bluuebunny/crossref_metadata_2025_split huggingface dataset:
Correspondence on “Synergy and Antagonism between Allosteric and Active‐Site Inhibitors of Abl Tyrosine Kinase”**
Authors: Jahnke Wolfgang , Paladini Johannes , Habazettl Judith M. , Wiget Andrea , Loo Alice , Cowan Jacob Sandra W. , Grzesiek Stephan , Manley Paul W. 
Published: October 2022

AbstractSoellner published on the interplay between allosteric and adenosine triphosphate (ATP)‐competitive inhibitors of ABL kinase, showing that the latter preferably binds to different conformational states of ABL compared to allosteric agents that specifically target the ABL myristate pocket (STAMP) and deducing that asciminib cannot bind to ABL simultaneously with ATP‐competitive drugs. These results are to some extent in line with ours, although our analyses of dose–response matrices from combinations of asciminib with imatinib, nilotinib or dasatinib, show neither synergy nor antagonism, but suggest additive antiproliferative effects on BCR‐ABL‐dependent KCL22 cells. Furthermore, our X‐ray crystallographic, solution nuclear magnetic resonance (NMR), and isothermal titration calorimetry studies show that asciminib can bind ABL concomitantly with type‐1 or ‐2 ATP‐competitive inhibitors to form ternary complexes. Concomitant binding of asciminib with imatinib, nilotinib, or dasatinib might translate to benefit some chronic myeloid leukaemia patients.
Design of a Protein with Improved Thermal Stability by an Evolution‐Based Generative Model
Authors: Tian Pengfei , Lemaire Adrien , Sénéchal Fabien , Habrylo Olivier , Antonietti Viviane , Sonnet Pascal , Lefebvre Valérie , Isa Marin Frederikke , Best Robert B. , Pelloux Jérôme , Mercadante Davide 
Published: October 2022

AbstractEfficient design of functional proteins with higher thermal stability remains challenging especially for highly diverse sequence variants. Considering the evolutionary pressure on protein folds, sequence design optimizing evolutionary fitness could help designing folds with higher stability. Using a generative evolution fitness model trained to capture variation patterns in natural sequences, we designed artificial sequences of a proteinaceous inhibitor of pectin methylesterase enzymes. These inhibitors have considerable industrial interest to avoid phase separation in fruit juice manufacturing or reduce methanol in distillates, averting chromatographic passages triggering unwanted aroma loss. Six out of seven designs with up to 30 % divergence to other inhibitor sequences are functional and two have improved thermal stability. This method can improve protein stability expanding functional protein sequence space, with traits valuable for industrial applications and scientific research.
Photoinduced Promiscuity of Cyclohexanone Monooxygenase for the Enantioselective Synthesis of α‐Fluoroketones
Authors: Peng Yongzhen , Wang Zhiguo , Chen Yang , Xu Weihua , Hu Yujing , Chen Zhichun , Xu Jian , Wu Qi 
Published: October 2022

AbstractThe development of mild, efficient, and enantioselective methods for preparing chiral fluorinated compounds has been a long‐standing challenge. Herein, we report a promiscuous cyclohexanone monooxygenase (CHMO) for the photoinduced synthesis of chiral α‐fluoroketones via enantioselective reductive dehalogenation of α,α‐halofluoroketones. Wild‐type CHMO from Acinetobacter sp. possesses this promiscuous ability innately; however, the yield and stereoselectivity are low. A structure‐guided rational design of CHMO improved the yield and stereoselectivity remarkably. Mechanistic studies and molecular simulations demonstrated that this photoinduced CHMO catalyzes the reductive dehalogenation via a novel electron transfer (ET)/proton transfer (PT) mechanism, distinct from that of previously reported reductases with similar promiscuity. This methodology was expanded to various substrates, and desirable chiral α‐fluoroketones were obtained in high yields (up to 99 %) and e.r. values (up to 99:1).
Bioactive Ion‐Based Switchable Supercapacitors
Authors: Li Panlong , Bräuniger Yannik , Kunigkeit Jonas , Zhou Hanfeng , Ortega Vega Maria Rita , Zhang En , Grothe Julia , Brunner Eike , Kaskel Stefan 
Published: October 2022

