bluuebunny/crossref_metadata_2025_split huggingface dataset:
Random epigenetic modulation of CHO cells by repeated knockdown of DNA methyltransferases increases population diversity and enables sorting of cells with higher production capacities
Authors: Weinguny Marcus , Eisenhut Peter , Klanert Gerald , Virgolini Nikolaus , Marx Nicolas , Jonsson Andreas , Ivansson Daniel , Lövgren Ann , Borth Nicole 
Published: July 2020

AbstractChinese hamster ovary (CHO) cells produce a large share of today's biopharmaceuticals. Still, the generation of satisfactory producer cell lines is a tedious undertaking. Recently, it was found that CHO cells, when exposed to new environmental conditions, modify their epigenome, suggesting that cells adapt their gene expression pattern to handle new challenges. The major aim of the present study was to employ artificially induced, random changes in the DNA‐methylation pattern of CHO cells to diversify cell populations and consequently increase the finding of cell lines with improved cellular characteristics. To achieve this, DNA methyltransferases and/or the ten‐eleven translocation enzymes were downregulated by RNA interference over a time span of ∼16 days. Methylation analysis of the resulting cell pools revealed that the knockdown of DNA methyltransferases was highly effective in randomly demethylating the genome. The same approach, when applied to stable CHO producer cells resulted in (a) an increased productivity diversity in the cell population, and (b) a higher number of outliers within the population, which resulted in higher specific productivity and titer in the sorted cells. These findings suggest that epigenetics play a previously underestimated, but actually important role in defining the overall cellular behavior of production clones.
Media supplementation for targeted manipulation of monoclonal antibody galactosylation and fucosylation
Authors: Wells Evan , Song Liqing , Greer Madison , Luo Yu , Kurian Varghese , Ogunnaike Babatunde , Robinson Anne S. 
Published: July 2020

AbstractMonoclonal antibodies are critically important biologics as the largest class of molecules used to treat cancers, rheumatoid arthritis, and other chronic diseases. Antibody glycosylation is a critical quality attribute that has ramifications for patient safety and physiological efficacy—one that can be modified by such factors as media formulation and process conditions during production. Using a design‐of‐experiments approach, we examined the effect of 2‐F‐peracetyl fucose (2FP), uridine, and galactose on cell growth and metabolism, titer, and gene expression of key glycosylation‐related proteins, and report how the glycoform distribution changed from Days 4 to 7 in a batch process used for IgG1 production from Chinese hamster ovary cells. We observed major glycosylation changes upon supplement addition, where the addition of 2FP decreased antibody fucosylation by up to 48%, galactose addition increased galactosylation by up to 21%, and uridine addition decreased fucosylation and increased galactosylation by 6% and 2%, respectively. Despite having major effects on glycosylation, neither galactose nor 2FP significantly affected cell culture growth, metabolism, or titer. Uridine improved peak cell densities by 23% but also reduced titer by ∼30%. The supplements caused significant changes in gene expression by Day 4 of the cultures where 2FP addition significantly reduced fucosyltransferase 8 and nucleotide sugar transporter gene expression (by ∼2‐fold), and uridine addition significantly increased expression of UDP‐GlcNAcT (SLC35A3) and B4GALT1–6 genes (by 1.5–3‐fold). These gene expression data alongside glycosylation, metabolic, and growth data improve our understanding of the cellular mechanisms affected by media supplementation and suggest approaches for modifying antibody glycosylation in antibody production processes.
Metabolome responses of Enterococcus faecium to acid shock and nitrite stress
Authors: Yu Zhong , Shi Dongchen , Liu Wencong , Meng Yabing , Meng Fangang 
Published: July 2020

