High pathogenicity avian influenza (HPAI) is a highly infectious and lethal disease of birds that causes systemic symptoms and has been spreading globally, including in Japan. The Okinawa rail (Hypotaenidia okinawae), a flightless bird endemic to Japan, is classified as an endangered species on the Red List. In 2004, the Ministry of the Environment of Japan began implementing a conservation breeding program for Okinawa rails, focusing on maintaining the species' genetic diversity, captive breeding, and reintroduction to the wild. Given the potential for significant losses due to HPAI in Okinawa rails, the establishment of a treatment protocol as a preparedness measure is essential. The aim of this study was to determine an appropriate treatment method for HPAI in Okinawa rails using baloxavir marboxil (BXM), a drug shown to be effective in an avian laboratory model of HPAI virus infection. Single oral administration of BXM at 2.5 or 12.5 mg/kg did not produce plasma concentrations sufficient to achieve the expected therapeutic efficacy. Therefore, oral administration was deemed inadequate for generating the desired pharmacological effects. Consequently, subcutaneous administration of BXM to Okinawa rails at a dose of 2.5 or 7.5 mg/kg was explored as an alternative protocol, which resulted in higher systemic exposure compared with oral administration. Furthermore, plasma concentrations were maintained at therapeutically relevant levels up to 24 hours after subcutaneous administration at 7.5 mg/kg, with mild and reversible injection site irritation the main adverse effect. Based on these results, subcutaneous administration of BXM is proposed as a viable treatment protocol for HPAI in the conservation of endangered Okinawa rails.
Development and validation of an online adaptive proton therapy workflow for clinical use. A script-based online adaptive proton therapy workflow was developed in a graphics processing unit (GPU)-accelerated treatment planning system (TPS) to automate plan adaptation using traditional CT images acquired on an in-room CT-on-rails. Monte Carlo (MC) -based secondary dose calculation and log file analysis of machine parameters were integrated into the workflow to provide quality assurance (QA) pre- and post- plan delivery for the adapted treatment plan. In silico retrospective testing was performed with ten previously treated pelvic patients for validation of the workflow, a total of 50 fractions were included in this study. The fidelity of adapted dose distributions, time required for the in-silico workflow, and QA results were recorded and analyzed. The median (inter-quartile range, IQR) time required for this workflow was 61.9 (12.2) minutes, demonstrating technical feasibility for online adaptation. Of the 50 evaluated fractions, 15 (30%) showed clinically meaningful improvements in sparing of highest-priority organ-at-risk (OAR) using the adaptive plans (PA), and 8 (16%) showed improved target coverage relative to the scheduled plan. Both MC-based secondary dose checks and log file-based machine QA were within institutional tolerance criteria, confirming the dosimetric accuracy and delivery fidelity of the workflow. A fully integrated, QA-embedded online adaptive proton therapy workflow using in-room CT-on-rails imaging was developed and validated in silico on a clinical proton beamline. The workflow demonstrated clinically acceptable treatment times and reliable dosimetric accuracy and provided measurable benefits in OAR sparing and target coverage for a substantial subset of fractions. These results support the readiness of this workflow for clinical use.
Insular (island-limited) populations typically show signatures of weak purifying selection, indicating high genetic load and reduced fitness compared with mainland populations. However, the source of this pattern is often unclear-it may reflect residual signatures from a temporary period of small effective population size (Ne) associated with island colonization (founder effects), persistently small Ne due to the lower carrying capacity of islands (range limitations), or relaxed selective constraints unrelated to Ne. Here, we disentangle these hypotheses by analyzing the drivers of variation in evolutionary rates of nonsynonymous (dN) and synonymous (dS) sites in nine mitochondrial genes (8001 bp) from 40 rail species (Aves: Rallidae). We find that insular species with short terminal branches (indicating recent island colonization) have highly elevated mitochondrial dN/dS across multiple mitochondrial genes. In contrast, rails representing more ancient island colonizations have dN/dS ratios that are indistinguishable from mainland/widespread species. Furthermore, we find that island size is unrelated to dN/dS among island species. These results indicate that insular rails suffer a high initial cost of island colonization and undergo a period of inefficient selection due to founder effects, but that there is little impact from longer-term range limitations or relaxed selection.
