General Design Research Articles

Rational Design of Activatable Lanthanide NIR-IIb Emissive Nanoprobe for In Situ Specific Imaging of HOCl In Vivo.

Hypochlorous acid (HOCl), as an indispensable signaling molecule in organisms, is one of the key members of reactive oxygen species (ROS). However, in vivo, real-time dynamic near-infrared fluorescence imaging of HOCl levels in the 1400-1700nm sub-window (NIR-IIb) remains a major challenge due to the lack of suitable detection methods. Herein, a general design of HOCl-responsive NIR-IIb fluorescence nanoprobe is proposed by integrating NaLuF4Yb/Er@NaLuF4 downshift nanoparticles (DSNPs) and HOCl recognition/NIR-IIb emissive modulation unit of M2-xS (M = Cu, Co, Pb) nanodots for real-time monitoring of HOCl levels. The fluorescence modulation unit of M2-xS nanodots presents remarkably enhanced absorption than Yb sensitizer at 980nm and greatly inhibits the NIR-IIb fluorescence emission via competitive absorption mechanism. While, the M2-xS nanodots are easily degraded after triggering by HOCl, resulting in HOCl responsive turn-on (≈ten folds) NIR-IIb emission at 1532nm. More importantly, in vivo highly precise and specific monitoring of inflammatory with abnormal HOCl expression is successfully achieved. Thus, the explored competitive absorption mediated quenching-activation mechanism provides a new general strategy of designing HOCl-responsive NIR-IIb fluorescence nanoprobe for highly specific and sensitive HOCl detection.

Integration of 3D printing with acoustic-assisted assembly of nanomaterials for tunable strain sensors

This study reports a novel methodology for the development of tunable strain sensors by leveraging 3D printing for structural designs and nanomaterial assembly for functional layer coating. We utilized material extrusion (MEX) to print sensor substrates using composite ink of polydimethylsiloxane (PDMS) and silica nanoparticles. MEX allows us to create a non-uniform strain distribution of the sensor substrate by designing alternating wide and thin strips with different mechanical properties along the stretching direction. Then, we assembled nanometer-thick graphene flakes on the surface of the substrate using an acoustic-assisted dip-coating method to construct strain sensors. The graphene network on the narrow strips will experience large deformation leading to significantly increased resistance. By fixing the width of wide strips and tailoring the width ratio of the wide strip over narrow strips (r), the gauge factor can be controlled from 8.53 (r = 1:1) to 33.15 (r = 16:1). Also, by printing the narrow strips with softer PDMS, the sensitivity of the sensor can be further increased. The research pioneers the integration of 3D printing and nanomaterial assembly for strain sensors. More importantly, it paves the way for the generic design of flexible electronics and other hybrid systems of polymer and nanomaterials.

Emerging Themes and Future Directions in Neurodesign and Human-Computer Interaction: A Systematic Review

While considerable research has been conducted, the field of neurodesign and human-computer interaction (N-HCI) has yet to be methodically delineated in light of contemporary studies. In this context, this paper undertakes a systematic review with dual objectives: (a) to uncover emerging research themes within N-HCI, and (b) to provide future directions for research on N-HCI. Employing robust systematic review methodologies, this paper scrutinized 122 pertinent documents, revealing four principal emerging research themes and constructing a conceptual framework that synthesized key concepts in N-HCI. The results underscored the relative underdevelopment in research that leverages neural evidence to enhance general human-computer interface design, and the notable absence of research at the intersections of the “user” and “environment” aspects of neurodesign with HCI. Accordingly, this paper identifies underdeveloped areas in existing research that require more depth and blank areas in the conceptual framework that call for exploration as future directions.

Multiaction Pt(IV) Prodrugs Releasing Cisplatin and Dasatinib Are Potent Anticancer and Anti-Invasive Agents Displaying Synergism between the Two Drugs.