AbstractSwitchable supercapacitors (SCs) enable a reversible electrically‐driven uptake/release of bioactive ions by polarizing porous carbon electrodes. Herein we demonstrate the first example of a bioactive ion‐based switchable supercapacitor. Based on choline chloride and porous carbons we unravel the mechanism of physisorption vs. electrosorption by nuclear magnetic resonance, Raman, and impedance spectroscopy. Weak physisorption facilitates electrically‐driven electrolyte depletion enabling the controllable uptake/release of electrolyte ions. A new 4‐terminal device is proposed, with a main capacitor and a detective capacitor for monitoring bioactive ion adsorption in situ. Ion‐concentration control in printed choline‐based switchable SCs realizes switching down to 8.3 % residual capacitance. The exploration of adsorption mechanisms in printable microdevices will open an avenue of manipulating bioactive ions for the application of drug delivery, neuromodulation, or neuromorphic devices.
Native Top‐Down Mass Spectrometry Reveals a Role for Interfacial Glycans on Therapeutic Cytokine and Hormone Assemblies
Authors: Wu Di , Robinson Carol V. 
Published: October 2022

AbstractOligomerization and glycosylation modulate therapeutic glycoprotein stability and efficacy. The interplay between these two critical attributes on therapeutic glycoproteins, is however often hard to define. Here, we present a native top‐down mass spectrometry (MS) approach to assess the glycosylation status of therapeutic cytokine and hormone assemblies and relate interfacial glycan occupancy to complex stability. We found that interfacial O‐glycan stabilizes tumor necrosis factor‐α trimer. On the contrary, interferon‐β1a dimerization is independent of glycosylation. Moreover, we discovered a unique distribution of N‐glycans on the follicle‐stimulating hormone α subunit. We found that the interfacial N‐glycan, at Asn52 of the α subunit, interacts extensively with the β subunit to regulate the dimer assembly. Overall, we have exemplified a method to link glycosylation with assembly status, for cytokines and hormones, critical for informing optimal stability and bioavailability.
Orthogonally Integrating Programmable Structural Color and Photo‐Rewritable Fluorescence in Hydrazone Photoswitch‐bonded Cholesteric Liquid Crystalline Network
Authors: Lan Ruochen , Bao Jinying , Li Zhaozhong , Wang Zizheng , Song Chenjie , Shen Chen , Huang Rui , Sun Jian , Wang Qian , Zhang Lanying , Yang Huai 
Published: October 2022

AbstractDesign and fabrication of advanced security label showing superior performance in data encryption has attracted tremendous scientific interests. Especially, multifunctional optical labels capable of storing distinct information in different modes are highly demanded. Here, a fluorescent cholesteric liquid crystalline network (CLCN) film with programmable visible patterns and photo‐rewritable fluorescent patterns was designed and prepared. The visible patterns were fixed by helical network and the colors of visible patterns were tunable by changing relative humidity (RH). The fluorescent patterns originated from dynamic isomerization of fluorescent hydrazones, exhibiting highly thermal stability and switching‐ability controlled by light. The orthogonal construction of visible and fluorescent pattern enabled the novel CLCN to encrypt distinct information in reflective mode and in emissive mode, indicating its potential in anti‐counterfeiting and information encryptions.
Coordination Switch Drives Selective C−S Bond Formation by the Non‐Heme Sulfoxide Synthases**
Authors: Wu Peng , Gu Yang , Liao Langxing , Wu Yanfei , Jin Jiaoyu , Wang Zhanfeng , Zhou Jiahai , Shaik Sason , Wang Binju 
Published: October 2022

AbstractThe non‐heme iron ergothioneine synthase (EgtB) is a sulfoxide synthase that catalyzes oxidative C−S bond formation in the synthesis of ergothioneine, which plays roles against oxidative stress in cells. Despite extensive experimental and computational studies of the catalytic mechanisms of EgtB, the root causes for the selective C−S bond formation remain elusive. Using quantum mechanics/molecular mechanics (QM/MM) calculations, we show herein that a coordination switch of the sulfoxide intermediate is involved in the catalysis of the non‐heme iron EgtB. This coordination switch from the S to the O atom is driven by the S/π electrostatic interactions, which efficiently promotes the observed stereoselective C−S bond formation while bypassing cysteine dioxygenation. The present mechanism is in agreement with all available experimental data, including regioselectivity, stereoselectivity and KIE results. This match underscores the critical role of coordination switching in the catalysis of non‐heme enzymes.
The Essential Role of Water Molecules in the Reaction Mechanism of Protein O‐Fucosyltransferase 2
Authors: Sanz‐Martínez Ignacio , García‐García Ana , Tejero Tomás , Hurtado‐Guerrero Ramón , Merino Pedro 
Published: October 2022