AbstractEnterococcus faecium is gaining increasing interest due to its virulence and tolerance to a range of stresses (e.g., acid shock and nitrite stress in human stomach). The chemical taxonomy and basic structural features of cellular metabolite can provide us a deeper understanding of bacterial tolerance at molecular level. Here, we used hierarchical classification and molecular composition analysis to investigate the metabolome responses of E. faecium to acid shock and nitrite stress. Our results showed that considerable high biodegradable compounds (e.g., dipeptides) were produced by E. faecium under acid shock, while nitrite stress induced the accumulations of some low biodegradable compounds (e.g., organoheterocyclic compounds and benzenoids). Complete genome analysis and metabolic pathway profiling suggested that E. faecium produced high biodegradable metabolites responsible for the proton‐translocation and biofilm formation, which increase its tolerance to acid shock. Yet, the presence of low biodegradable metabolites due to the nitrite exposure could disturb the bacterial productions of surface proteins, and thus inhibiting biofilm formation. Our approach uncovered the hidden interactions between intracellular metabolites and exogenous stress, and will improve the understanding of host‐microbe interactions.
Addressing endogeneity by proposing novel instrumental variables in the nexus of sustainability reporting and firm financial performance: A step‐by‐step procedure for non‐experts
Authors: Zahid Muhammad , Rahman Haseeb Ur , Khan Musa , Ali Wajahat , Shad Fazaila 
Published: July 2020

AbstractMost of the prior literature that investigated the nexus between corporate sustainability disclosures (CSD) and firm financial performance (FFP) has largely been ignored the potential problem of endogeneity. The omitted variable(s), measurement error, and reverse causality, which are the known causes of endogeneity, may also be the possible reasons for the indecisive and inconsistent relationship between CSD and FFP. Accordingly, this study reinvestigates the relationship by addressing the problem of endogeneity through applying the two‐stage least squares (2SLS) estimator to data collected from the annual reports of the top 10 Pakistani banks through content analysis from 2013 to 2017. The results show a positive impact of the CSD and social sustainability on FFP. However, environmental sustainability exerted a negative impact on FFP. The statistics for 2SLS are much different than those of the ordinary least squares (OLS), which explain the importance of addressing the endogeneity bias. The study offers a methodological procedure that identifies and addresses the endogeneity through a step‐by‐step process in Stata 13.0. Besides, the study also has a novelty to propose and validate additional instrumental variables for the research in the future. Overall, the study has many contributions and implications for different stakeholders such as academia, regulatory bodies, and practitioners in the field of corporate sustainability.
An optimization‐based decision support system for students' personalized long‐term course planning
Authors: Shakhsi‐Niaei Majid , Abuei‐Mehrizi Hossein 
Published: July 2020

AbstractThis paper intends to facilitate academic advising by means of optimal long‐term course planning (LTCP), which is instrumental in students' retention and success. LTCP ensures that students will satisfy the educational requirements without facing unnecessary delays. The proposed decision support system is based on an optimization model which deals with several student preferences, that is, maximum credits per semester, difficulty of courses, graduation semester, and elective courses priorities. The proposed system has been implemented in an industrial engineering department, and several improvements and modifications have been done based on student feedback. The developed system supports two kind of users, that is, educational staff and the students. The courses, their relationships, and regulation parameters are defined/set by educational staff, whereas students determine their own information and preferences, for example, finished courses, graduation target, interest for each elective course, complexity of courses, course load and complexity for each semester, and relative weights of objective functions. Considering theoretical issues, common applications have been integrated to form this system with simple and user‐friendly interfaces.
Towards Zwitterionic Oligonucleotides with Improved Properties: the NAA/LNA‐Gapmer Approach
Authors: Wojtyniak Melissa , Schmidtgall Boris , Kirsch Philine , Ducho Christian 
Published: July 2020

AbstractOligonucleotides (ON) are promising therapeutic candidates, for instance by blocking endogenous mRNA (antisense mechanism). However, ON usually require structural modifications of the native nucleic acid backbone to ensure satisfying pharmacokinetic properties. One such strategy to design novel antisense oligonucleotides is to replace native phosphate diester units by positively charged artificial linkages, thus leading to (partially) zwitterionic backbone structures. Herein, we report a “gapmer” architecture comprised of one zwitterionic central segment (“gap”) containing nucleosyl amino acid (NAA) modifications and two outer segments of locked nucleic acid (LNA). This NAA/LNA‐gapmer approach furnished a partially zwitterionic ON with optimised properties: i) the formation of stable ON‐RNA duplexes with base‐pairing fidelity and superior target selectivity at 37 °C; and ii) excellent stability in complex biological media. Overall, the NAA/LNA‐gapmer approach is thus established as a strategy to design partially zwitterionic ON for the future development of novel antisense agents.
Analysis of the expression and association of retinoblastoma binding protein 6 with the JNK signaling pathway in prostate cancers
Authors: Guan Wen‐Ying , Zhao Sheng , Luo Yun‐Na 
Published: July 2020

