Advancing Sustainability and Performance with Crushed Bottom Ash as Filler in Polymer-Modified Asphalt Concrete Mixtures.

Amid the growing demand for sustainable pavement solutions and the need to incorporate recycled materials into construction practices, this study explored the viability of using crushed thermal power plant bottom ash as a filler in polymer-modified asphalt concrete mixtures. Conventional lime filler was replaced with bottom ash at varying levels (0%, 25%, 50%, and 75%), and the resulting mixtures were evaluated using several performance tests. The optimal replacement level was determined to be 25%, based on the results of the indirect tensile strength (ITS) test. Comparisons between the control mixture and the 25% bottom ash-modified mixture were conducted using the dynamic modulus test, Cantabro test, Hamburg wheel tracking (HWT) test, and tensile strength ratio (TSR) test. The findings indicate that the 25% bottom ash-modified mixture demonstrated improved performance across multiple parameters. The HWT test showed enhanced rut durability, with a recorded depth of 7.56 mm compared to 8.9 mm for the control mixture. The Cantabro test results revealed lower weight loss percentages for the modified mixture, indicating better abrasion resistance. The dynamic modulus test indicated higher resilience and stiffness in both high- and low-frequency stages. The TSR test highlighted improved moisture resistance, with higher TSR values after 10 wet-drying cycles. These improvements are attributed to the fine particle size and beneficial chemical composition of bottom ash, which enhance the asphalt mixture's density, binder-aggregate adhesion, and overall durability. The results suggest that incorporating 25% crushed bottom ash as a filler in polymer-modified asphalt concrete mixtures is a viable and sustainable approach to improving pavement performance and longevity.

PI 3-Kinase and the Histone Methyl-Transferase KMT2D Collaborate to Induce Arp2/3-Dependent Migration of Mammary Epithelial Cells.

Breast cancer develops upon sequential acquisition of driver mutations in mammary epithelial cells; however, how these mutations collaborate to transform normal cells remains unclear in most cases. We aimed to reconstitute this process in a particular case. To this end, we combined the activated form of the PI 3-kinase harboring the H1047R mutation with the inactivation of the histone lysine methyl-transferase KMT2D in the non-tumorigenic human mammary epithelial cell line MCF10A. We found that PI 3-kinase activation promoted cell-cycle progression, especially when growth signals were limiting, as well as cell migration, both in a collective monolayer and as single cells. Furthermore, we showed that KMT2D inactivation had relatively little influence on these processes, except for single-cell migration, which KMT2D inactivation promoted in synergy with PI 3-kinase activation. The combination of these two genetic alterations induced expression of the ARPC5L gene that encodes a subunit of the Arp2/3 complex. ARPC5L depletion fully abolished the enhanced migration persistence exhibited by double-mutant cells. Our reconstitution approach in MCF10A has thus revealed both the cell function and the single-cell migration, and the underlying Arp2/3-dependent mechanism, which are synergistically regulated when KMT2D inactivation is combined with the activation of the PI 3-kinase.

Assessing the Performance of Peptide Force Fields for Modeling the Solution Structural Ensembles of Cyclic Peptides.

Molecular dynamics simulation is a powerful tool for characterizing the solution structural ensembles of cyclic peptides. However, the ability of simulation to recapitulate experimental results and make accurate predictions largely depends on the force fields used. In our work here, we evaluate the performance of seven state-of-the-art force fields in recapitulating the experimental NMR results in water of 12 benchmark cyclic peptides, consisting of 6 cyclic pentapeptides, 4 cyclic hexapeptides, and 2 cyclic heptapeptides. The results show that RSFF2+TIP3P, RSFF2C+TIP3P, and Amber14SB+TIP3P exhibit similar and the best performance, all recapitulating the NMR-derived structure information on 10 cyclic peptides. Amber19SB+OPC successfully recapitulates the NMR-derived structure information on 8 cyclic peptides. In contrast, OPLS-AA/M+TIP4P, Amber03+TIP3P, and Amber14SBonlysc+GB-neck2 could only recapitulate the NMR-derived structure information on 5 cyclic peptides, the majority of which are not well-structured.

