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Background: Type 1 diabetes, an autoimmune disorder leading to the destruction of pancreatic β-cells, requires lifelong insulin therapy. Islet transplantation offers a promising solution but faces challenges such as limited availability and the need for immunosuppression. Induced pluripotent stem cells (iPSCs) provide a potential alternative source of functional β-cells and have the capability for large-scale production. However, current differentiation protocols, predominantly conducted in hybrid or 2D settings, lack scalability and optimal conditions for suspension culture. Methods: We examined a range of bioreactor scaleup process parameters and quality target product profiles that might affect the differentiation process. This investigation was conducted using an optimized High Dimensional Design of Experiments (HD-DoE) protocol designed for scalability and implemented in 0.5L (PBS-0.5 Mini) vertical wheel bioreactors. Results: A three stage suspension manufacturing process is developed, transitioning from adherent to suspension culture, with TB2 media supporting iPSC growth during scaling. Stage-wise optimization approaches and extended differentiation times are used to enhance marker expression and maturation of iPSC-derived islet-like clusters. Continuous bioreactor runs were used to study nutrient and growth limitations and impact on differentiation. The continuous bioreactors were compared to a Control media change bioreactor showing metabolic shifts and a more β-cell-like differentiation profile. Cryopreserved aggregates harvested from the runs were recovered and showed maintenance of viability and insulin secretion capacity post-recovery, indicating their potential for storage and future transplantation therapies. Conclusion: This study demonstrated that stage time increase and limited media replenishing with lactate accumulation can increase the differentiation capacity of insulin producing cells cultured in a large-scale suspension environment. [ABSTRACT FROM AUTHOR]

Thermoresponsive self-nanoemulsifying drug delivery systems (T-SNEDDS) offer a promising solution to the limitations of conventional SNEDDS formulations. Liquid SNEDDS are expected to enhance drug solubility; however, they are susceptible to leakage during storage. Even though solid SNEDDS offers a solution to this storage instability, they introduce new challenges, namely increased total dosage and potential for drug trapping within the formulation. The invented T-SNEDDS was used to overcome these limitations and improve the dissolution of glibenclamide (GBC). Solubility and transmittance studies were performed to select a suitable oil and surfactant. Design of Experiments (DoE) software was used to study the impact of propylene glycol and Poloxamer 188 concentrations on measured responses (liquefying temperature, liquefying time, and GBC solubility). The optimized formulation was subjected to an in vitro dissolution study. The optimized T-SNEDDS consisted of Kolliphor EL and Imwitor 308 as surfactants and oil. The optimized propylene glycol and Poloxamer 188 concentrations were 13.7 and 7.9% w/w, respectively. It exhibited a liquefying temperature of 35.0 °C, a liquefying time of 119 s, and a GBC solubility of 5.51 mg/g. In vitro dissolution study showed that optimized T-SNEDDS exhibited 98.8% dissolution efficiency compared with 2.5% for raw drugs. This study presents a promising approach to enhance pharmaceutical applicability by resolving the limitations of traditional SNEDDS. [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.)

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]

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]

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]

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]

Abstract Background Type 1 diabetes, an autoimmune disorder leading to the destruction of pancreatic β-cells, requires lifelong insulin therapy. Islet transplantation offers a promising solution but faces challenges such as limited availability and the need for immunosuppression. Induced pluripotent stem cells (iPSCs) provide a potential alternative source of functional β-cells and have the capability for large-scale production. However, current differentiation protocols, predominantly conducted in hybrid or 2D settings, lack scalability and optimal conditions for suspension culture. Methods We examined a range of bioreactor scaleup process parameters and quality target product profiles that might affect the differentiation process. This investigation was conducted using an optimized High Dimensional Design of Experiments (HD-DoE) protocol designed for scalability and implemented in 0.5L (PBS-0.5 Mini) vertical wheel bioreactors. Results A three stage suspension manufacturing process is developed, transitioning from adherent to suspension culture, with TB2 media supporting iPSC growth during scaling. Stage-wise optimization approaches and extended differentiation times are used to enhance marker expression and maturation of iPSC-derived islet-like clusters. Continuous bioreactor runs were used to study nutrient and growth limitations and impact on differentiation. The continuous bioreactors were compared to a Control media change bioreactor showing metabolic shifts and a more β-cell-like differentiation profile. Cryopreserved aggregates harvested from the runs were recovered and showed maintenance of viability and insulin secretion capacity post-recovery, indicating their potential for storage and future transplantation therapies. Conclusion This study demonstrated that stage time increase and limited media replenishing with lactate accumulation can increase the differentiation capacity of insulin producing cells cultured in a large-scale suspension environment.

