How Does Escherichia coli Allocate Proteome?

Microorganisms are shown to actively partition their intracellular resources, such as proteins, for growth optimization. Recent experiments have begun to reveal molecular components unpinning the partition; however, quantitatively, it remains unclear how individual parts orchestrate to yield precise resource allocation that is both robust and dynamic. Here, we developed a coarse-grained mathematical framework that centers on guanosine pentaphosphate (ppGpp)-mediated regulation and used it to systematically uncover the design principles of proteome allocation in Escherichia coli. Our results showed that the cellular ability of resource partition lies in an ultrasensitive, negative feedback-controlling topology with the ultrasensitivity arising from zero-order amino acid kinetics and the negative feedback from ppGpp-controlled ribosome synthesis. In addition, together with the time-scale separation between slow ribosome kinetics and fast turnovers of ppGpp and amino acids, the network topology confers the organism an optimization mechanism that mimics sliding mode control, a nonlinear optimization strategy that is widely used in man-made systems. We further showed that such a controlling mechanism is robust against parameter variations and molecular fluctuations and is also efficient for biomass production over time. This work elucidates the fundamental controlling mechanism of E. coli proteome allocation, thereby providing insights into quantitative microbial physiology as well as the design of synthetic gene networks.

Rational Design of Earth-Abundant Catalysts toward Sustainability.

Catalysis is crucial for clean energy, green chemistry, and environmental remediation, but traditional methods rely on expensive and scarce precious metals. This review addresses this challenge by highlighting the promise of earth-abundant catalysts and the recent advancements in their rational design. Innovative strategies such as physics-inspired descriptors, high-throughput computational techniques, and artificial intelligence (AI)-assisted design with machine learning (ML) are explored, moving beyond time-consuming trial-and-error approaches. Additionally, biomimicry, inspired by efficient enzymes in nature, offers valuable insights. This review systematically analyses these design strategies, providing a roadmap for developing high-performance catalysts from abundant elements. Clean energy applications (water splitting, fuel cells, batteries) and green chemistry (ammonia synthesis, CO2 reduction) are targeted while delving into the fundamental principles, biomimetic approaches, and current challenges in this field. The way to a more sustainable future is paved by overcoming catalyst scarcity through rational design.

Universal Strike-Plating Strategy to Suppress Hydrogen Evolution for Improving Zinc Metal Reversibility.

The development of highly reversible zinc (Zn) metal anodes is pivotal for determining the feasibility of rechargeable aqueous Zn batteries. Our research quantitively evalulates how the hydrogen evolution reaction (HER) adversely affects Zn reversibility in batteries and emphasizes the importance of substrate design in modulating HER and its associated side reactions. When the cathodic reaction is dominated by HER, the Zn electrode exhibits low plating/stripping efficiency, characterized by extensive coverage of a passivation layer that encompasses the electrochemical inactive Zn. Therefore, we propose a strike-plating strategy that modifies the pristine substrate by initiating Zn plating at a high current density for a short time. This straightforward and effective approach has been proven to suppress hydrogen evolution and transform the electrodeposition mode into one dominated by Zn reduction. Notably, Zn metal exhibits exceptionally high average reversibility of 98.80% over 200 h on a stainless steel substrate, which was typically precluded in aqueous electrolytes because of their favorable HER capability. Additionally, our strike-plating strategy demonstrates an appliable pathway to achieve high Zn reversibility on Cu substrate, showing an average efficiency of 99.83% over 540 h at a high areal capacity of 10 mAh cm-2 and high-performance Zn full cells with low N/P ratios. This research provides a foundation for future investigations into the underlying mechanisms of HER and strategies to optimize Zn-based battery performance.

Navigating Alert Fatigue: A Case Study in Electronic Health Record Alert Design Optimization.

