bluuebunny/crossref_metadata_2025_split huggingface dataset:
Exploring the Impact of Active Site Structure on the Conversion of Methane to Methanol in Cu‐Exchanged Zeolites
Authors: Göltl Florian , Bhandari Saurabh , Lebrón‐Rodríguez Edgard A. , Gold Jake I. , Hutton Daniel J. , Zones Stacey I. , Hermans Ive , Dumesic James A. , Mavrikakis Manos 
Published: April 2024

AbstractIn the past, Cu‐oxo or ‐hydroxy clusters hosted in zeolites have been suggested to enable the selective conversion of methane to methanol, but the impact of the active site's stoichiometry and structure on methanol production is still poorly understood. Herein, we apply theoretical modeling in conjunction with experiments to study the impact of these two factors on partial methane oxidation in the Cu‐exchanged zeolite SSZ‐13. Phase diagrams developed from first‐principles suggest that Cu‐hydroxy or Cu‐oxo dimers are stabilized when O2 or N2O are used to activate the catalyst, respectively. We confirm these predictions experimentally and determine that in a stepwise conversion process, Cu‐oxo dimers can convert twice as much methane to methanol compared to Cu‐hydroxyl dimers. Our theoretical models rationalize how Cu‐di‐oxo dimers can convert up to two methane molecules to methanol, while Cu‐di‐hydroxyl dimers can convert only one methane molecule to methanol per catalytic cycle. These findings imply that in Cu clusters, at least one oxo group or two hydroxyl groups are needed to convert one methane molecule to methanol per cycle. This simple structure–activity relationship allows to intuitively understand the potential of small oxygenated or hydroxylated transition metal clusters to convert methane to methanol.
CYP3A Mediates an Unusual C(sp2)−C(sp3) Bond Cleavage via Ipso‐Addition of Oxygen in Drug Metabolism
Authors: Qin Xuan , Wang Yong , Ye Qiuji , Hakenjos John M. , Wang Jin , Teng Mingxing , Guo Lei , Tan Zhi , Young Damian W. , MacKenzie Kevin R. , Li Feng 
Published: April 2024

AbstractMammalian cytochrome P450 drug‐metabolizing enzymes rarely cleave carbon–carbon (C−C) bonds and the mechanisms of such cleavages are largely unknown. We identified two unusual cleavages of non‐polar, unstrained C(sp2)−C(sp3) bonds in the FDA‐approved tyrosine kinase inhibitor pexidartinib that are mediated by CYP3A4/5, the major human phase I drug metabolizing enzymes. Using a synthetic ketone, we rule out the Baeyer–Villiger oxidation mechanism that is commonly invoked to address P450‐mediated C−C bond cleavages. Our studies in 18O2 and H218O enriched systems reveal two unusual distinct mechanisms of C−C bond cleavage: one bond is cleaved by CYP3A‐mediated ipso‐addition of oxygen to a C(sp2) site of N‐protected pyridin‐2‐amines, and the other occurs by a pseudo‐retro‐aldol reaction after hydroxylation of a C(sp3) site. This is the first report of CYP3A‐mediated C−C bond cleavage in drug metabolism via ipso‐addition of oxygen mediated mechanism. CYP3A‐mediated ipso‐addition is also implicated in the regioselective C−C cleavages of several pexidartinib analogs. The regiospecificity of CYP3A‐catalyzed oxygen ipso‐addition under environmentally friendly conditions may be attractive and inspire biomimetic or P450‐engineering methods to address the challenging task of C−C bond cleavages.
L‐kynurenine and quinolinic acid inhibited markers of cell survival in B16 F10 melanoma cells in vitro
Authors: Basson Charlise , Serem June Cheptoo , Bipath Priyesh , Hlophe Yvette Nkondo 
Published: April 2024