Herein, we describe the general design, synthesis, characterization, and biological activity of new multitargeting Pt(IV) prodrugs that combine antitumor cisplatin and dasatinib, a potent inhibitor of Src kinase. These prodrugs exhibit impressive antiproliferative and anti-invasive activities in tumor cell lines in both two-dimensional (2D) monolayers of cell cultures and three-dimensional (3D) spheroids. We show that the cisplatin moiety and dasatinib in the investigated Pt(IV) complexes are both involved in the mechanism of action in MCF7 breast cancer cells and act synergistically. Thus, combining dasatinib and cisplatin into one molecule, compared to using individual components in a mix, may bring several advantages, such as significantly higher activity in cancer cell lines and higher selectivity for tumor cells. Most importantly, Pt(IV)-dasatinib complexes hold significant promise for potential anticancer therapies by targeting epithelial-mesenchymal transition, thus preventing the spread and metastasis of tumors, a value unachievable by a simple combination of both individual components.

Thymoquinone as an electron transfer mediator to convert Type II photosensitizers to Type I photosensitizers

The development of Type I photosensitizers (PSs) is of great importance due to the inherent hypoxic intolerance of photodynamic therapy (PDT) in the hypoxic microenvironment. Compared to Type II PSs, Type I PSs are less reported due to the absence of a general molecular design strategy. Herein, we report that the combination of typical Type II PS and natural substrate carvacrol (CA) can significantly facilitate the Type I pathway to efficiently generate superoxide radical (O2–•). Detailed mechanism study suggests that CA is activated into thymoquinone (TQ) by local singlet oxygen generated from the PS upon light irradiation. With TQ as an efficient electron transfer mediator, it promotes the conversion of O2 to O2–• by PS via electron transfer-based Type I pathway. Notably, three classical Type II PSs are employed to demonstrate the universality of the proposed approach. The Type I PDT against S. aureus has been demonstrated under hypoxic conditions in vitro. Furthermore, this coupled photodynamic agent exhibits significant bactericidal activity with an antibacterial rate of 99.6% for the bacterial-infection female mice in the in vivo experiments. Here, we show a simple, effective, and universal method to endow traditional Type II PSs with hypoxic tolerance.

Constructing heterogeneous micro/nano multilayer structure in Al alloys via solute grain boundary segregation for superior strength-ductility synergy

A heterogeneous micro/nano multilayered (HM/NMed) Al/Al-0.5 wt%Cu composite, composed of alternating coarse-grained pure Al layers and nanostructured Al-0.5 wt%Cu alloy layers containing a nanolamellar structure (NLS) with lamellar thickness as small as ∼60 nm, was developed by accumulative roll bonding (ARB) followed by low temperature annealing. Deformation induced Cu atoms grain boundary (GB) segregation was observed in Al-0.5 wt%Cu layer, which is responsible for the formation and stabilization of the NLS in the Al-0.5 wt%Cu alloy layers. This resultant HM/NMed Al/Al-0.5 wt%Cu composite with dramatic difference in microstructure and strength/hardness between neighboring pure Al and Al-0.5 wt%Cu alloy layers can achieve an exceptional strength-ductility combination: a yield strength close to the NLSed Al-0.5 wt%Cu alloy, and a tensile ductility comparable to coarse-grained pure Al. Strong hetero-deformation-induced (HDI) strengthening associated with the activation of stacking faults, are responsible for this exceptional strength-ductility synergy. The results presented here demonstrate a general design strategy based on solute GB segregation that enables the fabrication of HM/NMed Al-based materials with multi-scale hierarchical microstructures and improved mechanical properties.

Inductive detection of temperature-induced magnetization dynamics of molecular spin systems