Clinical decision support (CDS) systems play a crucial role in enhancing patient outcomes, but inadequate design contributes to alert fatigue, inundating clinicians with disruptive alerts that lack clinical relevance. This case study delves into a quality improvement (QI) project addressing nursing electronic health record (EHR) alert fatigue by strategically redesigning four high-firing/low action alerts. Employing a mixed-methods approach, including quantitative analysis, empathy mapping sessions, and user feedback, the project sought to understand and alleviate the challenges posed by these alerts. Virtual empathy mapping sessions with clinical nurses provided valuable insights into user experiences. Qualitative findings, CDS design principles, and organizational practice expectations informed the redesign process, resulting in the removal of all four identified disruptive alerts and redesign of passive alerts. This initiative released 877 unactionable disruptive nursing hours, emphasizing the significance of proper alert design and the necessity for organizational structures ensuring sustained governance in healthcare system optimization.

Capturing Usability Problems for People Living With Dementia by Applying the DEMIGNED Principles in Usability Evaluation Methods: Mixed Methods Study.

BACKGROUND: Dementia-related impairments can cause complex barriers to access, use, and adopt digital health technologies (DHTs). These barriers can contribute to digital health inequities. Therefore, literature-based design principles called DEMIGNED have been developed to support the design and evaluation of DHTs for this rapidly increasing population. OBJECTIVE: This study aims to apply the DEMIGNED principles in usability evaluation methods to (1) capture usability problems on a mobile website providing information resources for people visiting a memory clinic, including those living with subjective cognitive decline (SCD), mild cognitive impairment (MCI), or dementia, and (2) investigate the realness of usability problems captured by the DEMIGNED principles in expert testing, specifically for mobile websites that act as a means of providing DHTs. METHODS: First, a heuristic evaluation was conducted, with the DEMIGNED principles serving as domain-specific guidelines, with 3 double experts (experienced in both usability and dementia) and 2 usability engineering experts. Second, think-aloud sessions were conducted with patients visiting a memory clinic who were living with SCD, MCI, or dementia. RESULTS: The heuristic evaluation resulted in 36 unique usability problems. A representative sample of 7 people visiting a memory clinic participated in a think-aloud session, including 4 (57%) with SCD, 1 (14%) with MCI, and 2 (29%) with dementia. The analysis of the think-aloud sessions revealed 181 encounters with usability problems. Of these encounters, 144 (79.6%) could be mapped to 18 usability problems identified in the heuristic evaluation. The remaining 37 (20.4%) encounters from the user testing revealed another 10 unique usability problems. Usability problems frequently described in the think-aloud sessions encompassed difficulties with using the search function, discrepancies between the user's expectations and the content organization, the need for scrolling, information overload, and unclear system feedback. CONCLUSIONS: By applying the DEMIGNED principles in expert testing, evaluators were able to capture 79.6% (144/181) of all usability problem encounters in the user testing of a mobile website for people visiting a memory clinic, including people living with dementia. Regarding unique usability problems, 50% (18/36) of the unique usability problems identified during the heuristic evaluation were captured by the user-testing sessions. Future research should look into the applicability of the DEMIGNED principles to other digital health functionalities to increase the accessibility of digital health and decrease digital health inequity for this complex and rapidly increasing population.

Physiochemically and Genetically Engineered Bacteria: Instructive Design Principles and Diverse Applications.

With the comprehensive understanding of microorganisms and the rapid advances of physiochemical engineering and bioengineering technologies, scientists are advancing rationally-engineered bacteria as emerging drugs for treating various diseases in clinical disease management. Engineered bacteria specifically refer to advanced physiochemical or genetic technologies in combination with cutting edge nanotechnology or physical technologies, which have been validated to play significant roles in lysing tumors, regulating immunity, influencing the metabolic pathways, etc. However, there has no specific reviews that concurrently cover physiochemically- and genetically-engineered bacteria and their derivatives yet, let alone their distinctive design principles and various functions and applications. Herein, the applications of physiochemically and genetically-engineered bacteria, and classify and discuss significant breakthroughs with an emphasis on their specific design principles and engineering methods objective to different specific uses and diseases beyond cancer is described. The combined strategies for developing in vivo biotherapeutic agents based on these physiochemically- and genetically-engineered bacteria or bacterial derivatives, and elucidated how they repress cancer and other diseases is also underlined. Additionally, the challenges faced by clinical translation and the future development directions are discussed. This review is expected to provide an overall impression on physiochemically- and genetically-engineered bacteria and enlighten more researchers.

Material Engineering Strategies for Efficient Hydrogen Evolution Reaction Catalysts.

