bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identification of a novel DNA repair inhibitor using an in silico driven approach shows effective combinatorial activity with genotoxic agents against multidrug‐resistant Escherichia coli
Authors: Bernacchia Lorenzo , Paris Antoine , Gupta Arya , Charman Robert J. , McGreig Jake , Wass Mark N. , Kad Neil M. 
Published: March 2024

AbstractIncreasing antimicrobial drug resistance represents a global existential threat. Infection is a particular problem in immunocompromised individuals, such as patients undergoing cancer chemotherapy, due to the targeting of rapidly dividing cells by antineoplastic agents. We recently developed a strategy that targets bacterial nucleotide excision DNA repair (NER) to identify compounds that act as antimicrobial sensitizers specific for patients undergoing cancer chemotherapy. Building on this, we performed a virtual drug screening of a ~120,000 compound library against the key NER protein UvrA. From this, numerous target compounds were identified and of those a candidate compound, Bemcentinib (R428), showed a strong affinity toward UvrA. This NER protein possesses four ATPase sites in its dimeric state, and we found that Bemcentinib could inhibit UvrA's ATPase activity by ~90% and also impair its ability to bind DNA. As a result, Bemcentinib strongly diminishes NER's ability to repair DNA in vitro. To provide a measure of in vivo activity we discovered that the growth of Escherichia coli MG1655 was significantly inhibited when Bemcentinib was combined with the DNA damaging agent 4‐NQO, which is analogous to UV. Using the clinically relevant DNA‐damaging antineoplastic cisplatin in combination with Bemcentinib against the urological sepsis‐causing E. coli strain EC958 caused complete growth inhibition. This study offers a novel approach for the potential development of new compounds for use as adjuvants in antineoplastic therapy.
MA‐PEP: A novel anticancer peptide prediction framework with multimodal feature fusion based on attention mechanism
Authors: Liang Xiao , Zhao Haochen , Wang Jianxin 
Published: March 2024

AbstractAntiCancer Peptides (ACPs) have emerged as promising therapeutic agents for cancer treatment. The time‐consuming and costly nature of wet‐lab discriminatory methods has spurred the development of various machine learning and deep learning‐based ACP classification methods. Nonetheless, current methods encountered challenges in efficiently integrating features from various peptide modalities, thereby limiting a more comprehensive understanding of ACPs and further restricting the improvement of prediction model performance. In this study, we introduce a novel ACP prediction method, MA‐PEP, which leverages multiple attention mechanisms for feature enhancement and fusion to improve ACP prediction. By integrating the enhanced molecular‐level chemical features and sequence information of peptides, MA‐PEP demonstrates superior prediction performance across several benchmark datasets, highlighting its efficacy in ACP prediction. Moreover, the visual analysis and case studies further demonstrate MA‐PEP's reliable feature extraction capability and its promise in the realm of ACP exploration. The code and datasets for MA‐PEP are available at https://github.com/liangxiaodata/MA-PEP.
Role of UDP‐N‐acetylmuramic acid in the regulation of MurA activity revealed by molecular dynamics simulations
Authors: de Oliveira Maycon Vinicius Damasceno , da Costa Kauê S. , Silva José Rogério A. , Lameira Jerônimo , Lima Anderson H. 
Published: March 2024