Similar phenotypic traits can evolve independently in response to comparable environmental challenges. A striking example of this process is the repeated and irreversible loss of flight in birds, particularly on islands. The rail family (Rallidae) provides an exceptional model for studying this phenomenon, as nearly a quarter of the 130 extant species have independently become flightless. Here, we present the first genome-wide comparative analysis of multiple independent flightless rail lineages to identify the molecular basis of flight loss. We compared coding regions from seven rail species (four flightless and three volant) using more than 11,000 alignments and multiple phylogeny-based tests, including branch-site models of selection, relative evolutionary rate analyses, and assessments of function-altering amino acid substitutions. Across all analyses, 116 genes showed significant associations with flightlessness, of which 37 were linked to biological functions related to flight capacity-such as muscle, bone, limb, and heart development-or to traits reflecting ecological consequences of flight loss, including immune response, renal function, lipid metabolism, cognition, and sensory perception. Many genes under selection in flightless species were also involved in gene regulation and post-translational modification. These findings suggest that convergent loss of flight in rails arises not from major mutations in a few key loci but from numerous small, repeated genetic changes affecting both developmental pathways and regulatory mechanisms.
Ultrasonic testing is a prevalent method for non-destructive evaluation of railway rails; however, conventional Time-of-Flight (ToF) approaches applied in practical dry-coupled inspections often rely on simplified assumptions regarding wave propagation velocity and neglect complex waveform characteristics. This paper presents a robust depth estimation framework for surface-breaking cracks that enhances sizing accuracy through effective velocity calibration and Hilbert envelope extraction. Unlike standard methods that assume the free-space speed of sound in air (343 m/s) for wave propagation within the air-filled gap of a surface-breaking crack, we propose an effective velocity model derived from in situ calibration to account for the boundary layer viscosity and thermal conduction effects within narrow crack geometries. The signal processing chain incorporates spectral analysis, band-pass filtering, and Hilbert Transform-based envelope detection to mitigate noise and resolve phase ambiguities. Experimental validation on steel specimens with controlled defects (0.2-10.0 mm) demonstrates that the proposed method achieves an exceptional linear correlation (R2 ≈ 0.9976). The calibrated effective velocity was determined to be 289.3 m/s, approximately 15.6% lower than the speed of sound in air, confirming the significant influence of confinement effects. Furthermore, excitation parameters were optimized, identifying that high-voltage excitation (≥110 V) and a tuned pulse width (≈150 ns) are critical for maximizing the signal-to-noise ratio. The results confirm that combining physical model calibration with advanced signal analysis significantly reduces systematic errors, paving the way for portable, high-precision rail inspection systems.
Ultrasonic guided waves have emerged as an essential technique for rail nondestructive evaluation(NDE) owing to long-range propagation and high defect sensitivity, yet multimode coexistence produces strongly overlapping responses that challenge conventional excitation-based mode selection. This study develops a mathematical model in which excitation position and input energy are treated as optimization variables to identify the most effective configuration for the selective excitation of targeted guided wave modes. Optimization is cast with mode purity (the ratio of the target-mode response amplitude to the overall guided-wave response) as the primary objective and directional matching as an auxiliary constraint to enhance excitation selectivity. Leveraging particle swarm optimization (PSO) the proposed scheme identifies optimal excitation parameters that realize efficient selective mode generation with only two excitation points and yields a simplified and practical transducer configuration. Numerical simulations and full-scale rail experiments across multiple frequency bands, including 400 Hz and 35 kHz, indicate that the proposed approach markedly enhances target-mode purity and enables reliable detection of defect echoes not observable with conventional single-point excitation. Taken together, these results support a new route to selective mode generation for rail NDE while avoiding complex phased array systems.
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Fall induced traumatic brain injury (TBI) accounts for approximately 20% of reported TBI in military personnel. Consequently, evaluating military headgear with methods that provide an accurate representation of real-world falls is important to ensuring test fidelity. Guided drop towers aim to provide such a representation, yet are constrained to a single degree-of-freedom and, typically, exclude the mass of the full body from the system. The present work sought to test the hypothesis that guided falls and full dummy falls are kinematically similar. If not, then document key differences and implications for helmet assessment. An impact study was conducted for two impact velocities (3.0 m/s, 4.5 m/s) onto a rigid impact surface at 30° (body near supine) and 75° (body nearly upright, with head down) with measures of head center of gravity linear acceleration, angular acceleration, and angular velocity. A guided drop carriage with variable mass and Hybrid III head-neck were compared to a full Hybrid III mannequin, both simulating helmeted impacts. Results of the impact study showed that a guided drop tower yields varying estimations of peak kinematics, relative to a full surrogate. While the results do indicate that guided linear drops are adequate for assessing impact attenuation of military helmets, they do not recreate the helmet, head, and neck mechanics of a full ATD drop across all of the tested configurations for the measures of interest. Kinematically, a drop tower is not a direct substitute nor predictably correlated model for a full-sized dummy when assessing military helmets.
