Design Aid Research Articles

Engineering dimer mutants of human geranylgeranyl pyrophosphate synthase

Geranylgeranyl pyrophosphate synthase (GGPPS), a key enzyme in protein prenylation, plays a critical role in cellular signal transduction and is a promising target for cancer therapy. However, the enzyme’s native hexameric quaternary structure presents challenges for crystallographic studies. The primary objective of this study was to engineer dimeric forms of human GGPPS to facilitate high-resolution crystallographic analysis of its ligand binding interactions. Through site-directed mutagenesis, we disrupted the inter-dimer interactions required for hexamer assembly, generating three stable double-site mutants: Y246D/C247L, Y246D/C205A, and Y246K/C247L. Enzyme assays confirmed that all mutants retained wild-type catalytic activity under both saturating and subsaturating substrate conditions. Differential scanning fluorimetry showed that the mutant proteins had a ~10°C lower melting temperature than the wild-type enzyme but exhibited similar shifts in melting temperature in the presence of the known inhibitors risedronate and zoledronate. Crystallographic analysis of the Y246D/C247L mutant yielded a 2.1 Å resolution structure, providing detailed insights into the binding of isopentenyl pyrophosphate. Closer inspection also revealed the unexpected formation of intermolecular disulfide bonds connecting neighboring dimers, which may explain the enhanced crystallizability of the Y246D/C247L mutant compared to the wild-type and other mutants. These findings highlight the potential of the dimeric mutants as substitutes for wild-type GGPPS in future studies. Optimized dimeric mutants could serve as valuable molecular tools to further our understanding of the enzyme’s structural and functional properties and aid in the rational design of novel therapeutic agents targeting GGPPS.

"It's a Good Idea to Put It Into Words": Writing 'Rudders' in the Initial Stages of Visualization Design.

Written language is a useful tool for non-visual creative activities like composing essays and planning searches. This paper investigates the integration of written language into the visualization design process. We create the idea of a 'writing rudder,' which acts as a guiding force or strategy for the designer. Via an interview study of 24 working visualization designers, we first established that only a minority of participants systematically use writing to aid in design. A second study with 15 visualization designers examined four different variants of written rudders: asking questions, stating conclusions, composing a narrative, and writing titles. Overall, participants had a positive reaction; designers recognized the benefits of explicitly writing down components of the design and indicated that they would use this approach in future design work. More specifically, two approaches - writing questions and writing conclusions/takeaways - were seen as beneficial across the design process, while writing narratives showed promise mainly for the creation stage. Although concerns around potential bias during data exploration were raised, participants also discussed strategies to mitigate such concerns. This paper contributes to a deeper understanding of the interplay between language and visualization, and proposes a straightforward, lightweight addition to the visualization design process.

PhenoFlow: A Human-LLM Driven Visual Analytics System for Exploring Large and Complex Stroke Datasets.

Acute stroke demands prompt diagnosis and treatment to achieve optimal patient outcomes. However, the intricate and irregular nature of clinical data associated with acute stroke, particularly blood pressure (BP) measurements, presents substantial obstacles to effective visual analytics and decision-making. Through a year-long collaboration with experienced neurologists, we developed PhenoFlow, a visual analytics system that leverages the collaboration between human and Large Language Models (LLMs) to analyze the extensive and complex data of acute ischemic stroke patients. PhenoFlow pioneers an innovative workflow, where the LLM serves as a data wrangler while neurologists explore and supervise the output using visualizations and natural language interactions. This approach enables neurologists to focus more on decision-making with reduced cognitive load. To protect sensitive patient information, PhenoFlow only utilizes metadata to make inferences and synthesize executable codes, without accessing raw patient data. This ensures that the results are both reproducible and interpretable while maintaining patient privacy. The system incorporates a slice-and-wrap design that employs temporal folding to create an overlaid circular visualization. Combined with a linear bar graph, this design aids in exploring meaningful patterns within irregularly measured BP data. Through case studies, PhenoFlow has demonstrated its capability to support iterative analysis of extensive clinical datasets, reducing cognitive load and enabling neurologists to make well-informed decisions. Grounded in long-term collaboration with domain experts, our research demonstrates the potential of utilizing LLMs to tackle current challenges in data-driven clinical decision-making for acute ischemic stroke patients.

