Search Results (280)

We present a multiscale model of taste that is both biophysically faithful and computationally efficient, enabling end-to-end simulation from receptor transduction to network-level coding. The novelty lies in coupling Hodgkin–Huxley taste receptor cells with Goldman–Hodgkin–Katz ion currents and modality-specific receptors (T1R/T2R, ENaC), to an Izhikevich spiking network equipped with realistic glutamatergic synapses and spike-timing-dependent plasticity. Training combines spike synchrony and a genetic approach in order to reach both globally optimized network structure and biomorphic synaptic plasticity. This hybrid design yields distinct, sparse spiking “fingerprints” for taste qualities and mixtures, and provides a practical foundation for neuromorphic gustatory sensors that require real-time, energy-efficient operation. Full article

Model-Based Systems Engineering (MBSE) is employing systems analysis, design, and development on models of these systems, bringing together different viewpoints, with a step-by-step increase of detail. As such, it replaces traditional document-centric approaches with a methodology that uses structured domain models for information exchange and system representation throughout the engineering lifecycle. MBSE comprises different languages, each with distinct features and approaches. SysML is a widely used language in MBSE, and many tools exist for it. This paper is interested in the complexity of SysML models, as it may yield useful quantitative indicators to assess and predict the complexity of systems modeled in SysML, and, by extension, the complexity of their subsequent development. Two avenues are explored: objective structural metrics applied to the SysML model and assessment of the team experience. The proposed approach is implemented as a Java prototype. Although simpler models are easier to comprehend and modify, they may fail to capture the full scope of system functionality. Conversely, more complex models, though richer in detail, require greater development effort and pose challenges for maintenance and stakeholder communication. Technical and environmental factors are integrated into the complexity assessment to reflect real-world project conditions. A drone-based image acquisition system serves as a case study. Full article

The paper presents a methodology aiming to assess the impact of operations of a short- and medium-range fleet transitioning from jet fuel to hydrogen propulsion, considering the constraint arising from the distribution of hydrogen refueling infrastructures across airports, leveraging on the different performance of the two sub-fleets to obtain the least climate-impacting transition. Hydrogen tankering will enable flights to airports that have no hydrogen refueling capabilities, as long as the destination is within half of the operational range of the selected aircraft, at the cost of a slight increase in fuel burn. The proposed methodology aims to assess said increase, while minimizing the expenditure for hydrogen, and the coverage of a reference network, achievable when considering aircraft performance and assumptions on the availability and cost of hydrogen at various airports. The results of such analysis can be used to determine whether a reduction in the design range of a given aircraft is acceptable. Such a reduction would mitigate the impact that the hydrogen tank has on the sizing of the aircraft and its performance. Depending on the considered scenario, a network potential coverage spanning from 81% to 96% can be achieved. Starting from this result, it is possible to assess the transition of a short-haul airliner fleet from jet fuel to hydrogen propulsion, considering the constraint arising from the distribution of hydrogen refueling infrastructures across airports and the different performances (energetic, environmental and economic) of the two sub-fleets. The aircraft assignment to each route is performed with the objective of minimizing either the energy, the carbon intensity or the fuel cost of the overall network, obtaining different route assignment distributions. The results show that the aviation-induced temperature change can be reduced by up to 57% compared to an all-jet-fuel fleet. Full article

Drones are increasingly vital for disaster management, yet emergency fleets often consist of heterogeneous platforms, complicating task allocation. Efficient deployment requires rapid assignment based on vehicle and payload characteristics. This work proposes a three-step method composed of fleet analysis, area decomposition and trajectory generation for multi-rotor drone surveillance, aiming to achieve complete area coverage in minimal time while respecting no-fly zones. The three-step method generates optimized trajectories for all drones in less than 2 min, ensuring uniform precision and reduced flight distance compared to state-of-the-art methods, achieving mean distance gains of up to 9.31% with a homogeneous fleet of 10 drones. Additionally, a comparative analysis of area partitioning algorithms reveals that simplifying the geometry of the surveillance region can lead to more effective divisions and less complex trajectories. This simplification results in approximately 8.4% fewer turns, even if it slightly increases the total area to be covered. Full article

