4,755 results on '"Arthur, J. A."'
Search Results
2. A Fast-Binding, Functionally Reversible, COX‑2 Radiotracer for CNS PET Imaging
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Michael S. Placzek, Daniel K. Wilton, Michel Weïwer, Mariah A. Manter, Sarah E. Reid, Christopher J. Meyer, Arthur J. Campbell, Besnik Bajrami, Antoine Bigot, Sarah Bricault, Agathe Fayet, Arnaud Frouin, Frederick Gergits, Mehak Gupta, Wei Jiang, Michelle Melanson, Chiara D. Romano, Misha M. Riley, Jessica M. Wang, Hsiao-Ying Wey, Florence F. Wagner, Beth Stevens, and Jacob M. Hooker
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Chemistry ,QD1-999 - Published
- 2024
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3. Synthesis of Red, Green, and Blue Carbon Quantum Dots and Construction of Multicolor Cellulose‐Based Light‐Emitting Diodes
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Xinrui Chen, Xing Han, Caixia Zhang, Xue Ou, Xiaoli Liu, Junhua Zhang, Wei Liu, Arthur J. Ragauskas, Xueping Song, and Zhanying Zhang
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carbon quantum dots ,cellulose nanofibrils ,light‐emitting diodes ,thin‐film encapsulation ,UV curable acrylic resins ,Physics ,QC1-999 ,Chemistry ,QD1-999 - Abstract
Light‐emitting diodes (LEDs) are widely used in lighting and display applications. Carbon quantum dots (CQDs), which have high biocompatibility, high resistance to photobleaching, and full‐spectrum luminescence, have inherent advantages as fluorescent materials for LED devices. Herein, multicolor CQDs are prepared by a new reagent engineering strategy due to the difference of effective conjugate length and the surface electron‐withdrawing groups of CQDs. White CQDs are realized by mixing blue, green, and red CQDs proportionally. Then, the aggregation‐caused quenching phenomenon of CQDs is suppressed through the hydrogen‐bonding network of cellulose nanofibrils (CNFs). Multicolor fluorescent films are prepared from CQDs and CNFs by simple mixing and casting methods. Finally, thin‐film encapsulation based on the photosensitive resin ABPE‐10 coating can be realized and rapidly assembles into fluorescent films with different light‐emitting colors into LED devices, leading to have superior thermal performance compared with conventional LEDs. White LEDs have excellent white‐light illumination performance, with Commission Internationale de L’Eclairage color coordinates of (0.33, 0.37), a correlated color temperature of 5688 K, and a color rendering index of 86. This strategy provides a convenient and scalable pathway for low‐cost, environmentally friendly, and high‐performance CQDs‐based LEDs.
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- 2024
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4. Some Experiments in Sulfur-Nitrogen Chemistry.
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Banister, Arthur J. and Smith, Nigel R. M.
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Briefly surveys the main structural types of sulfur-nitrogen compounds, and describes syntheses, suitable as undergraduate experiments, which illustrate four of the five types of cyclic species. Laboratory procedures, background information, and discussion of results for these experiments are provided. (Author/JN)
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- 1982
5. Terephthalic Acid Copolyesters Containing Tetramethylcyclobutanediol for High‐Performance Plastics
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Dr. Samarthya Bhagia, Dr. Kamlesh Bornani, Dr. Soydan Ozcan, and Dr. Arthur J. Ragauskas
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polyester ,copolyesters ,plastic recycling ,terephthalic acid ,tetramethylcyclobutanediol ,ethylene glycol ,Chemistry ,QD1-999 - Abstract
Abstract There is a need for high‐performance applications for terephthalic acid (TPA) polyesters with high heat resistance, impact toughness, and optical clarity. Bisphenol A (BPA) based polycarbonates and polyarylates have such properties, but BPA is an endocrine disruptor. Therefore, new TPA polyesters that are less hazardous to health and the environment are becoming popular. Tetramethylcyclobutanediol (TMCD) is a difunctional monomer that can be polymerized with TPA and other diols to yield copolyesters with superior properties to conventional TPA polyesters. It has a cyclobutyl ring that makes it more rigid than cyclohexanedimethanol (CHDM) and EG. Thus, TMCD containing TPA copolyesters can have high heat resistance and impact strength. TPA can be made from abundantly available upcycled polyethylene terephthalate (PET). Therefore, this review discusses the synthesis of monomers and copolyesters, the impact of diol composition on material properties, molecular weight, effects of photodegradation, health safety, and substitution of cyclobutane diols for future polyesters.
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- 2021
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6. Synthesis, Characterization, and Utilization of a Lignin-Based Adsorbent for Effective Removal of Azo Dye from Aqueous Solution
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Xianzhi Meng, Brent Scheidemantle, Mi Li, Yun-yan Wang, Xianhui Zhao, Miguel Toro-González, Priyanka Singh, Yunqiao Pu, Charles E. Wyman, Soydan Ozcan, Charles M. Cai, and Arthur J. Ragauskas
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Chemistry ,QD1-999 - Published
- 2020
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7. Electrochemical Deposition of Conformal Semiconductor Layers in Nanoporous Oxides for Sensitized Photoelectrodes
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Jae Hyun Park, Qing Wang, Kai Zhu, Arthur J. Frank, and Jin Young Kim
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Chemistry ,QD1-999 - Published
- 2019
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8. Stereolithography 3D Printing of Lignin-Reinforced Composites with Enhanced Mechanical Properties
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Shuyang Zhang, Mi Li, Naijia Hao, and Arthur J. Ragauskas
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Chemistry ,QD1-999 - Published
- 2019
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9. ATP8B1 Deficiency Results in Elevated Mitochondrial Phosphatidylethanolamine Levels and Increased Mitochondrial Oxidative Phosphorylation in Human Hepatoma Cells
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Valentina E. Gómez-Mellado, Jung-Chin Chang, Kam S. Ho-Mok, Carmen Bernardino Morcillo, Remco H. J. Kersten, Ronald P. J. Oude Elferink, Arthur J. Verhoeven, and Coen C. Paulusma
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phosphatidylethanolamine ,flippase ,ATP8B1 ,mitochondria ,OXPHOS ,LDLR ,Biology (General) ,QH301-705.5 ,Chemistry ,QD1-999 - Abstract
ATP8B1 is a phospholipid flippase that is deficient in patients with progressive familial intrahepatic cholestasis type 1 (PFIC1). PFIC1 patients suffer from severe liver disease but also present with dyslipidemia, including low plasma cholesterol, of yet unknown etiology. Here we show that ATP8B1 knockdown in HepG2 cells leads to a strong increase in the mitochondrial oxidative phosphorylation (OXPHOS) without a change in glycolysis. The enhanced OXPHOS coincides with elevated low-density lipoprotein receptor protein and increased mitochondrial fragmentation and phosphatidylethanolamine levels. Furthermore, expression of phosphatidylethanolamine N-methyltransferase, an enzyme that catalyzes the conversion of mitochondrial-derived phosphatidylethanolamine to phosphatidylcholine, was reduced in ATP8B1 knockdown cells. We conclude that ATP8B1 deficiency results in elevated mitochondrial PE levels that stimulate mitochondrial OXPHOS. The increased OXPHOS leads to elevated LDLR levels, which provides a possible explanation for the reduced plasma cholesterol levels in PFIC1 disease.
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- 2022
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10. 4D Flow MRI in Ascending Aortic Aneurysms: Reproducibility of Hemodynamic Parameters
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Joe F. Juffermans, Hans C. van Assen, Bastiaan J. C. te Kiefte, Mitch J. F. G. Ramaekers, Roel L. F. van der Palen, Pieter van den Boogaard, Bouke P. Adriaans, Joachim E. Wildberger, Ilona A. Dekkers, Arthur J. H. A. Scholte, Simon Schalla, Hildo J. Lamb, and Jos J. M. Westenberg
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aorta ,aneurysm ,hemodynamic ,4D flow MRI ,reproducibility ,Technology ,Engineering (General). Civil engineering (General) ,TA1-2040 ,Biology (General) ,QH301-705.5 ,Physics ,QC1-999 ,Chemistry ,QD1-999 - Abstract
(1) Background: Aorta hemodynamics have been associated with aortic remodeling, but the reproducibility of its assessment has been evaluated marginally in patients with thoracic aortic aneurysm (TAA). The current study evaluated intra- and interobserver reproducibility of 4D flow MRI-derived hemodynamic parameters (normalized flow displacement, flow jet angle, wall shear stress (WSS) magnitude, axial WSS, circumferential WSS, WSS angle, vorticity, helicity, and local normalized helicity (LNH)) in TAA patients; (2) Methods: The thoracic aorta of 20 patients was semi-automatically segmented on 4D flow MRI data in 5 systolic phases by 3 different observers. Each time-dependent segmentation was manually improved and partitioned into six anatomical segments. The hemodynamic parameters were quantified per phase and segment. The coefficient of variation (COV) and intraclass correlation coefficient (ICC) were calculated; (3) Results: A total of 2400 lumen segments were analyzed. The mean aneurysm diameter was 50.8 ± 2.7 mm. The intra- and interobserver analysis demonstrated a good reproducibility (COV = 16–30% and ICC = 0.84–0.94) for normalized flow displacement and jet angle, a very good-to-excellent reproducibility (COV = 3–26% and ICC = 0.87–1.00) for all WSS components, helicity and LNH, and an excellent reproducibility (COV = 3–10% and ICC = 0.96–1.00) for vorticity; (4) Conclusion: 4D flow MRI-derived hemodynamic parameters are reproducible within the thoracic aorta in TAA patients.
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- 2022
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11. Chemically Cross-Linked Cellulose Nanocrystal Aerogels for Effective Removal of Cation Dye
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Luna Liang, Shuyang Zhang, Gabriel A. Goenaga, Xianzhi Meng, Thomas A. Zawodzinski, and Arthur J. Ragauskas
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cellulose nanocrystals ,aerogel ,chemical cross-linking ,adsorption ,cation dye ,Chemistry ,QD1-999 - Abstract
In this study, porous aerogels were prepared by directional freeze-drying via cross-linking cellulose nanocrystals (CNCs) with poly(methyl vinyl ether-co-maleic acid) (PMVEMA) and poly(ethylene glycol) (PEG). The thermal properties and physical adsorption performance toward cation methylene blue dye of the obtained CNC aerogels were investigated. The maximum degradation temperature was increased from 324°C of CNCs to 355°C of cross-linked CNC aerogels. The dye adsorption isotherm results showed that the maximum methylene blue adsorption capacity of CNC aerogels was 116.2 mg g−1, according to the Langmuir model, which was mainly due to the electrostatic attractions between negatively charged carboxyl groups or sulfonate groups on the CNC aerogles and cation MB molecules. The reusability test showed that the CNC aerogels contained the same dye adsorption performance in five adsorption/desorption cycles. Overall, this study described an ideal alternative for water purification with high dye adsorption capacity and enhanced physical performance.
