bluuebunny/crossref_metadata_2025_split huggingface dataset:
Experimental characterization and numerical prediction for mechanical aging of epoxy and its carbon fiber‐reinforced composite under hydrothermal conditions
Authors: Zhang Wanrui , Liu Meiyu , Zou Jianchao , Han Zhibin , Xiong Yifeng , Liang Biao , Zhang Weizhao 
Published: May 2024

AbstractThe Aqueous environment impairs the mechanical performance of carbon fiber‐reinforced polymers (CFRPs) and decreases the durability of engineering structures made of CFRPs primarily by degrading the resin matrix. Hence, the objective of this study is to investigate and accurately predict the influence of hydrothermal aging on the epoxy and its carbon fiber reinforced polymer (CFRP). Particularly, this work developed a modeling method that combined Fick's model, empirical aging model and elastoplastic constitutive model to predict the mechanical behavior of hydrothermally aged epoxy matrix. After the experimental characterization, this epoxy modeling method demonstrated its predictive capability on the mechanical response of the deteriorated epoxy under different hydro‐thermal‐salt conditions, with the mean absolute percent error (MAPE) of approximately 4.61%. Furthermore, the transverse compressive behavior of unidirectional (UD) CFRPs could be predicted by using the representative volume element (RVE) model with the degraded matrix behavior predicted via this epoxy modeling method. Integrated with this CFRP modeling, results from mechanical tests and fracture analysis further demonstrated that the hydrothermal aging effect on the transverse compressive performance of the UD CFRPs was dominated by the deterioration of their resin matrix. Therefore, this study demonstrates the feasibility of the finite element analysis (FEA) for mechanical aging of the epoxy matrix and its CFRP under hydrothermal conditions via employing the proposed integrated modeling method.Highlights
Degradation of epoxy polymer under hydro‐thermal‐salt aging conditions.
Integrated model to predict mechanical response of hydrothermally aged epoxy.
RVE model to predict the mechanical behavior of hydrothermally aged CFRP.
Hydrothermal aging on the transverse compressive behavior of UD CFRP.
Quantitative detection of aging damage of solid propellant based on frequency impedance spectroscopy combined with CARS‐SVM algorithm
Authors: Duan Leiguang , Wang Xueren , Zhang Binbin , Qiang Hongfu 
Published: May 2024

AbstractSolid propellant, as the energy source for solid rocket engines, it is of great significance to achieve accurate quantitative detection of aging damage of solid propellant. In this paper, a novel approach based on frequency impedance spectroscopy impedance combined with CARS‐SVM algorithm was proposed. First, the temperature, humidity, and pressure of environmental information around the solid rocket motor were sampled, and then the impedance at corresponding frequencies of the propellant was obtained by AD5933 chip. Second, the processed experimental data were subjected to abnormal sample detection before further variables selection using uninformative variables elimination (UVE) competitive adaptive reweighted sampling (CARS), respectively. Finally, support vector machine (SVM), UVE‐SVM and CARS‐SVM quantitative calibration methods were established. The results showed that the determination coefficient (R2), root mean square error (RMSE), and mean absolute percentage error (MAPE) of CARS‐SVM model were 0.9919, 0.7540, and 0.0480, respectively. Therefore, the results prove that impedance of solid propellant combined with CARS‐SVM model can effectively achieve high precision quantitative detection of aging damage of solid propellant, which lays a new method for the application of solid propellants aging damage in the online quantitative detection.
A numerical determination of complex solid gun propellant burn rates through closed bomb simulation
Authors: Houthuysen Christopher , Parziale Nicholaus 
Published: May 2024

AbstractClosed bomb testing is a prominent means of characterizing the combustion behavior of solid gun propellants. This sub‐scale test allows the propellant to burn in a constant volume environment, where the resulting pressure‐time trace can be collected via a pressure transducer. Historically, numerical procedures have been developed to determine the burn rates of the gun propellants from these pressure‐time traces; however, no standardized procedure exists to determine the burn rates of grains with variable surface thermochemistry and ignition criteria. To address this capability gap, a non‐linearly constrained, multivariate optimization algorithm has been developed to decouple propellant grain surfaces and determine surface‐specific burn rates [1]. In this work, the optimization algorithm as well as the legacy Excel‐based Closed Bomb (XLCB) program [2] were used to determine the burn rates of homogeneous, deterred, and layered propellants from experimental data. Closed bomb simulations using these burn rates were then conducted with the two‐phase, multidimensional, interior ballistics solver, iBallistix [3]. The maximum mean error between the simulated and experimental pressure‐time curves was 6.8 % for the optimization algorithm and 23.8 % for XLCB, showing a marked improvement with our new approach. Furthermore, the approach discussed herein improves burn rate predictions of complex solid gun propellants when compared with legacy closed bomb data reduction analysis programs.
Hydroxyl‐terminated polybutadiene(HTPB) propellants cross‐linked by dimer acid diisocyanate (DDI): Cross‐linking network and properties
Authors: Xin Kai , Yang Rongjie , Yang Kairui , Li Jianmin , Zhai Jinxian 
Published: May 2024