Comparison of Reinforcement of High Rise Structure in Different Seismic Zones Using Staad Pro

Abstract: In this research design of G+10 High Rise Structure has been analyzed. The earthquake is most dangerous natural hazard in manmade structure. The demand of earthquake resisting building has been increased which can be fulfilled by providing the shear wall , Structure reinforcement and the appropriate sizing of beams and columns in the structure for resisting lateral forces. Shear walls also have high stiffness and strength which can be used to resist horizontal loads and gravity loads making useful in various structural engineering design. The study focuses on G+ 10 high rise structures located in seismic zones II, III, IV and V of India with shear walls at corners of the external walls . A Comparison of reinforcement for both flexural and compression members across different seismic zone is included . The analysis is done by using STAAD-Pro Connect Edition V22 software. The IS codes used for the analysis and designing is IS 1893 (Part-1):2016 (criteria for earthquake resistant design of structures), IS 456:2000 (plain and reinforced concrete) and SP 16: 1980 (design aids for reinforced concrete to IS : 456 )

Parametric Design and Mechanical Characterization of a Selective Laser Sintering Additively Manufactured Biomimetic Ribbed Dome Inspired by the Chorion of Lepidopteran Eggs

The current research aims to analyze the shape and structural features of the eggs of the lepidoptera species Melitaea sp. (Lepidoptera, Nympalidae) and develop design solutions through the implementation of a novel strategy of biomimetic design. Scanning electron microscopy (SEM) analysis of the chorion reveals a medial zone that forms an arachnoid grid resembling a ribbed dome with convex longitudinal ribs and concave transverse ring members. A parametric design algorithm was created with the aid of computer-aided design (CAD) software Rhinoceros 3D and Grasshopper3D in order to abstract and emulate the biological model. A series of physical models were manufactured with variations in geometric parameters like the number of ribs and rings, their thickness, and curvature. Selective laser sintering (SLS) technology and Polyamide12 (nylon) material were utilized for the prototyping process. Quasi-static compression testing was carried out in conjunction with finite element analysis (FEA) to investigate the deformation patterns and stress dispersion of the models. The biomimetic ribbed dome appears to significantly dampen the snap-through behavior that is observed in typical solid and lattice domes, decreasing dynamic stresses developed during the response and preventing catastrophic failure of the structure. Increasing the curvature of the ring segments further reduces the snap-through phenomenon and improves the overall strength. However, excessive curvature has a negative effect on the maximum sustained load. Increasing the number and thickness of the transverse rings and the number of the longitudinal ribs also increases the strength of the dome. However, excessive increase in the rib radius leads to more acute snap-through behavior and an earlier failure. The above results were validated using respective finite element analyses.

Mobile App for Patients With Chronic Obstructive Pulmonary Diseases During Home-Based Exercise Care: Usability Study.

Digital health tools have demonstrated promise in the treatment and self-management of chronic diseases while also serving as an important means for reducing the workload of health care professionals (HCPs) and enhancing the quality of care. However, these tools often merely undergo large-scale testing or enter the market without undergoing rigorous user experience analysis in the early stages of their development, leading to frequent instances of low use or failure. This study aims to assess the usability of and satisfaction with a mobile app designed for the clinical monitoring of patients with chronic obstructive pulmonary disease undergoing pulmonary rehabilitation at home. This study used a mixed methods approach involving two key stakeholders-patients with chronic obstructive pulmonary disease and HCPs-across three phases: (1) mobile app mock-up design, (2) usability testing, and (3) satisfaction evaluation. Using convenience sampling, participants were grouped as HCPs (n=12) and patients (n=18). Each received a tablet with mock-ups for usability testing through interviews, with audio recordings transcribed and analyzed anonymously in NVivo12.0, focusing on mock-up features and usability insights. Task difficulty was rated from 1 (very easy) to 5 (very difficult), with noncompletion deemed a critical error. Usability satisfaction was measured on a 5-point Likert scale from 1 (strongly disagree) to 5 (strongly agree). The research indicated a notable difference in app usability perceptions: 66% (8/12) of HCPs found tasks "very easy," compared to only 22% (4/18) of patients. Despite this, no participant made critical errors or withdrew, and satisfaction was high. HCPs completed tasks in about 20 minutes, while patients took 30. Older adults faced challenges with touch screens and scroll menus, suggesting the need for intuitive design aids like auditory support and visual health progress indicators, such as graphs. HCPs noted potential data delays affecting service, while non-native-speaking caregivers faced interpretation challenges. A secure pairing system for privacy in teleconsultations proved difficult for older users; a simpler icon-based system is recommended. This study highlights the need to consider stakeholder abilities in medical app design to enhance function implementation. Most HCPs (11/12, 91%) found the app intuitive, though they recommended adding icons to show patient progress to support clinical decisions. In contrast, 62% (11/18) of patients struggled with tablet navigation, especially with connectivity features. To ensure equitable access, the design should accommodate older users with diverse abilities. Despite challenges, both groups reported high satisfaction, with patients expressing a willingness to learn and recommending the app. These positive usability evaluations suggest that, with design improvements, such apps could see increased use in home-based care.

