Search Results (973)

The MERS-CoV (Middle East respiratory syndrome coronavirus) is a zoonotic virus with a high mortality rate and a lack of antiviral drugs, underscoring the need for effective therapeutic methods. Viral entry depends on interactions between viral surface proteins and human receptors, with Dipeptidyl Peptidase-4 (DPP4), a transmembrane glycoprotein, acting as the receptor for MERS-CoV. We employed Molecular Dynamics (MD) Simulations to identify critical interface residues under a high-performance computing (HPC) workflow for accelerated results. Target residue pairs were identified through analysis of salt bridge and hydrogen bond occupancy. The stability of these residues was confirmed through three independent MD Simulations at human body temperature and constant pressure. Additionally, binding affinity predictions were calculated to determine the interaction strength between the virus and human receptors. Applying the scientific threshold criteria, we narrowed our results to seven key interaction pairs; two of the identified pairs (Asp510-Arg317, and Arg511-Asp393) are consistent with findings published in previous research studies, and five novel interactions are proposed for future experimental studies with our active collaborators in Pharmacology. The results provide a molecular basis for targeted mutation-based experiments and support the rational design of structure-based inhibitors aimed at disrupting the MERS-CoV-DPP4 complex, thereby facilitating the translation of computational findings into antiviral drug discovery. Full article

This study evaluates the hydrodynamic performance of a displacement-type FAO longliner fishing vessel fitted with a surface-piercing dihedral bulbous bow. Unlike conventional submerged bulbs, this configuration partially emerges at the free surface. Hydrodynamic behaviour was analysed under heavy- and light-load conditions using both computational and experimental fluid dynamics. Results show that the dihedral bulb significantly reduces total resistance beyond a critical speed of approximately 6 knots, whilst also affecting dynamic trim and vertical hydrodynamic forces. Full-scale effective power was estimated by extrapolating model results according to ITTC procedures. This study confirms that dihedral bulbous bows are well suited for retrofit applications on small fishing vessels under 20 m in length, achieving maximum resistance reductions of about 18% at higher speeds. These gains translate into notable fuel savings and reduced greenhouse gas emissions, making the retrofit both economically and environmentally advantageous. Full article

Background: Buccal administration offers direct access to systemic circulation, improving drug bioavailability when compared with the conventional oral route. This advantage depends on the formulation’s ability to remain in contact with the buccal mucosa. Attributes such as adhesion and viscosity are suggested to be correlated and contribute to enhanced residence time at the administration site. Methods: Buccal formulations with varying hydroxypropyl cellulose concentrations were prepared. Adhesion, viscosity, and residence time were assessed using a novel combined qualitative and quantitative approach. Drug permeation was evaluated in vitro using a biomimetic membrane and ex vivo using porcine buccal tissue, and it was further enhanced by adding the permeation enhancer benzalkonium chloride. Permeability measurements were integrated with residence time to estimate effective drug delivery. Results: Increasing HPC concentration improved both adhesion and viscosity, with 2% HPCs (F2) showing the strongest effect (45.5 ± 13.7 g), correlating with longer residence time (43.4% drug retained at 2 min vs. ~20% for 0–1% HPC). Although the polymer slightly reduced apparent permeability, when residence time was considered, drug flux increased 1.6-fold compared to the polymer-free formulation (F0), rising from 12.9 × 10⁻⁵ cm/min (F0) to 19.4 × 10⁻⁵ cm/min (F2) after 2 min. The addition of BKC further enhanced permeation, with apparent permeability increasing 1.5-fold vs. F2 and 2.5-fold vs. F0. Conclusions: Buccal liquid preparations’ efficacy is influenced by residence time and subsequent drug permeation. Residence time benefits from the synergistic effects of adhesion and viscosity, highlighting the importance of experimentally assessing these parameters during the development of oromucosal products. Full article

