Search Results (157)

The SARS-CoV-2 nucleocapsid protein (Np) is essential for viral RNA replication and genomic RNA packaging. Phosphorylation of Np within its central Ser-Arg-rich (SRR) linker is proposed to modulate these functions. To gain mechanistic insights into these distinct roles, we performed in vitro biophysical and biochemical studies using recombinantly expressed ancestral Np and phosphomimetic SRR variants. Limited-proteolysis showed minor cleavage differences between wild-type (WT) and phosphomimetic Np, but no major structure or stability changes in the N- and C-terminal domains were observed by circular dichroism spectroscopy and differential scanning fluorimetry, respectively. Mass photometry (MP) revealed that WT Np dimerized more readily than phosphomimetic variants. Crosslinking-MP showed that WT Np formed discrete complexes on viral 5′ UTR stem-loop (SL) 5 RNA, whereas phosphomimetic Np assembled preferentially on SL1–4. WT Np bound non-specifically to all RNAs tested primarily via hydrophobic interactions, whereas phosphomimetic Np showed selectivity for SARS-CoV-2-derived RNAs despite binding more electrostatically. A major difference was observed in the binding kinetics; WT Np compacted and irreversibly bound single-stranded DNA, whereas phosphomimetic Np displayed reduced compaction and fast on/off binding kinetics. These mechanistic insights support a model where phosphorylated Np functions in RNA replication and chaperoning, while non-phosphorylated Np facilitates genomic RNA packaging. The findings also help to explain infectivity differences and clinical outcomes associated with SRR linker variants. Full article

The Wiegand effect is a nonlinear magnetic phenomenon observed in specially processed Wiegand wires, representing a macroscopic manifestation of the Barkhausen effect. It is characterized by a large, sharp Barkhausen jump in the wire’s magnetization curve under an external alternating magnetic field. However, the underlying magnetic structure of these wires and the precise mechanism responsible for the Wiegand effect remain inadequately understood. In this study, we propose a conceptual model for the magnetic structure of Wiegand wires. Experimental samples with varying diameters were prepared through FeCl₃ solution etching. The magnetic properties of individual layers within the wire were systematically investigated using the surface magneto-optic Kerr effect, Wiegand pulse measurements, and minor hysteresis loop analysis. By correlating these experimental results with JMAG simulations based on the proposed magnetic structure model, we elucidate the layer-by-layer magnetization reversal processes under alternating magnetic fields and clarify the fundamental mechanism that triggers the large Barkhausen jump. Full article

Intrusion detection systems (IDSs) must operate under severe class imbalance, evolving attack behavior, and the need for calibrated decisions that integrate smoothly with security operations. We propose a human-in-the-loop IDS that combines a convolutional neural network and a long short-term memory network (CNN–LSTM) classifier with a variational autoencoder (VAE)-seeded conditional Wasserstein generative adversarial network with gradient penalty (cWGAN-GP) augmentation and entropy-based abstention. Minority classes are reinforced offline via conditional generative adversarial (GAN) sampling, whereas high-entropy predictions are escalated for analysts and are incorporated into a curated retraining set. On CIC-IDS2017, the resulting framework delivered well-calibrated binary performance (ACC = 98.0%, DR = 96.6%, precision = 92.1%, F1 = 94.3%; baseline ECE ≈ 0.04, Brier ≈ 0.11) and substantially improved minority recall (e.g., Infiltration from 0% to >80%, Web Attack–XSS +25 pp, and DoS Slowhttptest +15 pp, for an overall +11 pp macro-recall gain). The deployed model remained lightweight (~42 MB, <10 ms per batch; ≈32 k flows/s on RTX-3050 Ti), and only approximately 1% of the flows were routed for human review. Extensive evaluation, including ROC/PR sweeps, reliability diagrams, cross-domain tests on CIC-IoT2023, and FGSM/PGD adversarial stress, highlights both the strengths and remaining limitations, notably residual errors on rare web attacks and limited IoT transfer. Overall, the framework provides a practical, calibrated, and extensible machine learning (ML) tier for modern IDS deployment and motivates future research on domain alignment and adversarial defense. Full article

