed using response surface methodology and central composite design.

PubMed

Daneshvand, Behnaz; Ara, Katayoun Mahdavi; Raofie, Farhad

2012-08-24

Fatty acids of Cydonia oblonga Miller cultivated in Iran were obtained by supercritical (carbon dioxide) extraction and ultrasound-assisted extraction methods. The oils were analyzed by capillary gas chromatography using mass spectrometric detections. The compounds were identified according to their retention indices and mass spectra (EI, 70eV). The experimental parameters of SFE such as pressure, temperature, modifier volume, static and dynamic extraction time were optimized using a Central Composite Design (CCD) after a 2(5) factorial design. Pressure and dynamic extraction time had significant effect on the extraction yield, while the other factors (temperature, static extraction time and modifier volume) were not identified as significant factors under the selected conditions. The results of chemometrics analysis showed the highest yield for SFE (24.32%), which was obtained at a pressure of 353bar, temperature of 35°C, modifier (methanol) volume of 150μL, and static and dynamic extraction times of 10 and 60min, respectively. Ultrasound-assisted extraction (UAE) of Fatty acids from C. oblonga Miller was optimized, using a rotatable central composite design. The optimum conditions were as follows: solvent (n-hexane) volume, 22mL; extraction time, 30min; and extraction temperature, 55°C. This resulted in a maximum oil recovery of 19.5%. The extracts with higher yield from both methods were subjected to transesterification and GC-MS analysis. The results show that the oil obtained by SFE with the optimal operating conditions allowed a fatty acid composition similar to the oil obtained by UAE in optimum condition and no significant differences were found. The major components of oil extract were Linoleic, Palmitic, Oleic, Stearic and Eicosanoic acids. Copyright © 2012 Elsevier B.V. All rights reserved.

Effect of mineral nutrients on cell growth and self-flocculation of Tolypothrix tenuis for the production of a biofertilizer.

PubMed

Silva, P G; Silva, H J

2007-02-01

The influence of mineral nutrients on the growth and self-flocculation of Tolypothrix tenuis was studied. The identification of possible limiting nutrients in the culture medium was performed by the biomass elemental composition approach. A factorial experimental design was used in order to estimate the contribution of macronutrients and micronutrients, as well as their interactions. Iron was identified to be limiting in the culture medium. The micronutrients influenced mainly cellular growth without effects on self-flocculation. Conversely, the self-flocculation capacity of the biomass increased at higher concentrations of macronutrients. The optimization of mineral nutrition of T. tenuis allowed a 73% increase in the final biomass level and 3.5 times higher flocculation rates.

Optimal exploitation of spatially distributed trophic resources and population stability

USGS Publications Warehouse

Basset, A.; Fedele, M.; DeAngelis, D.L.

2002-01-01

The relationships between optimal foraging of individuals and population stability are addressed by testing, with a spatially explicit model, the effect of patch departure behaviour on individual energetics and population stability. A factorial experimental design was used to analyse the relevance of the behavioural factor in relation to three factors that are known to affect individual energetics; i.e. resource growth rate (RGR), assimilation efficiency (AE), and body size of individuals. The factorial combination of these factors produced 432 cases, and 1000 replicate simulations were run for each case. Net energy intake rates of the modelled consumers increased with increasing RGR, consumer AE, and consumer body size, as expected. Moreover, through their patch departure behaviour, by selecting the resource level at which they departed from the patch, individuals managed to substantially increase their net energy intake rates. Population stability was also affected by the behavioural factors and by the other factors, but with highly non-linear responses. Whenever resources were limiting for the consumers because of low RGR, large individual body size or low AE, population density at the equilibrium was directly related to the patch departure behaviour; on the other hand, optimal patch departure behaviour, which maximised the net energy intake at the individual level, had a negative influence on population stability whenever resource availability was high for the consumers. The consumer growth rate (r) and numerical dynamics, as well as the spatial and temporal fluctuations of resource density, which were the proximate causes of population stability or instability, were affected by the behavioural factor as strongly or even more strongly than by the others factors considered here. Therefore, patch departure behaviour can act as a feedback control of individual energetics, allowing consumers to optimise a potential trade-off between short-term individual fitness and long-term population stability. ?? 2002 Elsevier Science B.V. All rights reserved.

Managing Space Radiation Risks on Lunar and Mars Missions: Risk Assessment and Mitigation

NASA Technical Reports Server (NTRS)

Cucinotta, F. A.; George, K.; Hu, X.; Kim, M. H.; Nikjoo, H.

2006-01-01

Radiation-induced health risks are a primary concern for human exploration outside the Earth's magnetosphere, and require improved approaches to risk estimation and tools for mitigation including shielding and biological countermeasures. Solar proton events are the major concern for short-term lunar missions (<60 d), and for long-term missions (>60 d) such as Mars exploration, the exposures to the high energy and charge (HZE) ions that make-up the galactic cosmic rays are the major concern. Health risks from radiation exposure are chronic risks including carcinogenesis and degenerative tissue risks, central nervous system effects, and acute risk such as radiation sickness or early lethality. The current estimate is that a more than four-fold uncertainty exists in the projection of lifetime mortality risk from cosmic rays, which severely limits analysis of possible benefits of shielding or biological countermeasure designs. Uncertainties in risk projections are largely due to insufficient knowledge of HZE ion radiobiology, which has led NASA to develop a unique probabilistic approach to radiation protection. We review NASA's approach to radiation risk assessment including its impact on astronaut dose limits and application of the ALARA (As Low as Reasonably Achievable) principle. The recently opened NASA Space Radiation Laboratory (NSRL) provides the capability to simulate the cosmic rays in controlled ground-based experiments with biological and shielding models. We discuss how research at NSRL will lead to reductions in the uncertainties in risk projection models. In developing mission designs, the reduction of health risks and mission constraints including costs are competing concerns that need to be addressed through optimization procedures. Mitigating the risks from space radiation is a multi-factorial problem involving individual factors (age, gender, genetic makeup, and exposure history), operational factors (planetary destination, mission length, and period in the solar cycle), and shielding characteristics (materials, mass, and topology). We review optimization metrics for radiation protection including scenarios that integrate biophysics models of radiation risks, operational variables, and shielding design tools needed to assess exploration mission designs. We discuss the application of a crosscutting metric, based on probabilistic risk assessment, to lunar and Mars mission trade studies including the assessment of multi-factorial problems and the potential benefits of new radiation health research strategies or mitigation technologies.

Managing Space Radiation Risks On Lunar and Mars Missions: Risk Assessment and Mitigation

NASA Technical Reports Server (NTRS)

Cucinotta, F. A.; George, K.; Hu, X.; Kim, M. H.; Nikjoo, H.

2005-01-01

Radiation-induced health risks are a primary concern for human exploration outside the Earth's magnetosphere, and require improved approaches to risk estimation and tools for mitigation including shielding and biological countermeasures. Solar proton events are the major concern for short-term lunar missions (<60 d), and for long-term missions (>60 d) such as Mars exploration, the exposures to the high energy and charge (HZE) ions that make-up the galactic cosmic rays are the major concern. Health risks from radiation exposure are chronic risks including carcinogenesis and degenerative tissue risks, central nervous system effects, and acute risk such as radiation sickness or early lethality. The current estimate is that a more than four-fold uncertainty exists in the projection of lifetime mortality risk from cosmic rays, which severely limits analysis of possible benefits of shielding or biological countermeasure designs. Uncertainties in risk projections are largely due to insufficient knowledge of HZE ion radiobiology, which has led NASA to develop a unique probabilistic approach to radiation protection. We review NASA's approach to radiation risk assessment including its impact on astronaut dose limits and application of the ALARA (As Low as Reasonably Achievable) principle. The recently opened NASA Space Radiation Laboratory (NSRL) provides the capability to simulate the cosmic rays in controlled ground-based experiments with biological and shielding models. We discuss how research at NSRL will lead to reductions in the uncertainties in risk projection models. In developing mission designs, the reduction of health risks and mission constraints including costs are competing concerns that need to be addressed through optimization procedures. Mitigating the risks from space radiation is a multi-factorial problem involving individual factors (age, gender, genetic makeup, and exposure history), operational factors (planetary destination, mission length, and period in the solar cycle), and shielding characteristics (materials, mass, and topology). We review optimization metrics for radiation protection including scenarios that integrate biophysics models of radiation risks, operational variables, and shielding design tools needed to assess exploration mission designs. We discuss the application of a crosscutting metric, based on probabilistic risk assessment, to lunar and Mars mission trade studies including the assessment of multi-factorial problems and the potential benefits of new radiation health research strategies or mitigation technologies.

Managing Space Radiation Risks on Lunar and Mars Missions: Risk Assessment and Mitigation

NASA Technical Reports Server (NTRS)

Cucinotta, F. A.; George, K.; Hu, X.; Kim, M. H.; Nikjoo, H.; Ponomarev, A.; Ren, L.; Shavers, M. R.; Wu, H.

