bluuebunny/crossref_metadata_2025_split huggingface dataset:
An adaptive soft‐sensor for advanced real‐time monitoring of an antibody‐drug conjugation reaction
Authors: Schiemer Robin , Weggen Jan Tobias , Schmitt Katrin Marianne , Hubbuch Jürgen 
Published: May 2023

AbstractIn the production of antibody‐drug conjugates (ADCs), the conjugation reaction is a central step defining the final product composition and, hence, directly affecting product safety and efficacy. To enable real‐time monitoring, spectroscopic sensors in combination with multivariate regression models have gained popularity in recent years. The extended Kalman filter (EKF) can be used as so‐called soft‐sensor to fuse sensor predictions with long‐horizon forecasts by process models. This enables the dynamic update of the current state and provides increased robustness against experimental noise or model errors. Due to the uncertainty associated with sensor and process models in biopharmaceutical applications, the deployment of such soft‐sensors is challenging. In this study, we demonstrate the combination of an uncertainty‐aware sensor model with a kinetic reaction model using an EKF to monitor a site‐directed ADC conjugation reaction. As the sensor model, a Gaussian process regression model is presented to realize a time‐variant determination of the sensor uncertainty. The EKF fuses the time‐discrete predictions of the amount of conjugated drug from the sensor model with the time‐continuous predictions from the kinetic model. While the ADC species are not distinguishable by on‐line recorded UV/Vis spectra, the developed soft‐sensor is able to dynamically update all relevant reaction species. It could be shown that the use of time‐variant process and sensor noise computation approaches improved the performance of the EKF and achieved a reduction of the prediction error of up to 23% compared with the kinetic model. The developed framework proved to enhance robustness against noisy sensor measurements or wrong model initialization and was successfully transferred from batch to fed‐batch mode. In future, this framework could be implemented for model‐based process control and be adopted for other ADC conjugation reaction types.
Preclinical pharmacokinetics and metabolism study of SCO‐267, a GPR40 full agonist, in beagle dogs using ultra‐high performance liquid chromatography coupled to tandem mass spectrometry
Authors: Li Hongxia , Liu Yanan , Xiao Jiachao , Huang Jin , Zhang Yue 
Published: May 2023

AbstractSCO‐267 is a GPR40 full agonist that has been developed for the treatment of diabetes. To support its preclinical and clinical development, in this study, we developed an ultra‐high performance liquid chromatography tandem mass spectrometric method for the determination of SCO‐267 in dog plasma using cabozantinib as internal standard (IS). The chromatographic separation was obtained on a Waters acquity BEH C18 column (50 × 2.1 mm, i.d., 1.7 μm) and the detection was performed using Thermo TSQ triple quadrupole mass spectrometer with multiple reaction monitoring positive mode at m/z 615.3 > 230.1 for SCO‐267 and m/z 502.5 > 323.3 for IS. The method was validated over the concentration range of 1–2,000 ng/ml with the lower limit of quantification of 1 ng/ml. The selectivity, linearity, precision and accuracy over this range were acceptable. The extraction recovery was more than 88.73% and no matrix effect was observed. SCO‐267 was demonstrated to be stable during the storage and processing period. The new method was successfully applied to the pharmacokinetic study in beagle dogs following a single oral and intravenous administration. The oral bioavailability was 64.34%. In addition, the metabolites from dog liver microsomal incubation and plasma collected after an oral administration were identified by a UHPLC–HRMS method. The biotransformation pathways of SCO‐267 involved oxygenation, O‐demethylation, N‐dealkylation and acyl glucuronidation.
The model practice of reconstructing education management based on Web 3.0 technology blended learning under the people‐oriented concept
Authors: Sun Xiaofeng , Qin Yekun 
Published: May 2023

AbstractThis paper deeply analyzes the mode of blended learning based on network 3.0 technology under the people‐oriented concept, and introduces the characteristics and essence of blended learning based on network 3.0 technology. On this basis, this paper discusses the dilemma of the traditional educational management mode, puts forward the educational practice design based on Web 3.0 technology blended learning under the people‐oriented concept, and finally summarizes the practice.
6‐Bromoquinazoline Derivatives as Potent Anticancer Agents: Synthesis, Cytotoxic Evaluation, and Computational Studies
Authors: Zare Somayeh , Emami Leila , Behrouz Marzieh , Khankahdani Reza Abbasi , Nickpour Shirin , Emami Mina , Faghih Zeinab , Khabnadideh Soghra 
Published: May 2023