AbstractThis study aims to investigate the expression of retinoblastoma binding protein 6 (RBBP6) in prostate cancer (PCa) and its association with the c‐Jun N‐terminal kinase (JNK) pathway. Immunohistochemistry was used to detect RBBP6 and JNK1/2 expression in PCa and benign prostatic hyperplasia tissues. RBBP6 expression in PCa cells (LNCap, PC3, and DU145) and noncancerous prostate epithelial cells (RWPE‐1) was determined by quantitative real‐time polymerase chain reaction and western blot analysis. PC3 and DU145 cells were transfected with RBBP6 small interfering RNAs (siRNAs) to examine the biological characteristics. Anisomycin (a JNK activator) with/without RBBP6 siRNA was used to treat PC3 cells for further investigating the ramification of the RBBP6‐mediated JNK pathway in PCa. PCa tissues and cells showed higher RBBP6 and JNK1/2 expression. RBBP6 was positively correlated with JNK1/2 in PCa tissues. Besides, RBBP6 expression was correlated to clinical tumor stage, lymph node metastasis, Gleason grade, preoperative prostate‐specific antigen level, as well as prognosis of PCa. RBBP6 siRNA reduced cell proliferation, arrested cells at G2/M, and promoted cell apoptosis, and suppressed JNK pathway. In addition, migration and invasion decreased after the RBBP6 siRNA transfection with downregulated matrix metallopeptidase‐2 (MMP‐2) and MMP‐9. Anisomycin promoted the proliferation, invasion, and migration of PC3 cells and inhibited PC3 cell apoptosis, which could be reversed by RBBP6 siRNA. RBBP6 expression was upregulated in PCa tissues and positively correlated with expression level of JNK1/2. With inhibition of RBBP6 expression, the proliferation, invasion, and migration of PCa cells decreased dramatically, while PC3 cell apoptosis increased appreciably, accompanied by the suppression of the JNK pathway.
Macroscopic MXene ribbon with oriented sheet stacking for high‐performance flexible supercapacitors
Authors: Zhu Chao , Geng Fengxia 
Published: July 2020

AbstractFlexible and wearable fiber electrodes with high conductivity and acceptable electrochemical behavior are crucial for extending the application of next‐generation portable electronics, the development of which, however, is very challenging. Two‐dimensional sheets are known to be excellent units for assembling fiber entities, particularly when sheets are oriented in a stacking manner, which helps integrate their intrinsic in‐plane advantages, especially those related with mechanical and electronic performances. In this study, we developed a flexible macroscopic and continuous fiber in an unusual ribbon shape composed solely of Ti3C2 sheets, a typical member of the MXene family. The ribbon morphology was realized through highly ordered stacking of Ti3C2, which imparts fibers with favorable mechanical characteristics. Based on the intrinsic metallic conductivity of Ti3C2 sheets and the oriented stacking structure, the developed macroscopic ribbon exhibited excellent conductivity for both electrons (up to 2458 S/cm) and ions. A fiber‐shaped asymmetric supercapacitor using the developed macroscopic ribbon as a cathode coupled with reduced graphene oxide fibers as an anode delivered a competitive maximum volumetric energy density of 58.4 mWh/cm3 (20.0 Wh/kg) while maintaining a power level of 1679.0 mW/cm3 (581.0 W/kg) and excellent cycling stability (92.4% retention after 10 000 cycles at 10 A/g). This study highlights the excellent potential of MXene as a platform for macroscopic assembly and definitely broadens the applications of MXene materials in wearable electronics.
Insight into the Effect of ZIF‐8 Particle Size on the Performance in Nanocarbon‐Based Supercapacitors
Authors: Wen Yanliang , Chen Xuecheng , Mijowska Ewa 
Published: July 2020

