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| 2. |
- Maccubbin, D., et al.
(author)
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Lipid-modifying efficacy and tolerability of extended-release niacin/laropiprant in patients with primary hypercholesterolaemia or mixed dyslipidaemia
- 2008
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In: International journal of clinical practice (Esher). - : Hindawi Limited. - 1368-5031 .- 1742-1241. ; 62:12, s. 1959-1970
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Journal article (peer-reviewed)abstract
- Background: Improving lipids beyond low-density lipoprotein cholesterol (LDL-C) lowering with statin monotherapy may further reduce cardiovascular risk. Niacin has complementary lipid-modifying efficacy to statins and cardiovascular benefit, but is underutilised because of flushing, mediated primarily by prostaglandin D2 (PGD2). Laropiprant (LRPT), a PGD 2 receptor (DP1) antagonist that reduces niacin-induced flushing has been combined with extended-release niacin (ERN) into a fixed-dose tablet. Methods and results: Dyslipidaemic patients were randomised to ERN/LRPT 1 g (n = 800), ERN 1 g (n = 543) or placebo (n = 270) for 4 weeks. Doses were doubled (2 tablets/day, i.e. 2 g for active treatments) for 20 weeks. ERN/LRPT 2 g produced significant changes vs. placebo in LDL-C (-18.4%), high-density lipoprotein cholesterol (HDL-C, 20.0%), LDL-C:HDL-C (-31.2%), non-HDL-C (-19.8%), triglycerides (TG, -25.8%), apolipoprotein (Apo) B (-18.8%), Apo A-I (6.9%), total cholesterol (TC, -8.5%), TC:HDL-C (-23.1%) and lipoprotein(a) (-20.8%) across weeks 12-24. ERN/LRPT produced significantly less flushing than ERN during initiation (week 1) and maintenance (weeks 2-24) for all prespecified flushing end-points (incidence, intensity and discontinuation because of flushing). Except for flushing, ERN/LRPT had a safety/tolerability profile comparable with ERN. Conclusion: Extended-release niacin/LRPT 2 g produced significant, durable improvements in multiple lipid/lipoprotein parameters. The improved tolerability of ERN/LRPT supports a simplified 1 g?2 g dosing regimen of niacin, a therapy proven to reduce cardiovascular risk. © 2008 Merck & Co.
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| 3. |
- Paris, Josephine R., et al.
(author)
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A large and diverse autosomal haplotype is associated with sex-linked colour polymorphism in the guppy
- 2022
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In: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 13:1
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Journal article (peer-reviewed)abstract
- Male colour patterns of the Trinidadian guppy (Poecilia reticulata) are typified by extreme variation governed by both natural and sexual selection. Since guppy colour patterns are often inherited faithfully from fathers to sons, it has been hypothesised that many of the colour trait genes must be physically linked to sex determining loci as a ‘supergene’ on the sex chromosome. Here, we phenotype and genotype four guppy ‘Iso-Y lines’, where colour was inherited along the patriline for 40 generations. Using an unbiased phenotyping method, we confirm the breeding design was successful in creating four distinct colour patterns. We find that genetic differentiation among the Iso-Y lines is repeatedly associated with a diverse haplotype on an autosome (LG1), not the sex chromosome (LG12). Moreover, the LG1 haplotype exhibits elevated linkage disequilibrium and evidence of sex-specific diversity in the natural source population. We hypothesise that colour pattern polymorphism is driven by Y-autosome epistasis.
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| 4. |
- Persson, Anders I, et al.
(author)
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Non-stem cell origin for oligodendroglioma
- 2010
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In: Cancer Cell. - : Elsevier BV. - 1535-6108 .- 1878-3686. ; 18:6, s. 669-682
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Journal article (peer-reviewed)abstract
- Malignant astrocytic brain tumors are among the most lethal cancers. Quiescent and therapy-resistant neural stem cell (NSC)-like cells in astrocytomas are likely to contribute to poor outcome. Malignant oligodendroglial brain tumors, in contrast, are therapy sensitive. Using magnetic resonance imaging (MRI) and detailed developmental analyses, we demonstrated that murine oligodendroglioma cells show characteristics of oligodendrocyte progenitor cells (OPCs) and are therapy sensitive, and that OPC rather than NSC markers enriched for tumor formation. MRI of human oligodendroglioma also suggested a white matter (WM) origin, with markers for OPCs rather than NSCs similarly enriching for tumor formation. Our results suggest that oligodendroglioma cells show hallmarks of OPCs, and that a progenitor rather than a NSC origin underlies improved prognosis in patients with this tumor.
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| 5. |
- Abrahamson, Dor, et al.