Altered skin microbiome, inflammation, and JAK/STAT signaling in Southeast Asian ichthyosis patients.

BACKGROUND: Congenital ichthyosis (CI) is a collective group of rare hereditary skin disorders. Patients present with epidermal scaling, fissuring, chronic inflammation, and increased susceptibility to infections. Recently, there is increased interest in the skin microbiome; therefore, we hypothesized that CI patients likely exhibit an abnormal profile of epidermal microbes because of their various underlying skin barrier defects. Among recruited individuals of Southeast Asian ethnicity, we performed skin meta-genomics (i.e., whole-exome sequencing to capture the entire multi-kingdom profile, including fungi, protists, archaea, bacteria, and viruses), comparing 36 CI patients (representing seven subtypes) with that of 15 CI age-and gender-matched controls who had no family history of CI. RESULTS: This case-control study revealed 20 novel and 31 recurrent pathogenic variants. Microbiome meta-analysis showed distinct microbial populations, decreases in commensal microbiota, and higher colonization by pathogenic species associated with CI; these were correlated with increased production of inflammatory cytokines and Th17- and JAK/STAT-signaling pathways in peripheral blood mononuclear cells. In the wounds of CI patients, we identified specific changes in microbiota and alterations in inflammatory pathways, which are likely responsible for impaired wound healing. CONCLUSIONS: Together, this research enhances our understanding of the microbiological, immunological, and molecular properties of CI and should provide critical information for improving therapeutic management of CI patients.

Particle-Based Artificial Antigen-Presenting Cell Systems for T Cell Activation in Adoptive T Cell Therapy.

T cell-based adoptive cell therapy (ACT) has emerged as a promising treatment for various diseases, particularly cancers. Unlike other immunotherapy modalities, ACT involves directly transferring engineered T cells into patients to eradicate diseased cells; hence, it necessitates methods for effectively activating and expanding T cells in vitro. Artificial antigen-presenting cells (aAPCs) have been widely developed based on biomaterials, particularly micro- and nanoparticles, and functionalized with T cell stimulatory antibodies to closely mimic the natural T cell-APC interactions. Due to their vast clinical utility, aAPCs have been employed as an off-the-shelf technology for T cell activation in FDA-approved ACTs, and the development of aAPCs is constantly advancing with the emergence of aAPCs with more sophisticated designs and additional functionalities. Here, we review the recent advancements in particle-based aAPCs for T cell activation in ACTs. Following a brief introduction, we first describe the manufacturing processes of ACT products. Next, the design and synthetic strategies for micro- and nanoparticle-based aAPCs are discussed separately to emphasize their features, advantages, and limitations. Then, the impact of design parameters of aAPCs, such as size, shape, ligand density/mobility, and stiffness, on their functionality and biomedical performance is explored to provide deeper insights into the design concepts and principles for more efficient and safer aAPCs. The review concludes by discussing current challenges and proposing future perspectives for the development of more advanced aAPCs.

Sustainable Asphalt Mixtures with Enhanced Water Resistance for Flood-Prone Regions Using Recycled LDPE and Carnauba-Soybean Oil Additive.

