bluuebunny/crossref_metadata_2025_split huggingface dataset:
Engineering a Non‐Natural Photoenzyme for Improved Photon Efficiency**
Authors: Nicholls Bryce T. , Oblinsky Daniel G. , Kurtoic Sarah I. , Grosheva Daria , Ye Yuxuan , Scholes Gregory D. , Hyster Todd K. 
Published: November 2021

AbstractPhotoenzymes are biological catalysts that use light to convert starting materials into products. These catalysts require photon absorption for each turnover, making quantum efficiency an important optimization parameter. Flavin‐dependent “ene”‐reductases (EREDs) display latent photoenzymatic activity for synthetically valuable hydroalkylations; however, protein engineering has not been used to optimize this non‐natural function. We describe a protein engineering platform for the high throughput optimization of photoenzymes. A single round of engineering results in improved catalytic function toward the synthesis of γ, δ, ϵ‐lactams, and acyclic amides. Mechanistic studies show that key mutations can alter the enzyme's excited state dynamics, enhance its photon efficiency, and ultimately increase catalyst performance. Transient absorption spectroscopy reveals that engineered variants display dramatically decreased radical lifetimes, indicating an evolution toward a concerted mechanism.
Type I ‘Lighted Metal‐free’ Photosensitizing Assemblies of Phenazine for Aerobic Oxidative Transformations
Authors: Kaur Lovjot , Kaur Harpreet , Kumar Manoj , Bhalla Vandana 
Published: November 2021

AbstractHighly photostable supramolecular photosensitizing ‘lighted metal‐free’ assemblies of DPZ‐Th have been developed which show strong absorption in the visible region and excellent electron transportation potential from donor to acceptor units. The as‐prepared assemblies of DPZ‐Th activate aerial oxygen to generate Type I reactive oxygen species (ROS) under visible‐light irradiation in mixed aqueous media. Owing to these properties, the as‐prepared DPZ‐Th assemblies exhibit high photocatalytic activity in catalyzing the aerobic oxidative coupling of benzylamines and synthesis of quinazolines. Various spectroscopic studies support the participation of Type I reactive species in the reaction mechanism. The ‘pure’ oxygen environment was not needed for carrying out these transformations and all the reactions proceed very well under aerial conditions to furnish the desired products in high yields.
Raman based chemometric model development for glycation and glycosylation real time monitoring in a manufacturing scale CHO cell bioreactor process
Authors: A. Gibbons Luke , Rafferty Carl , Robinson Kerry , Abad Marta , Maslanka Francis , Le Nikky , Mo Jingjie , Clark Kevin , Madden Fiona , Hayes Ronan , McCarthy Barry , Rode Christopher , O'Mahony Jim , Rea Rosemary , O'Mahony Hartnett Caitlin 
Published: November 2021

AbstractThe Quality by Design (QbD) approach to the production of therapeutic monoclonal antibodies (mAbs) emphasizes an understanding of the production process ensuring product quality is maintained throughout. Current methods for measuring critical quality attributes (CQAs) such as glycation and glycosylation are time and resource intensive, often, only tested offline once per batch process. Process analytical technology (PAT) tools such as Raman spectroscopy combined with chemometric modeling can provide real time measurements process variables and are aligned with the QbD approach. This study utilizes these tools to build partial least squares (PLS) regression models to provide real time monitoring of glycation and glycosylation profiles. In total, seven cell line specific chemometric PLS models; % mono‐glycated, % non‐glycated, % G0F‐GlcNac, % G0, % G0F, % G1F, and % G2F were considered. PLS models were initially developed using small scale data to verify the capability of Raman to measure these CQAs effectively. Accurate PLS model predictions were observed at small scale (5 L). At manufacturing scale (2000 L) some glycosylation models showed higher error, indicating that scale may be a key consideration in glycosylation profile PLS model development. Model robustness was then considered by supplementing models with a single batch of manufacturing scale data. This data addition had a significant impact on the predictive capability of each model, with an improvement of 77.5% in the case of the G2F. The finalized models show the capability of Raman as a PAT tool to deliver real time monitoring of glycation and glycosylation profiles at manufacturing scale.
Synthesis and Antiproliferative Activity of New Thiosemicarboxamide Derivatives
Authors: Wu Jun , Guo Yafei , Chen Jun , Hu Sangsang , Sun Ke , Hu Hongyu , Fang Meijuan , Xue Yuhua 
Published: November 2021

