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This study investigates the effect of activated fluxes TiO2, SiO2, and Fe2O3 and their mixtures on the microstructure and hardness of tungsten inert gas welded austenitic stainless steel SS304. Regression models were developed for all the responses. Bead-on plate welds were fabricated using optimized process parameters and characterized for microstructure and hardness. The activated fluxes significantly impacted the bead's appearance, shape, microstructure, and hardness. A layer of residual slag was seen over the weld metal for all the fluxes and their mixtures. No critical defect was seen except a little spattering for a few fluxes. Activated fluxes exhibited different impacts on penetration, bead width, and HAZ width without any correlation. SiO2 produced the greatest penetration and aspect ratio. Penetration varied in direct proportion with the amount of SiO2 and inversely with the amount of TiO2 and Fe2O3. No such relation could be seen for other responses. Welds displayed the usual vermicular delta-ferrite morphology together with an austenite matrix microstructure without any significant influence of fluxes on microstructure. A marginal change in bead and HAZ hardness was observed for all activated oxide fluxes. Mixture design using analysis of variance is a decent technique for optimizing flux compositions as predicted results are in good agreement with experimental ones. [ABSTRACT FROM AUTHOR]

In vitro transcription (IVT) reaction is an RNA polymerase‐catalyzed production of messenger RNA (mRNA) from DNA template, and the unit operation with highest cost of goods in the mRNA drug substance production process. To decrease the cost of mRNA production, reagents should be optimally utilized. Due to the catalytic, multicomponent nature of the IVT reaction, optimization is a multi‐factorial problem, ideally suited to design‐of‐experiment approach for optimization and identification of design space. We derived a data‐driven model of the IVT reaction and explored factors that drive process yield (in g/L), including impact of nucleoside triphosphate (NTP) concentration and Mg:NTP ratio on reaction yield and how to optimize the main cost drivers RNA polymerase and DNA template, while minimizing dsRNA formation, a critical quality attribute in mRNA products. We report a methodological approach to derive an optimum reaction design, with which cost efficiency of the reaction was improved by 44%. We demonstrate the validity of the model on mRNA construct of different lengths. Finally, we maximized the yield of the IVT reaction to 24.9 ± 1.5 g/L in batch, thus doubling the highest ever reported IVT yield. [ABSTRACT FROM AUTHOR]

An important aspect for the analysis of irradiation path of the laser beam opens a way to explore the diverse phenomena involved in the laser forming process that led to control the final forming magnitude of the irradiated sheets. In this research, laser forming of 6061 aluminium alloy sheets by introducing an angular segment irradiating scheme is investigated using the finite-element based numerical model. Fiber laser machine with a 1 kW maximum power is used during the forming of 1.5 mm thick aluminium sheets. The experimental observations in terms of bend angle are found to be in good agreement with numerical simulations, providing substantial evidence to support the validity and effectiveness of the suggested numerical model. At the same time, analysis of variance is conducted for examining the effects of influential parameters including laser power, scan speed, and segment angle on the forming magnitude and a closed form mathematical equation is presented. The ranges for the parameters are: laser power 400–500 W, scan speed 1250–1750 mm/min, and segment angle 30–60 degree. The results indicate that two parameters laser power and segment angle have the increasing effect on the bending angle and also that the scan speed has a negative effect on increase of bending angle. It is also observed that the final shape of the formed sheet is affected by the angular segment irradiation scheme. According to the results, higher segment angles exhibit a greater degree of warping at the free edge, resulting in the formation of a concave shape after the forming. Research results suggest confidence in using the proposed irradiation scheme for controlling the final forming magnitude of the sheet metal components in the field of laser processing. [ABSTRACT FROM AUTHOR]

The increasing demand for effective cosmetics has driven the development of innovative analytical techniques to ensure product quality. This work presents the development and validation of a zwitterionic hydrophilic interaction liquid chromatography method, coupled with ultraviolet detection, for the quantification of copper tripeptide in cosmetics. A novel protocol for sample preparation was developed using fabric phase sorptive extraction to extract the targeted analyte from the complex cosmetic cream matrix, followed by chromatographic separation on a ZIC®-pHILIC analytical column. A thorough investigation of the chromatographic behavior of the copper tripeptide on the HILIC column was performed during method development. The mobile phase consisted of 133 mM ammonium formate (pH 9, adjusted with ammonium hydroxide) and acetonitrile at a 40:60 (v/v) ratio, with a flow rate of 0.2 mL/min. A design of experiments (DOE) approach allowed precise adjustments to various factors influencing the extraction process, leading to the optimization of the fabric phase sorptive extraction protocol for copper tripeptide analysis. The method demonstrated excellent linearity over a concentration range of 0.002 to 0.005% w/w for copper tripeptide, with a correlation coefficient exceeding 0.998. The limits of detection and quantitation were 5.3 × 10−4% w/w and 2.0 × 10−3% w/w, respectively. The selectivity of the method was verified through successful separation of copper tripeptide from other cream components within 10 min, establishing its suitability for high-throughput quality control of cosmetic formulations. [ABSTRACT FROM AUTHOR]

Simple Summary: This study investigates the structural and functional changes in the cervix of doe goats during different reproductive stages using advanced imaging techniques and biochemical markers. By analyzing the cervix at various stages of the estrous cycle and early pregnancy, the study aims to provide insights into reproductive management strategies. The results highlight the dynamic changes in cervical morphology and oxytocin receptor expression, which are crucial for reproductive success in goats. This research may contribute to improve artificial insemination techniques and overall reproductive health in veterinary practice. This study aimed to elucidate the morphophysiology and oxytocin receptor (OXTR) expression in the cervix of doe goats during various reproductive stages to enhance reproductive management strategies. A total of 40 cervical samples were categorized into follicular (n = 15), luteal (n = 10), and early pregnancy (n = 15) stages. Utilizing advanced imaging based on functional and morphological markers, the study employed computed tomography (CT) scans, histochemical staining (Masson trichrome and alcian blue), immunohistochemistry, Western blotting, and quantitative PCR (qPCR) to assess structural changes in the cervix and in OXTR expression during the estrous cycle and early pregnancy. CT scans revealed consistent cervical folds and a significant reduction in cervical width during pregnancy, suggesting structural adaptations for gestational integrity. Histochemical analyses indicated a well-organized collagen network and presence of mucins, essential for cervical function and integrity. Immunohistochemistry and Western blotting demonstrated elevated OXTR protein levels during the follicular stage, which were markedly reduced during pregnancy, indicating a role in facilitating cervical relaxation and sperm transport during estrus and maintaining cervical closure during gestation. qPCR analysis showed stable OXTR mRNA levels during follicular and luteal stages with a slight, non-significant increase during pregnancy, pointing towards posttranscriptional regulatory mechanisms. In conclusion, this study demonstrates that cervical morphology and OXTR expression in doe goats undergo significant changes across reproductive stages, with elevated OXTR protein levels during the follicular phase and notable reductions in cervical width and OXTR protein levels during pregnancy, indicating structural and functional adaptations for both reproductive processes and gestational integrity. [ABSTRACT FROM AUTHOR]