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- 2020
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12. HDAC6 Brain Mapping with [18F]Bavarostat Enabled by a Ru-Mediated Deoxyfluorination
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Martin G. Strebl, Arthur J. Campbell, Wen-Ning Zhao, Frederick A. Schroeder, Misha M. Riley, Peter S. Chindavong, Thomas M. Morin, Stephen J. Haggarty, Florence F. Wagner, Tobias Ritter, and Jacob M. Hooker
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Chemistry ,QD1-999 - Published
- 2017
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13. Highly selective hydrogenation of phenol to cyclohexanone over a Pd-loaded N-doped carbon catalyst derived from chitosan
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Shitao Yu, Lu Wang, Arthur J. Ragauskas, Lang Huang, Qiong Wu, and Baozheng Zhao
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Chitosan ,Phenol ,Cyclohexanones ,Cyclohexanol ,Cyclohexanone ,chemistry.chemical_element ,Carbon ,Surfaces, Coatings and Films ,Electronic, Optical and Magnetic Materials ,Catalysis ,Biomaterials ,chemistry.chemical_compound ,Hydrothermal carbonization ,Colloid and Surface Chemistry ,Phenols ,chemistry ,Organic chemistry ,Hydrogenation ,Lewis acids and bases ,Selectivity - Abstract
A highly stable Pd-loaded N-doped carbon catalyst (ACNpd) for phenol hydrogenation was prepared from chitosan by hydrothermal carbonization. ACNpd does not require a reduction step before catalytic use due to the Pd in the as-prepared catalyst mainly exists in the form of Pd0 (80%). The carbon support involves N-containing groups such as pyridinic nitrogen and pyrrolic nitrogen, which could provide basic sites to adsorb phenol effectively. The as-fabricated ACNpd shows high catalytic performance with turnover frequency (TOF) of 29.34 h−1. Accordingly, a phenol conversion of 100% and a cyclohexanone selectivity of 99.1% are achieved in 5 h at 100 °C and 1 MPa H2. This outstanding performance is attributed to the synergetic effects of the Pd particles, the N-functional groups, and the Lewis acid sites on the support. The carbon support presents intrinsic Lewis acid sites due to its electrophilicity, and Pd doping further increases the strength of such acid sites as it causes electron-deficient structural features. Moreover, the Lewis acid sites inhibit the over-hydrogenation from cyclohexanone to cyclohexanol. This study provides new insights into the application of functional biomass-based carbon materials as catalyst supports.
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- 2022
14. Changes of Coenzyme A and Acetyl-Coenzyme A Concentrations in Rats after a Single-Dose Intraperitoneal Injection of Hepatotoxic Thioacetamide Are Not Consistent with Rapid Recovery
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Yevgeniya I. Shurubor, Arthur J. L. Cooper, Andrey B. Krasnikov, Elena P. Isakova, Yulia I. Deryabina, M. Flint Beal, and Boris F. Krasnikov
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acetyl-coenzyme A ,coenzyme A ,hepatic encephalopathy ,high performance liquid chromatography ,thioacetamide ,Biology (General) ,QH301-705.5 ,Chemistry ,QD1-999 - Abstract
Small biomolecules, such as coenzyme A (CoA) and acetyl coenzyme A (acetyl-CoA), play vital roles in the regulation of cellular energy metabolism. In this paper, we evaluated the delayed effect of the potent hepatotoxin thioacetamide (TAA) on the concentrations of CoA and acetyl-CoA in plasma and in different rat tissues. Administration of TAA negatively affects liver function and leads to the development of hepatic encephalopathy (HE). In our experiments, rats were administered a single intraperitoneal injection of TAA at doses of 200, 400, or 600 mg/kg. Plasma, liver, kidney, and brain samples were collected six days after the TAA administration, a period that has been suggested to allow for restoration of liver function. The concentrations of CoA and acetyl-CoA in the group of rats exposed to different doses of TAA were compared to those observed in healthy rats. The results obtained indicate that even a single administration of TAA to rats is sufficient to alter the physiological balance of CoA and acetyl-CoA in the plasma and tissues of rats for an extended period of time. The initial concentrations of CoA and acetyl-CoA were not restored even after the completion of the liver regeneration process.
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- 2020
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15. The Resolution of DL-Histidine, An Organic Chemistry Experiment Using an Ion Exchange Resin
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Bosch, Arthur J.
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- 1969
16. Aqueous angiography in pre‐glaucomatous and glaucomatous ADAMTS10 ‐mutant canine eyes: A pilot study
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Jessica B Burn, Chris G Pirie, András M. Komáromy, Alex S. Huang, and Arthur J. Weber
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Indocyanine Green ,medicine.medical_specialty ,genetic structures ,Pulsatile flow ,Lumen (anatomy) ,Pilot Projects ,Article ,Aqueous Humor ,Recovery period ,chemistry.chemical_compound ,Dogs ,Optical coherence tomography ,Ophthalmology ,Computer software ,medicine ,Animals ,Dog Diseases ,Fluorescein Angiography ,Intraocular Pressure ,General Veterinary ,medicine.diagnostic_test ,business.industry ,Glaucoma ,eye diseases ,Sclera ,medicine.anatomical_structure ,chemistry ,Angiography ,sense organs ,business ,Indocyanine green ,Tomography, Optical Coherence - Abstract
Objective To evaluate intravenous scleral and intracameral aqueous angiography in normotensive (n = 4) and hypertensive glaucomatous (n = 6) ADAMTS10-mutant canine eyes. Animals studied Ten ADAMTS10-mutant dogs were used in this study. Procedures Dogs were sedated and one eye from each dog underwent scleral angiography following intravenous injection of 0.25% indocyanine green (ICG). After a 24-h recovery period, the same eye underwent aqueous angiography via intracameral administration of ICG. Imaging of identical scleral sectors from the same eye was performed using a Heidelberg Spectralis® Confocal Scanning Laser Ophthalmoscope. Intrascleral vessel depth and lumen diameters were measured using Heidelberg Spectralis® optical coherence tomography and computer software. Results Scleral angiography permitted visualization of vascular components associated with conventional aqueous humor outflow pathways with an average time from injection to fluorescence of 35.8 ± 10.6 s (mean ± SD). Two normotensive eyes (2/10;20%) demonstrated turbulent dye movement, while 4 hypertensive eyes (4/10;40%) exhibited laminar flow. Aqueous angiography demonstrated dye fluorescence within the post-trabecular conventional aqueous humor outflow pathways in all 10 eyes at 34.3 ± 11.0 s post-injection. Sectoral and dynamic outflow patterns were observed primarily within the superotemporal sector in nine eyes (9/10; 90%). Seven eyes (7/10; 70%) demonstrated pulsatile dye movement and five eyes (5/10; 50%) exhibited laminar flow. The degree of laminar movement of dye was greatest in hypertensive eyes. Vessel lumen diameters measured 133.85 ± 28.36 µm and 161.18 ± 6.02 µm in hypertensive and normotensive eyes, respectively. Conclusions Aqueous angiography allowed for visualization of fluorescent dye in the superotemporal sclera. Laminar flow and smaller lumen vessels were observed mainly in hypertensive eyes.
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- 2021
17. Recycled Cardboard Containers as a Low Energy Source for Cellulose Nanofibrils and Their Use in Poly(<scp>l</scp>-lactide) Nanocomposites
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Douglas J. Gardner, Lu Wang, Katie Copenhaver, Arthur J. Ragauskas, Holly E. Hinton, Halil Tekinalp, Meghan E. Lamm, Yunqiao Pu, Yousoo Han, Soydan Ozcan, Colleen C. Walker, Kai Li, Xianhui Zhao, Samarthya Bhagia, and Donna Johnson
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Nanocomposite ,Materials science ,Renewable Energy, Sustainability and the Environment ,General Chemical Engineering ,cardboard ,General Chemistry ,chemistry.chemical_compound ,Low energy ,Chemical engineering ,chemistry ,visual_art ,Poly-L-lactide ,visual_art.visual_art_medium ,Environmental Chemistry ,Cellulose - Published
- 2021
18. Structural basis for tRNA methylthiolation by the radical SAM enzyme MiaB
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Arthur J. Arcinas, Tyler L. Grove, Bo Wang, Carsten Krebs, Neela H. Yennawar, Squire J. Booker, Olga Esakova, and Steven C. Almo
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Models, Molecular ,S-Adenosylmethionine ,Adenosine ,Stereochemistry ,Article ,Substrate Specificity ,Isopentenyladenosine ,Protein Domains ,RNA, Transfer ,Metalloprotein ,Bacteroides ,Molecule ,Sulfhydryl Compounds ,chemistry.chemical_classification ,Binding Sites ,Multidisciplinary ,Chemistry ,RNA-Binding Proteins ,Substrate (chemistry) ,Translation (biology) ,Methyltransferases ,TRNA methylthiolation ,Sulfurtransferases ,Transfer RNA ,Biocatalysis ,RNA ,Radical SAM - Abstract
Numerous post-transcriptional modifications of transfer RNAs have vital roles in translation. The 2-methylthio-N6-isopentenyladenosine (ms2i6A) modification occurs at position 37 (A37) in transfer RNAs that contain adenine in position 36 of the anticodon, and serves to promote efficient A:U codon–anticodon base-pairing and to prevent unintended base pairing by near cognates, thus enhancing translational fidelity1–4. The ms2i6A modification is installed onto isopentenyladenosine (i6A) by MiaB, a radical S-adenosylmethionine (SAM) methylthiotransferase. As a radical SAM protein, MiaB contains one [Fe4S4]RS cluster used in the reductive cleavage of SAM to form a 5ʹ-deoxyadenosyl 5ʹ-radical, which is responsible for removing the C2 hydrogen of the substrate5. MiaB also contains an auxiliary [Fe4S4]aux cluster, which has been implicated6–9 in sulfur transfer to C2 of i6A37. How this transfer takes place is largely unknown. Here we present several structures of MiaB from Bacteroides uniformis. These structures are consistent with a two-step mechanism, in which one molecule of SAM is first used to methylate a bridging µ-sulfido ion of the auxiliary cluster. In the second step, a second SAM molecule is cleaved to a 5ʹ-deoxyadenosyl 5ʹ-radical, which abstracts the C2 hydrogen of the substrate but only after C2 has undergone rehybridization from sp2 to sp3. This work advances our understanding of how enzymes functionalize inert C–H bonds with sulfur. Crystal structures reveal the catalytic mechanism through which the radical S-adenosylmethionine enzyme MiaB adds a methylthio group onto tRNA.
