Hub Structure Research Articles

Optimization of hub geometry of a double suction pump as a turbine

The double suction pump as a turbine plays an increasingly important role in energy recovery and hydropower generation due to its stable operation and simple structure. Therefore, optimization research on it is of great significance. In this article, the unique design of the hub structure in double suction pumps consisting of conventional half hubs is proposed to be modified to extend the hub until the outer diameter and analyzed. Numerical calculations based on the shear stress transport (SST) k-ω model and verified by experiments show that the full hub impeller exhibited superior hydraulic performance, with an efficiency about 1%–2% higher than the half hub impeller under all operating conditions. Entropy production theory is employed to analyze energy losses, we found that full hub impellers, compared to half hub models, significantly reduce energy loss, with a maximum reduction of about 5.45%. In addition, the full hub impeller reduces turbulence losses up to 5.32% on the one hand and increases friction losses up to 4.52% on the other hand, but turbulence losses account for a larger proportion of the total losses, so the overall efficiency is improved.

Vocabulary mapping for archaeological infrastructure

This article reports and reflects on vocabulary mapping techniques, tools and experience from the ARIADNE European archaeological infrastructure projects, where the widely differing terminology of subject indexing in the different partner languages posed significant challenges for effective data integration. The Getty Art & Architecture Thesaurus is employed as a central spine vocabulary for partners to map their native vocabularies and term lists – a hub structure enables a multilingual search capability via vocabulary mapping. Mappings are expressed via SKOS mapping relationships and output as structured JSON for use in the overall data aggregation process and in the ARIADNE portal. The approach followed offers some automatic support for final intellectual judgement. The method can be characterised as providing lexical support in an interactive tool that aims to intuitively visualise semantic context. The experience of partners in producing the vocabulary mappings is discussed in light of previous work in this area. Reflections on lessons learned both for the immediate project and for vocabulary mapping in general contribute to the conclusions. Future search functionality could take account of available vocabulary mappings via a range of search options, such as query expansion including compound mappings and mapping types. Further work on mapping guidelines and metadata is recommended.

Bionic Optimization Design and Fatigue Life Prediction of a Honeycomb-Structured Wheel Hub.

The wheel hub is an important component of the wheel, and a good hub design can significantly improve vehicle handling, stability, and braking performance, ensuring safe driving. This article optimized the hub structure through morphological aspects, where reducing the hub weight contributed to enhanced fuel efficiency and overall vehicle performance. By referencing honeycombed structures, a bionic hub design is numerically simulated using finite element analysis and response surface optimization. The results showed that under the optimization of the response surface analytical model, the maximum stress of the optimized bionic hub was 109.34 MPa, compared to 119.77 MPa for the standard hub, representing an 8.7% reduction in maximum stress. The standard hub weighs 34.02 kg, while the optimized hub weight was reduced to 29.89 kg, a decrease of 12.13%. A fatigue analysis on the optimized hub indicated that at a stress of 109.34 MPa, the minimum load cycles were 4.217 × 105 at the connection point with the half-shaft, meeting the fatigue life requirements for commercial vehicle hubs outlined in the national standard GB/T 5334-2021.

Instability and Evolution of Shocked Clouds Formed by Orthogonal Collisions between Magnetized Filamentary Molecular Clouds

Filamentary molecular clouds are recognized as primary sites for the formation of stars. Specifically, regions characterized by the overlapping point of multiple filaments, known as hub regions, are often associated with active star formation. However, the formation mechanism of this hub structure is not well understood. Therefore, to understand the formation mechanism and star formation in hub structures, as a first step, we investigate the orthogonal collisions between two filaments using three-dimensional ideal magnetohydrodynamical simulations. As a model of initial filaments, we use an infinitely long filament in magnetohydrostatic equilibrium under a global magnetic field running perpendicular to the filament axis. Two identical equilibrium filaments, sharing the same magnetic flux, are arranged with their long axes perpendicular to each other and given an initial velocity perpendicular to their long axes to replicate an orthogonal collision. We find three types of evolution after the shocked cloud is formed: collapse, stable, and expansion modes. The energy balance just after the filaments completely collide explains the future evolution of the shocked cloud. If the magnitude of gravitational energy is larger than the sum of the kinetic, thermal, and magnetic energies, the shocked cloud evolves in collapse mode. If the magnitude of gravitational energy is less than the sum of these energies, the cloud evolves in stable mode when the kinetic energy is relatively small and in expansion mode when the kinetic energy is sufficiently large.