An Experimentally Designed Sertaconazole Sensor for Selective and Enhanced Potentiometric Response: Determination in Cream, Plasma & in Presence of Other Imidazoles

AbstractA two‐step experimental design was followed to develop a potentiometric solid contact ion‐selective electrode for sertaconazole (STN) determination. A full factorial design was first employed in screening for the best cation exchanger, ionophore and conducting polymer. Amounts of the selected cation exchanger; tetrakis[3,5‐bis(trifluoromethyl)phenyl] borate (TFPB), and ionophore; calix[6]arene (CX6), incorporated in STN sensing membrane were then optimized with the aid of face centered composite design. Calibration slope, detection limit and electrode selectivity in presence of another imidazole‐classified drug; econazole, were the selected responses in both designs. The optimized ion‐sensing membrane, containing 1.0 mg TFPB and 9.9 mg CX6, showed enhanced responses compared to the primarily screened ones. This optimized electrode exhibited a linear response over a concentration range of 1.0×10−6‐−1.0×10−3 M with a Nernstian slope of 57.50 mV/decade. The detection limit was lowered by about one order of magnitude via this optimization to equal 3.16×10−7 M. The proposed electrode was successfully challenged for STN determination in the presence of other imidazoles. It was then used for STN determination in cream and spiked plasma as an example of biological fluid. Our proposed potentiometric method was finally compared to the reported chromatographic ones in terms of sensitivity, and greenness evaluation by the widely applicable Analytical GREEnness (AGREE) tool. The comparison revealed the superiority of our method in terms of sensitivity and sustainability.

Enhancing User Experience in Private Bank Mobile Banking: Insights from Management Information System Analysis

This research explores the impact of Management Information Systems (MIS) on user experience in private bank mobile banking, focusing specifically on the effectiveness of m-BCA. Utilizing a descriptive quantitative approach, the study aims to understand how mobile banking features, including accessibility, user interface, security, and functionality, influence user satisfaction. Data were collected through direct experimentation with the m-BCA application, complemented by analysis from secondary data sources and a survey of 30 users. Results indicate that 93.3% of users find m-BCA effective for routine banking needs, attributing high ratings to its convenience and functionality. However, while 80% of respondents appreciate the current security measures, 20% cite the absence of advanced security features such as fingerprint and facial recognition as a drawback. The study also reveals mixed feedback on the user interface; while the straightforward design aids usability, 10% of users express a desire for a more visually appealing interface. Despite these areas for improvement, m-BCA’s comprehensive set of features is generally seen as effective, supporting users in performing essential transactions with ease and reliability. The findings suggest that enhancing interface aesthetics and integrating advanced security options could further boost user engagement and trust in mobile banking applications, underscoring MIS’s role in meeting evolving customer expectations in digital banking.

Editorial Note, Issue 2, Vol 18 – 2024

This series of papers feature a very practical array of applied research studies and case histories with findings to advance the deep foundation industry. Volume 18 Issue 2 includes interesting numerical 3D studies on the performance of onshore wind turbine foundations written by an author team affiliated with the Southwest Jiaotong University in Chengdu, China. This issue also highlights papers focused on a practical study of driven steel piles in sandy soils; critical insight into better characterizing the residual strength in p-y curves for rock-socketed pile shafts, particularly the Strong Rock (SR) p-y curves commonly used in practical applications; design aids for selecting steel HP sections for driven piles, based on the AISC Specification 360-22 for Structural Steel Buildings; and an investigation of the behavior of walls reinforced by screw and grouted nails in both sandy and clayey soils through 3D numerical modeling with Abaqus.