Water electrolysis, a key enabler of hydrogen energy production, presents significant potential as a strategy for achieving net-zero emissions. However, the widespread deployment of water electrolysis is currently limited by the high-cost and scarce noble metal electrocatalysts in hydrogen evolution reaction (HER). Given this challenge, design and synthesis of cost-effective and high-performance alternative catalysts have become a research focus, which necessitates insightful understandings of HER fundamentals and material engineering strategies. Distinct from typical reviews that concentrate only on the summary of recent catalyst materials, this review article shifts focus to material engineering strategies for developing efficient HER catalysts. In-depth analysis of key material design approaches for HER catalysts, such as doping, vacancy defect creation, phase engineering, and metal-support engineering, are illustrated along with typical research cases. A special emphasis is placed on designing noble metal-free catalysts with a brief discussion on recent advancements in electrocatalytic water-splitting technology. The article also delves into important descriptors, reliable evaluation parameters and characterization techniques, aiming to link the fundamental mechanisms of HER with its catalytic performance. In conclusion, it explores future trends in HER catalysts by integrating theoretical, experimental and industrial perspectives, while acknowledging the challenges that remain.

Design Principles Guided by DFT Calculations and High-Throughput Frameworks for the Discovery of New Diamond-like Chalcogenide Thermoelectric Materials.

Rational design principles are one pathway to discovering new materials. However, technological breakthroughs rarely occur in this way because these design principles are usually based on incremental advances that seldom lead to disruptive applications. The emergence of machine-learning (ML) and high-throughput (HT) techniques has changed the paradigm, opening up new possibilities for efficiently screening large chemical spaces and creating on-the-fly design principles for the discovery of novel materials with desired properties. In this work, the approach is used to discover novel thermoelectric (TE) materials based on quaternary diamond-like chalcogenides. A HT framework that integrates density functional theory calculations, ML, and the solution of the Boltzmann transport equation is used to efficiently rationalize the transport properties of these compounds and identify those with potential as TE materials, achieving ZT values above 2.

Rational design of bimetallic MBene for efficient electrocatalytic nitrogen reduction.

Electrocatalytic nitrogen reduction reaction (NRR) is one of the most promising approaches to achieving green and efficient NH3 production. However, the designs of efficient NRR catalysts with high activity and selectivity still are severely hampered by inherent linear scaling relations among the adsorption energies of NRR intermediates. Herein, the properties of ten M3B4 type MBenes have been initially investigated for efficient N2 activation and reduction to NH3via first-principles calculations. We highlight that Cr3B4 MBene possesses remarkable NRR activity with a record-low limiting potential (-0.13 V). Then, this work proposes descriptor-based design principles that can effectively evaluate the catalytic activity of MBenes, which have been further employed to design bimetallic M2M'B4 MBenes. As a result, 5 promising candidates including Ti2YB4, V2YB4, V2MoB4, Nb2YB4, and Nb2CrB4 with excellent NRR performance have been extracted from 20 bimetallic MBenes. Further analysis illuminates that constructing bimetallic MBenes can selectively tune the adsorption strength of NHNH2** and NH2NH2**, and break the linear scaling relations between their adsorption energies, rendering them ideal for NRR. This work not only pioneers the application of MBenes as efficient NRR catalysts but also proposes rational design principles for boosting their catalytic performance.

Design Principles and Mechanistic Understandings of Non-Noble-Metal Bifunctional Electrocatalysts for Zinc-Air Batteries.

Zinc-air batteries (ZABs) are promising energy storage systems because of high theoretical energy density, safety, low cost, and abundance of zinc. However, the slow multi-step reaction of oxygen and heavy reliance on noble-metal catalysts hinder the practical applications of ZABs. Therefore, feasible and advanced non-noble-metal electrocatalysts for air cathodes need to be identified to promote the oxygen catalytic reaction. In this review, we initially introduced the advancement of ZABs in the past two decades and provided an overview of key developments in this field. Then, we discussed the working mechanism and the design of bifunctional electrocatalysts from the perspective of morphology design, crystal structure tuning, interface strategy, and atomic engineering. We also included theoretical studies, machine learning, and advanced characterization technologies to provide a comprehensive understanding of the structure-performance relationship of electrocatalysts and the reaction pathways of the oxygen redox reactions. Finally, we discussed the challenges and prospects related to designing advanced non-noble-metal bifunctional electrocatalysts for ZABs.