AbstractMelanoma is an aggressive malignancy and remains a major cause of skin cancer mortality, highlighting the need for new treatment strategies. Recent findings revealed that L‐kynurenine and quinolinic acid induce cytotoxicity and morphological changes in B16 F10 melanoma cells in vitro. This paper highlights the effects of
L‐kynurenine and quinolinic acid at previously determined half‐maximal inhibitory concentrations on cell cycle progression, cell death and extracellular signal‐regulated protein kinase inhibition. Melanoma, B16 F10 and murine macrophages, RAW 264.7 cells were used in this study, as both cell lines express all the enzymes associated with the kynurenine pathway. Post exposure to the compounds at half‐maximal inhibitory concentrations, transmission electron microscopy was used to assess intracellular morphological changes. Flow cytometry was used to analyse cell cycle progression and quantify apoptosis via the dual staining of Annexin V and propidium iodide and cell survival via extracellular signal‐regulated protein kinase.
L‐kynurenine and quinolinic acid at half‐maximal inhibitory concentrations induced intracellular morphological changes representative of cell death. Flow cytometry revealed alterations in cell cycle distribution, increased apoptosis and significantly inhibition of cell survival.
L‐kynurenine and quinolinic acid are exogenous kynurenine compounds which inhibited cell survival through extracellular signal‐regulated protein kinase inhibition, induced cell cycle alterations and induced apoptosis in B16 F10 melanoma cells.
Potent Anthelmintic Activity of Chalcones Synthesized by an Effective Green Approach
Authors: Turani Ornella , Castro M. Julia , Vazzana Juliana , Mendioroz Pamela , Volpe María A. , Gerbino Darío C. , Bouzat Cecilia 
Published: April 2024

AbstractThere is currently an urgent need for new anthelmintic agents due to increasing resistance to the limited available drugs. The chalcone scaffold is a privileged structure for developing new drugs and has been shown to exhibit potential antiparasitic properties. We synthesized a series of chalcones via Claisen‐Schmidt condensation, introducing a novel recoverable catalyst derived from biochar obtained from the pyrolysis of tree pruning waste. Employing microwave irradiation and a green solvent, this approach demonstrated significantly reduced reaction times and excellent compatibility with various functional groups. The result was the generation of a library of functionalized chalcones, exhibiting exclusive (E)‐selectivity and high to excellent yields. The chalcone derivatives were evaluated on the free‐living nematode Caenorhabditis elegans. The chalcone scaffold, along with two derivatives incorporating a methoxy substituent in either ring, caused a concentration‐dependent decrease of worm motility, revealing potent anthelmintic activity and spastic paralysis not mediated by the nematode levamisole‐sensitive nicotinic receptor. The combination of both methoxy groups in the chalcone scaffold resulted in a less potent compound causing worm hypermotility at the short term, indicating a distinct molecular mechanism. Through the identification of promising drug candidates, this work addresses the demand for new anthelmintic drugs while promoting sustainable chemistry.
Suppressing the background of LC–ESI–MS analysis of permethylated glycans using the active background ion reduction device
Authors: Fowowe Mojibola , Yu Aiying , Wang Junyao , Onigbinde Sherifdeen , Nwaiwu Judith , Bennett Andrew I. , Mechref Yehia 
Published: April 2024

AbstractMass spectrometry (MS) has revolutionized analytical chemistry, enabling precise identification and quantification of chemical species, which is pivotal for biomarker discovery and understanding complex biological systems. Despite its versatility, the presence of background ions in MS analysis hinders the sensitive detection of low‐abundance analytes. Therefore, studies aimed at lowering background ion levels have become increasingly important. Here, we utilized the commercially available Active Background Ion Reduction Device (ABIRD) to suppress background ions and assess its effect on the liquid chromatography–electrospray ionization (LC–ESI)–MS analyses of N‐glycans on the Q Exactive HF mass spectrometer. We also investigated the effect of different solvent vapors in the ESI source on N‐glycan analysis by MS. ABIRD generally had no effect on high‐mannose and neutral structures but reduced the intensity of some structures that contained sialic acid, fucose, or both when methanol vapor filled the ESI source. Based on our findings on the highest number of identified N‐glycans from human serum, methanol vapor in the ion source compartment may enhance N‐glycan LC–ESI–MS analyses by improving the desolvation of droplets formed during the ESI process due to its high volatility. This protocol may be further validated and extended to advanced bottom‐up proteomic/glycoproteomic studies for the analysis of peptide/glycopeptide ions by MS.
Pro+: Automated protrusion and critical shear stress estimates from 3D point clouds of gravel beds
Authors: Yager Elowyn M. , Shim Jaeho , Hodge Rebecca , Monsalve Angel , Tonina Daniele , Johnson Joel P. L. , Telfer Luke 
Published: April 2024

