bluuebunny/crossref_metadata_2025_split huggingface dataset:
Heterogeneous nucleation of calcium sulfate whisker in polyamide 6 and its efficient reinforcement on tribology performance
Authors: Sun Shaojie , Ye Jinqiao , Cai Ziqing 
Published: September 2024

AbstractFor traditional materials, a polymer composite with high performance and large‐scale production is still the goal pursued by researchers. In our work, polyamide 6/calcium sulfate whiskers (PA6/SCW) composites were fabricated via melt‐compouding method. The calcium sulfate whisker based on gypsum mineral was used as reinforcement. After grafting silane coupling agent on the whisker surface, the whiskers showed a significant reinforcing effect in polyamide. The mechanics and tribology performance of the samples had been significantly inhanced. Based on the nucleation mechanism of lattice matching, calcium sulfate whiskers have obvious heterogeneous nucleation effect in PA6 matrix, while the crystallization period was slightly prolonged. This was caused by the network structure formed by the whiskers in the matrix, which impeded the free movement of polymer chain segments. In combination with the orientation degree of the molecular chains measured by the interdigital electrode, the reinforcing effect of the oriented PA6 specimens was derived from the orientation arrangement of the whiskers and the efficient load transfer.Highlights
Mechanical and tribological properties of composite were significantly improved.
The composite could achieved large‐scale production due to simple preparation.
The whiskers had obvious heterogeneous nucleation effect in matrix.
The reinforcing effect was derived from efficient load transfer from whiskers.
Dental composite materials based on Zn/Al‐layered double hydroxide and their physical mechanical properties
Authors: Edkheil Akram , Vuksanović Marija M. , Savić Andrija , Šaponjić Aleksandra , Petrović Miloš , Radojević Vesna , Heinemann Radmila Jančić 
Published: September 2024

AbstractDental materials' demands can be answered using composite materials, as composite properties are suitable for tailoring the material's behavior. Poly (methyl methacrylate) (PMMA) is usually a material of choice in dental applications, and its mechanical properties can be improved in terms of modulus, strength, and hardness. The chosen reinforcement in this publication was Zn/Al‐layered double hydroxide (LDH), as this material has functional property modification possibilities. The reinforcement was synthesized using the coprecipitation process on a laboratory scale. The dispersion of the reinforcement was done with ultrasonication, and the composites prepared contained 1, 3, and 5 wt% of reinforcement, and the so‐prepared composites were compared to the matrix. Improvements were observed in terms of the elastic modulus and tensile strength, and the best performance was observed in the composite with 3 wt% of particles. Hardness increased with the addition of particles and the higher the particle content, the better the hardness. Materials were tested using dynamic mechanical techniques, and it was proven that the addition of particles lowers the Tg of the composite compared to the pure matrix. The addition of particles diminished the affinity of the material for polar liquids such as water.Highlights
Zn/Al‐layered double hydroxide is used to reinforce acrylic matrix.
Composite with improved strength, modulus, and microhardness.
Addition of a layered double hydroxide decreases hydrophobicity of composite.
Analysis of EGFR binding hotspots for design of new EGFR inhibitory biologics
Authors: Tydings Claiborne W. , Singh Bhuminder , Smith Adam W. , Ledwitch Kaitlyn V. , Brown Benjamin P. , Lovly Christine M. , Walker Allison S. , Meiler Jens 
Published: September 2024

