Fractional Factorial Approach Research Articles

The Optimization of Vacuum-Bagging Processing in Oven Cure for Tensile Strength in Composite Laminate

The implementation of autoclaves has been limited due to high production costs and an excess of residual stress. These drawbacks have led to the exploration and development of an alternative method known as out-of-autoclave (OoA) manufacturing process. This research study was proposed to enhance the production of high tensile strength in composite laminate by optimizing the vacuum-bagging-only (VBO) pre-forming process. The impacts of both individual and combined pre-forming parameters in VBO-oven cure processing were measured for traditional low-cost glass/epoxy composite material with respect to the tensile strength of the cured laminates. Twenty composite panels were produced according to specified parameter combinations using central composite design in a fractional factorial approach for creating a response surface model. The study examined three variables, namely the duration of vacuum debulking, the number of sides with edge breather, and the weight of the intensifier. Two laminates were manufactured without additional processing parameters using both the oven (baseline) and autoclave methods for validation purpose. Subsequently, a tensile test was carried out following ASTM D 3039. The interaction among the combined parameters was examined using analysis of variance (ANOVA). The laminates exhibited the lowest tensile strength when the intensifier was not present, while the highest tensile strength was recorded when edge breather, debulk, and intensifier were applied at varying levels. An ideal processing configuration of 30 minute-debulk, each side of edge breather and 1kg-intensifier had resulted in the production of laminate with the highest tensile strength, measuring 407.44 MPa. This value was roughly 17.2% higher than that of the baseline laminate and 3.77% higher than the autoclave laminate.

Prediction of Angular Distortion in Gas Metal Arc Welding of Structural Steel Plates Using Artificial Neural Networks

The manufacturing of structures ranging from bridges and machinery to all types of seaborne vehicles to nuclear reactors and space rockets has made considerable use of arc welding technologies. This is as a result of benefits including increased joint efficiency, air and water tightness, no thickness restriction (0.6 to 25 mm), decreased fabrication time and cost, etc. when compared to alternative fabrication methods. Gas metal arc welding (GMAW) is a frequently used welding technology in industries due to its inherent benefits, including deeper penetration, a smooth bead, etc. Local heating and cooling that takes place during the multi-pass welding process causes complicated stresses to develop at the weld zone, which ultimately causes angular distortion in the weldment. Angular distortion is a major flaw that affects the weld’s properties as well as the cracking and misalignment of the welded joints. The issue of angular distortion can be successfully solved by predicting it in relation to certain GMAW process variables. A neural network model was created in this research to predict angular distortion. A fractional factorial approach with 125 runs was used to conduct the exploratory experiments. A neural network model with feed forward and backward propagation was developed using the experimental data. To train the neural network model, the Levenberg–Marquardt method was utilised. The results indicate that the model based on network 4-9-3 is more effective in forecasting angular distortion with time gaps between two, three, and four passes than the other three networks (4-2-3, 4-4-3, 797 and 4-8-3). Prediction accuracy is more than 95 percent. The neural network model developed in this study can be used to manage the welding cycle in structural steel weld plates to achieve the best possible weld quality with the least amount of angular distortion.

Production of Antioxidants and High Value Biomass from Nannochloropsis oculata: Effects of pH, Temperature and Light Period in Batch Photobioreactors

Nannochloropsis oculata is a marine microalgal species with a great potential as food or feed due to its high pigment, protein and eicosapentaenoic acid contents. However, for such an application to be realized on a large scale, a biorefinery approach is necessary due to the high cost of microalgal biomass production. For example, techno economic analyses have suggested the co-production of food or feed with antioxidants, which can be extracted and supplied separately to the market. The aim of this study was to investigate the effect of cultivation conditions on the antioxidant capacity of Nannochlosopsis oculata extracts, derived with ultrasound-assisted extraction at room temperature, as well as the proximate composition and fatty acid profile of the biomass. A fractional factorial approach was applied to examine the effects of temperature (20–35 °C), pH (6.5–9.5) and light period (24:0, 12:12). At the end of each run, biomass was collected, washed with 0.5M ammonium bicarbonate and freeze-dried. Antioxidant capacity as gallic acid equivalents as well as pigment content were measured in the ethanolic extracts. Optimal conditions were different for productivity and biomass composition. Interesting results regarding the effect of light period (LP) and pH require further investigation, whereas the effect of moisture on the extraction process was confounded with biomass composition. Finally, further data is provided regarding the relation between chlorophyll content and apparent phenolic content using the Folin–Ciocalteu assay, in agreement with our previous work.