AbstractThe dimensionless critical shear stress (τ*c) needed for the onset of sediment motion is important for a range of studies from river restoration projects to landscape evolution calculations. Many studies simply assume a τ*c value within the large range of scatter observed in gravel‐bedded rivers because direct field estimates are difficult to obtain. Informed choices of reach‐scale τ*c values could instead be obtained from force balance calculations that include particle‐scale bed structure and flow conditions. Particle‐scale bed structure is also difficult to measure, precluding wide adoption of such force‐balance τ*c values. Recent studies have demonstrated that bed grain size distributions (GSD) can be determined from detailed point clouds (e.g. using G3Point open‐source software). We build on these point cloud methods to introduce Pro+, software that estimates particle‐scale protrusion distributions and τ*c for each grain size and for the entire bed using a force‐balance model. We validated G3Point and Pro+ using two laboratory flume experiments with different grain size distributions and bed topographies. Commonly used definitions of protrusion may not produce representative τ*c distributions, and Pro+ includes new protrusion definitions to better include flow and bed structure influences on particle mobility. The combined G3Point/Pro+ provided accurate grain size, protrusion and τ*c distributions with simple GSD calibration. The largest source of error in protrusion and τ*c distributions were from incorrect grain boundaries and grain locations in G3Point, and calibration of grain software beyond comparing GSD is likely needed. Pro+ can be coupled with grain identifying software and relatively easily obtainable data to provide informed estimates of τ*c. These could replace arbitrary choices of τ*c and potentially improve channel stability and sediment transport estimates.
Tree peony seed oil alleviates hyperlipidemia and hyperglycemia by modulating gut microbiota and metabolites in high‐fat diet mice
Authors: Liang Ziyue , He Yinglong , Wei Dongfeng , Fu Peixin , Li Yuying , Wang Hao , Yang Di , Hou Xiaogai 
Published: April 2024

AbstractWith the changes of people's lifestyle, hyperlipidemia and hyperglycemia which were induced from a diet high in both fat and sugar have become serious health concerns. Tree peony seed oil (PSO) is a novel kind of edible oil that shows great potential in the food industry because of its high constituent of unsaturated fatty acids. Based 16S rRNA and gut untargeted metabolomics, this study elucidated that the mechanism of PSO regulating blood glucose (Glu) and lipids. The impact of PSO on gut microbiota balance and gut metabolites of mice with a high‐fat diet (HFD) was evaluated. The findings indicated that PSO decreased HFD mice's body weight and fat accumulation, ameliorating the levels of blood lipid, reduced liver fat vacuole levels. What's more PSO modulated the proportion of gut microbiota in HFD mice and enhanced the abundance of probiotics. Furthermore, untargeted metabolomic analysis revealed that PSO not only impacted the generation of short‐chain fatty acids (SCFAs) by gut microorganism and altered metabolic pathway but exerted influence on secondary bile acids (BA), amino acid metabolism, and various other metabolites. These results suggested that PSO has the potential function for mitigating HFD‐induced hyperlipidemia and hyperglycemia by regulating gut microbiota and host metabolism.
Modelling Systems with Intangible Boundaries Using SysML: An Automotive Feature Modelling Guideline
Authors: Digraskar Ruturaj , Singh Dhirendra , Raje Shruti , Mittal Mudit 
Published: April 2024