Despite extensive research on blast-resistant concrete structures, a clear scientific deficiency remains in the quantitative understanding of how fiber-reinforced concrete slabs behave under blast loading, particularly when experimental and numerical investigations are not conducted together under identical loading conditions. Existing studies often focus on either conventional reinforced concrete or isolated material systems, providing limited validation of comparative blast performance across different fiber-reinforced concretes. This study addresses this gap by investigating the blast resistance performance of four types of reinforced concrete slabs: normal concrete (NC), ultra-high-performance fiber-reinforced concrete (UHPFRC), organic fiber-reinforced high-performance concrete (O-HPC), and basalt FRP-sheet-strengthened slurry-infiltrated fiber concrete (F-SIFCON), using full-scale blast experiments and validated numerical simulations conducted with ANSYS Explicit Dynamics. Blast tests were performed to obtain time histories of reflected pressure, displacement, acceleration, reaction force, and internal energy. The influence of different fiber systems and FRP strengthening on dynamic response and failure mechanisms was systematically analyzed. The numerical models showed good agreement with experimental measurements, confirming their reliability. The results indicate that the normal concrete slab exhibited brittle failure and poor blast resistance, whereas the F-SIFCON slab demonstrated the best overall performance. Compared with the normal concrete slab, the F-SIFCON slab achieved approximately a 47% reduction in maximum displacement, a 56% increase in peak reaction force, and the highest internal energy absorption of 236 kJ. The UHPFRC and O-HPC slabs also showed improved blast resistance, although with different post-peak response characteristics. These findings demonstrate that hybrid fiber reinforcement combined with FRP strengthening can significantly enhance the blast resistance of concrete slabs and that coupled experimental–numerical approaches provide a robust framework for evaluating structural performance under extreme dynamic loading. Full article

Background/Objectives: Health Promotion Centres (HPCs) in Slovenia represent a European best practice for integrated prevention and health promotion. This study explores the feasibility of adapting the Slovenian HPC model to Bergamo Province, Lombardy, considering local population needs and health system characteristics. Methods: We conducted a qualitative feasibility and policy analysis based primarily on documentary review, complemented by a webinar, a study visit to Slovenia, and expert consultations (conducted in two group discussions) with professionals from ATS (Agenzia Tutela della Salute) Bergamo and local ASST (Azienda Socio-Sanitaria Territoriale) providers. Data were analysed using the PIET-T framework (Population–Intervention–Environment–Transfer). Results: Eight key elements define the Slovenian model: (1) governance and stewardship; (2) structural financing; (3) standardized service portfolio; (4) systematic preventive referrals; (5) integration with primary care and screening; (6) multidisciplinary teams with codified training; (7) community outreach and equity orientation; and (8) information systems and reporting. While Bergamo shares similar demographic and epidemiological profiles, differences in behavioral risk factors, project-based financing, fragmented initiatives, and limited digital integration necessitate adaptation. The comparative assessment highlighted key areas requiring contextual adaptation, including financing mechanisms, organisational coordination, workforce capacity, digital interoperability, and approaches to equity. Conclusions: The Slovenian HPC experience demonstrates the potential of integrated, community-based health promotion. Its adaptation to Lombardy appears feasible if core components are preserved and tailored to local governance, population, and health system conditions. These organisational features may be particularly relevant for time-dependent conditions, such as acute cardiovascular and cerebrovascular events, by potentially supporting more timely risk-factor management and coordination across diagnostic and emergency pathways. Rather than a blueprint for reform, this experience offers useful insights to reinforce prevention and health promotion within the ongoing territorial care reform in Lombardy. Full article

Alzheimer’s disease (AD) is a progressive neurodegenerative disorder characterized by irreversible cognitive decline and synaptic dysfunction and represents the most prevalent etiology of dementia, accounting for an estimated 60–70% of all clinically diagnosed cases worldwide. The growing focus on microglia–neuron interactions in AD research highlights their diverse, region-specific responses, which are driven by the functional and pathological heterogeneity across different brain regions. Therefore, investigating the interactions between microglia and neurons is of crucial importance. To explore the regional heterogeneity of microglia–neuron crosstalk in AD, we integrated human single-nucleus RNA sequencing data from the prefrontal cortex (PFC), hippocampus (HPC), and occipital lobe (OL) provided by the ssREAD database. Our study delineated four microglial subtypes and uncovered a pseudotime trajectory activation trajectory leading to the disease-associated microglia (DAM) phenotype. The transition along this trajectory is driven and stabilized by a key molecular switch: the coordinated downregulation of inhibitory factors (e.g., LINGO1) and upregulation of immune-effector and antigen-presentation programs, which collectively establish the pro-inflammatory DAM state. Furthermore, we observed that each brain region displayed unique microglia–neuron communication patterns in response to AD pathology. The PFC and OL engage a THY1-ITGAX/ITGB2 signaling axis; the HPC predominantly utilizes the PTPRM pathway. Notably, THY1 dysregulation strongly correlates with pathology in the PFC, HPC, and OL, suggesting that microglia–neuron crosstalk in AD possesses both heterogeneity and commonality. The main contribution of this study is the systematic characterization of region-specific microglia-neuron interactions and the identification of THY1 as a potential mediator that may be targeted therapeutically to modulate microglial function in affected brain regions. Full article

