Face-centered Cube Design Research Articles

Optimization of a Validated Liquid Chromatographic Method with Chemometric Approach for Estimation of Eugenol from Seed Powder Extract and Perform Anti-oxidant Activity

Background:: Developed and validated a new reverse phase high-performance liquid chromatographic (RP-HPLC) method, and it is prompt, precise, sensitive and robust for the esti-mation of eugenol in seed powder extract of Myristica fragrans. Objective:: The chemometric approach was utilized to obtain a rugged and definitive chromato-graphic method for the purpose. Methods:: Method variables such as acetonitrile (%) and flow rate were investigated for robust-ness and optimization by using a face-centered cubic design (FCCD). The Design Expert 12.0.1.0 software has been employed for this optimization. Further, the effects of factors were monitored on the concentrations of eugenol recovered from seed powder extract. Chromatograms have been developed by using an optimized mobile phase mixture containing methanol-water-acetonitrile (10:40:50, v/v/v) and Symmetry® C18 column (5 μm, 3.9 ×150 mm). The mobile phase was de-rived at a flow rate of 1 mL/min, and estimation of eugenol was performed at ʎmax 272 nm. Results:: Validation of the method has been carried out to reveal its selectivity, linearity, preci-sion, accuracy, LOD, and LOQ. Linear calibration plot for eugenol was held over the concentra-tion across 6.25 and 100 μg/mL (R2 = 0.999). The coefficient of variation was less than 1%, and accurate recovery of eugenol was observed between 96.80 and 99.56 %. The LOD and LOQ have been established to be 1.97 and 6.25 μg/mL, respectively. Intraday and Inter-day coefficients of variation have 1.81-1.91 and 1.92-1.57, respectively. Antioxidant activity (AA) by DPPH assay of seed powder extract in five different solvents was performed, and % AA activity was calculat-ed against ascorbic acid. Conclusion:: The validated method has been found to be highly robust and will be applied for the analysis of eugenol in formulation. The highest % AA has been reported in hexane solvent.

Mixing assisted oxidative desulfurization using a synthesized catalyst of the activated carbon supported phosphotungstic acid: A process optimization study

Desulfurization technology is vital in the removal of sulfur compounds in diesel to attain clean fuels. In this research, the mixing assisted oxidative desulfurization (MAOD) in conjunction with a high shear mixer was used with the catalyst of the activated carbon supported phosphotungstic acid. This study discusses the desulfurization of a simulated diesel, containing 2.3 wt% S of dibenzothiophene and benzothiophene in real fuel oil. The influences of mixing speed (8,000 rpm to 16,800 rpm), mixing time (30 min to 90 min), and mixing temperature (25°C to 65°C) were examined for the sulfur oxidation. A 2k full factorial design and a face-centered cube design were utilized for the screening and optimization studies, respectively, in the experimental runs. The analysis of variance was able to determine and generate a simplified quadratic model to predict the response in the MAOD process. The optimum variables for sulfur conversion were achieved at 88.5 min (mixing time), 16,800 rpm (mixing speed), and 63.28°C (mixing temperature). The confirmatory run resulted in percent oxidation of 62.37 % and validated the generated model. Moreover, the fundamental properties of diesel oil were analyzed for comparison prior to and after the MAOD method. The results revealed the retention of essential properties of the simulated diesel oil even after the MAOD treatment step. Thus, the MAOD process has successfully preserved the properties of diesel oil even after its treatment process. This indicates a promising result of the MAOD process favorable for its future applications.

An evaluation of factors influencing drag coefficient in double-deck tunnels by CFD simulations using factorial design method

Vehicular drag coefficients in road-tunnel systems are complexly affected by traffic conditions, in terms of vehicle speed and density. Using computational fluid dynamics (CFD)-based factorial design, this study evaluates factors influencing the drag coefficient of a sedan in the Korean double-deck tunnel (KDDT) system, which divides the roadway into upper and lower levels within a single-tube tunnel. The tested factors included blockage ratio, Reynolds number, spacing ratio, and roughness height of the vehicular surface. Results showed that the blockage ratio had the most significant effect in the KDDT system, followed by the spacing ratio and the Reynolds number. A negative interaction effect was observed between the Reynolds number and spacing ratio, thereby indicating that dense traffic scenarios with fast-moving dense vehicles serve to reduce the averaged drag coefficient. In conjunction with the face-centered cube design, a response surface model (RSM) was constructed using a second-order polynomial model. For various tunnel configurations, data predicted by RSM were compared against results obtained from CFD simulations. A good agreement was observed between CFD and RSM with relative errors not exceeding 8.3% in most tunnel configurations investigated. Findings of this study suggest that the RSM can provide accurate estimates of the drag coefficient.

