bluuebunny/crossref_metadata_2025_split huggingface dataset:
ICBP90 Regulates MIF Expression, Glucocorticoid Sensitivity, and Apoptosis at the MIF Immune Susceptibility Locus
Authors: Yao Jie , Leng Lin , Fu Weiling , Li Jia , Bronner Christian , Bucala Richard 
Published: April 2021

ObjectiveMacrophage migration inhibitory factor (MIF) is an inflammatory and neurorendocrine mediator that counterregulates glucocorticoid immunosuppression. MIF polymorphisms, which comprise a variant promoter microsatellite (−794 CATT5–8), are linked genetically to autoimmune disease severity and to glucocorticoid resistance. While invasive stimuli increase MIF expression, MIF also is up‐regulated by glucocorticoids, which serve as a physiologic regulator of inflammatory responses. This study was undertaken to define interactions between the MIF promoter, the glucocorticoid receptor (GR), and the transcription factor inverted CCAAT box binding protein 90 kd (ICBP90) (also referred to as UHRF1), which binds to the promoter in a −794 CATT5–8 length–dependent manner, to regulate MIF transcription.MethodsInteractions of ICBP90, GR, and activator protein 1 (AP‐1) with MIF −794 CATT5–8 promoter constructs were assessed by coimmunoprecipitation, Western blotting, and genetic knockdown. Nuclear colocalization studies were performed using anti–transcription factor antibodies and confocal microscopy of glucocorticoid‐treated cells. MIF transcription was studied in CEM‐C7 T cells, and the impact of the MIF −794 CATT5–8 microsatellite variation confirmed in peripheral blood T cells and in rheumatoid synovial fibroblasts of defined MIF genotype. Functional interactions were quantified by apoptosis and apoptotic signaling in high‐ and low‐genotypic MIF–expressing human cells.ResultsWe defined functional interactions between the transcription factors ICBP90, the GR, and AP‐1 that up‐regulated MIF transcription in a −794 CATT5–8 length–dependent manner. Experimental reduction of ICBP90, GR, or AP‐1 decreased MIF expression and increased glucocorticoid sensitivity, leading to enhanced apoptosis in T lymphocytes and in rheumatoid synovial fibroblasts.ConclusionThese findings suggest a mechanism for genetic variation of glucocorticoid‐regulated MIF transcription, with implications for autoimmune disease severity and glucocorticoid responsiveness.
Transcriptomic Evaluation of Juvenile Localized Scleroderma Skin With Histologic and Clinical Correlation
Authors: Schutt Christina , Mirizio Emily , Salgado Claudia , Reyes‐Mugica Miguel , Wang Xinjun , Chen Wei , Grunwaldt Lorelei , Schollaert Kaila L. , Torok Kathryn S. 
Published: April 2021

ObjectiveJuvenile localized scleroderma (LS) is an autoimmune disease of the skin whose pathogenesis is not well understood due to the rarity of the disease. This study was undertaken to determine the skin transcriptome in skin biopsy tissue from children with juvenile LS compared to pediatric healthy controls, with identification of significant molecular targets using RNA sequencing (RNA‐Seq). In this study, differentially expressed genes (DEGs) were assessed for correlations with histopathologic and clinical features in children with juvenile LS, and were used to group the children into distinct genetic clusters based on immunophenotype.MethodsRNA‐Seq was performed on sections of paraffin‐embedded skin tissue obtained from 28 children with juvenile LS and 10 pediatric healthy controls. RNA‐Seq was carried out using an Illumina HTS TruSeq RNA Access library prep kit, with data aligned using STAR and data analysis using a DESeq2 platform. A standardized histologic scoring system was used to score skin sections for the severity of inflammation and levels of collagen deposition. Histologic scoring was completed by 2 pathologists who were blinded with regard to the status of each sample. Spearman’s rank correlation coefficients were used to assess significant correlations between DEG expression profiles and skin histologic findings in patients with juvenile LS.ResultsWe identified 589 significant DEGs in children with juvenile LS as compared to healthy controls. Hierarchical clustering was used to demonstrate 3 distinct juvenile LS immunophenotype clusters. The histologic scores of skin inflammation (based on numbers and categories of inflammatory cell infiltrates) were significantly correlated with the expression levels of HLA–DPB1, HLA–DQA2, HLA–DRA, and STAT1 genes (rs > 0.5, P < 0.01). Collagen thickness correlated with the expression levels of collagen organization genes as well as with genes found to be correlated with the severity of inflammation, including genes for major histocompatibility complex (MHC) class I, MHC class II, and interferon‐γ signaling.ConclusionAmong children with juvenile LS, 3 distinct genetic signatures, or clusters, were identified. In one cluster, inflammation‐related pathways were up‐regulated, corresponding to the histologic skin inflammation score. In the second cluster, fibrosis‐related pathways were up‐regulated. In the third cluster, gene expression in the skin corresponded to the patterns seen in healthy controls. Up‐regulation of HLA class II genes was observed within the first cluster (characterized by predominant inflammation), a feature that has also been observed in the peripheral blood of patients with morphea and in the skin of patients with systemic sclerosis.
Bioinspired Heterocyclic Compounds as Corrosion Inhibitors: A Comprehensive Review
Authors: Goni Lipiar K. M. O. , Jafar Mazumder Mohammad A. , Quraishi M. A. , Mizanur Rahman Mohammad 
Published: April 2021

