Bakul Akter, Silvia Aishee, Abdullah Hridoy
et al.
Etoricoxib (ETC), a selective cyclooxygenase enzyme (COX-2) inhibitor, is widely utilized to manage pain and inflammation. Nevertheless, its therapeutic efficacy is limited by poor aqueous solubility, low bioavailability, and significant cardiovascular risks, including increased blood pressure, thrombosis, and the potential for myocardial infarction. This study aimed to address these limitations through structural modifications of etoricoxib. A total of 21 derivatives were designed by introducing various functioning sets at the R3, R2, and R1 sites of ETC. Quantum chemical calculations were performed to assess alterations in physicochemical properties, such as HOMO–LUMO energy gaps, electrostatic potential, enthalpy, and dipole moments. Notably, most of the derivatives showed improved binding affinities, particularly ETC9 and ETC19, demonstrating the highest binding interactions in molecular docking studies (-10.1 and -10.8 kcal/mol, respectively). Furthermore, molecular dynamics (MD) simulations accomplished by exploiting the YASARA dynamics software program with the AMBER14 energy field throughout 100 ns revealed that the ETC9 and ETC19 derivatives exhibited enhanced stability and flexibility profiles compared to the parent drug, ETC. ADMET and PASS predictions confirmed the drug-like properties of most derivatives, particularly ETC19 and ETC9, which also showed improved absorption, better blood-brain barrier penetration, and reduced toxicity. These outcomes underscore the prospect of the de novo-designed etoricoxib analogues as safer and more effective alternatives, effectively addressing the pharmacological limitations and safety concerns associated with the parent drug.
Within the field of permanent magnet synchronous motor sensorless speed control systems, we present a novel scheme with a Multi-dimensional Taylor Network (MTN)-based nonlinear observer as the core, supplemented by two auxiliary MTN modules to realize closed-loop control: (1) MTN Model Identifier: Provides real-time PMSM nonlinear dynamic feedback for the observer; (2) MTN Adaptive Inverse Controller: Compensates for load disturbances using the observer’s estimated states. The study focuses on optimizing the MTN observer to address key limitations of existing methods (high computational complexity, lack of stability guarantees, and low estimation accuracy). Compared with the neural network observer, this MTN-based scheme stands out due to its straightforward structure and significantly reduced approximately 40% computational complexity. Specifically, the intricate calculations and high resource consumption typically associated with neural network observers are circumvented. Subsequently, by leveraging Lyapunov theory, an adaptive learning rule for the MTN weights is meticulously devised, which seamlessly bridges the theoretical proof of the nonlinear observer’s stability. Simulation results demonstrate that the proposed MTN observer achieves rapid convergence of speed and position estimation errors (with steady-state errors within ±0.5% of the rated speed and ±0.02 rad for rotor position) after a transient period of less than 0.2 s. Even when stator resistance is increased by tenfold to simulate parameter variations, the observer maintains high estimation accuracy, with speed and position errors increasing by no more than 1.2% and 0.05 rad, respectively, showcasing strong robustness. These results collectively confirm the efficacy and practical value of the proposed scheme in PMSM sensorless speed control.
Abstract Based on the emergency rescue, the subsequent disposal, and the development and utilization projects of the Hongshiyan Landside Dam in Ludian, Yunnan, China, research has been conducted on key technical issues facing the development and utilization of landside dams, including the possibilty evaluation of development and utilization, structure analysis of wide gradation material, performance evaluation, investigation and design, dam seepage control, construction technology and equipment, and safe operation assessment. And innovative results has made in all seven aspects mentioned above, writing the history in this field. The achievements were directly applied to the development planning, investigation and design, construction, and operation and maintenance of the Hongshiyan Landside Dam, a comprehensive water conservancy project that integrates flood control, water supply, irrigation, and power generation, with significant comprehensive benefits.
Oceanography, River, lake, and water-supply engineering (General)
Nader Mohamed, Jameela Al-Jaroodi, Imad Jawhar
et al.