This manuscript presents a comprehensive study on the sustainable optimization of asphalt mixtures tailored for regions prone to flooding. The research addresses the challenges associated with water damage to asphalt pavements by incorporating innovative additives. The study centers on incorporating recycled Low-Density Polyethylene (LDPE) and a tailored Carnauba-Soybean Oil Additive, advancing asphalt mixtures with a Control mix, LDPE (5%) + Control, and LDPE (5%) + 3% Oil + Control. A critical aspect of the research involves subjecting these mixtures to 30 wetting and drying cycles, simulating the conditions prevalent in tropical flood-prone areas. The incorporation of innovative additives in asphalt mixtures has demonstrated significant improvements across various performance parameters. Tensile Strength Ratio (TSR) tests revealed enhanced tensile strength, with the LDPE (5%) + 3% Oil-modified mixture exhibiting an impressive TSR of 85.7%. Dynamic Modulus tests highlighted improved rutting resistance, showcasing a remarkable increase to 214 MPa in the LDPE (5%) with a 3% Oil-modified mixture. The Semi-Circular Bending (SCB) test demonstrated increased fracture resistance and energy absorption, particularly in the LDPE (5%) with 3% Oil-modified mixture. Hamburg Wheel-Tracking (HWT) tests indicated enhanced moisture resistance and superior rutting resistance at 20,000 cycles for the same mixture. Cantabro tests underscored improved aggregate shatter resistance, with the LDPE (5%) + 3% Oil-modified mixture exhibiting the lowest weight loss rate at 9.820%. Field tests provided real-world insights, with the LDPE (5%) + 3% Oil mixture displaying superior stability, a 61% reduction in deflection, and a 256% improvement in surface modulus over the control mixture. This research lays the groundwork for advancing the development of sustainable, high-performance road pavement materials, marking a significant stride towards resilient infrastructure in flood-prone areas.

Structural Basis for p19 Targeting by Anti-IL-23 Biologics: Correlations with Short- and Long-Term Efficacy in Psoriasis.

IL-23 is central to psoriasis pathogenesis. Biologics targeting IL-23 are important therapies against psoriasis. IL-23 inhibitors risankizumab, tildrakizumab, and guselkumab bind the IL-23 p19 subunit, whereas ustekinumab binds p40; however, the structural composition of the IL-23-binding epitopes and how these molecular properties relate to clinical efficacy are not known. Utilizing epitope data derived from hydrogen-deuterium exchange or crystallographic experiments, we mapped inhibitor epitope locations, hydrophobicity, and surface charge onto the IL-23 surface. Molecular properties of each inhibitor epitope, including solvent-accessible surface area, were correlated to binding affinity, kinetic values, and clinical efficacy scores for plaque psoriasis through linear regression analysis. Each IL-23 inhibitor binds an epitope with a unique size, composition, and location except for a 10-residue overlap region outside of the IL-23 receptor epitope. We observed strong correlations between epitope surface area and KD and koff but not kon. Epitope surface area, KD, and koff were further associated with short-term (10-16 weeks) and long-term (44-60 weeks) clinical efficacy according to PASI-90 responses, with risankizumab demonstrating highest efficacy among IL-23 biologics. In contrast, kon, epitope hydrophobicity, polarity, and charge content did not correlate with efficacy. These data exemplify how molecular principles of medications within a therapeutic class can explain their differential clinical responses.

Diphenyl ethers from the cultured lichen mycobiont of Graphis handelii Zahlbr.

Purpose: Cultured lichen mycobionts are valuable sources of new natural compounds. Mycobiont of Graphis handelii growing in Vietnam was isolated, cultivated and chemically investigated. The crude extract of this cultured mycobiont showed potent alpha-glucosidase inhibition with an IC50 value of 50 µg/mL. Methods: Multiple chromatographic methods were applied to the extract to isolate compounds. The combination of Nuclear Magnetic Resonance analysis and high-resolution mass spectroscopy determined their chemical structures. Electrophilic bromination/chlorination was applied to obtain new derivatives using NaBr/H2O2 and NaCl/H2O2 reagents. Compounds were evaluated for enzyme inhibitory activities, including alpha-glucosidase inhibition, HIV-1 reverse transcriptase inhibition, SARS-CoV-2 main protease (Mpro) inhibition, anti-inflammatory activity, and cytotoxicity against several cancer cell lines. A molecular docking study for anti-SARS-CoV-2 was conducted to understand the inhibitory mechanism. Results: A new diphenyl ether, handelone (1) and a known compound xylarinic acid A (2) were isolated and elucidated. Four synthetic products 6'-bromohandelone (1a), 2'-bromohandelone (1b), 2',6'-dibromohandelone (1c), and 2',6'-dichlorohandelone (1d) were prepared. Compound 1 showed good activity against Mpro with an IC50 value of 5.2 µM but it showed weak or inactive activity in other tests. Other compounds were inactive in all assays. Conclusion: A new compound, handelone (1) was isolated from the cultured mycobiont of Graphis handelii. From these compounds, four new derivatives were prepared. Compound 1 showed good activity against Mpro with an IC50 value of 5.2 µM but it showed weak or inactive activity in other tests. Other compounds were inactive in all assays.