AbstractCorrosion is a phenomenon that devastatingly affects innovative, industrial, and mechanical applications, especially in the oil and gas industries. The corrosion conceivably influences industrial equipment; it deteriorates the environment and lessens the equipment/infrastructure's lifetime. Considering the significant impact of corrosion in our daily lives, this review article aims to briefly discuss the significance of corrosion and different control methods with special attention on corrosion inhibitors. The classification of corrosion inhibitors based on types and their advantage/limitations, and heterocyclic compounds as potential corrosion inhibitors, mainly nitrogen‐based compounds (pyridine (1N), pyrimidine (2N), and triazines (3N) fused ring benzimidazole, etc.), and their biological significance has been discussed in detail. The mechanism, challenges, and applications of heterocyclic compounds as corrosion inhibitors in various industrial relevant corrosive environments such as acid pickling, descaling operation in the desalination plant, oil gas industry, etc., have also been highlighted in the review.
Characterization of HIV‐1 virus‐like particles and determination of Gag stoichiometry for different production platforms
Authors: Lavado‐García Jesús , Jorge Inmaculada , Boix‐Besora Arnau , Vázquez Jesús , Gòdia Francesc , Cervera Laura 
Published: April 2021

AbstractThe importance of developing new vaccine technologies towards versatile platforms that can cope with global virus outbreaks has been evidenced with the most recent severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) pandemic. Virus‐like particles (VLPs) are a highly immunogenic, safe, and robust approach that can be used to base several vaccine candidates on. Particularly, HIV‐1 Gag VLPs is a flexible system comprising a Gag core surrounded by a lipid bilayer that can be modified to present diverse types of membrane proteins or antigens against several diseases, like influenza, dengue, West Nile virus, or human papillomavirus, where it has been proven successful. The size distribution and structural characteristics of produced VLPs vary depending on the cell line used to produce them. In this study, we established an analytical method of characterization for the Gag protein core and clarified the current variability of Gag stoichiometry in HIV‐1 VLPs depending on the cell‐based production platform, directly determining the number of Gag molecules per VLP in each case. Three Gag peptides have been validated to quantify the number of monomers using parallel reaction monitoring, an accurate and fast, mass‐spectrometry‐based method that can be used to assess the quality of the produced Gag VLPs regardless of the cell line used. An average of 3617 ± 17 monomers per VLP was obtained for HEK293, substantially varying between platforms, including mammalian and insect cells. This offers a key advantage in quantification and quality control methods to characterize VLP production at a large scale to accelerate new recombinant vaccine production technologies.
Gram‐scale production of the sesquiterpene α‐humulene with Cupriavidus necator
Authors: Milker Sofia , Sydow Anne , Torres‐Monroy Ingrid , Jach Guido , Faust Frederik , Kranz Lea , Tkatschuk Ljubov , Holtmann Dirk 
Published: April 2021