AbstractConsidering the high toxicity of toluene diisocyanate (TDI) and the low reactivity of isophorone diisocyanate (IPDI), a low‐toxicity curing agent, dimer acid diisocyanate (DDI), was used to cross‐link HTPB elastomers and propellants. The unique long‐chain structure of DDI not only ensures the elastic modulus and tensile strength of the elastomer, but also improves the flexibility to some extent. The long flexible chains promote the segment movement, which is very important for the formation of hydrogen bonds between segments. The chemical cross‐linking network and hydrogen bonding association play a significant role in the mechanical properties of the HTPB/DDI system. The relationship between the mole ratio of ‐NCO to ‐OH (R‐value) and the mechanical properties of HTPB/DDI elastomers were also investigated. In the range of R‐value from 0.85 to 1.2, the elastic modulus and tensile strength first increase and then decrease, and the elongation at break first decreases and then increases. Under the same curing conditions, the elastic modulus and tensile strength of the HTPB/DDI propellant are similar to the HTPB/TDI propellant. For the HTPB/AP/Al propellants and HTPB/AP/RDX/Al propellants, the HTPB/DDI system has lower burning rates in the range of 5–19 MPa than the HTPB/TDI system and HTPB/IPDI system. The application of DDI can reduce the burning rates of the propellant without adding any burning rate modifiers. It is considered that DDI can replace TDI and IPDI as a new curing agent with low toxicity and moderate reactivity for HTPB systems.
Analysis of thermomechanical coupled accelerated aging of HTPB propellants
Authors: Zeng Yi , Huang Wei , Chen Jia‐Xing , Xu Jin‐Sheng , Chen Xiong , Wu Rui , Song Qi‐Xuan 
Published: May 2024

AbstractThis study employed macroscopic uniaxial compression tests at low and medium strain rates, coupled with microscopic electron microscopy, to extensively analyse the impact of thermomechanical coupled aging on the accelerated aging of Hydroxyl‐terminated Polybutadiene (HTPB) propellants, contrasting it with the effects of isolated factors such as heat and dynamic reciprocating force. Results indicate that at various environmental temperatures (323 K, 343 K, and 363 K), thermomechanical coupled aging more significantly affects HTPB propellants than isolated factors. This effect is macroscopically evident in increased ease of deformation, permanent deformation during aging, continual increase in dissipated energy, and a decrease in average stress and ultimate strain post‐aging. Microscopically, the effect predominantly arises from the interplay between matrix thermal degradation and particle fragmentation, which rapidly accumulate and substantially impact the material's macroscopic mechanical properties. Furthermore, as the aging temperature rises, the alterations in both macroscopic mechanical properties and microscopic morphology of HTPB propellants become more pronounced. However, overly high temperatures may swiftly result in substantial material performance deterioration. Consequently, while elevating temperature effectively accelerates thermomechanical aging, the potential adverse effects on material performance must be judiciously considered. This underscores the necessity of balancing temperature regulation with aging efficiency enhancement in HTPB propellants to ensure effective control and quantitative assessment of the aging process, while minimizing material degradation.
Characterization of the interaction between the Sec61 translocon complex and ppαF using optical tweezers
Authors: Robeson Luka , Casanova‐Morales Nathalie , Burgos‐Bravo Francesca , Alfaro‐Valdés Hilda M. , Lesch Robert , Ramírez‐Álvarez Carolina , Valdivia‐Delgado Mauricio , Vega Marcela , Matute Ricardo A. , Schekman Randy , Wilson Christian A. M. 
Published: May 2024

