Search Results (93)

The primary objective of this study is to bridge the gap between descriptive geometry and mechanistic design by establishing a dual-domain fractal framework to analyze the internal architecture of asphalt mixtures. This research quantitatively assesses the sensitivity of volumetric indicators—namely air voids (VV), voids in mineral aggregate (VMA), and voids filled with asphalt (VFA)—by employing the coarse aggregate fractal dimension (D_c), the fine aggregate fractal dimension (D_f), and the coarse-to-fine ratio (k) through Grey Relational Analysis (GRA). The findings demonstrate that whereas D_f and k substantially influence macro-volumetric parameters, the mesoscopic void fractal dimension (D_V) remains structurally unchanged, indicating that gradation predominantly dictates void volume rather than geometric intricacy. Sensitivity rankings create a prevailing hierarchy: Process Control (Compaction) > Skeleton Regulation (D_c) > Phase Filling (Pb) > Gradation Adjustment (k, D_f). D_c is recognized as the principal regulator of VMA, while binder content (Pb) governs VFA. A “Robust Design” methodology is suggested, emphasizing D_c to stabilize the mineral framework and reduce sensitivity to construction variations. A comparative investigation reveals that the optimized gradation (OG) achieves a more stable volumetric condition and enhanced mechanical performance relative to conventional empirical gradations. Specifically, the OG group demonstrated a substantial 112% enhancement in dynamic stability (2617 times/mm compared to 1230 times/mm) and a 75% increase in average film thickness (AFT), while ensuring consistent moisture and low-temperature resistance. In conclusion, this study transforms asphalt mixture design from empirical trial-and-error to a precision-engineered methodology, providing a robust instrument for optimizing the long-term durability of pavements in extreme cold and arid environments. Full article

Directional swelling pressure is a critical yet often overlooked factor governing the instability of expansive soil slopes. Most existing studies simplify swelling behavior as a uniform or purely vertical stress, thereby underestimating the distinct contribution of horizontal swelling pressure. In this study, an integrated framework combining the Fuzzy Analytic Hierarchy Process (FAHP), multivariate regression analysis based on 35 expansive soil samples, and three-dimensional strength-reduction numerical modeling was developed to systematically evaluate the mechanistic roles of vertical and horizontal swelling pressures in slope deformation. The FAHP and regression analyses indicate that water content is the dominant factor controlling both the free swell ratio and swelling pressure, leading to predictive relationships that link swelling behavior to fundamental physical indices. These empirical correlations were subsequently incorporated into a three-dimensional numerical model of a representative Neogene expansive soil slope. The simulation results demonstrate that neglecting swelling pressure results in substantial discrepancies between predicted and observed displacements. Vertical swelling pressure induces moderate surface uplift but exerts a limited influence on overall failure patterns. In contrast, horizontal swelling pressure markedly amplifies downslope displacement—by more than four times under saturated conditions—reduces the factor of safety by 24.7%, and promotes the progressive development of a continuous slip surface. These findings clearly demonstrate that horizontal swelling pressure is the dominant driver of progressive failure in expansive soil slopes. This study provides new mechanistic insights into swelling-induced deformation and offers a quantitative framework for incorporating directional swelling stresses into slope stability assessment, design optimization, and mitigation strategies for geotechnical structures in expansive soil regions. Full article

This study presents a comprehensive material characterization program to develop the database inputs required for implementing the Mechanistic–Empirical Pavement Design Guide (MEPDG) in the United Arab Emirates (UAE). Five asphalt concrete (AC) mixtures were evaluated, including two conventional penetration-grade binders (PEN 40/50 and PEN 60/70) and three SBS-modified binders (PG70E–0, PG76E–10, and PG82E–22). The experimental program followed AASHTOWare Pavement ME Design requirements and included asphalt binder testing (penetration, softening point, rotational viscosity, DSR, and BBR) and AC mixture testing (dynamic modulus, flow number, axial fatigue, and indirect tensile strength). The results showed that SBS-modified binders and mixtures, particularly PG70E–10 and PG82E–22, exhibited improved rheological behavior, reduced permanent deformation, and enhanced fatigue resistance, while PG76E–10 demonstrated intermediate performance, highlighting the influence of polymer formulation and mixture structure. Pavement ME simulations indicated that Level 1 material inputs preserved laboratory-observed performance trends, resulting in lower predicted rutting, fatigue cracking, and International Roughness Index (IRI). In contrast, Level 3 inputs masked material-specific behavior and, in some cases, altered mixture performance rankings. These findings emphasize the necessity of mixture-level testing and Level 1 inputs for reliable mechanistic–empirical pavement design under UAE climatic and traffic conditions. Full article