2005-01-01

Radiation-induced health risks are a primary concern for human exploration outside the Earth's magnetosphere, and require improved approaches to risk estimation and tools for mitigation including shielding and biological countermeasures. Solar proton events are the major concern for short-term lunar missions (<60 d), and for long-term missions (>60 d) such as Mars exploration, the exposures to the high energy and charge (HZE) ions that make-up the galactic cosmic rays are the major concern. Health risks from radiation exposure are chronic risks including carcinogenesis and degenerative tissue risks, central nervous system effects, and acute risk such as radiation sickness or early lethality. The current estimate is that a more than four-fold uncertainty exists in the projection of lifetime mortality risk from cosmic rays, which severely limits analysis of possible benefits of shielding or biological countermeasure designs. Uncertainties in risk projections are largely due to insufficient knowledge of HZE ion radiobiology, which has led NASA to develop a unique probabilistic approach to radiation protection. We review NASA's approach to radiation risk assessment including its impact on astronaut dose limits and application of the ALARA (As Low as Reasonably Achievable) principle. The recently opened NASA Space Radiation Laboratory (NSRL) provides the capability to simulate the cosmic rays in controlled ground-based experiments with biological and shielding models. We discuss how research at NSRL will lead to reductions in the uncertainties in risk projection models. In developing mission designs, the reduction of health risks and mission constraints including costs are competing concerns that need to be addressed through optimization procedures. Mitigating the risks from space radiation is a multi-factorial problem involving individual factors (age, gender, genetic makeup, and exposure history), operational factors (planetary destination, mission length, and period in the solar cycle), and shielding characteristics (materials, mass, and topology). We review optimization metrics for radiation protection including scenarios that integrate biophysics models of radiation risks, operational variables, and shielding design tools needed to assess exploration mission designs. We discuss the application of a crosscutting metric, based on probabilistic risk assessment, to lunar and Mars mission trade studies including the assessment of multi-factorial problems and the potential benefits of new radiation health research strategies or mitigation technologies.

Lithium D-cell study

NASA Technical Reports Server (NTRS)

Size, P.; Takeuchi, Esther S.

1993-01-01

The purpose of this contract is to evaluate parametrically the effects of various factors including the electrolyte type, electrolyte concentration, depolarizer type, and cell configuration on lithium cell electrical performance and safety. This effort shall allow for the selection and optimization of cell design for future NASA applications while maintaining close ties with WGL's continuous improvements in manufacturing processes and lithium cell design. Taguchi experimental design techniques are employed in this task, and allow for a maximum amount of information to be obtained while requiring significantly less cells than if a full factorial design were employed. Acceptance testing for this task is modeled after the NASA Document EP5-83-025, Revision C, for cell weights, OCV's and load voltages. The performance attributes that are studied in this effort are fresh capacity and start-up characteristics evaluated at two rates and two temperatures, shelf-life characteristics including start-up and capacity retention, and iterative microcalorimetry measurements. Abuse testing includes forced over discharge at two rates with and without diode protection, temperature tolerance testing, and shorting tests at three rates with the measurement of heat generated during shorting conditions.

A framework for learning about improvement: embedded implementation and evaluation design to optimize learning

PubMed Central

Barry, Danika; Kimble, Leighann E; Nambiar, Bejoy; Parry, Gareth; Jha, Ashish; Chattu, Vijay Kumar; Massoud, M Rashad; Goldmann, Don

2018-01-01

Abstract Improving health care involves many actors, often working in complex adaptive systems. Interventions tend to be multi-factorial, implementation activities diverse, and contexts dynamic and complicated. This makes improvement initiatives challenging to describe and evaluate as matching evaluation and program designs can be difficult, requiring collaboration, trust and transparency. Collaboration is required to address important epidemiological principles of bias and confounding. If this does not take place, results may lack credibility because the association between interventions implemented and outcomes achieved is obscure and attribution uncertain. Moreover, lack of clarity about what was implemented, how it was implemented, and the context in which it was implemented often lead to disappointment or outright failure of spread and scale-up efforts. The input of skilled evaluators into the design and conduct of improvement initiatives can be helpful in mitigating these potential problems. While evaluation must be rigorous, if it is too rigid necessary adaptation and learning may be compromised. This article provides a framework and guidance on how improvers and evaluators can work together to design, implement and learn about improvement interventions more effectively. PMID:29873794

Formulation and evaluation of optimized oxybenzone microsponge gel for topical delivery.

PubMed

Pawar, Atmaram P; Gholap, Aditya P; Kuchekar, Ashwin B; Bothiraja, C; Mali, Ashwin J

2015-01-01

Background. Oxybenzone, a broad spectrum sunscreen agent widely used in the form of lotion and cream, has been reported to cause skin irritation, dermatitis, and systemic absorption. Aim. The objective of the present study was to formulate oxybenzone loaded microsponge gel for enhanced sun protection factor with reduced toxicity. Material and Method. Microsponge for topical delivery of oxybenzone was successfully prepared by quasiemulsion solvent diffusion method. The effects of ethyl cellulose and dichloromethane were optimized by the 3(2) factorial design. The optimized microsponges were dispersed into the hydrogel and further evaluated. Results. The microsponges were spherical with pore size in the range of 0.10-0.22 µm. The optimized formulation possesses the particle size and entrapment efficiency of 72 ± 0.77 µm and 96.9 ± 0.52%, respectively. The microsponge gel showed the controlled release and was nonirritant to the rat skin. In creep recovery test it had shown highest recovery indicating elasticity. The controlled release of oxybenzone from microsponge and barrier effect of gel result in prolonged retention of oxybenzone with reduced permeation activity. Conclusion. Evaluation study revealed remarkable and enhanced topical retention of oxybenzone for prolonged period of time. It also showed the enhanced sun protection factor compared to the marketed preparation with reduced irritation and toxicity.

Lactic acid production from submerged fermentation of broken rice using undefined mixed culture.

PubMed

Nunes, Luiza Varela; de Barros Correa, Fabiane Fernanda; de Oliva Neto, Pedro; Mayer, Cassia Roberta Malacrida; Escaramboni, Bruna; Campioni, Tania Sila; de Barros, Natan Roberto; Herculano, Rondinelli Donizetti; Fernández Núñez, Eutimio Gustavo

2017-04-01

The present work aimed to characterize and optimize the submerged fermentation of broken rice for lactic acid (LA) production using undefined mixed culture from dewatered activated sludge. A microorganism with amylolytic activity, which also produces LA, Lactobacillus amylovorus, was used as a control to assess the extent of mixed culture on LA yield. Three level full factorial designs were performed to optimize and define the influence of fermentation temperature (20-50 °C), gelatinization time (30-60 min) and broken rice concentration in culture medium (40-80 g L -1 ) on LA production in pure and undefined mixed culture. LA production in mixed culture (9.76 g L -1 ) increased in sixfold respect to pure culture in optimal assessed experimental conditions. The optimal conditions for maximizing LA yield in mixed culture bioprocess were 31 °C temperature, 45 min gelatinization time and 79 g L -1 broken rice concentration in culture medium. This study demonstrated the positive effect of undefined mixed culture from dewatered activated sludge to produce LA from culture medium formulated with broken rice. In addition, this work establishes the basis for an efficient and low-cost bioprocess to manufacture LA from this booming agro-industrial by-product.

Optimization simulated injection molding process for ultrahigh molecular weight polyethylene nanocomposite hip liner using response surface methodology and simulation of mechanical behavior.

PubMed

Heidari, Behzad Shiroud; Davachi, Seyed Mohammad; Moghaddam, Amin Hedayati; Seyfi, Javad; Hejazi, Iman; Sahraeian, Razi; Rashedi, Hamid

2018-05-01

In this study, injection molding process of ultrahigh molecular weight polyethylene (UHMWPE) reinforced with nano-hydroxyapatite (nHA) was simulated and optimized through minimizing the shrinkage and warpage of the hip liners as an essential part of a hip prosthesis. Fractional factorial design (FFD) was applied to the design of the experiment, modeling, and optimizing the shrinkage and warpage of UHMWPE/nHA composite liners. The Analysis of variance (ANOVA) was applied to find the importance of operative parameters and their effects. In this experiment, seven input parameters were surveyed, including mold temperature (A), melt temperature (B), injection time (C), packing time (D), packing pressure (E), coolant temperature (F), and type of liner (G). Two models were capable of predicting warpage and volumetric shrinkage (%) in different conditions with R 2 of 0.9949 and 0.9989, respectively. According to the models, the optimized values of warpage and volumetric shrinkage are 0.287222 mm and 13.6613%, respectively. Meanwhile, a finite element analysis (FE analysis) was also carried out to examine the stress distribution in liners under the force values of demanding and daily activities. The Von-Mises stress distribution showed that both of the liners can be applied to all activities with no failure. However, UHMWPE/nHA liner is more resistant to the highest loads than UHMWPE liner due to the effect of nHA in the nanocomposite. Finally, according to the results of injection molding simulations, optimization, structural analysis as well as the tensile strength and wear resistance, UHMWPE/nHA liner is recommended for the production of a hip prosthesis. Copyright © 2018 Elsevier Ltd. All rights reserved.

Benzocaine loaded solid lipid nanoparticles: Formulation design, in vitro and in vivo evaluation of local anesthetic effect.

PubMed

Basha, Mona; Abd El-Alim, Sameh Hosam; Kassem, Ahmed Alaa; El Awdan, Sally; Awad, Gamal

2015-01-01

The aim of the present work is the development and evaluation of solid lipid nanoparticles (SLNs) as carrier system for topical delivery of benzocaine (BZC) improving its local anesthesia aiming to produce a fast acting and long lasting topical formulation. BZC loaded SLNs were prepared using a full factorial design to study the influence of the type of polyoxyethylene sorbitan ester surfactants as well as their concentration as independent variables on the particle size, entrapment efficacy and zeta potential selected as dependent variables. Design of experiment (DOE) and the analysis of variance (ANOVA) were conducted to assess the optimization of the developed formulations. The results indicated that the fatty acid chain length of tested surfactants and their concentration had a significant effect on the studied responses. The optimized formulations were spherical in shape of mean particle diameters<350 nm with negatively charged surface <-20mV. Particles were characterized using differential scanning calorimetry and X-ray powder diffraction confirming the amorphous nature and the uniformity of drug inclusion in the lipid matrix. Optimized BZC-SLNs were incorporated into hydrogels characterized by a pseudoplastic non-Newtonian behavior. In vitro release study revealed an apparently biphasic release process with sustained release profile following Higuchi kinetics. BZC loaded SLNs hydrogels showed more potent anesthetic effect compared to BZC hydrogel evaluated using tail-flick analgesimeter, confirming significant improvement in both the intensity and duration of anesthetic effect. The above results proved that SLNs represent good candidates to encapsulate BZC improving its therapeutic efficacy for the topical treatment of pain.