AbstractTo discover new anticancer agents, two series of thiosemicarboxamide derivatives were synthesized and evaluated for their antiproliferative activity against human cancer cells in vitro. Most target compounds (especially 3f, 3g, and 3h) exhibit potent antiproliferative activity against HeLa cells. Importantly, compound 3h, bearing a 4‐methylphenyl substituent at N position of thiourea moiety, has significant and broad‐spectrum inhibitory activities against cancer cells (HepG2, HeLa, MDA‐MB231, A875, and H460 cells) with low IC50 values (<5.0 μM) and shows low toxicity to normal LO2 and MRC‐5 cells. Further studies show that compound 3h exerts high inhibitory activity in cancer cells by inducing the G2/M‐phase arrest of cancer cells. Collectively, this study presents compound 3h as a new entity for the development of cell cycle arrest inducers for the treatment of cancer.
Gold N‐Heterocyclic Carbene Catalysts for the Hydrofluorination of Alkynes Using Hydrofluoric Acid: Reaction Scope, Mechanistic Studies and the Tracking of Elusive Intermediates
Authors: Gauthier Raphaël , Tzouras Nikolaos V. , Zhang Ziyun , Bédard Sandrine , Saab Marina , Falivene Laura , Van Hecke Kristof , Cavallo Luigi , Nolan Steven P. , Paquin Jean‐François 
Published: November 2021

AbstractAn efficient and chemoselective methodology deploying gold‐N‐heterocyclic carbene (NHC) complexes as catalysts in the hydrofluorination of terminal alkynes using aqueous HF has been developed. Mechanistic studies shed light on an in situ generated catalyst, formed by the reaction of Brønsted basic gold pre‐catalysts with HF in water, which exhibits the highest reactivity and chemoselectivity. The catalytic system has a wide alkyl substituted‐substrate scope, and stoichiometric as well as catalytic reactions with tailor‐designed gold pre‐catalysts enable the identification of various gold species involved along the catalytic cycle. Computational studies aid in understanding the chemoselectivity observed through examination of key mechanistic steps for phosphine‐ and NHC‐coordinated gold species bearing the triflate counterion and the elusive key complex bearing a bifluoride counterion.
CD69 mediates the protective role of adipose tissue‐derived mesenchymal stem cells against Pseudomonas aeruginosa pulmonary infection
Authors: Jiang Yanshan , Li Fan , Li Yanan , Duan Jielin , Di Caixia , Zhu Yinggang , Zhao Jingya , Jia Xinming , Qu Jieming 
Published: November 2021

AbstractBackgroundOur previous study shows that Adipose tissue‐derived mesenchymal stem cells (ASCs) are a promising strategy for cell‐based therapy against pulmonary infection with Pseudomonas aeruginosa (P. aeruginosa), but the underlying mechanisms remain unclear.MethodscDNA microarray assay was performed to explore the transcriptome of ASCs primed by P. aeruginosa. Small interfering RNA (siRNA) was constructed to select the receptor candidates for P. aeruginosa recognition and granulocyte‐macrophage colony‐stimulating factor (GM‐CSF) production in ASCs. The soluble protein chimeras containing the extracellular domain of human CD69 fused to the Fc region of human immunoglobulin IgG1 were used as a probe to validate the recognition of P. aeruginosa. The association between CD69 and extracellular regulated protein kinases 1/2 (ERK1/2) was explored via co‐immunoprecipitation, siRNA, and inhibitor. The murine models of P. aeruginosa pneumonia treated with WT‐ASCs, GM‐CSF−/−‐ASCs Cd69−/−‐ASCs or Erk1−/−‐ASCs were used to determine the role of GM‐CSF, CD69, and ERK1 in ASCs against P. aeruginosa infection.ResultsWe showed that C‐type lectin receptor CD69 mediated the protective effects of ASCs partly through GM‐CSF. CD69 could specifically recognize P. aeruginosa and regulate GM‐CSF secretion of ASCs. CD69 regulated the production of GM‐CSF via ERK1 in ASCs after P. aeruginosa infection. Moreover, the Administration of ASCs with deficiency of CD69 or ERK1 completely blocked its protective effects in a murine model of P. aeruginosa pneumonia.ConclusionsCD69 recognizes P. aeruginosa and further facilitates ERK1 activation, which plays a crucial role in ASCs‐based therapy against P. aeruginosa pneumonia. CD69 may be a novel target molecule to improve ASCs‐based therapy against P. aeruginosa infection.
Fast generalized threshold‐based signal detection for multiuser downlink NOMA systems with arbitrary power allocation
Authors: Xu Hongjun , Pillay Narushan 
Published: November 2021