A Factorial Approach for Optimizing the Design Parameters of a Tissue Attachment Mechanism for Drug Delivery.

Biological macromolecule drugs or biologics are not suited for commonly preferred oral delivery due to their intrinsic instability and physical, chemical, or immunological barriers to the gastrointestinal tract. Ingestible capsule robots (ICR) have become a versatile platform, including use for drug delivery applications for various gastrointestinal pathologies with future potential for systemic drug delivery. In this work, a tissue attachment mechanism (TAM) for a drug delivery ICR is introduced that can facilitate a non-invasive systemic delivery of unaltered biologics via direct injection through the insensate layers of the small intestine. The main prerequisite for achieving systemic drug delivery via this device is to have a strong tissue attachment of the TAM. This study aimed to optimize the attachment success rate for drug delivery and characterize attachment duration in vivo. A fractional factorial approach was used in vivo to identify and optimize factors that most influence attachment of the TAM to maximize attachment rate. Multiple in vivo optimization levels were performed using the small intestine of anesthetized pigs, and an attachment success rate of 92% was achieved. Optimal TAMs were surgically placed in vivo to determine the duration of attachment following anesthetization and surgery recovery. The average in vivo attachment duration was 32.2±9.4 hours. This work establishes a device for consistent and reliable attachment duration, making the TAM a suitable candidate for a 24-hour systemic drug delivery platform.

Parametric Investigation on Different Bone Densities to avoid Thermal Necrosis during Bone Drilling Process

Bone drilling is a universal surgical procedure commonly used for internal fracture fixation, implant placement, or reconstructive surgery in orthopedics and dentistry. The increased temperature during such treatment increases the risk of thermal penetration of the bone, which may delay healing or compromise the fixation’s integrity. Thus, avoiding penetration during bone drilling is critical to ensuring the implant’s stability, which needs surgical drills with an optimized design. Bovine femur and mandible bones are chosen as the work material since human bones are not available, and they are the closest animal bone to human bone in terms of properties. In the present study, the Taguchi fractional factorial approach was used to determine the best design of surgical drills by comparing the drilling properties (i.e., signal-to-noise ratio and temperature rise). The control factors (spindle speed, drill bit diameter, drill site depth, and their levels) were arranged in an L9 orthogonal array. Drilling experiments were done using nine experimental drills with three repetitions. The findings of this study indicate that the ideal values of the surgical drill’s three parameters combination (S1D1Di2) and their percentage contribution are dependent on the drilling levels of the parameters. However, the result shows that the spindle speed has the highest temperature effect among other parameters in both (femur and mandible) bones.

Investigation on turning operation using die sinking EDM process

Electrical discharge turning (EDT) operation produces a cylindrical component using an electrical discharge machining method. Unlike a traditional turning process, it is a non-contact operation between the tool electrode and workpiece. Therefore, the design of electrode may influence the quality of turned workpiece. The present study investigates the effect of various processing parameters in EDT namely the electrode shape, workpiece rotational speed and jump down time. The analysis was conducted in terms of the surface roughness, circularity deviation and electrode wear rate. A special jig and fixture for the turning operation was developed as to fit on the commercial die sinking EDM machine. A fractional factorial approach using Taguchi orthogonal array of L9 was utilized in the present study. It was found that both shape of electrode and workpiece rotational speed had a greater influence on the surface roughness followed by the electrode jump down time. The surface roughness increases with an increase of quantity and duration of sparks during the process due to formation of a higher amount of debris. The circularity deviation has improved with a higher sparking area and faster duration of sparks since a smaller amount of workpiece material was removed thus improving its circularity. Furthermore, the highest electrode wear rate was produced using the electrode with a curvature shape which generated wider sparking area thus experiencing more erosion.