Background/Objectives: Mathematical modelling provides a quantitative way to describe the fate and action of drugs in the oral cavity, where transport processes are shaped by salivary flow, pellicle formation, biofilm structure and the wash-out effect of gingival crevicular fluid (GCF). Local pharmacokinetics in the mouth differ substantially from systemic models, and therefore a dedicated framework is required. The aim of this work was to present a structured, physiologically based concept that links in vitro release testing with local pharmacokinetics and pharmacodynamics. Methods: A narrative review with elements of systematic search was conducted in PubMed, Scopus and Web of Science (1980–2025) for publications describing drug release, local PBPK, and PK/PD modelling in the oral cavity. Mathematical formulations were grouped into release kinetics, mini-PBPK transport and local PK/PD relations. Classical models (Higuchi, Korsmeyer–Peppas, Peppas–Sahlin) were integrated with a mini-PBPK structure describing saliva–mucosa–biofilm–pocket interactions. Results: The combined model captures adsorption to pellicle, diffusion within biofilm and wash-out by GCF. It allows simulation of variable clinical conditions, such as inflammation-related changes in Q_GCF, and links local exposure to pharmacodynamic outcomes. Case studies with PerioChip^®, Arestin^®, and Atridox^® demonstrate how mechanistic models explain observed therapeutic duration and low-systemic exposure. Conclusions: The proposed mini-PBPK framework bridges empirical release data and physiological transport in the oral cavity. It supports rational formulation design, optimisation of local dosage, and personalised prediction of drug retention in gingival pockets. This modelling approach can become a practical tool for the development of dental biomaterials and subgingival therapies. Full article

Modernizing municipal roads requires rehabilitation strategies that ensure adequate structural performance while reducing environmental and economic burdens. Although cold in-place recycling with foamed bitumen (CIR-FB) has been widely investigated, integrated assessments combining mechanistic–empirical modeling with LCA and LCCA remain limited—particularly for municipal roads in Central and Eastern Europe, where reclaimed asphalt pavement (RAP) quality, climatic conditions and budget constraints differ from commonly studied regions. This study compares two reconstruction variants for a 1 km road section: a conventional design using virgin materials (V₁-N) and a recycling-based alternative (V2-Rc) incorporating RAP from the existing wearing and binder layers and reclaimed aggregate (RA) from the existing base. CIR-FB mixture testing (stiffness ≈ 5.25 GPa; foamed bitumen = 2.5%, cement = 2.0%) was integrated into mechanistic–empirical fatigue analysis, material-flow quantification, LCA and LCCA. The V₂-Rc variant achieved a 3–21-fold increase in fatigue life compared to V₁-N at equal thickness. Material demand decreased by approximately 27%, demolition waste by approximately 39%, and approximately 92% of the existing pavement was reused in situ. Transport work was reduced five-fold (veh-km) and more than six-fold (t-km). LCA showed a 15.9% reduction in CO₂-eq emissions, while LCCA indicated approximately 19% lower construction cost, with advantages remaining robust under ±20% sensitivity. The results demonstrate that CIR-FB, when supported by proper RAP/RA characterization, can substantially improve structural, environmental and economic performance in municipal road rehabilitation. Full article

Tablet film coating is governed by three interrelated phenomena, namely, tablet mixing, coating-liquid spraying, and liquid evaporation, which dominate the critical quality attributes ($CQAs$) of the final product. This review examines how differences in coater design, key process parameters, and quality control strategies impact these phenomena and ultimately affect inter-tablet and intra-tablet coating variability. Two complementary approaches for understanding and optimizing the process are evaluated. The experimental approach, involving Design of Experiments (DoE), retrospective data analysis, and advanced Process Analytical Technology ($PAT$), provides empirical insight into factor–response relationships and enables real-time quality assurance. Simultaneously, model-based approaches, including thermodynamic, spray-dynamics, and particle-dynamics modelling, offer mechanistic understanding of heat and mass transfer, droplet deposition patterns, and tablet motion. Although these sub-models have advanced considerably over the years, a predictive model that treats the coating process in its entirety is still missing. Overall, this review underscores that future advancements will require integrating experimental and model-based methodologies to achieve robust, quality-driven, and predictive control of tablet film coating processes. Full article

