| 91. |
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| 92. |
- Hedbys, Lars, et al.
(författare)
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Synthesis of Galβ1-3GlcNAc and Galβ1-3GlcNAcβ-SEt by an enzymatic method comprising the sequential use of β-galactosidases from bovine testes and Escherichia coli
- 1989
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Ingår i: Glycoconjugate Journal. - 1573-4986. ; 6, s. 161-168
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Tidskriftsartikel (refereegranskat)abstract
- Galβ1-3GlcNAc (1) and Galβ1-3GlcNAcβ-SEt (2) were synthesized on a 100 mg scale by the transgalactosylation reaction of bovine testes β-galactosidase with lactose as donor andN-acetylglucosamine and GlcNAcβ-SEt as acceptors. In both cases the product mixtures contained unwanted isomers and were treated with β-galactosidase from Escherichia coli which has a different specificity, under conditions favouring hydrolysis, yielding besides the desired products, monosaccharides and traces of trisaccharides. The products were purified to >95% by gel filtration, with a final yield of 12% of 1 and 17% of 2, based on added acceptor. In a separate experiment Galβ1-6GlcNAcβ-SEt (3) was synthesized by the transglycosylation reaction using β-galactosidase from Escherichia coli. No other isomers were detected. Compound 3 was purified by HPLC.
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| 93. |
- Hedbys, Lars, et al.
(författare)
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Synthesis of the disaccharide 6-O-β-d-galactopyranosyl-2-acetamido-2-deoxy-d-galactose using immobilized β-galactosidase
- 1984
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Ingår i: Biochemical and Biophysical Research Communications. - 0006-291X. ; 123:1, s. 8-15
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Tidskriftsartikel (refereegranskat)abstract
- The disaccharide 6-O-β-d-galactopyranosyl-2-acetamido-2-deoxy-d-galactose has been synthesized by transfer of the β-d-galactopyranosyl residue from lactose to 2-acetamido-2-deoxy-d-galactose utilizing the transferase activity of β-galactosidase from . To make the enzyme reusable, it was applied in an immobilized form covalently bound to Sepharose CL-4B. The yield of the disaccharide was about 20%, calculated on the amount of acetamido-deoxy-d-galactose added. The disaccharide could also be obtained by reversal of the hydrolytic activity of the enzyme, using d-galactose and 2-acetamido-2-deoxy-d-galactose as substrate. The yield in this reaction, however, was only 2–3 % under the conditions applied.
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| 94. |
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| 95. |
- Hemmingsson, Jens, 1986, et al.
(författare)
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Autoradiography and biopsy measurements of a resected hepatocellular carcinoma treated with 90 yttrium radioembolization demonstrate large absorbed dose heterogeneities
- 2018
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Ingår i: Advances in Radiation Oncology. - : Elsevier BV. - 2452-1094. ; 3:3, s. 439-446
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Tidskriftsartikel (refereegranskat)abstract
- © 2018 The Authors Purpose: Radioembolization is an alternative palliative treatment for hepatocellular carcinoma. Here, we examine the uptake differences between tumor tissue phenotypes and present a cross-section of the absorbed dose throughout a liver tissue specimen. Methods and materials: A patient with hepatocellular carcinoma was treated with90Y radioembolization followed by liver tissue resection. Gamma camera images and autoradiographs were collected and biopsy tissue samples were analyzed using a gamma well counter and light microscopy. Results: An analysis of 25 punched biopsy tissue samples identified 4 tissue regions: Normal tissue, viable tumor tissue with and without infarcted areas, and tumor areas with postnecrotic scar tissue. Autoradiography and biopsy tissue sample measurements showed large dose differences between viable and postnecrotic tumor tissue (159 Gy vs 23 Gy). Conclusions: Radioembolization of 90 yttrium with resin microspheres produces heterogeneous-absorbed dose distributions in the treatment of unifocal hepatic malignancies that could not be accurately determined with current gamma camera imaging techniques.
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| 96. |
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| 97. |
- Hendrikse, Natalie, et al.