Copyright of Environmental & Social Management Journal / Revista de Gestão Social e Ambiental is the property of Environmental & Social Management Journal and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Normal skin is the first line of defense in the human body. A burn injury makes the skin susceptible to bacterial infection, thereby delaying wound healing and ultimately leading to sepsis. The chances of biofilm formation are high in burn wounds due to the presence of avascular necrotic tissue. The most common pathogen to cause burn infection and biofilm is Pseudomonas aeruginosa. The purpose of this study was to create a microemulsion (ME) formulation for topical application to treat bacterial burn infection. In the present study, tea tree oil was used as the oil phase, Tween 80 and transcutol were used as surfactants, and water served as the aqueous phase. Pseudo ternary phase diagrams were used to determine the design space. The ranges of components as suggested by the design were chosen, optimization of the microemulsion was performed, and in vitro drug release was assessed. Based on the characterization studies performed, it was found that the microemulsion were formulated properly, and the particle size obtained was within the desired microemulsion range of 10 to 300 nm. The I release study showed that the microemulsion followed an immediate release profile. The formulation was further tested based on its ability to inhibit biofilm formation and bacterial growth. The prepared microemulsion was capable of inhibiting biofilm formation. [ABSTRACT FROM AUTHOR]

Background: Hypertension is a prevalent health condition with severe implications for cardiovascular health. Combination therapy involving Candesartan and Nifedipine has emerged as a promising approach for managing hypertension due to the synergistic effects of these medications. Methods: This study aimed to develop a Design of Experiment (DoE) based Green High-Performance Liquid Chromatography (HPLC) method for the simultaneous estimation of Candesartan and Nifedipine in a combined dosage form. Reversed-phase HPLC was utilized with UV-Vis spectrophotometry for detection. DoE principles were applied to optimize chromatographic conditions, including pH, ethanol percentage in the mobile phase, and flow rate. Results: Optimal chromatographic separation was achieved using a composite mobile phase comprising ethanol and potassium dihydrogen phosphate buffer (45:55, v/v) at pH 3.7, with a flow rate of 1 mL/min. Statistical analysis confirmed the significance of these parameters in achieving efficient separation. The developed method exhibited high precision, accuracy, and reliability across various validation parameters, including specificity, linearity, repeatability, and robustness. Conclusion: The proposed DoE-based Green HPLC method offers a sustainable and efficient approach for the simultaneous estimation of Candesartan and Nifedipine in hypertension management. By integrating green chemistry principles with systematic method development, this method provides a reliable analytical tool for routine quality control purposes in pharmaceutical formulations containing these medications. [ABSTRACT FROM AUTHOR]

Levulinic acid (LA) is one of the top bio‐based platform molecules that can be converted into many valuable chemicals. Herein, we report the sustainable synthesis of LA acid from various sugars using heteropolyacid catalysts. By using a Box–Behnken design of experiment, both LA yield (up to 69 mol%) and complete suppression of parasitic humin formation could be achieved within a 5 h reaction time at 140°C using fructose as a substrate. The effects of various reaction parameters like temperature, sugar concentration, addition of organic co‐solvent and reaction time on LA yield and humin formation were examined in a three‐dimensional space. Moreover, the results could be successfully transferred to other sugars like glucose or cellobiose, paving the way for an atom‐efficient and sustainable LA synthesis process. [ABSTRACT FROM AUTHOR]

The layer-by-layer deposition of molten polymer filament in fused deposition modeling (FDM) has evolved as a disruptive technology for building complex parts. This technology has drawbacks such as the anisotropic property of the printed parts resulting in lower strength for parts printed in the vertical Z direction compared with the other two planes. In this manuscript, we attempt to address these challenges as well as the lack of standardization in sample preparation and mechanical testing of the printed parts. The paper focuses on process parameters and design optimization of the ZX build orientation. Type I tensile bars in ZX orientation were printed as per the ASTM D638 standard using two (2B) and four (4B) tensile bar designs. The proposed design reduces material loss and post-processing to extract the test coupons. Printing a type I tensile bar in the ZX orientation is more challenging than type IV and type V due to the increased length of the specimen and changes in additional heat buildup during layer-by-layer deposition. Three different polymer composite systems were studied: fast-crystallizing nanofiller-based high-temperature nylon (HTN), slow-crystallizing nanofiller-based polycyclohexylene diethylene terephthalate glycol-modified (PCTG), and amorphous carbon fiber-filled polyetherimide (PEI-CF). For all the polymer composite systems, the 2B showed the highest strength properties due to the shorter layer time aiding the diffusion in the interlayers. Further, rheological studies and SEM imaging were carried out to understand the influence of the two designs on fracture mechanics and interlayer bonding, providing valuable insights for the field of additive manufacturing and material science. [ABSTRACT FROM AUTHOR]

This paper explores and presents the importance and application of the Design of Experiments (DOE) method in scientific and industrial research. It analysed the theoretical foundations of the method in detail and then illustrated concrete examples as well as benefits of its use in an automotive environment. The introduction outlined the key principles and objectives of the DOE method, including optimisation of experimental processes and minimisation of variability of results. The publication focused on the significant impact of this method in improving the efficiency of experiments and achieving reliable and reproducible results. The practical part of the paper presented concrete examples of the application of the DOE method in the automotive industry. Through this case study, it was highlighted how the DOE method enables the systematic investigation of the influence of different factors on experimental results, leading to a better understanding of the phenomena under investigation and an increase in process efficiency. Emphasis was also placed on the practical aspects of using the DOE method, including the design of experimental plans and the analysis of the data obtained. The case study outlined the challenges and benefits that can arise when implementing this method and presents new perspectives for future research in statistical experimental analysis. Overall, this research paper can be considered an important resource for researchers and practitioners seeking effective methods for planning and conducting experiments to achieve significant research results in various disciplines. [ABSTRACT FROM AUTHOR]

