Key Design Research Articles

Prediction of Membrane Flux in Membrane Bioreactors through Dimensionless Analysis and Correlations

Membrane flux (J, m3/m2·s) is a key design and operation parameter of membrane bioreactor (MBR) wastewater treatment plants. In this study, the impact of mixed liquor properties (mixed liquor density (ρ, kg/m3), mixed liquor dynamic viscosity (μs, kg/m.s)), hydrodynamic conditions (mixed liquor cross-flow velocity Vm in tubular MBRs or air-mixed liquor two-phase cross-low velocity Vam in the riser zone of the filtration tank of submerged MBRs, generalized as V (m/s)), trans-membrane pressure ΔP (Pa), membrane module geometry (tubular membrane channel diameter (Dt) or the hydraulic diameter (Ds) of the submerged bioreactor filtration riser zone, generalized as D (m)), and membrane filtration characteristics (total membrane filtration resistance (Rt, 1/m)) on membrane flux J in MBRs was analyzed and investigated using the dimensionless analysis and correlation approach. Four dimensionless groups, the ratio of membrane flux J to mixed liquor or air-mixed liquor generalized cross-flow velocity V (J/V), Reynolds number of mixed liquor (ρVD/μs), Euler number of mixed liquor (ΔP/(ρV2), and a new dimensionless group, fouling number of mixed liquor, (μsRt/(ρV)), were derived to correlate the impact of these parameters on membrane flux J in MBRs as seen in Equation (i):Based on experimental data of MBRs from the literature, the coefficients (m, a, b, c) in Equation (i) were calibrated. The J/V values predicted using Equation (i) are in reasonably good agreement with the experimental J/V values from the literature with a typical relative error smaller than 20% in most cases. Sensitivity analysis showed that trans-membrane pressure, ΔP, and total membrane filtration resistance, Rt, are the two most important parameters affecting the prediction of the derived dimensionless correlations (J/V) for both side-stream tubular MBRs and submerged MBRs. These new dimensionless group correlations provide a new mathematical tool for representing in-depth insights of how mixed liquor properties, hydrodynamic conditions, membrane module geometry, and total membrane filtration characteristics affect membrane flux J in MBRs. They can then be used to predict the membrane performance and to guide the optimal design and operation of MBR plants.

Revolutionizing lung cancer treatment: Introducing PROTAC therapy as a novel paradigm in targeted therapeutics.

This comprehensive review explores the transformative potential of PROTAC (Proteolysis-Targeting Chimeras) therapy as a groundbreaking approach in the landscape of lung cancer treatment. The introduction provides a succinct overview of current challenges in lung cancer treatment, emphasizing the significance of targeted therapies. Focusing on PROTAC therapy, the article elucidates its mechanism of action, comparing it with traditional targeted therapies and highlighting the key components and design principles of PROTAC molecules. In the context of lung cancer, the review meticulously summarizes preclinical evidence, emphasizing efficacy and specificity gleaned from studies evaluating PROTAC therapy. It delves into the implications of this preclinical data, discussing potential advantages over existing targeted therapies. An update on ongoing clinical trials involving PROTAC therapy for lung cancer offers a snapshot of the current progress, with a summary of key outcomes and advancements in early-phase trials. The mechanistic insights into PROTAC therapy's impact on lung cancer cells are explored, alongside a discussion on potential biomarkers for patient stratification and response prediction. The influence of tumor heterogeneity on PROTAC therapy outcomes is also addressed. Safety and tolerability assessments, encompassing preclinical and clinical studies, are comprehensively evaluated, including a comparative analysis with traditional targeted therapies and strategies to mitigate side effects. Looking forward, the article discusses the future perspectives of PROTAC therapy in lung cancer treatment and addresses ongoing challenges, providing a nuanced exploration of potential combination therapies and synergistic approaches. In conclusion, the review summarizes key findings and insights, underscoring the tremendous potential of PROTAC therapy as a promising and innovative avenue in pursuing more effective lung cancer treatments.