AbstractThe epidermal growth factor (EGF) receptor (EGFR) is activated by the binding of one of seven EGF‐like ligands to its ectodomain. Ligand binding results in EGFR dimerization and stabilization of the active receptor conformation subsequently leading to activation of downstream signaling. Aberrant activation of EGFR contributes to cancer progression through EGFR overexpression/amplification, modulation of its positive and negative regulators, and/or activating mutations within EGFR. EGFR targeted therapeutic antibodies prevent dimerization and interaction with endogenous ligands by binding the ectodomain of EGFR. However, these antibodies have had limited success in the clinic, partially due to EGFR ectodomain resistance mutations, and are only applicable to a subset of patients with EGFR‐driven cancers. These limitations suggest that alternative EGFR targeted biologics need to be explored for EGFR‐driven cancer therapy. To this end, we analyze the EGFR interfaces of known inhibitory biologics with determined structures in the context of endogenous ligands, using the Rosetta macromolecular modeling software to highlight the most important interactions on a per‐residue basis. We use this analysis to identify the structural determinants of EGFR targeted biologics. We suggest that commonly observed binding motifs serve as the basis for rational design of new EGFR targeted biologics, such as peptides, antibodies, and nanobodies.
Integration of proteomic data with genome‐scale metabolic models: A methodological overview
Authors: Zare Farid , Fleming Ronan M. T. 
Published: September 2024

AbstractThe integration of proteomics data with constraint‐based reconstruction and analysis (COBRA) models plays a pivotal role in understanding the relationship between genotype and phenotype and bridges the gap between genome‐level phenomena and functional adaptations. Integrating a generic genome‐scale model with information on proteins enables generation of a context‐specific metabolic model which improves the accuracy of model prediction. This review explores methodologies for incorporating proteomics data into genome‐scale models. Available methods are grouped into four distinct categories based on their approach to integrate proteomics data and their depth of modeling. Within each category section various methods are introduced in chronological order of publication demonstrating the progress of this field. Furthermore, challenges and potential solutions to further progress are outlined, including the limited availability of appropriate in vitro data, experimental enzyme turnover rates, and the trade‐off between model accuracy, computational tractability, and data scarcity. In conclusion, methods employing simpler approaches demand fewer kinetic and omics data, consequently leading to a less complex mathematical problem and reduced computational expenses. On the other hand, approaches that delve deeper into cellular mechanisms and aim to create detailed mathematical models necessitate more extensive kinetic and omics data, resulting in a more complex and computationally demanding problem. However, in some cases, this increased cost can be justified by the potential for more precise predictions.
Peptides inhibiting the assembly of monomeric human l‐lactate dehydrogenase into catalytically active homotetramer decrease the synthesis of lactate in cultured cells
Authors: Stefan Alessandra , Gentilucci Luca , Ruffolo Francesca , Rossi Valentina , Sordi Sofia , He Tingting , di Stefano Giuseppina , Santino Federica , Brigotti Maurizio , Scotti Claudia , Iamele Luisa , de Jonge Hugo , Piaz Fabrizio Dal , Santarcangelo Danilo Rocco , Hochkoeppler Alejandro 
Published: September 2024

AbstractThe energetic metabolism of cancer cells relies on a substantial commitment of pyruvate to the catalytic action of lactate‐generating dehydrogenases. This coupling mainly depends on lactate dehydrogenase A (LDH‐A), which is overexpressed in different types of cancers, and therefore represents an appealing therapeutic target. Taking into account that the activity of LDHs is exclusively exerted by their tetrameric forms, it was recently shown that peptides perturbing the monomers‐to‐tetramer assembly inhibit human LDH‐A (hLDH‐A). However, to identify these peptides, tetrameric hLDH‐A was transiently exposed to strongly acidic conditions inducing its dissociation into monomers, which were tested as a target for peptides at low pH. Nevertheless, the availability of native monomeric hLDH‐A would allow performing similar screenings under physiological conditions. Here we report on the unprecedented isolation of recombinant monomeric hLDH‐A at neutral pH, and on its use to identify peptides inhibiting the assembly of the tetrameric enzyme. Remarkably, the GQNGISDL octapeptide, mimicking the 296–303 portion of hLDH‐A C‐terminal region, was observed to effectively inhibit the target enzyme. Moreover, by dissecting the action of this octapeptide, the cGQND cyclic tetrapeptide was found to act as the parental compound. Furthermore, we performed assays using MCF7 and BxPC3 cultured cells, exclusively expressing hLDH‐A and hLDH‐B, respectively. By means of these assays we detected a selective action of linear and cyclic GQND tetrapeptides, inhibiting lactate secretion in MCF7 cells only. Overall, our observations suggest that peptides mimicking the C‐terminal region of hLDH‐A effectively interfere with protein–protein interactions responsible for the assembly of the tetrameric enzyme.
Benchmarking reverse docking through AlphaFold2 human proteome
Authors: Luo Qing , Wang Sheng , Li Hoi Yeung , Zheng Liangzhen , Mu Yuguang , Guo Jingjing 
Published: September 2024