(författare)
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Ancestral lysosomal enzymes with increased activity harbor therapeutic potential for treatment of Hunter syndrome
- 2021
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Ingår i: ISCIENCE. - : Elsevier BV. - 2589-0042. ; 24:3
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Tidskriftsartikel (refereegranskat)abstract
- We show the successful application of ancestral sequence reconstruction to enhance the activity of iduronate-2-sulfatase (IDS), thereby increasing its therapeutic potential for the treatment of Hunter syndrome-a lysosomal storage disease caused by impaired function of IDS. Current treatment, enzyme replacement therapy with recombinant human IDS, does not alleviate all symptoms, and an unmet medical need remains. We reconstructed putative ancestral sequences of mammalian IDS and compared them with extant IDS. Some ancestral variants displayed up to 2-fold higher activity than human IDS in in vitro assays and cleared more substrate in ex vivo experiments in patient fibroblasts. This could potentially allow for lower dosage or enhanced therapeutic effect in enzyme replacement therapy, thereby improving treatment outcomes and cost efficiency, as well as reducing treatment burden. In summary, we showed that ancestral sequence reconstruction can be applied to lysosomal enzymes that function in concert with modern enzymes and receptors in cells.
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| 98. |
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| 99. |
- Hendrikse, Natalie M., et al.
(författare)
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Exploring the therapeutic potential of modern and ancestral phenylalanine/tyrosine ammonia-lyases as supplementary treatment of hereditary tyrosinemia
- 2020
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Ingår i: Scientific Reports. - : Nature Research. - 2045-2322. ; 10:1
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Tidskriftsartikel (refereegranskat)abstract
- Phenylalanine/tyrosine ammonia-lyases (PAL/TALs) have been approved by the FDA for treatment of phenylketonuria and may harbour potential for complementary treatment of hereditary tyrosinemia Type I. Herein, we explore ancestral sequence reconstruction as an enzyme engineering tool to enhance the therapeutic potential of PAL/TALs. We reconstructed putative ancestors from fungi and compared their catalytic activity and stability to two modern fungal PAL/TALs. Surprisingly, most putative ancestors could be expressed as functional tetramers in Escherichia coli and thus retained their ability to oligomerize. All ancestral enzymes displayed increased thermostability compared to both modern enzymes, however, the increase in thermostability was accompanied by a loss in catalytic turnover. One reconstructed ancestral enzyme in particular could be interesting for further drug development, as its ratio of specific activities is more favourable towards tyrosine and it is more thermostable than both modern enzymes. Moreover, long-term stability assessment showed that this variant retained substantially more activity after prolonged incubation at 25 °C and 37 °C, as well as an increased resistance to incubation at 60 °C. Both of these factors are indicative of an extended shelf-life of biopharmaceuticals. We believe that ancestral sequence reconstruction has potential for enhancing the properties of enzyme therapeutics, especially with respect to stability. This work further illustrates that resurrection of putative ancestral oligomeric proteins is feasible and provides insight into the extent of conservation of a functional oligomerization surface area from ancestor to modern enzyme.
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| 100. |
- Hentati-Sundberg, Jonas, et al.
(författare)
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Seabird surveillance: combining CCTV and artificial intelligence for monitoring and research
- 2023
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Ingår i: Remote Sensing in Ecology and Conservation. - : Wiley. - 2056-3485. ; 9:4, s. 568-581
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Tidskriftsartikel (refereegranskat)abstract
- Ecological research and monitoring need to be able to rapidly convey information that can form the basis of scientifically sound management. Automated sensor systems, especially if combined with artificial intelligence, can contribute to such rapid high-resolution data retrieval. Here, we explore the prospects of automated methods to generate insights for seabirds, which are often monitored for their high conservation value and for being sentinels for marine ecosystem changes. We have developed a system of video surveillance combined with automated image processing, which we apply to common murres Uria aalge. The system uses a deep learning algorithm for object detection (YOLOv5) that has been trained on annotated images of adult birds, chicks and eggs, and outputs time, location, size and confidence level of all detections, frame-by-frame, in the supplied video material. A total of 144 million bird detections were generated from a breeding cliff over three complete breeding seasons (2019–2021). We demonstrate how object detection can be used to accurately monitor breeding phenology and chick growth. Our automated monitoring approach can also identify and quantify rare events that are easily missed in traditional monitoring, such as disturbances from predators. Further, combining automated video analysis with continuous measurements from a temperature logger allows us to study impacts of heat waves on nest attendance in high detail. Our automated system thus produces comparable, and in several cases significantly more detailed, data than those generated from observational field studies. By running in real time on the camera streams, it has the potential to supply researchers and managers with high-resolution up-to-date information on seabird population status. We describe how the system can be modified to fit various types of ecological research and monitoring goals and thereby provide up-to-date support for conservation and ecosystem management.
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