Melatonin's antioxidant properties make it a valuable component in anti-aging semisolid topical products. This study explores the role of Pemulen®, an acrylic-based viscosifying agent, in stabilizing cream-gel formulations. Remarkably, even at low concentrations (0.4%), Pemulen® successfully produced physicochemical stable topical formulations. In this work, the impact of the ratio of the oily phase—comprising olive oil and isopropyl myristate from 0 to 20%—was investigated to understand the internal microstructure effect on skin permeability, rheological properties, and stability. The formulations exhibited pseudoplastic behavior, with a significant positive correlation (p-value < 0.1) between the oily phase ratio, viscosity, spreadability, skin adhesiveness, and permeability. Formulations without the oil phase exhibited greater skin permeability. However, higher oily phase content enhanced viscosity, spreadability, and skin adhesion. Given that melatonin primarily degrades through oxidation, incorporating antioxidant excipients in semisolid formulations is crucial for maintaining its chemical stability. A quality by design (QbD) approach was used to assess the impact of four excipients—(a) DL-α-tocopheryl acetate (0.05%), (b) ascorbic acid (0.1%), (c) ethylene diamine tetraacetic acid (0.1%), and (d) sodium metabisulphite (0.5%)—on melatonin's stability. Our findings indicate that maintaining the physical stability of the formulation with a 20% oil phase is more critical for protecting melatonin from oxidation than merely adding antioxidant excipients. [ABSTRACT FROM AUTHOR]

This paper explores and presents the importance and application of the Design of Experiments (DOE) method in scientific and industrial research. It analyses in detail the theoretical foundations of the method and then illustrates concrete examples and benefits of its use in an automotive environment. The introduction outlines the key principles and objectives of the DOE method, including optimization of experimental processes and minimization of variability of results. The publication focuses on the significant impact of this method in improving the efficiency of experiments and achieving reliable and reproducible results. The practical part of the paper presents concrete examples of the application of the DOE method in the automotive industry. Through this case study, it is highlighted how the DOE method enables the systematic investigation of the influence of different factors on experimental results, leading to a better understanding of the phenomena under investigation and an increase in process efficiency. Emphasis is also placed on the practical aspects of using the DOE method, including the design of experimental plans and the analysis of the data obtained. The case study outlines the challenges and benefits that can arise when implementing this method and presents new perspectives for future research in statistical experimental analysis. Overall, this research paper can be considered an important resource for researchers and practitioners seeking effective methods for planning and conducting experiments to achieve significant research results in various disciplines.

Objective A finite element model of metro vehicle air compressor frame is established and verified through modal testing and vibration testing. It is found that the vertical bending modal frequency of the dryer frame coincides with motor harmonic frequency and the vibration isolation rate is relatively low. Under the premise of meeting modal frequency and vibration isolation rate requirements, a structural optimization design of air compressor frame is carried out by integrating finite element method and optimization techniques. Method Taking the thickness of the air compressor frame as the optimization variable, DOE (design of experiment) is firstly carried out to obtain different samples of air compressor frame, then an approximate model of air compressor frame is established using the Moving Least Squares method. Based on this approximate model, with vertical first-order bending modal frequency of the frame, vertical bending modal frequency of dryer frame and vibration isolation rate as optimization objectives, an optimization design is performed using the adaptive response surface method to obtain the optimal scheme of frame parameters. Result & Conclusion Results show that, compared to before optimization, the vertical first-order bending and the dryer frame vertical bending modal frequencies after optimization are both more than 3.0 Hz different from the rail excitation frequency (typically 15.0 Hz), motor rotation fundamental frequency (24.5 Hz), and harmonics; reaching the optimal avoidance of resonance conditions, and the vibration isolation rate can be increased by 20% to 25%, while the total mass only increases by 6%.

Abstract Background Stem cell-derived therapies hold the potential for treatment of regenerative clinical indications. Static culture has a limited ability to scale up thus restricting its use. Suspension culturing can be used to produce target cells in large quantities, but also presents challenges related to stress and aggregation stability. Methods Utilizing a design of experiments (DoE) approach in vertical wheel bioreactors, we evaluated media additives that have versatile properties. The additives evaluated are Heparin sodium salt (HS), polyethylene glycol (PEG), poly (vinyl alcohol) (PVA), Pluronic F68 and dextran sulfate (DS). Multiple response variables were chosen to assess cell growth, pluripotency maintenance and aggregate stability in response to the additive inputs, and mathematical models were generated and tuned for maximal predictive power. Results Expansion of iPSCs using 100 ml vertical wheel bioreactor assay for 4 days on 19 different media combinations resulted in models that can optimize pluripotency, stability, and expansion. The expansion optimization resulted in the combination of PA, PVA and PEG with E8. This mixture resulted in an expansion doubling time that was 40% shorter than that of E8 alone. Pluripotency optimizer highlighted the importance of adding 1% PEG to the E8 medium. Aggregate stability optimization that minimizes aggregate fusion in 3D culture indicated that the interaction of both Heparin and PEG can limit aggregation as well as increase the maintenance capacity and expansion of hiPSCs, suggesting that controlling fusion is a critical parameter for expansion and maintenance. Validation of optimized solution on two cell lines in bioreactors with decreased speed of 40 RPM, showed consistency and prolonged control over aggregates that have high frequency of pluripotency markers of OCT4 and SOX2 (> 90%). A doubling time of around 1–1.4 days was maintained after passaging as clumps in the optimized medium. Controlling aggregate fusion allowed for a decrease in bioreactor speed and therefore shear stress exerted on the cells in a large-scale expansion. Conclusion This study resulted in a control of aggregate size within suspension cultures, while informing about concomitant state control of the iPSC state. Wider application of this approach can address media optimization complexity and bioreactor scale-up challenges.