Enhancing energy hub efficiency through advanced modelling and optimization techniques: A case study on micro-refinery output products and parking lot integration

A new model of energy carriers (micro-refinery output products) in the concept of an energy hub is presented. In addition, in the presented model, the effect of different models of parking lot in an energy hub is analyzed. In this study, the uncertainty of the number of electric vehicles was modeled using the Monte Carlo method, and then considering the same conditions, the uncertainty of the number of electric vehicles was calculated using the Probability-Possibility hybrid method. In addition, the study uses a scenario-based approach to address uncertainties related to multi-carrier energy demand and multi-carrier energy prices. In the present paper, ensuring water demand is of great importance, which is why the proposed energy hub structure of a sea desalination unit and sour water treatment that is extracted from the micro refinery output was analyzed. The optimization model presented in this paper for the energy hub is a complex integer linear programming (MILP) that is solved using a CPLEX solver in the GAMS environment. The results show that the use of the Probability-Possibility method resulted in an 8 % reduction in the final energy supply cost in the energy hub compared to the Monte Carlo method.

Bridging the gap: national virtual education programme for professionals caring for adults with intellectual and developmental disabilities at the time of COVID-19.

The COVID-19 pandemic significantly impacted the mental health of adults with intellectual and developmental disabilities (IDD). During this period of uncertainty and need for up-to-date information, various virtual training programmes demonstrated the role of tele-mentoring programmes. The aim of this paper is to describe the educational evaluation of the National Extension for Community Healthcare Outcomes - Adults with Intellectual and Developmental Disabilities (ECHO-AIDD), a programme for service providers working with adults with IDD during COVID-19. The programme consisted of six sessions, conducted weekly, over two cycles. Each session included didactic teaching by hub team members, COVID-19 news updates, wellness check-ins and a brief mindfulness activity, followed by a 30 to 45 min case-based discussion. The hub structure had an inter-professional approach to team expertise. Those with lived experience were an integral part of the content experts' hub. Pre-, post- and follow-up evaluation data were collected. Care providers from health and social care sectors (n = 230) participated in the programme. High levels of engagement and satisfaction were reported. Self-efficacy ratings improved from pre- to post-, and were maintained at 8-week follow-up; improvement from pre- to post- was significant (P < 0.0001). Exposure to National ECHO-AIDD educational intervention led to improvement in perceived competencies. This study also shows the valuable role of people with lived experience in fostering adaptive expertise in learners. The outreach and scalability support the feasibility of building a national virtual community of practice for IDD service providers. Future studies should focus on studying the impact of these programmes on the health outcomes of people with IDD.

Hub stability in the calcium calmodulin-dependent protein kinase II

The calcium calmodulin protein kinase II (CaMKII) is a multi-subunit ring assembly with a central hub formed by the association domains. There is evidence for hub polymorphism between and within CaMKII isoforms, but the link between polymorphism and subunit exchange has not been resolved. Here, we present near-atomic resolution cryogenic electron microscopy (cryo-EM) structures revealing that hubs from the α and β isoforms, either standalone or within an β holoenzyme, coexist as 12 and 14 subunit assemblies. Single-molecule fluorescence microscopy of Venus-tagged holoenzymes detects intermediate assemblies and progressive dimer loss due to intrinsic holoenzyme lability, and holoenzyme disassembly into dimers upon mutagenesis of a conserved inter-domain contact. Molecular dynamics (MD) simulations show the flexibility of 4-subunit precursors, extracted in-silico from the β hub polymorphs, encompassing the curvature of both polymorphs. The MD explains how an open hub structure also obtained from the β holoenzyme sample could be created by dimer loss and analysis of its cryo-EM dataset reveals how the gap could open further. An assembly model, considering dimer concentration dependence and strain differences between polymorphs, proposes a mechanism for intrinsic hub lability to fine-tune the stoichiometry of αβ heterooligomers for their dynamic localization within synapses in neurons.

