| 21. |
- Adman, Per, et al.
(författare)
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171 forskare: ”Vi vuxna bör också klimatprotestera”
- 2019
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Ingår i: Dagens nyheter (DN debatt). - Stockholm. - 1101-2447.
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Tidskriftsartikel (populärvet., debatt m.m.)abstract
- DN DEBATT 26/9. Vuxna bör följa uppmaningen från ungdomarna i Fridays for future-rörelsen och protestera eftersom det politiska ledarskapet är otillräckligt. Omfattande och långvariga påtryckningar från hela samhället behövs för att få de politiskt ansvariga att utöva det ledarskap som klimatkrisen kräver, skriver 171 forskare i samhällsvetenskap och humaniora.
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| 22. |
- Altai, Mohamed, et al.
(författare)
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Feasibility of Affibody-Based Bioorthogonal Chemistry Mediated Radionuclide Pretargeting
- 2016
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Ingår i: Journal of Nuclear Medicine. - : SOC NUCLEAR MEDICINE. - 0161-5505 .- 1535-5667 .- 2159-662X. ; 57:3, s. 431-436
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Tidskriftsartikel (refereegranskat)abstract
- Affibody molecules constitute a new class of probes for radionuclide tumor targeting. The small size of Affibody molecules is favorable for rapid localization in tumors and clearance from circulation. However, high renal reabsorption of Affibody molecules prevents the use of residualizing radiometals, including several promising low-energy (beta- and alpha-emitters, for radionuclide therapy. We tested a hypothesis that Affibody-based pretargeting mediated by a bioorthogonal interaction between trans-cyclooctene (TCO) and tetrazine would provide higher accumulation of radiometals in tumor xenografts than in the kidneys. Methods: TCO was conjugated to the anti-human epidermal growth factor receptor 2 (HER2) Affibody molecule Z(2395). DOTA-tetrazine was labeled with In-111 and Lu-177. In vitro pretargeting was studied in HER2-expressing SKOV-3 and BT474 cell lines. In vivo studies were performed on BALB/C nu/nu mice bearing SKOV-3 xenografts. Results: I-125-Z(2395)-TCO bound specifically to HER2-expressing cells in vitro with an affinity of 45 +/- 16 pM. In-111-tetrazine bound specifically and selectively to Z(2325)-TCO pretreated cells. In vivo studies demonstrated HER2-specific I-125-Z(2395)-TCO accumulation in xenografts. TCO-mediated In-111-tetrazine localization was shown in tumors, when the radiolabeled tracer was injected 4 h after an injection of Z(2395)-TCO. At 1 h after injection, the tumor uptake of In-111-tetrazine and Lu-177-tetrazine was approximately 2-fold higher than the renal uptake. Pretargeting provided more than a 56-fold reduction of renal uptake of In-111 in comparison with direct targeting. Conclusion: The feasibility of Affibody-based bioorthogonal chemistry-mediated pretargeting was demonstrated. The use of pre-targeting provides a substantial reduction of radiometal accumulation in kidneys, creating preconditions for palliative radionuclide therapy.
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| 23. |
- Altai, Mohamed, et al.
(författare)
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Preclinical evaluation of anti-HER2 Affibody molecules site-specifically labeled with In-111 using a maleimido derivative of NODAGA
- 2012
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Ingår i: Nuclear Medicine and Biology. - : Elsevier BV. - 0969-8051 .- 1872-9614. ; 39:4, s. 518-529
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Affibody molecules have demonstrated potential for radionuclide molecular imaging. The aim of this study was to synthesize and evaluate a maleimido derivative of the 1,4,7-triazacyclononane-l-glutaric acid-4,7-diacetic acid (NODAGA) for site-specific labeling of anti-HER2 Affibody molecule. Methods: The maleimidoethylmonoamide NODAGA (MMA-NODAGA) was synthesized and conjugated to Z(HER2:2395) Affibody molecule having a C-terminal cysteine. Labeling efficiency, binding specificity to and cell internalization by HER2-expressing cells of [In-111-MMA-NODAGA-Cys(61)]-Z(HER2:2395) were studied. Biodistribution of [In-111-MMA-NODAGA-Cys(61)]-Z(HER2:2395) and [In-111-MMA-DOTA-Cys(61)]-Z(HER2:2395) was compared in mice. Results: The affinity of [MMA-NODAGA-Cys(61)]-Z(HER2:2395) binding to HER2 was 67 pM. The In-1111-labeling yield was 99.6%+/- 0.5% after 30 min at 60 degrees C. [In-111-MMA-NODAGA-Cys(61)]-Z(HER2:2395) bound specifically to HER2-expressing cells in vitro and in vivo. Tumor uptake of [In-111-MMA-NODAGA-Cys(61)]-ZHER(2:2395) in mice bearing DU-145 xenografts (4.7%+/- 0.8% ID/g) was lower than uptake of [In-111-MMA-DOTA-Cys(61)]-Z(HER2:2395) (7.5%+/- 1.6% ID/g). However, tumor-to-organ ratios were higher for [In-111-MMA-NODAGA-Cys(61)]-Z(HER2:2395) due to higher clearance rate from normal tissues. Conclusions: MMA-NODAGA is a promising chelator for site-specific labeling of targeting proteins containing unpaired cysteine. Appreciable influence of chelators on targeting properties of Affibody molecules was demonstrated.
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| 24. |
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| 25. |
- Andréasson, Måns, 1994-, et al.