AbstractProtein O‐fucosyltransferase 2 (PoFUT2) is an inverting glycosyltransferase (GT) that fucosylates thrombospondin repeats (TSRs) from group 1 and 2. PoFUT2 recognizes a large and diverse number of TSRs through a dynamic network of water‐mediated interactions. By X‐ray structural studies of C. elegans PoFUT2 complexed to a TSR of group 2, we demonstrate that this GT recognizes similarly the 3D structure of TSRs from both groups 1 and 2. Its active site is highly exposed to the solvent, suggesting that water molecules might also play an essential role in the fucosylation mechanism. We applied QM/MM methods using human PoFUT2 as a model, and found that HsPoFUT2 follows a classical SN2 reaction mechanism in which water molecules contribute to a great extent in facilitating the release of the leaving pyrophosphate unit, causing the H transfer from the acceptor nucleophile (Thr/Ser) to the catalytic base, which is the last event in the reaction. This demonstrates the importance of water molecules not only in recognition of the ligands but also in catalysis.
A Flexible Hydrogen‐Bonded Organic Framework Constructed from a Tetrabenzaldehyde with a Carbazole N−H Binding Site for the Highly Selective Recognition and Separation of Acetone
Authors: Chen Liangji , Yuan Zhen , Zhang Hao , Ye Yingxiang , Yang Yisi , Xiang Fahui , Cai Kaicong , Xiang Shengchang , Chen Banglin , Zhang Zhangjing 
Published: October 2022

AbstractRational design of hydrogen‐bonded organic frameworks (HOFs) with multiple functionalities is highly sought after but challenging. Herein, we report a multifunctional HOF (HOF‐FJU‐2) built from 4,4′,4′′,4′′′‐(9H‐carbazole‐1,3,6,8‐tetrayl)tetrabenzaldehyde molecule with tetrabenzaldeyde for their H bonding interactions and carbazole N−H site for its specific recognition of small molecules. The Lewis acid N−H sites allowHOF‐FJU‐2facilely separate acetone from its mixture with another solvent like methanol with smaller pKavalue. The donor (D)‐π‐acceptor (A) aromatic nature of the organic building molecule endows this HOF with solvent dependent luminescent/chromic properties, so the column acetone/methanol separation onHOF‐FJU‐2can be readily visualized.
Alkyl Formates as Transfer Hydroalkylation Reagents and Their Use in the Catalytic Conversion of Imines to Alkylamines**
Authors: Crochet Etienne , Anthore‐Dalion Lucile , Cantat Thibault 
Published: October 2022

AbstractEasily accessible via a simple esterification of alcohols with formic acid, alkyl formates are used as a novel class of transfer hydroalkylation reagents, CO2 acting as a traceless linker. As a proof‐of‐concept, their reactivity in the transfer hydroalkylation of imines is investigated, using a ruthenium‐based catalyst and LiI as promoter to cleave the C−O σ‐bond of the formate scaffold. Providing tertiary amines, the reaction displays a divergent regioselectivity compared to previously reported transfer hydroalkylation strategies.
Correlation between Electrolyte Chemistry and Solid Electrolyte Interphase for Reversible Ca Metal Anodes
Authors: Hou Zhen , Zhou Rui , Yao Yunduo , Min Zhiwen , Lu Ziheng , Zhu Ye , Tarascon Jean‐Marie , Zhang Biao 
Published: October 2022

AbstractThe development of rechargeable Ca metal batteries (RCMBs) is hindered by the Ca2+ passivating solid electrolyte interphases (SEIs). The cation solvation structure dictated by electrolyte chemistry plays a critical role in the SEIs properties. While a relatively weak cation‐solvent binding is preferred in Li metal anodes to promote anion‐derived SEIs, we demonstrate an enhanced Ca deposition/stripping reversibility under a strong cation‐solvent interaction, which is materialized in strongly‐solvating solvent and highly‐dissociated salt combinations. Such electrolyte formulations benefit the formation of solvent‐occupied solvation structure and minimize the anion reduction, resulting in organic‐rich/CaF2‐poor SEIs for reversible Ca metal anodes. Furthermore, RCMBs paired with an organic cathode using the optimized electrolytes are demonstrated as a proof‐of‐concept. Our work reveals the paradigm shift in SEIs design for Ca metal anodes, opening up new opportunities for emerging RCMBs.
“A whole new perspective on how the body fits together”—An evaluation of a cadaver laboratory experience for high school students
Authors: Cale Andrew S. , Byram Jessica N. , Organ Jason M. , Schmalz Naomi A. 
Published: October 2022

