| 1. |
- Danared, Håkan, et al.
(författare)
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Preface
- 2017
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Ingår i: IPAC 2018 : Proceedings of the 8th International Particle Accelerator Conference - Proceedings of the 8th International Particle Accelerator Conference. - 9783954501823
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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| 2. |
- Dolinska, Monika, et al.
(författare)
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Characterization of the bone marrow niche in patients with chronic myeloid leukemia identifies CXCL14 as a new therapeutic option
- 2023
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Ingår i: Blood. - : American Society of Hematology. - 0006-4971 .- 1528-0020. ; 142:1, s. 73-89
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Tidskriftsartikel (refereegranskat)abstract
- Although tyrosine kinase inhibitors (TKIs) are effective in treating chronic myeloid leukemia (CML), they often fail to eradicate the leukemia-initiating stem cells (LSCs), causing disease persistence and relapse. Evidence indicates that LSC persistence may be because of bone marrow (BM) niche protection; however, little is known about the underlying mechanisms. Herein, we molecularly and functionally characterize BM niches in patients with CML at diagnosis and reveal the altered niche composition and function in these patients. Long -term culture initiating cell assay showed that the mesenchymal stem cells from patients with CML displayed an enhanced supporting capacity for normal and CML BM CD34+CD38- cells. Molecularly, RNA sequencing detected dysregulated cytokine and growth factor expression in the BM cellular niches of patients with CML. Among them, CXCL14 was lost in the BM cellular niches in contrast to its expression in healthy BM. Restoring CXCL14 significantly inhibited CML LSC maintenance and enhanced their response to imatinib in vitro, and CML engraftment in vivo in NSG-SGM3 mice. Importantly, CXCL14 treatment dramatically inhibited CML engraftment in patient-derived xenografted NSG-SGM3 mice, even to a greater degree than imatinib, and this inhibition persisted in patients with suboptimal TKI response. Mechanistically, CXCL14 upregulated inflammatory cytokine signaling but downregulated mTOR signaling and oxidative phosphorylation in CML LSCs. Together, we have discovered a suppressive role of CXCL14 in CML LSC growth. CXCL14 might offer a treatment option targeting CML LSCs.
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| 3. |
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| 4. |
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| 5. |
- Abildgaard, Amanda B., et al.
(författare)
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HSP70-binding motifs function as protein quality control degrons
- 2023
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Ingår i: Cellular and Molecular Life Sciences (CMLS). - : Springer Science and Business Media LLC. - 1420-682X .- 1420-9071. ; 80:1
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Tidskriftsartikel (refereegranskat)abstract
- Protein quality control (PQC) degrons are short protein segments that target misfolded proteins for proteasomal degradation, and thus protect cells against the accumulation of potentially toxic non-native proteins. Studies have shown that PQC degrons are hydrophobic and rarely contain negatively charged residues, features which are shared with chaperone-binding regions. Here we explore the notion that chaperone-binding regions may function as PQC degrons. When directly tested, we found that a canonical Hsp70-binding motif (the APPY peptide) functioned as a dose-dependent PQC degron both in yeast and in human cells. In yeast, Hsp70, Hsp110, Fes1, and the E3 Ubr1 target the APPY degron. Screening revealed that the sequence space within the chaperone-binding region of APPY that is compatible with degron function is vast. We find that the number of exposed Hsp70-binding sites in the yeast proteome correlates with a reduced protein abundance and half-life. Our results suggest that when protein folding fails, chaperone-binding sites may operate as PQC degrons, and that the sequence properties leading to PQC-linked degradation therefore overlap with those of chaperone binding.
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| 6. |
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| 7. |
- Andersen, Paul Krüger, et al.
(författare)
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Response to the Proposal for a Directive on Corporate Sustainability Due Diligence by Nordic and Baltic Company Law Scholars
- 2022
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- On February 23, 2022, The EU Commission published its Proposal for a Directive of the European Parliament and of the Council on Corporate Sustainability Due Diligence and amending Directive (EU) 2019/1937 (“CSDDD” or “the Proposal”). The purpose of the Proposal, to further the “Union’s transition to a climate-neutral and green economy in line with the European Green Deal and in delivering on the UN Sustainable Development Goals”, is of great importance, and the Commission’s initiative is therefore commendable. However, it is our firm opinion that the Proposal should not be enacted in its present form, and that if it were to be, it would not only damage European businesses but also run the risk of having an adverse effect on both the transition to a climate-neutral economy as well as the goal of delivering on the UN Sustainable Development Goals. This is to a large extent because many of the Proposal’s provisions are excessive, unfounded and disproportionate and as such in violation of the fundamental principles of subsidiarity and proportionality safeguarded by Art. 5 TEU as well as having a questionable basis in Art. 50 TFEU. Furthermore and in regard of procedure, we find that the presentation of the Proposal by the Commission represents a disregard for the principles of better regulation that should not pass unnoticed and must be observed in the future to maintain trust in the legislative process of the Union.In this response to the consultation, we have presented an analysis of the key issues of the Proposal from a corporate governance perspective. We have divided the response into two parts: one on the pure corporate governance parts of the Proposal (article 15, 25 and 26) and one of the due diligence parts of the Proposal. With regards to the corporate governance parts of the Proposal, our conclusion is that they, by and large, should not be included in the proposed directive at all. Including them would in several ways be in breach of the EU principles on subsidiarity and proportionality, but perhaps more importantly, they are not only unsubstantiated by available empirical evidence on corporate behaviour, but also refuted by what we know. There is also good reason to believe that the proposed rules on director’s duties and environmental remuneration would risk decreasing the effectiveness of the stock markets within the EU contrary to the goal of a Capital Market Union, which also risk slowing down the necessary transition to a green economy and the goals of the EU Green Deal. The regulation necessary for the Capital Market Union and the EU Green Deal should complement each other, not collide as would be the outcome if the Proposal is adopted in its present form.With regards to the due diligence parts of the Proposal, our criticism is limited to corporate governance aspects and far less fundamental. We primarily believe that grounds for harmonisation needs further consideration in the present very challenging times, that Article 22 on Civil Liability might in several ways be counter-productive to the goals of the Proposal, that the effects on SMEs as well as for the financial companies included covered by the Proposal warrants further analysis, that the choice to focus the Proposal on individual companies instead of company groups needs to be reviewed, and that a risk based approach should be taken rather than an approach were companies are unable to focus their efforts to where they can be most effective. Overall, these issues can be worked out, but if they are not, then the proposed directive would not only have a severe adverse impact on EU companies and possibly capital markets, but might actually hinder EU companies from acting in the way that the Proposal aims for them to do.This joint response to the public consultation is made by a group of Nordic and Baltic company law scholars who, although we may not agree on every detail, do share the main arguments and grave concerns expressed here.
