| 11. |
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| 12. |
- Arvidsson, Anna K, et al.
(författare)
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Klimatanpassning av vägkonstruktion, drift och underhåll
- 2012
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- Klimatförändringarna är en realitet och påverkar vårt samhälle och därigenom även våra transporter. Genom att klimatanpassa transportsystemen blir systemen mer robusta och risken för transportstörningar blir mindre. För vägars konstruktion, drift och underhåll innebär klimatanpassningen i de flesta fall relativt stora förändringar men det saknas idag en övergripande bild av det totala klimatanpassningsbehovet nationellt sett samt vilka åtgärder som behöver tas och som är rimliga att tas. Eftersom klimatförändringarna generellt varierar mellan Sveriges klimatzoner är det förenat med stora svårigheter att förutsäga vilken påverkan klimatförändringarna får på vägarnas beteende och livslängd. Inom vinterväghållningen i Sverige kommer saltanvändandet totalt sett att minska på grund av det varmare klimatet. Plogningstillfällena kommer antagligen minska, men beredskapen bör inte minskas för mycket eftersom de mer extrema tillfällena kommer att öka. För att lyckas klimatanpassa vägtransportsystemen så att de blir robusta konstaterar vi att det finns ett stort behov för att ta fram mer kunskap om vägkonstruktionens påverkan av ett förändrat klimat, samt inom drift och underhåll hur man skall anpassa sig genom olika typer av varierande och flexibla klimatanpassningsåtgärder och till effekterna av extrema väderhändelser.
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| 13. |
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| 14. |
- Atienza-Párraga, Alba, et al.
(författare)
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Epigenomic re-configuration of primary multiple myeloma underlies the synergistic effect of combined DNMT and EZH2 inhibition.
-
Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Multiple myeloma (MM) is characterized by an overexpression of EZH2 and a subsequent increase in H3K27me3-mediated silencing. However, the genome-wide redistribution of this mark in context with other epigenetic tags remains largely unexplored. Here, we show that EZH2 physically interacts with DNMT1 and that combined inhibition leads to a reduced G2/M arrest and increased apoptosis in MM. In addition, we present a catalogue of the genomic regulatory regions in normal plasma cells (NPC) as defined by their individual combination of histone marks. We used ChIP-seq and ATAC-seq data to generate whole-genome NPC chromatin annotations which we further analysed using DNA methylation arrays and RNA-seq. Comparison between NPC and MM demonstrated that, despite the global hypomethylation, enhancers show a tendency towards a higher DNA methylation levels in MM, whereas Polycomb and heterochromatic sites, highly methylated in NPC, show intermediate levels of the mark. Across all examined regulatory regions, 5-azacytidine treatment strongly reduced DNA methylation in MM. Furthermore, we find an extensive re-structuration of the global histone patterns in MM. We noticed a widespread increase in H3K27me3 except at active TSSs/promoters and enhancers, where we found a selective gain of the mark, suggestive of a directed silencing. In contrast, poised TSSs lose H3K27me3 and gain the activation mark H3K27ac, reflecting potential activation. Taken together, we present a comprehensive map of the epigenomic changes in MM as compared to NPC and provide insights into the interplay between EZH2 and DNMT1 in MM.
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| 15. |
- Bahram, Fuad, et al.
(författare)
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Posttranslational regulation of Myc function in response to phorbol ester/interferon-gamma-induced differentiation of v-Myc-transformed U-937 monoblasts
- 1999
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Ingår i: Blood. - 0006-4971 .- 1528-0020. ; 93:11, s. 3900-3912
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Tidskriftsartikel (refereegranskat)abstract
- The transcription factors of the Myc/Max/Mad network are important regulators of cell growth, differentiation, and apoptosis and are frequently involved in tumor development. Constitutive expression of v-Myc blocks phorbol ester (TPA)-induced differentiation of human U-937 monoblasts. However, costimulation with interferon-gamma (IFN-gamma) and TPA restores terminal differentiation and G1 cell-cycle arrest despite continuous expression of v-Myc. The mechanism by which TPA + IFN-gamma counteract v-Myc activity has not been unravelled. Our results show that TPA + IFN-gamma treatment led to an inhibition of v-Myc- and c-Myc-dependent transcription, and a specific reduction of v-Myc:Max complexes and associated DNA-binding activity, whereas the steady state level of the v-Myc protein was only marginally affected. In contrast, TPA + IFN-gamma costimulation neither increased the expression of Mad1 or other mad/mnt family genes nor altered heterodimerization or DNA-binding activity of Mad1. The reduced amount of v-Myc:Max heterodimers in response to treatment was accompanied by partial dephosphorylation of v-Myc and c-Myc. Phosphatase treatment of Myc:Max complexes lead to their dissociation, thus mimicking the effect of TPA + IFN-gamma. In addition to modulation of the expression of Myc/Max/Mad network proteins, posttranslational negative regulation of Myc by external signals may, therefore, be an alternative biologically important level of control with potential therapeutic relevance for hematopoietic and other tumors with deregulated Myc expression.