(author)
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Moving Forward: In Search of Synergy Across Diverse Views on the Role of Physical Movement in Design for STEM Education
- 2018
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In: Rethinking Learning in the Digital Age: Making the Learning Sciences Count, 13th International Conference of the Learning Sciences (ICLS) 2018, Volume 2. - : International Society of the Learning Sciences.. - 1573-4552. - 9781732467217
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Conference paper (peer-reviewed)abstract
- Inspired by the current embodiment turn in the cognitive sciences, researchers of STEM teaching and learning have been evaluating implications of this turn for educational theory and practice. But whereas design researchers have been developing domain-specific theories that implicate the role of physical movement in conceptual learning, the field has yet to agree on a conceptually coherent and empirically validated framework for leveraging and shaping students’ capacity for physical movement as a socio–cognitive educational resource. This symposium thus convenes to ask, “What is movement in relation to concepts such that we can design for learning?” To stimulate discussion, we highlight an emerging tension across a set of innovative technological designs with respect to the framing question of whether students should discover an activity’s targeted movement forms themselves or that these forms should be cued directly. Our content domains span mathematics (proportions, geometry), physics, chemistry, and ecological system dynamics (predator–prey, bees).
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| 6. |
- Fan, Peng, et al.
(author)
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Scatter and crosstalk corrections for (99m)Tc/(123)I dual-radionuclide imaging using a CZT SPECT system with pinhole collimators.
- 2015
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In: Medical Physics. - : Wiley. - 0094-2405 .- 2473-4209. ; 42:12, s. 6895-6911
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Journal article (peer-reviewed)abstract
- The energy spectrum for a cadmium zinc telluride (CZT) detector has a low energy tail due to incomplete charge collection and intercrystal scattering. Due to these solid-state detector effects, scatter would be overestimated if the conventional triple-energy window (TEW) method is used for scatter and crosstalk corrections in CZT-based imaging systems. The objective of this work is to develop a scatter and crosstalk correction method for (99m)Tc/(123)I dual-radionuclide imaging for a CZT-based dedicated cardiac SPECT system with pinhole collimators (GE Discovery NM 530c/570c).
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| 8. |
- Reithmaier, Gloria M.S., et al.
(author)
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Carbonate chemistry and carbon sequestration driven by inorganic carbon outwelling from mangroves and saltmarshes
- 2023
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In: Nature Communications. - 2041-1723. ; 14:1
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Journal article (peer-reviewed)abstract
- Mangroves and saltmarshes are biogeochemical hotspots storing carbon in sediments and in the ocean following lateral carbon export (outwelling). Coastal seawater pH is modified by both uptake of anthropogenic carbon dioxide and natural biogeochemical processes, e.g., wetland inputs. Here, we investigate how mangroves and saltmarshes influence coastal carbonate chemistry and quantify the contribution of alkalinity and dissolved inorganic carbon (DIC) outwelling to blue carbon budgets. Observations from 45 mangroves and 16 saltmarshes worldwide revealed that >70% of intertidal wetlands export more DIC than alkalinity, potentially decreasing thepH of coastal waters. Porewater-derived DIC outwelling (81 ± 47 mmol m−2 d−1 in mangroves and 57 ± 104 mmol m−2 d−1 in saltmarshes) was the major term in blue carbon budgets. However, substantial amounts of fixed carbon remain unaccounted for. Concurrently, alkalinity outwelling was similar or higher than sediment carbon burial and is therefore a significant but often overlooked carbon sequestration mechanism.
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| 9. |
- Sabelström, H., et al.
(author)
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Driving Neuronal Differentiation through Reversal of an ERK1/2-miR-124-SOX9 Axis Abrogates Glioblastoma Aggressiveness
- 2019
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In: Cell Reports. - : Elsevier BV. - 2211-1247. ; 28:8, s. 11-2079
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Journal article (peer-reviewed)abstract
- Identifying cellular programs that drive cancers to be stem-like and treatment resistant is critical to improving outcomes in patients. Here, we demonstrate that constitutive extracellular signal-regulated kinase 1/2 (ERK1/2) activation sustains a stem-like state in glioblastoma (GBM), the most common primary malignant brain tumor. Pharmacological inhibition of ERK1/2 activation restores neurogenesis during murine astrocytoma formation, inducing neuronal differentiation in tumorspheres. Constitutive ERK1/2 activation globally regulates miRNA expression in murine and human GBMs, while neuronal differentiation of GBM tumorspheres following the inhibition of ERK1/2 activation requires the functional expression of miR-124 and the depletion of its target gene SOX9. Overexpression of miR124 depletes SOX9 in vivo and promotes a stem-like-to-neuronal transition, with reduced tumorigenicity and increased radiation sensitivity. Providing a rationale for reports demonstrating miR-124-induced abrogation of GBM aggressiveness, we conclude that reversal of an ERK1/2-miR-124-SOX9 axis induces a neuronal phenotype and that enforcing neuronal differentiation represents a therapeutic strategy to improve outcomes in GBM. Sabelström et al. show that the loss of neurogenesis is reversible during neural stem cell-derived glioma formation. Pharmacological inhibition of ERK1/2 globally regulates miRNAs and induces neuronal differentiation, a process that is dependent on the modulation of an miR-124-SOX9 axis in glioblastoma (GBM) cells. The overexpression of miR-124 induces neuronal differentiation that abrogates GBM aggressiveness.
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