Healthcare systems are complex systems that need effective and efficient operations, optimizations, management, and control to offer reliable, high-quality, and cost-effective healthcare services. There are different approaches to improve the management of healthcare systems including utilizing the healthcare systems engineering principles. Healthcare systems engineering views a healthcare organization as a system and applies the engineering analysis and design principles to improve different aspects of healthcare services provided in that system. While this approach can provide many advantages for healthcare organizations, there are also many challenges hindering the ability of healthcare systems engineers from effectively accomplishing their mission. The initiation of the digital twin technology formed several potential methods for various industrial sectors to enhance their operations. Accordingly, they can help improve productivity, cost-effectiveness, reliability, quality, and flexibility. This paper studies how digital twins can be utilized for improving healthcare systems engineering processes and outcomes to enhance different aspects of healthcare systems. The paper discusses some of the challenges of healthcare systems engineering and how these challenges can be relaxed by utilizing digital twins. The paper also develops a conceptual framework to utilize digital twins for improving healthcare systems engineering processes and outcomes and discusses the prospects of such utilization on achieving the goals of healthcare systems engineering. In addition, the paper provides some discussions on the impact of this utilization and the future research and development projections of the employment of digital twins for healthcare systems engineering.
Petros Petrounias, Panagiota P. Giannakopoulou, Aikaterini Rogkala
et al.
This study was based on the reduction of the extraction of natural resources and, at the same time, was focused on the use of by-products and various wastes in construction applications by following the principles of circular economy. Sterile natural rocks (limestones, basalts), industrial by-products (slags), hotel construction wastes (bathroom wastes) and electronic wastes (e-wastes) were tested for pervious concrete aggregates. For this reason, ten concrete specimens were prepared and tested petrographically, structurally, and physically. The physical properties of the tested raw materials directly depended on their petrographic characteristics and played crucial role for the permeability of the produced concrete specimens, for their mechanical behavior, and for the freeze–thaw test results. Generally, from this study, strong encouraging results were achieved as concrete made by variable wastes and by-products can be compatible for concrete production as they show similar performance both in the mechanical strength test and in the freeze–thaw test with those made by natural aggregates. Another goal of this study was to recommend to other researchers the extended use of by-products, construction wastes, and e-wastes as concrete aggregates for producing eco-friendly constructions.
Control of the disturbed displacement of adjacent tunnel during excavation is a significant issue for design and construction. Based on the multi-objective optimization method, the multi-type monitoring data in the excavation of the excavation are integrated, the key soil parameters are inverted and identified, and the time effect of the tunnel displacement is quantified and corrected. A dynamic multi-objective optimization method with adaptive infill criterion (DMO-AIC) is proposed to improve the updating efficiency of dynamic surrogate models. The proposed method takes into account the computational redundancy of dynamic surrogate models in engineering optimization, and designs an adaptive point-adding discrimination strategy, which can autonomously identify invalid updates of surrogate models on the optimization path. The results show that the proposed DMO-AIC significantly reduces the invocations of the black-box model during optimization while ensuring the good search performance and the convergence speed of the algorithm. The improved computational efficiency of DMO-AIC is helpful for the application of dynamic surrogate models in engineering optimization. The results of the virtual numerical example show that DMO-AIC can predict and update multiple model responses during excavation, such as wall deflections and tunnel displacements. The engineering practice of Shanghai Bund 596 excavation indicates that the time effect is properly updated, and the staged vertical displacements of the adjacent tunnel are accurately predicted.