AbstractA series of 6‐bromoquinazoline derivatives (5a–j) were synthesized. Cytotoxic effectiveness of compounds was done against two cancerous cell lines (MCF‐7 and SW480) by standard MTT method. Fortunately, all of the compounds showed desirable activity in reducing the viability of the studied cancerous cell lines with IC50value in the range of 0.53–46.6 μM. Compound5bwith a fluoro substitution atmetaposition of the phenyl moiety showed stronger activity than cisplatin with IC50=0.53–1.95 μM. Studies on the hit compound (5b) through apoptosis assay illustrated that it could induce apoptosis in MCF‐7 cell lines in dose dependent manner. Molecular docking study was done to investigate the detailed binding modes and interactions with EGFR as a plausible mechanism. The drug‐ likeness was predicted. To survey the reactivity of compounds, DFT calculation was performed. Taken together, 6‐bromoquinazoline derivatives, especially5bcan be considered as hit compounds to rational drug designing as antiproliferative agents.
α‐C−H Arylation of N‐Sulfonyl Amines by Dual Palladium Catalysis
Authors: Liu Yu‐Cheng , Shi Hang 
Published: May 2023

AbstractFunctionalization of C(sp3)−H bonds adjacent to a nitrogen atom is an efficient means of preparing structurally complex amines and has long been of interest to synthetic chemists. Herein, dual palladium catalysis is used to achieve α‐C−H arylation of linear N‐sulfonyl amines with aryl boroxines, rather than N‐arylation (C−N bond formation). This method has a broad scope with respect to both the amine and the boroxine, providing convenient access to α‐branched amines. During the dehydrogenation step of the catalytic cycle, bromobenzene accepts a hydride from the α‐carbon on the amine, producing an imine that subsequently undergoes Pd‐catalyzed C‐arylation with the boroxine. Mechanistic studies revealed that imine arylation proceeds through an unusual Pd0/PdII catalytic cycle, in which oxidative cyclization of a palladium η2‐imine complex generates a three‐membered palladacycle that subsequently undergoes transmetallation reaction with the boroxine.
Fluid Flow Modeling and Analysis of Low‐ and High‐Gravity Spiral Concentrators: Experimental and Analytical Approaches
Authors: Ankireddy Prudhvinath Reddy , Purushotham Sudikondala , Narasimha Mangadoddy 
Published: May 2023

AbstractAn experimental evaluation of the flow field on two high‐gravity spiral concentrators is presented along with the analytical solutions. A digital depth gauge was used to measure the liquid level on the spiral troughs. The tracer particle trajectories and the free surface velocity of a spiral were determined with a high‐speed camera. An increase in the flow rate leads to an increase in the liquid depth and free surface velocity along the trough surface. Three full turns of the high gravity spiral concentrator are sufficient for achieving a stabilized flow. High‐gravity spirals show lower flow depths and free surface velocities but steeper depths on the outer trough zone than low‐gravity spirals. Higher flow depths contribute to larger circulation zones, which eventually help in greater separation of heavier minerals from gangue particles.
Beyond the Limits of Atropochirality: Design of Highly Conformationally Restrained Biaryls with Bridgehead Phosphine Oxide
Authors: Mele Lucas , Babouri Rachida , Pirat Jean‐Luc , Tomás‐Mendivil Eder , Martin David , Ayad Tahar , Virieux David 
Published: May 2023