Low-pressure N₂ adsorption experiments were conducted on 20 samples from the Doushantuo Formation in the Yichang area to quantitatively characterize their pore structures and fractal properties. The samples are mainly composed of quartz, dolomite, and clay minerals, with minor amounts of feldspar, calcite, and pyrite. The N₂ adsorption–desorption isotherms display typical type IV characteristics with a pronounced hysteresis loop, indicating that mesopores are dominant. The specific surface areas range from 3.78 to 11.49 m²/g, and the total pore volumes range from 0.0039 to 0.0169 mL/g, with mesopores contributing most of the total pore volume. Fractal analysis based on the FHH model reveals two distinct fractal dimensions (D_f): D_f1 = 2.5–2.9 for small pores and D_f2 = 2.0–2.3 for large pores. The fractal dimensions are negatively correlated with TOC, quartz, and carbonate contents but positively correlated with clay and pyrite contents. Higher organic matter content tends to produce relatively smooth organic pores, reducing pore heterogeneity, whereas higher clay content increases surface roughness and structural complexity. Overall, the heterogeneity of pore structures in the Doushantuo Formation shales is primarily controlled by mineral composition and organic matter content. These results provide new insights into the pore characteristics and storage potential of Ediacaran marine shales. Full article

Wide bandgap (WBG) power semiconductors such as silicon carbide (SiC) can significantly improve the performance of multilevel converters. However, there are three challenges for large-scale application: high cost, limited power ratings, and reliability issues. In this paper, we propose a Si and SiC hybrid arms active neutral-point-clamped (ANPC) converter, using smaller current rating SiC devices compared to other Si devices in this topology. By employing the hybrid-frequency modulation scheme, the Si devices switch at fundamental frequency (FF) or low frequency (LF), while the SiC devices switch at high frequency (HF). The equivalent circuit of the proposed converter is derived to analyze the principle of LF current ripple compensation. The closed-loop cooperative current control strategy is proposed to realize unequal current sharing in two arms and complete LF current ripple compensation. The Si arm processes major power, while the SiC arm compensates the LF current ripple generated by the Si arm and processes minor power. The proposed topology and control strategy are validated by simulation and experimental results. Compared with the existing typical topologies, the comprehensive optimization of power quality, efficiency, and cost is realized. Full article

Background/Objectives: Single-domain antibodies (sdAbs) are derived from camelid heavy-chain antibodies (HCAb). Their small size, high stability, and ease of production, among other properties, makes them highly valuable in biomedical research and therapeutic development. Several sdAb-based molecules are currently progressing through clinical trials, highlighting their translational relevance. As sdAbs originate from HCAb of Camelidae family, they can originate from multiple species including Vicugna pacos, Lama glama, Camelus dromedarius and Camelus bactrianus. Although several reports and databases analyze the structure of sdAbs, comprehensive evaluations on species-dependent structural differences remain scarce. Methods: We assembled MO-IISA, an open-access curated database of sdAbs with known antigen targets by integrating six public resources (iCAN, INDI, SAbDab-nano, sdAb-DB, PLabDab-nano, NbThermo) under harmonized eligibility criteria. Results: The final dataset comprises 2053 sdAbs derived from llamas (Lama glama, n = 1316); alpacas (Vicugna pacos, n = 325), dromedary camels (Camelus dromedarius, n = 377) and Bactrian camels (Camelus bactrianus, n = 35). We quantified region lengths, amino acid frequency, and conservation/entropy across frameworks (FR1–FR4). The average length of all sdAbs was about 124 ± 8 amino acids, with minor interspecies differences. We observed a consistent enrichment of lysines in FR3 (and secondarily FR2) and cysteines primarily in FR1 and FR3, with non-canonical cysteines more frequent in Bactrian and dromedary sdAbs CDRs. CDR2 and, particularly CDR3, contributed most to inter- and intra-species variability, whereas FRs were highly conserved. Conclusions: Species-neutral framework constraints and species-tuned loop adaptations have practical implications for sdAb engineering, species selection, and conjugation strategies. These features are captured in MO-IISA, an open-access database of known-target sdAbs from different species. Full article

The increasing share of renewable energy sources in power grids demands greater load flexibility from thermal power plants. Circulating Fluidized Bed (CFB) combustion systems, while offering fuel flexibility and high thermal inertia, face challenges in maintaining hydrodynamic and thermal stability during load transitions. This study investigates partial flue gas recirculation (FGR) as a strategy to enhance short-term load flexibility in a 1 MW_th CFB pilot plant fired exclusively with solid recovered fuel. Two experimental test series were conducted. Under conventional operation, where fuel and fluidization air are reduced proportionally, load reductions to 86% and 80% led to operating regime shift. Particle entrainment from the riser to the freeboard and loop seal decreased, circulation weakened, and the temperature difference between bed and freeboard zone increased by 71 K. Grace diagram analysis confirmed that the system approached the boundary of the circulating regime. In contrast, the partial FGR strategy maintained total fluidization rates by replacing part of the combustion air with recirculated flue gas. This stabilized pressure conditions, sustained particle circulation, and limited the increase in the temperature difference to just 7 K. Heat extraction in the freeboard remained constant or improved, despite slightly lower flue gas temperatures. While partial FGR introduces a minor efficiency loss due to the reheating of recirculated gases, it significantly enhances combustion stability and enables low-load operation without compromising fluidization quality. These findings demonstrate the potential of partial FGR as a control strategy for flexible, waste-fueled CFB systems and supports its application in future low-carbon energy systems. Full article