Optimizing extraction conditions of crude fiber, phenolic compounds, flavonoids and antioxidant activity of date seed powder.

The objective of this study was to optimize the extraction conditions of crude fiber, phenolic compounds, flavonoids, and antioxidant activity from date seeds powder, using Response Surface Methodology. A central composite design with four independent variables; concentration of ethanol (X1=25, 50 and 75%v/v), solvent: sample ratio (X2=40:1, 50:1 and 60:1 v/w), temperature (X3=45, 55 and 65°C), and extraction time (X4=1, 2 and 3h) and a three level face centered cube design were used. A total of twenty nine experimental runs with five replicates at the central point were used to study the response variables using two extraction cycles. Maximum phenolic compound content (71.6mg GAE/100g) was extracted using 50% ethanol solution with 40:1 solvent: sample ratio for 1h at 55°C. While the maximum antioxidant activity (55.02µmol Fe(II)/g) was obtained using similar ethanol concentration and solvent: sample ratio except at lower temperature (45°C) for 2h. On other hand, the maximum flavonoids content (455.77mg CEQ/100g) was reached by using 50% concentration, 50:1 solvent: sample ratio at 65°C for 3h. In contrast, the content of fiber was not affected by the different extraction conditions. Results indicate that using combination of extracted conditions, have a great potential for extracting all depending compounds except crude fiber.

Supramolecular nano-engineered lipidic carriers based on diflunisal-phospholipid complex for transdermal delivery: QbD based optimization, characterization and preclinical investigations for management of rheumatoid arthritis

Diflunisal (DIF) is used for treatment of rheumatoid arthritis, osteoarthritis etc. DIF-phospholipid complex (DIF-PL complex) was prepared by solvent-evaporation method and characterized by molecular docking studies, SEM, FTIR, DSC, PXRD studies. Further, the DIF-PL complex was incorporated into supramolecular nano-engineered lipidic carriers (SNLCs) for transdermal delivery. The optimization exercise was done using Face centered cubic design (FCCD) after screening of variables by L8 Taguchi orthogonal array design. The optimized SNLC formulation depicted average particle size (188.1nm), degree of entrapment (86.77±3.33%), permeation flux (5.47±0.48μg/cm2/h) and skin retention (17.72±0.68μg/cm2). The dermatokinetic studies revealed the higher concentration of DIF in dermis. The Confocal laser scanning microscopy (CSLM) studies revealed penetration of SNLCs into the deeper layers of skin. The results of mice ear edema depicted significant inhibition of ear edema (76.37±12.52%; p<0.05). In CFA induced rheumatoid arthritis model, the inhibition of paw edema was significantly higher (73.85±14.5%). The levels of TNF-α were reduced in synovial fluid (146.74±1.69pg/mL) and serum (132.43±2.70pg/mL). Furthermore, the licking and biting time was reduced in formalin induced hyperalgesia model. Hence, it can be concluded that dual formulation strategy based SNLCs were promising in treatment of pain and inflammation associated with rheumatoid arthritis.

NOVEL CHRONOTHERAPEUTIC MULTIPARTICULATE DRUG DELIVERY SYSTEM OF FELODIPINE: AN EFFECTIVE TREATMENT FOR CARDIAC ARRHYTHMIA

Arrhythmia follows chronobiology, thus necessitating development of time-dependent formulation for its treatment. The aim of the current work was to develop a solubility-enhanced chronotherapeutic system of felodipine, a widely prescribed anti-arrhythmic. Systematically optimized hot-melt extrusion process was employed to formulate solubility-enhanced extrudates. Film-casting method was adopted for the selection of polymers. Drug released at 5, 15, 30min was taken as response variables in 3 2 face-centered cube design. Nearly 10-fold increase was observed in the solubility of the optimized extrudates in comparison to pure drug. Physical characterization of the extrudates depicted complete amorphization of drug. Sequential coating was performed on to the extrudates to enable a time-dependent release. In-vitro studies clearly demonstrated that 25% of drug was available rapidly within 10 min of administration. The remaining 75% of drug was available over a period of 4, 8 and 12h. Stability studies performed for 6 months at accelerated conditions depicted no significant change in the physicochemical characteristics of the optimized formulation. In-vivo pharmacokinetic studies conducted in beagle dogs ratified the results of in-vitro studies where a sequential time dependent absorption of felodipine was observed over a period of 12h. Concisely, the studies demonstrated successful development of solubility-enhanced chronotherapeutic system of felodipine.

