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- Lawrenson, Kate, et al.
(författare)
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Functional mechanisms underlying pleiotropic risk alleles at the 19p13.1 breast-ovarian cancer susceptibility locus
- 2016
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 7
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Tidskriftsartikel (refereegranskat)abstract
- A locus at 19p13 is associated with breast cancer (BC) and ovarian cancer (OC) risk. Here we analyse 438 SNPs in this region in 46,451 BC and 15,438 OC cases, 15,252 BRCA1 mutation carriers and 73,444 controls and identify 13 candidate causal SNPs associated with serous OC (P=9.2 × 10-20), ER-negative BC (P=1.1 × 10-13), BRCA1-associated BC (P=7.7 × 10-16) and triple negative BC (P-diff=2 × 10-5). Genotype-gene expression associations are identified for candidate target genes ANKLE1 (P=2 × 10-3) and ABHD8 (P<2 × 10-3). Chromosome conformation capture identifies interactions between four candidate SNPs and ABHD8, and luciferase assays indicate six risk alleles increased transactivation of the ADHD8 promoter. Targeted deletion of a region containing risk SNP rs56069439 in a putative enhancer induces ANKLE1 downregulation; and mRNA stability assays indicate functional effects for an ANKLE1 3′-UTR SNP. Altogether, these data suggest that multiple SNPs at 19p13 regulate ABHD8 and perhaps ANKLE1 expression, and indicate common mechanisms underlying breast and ovarian cancer risk.
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- Ahlquist, Mårten, et al.
(författare)
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On the performance of continuum solvation models for the solvation energy of small anions
- 2006
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Ingår i: Organometallics. - : American Chemical Society (ACS). - 0276-7333 .- 1520-6041. ; 25:1, s. 45-47
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Tidskriftsartikel (refereegranskat)abstract
- The determination of continuum solvation models for the solvation energy of anions, was described. To investigate the reliability of the solvent model, a few explicit THF molecules were incorporated. A set of anions was chosen for which the experimental free energiesof solvation were available for both H 2O and DMSO solutions. A major difference between the water model and the DMSO model is that the latter systematically overestimates the free energy of solvation. The full water model in Jaguar v 4.2, including also nonelectrostatic terms, gives good correlation with experimental values for energy of solvation.
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- Alharbi, Essa A., et al.
(författare)
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Formation of High-Performance Multi-Cation Halide Perovskites Photovoltaics by delta-CsPbI3/delta-RbPbI3 Seed-Assisted Heterogeneous Nucleation
- 2021
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Ingår i: Advanced Energy Materials. - : John Wiley & Sons. - 1614-6832 .- 1614-6840. ; 11:16
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Tidskriftsartikel (refereegranskat)abstract
- The performance of perovskite solar cells is highly dependent on the fabrication method; thus, controlling the growth mechanism of perovskite crystals is a promising way towards increasing their efficiency and stability. Herein, a multi-cation halide composition of perovskite solar cells is engineered via the two-step sequential deposition method. Strikingly, it is found that adding mixtures of 1D polymorphs of orthorhombic delta-RbPbI3 and delta-CsPbI3 to the PbI2 precursor solution induces the formation of porous mesostructured hexagonal films. This porosity greatly facilitates the heterogeneous nucleation and the penetration of FA (formamidinium)/MA (methylammonium) cations within the PbI2 film. Thus, the subsequent conversion of PbI2 into the desired multication cubic alpha-structure by exposing it to a solution of formamidinium methylammonium halides is greatly enhanced. During the conversion step, the delta-CsPbI3 also is fully integrated into the 3D mixed cation perovskite lattice, which exhibits high crystallinity and superior optoelectronic properties. The champion device shows a power conversion efficiency (PCE) over 22%. Furthermore, these devices exhibit enhanced operational stability, with the best device retaining more than 90% of its initial value of PCE under 1 Sun illumination with maximum power point tracking for 400 h.
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- Almén, Markus Sällman, et al.
(författare)
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The obesity gene, TMEM18, is of ancient origin, found in majority of neuronal cells in all major brain regions and associated with obesity in severely obese children
- 2010
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Ingår i: BMC Medical Genetics. - : Springer Science and Business Media LLC. - 1471-2350. ; 11, s. 58-
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: TMEM18 is a hypothalamic gene that has recently been linked to obesity and BMI in genome wide association studies. However, the functional properties of TMEM18 are obscure. METHODS: The evolutionary history of TMEM18 was inferred using phylogenetic and bioinformatic methods. The gene's expression profile was investigated with real-time PCR in a panel of rat and mouse tissues and with immunohistochemistry in the mouse brain. Also, gene expression changes were analyzed in three feeding-related mouse models: food deprivation, reward and diet-induced increase in body weight. Finally, we genotyped 502 severely obese and 527 healthy Swedish children for two SNPs near TMEM18 (rs6548238 and rs756131). RESULTS: TMEM18 was found to be remarkably conserved and present in species that diverged from the human lineage over 1500 million years ago. The TMEM18 gene was widely expressed and detected in the majority of cells in all major brain regions, but was more abundant in neurons than other cell types. We found no significant changes in the hypothalamic and brainstem expression in the feeding-related mouse models. There was a strong association for two SNPs (rs6548238 and rs756131) of the TMEM18 locus with an increased risk for obesity (p = 0.001 and p = 0.002). CONCLUSION: We conclude that TMEM18 is involved in both adult and childhood obesity. It is one of the most conserved human obesity genes and it is found in the majority of all brain sites, including the hypothalamus and the brain stem, but it is not regulated in these regions in classical energy homeostatic models.
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- Simons, Michelle, et al.