A Boron-Dependent Antibiotic Derived from a Calcium-Dependent Antibiotic.

The prevalence of drug-resistant bacterial pathogens foreshadows a healthcare crisis. Calcium-dependent antibiotics (CDAs) are promising candidates to combat infectious diseases as many of them show modes of action (MOA) orthogonal to widespread resistance mechanisms. The calcium dependence is nonetheless one of the hurdles toward realizing their full potential. Using laspartomycin C (LspC) as a model, we explored the possibility of reducing, or even eliminating, its calcium dependence. We report herein a synthetic LspC analogue (B1) whose activity no longer depends on calcium and is instead induced by phenylboronic acid (PBA). In LspC, Asp1 and Asp7 coordinate to calcium to anchor it in the active conformation; these residues are replaced by serine in B1 and condense with PBA to form a boronic ester with the same anchoring effect. Using thin-layer chromatography, MS, NMR, and complementation assays, we demonstrate that B1 inhibits bacterial growth via the same MOA as LspC, i.e., sequestering the cell wall biosynthetic intermediate undecaprenyl phosphate. B1 is as potent and effective as LspC against several Gram-positive bacteria, including methicillin-resistant Staphylococcus aureus and vancomycin-resistant Enterococcus. Our success in converting a CDA to a boron-dependent antibiotic opens a new avenue in the design and functional control of drug molecules.

Harm reduction stories: leveraging graphic medicine to engage veterans in substance use services within the VA.

BACKGROUND: Harm reduction strategies can decrease morbidity and mortality associated with substance use. Various barriers limit conversation around substance use between clinicians and patients. Graphic medicine techniques can inform and encourage patient-centered conversations about substance use. We describe the co-development of a harm reduction-focused graphic medicine comic that depicts the infectious risks associated with injection drug use and patient-centered approaches to providing education about potential risk mitigation strategies. METHODS: We formed a co-design group of veterans with lived experience with substance use, physicians, health services researchers, and community-based harm reduction leaders. Over the course of ten sessions, the co-design team developed a storyline and key messages, reviewed draft content and worked with a graphic designer to develop a comic incorporating the veterans' input. During each session, co-design leads presented drafts of the comic and invited feedback from the group. The comic was edited and adapted via this iterative process. RESULTS: The comic depicts a fictionalized clinical vignette in which a patient develops an injection-related abscess and presents to their primary care provider. The dialogue highlights key healthcare principles, including patient autonomy and agency, and highlights strategies for safer use, rather than emphasizing abstinence. Feedback from co-design group participants highlights lessons learned during the development process. DISCUSSION: Graphic medicine is ideally suited for a patient-centered curriculum about harm reduction. This project is one of several interventions that will be integrated into VA facilities nationally to support incorporation of harm reduction principles into the care of persons who inject drugs.

Development of Plug Joint with Polymer-Modified Rubber Asphalt as Filling Material.