AbstractPredicting the binding of ligands to the human proteome via reverse‐docking methods enables the understanding of ligand's interactions with potential protein targets in the human body, thereby facilitating drug repositioning and the evaluation of potential off‐target effects or toxic side effects of drugs. In this study, we constructed 11 reverse docking pipelines by integrating site prediction tools (PointSite and SiteMap), docking programs (Glide and AutoDock Vina), and scoring functions (Glide, Autodock Vina, RTMScore, DeepRMSD, and OnionNet‐SFCT), and then thoroughly benchmarked their predictive capabilities. The results show that the Glide_SFCT (PS) pipeline exhibited the best target prediction performance based on the atomic structure models in AlphaFold2 human proteome. It achieved a success rate of 27.8% when considering the top 100 ranked prediction. This pipeline effectively narrows the range of potential targets within the human proteome, laying a foundation for drug target prediction, off‐target assessment, and toxicity prediction, ultimately boosting drug development. By facilitating these critical aspects of drug discovery and development, our work has the potential to ultimately accelerate the identification of new therapeutic agents and improve drug safety.
HER4 is a high‐affinity dimerization partner for all EGFR/HER/ErbB family proteins
Authors: Singh Pradeep Kumar , Kim Soyeon , Smith Adam W. 
Published: September 2024

AbstractHuman epidermal growth factor receptors (HER)—also known as EGFR or ErbB receptors—are a subfamily of receptor tyrosine kinases (RTKs) that play crucial roles in cell growth, division, and differentiation. HER4 (ErbB4) is the least studied member of this family, partly because its expression is lower in later stages of development. Recent work has suggested that HER4 can play a role in metastasis by regulating cell migration and invasiveness; however, unlike EGFR and HER2, the precise role that HER4 plays in tumorigenesis is still unresolved. Early work on HER family proteins suggested that there are direct interactions between the four members, but to date, there has been no single study of all four receptors in the same cell line with the same biophysical method. Here, we quantitatively measure the degree of association between HER4 and the other HER family proteins in live cells with a time‐resolved fluorescence technique called pulsed interleaved excitation fluorescence cross‐correlation spectroscopy (PIE‐FCCS). PIE‐FCCS is sensitive to the oligomerization state of membrane proteins in live cells, while simultaneously measuring single‐cell protein expression levels and diffusion coefficients. Our PIE‐FCCS results demonstrate that HER4 interacts directly with all HER family members in the cell plasma membrane. The interaction between HER4 and other HER family members intensified in the presence of a HER4‐specific ligand. Our work suggests that HER4 is a preferred dimerization partner for all HER family proteins, even in the absence of ligands.
BracketMaker: Visualization and optimization of chemical protein synthesis
Authors: Evangelista Judah L. , Kay Michael S. 
Published: September 2024

AbstractChemical protein synthesis (CPS), in which custom peptide segments of ~20–60 aa are produced by solid‐phase peptide synthesis and then stitched together through sequential ligation reactions, is an increasingly popular technique. The workflow of CPS is often depicted with a “bracket” style diagram detailing the starting segments and the order of all ligation, desulfurization, and/or deprotection steps to obtain the product protein. Brackets are invaluable tools for comparing multiple possible synthetic approaches and serve as blueprints throughout a synthesis. Drawing CPS brackets by hand or in standard graphics software, however, is a painstaking and error‐prone process. Furthermore, the CPS field lacks a standard bracket format, making side‐by‐side comparisons difficult. To address these problems, we developed BracketMaker, an open‐source Python program with built‐in graphic user interface (GUI) for the rapid creation and analysis of CPS brackets. BracketMaker contains a custom graphics engine which converts a text string (a protein sequence annotated with reaction steps, introduced herein as a standardized format for brackets) into a high‐quality vector or PNG image. To aid with new syntheses, BracketMaker's “AutoBracket” tool automatically performs retrosynthetic analysis on a set of segments to draft and rank all possible ligation orders using standard native chemical ligation, protection, and desulfurization techniques. AutoBracket, in conjunction with an improved version of our previously reported Automated Ligator (Aligator) program, provides a pipeline to rapidly develop synthesis plans for a given protein sequence. We demonstrate the application of both programs to develop a blueprint for 65 proteins of the minimal Escherichia coli ribosome.
Molecular mechanics studies of factors affecting overall rate in cascade reactions: Multi‐enzyme colocalization and environment
Authors: Kaushik Shivansh , Hung Ta I , Chang Chia‐en A. 
Published: September 2024