The development and technological applications of molecular spin systems require versatile experimental techniques to characterize and control their static and dynamic magnetic properties. In the latter case, bulk spectroscopic and magnetometric techniques, such as AC magnetometry and pulsed electron paramagnetic resonance, are usually employed, showing high sensitivity, wide dynamic range, and flexibility. They are based on creating a nonequilibrium state either by changing the magnetic field or by applying resonant microwave radiation. Another possible source of perturbation is a laser pulse that rapidly heats the sample. This approach has proven to be one of the most useful techniques for studying the kinetics and mechanism of chemical and biochemical reactions. Inspired by these works, we propose an inductive detection of temperature-induced magnetization dynamics as applied to the study of molecular spin systems and describe the general design and construction of a particular induction probehead, taking into account the constraints imposed by the cryostat and electromagnet. To evaluate the performance, several coordination compounds of VO2+, Co2+, and Dy3+ were investigated using low-energy pulses of a terahertz free electron laser of the Novosibirsk free electron laser facility as a heat source. All measured magnetization dynamics were qualitatively or quantitatively described using a proposed basic theoretical model and compared with the data obtained by alternating current magnetometry. Based on the results of the research, the possible scope of applications of inductive detection and its advantages and disadvantages in comparison with standard methods are discussed.

A collective agenda: A qualitative study on Exercise is Medicine® On Campus gold-level institutions

ObjectiveThe Exercise is Medicine® On Campus (EIM-OC) international campaign leverages university resources (e.g., health centers, recreation, and kinesiology departments) to encourage students, faculty, and staff to integrate physical activity into campus culture. This involves evaluating student physical activity levels during health visits and establishing referral systems for exercise prescriptions. EIM-OC allows universities to earn tiered recognition (Gold, Silver, or Bronze) based on their on-campus physical activity promotion and integration. For Gold recognition, schools must incorporate routine physical activity assessments into their health system, ultimately connecting healthcare providers with health/fitness professionals (HFPs, e.g., campus recreation professionals, kinesiology professors). This research worked to uncover pivotal factors driving EIM-OC on-campus collaborations through HFPs’ perspectives. MethodsHFPs (n = 11) working full-time at a Gold-level institution (n = 10 in United States) participated. Semi-structured, Zoom-recorded interviews with a generic qualitative research design were completed between June and September 2022. ResultsMajor thematic findings included the importance of tangible support (e.g., personnel), encounters with both trust and tension cross-campus, positive student development opportunities, and variations in outcome reporting and program evaluation. Faculty and staff emphasized the need for methods to obtain and sustain program funding. Participants also expressed the importance of interdisciplinary collaboration to increase the collective impact of EIM-OC on student health and overall collegiate success. ConclusionHFPs expanded on their EIM-OC experiences and program sustainment or growth requirements. With increased interdisciplinary collaboration, rigor in outcome reporting, and tangible resources, the collective impact of EIM-OC on student health outcomes and overall collegiate success could be greatly perpetuated.

Topological and lattice-based AM optimization for improving the structural efficiency of robotic arms

The robotic arm is one of the vital components of robot assembly. The purpose of the robotic arm is to transmit power and conduct the desired motion, i.e., translation or rotation. Robotic limbs are designed and constructed to execute certain tasks with a high degree of speed, accuracy, and efficiency. This research focuses on to enhancing the strength-to-weight ratio of robotic arm using certain techniques of additive manufacturing, i.e., topology optimization and lattice structure. Employing the finite element analysis, the impact of weight reduction optimization on structural parameters such as stress and deformation in the current design is assessed using ANSYS R18.1 for FE analysis and Creo parametric 7.0 design software for computer-aided design modeling. Observations reveal that the 0.5 and .4 scale lattice structure designs have deformation of 0.01453mm and 0.01453 mm respectively though the generic design has 0.01043 mm deformation. Notably, the 0.5 scale lattice of the robotic arm exhibits a 31.08% higher equivalent stress than the generic design with 29.3%. reduction in mass of the robotic arm. These findings highlight the efficacy of lattice structures for optimizing the robotic arm’s performance, contributing to advancements in power-efficient robot assembly processes.

Accelerated Predictive Stability Study of a Pediatric Drug Product for a Supplemental New Drug Application.

In this paper, we report two Accelerated Stability Assessment Program (ASAP) studies for a pediatric drug product. Whereas the first study using a generic design failed to establish a predictive model, the second one was successful after troubleshooting the first study and customizing the study conditions. This work highlighted important lessons learned from designing an ASAP study for formulations containing excipients that could undergo phase change at high humidity levels. The stability predictions by the second ASAP model were consistent with available long-term stability data of the drug product under various storage conditions in two different packaging configurations. The ASAP model was part of the justifications accepted by the health authority to submit a stability package with reduced long-term stability data from the primary stability batches for a Supplemental New Drug Application (sNDA).