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]

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]

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]

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.)

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]

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]

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]

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]

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]

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]

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]

High performing hemodialyzers membranes such as high flux membranes, high cut-off membranes and medium cut-off membranes are always at research interest due to their better efficiency than conventional membranes. These membranes provide greater toxin clearance, however retention of essential solutes in a preferable way are still under study. This paper aims at the design of high performing membrane to study the role of its parameters in solute removal and its capability of holding back important molecules. One of the most effective design of experiments (DOE) tool, namely Taguchi Algorithm was used for the formation of fractional factorial design of parameters. The simulation results were benchmarked with that of experimental data from literature and with manufacturers data sheets. Once the benchmarking was done, the error quantification and significance of each design were analysed using statistical method, Analysis of Variance (ANOVA) testing. The most relevant parameters that helped in better clearance in these membranes were thus identified and substantial conclusions were drawn which can be used in the future for designing optimal dialyzer designs. Results shows that clinically used dialyzer membranes such as RevaclearMax and FxCorDiax series on modelling using COMSOL Multiphysics with a blood flow rate of 400 ml/min and dialysate flow of 500 ml/min showed better urea clearance rate of above 300 indicating that the membranes thus designed was superior to the conventional high flux membranes that have a clearance rate of 297 of less for the exact same functional, geometrical, and parametric conditions. The model replication and thus validation of the design helped in understanding the influence of various parameters in toxin clearance. These parameters can be further investigated, and optimal models can be delivered with more of clinical examinations and trials.

Producing recombinant adeno-associated virus (rAAV) for gene therapy via triple transfection is an intricate process involving many cellular interactions. Each of the different elements encoded in the three required plasmids—pHelper, pRepCap, and pGOI—plays a distinct role, affecting different cellular pathways when producing rAAVs. The required expression balance emphasizes the critical need to fine-tune the concentration of all these different elements. The use of design of experiments (DOE) to find optimal ratios is a powerful method to streamline the process. However, the choice of the DOE method and design construction is crucial to avoid misleading results. In this work, we examined and compared four distinct DOE approaches: rotatable central composite design (RCCD), Box-Behnken design (BBD), face-centered central composite design (FCCD), and mixture design (MD). We compared the abilities of the different models to predict optimal ratios and interactions among the plasmids and the transfection reagent. Our findings revealed that blocking is essential to reduce the variability caused by uncontrolled random effects and that MD coupled with FCCD outperformed all other approaches, improving volumetric productivity 109-fold. These outcomes underscore the importance of selecting a model that can effectively account for the biological context, ultimately yielding superior results in optimizing rAAV production.

Seaweed is becoming increasingly popular in the Western diet as consumers opt for more sustainable food sources. However, seaweed is known to accumulate high levels of arsenic—which may be in the form of carcinogenic inorganic arsenic (iAs). Here we propose a fast method for the routine measurement of iAs in seaweed using HPLC-ICP-MS without coelution of arsenosugars that may complicate quantification. The developed method was optimised using design of experiments (DOE) and tested on a range of reference materials including TORT-3 (0.36 ± 0.03 mg kg−1), DORM-5 (0.02 ± 0.003 mg kg−1), and DOLT-5 (0.07 ± 0.007 mg kg−1). The use of nitric acid in the extraction solution allowed for the successful removal of interferences from arsenosugars by causing degradation to an unretained arsenosugar species, and a recovery of 99 ± 9% was obtained for iAs in Hijiki 7405-b when compared with the certified value. The method was found to be suitable for high-throughput analysis of iAs in a range of food and feed matrices including Asparagopsis taxiformis seaweed, grass silage, and insect proteins, and offers a cost-effective, fast, and robust option for routine analysis that requires minimal sample preparation. The method may be limited with regards to the quantification of dimethylarsenate (DMA) in seaweed, as the acidic extraction may lead to overestimation of this analyte by causing degradation of lipid species that are typically more abundant in seaweed than other marine matrices (i.e. arsenophospholipids). However, the concentrations of DMA quantified using this method may provide a better estimation with regard to exposure after ingestion and subsequent digestion of seaweed. [ABSTRACT FROM AUTHOR]