Electrical Discharging Machining (EDM) offers broad capabilities that allow it to be used in the manufacturing, automotive, and aviation industries, as well as practically all disciplines of conductive material machining. This experimental and numerical work aims to use EDM to evaluate the surface of Alloy Steel (X210). The experiments used the EDM copper electrode with a novel horizontal flushing hole. The findings of the investigations have been analyzed so that the best settings for the input process factors can be determined. Alloy tool steel (X210) is cut in dimensions by the Wire EDM (dk7740) (15 × 15 × 10 mm) with very little research dealing with this alloy. ARL spectrometer method was used to determine the percentage chemical composition. In the current experimental work, the Effect of different parameters such as electrode angle (EA), peak current (Ip), pulse on time (Pon), and pulse off time (Poff) have been investigated using response surface methodology (RSM). Microhardness reaches the maximum value with an electrode angle of 67.5º with increasing current and pulse. Responses (SR and MH) were modeled using RSM. It is found that the lowest SR is achieved when conducted with an electrode tilt of 45º. A high peak current (Ip) has also been discovered to raise SR further while decreasing pulse-off time. The primary effects of input parameters, specifically E.A, Ip, Pon, and Poff, were determined to impact the Ra and MH considerably. Peak current greatly affects 45º angled electrodes while keeping other parameters constant.

Erectile dysfunction (ED) refers to the inability of the penis to maintain a firm erection during sexual activity. Mucuna, or M. pruriens, contains levodopa, a compound showing promise in ED treatment. However, formulating Mucuna extract into tablet dosage forms is challenging due to its semisolid nature. This study aimed to develop sustained-release tablets containing Mucuna extract via semisolid extrusion 3D printing. Eudragit RS PO (Eudragit) served as a sustained-release polymer, with poly (vinyl alcohol) (PVA) as a co-polymer for forming the tablet matrices. This study had the following two main phases: screening, which identified the factors affecting the printability, and optimization, which focused on the factors influencing the levodopa release and its consistency. The results showed that both the polymeric solid percentage content (PSPC) in the semisolid slurry and the Eudragit-PVA ratio significantly affected the printability. All of the formulations were printable, and the PSPC and Eudragit-PVA ratios were incorporated into the optimized model. The desired formulation, achieving targeted levodopa release and consistency, had a PSPC of 58.8% and a Eudragit-PVA ratio of 2.87:1. In conclusion, semisolid extrusion 3D printing guided by the design of experiments (DoE) proved feasible for producing reliable 3D-printed tablets with consistent active ingredients and desired release rates. [ABSTRACT FROM AUTHOR]

The investigation aimed to determine the optimal value of process parameters to minimize distortion while reducing the overall printing time. To achieve this, different combinations of process parameters are selected, and 25 sets of FE experiments are prepared using an orthogonal matrix. The coupled thermomechanical analysis with the element birth technique is used to mimic the behavior of Selective Laser Melting (SLM). Initially, a mesh convergence study is performed to reduce computation time with the least sacrifice in results. To minimize the temperature gradient, simulations are performed at different levels of bed temperature ranging from 303 K to 843 K. The minimum distortion was observed for a higher bed temperature of 843 K, as at this temperature, the gradient in temperature is minimum, resulting in the least development of residual stresses. The interactive behavior between laser power and scanning speed is studied, revealing an approximately linear trend with respect to distortion while keeping all other parameters constant. Additionally, it was observed that laser power and layer thickness also exhibited a similar linear trend with respect to distortion. To identify the optimal process parameter value within the design space, the Multi-Island Genetic Algorithms (MIGA) technique is employed, leading to a remarkable minimum distortion of 0.45 mm for a specific set of input process parameters. [ABSTRACT FROM AUTHOR]

Monacolin K (MK), in red yeast rice (RYR) in the forms of lactone (LMK) and hydroxy acid (AMK), is known for its anti-hypercholesterolemic activity. Under the rising demand for natural bioactive molecules, we present a green ultrasound-assisted extraction (UAE) optimization study for MK in RYR. The development and validation of a fast, sensitive, selective, reproducible, and accurate ultra-high-performance liquid chromatography (UHPLC) method coupled to diode array detection for LMK and AMK allowed us to evaluate the MK recovery in different extract media. Firstly, the ethanol comparability to acetonitrile was assessed (recovery of 80.7 ± 0.1% for ethanol and 85.5 ± 0.2% for acetonitrile). Then, water/ethanol mixtures, with decreasing percentages of organic solvent, were tested by modulating temperature and extraction times. Water extractions at 80 °C for 10 min produced MK yield > 85%. Thus, UAE conditions were optimized by a DOE study using a water-based formulation (mouthwash). The optimal total MK extraction yield (86.6 ± 0.4%) was found under the following conditions: 80 °C, 45 min, 5 mg mL−1 (RYR powder/solvent). Therefore, the new single-process green approach allowed the simultaneous direct extraction of MK and mouthwash enrichment (MK concentration = 130.0 ± 0.6 µg mL−1), which might be tested for the prevention and treatment of periodontitis or oral candidiasis. [ABSTRACT FROM AUTHOR]

Introduction: Thunbergia laurifolia is used in traditional Thai medicine to reduce fever and treat mouth ulcers. However, the quantitative analysis of chemical markers has not yet been officially defined. Objective: The objective of this study is to develop a high‐performance liquid chromatography (HPLC) method using a design of experiment (DoE) for the quantitative analysis of multicomponents by single marker (QAMS) and fingerprinting of the T. laurifolia aqueous extract. Materials and Methods: Critical variables were screened using a two‐level fractional factorial design, followed by the optimization of the selected variables using a central composite design. The validated method was applied for quality assessment based on QAMS and fingerprinting of the extract. Results: Optimum conditions of DoE for the analysis of caffeic acid, vicenin‐2, and rosmarinic acid were determined. The relative correction factors for caffeic acid and vicenin‐2 were calculated using rosmarinic acid as an internal reference standard, and their contents in 30 samples were determined. The differences between the external standard method (ESM) and QAMS were compared. No significant difference was observed in the quantitative determination, proving the consistency QAMS and ESM. HPLC fingerprints of T. laurifolia were established with 8 of 12 characteristic peaks that were structurally characterized using HPLC‐diode array detection‐electrospray ionization/tandem mass spectrometry. The similarity of the fingerprints in all samples was ≥0.74, and the pattern recognition of the characteristic peaks was satisfied. Conclusion: The proposed method efficiently detected multiple components of the T. laurifolia extract. Thus, the method is beneficial in providing references for enhancing the quality control of other herbal medicines. The DoE approach was applied to develop an HPLC method for analyzing multicomponents by a single marker as well as fingerprinting the T. laurifolia aqueous extract. There was no significant difference between QAMS and ESM. HPLC fingerprints in all samples were found to be comparable, with 12 characteristic peaks. The proposed method was successful in determining various components of the T. laurifolia aqueous extract. As a result, the approach has the potential to improve quality control for other herbal medicines. [ABSTRACT FROM AUTHOR]