Pivotal trial characteristics and types of endpoints used to support Food and Drug Administration rare disease drug approvals between 2013 and 2022.

Rare disease drug development faces unique challenges, such as genotypic and phenotypic heterogeneity within small patient populations and a lack of established outcome measures for conditions without previously successful drug development programs. These challenges complicate the process of selecting the appropriate trial endpoints and conducting clinical trials in rare diseases. In this descriptive study, we examined novel drug approvals for non-oncologic rare diseases by the U.S. Food and Drug Administration's Center for Drug Evaluation and Research over the past decade and characterized key regulatory and trial design elements with a focus on the primary efficacy endpoint utilized as the basis of approval. Using the Food and Drug Administration's Data Analysis Search Host database, we identified novel new drug applications and biologics license applications with orphan drug designation that were approved between 2013 and 2022 for non-oncologic indications. From Food and Drug Administration review documents and other external databases, we examined characteristics of pivotal trials for the included drugs, such as therapeutic area, trial design, and type of primary efficacy endpoints. Differences in trial design elements associated with primary efficacy endpoint type were assessed such as randomization and blinding. Then, we summarized the primary efficacy endpoint types utilized in pivotal trials by therapeutic area, approval pathway, and whether the disease etiology is well defined. One hundred and seven drugs that met our inclusion criteria were approved between 2013 and 2022. Assessment of the 107 drug development programs identified 150 pivotal trials that were subsequently analyzed. The pivotal trials were mostly randomized (80%) and blinded (69.3%). Biomarkers (41.1%) and clinical outcomes (42.1%) were commonly utilized as primary efficacy endpoints. Analysis of the use of clinical trial design elements across trials that utilized biomarkers, clinical outcomes, or composite endpoints did not reveal statistically significant differences. The choice of primary efficacy endpoint varied by the drug's therapeutic area, approval pathway, and whether the indicated disease etiology was well defined. For example, biomarkers were commonly selected as primary efficacy endpoints in hematology drug approvals (70.6%), whereas clinical outcomes were commonly selected in neurology drug approvals (69.6%). Further, if the disease etiology was well defined, biomarkers were more commonly used as primary efficacy endpoints in pivotal trials (44.7%) than if the disease etiology was not well defined (27.3%). In the past 10 years, numerous novel drugs have been approved to treat non-oncologic rare diseases in various therapeutic areas. To demonstrate their efficacy for regulatory approval, biomarkers and clinical outcomes were commonly utilized as primary efficacy endpoints. Biomarkers were not only frequently used as surrogate efficacy endpoints in accelerated approvals, but also in traditionally approved rare disease drugs. The choice of primary efficacy endpoints varied by therapeutic area, approval pathway, and understanding of disease etiology.

Экологические тропы: международный опыт создания и перспективы развития

The article focuses on the design and development of ecological trails, examining their significance for sustainable tourism, environmental protection, and the enhancement of ecological awareness. It emphasizes the analysis of international experiences in creating ecological trails, highlighting their ecological benefits, accessibility for visitors, and educational aspects.An overview of key design methodologies is provided, which includes the use of local materials, comprehensive development, and the incorporation of educational elements. The article also discusses examples of successful trails from various countries such as New Zealand, Sweden, Canada, and Australia, where the focus is on biodiversity conservation and minimizing environmental impact.Furthermore, the article underscores the importance of involving local populations and indigenous peoples in the process of developing and maintaining ecological trails. It also discusses future directions in design, including the integration of modern technologies and adaptive management.

Vitrimeric electrolytes - overview and perspectives.

Lithium batteries, essential for consumer electronics, transportation and the energy sector, still require further improvement in performance, safety, and sustainability. Traditonal organic solvent-based electrolytes, widely used in current systems, pose significant safety risks and restrict the development of next generation devices. Vitrimers are materials with unique physical and chemical properties, which offer a promising alternative to overcome these limitations, finally reaching processability and recyclability of solid electrolytes. Despite their potential a comprehensive overview of vitrimeric electrolytes' design and application in lithium batteries is lacking. This review article summarizes the key concepts, design principles, and notable advancements in vitrimeric electrolytes. We will also discuss the challenges still restricting the widespread adoption of vitrimeric electrolytes and explore future perspectives for leveraging vitrimeric materials in high-performance, safer, and more sustainable lithium battery technologies.