This work is focused on performing a quantitative assessment of the environmental impacts associated with an organic synthesis reaction, optimized using an experimental design approach. A nucleophilic substitution reaction was selected, employing vanillin as the substrate, a phenolic compound widely used in the food industry and of pharmaceutical interest, considering its antioxidant and antitumoral potential. To carry out the reaction, three different solvents have been chosen, namely acetonitrile (ACN), acetone (Ace), and dimethylformamide (DMF). The syntheses were planned with the aid of a multivariate experimental design to estimate the best reaction conditions, which simultaneously allow a high product yield and a reduced environmental impact as computed by Life Cycle Assessment (LCA) methodology. The experimental results highlighted that the reactions carried out in DMF resulted in higher yields with respect to ACN and Ace; these reactions were also the ones with lower environmental impacts. The multilinear regression models allowed us to identify the optimal experimental conditions able to guarantee the highest reaction yields and lowest environmental impacts for the studied reaction. The identified optimal experimental conditions were also validated by experimentally conducting the reaction in those conditions, which indeed led to the highest yield (i.e., 93%) and the lowest environmental impacts among the performed experiments. This work proposes, for the first time, an integrated approach of DoE and LCA applied to an organic reaction with the aim of considering both conventional metrics, such as reaction yield, and unconventional ones, such as environmental impacts, during its lab-scale optimization. [ABSTRACT FROM AUTHOR]

The work is focused on experimental research of deformation characteristics on three grades of hot-dip galvanized steels for the automotive industry. Deformation maps were obtained using the DIC (Digital Image Correlation) method. The map documents the development of longitudinal and transverse deformations under tensile stress. In addition to uniaxial tension, the investigated specimens were subjected to eccentric tension. The stable crack growth (SCG) was evaluated using a non-contact measurement technique on CT (compact tension) specimens. The deformation of steels, which affects the resistance to stable crack growth (confirmed by the Design of Experiments—DOE method), was manifested in the first stages of eccentric loading of specimens. The notch root radius varies considerably due to the blunting of the starting fatigue crack. The resistance to stable crack growth, which represents a safety reserve during a vehicle crash, was obtained. [ABSTRACT FROM AUTHOR]

Metabolic syndrome is an associated condition that occurs together and increases the risk of heart disease and diabetes. These conditions include high blood pressure, high blood sugar, and high body mass index (BMI) in terms of cholesterol and triglyceride levels. Most of the elderly population may administer three drugs to control the above conditions. Therefore, this study aims to develop an analytical assay for the precise analysis of three components and to formulate a Self-Nanoemulsifying Drug-Delivery System (SNEDDS) loaded with three drugs: Rosuvastatin Calcium (RC; antilipidemic), Glibenclamide (GB; antidiabetic), and Candesartan Cilexetil (CC; antihypertensive). A design of the experiment was developed at a level of 32, and the influence of column temperature and flow rate was studied in terms of retention time, peak area, peak asymmetry, and resolution. The assay was subjected to several studies to ensure its validation. Under the optimized conditions—column temperature at 50 °C and flow rate at 0.25 mL/min—the three drugs, RC, GB, and CC, are separated. Their retention times are 0.840, 1.800, and 5.803 min, respectively. The assay was valid in terms of linearity, accuracy, and precision. Moreover, the developed assay shows a good tolerance against any change in the condition. The assay was tested also to separate the drugs in a pharmaceutical formulation as SNEDDs. The assay successfully separates the drug with a good resolution. [ABSTRACT FROM AUTHOR]

