Statistical Experimental Design Research Articles

Bridging statistics and life sciences education for immunologists: Exploring significantly impactful teaching strategies and collaborations

Abstract The widespread misuse of statistics is one of the contributing factors to reproducibility concerns in immunological research. However, not all immunologists have the statistical expertise to choose the best methods to evaluate and represent their experiments, and the formal statistics training required by undergraduate and graduate immunology curricula is often quite limited. How can we prepare immunologists for statistical practice in research? We previously developed a second-year undergraduate course to integrate statistics instruction with research design to improve the quantitative training of life sciences students. In a Scholarship of Teaching and Learning (SoTL) study conducted within the course, student attitudes and self-efficacies for statistics, as well as their abilities to recognize and handle problems related to statistical practice in life sciences research, were assessed through surveys administered at the beginning and end of the course (n=126). Here, we present our team-teaching model and strategies for promoting meaningful connections between statistics and immunological research through course design, activities and assessments. We also highlight the results from our SoTL study, which have guided the development of several specialized immunology courses focusing on statistical practice and experimental design at the University of Toronto. We hope that insights from this teaching partnership and our SoTL findings will help inform future quantitative course offerings and training initiatives, and ultimately, better prepare students to effectively engage with statistics in immunological research.

Design of Manufacturing Systems Based on Digital Shadow and Robust Engineering

In the era of digital transformation, industry is facing multiple challenges due to the need for implementation of the Industry 4.0 standards, as well as the volatility of customer demands. The latter has created the need for the design and operation of more complex manufacturing systems and networks. A case study derived from Process Industries (PIs) is adopted in this research work in order to design a framework for flexible design of production lines, automation of quality control points, and improvement of the performance of the manufacturing system. Therefore, a Digital Shadow of a production line is developed to collect, analyze and identify potential issues (bottlenecks). An edge computing system for reliable and low-latency communications is also implemented. The digital model is validated using statistical Design Of Experiments (DOE) and ANalysis Of VAriance (ANOVA). For the assessment of what-if scenarios, the Digital Shadow model will be used in order to evaluate and find the desired solution. Ultimately, the goal of this research work is to improve the design and performance of the industry’s production section, as well as to increase the production rate and the product mix.

Validation of Bromide Leaching through Response Surface Methodology and Separation of Gold from Waste Printed Circuit Boards

The daily consumption of gold is increasing worldwide; however, its availability from conventional ores is reducing. Alternatively, the presence of gold in waste electrical and electronic equipment (WEEE) is nearly 100 times higher than in natural ore. Therefore, the possibility of the recovery and separation of gold from waste printed circuit boards of obsolete mobile phones is studied in the present work. Initially, the optimization of parameters for the quantitative gold leaching from metal clads of PCBs with halide salts at acidic conditions is studied through response surface methodology. Three factors (parameters), viz. temperature, time and stirring speed are altered during the experiments based on the central composite design (CCD). Leaching parameters have been optimized with the help of the second-order empirical equations and analysis of variance (ANOVA) for maximum gold dissolution. The selective recovery and separation of gold from leach liquor have been achieved with solvent extraction with an organic amide as extractant followed by cementation with zinc powder. The separated gold powder has also been analyzed with XRD and SEM-EDS to check the purity and homogeneous elemental distribution. The statistical design of experiments and separation processes for the effective recovery of gold corroborates the economic feasibility of the proposed process.

A microwave-induced plasma jet for efficient degradation of methomyl in aqueous solution.

As a typical carbamate pesticide, methomyl was once widely used in agriculture for its excellent broad-spectrum insecticidal effect. However, due to its high toxicity, long half-life, and difficult degradation properties, it poses a serious challenge to water environment pollution. In this study, an electrode-free discharge microwave-induced plasma technology was used to rapidly and efficiently degrade methomyl in aqueous solution. In this experiment, the statistical design of experiments (DOE) was adopted to optimize the plasma degradation parameters. Under the optimized parameters (P = 140 W, D = 0mm, R = 0.5 L/min), 78.4% removal of 50mg/L of methomyl was achieved after 8min. The optical emission spectrometry and free radical detection experiments showed that the active substances generated by the collision reaction between plasma and water molecules occurring at the gas-liquid interface were the key factors to exert the degradation effect. The degradation rate of methomyl decreased by 73.2% after the addition of tert-butanol (OH burster), while it decreased by only about 12.0% after the addition of peroxidase. These implied that ∙OH was largely responsible for methomyl degradation. In addition, based on the detected intermediates, possible degradation mechanisms and pathways were analyzed.

