| 1. |
- Schmit, Stephanie L, et al.
(författare)
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Novel Common Genetic Susceptibility Loci for Colorectal Cancer.
- 2019
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Ingår i: Journal of the National Cancer Institute. - : Oxford University Press (OUP). - 0027-8874 .- 1460-2105. ; 111:2, s. 146-157
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Tidskriftsartikel (refereegranskat)abstract
- Background: Previous genome-wide association studies (GWAS) have identified 42 loci (P < 5 × 10-8) associated with risk of colorectal cancer (CRC). Expanded consortium efforts facilitating the discovery of additional susceptibility loci may capture unexplained familial risk.Methods: We conducted a GWAS in European descent CRC cases and control subjects using a discovery-replication design, followed by examination of novel findings in a multiethnic sample (cumulative n = 163 315). In the discovery stage (36 948 case subjects/30 864 control subjects), we identified genetic variants with a minor allele frequency of 1% or greater associated with risk of CRC using logistic regression followed by a fixed-effects inverse variance weighted meta-analysis. All novel independent variants reaching genome-wide statistical significance (two-sided P < 5 × 10-8) were tested for replication in separate European ancestry samples (12 952 case subjects/48 383 control subjects). Next, we examined the generalizability of discovered variants in East Asians, African Americans, and Hispanics (12 085 case subjects/22 083 control subjects). Finally, we examined the contributions of novel risk variants to familial relative risk and examined the prediction capabilities of a polygenic risk score. All statistical tests were two-sided.Results: The discovery GWAS identified 11 variants associated with CRC at P < 5 × 10-8, of which nine (at 4q22.2/5p15.33/5p13.1/6p21.31/6p12.1/10q11.23/12q24.21/16q24.1/20q13.13) independently replicated at a P value of less than .05. Multiethnic follow-up supported the generalizability of discovery findings. These results demonstrated a 14.7% increase in familial relative risk explained by common risk alleles from 10.3% (95% confidence interval [CI] = 7.9% to 13.7%; known variants) to 11.9% (95% CI = 9.2% to 15.5%; known and novel variants). A polygenic risk score identified 4.3% of the population at an odds ratio for developing CRC of at least 2.0.Conclusions: This study provides insight into the architecture of common genetic variation contributing to CRC etiology and improves risk prediction for individualized screening.
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| 2. |
- Huang, He, et al.
(författare)
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Critical stress for twinning nucleation in CrCoNi-based medium and high entropy alloys
- 2018
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Ingår i: Acta Materialia. - : PERGAMON-ELSEVIER SCIENCE LTD. - 1359-6454 .- 1873-2453. ; 149, s. 388-396
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Tidskriftsartikel (refereegranskat)abstract
- The CrCoNi-based medium and high entropy alloys (MHEAs) have drawn much attention due to their exceptional mechanical properties at cryogenic temperatures. The twinning critical resolved shear stress (CRSS) is a fundamental parameter for evaluating the strength-ductility properties of MHEAs. Here we construct and apply an extended twinning nucleation Peierls-Nabarro (P-N) model to predict the twinning CRSSes of face-centered cubic (FCC) CrCoNi-based MHEAs. The order of the twinning CRSSes of the selected alloys is CrCoNi > CrCoNiMn > CrCoNiFe > CrCoNiFeMn and the values are 291, 277, 274 and 236 MPa, respectively. These theoretical predictions agree very well with the experimental twinning CRSSes of CrCoNi and CrCoNiFeMn accounting for 260 +/- 30 and 235 +/- 10 MPa, respectively and are perfectly consistent with the strength-ductility properties including yield stress, ultimate tensile stress and uniform elongation for fracture of the FCC CrCoNi-based MHEAs obtained at cryogenic temperatures. The present method offers a first-principle quantum-mechanical tool for optimizing and designing new MHEAs with exceptional mechanical properties.
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| 3. |
- Huang, Shuo, et al.