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| 16. |
- Botling, Johan, et al.
(författare)
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CD49f (alpha 6 integrin) and CD66a (BGP) are specifically induced by retinoids during human monocytic differentiation
- 1995
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Ingår i: Leukemia. - 0887-6924 .- 1476-5551. ; 9:12, s. 2034-41
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Tidskriftsartikel (refereegranskat)abstract
- Retinoic acid (RA) and 1,25(OH)2-cholecalciferol (VitD3) are potent regulators of normal and malignant myeloid cells. In the human monoblast cell line U-937 they induce terminal differentiation, and the resulting phenotypes display both common and distinct, inducer-specific, properties. This paper shows that in U-937 cells the two retinoids, all-trans and 9-cis RA, induced the expression of CD49f (alpha 6 integrin subunit) and CD66a (biliary glycoprotein, BGP) mRNA and protein. In contrast, expression of CD49f and CD66a was not found in untreated or VitD3-induced cells. Cytokine-induced modulation of CD49f and CD66a expression was restricted to the retinoid-induced U-937 cells. The retinoid specific induction of CD49f and CD66a was confirmed in the related monoblastic cell line THP-1. Human blood monocytes and the monocytic cell line Mono Mac 6 responded poorly to RA, with respect to the regulation of CD49f and CD66a expression, indicating that early monocytic precursors were targets for the retinoid-specific regulation. Thus, the expression of CD49f and CD66a is developmentally regulated and specifically induced by all-trans and 9-cis Ra in human monocytic cells.
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| 17. |
- Botling, Johan, et al.
(författare)
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Retinoic acid receptor/retinoid X receptor heterodimers can be activated through both subunits providing a basis for synergistic transactivation and cellular differentiation
- 1997
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Ingår i: Journal of Biological Chemistry. - : Elsevier BV. - 0021-9258 .- 1083-351X. ; 272:14, s. 9443-9
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Tidskriftsartikel (refereegranskat)abstract
- The receptor for 9-cis-retinoic acid, retinoid X receptor (RXR), forms heterodimers with several nuclear receptors, including the receptor for all-trans-retinoic acid, RAR. Previous studies have shown that retinoic acid receptor can be activated in RAR/RXR heterodimers, whereas RXR is believed to be a silent co-factor. In this report we show that efficient growth arrest and differentiation of the human monocytic cell line U-937 require activation of both RAR and RXR. Also, we demonstrate that the allosteric inhibition of RXR is not obligatory and that RXR can be activated in the RAR/RXR heterodimer in the presence of RAR ligands. Remarkably, RXR inhibition by RAR can also be relieved by an RAR antagonist. Moreover, the dose response of RXR agonists differ between RXR homodimers and RAR/RXR heterodimers, indicating that these complexes are pharmacologically distinct. Finally, the AF2 activation domain of both subunits contribute to activation even if only one of the receptors is associated with ligand. Our data emphasize the importance of signaling through both subunits of a heterodimer in the physiological response to retinoids and show that the activity of RXR is dependent on both the identity and the ligand binding state of its partner.
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| 18. |
- Botling, Johan, et al.