AbstractMillions of years of evolution have optimized many biosynthetic pathways by use of multi‐step catalysis. In addition, multi‐step metabolic pathways are commonly found in and on membrane‐bound organelles in eukaryotic biochemistry. The fundamental mechanisms that facilitate these reaction processes provide strategies to bioengineer metabolic pathways in synthetic chemistry. Using Brownian dynamics simulations, here we modeled intermediate substrate transportation of colocalized yeast–ester biosynthesis enzymes on the membrane. The substrate acetate ion traveled from the pocket of aldehyde dehydrogenase to its target enzyme acetyl‐CoA synthetase, then the substrate acetyl CoA diffused from Acs1 to the active site of the next enzyme, alcohol‐O‐acetyltransferase. Arranging two enzymes with the smallest inter‐enzyme distance of 60 Å had the fastest average substrate association time as compared with anchoring enzymes with larger inter‐enzyme distances. When the off‐target side reactions were turned on, most substrates were lost, which suggests that native localization is necessary for efficient final product synthesis. We also evaluated the effects of intermolecular interactions, local substrate concentrations, and membrane environment to bring mechanistic insights into the colocalization pathways. The computation work demonstrates that creating spatially organized multi‐enzymes on membranes can be an effective strategy to increase final product synthesis in bioengineering systems.
Developing and evaluating the extended epistemic vigilance framework
Authors: Bielik Tom , Krell Moritz 
Published: September 2024

AbstractIn science education, epistemic vigilance plays a key role in the development of students' critical thinking by supporting students' abilities to evaluate the expertise level of the source and to evaluate the claim itself, using rigorous scientific standards and appropriate argumentation heuristics. Based on previous studies, which suggested two aspects of epistemic vigilance—reflecting the source of information and the claim that is made—we developed the Extended Epistemic Vigilance Framework (EEVF) that includes an additional aspect of evaluating the receiver. In an empirical exploratory pilot study, we evaluated the reliability and validity of an EEVF‐based category system and investigated to what extent the EEVF can be used to characterize changes in biology graduate students' epistemic vigilance after participating in a critical thinking course. Results show that the EEVF‐based category system includes reliable and valid categories for identifying students' epistemic vigilance. A statistically significant increase with a small effect size was found in students' epistemic vigilance regarding the reliability of the source and the references used to support the claim following their participation in the critical thinking course. However, a statistically significant decrease with a small effect size was found regarding the awareness of the aspects of the one‐sidedness of the claim, the context of the claim, and cognitive biases and socioemotional influences on the receiver. In general, these findings indicate that the EEVF offers an improved framework to analyze students' epistemic vigilance more comprehensively.
Intraocular malignant nerve sheath tumour in a brown eyed labrador retriever
Authors: Salter Lauren , Scurrell Emma , Mignan Thomas 
Published: September 2024