In this work, a multivariate approach was utilized for gaining some insights into the processing–structure–properties relationships in polyethylene-based blends. In particular, two high-density polyethylenes (HDPEs) with different molecular weights were melt-compounded using a twin-screw extruder, and the effects of the screw speed, processing temperature and composition on the microstructure of the blends were evaluated based on a Design of Experiment–multilinear regression (DoE-MLR) approach. The results of the thermal characterization, interpreted trough the MLR (multilinear regression) response surfaces, demonstrated that the composition of the blends and the screw rotation speed are the two most important parameters in determining the crystallinity of the materials. Furthermore, the rheological data were examined using a Principal Component Analysis (PCA) multivariate approach, highlighting also in this case the most prominent effect of the weight ratio of the two base polymers and the screw rotation speed. [ABSTRACT FROM AUTHOR]

A Novel Technique is proposed in this investigation called Double Stage Friction Stir Spot Extrusion Welding (DSFSSEW). It is carried out in two stages by using a pin-shoulder tool in step 1 and a pin-less tool in step 2 to investigate the joint strength of the AA1050 sheet. The advantage of this new double-stage FSSEW technique compared to the classical FSSW led to the elimination of the keyhole, which is an intrinsic flaw of the Friction Stir Spot Welding (FSSW) process resulting in higher mechanical joint properties. The impact of the plunge depth and tool revolving speed on the characteristics of the bond was investigated. The height of the extruded aluminium was increased by increasing the tool rotation speed and the plunging depth which was the effective variable. The joint strength was increased in step 2. The two sheets are bonding together at a line of the interface by a mechanical interlock formed by a continuous metal flow of aluminium extrusion that is free of flaws. There were two mechanisms of failure in the studied samples: cleavage of the aluminium metal at the tool trace and shearing of the extruded aluminium, respectively. The suggested method is novel and has a great potential for future investigation, this work might pave the way for studies of welding with additional alloys, both similar and dissimilar to those already studied. [ABSTRACT FROM AUTHOR]

The objective of this research is to find the effectiveness factor of the catalyst particles for the most favorable conditions of the phthalic anhydride production in a fixed bed reactor, with the aim of achieving the highest rate of phthalic anhydride production compared to other secondary products and analyzing the areas of lower effectiveness for the modification of the reactor design. Initially, the material and the energy balances in the catalytic bed are solved to obtain the concentration and temperature profiles based on the radius and length of the reactor, using polymath software(Polymath® v6.2 Software Minitab 19 Matlab 2019) with the data from literature. Once the profiles reproducibility was verified using the initial data (inlet temperature, pressure in the reactor, reactor wall temperature, reactor radius and mass flow rate) the experimental design 35 carry out, which generates 243 "experiments", whose response variable (phthalic anhydride concentration) was obtained using Matlab. Subsequently, the variables were analyzed using the Minitab 18® that, through the response surface analysis method, allowed us to obtain the optimal values of the tested variables. Then, Subsequently, material and energy balances coupled with Fourier and Fick's laws, along with the effectiveness factor equation, were applied, resulting in the generation of 9 coupled differential equations. Upon implementing the finite difference method, this yielded 90 nonlinear algebraic equations, which were solved using the Polymath software. A total of 78 particles were preselected based on their radial and axial positions to determine the effectiveness factor profile, with values ranging from 0.83 to near unity. The lower values correspond to the points with higher temperature, as evidenced by the calculations performed. [ABSTRACT FROM AUTHOR]

The intricate nature of ships and floating structures presents a significant challenge for ship designers when determining suitable structural dimensions for maritime applications. This study addresses a critical research gap by focusing on a three-cargo hold model for a multipurpose cargo ship. The complex composition of these structures, including stiffening plates, deck plates, bottom plates, frames, and bulkheads, necessitates thorough structural analysis to facilitate effective and cost-efficient design evaluation. To address this challenge, the research utilises FEMAP-integrated NX NASTRAN software (2021.2) to assess hull girder stress. Furthermore, a novel approach is introduced, integrating the Design of Experiments (DOE) principles within Minitab 21.4.1 software to identify critical parameters affecting hull girder stress and production costs. This method determined the top five key parameters influencing hull girder stress: Hatch coaming plate, Hatch coaming top plate, Main deck plate, Shear strake plate, and Bottom plate, while also highlighting key parameters that impact production costs: the inner bottom plate, Inner side shell plate, Bottom plate, Web frame spacing, and Side shell plate. Ship design optimisation is then carried out by incorporating regression equations from Minitab software into the Non-dominated Sorting Genetic Algorithm II (NSGA-II), which is managed using Python software (PyCharm Community Editon 2020.3.1). This optimisation process yields a significant 10% reduction in both ship weight and production costs compared to the previous design, achieved through prudent adjustments in plate thickness, web frame positioning, and stiffener arrangement. The optimally designed midship section undergoes rigorous validation to ensure conformity with industry standards and classification society regulations. Necessary adjustments to inner bottom plates and double bottom side girders are made to meet these stringent requirements. This research offers a comprehensive framework for the structural optimisation of ship hulls, potentially enhancing safety, sustainability, and competitiveness within the maritime engineering industry. [ABSTRACT FROM AUTHOR]