We discuss the design, the analysis and the parallel implementation of a dynamic programming approach for the computation of the density of state in the simulation of spin-crossover nanoparticles. The motivation is the computation of a Hamiltonian, which is usually approximated using Monte Carlo techniques. However, physicists need better control of the accuracy of this approximation. An exact counting algorithm allows this error to be controlled, and also measures the impact on accuracy for the entire simulation. We propose an exact parallel counting algorithm and its two-level parallel implementation to tackle nanoscale problems on HPC architecture. We discuss its scalability and feasibility for $2D$ grids of n molecules. The new algorithm enables the exact computation for a three-variable density of state at nanoscale, which is seen as intractable. A comparison between the expectation of the model and implementation is proposed. The parallel complexity achieved is $O(n^{{\displaystyle \frac{5}{2}}}{2}^{\sqrt{n}})$ and the results allow the prediction of never-before-seen phenomena. Full article

Background/Objectives: This pilot study aimed to evaluate the feasibility of applying the Beers criteria in the community pharmacy setting and aid pharmacists in identifying and emphasizing adverse effects from potentially inappropriate medications (PIMs) for older adults. Methods: We applied a single-center retrospective study to collect demographic and outcome data in order to analyze dispensed PIMs for older adults. We used an evaluation tool to compare warnings between pharmacy dispensing software and the Beers criteria. Descriptive statistics were computed via standard statistical software. Results: Culled from a random selection of 215 patients, the medical records from 50 subjects ≥65 years old were reviewed, including 440 of their medications. Our data demonstrated that 96% of subjects were dispensed at least one PIM, with a total of 34 different PIMs distributed at varying frequencies. A comparative analysis indicated that 74% of dispensed medications had similar, but not identical, warning profiles presented in the dispensing software and Beers criteria. Anticholinergic burden of dispensed PIMs indicated that older adults were at risk of falls and delirium. By supplementing the dispensing software with Beers criteria, we were able to create clinical communication notes for providers, patients, and pharmacy students to emphasize the role pharmacists can play to minimize PIM’s adverse effects on older adults. Conclusions: Our data indicates the feasibility of implementing the Beers criteria in the community pharmacy setting. Integrating the dispensing software warnings with Beers criteria created a structured intervention strategy to prevent potential adverse effects and develop clinical communication notes to emphasize a more engaging role that the community pharmacy setting can play to optimize therapeutic outcomes for older adults. Full article

The thermally efficient and lightweight TRC/CLCi composite panels for functional and smart building envelopes, funded by the iclimabuilt project (Grant Agreement no. 952886), offer innovative solutions to sustainably address common failure risks in facade systems. This work specifically emphasizes strategies for mitigating structural, thermal, and fire-related failures through targeted material selection, advanced design methodologies, and rigorous validation protocols. To effectively mitigate structural failures, high-pressure concrete (HPC) reinforced with carbon fibers is utilized, significantly enhancing tensile strength, reducing susceptibility to cracking, and improving overall durability. To counteract thermal bridging—a critical failure mode compromising energy efficiency and structural integrity—the panels employ specially designed glass-fiber reinforced pins connecting HPC outer layers through the cellular lightweight concrete (CLC) insulation core that has a density of around 70 kg/m³ and a thermal conductivity in the range 35 mW/m∙K comparable to those of expanded polystyrene and Rockwool. These connectors ensure effective load transfer and maintain optimal thermal performance. A central focus of the failure mitigation strategy is robust fire behavior. The developed panels undergo rigorous standardized fire tests, achieving an exceptional reaction to fire classification of A2. This outcome confirms that HPC layers maintain structural stability and integrity even under prolonged fire exposure, effectively preventing catastrophic failures and ensuring occupant safety. In conclusion, this work highlights explicit failure mitigation strategies—reinforced concrete materials for structural stability, specialized glass-fiber connectors to prevent thermal bridging, rigorous fire behavior protocols, and comprehensive thermal performance validation—to produce a facade system that is robust, energy-efficient, fire-safe, and sustainable for modern buildings. Full article