Design Aid for Selection of H-Piles

This paper presents design aids for the selection of HP sections for driven piles according to the American Institute of Steel Construction Specification 360-22 “Specification of Structural Steel Buildings.” Graphical aids for the design selection of W-shapes have been provided by Keil (2000), Hosur and Augustine (2007), and Sa’Adat and Banan (2014). However, to date there are no aids available for the design of H-Piles. This work seeks to eliminate that gap by providing the data necessary to create interaction diagrams for combined stresses including compression, bending, and tension in both the strong and weak axes for 50 ksi grade steel HP sections.

Nature redux: interrogating biomorphism and soft robot aesthetics through generative AI.

Artificial Intelligence (AI) has rapidly become a widespread design aid through the recent proliferation of generative AI tools. In this work we use generative AI to explore soft robotics designs, specifically Soft Biomorphism, an aesthetic design paradigm emphasizing the inherent biomorphic qualities of soft robots to leverage them as affordances for interactions with humans. The work comprises two experiments aimed at uncovering how generative AI can articulate and expand the design space of soft biomorphic robotics using text-to-image (TTI) and image-to-image (ITI) generation techniques. Through TTI generation, Experiment 1 uncovered alternative interpretations of soft biomorphism, emphasizing the novel incorporation of, e.g., fur, which adds a new dimension to the material aesthetics of soft robotics. In Experiment 2, TTI and ITI generation were combined and a category of hybrid techno-organic robot designs discovered, which combined rigid and pliable materials. The work thus demonstrates in practice the specific ways in which AI image generation can contribute towards expanding the design space of soft robotics.

An elastoplastic beam bond model for DEM simulation of deformable materials and breakage behaviors

AbstractIn modern chemical engineering production, numerous elastoplastic materials, often formed into agglomerates, frequently undergo plastic deformation and rupture. Understanding how these materials behave under different conditions is crucial for improving manufacturing processes and material design. In this work, an elastoplastic beam bond model for discrete element method (DEM) simulation was developed, in which a yield criterion is introduced into Timoshenko beam bond method. The model can simulate not just the initial elastic (stretchy) behavior of the materials but also their plastic (permanent) deformation behaviors. The model was applied to central collision of two agglomerates, agglomerate uniaxial compression, and agglomerate‐wall impact cases. It is shown that the updated model could predict the behavior of materials that undergo permanent changes under stress, compared to previous models that only considered elastic behaviors. This could enable more accurate simulations of particulate materials and aid in better process design.

Inactivating Alicyclobacillus acidoterrestris spores with UVLED: Unraveling the role of turbidity, reactive oxygen species, and water dynamics

Alicyclobacillus acidoterrestris (AAT) is a spore-forming bacterium that can survive thermal pasteurization and acidic conditions. Ultraviolet light emitting diode (UVLED) has received extensive attention as a new technology to replace traditional mercury lamps for fruit juice decontamination, however, very few studies on fruit juice have been reported to investigate the sporicidal effect of UVLED on A. acidoterrestris. This research investigated for the first time the application of UVLEDs at 254 nm for the treatment of AAT in tomato juice. The optimized conditions for UVLED, achieved with the aid of Box Behnken design, were 6 cm, 12 min, and 250 mL/min. The results showed that the AAT spores in citrate buffer solution and tomato juice were inactivated by 3-log reduction with a required fluence of 53.67 mJ/cm2. Additionally, UVLED induced an exclusively cellular damage through direct absorption of UV light and direct DNA damage, and indirectly via reactive oxygen species. Besides, the deactivation of AAT spores, validated by LF-NMR analysis, indicated that the free water in AAT might be due to the rehydration of the spore core by the process of germination and then dehydration. This dehydration was further confirmed by the shrinking of spores observed through SEM and AFM imaging. These outcomes were also correlated with those of potassium ions and DPA leakage. This study emphasizes the energy-saving and resistance-reducing features of UVLED in effectively inactivating AAT.