Molecular recording using DNA Typewriter.

Recording molecular information to genomic DNA is a powerful means of investigating topics ranging from multicellular development to cancer evolution. With molecular recording based on genome editing, events such as cell divisions and signaling pathway activity drive specific alterations in a cell's DNA, marking the genome with information about a cell's history that can be read out after the fact. Although genome editing has been used for molecular recording, capturing the temporal relationships among recorded events in mammalian cells remains challenging. The DNA Typewriter system overcomes this limitation by leveraging prime editing to facilitate sequential insertions to an engineered genomic region. DNA Typewriter includes three distinct components: DNA Tape as the 'substrate' to which edits accrue in an ordered manner, the prime editor enzyme, and prime editing guide RNAs, which program insertional edits to DNA Tape. In this protocol, we describe general design considerations for DNA Typewriter, step-by-step instructions on how to perform recording experiments by using DNA Typewriter in HEK293T cells, and example scripts for analyzing DNA Typewriter data ( https://doi.org/10.6084/m9.figshare.22728758 ). This protocol covers two main applications of DNA Typewriter: recording sequential transfection events with programmed barcode insertions by using prime editing and recording lineage information during the expansion of a single cell to many. Compared with other methods that are compatible with mammalian cells, DNA Typewriter enables the recording of temporal information with higher recording capacities and can be completed within 4-6 weeks with basic expertise in molecular cloning, mammalian cell culturing and DNA sequencing data analysis.

Flat optics of nonuniform phase gradient metasurfaces

Flat optics of uniform phase gradient metasurfaces based on the generalized Snell’s law has been extensively studied. The optics of nonuniform phase gradient metasurfaces (NPGMs) is less clear. Here based on Huygens’ principle and finite-difference time-domain (FDTD) simulation, we explore the optical properties of NPGMs made of nanorods (meta-atoms), which can be tuned by modulation of propagation phase and geometric phase. It is found that the nonuniformity of phase gradient may lead to multichannel anomalous reflection/refraction. The multiple beam splitters with arbitrary intensity ratio can be achieved by using the amplitude/phase modulation. Based on our design principle, we can obtain different anomalous reflection patterns (with channels ±1, ±2, both ±1 and ±2, or no reflection at anomalous angle) by different arrangement of just two types of meta-atoms. In addition, we are able to achieve chiral anomalous reflections for designed NPGMs made of nanorods and L-shaped nanoparticles. Our formulism provides general design guidance for NPGMs and can be used to realize the beam splitting function with adjustable angle and intensity ratio.

Thermodynamic optimization of heat exchanger circuitry via genetic programming

In this study, an evolutionary thermodynamic technique was developed for the optimization of heat exchanger circuitry. The proposed technique is capable of handling the unrestrained implementation of genetic operators while ensuring circuitry feasibility and basic manufacturability. The optimization tool was used to clarify the optimal heat transfer features in relation to the characteristics of the refrigerant and to provide a thermodynamic interpretation of the optimization results to extract general design guidelines. Evaporator circuitry optimization was conducted under given cooling capacity, superheating degree, and boundary conditions representative of air-conditioning applications. The consistency between the minimum entropy generation and the maximum coefficient of performance (COP) was demonstrated under these settings. Accordingly, heat exchanger configurations that take maximum advantage of the thermodynamic benefits of each refrigerant are proposed by optimizing the distribution of friction and heat transfer irreversibility. Consequently, the evaporator outlet pressure increases, thus lowering the compression ratio and maximizing the COP. The developed optimization method maximizes the benefits of low-GWP alternative refrigerants and shows that zeotropic mixtures may exhibit performance analogous to that of R32 and higher than that of R410A by approaching a Lorenz cycle operation.