Foam mixers are classified as low-pressure and high-pressure types. Low-pressure mixers rely on agitator rotation, facing cleaning challenges and complex designs. High-pressure mixers are simple and require no cleaning but struggle with uneven mixing for high-viscosity substances. Traditionally, increasing the working pressure resolved this, but material quality limits it at higher pressures. To address the issues faced by high-pressure mixers when handling high-viscosity materials and to further improve the mixing performance of the mixer, this study focuses on a polyimide high-pressure mixer, identifying four design variables: impingement angle, inlet and outlet diameters, and impingement pressure. Using a Full Factorial Design of Experiments (DOE), the study investigates the impacts of these variables on mixing unevenness. Sample points were generated using Optimal Latin Hypercube Sampling—OLH. Combining the Sparrow Search Algorithm (SSA), Convolutional Neural Network (CNN), and Long Short-Term Memory Network (LSTM), the SSA-CNN-LSTM model was constructed for predictive analysis. The Whale Optimization Algorithm (WOA) optimized the model, to find an optimal design variable combination. The Computational Fluid Dynamics (CFD) simulation results indicate a 70% reduction in mixing unevenness through algorithmic optimization, significantly improving the mixer's performance. [ABSTRACT FROM AUTHOR]

Bedaquiline (BQ) solid lipid nanoparticles (SLNs), which have previously been formulated for parenteral administration, have a risk of patient non-compliance in treating tuberculosis. This research presents a strategy to develop BQ SLNs for oral delivery to improve patient adherence, The upper and lower levels for the formulation excipients were generated from screening experiments. Using 4 input factors (BQ, lecithin, Tween 80, and PEG), a full factorial design from 3 × 2x2 × 2 experiments was randomly arranged to investigate 3 response variables: Particle size distribution (PSD), polydispersity index (PdI), and zeta potential (ZP). High shear homogenization was used to mix the solvent and aqueous phases, with 15% sucrose as a cryoprotectant. The response variables were assessed using a zeta sizer while TEM micrographs confirmed the PSD data. Solid-state assessments were conducted using powdered X-ray diffraction and scanning electron microscopy (SEM) imaging. A comparative invitro assessment was used to determine drug release from an equivalent dose of BQ free base powder and BQ-SLN, both packed in hard gelatin capsules. The sonicated formulations obtained significant effects for PSD, PdI, and ZP. The p-values (0.0001 for PdI, 0.0091 for PSD) for BQ as an independent variable in the sonicated formulation were notably higher than those in the unsonicated formulation (0.1336 for PdI, 0.0117 for PSD). The SEM images were between 100 – 400 nm and delineated nanocrystals of BQ embedded in the lipid matrix. The SLN formulation provides higher drug levels over the drug's free base; a similarity factor (f2 = 18.3) was estimated from the dissolution profiles. [ABSTRACT FROM AUTHOR]

This study employed a Quality by Design (QbD) approach to spray dry amorphousclotrimazole nanosuspension (CLT-NS) consisting of Soluplus® and microcrystallinecellulose. Using the Box-Behnken Design, a systematic evaluation was conducted toanalyze the impact of inlet temperature, % aspiration, and feed rate on the criticalquality attributes (CQAs) of the clotrimazole spray-dried nanosuspension (CLT-SDNS). In this study, regression analysis and ANOVA were employed to detect significantfactors and interactions, enabling the development of a predictive model for the spraydrying process. Following optimization, the CLT-SD-NS underwent analysis using Xraypowder diffraction (XRPD), Fourier transform infrared spectroscopy (FTIR), Dynamic Scanning Calorimetry (DSC), and in vitro dissolution studies. The resultsshowed significant variables, including inlet temperature, feed rate, and aspiration rate,affecting yield, redispersibility index (RDI), and moisture content of the final product. The models created for critical quality attributes (CQAs) showed statistical significanceat a p-value of 0.05. XRPD and DSC confirmed the amorphous state of CLT in theCLT-SD-NS, and FTIR indicated no interactions between CLT and excipients. In vitrodissolution studies showed improved dissolution rates for the CLT-SD-NS (3.12-foldincrease in DI water and 5.88-fold increase at pH 7.2 dissolution media), attributed torapidly redispersing nanosized amorphous CLT particles. The well-designed studyutilizing the Design of Experiments (DoE) methodology. [ABSTRACT FROM AUTHOR]

Cleansing products, particularly innovative cosmetic foams, must efficiently remove impurities with minimal impact on the skin barrier and have a favorable sensory profile. The choice of product ingredients is crucial to ensure the optimal characteristics. The current study aims to provide a comprehensive framework for understanding the variability in the characteristics of a cleansing foam to achieve desired properties. The novelty of this study lies in the combination of ingredients for their potential synergistic and complementary effects in cleansing dry skin, as well as the application of Quality by Design (QbD) elements to develop and optimize the formulation of cleansing foam. The effects of varying the concentration of mild surfactants, polyols, and gel-forming agents on the properties of the gels and of the generated foams were studied. Significant influences of the formulation factors were observed: an increased ratio of xanthan gum positively impacted the texture properties of the gel, whereas higher concentrations of surfactants had a negative impact on these parameters. Additionally, increasing the polyols ratio was found to negatively influence the foaming property and stability of the foam. The study established an optimal formulation of a cleansing foam with a ratio of 0.45% xanthan gum, 26.19% surfactants and 2.16% polyols to be used for dry skin hygiene. [ABSTRACT FROM AUTHOR]

Copyright of Urban Mass Transit is the property of Urban Mass Transit Editorial Office and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