This study evaluates the mechanical properties and durability of novel self-shrinking chitosan fibers incorporated into a High-Performance Concrete (HPC) matrix. The cementitious system comprised a 75–25% blend of Portland Limestone Cement (PLC) and Ground Glass Pozzolan (GGP). Two variants of chitosan—food-grade and high-grade—were processed into fibers and integrated at dosages of 0.36%, 0.73%, and 1.45% by weight of binder, alongside a 0% control group. The experimental program assessed eight distinct mixtures through extended freeze–thaw testing (up to 602 cycles), electrical resistance monitoring, and compressive strength evaluation at 56 and 90 days. Results indicated that food-grade chitosan fibers caused a substantial reduction in compressive strength, ranging from 40% to 70% depending on the dosage. Despite this mechanical loss, these mixtures showed localized improvements in freeze–thaw resistance and electrical resistivity. Conversely, the high-grade chitosan fibers exhibited severe performance degradation under freeze–thaw cycling; all reinforced groups fell below 80% relative dynamic modulus, with two mixtures dropping below the 60% failure threshold. In comparison, the control mixture retained 98% of its dynamic modulus after 602 cycles. Ultimately, the findings suggest that, in their current formulation, self-shrinking chitosan fibers do not provide consistent or reliable enhancements to the structural integrity or durability of high-performance concrete. Full article

Dragonfly networks $D(n,h)$ are a class of interconnection topologies widely used for large-scale high-performance computing (HPC) systems. In such networks, path connectivity serves as a fundamental metric for evaluating fault tolerance and operational reliability. Let G be a connected simple graph with vertex set $V\left(G\right)$. Let $\mathrm{\Omega }$ be a subset of $V\left(G\right)$ with cardinality at least two. A path containing all vertices of $\mathrm{\Omega }$ is said to be an $\mathrm{\Omega }$-path of G. Two paths ($T_1$ and $T_2$) of G are internally disjoint if $V\left(T_1\right)\cap V\left(T_2\right)=\mathrm{\Omega }$ and $E\left(T_1\right)\cap E\left(T_2\right)=\varnothing$. For an integer with $2\le \ell$, the ℓ-path connectivity ${\pi }_{\ell }\left(G\right)$ is defined as ${\pi }_{\ell }\left(G\right)=min\{{\pi }_G\left(\mathrm{\Omega }\right)|\mathrm{\Omega }\subseteq V\left(G\right)\mathrm{and}|\mathrm{\Omega }|=\ell \}$, where ${\pi }_G\left(\mathrm{\Omega }\right)$ represents the maximum number of internally disjoint $\mathrm{\Omega }$-paths. This paper focuses on resolving the exact value of 3-path connectivity of dragonfly networks, ${\pi }_3\left(D(n,h)\right)$, defined as the maximum number of internally disjoint paths among any three distinct vertices in $D(n,h)$. For $D(n,h)$ with $n\ge 5$ and $h\ge 2$, the exact 3-path connectivity is ${\pi }_3\left(D(n,h)\right)=\lfloor {\displaystyle \frac{3h+2n}{4}}\rfloor$ if $h\le n-2$, and ${\pi }_3\left(D(n,h)\right)=\lfloor {\displaystyle \frac{3n+2h-2}{4}}\rfloor$ if $h\ge n-1$. Full article

The connectivity demands of high-performance computing (HPC), artificial intelligence (AI) and data centers are driving the development of a new generation of multimode optical components. This paper discusses the vertical cavity surface emitting laser (VCSEL) bandwidth and noise performance needed to support 106 Gbd line rates with PAM4 modulation for 200 Gbps per lane multimode optical links. A −3 dB bandwidth greater than 35 GHz and a RIN of less than −152 dB/Hz are demonstrated. No uncorrectable errors were observed over 50 m of OM4 fiber, demonstrating good link stability. VCSEL device performance and the associated wear-out life are presented. Leveraging good device reliability and low power consumption of VCSEL-based links, a novel VCSEL near-packaged optics (NPO) concept is proposed for optical interconnects in AI scale-up network applications. Optical interconnects allow for longer reaches, compared to copper interconnects, which facilitate larger AI clusters with network disaggregation. The proposed VCSEL NPO can achieve an energy efficiency of ~1 pJ/bit, which is the highest among optical interconnects. Full article