Engineering (General). Civil engineering (General), Chemical engineering
The non-uniform temperature distribution in large-format lithium-ion batteries (LIBs) can lead to thermal runaway or performance degradation. This study develops a three-dimensional electrochemical–thermal model of a 55-Ah large-format LiFePO4/graphite pouch cell and statistically analyzes the effects of width, height, and attachment positions of the nominal tab (NT), lateral tab (LT), and counter tab (CT) on the temperature distribution. The temperature difference that occurs across the cell is analyzed separately for each design factor through design of experiments (DOE) and analysis of variance (ANOVA). Accordingly, wider tabs reduce the maximum temperature and temperature difference irrespective of the tab type. Taller tabs yield higher maximum temperatures, resulting in a larger temperature difference. Attaching tabs to the edge of the cell increases the maximum temperature and temperature difference. The locations of the negative NTs and CTs do not affect the temperature difference. However, the location of the negative LT increases the minimum temperature, thereby decreasing the temperature difference. The ANOVA revealed that the p-value of the width, height, and attachment position of the positive tab is lower than 0.05 which means the factors strongly influence the temperature difference for all tab-types. Also, the attachment position of the negative tab affects only the LT-type.
Sara Abbaspour, Autumn Naber, Max Ortiz-Catalan
et al.
Pattern recognition algorithms have been widely used to map surface electromyographic signals to target movements as a source for prosthetic control. However, most investigations have been conducted offline by performing the analysis on pre-recorded datasets. While real-time data analysis (i.e., classification when new data becomes available, with limits on latency under 200–300 milliseconds) plays an important role in the control of prosthetics, less knowledge has been gained with respect to real-time performance. Recent literature has underscored the differences between offline classification accuracy, the most common performance metric, and the usability of upper limb prostheses. Therefore, a comparative offline and real-time performance analysis between common algorithms had yet to be performed. In this study, we investigated the offline and real-time performance of nine different classification algorithms, decoding ten individual hand and wrist movements. Surface myoelectric signals were recorded from fifteen able-bodied subjects while performing the ten movements. The offline decoding demonstrated that linear discriminant analysis (LDA) and maximum likelihood estimation (MLE) significantly (<i>p</i> < 0.05) outperformed other classifiers, with an average classification accuracy of above 97%. On the other hand, the real-time investigation revealed that, in addition to the LDA and MLE, multilayer perceptron also outperformed the other algorithms and achieved a classification accuracy and completion rate of above 68% and 69%, respectively.
Summary: Nature does nothing in vain. Through millions of years of revolution, living organisms have evolved hierarchical and anisotropic structures to maximize their survival in complex and dynamic environments. Many of these structures are intrinsically heterogeneous and often with functional gradient distributions. Understanding the convergent and divergent gradient designs in the natural material systems may lead to a new paradigm shift in the development of next-generation high-performance bio-/nano-materials and devices that are critically needed in energy, environmental remediation, and biomedical fields. Herein, we review the basic design principles and highlight some of the prominent examples of gradient biological materials/structures discovered over the past few decades. Interestingly, despite the anisotropic features in one direction (i.e., in terms of gradient compositions and properties), these natural structures retain certain levels of symmetry, including point symmetry, axial symmetry, mirror symmetry, and 3D symmetry. We further demonstrate the state-of-the-art fabrication techniques and procedures in making the biomimetic counterparts. Some prototypes showcase optimized properties surpassing those seen in the biological model systems. Finally, we summarize the latest applications of these synthetic functional gradient materials and structures in robotics, biomedical, energy, and environmental fields, along with their future perspectives. This review may stimulate scientists, engineers, and inventors to explore this emerging and disruptive research methodology and endeavors.
Pedro V. Munuera-Martínez, Priscila Távara-Vidalón, Manuel A. Monge-Vera
et al.