High-yield production of recombinant platelet factor 4 by harnessing and honing the gram-negative bacterial secretory apparatus

Platelet factor 4 is a cytokine released into the bloodstream by activated platelets where it plays a pivotal role in etiology and diagnosis of heparin-induced thrombocytopenia. Therefore, a sustainable source of recombinant PF4 with structural and functional similarity to its native form is urgently needed to be used in diagnostic procedures. To this end, a three-in-one primary construct was designed from which three secondary constructs can be derived each capable of employing either type I, type II secretory or cytoplasmic pathways. Protein expression and secretion were performed in Escherichia coli BL21 (DE3) and confirmed by SDS-PAGE and Western blotting. To further enhance protein secretion, the effect of several controllable chemical factors including IPTG, Triton X-100, sucrose, and glycine were individually investigated at the outset. In the next step, according to a fractional factorial approach, the synergistic effects of IPTG, Triton X-100, and glycine on secretion were further investigated. To ascertain the structure and function of the secreted recombinant proteins, dynamic light scattering was utilized to confirm the rPF4 tetramerization and heparin-mediated ultra-large complex formation. Moreover, Raman spectroscopy and Western blotting were exploited to evaluate the secondary and quaternary structures, respectively. The type II secretory pathway was proven to be superior to type I in the case of rPF4 secretion. Supplementation with chemical enhancers improved the protein secretion mediated by the Type II system to approximately more than 500 μg/mL. Large quantities of native rPF4 up to 20 mg were purified as the culture medium was scaled up to 40 mL. Western blotting confirmed the formation of dimers and tetramers in the secreted rPF4 proteins. Dynamic light scattering revealed the rPF4 oligomerization into of larger complexes of approximately 100–1200 nm in size following heparin supplementation, implying proper protein folding and tetramerization. Moreover, the rPF4 secondary structure was found to be 43.5% Random coil, 32.5% β-sheet, 18.6% α-helix and 4.9% Turn, which is in perfect agreement with the native structure. Our results indicate that the gram-negative type II bacterial secretory system holds a great promise as a reliable protein production strategy with industrial applications. However, further efforts are required to realize the full potential of secretory pathways regarding their application to proteins with distinct characteristics.

The Opportunity – VAWA 2013 Reauthorization Provides a Natural Experiment for Bystander Efficacy Evaluation

This methods paper describes the fractional factorial design within the context of an evaluation of campus bystander programming. Prior evaluations include relative program comparisons, but do not reflect campus implementation of specific aspects of prevention programming. Campuses use combinations of programs, delivered across modalities, audiences, intensity, and degrees of requirement. Bystander program evaluation, in a natural experiment, must consider combinations of these components. This evaluation offers a novel application of the fractional factorial framework, considering combinations of program components, as implemented, within a multi-campus quasi-experimental design. Leveraging qualitative data, cluster analysis provides an initial identification of bystander program component combinations, mapped to experimental conditions. SAS v9.4 PROC FACTEX constructs possible fractional factorial designs to estimate main effects. From key informant interviews, primary program components are determined: delivery method, level of skill-building, degree of requirement, and intended audience. A total of seven combinations are identified. Using presence or absence of program components, a partial factorial structure is identified, where component clusters comprised seven of the 24 = 16 possible combinations. The smallest number of experimental conditions necessary for estimating these effects is determined with PROC FACTEX. Resulting designs indicate the necessary experimental conditions for determining bystander program component effectiveness available within this study. Our fractional factorial approach offers a novel strategy for planning an evaluation of several bystander program component combinations. This paper provides foundational elements needed to implement a bystander evaluation design, with the requisite emphasis on program components and relevant combinations, while optimizing number of participating campuses.

A General Guide for the Optimization of Enzyme Assay Conditions Using the Design of Experiments Approach

Many factors must be considered during the optimization of an enzyme assay. These include the choice of buffer and its composition, the type of enzyme and its concentration, as well as the type of substrate and concentrations, the reaction conditions, and the appropriate assay technology. The process of an enzyme assay optimization, in our experience, can take more than 12 weeks using the traditional one-factor-at-a-time approach. In contrast, the design of experiments (DoE) approaches have the potential to speed up the assay optimization process and provide a more detailed evaluation of tested variables. However, not all researchers are aware of DoE approaches or believe that it is easy to employ a DoE approach for the optimization of an assay. In order to facilitate enzyme assay developers to use DoE methodologies, we present in detail the steps required to identify in less than 3 days (1) the factors that significantly affect the activity of an enzyme and (2) the optimal assay conditions using a fractional factorial approach and response surface methodology. This is exemplified with the optimization of assay conditions for the human rhinovirus-3C protease, and the methodology used could be employed as a basic guide for the speedy identification of the optimum assay conditions for any enzyme.