This study aims to investigate the effects of Chan-Hom (2015) typhoon-induced variations in enthalpy flux (EF) and moisture flux (MF) on intensity variations and rainfall. Chan-Hom (2015) made landfall at Zhoushan, then changed its direction and moved towards Korea. This analysis used ERA5 reanalyzed data, encompassing daily surface latent and sensible heat flux, along with wind measurements at a height of 10 m. Furthermore, wind components and specific humidity data from the 1000–200 hPa level in ERA5 were utilized to compute the MF and MF convergence, in accordance with the equations outlined in the methodology. This study examines the correlation among typhoon intensity, precipitation, MF, and EF. The mechanism by which Typhoon Chan-Hom has caused a decline in sea surface temperature (SST) was analyzed. Typhoons need a higher EF that can affect them before landfall to maintain their intensity. The highest LHF was observed (340 W/m²) prior to typhoon landfall, indicating that LHF responds to intensity-induced wind during Chan-Hom. Typhoon-induced rainfall is mainly controlled by the MF convergence, rather than the typhoon intensity. The spatial and temporal distributions of MF and MF convergence (MFC) during typhoon formation to landfall reveal that the symmetric MFC is dominated by typhoon intensity; a symmetrical structure is observed when the intensity is high. MFC includes wind convergence and moisture advection. Wind convergence dominates the MFC during typhoons, but moisture advection forms at the eyewall. MF during the typhoon’s landfall can relate to the amount of rainfall that occurred over the land. However, the rainfall pattern changed after landfall, and the typhoon changed its direction. SST cooling observed in the study area is mainly due to the upwelling process with strong cyclonic winds. Full article

High-Performance Computing (HPC) has become essential for training medium- and large-scale Artificial Intelligence (AI) models, yet two bottlenecks remain under-exploited: the semantic coherence of training data and the interaction between distributed deep learning runtimes and heterogeneous HPC architectures. Existing work tends to optimise multi-node, multi-GPU training in isolation from data semantics or to apply semantic technologies to data curation without considering the constraints of large-scale training on modern clusters. This paper introduces SemanticHPC, an experimental framework that integrates ontology and Resource Description Framework (RDF)-based semantic preprocessing with distributed AI training (Horovod/PyTorch Distributed Data Parallel) and hardware-aware optimisations for Non-Uniform Memory Access (NUMA), multi-GPU and high-speed interconnects. The framework has been evaluated on 1–8 node configurations (4–32 GPUs) on a production-grade cluster. Experiments on a medium-size Open Images V7 workload show that semantic enrichment improves validation accuracy by 3.5–4.4 absolute percentage points while keeping the additional end-to-end overhead below 8% and preserving strong scaling efficiency above 79% on eight nodes. We argue that bringing semantic technologies into the training workflow—rather than treating them as an offline, detached phase—is a promising direction for large-scale AI on HPC systems. We detail an implementation based on standard Python libraries, RDF tooling and widely adopted deep learning runtimes, and we discuss the limitations and practical hurdles that need to be addressed for broader adoption. Full article

This paper presents an experimental investigation of the shear connection between outer layers of lightweight precast concrete sandwich panels (PCSP) made of high-performance concrete (HPC). The shear-transfer mechanism is based on reinforcing ribs composed of rigid polymer-based thermal insulation combined with carbon-fibre-reinforced polymer (CFRP) shear reinforcement. A total of seven full-scale sandwich panels were tested in four-point bending. This study compares three types of rigid thermal insulation used in the shear ribs—Purenit, Compacfoam CF400, and Foamglass F—and investigates the influence of the amount of CFRP shear reinforcement on the structural behavior of the panels. Additional specimens were used to evaluate the effect of reinforcing ribs and of polymer-based thermal insulation placed between the ribs. The experimental results show that panels with shear ribs made of Purenit and Compacfoam CF400 achieved significantly higher load-bearing capacities compared to Foamglass F, which proved unsuitable due to its brittle behavior. Increasing the amount of CFRP shear reinforcement increased the load-bearing capacity but had a limited effect on panel stiffness. The experimentally determined composite interaction coefficient ranged around α ≈ 0.03, indicating partial shear interaction between the outer concrete layers. A simplified strut-and-tie model was applied to predict the load-bearing capacity and showed conservative agreement with experimental results. The findings demonstrate that polymer-based materials, particularly CFRP reinforcement combined with rigid polymer insulation, enable efficient shear transfer without thermal bridging, making them suitable for lightweight and thermally efficient precast concrete sandwich panels. Full article