The Heck reaction is widely employed to build a variety of biologically relevant scaffolds and has been successfully implemented in the production of active pharmaceutical ingredients (APIs). Typically, the reaction with terminal alkenes gives high yields and stereoselectivity toward the trans-substituted alkenes product, and many green variants of the original protocol have been developed for such substrates. However, these methodologies may not be applied with the same efficiency to reactions with challenging substrates, such as internal olefins, providing trisubstituted alkenes. In the present work, we have implemented a Heck reaction protocol under green conditions to access trisubstituted alkenes as final products or key intermediates of pharmaceutical interest. A set of preliminary experiments performed on a model reaction led to selecting a simple and green setup based on a design of experiments (DoE) study. In such a way, the best experimental conditions (catalyst loading, equivalents of alkene, base and tetraalkylammonium salt, composition, and amount of solvent) have been identified. Then, a second set of experiments were performed, bringing the reaction to completion and considering additional factors. The protocol thus defined involves using EtOH as the solvent, microwave (mw) irradiation to achieve short reaction times, and the supported catalyst Pd EnCat®40, which affords an easier recovery and reuse. These conditions were tested on different aryl bromides and internal olefines to evaluate the substrate scope. Furthermore, with the aim to limit as much as possible the production of waste, a simple isomerization procedure was developed to convert the isomeric byproducts into the desired conjugated E alkene, which is also the thermodynamically favoured product. The approach herein disclosed represents a green, efficient, and easy-to-use handle towards different trisubstituted alkenes via the Heck reaction. [ABSTRACT FROM AUTHOR]

Abrasion wear is a significant concern for cutting tools, particularly when milling asphalt concrete due to the presence of hard mineral aggregate particles. The pressure exerted on the cutting tool by the chipped material and the resulting cutting forces directly influence tool wear. To estimate the cutting forces in asphalt milling, the authors propose using either laboratory experiments or cost-effective Discrete Element Method (DEM) modeling—by simulating the real conditions—as direct measurement under real conditions is challenging. This article presents results from an original experimental program aimed at determining the cutting forces during asphalt pavement milling. A specialized stand equipped with a moving plate and recording devices was designed to vary milling depth, rotational speed, and advance speed. The experimental results for horizontal force values were compared with numerical results from DEM modeling. It was found that both increasing the milling depth and the advance speed lead to higher cutting forces. Generally, DEM modeling trends align with experimental results, although DEM values are generally higher. The statistical analysis allowed identification of the milling depth as the most significant parameter influencing cutting force and the optimal combination of milling parameters to achieve minimum horizontal force acting on cutting tooth, namely, 15 mm milling depth and 190 mm/min advanced speed. [ABSTRACT FROM AUTHOR]

Mitapivat is a novel, first‐in‐class orally active pyruvate kinase activator approved by the US Food and Drug Administration in 2022 for the treatment of hemolytic anemia. There is no literature available regarding the identification of degradation impurities of mitapivat. The present study deals with the degradation behavior of mitapivat under various stress conditions such as hydrolytic, photolytic, thermal, and oxidative stress. The multivariate analysis found that the independent variables, that is, molarity, temperature, and time, are interacting with each other to affect the degradation of mitapivat. A specific, accurate, and precise high‐performance liquid chromatographic (HPLC) method was developed to separate mitapivat from its degradation products. The separation was achieved on the C‐18 column (250 mm × 4.6 mm × 5 µm) using the combination of 0.1% formic acid buffer and acetonitrile in gradient elution profile. The method was validated as per the International Council for Harmonization of Technical Requirements for Pharmaceuticals for Human Use Q2(R2) guideline. LC‐electrospray ionization‐Quadrupole‐time of flight was employed to identify degradation products. A total of seven novel degradation products of mitapivat were identified based on tandem mass spectrometry and accurate mass measurement. In‐silico toxicity of mitapivat and its degradation products was qualitatively evaluated by the DEREK toxicity prediction tool. [ABSTRACT FROM AUTHOR]

Background: Stem cell-derived therapies hold the potential for treatment of regenerative clinical indications. Static culture has a limited ability to scale up thus restricting its use. Suspension culturing can be used to produce target cells in large quantities, but also presents challenges related to stress and aggregation stability. Methods: Utilizing a design of experiments (DoE) approach in vertical wheel bioreactors, we evaluated media additives that have versatile properties. The additives evaluated are Heparin sodium salt (HS), polyethylene glycol (PEG), poly (vinyl alcohol) (PVA), Pluronic F68 and dextran sulfate (DS). Multiple response variables were chosen to assess cell growth, pluripotency maintenance and aggregate stability in response to the additive inputs, and mathematical models were generated and tuned for maximal predictive power. Results: Expansion of iPSCs using 100 ml vertical wheel bioreactor assay for 4 days on 19 different media combinations resulted in models that can optimize pluripotency, stability, and expansion. The expansion optimization resulted in the combination of PA, PVA and PEG with E8. This mixture resulted in an expansion doubling time that was 40% shorter than that of E8 alone. Pluripotency optimizer highlighted the importance of adding 1% PEG to the E8 medium. Aggregate stability optimization that minimizes aggregate fusion in 3D culture indicated that the interaction of both Heparin and PEG can limit aggregation as well as increase the maintenance capacity and expansion of hiPSCs, suggesting that controlling fusion is a critical parameter for expansion and maintenance. Validation of optimized solution on two cell lines in bioreactors with decreased speed of 40 RPM, showed consistency and prolonged control over aggregates that have high frequency of pluripotency markers of OCT4 and SOX2 (> 90%). A doubling time of around 1–1.4 days was maintained after passaging as clumps in the optimized medium. Controlling aggregate fusion allowed for a decrease in bioreactor speed and therefore shear stress exerted on the cells in a large-scale expansion. Conclusion: This study resulted in a control of aggregate size within suspension cultures, while informing about concomitant state control of the iPSC state. Wider application of this approach can address media optimization complexity and bioreactor scale-up challenges. [ABSTRACT FROM AUTHOR]