This study employed molecular dynamics simulations to investigate the impact of N-linked glycosylation (GlcNAc₂) at the K20N position on the structural dynamics and stability of the bacterial immunity protein Im7. Simulations were conducted in both aqueous and 2 M urea denaturing environments. The simulation results in aqueous solution indicate that glycosylation has only a minor effect on the protein, consistent with expectations. In contrast, simulations in urea reveal that K20N glycosylation significantly destabilizes Im7. Analyses of RMSD, native contacts, SASA, RMSF, correlation matrix, PCA, helical content and hydrophobic centroid distance consistently demonstrate that K20N glycosylation increases the flexibility of Helix I and Helix II and weakens the concerted motion among helical domains (particularly between Helix I and Helix II/IV). The destabilizing effect of K20N glycosylation on Im7 originates in Helix I (where glycan attaches) and propagates to Helix II and the loop region connecting Helix I and Helix II. The instability of Helix II is closely associated with the disruption of hydrophobic interactions within the hydrophobic core. These findings provide new insights into the relationship between site-specific glycosylation and protein stability. Full article

Objectives: The adoption of telemedicine, which is the delivery of healthcare services through digital platforms, exploded during the COVID-19 pandemic as a means to ensure the continuity of care while minimizing infection risks. While this modality improved access and convenience for many, disparities in adoption have emerged, particularly in rural and underserved populations. This study aims to evaluate the impact of telemedicine on patient satisfaction before and during the pandemic, with a focus on chronic disease management—notably hypertension—and to identify factors influencing the equitable adoption of telehealth. Methods and Procedures: This study used a mixed method approach, combining quantitative survey data and causal loop modeling to analyze patient satisfaction levels and the interplay between telehealth adoption, healthcare access, and demographic disparities. Patient-reported satisfaction data were collected in two time periods—before and during the pandemic. Causal modeling was used to explore systemic relationships between provider support, technology access, patient engagement, and health equity. Results: The findings revealed that telemedicine significantly enhanced healthcare access during the pandemic, with a notable increase in patient satisfaction scores. Patients with chronic conditions, especially those diagnosed with hypertension, reported the improved continuity of care and reduced geographic barriers. However, disparities in telehealth access were more pronounced in non-metropolitan areas and among older adults and minority populations. Causal analysis highlighted key enablers of telehealth success, i.e., provider support, digital literacy, and access to reliable internet and devices. Conclusions: Telemedicine presents a transformative solution for equitable healthcare delivery, especially in chronic disease management. Strategic efforts are needed to address adoption disparities and ensure the sustained and inclusive integration of telehealth after the pandemic. Full article

Background: Subacromial impingement or pain syndrome (SAPS) is the most common diagnosis for chronic shoulder pain. Current surgeries do not reduce long-term pain, suggesting they miss the root etiology. Previously, we described the Human Disharmony Loop (HDL), where the unique lower trunk innervation to the pectoralis minor (PM) causes scapular dyskinesis and deforms its connections, including tugging the acromion down and impinging the subacromial structures. We hypothesize that SAPS patients who meet HDL criteria would benefit significantly from PM tenotomy with infraclavicular brachial plexus neurolysis (PM + ICN) alone. Methods: SAPS patients who met HDL diagnostic criteria were treated with PM + ICN, with secondary distal neurolysis if needed. Outcomes included pain and shoulder abduction ROM. Six-month follow-up minimum was required. Results: N = 140 patients were included. Median age was 49. Prior surgeries included 27% subacromial decompression/acromioplasty, 21% rotator cuff repair, 16% biceps tenodesis, 4% SLAP repair, 2% labral repair, 7% distal clavicle resection, 10% reverse total shoulder arthroplasty (rTSA), 1% rib resection with scalenectomy, 16% cervical spine fusion, 28% distal neurolysis. Median pain decreased from 8 to 2 and median shoulder ROM increased from 90 to 180 degrees. Positive impingement signs on exam decreased from 100% to 11%. (p < 0.01) Conclusions: In a large series of SAPS patients, evaluation and treatment for the HDL significantly reduced pain and restored motion. These findings suggest that in many patients SAPS may be a subset of the HDL: the ventral PM disturbing the scapula constitutes the anatomic basis and optimal surgical target behind SAPS. Full article