Robust design optimization of Critical Quality Indicators (CQIs) of medical-graded polycaprolactone (PCL) in bioplotting

Polycaprolactone (PCL), either in its pure grade or as a polymeric matrix for bio-composites, plays a key role in the biomedical and bioengineering industries. It is also considered a multifunctional and versatile polymer for bioprinting and bioplotting purposes, especially in tissue engineering. Herein, an undiscovered yet valuable aspect of PCL extrusion-based bioprinting, such as the predictability of Critical Quality Indicators (CQIs), is investigated in depth. With the aid of the robust L25 orthogonal matrix design, the six most generic and device-independent control factors proved their impact on quality metrics such as global porosity, dimensional conformity, and surface roughness, determined with the aid of highly evolved Nondestructive Testing (NDT) and algorithms. To this end, 25 experimental runs were set, and 125 specimens were fabricated using an industrial-scale bio-plotter and medical-graded polycaprolactone. Various infill densities (ID), layer thicknesses (LT), raster deposition angles (RDA), printing speeds (PS), nozzle temperatures (NT), and bed temperatures (BT) were applied. CQIs were determined using optical profilometry and microscopy, and micro-computed tomography. Quadratic predictive equations were compiled and verified using two additional, well-chosen experimental runs. These generally applicable predictive models carry a massive amount of research and industrial merit, as they ensure visibility in bioprinting with PCL.

A revised online tool for room acoustic prediction of open-plan offices

Room acoustic conditions in open-plan offices are usually measured using ISO 3382-3 standard. The essential single-number quantities obtained from the measurement are comfort distance and distraction distance. Their values can also be predicted using a regression model of Keränen & Hongisto (2013). The prediction accuracy of the model has been proven to be high. The input variables for the model are simple to obtain: room dimensions, screen height, ceiling absorption, vertical absorption, speech level, and background noise level. The prediction model was published online in 2008 but withdrawn in 2013. Since then, we have been repeatedly asked to return the online tool. Since the standard was updated in 2022, we developed a revised online tool that predicts the single-number values of ISO 3382-3 standard. The purpose of this study is to present the online tool and validate its reliability by comparing online tool results to previously published results. The comparison shows that the online tool results agree with the above-mentioned studies. Therefore, the online tool can be safely used. It is a valuable aid in workplace design, demonstrations, research, and education.

Investigation of light earth sound transmission loss at the wall scale

A fine understanding of the acoustic dissipation in walls made from biobased concrete is needed to predict and design properly their performances and to create comfortable spaces. This understanding is one of the objective of LOB+HIE (LOW BETON / HIGH EARTH) project, funded by Ademe, and focusing on the use of light earth (a biobased concrete resulting from the mix between clay and hemp shiv) to meet acoustic requirements in a public worksite. Acoustic data are already available in the literature at the material scale for this kind of solution. The aim of the present work is to provide experimental reference data at the wall scale for sound transmission on full-scale vertical walls, and then to extend it to other configurations by numerical simulations. The work is organised in three parts, including the transmission loss measurements on two different walls, the modelling of the walls with numerical simulations using a transfer matrix method approach, and finally the extension by simulation to other wall configurations, with a view to producing design aids for use by building professionals.

A platform for the rapid screening of equine immunoglobins F (ab)2 derived from single equine memory B cells able to cross-neutralize to influenza virus

ABSTRACT Single B cells-based antibody platforms offer an effective approach for the discovery of useful antibodies for therapeutic or research purposes. Here we present a method for screening equine immunoglobins F(ab)2, which offers the potential advantage of reacting with multiple epitopes on the virus. Using equine influenza virus (EIV) as model, a hemagglutinin (HA) trimer was constructed to bait B cells in vaccinated horses. We screened 370 HA-specific B cells from 1 × 106 PBMCs and identified a diverse set of equine variable region gene sequences of heavy and light chains and then recombined with humanized Ig Fc. Recombinant equine Ig was then self-assembled in co-transfected 293 T cells, and subsequently optimized to obtain HA binding B-cell receptor (s). The recombinant antibodies exhibited a high binding affinity to the HA protein. Antibody H81 exhibited the highest cross neutralizing activities against EIV strains in vitro. Furthermore, it effectively protected EIV-challenged mice, resulting in significantly improved survival, reduced pulmonary inflammation and decreased viral titers. In silico predication identified a functional region of H81 comprising 27 key amino acids cross the main circulating EIV strains. The 12 amino acid residues in this region with the highest binding affinities were screened. Notably, the predicted epitopes of H81 encompassed the documented equine HA receptor binding site, validating its cross-neutralization. In summary, a rapid platform was successfully established to investigate the profiling of equine antigen-recognizing receptors (BCRs) following infection. This platform has the potential to optimize the screening of virus-neutralizing antibodies and aid in vaccine design.