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- 2021
19. Recent Advances in the Synthesis of Deuterium‐Labeled Compounds
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Arthur J. Ragauskas, Haoxi Ben, and Xiaoli Yang
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Chemistry ,Organic Chemistry ,Radiochemistry ,Regioselectivity ,Hydrogen–deuterium exchange ,Deuterium labeled - Published
- 2021
20. Effect of Dilute Acetic Acid Hydrolysis on Xylooligosaccharide Production and the Inhibitory Effect of Cellulolytic Enzyme Lignin from Poplar
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Ying Zhang, Peiyao Wen, Junhua Zhang, Jinye Wang, Liting Wei, Arthur J. Ragauskas, Tian Zhang, and Yong Xu
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chemistry.chemical_classification ,Renewable Energy, Sustainability and the Environment ,General Chemical Engineering ,General Chemistry ,chemistry.chemical_compound ,Acetic acid ,Hydrolysis ,Enzyme ,chemistry ,Environmental Chemistry ,Lignin ,Organic chemistry ,Inhibitory effect ,Xylooligosaccharide - Published
- 2021
21. Phototunable Lignin Plastics to Enable Recyclability
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Furong Lin, Hung-Jue Sue, Arthur J. Ragauskas, Chenxuan Li, Jinghao Li, Xianzhi Meng, Zhi-Hua Liu, Susie Y. Dai, Cheng Hu, Mingzhen Zhao, Qiang Li, Lei Fang, Naijia Hao, and Joshua S. Yuan
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Materials science ,Depolymerization ,Bioconversion ,General Chemical Engineering ,Material Design ,Methacrylate ,chemistry.chemical_compound ,General Energy ,Petrochemical ,Chemical engineering ,chemistry ,Photocatalysis ,Environmental Chemistry ,Lignin ,General Materials Science ,Polymer blend - Abstract
The accumulation of non-degradable petrochemical plastics imposes a significant threat to the environment and ecosystems. We addressed this challenge by designing a new type of phototunable plastics based on the unique lignin chemistry to enable readily end-life recycling. The advanced material design leveraged the efficient photocatalytic lignin depolymerization by ZnO nanoparticles to build lignin-polymethyl methacrylate (PMMA)-ZnO blends. We first demonstrated the highly effective phototunable lignin depolymerization in the complex polymer blend matrix and explored the molecular mechanisms. The technical barriers of mechanical property and recycling processing were then addressed by a new blend design with lignin core grafted with PMMA polymer. The new process has resulted in a new type of PMMA-g-lignin blend, which significantly improved the mechanical properties, making it comparable to PMMA alone. More importantly, the mechanical properties of the UV-treated blend decreased drastically in the new design, whereas the properties did not reduce in the non-grafted blends upon UV exposure. The results highlighted that the new blend design based on graftization maximized the impact of lignin depolymerization on blend structure and recyclability. Based on the results, we developed a process integrating UV and alkaline treatments to recycle PMMA for plastics and fractionated lignin for bioconversion or other applications in the new phototunable plastics.
- Published
- 2021
22. Influence of ZCuOH, Z2Cu, and Extraframework CuxOy Species in Cu-SSZ-13 on N2O Formation during the Selective Catalytic Reduction of NOx with NH3
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Ishant Khurana, Arthur J. Shih, Aída Luz Villa, Lucía Pérez Ramírez, Ashok Kumar, L Andres Peña, and Juan M. González
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SSZ-13 ,Chemistry ,Selective catalytic reduction ,General Chemistry ,Photochemistry ,Catalysis ,NOx - Published
- 2021
23. Discovery of a First-in-Class Inhibitor of the PRMT5–Substrate Adaptor Interaction
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Dale Porter, Alessandra Ianari, Merissa Brousseau, Patrick McCarren, Foxy P. Robinson, Adam Skepner, Virendar K. Kaushik, Kathleen M. Mulvaney, Arthur J. Campbell, Martin J Drysdale, Zachary Mullin-Bernstein, Brian J. McMillan, Robert Hilgraf, Ritu Singh, Matthew J. Ranaghan, Meghan O’Keefe, William R. Sellers, David C. McKinney, Jamie A. Moroco, Michael F. Mesleh, David E. Timm, Besnik Bajrami, and Florence F. Wagner
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Models, Molecular ,Protein-Arginine N-Methyltransferases ,Spliceosome ,Dose-Response Relationship, Drug ,Molecular Structure ,biology ,Stereochemistry ,fungi ,Signal transducing adaptor protein ,Methylation ,Small molecule ,Article ,Pyridazines ,Structure-Activity Relationship ,chemistry.chemical_compound ,Histone ,chemistry ,Covalent bond ,Drug Discovery ,biology.protein ,Humans ,Molecular Medicine ,Lead compound ,Adaptor Proteins, Signal Transducing ,Cysteine - Abstract
PRMT5 and its substrate adaptor proteins (SAPs), pICln and Riok1, are synthetic lethal dependencies in MTAP-deleted cancer cells. SAPs share a conserved PRMT5 binding motif (PBM) which mediates binding to a surface of PRMT5 distal to the catalytic site. This interaction is required for methylation of several PRMT5 substrates, including histone and spliceosome complexes. We screened for small molecule inhibitors of the PRMT5-PBM interaction and validated a compound series which binds to the PRMT5-PBM interface and directly inhibits binding of SAPs. Mode of action studies revealed the formation of a covalent bond between a halogenated pyridazinone group and cysteine 278 of PRMT5. Optimization of the starting hit produced a lead compound, BRD0639, which engages the target in cells, disrupts PRMT5-RIOK1 complexes, and reduces substrate methylation. BRD0639 is a first-in-class PBM-competitive inhibitor that can support studies of PBM-dependent PRMT5 activities and the development of novel PRMT5 inhibitors that selectively target these functions.
- Published
- 2021
24. OCT Angiography for the Diagnosis of Glaucoma
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Arthur J. Sit, Hana L. Takusagawa, Sunita Radhakrishnan, Jullia A Rosdahl, Ambika Hoguet, Teresa C. Chen, Ying Han, and Darrell WuDunn
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medicine.medical_specialty ,genetic structures ,Nerve fiber layer ,Glaucoma ,Nerve fiber ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Ophthalmology ,medicine ,030304 developmental biology ,0303 health sciences ,Receiver operating characteristic ,business.industry ,Retinal ,medicine.disease ,eye diseases ,Ganglion ,Visual field ,medicine.anatomical_structure ,chemistry ,Inclusion and exclusion criteria ,030221 ophthalmology & optometry ,sense organs ,business - Abstract
Purpose To review the current published literature on the use of OCT angiography (OCTA) to help detect changes associated with the diagnosis of primary open-angle glaucoma. Methods Searches of the peer-reviewed literature were conducted in March 2018, June 2018, April 2019, December 2019, and June 2020 in the PubMed and Cochrane Library databases. Abstracts of 459 articles were examined to exclude reviews and non-English articles. After inclusion and exclusion criteria were applied, 75 articles were selected and the panel methodologist rated them for strength of evidence. Three articles were rated level I and 57 articles were rated level II. The 15 level III articles were excluded. Results OCT angiography can detect decreased capillary vessel density within the peripapillary nerve fiber layer (level II) and macula (level I and II) in patients with suspected glaucoma, preperimetric glaucoma, and perimetric glaucoma. The degree of vessel density loss correlates significantly with glaucoma severity both overall and topographically (level II) as well as longitudinally (level I). For differentiating glaucomatous from healthy eyes, some studies found that peripapillary and macular vessel density measurements by OCTA show a diagnostic ability (area under the receiver operating characteristic curve) that is comparable with structural OCT retinal nerve fiber and ganglion cell thickness measurements, whereas other studies found that structural OCT measurements perform better. Choroidal or deep-layer microvasculature dropout as measured by OCTA is also associated with glaucoma damage (level I and II). Lower peripapillary and macular vessel density and choroidal microvasculature dropout are associated with faster rates of disease progression (level I and II). Conclusions Vessel density loss associated with glaucoma can be detected by OCTA. Peripapillary, macular, and choroidal vessel density parameters may complement visual field and structural OCT measurements in the diagnosis of glaucoma.
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- 2021
25. Antifungal susceptibility of clinical mould isolates in New Zealand, 2001–2019
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Sally A. Roberts, Karen Rogers, Arthur J. Morris, Joshua T. Freeman, and Wendy P. McKinney
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0301 basic medicine ,Fusarium ,Mucorales ,Antifungal ,Antifungal Agents ,medicine.drug_class ,Microbial Sensitivity Tests ,Pathology and Forensic Medicine ,Microbiology ,Echinocandins ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Drug Resistance, Fungal ,Amphotericin B ,Mycology ,medicine ,Humans ,Voriconazole ,Aspergillus ,biology ,Fungi ,biology.organism_classification ,030104 developmental biology ,chemistry ,030220 oncology & carcinogenesis ,Caspofungin ,New Zealand ,medicine.drug - Abstract
Summary The objective of this study was to review the antifungal susceptibility of clinical mould isolates performed by the New Zealand Mycology Reference Laboratory. Isolates were either local or referred for testing from other New Zealand laboratories. All isolates were tested by the broth colorimetric microdilution method, Sensititre YeastOne (SYO). Epidemiological cut-off values (ECVs) derived from either the Clinical and Laboratory Standards Institute (CLSI) method or SYO were used to determine the proportion of non-wild type (non-WT) isolates, i.e., those with an increased likelihood to harbour acquired mechanisms of resistance. A total of 614 isolates were tested. Most isolates (55%) were from the respiratory tract followed by musculoskeletal tissue (17%), eye (10%) and abdomen (5%). The azoles had similar activity except for voriconazole which was less active against the Mucorales. The echinocandins had good activity against Aspergillus spp., other hyaline moulds and dematiaceous isolates but were inactive against Fusarium spp., Lomentospora prolificans and the Mucorales. Amphotericin B had best activity against the Mucorales. The two least susceptible groups were Fusarium spp. and L. prolificans isolates. Three Aspergillus isolates were non-WT for amphotericin B, and four non-WT for azoles. Non-WT were not encountered for caspofungin. Non-Aspergillus isolates in New Zealand have susceptibility patterns similar to those reported elsewhere. In contrast to a growing number of other countries, azole resistance was rare in A. fumigatus sensu stricto. Non-WT isolates were uncommon. The results provide a baseline for monitoring emerging antifungal resistance in New Zealand and support current Australasian treatment guidelines for invasive fungal infections.
