| 1. |
- Allard, Christina, et al.
(författare)
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Rasbiologiskt språkbruk i statens rättsprocess mot sameby : DN Debatt 2015-06-11
- 2015
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Annan publikation (populärvet., debatt m.m.)abstract
- Statens hantering av forskningsresultat i rättsprocessen med Girjas sameby utgör ett hot mot Sverige som rättsstat och kunskapsnation. Åratal av svensk och internationell forskning underkänns och man använder ett språkbruk som skulle kunna vara hämtat från rasbiologins tid. Nu måste staten ta sitt ansvar och börja agera som en demokratisk rättsstat, skriver 59 forskare.
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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. |
- Evander, Mikael, et al.
(författare)
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Noninvasive acoustic cell trapping in a microfluidic perfusion system for online bioassays
- 2007
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Ingår i: Analytical Chemistry. - : American Chemical Society (ACS). - 0003-2700 .- 1520-6882. ; 79:7, s. 2984-2991
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Tidskriftsartikel (refereegranskat)abstract
- Techniques for manipulating, separating, and trapping particles and cells are highly desired in today's bioanalytical and biomedical field. The microfluidic chip-based acoustic noncontact trapping method earlier developed within the group now provides a flexible platform for performing cell- and particle-based assays in continuous flow microsystems. An acoustic standing wave is generated in etched glass channels (600x61 microm2) by miniature ultrasonic transducers (550x550x200 microm3). Particles or cells passing the transducer will be retained and levitated in the center of the channel without any contact with the channel walls. The maximum trapping force was calculated to be 430+/-135 pN by measuring the drag force exerted on a single particle levitated in the standing wave. The temperature increase in the channel was characterized by fluorescence measurements using rhodamine B, and levels of moderate temperature increase were noted. Neural stem cells were acoustically trapped and shown to be viable after 15 min. Further evidence of the mild cell handling conditions was demonstrated as yeast cells were successfully cultured for 6 h in the acoustic trap while being perfused by the cell medium at a flowrate of 1 microL/min. The acoustic microchip method facilitates trapping of single cells as well as larger cell clusters. The noncontact mode of cell handling is especially important when studies on nonadherent cells are performed, e.g., stem cells, yeast cells, or blood cells, as mechanical stress and surface interaction are minimized. The demonstrated acoustic trapping of cells and particles enables cell- or particle-based bioassays to be performed in a continuous flow format.
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| 4. |
- Fröbert, Ole, et al.
(författare)
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Thrombus Aspiration during ST-Segment Elevation Myocardial Infarction
- 2013
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Ingår i: New England Journal of Medicine. - : Massachusetts Medical Society. - 0028-4793 .- 1533-4406. ; 369:17, s. 1587-1597
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundThe clinical effect of routine intracoronary thrombus aspiration before primary percutaneous coronary intervention (PCI) in patients with ST-segment elevation myocardial infarction (STEMI) is uncertain. We aimed to evaluate whether thrombus aspiration reduces mortality. MethodsWe conducted a multicenter, prospective, randomized, controlled, open-label clinical trial, with enrollment of patients from the national comprehensive Swedish Coronary Angiography and Angioplasty Registry (SCAAR) and end points evaluated through national registries. A total of 7244 patients with STEMI undergoing PCI were randomly assigned to manual thrombus aspiration followed by PCI or to PCI only. The primary end point was all-cause mortality at 30 days. ResultsNo patients were lost to follow-up. Death from any cause occurred in 2.8% of the patients in the thrombus-aspiration group (103 of 3621), as compared with 3.0% in the PCI-only group (110 of 3623) (hazard ratio, 0.94; 95% confidence interval [CI], 0.72 to 1.22; P=0.63). The rates of hospitalization for recurrent myocardial infarction at 30 days were 0.5% and 0.9% in the two groups, respectively (hazard ratio, 0.61; 95% CI, 0.34 to 1.07; P=0.09), and the rates of stent thrombosis were 0.2% and 0.5%, respectively (hazard ratio, 0.47; 95% CI, 0.20 to 1.02; P=0.06). There were no significant differences between the groups with respect to the rate of stroke or neurologic complications at the time of discharge (P=0.87). The results were consistent across all major prespecified subgroups, including subgroups defined according to thrombus burden and coronary flow before PCI. ConclusionsRoutine thrombus aspiration before PCI as compared with PCI alone did not reduce 30-day mortality among patients with STEMI. (Funded by the Swedish Research Council and others; ClinicalTrials.gov number, NCT01093404.)
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| 5. |
- 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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| 6. |
- Jiang, X., et al.