AbstractThe peptidoglycan biosynthesis pathway plays a vital role in bacterial cells, and facilitates peptidoglycan layer formation, a fundamental structural component of the bacterial cell wall. The enzymes in this pathway are candidates for antibiotic development, as most do not have mammalian homologues. The UDP‐N‐acetylglucosamine (UNAG) enolpyruvyl transferase enzyme (MurA) in the peptidoglycan pathway cytoplasmic step is responsible for the phosphoenolpyruvate (PEP)–UNAG catalytic reaction, forming UNAG enolpyruvate and inorganic phosphate. Reportedly, UDP‐N‐acetylmuramic acid (UNAM) binds tightly to MurA forming a dormant UNAM–PEP–MurA complex and acting as a MurA feedback inhibitor. MurA inhibitors are complex, owing to competitive binding interactions with PEP, UNAM, and UNAG at the MurA active site. We used computational methods to explore UNAM and UNAG binding. UNAM showed stronger hydrogen‐bond interactions with the Arg120 and Arg91 residues, which help to stabilize the closed conformation of MurA, than UNAG. Binding free energy calculations using end‐point computational methods showed that UNAM has a higher binding affinity than UNAG, when PEP is attached to Cys115. The unbinding process, simulated using τ–random acceleration molecular dynamics, showed that UNAM has a longer relative residence time than UNAG, which is related to several complex dissociation pathways, each with multiple intermediate metastable states. This prevents the loop from opening and exposing the Arg120 residue to accommodate UNAG and potential new ligands. Moreover, we demonstrate the importance of Cys115‐linked PEP in closed‐state loop stabilization. We provide a basis for evaluating novel UNAM analogues as potential MurA inhibitors.Public significanceMurA is a critical enzyme involved in bacterial cell wall biosynthesis and is involved in antibiotic resistance development. UNAM can remain in the target protein's active site for an extended time compared to its natural substrate, UNAG. The prolonged interaction of this highly stable complex known as the ‘dormant complex’ comprises UNAM–PEP–MurA and offers insights into antibiotic development, providing potential options against drug‐resistant bacteria and advancing our understanding of microbial biology.
Design of a symmetry‐broken tetrahedral protein cage by a method of internal steric occlusion
Authors: Gladkov Nika , Scott Elena A. , Meador Kyle , Lee Eric J. , Laganowsky Arthur D. , Yeates Todd O. , Castells‐Graells Roger 
Published: March 2024

AbstractMethods in protein design have made it possible to create large and complex, self‐assembling protein cages with diverse applications. These have largely been based on highly symmetric forms exemplified by the Platonic solids. Prospective applications of protein cages would be expanded by strategies for breaking the designed symmetry, for example, so that only one or a few (instead of many) copies of an exterior domain or motif might be displayed on their surfaces. Here we demonstrate a straightforward design approach for creating symmetry‐broken protein cages able to display singular copies of outward‐facing domains. We modify the subunit of an otherwise symmetric protein cage through fusion to a small inward‐facing domain, only one copy of which can be accommodated in the cage interior. Using biochemical methods and native mass spectrometry, we show that co‐expression of the original subunit and the modified subunit, which is further fused to an outward‐facing anti‐GFP DARPin domain, leads to self‐assembly of a protein cage presenting just one copy of the DARPin protein on its exterior. This strategy of designed occlusion provides a facile route for creating new types of protein cages with unique properties.
Viral envelope proteins fused to multiple distinct fluorescent reporters to probe receptor binding
Authors: Tomris Ilhan , van der Woude Roosmarijn , de Paiva Froes Rocha Rebeca , Torrents de la Peña Alba , Ward Andrew B. , de Vries Robert P. 
Published: March 2024

AbstractEnveloped viruses carry one or multiple proteins with receptor‐binding functionalities. Functional receptors can be glycans, proteinaceous, or both; therefore, recombinant protein approaches are instrumental in attaining new insights regarding viral envelope protein receptor‐binding properties. Visualizing and measuring receptor binding typically entails antibody detection or direct labeling, whereas direct fluorescent fusions are attractive tools in molecular biology. Here, we report a suite of distinct fluorescent fusions, both N‐ and C‐terminal, for influenza A virus hemagglutinins and SARS‐CoV‐2 spike RBD. The proteins contained three or six fluorescent protein barrels and were applied directly to cells to assess receptor binding properties.
Output feedback H∞$$ {H}_{\infty } $$ control of linear systems with infinite distributed input delays
Authors: Zhou Qianghui , Liu Lu , Feng Gang 
Published: March 2024

AbstractThis article investigates the output feedback control problem of linear systems with infinite distributed input delays. An observer‐based output feedback (OBOF) controller is proposed via the predictor feedback approach, and a sufficient condition for the existence of the OBOF controller is given in terms of a set of linear matrix inequalities. It is shown that the resulting closed‐loop system is globally exponentially stable with a prescribed performance. The obtained results include some results on the same problem for linear systems with bounded distributed input delays as special cases. Two numerical examples are finally presented to illustrate the effectiveness of the proposed controller.
How optimal distinctiveness shapes platform complementors' adoption of boundary resources
Authors: Kang Hye Young , Grodal Stine 
Published: March 2024