(författare)
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Exploring the dispersion and electrostatic components in arene-arene interactions between ligands and G4 DNA to develop G4-ligands
- 2024
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Ingår i: Journal of Medicinal Chemistry. - : American Chemical Society (ACS). - 0022-2623 .- 1520-4804. ; 67:3, s. 2202-2219
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Tidskriftsartikel (refereegranskat)abstract
- G-Quadruplex (G4) DNA structures are important regulatory elements in central biological processes. Small molecules that selectively bind and stabilize G4 structures have therapeutic potential, and there are currently >1000 known G4 ligands. Despite this, only two G4 ligands ever made it to clinical trials. In this work, we synthesized several heterocyclic G4 ligands and studied their interactions with G4s (e.g., G4s from the c-MYC, c-KIT, and BCL-2 promoters) using biochemical assays. We further studied the effect of selected compounds on cell viability, the effect on the number of G4s in cells, and their pharmacokinetic properties. This identified potent G4 ligands with suitable properties and further revealed that the dispersion component in arene-arene interactions in combination with electron-deficient electrostatics is central for the ligand to bind with the G4 efficiently. The presented design strategy can be applied in the further development of G4-ligands with suitable properties to explore G4s as therapeutic targets.
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| 26. |
- Asplund, Lillemor, et al.
(författare)
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Screening av Tetrabrombisfenol A
- 2004
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- Tetrabrombisfenol A (TBBPA), CAS nr 79-94-7, är ett flamskyddsmedel med stor användning. Till största delen används det som reaktivt flamskyddsmedel, dvs. TBBPA binds in kemiskt i polymera material. Allt binds dock inte in utan en mindre del kan läcka ut från den flamskyddade produkten (Sellström och Jansson, 1995). En viss användning av TBBPA som additivt flamskyddsmedel förekommer också (KemI, 2000). TBBPA är det flamskyddsmedel som omsätts mest i Sverige, 2001 omsattes 203 ton vilket kan jämföras med 58 ton för hexabromcyklododekan (HBCD). Användningen av HBCD ökade medan användningen av TBBPA minskade enligt KEMI (KemI, 2003, 4/03 ). TBBPA används främst vid tillverkning av flamskyddad epoxy- och polykarbonatplast men även i omättad polyester (WHO/IPCS, 1995). Epoxyplast som flamskyddats med TBBPA används huvudsakligen i kretskort. TBBPA används också i plastinkapslingar av elektroniska komponenter, i kåpor och i höljen till elektrisk utrustning.
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| 27. |
- Backmark, Anna, 1979, et al.
(författare)
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Affinity tags can reduce merohedral twinning of membrane protein crystals
- 2008
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Ingår i: Acta Crystallographica. Section D: Biological Crystallography. - 1399-0047 .- 0907-4449. ; D64, s. 1183-1186
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Tidskriftsartikel (refereegranskat)abstract
- This work presents a comparison of the crystal packing of three eukaryotic membrane proteins: human aquaporin 1, human aquaporin 5 and a spinach plasma membrane aquaporin. All were purified from expression constructs both with and without affinity tags. With the exception of tagged aquaporin 1, all constructs yielded crystals. Two significant effects of the affinity tags were observed: crystals containing a tag typically diffracted to lower resolution than those from constructs encoding the protein sequence alone and constructs without a tag frequently produced crystals that suffered from merohedral twinning. Twinning is a challenging crystallographic problem that can seriously hinder solution of the structure. Thus, for integral membrane proteins, the addition of an affinity tag may help to disrupt the approximate symmetry of the protein and thereby reduce or avoid merohedral twinning.
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| 28. |
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| 29. |
- Beausang, Angela, et al.
(författare)
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"Möjligheten att rädda några av dessa kvinnors liv har inte vägts in"
- 2014
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Ingår i: Dagens Medicin. - : Dagens Medicin.
-
Tidskriftsartikel (populärvet., debatt m.m.)abstract
- Namnet på Socialstyrelsens vägledning lyder: Hur upptäcka våldsutsatthet? Ja, det kan man verkligen fråga sig efter att ha läst detta föga vägledande dokument, skriver ett stort antal kritiska debattörer.
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| 30. |
- Beers, Timothy C., et al.
(författare)
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Broadband UBVRCIC photometry of horizontal-branch and metal-poor candidates from the HK and Hamburg/ESO surveys. I.
- 2007
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Ingår i: Astrophysical Journal Supplement Series. - : American Astronomical Society. - 0067-0049 .- 1538-4365. ; 168:1, s. 128-139
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Tidskriftsartikel (refereegranskat)abstract
- We report broadband UBV and/or BVRCIC CCD photometry for a total of 1857 stars in the thick-disk and halo populations of the Galaxy. The majority of our targets were selected as candidate field horizontal-branch or other A-type stars (FHB/ A, N = 576), or candidate low-metallicity stars (N = 1221), from the HK and Hamburg/ESO objective-prism surveys. Similar data for a small number of additional stars from other samples are also reported. These data are being used for several purposes. In the case of the FHB/ A candidates they are used to accurately separate the lower gravity FHB stars from various higher gravity A-type stars, a subsample that includes the so-called blue metal poor stars, halo and thick-disk blue stragglers, main-sequence A-type dwarfs, and Am and Ap stars. These data are also being used to derive photometric distance estimates to high-velocity hydrogen clouds in the Galaxy and for improved measurements of the mass of the Galaxy. Photometric data for the metal-poor candidates are being used to refine estimates of stellar metallicity for objects with available medium-resolution spectroscopy, to obtain distance estimates for kinematic analyses, and to establish initial estimates of effective temperature for analysis of high-resolution spectroscopy of the stars for which this information now exists.
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