Eosinophilic esophagitis (EoE) has emerged as a major cause of dysphagia and food impaction worldwide. This narrative review traces the evolving therapeutic pipeline for EoE, highlighting agents spanning from late-stage clinical development to final approval. We summarize mechanistic insights that have driven a shift from broad immunosuppression to precise inhibition of type-2 inflammatory pathways, including blockade of key interleukin pathways. Randomized trials have demonstrated histologic and symptomatic gains, yet regulatory approvals and optimal positioning within treatment algorithms are pending. Parallel innovations in drug delivery aim to maximize mucosal exposure while minimizing systemic burden. Key challenges include heterogeneity in disease phenotype, paucity of long-term safety data, and the need for non-invasive biomarkers to guide precision prescribing. Cost considerations and patient preferences will shape adoption. By integrating advances across immunology, formulation science and clinical trial design, the therapeutic pipeline for EoE holds promise to transform care from empirical suppression to mechanism-based disease modification. Full article

In continuous strata engineering, such as foundations and underground caverns, the differences in shear strength between sandstone and mudstone rock mass–structural plane–structural block systems critically affect design and safety. However, the underlying mechanisms and controlling factors of these shear strength parameters remain poorly understood, leading to challenges in optimizing engineering strategies. This study investigates the differences in shear strength parameter correlations between sandstone and mudstone and develops an intelligent model for predicting rock mass displacement. We constructed multi-parameter correlation models using laboratory and field shear test data combined with a random forest algorithm. The results show that the model achieved high prediction accuracy (R² = 0.997–0.998, RMSE = 1.649–3.898, MAE = 1.110–2.991). For instance, the peak shear strength of sandstone structural planes was approximately 54% higher than that of mudstone. Sensitivity analysis revealed that for sandstone, structural plane shear stress (27.80%) and structural block stress (25.50%) are the most sensitive factors, while for mudstone, structural plane shear displacement (35.20%) and structural block strain (34.20%) dominate. These correlations are model-predicted based on empirical data from shear tests. These findings provide a mechanistic understanding of plastic instability in sandstone and slip-strain-induced fissure extension in mudstone, and they can guide shear strength prediction and stability assessment in mixed sandstone–mudstone strata. The study contributes to the field by offering a quantitative basis for stratified adaptive design in continuous strata engineering, enhancing the efficiency and safety of foundation treatment and cavern support. Full article

The current global economic challenges and resource scarcity necessitate the development of cost-effective and sustainable pavement solutions. This study investigates the performance of asphalt mixtures modified with Low-Density Polyethylene (LDPE) and Styrene–Butadiene–Styrene (SBS) as binder modifiers, and Hydrated Lime (Ca(OH)₂) and Reclaimed Asphalt Pavement (RAP) as aggregate replacements. The research aims to optimize the combination of these materials for enhancing the durability, sustainability, and mechanical properties of asphalt mixtures under various climatic and traffic conditions. Asphalt mixtures were modified with 5% LDPE and 2–6% SBS (by bitumen weight), with 2% Hydrated Lime and 15% RAP added to the mix. The performance of these mixtures was evaluated using the Simple Performance Tester (SPT), focusing on rutting, cracking, and fatigue resistance at varying temperatures and loading frequencies. The NCHRP 09-29 Master Solver was employed to generate master curves for input into the AASHTOWare Mechanistic-Empirical Pavement Design Guide (MEPDG), allowing for an in-depth analysis of the modified mixes under different traffic and climatic conditions. Results indicated that the mix containing 5% LDPE, 2% SBS, 2% Hydrated Lime, and 15% RAP achieved the best performance, reducing rutting, fatigue cracking, and the International Roughness Index (IRI), and improving overall pavement durability. The combination of these modifiers showed enhanced moisture resistance, high-temperature rutting resistance, and improved dynamic modulus. Notably, the study revealed that in warm climates, thicker pavements with this optimal mix exhibited reduced permanent deformation and better fatigue resistance, while in cold climates, the inclusion of 2% SBS further improved the mix’s low-temperature performance. The findings suggest that the incorporation of LDPE, SBS, Hydrated Lime, and RAP offers a sustainable and cost-effective solution for improving the mechanical properties and lifespan of asphalt pavements. Full article

