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| 2. |
- Ferreira, Mjv, et al.
(författare)
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Poster Session 3 : Tuesday 5 May 2015, 08
- 2015
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Ingår i: European Heart Journal Cardiovascular Imaging. - : Oxford University Press (OUP). - 2047-2404 .- 2047-2412. ; 16 Suppl 1
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Tidskriftsartikel (refereegranskat)
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| 3. |
- Gad, Helge, et al.
(författare)
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MTH1 inhibition eradicates cancer by preventing sanitation of the dNTP pool
- 2014
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Ingår i: Nature. - : Nature Publishing Group. - 0028-0836 .- 1476-4687. ; 508:7495, s. 215-221
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Tidskriftsartikel (refereegranskat)abstract
- Cancers have dysfunctional redox regulation resulting in reactive oxygen species production, damaging both DNA and free dNTPs. The MTH1 protein sanitizes oxidized dNTP pools to prevent incorporation of damaged bases during DNA replication. Although MTH1 is non-essential in normal cells, we show that cancer cells require MTH1 activity to avoid incorporation of oxidized dNTPs, resulting in DNA damage and cell death. We validate MTH1 as an anticancer target in vivo and describe small molecules TH287 and TH588 as first-in-class nudix hydrolase family inhibitors that potently and selectively engage and inhibit the MTH1 protein in cells. Protein co-crystal structures demonstrate that the inhibitors bindin the active site of MTH1. The inhibitors cause incorporation of oxidized dNTPs in cancer cells, leading to DNA damage, cytotoxicity and therapeutic responses in patient-derived mouse xenografts. This study exemplifies the non-oncogene addiction concept for anticancer treatment and validates MTH1 as being cancer phenotypic lethal.
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| 4. |
- Lange, Jonathan, et al.
(författare)
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Novel lithographic printing techniques enabling sustainable and high quality multi material manufacturing process for future space outposts
- 2021
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Ingår i: IAC 2021 Congress Proceedings, 72nd International Astronautical Congress (IAC), Dubai, United Arab Emirates. - : International Astronautical Federation (IAF).
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Konferensbidrag (refereegranskat)abstract
- Several challenges remain before the full potential of on-orbit manufacturing can be realized. There may be some limitations to the types of items that can be manufactured in space. Such limitations could be caused by a variety of factors, including the materials required for a particular structure, the size of the object to be manufactured, the time required to execute the architecture, the configuration of the object being manufactured, and the raw material needed to support the manufacturing process. The complementary challenge to the relevant fabrication processes is the possibility to achieve the required precision demanded by geometrically complex structures and the ability to be versatile in processing a broad material spectrum. In this context, novel lithographic 3D printing techniques will be an asset to pave the way towards overcoming these challenges. Currently, the European Space Agency (ESA) is investigating the implementation of such technology in the context of a lunar base. In particular, two different applications are being studied: • Lithography-Based Ceramic Manufacturing (LCM), where the ceramic powder is distributed in a photocurable monomer formulation in presence of a photoinitiator. Ceramic materials are extensively used in a vast number of technological processes as well as in space applications. They are usually considered as the material of choice for applications where other materials such as plastic and metal fail to deliver the required performance. The LCM process will also allow processing lunar regolith simulant adding value to the current material portfolio of this technique, as well as to the range of processes potentially applicable on the lunar or Martian surface. • Lithography-based Metal Manufacturing (LMM) for processing metallic powders. In contrast to the currently predominantly used powder bed fusion (direct metal laser melting) techniques, this process uses a paste/suspension as feedstock and hence, does not rely on the use of highly spherical gas atomized powders. This will enable the utilization of recycled powders from scrap metals that are available at Moon bases or of metallic alloys reduced from lunar regolith, thus providing higher flexibility in accepting raw material with poor quality and purity. The paper addresses the results from both activities in terms of printed parts quality (roughness, density, resolution and accuracy) as well as the implementation requirements for the whole process chain, including suitable pre- and post-processing steps, with the aim to achieve a zero-waste flow in a lunar environment.
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| 7. |
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| 8. |
- Lovric, A, et al.
(författare)
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Single-cell sequencing deconvolutes cellular responses to exercise in human skeletal muscle
- 2022
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Ingår i: Communications biology. - : Springer Science and Business Media LLC. - 2399-3642. ; 5:1, s. 1121-
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Tidskriftsartikel (refereegranskat)abstract
- Skeletal muscle adaptations to exercise have been associated with a range of health-related benefits, but cell type-specific adaptations within the muscle are incompletely understood. Here we use single-cell sequencing to determine the effects of exercise on cellular composition and cell type-specific processes in human skeletal muscle before and after intense exercise. Fifteen clusters originating from six different cell populations were identified. Most cell populations remained quantitatively stable after exercise, but a large transcriptional response was observed in mesenchymal, endothelial, and myogenic cells, suggesting that these cells are specifically involved in skeletal muscle remodeling. We found three subpopulations of myogenic cells characterized by different maturation stages based on the expression of markers such asPAX7,MYOD1,TNNI1, andTNNI2. Exercise accelerated the trajectory of myogenic progenitor cells towards maturation by increasing the transcriptional features of fast- and slow-twitch muscle fibers. The transcriptional regulation of these contractile elements upon differentiation was validated in vitro on primary myoblast cells. The cell type-specific adaptive mechanisms induced by exercise presented here contribute to the understanding of the skeletal muscle adaptations triggered by physical activity and may ultimately have implications for physiological and pathological processes affecting skeletal muscle, such as sarcopenia, cachexia, and glucose homeostasis.
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