(författare)
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Vitamin D3 and retinoic acid induced monocytic differentiation : Interactions between the endogenous vitamin D3, retinoic acid and retinoid X receptors in U-937 cells
- 1996
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Ingår i: Cell growth & differentiation. - 1044-9523. ; 7:9, s. 1239-49
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Tidskriftsartikel (refereegranskat)abstract
- Retinoic acid (RA) and 1,25 alpha-dihydroxycholecalciferol (VitD3) are potent regulators of hematopoletic differentiation. Yet, little is known as to how the RA and VitD3 receptor network operates in hematopoietic cells, and whether receptor interactions can explain the interplay between the RA- and VitD3-signaling pathways during differentiation. Therefore, we analyzed the expression, DNA binding, and transcriptional activity of the endogenous RA and VitD3 receptors [retinoic acid receptors (RARs), retinoid X receptors (RXRs), and VitD3 receptor (VDR)] in the U-937 cell line, in which RA and VitD3 induce distinct monocytic differentiation pathways. VitD3 induction resulted in the formation of VDR/RXR DNA-binding complexes on both VitD3 response elements and RA response elements (RAREs). However, transcriptional activation was only observed from a VitD3 response element-driven reporter construct. Several DNA-binding complexes were detected on RAREs in undifferentiated cells. Stimulation by RA resulted in increased RAR beta/RXR DNA binding, activated RARE-dependent transcription, and increased expression of RAR-beta. Concomitant stimulation by VitD3 inhibited the RA-stimulated formation of RAR beta/RXR heterodimers, favoring VDR/RXR binding to the RARE. Also, VitD3 inhibited the expression of CD23 and CD49f, characteristic markers of retinoid-induced U-937 cell differentiation. In contrast, neither the RA-stimulated, RARE-mediated transcription nor the induced RAR-beta expression was suppressed by VitD3, suggesting that VitD3 selectively inhibited the retinoid-induced differentiation program but not the RARE-mediated signal. These results demonstrate a complex role for VitD3 in modifying the retinoid differentiation pathway and may have implications for differentiation-inducing therapy of hematopoietic tumors.
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| 19. |
- Carlborg, Carl Fredrik, 1981-, et al.
(författare)
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BEYOND PDMS: : OFF-STOCHIOMETRY THIOL-ENE BASED SOFT LITHOGRAPHY FOR RAPID PROTOTYPING OF MICROFLUIDIC DEVICES
- 2010
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Ingår i: 14th International Conference on Miniaturized Systems for Chemistry and Life Sciences (micro TAS 2010). - 9781618390622 ; , s. 70-72
-
Konferensbidrag (refereegranskat)abstract
- We present an easy to use, rapid fabrication platform for microfluidic systems, based on micro-molding of novel thiolene based polymer formulations. The novel fabrication platform addresses major drawbacks of PDMS by allowing large freedom in material and surface properties, including: (photo)patterning of stable surface modifications, bonding without plasma treatment, rapid UV or thermal curing, variable E-modulus, minimized leaching of uncured components [1] and suppressed non-specific binding of biomolecules [2]. This process is potentially suited for both rapid prototyping in the laboratory and medium-scale commercial production, bridging the “development gap”.
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| 20. |
- Carlborg, Carl Fredrik, et al.
(författare)
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Beyond PDMS: off-stoichiometry thiol–ene (OSTE) based soft lithography for rapid prototyping of microfluidic devices
- 2011
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Ingår i: Lab on a Chip. - : RSC Publishing. - 1473-0197 .- 1473-0189. ; 11:18, s. 3136-3147
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Tidskriftsartikel (refereegranskat)abstract
- In this article we introduce a novel polymer platform based on off-stoichiometry thiol–enes (OSTEs), aiming to bridge the gap between research prototyping and commercial production of microfluidic devices. The polymers are based on the versatile UV-curable thiol–ene chemistry but takes advantage of off-stoichiometry ratios to enable important features for a prototyping system, such as one-step surface modifications, tuneable mechanical properties and leakage free sealing through direct UV-bonding. The platform exhibits many similarities with PDMS, such as rapid prototyping and uncomplicated processing but can at the same time mirror the mechanical and chemical properties of both PDMS as well as commercial grade thermoplastics. The OSTE-prepolymer can be cast using standard SU-8 on silicon masters and a table-top UV-lamp, the surface modifications are precisely grafted using a stencil mask and the bonding requires only a single UV-exposure. To illustrate the potential of the material we demonstrate key concepts important in microfluidic chip fabrication such as patterned surface modifications for hydrophobic stops, pneumatic valves using UV-lamination of stiff and rubbery materials as well as micromachining of chip-to-world connectors in the OSTE-materials.
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