| 1. |
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| 2. |
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| 3. |
- Abe, K., et al.
(author)
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J-PARC Neutrino Beamline Upgrade Technical Design Report
- 2019
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Reports (peer-reviewed)abstract
- In this document, technical details of the upgrade plan of the J-PARC neutrino beamline for the extension of the T2K experiment are described. T2K has proposed to accumulate data corresponding to 2×1022 protons-on-target in the next decade, aiming at an initial observation of CP violation with 3σ or higher significance in the case of maximal CP violation. Methods to increase the neutrino beam intensity, which are necessary to achieve the proposed data increase, are described.
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| 4. |
- Chirapatpimol, K, et al.
(author)
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Precision Measurement of the p(e,e′p)π0 Reaction at Threshold
- 2015
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In: Physical Review Letters. - 1079-7114. ; 114:19
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Journal article (peer-reviewed)abstract
- New results are reported from a measurement of π^{0} electroproduction near threshold using the p(e,e^{'}p)π^{0} reaction. The experiment was designed to determine precisely the energy dependence of s- and p-wave electromagnetic multipoles as a stringent test of the predictions of chiral perturbation theory (ChPT). The data were taken with an electron beam energy of 1192 MeV using a two-spectrometer setup in Hall A at Jefferson Lab. For the first time, complete coverage of the ϕ_{π}^{*} and θ_{π}^{*} angles in the pπ^{0} center of mass was obtained for invariant energies above threshold from 0.5 up to 15 MeV. The 4-momentum transfer Q^{2} coverage ranges from 0.05 to 0.155 (GeV/c)^{2} in fine steps. A simple phenomenological analysis of our data shows strong disagreement with p-wave predictions from ChPT for Q^{2}>0.07 (GeV/c)^{2}, while the s-wave predictions are in reasonable agreement.
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| 5. |
- Namkoong, H, et al.
(author)
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DOCK2 is involved in the host genetics and biology of severe COVID-19
- 2022
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In: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 609:7928, s. 754-
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Journal article (peer-reviewed)abstract
- Identifying the host genetic factors underlying severe COVID-19 is an emerging challenge1–5. Here we conducted a genome-wide association study (GWAS) involving 2,393 cases of COVID-19 in a cohort of Japanese individuals collected during the initial waves of the pandemic, with 3,289 unaffected controls. We identified a variant on chromosome 5 at 5q35 (rs60200309-A), close to the dedicator of cytokinesis 2 gene (DOCK2), which was associated with severe COVID-19 in patients less than 65 years of age. This risk allele was prevalent in East Asian individuals but rare in Europeans, highlighting the value of genome-wide association studies in non-European populations. RNA-sequencing analysis of 473 bulk peripheral blood samples identified decreased expression of DOCK2 associated with the risk allele in these younger patients. DOCK2 expression was suppressed in patients with severe cases of COVID-19. Single-cell RNA-sequencing analysis (n = 61 individuals) identified cell-type-specific downregulation of DOCK2 and a COVID-19-specific decreasing effect of the risk allele on DOCK2 expression in non-classical monocytes. Immunohistochemistry of lung specimens from patients with severe COVID-19 pneumonia showed suppressed DOCK2 expression. Moreover, inhibition of DOCK2 function with CPYPP increased the severity of pneumonia in a Syrian hamster model of SARS-CoV-2 infection, characterized by weight loss, lung oedema, enhanced viral loads, impaired macrophage recruitment and dysregulated type I interferon responses. We conclude that DOCK2 has an important role in the host immune response to SARS-CoV-2 infection and the development of severe COVID-19, and could be further explored as a potential biomarker and/or therapeutic target.
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| 6. |
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| 7. |
- Wang, QBS, et al.