Dynamical changes of interaction across functional brain communities during propofol-induced sedation.

It is crucial to understand how anesthetics disrupt information transmission within the whole-brain network and its hub structure to gain insight into the network-level mechanisms underlying propofol-induced sedation. However, the influence of propofol on functional integration, segregation, and community structure of whole-brain networks were still unclear. We recruited 12 healthy subjects and acquired resting-state functional magnetic resonance imaging data during 5 different propofol-induced effect-site concentrations (CEs): 0, 0.5, 1.0, 1.5, and 2.0μg/ml. We constructed whole-brain functional networks for each subject under different conditions and identify community structures. Subsequently, we calculated the global and local topological properties of whole-brain network to investigate the alterations in functional integration and segregation with deepening propofol sedation. Additionally, we assessed the alteration of key nodes within the whole-brain community structure at each effect-site concentrations level. We found that global participation was significantly increased at high effect-site concentrations, which was mediated by bilateral postcentral gyrus. Meanwhile, connector hubs appeared and were located in posterior cingulate cortex and precentral gyrus at high effect-site concentrations. Finally, nodal participation coefficients of connector hubs were closely associated to the level of sedation. These findings provide valuable insights into the relationship between increasing propofol dosage and enhanced functional interaction within the whole-brain networks.

Alterations in the hub structure of whole-brain functional networks in patients with drug-naïve schizophrenia: Insights from electroencephalography-based research.

This study aimed to identify atypical hubs in the whole-brain networks of patients with schizophrenia (SZ) and examine the effects of antipsychotic medications, using electroencephalography (EEG) data. We estimated the functional connectivity across all electrodes by applying the phase lag index to the EEG signals of 21 drug-naïve patients with SZ and 31 age-matched healthy controls. Betweenness centrality (BC), a measure of hub status, was calculated for each electrode and frequency band. Data from 14 patients were re-evaluated after initiating treatment with antipsychotic medications. BC values decreased significantly at the Fz site in the beta band, decreased significantly at Pz in the gamma band, and increased significantly at O1 in the gamma band among patients with SZ. These changes persisted after antipsychotic treatment and were unrelated to clinical symptoms. The abnormal hub topology we observed, especially in the high-frequency band, may reflect the pathophysiology of SZ, and this study highlights the utility of BC analysis of EEG data for detecting alterations in the whole-brain networks of patients with SZ.

Hetero-grafting affects flavonoid biosynthesis in sweet orange 'Newhall' (Citrus sinensis) peels: a metabolomics and transcriptomics analysis.

Citrus cultivation involves the widespread practice of grafting, which has a significant impact on citrus development and fruit quality and yield. However, understanding the effect of flavonoid compounds after different rootstock grafting have been limited. Flavonoid compounds, found at the highest levels in citrus peels, contribute to improving fruit quality and nutritional value. In this study, scion-rootstock interaction was investigated at various developmental stages when sweet orange 'Newhall' was hetero-grafted with two commonly used rootstocks (Poncirus trifoliate population, C. junos Siebold ex Tanaka). Physiological index detection showed a higher concentration of total flavonoid content in peels of sweet orange 'Newhall' grafted on Poncirus trifoliate population (ct) than C. junos Siebold ex Tanaka (cj). Further metabolomic analysis identified 703 flavonoid compounds, including flavones, flavonols, and flavanones. Out of the 25 flavonoids affected by different rootstock grafting and developmental stages, most were flavones. Transcriptomic analysis identified 8,562 differentially expressed genes (DEGs). Co-expression and Pearson's correlation analysis discovered six hub structure genes and 19 transcription factors (TFs) that affected flavonoid biosynthesis. In addition to increasing the transcript levels of genes that synthesize flavones, flavonols, and flavanones, the scion-rootstock interaction also affected the expression of many TFs. Taken together, our findings suggested that hetero-grafting could promote the accumulation of flavonoid compounds in citrus peels during the development stages. These results offered fresh perspectives on grafting's application usefulness and the enhancement of the accumulation of nutritive flavonoid components by grafting in citrus.