AbstractCarbon materials derived from zeolitic imidazolate framework‐8 (ZIF‐8) and composites thereof have been intensively investigated in supercapacitors. The particle size of the used ZIF‐8 ranges from dozens of nanometers to several microns. However, the influence of the particle size of ZIF‐8 on the capacitive performances is still not clear. A series of ZIF‐8 with different particle sizes (from 25 to 296 nm) has been synthesized and carbonized for supercapacitors. Based on TEM, EDX mapping, XRD, Raman, nitrogen adsorption–desorption, XPS, and the results of electrochemical tests, the optimal particle size (≈70 nm) for superior supercapacitor performances in both acidic and alkaline electrolytes has been obtained. This important result provides a significant reference to guide future ZIF‐8 related research to achieve the best electrochemical performance.
[Ga3+8Sm3+2, Ga3+8Tb3+2] Metallacrowns are Highly Promising Ratiometric Luminescent Molecular Nanothermometers Operating at Physiologically Relevant Temperatures
Authors: Salerno Elvin V. , Zeler Justyna , Eliseeva Svetlana V. , Hernández‐Rodríguez Miguel A. , Carneiro Neto Albano N. , Petoud Stéphane , Pecoraro Vincent L. , Carlos Luís D. 
Published: July 2020

AbstractNanothermometry is the study of temperature at the submicron scale with a broad range of potential applications, such as cellular studies or electronics. Molecular luminescent‐based nanothermometers offer a non‐contact means to record these temperatures with high spatial resolution and thermal sensitivity. A luminescent‐based molecular thermometer comprised of visible‐emitting Ga3+/Tb3+ and Ga3+/Sm3+ metallacrowns (MCs) achieved remarkable relative thermal sensitivity associated with very low temperature uncertainty of Sr=1.9 % K−1 and δT<0.045 K, respectively, at 328 K, as an aqueous suspension of polystyrene nanobeads loaded with the corresponding MCs. To date, they are the ratiometric molecular nanothermometers offering the highest level of sensitivity in the physiologically relevant temperature range.
ACE2, the Receptor that Enables Infection by SARS‐CoV‐2: Biochemistry, Structure, Allostery and Evaluation of the Potential Development of ACE2 Modulators
Authors: Gross Lissy Z. F. , Sacerdoti Mariana , Piiper Albrecht , Zeuzem Stefan , Leroux Alejandro E. , Biondi Ricardo M. 
Published: July 2020

AbstractAngiotensin converting enzyme 2 (ACE2) is the human receptor that interacts with the spike protein of coronaviruses, including the one that produced the 2020 coronavirus pandemic (COVID‐19). Thus, ACE2 is a potential target for drugs that disrupt the interaction of human cells with SARS‐CoV‐2 to abolish infection. There is also interest in drugs that inhibit or activate ACE2, that is, for cardiovascular disorders or colitis. Compounds binding at alternative sites could allosterically affect the interaction with the spike protein. Herein, we review biochemical, chemical biology, and structural information on ACE2, including the recent cryoEM structures of full‐length ACE2. We conclude that ACE2 is very dynamic and that allosteric drugs could be developed to target ACE2. At the time of the 2020 pandemic, we suggest that available ACE2 inhibitors or activators in advanced development should be tested for their ability to allosterically displace the interaction between ACE2 and the spike protein.
The Bouguer‐Beer‐Lambert Law: Shining Light on the Obscure
Authors: Mayerhöfer Thomas G. , Pahlow Susanne , Popp Jürgen 
Published: July 2020

AbstractThe Beer‐Lambert law is unquestionably the most important law in optical spectroscopy and indispensable for the qualitative and quantitative interpretation of spectroscopic data. As such, every spectroscopist should know its limits and potential pitfalls, arising from its application, by heart. It is the goal of this work to review these limits and pitfalls, as well as to provide solutions and explanations to guide the reader. This guidance will allow a deeper understanding of spectral features, which cannot be explained by the Beer‐Lambert law, because they arise from electromagnetic effects/the wave nature of light. Those features include band shifts and intensity changes based exclusively upon optical conditions, i. e. the method chosen to record the spectra, the substrate and the form of the sample. As such, the review will be an essential tool towards a full understanding of optical spectra and their quantitative interpretation based not only on oscillator positions, but also on their strengths and damping constants.
Clinical and radiographic comparative study to evaluate the efficacy of restoring destroyed primary incisors using two different techniques—A pilot study
Authors: Ibrahim Seba , Nourallah Abdul Wahab 
Published: July 2020