Silymarin, a flavonolignan-rich extract of Silybum marianum, is widely recognized for its hepatoprotective potential. While rodent studies predominate, pigs (Sus scrofa) offer a more translationally relevant model due to their hepatic architecture, bile acid composition, and transporter expression, which closely resemble those of humans. This narrative review synthesises current evidence on the chemistry, pharmacokinetics, biodistribution, and hepatoprotective activity of silymarin in porcine models. Available studies demonstrate that when adequate intrahepatic exposure is achieved, particularly through optimised formulations, silymarin can attenuate oxidative stress, suppress inflammatory signalling, stabilise mitochondria, and modulate fibrogenic pathways. Protective effects have been reported across diverse porcine injury paradigms, including toxin-induced necrosis, ethanol- and diet-associated steatosis, metabolic dysfunction, ischemia–reperfusion injury, and partial hepatectomy. However, the evidence base remains limited, with few long-term studies addressing fibrosis or regeneration, and methodological heterogeneity complicates the comparison of data across studies. Current knowledge gaps in silymarin research include inconsistent chemotype characterization among plant sources, limited reporting of unbound pharmacokinetic parameters, and variability in histological scoring criteria across studies, which collectively hinder cross-study comparability and mechanistic interpretation. Advances in analytical chemistry, transporter biology, and formulation design are beginning to refine the interpretation of exposure–response relationships. Advances in analytical chemistry, transporter biology, and formulation design are beginning to refine the interpretation of exposure–response relationships. In parallel, emerging computational approaches, including machine-learning-assisted chemotype fingerprinting, automated histology scoring, and Bayesian exposure modeling, are being explored as supportive tools to enhance reproducibility and translational relevance; however, these frameworks remain exploratory and require empirical validation, particularly in modeling enterohepatic recirculation. Collectively, current porcine evidence supports silymarin as a context-dependent yet credible hepatoprotective agent, highlighting priorities for future research to better define its therapeutic potential in clinical nutrition and veterinary practice. Full article

The dynamic modulus of asphalt mixtures (|E*|) is a key mechanical parameter in the design of road pavements, yet direct laboratory testing is time- and resource-intensive. This study evaluates two predictive models for estimating |E*| using data from 62 asphalt mixtures containing reclaimed asphalt: a grey relational analysis–multiple linear regression (GRA-MLR) hybrid model and a mechanistic sigmoidal model. The results showed that the GRA-MLR model effectively identifies influential variables but achieved moderate predictive accuracy (R² values varying from 0.4743 to 0.6547). In contrast, the sigmoidal model outperformed across all temperature conditions (R² > 0.96) and produced predictions deviating by less than ±20% from measured values. Temperature-dependent shifts in factor influence were observed, with stiffness and gradation dominating at low temperatures and reclaimed asphalt (RA) content becoming more significant at higher temperatures. While the GRA-MLR model is advantageous, offering rapid assessments and early-stage evaluations, the sigmoidal model offers the precision suited for detailed design. Integrating both models can balance computational efficiency and provide a balanced strategy, with strong predictive reliability to advance mechanistic–empirical pavement design. Full article

Background/Objectives: Hospital compounding is essential for the delivery of patient-tailored therapies—particularly for pediatric and oncology patients and other groups requiring precise dosing. Its role is expected to grow as, for instance, the UK MHRA’s new Guidance on Decentralised Manufacturing promotes alternative manufacturing pathways that integrate hospital preparation units. However, drug substances that remain stable in commercial oral formulations may undergo rapid degradation under alternative conditions (e.g., aqueous suspension, light exposure, or in the presence of specific excipients). Despite these risks, formulation strategies in hospital compounding often rely on empirical practices and lack structured guidance regarding stability, impurity control, and reproducibility. Methods: This study proposes a risk-based scientific framework for formulation design, integrating degradation profiling with predictive toxicology. Potential degradation pathways (hydrolytic, oxidative, and photolytic) are systematically identified through forced-degradation studies combined with ab initio modeling. These risks are translated into formulation strategies using a structured decision tree encompassing solvent selection, pH adjustment, excipient compatibility, and packaging considerations, even in the absence of a pharmacopeial monograph. The toxicological relevance of degradation products is evaluated using in silico approaches aligned with ICH M7 guidelines, thereby defining critical quality attributes (cQAs) and critical process parameters (CPPs). Results: The applicability of the framework is demonstrated through hospital compounding case studies, with further extension toward advanced applications such as semi-solid extrusion (SSE) 3D printing. Conclusions: By integrating mechanistic understanding of drug degradation into formulation planning, the proposed framework enhances the safety, reproducibility, and quality of compounded preparations. This approach reinforces Good Preparation Practices (GPPs) and is consistent with international quality-by-design (QbD) principles in the context of personalized medicine. Full article