- Published
- 2021
26. Degradation of aromatic compounds and lignin by marine protist Thraustochytrium striatum
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Jiale Huang, Xiang Li, Arthur J. Ragauskas, Nishanth Tharayil, Yunqiao Pu, Mi Li, and Yi Zheng
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chemistry.chemical_classification ,Strain (chemistry) ,Depolymerization ,food and beverages ,Biomass ,Bioengineering ,Applied Microbiology and Biotechnology ,Biochemistry ,chemistry.chemical_compound ,chemistry ,Lignin ,Degradation (geology) ,Equivalent concentration ,Fermentation ,Food science ,Carotenoid - Abstract
This paper aimed at studying a novel high biomass strain (HBS) of marine protist, Thraustochytrium striatum, for lignin valorization to lipids and carotenoids. In the screening of 15 aromatic compounds, T. striatum HBS can utilize most compounds while achieving the best growth on 3,4-dihydroxybenzoic acid (3,4-DHBA) and 4-hydroxybenzoic acid (4-HBA). The maximum cell mass concentration reached 2−3 g/L under 5 g/L of 3,4-DHBA or 2 g/L of 4-HBA, which was comparable to that under equivalent concentration of glucose. The long-chain fatty acids content was 13 % and 7 % with 3,4-DHBA and 4-HBA, respectively. The adoption of fed-batch fermentation mode improved the degradation of carbon source and prevented the inhibitory effect caused by overloading of aromatic compounds. Both final cellular fatty acids and carotenoids contents were doubled in the fermentation of 3,4-DHBA. T. striatum HBS exhibited limited lignin depolymerization (∼24 %) ability on technical lignins.
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- 2021
27. Terephthalic Acid Copolyesters Containing Tetramethylcyclobutanediol for High‐Performance Plastics
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Arthur J. Ragauskas, Soydan Ozcan, Samarthya Bhagia, and Kamlesh Bornani
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Terephthalic acid ,Bisphenol A ,plastic recycling ,terephthalic acid ,Diol ,Cyclohexanedimethanol ,Reviews ,ethylene glycol ,Review ,General Chemistry ,cyclohexanedimethanol ,copolyesters ,Polyester ,Chemistry ,chemistry.chemical_compound ,Monomer ,chemistry ,Polyethylene terephthalate ,tetramethylcyclobutanediol ,Organic chemistry ,polyester ,QD1-999 ,Ethylene glycol - Abstract
There is a need for high‐performance applications for terephthalic acid (TPA) polyesters with high heat resistance, impact toughness, and optical clarity. Bisphenol A (BPA) based polycarbonates and polyarylates have such properties, but BPA is an endocrine disruptor. Therefore, new TPA polyesters that are less hazardous to health and the environment are becoming popular. Tetramethylcyclobutanediol (TMCD) is a difunctional monomer that can be polymerized with TPA and other diols to yield copolyesters with superior properties to conventional TPA polyesters. It has a cyclobutyl ring that makes it more rigid than cyclohexanedimethanol (CHDM) and EG. Thus, TMCD containing TPA copolyesters can have high heat resistance and impact strength. TPA can be made from abundantly available upcycled polyethylene terephthalate (PET). Therefore, this review discusses the synthesis of monomers and copolyesters, the impact of diol composition on material properties, molecular weight, effects of photodegradation, health safety, and substitution of cyclobutane diols for future polyesters., High‐performance plastics: Tetramethylcyclobutanediol containing terephthalic acid based copolyesters can give high heat resistance and impact toughness which are useful in the manufacturing of high‐performance plastic parts.
- Published
- 2021
28. Understanding Loss of Soluble High Molecular Weight Species during Filtration of Low Concentration Therapeutic Monoclonal Antibodies
- Author
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Li Yi, Philippe Lam, Jacqueline Y. Tyler, Arthur J. Schick, Preston Pallante, and Nathaniel Swanson
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Low protein ,Chromatography ,Chemistry ,Antibodies, Monoclonal ,Pharmaceutical Science ,02 engineering and technology ,021001 nanoscience & nanotechnology ,030226 pharmacology & pharmacy ,Polyvinylidene fluoride ,law.invention ,Molecular Weight ,Matrix (chemical analysis) ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Adsorption ,law ,Ionic strength ,Absorption (chemistry) ,0210 nano-technology ,Hydrophobic and Hydrophilic Interactions ,Filtration ,Protein adsorption - Abstract
Sterile filtration is an integral step in the manufacturing process of biological therapeutics. Protein adsorption to the surface of the filter is an unfortunate, common occurrence that can result in manufacturing difficulties, such as filter fouling or product loss. Although many filters have surface modifications to minimize adsorption, under certain conditions binding can still occur. We observed the loss of high molecular weight species (HMWS) during sterile filtration of eight different therapeutic monoclonal antibodies formulated at low protein concentrations across a commonly used hydrophilic polyvinylidene fluoride or polyvinylidene difluoride (PVDF) filter membrane. The protein absorption was specific to HMWS, and each antibody exhibited different degrees of filter adsorption. Debye screening length parameters of the solution (e.g. ionic strength) were adjusted, and influenced the amount of HMWS lost during filtration. Additionally, HMWS of a representative antibody (mAb1) were observed to be more positively charged than other size variants by ion-exchange chromatography. From these results, it is concluded that this HMWS loss is due to electrostatic interactions between HMWS and the filter surface. This adsorption can be reduced by increasing the ionic strength of the buffer matrix, demonstrating the influence of the Debye screening length in the filtration of low concentration proteins.
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- 2021
29. Dilution impacts on smoke aging: evidence in Biomass Burning Observation Project (BBOP) data
- Author
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Anna L. Hodshire, C. R. Lonsdale, Yang Wang, Sonia M. Kreidenweis, Jian Wang, Delphine K. Farmer, Lawrence I. Kleinman, Shantanu H. Jathar, Matthew L. Alvarado, Timothy B. Onasch, Arthur J. Sedlacek, Stephen R. Springston, Ali Akherati, Emily Ramnarine, and Jeffrey R. Pierce
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Smoke ,Atmospheric Science ,010504 meteorology & atmospheric sciences ,Physics ,QC1-999 ,Evaporation ,010501 environmental sciences ,Atmospheric sciences ,01 natural sciences ,humanities ,Aerosol ,Plume ,Dilution ,Atmosphere ,Chemistry ,Particle ,Environmental science ,Biomass burning ,QD1-999 ,0105 earth and related environmental sciences - Abstract
Biomass burning emits vapors and aerosols into the atmosphere that can rapidly evolve as smoke plumes travel downwind and dilute, affecting climate- and health-relevant properties of the smoke. To date, theory has been unable to explain observed variability in smoke evolution. Here, we use observational data from the Biomass Burning Observation Project (BBOP) field campaign and show that initial smoke organic aerosol mass concentrations can help predict changes in smoke aerosol aging markers, number concentration, and number mean diameter between 40–262 nm. Because initial field measurements of plumes are generally >10 min downwind, smaller plumes will have already undergone substantial dilution relative to larger plumes and have lower concentrations of smoke species at these observations closest to the fire. The extent to which dilution has occurred prior to the first observation is not a directly measurable quantity. We show that initial observed plume concentrations can serve as a rough indicator of the extent of dilution prior to the first measurement, which impacts photochemistry, aerosol evaporation, and coagulation. Cores of plumes have higher concentrations than edges. By segregating the observed plumes into cores and edges, we find evidence that particle aging, evaporation, and coagulation occurred before the first measurement. We further find that on the plume edges, the organic aerosol is more oxygenated, while a marker for primary biomass burning aerosol emissions has decreased in relative abundance compared to the plume cores. Finally, we attempt to decouple the roles of the initial concentrations and physical age since emission by performing multivariate linear regression of various aerosol properties (composition, size) on these two factors.