Rehabilitation devices such as actuated lower-limb exoskeletons can provide essential mobility assistance for pediatric patients with gait impairments. Enhancing their control systems under conditions of user variability and dynamic disturbances remains a significant challenge, particularly in active-assist modes. This study presents a human-in-the-loop control architecture for a pediatric lower-limb exoskeleton, combining outer-loop admittance control with robust inner-loop trajectory tracking via a non-singular terminal sliding-mode (NSTSM) controller. Designed for active-assist gait rehabilitation in children aged 8–12 years, the exoskeleton dynamically responds to user interaction forces while ensuring finite-time convergence under system uncertainties. To enhance adaptability, we augment the inner-loop control with a twin delayed deep deterministic policy gradient (TD3) reinforcement learning framework. The actor–critic RL agent tunes NSTSM gains in real-time, enabling personalized model-free adaptation to subject-specific gait dynamics and external disturbances. The numerical simulations show improved trajectory tracking, with RMSE reductions of 27.82% (hip) and 5.43% (knee), and IAE improvements of 40.85% and 10.20%, respectively, over the baseline NSTSM controller. The proposed approach also reduced the peak interaction torques across all the joints, suggesting more compliant and comfortable assistance for users. While minor degradation is observed at the ankle joint, the TD3-NSTSM controller demonstrates improved responsiveness and stability, particularly in high-load joints. This research contributes to advancing pediatric gait rehabilitation using RL-enhanced control, offering improved mobility support and adaptive rehabilitation outcomes. Full article

This study aims to explore the tracking control challenge in a swarm of multiple nonholonomic wheeled mobile robots (NWMRs) by utilizing a distributed leader–follower strategy grounded in the cascade system theory. Firstly, the kinematic control law is developed for the leader by constructing a sliding surface based on the error tracking model with a virtual reference trajectory. Secondly, a communication topology with the desired formation pattern is modeled for the multiple robots by using the graph theory. Further, in the leader–follower NWMR system, each follower lacks direct access to the leader’s information. Therefore, a novel distributed-based controller by PD-based controller for the follower is developed, enabling each follower to obtain the leader’s information. Thirdly, for each case, we give a further analysis of the closed-loop system to guarantee uniform global asymptotic stability with the conditions based on the cascade system theory. Finally, the trajectory tracking performance of the proposed controllers for the NWMR system is illustrated through simulation results. The leader robot achieved a low RMSE of 1.6572 (Robot 1), indicating accurate trajectory tracking. Follower robots showed RMSEs of 2.6425 (Robot 2), 3.0132 (Robot 3), and 4.2132 (Robot 3), reflecting minor variations due to the distributed control strategy and local disturbances. Full article

Türkiye represents an important biogeographic region connecting Southeast Europe with Southwest Asia, where pig domestication began in the western Palearctic. We studied the phylogenetic relationships and spatial distribution of new and published mitochondrial D-loop sequences of wild boars from Türkiye, other parts of the Middle East, and from around the world to understand migration patterns within Asia Minor and other parts of the Middle East as well as across the Bosphorus/Sea of Marmara/Dardanelles, a current migration barrier to Southwest Europe. Our phylogenetic (ML, BI) and spatial (Geneland) analyses revealed haplotypes both endemic to Anatolia and with a wider distribution in the Middle East as well as European (E1) lineages. The latter suggested possible rare immigration into Anatolia at present times and prehistorical/historical anthropogenic translocations of wild boars or pigs, such as during the pre-Hellenic, Roman, and Byzantine periods or during the European crusades, and subsequent introgression into Anatolian wild boars. Import of pigs with E1 haplotypes and introgression into wild boars during the medieval Empire of Trebizond particularly by Italian merchants or settlers, is also suggested. Anatolian lineages that may have formed the basis of the archaic domestication process of pigs in the western Palearctic are discussed. Full article