Design Principles for Biological Adaptation: A Systems and Control-Theoretic Treatment.

Establishing a mapping between (from and to) the functionality of interest and the underlying network structure (design principles) remains a crucial step toward understanding and design of bio-systems. Perfect adaptation is one such crucial functionality that enables every living organism to regulate its essential activities in the presence of external disturbances. Previous approaches to deducing the design principles for adaptation have either relied on computationally burdensome brute-force methods or rule-based design strategies detecting only a subset of all possible adaptive network structures. This chapter outlines a scalable and generalizable method inspired by systems theory that unravels an exhaustive set of adaptation-capable structures. We first use the well-known performance parameters to characterize perfect adaptation. These performance parameters are then mapped back to a few parameters (poles, zeros, gain) characteristic of the underlying dynamical system constituted by the rate equations. Therefore, the performance parameters evaluated for the scenario of perfect adaptation can be expressed as a set of precise mathematical conditions involving the system parameters. Finally, we use algebraic graph theory to translate these abstract mathematical conditions to certain structural requirements for adaptation. The proposed algorithm does not assume any particular dynamics and is applicable to networks of any size. Moreover, the results offer a significant advancement in the realm of understanding and designing complex biochemical networks.

Multimedia design for learner interest and achievement: a visual guide to pharmacology.

BACKGROUND: Medical education increasingly relies on digital learning materials. Despite recognition by the Association of American Medical Colleges Institute for Improving Medical Education, medical education design often fails to consider quality multimedia design principles. Further, the AAMC-IIME issued a call to study the role of design principles in medical education. Thus, the current study investigated the cognitive and affective effects of redesigning PowerPoint slides used to support pharmacology content during the preclinical years of medical school training. METHODS: Researchers implemented a quasi-experimental design, using traditionally-designed (original) slides with a Traditional group (n = 100) and slides redesigned to follow principles from the Cognitive Theory of Multimedia Learning with an Experimental group (n = 40). Participants in the Experimental group completed a post-survey incorporating the Situational Interest Survey for Multimedia to indicate motivational engagement with the media. Students in the Experimental group also responded to additional preference questions. Researchers analyzed survey responses and students' scores in pharmacology-related coursework across the preclinical Foundations Phase of training to determine the impact on achievement and motivation. RESULTS: Findings related to learner achievement showed a modest but significant increase in the Experimental group compared to the Traditional group in the Cardiac, Pulmonary, and Renal (CPR) educational block (105%, normalized to Traditional group, p = 0.013) and cumulative pharmacology grades (101%, normalized to Traditional group, p = 0.043). Additionally, participants in the Experimental group indicated a significantly higher average triggered situational interest in redesigned slides (M = 4.85, SD = 0.25) than the original slides (M = 3.23, SD = 1.40, t=-6.33, p < 0.001). Similarly, the interest rating of the redesigned slides (M = 4.87, SD = 0.24) was significantly greater than that of the original slides (M = 3.89, SD = 0.86, t=-6.824, p < 0.001). Moreover, results further indicated significant differences in the maintained-feeling and maintained-value constructs, and all participants in the Experimental group indicated a preference for the redesigned slides. CONCLUSIONS: The findings provide strong evidence in support of using the Cognitive Theory of Multimedia Learning design principles to intentionally design media in medical education. In addition to increased achievement scores, students in the Experimental group demonstrated significantly higher levels of situational interest in the redesigned slides, especially triggered interest and maintained-feeling interest. Medical education learning designers should seriously consider redesigning media to achieve similar results.

Tibial fractures treated with mono-lateral fixation: Principles of design and application.