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- 2021
30. THF co-solvent pretreatment prevents lignin redeposition from interfering with enzymes yielding prolonged cellulase activity
- Author
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Yunqiao Pu, Ramya Mohan, Chang Geun Yoo, Abhishek S. Patri, Charles M. Cai, David Kisailus, Arthur J. Ragauskas, Charles E. Wyman, and Rajeev Kumar
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0106 biological sciences ,lcsh:Biotechnology ,Lignocellulosic biomass ,Cellulase ,Management, Monitoring, Policy and Law ,01 natural sciences ,Applied Microbiology and Biotechnology ,complex mixtures ,Lignin ,lcsh:Fuel ,Dilute acid ,Hydrolysis ,chemistry.chemical_compound ,lcsh:TP315-360 ,010608 biotechnology ,Enzymatic hydrolysis ,lcsh:TP248.13-248.65 ,Hemicellulose ,Biomass ,Cellulose ,Chromatography ,biology ,010405 organic chemistry ,Renewable Energy, Sustainability and the Environment ,Chemistry ,Research ,Protein ,food and beverages ,Enzyme assay ,0104 chemical sciences ,General Energy ,Tetrahydrofuran ,Enzyme ,biology.protein ,Scanning electron microscopy ,Pretreatment ,Biotechnology - Abstract
Background Conventional aqueous dilute sulfuric acid (DSA) pretreatment of lignocellulosic biomass facilitates hemicellulose solubilization and can improve subsequent enzymatic digestibility of cellulose to fermentable glucose. However, much of the lignin after DSA pretreatment either remains intact within the cell wall or readily redeposits back onto the biomass surface. This redeposited lignin has been shown to reduce enzyme activity and contribute to rapid enzyme deactivation, thus, necessitating significantly higher enzyme loadings than deemed economical for biofuel production from biomass. Results In this study, we demonstrate how detrimental lignin redeposition on biomass surface after pretreatment can be prevented by employing Co-solvent Enhanced Lignocellulosic Fractionation (CELF) pretreatment that uses THF–water co-solvents with dilute sulfuric acid to solubilize lignin and overcome limitations of DSA pretreatment. We first find that enzymatic hydrolysis of CELF-pretreated switchgrass can sustain a high enzyme activity over incubation periods as long as 5 weeks with enzyme doses as low as 2 mg protein/g glucan to achieve 90% yield to glucose. A modified Ninhydrin-based protein assay revealed that the free-enzyme concentration in the hydrolysate liquor, related to enzyme activity, remained unchanged over long hydrolysis times. DSA-pretreated switchgrass, by contrast, had a 40% drop in free enzymes in solution during incubation, providing evidence of enzyme deactivation. Furthermore, measurements of enzyme adsorption per gram of lignin suggested that CELF prevented lignin redeposition onto the biomass surface, and the little lignin left in the solids was mostly integral to the original lignin–carbohydrate complex (LCC). Scanning electron micrographs and NMR characterization of lignin supported this observation. Conclusions Enzymatic hydrolysis of solids from CELF pretreatment of switchgrass at low enzyme loadings was sustained for considerably longer times and reached higher conversions than for DSA solids. Analysis of solids following pretreatment and enzymatic hydrolysis showed that prolonged cellulase activity could be attributed to the limited lignin redeposition on the biomass surface making more enzymes available for hydrolysis of more accessible glucan.
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- 2021
31. Alignment of Cellulose Nanofibers: Harnessing Nanoscale Properties to Macroscale Benefits
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Teng Li, Soydan Ozcan, Arthur J. Ragauskas, Meghan E. Lamm, Liangbing Hu, Lu Wang, Mehdi Tajvidi, Jeffrey P. Youngblood, Caitlyn M. Clarkson, Douglas J. Gardner, Ji Qian, Zhenqian Pang, Yu Liu, Halil Tekinalp, Yubing Zhou, and Kai Li
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Materials science ,General Engineering ,General Physics and Astronomy ,Nanotechnology ,02 engineering and technology ,010402 general chemistry ,021001 nanoscience & nanotechnology ,01 natural sciences ,0104 chemical sciences ,Nanocellulose ,chemistry.chemical_compound ,Cellulose nanocrystals ,chemistry ,13. Climate action ,Bacterial cellulose ,Nanofiber ,General Materials Science ,Cellulose ,0210 nano-technology ,Nanoscopic scale - Abstract
In nature, cellulose nanofibers form hierarchical structures across multiple length scales to achieve high-performance properties and different functionalities. Cellulose nanofibers, which are separated from plants or synthesized biologically, are being extensively investigated and processed into different materials owing to their good properties. The alignment of cellulose nanofibers is reported to significantly influence the performance of cellulose nanofiber-based materials. The alignment of cellulose nanofibers can bridge the nanoscale and macroscale, bringing enhanced nanoscale properties to high-performance macroscale materials. However, compared with extensive reviews on the alignment of cellulose nanocrystals, reviews focusing on cellulose nanofibers are seldom reported, possibly because of the challenge of aligning cellulose nanofibers. In this review, the alignment of cellulose nanofibers, including cellulose nanofibrils and bacterial cellulose, is extensively discussed from different aspects of the driving force, evaluation, strategies, properties, and applications. Future perspectives on challenges and opportunities in cellulose nanofiber alignment are also briefly highlighted.
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- 2021
32. Carbohydrate restriction following strenuous glycogen-depleting exercise does not potentiate the acute molecular response associated with mitochondrial biogenesis in human skeletal muscle
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Andrejus Subocius, Thomas Chaillou, Arthur J. Cheng, Tomas Venckunas, Marius Brazaitis, Sigitas Kamandulis, Catarina Ramos, and Springer Verlag
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Adult ,Male ,medicine.medical_specialty ,Physiology ,PGC1A ,PDK4 ,030209 endocrinology & metabolism ,Biology ,Muscle glycogen ,Diet, Carbohydrate-Restricted ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Endurance training ,Physiology (medical) ,Internal medicine ,Gene expression ,Dietary Carbohydrates ,medicine ,Humans ,Ingestion ,Orthopedics and Sports Medicine ,Muscle, Skeletal ,endurance exercise ,muscle glycogen ,oxidative metabolism ,pgc1a ,sprint interval exercise ,train-low ,Organelle Biogenesis ,Glycogen ,Muscle adaptation ,Public Health, Environmental and Occupational Health ,Pyruvate Dehydrogenase Acetyl-Transferring Kinase ,Skeletal muscle ,030229 sport sciences ,General Medicine ,Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha ,Endurance exercise ,Mitochondria, Muscle ,medicine.anatomical_structure ,Endocrinology ,Mitochondrial biogenesis ,chemistry ,Sprint interval exercise ,Oxidative metabolism ,Original Article ,Train-low ,Physical Conditioning, Human - Abstract
Purpose Carbohydrate (CHO) restriction could be a potent metabolic regulator of endurance exercise-induced muscle adaptations. Here, we determined whether post-exercise CHO restriction following strenuous exercise combining continuous cycling exercise (CCE) and sprint interval exercise could affect the gene expression related to mitochondrial biogenesis and oxidative metabolism in human skeletal muscle. Methods In a randomized cross-over design, 8 recreationally active males performed two cycling exercise sessions separated by 4 weeks. Each session consisted of 60-min CCE and six 30-s all-out sprints, which was followed by ingestion of either a CHO or placebo beverage in the post-exercise recovery period. Muscle glycogen concentration and the mRNA levels of several genes related to mitochondrial biogenesis and oxidative metabolism were determined before, immediately after, and at 3 h after exercise. Results Compared to pre-exercise, strenuous cycling led to a severe muscle glycogen depletion (> 90%) and induced a large increase in PGC1A and PDK4 mRNA levels (~ 20-fold and ~ 10-fold, respectively) during the acute recovery period in both trials. The abundance of the other transcripts was not changed or was only moderately increased during this period. CHO restriction during the 3-h post-exercise period blunted muscle glycogen resynthesis but did not increase the mRNA levels of genes associated with muscle adaptation to endurance exercise, as compared with abundant post-exercise CHO consumption. Conclusion CHO restriction after a glycogen-depleting and metabolically-demanding cycling session is not effective for increasing the acute mRNA levels of genes involved in mitochondrial biogenesis and oxidative metabolism in human skeletal muscle.
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- 2021
33. Predicting Tumor Killing and T-Cell Activation by T-Cell Bispecific Antibodies as a Function of Target Expression: CombiningIn VitroExperiments with Systems Modeling
- Author
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Florian Limani, Tina Weinzierl, Arthur J Van De Vyver, Marina Bacac, Thorsten Lehr, Nicolas Frances, Sarah Diggelmann, Miro J. Eigenmann, Regula B. Buser, Sylvia Herter, Antje-Christine Walz, and Jitka Somandin
- Subjects
0301 basic medicine ,Cancer Research ,biology ,Chemistry ,T cell ,medicine.medical_treatment ,Tumor antigen ,Immunological synapse ,03 medical and health sciences ,030104 developmental biology ,0302 clinical medicine ,medicine.anatomical_structure ,Carcinoembryonic antigen ,Oncology ,Antigen ,Cancer immunotherapy ,030220 oncology & carcinogenesis ,biology.protein ,medicine ,Cancer research ,Cytotoxic T cell ,Antibody - Abstract
Targeted T-cell redirection is a promising field in cancer immunotherapy. T-cell bispecific antibodies (TCB) are novel antibody constructs capable of binding simultaneously to T cells and tumor cells, allowing cross-linking and the formation of immunologic synapses. This in turn results in T-cell activation, expansion, and tumor killing. TCB activity depends on system-related properties such as tumor target antigen expression as well as antibody properties such as binding affinities to target and T cells. Here, we developed a systems model integrating in vitro data to elucidate further the mechanism of action and to quantify the cytotoxic effects as the relationship between targeted antigen expression and corresponding TCB activity. In the proposed model, we capture relevant processes, linking immune synapse formation to T-cell activation, expansion, and tumor killing for TCBs in vitro to differentiate the effect between tumor cells expressing high or low levels of the tumor antigen. We used cibisatamab, a TCB binding to carcinoembryonic antigen (CEA), to target different tumor cell lines with high and low CEA expression in vitro. We developed a model to capture and predict our observations, as a learn-and-confirm cycle. Although full tumor killing and substantial T-cell activation was observed in high expressing tumor cells, the model correctly predicted partial tumor killing and minimal T-cell activation in low expressing tumor cells when exposed to cibisatamab. Furthermore, the model successfully predicted cytotoxicity across a wide range of tumor cell lines, spanning from very low to high CEA expression.
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- 2021
34. Synthesis and Characterization of Lignin-grafted-poly(ε-caprolactone) from Different Biomass Sources
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Fang Chen, Mi Li, Yunqiao Pu, and Arthur J. Ragauskas
- Subjects
0106 biological sciences ,Polyesters ,Organosolv ,Molecular Conformation ,Bioengineering ,Lignin ,01 natural sciences ,Polymerization ,Gel permeation chromatography ,03 medical and health sciences ,chemistry.chemical_compound ,Differential scanning calorimetry ,010608 biotechnology ,Copolymer ,Organic chemistry ,Biomass ,Molecular Biology ,030304 developmental biology ,0303 health sciences ,General Medicine ,Plants ,chemistry ,Caprolactone ,Kraft paper ,Biotechnology - Abstract
Modification of lignin with poly(e-caprolactone) is a promising approach to valorize industrial low-value lignins and to advance the bioeconomy. We have synthesized lignin grafted poly(e-caprolactone) (lignin-g-PCL) copolymers via ring-opening polymerization of e-caprolactone with different types of lignins of varying botanical sources (G-type pine lignin, S/G-type poplar lignin, and C-type Vanilla seeds lignin) and lignin extraction methods (Kraft and ethanol organosolv pulping). The lignin-g-PCL copolymer showed remarkably improved compatibility and dispersion in acetone, chloroform, and toluene in comparison to non-modified lignins. The structure and thermal properties of the lignin-g-PCL were investigated using Fourier-transform infrared spectroscopy (FTIR), 31P nuclear magnetic resonance (NMR), 2D heteronuclear single quantum correlation (HSQC) NMR, gel permeation chromatography (GPC), and differential scanning calorimetry (DSC). We have found that all the technical lignins were reactive to the copolymerization reaction regardless of their plant source and isolation methods. The molecular weights of the synthesized lignin-g-PCL copolymers were positively correlated with the content of aliphatic lignin hydroxyls, suggesting that the copolymerization reaction tends to occur preferentially at the aliphatic hydroxyls rather than the phenolic hydroxyls of lignin. Thermal analyses of the lignin-g-PCL copolymers were studied, and in general, a reduction of melting temperature and crystallinity percentage in comparison to the neat PCL was observed. However, the thermal behavior of lignin-g-PCL copolymers varied depending on the lignin feedstocks employed in the copolymerization reaction.