AbstractThe Sec61 translocon allows the translocation of secretory preproteins from the cytosol to the endoplasmic reticulum lumen during polypeptide biosynthesis. These proteins possess an N‐terminal signal peptide (SP) which docks at the translocon. SP mutations can abolish translocation and cause diseases, suggesting an essential role for this SP/Sec61 interaction. However, a detailed biophysical characterization of this binding is still missing. Here, optical tweezers force spectroscopy was used to characterize the kinetic parameters of the dissociation process between Sec61 and the SP of prepro‐alpha‐factor. The unbinding parameters including off‐rate constant and distance to the transition state were obtained by fitting rupture force data to Dudko–Hummer–Szabo models. Interestingly, the translocation inhibitor mycolactone increases the off‐rate and accelerates the SP/Sec61 dissociation, while also weakening the interaction. Whereas the translocation deficient mutant containing a single point mutation in the SP abolished the specificity of the SP/Sec61 binding, resulting in an unstable interaction. In conclusion, we characterize quantitatively the dissociation process between the signal peptide and the translocon, and how the unbinding parameters are modified by a translocation inhibitor.
Engineering G protein‐coupled receptors for stabilization
Authors: Velloso João Paulo L. , de Sá Alex G. C. , Pires Douglas E. V. , Ascher David B. 
Published: May 2024

AbstractG protein‐coupled receptors (GPCRs) are one of the most important families of targets for drug discovery. One of the limiting steps in the study of GPCRs has been their stability, with significant and time‐consuming protein engineering often used to stabilize GPCRs for structural characterization and drug screening. Unfortunately, computational methods developed using globular soluble proteins have translated poorly to the rational engineering of GPCRs. To fill this gap, we propose GPCR‐tm, a novel and personalized structurally driven web‐based machine learning tool to study the impacts of mutations on GPCR stability. We show that GPCR‐tm performs as well as or better than alternative methods, and that it can accurately rank the stability changes of a wide range of mutations occurring in various types of class A GPCRs. GPCR‐tm achieved Pearson's correlation coefficients of 0.74 and 0.46 on 10‐fold cross‐validation and blind test sets, respectively. We observed that the (structural) graph‐based signatures were the most important set of features for predicting destabilizing mutations, which points out that these signatures properly describe the changes in the environment where the mutations occur. More specifically, GPCR‐tm was able to accurately rank mutations based on their effect on protein stability, guiding their rational stabilization. GPCR‐tm is available through a user‐friendly web server at https://biosig.lab.uq.edu.au/gpcr_tm/.
A salt bridge of the C‐terminal carboxyl group regulates PHPT1 substrate affinity and catalytic activity
Authors: Zavala Erik , Dansereau Stephen , Burke Michael J. , Lipchock James M. , Maschietto Federica , Batista Victor , Loria J. Patrick 
Published: May 2024

AbstractPHPT1 is a histidine phosphatase that modulates signaling in eukaryotes through its catalytic activity. Here, we present an analysis of the structure and dynamics of PHPT1 through a combination of solution NMR, molecular dynamics, and biochemical experiments. We identify a salt bridge formed between the R78 guanidinium moiety and the C‐terminal carboxyl group on Y125 that is critical for ligand binding. Disruption of the salt bridge by appending a glycine residue at the C‐terminus (G126) leads to a decrease in catalytic activity and binding affinity for the pseudo substrate, para‐nitrophenylphosphate (pNPP), as well as the active site inhibitor, phenylphosphonic acid (PPA). We show through NMR chemical shift, 15N relaxation measurements, and analysis of molecular dynamics trajectories, that removal of this salt bridge results in an active site that is altered both structurally and dynamically thereby significantly impacting enzymatic function and confirming the importance of this electrostatic interaction.
Reconstitution and characterization of BRAF in complex with 14‐3‐3 and KRAS4B on nanodiscs
Authors: Liu Ningdi F. , Enomoto Masahiro , Marshall Christopher B. , Ikura Mitsuhiko 
Published: May 2024