Electrochemical removal of carbamazepine in water with Ti/PbO2 cylindrical mesh anode.

PubMed

García-Espinoza, J D; Gortáres-Moroyoqui, P; Orta-Ledesma, M T; Drogui, P; Mijaylova-Nacheva, P

2016-01-01

Carbamazepine (CBZ) is one of the most frequently detected organic compounds in the aquatic environment. Due to its bio-persistence and toxicity for humans and the environment its removal has become an important issue. The performance of the electrochemical oxidation process and in situ production of reactive oxygen species (ROS), such as O3 and H2O2, for CBZ removal have been studied using Ti/PbO2 cylindrical mesh anode in the presence of Na2SO4 as supporting electrolyte in a batch electrochemical reactor. In this integrated process, direct oxidation at anode and indirect oxidation by in situ electrogenerated ROS can occur simultaneously. The effect of several factors such as electrolysis time, current intensity, initial pH and oxygen flux was investigated by means of an experimental design methodology, using a 2(4) factorial matrix. CBZ removal of 83.93% was obtained and the most influential parameters turned out to be electrolysis time, current intensity and oxygen flux. Later, the optimal experimental values for CBZ degradation were obtained by means of a central composite design. The best operating conditions, analyzed by Design Expert(®) software, are the following: 110 min of electrolysis at 3.0 A, pH = 7.05 and 2.8 L O2/min. Under these optimal conditions, the model prediction (82.44%) fits very well with the experimental response (83.90 ± 0.8%). Furthermore, chemical oxygen demand decrease was quantified. Our results illustrated significant removal efficiency for the CBZ in optimized condition with second order kinetic reaction.

Commercialization of Medium Voltage HTS Triax TM Cable Systems

DOE Office of Scientific and Technical Information (OSTI.GOV)

Knoll, David

2012-12-31

The original project scope that was established in 2007 aimed to install a 1,700 meter (1.1 mile) medium voltage HTS Triax{TM} cable system into the utility grid in New Orleans, LA. In 2010, however, the utility partner withdrew from the project, so the 1,700 meter cable installation was cancelled and the scope of work was reduced. The work then concentrated on the specific barriers to commercialization of HTS cable technology. The modified scope included long-length HTS cable design and testing, high voltage factory test development, optimized cooling system development, and HTS cable life-cycle analysis. In 2012, Southwire again analyzed themore » market for HTS cables and deemed the near term market acceptance to be low. The scope of work was further reduced to the completion of tasks already started and to testing of the existing HTS cable system in Columbus, OH. The work completed under the project included: • Long-length cable modeling and analysis • HTS wire evaluation and testing • Cable testing for AC losses • Optimized cooling system design • Life cycle testing of the HTS cable in Columbus, OH • Project management. The 200 meter long HTS Triax{TM} cable in Columbus, OH was incorporated into the project under the initial scope changes as a test bed for life cycle testing as well as the site for an optimized HTS cable cooling system. The Columbus cable utilizes the HTS TriaxTM design, so it provided an economical tool for these of the project tasks.« less

Design of experiments to optimize an in vitro cast to predict human nasal drug deposition.

PubMed

Shah, Samir A; Dickens, Colin J; Ward, David J; Banaszek, Anna A; George, Chris; Horodnik, Walter

2014-02-01

Previous studies showed nasal spray in vitro tests cannot predict in vivo deposition, pharmacokinetics, or pharmacodynamics. This challenge makes it difficult to assess deposition achieved with new technologies delivering to the therapeutically beneficial posterior nasal cavity. In this study, we determined best parameters for using a regionally divided nasal cast to predict deposition. Our study used a model suspension and a design of experiments to produce repeatable deposition results that mimic nasal deposition patterns of nasal suspensions from the literature. The seven-section (the nozzle locator, nasal vestibule, front turbinate, rear turbinate, olfactory region, nasopharynx, and throat filter) nylon nasal cast was based on computed tomography images of healthy humans. It was coated with a glycerol/Brij-35 solution to mimic mucus. After assembling and orienting, airflow was applied and nasal spray containing a model suspension was sprayed. After disassembling the cast, drug depositing in each section was assayed by HPLC. The success criteria for optimal settings were based on nine in vivo studies in the literature. The design of experiments included exploratory and half factorial screening experiments to identify variables affecting deposition (angles, airflow, and airflow time), optimization experiments, and then repeatability and reproducibility experiments. We found tilt angle and airflow time after actuation affected deposition the most. The optimized settings were flow rate of 16 L/min, postactuation flow time of 12 sec, a tilt angle of 23°, nozzle angles of 0°, and actuation speed of 5 cm/sec. Neither cast nor operator caused significant variation of results. We determined cast parameters to produce results resembling suspension nasal sprays in the literature. The results were repeatable and unaffected by operator or cast. These nasal spray parameters could be used to assess deposition from new devices or formulations. For human deposition studies using radiolabeled formulations, this cast could show that radiolabel deposition represents drug deposition. Our methods could also be used to optimize settings for other casts.

Iontophoretic delivery of lisinopril: Optimization of process variables by Box-Behnken statistical design.

PubMed

Gannu, Ramesh; Yamsani, Vamshi Vishnu; Palem, Chinna Reddy; Yamsani, Shravan Kumar; Yamsani, Madhusudan Rao

2010-01-01

The objective of the investigation was to optimize the iontophoresis process parameters of lisinopril (LSP) by 3 x 3 factorial design, Box-Behnken statistical design. LSP is an ideal candidate for iontophoretic delivery to avoid the incomplete absorption problem associated after its oral administration. Independent variables selected were current (X(1)), salt (sodium chloride) concentration (X(2)) and medium/pH (X(3)). The dependent variables studied were amount of LSP permeated in 4 h (Y(1): Q(4)), 24 h (Y(2): Q(24)) and lag time (Y(3)). Mathematical equations and response surface plots were used to relate the dependent and independent variables. The regression equation generated for the iontophoretic permeation was Y(1) = 1.98 + 1.23X(1) - 0.49X(2) + 0.025X(3) - 0.49X(1)X(2) + 0.040X(1)X(3) - 0.010X(2)X(3) + 0.58X(1)(2) - 0.17X(2)(2) - 0.18X(3)(2); Y(2) = 7.28 + 3.32X(1) - 1.52X(2) + 0.22X(3) - 1.30X(1)X(2) + 0.49X(1)X(3) - 0.090X(2)X(3) + 0.79X(1)(2) - 0.62X(2)(2) - 0.33X(3)(2) and Y(3) = 0.60 + 0.0038X(1) + 0.12X(2) - 0.011X(3) + 0.005X(1)X(2) - 0.018X(1)X(3) - 0.015X(2)X(3) - 0.00075X(1)(2) + 0.017X(2)(2) - 0.11X(3)(2). The statistical validity of the polynomials was established and optimized process parameters were selected by feasibility and grid search. Validation of the optimization study with 8 confirmatory runs indicated high degree of prognostic ability of response surface methodology. The use of Box-Behnken design approach helped in identifying the critical process parameters in the iontophoretic delivery of lisinopril.

Virtual Collaborative Simulation Environment for Integrated Product and Process Development

NASA Technical Reports Server (NTRS)

Gulli, Michael A.

1997-01-01

Deneb Robotics is a leader in the development of commercially available, leading edge three- dimensional simulation software tools for virtual prototyping,, simulation-based design, manufacturing process simulation, and factory floor simulation and training applications. Deneb has developed and commercially released a preliminary Virtual Collaborative Engineering (VCE) capability for Integrated Product and Process Development (IPPD). This capability allows distributed, real-time visualization and evaluation of design concepts, manufacturing processes, and total factory and enterprises in one seamless simulation environment.

Design and Construction of a High-speed Network Connecting All the Protein Crystallography Beamlines at the Photon Factory

DOE Office of Scientific and Technical Information (OSTI.GOV)

Matsugaki, Naohiro; Yamada, Yusuke; Igarashi, Noriyuki

2007-01-19

A private network, physically separated from the facility network, was designed and constructed which covered all the four protein crystallography beamlines at the Photon Factory (PF) and Structural Biology Research Center (SBRC). Connecting all the beamlines in the same network allows for simple authentication and a common working environment for a user who uses multiple beamlines. Giga-bit Ethernet wire-speed was achieved for the communication among the beamlines and SBRC buildings.