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- 2021
35. Elucidating the mechanisms of enhanced lignin bioconversion by an alkali sterilization strategy
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Zhi-Min Zhao, Yunqiao Pu, Zhi-Hua Liu, William K. Ledford, Xianzhi Meng, Bing-Zhi Li, S. Michael Kilbey, Shuyang Zhang, and Arthur J. Ragauskas
- Subjects
Aqueous solution ,Chemistry ,Bioconversion ,fungi ,Dispersity ,technology, industry, and agriculture ,food and beverages ,macromolecular substances ,Sterilization (microbiology) ,complex mixtures ,Pollution ,Gel permeation chromatography ,chemistry.chemical_compound ,Dynamic light scattering ,Chemical engineering ,Environmental Chemistry ,Lignin ,Fermentation - Abstract
Biological lignin valorization represents an emerging green approach to upgrade lignin for sustainable and economic biorefineries. However, lignin generally exhibits poor water solubility and inhomogeneous distribution in an aqueous medium, significantly limiting its bioconversion efficiency. Herein, we develop a novel alkali sterilization strategy to effectively enhance the dispersion and fermentation performance of lignin substrates. The colloidal particle size and molecular structure variations of lignin during the sterilization were thoroughly investigated to reveal the mechanisms of enhanced fermentation performance. Results showed that alkali sterilization achieved a completely aseptic effect when mixing lignin medium at an initial pH of 12.7 for 24 h. Dynamic light scattering (DLS) analysis demonstrated that the hydrodynamic volume of colloidal lignin particles decreased by 96.3% by alkali sterilization compared with the conventional thermal sterilization. Moreover, lignin characterizations by nuclear magnetic resonance (NMR) spectroscopy and gel permeation chromatography (GPC) suggested that alkali sterilization modified the lignin molecular structure by generating 50% more hydrophilic carboxyl groups, reducing the weight-average molecular weight (Mw) by 23.0%, and narrowing the molar-mass dispersity (ĐM) by 23.8%. The generation of lignin substrates with more uniform distribution and lower molecular weight improved Rhodococcus opacus PD630 cell growth and metabolism. Microbial cell amount, lignin degradation, and lipid production in alkali sterilized medium increased by 309%, 30.3%, and 48.3%, respectively, compared to those in thermally sterilized medium. These results clearly demonstrated that alkali sterilization dramatically improved the lignin bioconversion performance. This work presents a facile and effective sterilization strategy to overcome inhomogeneous lignin distribution in aqueous fermentation media, showing great potentials as a platform technique for promoting biological lignin valorization.
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- 2021
36. Enhancing the multi-functional properties of renewable lignin carbon fibers via defining the structure–property relationship using different biomass feedstocks
- Author
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Joshua S. Yuan, Yunqiao Pu, Cheng Hu, Sisi Xiang, Qiang Li, Hao-Sheng Lin, Wenhao Wu, Winson C. H. Kuo, Jinghao Li, Mandar T. Naik, Phuc Truong, Mengjie Li, Arthur J. Ragauskas, and Brian E. Jackson
- Subjects
chemistry.chemical_compound ,Softwood ,Corn stover ,Chemical engineering ,Chemistry ,Hardwood ,Environmental Chemistry ,Biomass ,Lignin ,Raw material ,Biorefinery ,Microstructure ,Pollution - Abstract
Lignin has been explored extensively as a renewable precursor for carbon materials, considering its abundance as a major component of plant cell walls and its sustainability as a byproduct of both lignocellulosic biorefinery and the paper-making industry. Despite the extensive efforts to define the process–property relationship, it remains largely unknown how lignin biosynthesis and its chemistry would impact the resultant carbon fiber properties, for both mechanical and electroconductive performances. Such inadequate understanding fundamentally limits feedstock design and selection to improve carbon fiber properties toward broader commercial applications. Using lignin from a broad range of biomass feedstocks for carbon fiber manufacturing, we have fundamentally explored the structure–function relationship between lignin chemistry and carbon fiber performance. Specifically, lignin extracted from hardwood (sugar maple), softwood (loblolly pine and red cedar), and herbaceous plants (corn stover and switchgrass) was used for carbon fiber manufacturing, considering the very different lignin structures from these feedstocks. Linear regression models were established to define the relationship between carbon fiber mechanical properties and lignin structural characteristics. The results highlighted that the content of β-O-4 linkages correlates significantly with the tensile strength and elastic modulus of lignin carbon fibers, indicating that more linear β-O-4 linkages would promote the carbon fiber mechanical performance. Moreover, electroconductive properties are essential for broader energy device application of lignin-based carbon fibers, yet the mechanisms controlling their electroconductivity are largely unknown. We hereby demonstrated that a higher β-O-4 content also promotes the electroconductivity of lignin carbon fibers. Microstructure analysis further revealed that the crystallite size and content of the pre-graphitic turbostratic carbon structure in lignin-based carbon fibers were enhanced as the β-O-4 linkages increased. The content of β-O-4 linkages has shown a strong correlation with the crystallite content in a linear regression model. This study thus revealed the underlying mechanisms regarding how the lignin structure in planta defines the resultant carbon fiber properties. Moreover, the study also highlighted the correlation between the mechanical and electroconductive properties of lignin-based carbon fibers, both of which were defined by the lignin structure.
- Published
- 2021
37. Use of a Lewis acid, a Brønsted acid, and their binary mixtures for the liquefaction of lignocellulose by supercritical ethanol processing
- Author
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Koray Alper, Kubilay Tekin, Xianzhi Meng, Selhan Karagöz, Yun-Yan Wang, and Arthur J. Ragauskas
- Subjects
Ethanol ,Renewable Energy, Sustainability and the Environment ,Energy Engineering and Power Technology ,Liquefaction ,Supercritical fluid ,Catalysis ,chemistry.chemical_compound ,Fuel Technology ,chemistry ,Yield (chemistry) ,Ethyl lactate ,Lewis acids and bases ,Brønsted–Lowry acid–base theory ,Nuclear chemistry - Abstract
Supercritical ethanol liquefaction of teak wood was carried out at 300 °C for 30 min without and with the use of Mg(ClO4)2, HClO4, and HClO4/Mg(ClO4)2 at various loadings (2–10 mmol). The bio-oil yield from the non-catalytic supercritical ethanol liquefaction of teak wood was ∼41 wt%. The highest bio-oil yield (∼58.2 wt%) was obtained with the catalytic run using 2 mmol of Mg(ClO4)2. In the catalyzed trials, with the use of either Mg(ClO4)2 or HClO4, an increase in catalyst amounts resulted in a decrease in bio-oil yields. There was no clear trend for the use of co-catalysts. A degree of de-oxygenation was observed with the use of the catalysts studied. The O/C atomic ratio of the bio-oil from the non-catalytic was 0.44. The O/C atomic ratios in the bio-oil produced from catalytic runs ranged from 0.25 to 0.38. In the bio-oil from the non-catalytic run, the major compound was phenolic species, whereas esters were dominant in the bio-oils from the catalytic runs. The type of catalyst and its amount had significant effects on the product distributions and compositions. The prominent ester compounds were ethyl lactate and ethyl levulinate. The highest relative yield of ethyl levulinate was 49.1% and obtained with the use of the Mg(ClO4)2/HClO4 (2 mmol : 10 mmol) catalyst. The heating values of the bio-oils from catalytic runs were higher than that of the non-catalytic run. The highest heating value of 31.21 MJ kg−1 was obtained with the Mg(ClO4)2/HClO4 (2 mmol : 10 mmol) catalyst.
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- 2021
38. Double bonus: surfactant-assisted biomass pelleting benefits both the pelleting process and subsequent enzymatic saccharification of the pretreated pellets
- Author
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Xianzhi Meng, Yunqiao Pu, Samarthya Bhagia, Nathan Bryant, Sune Tjalfe Thomsen, Arthur J. Ragauskas, Donglin Xin, Claus Felby, Lisbeth Garbrecht Thygesen, Christian Koch, and Chunxiao Gong
- Subjects
0106 biological sciences ,animal structures ,Chemistry ,020209 energy ,digestive, oral, and skin physiology ,Pellets ,food and beverages ,Biomass ,Lignocellulosic biomass ,02 engineering and technology ,Straw ,Pulp and paper industry ,Pelletizing ,Biorefinery ,01 natural sciences ,Pollution ,Hydrolysis ,010608 biotechnology ,PEG ratio ,0202 electrical engineering, electronic engineering, information engineering ,Environmental Chemistry - Abstract
Pelleting overcomes the utilization limitation of lignocellulosic biomass due to its low density and related processing costs. Efficiently combining biomass pelleting and enzymatic saccharification is a challenge for applying biomass with low density in a biorefinery. In this study, we propose a novel biomass processing approach involving the addition of surfactant during pelleting and using the pellets for pretreatment and enzymatic saccharification. We investigated the effects of polyethylene glycol (PEG) 6000 assisted pelleting on pelleting specific energy consumption and friction, and on subsequent pretreatment as well as on enzymatic saccharification of the pretreated pellets. The results showed that PEG 6000 assisted pelleting decreased the total pelleting specific energy consumption by about 14% for wheat straw and 18% for pine, and reduced the maximum friction during ejection of pellets by about 34% for wheat straw and 29% for pine. PEG 6000 assisted pelleting enhanced subsequent enzymatic sugar yield effectively for both acid and alkaline pretreated wheat straw and pine, especially for acid-treated pine pellets, where a 256% increase in glucose yield was obtained. The results suggest that PEG 6000 decreases the cleavage of β-O-4′ linkages during pretreatment and thus hinders the formation of phenolic hydroxyl groups, contributing to the enhanced sugar yield in enzymatic saccharification. As surfactants were found to have beneficial effects on both biomass pelleting and the sugar yield obtained from the enzymatic saccharification of the pretreated pellets, it would be advantageous to add surfactants during pelletizing when the pellets are intended for application in a biorefinery.
