| 1501. |
- 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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| 1502. |
- Lee, James J, et al.
(författare)
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Gene discovery and polygenic prediction from a genome-wide association study of educational attainment in 1.1 million individuals.
- 2018
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Ingår i: Nature genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 50:8, s. 1112-1121
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Tidskriftsartikel (refereegranskat)abstract
- Here we conducted a large-scale genetic association analysis of educational attainment in a sample of approximately 1.1million individuals and identify 1,271independent genome-wide-significant SNPs. For the SNPs taken together, we found evidence of heterogeneous effects across environments. The SNPs implicate genes involved in brain-development processes and neuron-to-neuron communication. In a separate analysis of the X chromosome, we identify 10independent genome-wide-significant SNPs and estimate a SNP heritability of around 0.3% in both men and women, consistent with partial dosage compensation. A joint (multi-phenotype) analysis of educational attainment and three related cognitive phenotypes generates polygenic scores that explain 11-13% of the variance in educational attainment and 7-10% of the variance in cognitive performance. This prediction accuracy substantially increases the utility of polygenic scores as tools in research.
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| 1503. |
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| 1504. |
- Leisawitz, David, et al.
(författare)
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Origins Space Telescope: Baseline mission concept
- 2021
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Ingår i: Journal of Astronomical Telescopes, Instruments, and Systems. - 2329-4221 .- 2329-4124. ; 7:1
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Tidskriftsartikel (refereegranskat)abstract
- The Origins Space Telescope will trace the history of our origins from the time dust and heavy elements permanently altered the cosmic landscape to present-day life. How did galaxies evolve from the earliest galactic systems to those found in the Universe today? How do habitable planets form? How common are life-bearing worlds? To answer these alluring questions, Origins will operate at mid-and far-infrared (IR) wavelengths and offer powerful spectroscopic instruments and sensitivity three orders of magnitude better than that of the Herschel Space Observatory, the largest telescope flown in space to date. We describe the baseline concept for Origins recommended to the 2020 US Decadal Survey in Astronomy and Astrophysics. The baseline design includes a 5.9-m diameter telescope cryocooled to 4.5 K and equipped with three scientific instruments. A mid-infrared instrument (Mid-Infrared Spectrometer and Camera Transit spectrometer) will measure the spectra of transiting exoplanets in the 2.8 to 20 μm wavelength range and offer unprecedented spectrophotometric precision, enabling definitive exoplanet biosignature detections. The far-IR imager polarimeter will be able to survey thousands of square degrees with broadband imaging at 50 and 250 μm. The Origins Survey Spectrometer will cover wavelengths from 25 to 588 μm, making wide-area and deep spectroscopic surveys with spectral resolving power R ∼ 300, and pointed observations at R ∼ 40,000 and 300,000 with selectable instrument modes. Origins was designed to minimize complexity. The architecture is similar to that of the Spitzer Space Telescope and requires very few deployments after launch, while the cryothermal system design leverages James Webb Space Telescope technology and experience. A combination of current-state-of-the-art cryocoolers and next-generation detector technology will enable Origins' natural background-limited sensitivity.
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| 1505. |
- Leisawitz, David, et al.
(författare)
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The Origins Space Telescope: Mission concept overview
- 2018
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Ingår i: Proceedings of SPIE - The International Society for Optical Engineering. - : SPIE. - 0277-786X .- 1996-756X. ; 10698
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Konferensbidrag (refereegranskat)abstract
- Downloading of the abstract is permitted for personal use only. The Origins Space Telescope (OST) will trace the history of our origins from the time dust and heavy elements permanently altered the cosmic landscape to present-day life. How did the universe evolve in response to its changing ingredients? How common are life-bearing planets? To accomplish its scientific objectives, OST will operate at mid- and far-infrared wavelengths and offer superlative sensitivity and new spectroscopic capabilities. The OST study team will present a scientifically compelling, executable mission concept to the 2020 Decadal Survey in Astrophysics. To understand the concept solution space, our team studied two alternative mission concepts. We report on the study approach and describe both of these concepts, give the rationale for major design decisions, and briefly describe the mission-enabling technology.
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| 1506. |
- Levy, G., et al.