Rising traffic volume, heavy loads, and construction activities have raised concerns about expansion joint device damage. This study focuses on developing an innovative expansion joint using polymer-modified rubber asphalt as the filling material to enhance its service life. Styrene-butadiene-styrene (SBS) emerged as a suitable modifier for rubber-modified asphalt, significantly improving elasticity and adhesion. Through the strategic combination of 3- and 2-block linear SBS, the elasticity and adhesion properties were significantly improved, resulting in the formulation of a well-suited polymer-modified rubber asphalt binder. The developed asphalt binder exhibits impressive elastic recovery (61.1% to 66.1%), surpassing commercial products, with enhanced constructability and workability (15% to 21% viscosity reduction). The carefully engineered mastic asphalt mixture showcases self-leveling characteristics at a moderate 210 °C, addressing historical constructability challenges. Settlement is 40% less than traditional hot mix asphalt for surface layers, with improved moisture and stripping resistance, enhancing existing asphalt plug joint durability and workability. Collectively, this novel mixture, comprising polymer-modified rubber and mastic asphalt, showcases the potential to enhance the durability of existing asphalt plug joints while ensuring superior constructability and workability.

Enhancing Railway Track Stabilization with Epoxy Resin and Crumb Rubber Powder-Modified Cement Asphalt Mortar.

This research investigates the quantitative impact of incorporating epoxy resin and crumb rubber powder (CRP) into cement asphalt mortar (CAM) for railway track stabilization. The study reveals significant improvements in various key parameters compared to conventional CAM. The modified CAM exhibits a 12.7% reduction in flow time, indicative of enhanced flowability, and a substantial 62.4% decrease in the mixing stability gap, demonstrating superior mixing stability. Additionally, the modified CAM displays remarkable early-age compressive strength, with increases of up to 15.3% compared to traditional CAM formulations. Importantly, the modified CAM showcases robust resistance to challenging environmental conditions, with only a 6.7% strength reduction after exposure to sulfuric acid, highlighting its acid resistance, and exceptional freeze-thaw resistance, with a mere 1.5% strength reduction after undergoing six cycles. In a mock-up test simulating real-world conditions, the modified CAM effectively prevents ballast layer settlement, underscoring its potential to enhance the durability of railway track infrastructure. These quantitative findings not only endorse the practical feasibility of epoxy resin and CRP-enhanced CAM but also suggest its potential to contribute significantly to railway track longevity, reduce maintenance expenditures, and ensure operational reliability.

A comparative study on essential oils from the leaves and stems of Vietnamese Mikania micrantha Kunth.

Mikania micrantha Kunth is widely known as potential herbal medicine, although it is an invasive alien species in Southeast Asia. In this study, the essential oils from leaves and stems of M. micrantha were extracted by hydrodistillation method, and the chemical profiles of essential oils were then analysed by gas chromatography (GC) and gas chromatography coupled with mass spectrometry (GC/MS). It was found that there were similarities and differences in chemical compositions and their percentage between the essential oils obtained from these two parts. The dominant components of leaves essential oil are ß-Cubebene, Germacrene D, and α-Zingiberene, accounting for 11.34%, 10.96%, and 10.76%, respectively. Additionally, the major components of stems essential oils are D-Limonene (16.99%), ß-Pinene (7.91%), and α-Zingiberene (7.26%). The research sheds fresh light on the chemical makeup of M. micrantha essential oils, emphasising their potential for the future.

Feasibility of Sustainable Asphalt Concrete Materials Utilizing Waste Plastic Aggregate, Epoxy Resin, and Magnesium-Based Additive.

This research addresses the urgent need for sustainable and durable asphalt mixtures by quantitatively investigating the effects of incorporating waste plastic aggregate (WPA) and magnesium-based additives. This study explores WPA content levels of 3%, 5%, and 7% wt of aggregate in combination with a fixed 3% wt epoxy resin content to the asphalt binder, supplemented with the 1.5% wt magnesium-based additive. The novelty of this research lies in its comprehensive analysis of various performance parameters, including deformation strength, indirect tensile strength (ITS), rut depth, and dynamic stability, to assess the impact of WPA, epoxy resin, and the magnesium-based additive on asphalt mixture properties. The results demonstrate significant improvements in key performance aspects with increasing WPA content. The WPA mixtures exhibit enhanced deformation strength, with values of 4.01, 3.7, and 3.32 MPa for 3, 5, and 7% wt WPA content, respectively, compared to the control mixture. Furthermore, the inclusion of WPA and epoxy resin, along with the magnesium-based additive, contributes to improved adhesion, cohesion, and resistance to stripping damage. Notably, the 7% wt WPA mixture showcases exceptional performance, characterized by a final rut depth of 2.66 mm and a dynamic stability of 7519 passes per millimeter, highlighting its superior rutting resistance and load-bearing capacity. This study also reveals the influence of WPA content on ITS and stiffness properties, with the 5% wt WPA mixture achieving an optimal balance between strength and stiffness. Overall, this research highlights the potential of incorporating WPA, epoxy resin, and magnesium-based additives in asphalt mixtures to enhance their performance and durability. By utilizing plastic waste materials and optimizing their combination with epoxy reinforcement, along with the innovative use of magnesium-based additive, the findings contribute to the development of sustainable infrastructure materials and pave the way for further advancements in the field.