An optimization approach to financial and operational viabilities of spare aircraft

PurposeThe airlines cancel their flights frequently because of factors that they do not have any control over. Spare aircraft can potentially address some of the issues caused by cancelled flights. This paper aims to offer an exploratory study into the financial and operational viabilities of spare aircraft for airlines.Design/methodology/approachMathematical models are proposed to evaluate the financial and operational metrics under different scenarios. The models are applied to Delta, Spirit and Southwest Airlines with different business models. All data are extracted from US Bureau of Transport Statistics, Cirium Diio Mi and CAPA databases. The IBM Cplex solver was used to execute the binary linear program models.FindingsThe research revealed that factors such as airline network size, hub and spoke structure and average weekly flight cancellations are crucial in establishing the need for spare aircraft. For the number of weekly cancellations, there exist break-even values that reasonably justify spare aircraft.Practical implicationsModels can be customized and applied to other modes of transportations.Originality/valueThis study is the first to consider the use of spare aircraft in airlines from both financial and operational perspectives within the scope of the mathematical model. The analyses identify financial break-even points for a number of spare aircraft and their home base locations for three airlines. Operational utilization of spare aircraft is studied and contrasted with financial metrics.

P285 DESIGN OF A NETWORK FOR THE IN–SERVICE MANAGEMENT OF ACUTE CORONARY SYNDROMES IN THE PROVINCE OF TERAMO

Abstract Acute Coronary Syndrome (ACS) are events due to the rupture/erosion of a coronary atherosclerotic plaque, with activation of the coagulation cascade and critical reduction of the flow, which is expressed in a spectrum of clinical scenario ranging from infarction with ST elevation (STEMI)1, to non ST elevation ACS (NSTE–ACS)2. Timely reperfusion therapy, either pharmacological or via percutaneous coronary intervention (PCI)1, is indicated for patients with STEMI. Patients with NSTE–ACS should undergo initial risk stratification, followed by invasive evaluation, depending on the patient‘s risk profile2. (Figure 1). It is necessary to create an effective network among hospitals, to make available the fastest and most effective therapy for the greatest number of patients with ACS. The European Society of Cardiology (ESC) guidelines suggest the implementation of such regional networks1. Achieving this goal is possible only by sharing a common protocol. The province of Teramo was equipped with a cardiological network in 2011. There are 2 simple structures, a structure with a spoke CCU (Giulianova) and the Hub structure with CCU and Cath–lab (Teramo). The simple structures refer to the Hub center when direct access to cath–lab is required and to spoke CCU for those patients who do not require immediate coronary angiography. Spoke CCU unit refers to Hub center for the access of patients with ACS to the cath–lab3. On the basis of epidemiological data4 it can be expected that in the province of Teramo there are about 230–250 STEMI and 450–500 NSTE–ACS/year. Teramo‘s cath–lab performed 248 primary PCIs on STEMI, and 390 PCIs on NSTE–ACS. In the spoke CCU in 2021, there were 1005 patients hospitalized with ACS. Almost all of them were transferred/transported for coronary angiography according to risk stratification. There were 326 patients discharged with a diagnosis of ACS undergoing PCI. That data made it necessary to transport the patient in hemodynamics for angiography study and interventional procedure, and possible retransfer to the spoke center. This strategy is called service. The advantages and safety of this procedure have already been described7. The implementation of service strategy would make a clear increase in interventional procedures foreseeable (ideally the approximately 100 patients with ACS accessing the Spoke CCU should undergo PCI with adequate timing in 70% of cases) and an optimization of work for the centers and of patient care.