Design criteria for conformal integration of flexible electronics on advanced aircraft surfaces

This paper introduces a set of design criteria that aim to integrate flexible electronics onto three-dimensional surfaces in a mechanically adaptive manner. Previous studies have been limited to conformal integration on specific shapes (Such as spherical surfaces and corrugated surfaces) of rigid surfaces or soft substrates, there is a lack of a universal design strategy that takes into account the complexity of substrate shapes and varying hardness. To address this gap, the paper outlines a mechanical model that utilizes Hertzian contact theory to describe the interaction between the thin film and the substrate, and the conformal surface morphology and stress state were derived from minimizing the total energy of the island-substrate structure. The proposed formulations are verified through finite element methods and experiments, analyzing the effects of Young's modulus, in-plane size, and thickness of the “island” on its conformability. Therefore, this paper proposes a generic on-demand conformal design strategy that takes into account the complexity and hardness of the substrate. This study's findings will contribute to the development of conformal electronics that can be used in various fields, such as epidermal electronics, flexible robots, robot electronic skin, and aircraft smart skin.

Bioinspired Heterocoordination in Adaptable Cobalt Metal-Organic Framework for DNA Epigenetic Modification Detection.

Metal-organic frameworks (MOFs) show unique advantages in simulating the dynamics and fidelity of natural coordination. Inspired by zinc finger protein, a second linker was introduced to affect the homogeneous MOF system and thus facilitate the emergence of diverse functionalities. Under the systematic identification of 12 MOF species (i.e., metal ions, linkers) and 6 second linkers (trigger), a dissipative system consisting of Co-BDC-NO2 and o-phenylenediamine (oPD) was screened out, which can rapidly and in situ generate a high photothermal complex (η = 36.9%). Meanwhile, both the carboxylation of epigenetic modifications and metal ion (Fe3+, Ni2+, Cu2+, Zn2+, Co2+ and Mn2+) screening were utilized to improve the local coordination environment so that the adaptable Co-MOF growth on the DNA strand was realized. Thus, epigenetic modification information on DNA was converted to an amplified metal ion signal, and then oPD was further introduced to generate bimodal dissipative signals by which a simple, high-sensitivity detection strategy of 5-hydroxymethylcytosine (LOD = 0.02%) and 5-formylcytosine (LOD = 0.025‰) was developed. The strategy provides one low-cost method (< 0.01 $/sample) for quantifying global epigenetic modifications, which greatly promotes epigenetic modification-based early disease diagnosis. This work also proposes a general heterocoordination design concept for molecular recognition and signal transduction, opening a new MOF-based sensing paradigm.

No free lunch for avoiding clustering vulnerabilities in distributed systems

Emergent design failures are ubiquitous in complex systems, and often arise when system elements cluster. Approaches to systematically reduce clustering could improve a design’s resilience, but reducing clustering is difficult if it is driven by collective interactions among design elements. Here, we use techniques from statistical physics to identify mechanisms by which spatial clusters of design elements emerge in complex systems modelled by heterogeneous networks. We find that, in addition to naive, attraction-driven clustering, heterogeneous networks can exhibit emergent, repulsion-driven clustering. We draw quantitative connections between our results on a model system in naval engineering to entropy-driven phenomena in nanoscale self-assembly, and give a general argument that the clustering phenomena we observe should arise in many distributed systems. We identify circumstances under which generic design problems will exhibit trade-offs between clustering and uncertainty in design objectives, and we present a framework to identify and quantify trade-offs to manage clustering vulnerabilities.

"I Go Outdoors for Activities Every Day": Go-Along With Seniors With Slow Walking Speeds to Explore Environmental Factors Influencing Mobility.