Phytoinhibitory activities and extraction optimization of potent invasive plants as eco-friendly weed suppressant against Echinochloa colona (L.) Link

Parasitic Echinochloa colona (L.) Link has globally invaded paddy fields that could devote to severe grain yield loss. Prolonged extensive application of commercial synthetic herbicides could pose the weed evolved resistance, bioaccumulation and environmental deterioration. Hence, this paper pertains to the aim of investigating potent natural products which have shown considerable phytotoxic activities, subsequent phytotoxin studies and extraction optimization for pre-emergent control of E. colona. In the phytotoxicity study, a suite of invasive plants was procured and the leaf, stem and root extracts were evaluated by in vitro germination and seedling growth assays. The invasive plant extracts exhibited multiple magnitudes of inhibition against E. colona in the plant species-, plant part- and concentration-dependent manners. Along with the dose-response study, the leaf extracts of Mikania micrantha Kunth ex H.B.K., Clidemia hirta (L.) D. Don , Dicranopteris linearis (Burm.f.) Underw. and Ageratum conyzoides L. showed the attainable half maximal effective doses (ED50) below the concentration 100g biomass dry weight equivalent (BDWE)/L, indicating the top-ranked inhibition of E. colona among the investigated plant extracts. The top-ranked phytotoxic leaf extracts were subjected to qualitative and quantitative characterizations including extraction yield, total phenolic content, phytochemical screening and spectroscopic analysis of the phytochemicals with possible inhibitory effect. Joint putative allelochemicals consisting of 16 phenolics and 5 aromatics were detected concurrently by liquid chromatography-mass spectrometry (LC-MS), were found contributed to the appreciable germination inhibition. Amongst the abundant phenolic acids were protocatechuic acid, gallic acid, p-hydroxyphenylacetic acid and chlorogenic acid. To suit the industrial desire in product development, the phytotoxic leaves were processed through extraction optimization using response surface methodology (RSM). A multivariate face-centered cube design (FCCD) was established to seek the functional relationship between the process variables (extraction time, agitation speed and solvent consumption) and the response (germination inhibition). Quadratic response surface models were obtained with the models significance and significant effect of the process factors at 95% confidence interval were examined by various statistical analyses. Verification experiments at the optimal conditions were well matched with the predicted values, along with absolute errors in the range 3.63% to 6.70%, indicating the proposed quadratic models were valid and useful prediction of the extraction conditions. These outcomes provide the valuable findings on the possible use of potent invasive plants as bioeffective, economical and eco-friendly herbicide alternative towards fostering the sustainable weed management.

Enhancing biopharmaceutical attributes of phospholipid complex-loaded nanostructured lipidic carriers of mangiferin: Systematic development, characterization and evaluation

Mangiferin (Mgf), largely expressed out from the leaves and stem bark of Mango, is a potent antioxidant. However, its in vivo activity gets tremendously reduced owing to poor aqueous solubility and inconsistent gastrointestinal absorption, high hepatic first-pass metabolism and high P-gp efflux. The current research work, therefore, was undertaken to overcome the biopharmaceutical hiccups by developing the Mgf-phospholipid complex (PLCs) loaded in nanostructured lipidic carriers (NLCs). The PLCs and NLCs were prepared using refluxing, solvent evaporation and hot emulsification technique, respectively with three molar ratios of Mgf and Phospholipon 90G, i.e., 1:1; 1:2; and 1:3. The complex was evaluated for various physicochemical parameters like drug content (96.57%), aqueous solubility (25-fold improved) and oil-water partition coefficient (10-fold enhanced). Diverse studies on the prepared complex using FTIR, DSC, PXRD and SEM studies ratified the formation of PLCs at 1:1 ratio. The PLCs were further incorporated onto NLCs, which were systematically optimized employing a face centered cubic design (FCCD), while evaluating for particle size, zeta potential, encapsulation efficiency and in vitro drug release as the CQAs. Caco-2 cell line studies indicated insignificant cytotoxicity, and P-gp efflux, while bi-directional permeability model and in situ perfusion studies specified enhanced intestinal permeation parameters. In vivo pharmacokinetic studies revealed notable increase in the values of Cmax (4.7-fold) and AUC (2.1-fold), respectively, from PLCs-loaded NLCs vis-à-vis Mgf solution. In a nutshell, the promising results observed from the present research work signify enhanced biopharmaceutical attributes of the novel PLCs-loaded NLCs for potentially augmenting the therapeutic efficacy of Mgf.