This research presents the results of a fin heat transfer study of three different models of the motorcycle engine. The objective of this study is to minimize the external body temperature because the optimum design will be found when the heat transfer rate is maximized. The study obtains the procurement of a balance between the outer boundary temperature due to convective heat transfer and air-cooled fin design. Heat transfer coefficient varies according to wind velocity (Km/hr) and Nusselt Number. The analysis was performed on three different engine models, named A, B and C. The optimum design was design B through simulation which has lower temperature gain, lower deformation and lower normal stress. DOE (Design of Experiments) was performed on the optimum design of the engine among all with three parameters thickness of fin, size of fin, and shape of fin, and again analysis was performed according to DOE cases. The material used for manufacturing the models was aluminum alloy 6061 which has a thermal conductivity of 200 W/mK. The study was performed on the designed models by taking the outer boundary temperature of 750oC. The heat transfer coefficient was about 77.28 W/m2K at 40 Km/h velocity.

Design of experiments (DOE) is very meaningful and applied in various investigations from science to the industry in order to optimize the process itself. There are several such techniques and each of them has its own advantages, so it is very important to know the basics of DOE. Besides that, every problem, technology, product etc. is unique, so the knowledge about those is crucial as the first step. The most relevant fact is the dependence among variables-input factors and output responses as well as mutual connection between factors. In order to demonstrate the usability and adaptability of DOE for various purposes, some examples are given in this paper.

Tool wear is a natural phenomenon in machining process and it leads to get damage to tool. According to more demand in the market, the selection of high speed, feed rate and depth of cut of machining process are latest trends in all industry. Such machining process creates high cutting temperature, which not only reduces tool life but also induces the product quality. Cutting fluids are used to maintain the tool life and to preserve the workpiece surface properties without damages. To avoid this imperfection, it is necessary to use standard coolants during machining operations. The temperature and surface finish play a vital role in a machining process. In this work, three different nano fluids, like aluminium oxide, copper oxide and titanium oxide,are introduced, and used as a coolant in CNC lathe for turning operation. The output responses of temperature and surface roughness of the workpieces are analyzed with the help of Design of Experiment (DOE) by using L9 orthogonal array of each nano coolant. The result of output responses like temperature and surface roughness are compared with three nano fluids. The copper oxide nano fluid gives a better surface finish as compared to aluminium oxides and titanium oxide.

The cause of dystocia in the present case was a dead fetus in dorso-transverse position. The dam was managed with antibiosis, intra-uterine therapy and uterine ecbolic drug successfully. [ABSTRACT FROM AUTHOR]

Mn-Al alloys are important alloys due to their magnetic properties and have been identified as permanent magnets. This alloy possesses magnetic properties and can be manufactured at a relatively low cost. Mn-Al alloys could be an alternative to rare earth magnets and hard ferrites and have a promising future. In this study, the effects of sintering temperature, holding time and pressure on densification, average grain size and magnetic properties of the SPS-ed Mn-Al alloys were observed. However, with the different sintering parameters, the magnetic phase τ phase could be achieved. To obtain the τ phase, different annealing methods were tried, yet samples heated to 650°C and air cooled exhibited magnetic properties. This sample was selected from various sintering parameters due to its high density of 99% N6 (800°C – 300 sec – 60 MPa) and has an average grain size of 137±18.1 µm. The uniqueness of this work is that statistical approaches such as Taguchi design of experiment (DOE) and regression were used for optimization of the manufacturing process.