AbstractRAF kinases are key components of the RAS‐MAPK signaling pathway, which drives cell growth and is frequently overactivated in cancer. Upstream signaling activates the small GTPase RAS, which recruits RAF to the cell membrane, driving a transition of the latter from an auto‐inhibited monomeric conformation to an active dimer. Despite recent progress, mechanistic details underlying RAF activation remain unclear, particularly the role of RAS and the membrane in mediating this conformational rearrangement of RAF together with 14‐3‐3 to permit RAF kinase domain dimerization. Here, we reconstituted an active complex of dimeric BRAF, a 14‐3‐3 dimer and two KRAS4B on a nanodisc bilayer and verified that its assembly is GTP‐dependent. Biolayer interferometry (BLI) was used to compare the binding affinities of monomeric versus dimeric full‐length BRAF:14‐3‐3 complexes for KRAS4B‐conjugated nanodiscs (RAS‐ND) and to investigate the effects of membrane lipid composition and spatial density of KRAS4B on binding. 1,2‐Dioleoyl‐sn‐glycero‐3‐phospho‐L‐serine (DOPS) and higher KRAS4B density enhanced the interaction of BRAF:14‐3‐3 with RAS‐ND to different degrees depending on BRAF oligomeric state. We utilized our reconstituted system to dissect the effects of KRAS4B and the membrane on the kinase activity of monomeric and dimeric BRAF:14‐3‐3 complexes, finding that KRAS4B or nanodiscs alone were insufficient to stimulate activity, whereas RAS‐ND increased activity of both states of BRAF. The reconstituted assembly of full‐length BRAF with 14‐3‐3 and KRAS on a cell‐free, defined lipid bilayer offers a more holistic biophysical perspective to probe regulation of this multimeric signaling complex at the membrane surface.
Characterization of a novel format scFv×VHH single‐chain biparatopic antibody against metal binding protein MtsA
Authors: Asano Risa , Takeuchi Miyu , Nakakido Makoto , Ito Sho , Aikawa Chihiro , Yokoyama Takeshi , Senoo Akinobu , Ueno Go , Nagatoishi Satoru , Tanaka Yoshikazu , Nakagawa Ichiro , Tsumoto Kouhei 
Published: May 2024

AbstractBiparatopic antibodies (bpAbs) are engineered antibodies that bind to multiple different epitopes within the same antigens. bpAbs comprise diverse formats, including fragment‐based formats, and choosing the appropriate molecular format for a desired function against a target molecule is a challenging task. Moreover, optimizing the design of constructs requires selecting appropriate antibody modalities and adjusting linker length for individual bpAbs. Therefore, it is crucial to understand the characteristics of bpAbs at the molecular level. In this study, we first obtained single‐chain variable fragments and camelid heavy‐chain variable domains targeting distinct epitopes of the metal binding protein MtsA and then developed a novel format single‐chain bpAb connecting these fragment antibodies with various linkers. The physicochemical properties, binding activities, complex formation states with antigen, and functions of the bpAb were analyzed using multiple approaches. Notably, we found that the assembly state of the complexes was controlled by a linker and that longer linkers tended to form more compact complexes. These observations provide detailed molecular information that should be considered in the design of bpAbs.
Structural studies of intrinsically disordered MLL‐fusion protein AF9 in complex with peptidomimetic inhibitors
Authors: Yang Yuting , Ahmad Ejaz , Premkumar Vidhya , Liu Alicen , Ashikur Rahman S. M. , Nikolovska‐Coleska Zaneta 
Published: May 2024

AbstractAF9 (MLLT3) and its paralog ENL(MLLT1) are members of the YEATS family of proteins with important role in transcriptional and epigenetic regulatory complexes. These proteins are two common MLL fusion partners in MLL‐rearranged leukemias. The oncofusion proteins MLL‐AF9/ENL recruit multiple binding partners, including the histone methyltransferase DOT1L, leading to aberrant transcriptional activation and enhancing the expression of a characteristic set of genes that drive leukemogenesis. The interaction between AF9 and DOT1L is mediated by an intrinsically disordered C‐terminal ANC1 homology domain (AHD) in AF9, which undergoes folding upon binding of DOT1L and other partner proteins. We have recently reported peptidomimetics that disrupt the recruitment of DOT1L by AF9 and ENL, providing a proof‐of‐concept for targeting AHD and assessing its druggability. Intrinsically disordered proteins, such as AF9 AHD, are difficult to study and characterize experimentally on a structural level. In this study, we present a successful protein engineering strategy to facilitate structural investigation of the intrinsically disordered AF9 AHD domain in complex with peptidomimetic inhibitors by using maltose binding protein (MBP) as a crystallization chaperone connected with linkers of varying flexibility and length. The strategic incorporation of disulfide bonds provided diffraction‐quality crystals of the two disulfide‐bridged MBP–AF9 AHD fusion proteins in complex with the peptidomimetics. These successfully determined first series of 2.1–2.6 Å crystal complex structures provide high‐resolution insights into the interactions between AHD and its inhibitors, shedding light on the role of AHD in recruiting various binding partner proteins. We show that the overall complex structures closely resemble the reported NMR structure of AF9 AHD/DOT1L with notable difference in the conformation of the β‐hairpin region, stabilized through conserved hydrogen bonds network. These first series of AF9 AHD/peptidomimetics complex structures are providing insights of the protein–inhibitor interactions and will facilitate further development of novel inhibitors targeting the AF9/ENL AHD domain.
Isolation of anthraquinone derivatives from Rubia cordifolia (Rubiaceae) and their bioactivities against plant pathogenic microorganisms
Authors: Wang Wenhao , Guo Yifei , Xu Jialu , Zhang Hao , Ma Zhiqing , Wu Hua 
Published: May 2024