Metabolic modelling in the development of cell factories by synthetic biology

PubMed Central

Jouhten, Paula

2012-01-01

Cell factories are commonly microbial organisms utilized for bioconversion of renewable resources to bulk or high value chemicals. Introduction of novel production pathways in chassis strains is the core of the development of cell factories by synthetic biology. Synthetic biology aims to create novel biological functions and systems not found in nature by combining biology with engineering. The workflow of the development of novel cell factories with synthetic biology is ideally linear which will be attainable with the quantitative engineering approach, high-quality predictive models, and libraries of well-characterized parts. Different types of metabolic models, mathematical representations of metabolism and its components, enzymes and metabolites, are useful in particular phases of the synthetic biology workflow. In this minireview, the role of metabolic modelling in synthetic biology will be discussed with a review of current status of compatible methods and models for the in silico design and quantitative evaluation of a cell factory. PMID:24688669

Optimization of remotely delivered intensive lifestyle treatment for obesity using the Multiphase Optimization Strategy: Opt-IN study protocol.

PubMed

Pellegrini, Christine A; Hoffman, Sara A; Collins, Linda M; Spring, Bonnie

2014-07-01

Obesity-attributable medical expenditures remain high, and interventions that are both effective and cost-effective have not been adequately developed. The Opt-IN study is a theory-guided trial using the Multiphase Optimization Strategy (MOST) to develop an optimized, scalable version of a technology-supported weight loss intervention. Opt-IN aims to identify which of 5 treatment components or component levels contribute most meaningfully and cost-efficiently to the improvement of weight loss over a 6 month period. Five hundred and sixty obese adults (BMI 30-40 kg/m(2)) between 18 and 60 years old will be randomized to one of 16 conditions in a fractional factorial design involving five intervention components: treatment intensity (12 vs. 24 coaching calls), reports sent to primary care physician (No vs. Yes), text messaging (No vs. Yes), meal replacement recommendations (No vs. Yes), and training of a participant's self-selected support buddy (No vs. Yes). During the 6-month intervention, participants will monitor weight, diet, and physical activity on the Opt-IN smartphone application downloaded to their personal phone. Weight will be assessed at baseline, 3, and 6 months. The Opt-IN trial is the first study to use the MOST framework to develop a weight loss treatment that will be optimized to yield the best weight loss outcome attainable for $500 or less. Copyright © 2014 Elsevier Inc. All rights reserved.

Optimization of Milk-Based Medium for Efficient Cultivation of Bifidobacterium pseudocatenulatum G4 Using Face-Centered Central Composite-Response Surface Methodology

PubMed Central

Abdul Khalil, Khalilah; Mustafa, Shuhaimi; Mohammad, Rosfarizan; Bin Ariff, Arbakariya; Shaari, Yamin; Abdul Manap, Yazid; Dahalan, Farrah Aini

2014-01-01

This study was undertaken to optimize skim milk and yeast extract concentration as a cultivation medium for optimal Bifidobacteria pseudocatenulatum G4 (G4) biomass and β-galactosidase production as well as lactose and free amino nitrogen (FAN) balance after cultivation period. Optimization process in this study involved four steps: screening for significant factors using 23 full factorial design, steepest ascent, optimization using FCCD-RSM, and verification. From screening steps, skim milk and yeast extract showed significant influence on the biomass production and, based on the steepest ascent step, middle points of skim milk (6% wt/vol) and yeast extract (1.89% wt/vol) were obtained. A polynomial regression model in FCCD-RSM revealed that both factors were found significant and the strongest influence was given by skim milk concentration. Optimum concentrations of skim milk and yeast extract for maximum biomass G4 and β-galactosidase production meanwhile low in lactose and FAN balance after cultivation period were 5.89% (wt/vol) and 2.31% (wt/vol), respectively. The validation experiments showed that the predicted and experimental values are not significantly different, indicating that the FCCD-RSM model developed is sufficient to describe the cultivation process of G4 using skim-milk-based medium with the addition of yeast extract. PMID:24527457

Optimizing Partner Notification Programs for Men Who Have Sex with Men: Factorial Survey Results from South China

PubMed Central

Tucker, Joseph D.; Chakraborty, Hrishikesh; Cohen, Myron S.; Chen, Xiang-Sheng

2016-01-01

Background Syphilis is prevalent among men who have sex with men (MSM) in China. Syphilis partner notification (PN) programs targeting MSM has been considered as one of effective strategies to prevention and control of the infection in the population. We examined willingness and preferences for PN among MSM to measure feasibility and optimize uptake. Methods Participation in a syphilis PN program was measured using a factorial survey from both the perspective of the index patient and the partner. Respondents were recruited from April-July 2011 using convenience sampling at two sites—a MSM sexually transmitted disease (STD) clinic and a MSM community based organization (CBO). Respondents first evaluated three factorial survey vignettes to measure probability of participation and then an anonymous sociodemographic questionnaire. A two-level mixed linear model was fitted for the factorial survey analysis. Results In 372 respondents with mean age (± SD) 28.5 (± 6.0) years, most were single (82.0%) and closeted gays (66.7%). The Internet was the most frequent place to search for sex. Few (31.2%) had legal names for casual partners, but most had instant messenger (86.5%) and mobile phone numbers (77.7%). The mean probability of participation in a syphilis PN program was 64.5% (± 32.4%) for index patients and 63.7% (± 32.6%) for partners. Referral of the partner to a private clinic or MSM CBO for follow-up decreased participation compared to the local Center for Disease Control and Prevention (CDC) or public STD clinic. Conclusions Enhanced PN services may be feasible among MSM in South China. Internet and mobile phone PN may contact partners untraceable by traditional PN. Referral of partners to the local CDC or public STD clinic may maximize PN participation. PMID:27462724

The Genome-Based Metabolic Systems Engineering to Boost Levan Production in a Halophilic Bacterial Model.

PubMed

Aydin, Busra; Ozer, Tugba; Oner, Ebru Toksoy; Arga, Kazim Yalcin

2018-03-01

Metabolic systems engineering is being used to redirect microbial metabolism for the overproduction of chemicals of interest with the aim of transforming microbial hosts into cellular factories. In this study, a genome-based metabolic systems engineering approach was designed and performed to improve biopolymer biosynthesis capability of a moderately halophilic bacterium Halomonas smyrnensis AAD6 T producing levan, which is a fructose homopolymer with many potential uses in various industries and medicine. For this purpose, the genome-scale metabolic model for AAD6 T was used to characterize the metabolic resource allocation, specifically to design metabolic engineering strategies for engineered bacteria with enhanced levan production capability. Simulations were performed in silico to determine optimal gene knockout strategies to develop new strains with enhanced levan production capability. The majority of the gene knockout strategies emphasized the vital role of the fructose uptake mechanism, and pointed out the fructose-specific phosphotransferase system (PTS fru ) as the most promising target for further metabolic engineering studies. Therefore, the PTS fru of AAD6 T was restructured with insertional mutagenesis and triparental mating techniques to construct a novel, engineered H. smyrnensis strain, BMA14. Fermentation experiments were carried out to demonstrate the high efficiency of the mutant strain BMA14 in terms of final levan concentration, sucrose consumption rate, and sucrose conversion efficiency, when compared to the AAD6 T . The genome-based metabolic systems engineering approach presented in this study might be considered an efficient framework to redirect microbial metabolism for the overproduction of chemicals of interest, and the novel strain BMA14 might be considered a potential microbial cell factory for further studies aimed to design levan production processes with lower production costs.

Investigation Of The Effects Of Reflow Profile Parameters On Lead-free Solder Bump Volumes And Joint Integrity

NASA Astrophysics Data System (ADS)

Amalu, E. H.; Lui, Y. T.; Ekere, N. N.; Bhatti, R. S.; Takyi, G.

2011-01-01

The electronics manufacturing industry was quick to adopt and use the Surface Mount Technology (SMT) assembly technique on realization of its huge potentials in achieving smaller, lighter and low cost product implementations. Increasing global customer demand for miniaturized electronic products is a key driver in the design, development and wide application of high-density area array package format. Electronic components and their associated solder joints have reduced in size as the miniaturization trend in packaging continues to be challenged by printing through very small stencil apertures required for fine pitch flip-chip applications. At very narrow aperture sizes, solder paste rheology becomes crucial for consistent paste withdrawal. The deposition of consistent volume of solder from pad-to-pad is fundamental to minimizing surface mount assembly defects. This study investigates the relationship between volume of solder paste deposit (VSPD) and the volume of solder bump formed (VSBF) after reflow, and the effect of reflow profile parameters on lead-free solder bump formation and the associated solder joint integrity. The study uses a fractional factorial design (FFD) of 24-1 Ramp-Soak-Spike reflow profile, with all main effects and two-way interactions estimable to determine the optimal factorial combination. The results from the study show that the percentage change in the VSPD depends on the combination of the process parameters and reliability issues could become critical as the size of solder joints soldered on the same board assembly vary greatly. Mathematical models describe the relationships among VSPD, VSBF and theoretical volume of solder paste. Some factors have main effects across the volumes and a number of interactions exist among them. These results would be useful for R&D personnel in designing and implementing newer applications with finer-pitch interconnect.

Physiological responses of lichens to factorial fumigations with nitric acid and ozone

Treesearch

J. Riddell; P.E. Padgett; T. Nash

2012-01-01

This paper addresses the effects of gaseous nitric acid (HNO3) and ozone (O3), two important air pollutants, on six lichen species with different morphological, ecological, and biological characteristics. The treatment chambers were set up in a factorial design consisting of control chambers, chambers fumigated with HNO

The Use of Factorial Forecasting to Predict Public Response

ERIC Educational Resources Information Center

Weiss, David J.