Statistical Medium Optimization for the Production of Anti-Methicillin-Resistant Staphylococcus aureus Metabolites from a Coal-Mining-Soil-Derived Streptomyces rochei CMB47

The development of novel antibacterial drugs needs urgent action due to the global emergence of antibiotic resistance. In this challenge, actinobacterial strains from arid ecosystems are proving to be promising sources of new bioactive metabolites. The identified Streptomyces rochei strain CMB47, isolated from coal mine Saharan soil, provided an ethyl acetate extract which tested against a series of pathogens. It displayed a minimum inhibitory concentration of <0.439 µg/mL against MRSA. A statistical experimental design using a response surface methodology (RSM) based on the second-order rotatable central composite design (RCCD) was planned to develop an efficient fermentation process able to improve the bioactive metabolite production. The optimal conditions were determined for starch and NaNO3 concentrations, incubation time and the initial pH value, reaching the inhibition zone diameter of 20 mm, close to the experimental value, after validation of the model. A bioassay-guided fractionation of the crude extract provided the most active fractions, which were analyzed by HPLC equipped with a photodiode array detector and coupled online with an electrospray mass spectrometer (HPLC-DAD/ESI-MS), obtaining preliminary indications on the molecular structures of the metabolites. These results support the potential interest in further investigations into the purification and full characterization of the metabolites responsible for the biological activity observed so far.

Economic and environmental impact of circular business models: A case study of White Goods-as-a-Service using multi-method simulation modelling

Circular business models are gaining traction in academia and industry as an instrument to deliver environmental benefits while being economically profitable. Despite this increased interest, studies that quantitatively assess the impact of circular business models are limited. This study provides researchers and practitioners with a quantitative analysis tool to assess the dynamics of circular business models from both an economic and environmental perspective. Using the case study of white goods-as-a-service, this study employs multi-method simulation modelling in combination with statistical design and analysis of simulation experiments to investigate the effect of different factors including payment schemes (i.e., fixed fee, pay-per-use, and hybrid) and subscription contract duration (i.e., long-term, mid-term, and short-term) on the economic and environmental performance of access-based models. In addition, as the adoption of access-based models is economically challenging for manufacturers due to a discrepancy between costs and revenue streams, this study analyses the effect of different levers to improve the liquidity performance of access-based business models including deposit schemes, cancellation and collection fees, as well as partnering with financial institutions to cover the initial revenue gap.

Statistical Investigation of Rotary Fluidized Bed Agglomeration Process with Tangential Spray and In-Line Particle Size Measurement for PAT Process Control

A statistical design of experiments for a rotary fluidized bed agglomeration process is performed to improve both the knowledge of the process and the influence of the process parameters. Agglomerates of a pharmaceutical formulation are manufactured in a laboratory fluidized bed rotor apparatus with a tangential spray nozzle. Particle size is measured in-line over the entire agglomeration process with a spatial filter velocimetry probe installed directly in the process chamber and off-line with dynamic image analysis for comparison. The influence of the process parameters spray rate, spray pressure, rotor speed, and process air temperature on the fluidized bed is investigated using a central composite design. In-line measurement of particle size is possible over the entire rotor process. Spray pressure, spray rate, square of process air temperature, and some interactions proved to be statistically significant. Particle size measured with spatial filter velocimetry and dynamic image analysis indicates good agreement and a similar trend. The successful application of particle size measurement in a fluidized bed rotor agglomeration at a laboratory scale using spatial filter velocimetry to improve process control and reduce the risk of failed batches serves as the basis for transferring to a production scale.

Is designed data collection still relevant in the big data era?