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| 8. |
- Andersson, Martin, et al.
(författare)
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A biokinetic and dosimetric model for ionic indium in humans
- 2017
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Ingår i: Physics in Medicine and Biology. - : IOP Publishing. - 0031-9155 .- 1361-6560. ; 62:16, s. 6397-6407
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Tidskriftsartikel (refereegranskat)abstract
- This paper reviews biokinetic data for ionic indium, and proposes a biokinetic model for systemic indium in adult humans. The development of parameter values focuses on human data and indium in the form of ionic indium(III), as indium chloride and indium arsenide. The model presented for systemic indium is defined by five different pools: plasma, bone marrow, liver, kidneys and other soft tissues. The model is based on two subsystems: one corresponding to indium bound to transferrin and one where indium is transported back to the plasma, binds to red blood cell transferrin and is then excreted through the kidneys to the urinary bladder. Absorbed doses to several organs and the effective dose are calculated for 111In- and 113mIn-ions. The proposed biokinetic model is compared with previously published biokinetic indium models published by the ICRP. The absorbed doses are calculated using the ICRP/ICRU adult reference phantoms and the effective dose is estimated according to ICRP Publication 103. The effective doses for 111In and 113mIn are 0.25 mSv MBq-1 and 0.013 mSv MBq-1 respectively. The updated biokinetic and dosimetric models presented in this paper take into account human data and new animal data, which represent more detailed and presumably more accurate dosimetric data than that underlying previous models for indium.
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| 9. |
- Andersson, Martin, et al.
(författare)
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An internal radiation dosimetry computer program, IDAC 2.0, for estimation of patient doses from radiopharmaceuticals
- 2014
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Ingår i: Radiation Protection Dosimetry. - : Oxford University Press (OUP). - 0144-8420 .- 1742-3406. ; 162:3, s. 299-305
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Tidskriftsartikel (refereegranskat)abstract
- The internal dosimetry computer program internal dose assessment by computer (IDAC) for calculations of absorbed doses to organs and tissues as well as effective doses to patients from examinations with radiopharmaceuticals has been developed. The new version, IDAC2.0, incorporates the International Commission on Radiation Protection (ICRP)/ICRU computational adult male and female voxel phantoms and decay data from the ICRP publication 107. Instead of only 25 source and target regions, calculation can now be made with 63 source regions to 73 target regions. The major advantage of having the new phantom is that the calculations of the effective doses can be made with the latest tissue weighting factors of ICRP publication 103. IDAC2.0 uses the ICRP human alimentary tract (HAT) model for orally administrated activity and for excretion through the gastrointestinal tract and effective doses have been recalculated for radiopharmaceuticals that are orally administered. The results of the program are consistent with published data using the same specific absorption fractions and also compared with published data from the same computational phantoms but with segmentation of organs leading to another set of specific absorption fractions. The effective dose is recalculated for all the 34 radiopharmaceuticals that are administered orally and has been published by the ICRP. Using the new HAT model, new tissue weighting factors and the new adult computational voxel phantoms lead to an average effective dose of half of its earlier estimated value. The reduction mainly depends on electron transport simulations to walled organs and the transition from the stylised phantom with unrealistic interorgan distances to more realistic voxel phantoms.
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| 10. |
- Andersson, Martin, et al.
(författare)
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An upgrade of the internal dosimetry computer program IDAC
- 2012
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Ingår i: Medical Physics in the Baltic States. - : Kaunas University of Technology. - 1822-5721. ; , s. 120-123
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Konferensbidrag (refereegranskat)abstract
- A full update of the internal dosimetry computer program IDAC has been conducted. The new update is based on new and more accurate computational phantoms to calculate effective dose and absorbed dose to organs and tissues. The new ICRP Adult Reference Computational Phantoms has been adopted as well as the latest of the ICRP standardized biokinetic models. The updated computer program includes a user-friendly graphical user interface.
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