AbstractA lot has been published around the methodology of using SysML (Systems Modeling Language) for modelling tangible systems, i.e., systems with fixed and real boundaries. However, automotive features when observed as systems become both challenging and interesting. These features are culminations of behaviors synchronizing from various components, where none of them is fully responsible for the feature, nor can be termed as a “system” representing the feature. Through modelling several features and analyzing on what is the best way to represent such an “Intangible” system, a pattern has emerged. In this paper, we will be sharing a process involving application of SysML and a tailored framework for modelling such systems. This application can be used to accurately represent “Features” as “Systems,” defining boundaries using structure, behavior, and requirements. Using this process for modelling such systems, i.e., systems with intangible boundaries, we can completely define the scope and boundary of “system” for various analysis to develop and define such “system,” but also improve the completeness & correctness of the model and reduce the overall process time by elimination multiple iteration due to issue faced during verification and validation stages.
Systemic Model of Leadership Approaches
Authors: Myla Srimannarayana , Marshall Karel , Mabuza BCM , Scalco Aleksandra , Sutherland Jack 
Published: April 2024

AbstractThis paper introduces a Technical Leadership Model designed to address the challenges posed by diverse businesses, the global context, and the technological landscape. The model's development involved a synthesis of cognitive studies on organizational leadership and a literature analysis of INCOSE SE Vision 2035 [Vision 35]. This vision offers insights into present and future Systems Engineering challenges, global megatrends, technological shifts, and a roadmap for enhancing competencies, skills, theoretical foundations, and collaborative opportunities within the systems engineering community.The research was spearheaded by a team within Cohort 7 of the INCOSE Technical Leadership Institute (TLI), aided by coaches and other cohort members. Through structured interviews, surveys, and workshops, these cohort members engaged senior organizational leaders to gather their viewpoints. These insights were amalgamated with the pre‐existing Leadership Model initially developed by a distinguished TLI coach with support from Cohort 1 in 2015 [Godfrey 2015]. The outcomes and conclusions are derived from a diverse range of collaborative methodologies utilized to forge this shared model. Moreover, input from senior leaders across various industries, organizations, and INCOSE TLI members, projecting future leadership trends, enriched the model. This body of work yields an enhanced, collective leadership model encompassing behavioral attributes such as vision, emotional intelligence, communication, effective team management, and an additional layer of dynamism.
Neural Network‐based Method to Compute Recommended Cruise Level and Optimal Climb Location
Authors: Kushwaha Dinesh Kumar , Volner Mark , Young Shih‐Yih (Ryan) , Kottackal Sebin K 
Published: April 2024

AbstractSystem engineering towards utilizing machine learning solutions in the aviation domain is a fast‐progressing discipline. This paper tries to bring out the system engineering and implementation aspects of ML solution as an improvement in a sub‐system of an existing aviation system. The flight management systems (FMSs) compute the recommended cruise level (RCL) considering the aircraft's gross weight, its speed schedule, and the forecast wind. The RCL increases with distance in the no wind conditions as the fuel get consumed, reducing the gross aircraft weight. The RCL profile may have frequent climbs and descents in the presence of winds, which is not desired for flight operations.The document proposes a neural network‐based method for computing an operationally acceptable cruise profile considering the wind and temperature weather forecast. The method recommends step climbs and step descents (optimal level and optimal step location) in such a way that they are separated by a large enough cruise phase. From system engineering point of view two guiding documents for such an implementation to look forward are “EASA Concept Paper: First usable guidance for Level 1 machine learning applications” [12] and “Process Standard for Development and Certification/Approval of Aeronautical Safety‐Related Products Implementing AI” [13].Two neural networks have been created to estimate wind compensated ECON cruise speeds and required time‐fuel to cover the next 500NM distance. The RCL profiles are generated for various test wind scenarios for Airbus A220 aircraft. It has been recorded the proposed neural network‐based method is better at recommending a cruise altitude and it is 9X faster than the existing method to calculate the RCL and optimal climb location. The neural network‐based design also helped in reducing the memory footprint by more than 100 times as there is no requirement of storing the performance database files required by the existing system. Only the parameters of the trained neural networks are required to be stored. Most importantly, the RCL computed by the proposed neural network‐based method yields a smaller operational cost than that determined by the existing method. The proposed method is designed to replace the existing traditional subsystem to give an overall improved performance while the functionalities of other subsystems remain unaffected.
FPGA Implementation of Adaptive PID Control for Quadcopter Position Tracking
Authors: Bhat N. Harish , Chokkadi Shreesha , Shenoy B. Satish 
Published: April 2024