Evaluation of the Polymer Modified Tack Coat on Aged Concrete Pavement: An Experimental Study on Adhesion Properties.

This study addresses the challenges of overlaying old concrete pavement with asphalt by introducing a new trackless tack coat material containing polymer. The aim is to enhance the durability of asphalt concrete overlay pavement on old cement concrete pavement. It contributes to the development of improved construction techniques for pavement rehabilitation and highlights the need for reliable adhesion performance evaluation based on different spray amounts and surface conditions. Additionally, to evaluate the effect of the adhesion performance based on the spraying amount, a tensile adhesion test was conducted by applying spray amounts of 0.30, 0.45, and 0.60 l/m2 on different surface conditions. The basic and adhesion performances of the polymer-modified tack coat material are evaluated through direct tensile and shear bond strength tests. The test outcomes demonstrated that the newly developed polymer-modified tack coat material had considerably greater adhesion strength compared to the traditional rapid-setting products. Its adhesive strength was 1.68 times higher on concrete and 1.78 times higher on asphalt. The new trackless tack coat material exhibited an adhesion performance of 1.05 MPa in direct tensile strength at 0.45 l/m2, which was 1.21 times higher than the rapid-setting tack coat. Results also confirmed that the new tack coat material exhibits values 1.90 times greater than the conventional rapid-setting tack coat material in shear bond strength, respectively. By simulating the process of separation and re-adhesion of pavement layers caused, the new tack coat material shows a tensile adhesion strength of 63% of the original state, which is advantageous for securing the durability of the pavement. Overall, the newly developed polymer-modified trackless tack coat has been shown to effectively enhance the adhesion performance between pavement layers without process delay, highlighting the potential of the new tack coat material to enhance the durability of asphalt concrete overlay pavement on old cement concrete pavement.

Durability of Polymer-Modified Asphalt Mixture with Wasted Tire Powder and Epoxy Resin under Tropical Climate Curing Conditions.

The quality of pavements in tropical climates is negatively affected by the frequent wet and dry cycles during the rainy season, as well as by issues related to overloading from heavy trucks and traffic congestion. Contributing to this deterioration are factors such as acid rainwater, heavy traffic oils, and municipal debris. In light of these challenges, this study aims to assess the viability of a polymer-modified asphalt concrete mixture. This study investigates the feasibility of a polymer-modified asphalt concrete mixture with the addition of 6% crumb rubber powder from waste car tires and 3% epoxy resin to counter the harsh conditions of tropical climate weather. The study involved subjecting test specimens to five to 10 cycles of contaminated water (100% rainwater + 10% used oil from trucks), curing for 12 h, and air drying in a chamber of 50 °C for 12 h to simulate critical curing conditions. The specimens underwent fundamental laboratory performance tests such as the indirect tensile strength test, dynamic modulus test, four points bending test, and Cantabro test, as well as the double load condition in the Hamburg wheel tracking test to determine the effectiveness of the proposed polymer-modified material in actual conditions. The test results confirmed that the simulated curing cycles had a critical impact on the durability of the specimens, with the greater curing cycles leading to a significant drop in the strength of the material. For example, the TSR ratio of the control mixture dropped from 90% to 83% and 76% after five and 10 curing cycles, respectively. Meanwhile, the modified mixture showed a decrease from 93% to 88% and 85% under the same conditions. The test results revealed that the effectiveness of the modified mixture outperformed the conventional condition in all tests, with a more prominent impact observed under overload conditions. Under double conditions in the Hamburg wheel tracking test and a curing condition of 10 cycles, the maximum deformation of the control mixture sharply increased from 6.91 to 22.7 mm, whereas the modified mixture increased from 5.21 to 12.4 mm. Overall, the test results confirm the durability of the polymer-modified asphalt concrete mixture under harsh tropical climate conditions, promoting its application for sustainable pavements, especially in Southeast Asian countries.