This paper presents the outcome of a data review of patients treated with the IOS external fixation system at the Royal Stoke University Hospital: a fixation designed to meet four requirements for external fixation proposed in this paper. Demographic data and outcome were collected and assessed. From 69 initial patients, 64 patients (55 males and 9 females) had an average age of 35.9 years. The mean time to union was 127 days. There were no incidences of malunion, or refracture post fixation removal attributable to the treatment method. In addition, in this cohort, there was no incidence of pin tract infection resulting in osteomyelitis. Of all the factors assessed the only factor to have any significant effect on healing was smoking: an average delay of 31 days. An examination of RUST (radiographic union score tibia) and modified RUST scores illustrated a potential false negative of up to 80%. Hence, this study cannot support the use of either scoring system to diagnose fracture healing. IOS external fixation was shown to be an effective method for the treatment of unstable tibial fractures. The reduction at fixation removal was shown to be very good. There was no incidence of osteomyelitis. It is, therefore, suggested that appropriately used external fixation is a viable alternative to intramedullary nailing if designed and surgically applied using four design principles outlined in this paper. Furthermore, it is proposed that external fixation be designed and applied to meet these four principles.

Effects of In-Vehicle Touchscreen Location on Driver Task Performance, Eye Gaze Behavior, and Workload During Conditionally Automated Driving: Nondriving-Related Task and Take-Over.

OBJECTIVE: This study investigated the effects of nondriving-related task (NDRT) touchscreen location and NDRT difficulty level on the driver task performance, eye gaze behavior, and workload during SAE Level 3 conditionally automated driving. Two driver tasks were considered: a visuomanual NDRT and a take-over task. BACKGROUND: Touchscreens are expected to play important roles inside automated vehicles. However, few studies have investigated the driver-touchscreen interaction during automated driving. METHOD: A driving simulator experiment was conducted. The experimental task consisted of two successive subtasks: an NDRT followed by a take-over task. NDRT touchscreen location (Upper Left, Upper Right, and Lower Right) and NDRT difficulty level (Easy and Hard) were the independent variables. A set of driver task performance, eye gaze behavior, and perceived workload measures were employed for each subtask as the dependent variables. RESULTS: NDRT touchscreen location significantly affected both the NDRT and the take-over task performance. Lower Right was superior to Upper Right in the NDRT performance but was inferior in the take-over task performance. NDRT touchscreen location affected the perceived physical workload of the NDRT. NDRT difficulty level affected the perceived workload of the take-over task. CONCLUSION: The research findings enhance our understanding of how NDRT touchscreen location and NDRT difficulty level impact the driver task performance during conditionally automated driving, and, further provide useful design implications and knowledge. APPLICATION: The study results would inform the NDRT touchscreen interface design and the NDRT design for conditionally automated vehicles.

A Distinctive Insight into Inorganic Sonosensitizers: Design Principles and Application Domains.

Sonodynamic therapy (SDT) as a promising non-invasive anti-tumor means features the preferable penetration depth, which nevertheless, usually can't work without sonosensitizers. Sonosensitizers produce reactive oxygen species (ROS) in the presence of ultrasound to directly kill tumor cells, and concurrently activate anti-tumor immunity especially after integration with tumor microenvironment (TME)-engineered nanobiotechnologies and combined therapy. Current sonosensitizers are classified into organic and inorganic ones, and current most reviews only cover organic sonosensitizers and highlighted their anti-tumor applications. However, there have few specific reviews that focus on inorganic sonosensitizers including their design principles, microenvironment regulation, etc. In this review, inorganic sonosensitizers are first classified according to their design rationales rather than composition, and the action rationales and underlying chemistry features are highlighted. Afterward, what and how TME is regulated based on the inorganic sonosensitizers-based SDT nanoplatform with an emphasis on the TME targets-engineered nanobiotechnologies are elucidated. Additionally, the combined therapy and their applications in non-cancer diseases are also outlined. Finally, the setbacks and challenges, and proposed the potential solutions and future directions is pointed out. This review provides a comprehensive and detailed horizon on inorganic sonosensitizers, and will arouse more attentions on SDT.

"Covalent-Disassembly"-Based Approaches For Sensing Applications.