AbstractThe excitement and buzz around big data (BD) has been so prevalent that it seems BD has become thought of as a panacea for solving all challenges. But there are in fact limitations to what BD can do, which has led to missed opportunities and potentially suboptimal problem‐solving and decision‐making. Hence the answer to the question posed in the title is an emphatic ‘Yes!’ The intentional strategic use of designed data collection (DDC) represents an opportunity to elevate how studies involving BD are planned, executed, and interpreted to deliver more satisfying solutions. In this paper, we outline eleven opportunities for integrating DDC strategies, including statistical design of experiments (DoE) and sampling techniques, with BD at all stages of the study. There are opportunities for building background understanding of the problem and improving the quality of the data via strategic planning before acquiring BD. In addition, incorporating DDC into the collection and processing of the actual BD, and strengthening conclusions or augmenting with supplementary designed data after BD also represent key opportunities to increase the impact of BD in the era of Industry 4.0 and Quality 4.0.

Effect of different soluble salt ions on deformation of desulfurization gypsum in high humidity environment: a statistically designed experimental analysis method

In response to the green energy-saving goal of carbon neutralization and carbon peak, the research and development of green building materials have become a key research direction. Desulfurization gypsum is widely used in building materials because of its good energy saving, but it cannot be used in high humidity areas because of its highly soluble salt. Based on this reason, this paper uses statistically designed experiments (SDE) to design the experiments on the influence of four common soluble salt ions and on the sagging deformation of desulfurization gypsum, and studies the significance of their influence by SDE experimental analysis method. The results show that: (1) in the environment of a single salt solution, ion, ion, ion, and ion will cause sagging deformation of desulfurization gypsum, and their values are 0.432 mm, 1.933 mm, 0.942 mm, and 0.940 mm respectively. It can be seen that the effect of the ion is the most significant. (2) In the environment of composite salt solution, ions will inhibit the sagging deformation of desulfurization gypsum. Specifically, in the compound salt solution environment of and the deformation values are 0.605 mm and 0.596 mm respectively.

Microabrasive wear behavior of different stellites obtained by laser cladding and casting processes

Cobalt superalloys are used in several applications, mainly involving corrosive environments and high temperatures, in which wear and corrosion resistance are key factors in their performance. These alloys can be produced by a variety of manufacturing processes. Among these, the technology of laser cladding coatings has emerged as a promising and economically viable alternative to produce coatings from cobalt-based alloys. One of the applications of these alloys is in the production of components to obtain second-generation ethanol. In this application, about 8% of the processed material is composed of micrometric abrasive particles, mainly silica, among others, which cause wear of components. In order to better understand the tribological behavior of these alloys in microabrasion, three coatings of commercial cobalt-based superalloys, Stellite 1, 6 and 12, were produced by laser cladding. Additionally, two cast alloys, Stellite 250 and an experimental Stellite alloy, were also evaluated. Microabrasion tests using a statistical design of experiments were performed with SiO2, Al2O3 and SiC abrasives in a suspension of distilled water. Statistical analysis revealed that the wear coefficients of these alloys are influenced by both the abrasives and the alloy. The as-cast Stellite 250 alloy showed the highest wear coefficients, while the coated Stellite 1 and the as-cast experimental Stellite showed the lowest wear coefficients. The predominant wear micromechanism was scratching, except for Stellite 6 and 12 coated alloys in SiC tests, in which predominant mechanism were mixed and rolling, respectively. The presence of secondary micromechanism of rolling wear was also observed and associated with the granulometric distribution of the abrasives. The analysis of wear severity allowed the comprehension of the granulometric distribution influence of abrasive particles on wear.

Route of biofuel production from macadamia nut shells: effect of parameters on the particles mixing index in fluidized beds

Pyrolysis of macadamia nut shells (MNS) in a fluidized bed reactor has excellent potential to produce bio-oil. High heat transfer rates and uniform temperature in the fluidized bed can be achieved due to effective gas-solid contact in the reactor. However, binary mixtures can lead to the segregation of particles, which negatively affects heat and mass transfer in such a reactor. Therefore, a 2³ statistical experimental design was used to assess the effects of parameters (i.e., air velocity, particle diameter ratio, and mass fraction of MNS) on the mixing index of the bed of MNS and sand. Among the analyzed factors, only DMNS/DS and V/VMF influenced the mixing index (Im) within a confidence interval of 95%. Based on statistical data analysis, an air velocity 20% above the minimum fluidization and particle diameter ratio (DMNS/DS) smaller than 3 results in uniform particle mixing in the bed (i.e., reaching ideal mixing index values). Moreover, the experimental results indicate that fluidized be used for biofuel production from Macadamia nut Shells.