2012-01-01

Policies that call for members of the public to change their behavior fail if people don't change; predictions of whether the requisite changes will take place are needed prior to implementation. I propose to solve the prediction problem with Factorial Forecasting, a version of functional measurement methodology that employs group designs. Aspects…

The Game Factory: Using Cooperative Games to Promote Pro-Social Behaviour among Children

ERIC Educational Resources Information Center

Street, Helen; Hoppe, David; Kingsbury, David; Ma, Tony

2004-01-01

This study examines the use of a cooperative physical games program "The Game Factory" on social behaviour among children. Children are required to work together towards positive collective outcomes. A pretest-intervention-posttest design is used. Parents and teachers assessed 90 Australian primary school children in two experimental…

Optimization of critical medium components using response surface methodology for biomass and extracellular polysaccharide production by Agaricus blazei.

PubMed

Liu, Gao-Qiang; Wang, Xiao-Ling

2007-02-01

Response surface methodology (RSM) was applied to optimize the critical medium ingredients of Agaricus blazei. A three-level Box-Behnken factorial design was employed to determine the maximum biomass and extracellular polysaccharide (EPS) yields at optimum levels for glucose, yeast extract (YE), and peptone. A mathematical model was then developed to show the effect of each medium composition and its interactions on the production of mycelial biomass and EPS. The model predicted the maximum biomass yield of 10.86 g/l that appeared at glucose, YE, peptone of 26.3, 6.84, and 6.62 g/l, respectively, while a maximum EPS yield of 348.4 mg/l appeared at glucose, YE, peptone of 28.4, 4.96, 5.60 g/l, respectively. These predicted values were also verified by validation experiments. The excellent correlation between predicted and measured values of each model justifies the validity of both the response models. The results of bioreactor fermentation also show that the optimized culture medium enhanced both biomass (13.91 +/- 0.71 g/l) and EPS (363 +/- 4.1 mg/l) production by Agaricus blazei in a large-scale fermentation process.

The SED Machine: A Robotic Spectrograph for Fast Transient Classification

NASA Astrophysics Data System (ADS)

Blagorodnova, Nadejda; Neill, James D.; Walters, Richard; Kulkarni, Shrinivas R.; Fremling, Christoffer; Ben-Ami, Sagi; Dekany, Richard G.; Fucik, Jason R.; Konidaris, Nick; Nash, Reston; Ngeow, Chow-Choong; Ofek, Eran O.; O’ Sullivan, Donal; Quimby, Robert; Ritter, Andreas; Vyhmeister, Karl E.

2018-03-01

Current time domain facilities are finding several hundreds of transient astronomical events a year. The discovery rate is expected to increase in the future as soon as new surveys such as the Zwicky Transient Facility (ZTF) and the Large Synoptic Sky Survey (LSST) come online. Presently, the rate at which transients are classified is approximately one order or magnitude lower than the discovery rate, leading to an increasing “follow-up drought”. Existing telescopes with moderate aperture can help address this deficit when equipped with spectrographs optimized for spectral classification. Here, we provide an overview of the design, operations and first results of the Spectral Energy Distribution Machine (SEDM), operating on the Palomar 60-inch telescope (P60). The instrument is optimized for classification and high observing efficiency. It combines a low-resolution (R ∼ 100) integral field unit (IFU) spectrograph with “Rainbow Camera” (RC), a multi-band field acquisition camera which also serves as multi-band (ugri) photometer. The SEDM was commissioned during the operation of the intermediate Palomar Transient Factory (iPTF) and has already lived up to its promise. The success of the SEDM demonstrates the value of spectrographs optimized for spectral classification.

Optimization of the anaerobic treatment of a waste stream from an enhanced oil recovery process.

PubMed

Alimahmoodi, Mahmood; Mulligan, Catherine N

2011-01-01

The aim of this work was to optimize the anaerobic treatment of a waste stream from an enhanced oil recovery (EOR) process. The treatment of a simulated waste water containing about 150 mg chemical oxygen demand (COD)/L of total petroleum hydrocarbons (TPH) and the saturation level of CO2 was evaluated. A two-step anaerobic system was undertaken in the mesophilic temperature range (30-40°C). The method of evolutionary operation EVOP factorial design was used to optimize pH, temperature and organic loading rate with the target parameters of CO2 reduction and CH4 production in the first reactor and TPH removal in the second reactor. The results showed 98% methanogenic removal of CO2 and CH4 yield of 0.38 L/gCOD in the first reactor and 83% TPH removal in the second reactor. In addition to enhancing CO2 and TPH removal and CH4 production, application of this method showed the degree of importance of the operational variables and their interactive effects for the two reactors in series. Copyright © 2010 Elsevier Ltd. All rights reserved.

Design Learning of Teaching Factory in Mechanical Engineering

NASA Astrophysics Data System (ADS)

Putra, R. C.; Kusumah, I. H.; Komaro, M.; Rahayu, Y.; Asfiyanur, E. P.

2018-02-01

The industrial world that is the target of the process and learning outcomes of vocational high school (SMK) has its own character and nuance. Therefore, vocational education institutions in the learning process should be able to make the appropriate learning approach and in accordance with the industrial world. One approach to learning that is based on production and learning in the world of work is by industry-based learning or known as Teaching Factory, where in this model apply learning that involves direct students in goods or service activities are expected to have the quality so it is worth selling and accepted by consumers. The method used is descriptive approach. The purpose of this research is to get the design of the teaching factory based on the competency requirements of the graduates of the spouse industry, especially in the engineering department. The results of this study is expected to be one of the choice of model factory teaching in the field of machinery engineering in accordance with the products and competencies of the graduates that the industry needs.

Testing Nelder-Mead based repulsion algorithms for multiple roots of nonlinear systems via a two-level factorial design of experiments.

PubMed

Ramadas, Gisela C V; Rocha, Ana Maria A C; Fernandes, Edite M G P

2015-01-01

This paper addresses the challenging task of computing multiple roots of a system of nonlinear equations. A repulsion algorithm that invokes the Nelder-Mead (N-M) local search method and uses a penalty-type merit function based on the error function, known as 'erf', is presented. In the N-M algorithm context, different strategies are proposed to enhance the quality of the solutions and improve the overall efficiency. The main goal of this paper is to use a two-level factorial design of experiments to analyze the statistical significance of the observed differences in selected performance criteria produced when testing different strategies in the N-M based repulsion algorithm. The main goal of this paper is to use a two-level factorial design of experiments to analyze the statistical significance of the observed differences in selected performance criteria produced when testing different strategies in the N-M based repulsion algorithm.

The Japanese Positron Factory

NASA Astrophysics Data System (ADS)

Okada, S.; Sunaga, H.; Kaneko, H.; Takizawa, H.; Kawasuso, A.; Yotsumoto, K.; Tanaka, R.

1999-06-01

The Positron Factory has been planned at Japan Atomic Energy Research Institute (JAERI). The factory is expected to produce linac-based monoenergetic positron beams having world-highest intensities of more than 1010e+/sec, which will be applied for R&D of materials science, biotechnology and basic physics & chemistry. In this article, results of the design studies are demonstrated for the following essential components of the facilities: 1) Conceptual design of a high-power electron linac with 100 MeV in beam energy and 100 kW in averaged beam power, 2) Performance tests of the RF window in the high-power klystron and of the electron beam window, 3) Development of a self-driven rotating electron-to-positron converter and the performance tests, 4) Proposal of multi-channel beam generation system for monoenergetic positrons, with a series of moderator assemblies based on a newly developed Monte Carlo simulation and the demonstrative experiment, 5) Proposal of highly efficient moderator structures, 6) Conceptual design of a local shield to suppress the surrounding radiation and activation levels.

Rank-based permutation approaches for non-parametric factorial designs.

PubMed

Umlauft, Maria; Konietschke, Frank; Pauly, Markus

2017-11-01

Inference methods for null hypotheses formulated in terms of distribution functions in general non-parametric factorial designs are studied. The methods can be applied to continuous, ordinal or even ordered categorical data in a unified way, and are based only on ranks. In this set-up Wald-type statistics and ANOVA-type statistics are the current state of the art. The first method is asymptotically exact but a rather liberal statistical testing procedure for small to moderate sample size, while the latter is only an approximation which does not possess the correct asymptotic α level under the null. To bridge these gaps, a novel permutation approach is proposed which can be seen as a flexible generalization of the Kruskal-Wallis test to all kinds of factorial designs with independent observations. It is proven that the permutation principle is asymptotically correct while keeping its finite exactness property when data are exchangeable. The results of extensive simulation studies foster these theoretical findings. A real data set exemplifies its applicability. © 2017 The British Psychological Society.

Efficient production of soluble recombinant single chain Fv fragments by a Pseudomonas putida strain KT2440 cell factory.

PubMed

Dammeyer, Thorben; Steinwand, Miriam; Krüger, Sarah-C; Dübel, Stefan; Hust, Michael; Timmis, Kenneth N

2011-02-21

Recombinant antibody fragments have a wide range of applications in research, diagnostics and therapy. For many of these, small fragments like single chain fragment variables (scFv) function well and can be produced inexpensively in bacterial expression systems. Although Escherichia coli K-12 production systems are convenient, yields of different fragments, even those produced from codon-optimized expression systems, vary significantly. Where yields are inadequate, alternative production systems are needed. Pseudomonas putida strain KT2440 is a versatile biosafety strain known for good expression of heterologous genes, so we have explored its utility as a cell factory for production of scFvs. We have generated new broad host range scFv expression constructs and assessed their production in the Pseudomonas putida KT2440 host. Two scFvs bind either to human C-reactive protein or to mucin1, proteins of significant medical diagnostic and therapeutic interest, whereas a third is a model anti-lysozyme scFv. The KT2440 antibody expression systems produce scFvs targeted to the periplasmic space that were processed precisely and were easily recovered and purified by single-step or tandem affinity chromatography. The influence of promoter system, codon optimization for P. putida, and medium on scFv yield was examined. Yields of up to 3.5 mg/l of pure, soluble, active scFv fragments were obtained from shake flask cultures of constructs based on the original codon usage and expressed from the Ptac expression system, yields that were 2.5-4 times higher than those from equivalent cultures of an E. coli K-12 expression host. Pseudomonas putida KT2440 is a good cell factory for the production of scFvs, and the broad host range constructs we have produced allow yield assessment in a number of different expression hosts when yields in one initially selected are insufficient. High cell density cultivation and further optimization and refinement of the KT2440 cell factory will achieve additional increases in the yields of scFvs.