Background: Degenerin proteins, such as Acid-Sensing Ion Channel 2 (ASIC2) and β Epithelial Na⁺ Channel (βENaC), have been implicated in cardiovascular function. We previously demonstrated that mice lacking normal levels of βENaC and ASIC2 are protected from diet-induced obesity, metabolic disruption, and hepatic steatosis. Methods: To investigate the specific role of βENaC proteins in the progression of metabolic disease, we examined the impact of a high-fat diet (HFD) in the βENaC hypomorph mouse model (βMUT). Body composition and metabolic and behavioral phenotypes were examined in male and female and βMUT and WT mice (n = 6–14/group) fed a normal chow diet (NFD) from weaning until 16 weeks of age, then a 60% kcal-fat diet for 5 weeks. Results: Compared to WT mice, βMUT male mice have reduced lean and total body mass. No remarkable differences in energy expenditure, motor activity, or food consumption patterns were detected. HFD-fed male βMUT mice exhibited reduced liver fat content (mass and Oil Red O staining) yet increased abdominal fat depots. HFD-fed female βMUT mice exhibited lower heart mass. Conclusions: These novel findings suggest a role for βENaC in the maintenance of metabolic homeostasis and adipose tissue distribution. Full article

Lung-protective ventilation and other experimental conditions raise arterial carbon dioxide tension (PaCO₂) and alter pH. Short-term benefits are reported in non-infectious settings, whereas infection and/or prolonged exposure are typically harmful. This scoping review systematically maps immune-mediated effects of hypercapnia on innate immunity and alveolar epithelial repair. Scoping review per Levac et al. and PRISMA Extension for Scoping Reviews (Open Science Framework protocol: 10.17605/OSF.IO/WV85T; post hoc). We searched original preclinical studies (in vivo/in vitro) in PubMed, Web of Science, ScienceDirect, Cochrane Reviews, and SciELO (2008–2023). PaCO₂ (mmHg) was prioritized; %Fraction of inspired Carbon Dioxide (%FiCO₂) was recorded when PaCO₂ was unavailable; pH was classified as buffered/unbuffered. Data were organized by context, PaCO₂, and exposure duration; synthesis used heat maps (0–120 h) and a narrative description for >120 h. Mechanistic axes extracted the following: NF-κB (canonical/non-canonical), Bcl-2/Bcl-xL–Beclin-1/autophagy, AMPK/PKA/CaMKKβ/ERK1/2 and ENaC/Na,K-ATPase trafficking, Wnt/β-catenin in AT2 cells, and miR-183/IDH2/ATP. Thirty-five studies met the inclusion criteria. In non-infectious models, a “protective window” emerged, with moderate PaCO₂ and brief exposure (65–95 mmHg; ≤4–6 h), featuring NF-κB attenuation and preserved epithelial ion transport. In infectious models and/or with prolonged exposure or higher PaCO₂, harmful signals predominated: reduced phagocytosis/autophagy (Bcl-2/Bcl-xL–Beclin-1 axis), AMPK/PKA/ERK1/2-mediated internalization of ENaC/Na,K-ATPase, depressed β-catenin signaling in AT2 cells, impaired alveolar fluid clearance, and increased bacterial burden. Chronic exposures (>120 h) reinforced injury. Hypercapnia is a context-, dose-, time-, and pH-dependent double-edged modulator. The safe window is narrow; standardized, parallel reporting of PaCO₂ and pH—with explicit comparisons of buffered vs. unbuffered hypercapnia—is essential to guide clinical translation. Full article