(author)
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The whole blood transcriptional regulation landscape in 465 COVID-19 infected samples from Japan COVID-19 Task Force
- 2022
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In: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 13:1, s. 4830-
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Journal article (peer-reviewed)abstract
- Coronavirus disease 2019 (COVID-19) is a recently-emerged infectious disease that has caused millions of deaths, where comprehensive understanding of disease mechanisms is still unestablished. In particular, studies of gene expression dynamics and regulation landscape in COVID-19 infected individuals are limited. Here, we report on a thorough analysis of whole blood RNA-seq data from 465 genotyped samples from the Japan COVID-19 Task Force, including 359 severe and 106 non-severe COVID-19 cases. We discover 1169 putative causal expression quantitative trait loci (eQTLs) including 34 possible colocalizations with biobank fine-mapping results of hematopoietic traits in a Japanese population, 1549 putative causal splice QTLs (sQTLs; e.g. two independent sQTLs at TOR1AIP1), as well as biologically interpretable trans-eQTL examples (e.g., REST and STING1), all fine-mapped at single variant resolution. We perform differential gene expression analysis to elucidate 198 genes with increased expression in severe COVID-19 cases and enriched for innate immune-related functions. Finally, we evaluate the limited but non-zero effect of COVID-19 phenotype on eQTL discovery, and highlight the presence of COVID-19 severity-interaction eQTLs (ieQTLs; e.g., CLEC4C and MYBL2). Our study provides a comprehensive catalog of whole blood regulatory variants in Japanese, as well as a reference for transcriptional landscapes in response to COVID-19 infection.
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| 8. |
- Tanaka, Y. K., et al.
(author)
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Search for eta '-mesic nuclei using (p,d) reaction with FRS/Super-FRS at GSI/FAIR
- 2020
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In: Journal of Physics, Conference Series. - : IOP Publishing. - 1742-6588 .- 1742-6596. ; 1643
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Journal article (peer-reviewed)abstract
- We plan a semi-exclusive measurement of the C-12(p,dp) reaction to search for eta'-mesic nuclei, aiming at investigating in-medium properties of the eta'-meson. We employ a 2.5 GeV proton beam impinging on a carbon target to produce eta'-mesic C-11 nuclei via the C-12(p,d)eta'circle times C-11 reaction. Using coincidence measurements of the forward going deuterons, important for missing-mass spectroscopy, and decay protons emitted from the eta'-mesic nuclei for event selection will provide a high experimental sensitivity to observe eta'-mesic nuclei. We will perform the measurements by combining the WASA detector system with the fragment separator FRS at GSI and also with the Super-FRS at FAIR in the future. The plan of the experiments and the present status are reported.
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| 9. |
- Adam, J., et al.
(author)
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Fumarate Hydratase Deletion in Pancreatic beta Cells Leads to Progressive Diabetes
- 2017
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In: Cell Reports. - : Elsevier BV. - 2211-1247. ; 20:13, s. 3135-3148
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Journal article (peer-reviewed)abstract
- We explored the role of the Krebs cycle enzyme fumarate hydratase (FH) in glucose-stimulated insulin secretion (GSIS). Mice lacking Fh1 in pancreatic beta cells (Fh1 beta KO mice) appear normal for 6-8 weeks but then develop progressive glucose intolerance and diabetes. Glucose tolerance is rescued by expression of mitochondrial or cytosolic FH but not by deletion of Hif1 alpha or Nrf2. Progressive hyperglycemia in Fh1bKO mice led to dysregulated metabolism in b cells, a decrease in glucose-induced ATP production, electrical activity, cytoplasmic [Ca2+](i) elevation, and GSIS. Fh1 loss resulted in elevated intracellular fumarate, promoting succination of critical cysteines in GAPDH, GMPR, and PARK 7/DJ-1 and cytoplasmic acidification. Intracellular fumarate levels were increased in islets exposed to high glucose and in islets from human donors with type 2 diabetes (T2D). The impaired GSIS in islets from diabetic Fh1bKO mice was ameliorated after culture under normoglycemic conditions. These studies highlight the role of FH and dysregulated mitochondrial metabolism in T2D.
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| 10. |
- Goni, Maria Fernanda Sanchez, et al.