SummaryNon‐orthogonal multiple access (NOMA) is a technique to improve spectral efficiency. Based on the constellation relationship (CR) between the superposition‐coded signal and individual user's signals, in the literature, a simple detection scheme threshold‐based signal detection has been proposed for the two‐user downlink NOMA (DL‐NOMA) system with specific power allocations, not arbitrary power allocation. Furthermore, the average symbol error probability (ASEP) with squared M‐ary quadrature amplitude modulation for two‐user DL‐NOMA systems has also been derived based on this CR. Based on the threshold‐based signal detection for the two‐user DL‐NOMA systems with specific power allocation, in this paper, a generalized threshold‐based signal detection is proposed for all users in the multiuser DL‐NOMA systems with arbitrary power allocation, and then a fast generalized threshold‐based signal detection is further proposed. The generalized ASEP for each individual user in the multiuser DL‐NOMA system is further derived in Rayleigh fading channels. Both theoretical ASEP and simulated symbol error rate results validate the fast generalized threshold‐based signal detection scheme and the generalized ASEP for multiuser DL‐NOMA systems with arbitrary power allocations.
Pentagon inscribed circular superwideband fractal MIMO antenna
Authors: Lodhi Deepshikha , Singhal Sarthak 
Published: November 2021

SummaryA compact circular fractal antenna element loaded with a central pentagonal slot is presented in this paper. This structure consists of a fourth iterative radiator fed by a partially tapered feed line and CPW defected ground plane. A superwide impedance bandwidth of 3.45–52.17 GHz (~175% fractional bandwidth) is achieved. Two multiple input multiple output (MIMO) configurations are also designed and analyzed by using this antenna element. For spatial and pattern diversity configurations, the impedance bandwidth of 3.45–52.2 and 3.1–52.2 GHz are achieved, respectively. The optimized footprints of antenna element, spatial diversity configuration, and pattern diversity configurations are 28 × 24, 28 × 53, and 45 × 48 mm2, respectively. The isolation for both MIMO configurations is more than 20 dB in maximum portion of the operating bandwidth. Desirable radiation and diversity performance characteristics are achieved for antenna element and MIMO configurations. The wide bandwidth, compact dimensions along with good radiation, and diversity performance characteristics make the proposed antenna configurations suitable for integration in superwideband wireless communication systems. A good agreement between the experimental and simulation results is observed.
Zebrafish models of fetal alcohol spectrum disorders
Authors: Fernandes Yohaan , Lovely C. Ben 
Published: November 2021

AbstractFetal alcohol spectrum disorder (FASD) describes a wide range of structural deficits and cognitive impairments. FASD impacts up to 5% of children born in the United States each year, making ethanol one of the most common teratogens. Due to limitations and ethical concerns, studies in humans are limited in their ability to study FASD. Animal models have proven critical in identifying and characterizing the mechanisms underlying FASD. In this review, we will focus on the attributes of zebrafish that make it a strong model in which to study ethanol‐induced developmental defects. Zebrafish have several attributes that make it an ideal model in which to study FASD. Zebrafish produced large numbers of externally fertilized, translucent embryos. With a high degree of genetic amenability, zebrafish are at the forefront of identifying and characterizing the gene‐ethanol interactions that underlie FASD. Work from multiple labs has shown that embryonic ethanol exposures result in defects in craniofacial, cardiac, ocular, and neural development. In addition to structural defects, ethanol‐induced cognitive and behavioral impairments have been studied in zebrafish. Building upon these studies, work has identified ethanol‐sensitive loci that underlie the developmental defects. However, analyses show there is still much to be learned of these gene‐ethanol interactions. The zebrafish is ideally suited to expand our understanding of gene‐ethanol interactions and their impact on FASD. Because of the conservation of gene function between zebrafish and humans, these studies will directly translate to studies of candidate genes in human populations and allow for better diagnosis and treatment of FASD.
Less loop diuretic use in patients on sacubitril/valsartan undergoing remote pulmonary artery pressure monitoring
Authors: Böhm Michael , Assmus Birgit , Anker Stefan D. , Asselbergs Folkert W. , Brachmann Johannes , Brett Marie‐Elena , Brugts Jasper J. , Ertl Georg , Wang AiJia , Hilker Lutz , Koehler Friedrich , Rosenkranz Stephan , Leistner David M. , Abdin Amr , Wintrich Jan , Zhou Qian , Adamson Philip B. , Angermann Christiane E. 
Published: November 2021