Opportunities and Challenges of a Cap-and-Trade System for Plastics.

Recently, the rapid increase in global plastics production has caused various ecological and economic issues, worsened by poor material and waste management. Among the market-based instruments that could help mitigate the environmental impacts of plastics throughout their life-cycle, we evaluate the advantages and limitations of incorporating a cap-and-trade (CAT) system into future policy mixes. Our aim is to inspire further investigation of CAT's feasibility rather than presenting it as the ultimate solution. Drawing from past CAT implementations in domains such as water resource management and carbon emissions, we outline three key policy design considerations: (1) material and target group identification, (2) cap establishment and permit allocation, and (3) development of a competitive market environment. We explore a three-tiered approach with global, national, and sectoral caps covering the plastic lifecycle from cradle to grave. While there are viable reasons to consider a plastics CAT, significant challenges persist, which may ultimately limit its implementation. In the context of ongoing UN Plastics Treaty negotiations or future policy developments, this evaluation of CAT can be beneficial for assessing when and how this tool can address the negative externalities of plastics.

Bi-Level Design Optimization for Demand-Side Interval Temperature Control in District Heating Systems

With China’s socio-economic growth, the demand for enhanced residential comfort in northern urban areas has surged. Traditional district heating systems often fail to meet modern users’ diverse needs, leading to inefficiencies and significant heat loss. This paper investigates optimization and transformation methods for demand-side-oriented heating systems. We propose key design parameters that facilitate a shift from source-end to demand-end dominance and develop a bi-level planning model for operational scheduling. The model integrates building thermal storage and adjustable user temperature ranges to optimize multi-thermal source systems. Key contributions include identifying critical renovation parameters and establishing the relationship between temperature control range and system capacity. Results demonstrate that the optimized system provides interval temperature control for 96.02% of the heating season and increases the full-load duration ratio of heat source equipment by 29.54% compared to traditional systems. These improvements enhance operational efficiency, reduce heat loss, and better align heating provision with users’ dynamic thermal demands. This research offers a robust theoretical foundation and practical guidelines for transitioning to demand-end dominated district heating systems, contributing to more sustainable and responsive heating solutions.

Design of IPMSM Considering Shaft Voltage and AC Copper Loss for EV Propulsion with Wide Operating Range

Abstract This study investigates the interrelationship between shaft voltage (SV) and AC copper loss (ACCL) based on design variables that influence both characteristics. In previous works, issues with SV and ACCL have been reported in electric vehicle propulsion motors operating at high speeds. While methods to individually reduce these characteristics are well established, the correlation between them with respect to design variables has not yet been explored. To analyze this correlation, an analysis of the equations related to parasitic capacitances and ACCL is conducted to identify the key design variables affecting both SV and ACCL. These variables include the distance between the winding and the rotor, slot opening width, and winding width. Based on these design variables, a correlation analysis is conducted to confirm how these characteristics change simultaneously, and the results are verified through finite element analysis. Finally, an optimization process is implemented to minimize SV and ACCL while achieving the target average torque. The results are validated experimentally.