(author)
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The ACER pollen and charcoal database : a global resource to document vegetation and fire response to abrupt climate changes during the last glacial period
- 2017
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In: Earth System Science Data. - : Copernicus GmbH. - 1866-3508 .- 1866-3516. ; 9:2, s. 679-695
-
Journal article (peer-reviewed)abstract
- Quaternary records provide an opportunity to examine the nature of the vegetation and fire responses to rapid past climate changes comparable in velocity and magnitude to those expected in the 21st-century. The best documented examples of rapid climate change in the past are the warming events associated with the Dansgaard-Oeschger (D-O) cycles during the last glacial period, which were sufficiently large to have had a potential feedback through changes in albedo and greenhouse gas emissions on climate. Previous reconstructions of vegetation and fire changes during the D-O cycles used independently constructed age models, making it difficult to compare the changes between different sites and regions. Here, we present the ACER (Abrupt Climate Changes and Environmental Responses) global database, which includes 93 pollen records from the last glacial period (73-15 ka) with a temporal resolution better than 1000 years, 32 of which also provide charcoal records. A harmonized and consistent chronology based on radiometric dating (C-14, U-234/Th-230, optically stimulated luminescence (OSL), Ar-40/Ar-39-dated tephra layers) has been constructed for 86 of these records, although in some cases additional information was derived using common control points based on event stratigraphy. The ACER database compiles metadata including geospatial and dating information, pollen and charcoal counts, and pollen percentages of the characteristic biomes and is archived in Microsoft Access (TM) at https://doi. org/10.1594/PANGAEA. 870867.
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| 11. |
- Adam, Julie, et al.
(author)
-
Fumarate Hydratase Deletion in Pancreatic β Cells Leads to Progressive Diabetes
- 2017
-
In: Cell Reports. - : Elsevier BV. - 2211-1247. ; 20:13, s. 3135-3148
-
Journal article (peer-reviewed)abstract
- We explored the role of the Krebs cycle enzyme fumarate hydratase (FH) in glucose-stimulated insulin secretion (GSIS). Mice lacking Fh1 in pancreatic β cells (Fh1βKO mice) appear normal for 6–8 weeks but then develop progressive glucose intolerance and diabetes. Glucose tolerance is rescued by expression of mitochondrial or cytosolic FH but not by deletion of Hif1α or Nrf2. Progressive hyperglycemia in Fh1βKO mice led to dysregulated metabolism in β cells, a decrease in glucose-induced ATP production, electrical activity, cytoplasmic [Ca2+]i elevation, and GSIS. Fh1 loss resulted in elevated intracellular fumarate, promoting succination of critical cysteines in GAPDH, GMPR, and PARK 7/DJ-1 and cytoplasmic acidification. Intracellular fumarate levels were increased in islets exposed to high glucose and in islets from human donors with type 2 diabetes (T2D). The impaired GSIS in islets from diabetic Fh1βKO mice was ameliorated after culture under normoglycemic conditions. These studies highlight the role of FH and dysregulated mitochondrial metabolism in T2D. Adam et al. have shown that progressive diabetes develops if fumarate hydratase is deleted in mouse pancreatic β cells. Such β cells exhibit elevated fumarate and protein succination and show progressively reduced ATP production and insulin secretion. The depleted insulin response to glucose recovers when diabetic islets are cultured in reduced glucose.
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| 12. |
- Adler, Jan-Olof, et al.
(author)
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The upgraded photon tagging facility at the MAX IV Laboratory
- 2013
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In: Nuclear Instruments & Methods in Physics Research. Section A: Accelerators, Spectrometers, Detectors, and Associated Equipment. - : Elsevier BV. - 0167-5087 .- 0168-9002. ; 715, s. 1-10
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Journal article (peer-reviewed)abstract
- A description is given of the upgraded photon tagging facility at the MAX IV Laboratory. Two magnetic spectrometers are used to momentum analyze post-bremsstrahlung electrons. The tagged photon range extends from 10 to 180 MeV with an energy resolution of about 300 keV. The system has been operated at rates up to 4 x 10(6) photons s(-1) MeV (-1). Different diagnostic tools are described as well as the experimental program.
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| 13. |
- Hahne, J., et al.