QbD-Oriented Development and Characterization of Effervescent Floating-Bioadhesive Tablets of Cefuroxime Axetil

The objective of the present studies was systematic development of floating-bioadhesive gastroretentive tablets of cefuroxime axetil employing rational blend of hydrophilic polymers for attaining controlled release drug delivery. As per the QbD-based approach, the patient-centric target product profile and quality attributes of tablet were earmarked, and preliminary studies were conducted for screening the suitability of type of polymers, polymer ratio, granulation technique, and granulation time for formulation of tablets. A face-centered cubic design (FCCD) was employed for optimization of the critical material attributes, i.e., concentration of release controlling polymers, PEO 303 and HPMC K100 LV CR, and evaluating in vitro buoyancy, drug release, and ex vivo mucoadhesion strength. The optimized formulation was embarked upon through numerical optimization, which yield excellent floatation characteristic with drug release control (i.e., T 60% > 6h) and bioadhesion strength. Drug-excipient compatibility studies through FTIR and P-XRD revealed the absence of any interaction between the drug and polymers. In vivo evaluation of the gastroretentive characteristics through X-ray imaging and in vivo pharmacokinetic studies in rabbits revealed significant extension in the rate of drug absorption (i.e., T max, K a, and MRT) from the optimized tablet formulation as compared to the marketed formulation. Successful establishment of various levels of in vitro/in vivo correlations (IVIVC) substantiated high degree of prognostic ability of in vitro dissolution conditions in predicting the in vivo performance. In a nutshell, the studies demonstrate successful development of the once-a-day gastroretentive formulations of cefuroxime axetil with controlled drug release profile and improved compliance.

Response surface modeling for hot, humid air decontamination of materials contaminated with Bacillus anthracis ∆Sterne and Bacillus thuringiensis Al Hakam spores.

Response surface methodology using a face-centered cube design was used to describe and predict spore inactivation of Bacillus anthracis ∆Sterne and Bacillus thuringiensis Al Hakam spores after exposure of six spore-contaminated materials to hot, humid air. For each strain/material pair, an attempt was made to fit a first or second order model. All three independent predictor variables (temperature, relative humidity, and time) were significant in the models except that time was not significant for B. thuringiensis Al Hakam on nylon. Modeling was unsuccessful for wiring insulation and wet spores because there was complete spore inactivation in the majority of the experimental space. In cases where a predictive equation could be fit, response surface plots with time set to four days were generated. The survival of highly purified Bacillus spores can be predicted for most materials tested when given the settings for temperature, relative humidity, and time. These predictions were cross-checked with spore inactivation measurements.

QbD-based systematic development of novel optimized solid self-nanoemulsifying drug delivery systems (SNEDDS) of lovastatin with enhanced biopharmaceutical performance

Of late, solid self-nanoemulsifying drug delivery systems (S-SNEDDS) have been extensively sought-after owing to their superior portability, drug loading, stability and patient compliance. The current studies, therefore, entail systematic development, optimization and evaluation (in vitro, in situ and in vivo) of the solid formulations of (SNEDDS) lovastatin employing rational quality by design (QbD)-based approach of formulation by design (FbD). The patient-centric quality target product profile (QTPP) and critical quality attributes (CQAs) were earmarked. Preformulation studies along with initial risk assessment facilitated the selection of lipid (i.e. Capmul MCM), surfactant (i.e. Nikkol HCO-50) and co-surfactant (i.e. Lutrol F127) as CMAs for formulation of S-SNEDDS. A face-centered cubic design (FCCD) was employed for optimization using Nikkol-HCO50 (X1) and Lutrol-F127 (X2), evaluating CQAs like globule size, liquefaction time, emulsification time, MDT, dissolution efficiency and permeation parameter. The design space was generated using apt mathematical models, and the optimum formulation was located, followed by validation of the FbD methodology. In situ SPIP and in vivo pharmacodynamic studies on the optimized formulation carried out in unisex Wistar rats, corroborated superior drug absorption and enhanced pharmacodynamic potential in regulating serum lipid levels. In a nutshell, the present studies report successful QbD-oriented development of novel oral S-SNEDDS of lovastatin with distinctly improved biopharmaceutical performance.