AbstractA 6‐year‐old, male, neutered, brown eyed labrador retriever was presented with an intraocular pale pink mass in the left eye. Enucleation of the globe was performed, and the mass was submitted for histopathology. Histology and immunohistochemistry confirmed the mass as a malignant nerve sheath tumour. There was no evidence of mass recurrence, and general and neurological examination remained normal at 9‐month follow‐up. While the majority of intraocular neoplasms are benign, a malignant neoplasm must be considered in all cases of intraocular mass. Differentiation between benign and malignant intraocular neoplasms is challenging and often requires enucleation with histopathology to confirm diagnosis. Tumour staging should be considered in the event of a malignant nerve sheath tumour. Finally, uveal malignant nerve sheath tumour should not only be considered in blue eyed dogs, but also in brown eyed dogs as in the present case.
Investigation of micropolar dusty fluid flow in a rotational frame with magnetic field: A meshless radial basis function pseudospectral approach
Authors: Himanshu  , Bhatia Gurpreet Singh , Chandrawat Rajesh Kumar 
Published: September 2024

AbstractRotational flow has numerous applications across a wide range of fields, including industrial processes for mixing, pumping, and processing materials, geophysical fluid dynamics for studying the Earth's atmosphere and oceans, aerospace engineering for designing and testing aircraft and spacecraft, medical imaging for creating detailed images of the human body, and environmental engineering for studying the transport of pollutants in water and air. In rotational flow, pumping power is an important parameter that measures the amount of energy required to maintain the flow of the fluid in a rotating frame. It is significant because the presence of the Coriolis force and other rotational effects can substantially alter the fluid dynamics, making it difficult to maintain a steady flow. The present study deals with the flow of micropolar dusty fluid in a rotating frame under the influence of the magnetic field, applied transversely to the flow in a horizontal channel. The fluid is induced to flow between two parallel plates by the movement of the upper plate and a constant pressure gradient. A meshless radial basis function pseudospectral approach is employed to derive a set of partial differential equations that determine the primary and secondary velocity profiles of the fluid, as well as the particle and microrotation velocities and temperature distribution. The pumping power required to sustain the flow in the absence of a pressure gradient is also calculated based on these velocity profiles. The findings provide valuable insights into the behavior of micropolar dusty fluids in a rotational channel and can potentially inform the design of industrial processes involving such fluids.
Flow around a slender body with sharp edges
Authors: Núñez Manuel 
Published: September 2024

AbstractThe behavior of harmonic functions near corners of the domain boundary has a universal character that may be applied to the study of the flow around slender bodies with sharp edges. Depending of the energy of the potential function near the tip of the corner, this may yield a fast rotating flow or a vortex in its vicinity. For internal angles, such as occur in grooves of the body, a stagnation region or an eddy may occur. Lateral forces are also affected by the presence of corners, yielding configurations that resemble either a circulation lift or a vortex lift.
Mosco Convergence of Gradient Forms with Non-Convex Interaction Potential
Authors: Grothaus Martin , Wittmann Simon 
Published: September 2024

AbstractThis article provides a new approach to address Mosco convergence of gradient-type Dirichlet forms, $${\mathcal {E}}^N$$

E

N

on $$L^2(E,\mu _N)$$

L
2

(
E
,

μ
N

)

for $$N\in {\mathbb {N}}$$

N
∈
N

, in the framework of converging Hilbert spaces by K. Kuwae and T. Shioya. The basic assumption is weak measure convergence of the family $${(\mu _N)}_{N}$$

(

μ
N

)

N

on the state space E—either a separable Hilbert space or a locally convex topological vector space. Apart from that, the conditions on $${(\mu _N)}_{N}$$

(

μ
N

)

N

try to impose as little restrictions as possible. The problem has fully been solved if the family $${(\mu _N)}_{N}$$

(

μ
N

)

N

contain only log-concave measures, due to Ambrosio et al. (Probab Theory Relat. Fields 145:517–564, 2009). However, for a large class of convergence problems the assumption of log-concavity fails. The article suggests a way to overcome this hindrance, as it presents a new approach. Combining the theory of Dirichlet forms with methods from numerical analysis we find abstract criteria for Mosco convergence of standard gradient forms with varying reference measures. These include cases in which the measures are not log-concave. To demonstrate the accessibility of our abstract theory we discuss a first application, generalizing an approximation result by Bounebache and Zambotti (J Theor Probab 27:168–201, 2014).