Aquaporin 1 is a membrane water channel protein, which was studied here in spiny dogfish (Squalus acanthias) osmoregulatory tissues using a variety of techniques. The cloning of aquaporin 1 (AQP1) in the spiny dogfish identified a splice variant version of the mRNA/protein (AQP1SV1/AQP1SV1). Polymerase chain reaction (PCR) in a range of tissues showed AQP1 to be expressed at very high levels in the rectal gland with ubiquitous mRNA expression at lower levels in other tissues. Northern blotting showed that AQP1 had a mRNA size of 5.3 kb in kidney total RNA. The level of AQP1 mRNA was significantly lower in the rectal glands of fish acclimated to 120% seawater (SW; vs. 75% SW (p = 0.0007) and 100% SW (p = 0.0025)) but was significantly higher in those fish in the kidney (vs. 100% SW (p = 0.0178)) and intestine (vs. 75% SW (p= 0.0355) and 100% SW (p = 0.0285)). Quantitative PCR determined that AQP1SV1 mRNA levels were also significantly lower in the rectal glands of both 120% (p = 0.0134) and 100% SW (p = 0.0343) fish in comparison to 75% SW-acclimated dogfish. Functional expression in Xenopus oocytes showed that AQP1 exhibited significant apparent membrane water permeability (p = 0.000008–0.0158) across a range of pH values, whereas AQP1SV1 showed no similar permeability. Polyclonal antibodies produced against AQP1 (AQP1 and AQP1/2 antibodies) and AQP1SV1 had bands at the expected sizes of 28 kDa and 24 kDa, respectively, as well as some other banding. The weak AQP1 antibody and the stronger AQP1/2 antibody exhibited staining in the apical membranes of rectal gland secretory tubules, particularly towards the periphery of the gland. In the gill, the AQP1/2 antibody in particular showed staining in secondary-lamellar pavement-cell basal membranes, and in blood vessels and connective tissue in the gill arch. In the spiral valve intestine side wall and valve flap, the AQP1/2 antibody stained muscle tissue and blood vessel walls and, after tyramide signal amplification, showed some staining in the apical membranes of epithelial cells at the ends of the luminal surface of epithelial folds. In the rectum/colon, there was also some muscle and blood vessel staining, but the AQP1 and AQP1/2 antibodies both stained a layer of cells at the base of the surface epithelium. In the kidney convoluted bundle zone, all three antibodies stained bundle sheath membranes to variable extents, and the AQP1/2 antibody also showed staining in the straight bundle zone bundle sheath. In the kidney sinus zone, the AQP1/2 antibody stained the apical membranes of late distal tubule (LDT) nephron loop cells most strongly, with the strongest staining in the middle of the LDT loop and in patches towards the start of the LDT loop. There was also a somewhat less strong staining of segments of the first sinus zone nephron loop, particularly in the intermediate I (IS-I) tubule segment. Some tubules appeared to show no or only low levels of staining. The results suggest that AQP1 plays a role in rectal gland fluid secretion, kidney fluid reabsorption and gill pavement-cell volume regulation and probably a minor role in intestinal/rectal/colon fluid absorption. Full article

Background: Stigma is a pervasive, though understudied, psychosocial factor affecting people with multiple sclerosis. This review synthesizes the literature on the impact of perceived, enacted, and internalized stigma on psychological health and illness identity in PwMS. Methods: A comprehensive narrative review approach was adopted, integrating findings from peer-reviewed quantitative and qualitative studies. Databases including PubMed, PsycINFO, and Scopus were searched using combinations of terms such as “multiple sclerosis”, “stigma”, “internalized stigma”, “mental health”, and “illness identity”. Studies were included if they reported on stigma-related outcomes in PwMS, discussed psychological or identity variables, or examined interventions aimed at reducing stigma or enhancing adaptive identity. The analysis focused on thematic synthesis, identifying recurrent findings, mediating mechanisms, and clinical implications. Results: Stigma in MS is consistently linked to higher depression, anxiety, and lower quality of life. Internalized stigma disrupts illness identity, often fostering engulfment and rejection of the self. Psychological mediators—such as cognitive fusion, diminished self-compassion, and weakened sense of coherence—amplify these outcomes. Particularly vulnerable are individuals with progressive disease, severe disability, minority status, or limited social support. A recursive loop emerges: stigma triggers psychological distress, which increases stigma awareness and social withdrawal. In addition to traditional psychological interventions, several emerging approaches have shown promise in reducing internalized stigma and fostering adaptive identity integration. Conclusions: Stigma is a central factor in emotional suffering and identity fragmentation in PwMS. Integrative, narrative-informed, and culturally sensitive interventions are essential to reduce stigma and foster resilience. Future research should prioritize longitudinal, mixed-method approaches to develop effective, scalable solutions. Full article