Modeling complex interactions in a disrupted environment: Relational events in the WTC response

AbstractWhen subjected to a sudden, unanticipated threat, human groups characteristically self-organize to identify the threat, determine potential responses, and act to reduce its impact. Central to this process is the challenge of coordinating information sharing and response activity within a disrupted environment. In this paper, we consider coordination in the context of responses to the 2001 World Trade Center (WTC) disaster. Using records of communications among 17 organizational units, we examine the mechanisms driving communication dynamics, with an emphasis on the emergence of coordinating roles. We employ relational event models (REMs) to identify the mechanisms shaping communications in each unit, finding a consistent pattern of behavior across units with very different characteristics. Using a simulation-based “knock-out” study, we also probe the importance of different mechanisms for hub formation. Our results suggest that, while preferential attachment and pre-disaster role structure generally contribute to the emergence of hub structure, temporally local conversational norms play a much larger role in the WTC case. We discuss broader implications for the role of microdynamics in driving macroscopic outcomes, and for the emergence of coordination in other settings.

Hub structure in functional network of EEG signals supporting high cognitive functions in older individuals.

Maintaining high cognitive functions is desirable for "wellbeing" in old age and is particularly relevant to a super-aging society. According to their individual cognitive functions, optimal intervention for older individuals facilitates the maintenance of cognitive functions. Cognitive function is a result of whole-brain interactions. These interactions are reflected in several measures in graph theory analysis for the topological characteristics of functional connectivity. Betweenness centrality (BC), which can identify the "hub" node, i.e., the most important node affecting whole-brain network activity, may be appropriate for capturing whole-brain interactions. During the past decade, BC has been applied to capture changes in brain networks related to cognitive deficits arising from pathological conditions. In this study, we hypothesized that the hub structure of functional networks would reflect cognitive function, even in healthy elderly individuals. To test this hypothesis, based on the BC value of the functional connectivity obtained using the phase lag index from the electroencephalogram under the eyes closed resting state, we examined the relationship between the BC value and cognitive function measured using the Five Cognitive Functions test total score. We found a significant positive correlation of BC with cognitive functioning and a significant enhancement in the BC value of individuals with high cognitive functioning, particularly in the frontal theta network. The hub structure may reflect the sophisticated integration and transmission of information in whole-brain networks to support high-level cognitive function. Our findings may contribute to the development of biomarkers for assessing cognitive function, enabling optimal interventions for maintaining cognitive function in older individuals.

A New Hybrid Multi-Objective Scheduling Model for Hierarchical Hub and Flexible Flow Shop Problems

In general, customers are looking to receive their orders in the fastest time possible and to make purchases at a reasonable price. Consequently, the importance of having an optimal delivery time is increasingly evident these days. One of the structures that can meet the demand for large supply chains with numerous orders is the hierarchical integrated hub structure. Such a structure improves efficiency and reduces chain costs. To make logistics more cost-effective, hub-and-spoke networks are necessary as a means to achieve economies of scale. Many hub network design models only consider hub type but do not take into account the hub scale measured using freight volume. This paper proposes a multi-objective scheduling model for hierarchical hub structures (HHS), which is layered from top to bottom. In the third layer, the central hub takes factory products from decentralized hubs and sends them to other decentralized hubs to which customers are connected. In the second layer, non-central hubs are responsible for receiving products from the factory and transferring them to central hubs. These hubs are also responsible for receiving products from central hubs and sending them to customers. Lastly, the first layer contains factories responsible for producing products and providing for their customers. The factory uses the flexible flow-shop platform and structure to produce its products. The model’s objective is to minimize transportation and production costs as well as product arrival times. To validate and evaluate the model, small instances have been solved and analyzed in detail with the weighted sum and ε-constraint method. Consequently, based on the mean ideal distance (MID) metric, two methods were compared for the designed instances.