AbstractResearch SummaryWhat drives platform complementors to adopt boundary resources? We address this question by drawing on optimal distinctiveness. We suggest that competitors' adoption of a platform boundary resource on the one hand increases the legitimacy of the resource, but on the other hand decreases a focal complementor's ability to differentiate by adopting it. We therefore hypothesize an inverted U‐shaped relationship between prior and future adoption of a platform boundary resource. In a dataset of health and fitness apps on the Apple iOS platform and through three online experiments, we find support for this relationship and for the existence of two important complementor‐specific contingencies that moderate this relationship. This paper expands our understanding of how optimal distinctiveness drives the dynamics of platform‐mediated markets.Managerial SummaryIn platform markets, complementors face a dilemma: which of the available platform boundary resources should they adopt? We show that a focal complementor's decision to adopt a boundary resource is the result of a strategic trade‐off between the desire to be both legitimate and to be differentiated from competitors. The result is that initially many complementors adopt the boundary resource and it becomes viewed as increasingly attractive by other platform complementors. However, over time as many complementors have adopted the boundary resource, the remaining complementors begin to shy away from adopting it because they worry that doing so might hurt their ability to be differentiated on the platform. These results are shaped by the complementors' performance and how dedicated they are to the platform.
The Future of ChatGPT in Medicinal Chemistry: Harnessing AI for Accelerated Drug Discovery
Authors: Pradhan Tathagata , Gupta Ojasvi , Chawla Gita 
Published: March 2024

AbstractArtificial Intelligence (AI) has emerged as a transformative tool in various fields, including medicinal chemistry and drug discovery. The integration of artificial intelligence (AI) and machine learning (ML) technologies in medicinal chemistry has revolutionized drug discovery processes. Among AI models, ChatGPT (Generative Pre‐trained Transformer) has shown remarkable capabilities in natural language understanding and generation. This review article delves into the potential applications and prospects of ChatGPT in the domain of medicinal chemistry, focusing on its contributions to drug discovery, compound design, virtual screening, target identification, and optimization of pharmacokinetic properties. ChatGPT′s ability to generate contextually relevant text makes it a valuable tool for data mining and analysis of vast chemical and biological information repositories. In this review article, the authors have discussed the challenges and ethical considerations associated with the implementation of ChatGPT 3.5 in medicinal chemistry research. Authors also extend their acknowledgment to ChatGPT (version 3.5) for its contribution in furnishing responses to the prompt, thereby shedding light on the applications of ChatGPT in the field of medicinal chemistry. The authors have analyzed the responses of ChatGPT.
The Stabilizing Effect of Chitosan‐Modified Biochar (β‐CD/C‐BC) on Agricultural Soil Contaminated by the Cd‐Pyr Complex
Authors: Lin Ying , Li Haibo , Li Xinjing , Wu Yingying 
Published: March 2024

AbstractThe composite pollution of heavy metals (HMs) and polycyclic aromatic hydrocarbons (PAHs) in agricultural soil is increasingly severe. HMs can undergo surface adsorption, complexation, or chemical reactions to transform from bioavailable species to residual species, achieving chemical morphological stability. However, these processes have no effect on PAHs. Biochar (BC), due to its inherent characteristics, can significantly enhance the stability of PAHs and is recommended as a potential co‐stabilizing material for both heavy metals and PAHs. In this study, rice husk biochar modified with β‐cyclodextrin and chitosan (β‐CD/C‐BC) was utilized to stabilize agricultural soil contaminated by Cd and Pyrene (Pyr). One‐way tests were conducted on the dosage and curing time of biochar after a complete cycle of treatment. The results demonstrated that the optimal effect was achieved when the dosage of β‐CD/C‐BC was 7.5 % or the curing time was 21 days. The removal efficiencies for Cd and Pyr were found to be 84.62 %, 64.22 % or 85.90 %, 65.78 %, respectively. Additionally, BCR testing revealed that β‐CD/C‐BC could convert HMs in soil into a residual state (from 32 % to 82 %) with the highest stabilization rate, thereby reducing their migration ability and ecological risk.
Influence of shear strengthening of reinforced normal concrete beams incorporating sustainable materials
Authors: Hamoda Ahmed , Emara Mohamed , Abadel Aref A. , Sennah K. 
Published: March 2024