4륜 운반차 수직형 손잡이에서 인간공학적 최적 높이 및 간격 결정

Among various manual materials handling tasks, pushing/pulling was known to be one of the risk factors for the low back and shoulder musculoskeletal disorders (MSDs). This study was conducted to find out an optimal solution set of the handle height and distance for 4-wheel cart with two vertical handles. Ten male college students participated in the pushing force measurement experiment. The face-centered cube design, one of the central composite designs, was applied for the experiment, and the isometric voluntary pushing force was measured in 9 treatment conditions. The second order response surface model was predicted by using the pushing strength as a response variable, and the handle height and distance as independent factors. According to the 2nd order response model, the handle height and distance showed nonlinear relationship with the isometric pushing strength. To maximize the 2nd order response model (pushing force), the handle height and distance were optimized. The optimal handle height was 'xyphoid process height - stature', and the optimal handle distance was '<TEX>$1.25{\times}shoulder$</TEX> width'. When calculated using the anthropometric data of the subjects of this study, the optimal handle height was <TEX>$115.4{\pm}3.4$</TEX> cm, slightly higher than the elbow height, and the handle distance was <TEX>$52.9{\pm}2.3$</TEX> cm.

Optimized nanoemulsifying systems with enhanced bioavailability of carvedilol

The current studies entail a novel approach of formulating the solid self-nanoemulsifying drug delivery systems (S-SNEDDS) of carvedilol solely using rational blends of lipidic and emulsifying excipients without using equipment-intensive techniques and/or inert porous carriers. Delineating the nanoemulsion regions, the amounts of Capmul MCM (i.e., lipid) and Nikkol HCO 50 (i.e., emulgent) were selected as the critical factors for systematically formulating the optimized S-SNEDDS employing face centered cube design. The optimized formulation (mean globule size: 40.8nm) indicated marked improvement in drug release profile vis-à-vis pure drug and marketed formulation. Augmentation in the values of Cmax (134.2%) and AUC (85.2%) indicated significant enhancement in the rate and extent of bioavailability by the S-SNEDDS formulation compared to pure drug. In situ SPIP studies ascribed the significant enhancement in absorptivity parameters of SNEDDS formulations to transport through the lymphatic system and reduced P-gp efflux. Successful establishment of various levels of in vitro/in vivo correlations (IVIVC's) substantiated the judicious choice of the in vitro dissolution milieu for simulating the in vivo conditions. The optimized formulation was found to be quite stable during six months of study period. The current investigations, therefore, report the successful development of systematically optimized S-SNEDDS with enhanced bioavailability potential of carvedilol.

Systematic formulation development of once-a-day gastroretentive controlled release tablets of rivastigmine using optimized polymer blends

Abstract Rivastigmine is a drug extensively prescribed for the treatment of Alzheimer’s disease. On therapeutic fronts, severe gastrointestinal (GI) adverse effects owing to a rapid rise and fall in drug plasma levels, and the high frequency of its dosing, tend to limit its usage. The present investigation, therefore, aimed at developing a gastroretentive floating-bioadhesive CR formulation for delivering rivastigmine in a sustained manner at the desired site of absorption. Employing 7-factor Taguchi design, the influential factors were embarked upon as Carbopol 971P and Methocel K15M CR. Effervescent floating-bioadhesive hydrophilic matrices were systematically formulated using a face-centered cube design (FCCD) and evaluated for in vitro drug release, floatation and ex vivo bioadhesive strength. Optimal composition of polymer blends systematically chosen using brute-force methodology, overlay plots and desirability function exhibited excellent bioadhesive and floatational characteristics besides possessing adequate drug release control (T 60 > 5 h). Pharmacokinetic studies carried out in rabbits showed the absence of any sharp peaks or troughs in the plasma drug levels, and various levels of in vitro/in vivo correlation (IVIVC) were successfully established. In vivo gamma scintigraphic studies in human volunteers ratified the gastroretentive characteristics of the optimized formulation with retention time of 6 h or more. Thus, besides unraveling the polymer synergism, the study helped in developing an optimal once-a-day gastroretentive drug delivery system exhibiting excellent swelling, floating, and bioadhesive characteristics.