(author)
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Including gap junctions into distributed neuronal network simulations
- 2016
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In: 2nd International Workshop on Brain-Inspired Computing, BrainComp 2015. - Cham : Springer Publishing Company. - 9783319508610 ; , s. 43-57
-
Conference paper (peer-reviewed)abstract
- Contemporary simulation technology for neuronal networks enables the simulation of brain-scale networks using neuron models with a single or a few compartments. However, distributed simulations at full cell density are still lacking the electrical coupling between cells via so called gap junctions. This is due to the absence of efficient algorithms to simulate gap junctions on large parallel computers. The difficulty is that gap junctions require an instantaneous interaction between the coupled neurons, whereas the efficiency of simulation codes for spiking neurons relies on delayed communication. In a recent paper [15] we describe a technology to overcome this obstacle. Here, we give an overview of the challenges to include gap junctions into a distributed simulation scheme for neuronal networks and present an implementation of the new technology available in the NEural Simulation Tool (NEST 2.10.0). Subsequently we introduce the usage of gap junctions in model scripts as well as benchmarks assessing the performance and overhead of the technology on the supercomputers JUQUEEN and K computer.
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| 14. |
- Isaksson, E, et al.
(author)
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Ice cores from Svalbard :useful archives of past climate and pollution history.
- 2003
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In: Physics and chemistry of the earth. Part A. - : Elsevier BV. - 1464-1895 .- 1873-4642 .- 1474-7065. ; 28:28-32, s. 1217-1228
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Journal article (peer-reviewed)abstract
- Ice cores from the relatively low-lying ice caps in Svalbard have not been widely exploited in climatic and environmental studies due to uncertainties about the effect of melt water percolation. However, results from two recent Svalbard ice cores, at Lomonosovfonna (1250 m asl) and Austfonna (750 m asl), have shown that with careful site selection, high-resolution sampling and multiple chemical analyses, it is possible to recover ice cores with partly preserved annual signals. These cores are estimated to cover at least the past 600 years and have been dated using a combination of known reference horizons and glacial modeling. The δ18O data from both Lomonosovfonna and Austfonna ice cores suggest that the 20th century was the warmest during the past 600 years. A comparison of the ice core and sea ice records from this period suggests that sea ice extent and Austfonna δ18O are linked over the past 400 years. This may reflect the position of the storm tracks and their direct influence on the relatively low altitude Austfonna. Lomonosovfonna may be less sensitive to such changes and primarily record atmospheric changes due to its higher elevation. The anthropogenic influence on Svalbard environment is illustrated by increased levels of non-sea-salt sulphate, nitrate, acidity, fly-ash and organic contaminants particularly during the second half of 1900s. Decreased concentrations of some components in recent decades most likely reflect emission and use restrictions. However, some current-use organic pesticide compounds show growing concentrations in near surface layers.
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| 15. |
- Larsson, Maria, et al.
(author)
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Procedural texturing of solid wood with knots
- 2022
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In: ACM Transactions on Graphics. - : Association for Computing Machinery. - 0730-0301 .- 1557-7368. ; 41:4
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Journal article (peer-reviewed)abstract
- We present a procedural framework for modeling the annual ring pattern of solid wood with knots. Although wood texturing is a well-studied topic, there have been few previous attempts at modeling knots inside the wood texture. Our method takes the skeletal structure of a tree log as input and produces a three-dimensional scalar field representing the time of added growth, which defines the volumetric annual ring pattern. First, separate fields are computed around each strand of the skeleton, i.e., the stem and each knot. The strands are then merged into a single field using smooth minimums. We further suggest techniques for controlling the smooth minimum to adjust the balance of smoothness and reproduce the distortion effects observed around dead knots. Our method is implemented as a shader program running on a GPU with computation times of approximately 0.5 s per image and an input data size of 600 KB. We present rendered images of solid wood from pine and spruce as well as plywood and cross-laminated timber (CLT). Our results were evaluated by wood experts, who confirmed the plausibility of the rendered annual ring patterns.
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| 16. |
- Masuda, Isao, et al.