Optimal operation framework of an energy hub with combined heat, hydrogen, and power (CHHP) system based on ammonia

With the growth of renewable energy sources, the operation of multi-energy systems, such as energy hubs has greatly interested researchers in recent years. In addition to common energy carriers, the role of hydrogen will also be essential in the future energy roadmap. This article proposes an energy hub structure based on ammonia fuel and other sources, such as solar, wind, and natural gas, as a combined heat, hydrogen, and power system, with various converters and energy storage systems to supply electricity, thermal, and hydrogen demands. Then, an optimal stochastic framework for the daily operation of this energy hub, considering electrical and thermal demand response programs, is presented. Another major contribution of this article is the comparison of four other structures to show the effectiveness of the proposed energy hub; in such a way, the existence of various elements, especially fuel cell and electrolyzer, are evaluated. Simulation of case studies using data from Finland shows that the proposed structure with the ammonia carrier has reduced operating costs by about 16.8%; so that 15.9% of the amount of gas purchased from the network decreased, but the sale of electricity to the upstream network has increased by 45% compared to the base case.

The German national public health institute’s journey to becoming a Key Climate Actor: The Robert Koch Institute’s strategy development process

Abstract The Robert Koch Institute (RKI) is Germany's national public health institute. It has been working for a number of years on One Health topics such as zoonotic diseases and antimicrobial resistance, as well as wider areas relevant to climate change such as environmental health. Climate change has, however, only been a specific area of focus since 2019. This was signalled through the creation of a coordination role called One Health Climate Change (OHCC). In addition, a number of projects on climate change have been initiated independently of one another during this time across the RKI. Since summer 2021, RKI has been more active in its strategic development and set up a climate change and health working group of over 50 members of staff representing all departments. This offers a hub structure for pulling the relevant work and activities together under one umbrella, thereby promoting exchange, cooperation and cohesion across RKI. The RKI is currently at an early and dynamic phase in its journey as a key Climate Actor. It is developing a strategy on the topic, guided by the “IANPHI Roadmap for Action on Health and Climate Change” in order to further strengthen its contribution in this area. This presentation will share how RKI has developed its strategy and its action plan for implementation, as well as some of the successes and challenges in their development. The presentation aims to: • promote shared learning between national public health institutes on climate change and health strategy development; • provide an opportunity for shaping future planning at RKI through audience input; • stimulate thinking on how national public health institutes can remain in exchange with key stakeholder groups and open to learning and adaptation of their strategies in order to be effective Key Climate Actors over the long term.

Modification of Brain Functional Connectivity in Adolescent Thoracic Idiopathic Scoliosis by Lower Extremities Position

The involvement of the brain motor system in idiopathic scoliosis remains unclear. In this paper, we question whether the functional connectivity (FC) of the central motor circuitry is abnormal in adolescent idiopathic scoliosis (AIS) and whether it can be modified by flexion of the lower extremities. Functional magnetic resonance imaging (fMRI) in 18 patients with a right thoracic idiopathic curve greater than 30° (mean angle 49.4°, mean age 15.3 years, 4 males) and 22 healthy controls (mean age 18.2 years, 4 males) was explored using a 3T MR scanner. We measured their resting-state fMRI: (a) with extended lower extremities; (b) with semiflexion of the left lower extremity and extended right lower extremity, with hip abduction. Decreased FC between the secondary motor area (SMA) and postcentral cortex, pallidum and cuneus, postcentral gyrus and cerebellum, putamen and temporal lateral neocortex was observed in AIS. This pathological connectivity was reversed by lower extremity semiflexion. The FC between cortical and subcortical motor structures is significantly decreased in AIS. The decreased FC of the SMA, basal ganglia, cuneus (a hub structure), and cerebellum indicates the functional impairment of structures involved in regulating muscular tone. FC impairment in patients with AIS appears to be a reaction to the pathological condition. This pathological pattern flexibly reacts to changes in the positioning of the lower extremities, showing that the functional impairment of brain motor circuitry in AIS is reversible. We suggest that the reactivity of cerebral activity leading to brain activity normalization could be used for a rehabilitation program for patients with AIS.