The extraction of nandrolone as a steroid hormone using fast methods is of high importance. This was done by dispersive micro-solid phase extraction in the presence of two widely used organometallic frameworks (MIL-53(Al) and ZIF-8). The extraction steps were optimized by an extensive study on the main factors affecting the absorption/desorption efficiency. The optimum conditions were obtained by design of experiments for the extraction and determination of nandrolone in a blank human plasma matrix. Maximum extraction of nandrolone was achieved in 8.5 min by 2.5 mg of MIL-53(Al) in the solution with 0.89% (w/v) salt concentration, while the maximum extraction by ZIF-8 as another sorbent required 10 min, 4.5 mg of sorbent, and 0.60% (w/v) of salt concentration. Batch experiments were carried out to find appropriate kinetic and isotherm models. Finally, the analytical validation of the proposed method was investigated. The dynamic range of the method was from 0.05 to 1 µg/mL. The precision (expressed as the relative standard deviation, RSD) and accuracy (expressed as the percentage error) of extraction by MIL-53(Al) were found 3.90 and 3.39%, respectively, while those by ZIF-8 were calculated as 4.59 and 4.50%, respectively. The proposed method was successfully applied for the determination of nandrolone in spiked samples, achieving high recovery rates of approximately 96% and 94% using MIL-53(Al) and ZIF-8. [ABSTRACT FROM AUTHOR]

We study the potential of infrared (IR) heaters in combination with IR reflective walls to reduce heating energy demand in buildings. Using IR heaters increases radiant temperature. Combined with IR reflective walls, less radiant heat is absorbed by the surrounding walls, and more is reflected to and absorbed by the occupants. This allows for lower air temperatures while maintaining constant thermal comfort. Lower air temperatures result in heating energy savings. In simulations, we examine the impact of four parameters on the thermal comfort indicator Predicted Mean Vote (PMV): wall temperature, inlet air temperature, IR heater power, and IR emissivity of the walls. To reduce the number of data points needed, we use a Central Composite Design for the layout of the simulation plan. The results show that the PMV can be changed from 0.15 to 1.16 only by lowering the emissivity of the surrounding walls from 0.9 to 0.1. At high IR heater power and at low wall temperature the impact of the emissivity on the PMV becomes larger. From the simulation data, we derive a response surface function to determine the required IR heating power for any given room conditions, which could be used for automated IR heater control. [ABSTRACT FROM AUTHOR]

The rapid development of potency assays is critical in the development of life-saving vaccines. The traditional plaque assay or fifty percent tissue culture infectious dose (TCID50) assay used to measure the potency of live virus vaccines is time consuming, labor intensive, low throughput and with high variability. Described here is the development and qualification of a cell-based reporter potency assay for two vaccines for respiratory viral infection, one based on the recombinant vesicular stomatitis virus (rVSV) backbone, termed Vaccine 1 in this paper, and the other based on the measles virus vector, termed Vaccine 2. The reporter potency assay used a Vero E6 cell line engineered to constitutively express NanuLuc® luciferase, termed the VeroE6-NLuc or JM-1 cell line. Infection of JM-1 cells by a live virus, such as rVSV or measles virus, causes a cytopathic effect (CPE) and release of NanuLuc® from the cytoplasm into the supernatant, the amount of which reflects the intensity of the viral infection. The relative potency was calculated by comparison to a reference standard using parallel line analysis (PLA) in a log–log linear model. The reporter assay demonstrated good linearity, accuracy, and precision, and is therefore suitable for a vaccine potency assay. Further evaluation of the Vaccine 1 reporter assay demonstrated the robustness to a range of deliberate variation of the selected assay parameters and correlation with the plaque assay. In conclusion, we have demonstrated that the reporter assay using the JM-1 cell line could be used as a potency assay to support the manufacturing and release of multiple live virus vaccines. [ABSTRACT FROM AUTHOR]

This study investigated the influence of two key printing parameters--namely, layer thickness and infill percentage and also the annealing effect, on the hardness of PLA and ABS components. Employing the design of experiment (DOE) methodology, the most significant factor influencing the Shore D hardness values for each material was established, in addition to determining the optimal printing parameters that yield maximum hardness in the printed parts. Our findings reveal that layer thickness significantly impacts the hardness of 3D printed PLA and ABS specimens, with printing infill percentage exerting a comparatively smaller influence, while in case of PLA annealed samples, the most significant factor is infill percentage. [ABSTRACT FROM AUTHOR]

Current research studies devoted to cutting forces in drilling are oriented toward predictive model development, however, in the case of mechanistic models, the material effect on the drilling process itself is mostly not considered. This research study aims to experimentally analyze how the machined material affects the feed force (Ff) during drilling, alongside developing predictive mathematical–statistical models to understand the main effects and interactions of the considered technological and tool factors on Ff. By conducting experiments involving six factors (feed, cutting speed, drill diameter, point angle, lip relief angle, and helix angle) at five levels, the drilling process of stainless steel AISI1045 and case-hardened steel 16MnCr5 is executed to validate the numerical accuracy of the established prediction models (AdjR = 99.600% for C45 and AdjR = 97.912% for 16MnCr5). The statistical evaluation (ANOVA, RSM, and Lack of Fit) of the data proves that the drilled material affects the Ff value at the level of 17.600% (p < 0.000). The effect of feed represents 44.867% in C45 and 34.087% in 16MnCr5; the cutting speed is significant when machining C45 steel only (9.109%). When machining 16MnCr5 compared to C45 steel, the influence of the point angle (lip relief angle) is lower by 49.198% (by 22.509%). The effect of the helix angle is 163.060% higher when machining 16MnCr5. [ABSTRACT FROM AUTHOR]

Fused Deposition Modelling (FDM) is one of the layer-based technologies that fall under the umbrella term "Additive Manufacturing", where the desired part is created through the successive layer-by-layer addition process with high accuracy using computer-aided design data. Additive manufacturing technology, or as it is commonly known, 3D (three-dimensional) printing, is a rapidly growing sector of manufacturing that is incorporated in automotive, aerospace, biomedical, and many other fields. This work explores the impact of the Additive Manufacturing process on the mechanical proprieties of the fabricated part. To conduct this study, the 3D printed tensile specimens are designed according to the ASTM D638 standards and printed from a digital template file using the FDM 3D printer Raise3D N2. The material chosen for this 3D printing parameter optimization is Polylactic acid (PLA). The FDM process parameters that were studied in this work are the infill pattern, the infill density, and the infill cell orientation. These factors' effects on the tensile behavior of printed parts were analyzed by the design of experiments method, using the statistical software MINITAB2020. [ABSTRACT FROM AUTHOR]