AbstractTerpenoids have an impressive structural diversity and provide valuable substances for a variety of industrial applications. Among terpenes, the sesquiterpenes (C15) are the largest subclass with bioactivities ranging from aroma to health promotion. In this article, we show a gram‐scale production of the sesquiterpene α‐humulene in final aqueous concentrations of 2 g L−1 with the recombinant strain Cupriavidus necator pKR‐hum in a fed‐batch mode on fructose as carbon source and n‐dodecane as an extracting organic phase for in situ product removal. Since C. necator is capable of both heterotrophic and autotrophic growth, we additionally modeled the theoretically possible yields of a heterotrophic versus an autotrophic process on CO2 in industrially relevant quantities. We compared the cost‐effectiveness of both processes based on a production of 10 t α‐humulene per year, with both processes performing equally with similar costs and gains. Furthermore, the expression and activity of 3‐hydroxymethylglutaryl‐CoA reductase (hmgR) from Myxococcus xanthus was identified as the main limitation of our constructed C. necator pKR‐hum strain. Thus, we outlined possible solutions for further improvement of our production strain, for example, the replacement of the hmgR from M. xanthus by a plant‐based variant to increase α‐humulene production titers in the future.
Engineering Clostridium cellulovorans for highly selective n‐butanol production from cellulose in consolidated bioprocessing
Authors: Bao Teng , Hou Wenjie , Wu Xuefeng , Lu Li , Zhang Xian , Yang Shang‐Tian 
Published: April 2021

AbstractCellulosic n‐butanol from renewable lignocellulosic biomass has gained increased interest. Previously, we have engineered Clostridium cellulovorans, a cellulolytic acidogen, to overexpress the bifunctional butyraldehyde/butanol dehydrogenase gene adhE2 from C. acetobutylicum for n‐butanol production from crystalline cellulose. However, butanol production by this engineered strain had a relatively low yield of approximately 0.22 g/g cellulose due to the coproduction of ethanol and acids. We hypothesized that strengthening the carbon flux through the central butyryl‐CoA biosynthesis pathway and increasing intracellular NADH availability in C. cellulovorans adhE2 would enhance n‐butanol production. In this study, thiolase (thlACA) from C. acetobutylicum and 3‐hydroxybutyryl‐CoA dehydrogenase (hbdCT) from C. tyrobutyricum were overexpressed in C. cellulovorans adhE2 to increase the flux from acetyl‐CoA to butyryl‐CoA. In addition, ferredoxin‐NAD(P)+ oxidoreductase (fnr), which can regenerate the intracellular NAD(P)H and thus increase butanol biosynthesis, was also overexpressed. Metabolic flux analyses showed that mutants overexpressing these genes had a significantly increased carbon flux toward butyryl‐CoA, which resulted in increased production of butyrate and butanol. The addition of methyl viologen as an electron carrier in batch fermentation further directed more carbon flux towards n‐butanol biosynthesis due to increased reducing equivalent or NADH. The engineered strain C. cellulovorans adhE2‐fnrCA‐thlACA‐hbdCT produced n‐butanol from cellulose at a 50% higher yield (0.34 g/g), the highest ever obtained in batch fermentation by any known bacterial strain. The engineered C. cellulovorans is thus a promising host for n‐butanol production from cellulosic biomass in consolidated bioprocessing.
Antibody disulfide bond reduction and recovery during biopharmaceutical process development—A review
Authors: Ren Tingwei , Tan Zhijun , Ehamparanathan Vivekh , Lewandowski Angela , Ghose Sanchayita , Li Zheng Jian 
Published: April 2021

AbstractAntibody disulfide bond reduction has been a challenging issue in monoclonal antibody manufacturing. It could lead to a decrease of product purity and failure to meet the targeted product profile and/or specifications. More importantly, disulfide bond reduction could also impact drug safety and efficacy. Scientists across the industry have been examining the root causes and developing mitigation strategies to address the challenge. In recent years, with the development of high titer mammalian cell culture processes to meet the rapidly growing demand for antibody biopharmaceuticals, disulfide bond reduction has been observed more frequently. Thus, it is necessary to continue evolving the disulfide reduction mitigation strategies and developing novel approaches to maintain high product quality. Additionally, in recent years as more complex molecules (such as bispecific and trispecific antibodies) emerge, the molecular heterogeneity due to incomplete formation of the interchain disulfide bonds becomes a more imperative challenging issue. Given the disulfide reduction challenges that biotech industry is facing, in this review, we provide a comprehensive scientific summary of the root cause analysis of disulfide reduction during process development of antibody therapeutics, mitigation strategies and its potential remediated recovery based on published papers. First, this paper intends to highlight different aspects of the root cause for disulfide reduction. Secondly, to provide a broader understanding of the disulfide bond reduction in downstream process, this paper discusses disulfide bond reduction impact on product stability, associated analytical methods for disulfide bond reduction detection and characterization, process control strategies as well as their manufacturing implementation. In addition, brief perspectives on the development of future mitigation strategies are also reviewed, including platform alignment, mitigation strategy application for the emerging new modalities such as bispecific and trispecific antibodies as well as using machine learning to identify molecule susceptibility of disulfide bond reduction. The data in this review are originated from the published papers.
Sustainable product innovation and changing consumer behavior: Sustainability affordances as triggers of adoption and usage
Authors: Pinkse Jonatan , Bohnsack René 
Published: April 2021