This study investigated the role of molecular mimicry in the context of autoimmunity associated with viral infection, using SARS-CoV-2 as a model system. A bioinformatic analysis was performed to identify sequence homologies between the SARS-CoV-2 Spike (S) protein and the human proteome, with a specific focus on immunogenic regions to assess potential cross-reactivity. The analysis revealed homologous regions between the viral S protein and several human proteins, including DAAM2, CHL1, HAVR2/TIM3, FSTL1, FHOD3, MYO18A, EMILIN3, LAMP1, and αENaC, which are predicted to be recognizable by B-cell receptors. Such recognition could potentially lead to the production of autoreactive antibodies, which can contribute to the development of autoimmune diseases. Furthermore, the study examined potential autoreactive CD4+ T-cell responses to human protein autoepitopes that could be presented by HLA class II molecules. Several HLA class II genetic variants were computationally associated with a higher likelihood of cross-reactive immune reactions following COVID-19, including HLA-DPA1*01:03/DPB1*02:01, HLA-DPA1*02:01/DPB1*01:01, HLA-DPA1*02:01/DPB1*05:01, HLA-DPA1*02:01/DPB1*14:01, HLA-DQA1*01:02/DQB1*06:02, HLA-DRB1*04:01, HLA-DRB1*04:05, HLA-DRB1*07:01, and HLA-DRB1*15:01. Additionally, seven T helper cell autoepitopes (YSEILDKYFKNFDNG, ERTRFQTLLNELDRS, AERTRFQTLLNELDR, RERKVEAEVQAIQEQ, NAINIGLTVLPPPRT, PQSAVYSTGSNGILL, TIRIGIYIGAGICAG) were identified that could be implicated in autoimmune T-cell responses through presentation by class II HLA molecules. These findings highlight the utility of viral B- and T-cell epitope prediction for investigating molecular mimicry as a possible mechanism in virus-associated autoimmunity. Full article

This study presents a high-fidelity digital twin (DT) framework designed to evaluate and improve vertiport operations for Advanced Air Mobility (AAM). By integrating Unreal Engine, AirSim, and Cesium, the framework enables real-time simulation of Unmanned Aerial Vehicles (UAVs), including unmanned electric vertical take-off and landing (eVTOL) operations under nominal and disrupted conditions, such as adverse weather and engine failures. The DT supports interactive visualisation and risk-free analysis of decision-making protocols, vertiport layouts, and UAV handling strategies across multi-scenarios. To validate system realism, mixed-reality experiments involving physical UAVs, acting as surrogates for eVTOL platforms, demonstrate consistency between simulations and real-world flight behaviours. These UAV-based tests confirm the applicability of the DT environment to AAM. Intelligent algorithms detect Final Approach and Take-Off (FATO) areas and adjust flight paths for seamless take-off and landing. Live environmental data are incorporated for dynamic risk assessment and operational adjustment. A structured capacity evaluation method is proposed, modelling constraints including turnaround time, infrastructure limits, charging requirements, and emergency delays. Mitigation strategies, such as ultra-fast charging and reconfiguring the layout, are introduced to restore throughput. This DT provides a scalable, drone-integrated, and data-driven foundation for vertiport optimisation and regulatory planning, supporting safe and resilient integration into the AAM ecosystem. Full article

Background/Objectives: Pseudohypoaldosteronism type 1 (PHA-1) is a rare disorder characterized by aldosterone resistance, leading to hyponatremia, hyperkalemia, and elevated renin and aldosterone levels in neonates and infants. While genetic mutations in NR3C2 (mineralocorticoid receptor, MR) and SCNN1A/B/G (epithelial sodium channel, ENaC) are established causes of primary PHA-1, cases without detectable mutations have also been reported. This study aimed to compare the clinical characteristics of genetically confirmed PHA-1 cases—with or without mutations—and to assess genotype–phenotype correlations. Methods: A literature review was conducted using the Medline database, covering studies published from 1966 to October 2023. Included cases were diagnosed with PHA-1 and had undergone genetic testing for NR3C2 and SCNN1A/B/G. Clinical and biochemical data were compared across three groups: MR, ENaC, and non-mutation. Additional subgroup analysis based on mutation type (truncating vs. non-truncating) was also performed. Results: A total of 164 patients from 64 studies met the inclusion criteria. The ENaC group showed significantly higher serum potassium levels than the MR and non-mutation groups. Serum aldosterone levels were significantly higher in the MR group compared to the non-mutation group. A genotype–phenotype correlation was evident in the ENaC group, with truncating variants associated with more severe hyperkalemia. No such correlation was observed in the MR group. Conclusions: This review highlights distinct clinical features of PHA-1 according to genetic status. Aldosterone levels may aid in guiding decisions regarding genetic testing. Furthermore, variant type in ENaC-related PHA-1 may predict biochemical severity and should be considered in clinical management strategies. Full article