Pillared bentonite from Al-Fe-Cu polymeric precursor in solid state for the catalytic oxidation of amoxicillin

A Colombian bentonite is successfully pillared with Al, Al-Fe, Al-Cu and Al-Fe-Cu polyhydroxications in solid state. The effect of the Fe and Cu content on the physicochemical properties of the pillared bentonite was evaluated using characterization techniques such as X-ray fluorescence (XRF), X-ray diffraction (XRD) and textural analysis (nitrogen physisorption). The Box-Behnken statistical experiment design was used to determine the optimal parameters of the independent variables hydrogen peroxide (0.120–0.144 M), catalyst load (0.5–1.5 g/L) and type of catalyst (PILC FeCu1, FeCu5, FeCu10) in the catalytic oxidation (CWPO) of amoxicillin. The optimized conditions of hydrogen peroxide (0.137 M) and catalyst loading (0.7 g/L) were used to compare the catalytic performance of the catalysts with 1%, 5% and 10% Al-Fe, Al-Cu and Al-Fe-Cu reaching a removal between 91% and 100% of amoxicillin at T and ambient pressure. The rate constants determined allowed the identification of the best catalyst of each series to study the degree of mineralization and choose the best catalyst: the pillared clay with AlFeCu10, with a TOC removal of 24.6% after 2 h of reaction. After three cycles of reuse, the catalyst maintained its catalytic activity in removing amoxicillin without leaching any metal.

The effect of operational conditions on the performance of granular ozone removal media: Statistical experimental design and kinetic modeling

Ozone, a strong oxidizer, and a hazardous air pollutant can adversely affect human health and the environment; therefore, its concentration must be kept within a specific limit. Several ozone removal technologies are available for this purpose, which may be used under different operational conditions. Despite the selection flexibility that these technologies bring about, they raise the need to better understand the feasibility of each technique for various applications. Such broad perspective however is currently lacking due mainly to the cost and resources required for comprehensive studies. Using a statistical design approach, this study aims to address this important gap. The fractional factorial method, as a reliable statistical technique, was used to study the effect of ozone concentration, humidity level, airflow rate, and media volume on the ozone removal performance of common granular materials including different types of activated carbon (CL-A: coal-based, CS-B: coconut shell-based, IM-l-A: coal-based impregnated with KOH) and a catalyst (CAT-E). The role of individual parameters and their interactions were studied. The results show that depending on the physicochemical properties of the material, humidity could substantially improve or deteriorate its performance. Among the materials tested across all operational conditions, on average, CL-A showed the poorest performance (mean efficiency = 62%, standard deviation = 0.31), CS-B was highly sensitive to operational conditions (efficiency was varied from 25% to 100% at different humidity levels), IM-l-A showed the highest efficiency robustness among activated carbon media (mean efficiency = 77.6%, standard deviation = 0.20), and CAT-E featured the best performance (mean efficiency = 86.5%, standard deviation = 0.16). Additionally, the data were fitted into a packed bed kinetic model that elucidated physicochemical mechanisms underlying distinctive behaviours of each tested material.

Accelerated solvent extraction for liquid chromatographic determination of carotenoids in durum wheat pasta: A chemometric approach using statistical experimental design

In recent decades, the consumption of wholegrain products associated with health benefits has become habitual. In this context, wholemeal pasta – rich in bioactive substances with antioxidant properties, such as carotenoids – has received particular interest among consumers over the years. Carotenoids, involved in the prevention of many degenerative diseases, are also used as markers of the color quality of durum wheat pasta. The present research aims to investigate the functional quality of wholemeal pasta compared to traditional durum wheat pasta in terms of carotenoid content. 50 commercially samples were extracted by accelerated solvent extraction (ASE) and analyzed by HPLC-DAD. A central composite design (CCD) was used to optimize the ASE extraction parameters. A classification method (partial least squares-discriminant analysis, PLS-DA) was then applied to the collected chromatographic profiles to build a model that could allow to differentiate refined pasta from wholemeal pasta in terms of carotenoid level.The resulting classification model made it possible to correctly predict more than 95% of the validation samples, highlighting a significant difference between the two types of pasta both in terms of the entire chromatographic profile and, specifically, of the amount of lutein. In fact, the highest lutein levels were found in all wholemeal pasta samples analyzed. Lutein is a promising biologically active component, also used in recent years as a food supplement. The results obtained could provide the food industry with an objective tool to enhance the use of raw materials with high nutritional content.