AbstractIn the last three decades, reacting sterically congested ortho‐substituted arenes to form atropochiral biaryls is an appealing venture and a challenging subject that has garnered significant attention. Therefore, there is interest in developing methods to prepare these compounds. In this study, an efficient approach to produce a new class 2,2’ disubstituted biaryls bridgehead phosphine oxides with an unusual topology and exceptional conformational stability is presented. Our methodology demonstrates that depending on the substitution pattern on the aryl moieties, the methanophosphocine backbone could be rigid enough to observe a double atropochirality, resulting in an under covered class of molecules. Notably, our studies revealed that replacing only one hydrogen at the ortho position by a fluorine atom led to sufficiently restricted rotation at temperatures below 80 °C, extending “far away” the limits of atropostability. Finally, our investigations, which employed variable‐temperature NMR spectroscopy and DFT calculations, yielded unique insights into the isomerisation mechanism, indicating that the two biaryl motifs are fully independent in spite of their proximity.
Copper‐Catalyzed Heterocyclic Recombination of Aziridine and Diazetidine for the Synthesis of Imidazolidine**
Authors: Higuchi Daiki , Matsubara Satoshi , Kadowaki Hiroki , Tanaka Daisuke , Murakami Kei 
Published: May 2023

AbstractThe discovery of new catalytic applications for metals remains an important goal in organic synthesis. If a catalyst has multiple functions, such as inducing bond cleavage and formation, it can streamline multi‐step transformations. Herein, the Cu‐catalyzed synthesis of imidazolidine through heterocyclic recombination between aziridine and diazetidine is reported. Mechanistically, Cu catalyzes the conversion of diazetidine into the corresponding imine, which then reacts with aziridine to form imidazolidine. The scope is sufficiently wide to form various imidazolidines, as many functional groups are compatible with the reaction conditions.
Manganese(I)‐Catalyzed Chemoselective Transfer Hydrogenation of the C=C Bond in Conjugated Ketones at Room Temperature
Authors: Sharma Dipesh M. , Shabade Anand B. , Gonnade Rajesh G. , Punji Benudhar 
Published: May 2023

AbstractChemoselective transfer hydrogenation of C=C bond in α,β‐unsaturated ketones is demonstrated at room temperature employing a manganese(I) catalyst and half an equivalent of ammonia‐borane (H3N−BH3). A series of mixed‐donor pincer‐ligated Mn(II) complexes, (tBu2PN3NPyz)MnX2 [κP,κN,κN‐(N‐(di‐tert‐butylphosphaneyl)‐6‐(1H‐pyrazol‐1‐yl)pyridin‐2‐amine)MnX2] {X=Cl (Mn2), X=Br (Mn3), X=I (Mn4)} were synthesized and characterized. Amongst the Mn(II) complexes, (Mn2, Mn3, Mn4) and Mn(I) complex, (tBu2PN3NPyz)Mn(CO)2Br (Mn1) screened; the Mn1 acts as an efficient catalyst for the chemoselective C=C bond reduction in α,β‐unsaturated ketones. Various synthetically important functionalities like halides, methoxy, trifluoromethyl, benzyloxy, nitro, amine, and unconjugated alkene and alkyne groups, including heteroarenes, were compatible and provided saturated ketones in excellent yields (up to 97 %). A preliminary mechanistic study highlighted the crucial role of metal–ligand (M–L) cooperation through the dearomatization‐aromatization process in catalyst Mn1 for the chemoselective C=C bond transfer hydrogenation.
Control of an Industrial Distillation Column Using a Hybrid Model with Adaptation of the Range of Validity and an ANN‐based Soft Sensor
Authors: Elsheikh Mohamed , Ortmanns Yak , Hecht Felix , Roßmann Volker , Krämer Stefan , Engell Sebastian 
Published: May 2023

AbstractAdvanced control schemes such as model predictive control can be used to minimize the use of resources while guaranteeing the specified product quality. In this paper, we consider an industrial mother liquor distillation column varying flow rate and composition of the feed. There are specifications of the composition for all product streams. To address this challenging control problem, we employ a nonlinear model‐predictive controller using a hybrid model, which consists of a simple phenomenological model augmented by a data‐based component to compensate the plant‐model mismatch. The trustworthiness of the data‐based model is addressed using a domain of validity of the data‐based model, which is estimated using a one‐class support vector machine. During operation, it may turn out that the model is also reliable in a wider range, therefore, data of recently visited operating points is recorded and the domain of validity is extended if the model is sufficiently accurate. To improve the performance of the controller, an artificial neural network model is used to estimate the product composition from available measurements.
A novel high‐precision single‐event transient hardened voltage comparator design
Authors: Xie Yuqiao , Liu Zhongyang , Xu Tao , Bi Dawei , Hu Zhiyuan , Zhang Zhengxuan , Zou Shichang 
Published: May 2023