Multivariate optimization of the hollow fibre liquid phase microextraction of muscimol in human urine samples.

A liquid phase microextraction based on hollow fibre followed by liquid chromatographic determination was developed for the extraction and quantitation of the hallucinogenic muscimol from urine samples. Method applicability on polar hallucinogens was also tested on two alkaloids, a psychedelic hallucinogen, tryptamine and a polar amino acid, tryptophan which exists in its charged state in the entire pH range. A multivariate design of experiments was used in which a half fractional factorial approach was applied to screen six factors (donor phase pH, acceptor phase HCl concentration, carrier composition, stirring rate, extraction time and salt content) for their extent of vitality in carrier mediated liquid microextractions. Four factors were deemed essential for the effective extraction of each analyte. The vital factors were further optimized for the extraction of single-spiked analyte solutions using a central composite design. When the simultaneous extraction of analytes was performed under universal factor conditions biased towards maximizing the enrichment of muscimol, a good composite desirability value of 0.687 was obtained. The method was finally applied on spiked urine samples with acceptable enrichments of 4.1, 19.7 and 24.1 obtained for muscimol, tryptophan and tryptamine respectively. Matrix-based calibration curves were used to address matrix effects. The r(2) values of the matrix-based linear regression prediction models ranged from 0.9933 to 0.9986. The linearity of the regression line of the matrix-based calibration curves for each analyte was directly linked to the analyte enrichment repeatability which ranged from an RSD value of 8.3-13.1%. Limits of detection for the developed method were 5.12, 3.10 and 0.21ngmL(-1) for muscimol, tryptophan and tryptamine respectively. The developed method has proven to offer a viable alternative for the quantitation of muscimol in human urine samples.

An efficient approach to understanding and predicting the effects of multiple task characteristics on performance

In ergonomics there is often a need to identify and predict the separate effects of multiple factors on performance. A cost-effective fractional factorial approach to understanding the relationship between task characteristics and task performance is presented. The method has been shown to provide sufficient independent variability to reveal and predict the effects of task characteristics on performance in two domains. The five steps outlined are: selection of performance measure, task characteristic identification, task design for user trials, data collection, regression model development and task characteristic analysis. The approach can be used for furthering knowledge of task performance, theoretical understanding, experimental control and prediction of task performance.Practitioner Summary: A cost-effective method to identify and predict the separate effects of multiple factors on performance is presented. The five steps allow a better understanding of task factors during the design process.

Fractional factorial design to investigate stromal cell regulation of macrophage plasticity.

Understanding the regulatory networks which control specific macrophage phenotypes is essential in identifying novel targets to correct macrophage mediated clinical disorders, often accompanied by inflammatory events. Since mesenchymal stromal cells (MSCs) have been shown to play key roles in regulating immune functions predominantly via a large number of secreted products, we used a fractional factorial approach to streamline experimental evaluation of MSC mediated inflammatory macrophage regulation. Our macrophage reprogramming metrics, human bone marrow MSC attenuation of macrophage pro-inflammatory M1 TNFα secretion and simultaneous enhanced expression of the M2 macrophage marker, CD206, were used as analysis endpoints. Objective evaluation of a panel of MSC secreted mediators indicated that PGE2 alone was sufficient in facilitating macrophage reprogramming, while IL4 only provided partial reprogramming. Inhibiting stromal cell PGE2 secretion with Indomethacin, reversed the macrophage reprogramming effect. PGE2 reprogramming was mediated through the EP4 receptor and indirectly through the CREB signaling pathway as GSK3 specific inhibitors induced M1 macrophages to express CD206. This reprogramming pathway functioned independently from the M1 suppression pathway, as neither CREB nor GSK3 inhibition reversed PGE2 TNF-α secretion attenuation. In conclusion, fractional factorial experimental design identified stromal derived PGE2 as the factor most important in facilitating macrophage reprogramming, albeit via two unique pathways.