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- 2021
39. A mechanistic study of cellulase adsorption onto lignin
- Author
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Haitao Yang, Chang Geun Yoo, Xianzhi Meng, Congxin Chen, Arthur J. Ragauskas, Xiong Chen, Chun-Lei Yang, Jun Dai, Lan Yao, and Jun Yu
- Subjects
0106 biological sciences ,endocrine system ,biology ,010405 organic chemistry ,Langmuir adsorption model ,DHPS ,Cellulase ,01 natural sciences ,Pollution ,0104 chemical sciences ,chemistry.chemical_compound ,symbols.namesake ,Adsorption ,chemistry ,Physisorption ,010608 biotechnology ,Enzymatic hydrolysis ,parasitic diseases ,biology.protein ,symbols ,Environmental Chemistry ,Organic chemistry ,Lignin ,Cellulose - Abstract
To explore the effect of lignin composition on cellulase adsorption, dehydrogenation polymers (DHPs) were prepared from p-glucocoumaryl alcohol/coniferin/syringin, giving rise to H-DHP, G-DHP, and S-DHP, respectively. The structures of DHPs were thoroughly characterized and compared by GPC and NMR techniques, and the Langmuir isotherm protocol was applied to determine the cellulase adsorption behaviors of these different types of DHPs. The adsorption study indicated that the binding strength between the DHPs and cellulase varied in the following order: G-DHP > H-DHP > S-DHP. The inhibition of different types of DHPs on enzymatic hydrolysis of cellulose was in the same order as the cellulase adsorption, indicating that non-productive adsorption was the main way to influence cellulase. The correlation analysis results showed a positive association between the phenolic hydroxyl group content in DHPs and their maximum adsorption capacity toward enzymes. A negative correlation between the PDI and binding strength was also observed. It was also found that the adsorbed cellulase could be desorbed and retained normal enzyme activity, and so it was presumed that DHPs and cellulase were mainly linked by physisorption such as hydrogen bonding. This study clearly showed that the composition of lignin had a great impact on cellulase, and that G-type lignin exhibited the most detrimental effect. The results could provide useful information on the mechanism of cellulase adsorption onto lignin using DHPs as lignin model compounds.
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- 2021
40. Supercritical water co-liquefaction of LLDPE and PP into oil: properties and synergy
- Author
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Zhilong Yuan, Xueping Song, Arthur J. Ragauskas, Cuiping Wang, Jing Zhang, Peitao Zhao, and Qingjie Guo
- Subjects
Polypropylene ,Materials science ,Renewable Energy, Sustainability and the Environment ,Energy Engineering and Power Technology ,Polyethylene ,Jet fuel ,Supercritical fluid ,Linear low-density polyethylene ,chemistry.chemical_compound ,Diesel fuel ,Fuel Technology ,chemistry ,Chemical engineering ,Gasoline ,Lubricant - Abstract
The major plastic wastes are always mixtures, which are difficult to separate to treat in practice. Because of some possible cross-reactions, the degradation behaviors of plastics could not be mathematically represented by a simple addition of each polymer according to their proportions. This work examines supercritical water (scH2O) to liquefy poly-ethylene and poly-propylene mixtures into an oil with special interest in the oil quality and positive effect. Linear low-density polyethylene (LLDPE) and polypropylene (PP) were chosen as parent materials because of their high proportions in plastic wastes. The results show that a high conversion rate of around 99.75% was achieved with as high as 90.7 wt% oil yield without additional catalysts or hydrogen. The scH2O co-liquefaction of the LLDPE/PP mixture was different from that of the single polymer along with an improvement in the oil yield. Cyclic hydrocarbon (i.e., cyclic) generation was promoted while the production of paraffins was hindered in scH2O co-liquefaction using a mixture of LLDPE/PP. TGA reveals that the scH2O co-liquefaction of LLDPE/PP mixtures generated more diesel and lubricant oils and less gasoline and (jet fuel + light diesel) oils, thus slightly lowering the oil quality. Overall, the supercritical fluid technology was a powerful and promising means to liquefy mixed plastic wastes into oil at a high conversion rate free of catalysts or hydrogen.
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- 2021
41. Effect of using regenerated combined FAU and MOR zeolites as catalysts during the pyrolysis of kraft lignin
- Author
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Arthur J. Ragauskas, Ajoy Kanti Mondal, Fang Huang, Chengrong Qin, and Yonghao Ni
- Subjects
Kraft lignin ,Environmental Engineering ,Chemistry ,Bioengineering ,Microporous material ,Catalysis ,Gel permeation chromatography ,chemistry.chemical_compound ,Lignin ,Zeolite ,Spectroscopy ,Waste Management and Disposal ,Pyrolysis ,Nuclear chemistry - Abstract
The SiO2/Al2O3 mole ratio, pore size, and acid sites are the key parameters of zeolite’s activity in lignin pyrolysis. In this study, the comparison of individual Y and M zeolites, the combined ‘Y + M’ sample after regeneration, and their effect on lignin pyrolysis were studied in five cycles (regeneration and reuse). The results were explained using Brunauer, Emmet, and Teller (BET), micropore surface area (MSA), and total acid sites (TAS) analyses. In comparison with the individual Y or M zeolite sample, the consistent higher catalytic activities of the combined ‘Y + M’ sample in repeated cycles were observed. Pyrolysis heavy oils were characterized by nuclear magnetic resonance (NMR) spectroscopy and gel permeation chromatography (GPC). The NMR analyses revealed that with increased zeolite regeneration cycles, p-hydroxy phenyl and methoxyl groups increased. Decreases in guaiacyl phenolic hydroxyl were less for the combined ‘Y + M’ sample than the individual Y and M zeolites. Lower weight average (Mw) of heavy oil for the combined ‘Y + M’ sample indicated the enhanced cleavage of lignin structures in pyrolysis. These results support the higher catalytic activity of regenerated zeolites for the combined ‘Y + M’ sample compared with individual Y and M zeolites due to the improved MSA and TAS.
- Published
- 2020
42. Electrochemical Reduction of the Simplest Monosaccharides: Dihydroxyacetone and Glyceraldehyde
- Author
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Arthur J. Shih, Z. Liang, Marc T. M. Koper, K. Ojha, Villalba, and Giulia Marcandalli
- Subjects
chemistry.chemical_classification ,010405 organic chemistry ,Dihydroxyacetone ,General Chemistry ,010402 general chemistry ,Electrochemistry ,01 natural sciences ,Catalysis ,0104 chemical sciences ,Reduction (complexity) ,chemistry.chemical_compound ,chemistry ,Glyceraldehyde ,Monosaccharide ,Organic chemistry ,Organic synthesis - Abstract
Dihydroxyacetone (DHA) and glyceraldehyde (GA)—the simplest monosaccharides in nature—are both essential building blocks in organic synthesis. There have been detailed investigations on the selecti...
- Published
- 2020
43. Fabrication of lignocellulosic biomass paper containing nanofibrillated biomass
- Author
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John R. Dunlap, Richard R. Lowden, Arthur J. Ragauskas, Samarthya Bhagia, Wellington Muchero, Uday Vaidya, Yunqiao Pu, and Mohammed Zahid A. Khuraishi
- Subjects
Thermogravimetric analysis ,Environmental Engineering ,Guar gum ,Materials science ,Starch ,Thermal decomposition ,Lignocellulosic biomass ,Biomass ,Bioengineering ,Pulp and paper industry ,chemistry.chemical_compound ,chemistry ,Ultimate tensile strength ,Cellulose ,Waste Management and Disposal - Abstract
Fibrillated cellulose has been frequently used for making nanopapers and thin films. However, limited work has been carried out in the construction of such materials using native lignocellulosic biomass. Making papers from fibrillated biomass allows complete utilization of whole plant material and may reduce chemical and energy consumption. Ultra-friction grinding was used to directly fibrillate knife-milled poplar into micro- to nano-sized biomass fibers. Papers were made using the fibrillated biomass containing nanofibrillated biomass and their mechanical properties were tested. Biomass papers made via press-drying had higher tensile strength than papers made by air-drying. A higher press-drying temperature of 180 °C produced stronger papers than at 150 °C. Guar gum substantially increased the strength of the press-dried papers in comparison to cationic starch. Press-drying increased the thermogravimetric peak decomposition temperature by 13 °C in comparison to air-drying.
- Published
- 2020
44. Compartmental analysis of drug distribution
- Author
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Arthur J. Atkinson
- Subjects
Drug ,Drug transfer ,Kinetic model ,Chemistry ,media_common.quotation_subject ,Central compartment ,Drug administration ,Blood volume ,Limiting ,Plasma levels ,Pharmacology ,Endocytosis ,Pharmacokinetics ,Biophysics ,Distribution (pharmacology) ,Biological system ,Compartment (pharmacokinetics) ,media_common ,Whole blood - Abstract
Publisher Summary This chapter discusses the compartmental analysis of drug distribution. Drug distribution can be defined as the postabsorptive transfer of a drug from one location in the body to another. Drug transfer between compartments is characterized by “intercompartmental clearance,” a term to describe the volume-independent parameter that quantifies the rate of analyte transfer between the compartments of a kinetic model. The central compartment of a pharmacokinetic (PK) model usually is the only one that is directly accessible to sampling. When attempting to identify this compartment as intravascular space, the erythrocyte/plasma partition ratio must be incorporated in comparisons of central compartment volume with expected blood volume if plasma levels, rather than whole blood levels are used for PK analysis. The physiological basis for the transfer of drugs and other compounds among compartments can only be inferred for mammillary systems in which the central compartment represents intravascular space and intercompartmental clearance can be equated with transcapillary exchange. The mechanism of transcapillary exchange is elaborated in the chapter.