AbstractAimsControl of pulmonary pressures monitored remotely reduced heart failure hospitalizations mainly by lowering filling pressures through the use of loop diuretics. Sacubitril/valsartan improves heart failure outcomes and increases the kidney sensitivity for diuretics. We explored whether sacubitril/valsartan is associated with less utilization of loop diuretics in patients guided with haemodynamic monitoring in the CardioMEMS European Monitoring Study for Heart Failure (MEMS‐HF).Methods and resultsThe MEMS‐HF population (n = 239) was separated by the use of sacubitril/valsartan (n = 68) or no use of it (n = 164). Utilization of diuretics and their doses was prespecified in the protocol and was monitored in both groups. Multivariable regression, ANCOVA, and a generalized linear model were used to fit baseline covariates with furosemide equivalents and changes for 12 months. MEMS‐HF participants (n = 239) were grouped in sacubitril/valsartan users [n = 68, 64 ± 11 years, left ventricular ejection fraction (LVEF) 25 ± 9%, cardiac index (CI) 1.89 ± 0.4 L/min/m2] vs. non‐users (n = 164, 70 ± 10 years, LVEF 36 ± 16%, CI 2.11 ± 0.58 L/min/m2, P = 0.0002, P < 0.0001, and P = 0.0015, respectively). In contrast, mean pulmonary artery pressure (PAP) values were comparable between groups (29 ± 11 vs. 31 ± 11 mmHg, P = 0.127). Utilization of loop diuretics was lower in patients taking sacubitril/valsartan compared with those without (P = 0.01). Significant predictor of loop diuretic use was a history of renal failure (P = 0.005) but not age (P = 0.091). After subjects were stratified by sacubitril/valsartan or other diuretic use, PAP was nominally, but not significantly lower in sacubitril/valsartan‐treated patients (baseline: P = 0.52; 6 months: P = 0.07; 12 months: P = 0.53), while there was no difference in outcome or PAP changes. This difference was observed despite lower CI (P = 0.0015). Comparable changes were not observed for other non‐loop diuretics (P = 0.21).ConclusionsIn patients whose treatment was guided by remote PAP monitoring, concomitant use of sacubitril/valsartan was associated with reduced utilization of loop diuretics, which could potentially be relevant for outcomes.
A state‐of‐the‐art review on the impact of fast EV charging on the utility sector
Authors: Shariff Samir M. , Alam Mohammad Saad , Hameed Salman , Khalid Mohd Rizwan , Ahmad Aqueel , Al‐Ammar Essam A. , Alsaidan Ibrahim , Alrajhi Hasan 
Published: November 2021