Off-Line Quality Control In Integrated Circuit Fabrication Using Experimental Design

NASA Astrophysics Data System (ADS)

Phadke, M. S.; Kackar, R. N.; Speeney, D. V.; Grieco, M. J.

1987-04-01

Off-line quality control is a systematic method of optimizing production processes and product designs. It is widely used in Japan to produce high quality products at low cost. The method was introduced to us by Professor Genichi Taguchi who is a Deming-award winner and a former Director of the Japanese Academy of Quality. In this paper we will i) describe the off-line quality control method, and ii) document our efforts to optimize the process for forming contact windows in 3.5 Aim CMOS circuits fabricated in the Murray Hill Integrated Circuit Design Capability Laboratory. In the fabrication of integrated circuits it is critically important to produce contact windows of size very near the target dimension. Windows which are too small or too large lead to loss of yield. The off-line quality control method has improved both the process quality and productivity. The variance of the window size has been reduced by a factor of four. Also, processing time for window photolithography has been substantially reduced. The key steps of off-line quality control are: i) Identify important manipulatable process factors and their potential working levels. ii) Perform fractional factorial experiments on the process using orthogonal array designs. iii) Analyze the resulting data to determine the optimum operating levels of the factors. Both the process mean and the process variance are considered in this analysis. iv) Conduct an additional experiment to verify that the new factor levels indeed give an improvement.

Quantum computation with realistic magic-state factories

NASA Astrophysics Data System (ADS)

O'Gorman, Joe; Campbell, Earl T.

2017-03-01

Leading approaches to fault-tolerant quantum computation dedicate a significant portion of the hardware to computational factories that churn out high-fidelity ancillas called magic states. Consequently, efficient and realistic factory design is of paramount importance. Here we present the most detailed resource assessment to date of magic-state factories within a surface code quantum computer, along the way introducing a number of techniques. We show that the block codes of Bravyi and Haah [Phys. Rev. A 86, 052329 (2012), 10.1103/PhysRevA.86.052329] have been systematically undervalued; we track correlated errors both numerically and analytically, providing fidelity estimates without appeal to the union bound. We also introduce a subsystem code realization of these protocols with constant time and low ancilla cost. Additionally, we confirm that magic-state factories have space-time costs that scale as a constant factor of surface code costs. We find that the magic-state factory required for postclassical factoring can be as small as 6.3 million data qubits, ignoring ancilla qubits, assuming 10-4 error gates and the availability of long-range interactions.

Molecular Breeding to Create Optimized Crops: From Genetic Manipulation to Potential Applications in Plant Factories.

PubMed

Hiwasa-Tanase, Kyoko; Ezura, Hiroshi

2016-01-01

Crop cultivation in controlled environment plant factories offers great potential to stabilize the yield and quality of agricultural products. However, many crops are currently unsuited to these environments, particularly closed cultivation systems, due to space limitations, low light intensity, high implementation costs, and high energy requirements. A major barrier to closed system cultivation is the high running cost, which necessitates the use of high-margin crops for economic viability. High-value crops include those with enhanced nutritional value or containing additional functional components for pharmaceutical production or with the aim of providing health benefits. In addition, it is important to develop cultivars equipped with growth parameters that are suitable for closed cultivation. Small plant size is of particular importance due to the limited cultivation space. Other advantageous traits are short production cycle, the ability to grow under low light, and high nutriculture availability. Cost-effectiveness is improved from the use of cultivars that are specifically optimized for closed system cultivation. This review describes the features of closed cultivation systems and the potential application of molecular breeding to create crops that are optimized for cost-effectiveness and productivity in closed cultivation systems.

Molecular Breeding to Create Optimized Crops: From Genetic Manipulation to Potential Applications in Plant Factories

PubMed Central

Hiwasa-Tanase, Kyoko; Ezura, Hiroshi

2016-01-01

Crop cultivation in controlled environment plant factories offers great potential to stabilize the yield and quality of agricultural products. However, many crops are currently unsuited to these environments, particularly closed cultivation systems, due to space limitations, low light intensity, high implementation costs, and high energy requirements. A major barrier to closed system cultivation is the high running cost, which necessitates the use of high-margin crops for economic viability. High-value crops include those with enhanced nutritional value or containing additional functional components for pharmaceutical production or with the aim of providing health benefits. In addition, it is important to develop cultivars equipped with growth parameters that are suitable for closed cultivation. Small plant size is of particular importance due to the limited cultivation space. Other advantageous traits are short production cycle, the ability to grow under low light, and high nutriculture availability. Cost-effectiveness is improved from the use of cultivars that are specifically optimized for closed system cultivation. This review describes the features of closed cultivation systems and the potential application of molecular breeding to create crops that are optimized for cost-effectiveness and productivity in closed cultivation systems. PMID:27200016

Vision-Based Sensor for Early Detection of Periodical Defects in Web Materials

PubMed Central

Bulnes, Francisco G.; Usamentiaga, Rubén; García, Daniel F.; Molleda, Julio

2012-01-01

During the production of web materials such as plastic, textiles or metal, where there are rolls involved in the production process, periodically generated defects may occur. If one of these rolls has some kind of flaw, it can generate a defect on the material surface each time it completes a full turn. This can cause the generation of a large number of surface defects, greatly degrading the product quality. For this reason, it is necessary to have a system that can detect these situations as soon as possible. This paper presents a vision-based sensor for the early detection of this kind of defects. It can be adapted to be used in the inspection of any web material, even when the input data are very noisy. To assess its performance, the sensor system was used to detect periodical defects in hot steel strips. A total of 36 strips produced in ArcelorMittal Avilés factory were used for this purpose, 18 to determine the optimal configuration of the proposed sensor using a full-factorial experimental design and the other 18 to verify the validity of the results. Next, they were compared with those provided by a commercial system used worldwide, showing a clear improvement. PMID:23112629

A Factorial Analysis Study on Enzymatic Hydrolysis of Fiber Pressed Oil Palm Frond for Bioethanol Production

NASA Astrophysics Data System (ADS)

Hashim, F. S.; Yussof, H. W.; Zahari, M. A. K. M.; Illias, R. M.; Rahman, R. A.

2016-03-01

Different technologies have been developed to for the conversion of lignocellulosic biomass to suitable fermentation substrates for bioethanol production. The enzymatic conversion of cellulose seems to be the most promising technology as it is highly specific and does not produce substantial amounts of unwanted byproducts. The effects of agitation speed, enzyme loading, temperature, pH and reaction time on the conversion of glucose from fiber pressed oil palm frond (FPOPF) for bioethanol production were screened by statistical analysis using response surface methodology (RSM). A half fraction two-level factorial analysis with five factors was selected for the experimental design to determine the best enzymatic conditions that produce maximum amount of glucose. FPOPF was pre-treated with alkaline prior to enzymatic hydrolysis. The enzymatic hydrolysis was performed using a commercial enzyme Cellic CTec2. From this study, the highest yield of glucose concentration was 9.736 g/L at 72 hours reaction time at 35 °C, pH 5.6, and 1.5% (w/v) of enzyme loading. The model obtained was significant with p-value <0.0001. It is suggested that this model had a maximum point which is likely to be the optimum point and possible for the optimization process.

Accelerator Physics Working Group Summary

NASA Astrophysics Data System (ADS)

Li, D.; Uesugi, T.; Wildnerc, E.

2010-03-01

The Accelerator Physics Working Group addressed the worldwide R&D activities performed in support of future neutrino facilities. These studies cover R&D activities for Super Beam, Beta Beam and muon-based Neutrino Factory facilities. Beta Beam activities reported the important progress made, together with the research activity planned for the coming years. Discussion sessions were also organized jointly with other working groups in order to define common ground for the optimization of a future neutrino facility. Lessons learned from already operating neutrino facilities provide key information for the design of any future neutrino facility, and were also discussed in this meeting. Radiation damage, remote handling for equipment maintenance and exchange, and primary proton beam stability and monitoring were among the important subjects presented and discussed. Status reports for each of the facility subsystems were presented: proton drivers, targets, capture systems, and muon cooling and acceleration systems. The preferred scenario for each type of possible future facility was presented, together with the challenges and remaining issues. The baseline specification for the muon-based Neutrino Factory was reviewed and updated where required. This report will emphasize new results and ideas and discuss possible changes in the baseline scenarios of the facilities. A list of possible future steps is proposed that should be followed up at NuFact10.

More ethical and more efficient clinical research: multiplex trial design.