AbstractThis research studies shear strengthening performance for Normal Concrete (NC) beams employing Engineered Cementitious Composite (ECC) reinforced with Galvanized Welded Wire Mesh (GWWM) in conjunction with/without a prestressing system. Six full‐scale Reinforced Concrete (RC) beams were experimented under static monotonic loading at critical shear span zone up to collapse. The investigated factors were: the type and technique of strengthening, materials used for strengthening, and size and configuration of shear reinforcement. Two techniques were introduced: ECC layer reinforced with GWWM and pretensioned steel bars recovered by ECC with one GWWM. GWWM with and without pretensioned steel bars were delivered as shear reinforcement for strengthening. Vertical and inclined steel bars were the two configurations selected for the prestressing technique for suppressing shear stress. The study was discussed through the experimented beams' crack load and pattern, collapse mode, elastic stiffness, absorbed energy, initial cracking load, and ultimate load, along with the corresponding defection. Experimental results showed that both exploited techniques could govern crack patterns, enhance the failure mode, and upgrade ultimate loading capacity up to 52%. Finite element models were built up, simulating those strengthened with an ECC covering layer augmented with GWWM extracting a model with an error of about 3%.
Modified plastic damage model for steel fiber reinforced concrete
Authors: Tran Tung T. , Pham Thong M. , Tran Duong T. , Ha Ngoc San , Hao Hong 
Published: March 2024

AbstractSteel fiber reinforced concrete (SFRC) structures have been widely adopted and attracted great research attention due to their excellent performance in resisting tension and flexure bending. However, the existing analytical and numerical analyses of SFRC structures rely mainly on the experimental data of material tests, thereby being suitable for a case‐by‐case basis. This is due to the lack of a general and reliable constitutive material model for SFRC, which analytically considers the fiber‐dependent parameters such as fiber geometry, fiber stiffness, and interface properties of fibers and concrete matrix. This study presents an approach to modify the concrete plastic damage model to represent the SFRC material constitutive relations for simulating the structural behavior of SFRC. In this approach, the general procedure to integrate the bridging effect of fibers through the pull‐out mechanism into the constitutive relation of SFRC was proposed. The comparison between the numerical and experimental results was conducted to verify the reliability of the proposed model. The results demonstrated the proposed model could well represent the material performance of SFRC and the numerical simulations could capture reasonably the effect of the volume fraction, geometry, and properties of fibers on the structural response of SFRC.
Dynamic compressive behaviors of polyethylene terephthalate fiber reinforced recycled aggregate concrete
Authors: Yan Zhi‐Wei , Bai Yu‐Lei , Chen Wensu 
Published: March 2024

AbstractPolyethylene terephthalate (PET) fibers are green, environmentally friendly materials. They mainly come from recycled plastic bottles and other products. The addition of PET fibers to recycled aggregate concrete (RAC) has the potential to reduce concrete damage and increase specimen toughness. In this study, the influences of recycled coarse aggregate (RCA) replacement ratio and fiber volume ratio on the impact response of PET fiber reinforced RAC at various strain rates were experimentally investigated. It was found that the compressive strength, critical strain, and toughness grew with the increasing strain rate, followed by the aggravation of the concrete damage. Owing to the strain rate effect, the failure mode of concrete specimen at a high strain rate was different from that under a quasi‐static loading. This led to the reduction of differences in the dynamic compressive strength between the natural and recycled aggregate concrete at a high strain rate. Although the replacement of natural coarse aggregates with RCAs resulted in the decrease in the dynamic compressive strength, it increased the critical strain of the specimen. To reduce the brittleness of concrete materials, flexible fibers, PET fibers were added into the concrete matrix. It was found that the addition of PET fibers increased the critical strain and significantly reduced concrete damage. The empirical equations were proposed to describe the rate‐dependent dynamic compressive strength, critical strain, and toughness based on experimental data.
Effect of fiber type, size, and utilization rate on mechanical and thermal properties of lightweight concrete facade panels
Authors: Beytekin Hatice Elif , Kaya Yahya , Mardani Ali , Sezer Filiz Şenkal 
Published: March 2024