Abstract The approach that could reduce the energy consumption of water-cooled chillers in office buildings was investigated through experimental and simulation methods. The chiller was modelled in TRNSYS and validated using physical measurements from an operational water-cooled water chiller and fan coil system. The validated model was used to analyse the energy consumption of the water chiller-fan coil system under a high chilled water temperature setpoint (CWTS) in a representative commercial office building. Subsequently, indoor thermal comfort was evaluated using the PMV-PPD model. Finally, the design of experiment (DOE) was employed using a statistical two-level non-randomized factorial design in Minitab to study the effects of high CWTS, number of rows, and tube diameter on the heat and mass transfer performance of the fan coil unit. The results showed that the CWTS can be increased by various degrees from 10 up to 18 °C for energy efficiency for a commercial office building in the tropics. This increase in CWTS would result in a daily energy saving potential of about 5% of the chiller as compared to the existing operational settings without any extra cost. Conversely, the daily energy consumption by the fan coil would increase by about 5.5% by this increment in the CWTS. It was determined that the chiller system can provide comfort even when the CWTS is increased to 14 °C. The DOE analysis showed that under the condition of high CWTS (14 °C), energy consumption that is less than the current energy consumption may be expected from the fan coil system when the number of rows increased from 3 to 6 and the tube diameter increased from 7 to 9 mm.

Thermoresponsive self-nanoemulsifying drug delivery systems (T-SNEDDS) offer a promising solution to the limitations of conventional SNEDDS formulations. Liquid SNEDDS are expected to enhance drug solubility; however, they are susceptible to leakage during storage. Even though solid SNEDDS offers a solution to this storage instability, they introduce new challenges, namely increased total dosage and potential for drug trapping within the formulation. The invented T-SNEDDS was used to overcome these limitations and improve the dissolution of glibenclamide (GBC). Solubility and transmittance studies were performed to select a suitable oil and surfactant. Design of Experiments (DoE) software was used to study the impact of propylene glycol and Poloxamer 188 concentrations on measured responses (liquefying temperature, liquefying time, and GBC solubility). The optimized formulation was subjected to an in vitro dissolution study. The optimized T-SNEDDS consisted of Kolliphor EL and Imwitor 308 as surfactants and oil. The optimized propylene glycol and Poloxamer 188 concentrations were 13.7 and 7.9% w/w, respectively. It exhibited a liquefying temperature of 35.0 °C, a liquefying time of 119 s, and a GBC solubility of 5.51 mg/g. In vitro dissolution study showed that optimized T-SNEDDS exhibited 98.8% dissolution efficiency compared with 2.5% for raw drugs. This study presents a promising approach to enhance pharmaceutical applicability by resolving the limitations of traditional SNEDDS.

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.

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.

A highly advanced thermo-electric machining technique called wire electrical discharge machining (WEDM) can effectively produce parts with varying hardness or complicated designs that have sharp edges and are very difficult to machine using standard machining procedures. This useful technology for the WEDM operation depends on the typical EDM sparking phenomena and makes use of the commonly used non-contact material removal approach. Since its inception, WEDM has developed from a simple approach for creating tools and grown to an outstanding option for creating micro-scale components having the greatest degree of dimensional precision and surface finish characteristics. The WEDM method has endured over time as an efficient and affordable machining alternative that can meet the stringent operating specifications enforced by rapid manufacturing cycles and increasing expense demands. The possibility of wire damage and bent, nevertheless, has severely hindered the process' maximum potential and decreased the precision as well as effectiveness of the WEDM process. The article examines the wide range of investigations that have been done; from the WEDM through the EDM process' spin-offs. It describes WEDM investigation that required variables optimization and an assessment of the many influences on machining efficiency and accuracy. Additionally, the research emphasizes adaptive monitoring and control of the process while examining the viability of multiple approaches to control for achieving the ideal machining parameters. Numerous industrial WEDM applications are described with the advancement of hybrid machining techniques. The paper's conclusion examines these advancements and identifies potential directions for subsequent WEDM research. The investigation on WEDM of metal matrix composites (MMCs) is also reviewed; along with the impacts of various cutting variables like wire feed rate (F), voltage (V), wire tension (WT), and dielectric flow rate on cutting processes outcomes like material removal rate (MRR), kerf width (Kw) and surface roughness (SR). In the present article, future directions for WEDM research were also suggested. [ABSTRACT FROM AUTHOR]