Autonomous Docking Manoeuvre Testing in the Framework of the ERMES Experiment

Abstract The rise of the “New Space Economy” has expanded access to low-Earth orbits for commercial, non-profit, and educational entities. This has driven significant growth in the small satellite market, offering a low-cost solution for various missions. Autonomous proximity operation systems for small satellites are actively studied for their wide-ranging applications. Experimental Rendezvous in Microgravity Environment Study (ERMES) is a student project, which aimed at testing an autonomous docking manoeuvre between two free-flying CubeSats mock-ups in a reduced gravity environment. The manoeuvre is characterized by an active Chaser and cooperative Target approach. In particular, the Chaser is equipped with a cold gas propulsive system based on expendable $$\hbox {CO}_{2}$$ CO 2 cartridges for three-dimensional manoeuvering, whereas the Target has a set of reaction wheels for attitude control. The magnetic post-manoeuvre connection is achieved thanks to a dedicated miniaturized docking interface. Moreover, the reduced gravity conditions have been achieved by participating in the European Space Agency (ESA) $$79^{th}$$ 79 th Parabolic Flight Campaign thanks to the selection in the ESA Fly Your Thesis! Programme 2022 (FYT). This article provides an overview of the ERMES experiment, discussing its main objectives and key design solutions. It first describes the design of the Guidance Navigation and Control subsystems of the two mock-ups, then discusses the results of the parabolic flight campaign, and finally focuses on the analysis of a specific parabolic test, where the Chaser was able to dock by recovering a high overall misalignment.

Tooth design and verification of face spline transmission in hub bearing

The hub bearing with face spline transmission is a new type of hub bearing. The design method and standards are lack. In this work, the geometric relationship of the tooth profile parameters and the meshing situation are derived for the hub bearing face spline. The outer diameter D, number of teeth Z, and face tooth profile angle φ are key design parameters. The verification conditions for preload, extrusion stress, tooth root bending stress, and shear stress are established based on strength theory and assumption of uniform load distribution. To validate the design, a case study is conducted on the hub bearing face spline in a certain vehicle model, with theoretical calculation and simulation of stress by using Finite Element Method. The present FEM results compare well with those of the literature data. Finally, through the incorporation the torque strength and durability tests of the face spline, the reliability of the design theory in this work is confirmed. The results indicates that, the tooth tip fillet r1 has a significant impact on the meshing area, the maximum principal stress near the tooth root is highest at the arc of the tooth root, proving that the selection of the dangerous section is appropriate. The work has value in promoting the development of automotive wheel hub bearings.

Standardized pipelines support and facilitate integration of diverse datasets at the Rat Genome Database.

The Rat Genome Database (RGD) is a multispecies knowledgebase which integrates genetic, multiomic, phenotypic, and disease data across 10 mammalian species. To support cross-species, multiomics studies and to enhance and expand on data manually extracted from the biomedical literature by the RGD team of expert curators, RGD imports and integrates data from multiple sources. These include major databases and a substantial number of domain-specific resources, as well as direct submissions by individual researchers. The incorporation of these diverse datatypes is handled by a growing list of automated import, export, data processing, and quality control pipelines. This article outlines the development over time of a standardized infrastructure for automated RGD pipelines with a summary of key design decisions and a focus on lessons learned.

Quantifying Older Adults’ Spatial Perceptions of Outdoor Activity Areas for Embedded Retirement Facilities

Outdoor activity areas for embedded retirement facilities (ERFs) are essential for providing older adults with access to outdoor environments within communities. However, there is limited evidence on how these areas influence older adults’ spatial perceptions. This study investigated the impact of ERFs’ spatial characteristics on older adults’ physiological and psychological perceptions. Three kinds of outdoor activity areas in a coastal city in eastern China were investigated, and older adults’ physiological data were collected through real environments from wearable sensors. Their subjective perception data were collected through subjective satisfaction questionnaires. By combining them, the authors identified correlations between older adults’ spatial perceptions and the characteristics of outdoor activity areas, quantifying the impact of various spatial features on their satisfaction. The results showed that areas with high subjective satisfaction were linked to strong emotional arousal and increased visual comfort. Spaces with favourable sky view factors and spatial openness significantly enhanced spatial perception satisfaction. Key design elements can shape older adults’ spatial perceptions. This study highlights the positive relationship between outdoor activity areas for ERFs and older adults’ spatial experiences, offering insights for age-friendly renovations and site selection to create supportive environments for ageing populations.