AbstractThis conceptual paper argues that for sustainable product innovation to make a contribution to addressing sustainability issues, we need to understand not only why consumers adopt sustainable products but also what makes them use these in sustainable way. To explain how specific product features can change the ways in which consumers engage with sustainable products in the adoption and usage phase, we draw on affordance theory. Affordances refer to the potential for agentic action of users in relation to a technological object. We develop a conceptual framework that explains how sustainable product innovation can lead to the design of sustainability affordances that stimulate adoption and sustainable usage. The framework shows how three forms of agency—material, firm, and user agency—interact and together influence a product's sustainability affordances that drive adoption and a change in consumer behavior. The framework explains how trade‐offs between a product's environmental features and consumer expectations regarding desired functionalities and user experience can be overcome.
A virtual reality experiment system for an introductory computer hardware course
Authors: Chen Xinrun , Chen Hengxin , Guo Songtao , Li Jie , Zhang Jie , Li Zihao 
Published: April 2021

AbstractThe University Computer Foundation (UCF) course, which is a compulsory theoretical course for freshmen, especially science and engineering department students, lays the foundation for more advanced courses. However, the UCF course covers a wide variety of concepts, including the computer hardware, which are difficult for freshmen to comprehend. In recent years, virtual reality (VR) has become prevalent in many educational settings. To improve the teaching of the UCF course, we developed a VR program about introductory computer hardware and invited freshmen from two universities in China to take part in the experiment as participants. Four aspects of computer contents, namely the evolutionary history of computers, the computer components, the computer assembly, and the workflow of computer hardware, are displayed in the program. During the experiment, students' behavioral data were recorded. Then, the data were analyzed and the reasons were speculated for the differences among groups of various categories. From the experiment, the relationships between the students' behavior and their groups were found, and we demonstrated that our VR program is effective at attracting the students' curiosity and increasing their understanding of computer hardware in the UCF course. The study concludes with suggestions for practitioners and researchers in the field of VR for university education.
Predictors and potential advantages of PERT and advanced therapy use in acute pulmonary embolism
Authors: Parikh Melanie , Chahine Nicole M. , Hammad Tarek A. , Tefera Leben , Li Jun , Carman Teresa , Schilz Robert , Shishehbor Mehdi H. 
Published: April 2021

AbstractObjectivesWe sought to examine predictors of pulmonary embolism response team (PERT) utilization and identify those who could benefit from advanced therapy.BackgroundPERT and advanced therapy use remain low. Current risk stratification tools heavily weight age and comorbidities, which may not always correlate with presentation's severity.MethodsWe prospectively studied patients with CT‐confirmed PE between January 2019 and December 2019 at our hospital. PERT activation was left to the treating physician. Multivariable analyses were utilized to identify predictors of PERT activation and advanced therapy. Using the log odd ratio of each significant predictor of advanced therapy, we created a scoring system and a score of 2 was associated with the highest use. Primary outcomes were 30‐ and 90‐day all‐cause mortality, readmission, and major bleed.ResultsOf the 307 patients, PERT was activated in 22.5%. While abnormal vital signs and right ventricular (RV) strain were associated with PERT activation, pulmonary embolism severity index (PESI) was not. Advanced therapy use was significantly higher in the PERT cohort (35% vs 2%). Predictors of advanced therapy use were composite variable (heart rate > 110 or systolic blood pressure < 100 or respiratory rate > 30 or oxygen saturation < 90%) and right‐to‐left ventricular ratio > 0.9. PERT patients with advanced therapy use, when compared to the no‐PERT patients who could have qualified (score of 2), had significantly lower 30‐ and 90‐day mortality and 30‐day readmission without difference in major bleed.ConclusionPERT has important therapeutic impact, yet no guidelines to direct activation. We recommend a multidisciplinary approach for higher acuity pulmonary embolism cases and physician education regarding PERT and the scope of advanced therapy use.
Study of CO2 Sorption Kinetics on Electrospun Polyacrylonitrile‐Based Carbon Nanofibers
Authors: Kretzschmar Ansgar , Selmert Victor , Weinrich Henning , Kungl Hans , Tempel Hermann , Eichel Rüdiger‐A. 
Published: April 2021