AbstractThe Center for Anatomy and Physiology Education has hosted interactive human cadaver laboratory tours for local high schools (ages 14–18) and undergraduate university students since 2014 to expose students to healthcare careers. Students receive information on the history of body donation and healthcare careers and observe human anatomy on prosections and with isolated organs. The goal of this study was to evaluate students' perceptions of the anatomy laboratory tours and their impact on students' interests in healthcare careers. Students completed pre‐ and post‐tour questionnaires. Responses were analyzed using thematic analysis and linguistic inquiry. Of the 261 students who completed pre‐tour questionnaires, 204 (78%) completed the post‐tour questionnaire. Before the tour, students anticipated learning about human anatomy and expected to only see but not touch a cadaver. Most students expressed excitement and/or nervousness. A few students viewed the laboratory tour as an opportunity to test if they could see themselves in a healthcare career. After the tour, most students indicated that the tour either met or exceeded their expectations. Students found the laboratory tour to be educational and interesting and were surprised by the opportunity to interact with the donor. Numerous students expressed an increased interest in healthcare careers after the tour. Overall, students perceived the tour as an engaging experience that improved their anatomical knowledge and reinforced/increased their interest in healthcare careers. Academic institutions can positively impact local students by implementing an anatomy tour, sharing access to their in‐house human cadaver laboratory, and recruiting instructors to share their anatomy expertise.
Metal free, one pot 1,6‐Conjugate Addition of Diol on para‐Quinone Methide followed by ipso cyclization: An Approach to Spiro 1,4‐Dioxane cyclohexadienone Derivatives
Authors: Gaikwad Ramesh A. , Kamble Sumit B. , Waghmode Suresh B. 
Published: October 2022

AbstractA novel one‐pot transition metal‐free and Brönsted acid mediated 1,6‐conjugate addition of bisnuleophilic diol on biselectrophilc para‐quinone methide followed by ipso cyclization assisted by NBS has been developed under mild reaction conditions, offers a new approach to synthesize spiro 1,4‐dioxane cyclohexadienone derivatives. This strategy features broad substrate scope of p‐QMs with high functional group tolerance and good yields of spirocyclic scaffolds (60–92 %). N‐Bromo succinimide an important role in an ipso spirocyclization with high efficiency.
An enhanced adaptive Kalman filtering for linear systems with inaccurate noise statistics
Authors: Fu Hongpo , Cheng Yongmei 
Published: October 2022

AbstractThis paper investigates the simultaneous state and noise covariance estimation for linear systems with inaccurate noise statistics. An enhanced adaptive Kalman filtering (EAKF) based on dynamic recursive nominal covariance estimation (DNRCE) and modified variational Bayesian (VB) inference is presented. The EAKF realizes the concurrently estimation of state and noise covariance matrices by introducing a nominal parameter in the traditional recursive covariance estimation and designing a new adaptive forgotten factor for the dynamic model of the estimated information propagation. The simulation of a target tracking example shows that, compared with the existing filters, the proposed filter has good adaptive performance for inaccurate and time‐varying noise covariance matrices.
Bayesian Parameterization of Continuum Battery Models from Featurized Electrochemical Measurements Considering Noise**
Authors: Kuhn Yannick , Wolf Hannes , Latz Arnulf , Horstmann Birger 
Published: October 2022

AbstractPhysico‐chemical continuum battery models are typically parameterized by manual fits, relying on the individual expertise of researchers. In this article, we introduce a computer algorithm that directly utilizes the experience of battery researchers to extract information from experimental data reproducibly. We extend Bayesian Optimization (BOLFI) with Expectation Propagation (EP) to create a black‐box optimizer suited for modular continuum battery models. Standard approaches compare the experimental data in its raw entirety to the model simulations. By dividing the data into physics‐based features, our data‐driven approach uses orders of magnitude less simulations. For validation, we process full‐cell GITT measurements to characterize the diffusivities of both electrodes non‐destructively. Our algorithm enables experimentators and theoreticians to investigate, verify, and record their insights. We intend this algorithm to be a tool for the accessible evaluation of experimental databases.
School age educational outcomes of infants born with congenital diaphragmatic hernia
Authors: Walden Alyssa R. , Nembhard Wendy N. , Akmyradov Chary , Goudie Anthony , ElHassan Nahed O. 
Published: October 2022