The rapid increase in the use and development of statistical design of experiments (DoE), particularly in pharmaceutical process development, has become increasingly important over the last decades. This rise aligns with Green Chemistry Principles, seeking reduced resource usage and heightened efficiency. In this study, we employed a comprehensive design of experiments (DoE) approach to optimize the catalytic conversion of 1-decene to n-decanal through direct Wacker-type oxidation using the previously determined efficient PdCl2(MeCN)2 catalytic system. The aim was to maximize selectivity and conversion efficiency. Through systematic variation of seven factors, including substrate amount, catalyst and co-catalyst amount, reaction temperature, reaction time, homogenization temperature, and water content, this study identified critical parameters influencing the process to direct the reaction toward the desired product. The statistical analysis revealed high significance for both selectivity and conversion, with surface diagrams illustrating optimal conditions. Notably, catalyst amount emerged as a pivotal factor influencing conversion, with reaction temperature and co-catalyst amount significantly affecting both conversion efficiency and selectivity. The refined model demonstrated strong correlations between predicted and observed values, highlighting the impact of these factors on both selectivity and conversion. [ABSTRACT FROM AUTHOR]

Purpose: The study aimed to develop and optimize apremilast (APST) solid dispersion formulations using copovidone (Kollidon VA64) as the carrier and vitamin E TPGS as the surfactant to enhance solubility and dissolution, and to utilize in silico Physiologically Based Biopharmaceutics Modeling (PBBM) in GastroPlus to simulate the in vivo behaviour of the optimized formulation, predicting its potential for enhancing oral bioavailability. Methods: Solid dispersion formulations of APST were prepared via the hot melt extrusion (HME) technique, utilizing copovidone (commercially known as Kollidon VA64) as the polymeric carrier. The selection of suitable polymeric carriers as well as surfactant was initially performed through phase solubility studies. The second-generation amorphous solid dispersion (ASD) was formulated with Kollidon VA64. Following this, the third-generation solid dispersions were engineered by choosing vitamin E TPGS as the surfactant carrier, a decision informed by comprehensive screening studies. The formulation of these batches employed a twin-screw configuration in the HME process. Design of Experiments (DoE) approach was utilized to ascertain the optimal ratio of drug: polymer: surfactant to achieve maximum solubility and dissolution enhancement. Drug release studies were conducted in 6.8 phosphate buffer solution. The developed formulations were subjected to a variety of characterization techniques to assess their properties. Stability studies were conducted for the final formulation over a period of up to three months. Results: Based on the DoE studies, the optimized formulation was identified as APST with copovidone (Kollidon VA64) in a 1:5 ratio, supplemented with 3% vitamin E TPGS. Furthermore, PBBM in GastroPlus was utilized to simulate the in vivo behaviour of the optimized formulation. Conclusion: The amorphous solid dispersion (ASD) of APST, developed via the HME technique, demonstrated a substantial enhancement in solubility, exhibiting an increase of up to 248-fold relative to the unprocessed drug over a 24-hour period. A noteworthy increase in the percentage of drug release during dissolution was observed in comparison to the pure drug. The observed improvements in solubility and dissolution were corroborated through PBBM in GastroPlus, thereby suggesting a viable strategy for enhancing the oral bioavailability of APST. This investigation effectively illustrates the formulation of a third-generation ASD of APST, significantly ameliorating its solubility and pharmacokinetic parameters, and indicating potential for industrial-scale manufacturing. [ABSTRACT FROM AUTHOR]

Purpose: Posaconazole (PSZ) is BCS class-II drug that displays variable bioavailability upon oral administration due to extremely low and pH-dependent solubility. Method: The present investigation was aimed to formulate and evaluate liquisolid pellets of PSZ for improving its dissolution. Liquisolid pellets were prepared using Transcutol® HP, Neusilin® US2, and Aerosil® 200 as non-volatile liquid, carrier, and coating materials respectively. A 32 full factorial design having excipient ratio (R) and spheronization speed as independent variables and the cumulative amount of drug dissolved at 135 min and 165 min as dependent variables were used for the process optimization. Result: The results of regression analysis indicated a significant effect of selected independent variables on the dependent variables (p-value < 0.05). Differential scanning calorimetry (DSC) studies revealed that the PSZ remained in an amorphous or molecular dispersed state within the liquisolid pellets. Powder X-ray diffraction (PXRD) analysis indicated a significant reduction in crystallinity of the entrapped drug compared to pure drugs. The Fourier-transform infrared (FTIR) analysis demonstrated the stability of the drug within the optimized pellets. SEM images confirmed uniform and well-shaped spherical liquisolid pellets. Conclusion: During In-vitro dissolution studies, the cumulative amount of the drug dissolved from the prepared pellets was less than 5% during the acid stage (750 ml 0.01 N HCL) whereas the improvement was significant during the buffer stage (750 ml 0.01 N HCL + 250 ml 0.2 M pH 6.8 Phosphate buffer + 1.46% polysorbate 80). [ABSTRACT FROM AUTHOR]

Fixed-dose combination therapy is considered a practical approach in the treatment of various diseases, as it can simultaneously target different mechanisms of action that achieve the required therapeutic efficacy through a synergistic effect. A combination of hydrochlorothiazide (HTZ), amlodipine (AMD), and valsartan (VLS) has been created for the treatment of hypertension. Therefore, the aim of this study was to develop an optimized UPLC method for the simultaneous quantification of this combination. A DoE at a level of 32 was used to investigate the effects of column temperature (20, 30, and 40 °C) and formic acid concentration (0.05, 0.15, and 0.25%) on the retention time of each active pharmaceutical ingredient (API), the peak area, and the peak symmetry, as well as the resolution between HTZ-AMD and AMD-VLS peaks. The optimized analytical method was validated and used to extract the three APIs from the marketed product. The optimized analytical condition with a column temperature of 27.86 °C and a formic acid concentration of 0.172% showed good separation of the three APIs in 1.62 ± 0.006, 3.59 ± 0.002, and 3.94 ± 0.002 min for HTZ, AMD, and VST, respectively. The developed method was linear with the LOQ for a HTC, AMD, and VST of 0.028, 0.038, and 0.101 ppm, respectively. Moreover, the developed assay was sustainable and robust, with an RSD % of less than 2%. The application of this method in the extraction of HTZ, AMD, and VST from the Exforge® marketed product showed good separation with a measurable drug content of 23.5 ± 0.7, 9.68 ± 0.1, and 165.2 ± 5.2 mg compared to the label claims of 25/10/160 for HTZ, AMD, and VST, respectively. [ABSTRACT FROM AUTHOR]