AbstractDeployment of fast‐charging stations for electrified transportation is currently one of the limiting factors in the commercial deployment and paradigm shift of the mobility sector. The rapidly increasing demand for electric vehicles (EVs) brings the demand for accessible and affordable charging infrastructure. The commercial EV fast‐charging load profile depends on the customer's EV charging demand, which poses challenges in determining the overall peak profile. This could lead to unprecedented challenges of harmonic disruption, system losses, supply‐demand balance, and grid reliability. The emergence of bidirectional charging infrastructure and the realization of controlled charging strategies in coordination with the cumulative contribution of renewable energy resources could potentially reduce the challenge of utility grid stability and reliability shortly. Furthermore, the parallel development of smart grid technologies has promising features. This paper aims to provide a comprehensive state‐of‐the‐art review of the major challenges of the utility grid in the swift adoption of fast charging infrastructures available in the open literature, as well as the sustainable implications and potential safety measures. Furthermore, the potential solutions and best practices for the synchronization of electrified transportation with the emerging ecosystem of renewable power systems and various controlled charging strategies are reviewed in detail.
Comparing pH differential and methanol‐based methods for anthocyanin assessments of strawberries
Authors: Taghavi Toktam , Patel Hiral , Rafie Reza 
Published: November 2021

AbstractAnthocyanins are a group of water‐soluble polyphenolic pigments found primarily in flowers, vegetables, and fruits. These pigments play critical roles in plant and human health. Spectrophotometric methods are a simple and inexpensive way to quantify anthocyanins in plant tissues. Two main spectrophotometric methods have been developed, organic solvent‐based, and pH differential methods. Both of these methods are subject to interference from light‐absorbing impurities and need to be optimized for different matrixes of different plant materials. Eight methods have been tested in this experiment to quantify anthocyanins in strawberry fruits. Six organic solvent‐based methods tested methanol, chloroform‐methanol, and MgO in different ratios. The other two methods were pH differential method and a combination of organic solvent‐based and pH differential method. Two methods used organic solvents (methanol and chloroform‐methanol) were the best in extracting anthocyanin from strawberry fruits. Adding MgO increased the pH of the extract and was less efficient in anthocyanin extraction. All other methods had lower anthocyanin yield compared with methanol and chloroform‐methanol methods and are not recommended for strawberry fruit anthocyanin extraction.
Facing successfully high mental workload and stressors: An fMRI study
Authors: Causse Mickaël , Lepron Evelyne , Mandrick Kevin , Peysakhovich Vsevolod , Berry Isabelle , Callan Daniel , Rémy Florence 
Published: November 2021

AbstractThe present fMRI study aimed at highlighting patterns of brain activations and autonomic activity when confronted with high mental workload and the threat of auditory stressors. Twenty participants performed a complex cognitive task in either safe or aversive conditions. Our results showed that increased mental workload induced recruitment of the lateral frontoparietal executive control network (ECN), along with disengagement of medial prefrontal and posterior cingulate regions of the default mode network (DMN). Mental workload also elicited an increase in heart rate and pupil diameter. Task performance did not decrease under the threat of stressors, most likely due to efficient inhibition of auditory regions, as reflected by a large decrement of activity in the superior temporal gyri. The threat of stressors was also accompanied with deactivations of limbic regions of the salience network (SN), possibly reflecting emotional regulation mechanisms through control from dorsal medial prefrontal and parietal regions, as indicated by functional connectivity analyses. Meanwhile, the threat of stressors induced enhanced ECN activity, likely for improved attentional and cognitive processes toward the task, as suggested by increased lateral prefrontal and parietal activations. These fMRI results suggest that measuring the balance between ECN, SN, and DMN recruitment could be used for objective mental state assessment. In this sense, an extra recruitment of task‐related regions and a high ratio of lateral versus medial prefrontal activity may represent a relevant marker of increased but efficient mental effort, while the opposite may indicate a disengagement from the task due to mental overload and/or stressors.
Hall current, chemical reaction, and radiation results on transient magnetohydrodynamic flow past an inclined plate: FEM
Authors: Sheri Siva Reddy , Peesu Megaraju , Mamidi Narsimha Rajashekar 
Published: November 2021

AbstractThis paper investigates the influence of Hall current, chemical reaction, and radiation on transient magnetohydrodynamics flow past an inclined plate. The basic nonlinear partial differential equations (PDEs) are converted to dimensionless nonlinear PDEs with similar transformations. The transformed flow equations are solved by the finite element method with appropriate initial conditions. The influence of physical parameters on velocities, temperature, as well as concentration dispensations is addressed computationally and demonstrated by graphs. The influence of flow parameters on skin‐friction coefficients and are discussed and presented in the form of a table. Finally, a qualitative similarity was made between the present paper and the earlier published results and it was initiated that there is tremendous conformity between the results.