AbstractBackgroundTo compare academic proficiency among children with congenital diaphragmatic hernia (CDH) versus controls and identify predictors of academic performance among children with CDH.MethodsInfants born with CDH in Arkansas, 2000–2005, were identified from the Arkansas Reproductive Health Monitoring System. For each case, two controls were selected from birth certificate data and matched for hospital and month of birth, sex, and race/ethnicity. Data on re‐hospitalization within the first 5 years and payer data were collected from the Arkansas Hospital Inpatient Discharge database. Surviving cases and controls were linked to the Arkansas Department of Education database. Primary outcomes were odds of proficiency on fourth grade literacy and mathematics achievement tests. Multivariable logistic regression models evaluated the association between study characteristics and academic proficiency.ResultsThe final study cohort included 25 surviving CDH cases and 31 controls who were linked to their education data. After adjusting for differences in characteristics (5‐min Apgar score and associated congenital anomalies) between cases and controls, there were no statistically significant differences in literacy (72% vs. 84%, p = .93) or mathematics (64% vs. 81%, p = .98) test proficiency between the two groups. In multivariable analyses, among CDH cases, oxygen at discharge and Medicaid payer/longer hospital stay were associated with worse fourth grade literacy and mathematics proficiency, respectively.ConclusionsOxygen at discharge, Medicaid payer, and longer hospital stay were associated with lower academic performance among CDH cases.
Gamifying structural analysis assessments for first‐year architecture engineering students
Authors: Micheal Amany G. B. 
Published: October 2022

AbstractThe structural analysis module is a challenge for both teachers and students. The module content is usually presented to students in the form of a set of equations when solved, the structure of internal forces is obtained. Usually, the assignments adopted in such modules are paper‐based exams. Such a strategy may assess the capacity of the students to employ different sets of equations to solve a problem. However, this is not enough for a vivid educational atmosphere. Transforming these equations into a digital simulation is the best solution for the education process. Digitalization is more appealing to nowadays students and it gives the teacher a wide spectrum of discussions without the hindrance of calculations time. It is also a mitigation for the online teaching process during the Covid‐19 pandemic. This paper presents a digital simulation of different structures using a simple tool that enables students to visualize the simultaneous interaction between geometry, loading, boundary conditions, and internal forces. Furthermore, transforming this tool into an offline mobile app helps both the teacher and the student to gamify the investigation of any structure.
Utility of BerEp4/calretinin and desmin/epithelial membrane antigen (EMA) dual immunocytochemical staining in effusion cytology
Authors: Hjerpe Anders , Demir Enes , Abd‐Own Sulaf , Dobra Katalin 
Published: October 2022

AbstractBackgroundPleural mesothelioma (PM) is typically diagnosed late during the disease. Earlier detection can increase the chance of effective therapy. Recurrent pleural effusions are the earliest symptoms displaying an array of cytomorphological changes from reactive atypia to malignancy. Diagnosis is possible on effusion cytology by applying molecular and immunocytochemical markers, the main difficulty being when to suspect PM and to differentiate PM from metastatic adenocarcinoma and reactive mesothelial proliferations.MethodsWe evaluated the diagnostic performance of two immunocytochemical dual stains (BerEp4/Calretinin and Desmin/Epithelial Membrane Antigen (EMA)) on 149 ethanol‐fixed cytospin preparation as an initial step to solve the mentioned diagnostic difficulty. The immunocytochemical reactivity pattern was evaluated by two independent investigators. The final diagnosis corresponded to PM (n = 20), metastatic adenocarcinoma (n = 83), and mesotheliosis (n = 46) in these cases.ResultsCalretinin had 99% specificity and 98% sensitivity for indicating a mesothelial phenotype, while BerEp4 distinguished the adenocarcinoma cases with 98% specificity and 99% sensitivity. EMA displayed 96% specificity and 99% sensitivity in malignant cases, while Desmin without EMA present showed 99% specificity and 96% sensitivity for indicating benign mesothelial proliferation.ConclusionsInterpretation of the four immunoreactions is improved when performed as dual stains. The dual staining is a useful tool in the initial handling of atypical effusions and guides the subsequent choice of antibody panels for more detailed subclassification of malignant effusions.