Optimized microwave-assisted extraction of total phenolics (TP) from Ipomoea batatas leaves and its antioxidant activity

Abstract An efficient microwave-assisted extraction (MAE) technique was employed to extract total phenolics (TP) from sweetpotato [Ipomoea batatas (L.) Lam.] leaves (TPSL). The optimal conditions for microwave-assisted extraction of TPSL were determined by response surface methodology. A face-centered cubic design (FCD) was applied to evaluate the effects of three independent variables (microwave power, extraction time and ethanol proportion) on the recovery of TPSL. The correlation analysis of the mathematical-regression model indicated that quadratic polynomial model could be employed to optimize the microwave extraction of TPSL. From response surface plots, microwave power, extraction time and ethanol proportion exhibited independent and interactive effects on the extraction of TPSL. The optimal conditions to obtain the highest recovery of TPSL were as follows: microwave power, 302 W; extraction time, 123 s; ethanol proportion, 53% (v/v). Under these optimal conditions, the experimental values agreed with the predicted ones by analysis of variance. It indicated high fitness of the model used and the success of response surface methodology for optimizing TPSL extraction. After method development, the antioxidant activity of the MAE extract was preliminarily evaluated. MAE showed obvious advantages in terms of high extraction efficiency and antioxidant activity of extract with in shortest extraction time. Industrial Relevance: Sweet potato leaves have been neglected except for a partial use as livestock feed in China. This study describes the response surface optimization of microwave-assisted extraction (MAE) process for the enhanced recovery of total phenolics from sweetpotato leaves (TPSL). MAE showed obvious advantages in terms of high extraction efficiency and antioxidant activity of extract within shortest extraction time. TPSL obtained using MAE showed potential for use in health-care food and pharmaceutical industry.

Optimization conditions for anthocyanin and phenolic content extraction form purple sweet potato using response surface methodology

Purple sweet potato flour could be used to enhance the bioactive components such as phenolic compounds and anthocyanin content that might be used as nutraceutical ingredients for formulated foods. Optimization of anthocyanin and phenolic contents of purple sweet potato were investigated using response surface methodology. A face-centered cube design was used to investigate the effects of three independent variables: namely, drying temperature 55–65°C, citric acid concentration 1–3% w/v and soaking time 1–3 min. The optimal conditions for anthocyanin and phenolic contents were 62.91°C, 1.38%, 2.53 min and 60.94°C, 1.04% and 2.24 min, respectively. However, optimal conditions of anthocyanin content were not apparent. The experimental value of anthocyanin content was 19.78 mg/100 g and total phenolic content was 61.55 mg/g. These data showed that the experimental responses were reasonably close to the predicted responses. Therefore, the results showed that treated flours could be used to enhance the antioxidant activities of functional foods.

Robust scaling parameters for composite dispatching rules

The successful implementation of composite dispatching rules depends on the values of their scaling parameters. A unified four-phase method to determine robust scaling parameters for composite dispatching rules is proposed, with the goal of achieving reasonably good scheduling performance with the least computational effort in implementation. In phase 1, factor ranges that characterize the problem instances in each tool group (one or more machines operating in parallel) are calculated. In phase 2, a face-centered cube design is used to decide the placement of design points in the factor region. The third phase involves using mixture experiments to find good scaling parameter values at each design point. In the last phase, the central point of the area in which all of the good scaling parameters lie is identified with the robust scaling parameter. The proposed method is applied to determine the robust scaling parameter for the Apparent Tardiness Cost with Setups (ATCS) rule to solve the Pm|s jk |Σ w j T j scheduling problem in a case study. The results of this case study show that the proposed method is more efficient and effective than existing methods in the literature. It requires many fewer experiments and achieves more than a 30% improvement in the average scheduling performance (i.e., total weighted tardiness) and more than a 60% improvement in the standard deviation of the scheduling performance.