SummaryTo reduce the impact of the single‐event transient (SET) effect on the high‐precision comparator, based on the common high‐gain pre‐amplification stage structure of the comparator, a new radiation hardened by design (RHBD) method, namely, the sensitive node transient detection feedback latch (SNTDFL) technique, is proposed. The hardening technique avoids comparator erroneous output by detecting the sensitive nodes of the high‐gain pre‐amplification stage. The detection circuit receives the response generated by the high energy particle impacts and feeds the high level back to the sensitive nodes to latch the current comparator state. In this paper, a novel high‐precision SET hardened voltage comparator based on this technique is developed. Through detailed circuit principle and simulation analysis, the functional characteristics and the hardening performance of the high‐precision hardened comparator are verified. Compared with the unhardened and the TMR technique hardened comparator, the SNTDFL technique hardened comparator effectively avoids the erroneous output caused by the SET effect with less overhead and still has excellent functional characteristics.
Design, synthesis, and biological evaluation of furan‐bearing pyrazolo[3,4‐b]pyridines as novel inhibitors of CDK2 and P53–MDM2 protein–protein interaction
Authors: Ezzat Manal Abdel Fattah , Elmasry Ghada F. , El‐Mageed Menna M. A. Abd , Fouad Marwa A. , Abdel‐Aziz Hatem A. , Elewa Safaa I. 
Published: May 2023

AbstractThe novel series of furan‐bearing pyrazolo[3,4‐b]pyridines were designed as cyclin‐dependent kinase 2 (CDK2) inhibitors and as p53–murine double minute 2 (MDM2) inhibitors. The newly synthesized compounds were screened for their antiproliferative activity toward hepatocellular carcinoma (HepG2) and breast cancer (MCF7) cell lines. The most active compounds on both cell lines were additionally evaluated for their in vitro CDK2 inhibitory activity. Compounds 7b and 12f displayed enhanced activity (half‐maximal inhibitory concentration [IC50] = 0.46 and 0.27 µM, respectively) in comparison to the standard roscovitine (IC50 = 1.41 ± 0.03 µM), in addition to, cell cycle arrest at S phase and G1/S transition phase in MCF7 cells treated with both compounds, respectively. Moreover, the most active spiro‐oxindole derivative against MCF7 cell line, 16a, exhibited enhanced inhibitory activity against p53–MDM2 interaction in vitro (IC50 = 3.09 ± 0.12 µM) compared to nutlin, and increased the levels of both p53 and p21 by nearly fourfold in comparison to the negative control. Molecular docking studies demonstrated the plausible interaction patterns of the most potent derivatives 17b and 12f in the CDK2 binding pocket and the spiro‐oxindole 16a with p53–MDM2 complex, respectively. Consequently, the new chemotypes 7b, 12f, and 16a can be presented as promising antitumor hits for further studies and optimization.
Behavioral and neurostructural correlates of childhood physical violence victimization: Interaction with family functioning
Authors: Delaney Scott W. , Cortes Hidalgo Andrea P. , White Tonya , Haneuse Sebastien , Ressler Kerry J. , Tiemeier Henning , Kubzansky Laura D. 
Published: May 2023

AbstractViolence victimization may cause child behavior problems and neurostructural differences associated with them. Healthy family environments may buffer these effects, but neural pathways explaining these associations remain inadequately understood. We used data from 3154 children (x̅age = 10.1) to test whether healthy family functioning moderated possible associations between violence victimization, behavior problems, and amygdala volume (a threat‐responsive brain region). Researchers collected data on childhood violence victimization, family functioning (McMaster Family Assessment Device, range 0–3, higher scores indicate healthier functioning), and behavior problems (Achenbach Child Behavior Checklist [CBCL] total problem score, range 0–117), and they scanned children with magnetic resonance imaging. We standardized amygdala volumes and fit confounder‐adjusted models with “victimization × family functioning” interaction terms. Family functioning moderated associations between victimization, behavior problems, and amygdala volume. Among lower functioning families (functioning score = 1.0), victimization was associated with a 26.1 (95% confidence interval [CI]: 9.9, 42.4) unit higher CBCL behavior problem score, yet victimized children from higher functioning families (score = 3.0) exhibited no such association. Unexpectedly, victimization was associated with higher standardized amygdala volume among lower functioning families (ŷ = 0.5; 95% CI: 0.1, 1.0) but lower volume among higher functioning families (ŷ = −0.4; 95% CI: −0.7, −0.2). Thus, healthy family environments may mitigate some neurobehavioral effects of childhood victimization.
Postpartum cessation of urban space use by a female baboon living at the edge of the City of Cape Town
Authors: Bracken Anna M. , Christensen Charlotte , O'Riain M. Justin , Fürtbauer Ines , King Andrew J. 
Published: May 2023