(författare)
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12-month follow-up analysis of a multicenter, randomized, prospective trial in de novo liver transplant recipients (LIS2T) comparing cyclosporine microemulsion (C2 monitoring) and tacrolimus
- 2006
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Ingår i: Liver transplantation. - 1527-6465. ; 12:10, s. 1464-72
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Tidskriftsartikel (refereegranskat)abstract
- The LIS2T study was an open-label, multicenter study in which recipients of a primary liver transplant were randomized to cyclosporine microemulsion (CsA-ME) (Neoral) (n = 250) (monitoring of blood concentration at 2 hours postdose) C2 or tacrolimus (n = 245) (monitoring of trough drug blood level [predose]) C0 to compare efficacy and safety at 3 and 6 months and to evaluate patient status at 12 months. All patients received steroids with or without azathioprine. At 12 months, 85% of CsA-ME patients and 86% of tacrolimus patients survived with a functioning graft (P not significant). Efficacy was similar in deceased- and living-donor recipients. Significantly fewer hepatitis C-positive patients died or lost their graft by 12 months with CsA-ME (5/88, 6%) than with tacrolimus (14/85, 16%) (P < 0.03). Recurrence of hepatitis C virus in liver grafts was similar in each group. Based on biopsies driven by clinical events, the mean time to histological diagnosis of hepatitis C virus recurrence was significantly longer with CsA-ME (100 +/- 50 days) than with tacrolimus (70 +/- 40 days) (P < 0.05). Median serum creatinine at 12 months was 106 mumol/L with CsA-ME and with tacrolimus. More patients who were nondiabetic at baseline received antihyperglycemic therapy in the tacrolimus group at 12 months (13% vs. 5%, P < 0.01). Of patients who were diabetic at baseline, more tacrolimus-treated individuals required anti-diabetic treatment at 12 months (70% vs. 49%, P = 0.02). Treatment for de novo or preexisting hypertension or hyperlipidemia was similar in both groups. In conclusion, the efficacy of CsA-ME monitored by blood concentration at 2 hours postdose and tacrolimus in liver transplant patients is equivalent to 12 months, and renal function is similar. More patients required antidiabetic therapy with tacrolimus regardless of diabetic status at baseline.
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| 1507. |
- Li, B., et al.
(författare)
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An Extended Hyperbolic Closure Model for Unmated Granite Fractures Subject to Normal Loading
- 2022
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Ingår i: Rock Mechanics and Rock Engineering. - : Springer Nature. - 0723-2632 .- 1434-453X. ; 55:7, s. 4139-4158
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Tidskriftsartikel (refereegranskat)abstract
- The closure behavior of rock fractures subject to normal loading is essential for deformation analysis of fractured rock masses and the modeling of associated coupled processes. Previous studies have mainly focused on characterizing the closure behavior of mated fractures, and the applicability of existing models to unmated fractures and characteristics of involved parameters have not been comprehensively investigated. We conducted normal loading tests on three tensile granite fractures with different mating degrees by dislocating the fracture surfaces with three offsets. A high-resolution contact model was used to simulate the fracture closure behavior, which was validated by comparing the simulated closure curves and the surface damage areas with experimental measurements. After that, it was applied to simulate the closure behavior for nine numerically generated surfaces with different surface roughness characteristics. The experimental and numerical results exhibit a downward bending trend in the stiffness versus stress curves, which existing models cannot accommodate. An extended hyperbolic model was established by introducing an exponent parameter into the classical Barton–Bandis hyperbolic model, which can better represent the experimental data than previous models. Via regression analysis, we found that the exponent parameter has an approximately constant value of 0.3. The maximum normal displacement is about two times of the mean aperture. The initial stiffness is positively correlated with the elastic modulus and the correlation length and negatively correlated with the mean aperture. Parameters involved in the extended model have precise physical meanings, and they are mathematically predictable based on measurable mechanical and geometrical properties of the rock fractures.
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| 1508. |
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| 1509. |
- Li, Hailong, 1976-, et al.
(författare)
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A self-powered smart wave energy converter for sustainable sea
- 2024
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Ingår i: Mechanical systems and signal processing. - : Academic Press. - 0888-3270 .- 1096-1216. ; 220
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Tidskriftsartikel (refereegranskat)abstract
- Self-powered smart buoys are widely used in sustainable sea, such as marine environmental monitoring. The article designs a self-powered and self-sensing point-absorber wave energy converter based on the two-arm mechanism. The system consists of the wave energy capture module, the power take-off module, the generator module and the energy storage module. As the core component of the wave energy converter, the power take-off module is mainly composed of a two-arm mechanism, which can convert the oscillation heave motion into unidirectional rotary motion. To evaluate the power generation performance of the system, the kinematic and dynamic models of the wave energy converter with the flywheel are established, and the disengagement and engagement phenomena of the flywheel are analyzed. The effectiveness of the prototype in capturing wave energy is verified through dry experiments in lab and field tests. The dry experiment reveals that the maximum output power of the system is 5.67 W, and the maximum and average mechanical efficiency are 66.63 % and 48.35 %, respectively. Additionally, the field test demonstrates that the peak output power can reach 92 W. Meanwhile, the generated electrical signals can be processed by deep learning algorithms to accurately identify different wave states. This high performance confirms that the proposed wave energy converter can meet its own energy needs by capturing wave energy in the marine environment, while also achieving self-sensing for wave condition monitoring. The system has great potential for promoting the development of intelligent sustainable sea in the future.
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| 1510. |
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