AbstractBACKGROUNDThe discovery of antimicrobial ingredients from natural products could be an effective way to create novel fungicides. Rubia cordifolia L., a traditional Chinese herb, may have antimicrobial effects on plant pathogens according to our previous screening study.RESULTSRubia cordifolia L. extracts had moderate inhibitory effects on apple Valsa canker (Valsa mali) and tomato grey mould (Botrytis cinerea) at a concentration of 10 mg mL−1. With the use of bioguided isolation methods, eight compounds (1–8) were obtained, including the new compound 2,2,6‐trimethyl‐6‐(4‐methylphenyl)‐tetrahydropyrano‐ 3‐ol (7), and seven quinone derivatives. Two compounds, mollugin (1) and 1,3,6‐trihydroxy‐2‐methylanthraquinone (6), were found to exhibit outstanding antifungal activities against V. mali and Phytophthora capsici Leon. The half maximal effective concentration (EC50) of compound 1 and compound 6 against V. mali were 79.08 and 81.78 μg mL−1, respectively, and the EC50 of compound 6 against P. capsici was 4.86 μg mL−1. Compound 1 also showed excellent activity against tobacco mosaic virus (TMV). The inactive, inductive, protective and curative activities against TMV were 84.29%, 83.38%, 86.81%, and 60.02%, respectively, at a concentration of 500 μg mL−1, which were all close to or greater than that of the positive control (100 μg mL−1 chitosan oligosaccharide, COS).CONCLUSIONMollugin and 1,3,6‐trihydroxy‐2‐methylanthraquinone are potentially valuable active compounds that lay a foundation for research on botanical fungicide products derived from R. cordifolia L. and provide lead structures for quinone derivative synthesis and structural modification. © 2024 Society of Chemical Industry.
Therapeutic effects of treat and repair strategy in pediatric patients with pulmonary arterial hypertension and simple congenital heart defects
Authors: Wang Xiaofeng , Wang Shilin , Lu Zhongyuan , Wang Wenlong , Wang Xu 
Published: May 2024

AbstractSurgical indications for patients with pulmonary arterial hypertension (PAH) and congenital heart defects are controversial. The treat and repair strategy has demonstrated efficacy in adult populations, but there have been no studies on pediatric patients. This study included pediatric patients with PAH and simple congenital heart defects who underwent corrective repair between 2012 and 2021. According to the preoperative treatment strategies, the patients were divided into a regular strategy group (Group 1) and a treat‐and‐repair strategy group (Group 2). Postoperative recovery and follow‐up results were compared between the two groups. A total of 33 patients were included in this study. Group 1 consisted of 19 patients, whereas Group 2 consisted of 14 patients. The pulmonary vascular resistance index in Group 2 was higher than that in Group 1 (10.9 ± 4.1 vs. 8.2 ± 1.6 WU, p = 0.031). There were no differences in postoperative recovery between the two groups (p > 0.05). During follow‐up, five patients were lost (three in Group 1 and two in Group 2). The median follow‐up period was 59 months. One patient died in Group 1, and two patients died in Group 2. There was no significant difference in the survival curve (p = 0.39). At the last follow‐up, another seven patients had experienced a non‐low‐risk condition, with a total of three non‐low‐risk patients in Group 1 and seven in Group 2, including one patient in each group who had a history of ICU admission. According to the ROC curve, a preoperative PVRi <8.2 WU×m2 can predict postoperative persistent low‐risk state, PVRi <5.2 WU×m2 can avoid postoperative death and/or ICU administration. In pediatric patients with PAH and simple congenital heart defects, the treat and repair strategies may provide surgery opportunities, PVRi should be <8 WU×m2, and <5.2 WU×m2 is the best choice.