AbstractElectrospun carbon nanofibers (CNFs) exhibit a decent CO2 sorption capacity and outstanding CO2/N2 selectivity. In this work, the sorption rate as another practically relevant parameter for CO2 adsorption is analyzed for different carbonization temperatures. Equilibration curves obtained from different CO2 sorption isotherms are discussed qualitatively and quantitatively, employing empirical models for pseudo‐first‐ and second‐order reactions. The sorption rate constants are found to be highly dependent on the carbonization temperature of the CNFs and the applied pressure during the measurement. Furthermore, two distinct processes of sorption are observed, which are attributed to different sorption sites on the surface and the inner volume of the CNFs.
Determination of Operating Parameters for the Use of an Electrostatically Charged Water Spray Mist
Authors: Zillgitt Marcel , Schmidt Eberhard 
Published: April 2021

AbstractTo reduce diffuse dust emissions for the small particle size range, the electrostatic charging of water droplets provided by spray nozzle systems is required. The electrostatic two‐fluid nozzle employed for this purpose was examined under laboratory conditions with regard to the applied voltage and the water volume flow rate. By determining the mass‐specific charge of the droplet collective and by evaluating the elementary charges as a function of the droplet residence time within a volume element of the electrode, an operating point for the real application of this new two‐fluid nozzle was found.
Origin of High Interfacial Resistance in Solid‐State Batteries: LLTO/LCO Half‐Cells**
Authors: Xu Pengyu , Rheinheimer Wolfgang , Mishra Avanish , Shuvo Shoumya Nandy , Qi Zhimin , Wang Haiyan , Dongare Avinash M. , Stanciu Lia A. 
Published: April 2021

AbstractThe interface between cathode and electrolyte is a significant source of large interfacial resistance in solid‐state batteries (SSBs). Spark plasma sintering (SPS) allows densifying electrolyte and electrodes in one step, which can improve the interfacial contact in SSBs and significantly shorten the processing time. In this work, we proposed a two‐step joining process to prepare cathode (LiCoO2, LCO)/electrolyte (Li0.33La0.57TiO3, LLTO) half cells via SPS. Interdiffusion between Ti4+/Co3+ was observed at the interface by SEM/STEM, resulting in the formation of the Li−Ti−La−Co−O and Li−Ti−Co−O phases in LLTO and the Li−Co−Ti−O phase in LCO. Computational modeling was performed to verify that the Li−Ti−Co−O phase has a LiTi2O4 host lattice. In a study of interfacial electrical properties, the resistance of this interdiffusion layer was found to be 105 Ω, which is 40 times higher than the resistance of the individual LLTO phase. The formation of an interdiffusion layer is identified as the origin of the high interface resistance in the LLTO/LCO half‐cell.
Formulation of Next‐Generation Multicompartment Microcapsules by Reversible Electrostatic Attraction
Authors: Neumann Christian , Bacher Lisa , Musyanovych Anna , Tutus Murat , Latnikova Alexandra 
Published: April 2021

AbstractThe combination of several active substances into one carrier is often limited due to solubility, stability and phase‐separation issues. These issues have been addressed by an innovative capsule design, in which nanocapsules are assembled on the microcapsule surface by electrostatic forces to form a pH‐responsive hierarchical capsule@capsule system. Here, melamine‐formaldehyde (MF) microcapsules with a negative surface charge were synthesized and coated with a novel MF‐polyethyleneimine (PEI) copolymer to achieve a positive charge of ζ=+28 mV. This novel coating procedure allows the electrostatic assembly of negatively charged poly‐l‐lactide (PLLA, ζ=−19 mV) and poly‐(lactide‐co‐glycolide) (PLGA, ζ=−56 mV) nanocapsules on the microcapsule surface. Assembly studies at pH 7 gave a partial surface coverage of PLLA nanocapsules and full surface coverage for PLGA nanocapsules. The pH‐responsive adsorption and desorption of nanocapsules was shown at pH 7 and pH 3.