Police departments and care continuity for autistic youth in suicidal crisis

PurposeAutistic youth face higher risks for experiencing mental health crises. To develop and test a county-level social network measure of care coordination between police departments and other systems that support autistic youth experiencing suicidal crisis.Design/methodology/approachTo measure the structure of care coordination for autistic youth experiencing suicidal crisis, the authors created a roster of all police departments and youth servicing organizations in two East Coast counties in the United States. They met or exceeded the whole network recruitment threshold of 70% completion in both counties. From the data, the authors created a directed matrix for each county of all reported connections, which they used to create sociograms and calculate standard network measures, including indegree, outdegree and total degree for each organization in the network. Data management and processing were done using R-programming and ORA.FindingsSocial network findings indicated that about half of all police departments surveyed coordinate care for autistic youth in suicidal crisis. Coordination varied by county, with nonpolice organizations acting as connectors between police and other nonpolice organizations. Two structural configurations were found, including a nonpolice organizational hub structure and a lead police structure. More research is needed to determine how different police integration structures shape care coordination for autistic youth.Research limitations/implicationsLimitations include the small number of counties included in the study. A larger sample of counties is required for generalizable results.Practical implicationsThis article introduces new tools and approaches to assist police in building their capacity to measure and improve their coordination of care with other community systems during crisis situations for youth on the autism spectrum. Network science (e.g. matrix and graph theoretic algebra methods) can be used to measure the configuration of relationships police departments have with complex multi-level healthcare systems.Social implicationsImplications for findings include the consideration of police integration across systems in ways that produce new collaboration possibilities to support autistic youth experiencing suicidal crisis.Originality/valueWhile police departments play a critical role in coordinating care for youth in suicidal crisis, little is known if or how police departments collaborate with other systems to provide assistance for autistic youth during a suicidal crisis. Improving care continuity within and between systems could potentially address clinical and structural challenges and reduce risk for autistic youth experiencing a suicidal crisis.

αα-hub coregulator structure and flexibility determine transcription factor binding and selection in regulatory interactomes

Formation of transcription factor (TF)–coregulator complexes is a key step in transcriptional regulation, with coregulators having essential functions as hub nodes in molecular networks. How specificity and selectivity are maintained in these nodes remain open questions. In this work, we addressed specificity in transcriptional networks using complexes formed between TFs and αα-hubs, which are defined by a common αα-hairpin secondary structure motif, as a model. Using NMR spectroscopy and binding thermodynamics, we analyzed the structure, dynamics, stability, and ligand-binding properties of the Arabidopsis thaliana RST domains from TAF4 and known binding partner RCD1, and the TAFH domain from human TAF4, allowing comparison across species, functions, and architectural contexts. While these αα-hubs shared the αα-hairpin motif, they differed in length and orientation of accessory helices as well as in their thermodynamic profiles of ligand binding. Whereas biologically relevant RCD1–ligand pairs displayed high affinity driven by enthalpy, TAF4–ligand interactions were entropy driven and exhibited less binding-induced structuring. We in addition identified a thermal unfolding state with a structured core for all three domains, although the temperature sensitivity differed. Thermal stability studies suggested that initial unfolding of the RCD1–RST domain localized around helix 1, lending this region structural malleability, while effects in TAF4–RST were more stochastic, suggesting variability in structural adaptability upon binding. Collectively, our results support a model in which hub structure, flexibility, and binding thermodynamics contribute to αα-hub–TF binding specificity, a finding of general relevance to the understanding of coregulator–ligand interactions and interactome sizes.