PubMed

Keus, Frederik; van der Horst, Iwan C C; Nijsten, Maarten W

2014-08-14

Today's clinical research faces challenges such as a lack of clinical equipoise between treatment arms, reluctance in randomizing for multiple treatments simultaneously, inability to address interactions and increasingly restricted resources. Furthermore, many trials are biased by extensive exclusion criteria, relatively small sample size and less appropriate outcome measures. We propose a 'Multiplex' trial design that preserves clinical equipoise with a continuous and factorial trial design that will also result in more efficient use of resources. This multiplex design accommodates subtrials with appropriate choice of treatment arms within each subtrial. Clinical equipoise should increase consent rates while the factorial design is the best way to identify interactions. The multiplex design may evolve naturally from today's research limitations and challenges, while principal objections seem absent. However this new design poses important infrastructural, organisational and psychological challenges that need in depth consideration.

Optimization of Maillard Reaction in Model System of Glucosamine and Cysteine Using Response Surface Methodology

PubMed Central

Arachchi, Shanika Jeewantha Thewarapperuma; Kim, Ye-Joo; Kim, Dae-Wook; Oh, Sang-Chul; Lee, Yang-Bong

2017-01-01

Sulfur-containing amino acids play important roles in good flavor generation in Maillard reaction of non-enzymatic browning, so aqueous model systems of glucosamine and cysteine were studied to investigate the effects of reaction temperature, initial pH, reaction time, and concentration ratio of glucosamine and cysteine. Response surface methodology was applied to optimize the independent reaction parameters of cysteine and glucosamine in Maillard reaction. Box-Behnken factorial design was used with 30 runs of 16 factorial levels, 8 axial levels and 6 central levels. The degree of Maillard reaction was determined by reading absorption at 425 nm in a spectrophotometer and Hunter’s L, a, and b values. ΔE was consequently set as the fifth response factor. In the statistical analyses, determination coefficients (R2) for their absorbance, Hunter’s L, a, b values, and ΔE were 0.94, 0.79, 0.73, 0.96, and 0.79, respectively, showing that the absorbance and Hunter’s b value were good dependent variables for this model system. The optimum processing parameters were determined to yield glucosamine-cysteine Maillard reaction product with higher absorbance and higher colour change. The optimum estimated absorbance was achieved at the condition of initial pH 8.0, 111°C reaction temperature, 2.47 h reaction time, and 1.30 concentration ratio. The optimum condition for colour change measured by Hunter’s b value was 2.41 h reaction time, 114°C reaction temperature, initial pH 8.3, and 1.26 concentration ratio. These results can provide the basic information for Maillard reaction of aqueous model system between glucosamine and cysteine. PMID:28401086

Optimization of Maillard Reaction in Model System of Glucosamine and Cysteine Using Response Surface Methodology.

PubMed

Arachchi, Shanika Jeewantha Thewarapperuma; Kim, Ye-Joo; Kim, Dae-Wook; Oh, Sang-Chul; Lee, Yang-Bong

2017-03-01

Sulfur-containing amino acids play important roles in good flavor generation in Maillard reaction of non-enzymatic browning, so aqueous model systems of glucosamine and cysteine were studied to investigate the effects of reaction temperature, initial pH, reaction time, and concentration ratio of glucosamine and cysteine. Response surface methodology was applied to optimize the independent reaction parameters of cysteine and glucosamine in Maillard reaction. Box-Behnken factorial design was used with 30 runs of 16 factorial levels, 8 axial levels and 6 central levels. The degree of Maillard reaction was determined by reading absorption at 425 nm in a spectrophotometer and Hunter's L, a, and b values. ΔE was consequently set as the fifth response factor. In the statistical analyses, determination coefficients (R 2 ) for their absorbance, Hunter's L, a, b values, and ΔE were 0.94, 0.79, 0.73, 0.96, and 0.79, respectively, showing that the absorbance and Hunter's b value were good dependent variables for this model system. The optimum processing parameters were determined to yield glucosamine-cysteine Maillard reaction product with higher absorbance and higher colour change. The optimum estimated absorbance was achieved at the condition of initial pH 8.0, 111°C reaction temperature, 2.47 h reaction time, and 1.30 concentration ratio. The optimum condition for colour change measured by Hunter's b value was 2.41 h reaction time, 114°C reaction temperature, initial pH 8.3, and 1.26 concentration ratio. These results can provide the basic information for Maillard reaction of aqueous model system between glucosamine and cysteine.

Evolutionary optimization methods for accelerator design

NASA Astrophysics Data System (ADS)

Poklonskiy, Alexey A.

Many problems from the fields of accelerator physics and beam theory can be formulated as optimization problems and, as such, solved using optimization methods. Despite growing efficiency of the optimization methods, the adoption of modern optimization techniques in these fields is rather limited. Evolutionary Algorithms (EAs) form a relatively new and actively developed optimization methods family. They possess many attractive features such as: ease of the implementation, modest requirements on the objective function, a good tolerance to noise, robustness, and the ability to perform a global search efficiently. In this work we study the application of EAs to problems from accelerator physics and beam theory. We review the most commonly used methods of unconstrained optimization and describe the GATool, evolutionary algorithm and the software package, used in this work, in detail. Then we use a set of test problems to assess its performance in terms of computational resources, quality of the obtained result, and the tradeoff between them. We justify the choice of GATool as a heuristic method to generate cutoff values for the COSY-GO rigorous global optimization package for the COSY Infinity scientific computing package. We design the model of their mutual interaction and demonstrate that the quality of the result obtained by GATool increases as the information about the search domain is refined, which supports the usefulness of this model. We Giscuss GATool's performance on the problems suffering from static and dynamic noise and study useful strategies of GATool parameter tuning for these and other difficult problems. We review the challenges of constrained optimization with EAs and methods commonly used to overcome them. We describe REPA, a new constrained optimization method based on repairing, in exquisite detail, including the properties of its two repairing techniques: REFIND and REPROPT. We assess REPROPT's performance on the standard constrained optimization test problems for EA with a variety of different configurations and suggest optimal default parameter values based on the results. Then we study the performance of the REPA method on the same set of test problems and compare the obtained results with those of several commonly used constrained optimization methods with EA. Based on the obtained results, particularly on the outstanding performance of REPA on test problem that presents significant difficulty for other reviewed EAs, we conclude that the proposed method is useful and competitive. We discuss REPA parameter tuning for difficult problems and critically review some of the problems from the de-facto standard test problem set for the constrained optimization with EA. In order to demonstrate the practical usefulness of the developed method, we study several problems of accelerator design and demonstrate how they can be solved with EAs. These problems include a simple accelerator design problem (design a quadrupole triplet to be stigmatically imaging, find all possible solutions), a complex real-life accelerator design problem (an optimization of the front end section for the future neutrino factory), and a problem of the normal form defect function optimization which is used to rigorously estimate the stability of the beam dynamics in circular accelerators. The positive results we obtained suggest that the application of EAs to problems from accelerator theory can be very beneficial and has large potential. The developed optimization scenarios and tools can be used to approach similar problems.

Tributes beyond Words: Art Educators' Use of Textiles to Memorialize the Triangle Shirtwaist Factory Fire

ERIC Educational Resources Information Center

Mercurio, Mia Lynn; Randall, Régine

2016-01-01

Through the study of The Triangle Shirtwaist Factory fire, pre-service art teachers learn the about interdisciplinary design and the importance of using discipline-specific literacy strategies alongside the materials and methods of their craft. The creativity and enthusiasm with which these preservice teachers approached the work convinced us that…

Engineering microbial cell factories for the production of plant natural products: from design principles to industrial-scale production.

PubMed

Liu, Xiaonan; Ding, Wentao; Jiang, Huifeng

2017-07-19

Plant natural products (PNPs) are widely used as pharmaceuticals, nutraceuticals, seasonings, pigments, etc., with a huge commercial value on the global market. However, most of these PNPs are still being extracted from plants. A resource-conserving and environment-friendly synthesis route for PNPs that utilizes microbial cell factories has attracted increasing attention since the 1940s. However, at the present only a handful of PNPs are being produced by microbial cell factories at an industrial scale, and there are still many challenges in their large-scale application. One of the challenges is that most biosynthetic pathways of PNPs are still unknown, which largely limits the number of candidate PNPs for heterologous microbial production. Another challenge is that the metabolic fluxes toward the target products in microbial hosts are often hindered by poor precursor supply, low catalytic activity of enzymes and obstructed product transport. Consequently, despite intensive studies on the metabolic engineering of microbial hosts, the fermentation costs of most heterologously produced PNPs are still too high for industrial-scale production. In this paper, we review several aspects of PNP production in microbial cell factories, including important design principles and recent progress in pathway mining and metabolic engineering. In addition, implemented cases of industrial-scale production of PNPs in microbial cell factories are also highlighted.

Artificial diet optimized to produce normative adults of Diaprepes abbreviatus (Coleoptera: Curculionidae)

USDA-ARS?s Scientific Manuscript database

Insect diets are often complex mixtures of vitamins, salts, preservatives, and nutrients (carbohydrates, lipids and proteins). To determine the effect of varying the doses of multiple components, the traditional approach requires large factorial experiments resulting in very large numbers of treat...

On the Optimization of the Doses of Chemical Fertilizers for Crops

NASA Astrophysics Data System (ADS)

Sala, Florin; Boldea, Marius

2011-09-01

The mono-factorial model, which gives the relation between the yield and the dose of chemical fertilizers, is based on the Mitscherlich function f1(x) = f1(0)+a1(1-e-11x). In addition to this function, we can consider f2(x) = f2(0)+a2 tanh(b2x), to be the basis for a new mathematical model, where tanh(b2x) represents the hyperbolic tangent. In the case of a bi-factorial model: f(x,y) = f(0,0)+a1 tanh(b1x)+a2 tanh(b2y)+a3 tanh(b1x)tanh(b2y) represents a generalization of the last relation. The constants that are involved in these functions are determined with the least squares method, by comparison with the experimental data. Taking into account both the market value of the products and the cost of fertilizers, we can find the optimal doses for maximizing certain economic indicators, such as revenue or profitability.