Revisiting the Reviewed: A Meta‐Analysis of Computational Studies on Transition Metal‐Catalyzed Hydrogenation Reactions

AbstractThis review of reviews attempts to systematically analyze the recent advancements in transition metal‐catalyzed hydrogenation reactions as discussed in previous review articles, emphasizing the computational insights that enhance our understanding of reaction mechanisms. It highlights the efficacy of density functional theory (DFT) in calculating free energies, exploring the mechanistic pathways and kinetics of hydrogenation processes and, focusing on substrates such as alkenes, alkynes, amides, imines, nitriles, and carbon dioxide. The review details significant studies where computational models help predict reaction outcomes and aid in catalyst design. Notable discussions include the role of solvent effects and metal‐ligand interactions, which are crucial for reactivity and selectivity but often underestimated in computational models. The review concludes with current computational challenges and prospects, suggesting enhanced models and experimental collaborations to refine catalyst design.

Box-Behnken design (BBD) for optimization and simulation of biolubricant production from biomass using aspen plus with techno-economic analysis

The growing concern and limitations for existing lubricants have driven the need for biolubricants, extensively proposed as the most suitable and sustainable lubricating oils. Biolubricant refers to lubricants that quickly biodegrade and are non-toxic to humans and aquatic habitats. Over the last decade, there has been a significant increase in the production of biolubricants due to the rising demand for replacing petroleum-based lubricants with those derived from renewable sources like vegetable oils and lipase that are used in various applications. In this study biodiesel (FAME) produced from blending animal fats and waste cooking was used as a raw material with ethylene glycol for biolubricant production using a transesterification reaction in the presence of calcium oxide which considers the newest and novel part as there is no production of biolubricant from animal fats and waste cooking oil in previous researches. The reaction parameters of biolubricant production were optimized using response surface methodology (RSM) with the aid of Box Behnken Design (BBD) to study the effect of independent variables on the yield of biolubricant. These variables are temperature ranging from (100–150 °C), reaction time ranging from 1 to 4 h, and FAME (Fatty Acid Methyl Ester) to alcohol molar ratio ranging from (2:1) to (4:1). The highest biolubricant yield is 91.56% at a temperature of 141 °C, a FAME/alcohol molar ratio of 2:1, and 3.3 h. Various analyses were performed on the produced biolubricant at the optimum conditions. The results include a pour point of -9 °C, a flash point of 192 °C, a kinematic viscosity at 40 °C of 10.35 cSt, a viscosity index of 183.6, an ash content of 0.76 wt.%, and a carbon residue of 1.5 wt.%, comparing favorably with the ISO VG 10 standard. The production process of biolubricant was simulated with Aspen Plus version 11 using a Non-Random Two-Liquid (NRTL) fluid package. The simulation results indicated that the production process can be applied on an industrial scale. Economic analysis was performed on the biolubricants production plant. The total capital investment was $12.7 M with a payback period of 1.48 years and an internal rate of return (IRR) of 67.5% indicating the suitability and profitability of the biolubricant production.

Determining What’s Next: Visual Analytics for Evaluating Human-Automation Coordination

As advanced automated systems become more complex, there is a greater need to analyze the difficulty of human-automation coordination. We developed a novel visual analytics tool to evaluate human-automation coordination by examining the relationship between projection, explanation (retrojection), and the understanding of current events through time. The What’s Next Diagram visualizes demands on human sensemaking as operators answer Wiener’s key automation surprise question: what will automation do next. The tool can assess whether operators can answer the question directly and quickly given the design and architecture of human-automation systems. It can be used as a model of multi-agent coordination, as a tool for post-mortem analysis, or an aid for design. We illustrate how the tool can be used to identify system requirements for anomaly response in the aviation domain.