A METHODOLOGY FOR EVALUATING THE COSTEFFECTIVENESS OF CRCP DESIGN FEATURES

Continuously reinforced concrete pavement (CRCP) evolved out of a desire to minimize joint-related distresses and improve long-term smoothness of the pavement by eliminating transverse contraction joints. In CRCP, longitudinal reinforcing steel is continuous throughout the pavement length to hold cracks tight. A methodology for evaluating the cost-effectiveness of key CRCP design features and optimizing CRCP design was developed and presented. In this methodology, performance and cost data are combined to evaluate the cost-effectiveness of pavement design features and to determine the optimum combination of these features which has lowest life cycle cost (LCC). The developed methodology was used to examine the cost-effectiveness of five of the more influential CRCP design features PCC slab thickness, longitudinal steel reinforcement content, base type and thickness, shoulder type and thickness, and PCC slab width. A detailed life-cycle cost analysis (LCCA) of 13 current CRCP designs utilizing different combinations of these five design features was conducted using best estimates of the relative costs and performance effects of each of these design features. The cost data were obtained from State and contractors surveys, as well as published cost data and bid tabs. The performance data were obtained from State and contractors surveys, as well as empirical and mechanistic-empirical pavement performance prediction models.

Revised Dowel Bar Tolerances for Ontario Concrete Pavements

Effective load transfer is a key design element for jointed plain concrete pavement and has a significant impact on long-term pavement performance. To facilitate load transfer and to allow expansion and contraction of the joints, dowel bars should be placed parallel to the vertical and horizontal planes of the pavement. In the past, it was difficult to verify the alignment of dowel bars within a concrete pavement. Recently, the Ontario Ministry of Transportation was given the opportunity to verify dowel bar alignment with an innovative non-destructive technique known as magnetic imaging tomography (MIT). The MIT scan was found to be a quick and accurate method of measuring dowel bar alignment across a transverse joint, allowing real-time, non-destructive assessment of the dowel bar alignment at joints throughout a concrete paving contract. In Ontario, MIT scan data collection and analysis during concrete paving led to process and equipment improvements. The MIT scan was rapidly adopted both as a quality control tool for the contractor and a quality assurance tool for the ministry. Based on data collected over several paving seasons, changes were made to ministry specifications and dowel bar tolerances. The revised dowel bar tolerances for Ontario pavements are presented in this paper.

Development of CPAP Overlay Interfaces for Efficient Administration of Aerosol Surfactant Therapy to Preterm Infants

The administration of surfactant aerosol therapy to preterm infants receiving continuous positive airway pressure (CPAP) respiratory support is highly challenging due to small flow passages, relatively high ventilation flow rates, rapid breathing and small inhalation volumes. To overcome these challenges, the objective of this study was to implement a validated computational fluid dynamics (CFD) model and develop an overlay nasal prong interface design for use with CPAP respiratory support that enables high efficiency powder aerosol delivery to the lungs of preterm infants when needed (i.e., on-demand) and can remain in place without increasing the work of breathing compared with a baseline CPAP interface. Realistic in vitro experiments were first conducted to generate baseline validation data, and then the CFD model, once validated, was used to explore key design parameters across a range of preterm infant nose-throat geometries and aerosol delivery conditions. The most important factors for efficient aerosol delivery were shown to be (i) maintaining the aerosol delivery flow rate below the tracheal flow rate (to minimize CPAP line loss) and (ii) concentrating the aerosol within the first portion of the inhalation waveform. An optimized design was shown to deliver approximately 37–60% of the nominal dose through the system and to the lungs with low intersubject variability (1050–2200 g infants) across two modes of device actuation (automated and manual) with room for further improvement. Ergonomic curvatures and streamlining of the prong geometries were also found to reduce work of breathing and flow resistance compared with a commercial alternative.Graphical

Compact High-Zoom-Ratio Mid-Wavelength Infrared Zoom Lens Design Based on Particle Swarm Optimization.