AbstractSpecies with slow life history strategies that invest in few offspring with extended parental care need to adapt their behavior to cope with anthropogenic changes that occur within their lifetime. Here we show that a female chacma baboon (Papio ursinus) that commonly ranges within urban space in the City of Cape Town, South Africa, stops using urban space after giving birth. This change of space use occurs without any significant change in daily distance traveled or social interactions that would be expected with general risk‐sensitive behavior after birth. Instead, we suggest this change occurs because of the specific and greater risks the baboons experience within the urban space compared to natural space, and because leaving the troop (to enter urban space) may increase infanticide risk. This case study can inform methods used to manage the baboons' urban space use in Cape Town and provides insight into how life history events alter individuals' use of anthropogenic environments.
Environmental DNA extraction method from water for a high and consistent DNA yield
Authors: Fukuzawa Takashi , Shirakura Hiromi , Nishizawa Naofumi , Nagata Hisao , Kameda Yuichi , Doi Hideyuki 
Published: May 2023

AbstractEnvironmental DNA (eDNA) measurements have been widely applied in the biomonitoring of organisms. However, different DNA extraction methods may cause changes in yield and consistency, resulting in an inaccurate estimation of eDNA, especially when quantitative measurements are performed. This study focused on evaluating the effects of DNA extraction methods on the magnitude and consistency of fish DNA yield from water samples. Samples were collected periodically over a year from river and lake water systems, and reference eDNA was spiked into them. The spiked samples were extracted using three methods: using lysis buffer for blood and cells (AL method) with the DNeasy Blood and Tissue Kit (Qiagen), using lysis buffer for tissue (ATL method), and the microfluidic‐channel method (BC method). DNA yields were compared by determining the copy number using qPCR. The ATL method showed better stability and a higher yield than the AL method. In addition, despite being comparatively simple, the BC method performed extractions stably and at relatively high yields. Based on the long‐term evaluation of eDNA measurements using various methods, we showed that differences in DNA extraction methods may alter DNA yield and stability.
Oleic acid‐rich waste fleshing oil as a secondary carbon source for the synthesis of sophorolipids
Authors: Velappan Brindha , Nagarajan Vedaraman , Narayana Murthy Venkatesh , Arumugam Sivasamy , Kandukalpatti Chinnaraj Velappan 
Published: May 2023

AbstractBiosurfactants are nontoxic, renewable, and environmentally benign; and have excellent emulsification and antibacterial properties. Oleic acid‐rich oils have a crucial role as a hydrophobic substrate in the biological production of sophorolipids (SL). The major purpose of this study is to identify a low‐cost oleic acid‐rich hydrophobic substrate that may be used as a secondary carbon source in the synthesis of SL by Starmerella bombicola (S. bombicola). Thus, the biosynthesis of SL was investigated utilizing a variety of edible and nonedible oils rich in oleic acid, which acts as a precursor. Characterization of SL generated from different oils using FT‐IR and NMR indicated the presence of both lactonic and acidic SL. SL production was greatest with secondary carbon sources, with 38.9, 27.57, and 19 g/L, respectively, in the order olive oil > sunflower oil > fleshing oil. Surprisingly, the cost analysis for fleshing oil synthesis indicated that it was the lowest at 0.43 INR/g, followed by sunflower oil at 0.52 INR/g and olive oil at 1.71 INR/g. Our findings indicate that fleshing oil is a potential secondary carbon source with significant SL yield as well as environmental and economic benefits.