AbstractObjective: The restoration of destroyed maxillary primary incisors is difficult because of the insufficient amount of coronal structure. This pilot study aimed to compare the efficacy of composite posts technique and glass fiber posts technique in restoring destroyed primary incisors.Materials and Methods: Thirty‐six destroyed maxillary primary incisors in 11 children with early childhood caries were randomly assigned after endodontic treatment into two groups: glass fiber posts (n = 18) and composite resin posts (n = 18). Blinded clinical evaluation was made at 3, 6, 9, and 12 months and Blinded radiographic evaluation was made at 6 and 12 months. The evaluation was according to the FDI criteria. Data were analyzed with Fisher's exact test (α = .05).Result: After 12 months post‐treatment, the success rates were 88.2% in glass fiber posts group and 70.6% in composite resin posts group. There was no statistically significant difference between the two groups according to the evaluation criteria (p‐value >.05).Conclusion: Glass fiber posts technique and Composite posts technique may be used in the restoration of destroyed primary incisors.
Crosslinked Resin‐Supported Bifunctional Organocatalyst for Conversion of CO2 into Cyclic Carbonates
Authors: Dong Tongfeng , Zheng Yu‐Jia , Yang Guan‐Wen , Zhang Yao‐Yao , Li Bo , Wu Guang‐Peng 
Published: July 2020

AbstractThe development of solvent‐free, metal‐free, recyclable organic catalysts is required for the current chemical fixation of carbon dioxide converted into cyclic carbonates. With the goal of reducing the cost, time, and energy consumption for the coupling reaction of CO2 and epoxides, a series of highly active heterogeneous catalysts, based on a thiourea and quaternary ammonium salt system, are synthesized by using a thiol‐ene click reaction under ultraviolet light. Benefitting from synergistic interactions of the electrophilic center (thiourea) and the nucleophilic site (ammonium bromide), the catalysts exhibit excellent catalytic selectivity (99 %) for the cycloaddition of carbon dioxide with a diverse range of epoxides under mild conditions (1.2 MPa, 100 °C). Moreover, the catalyst can be easily recycled by facile filtration and reused for 5 times without noticeable loss of activity and selectivity. This work provides a potential heterogeneous catalyst for the conversion of carbon dioxide into high value‐added chemicals with the combined advantages of low cost, easy recovery, and satisfactory catalytic properties.
Temperature‐dependent Battery Performance of a Na3V2(PO4)2F3@MWCNT Cathode and In‐situ Heat Generation on Cycling
Authors: Essehli Rachid , Amin Ruhul , Abouimrane Ali , Li Mengya , ben Yahia Hamdi , Maher Kenza , Zakaria Yahya , Belharouak Ilias 
Published: July 2020

AbstractExcellent structural stability, high operating voltage, and high capacity have made Na3V2(PO4)2F3 a promising cathode material for sodium‐ion batteries. However, high‐temperature battery performances and heat generation measurements have not been systematically reported yet. Carbon‐coated Na3V2(PO4)2F3@MWCNT (multi‐walled carbon nanotube) samples are fabricated by a hydrothermal‐assisted sol‐gel method and the electrochemical performances are evaluated at three different temperatures (25, 45, and 55 °C). The well‐crystallized Na3V2(PO4)2F3@MWCNT samples exhibit good cycling stability at both low and high temperatures; they deliver an initial discharge capacity of 120–125 mAhg−1 at a 1 C rate with a retention of 53 % capacity after 1,400 cycles with 99 % columbic efficiency. The half‐cell delivers a capacity of 100 mAhg−1 even at a high rate of 10 C at room temperature. Furthermore, the Na3V2(PO4)2F3@MWCNT samples show good long‐term durability; the capacity loss is an average of 0.05 % per cycle at a 1 C rate at 55 °C. Furthermore, ionic diffusivity and charge transfer resistance are evaluated as functions of state of charge, and they explain the high electrochemical performance of the Na3V2(PO4)2F3@MWCNT samples. In‐situ heat generation measurements reveal reversible results upon cycling owing to the high structural stability of the material. Excellent electrochemical performances are also demonstrated in the full‐cell configuration with hard carbon as well as antimony Sb/C anodes.