The detection of analytes with small molecular probes is crucial for the analysis and understanding of chemical, medicinal, environmental and biological situations as well as processes. Classic detection approaches rely on the concept of molecular recognition and bond formation reactions. Bond breakage reactions have been less explored in similar contexts. This concept article introduces metal-salen and metal-imine complexes as "covalent-disassembly"-based (DB)-probes for detecting polyoxophosphates, thiols, amino acids, HCN and changes in pH. It discusses the roles, importance and combinations of structurally functionalized molecular building blocks in the construction of DB-probes. Applications of optimized DB-probes for analyte detection in live cells and foodstuff are also discussed. Furthermore, the mechanism of the disassembly of a Fe(III)-salen probe upon pyrophosphate binding is presented. Extraordinary selectivity for this analyte was achieved by a multistep disassembly sequence including an unprecedented structural change of the metal complex (i. e. "induced-fit" principle). Design principles of probes for sensing applications following the "covalent-disassembly" approach are summarized, which will help improving current systems, but will also facilitate the development of new DB-probes for challenging analytic targets.

Atomic-Level Regulation of Cu-Based Electrocatalyst for Enhancing Oxygen Reduction Reaction: From Single Atoms to Polymetallic Active Sites.

The slow kinetics of cathodic oxygen reduction reactions (ORR) in fuel cells and the high cost of commercial Pt-based catalysts limit their large-scale application. Cu-based single-atom catalysts (SACs) have received increasing attention as a promising ORR catalyst due to their high atom utilization, high thermodynamic activity, adjustable electronic structure, and low cost. Herein, the recent research progress of Cu-based catalysts is reviewed from single atom to polymetallic active sites for ORR. First, the design and synthesis method of Cu-based SACs are summarized. Then the atomic-level structure regulation strategy of Cu-based catalyst is proposed to improve the ORR performance. The different ORR catalytic mechanism based on the different Cu active sites is further revealed. Finally, the design principle of high-performance Cu-based SACs is proposed for ORR and the opportunities and challenges are further prospected.

Pillars of theoretical biology: "Biochemical systems analysis, I, II and III".

Michael Savageau's Biochemical Systems Analysis I, II, IIIpapers, published in volumes 25 and 26 of the journal,kickstarted a research programme that originated many of the core concepts and tools of Systems Biology. This article briefly summarizes these papers anddiscusses the most relevant developments in Biochemical Systems Theory since their publication.

A unified approach to dissecting biphasic responses in cell signaling.

Biphasic responses are encountered at all levels in biological systems. At the cellular level, biphasic dose-responses are widely encountered in cell signaling and post-translational modification systems and represent safeguards against overactivation or overexpression of species. In this paper, we provide a unified theoretical synthesis of biphasic responses in cell signaling systems, by assessing signaling systems ranging from basic biochemical building blocks to canonical network structures to well-characterized exemplars on one hand, and examining different types of doses on the other. By using analytical and computational approaches applied to a range of systems across levels (described by broadly employed models), we reveal (i) design principles enabling the presence of biphasic responses, including in almost all instances, an explicit characterization of the parameter space (ii) structural factors which preclude the possibility of biphasic responses (iii) different combinations of the presence or absence of enzyme-biphasic and substrate-biphasic responses, representing safeguards against overactivation and overexpression, respectively (iv) the possibility of broadly robust biphasic responses (v) the complete alteration of signaling behavior in a network due to biphasic interactions between species (biphasic regulation) (vi) the propensity of different co-existing biphasic responses in the Erk signaling network. These results both individually and in totality have a number of important consequences for systems and synthetic biology.

Examining the effectiveness of gamification as a tool promoting teaching and learning in educational settings: a meta-analysis.

The integration of gamification into educational settings has gained recognition for its potential to boost student motivation, engagement, interest, and learning outcomes. Despite its popularity, research on gamification has produced mixed results regarding student learning outcomes. This meta-analysis aims to synthesize the existing empirical evidence on the effectiveness of gamification as a tool for promoting teaching and learning in educational settings. Forty-one studies with 49 independent samples involving more than 5,071 participants were included in our analysis. Results from random effects models showed an overall significant large effect size (g = 0.822 [0.567 to 1.078]). The research performed the moderator analysis to scrutinize the effects of a number of factors on the relationship between gamification and student learning outcomes. The study uncovered significant moderating effects for user type, educational discipline, design principles for educational gamification, duration of "gameful" experience, and learning environment. However, measurement of student outcomes and publication type did not appear to have any significant moderating effect. Those findings hold important implications for improving and implementing gamification to promote teaching and learning in future research.