(författare)
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Shared heritability and functional enrichment across six solid cancers
- 2019
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 10
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Tidskriftsartikel (refereegranskat)abstract
- Quantifying the genetic correlation between cancers can provide important insights into the mechanisms driving cancer etiology. Using genome-wide association study summary statistics across six cancer types based on a total of 296,215 cases and 301,319 controls of European ancestry, here we estimate the pair-wise genetic correlations between breast, colorectal, head/neck, lung, ovary and prostate cancer, and between cancers and 38 other diseases. We observed statistically significant genetic correlations between lung and head/neck cancer (r(g) = 0.57, p = 4.6 x 10(-8)), breast and ovarian cancer (r(g) = 0.24, p = 7 x 10(-5)), breast and lung cancer (r(g) = 0.18, p = 1.5 x 10(-6)) and breast and colorectal cancer (r(g) = 0.15, p = 1.1 x 10(-4)). We also found that multiple cancers are genetically correlated with non-cancer traits including smoking, psychiatric diseases and metabolic characteristics. Functional enrichment analysis revealed a significant excess contribution of conserved and regulatory regions to cancer heritability. Our comprehensive analysis of cross-cancer heritability suggests that solid tumors arising across tissues share in part a common germline genetic basis.
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| 7. |
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| 8. |
- Johansson, Linda, et al.
(författare)
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Temperature and trapping characterization of an acoustic trap with miniaturized integrated transducers - towards in-trap temperature regulation
- 2013
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Ingår i: Ultrasonics. - : Elsevier BV. - 0041-624X .- 1874-9968. ; 53:5, s. 1020-1032
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Tidskriftsartikel (refereegranskat)abstract
- An acoustic trap with miniaturized integrated transducers (MITs) for applications in non-contact trapping of cells or particles in a microfluidic channel was characterized by measuring the temperature increase and trapping strength. The fluid temperature was measured by the fluorescent response of Rhodamine B in the microchannel. The trapping strength was measured by the area of a trapped particle cluster counter-balanced by the hydrodynamic force. One of the main objectives was to obtain quantitative values of the temperature in the fluidic channel to ensure safe handling of cells and proteins. Another objective was to evaluate the trapping-to-temperature efficiency for the trap as a function of drive frequency. Thirdly, trapping-to-temperature efficiency data enables identifying frequencies and voltage values to use for in-trap temperature regulation. It is envisioned that operation with only in-trap temperature regulation enables the realization of small, simple and fast temperature-controlled trap systems. The significance of potential gradients at the trap edges due to the finite size of the miniaturized transducers for the operation was emphasized and expressed analytically. The influence of the acoustic near field was evaluated in FEM-simulation and compared with a more ideal 1D standing wave. The working principle of the trap was examined by comparing measurements of impedance, temperature increase and trapping strength with impedance transfer calculations of fluid-reflector resonances and frequencies of high reflectance at the fluid-reflector boundary. The temperature increase was found to be moderate, 7 degrees C for a high trapping strength, at a fluid flow of 0.5 mm s(-1) for the optimal driving frequency. A fast temperature response with a fall time of 8 s and a rise time of 11 s was observed. The results emphasize the importance of selecting the proper drive frequency for long term handling of cells, as opposed to the more pragmatic way of selecting the frequency of the highest acoustic output. Trapping was demonstrated in a large interval between 9 and 11.5 MHz, while the main trapping peak displayed FWHM of 0.5 MHz. A large bandwidth enables a more robust manufacturing and operation while allowing the trapping platform to be used in applications where the fluid wavelength varies due to external variations in fluid temperature, density and pressure.
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| 9. |
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| 10. |
- Abrahamsson, Maria, et al.
(författare)
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A new strategy for the improvement of photophysical properties in ruthenium(II) polypyridyl complexes. Synthesis and photophysical and electrochemical characterization of six mononuclear ruthenium(II) bisterpyridine-type complexes
- 2005
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Ingår i: Inorganic Chemistry. - : American Chemical Society (ACS). - 0020-1669 .- 1520-510X. ; 44:9, s. 3215-3225
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Tidskriftsartikel (refereegranskat)abstract
- The synthesis and characterization of six ruthenium(II) bistridentate polypyridyl complexes is described. These were designed on the basis of a new approach to increase the excited-state lifetime of ruthenium(II) bisterpyridine-type complexes. By the use of a bipyridylpyridyl methane ligand in place of terpyridine, the coordination environment of the metal ion becomes nearly octahedral and the rate of deactivation via ligand-field (i.e., metal-centered) states was reduced as shown by temperature-dependent emission lifetime studies. Still, the possibility to make quasi-linear donor-ruthenium-acceptor triads is maintained in the complexes. The most promising complex shows an excited-state lifet me of tau = 15 ns in alcohol solutions at room temperature, which should be compared to a lifetime of tau = 0.25 ns for [Ru(tpy)(2)](2+). The X-ray structure of the new complex indeed shows a more octahedral geometry than that of [Ru(tpy)(2)](2+). Most importantly, the high excited-state energy was retained, and thus, so was the potential high reactivity of the excited complex, which has not been the case with previously published strategies based on bistridentate complexes.
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