The transition to heavy-duty electric vehicles (HDEVs) offers substantial environmental benefits but raises concerns about increased pavement deterioration due to the added mass of large battery packs. A key research question is whether additional structural demands on road infrastructure could offset these benefits. This study investigates the impact of battery weight distribution on asphalt pavement performance by comparing conventional diesel trucks with electric trucks under equivalent gross vehicle weight (36 tons). Three battery placement scenarios were evaluated: (i) concentration at the steering axle, (ii) concentration at the rear tractor axles, and (iii) uniform distribution across all tractor axles. Pavement elastic response was analyzed using a representative cross-section using mechanistic–empirical modeling, with fatigue damage estimated according to the Mechanistic–Empirical Pavement Design Guide (MEPDG) fatigue law. Results indicate that tensile strains at the bottom of asphalt layers may increase by up to 60%, with relative fatigue damage rising by 185% and 34% for scenarios (i) and (iii), respectively, while scenario (ii) produced nearly equivalent damage to conventional trucks. These findings highlight the critical role of battery placement; the optimal performance seems to be achieved when weight is concentrated at the rear tractor axles. Full article

Deep eutectic solvents (DESs) have emerged as sustainable and tunable alternatives to conventional solvents for the extraction of polysaccharides. This review presents a structure-informed framework linking DES composition to polysaccharide solubility, emphasizing the differential responsiveness of amorphous, interfacial, and crystalline domains. Amorphous polysaccharides are efficiently extracted under mild DES conditions, while crystalline polymers often require stronger hydrogen bond acceptors or thermal/mechanical activation. Beyond dissolution, DESs modulate key properties of the extracted polysaccharides, including molecular weight, monomer composition, and bioactivity. Comparative analysis highlights how acidic, basic, or metal-coordinating DESs selectively target distinct polymer classes. Emerging innovations, such as in situ DES formation, mechanochemical systems, and switchable solvents, enhance efficiency and reduce downstream processing demands. Furthermore, the integration of machine learning and COSMO-RS modeling enables predictive solvent design, reducing reliance on empirical screening. By combining mechanistic insight, compositional tailoring, and computational tools, this review provides a scientifically grounded perspective for advancing DES-mediated extraction processes and enabling structure-preserving, application-oriented recovery of polysaccharides in food, pharmaceutical, and biorefinery domains. Full article

Sustainable pavement design requires a balanced consideration of economic, environmental, and social impacts. In line with Federal Highway Administration (FHWA) guidelines for sustainable roadway infrastructure, incorporating recycled materials such as reclaimed asphalt pavement (RAP), recycled pavement material (RPM), recycled asphalt shingles (RASs), and warm-mix asphalt (WMA) has been shown to reduce natural resource depletion while promoting circular construction practices. This study investigates the structural performance of Portland cement concrete (PCC) pavements constructed on RAP and RPM base layers. A series of design scenarios was modeled using site-specific laboratory and field data—particularly subgrade soil properties and climatic conditions—from El Paso and San Antonio, Texas. The analysis incorporates unsaturated soil parameters and follows the performance thresholds set by the Mechanistic-Empirical Pavement Design Guide (MEPDG). Findings indicate that concrete mixture design, pavement structure, and local weather conditions are the primary drivers of distress in jointed plain concrete pavements (JPCPs). However, subsoil characteristics have a significant impact on joint faulting in JPCP and punchout occurrences in continuously reinforced concrete pavements (CRCPs), especially in thinner sections. Notably, the use of up to 50% recycled material in the base layer had minimal adverse effects on pavement performance, underscoring its viability as a sustainable design strategy for rigid pavements. Full article