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With increasing rail traffic intensity, reliable detection of shallow subsurface rail damage is essential for operational safety. This critical narrative review evaluates non-destructive testing technologies relevant to defects whose active crack front or principal scattering zone lies within the upper approximately 0.5-10 mm of the rail, while treating the 10-15 mm range as a transition to deeper-defect verification. Magnetic flux leakage, magnetic particle inspection, visual inspection, eddy current testing, and conventional ultrasonic testing are first examined as screening or confirmatory comparators. The review then focuses on four ultrasonic surface-wave excitation routes-contact piezoelectric, active air-coupled, electromagnetic acoustic, and laser ultrasonic-and distinguishes source-specific laboratory capability from demonstrated field evidence. Because the cited studies use different defect geometries, rail conditions, sensor configurations, speeds, and decision criteria, their numerical values are reported as source-conditioned evidence rather than as a normalized ranking. An engineering decision matrix links defect depth and size, inspection speed, surface condition, and noise environment to a recommended screening-confirmation workflow. The synthesis identifies contact piezoelectric UT/PAUT as the most mature quantitative confirmation route, while EMAT, air-coupled UT, and laser UT retain method-specific advantages but require stronger natural-defect and in-service validation.
Quick and reliable in situ non-destructive assessment of the material structure is especially critical in the case of measurement of rail defects concerning the demands of quick, uninterrupted transportation and safety. This paper presents the test results of a patented measuring head that is able to perform ultrasonic rail defect detection at speeds of up to 120 km/h. The experimental data was collected and discussed. Statistical analysis was performed in terms of bottom echo drop as a function of velocity, pressing force, and film thickness between the sensor and the rail material surface, as well as the coupling fluid stream intensity. The results proved the feasibility of the device for usage at high speeds for the state monitoring of rails in service.
Ultrasonic guided wave technology offers advantages such as long-distance propagation and full-section detection for non-destructive testing of rails. However, operational rails are typically limited by fastener systems, resulting in increased guided wave energy attenuation and shorter propagation distances compared to free rails. Therefore, studying the mechanism by which fasteners influence guided wave attenuation is crucial. This paper presents a comprehensive three-dimensional solid fastener-rail contact mechanics and transient dynamics coupling model that considers the static action and complex contact relationship between fasteners and rails. The model uses an implicit-explicit combination method to simulate the propagation of guided waves in operational rails. This paper presents a simulation in which a preload force of 20 kN was applied to the fasteners, and the stress distribution of the model was analyzed. A transient analysis of the guided wave was performed under the preload force to investigate the influence of fasteners on guided wave attenuation in rails by comparing attenuation with and without fasteners. Additionally, this paper explores the impact of two contact types, penalty and motion, on wave attenuation in Abaqus/Explicit. The results demonstrate that fasteners significantly exacerbate wave attenuation in rails. The wave packet amplitude calculated using the penalty contact form is slightly greater than that calculated using the motion contact form, and this difference increases with propagation distance.
To improve testing methods to develop clinically applicable return-to-sport assessments in dogs by evaluating hind limb push-off symmetry while jumping onto a platform from a stationary position. The hypothesis was that normal dogs would demonstrate > 90% symmetry when performing the newly proposed jump tests. Jump tests included sit-to-withers-height jump, stand-to-head-height jump, and stand-to-withers-height jump with side rails. This was a prospective, methodological study in which orthopedically and neurologically normal dogs were asked to jump onto a platform, performing 5 valid trials of 3 separate jump tests within a 30-minute period of time. Peak vertical force of the hind limbs was measured and expressed as a percentage of symmetry for each trial. 20 dogs were included. The mean percentage of symmetry for each jump test variation was as follows: stand-to-head-height jump was 83.27% (SD, ± 5.20%), stand to withers with side rails was 73.49% (SD, ± 12.63%), and sit-to-withers-height box was 67.39% (SD, ± 20.96%). However, when selecting for each dog's best attempt, symmetry was 96.90% for stand to head height, 92.34% for side rails, and 94.39% for sit to withers height. Dogs were less than 90% symmetrical in the hind limbs when averaging 5 valid trials for each jump test. An unexpected finding was that when evaluating for each dog's best attempt, hind limb symmetry was above 90% for all modifications. The development of easy-to-perform, reliable, and repeatable return-to-sport assessment tests could provide objective data on canine recovery from orthopedic and neurologic injury.