Arterial hypertension (HTN) is a growing global health concern, with limited tools available for early detection. Previous studies identified the overexpression of the epithelial sodium channel (ENaC) as a potential biomarker for HTN. In this work, we optimized and clinically validated a lateral flow immunoassay (LFIA) using gold nanoparticles (AuNPs) functionalized with anti-ENaC antibodies. The test strips were prepared with 10 µL of each component and performed in a 9-point herringbone format. For validation, a double-blind study was conducted using platelet lysates from 200 individuals, classified based on real-time blood pressure measurements. ENaC expression was assessed via both LFIA and Western blotting, which served as the reference method. Receiver operating characteristic (ROC) analysis yielded an AUC of 0.7314 for LFIA and 0.6491 for the Western blot, with LFIA demonstrating higher sensitivity (76.24%) and comparable specificity (61.54%) compared to the Western blot (68.31% and 60.34%, respectively). These results support LFIA as a practical, rapid, and moderately accurate tool for screening ENaC levels and identifying individuals at risk of hypertension. Full article

Hydrogen-powered aircraft constitute a transformative innovation in aviation, motivated by the imperative for sustainable and environmentally friendly transportation solutions. This paper aims to concentrate on the design of hydrogen powertrains employing a system approach to propose representative design models for distribution and propulsion systems. Initially, the requirements for powertrain design are formalized, and a use-case-driven analysis is conducted to determine the functional and physical architectures. Subsequently, for each component pertinent to preliminary design, an analytical model is proposed for multidisciplinary analysis and optimization for powertrain sizing. A double-wall pipe model, incorporating foam and vacuum multi-layer insulation, was developed. The internal and outer pipes sizing were performed in accordance with standards for hydrogen piping design. Valves sizing is also considered in the present study, following current standards and using data available in the literature. Furthermore, models for booster pumps to compensate pressure drop and high-pressure pumps to elevate pressure at the combustion chamber entrance are proposed. Heat exchanger and evaporator models are also included and connected to a burning hydrogen engine in the sizing process. An optimal liner pipe diameter was identified, which minimizes distribution systems weight. We also expect a reduction in engine length and weight while maintaining equivalent thrust. Full article

This paper presents an uncertainty quantification analysis of the first fix in a time-differenced carrier phase (TDCP) observation model. TDCP is a widely used method in GNSS-based odometry for precise positioning and displacement estimation. A key point in the TDCP modeling is the assumption that the GNSS receiver’s initial position is perfectly known, which is never exactly the case in real-world applications. This study assesses the impact of initial position errors on estimated displacement by formulating a correct TDCP model and a misspecified one, where the first position is not correct. Theoretical derivations provide a generic framework of estimation under the misspecified model and its associated mean squared error (MSE), as well as estimation performance bounds through the misspecified Cramer Rao bound (MCRB) for the considered case. These theoretical considerations are then used to build an estimator of the receiver’s displacement, with comparisons to the MCRB for performance evaluation. Extensive simulations using realistic GNSS geometry assess the influence of a first-fix error under various conditions, including different time intervals, first-fix error norms, and first-fix error direction. As an example, it is shown that for the considered geometry, if a TDCP of $t_2-t_1=1$ s is built with an initial first fix error norm $\parallel \mathsf{\Delta }{\mathit{r}}_1\parallel =10 \mathrm{m}$, then it introduces an estimation of the displacement, with an error of norm equal to $1.3 \mathrm{m}\mathrm{m}$, at most. The results indicate that the displacement estimation error is linearly related to the initial position error and the time interval between observations, highlighting the importance of accurate first-fix estimation for reliable TDCP-based odometry. The findings contribute to highlighting the order of magnitude of errors on solutions as a function of the error on parameters. Full article