This paper presents an automated method for solving the initial structure of compact, high-zoom-ratio mid-wave infrared (MWIR) zoom lenses. Using differential analysis, the focal length variation process of zoom lenses under paraxial conditions is investigated, and a model for the focal power distribution and relative motion of three movable lens groups is established. The particle swarm optimization (PSO) algorithm is introduced into the zooming process analysis, and a program is developed in MATLAB to solve for the initial structure. This algorithm integrates physical constraints from lens analysis and evaluates candidate solutions based on key design parameters, such as total lens length, zoom ratio, Petzval field curvature, and focal length at tele end. The results demonstrate that the proposed method can efficiently and accurately determine the initial structure of compact MWIR zoom lenses. Using this method, a mid-wave infrared zoom lens with a zoom ratio of 50×, a total length of less than 530 mm, and the ratio of focal length to total length approximately 2:1 was successfully designed. The design validates the effectiveness and practicality of this method in solving the initial structure of zoom lenses that meet complex design requirements.

Tailoring Design of Microneedles for Drug Delivery and Biosensing.

Microneedles (MNs) are emerging as versatile tools for both therapeutic drug delivery and diagnostic monitoring. Unlike hypodermic needles, MNs achieve these applications with minimal or no pain and customizable designs, making them suitable for personalized medicine. Understanding the key design parameters and the challenges during contact with biofluids is crucial to optimizing their use across applications. This review summarizes the current fabrication techniques and design considerations tailored to meet the distinct requirements for drug delivery and biosensing applications. We further underscore the current state of theranostic MNs that integrate drug delivery and biosensing and propose future directions for advancing MNs toward clinical use.

Exploring the Design of Low Cd BEV by Comparing the Characteristic Parameters and Curves of the Li Auto Mega and ZEEKR 009

As the Battery Electric Vehicle (BEV) market expands, consumer expectations for BEV performance are rising rapidly, with range anxiety becoming a major concern. Merely increasing battery size isnt a long-term solution. Instead, optimizing key design parameters to enhance aerodynamic efficiency is crucial. This paper examines the evolution of Multi-Purpose Vehicles (MPVs) by comparing the traditional MPV designs with newer, low drag models. in terms of appearance parameters and explore the future development of MPVs appearance. Specifically, the Li Auto Mega and ZEEKR 009 are analyzed, highlighting the stark differences in their designs. The study finds that the more aggressive and innovative design elements of the Mega effectively reduce the drag coefficient (Cd), offering valuable insights for future MPV designs

Kinetic Control of Self-Assembly Pathway in Dual Dynamic Covalent Polymeric Systems.

Kinetically controlled self-assembly is garnering increasing interest in the field of supramolecular polymers and materials, yet examples involving dynamic covalent exchange remain relatively unexplored. Here we report an unexpected dynamic covalent polymeric system whose aqueous self-assembly pathway is strongly influenced by the kinetics of evaporation of water. The key design is to integrate dual dynamic covalent bonds-including disulfide bonds and boroxine/borate-into a dynamic equilibrium system of monomers, polymers, and materials. This dual dynamic covalent design allows polymer growth and crosslinking to occur with the same spatiotemporal characteristics, governed solely by solvent evaporation. We found that a single building block can assemble into two distinct types of polymeric materials, each characterized by unique crosslinking topologies, orders, solubility, and macroscopic properties. The dual dynamic nature of the materials imparts them with intrinsic reconfigurability, such as interfacial repairability and close-loop chemical recyclability.

Kinetic Control of Self‐Assembly Pathway in Dual Dynamic Covalent Polymeric Systems

Kinetically controlled self‐assembly is garnering increasing interest in the field of supramolecular polymers and materials, yet examples involving dynamic covalent exchange remain relatively unexplored. Here we report an unexpected dynamic covalent polymeric system whose aqueous self‐assembly pathway is strongly influenced by the kinetics of evaporation of water. The key design is to integrate dual dynamic covalent bonds—including disulfide bonds and boroxine/borate—into a dynamic equilibrium system of monomers, polymers, and materials. This dual dynamic covalent design allows polymer growth and crosslinking to occur with the same spatiotemporal characteristics, governed solely by solvent evaporation. We found that a single building block can assemble into two distinct types of polymeric materials, each characterized by unique crosslinking topologies, orders, solubility, and macroscopic properties. The dual dynamic nature of the materials imparts them with intrinsic reconfigurability, such as interfacial repairability and close‐loop chemical recyclability.