Ballastless track continuous welded rails (CWR) are used on a multi-span 100 m simply supported steel truss bridge of a mixed passenger and freight railway, to study the mechanical characteristics and influence factors of CWR on the 100 m simply supported steel truss bridge, a track-bridge-piers spatial finite element model was established based on the track-bridge interaction (TBI) principle. The influence of design parameters such as the number of bridge spans, the longitudinal stiffness of piers of the simply supported steel truss bridge, the arrangement of bridge bearings, the type of rail, and the track longitudinal resistance type on the mechanical characteristics of CWR on the simply supported steel truss bridge were systematically examined. The research results indicate that for multi-span simply supported steel truss bridges, the model can be simplified by considering 8 spans when the total number of spans exceeds 8. Likewise, when the number of adjacent concrete box girder spans exceeds 5, 5 spans can be adopted. The longitudinal stiffness of piers of the simply supported steel truss bridge has a significant influence on the rail braking force and the rail broken gap. Increasing the longitudinal stiffness of the piers from 399kN/cm to 5000kN/cm has a much greater effect on the forces and deformations of CWR on the bridge than increasing it further from 5000kN/cm to 10000kN/cm. The bridge expansion length is primarily governed by the arrangement of fixed bearings on the adjacent concrete box girder. Therefore, to reduce the forces in the CWR on the bridge, the simply supported steel truss bridges and the adjacent concrete box girders should adopt a consistent bearing arrangement. In addition, rails with a larger cross-sectional area can reduce the additional rail stress. The used of small resistance fastener systems for ballastless track decreases the rail expansion force and rail braking force by 56.72% and 18.05%, respectively, but it increases the rail broken gap by 37.49%. The research results can provide references for the design of CWR on the simply supported steel truss bridge.
To reduce fall risk in the homes of community-dwelling older adults, various home modifications (e.g. grab bars, handrails, raised toilets) are recommended. These home modifications might enable older adults to remain independent and are purported to reduce falls. The combined and independent impact on falls is poorly constructed. The objective of this review was to understand the independent and combined influence of the type and location of home modifications on fall-related outcomes in community-dwelling older adults. Three databases (Web of Science, CINAHL, Medline) were searched to identify relevant randomized controlled trials. Studies were synthesized in a narrative (descriptive) results summary grouped by fall outcome, and categorized according to the specific home modifications. Of the 209 studies evaluated, nine met inclusion criteria and were from four different countries. The most common home modifications made were grab bar and handrail implementation. The results suggest that secure rails reduce the number of fallers and fall rates among community-dwelling older adults and implementing a combination of home modifications might reduce the number of fallers or cause no change. Future studies should develop strategies to improve intervention adherence and use a combination of technologies in a randomized control study design.
Testes exist as a highly radiosensitive organ at risk (OAR) in which absorbed dose can be significantly impacted by small positional variations. In this case study, challenges arose during radiation therapy treatment regarding immobilization and positional reproducibility of the patient's left testis and penis related to the body's homeostatic response to variable room temperatures. Researchers aimed to describe how the OAR constraints were maintained when room temperatures impacted scrotal positioning by comparing daily localization scans using computed tomography on rails (CToR) to evaluate the dose distribution. In this single pediatric case study, a patient diagnosed with paratesticular sarcoma received intensity modulated proton therapy (IMPT) treatment to the right inguinal region. Immobilization and positional reproducibility inconsistencies of the penis and left testis led to multiple replans. A retrospective statistical analysis of the OAR metrics in 3 radiation treatment plans determined specific patient warming instructions yielded a consistent reproducible outcome along with increased dosimetric accuracy. Understanding the human physiological response to ambient factors, such as room temperature, led to stable reproducibility of the OAR using thermal management. Iterative planning and collaboration between radiation therapy professionals were also key elements that paved the way to maintain treatment planning constraints.