Aviation has become an essential part of the modern world’s ability to grow personal, market and international connections. To enable continued benefits while reducing emissions, future aircraft will need radical redesign and novel, complementary technologies. Hydrogen aircraft are potentially the means to emissions reduction. As part of the European Union’s (EU’s) Clean Aviation Joint Undertaking (CAJU), it is aimed to have hydrogen aircraft entering into service by 2035. To realise this, it would require the certification of these aircraft in a relatively short timeline, which the CONCERTO project aims to help enable. Given the lack of mature experimental designs and pending certification processes, this endeavour is ambitious. To accelerate this, dedicated preparation for the certification through regulatory analysis should be complete, requiring initial options for technologies and aircraft operations to be defined. The technologies and operations were defined, analysed and weighted in CONCERTO, upon which a Generic Concept was made, outlined in this paper, with Level 1 on the Certification Readiness Level Scale. The aircraft systems which are likely to experience the largest changes; Fuel Storage, Fuel Distribution, Propulsion, Auxiliary Power Unit (APU), Heat Exchange (HEX) System and Sensing and Monitoring for Hydrogen (H2), will be outlined in this paper with respect to their components and integration challenges, and the subsequent changes to operations to enable this. Full article

Dilution of Precision (DOP) is routinely used in GNSS to assess the quality of the constellation geometry for the positioning algorithm. Those DOP indicators are computed from the estimation covariance of a snapshot weighted least squares (WLS) estimate under certain hypotheses. This paper proposes to define DOP indicators for GNSS solutions based on Factor Graph Optimization (FGO). FGO solutions have become popular in the GNSS domain. They allow to easily model probabilistic contraints, called factors, over a large time window, by mixing observations and motion constraints accross consecutive epochs. The solution is solved by performing a batch WLS estimation for the states at all considered epochs, using all available factors. Due to the simple nature of the estimation algorithm—a WLS solution—it is possible to derive the theoretical estimation error covariance, which will indicate the accuracy of the computed solution. In this paper, a formula is proposed to approximate the DOP for the FGO solution. Then, the formula is validated in various scenarios involving fixed or changing satellite visibility. Full article

Physiological control of blood pressure (BP) and extracellular fluid volume is mediated by the action of the renin-angiotensin system (RAS). The presence of RAS components throughout the nephron has been widely discussed. The (pro)renin receptor (PRR) is a member of the RAS widely expressed in the body of humans and rodents. In the kidney, PRR is expressed in mesangial cells, renal vasculature, and tubules of the proximal and distal nephron. Binding of the PRR to renin and prorenin promotes angiotensin (Ang) I-mediated sodium (Na⁺) reabsorption via the epithelial sodium channel (ENaC). The Goldblatt 2-kidney 1-clip (2K1C) is a model of experimental renovascular hypertension that displays activation of systemic and intrarenal RAS. We use the 2K1C hypertension mouse model for 7 days to evaluate the role of the PRR on renal αENaC expression, Na⁺ reabsorption, and BP using pharmacological systemic blockade of the PRR with PRO20 peptide. Mice undergoing or not to 2K1C surgery (0.13 mm clip internal gap) were chronically infused with PRO20 and compared to sham (control) mice to assess changes in systolic BP (SBP) and diastolic BP (DBP), intrarenal angiotensin-converting enzyme (ACE) activity, Ang II, and renal αENaC expression and natriuretic responses after a saline challenge. Renal artery obstruction increased SBP and DBP, intrarenal ACE activity, Ang II levels, Na⁺ retention, and αENaC expression in both kidneys. PRO20 prevented the increases in SBP, DBP, attenuated Na⁺ retention, and blunted intrarenal Ang II and αENaC levels in non-clipped kidneys of 2K1C mice. Chronic infusion of the PRR for 7 days prevents hypertensive responses in part due to impaired αENaC upregulation and intrarenal Ang II formation in the early phase of the development of renovascular hypertension in 2K1C Goldblatt mice. Full article