| 1. |
- Fu, Yi-Ping, et al.
(författare)
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The 19q12 Bladder Cancer GWAS Signal : Association with Cyclin E Function and Aggressive Disease
- 2014
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Ingår i: Cancer Research. - 0008-5472 .- 1538-7445. ; 74:20, s. 5808-5818
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Tidskriftsartikel (refereegranskat)abstract
- A genome-wide association study (GWAS) of bladder cancer identified a genetic marker rs8102137 within the 19q12 region as a novel susceptibility variant. This marker is located upstream of the CCNE1 gene, which encodes cyclin E, a cell-cycle protein. We performed genetic fine-mapping analysis of the CCNE1 region using data from two bladder cancer GWAS (5,942 cases and 10,857 controls). We found that the original GWAS marker rs8102137 represents a group of 47 linked SNPs (with r(2) >= 0.7) associated with increased bladder cancer risk. From this group, we selected a functional promoter variant rs7257330, which showed strong allele-specific binding of nuclear proteins in several cell lines. In both GWASs, rs7257330 was associated only with aggressive bladder cancer, with a combined per-allele OR = 1.18 [95% confidence interval (CI), 1.09-1.27, P = 4.67 x 10(-5)] versus OR = 1.01 (95% CI, 0.93-1.10, P = 0.79) for nonaggressive disease, with P = 0.0015 for case-only analysis. Cyclin E protein expression analyzed in 265 bladder tumors was increased in aggressive tumors (P = 0.013) and, independently, with each rs7257330-A risk allele (P-trend = 0.024). Overexpression of recombinant cyclin E in cell lines caused significant acceleration of cell cycle. In conclusion, we defined the 19q12 signal as the first GWAS signal specific for aggressive bladder cancer. Molecular mechanisms of this genetic association may be related to cyclin E overexpression and alteration of cell cycle in carriers of CCNE1 risk variants. In combination with established bladder cancer risk factors and other somatic and germline genetic markers, the CCNE1 variants could be useful for inclusion into bladder cancer risk prediction models.
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| 2. |
- Xiao, S., et al.
(författare)
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Talking through the continuum : New manifestations of Fano-resonance phenomenology realized with mesoscopic nanostructures
- 2013
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Ingår i: Fortschritte der Physik. - : Wiley. - 0015-8208 .- 1521-3978. ; 61:2-3, s. 348-359
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Tidskriftsartikel (refereegranskat)abstract
- The focus of this review is recent work in which we have demonstrated a highly-flexible approach to the study of Fano-resonance phenomena, by making use of the mesoscopic devices known as quantum point contacts (QPCs). Utilizing the ability of these structures to function as an on-demand quantum state, we demonstrate a highly-flexible system for the investigation of Fano resonances. Our approach involves making measurements of non-locally coupled pairs of QPCs, one of which is used to form the discrete state needed for the Fano resonance, while the other serves as a detector whose conductance is sensitive to the energy of this state. As a demonstration of the flexibility of this approach, we show how it can be used to implement a multi-state Fano resonance, in which two discrete states undergo a robust interaction that is achieved by coupling them to each other through a common continuum.
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| 3. |
- Yoon, Y., et al.
(författare)
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Coupling Quantum States through a Continuum : A Mesoscopic Multistate Fano Resonance
- 2012
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Ingår i: Physical Review X. - 2160-3308. ; 2:2, s. 021003-
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Tidskriftsartikel (refereegranskat)abstract
- We demonstrate a fully tunable realization of a multistate Fano resonance, in which a pair of remote quantum states experience an effective coupling due to their mutual overlap with a continuum. Our mesoscopic implementation of this system exploits the ability of the semiconductor nanostructures known as quantum point contacts (QPCs) to serve, in the low-density limit close to pinch-off, as an on-demand localized state. By coupling the states formed on two separate QPCs, through a two-dimensional electron gas that serves as a continuum, we observe a robust effective interaction between the QPCs. To explain this result, we develop a theoretical formulation, based on the ideas of the Schrieffer-Wolff transformation, which is able to reproduce our key experimental findings. According to this model, the robust character of the interaction between the two remote states arises from the fact that the interaction is essentially mediated by a large number of degenerate continuum states. While the continuum is often viewed as a source of decoherence, our experiment therefore instead suggests the possibility of using this medium to support the interaction of quantum states, a result that may allow new approaches to coherently couple nanostructures in extended geometries.
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| 4. |
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| 5. |
- Yingsung, W, et al.
(författare)
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Molecular heterogeneity of the SHAP-hyaluronan complex - Isolation and characterization of the complex in synovial fluid from patients with rheumatoid arthritis
- 2003
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Ingår i: Journal of Biological Chemistry. - 1083-351X. ; 278:35, s. 32710-32718
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Tidskriftsartikel (refereegranskat)abstract
- We previously found that a covalent complex of SHAPs (serum-derived hyaluronan-associated proteins), the heavy chains of inter-alpha-trypsin inhibitor family molecules, with hyaluronan ( HA) is accumulated in synovial fluid of patients with rheumatoid arthritis, and the complex is circulated in patient plasma at high concentrations. How the SHAP-HA complex participates in this disease is unknown. To address this question, it is essential to clarify the structural features of this macromolecule. The SHAP-HA complex purified from synovial fluid of the patients by three sequential CsCl isopycnic centrifugations was heterogeneous in density, and the fractions with different densities had distinct SHAP-to-HA ratios. Agarose gel electrophoresis and column chromatography revealed that there was no apparent difference in the size distribution of HA to which SHAPs were bound between the fractions with different densities. The SHAP-HA complex in the higher density fraction had fewer SHAP molecules per HA chain. Therefore, the difference between the fractions with different densities was due to a heterogeneous population of the SHAP-HA complex, namely the different number of SHAP molecules bound to an HA chain. Based on the SHAP and HA contents of the purified preparations, we estimated that an HA chain with a molecular weight of 2 x 10(6) has as many as five covalently bound SHAPs, which could give a proteinaceous multivalency to HA. Furthermore, we also found that the SHAP-HA complex tends to form aggregates, judging from the migration and elution profiles in agarose gel electrophoresis and gel filtration, respectively. The multivalent feature of the SHAP-HA complex was also confirmed by the negative staining electron micrographic images of the purified fractions. Taken together, those structural characteristics may underlie the aggregate-forming and extracellular matrix-stabilizing ability of the SHAP-HA complex.
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