(author)
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A genetically encoded fluorescent tRNA is active in live-cell protein synthesis
- 2017
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In: Nucleic Acids Research. - : OXFORD UNIV PRESS. - 0305-1048 .- 1362-4962. ; 45:7, s. 4081-4093
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Journal article (peer-reviewed)abstract
- Transfer RNAs (tRNAs) perform essential tasks for all living cells. They are major components of the ribosomal machinery for protein synthesis and they also serve in non-ribosomal pathways for regulation and signaling metabolism. We describe the development of a genetically encoded fluorescent tRNA fusion with the potential for imaging in live Escherichia coli cells. This tRNA fusion carries a Spinach aptamer that becomes fluorescent upon binding of a cell-permeable and non-toxic fluorophore. We show that, despite having a structural framework significantly larger than any natural tRNA species, this fusion is a viable probe for monitoring tRNA stability in a cellular quality control mechanism that degrades structurally damaged tRNA. Importantly, this fusion is active in E. coli live-cell protein synthesis allowing peptidyl transfer at a rate sufficient to support cell growth, indicating that it is accommodated by translating ribosomes. Imaging analysis shows that this fusion and ribosomes are both excluded from the nucleoid, indicating that the fusion and ribosomes are in the cytosol together possibly engaged in protein synthesis. This fusion methodology has the potential for developing new tools for live-cell imaging of tRNA with the unique advantage of both stoichiometric labeling and broader application to all cells amenable to genetic engineering.
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| 17. |
- Nishimura, Toshiya, et al.
(author)
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Generation of Functional Organs Using a Cell-Competitive Niche in Intra- and Inter-species Rodent Chimeras.
- 2021
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In: Cell stem cell. - : Elsevier BV. - 1875-9777 .- 1934-5909. ; 28:1, s. 141-149
-
Journal article (peer-reviewed)abstract
- Interspecies organ generation via blastocyst complementation has succeeded in rodents, but not yet in evolutionally more distant species. Early developmental arrest hinders the formation of highly chimeric fetuses. We demonstrate that the deletion of insulin-like growth factor 1 receptor (Igf1r) in mouse embryos creates a permissive "cell-competitive niche" in several organs, significantly augmenting both mouse intraspecies and mouse/rat interspecies donor chimerism that continuously increases from embryonic day 11 onward, sometimes even taking over entire organs within intraspecies chimeras. Since Igf1r deletion allows the evasion of early developmental arrest, interspecies fetuses with high levels of organ chimerism can be generated via blastocyst complementation. This observation should facilitate donor cell contribution to host tissues, resulting in whole-organ generation via blastocyst complementation across wide evolutionary distances.
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| 18. |
- Okmane, Laura, et al.
(author)
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Glucomannan and beta-glucan degradation by Mytilus edulis Cel45A : Crystal structure and activity comparison with GH45 subfamily A, B and C
- 2022
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In: Carbohydrate Polymers. - : Elsevier. - 0144-8617 .- 1879-1344. ; 277
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Journal article (peer-reviewed)abstract
- The enzymatic hydrolysis of barley beta-glucan, konjac glucomannan and carboxymethyl cellulose by a beta-1,4-D-endoglucanase MeCel45A from blue mussel, Mytilus edulis, which belongs to subfamily B of glycoside hydrolase family 45 (GH45), was compared with GH45 members of subfamilies A (Humicola insolens HiCel45A), B (Trichoderma reesei TrCel45A) and C (Phanerochaete chrysosporium PcCel45A). Furthermore, the crystal structure of MeCel45A is reported.Initial rates and hydrolysis yields were determined by reducing sugar assays and product formation was characterized using NMR spectroscopy. The subfamily B and C enzymes exhibited mannanase activity, whereas the subfamily A member was uniquely able to produce monomeric glucose. All enzymes were confirmed to be inverting glycoside hydrolases. MeCel45A appears to be cold adapted by evolution, as it maintained 70% activity on cellohexaose at 4 degrees C relative to 30 degrees C, compared to 35% for TrCel45A. Both enzymes produced cellobiose and cellotetraose from cellohexaose, but TrCel45A additionally produced cellotriose.
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