Applying the Taguchi to Optimization the densification, and flexural strength of ZrB2–SiC–ZrC-CNFs

The purpose of this research is to optimize the densification, microstructure and flexural strength of ZrB2-25 vol% SiC composites reinforced by carbon nano fibers (CNFs) and zirconium carbide (ZrC). Spark Plasma Sintering (SPS) was applied for composites consolidation. Taguchi orthogonal array L9 as the design of statistical experiments (DOE) was evaluated to optimize the additives, as well as SPS parameters (temperature and time). Three levels were defined for each factor. The relative density (R.D%) and flexural strength of the samples were calculated based on Archimedes' law and the three-point bending test. Moreover, analysis of variance (ANOVA) was utilized to determine the importance of effective parameters and to optimize the SPS variables and compounds (the amount of CNFs and ZrC). The microscopic structure of surfaces was examined through field emission scanning electron microscopy equipped with energy dispersive spectroscopy (FE-SEM, EDS). The results showed that the best output of relative density and flexural strength was equal to 99.8% and 610 MPa, respectively, with an average ZrB2 grain size of 9.6 μm in a composite containing 15 vol% CNFs and 10 vol% ZrC and SPSed at 1875 °C for 7 min.

Experimental investigation of localized electrochemical deposition-based micro-additive manufacturing process

ABSTRACT Localized Electro-chemical Deposition (LED) is a non-thermal additive manufacturing process for fabricating micron-sized 3D metallic parts. In the present LED study, the process parameters, namely, applied voltage, frequency of current, inter-electrode gap (IEG), and scanning speed, are varied to determine their effect on layer height and width. An Analysis of Variance (ANOVA) study based on the statistical design of experiments (DOE) is conducted to determine the most significant process parameters and their impact on the percentage contribution of output responses. Response Surface Methodology (RSM) is utilized to determine the optimum values of the process parameters while achieving maximum and minimum values of the layer height and width, respectively. A single bead of 5 mm length is deposited over a brass substrate for all experiments during DOE. It is observed that a uniform deposition can be achieved up to a critical voltage of 4 V, and beyond that, the deposited structure becomes nonuniform.

Stability of Superhydrophobicity and Structure of PVDF Membranes Treated by Vacuum Oxygen Plasma and Organofluorosilanisation.

Superhydrophobic poly(vinylidene fluoride) (PVDF) membranes were obtained by a surface treatment consisting of oxygen plasma activation followed by functionalisation with a mixture of silica precursor (SiP) (tetraethyl-orthosilicate [TEOS] or 3-(triethoxysilyl)-propylamine [APTES]) and a fluoroalkylsilane (1H,1H,2H,2H-perfluorooctyltriethoxysilane), and were benchmarked with coated membranes without plasma activation. The modifications acted mainly on the surface, and the bulk properties remained stable. From a statistical design of experiments on surface hydrophobicity, the type of SiP was the most relevant factor, achieving the highest water contact angles (WCA) with the use of APTES, with a maximum WCA higher than 155° for membranes activated at a plasma power discharge of 15 W during 15 min, without membrane degradation. Morphological changes were observed on the membrane surfaces treated under these plasma conditions, showing a pillar-like structure with higher surface porosity. In long-term stability tests under moderate water flux conditions, the WCA of coated membranes which were not activated by oxygen plasma decreased to approximately 120° after the first 24 h (similar to the pristine membrane), whilst the WCA of plasma-treated membranes was maintained around 130° after 160 h. Thus, plasma pre-treatment led to membranes with a superhydrophobic performance and kept a higher hydrophobicity after long-term operations.

Chemometric study for the performances of deep eutectic solvents during the recovery of high-added-value substances from Moringa oleifera leaves: Principal component analysis.