Influence of milk components in establishing biofilm mediated bacterial mastitis infections in cattle: A fractional factorial approach

Biofilm formation is one of the factors responsible for antibiotic resistance. The involvement of biofilm formation in bacterial mastitis is well known. Milk composition varies during the lactation period and certain pathogens are producing more number of mastitis cases during particular periods of lactation. The present study elucidates the effects of different milk components on biofilm formation and the persistence of infection. The Plackett Burman screening design has been chosen for assessing the significance. Biofilm production of Staphylococcus aureus, Escherichia coli and Pseudomonas aeruginosa were assessed by crystal violet assay. Dipotassium hydrogen phosphate had a significant effect on biofilm formation by S. aureus (MTCC 1430) whereas it was pH in the case of biofilm formation by P. aeruginosa (NCIM 5029). Other independent factors were found to be insignificant.

An Analysis on the Influence of Surface Characteristics and Operating Parameters on the Wear of Hardened AISI 52100

The objective of the research was to analyze the influence of initial roughness on the wear rate of component samples made of bearing steels. AISI 52100 samples were prepared with three different roughness values by varying the depth of cut and feed rate in milling process. Dry reciprocating wear tests were performed under the same laboratory conditions and at different loads and sliding speeds. A fractional factorial approach with one-third of 33 experimental design without replication was followed here. The overall wear rate was found out by mass loss method. The results were analyzed using contour plots between the factors influencing the wear rate as well as mean coefficient of friction. The results indicated that the wear rate and coefficient of friction was influenced by load, roughness and their interaction.

Fractional factorial approach combining 4 Escherichia coli strains, 3 culture media, 3 expression temperatures and 5 N-terminal fusion tags for screening the soluble expression of recombinant proteins

Producing recombinant proteins in Escherichia coli (E. coli) is generally performed using a trial and error approach with the different expression variables being tested independently from each other. As a consequence, variable interactions are lost which makes the trial and error approach quite time-consuming. In this paper, we report how switching from a trial and error to a fractional factorial approach allows testing in less than 2weeks four expression variables (E. coli strains, culture media, expression temperatures and N-terminal fusion tags) in a single experiment. The method, called “Fusion-InFFact”, was validated using four test proteins. In all cases, Fusion-InFFact allowed finding conditions for expressing high yields of soluble proteins. The method was originally set-up for high throughput structural genomics programs, but can be used in any recombinant protein expression project.

Experimental design approach to optimize selective laser melting of martensitic 17‐4 PH powder: part I – single laser tracks and first layer

PurposeThe purpose of this paper is to investigate the effect of main process parameters of selective laser melting (SLM) technology on single lines and single layers manufactured from 17‐4 PH martensitic powder using the experimental design approach.Design/methodology/approachA fractional factorial approach has been applied to vary and to identify the optimal set of process parameters using three different powder particle size distributions for 17‐4 PH steel. This paper assesses the impact of influence factors such as process and material parameters on objective factors such as dimension of single lines and single layers, as well as surface roughness.FindingsThe influence of process parameters and materials properties on single line and single layer manufacture is shown and proved statistically. The effect of each process parameter and their interactions on single layer and single line stability and quality has been investigated, and a complex objective function analyzing geometrical stability of single lines has been proposed. The findings indicate the most appropriate 17‐4 PH powder particle size distribution.Originality/valueThe research provides a systematic scientific approach using fractional factorial experiment design to identify the influence of process parameters, materials parameters and their combinations on essential martensitic steels (17‐4 PH steel) single lines and single layers characteristics such as geometrical stability and surface roughness. This approach will be extended to 3D parts fabrication and reported in a later paper.

Optimisation and scale-up of a highly-loaded 5-ASA multi-particulate dosage form using a factorial approach

Pellets with high loading of 5-aminosalicylic acid (5-ASA, mesalamine) are desired to reduce the number of tablets required to deliver the daily dosing regimen. Recently, we reported an extrusion–spheronisation route for the development of a 90 wt% 5-ASA/microcrystalline cellulose formulation based on milled 5-ASA which gave good yields of pellets at the lab scale. In the present work, such formulation was optimised further by preliminary studies using a lab-scale ram extruder, and then scaled up to the pilot plant scale on a Nica screen extruder using a mixed fractional factorial approach. The final formulation featured 95 wt% 5-ASA and 5 wt% Avicel RC591 (all dry basis) and yielded spherical pellets suitable for use as the drug core of a multi-particulate DDS.