(författare)
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Comparison of the oxidative reactivity of recombinant fetal and adult human hemoglobin : implications for the design of hemoglobin-based oxygen carriers
- 2018
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Ingår i: Bioscience Reports. - 0144-8463. ; 38:4
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Tidskriftsartikel (refereegranskat)abstract
- Hemoglobin (Hb)-based oxygen carriers (HBOCs) have been engineered to replace or augment the oxygen carrying capacity of erythrocytes. However, clinical results have generally been disappointing, in part due to the intrinsic oxidative toxicity of Hb. The most common HBOC starting material is adult human or bovine Hb. However, it has been suggested that fetal Hb may offer advantages due to decreased oxidative reactivity. Large-scale manufacturing of HBOC will likely and ultimately require recombinant sources of human proteins. We, therefore, directly compared the functional properties and oxidative reactivity of recombinant fetal (rHbF) and recombinant adult (rHbA) Hb. rHbA and rHbF produced similar yields of purified functional protein. No differences were seen in the two proteins in: autoxidation rate; the rate of hydrogen peroxide reaction; NO scavenging dioxygenase activity; and the NO producing nitrite reductase activity. The rHbF protein was: less damaged by low levels of hydrogen peroxide; less damaging when added to human umbilical vein endothelial cells (HUVEC) in the ferric form; and had a slower rate of intrinsic heme loss. The rHbA protein was: more readily reducible by plasma antioxidants such as ascorbate in both the reactive ferryl and ferric states; less readily damaged by lipid peroxides; and less damaging to phosphatidylcholine liposomes. In conclusion in terms of oxidative reactivity, there are advantages and disadvantages to the use of rHbA or rHbF as the basis for an effective HBOC.
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- Sreedharan, Smitha, et al.
(författare)
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Glutamate, aspartate and nucleotide transporters in the SLC17 family form four main phylogenetic clusters : evolution and tissue expression
- 2010
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Ingår i: BMC Genomics. - : Springer Science and Business Media LLC. - 1471-2164. ; 11:1, s. 17-
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The SLC17 family of transporters transports the amino acids: glutamate and aspartate, and, as shown recently, also nucleotides. Vesicular glutamate transporters are found in distinct species, such as C. elegans, but the evolutionary origin of most of the genes in this family has been obscure. RESULTS: Our phylogenetic analysis shows that the SLC17 family consists of four main phylogenetic clades which were all present before the divergence of the insect lineage. One of these clades has not been previously described and it is not found in vertebrates. The clade containing Slc17a9 had the most restricted evolutionary history with only one member in most species. We detected expression of Slc17a1-17a4 only in the peripheral tissues but not in the CNS, while Slc17a5- Slc17a9 are highly expressed in both the CNS and periphery. CONCLUSIONS: The in situ hybridization studies on vesicular nucleotide transporter revealed high expression throughout the cerebral cortex, certain areas in the hippocampus and in specific nuclei of the hypothalamus and thalamus. Some of the regions with high expression, such as the medial habenula and the dentate gyrus of the hippocampus, are important sites for purinergic neurotransmission. Noteworthy, other areas relying on purine-mediated signaling, such as the molecular layer of the dentate gyrus and the periaqueductal gray, lack or have a very low expression of Slc17a9, suggesting that there could be another nucleotide transporter in these regions.
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| 13. |
- Wang, Qisi, et al.
(författare)
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Magnon interactions in a moderately correlated Mott insulator
- 2024
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Ingår i: Nature Communications. - : Springer Nature. - 2041-1723. ; 15:1
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Tidskriftsartikel (refereegranskat)abstract
- Quantum fluctuations in low-dimensional systems and near quantum phase transitions have significant influences on material properties. Yet, it is difficult to experimentally gauge the strength and importance of quantum fluctuations. Here we provide a resonant inelastic x-ray scattering study of magnon excitations in Mott insulating cuprates. From the thin film of SrCuO2, single- and bi-magnon dispersions are derived. Using an effective Heisenberg Hamiltonian generated from the Hubbard model, we show that the single-magnon dispersion is only described satisfactorily when including significant quantum corrections stemming from magnon-magnon interactions. Comparative results on La2CuO4 indicate that quantum fluctuations are much stronger in SrCuO2 suggesting closer proximity to a magnetic quantum critical point. Monte Carlo calculations reveal that other magnetic orders may compete with the antiferromagnetic Néel order as the ground state. Our results indicate that SrCuO2—due to strong quantum fluctuations—is a unique starting point for the exploration of novel magnetic ground states.
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| 14. |
- Zhang, Hong, et al.
(författare)
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A universal co-solvent dilution strategy enables facile and cost-effective fabrication of perovskite photovoltaics
- 2022
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Ingår i: Nature Communications. - : Springer Nature. - 2041-1723. ; 13:1
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Tidskriftsartikel (refereegranskat)abstract
- Cost management and toxic waste generation are two key issues that must be addressed before the commercialization of perovskite optoelectronic devices. We report a groundbreaking strategy for eco-friendly and cost-effective fabrication of highly efficient perovskite solar cells. This strategy involves the usage of a high volatility co-solvent, which dilutes perovskite precursors to a lower concentration (<0.5 M) while retaining similar film quality and device performance as a high concentration (>1.4 M) solution. More than 70% of toxic waste and material cost can be reduced. Mechanistic insights reveal ultra-rapid evaporation of the co-solvent together with beneficial alteration of the precursor colloidal chemistry upon dilution with co-solvent, which in-situ studies and theoretical simulations confirm. The co-solvent tuned precursor colloidal properties also contribute to the enhancement of the stability of precursor solution, which extends its processing window thus minimizing the waste. This strategy is universally successful across different perovskite compositions, and scales from small devices to large-scale modules using industrial spin-coating, potentially easing the lab-to-fab translation of perovskite technologies.
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