Several methods have been described to quantify the first ray mobility. They all have certain disadvantages (great size, sophistication, or lack of validation). The objective of this work was to study the validity and reliability of a new instrument for the measurement of first ray mobility. Anterior-posterior radiographs were obtained from 25 normal feet and 24 hallux valgus feet, with the first ray in a neutral position, maximally dorsiflexed and maximally plantarflexed. The first ray mobility was radiographicaly measured in both groups, and was also manually examined with the new device. A cluster analysis determined whether normal and hallux valgus feet were correctly classified, and a graphic analysis of Bland-Altman was performed to compare the radiographic and manual measurement techniques. Based on the radiographs, the first ray mobility only showed significant differences in dorsiflexion between both groups (<i>P</i> = 0.015). First ray dorsiflexion, plantarflexion and total range of motion measured with the new device were different between both groups (<i>P</i> = 0.040, <i>P</i> = 0.011 and <i>P</i> = 0.006, respectively). The silhouette measure of the cohesion and separation coefficients from the cluster analysis was greater than 0.50 for the dorsiflexion, plantarflexion and total range of motion obtained from the radiographs and from the new device. The Bland-Altman graph suggested that 96% of the data presented agreement between both measurement methods. These results suggested that the new instrument was valid and reliable.
Prior to planting, the soil must be prepared usually by machines called cultivators. Older field cultivators are suitable for modification for row cropping. The crops and the tractor power available will determine specific needs. Factors to consider include row spacing and row spacing flexibility, whether you need a towed or tractor mounted unit, frame size and layout, ease of levelling, ease of moving, removing, and replacing shanks, overall machine condition, and the robustness of the shanks. The paper describes the struggle concerning the 3D modelling of such a field cultivator with special features.
Architectural engineering. Structural engineering of buildings, Engineering design
Sonia Guedan, Hugo Calderon, Avery D. Posey, Jr.
et al.
T cells engineered with chimeric antigen receptors (CARs) have emerged as a potent new class of therapeutics for cancer, based on their remarkable potency in blood cancers. Since the first clinical reports of their efficacy emerged 7 years ago, investigators have focused on the mechanisms and properties that make CARs effective or toxic, and their effects on T cell biology. Novel CAR designs coupled with improvements in gene transfer technology, incorporating advances in gene editing, have the potential to increase access to engineered cell therapies, as well as improve their potency in solid tumors. Keywords: CAR T cells, immunotherapy, chimeric antigen receptors, cancer
The anchoring technology is extensively applied in reinforcing protection of the earth relics. Now that no specification is available for different new anchor rods in earth relics protection due to diversified destruction modes of earth relics and complexity of engineering technology conditions, it is urgent to guide reinforcing design and construction with a complete detailed anchor rod research document. With the new carbon fiber Phyllostachys pubescens anchor rod as the research object, six lots of in situ tests are designed to, respectively, study the destruction mode and anchoring performance of the carbon fiber Phyllostachys pubescens anchor rod under different anchor length L, anchor rod diameter D, bore diameter H, grouting material S, rib spacing R, and inclination angle A in this paper. By studying load shift curve experiment in drawing of the anchor rod, the destruction mode and ultimate bearing capacity of the carbon fiber Phyllostachys pubescens anchor rod in different experiment lots are obtained, and the concept of permitted application value N in anchor rod design is proposed. By studying strain distribution characteristics of anchor rods in experimental lots along the length direction under action of the permitted application value N and combining the existing destruction mode and ultimate bearing capacity, this paper analyzes influences of L, D, H, S, R, and A on anchoring effect of the carbon fiber Phyllostachys pubescens anchor rod; gives the reasonable value range of L, D, H, and R when the carbon fiber Phyllostachys pubescens anchor rod is used for reinforcing design of the earth relics; and provides favorable experiment basis for reinforcing design of the earth relics based on the carbon fiber Phyllostachys pubescens anchor rod.
Simulation in social sciences entrenches itself in research traditions whose disciplinary type and researcher style color its purpose. For some, the technology to be applied, for others the techniques that encourage debate - the possibilities are multifaceted. In this paper, we present an original way of mobilizing simulation, in a situation of collaborative research in the field of management sciences. After discussing the difference between dialogical investigation and the organizational design and dynamic of organizations approach, we show how organisational simulation can be used to articulate a company’s strategic reasoning, a new organizational design and deployment, and the activity of actors in the field. In so doing, we explore the possibility of operating improved integration between strategic decisions taken by high-level managers, the choices made by middle management concerning the deployment strategy, and how the activity is performed and experienced by the workers (intellectual in this case) who are responsible for it. At a time when we are reflecting upon its invisibility (Gomez, 2013), we thus discuss possible ways of bringing work back into the strategic decision-making and organizational design process in large companies.