AbstractIt was understood that various studies were carried out on the strength, permeability, durability, increasing the thermal performance of lightweight concrete facade panels, and sustainable and energy‐efficient concepts. It was observed that fiber was added to the mixture to improve the properties in question. However, it was determined that contradictory results were obtained due to the large number of active parameters and whether the fiber was distributed homogeneously in the matrix. In this study, the effects of fiber type, length and usage rate on the strength, energy absorption capacity, elasticity modulus, water absorption, and thermal performance of lightweight concrete mixtures were investigated. For this purpose, three different types of fibers of different lengths: polypropylene (3, 6, and 12 mm), glass (13 and 25 mm) and polyamide (6 and 12 mm) were used at 0%, 0.25%, 0.50%, and 0.75% of the total volume. It was determined that the mixture containing 0.25% polypropylene fiber with a length of 3 mm exhibited the best performance in terms of both mechanical and thermal properties. In terms of these features, it was understood that the mixtures with 12 mm polypropylene with a usage rate of 0.75% and 6 mm polyamide fibers with a usage rate of 0.50% had the weakest performance.
International business entry modes and consumer ethnocentrism: A multi country perspective
Authors: Bose Tarun Kanti , Chew Tze Cheng , Purohit Sonal , Moser Roger 
Published: March 2024

AbstractThis study aims to assess the impact of changes in international business modes on consumer ethnocentrism. The study utilizes a quantitative research approach and is theoretically grounded in the resource‐based view. Data was collected from Bangladesh, China, India, and Malaysia using the consumer ethnocentrism tendencies scale (CETSCALE), and analyzed using quantitative methods. The results indicate that changes in international entry modes have an impact on the degree of consumer ethnocentrism. Across all countries studied, the highest level of consumer ethnocentrism was found for imported products, and this degree and intensity decreased when the entry modes changed from importing to joint venturing and FDI. This study contributes to the literature on both international business and consumer behavior by integrating the two fields, resulting in a robust theoretical contribution. The findings also suggest that the appropriate IB mode can act as a resource.
Seroprevalence and renal carriage of pathogenic Leptospira in livestock in Cotonou, Benin
Authors: Her Rebecca , Crespin Laurent , Etougbétché Jonas , Groud Karine , Gnolonfoun Mathias , Chapron Audrey , Evenamia Camille , Houéménou Gualbert , Lurier Thibaut , Cappelle Julien , Dobigny Gauthier , Ayral Florence 
Published: March 2024

AbstractBackgroundLeptospirosis is a zoonotic disease. It is particularly prevalent in tropical countries and has major consequences for human and animal health. In Benin, the disease's epidemiology remains poorly understood, especially in livestock, for which data are lacking.ObjectivesTo characterise Leptospira seroprevalence and locally circulating serogroups in livestock from Cotonou and to estimate the prevalence of Leptospira renal carriage in cattle.MethodsWe conducted a cross‐sectional study in February 2020 during which livestock were sampled at an abattoir and in an impoverished city district. We analysed blood samples from 279 livestock animals (i.e. cattle, sheep, goats and pigs) using the microscopic agglutination test. Additionally, samples of renal tissue from 100 cattle underwent 16s rRNA (rrs) real‐time PCR analysis.ResultsFor the 131 cattle, 85 sheep, and 50 goats tested, seroprevalence was 18% (95% confidence interval [CI] [12%, 26%]), 9% (95% CI [4%, 17%] and 2% (95% CI [0%, 9%]), respectively, and most of the seropositive animals were associated with 1:100 titres. All 13 pigs were seronegative. Leptospira DNA was found in the renal tissue of 10% (95% CI [5%, 18%]) of the cattle tested (n = 100). Leptospira borgpetersenii was the main species present (n = 7), but Leptospira interrogans (n = 2) and Leptospira kirschneri (n = 1) were also detected. Various serogroups (Canicola, Grippotyphosa, Sejroe, Icterohaemorrhagiae, Pomona, Pyrogenes, Australis and Autumnalis) were detected using microscopic agglutination test without a clear predominance of any of them.ConclusionsThese results suggest that abattoir workers and people living in close contact with livestock in poor urban areas are exposed to the risk of Leptospira infection.