This study aims to: 1) Explore the mobility experiences of seniors with slow walking speeds (SSWS) in urban neighborhoods; and 2) Investigate their environmental barriers and supports. Go-along interviews were conducted with 36 SSWS residing in urban neighborhoods of Chongqing City, China. The mobility patterns and built environment factors influencing their mobility were revealed through cartographic analysis and thematic analysis. SSWS primarily focused their activities within a 400-meter radius of their homes. Built environment themes included topography, neighborhood services, sidewalks, seating, traffic safety, weather, greenery, and lighting. Significant mobility barriers included long stairs, steep slopes, fast-moving objects on sidewalks, road crossings, and fast traffic. Available handrails, nearby food-service places, ample seating, and greenery were identified as supportive factors for their mobility. This study stands out as the first to specifically examine the mobility of SSWS within the built environment. We suggest that SSWS should be taken into account when establishing a benchmark for general design frameworks. These improvements not only contribute to the mobility of slow walkers but also have positive impacts on the broader population.

Wake Effect Quantification using SCADA Data and LES Modelling of an Operational Offshore Wind Farm

Wake effects in the Anholt offshore wind farm have been investigated using both operational data and a Large Eddy Simulation (LES) model of a group of five turbines within the wind farm. Analysis of operational data showed that the variations of main shaft speeds of the downstream turbines were almost six times those of the upstream turbine at near-rated operation. The aim of the LES was to study the impact of atmospheric stability on the wind turbine array performance and compare this with the field data. An LES precursor method was used to model the near-neutral and unstably stratified atmospheric boundary layers that represent typical conditions in winter and summer, respectively, and the turbines in wind farm model were simulated using an actuator line method. It was found that LES with the actuator line method and generic turbine design data can generate a reasonable mean power generation trend for the Anholt wind farm under near-neutral and unstable conditions. The maximum difference in the mean power output between the LES and averaged operational data was approximately 20%.

Designing Behavior Change Support Systems Targeting Blood Donation Behavior

While blood is crucial for many surgeries and patient treatments worldwide, it cannot be produced artificially. Fulfilling the demand for blood products on average days is already a major challenge in countries like South Africa and Ghana. In these countries, less than 1 % of the population donates blood and most of the donations come from first-time donors who do not return. Sufficient new, first-time and even lapsed donors must be motivated to donate regularly. This study argues that blood donation behavior change support systems (BDBCSS) can be beneficially applied to support blood donor management in African countries. In this study, the design science research (DSR) approach is applied in order to derive generic design principles for BDBCSS and instantiate the design knowledge in prototypes for a blood donation app and a chatbot. The design principles were evaluated in a field study in South Africa. The results demonstrate the positive effects of BDBCSS on users’ intentional and developmental blood donation behavior. This study contributes to research and practice by proposing a new conceptualization of blood donation information systems support and a nascent design theory for BDBCSS that builds on behavioral theories as well as related work on blood donation information systems. Thus, the study provides valuable implications for designing preventive health BCSS by stating three design principles for a concrete application context in healthcare.

Efficiency and mass optimization for space nuclear power systems with closed Brayton cycle loops

Space nuclear power systems should be strictly limited in mass and size. Lack of detailed designs, mass estimation in the general design phase usually relies on simple and empirical models that leave too much design margin from the limits. Accurate mass estimation of space nuclear power systems is key to minimize the design margin and maximize the system performance in the general design phase. In this paper, new mass estimation models are proposed for the main components of space nuclear power systems, including nuclear reactor, shield, turbine, compressor, heat exchanger, and thermal radiator. The mass estimation models are more accurate by incorporating principles of nuclear physics, thermal hydraulics, and structural mechanics to the component designs. Combined with thermodynamic models and genetic algorithm, the MEGREZ code is developed to optimize the system performance by setting efficiency and mass as dual objectives. The code verification results indicate that the deviations between and the Jupiter Icy Moons Orbiter project parameters and the code calculated values are only 0.4% for system efficiency and 2.1% for system mass. The optimization for the Jupiter Icy Moons Orbiter project shows that the optimal molecular weight of helium-xenon mixture is the minimum value for single-stage turbomachinery limits. Additionally, the impacts of potential technological degradation, such as increased heat exchanger thermal resistances, higher frictional factors, and decreased turbomachinery efficiency, on system performances are discussed. The results show that turbomachinery efficiency presents the strongest influence on the system-specific mass; a 0.04 reduction in the polytropic efficiency of the compressor or turbine results in more than a 10% increase in system-specific mass.