Enhanced Production of Manganese-Peroxidase by the White-Rot Fungus Bjerkandera Adusta using Media Engineering

ABSTRACTManganese peroxidase (MnP) production by the white-rot fungus Bjerkandera adusta (Willdenow) P. Karsten was enhanced significantly through media engineering, using the statistical modeling approach called response surface methodology. Both fractional factorial and central composite designs were applied in the optimization studies to evaluate the effect of mycological peptone, KH2PO4, MnSO4, and glucose on MnP production. With a view to simultaneously reducing the number of experiments and obtaining more information on the mutual interactions between the variables, 24-1 fractional factorial and full 22 central composite design led to 12 sets of experiments. When the optimized amounts were used, MnP activity obtained was increased approximately 600% (from 0.40 U ml−1 to 2.41 U ml−1). The effect of central composite design coupled with fractional factorial approach was more profound on the increase of the MnP activity compared to that of fractional factorial approach alone. Our response surface methodological results showed for the first time that peptone but not Mn2+ was the most important ingredient affecting the level of MnP production by the fungus B. adusta. The significant increase in MnP activity via response surface methodology demonstrates the potential of this recent isolate to be considered as a good source of MnP for industrial applications.

Assessment of a redox alkaline/iron-chelate absorption process for the removal of dilute hydrogen sulfide in air emissions

The oxidative absorption of hydrogen sulfide ( H 2 S ) into a solution of ferric chelate of trans-1,2- diaminocyclohexanetetraacetate (CDTA) was studied in a counter-current laboratory column randomly packed with 15 mm plastic Ralu rings. The present investigation takes concern about the Kraft pulping situation where dilute H 2 S concentrations are omnipresent in large-volume gas effluents. A fractional two-level factorial approach was instigated to determine the significance of six operating variables, namely the solution's alkalinity (pH; 8.5–10.5), the liquid mass flow rate ( L ; 1.73 – 5.19 kg m - 2 s - 1 ), the solution's ionic strength ( I C ; 0.01 – 0.1 mol dm - 3 ), the gas mass flow rate ( G ; 0.19 – 0.57 kg m - 2 s - 1 ), the inlet H 2 S concentration ( C H 2 S , 0 ; 70 –430 ppm) and the initial ferric CDTA concentration ( C Fe , 0 ; 100 – 400 μ mol dm - 3 ). Initially, a Plackett–Burman design matrix of seven duplicated experiments revealed that pH is the leading factor controlling the H 2 S conversion rate while the ionic strength and ferric CDTA concentration effects remained negligible within the factorial domain. Surface response analysis based on 11 duplicated factorial experiments plus 10 central composite trials revealed that the H 2 S conversion significantly increases with liquid flow rate but decreases with growing H 2 S load up. Further examination about the influence of ferric CDTA on H 2 S absorption rate was set up over a broader concentration range ( C Fe , 0 ; 0 – 2000 μ mol dm - 3 ) at pH of 9.5 and 10.5. It showed good potential at 2000 μ mol dm - 3 as H 2 S conversion increased by a significant 25% for both pH values in comparison to pure alkaline solutions containing no ferric CDTA.

High-throughput automated refolding screening of inclusion bodies.

One of the main stumbling blocks encountered when attempting to express foreign proteins in Escherichia coli is the occurrence of amorphous aggregates of misfolded proteins, called inclusion bodies (IB). Developing efficient protein native structure recovery procedures based on IB refolding is therefore an important challenge. Unfortunately, there is no "universal" refolding buffer: Experience shows that refolding buffer composition varies from one protein to another. In addition, the methods developed so far for finding a suitable refolding buffer suffer from a number of weaknesses. These include the small number of refolding formulations, which often leads to negative results, solubility assays incompatible with high-throughput, and experiment formatting not suitable for automation. To overcome these problems, it was proposed in the present study to address some of these limitations. This resulted in the first completely automated IB refolding screening procedure to be developed using a 96-well format. The 96 refolding buffers were obtained using a fractional factorial approach. The screening procedure is potentially applicable to any nonmembrane protein, and was validated with 24 proteins in the framework of two Structural Genomics projects. The tests used for this purpose included the use of quality control methods such as circular dichroism, dynamic light scattering, and crystallogenesis. Out of the 24 proteins, 17 remained soluble in at least one of the 96 refolding buffers, 15 passed large-scale purification tests, and five gave crystals.