Silver nanoclusters merge atomically defined structures with intense, environment-responsive photoluminescence, yet their notorious lability in air and water has constrained real-world sensing. Here we convert fragility into a design principle by immobilizing a silver nanocluster motif inside a reticularly reinforced, recognition-active lattice. TUS 9 is a ladder-structured silver cluster-assembled material built from bow-shaped Ag13 units that first organize into one-dimensional chains ("rails") and are then stitched laterally by rigid 3,6-di(4-pyridyl)-1,2,4,5-tetrazine linkers ("rungs"). Single-crystal X-ray diffraction reveals a monoclinic C2/c framework in which argentophilic contacts and a mixed thiolate/trifluoroacetate ligand shell stabilize the cluster scaffold, while directional Ag-N coordination locks interchain registry. Bulk phase fidelity is confirmed by PXRD and XPS, and the ordered packing generates permanent microporosity. In water, TUS 9 retains strong emission with a sensing-ready band at 377 nm (λex = 295 nm), enabling selective luminescence quenching by basic amino acids. L-Lysine and L-arginine produce pronounced Stern-Volmer responses (KSV = 891.7 and 540.1 M-1) with detection limits of 407 and 162 μM, respectively, whereas acidic amino acids perturb the emission only weakly. The response is fully recyclable over 10 cycles and post-sensing XPS shows preserved coordination environments. This work demonstrates that electronically active linkers can simultaneously stabilize silver nanocluster frameworks against aqueous degradation and encode molecular selectivity, opening a modular route to robust, programmable luminescent sensors.
Bladder cancer is a long-standing clinical issue, with frequent recurrence and continuously disappointing results in patients, so that therapeutic development is primarily reliant on delineating the original molecular defects. Increasing interest has turned to the Kinesin Superfamily Proteins (KIFs), basic molecular motors that move along microtubule rails, and are now emerging as important key oncogenic derivers in bladder cancer pathogenesis. This review synthesizes available evidence indicating that several KIFs, specifically KIF4A, KIF14, KIF20A, and KIFC1, function as key oncogenic regulators and represent important prognostic biomarkers and therapeutic targets in bladder cancer. When KIF expression or activity is disrupted, it provides mechanical and signaling support for all the cancer hallmarks, facilitating cellular proliferation, invasion, metastasis, and resistance to highly effective cell death. Its oncogenic activity is generally facilitated by the activation of principal signaling pathways. A remarkable proportion of certain KIF isoforms are commonly overexpressed in cancer, and the scale of such overexpression increases with the severity of adverse clinical predictors, such as increasing disease stage, and patient survival worsens. This nuanced molecular image renders KIFs so highly promising targets for therapeutic intervention and prognostic stratification, and initial exploration of kinesin inhibitors is encouraging to abate chemoresistance, aside from optimizing the efficacy of current immunotherapies. Uncovering modalities that exploit the aggressive bladder cancer cell dependence on KIF motor activity is a highly promising path to clinical application.
Chemical synapses are fundamental units for the transmission of information throughout the nervous system. The cytoskeleton allows to build, maintain, and transform both pre- and postsynaptic contacts, yet its organization and the role of its unique synaptic nanostructures are still poorly understood. Here we present a presynapse-on-glass model based on cultured neurons from rat pups of either sex. Presynaptic specializations are robustly induced along axons by micropatterned dots of neuroligin, allowing the controlled orientation and easy optical visualization of functional induced presynapses. We demonstrate the relevance and usefulness of this presynapse-on-glass model for the study of presynaptic actin architecture, showing that a majority of induced presynapses are enriched in actin, with this enrichment being correlated to higher synaptic cycling activity. We confirm our previous results on bead-induced presynapses by identifying distinct actin nanostructures within presynapses: corrals, rails, and mesh. Furthermore, we leverage the controlled orientation of the presynapse-on-glass model, visualizing the arrangement of these actin structures relative to the active zone nanoclusters using multicolor 3D single-molecule localization microscopy (SMLM) and relative to the subdiffractive localization exocytic events using a correlative live-cell and SMLM approach.