- Published
- 2022
45. Seven-Membered Rings With Four or More Heteroatoms
- Author
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Floris P. J. T. Rutjes, Arthur J. Altunc, and Daniel Blanco-Ania
- Subjects
Chemistry ,Heteroatom ,Medicinal chemistry - Published
- 2022
46. Mechanistic Insight into Lignin Slow Pyrolysis by Linking Pyrolysis Chemistry and Carbon Material Properties
- Author
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Jian Shi, Xin Gao, Arthur J. Ragauskas, Mi Li, Wenqi Li, Doo Young Kim, Namal Wanninayake, and Yunqiao Pu
- Subjects
Renewable Energy, Sustainability and the Environment ,Chemistry ,General Chemical Engineering ,Thermal decomposition ,chemistry.chemical_element ,02 engineering and technology ,General Chemistry ,010402 general chemistry ,021001 nanoscience & nanotechnology ,Mass spectrometry ,01 natural sciences ,0104 chemical sciences ,chemistry.chemical_compound ,Chemical engineering ,Scientific method ,Carbon source ,Environmental Chemistry ,Lignin ,0210 nano-technology ,Material properties ,Carbon ,Pyrolysis - Abstract
As a highly abundant renewable carbon source, lignin can be converted to a variety of advanced carbon materials with tailorable properties through slow pyrolysis. In this study, slow pyrolysis of kraft lignin, for the first time, was investigated with a commercial pyrolysis–gas chromatography−mass spectrometry (Py-GC-MS) system through evolved gas analysis-MS (EGA-MS) and heart-cutting-GC-MS (HC-GC-MS) analyses. These analyses allow recovery and examination of the multi-phased gas products generated from thermal decomposition of lignin during slow pyrolysis over long time course thus making it possible to link pyrolysis chemistry and carbon material properties. The overall product distributions, including volatiles and solid product were quantitatively tracked at different heating rates (2, 20, 40 ℃/min) and different temperature regions (100-200, 200-300 and 300-600 ℃). Solid residues were further characterized using a suite of analytical tools, in correlation with the investigation of formation mechanisms of volatiles to reveal the reaction chemistry of lignin during slow pyrolysis, and to determine the morphology, pore structure, and interfacial chemical properties. This study provides critical insights into the slow pyrolysis chemistry of lignin and the properties of the resulting carbon material. These results will facilitate a better design and control of the lignin slow pyrolysis process for synthesizing functional carbon materials.
- Published
- 2020
47. Multimodal small-molecule screening for human prion protein binders
- Author
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Sonia M Vallabh, Arthur J. Campbell, Jayme L. Dahlin, Michael F. Mesleh, Kong T. Nguyen, Dominick Casalena, S. Kirk Wright, Dmitry L. Usanov, Christopher T. Lemke, Jamie A. Moroco, Joshua R. Sacher, Andrew G. Reidenbach, Murugappan Sathappa, Om K. Shrestha, Eric Vallabh Minikel, Jenna B. Yehl, Douglas S. Auld, Stuart L. Schreiber, V.L. Rangel, Alix I. Chan, Rishi N. Shah, Maria Cristina Nonato, David R. Liu, Florence F. Wagner, Alison Leed, and Virendar K. Kaushik
- Subjects
0301 basic medicine ,Benzimidazole ,Magnetic Resonance Spectroscopy ,animal diseases ,In silico ,Drug Evaluation, Preclinical ,Biochemistry ,Prion Proteins ,Prion Diseases ,Small Molecule Libraries ,03 medical and health sciences ,chemistry.chemical_compound ,Drug Discovery ,Screening method ,Humans ,Native protein ,Prion protein ,Molecular Biology ,030102 biochemistry & molecular biology ,Drug discovery ,Cell Biology ,Progressive neurodegenerative disorder ,Small molecule ,nervous system diseases ,030104 developmental biology ,chemistry ,Saturation transfer ,Benzimidazoles ,Molecular Biophysics - Abstract
Prion disease is a rapidly progressive neurodegenerative disorder caused by misfolding and aggregation of the prion protein (PrP), and there are currently no therapeutic options. PrP ligands could theoretically antagonize prion formation by protecting the native protein from misfolding or by targeting it for degradation, but no validated small-molecule binders have been discovered to date. We deployed a variety of screening methods in an effort to discover binders of PrP, including 19F-observed and saturation transfer difference (STD) nuclear magnetic resonance (NMR) spectroscopy, differential scanning fluorimetry (DSF), DNA-encoded library selection, and in silico screening. A single benzimidazole compound was confirmed in concentration-response, but affinity was very weak (Kd > 1 mM), and it could not be advanced further. The exceptionally low hit rate observed here suggests that PrP is a difficult target for small-molecule binders. While orthogonal binder discovery methods could yield high affinity compounds, non-small-molecule modalities may offer independent paths forward against prion disease.
- Published
- 2020
48. Consequences of product inhibition in the quantification of kinetic parameters
- Author
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Fabio H. Ribeiro, Jeremy W. Arvay, W. Nicholas Delgass, Arthur J. Shih, Anuj A. Verma, and James W. Harris
- Subjects
Order of reaction ,010405 organic chemistry ,Chemistry ,Batch reactor ,Kinetics ,Thermodynamics ,Activation energy ,010402 general chemistry ,Kinetic energy ,01 natural sciences ,Catalysis ,0104 chemical sciences ,Adsorption ,Product inhibition ,Physical and Theoretical Chemistry - Abstract
While the potential for product inhibition in catalytic reactions is well known, the impact of neglected inhibition on measured kinetic parameters is often overlooked. The presence of product inhibition, most often caused by the competitive adsorption of products with reactants on catalytic active sites, is difficult to determine a priori for an arbitrary catalytic system. The significance of product inhibition relies on the concentration of the products, their adsorption thermodynamics on catalytically relevant sites, and process parameters such as temperature and pressure. When inhibition is significant, however, apparent activation energies and reaction orders vary from the differential-reactor apparent activation energy by a factor of 1/(1 − δ), where δ is the total inhibition order (e.g., the factor (1 − δ) = 1.6 for a system with product inhibition of −0.6 order). This is illustrated here with the kinetics of NO oxidation over Cu ion clusters (CuxOy) in Cu-SSZ-13, for which the product NO2 inhibits the forward reaction. Furthermore, in the presence of inhibition, when only reactants are fed to a flow reactor or placed in a batch reactor, there is often no practical conversion that is low enough to guarantee differential behavior. Inclusion of products in the feed solves this problem, allowing accurate determination of kinetic parameters such as apparent reaction orders and activation energies. We also demonstrate that evaluation of the necessity of co-feeding products to assure measurement of differential-reactor data in a given catalytic system is straightforward from a plot of the log of the rate (or conversion) versus the log of the space time in a flow reactor or elapsed time in a batch reactor. We encourage inclusion of this test in all kinetic analyses that are reasonably approximated by power law rate expressions.
- Published
- 2020
49. Effects of dioxygen pressure on rates of NOx selective catalytic reduction with NH3 on Cu-CHA zeolites
- Author
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William F. Schneider, Fabio H. Ribeiro, Rajamani Gounder, Siddarth H. Krishna, W. Nicholas Delgass, Arthur J. Shih, Jeffrey T. Miller, Casey B. Jones, and Ishant Khurana
- Subjects
010405 organic chemistry ,Chemistry ,Inorganic chemistry ,Reactive intermediate ,Selective catalytic reduction ,Partial pressure ,010402 general chemistry ,01 natural sciences ,Redox ,Catalysis ,0104 chemical sciences ,Reaction rate constant ,Physical and Theoretical Chemistry ,Zeolite ,NOx - Abstract
At low temperatures (
- Published
- 2020
50. Diffusible GRAPHIC to visualize morphology of cells after specific cell–cell contact
- Author
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Nagatoki Kinoshita, Thomas J. McHugh, Tomomi Shimogori, Arthur J Huang, and Atsushi Miyawaki
- Subjects
0301 basic medicine ,Blastomeres ,Leucine zipper ,Swine ,Xenopus ,Science ,Green Fluorescent Proteins ,Motility ,GPI-Linked Proteins ,Protein Engineering ,Cell morphology ,Article ,Green fluorescent protein ,Rats, Sprague-Dawley ,Mice ,03 medical and health sciences ,0302 clinical medicine ,medicine ,Animals ,Humans ,Cells, Cultured ,Neurons ,Leucine Zippers ,Mice, Inbred ICR ,Multidisciplinary ,biology ,Chemistry ,Biological techniques ,biology.organism_classification ,Recombinant Proteins ,Epithelium ,Rats ,Cell biology ,HEK293 Cells ,Intercellular Junctions ,030104 developmental biology ,medicine.anatomical_structure ,Membrane ,Microscopy, Fluorescence ,Medicine ,030217 neurology & neurosurgery ,Function (biology) ,Neuroscience - Abstract
The ability to identify specific cell–cell contact in the highly heterogeneous mammalian body is crucial to revealing precise control of the body plan and correct function. To visualize local connections, we previously developed a genetically encoded fluorescent indicator, GRAPHIC, which labels cell–cell contacts by restricting the reconstituted green fluorescent protein (GFP) signal to the contact site. Here, we modify GRAPHIC to give the reconstituted GFP motility within the membrane, to detect cells that make contact with other specific cells. Removal of leucine zipper domains, located between the split GFP fragment and glycophosphatidylinositol anchor domain, allowed GFP reconstituted at the contact site to diffuse throughout the entire plasma membrane, revealing cell morphology. Further, depending on the structural spacers employed, the reconstituted GFP could be selectively targeted to N terminal (NT)- or C terminal (CT)-probe-expressing cells. Using these novel constructs, we demonstrated that we can specifically label NT-probe-expressing cells that made contact with CT-probe-expressing cells in an epithelial cell culture and in Xenopus 8-cell-stage blastomeres. Moreover, we showed that diffusible GRAPHIC (dGRAPHIC) can be used in neuronal circuits to trace neurons that make contact to reveal a connection map. Finally, application in the developing brain demonstrated that the dGRAPHIC signal remained on neurons that had transient contacts during circuit development to reveal the contact history. Altogether, dGRAPHIC is a unique probe that can visualize cells that made specific cell–cell contact.
- Published
- 2020
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