Production of medium-chain triacylglycerols from corn oil: Optimization by response surface methodology

Structured lipids (SLs) having long-chain fatty acids at sn-2 and medium-chain caprylic acid (CA, 8:0) at their sn-1,3-positions from corn oil (CO) were obtained and optimized by response surface methodology (RSM) with a three-level, three-factor face-centered cube design. Compositions of triacylglycerol species (TAGs) in SLs were also investigated by reverse-phase high performance liquid chromatography. Lipozyme TL IM from Thermomyces lanuginosa was used for the acidolysis of CO with CA in n-hexane. The effects of substrate molar ratio, enzyme amount, and reaction time on CA incorporation into CO were optimized. The optimum conditions were 13.2% (wt.) enzyme, 3.9:1 caprylic acid/corn oil molar ratio, and 3.1 h reaction time. At optimum conditions, 21.5 ± 0.8 mol.% caprylic acid containing SLs was obtained. This product was characterized by 50% of triacylglycerol species with equivalent carbon number (ECN) C30, C32, C36, and C38, and 50% of triacylglycerol species with ECN C42, C44, and C46.

Systematic delineation of optimal cytokine concentrations to expand hematopoietic stem/progenitor cells in co-culture with mesenchymal stem cells

The major obstacle to the widespread use of umbilical cord blood (UCB) in hematopoietic stem/progenitor (HSC) cell therapy is the low cell dose available. A cytokine cocktail for the ex vivo expansion of UCB HSC, in co-culture with a bone marrow (BM) mesenchymal stem cells (MSC)-derived stromal layer was optimized using an experimental design approach. Proliferation of total cells (TNC), stem/progenitor cells (CD34(+)) and colony-forming units (CFU) was assessed after 7 days in culture, while sole and interactive effects of each cytokine on HSC expansion were statistically determined using a two-level Face-Centered Cube Design. The optimal cytokine cocktail obtained for HSC-MSC co-cultures was composed by SCF, Flt-3L and TPO (60, 55 and 50 ng mL(-1), respectively), resulting in 33-fold expansion in TNC, 17-fold in CD34(+) cells, 3-fold in CD34(+)CD90(+) cells and 21-fold in CFU-MIX. More importantly, these short-term expanded cells preserved their telomere length and extensively generated cobblestone area-forming cells (CAFCs) in vitro. The statistical tools used herein contributed for the rational delineation of the cytokine concentration range, in a cost-effective way, while systematically addressing complex cytokine-to-cytokine interactions, for the efficient HSC expansion towards the generation of clinically significant cell numbers for transplantation.

Modeling of Phenol Degradation in Spouted Bed Contactor Using Artificial Neural Network (ANN)

Presence of phenol and phenolic compounds in various wastewaters and its harmful effects has led to the use of different treatment methods. Work on biological methods shows the use of different microorganisms and different bioreactors so as to improve the removal efficiency economically. The present work deals with the use of N. hydrocarbonoxydans (NCIM 2386), an actinomycetes, for the degradation of phenol. N. hydrocarbonoxydans was immobilized on GAC and used in a spouted bed contactor for effective contact of microorganisms and the substrate. The contactor performance was studied by varying flow rates, influent concentrations and the solids loading in the contactor. The effect of these variables on phenol degradation was investigated and modeling study was carried out using the artificial neural network (ANN). A feed forward neural network with back propagation was used for the model development. The experiments were planned as per the face centered cube design (FCCD) and used for training of the model, whereas data from four other experimental runs were used for testing and validation of the model. The network was optimized for the number of neurons based on the mean square error. The ANN model with three layers with three input neurons, eight neurons in hidden layers and one output neuron was found to predict effectively the effluent concentration for the given operating conditions in the spouted bed contactor. The mean square error was found to be 9.318e-12 for this ANN model. Also the experimental data was used to develop second order nonlinear empirical model obtained using multiple regression (MR) and the results compared with ANN using correlation coefficient (R2), average absolute error (AAE) and root mean square error (RMSE). Results show that R2, AAE and RMSE values of MR model were 0.9363, 2.085 % and 2.338 % respectively, while in case of ANN model these values were 0.9995, 0.59 % and 1.263 % respectively. This shows that ANN model prediction is better than multiple regression model prediction.