Influence of minerals on the foaming properties of milk.

A comprehensive study on the effect of mineral content on milk foaming properties was conducted. Samples with increased mineral concentration were prepared by adding four different types of minerals (KH2PO4, K3Cit, CaCl2 and MgCl2) at three different concentration levels (5, 10 and 20 mM) in both reconstituted skim milk powder and milk protein concentrate. Samples with reduced minerals were prepared by reconstituting milk protein concentrate in modified simulated milk ultrafiltrates. Different mineral types showed different effects on the physicochemical properties of milk samples. The addition of K3Cit increased the viscosity and decreased the surface tension while there were no significant differences between the samples added with KH2PO4, MgCl2, or CaCl2. In terms of foaming properties, the addition of CaCl2 or MgCl2 significantly increased the foam strength and stability while decreasing foamability. In contrast, the addition of K3Cit significantly decreased foam stability and foam strength while increasing foamability. It was also found that reduction in minerals in the range studied did not affect the foaming properties of milk. These results indicate that the effect of minerals on milk foaming properties depends on the type of mineral and the concentration. This provides an insight that while designing dairy-based food products, the mineral content can be manipulated to achieve the desired foaming properties.

Developing Performance-Based Mix Design Framework Using Asphalt Mixture Performance Tester and Mechanistic Models.

This paper proposes a performance-based mix design (PBMD) framework to support performance-related specifications (PRS) needed to establish relationships between acceptable quality characteristics (AQCs) and predicted performance, as well as to develop fatigue-preferred, rutting-preferred, and performance-balanced mix designs. The framework includes defining performance tests and threshold values, developing asphalt mix designs, identifying available performance levels, conducting sensitivity analysis, establishing the relationships between AQCs and predicted performance, and determining performance targets and AQC values for the three PBMDs using predicted performance criteria. Additionally, the framework recommends selecting the PBMD category for each asphalt layer to minimize pavement distresses. In this study, the proposed PBMD protocol was applied to FHWA accelerated loading facility (ALF) materials using asphalt mixture performance tester (AMPT) equipment coupled with mechanistic models. The study developed nine mix designs with varying design VMAs and air voids using the Bailey method. The cracking and rutting performance of the mix designs were determined by direct tension cyclic (DTC) fatigue testing, triaxial stress sweep (TSS) testing, and viscoelastic continuum damage (S-VECD) and viscoplastic shift models for temperature and stress effects. The study found that adjusting the design VMA was the primary way to achieve required performance targets. For fatigue-preferred mix design, the recommended targets were a cracking area of 0 to 1.9%, a rut depth of 10 mm, and a design VMA of 14.6 to 17.6%. For rutting-preferred mix design, the recommended targets were a cracking area of 18%, a rut depth of 0 to 3.8 mm, and a design VMA of 10.1 to 13.1%. For performance-balanced mix design, the recommended targets were a cracking area of 8.1 to 10.7%, a rut depth of 4.6 to 6.4 mm, and a design VMA of 12.6 to 14.3%. Finally, pavement simulation results verified that the proposed PBMD pavement design with fatigue-preferred mix in the bottom layer, performance-balanced mix in the intermediate layer, and rutting-preferred mix in the surface mix could minimize bottom-up cracking propagation without exceeding the proposed rutting performance criterion for long-life.