Moringa oleifera is a plant with high antioxidant content in its leaves, flowers and seeds. It attracts the attention of researchers with the effect of its nutritional and medical advantages. The purpose of the current study is to propose a deep eutectic solvent (DES)-based ultrasound-assisted extraction of bioactive substances from M. oleifera leaves by the application of a chemometric study. A total of 18 different choline chloride-based DESs were prepared by using several hydrogen bond donors (glucose, sucrose, glycerol, ethylene glycol, urea and dimethyl urea) with various molar ratios (1:1, 1:2 and 2:1) by addition of diluents (water and 50% methanol) or alone. In order to decide the best DES combination, principal component analysis (PCA) was applied. The response surface method (RSM) was used as statistical experimental design approach through the Box-Behnken design. The best phenolic (TPC), flavonoid (TFC) and antioxidant activity yields of M. oleifera leaf extract were found to be 19.102 mg-GAE, 10.47 mg-CE and 24.404 mg-TEAC per gram dried leaf under the optimal conditions (50% water content, 20% amplitude, 15 min time). The model fitting has been also found reliable depending on the statistical indicators such as p-value (<0.0001), coefficients of determination (R2 = 0.9827, 0.9916 and 0.9864) and root mean square error (RMSE = 1.0562, 2.4656 and 0.7713). A chemometric study through PCA was carried out to determine the similarities and differences between the solvent groups, and the ethylene glycol-based DES (1:2, molar ratio) with the addition of water showed the best performance.

Co-Electrodeposited Pi-MnO2-rGO as an Efficient Electrode for the Selective Oxidation of Piperonyl Alcohol

Pi-MnO2-rGO-CFP electrode was developed through a concurrent deposition of Pi-MnO2 and reduced graphene oxide (rGO) on carbon fiber paper (CFP). Cyclic voltammetry (CV) and electrochemical impedance studies (EIS) were applied for the electrochemical characterization of the electrode. The electro catalytic activity of the modified electrode was improved by the increased synergistic characteristics of the CFP and electrochemically deposited rGO-Pi-MnO2 composite. The performance of the modified electrode was remarkable due to its lowest charge transfer resistance (R ct), and highest surface area offering more active sites and quicker electron transport kinetics. X-ray diffraction spectroscopy (XRD), Raman spectroscopy, scanning electron microscopy (SEM), transmission electron microscopy (TEM), and optical profilometry (OP) were employed to study the physicochemical properties. Furthermore, the modified electrode was availed to oxidize piperonyl alcohol mediated by 4-acetamido-2,2,6,6-tetramethylpiperidine-1-oxyl (4-acetamido TEMPO or 4-ACT). The product obtained was purified and characterized by 1HNMR. The turnover frequency of 4-ACT was studied at different concentrations of the reactant, and the reaction parameters were also optimized using statistical tool design of experiment. This methodology is demonstrated to be economical, environmentally benign, and highly efficient in obtaining piperonal as it is carried out under milder reaction conditions.

Insights of Lipid-Based Drug Delivery Systems with an Emphasis on Quality by Design

Lipid-based drug delivery systems offer several advantages and have wide solubility, permeation, and bioavailability enhancement applications. This review provides detailed information on the fabrication, application and aspects of QbD of various lipid-based vesicles. Most of the review studies focused on lipid-based vesicles without the QbD aspect. This review article covers all the lipid-based systems in escalating on the method of QbD, which enhances the bioavailability of active pharmaceutical ingredients in different formulation approaches. Among all the different available approaches towards formulation development, lipid-based drug delivery systems (LBDDS) have continually maintained the limelight on themselves. One of the reasons for the popularity of LBDDS is their ability to solve problems with poorly water-soluble drugs and their bioavailability. Several drugs' efficacy was improved by utilizing this type of delivery system. Vesosomes, Phytosomes, Solid Lipid Nanoparticles (SLNs), Nanostructured Lipid Carriers (NLCs), and Archaeosomes are novel lipid-based systems with unique applications in drug delivery. Hence, the present perspective is to review the various LBDDS approaches utilized to enhance the formulations' performance while dissecting the studies systematically to get a clear outline of various LBDD subsystems, their applications, methods of preparation, and the mechanism of drug delivery. In addition to this, the review also focuses on overcoming the lacunas of the past literature by making an attempt to identify Quality target product profile (QTPP), Critical quality attributes (CQAs) and applying them for the statistical design of experiments and continuous strategy by QbD at the same time harnessing their potential in risk assessment. Applying QbD in developing lipid-based drug delivery systems reduces the number of trials and yields a product with in-built quality as it deliberates various critical variables, process parameters, risk assessment, and control strategy in formulation development.