Formulation and optimization of mouth dissolve tablets containing rofecoxib solid dispersion.

PubMed

Sammour, Omaima A; Hammad, Mohammed A; Megrab, Nagia A; Zidan, Ahmed S

2006-06-16

The purpose of the present investigation was to increase the solubility and dissolution rate of rofecoxib by the preparation of its solid dispersion with polyvinyl pyrrolidone K30 (PVP K30) using solvent evaporation method. Drug-polymer interactions were investigated using differential scanning calorimetry (DSC), x-ray diffraction (XRD), and Fourier transform infrared spectroscopy (FTIR). For the preparation of rofecoxib mouth dissolve tablets, its 1:9 solid dispersion with PVP K30 was used with various disintegrants and sublimable materials. In an attempt to construct a statistical model for the prediction of disintegration time and percentage friability, a 3(2) randomized full and reduced factorial design was used to optimize the influence of the amounts of superdisintegrant and subliming agent. The obtained results showed that dispersion of the drug in the polymer considerably enhanced the dissolution rate. The drug-to-carrier ratio was the controlling factor for dissolution improvement. FTIR spectra revealed no chemical incompatibility between the drug and PVP K30. As indicated from XRD and DSC data, rofecoxib was in the amorphous form, which explains the better dissolution rate of the drug from its solid dispersions. Concerning the optimization study, the multiple regression analysis revealed that an optimum concentration of camphor and a higher percentage of crospovidone are required for obtaining rapidly disintegrating tablets. In conclusion, this investigation demonstrated the potential of experimental design in understanding the effect of the formulation variables on the quality of mouth dissolve tablets containing solid dispersion of a hydrophobic drug.

The structure and photocatalytic activity of TiO2 thin films deposited by dc magnetron sputtering

NASA Astrophysics Data System (ADS)

Yang, W. J.; Hsu, C. Y.; Liu, Y. W.; Hsu, R. Q.; Lu, T. W.; Hu, C. C.

2012-12-01

This paper seeks to determine the optimal settings for the deposition parameters, for TiO2 thin film, prepared on non-alkali glass substrates, by direct current (dc) sputtering, using a ceramic TiO2 target in an argon gas environment. An orthogonal array, the signal-to-noise ratio and analysis of variance are used to analyze the effect of the deposition parameters. Using the Taguchi method for design of a robust experiment, the interactions between factors are also investigated. The main deposition parameters, such as dc power (W), sputtering pressure (Pa), substrate temperature (°C) and deposition time (min), were optimized, with reference to the structure and photocatalytic characteristics of TiO2. The results of this study show that substrate temperature and deposition time have the most significant effect on photocatalytic performance. For the optimal combination of deposition parameters, the (1 1 0) and (2 0 0) peaks of the rutile structure and the (2 0 0) peak of the anatase structure were observed, at 2θ ˜ 27.4°, 39.2° and 48°, respectively. The experimental results illustrate that the Taguchi method allowed a suitable solution to the problem, with the minimum number of trials, compared to a full factorial design. The adhesion of the coatings was also measured and evaluated, via a scratch test. Superior wear behavior was observed, for the TiO2 film, because of the increased strength of the interface of micro-blasted tools.

Nanostructured lipid carriers for oral bioavailability enhancement of raloxifene: Design and in vivo study.

PubMed

Shah, Nirmal V; Seth, Avinash K; Balaraman, R; Aundhia, Chintan J; Maheshwari, Rajesh A; Parmar, Ghanshyam R

2016-05-01

The objective of present work was to utilize potential of nanostructured lipid carriers (NLCs) for improvement in oral bioavailability of raloxifene hydrochloride (RLX). RLX loaded NLCs were prepared by solvent diffusion method using glyceryl monostearate and Capmul MCM C8 as solid lipid and liquid lipid, respectively. A full 3(2) factorial design was utilized to study the effect of two independent parameters namely solid lipid to liquid lipid ratio and concentration of stabilizer on the entrapment efficiency of prepared NLCs. The statistical evaluation confirmed pronounced improvement in entrapment efficiency when liquid lipid content in the formulation increased from 5% w/w to 15% w/w. Solid-state characterization studies (DSC and XRD) in optimized formulation NLC-8 revealed transformation of RLX from crystalline to amorphous form. Optimized formulation showed 32.50 ± 5.12 nm average particle size and -12.8 ± 3.2 mV zeta potential that impart good stability of NLCs dispersion. In vitro release study showed burst release for initial 8 h followed by sustained release up to 36 h. TEM study confirmed smooth surface discrete spherical nano sized particles. To draw final conclusion, in vivo pharmacokinetic study was carried out that showed 3.75-fold enhancements in bioavailability with optimized NLCs formulation than plain drug suspension. These results showed potential of NLCs for significant improvement in oral bioavailability of poorly soluble RLX.

Development and optimization of press coated tablets of release engineered valsartan for pulsatile delivery.

PubMed

Shah, Sunny; Patel, Romik; Soniwala, Moinuddin; Chavda, Jayant

2015-01-01

The present work is aimed to develop and optimize pulsatile delivery during dissolution of an improved formulation of valsartan to coordinate the drug release with circadian rhythm. Preliminary studies suggested that β cyclodextrin could improve the solubility of valsartan and showed AL type solubility curve. A 1:1 stoichiometric ratio of valsartan to β cyclodextrin was revealed from phase solubility studies and Job's plot. The prepared complex showed significantly better dissolution efficiency (p < 0.05) compared to pure drug, which could be due to the formation of inclusion complex as revealed from FTIR and DSC studies. Continuous dissolution-absorption studies revealed that absorption of drug from valsartan β cyclodextrin complex was significantly higher (p < 0.05) compared to pure drug, in second part press-coated tablets of valsartan β cyclodextrin complex were subsequently prepared and application of the Plackett-Burman screening design revealed that HPMC K4M and EC showed significant effect on lag time. A 3(2) full factorial design was used to measure the response of HPMC K4M and EC on lag time and time taken for 90% drug release (T90). The optimized batch prepared according to the levels obtained from the desirability function had a lag time of 6 h and consisted of HPMC K4M:ethylcellulose in a 1:1.5 ratio with 180 mg of coating and revealed a close agreement between observed and predicted value (R(2 )= 0.9694).

Electrochemical treatment of domestic wastewater using boron-doped diamond and nanostructured amorphous carbon electrodes.

PubMed

Daghrir, Rimeh; Drogui, Patrick; Tshibangu, Joel; Delegan, Nazar; El Khakani, My Ali

2014-05-01

The performance of the electrochemical oxidation process for efficient treatment of domestic wastewater loaded with organic matter was studied. The process was firstly evaluated in terms of its capability of producing an oxidant agent (H2O2) using amorphous carbon (or carbon felt) as cathode, whereas Ti/BDD electrode was used as anode. Relatively high concentrations of H2O2 (0.064 mM) was produced after 90 min of electrolysis time, at 4.0 A of current intensity and using amorphous carbon at the cathode. Factorial design and central composite design methodologies were successively used to define the optimal operating conditions to reach maximum removal of chemical oxygen demand (COD) and color. Current intensity and electrolysis time were found to influence the removal of COD and color. The contribution of current intensity on the removal of COD and color was around 59.1 and 58.8%, respectively, whereas the contribution of treatment time on the removal of COD and color was around 23.2 and 22.9%, respectively. The electrochemical treatment applied under 3.0 A of current intensity, during 120 min of electrolysis time and using Ti/BDD as anode, was found to be the optimal operating condition in terms of cost/effectiveness. Under these optimal conditions, the average removal rates of COD and color were 78.9 ± 2 and 85.5 ± 2 %, whereas 70% of total organic carbon removal was achieved.

Nanostructured lipid carriers for oral bioavailability enhancement of raloxifene: Design and in vivo study

PubMed Central

Shah, Nirmal V.; Seth, Avinash K.; Balaraman, R.; Aundhia, Chintan J.; Maheshwari, Rajesh A.; Parmar, Ghanshyam R.

2016-01-01

The objective of present work was to utilize potential of nanostructured lipid carriers (NLCs) for improvement in oral bioavailability of raloxifene hydrochloride (RLX). RLX loaded NLCs were prepared by solvent diffusion method using glyceryl monostearate and Capmul MCM C8 as solid lipid and liquid lipid, respectively. A full 32 factorial design was utilized to study the effect of two independent parameters namely solid lipid to liquid lipid ratio and concentration of stabilizer on the entrapment efficiency of prepared NLCs. The statistical evaluation confirmed pronounced improvement in entrapment efficiency when liquid lipid content in the formulation increased from 5% w/w to 15% w/w. Solid-state characterization studies (DSC and XRD) in optimized formulation NLC-8 revealed transformation of RLX from crystalline to amorphous form. Optimized formulation showed 32.50 ± 5.12 nm average particle size and −12.8 ± 3.2 mV zeta potential that impart good stability of NLCs dispersion. In vitro release study showed burst release for initial 8 h followed by sustained release up to 36 h. TEM study confirmed smooth surface discrete spherical nano sized particles. To draw final conclusion, in vivo pharmacokinetic study was carried out that showed 3.75-fold enhancements in bioavailability with optimized NLCs formulation than plain drug suspension. These results showed potential of NLCs for significant improvement in oral bioavailability of poorly soluble RLX. PMID:27222747