AbstractPID control is widely used for designing controllers in production plants and automotive and robotic applications. Although it suits linear systems, with minor modifications, it can also be applied to nonlinear plants. As a simple control approach, it can be easily realized conceptually, but there is a large cost involved in the production of the working controller. A digital PID controller based on a fixed point representation of the operands can be considered for approximate realization. The field programmable gate array (FPGA), with its concurrent architecture, is an ideal way of producing programmable, cost‐, power‐, and speed‐optimized controllers with a compromised controller area compared to application‐specific approaches. In this research, the PID controller for quadcopters is initially tested for performance using MATLAB/Simulink based on continuous/analog domain operations. Then, FPGA‐based architecture mapping is performed using HDL Coder, with fixed‐point‐based operands produced using the fixed‐point conversion toolbox. With satisfactory performance obtained with system generator‐based cosimulation of the controller, Vivado IDE is used to implement the controller on a Zynq Ultrascale+ based FPGA device. The realized cost‐efficient controller is analysed for logical resources, computation power and controller frequency and inferred to be optimal with reference to all these indices. By adapting the thrust, which is the control input for the translational motion of the quadcopter, robustness against coupled motion is ensured, with higher simultaneous tracking speeds.
High prevalence of “non‐pathogenic” POLE mutation with poor prognosis in a cohort of endometrial cancer from South India
Authors: Kuriakose Santhosh , Dhanasooraj Dhananjayan , Shiny P. M. , Shammy S. , Sona V. P. , Manjula Anupama A. , Ramachandran Amrutha , Vijaykumar Bindu , Susan Nayana , Dinesan M. , Sankar Uma V. , Ramachandran Kavitha , Sreedharan P. S. 
Published: April 2024

AbstractObjectiveThe Cancer Genome Atlas (TCGA) project identified favorable prognosis regarding the ultra‐mutated endometrial cancer (EC) subtype linked to polymerase epsilon gene (POLE) mutations. This study investigated POLE mutations in EC of Indian patients.MethodsThis retrospective analytical study was conducted between January 2016 and January 2023 at the Government Medical College, Kozhikode, and the MVR Cancer Center, Kozhikode, Kerala. Sanger sequencing of POLE gene exons 9 and 13 in 151 EC patients was carried out to analyze the relationship between mutations and epidemiological factors, clinicopathologic features, and treatment outcomes.ResultsAmong 151 cases enrolled, 39 were unique POLE‐mutated cases. Significant associations were high‐grade tumors, myometrial invasion >50%, and Lymph‐vascular space invasion (LVSI). The median follow‐up was 40 months (95% confidence interval [CI], 34–46). A lower mean disease‐specific survival (DSS) of 51.7 months (95% CI, 43.7–59.6) was noted in the POLE‐mutated group compared with 72.11 months (95% CI, 67.60–76.62) for the POLE wild‐type. A statistically significant hazard ratio (HR) of 2.683 for DSS in the POLE‐mutated group was noted. In advanced stages (FIGO stages II–IV), a nine‐fold HR for DSS and overall survival (OS) compared with POLE wild‐type was identified. After controlling for treatment effects using Cox proportional HR, advanced‐stage POLE‐mutated tumors had a significantly higher HR of 8.67 for DSS compared with POLE‐wild‐type tumors of the same stage.ConclusionThis study identified a unique set of POLE mutations in Indian EC patients associated with poor prognosis, which were particularly pronounced in advanced stages. Advanced stage of presentation, type of POLE mutations, and possibly ethnicity are predictors of adverse outcomes in POLE‐mutated EC. The present study highlights ethnicity as a determinant of phenotypic expression of genetic change.