Miguel Amado, Francesca Poggi, António Ribeiro Amado
et al.
Recent growth in the use of photovoltaic technology and a rapid reduction in its cost confirms the potential of solar power on a large scale. In this context, planning for the deployment of smart grids is among the most important challenges to support the increased penetration of solar energy in urban areas and to ensure the resilience of the electricity system. As part this effort, the present paper describes a cellular approach to a Net-Zero energy concept, based on the balance between the potential solar energy supply and the existing consumption patterns at the urban unit scale. To do that, the Geographical Urban Units Delimitation model (GUUD) has been developed and tested on a case study. By applying the GUUD model, which combines Geographic Information Systems (GIS), parametric modelling, and solar dynamic analysis, the whole area of the city was divided into urban cells, categorized as solar producers and energy consumers. The discussion around three theoretical scenarios permits us to explore how smart grids can be approached and promoted from an urban planning perspective. The paper provides insights into how urban planning can be a driver to optimize and manage energy balance across the city if the deployment of smart grids is correctly integrated in its operative process.
M. V. Vedernikova, I. A. Pron, M. N. Savkin
et al.
This paper focuses on occupational and public exposure during operation of disposal facilities receiving liquid and solid radioactive waste of various classes and provides a comparative analysis of the relevant doses: actual and calculated at the design stage. Occupational and public exposure study presented in this paper covers normal operations of a radioactive waste disposal facility receiving waste. Results: Analysis of individual and collective occupational doses was performed based on data collected during operation of near-surface disposal facilities for short-lived intermediate-, lowand very low-level waste in France, as well as nearsurface disposal facilities for long-lived waste in Russia. Further analysis of occupational and public doses calculated at the design stage was completed covering a near-surface disposal facility in Belgium and deep disposal facilities in the United Kingdom and the Nizhne-Kansk rock massive (Russia). The results show that engineering and technical solutions enable almost complete elimination of internal occupational exposure, whereas external exposure doses would fall within the range of values typical for a basic nuclear facility. Conclusion: radioactive waste disposal facilities being developed, constructed and operated meet the safety requirements effective in the Russian Federation and consistent with relevant international recommendations. It has been found that individual occupational exposure doses commensurate with those received by personnel of similar facilities abroad. Furthermore, according to the forecasts, mean individual doses for personnel during radioactive waste disposal would be an order of magnitude lower than the dose limit of 20 mSv/year. As for the public exposure, during normal operation, potential impact is virtually impossible by delaminating boundaries of a nuclear facility sanitary protection zone inside which the disposal facility is located and can be solely attributed to the use of public roads during radioactive waste transportation to the disposal facility site.
Medical physics. Medical radiology. Nuclear medicine, Radioactivity and radioactive substances
<p>Abstract</p> <p>Adeno-associated virus (AAV) is an important vector system for human gene therapy. Although use of AAV serotypes can result in efficient myocardial gene transfer, improvements in the transduction efficiency and specificity are still required. As a method for artificial modification and selection of gene function, directed evolution has been used for diverse applications in genetic engineering of enzymes and proteins. Since 2000, pioneering work has been performed on directed evolution of viral vectors. We further attempted to evolve the AAV using DNA shuffling and <it>in vivo</it> biopanning in a mouse model. An AAVM41 mutant was characterized, which was found to have improved transduction efficiency and specificity in myocardium, an attribute unknown for any natural AAV serotypes. This review focuses on the development of AAV vector for cardiac gene transfer, the history of directed evolution of viral vectors, and our creation of a cardiotropic AAV, which might have implications for the future design and application of viral vectors.</p>