(författare)
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Mechanism of magnetic transition in FeCrCoNi-based high entropy alloys
- 2016
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Ingår i: Materials & design. - : Elsevier. - 0264-1275 .- 1873-4197. ; 103, s. 71-74
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Tidskriftsartikel (refereegranskat)abstract
- First-principles alloy theory and Monte-Carlo simulations are performed to investigate the magnetic properties of FeCrCoNiAlx high entropy alloys. Results show that face-centered-cubic (fcc) and body-centered-cubic (bcc) structures possess significantly different magnetic behaviors uncovering that the alloy's Curie temperature is controlled by the stability of the Al-induced single phase or fcc-bcc dual-phase. We show that the appearance of the bcc phase with increasing Al content brings about the observed transition from the paramagnetic state for FeCrCoNi to the ferromagnetic state for FeCrCoNiAl at room-temperature. Similar mechanism is predicted to give rise to room-temperature ferromagnetism in FeCrCoNiGa high entropy alloy.
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| 4. |
- Huang, Shuo, et al.
(författare)
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Twinning in metastable high-entropy alloys
- 2018
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Ingår i: Nature Communications. - : Nature Publishing Group. - 2041-1723. ; 9:1
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Tidskriftsartikel (refereegranskat)abstract
- Twinning is a fundamental mechanism behind the simultaneous increase of strength and ductility in medium- and high-entropy alloys, but its operation is not yet well understood, which limits their exploitation. Since many high-entropy alloys showing outstanding mechanical properties are actually thermodynamically unstable at ambient and cryogenic conditions, the observed twinning challenges the existing phenomenological and theoretical plasticity models. Here, we adopt a transparent approach based on effective energy barriers in combination with first-principle calculations to shed light on the origin of twinning in high-entropy alloys. We demonstrate that twinning can be the primary deformation mode in metastable face-centered cubic alloys with a fraction that surpasses the previously established upper limit. The present advance in plasticity of metals opens opportunities for tailoring the mechanical response in engineering materials by optimizing metastable twinning in high-entropy alloys.
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| 5. |
- Satizabal, Claudia L., et al.
(författare)
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Genetic architecture of subcortical brain structures in 38,851 individuals
- 2019
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Ingår i: Nature Genetics. - : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 51:11, s. 1624-
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Tidskriftsartikel (refereegranskat)abstract
- Subcortical brain structures are integral to motion, consciousness, emotions and learning. We identified common genetic variation related to the volumes of the nucleus accumbens, amygdala, brainstem, caudate nucleus, globus pallidus, putamen and thalamus, using genome-wide association analyses in almost 40,000 individuals from CHARGE, ENIGMA and UK Biobank. We show that variability in subcortical volumes is heritable, and identify 48 significantly associated loci (40 novel at the time of analysis). Annotation of these loci by utilizing gene expression, methylation and neuropathological data identified 199 genes putatively implicated in neurodevelopment, synaptic signaling, axonal transport, apoptosis, inflammation/infection and susceptibility to neurological disorders. This set of genes is significantly enriched for Drosophila orthologs associated with neurodevelopmental phenotypes, suggesting evolutionarily conserved mechanisms. Our findings uncover novel biology and potential drug targets underlying brain development and disease.
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| 6. |
- Huang, Shuo, et al.
(författare)
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Chemical ordering controlled thermo-elasticity of AlTiVCr1-xNbx high-entropy alloys
- 2020
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Ingår i: Acta Materialia. - : Pergamon Press. - 1359-6454 .- 1873-2453. ; 199, s. 53-62
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Tidskriftsartikel (refereegranskat)abstract
- The stability of constituent phases in multi-component system always plays a prominent role in tailoring their mechanical performance at elevated temperatures. In this work, we highlight a chemical ordering feature in the AlTiVCr1-xNbx (0 <= x <= 1) alloys with body-centered cubic crystal structure. The quantum-mechanical first-principle investigations of these alloys on the elemental distribution identify a family of B2 type of partially ordered configurations. We map out the elastic parameters in detail as a function of composition and temperature for disordered and partially ordered phases. A great sensitivity to the order-disorder transformation is revealed, especially for the Cr-rich system. Our results demonstrate that a proper control of the ordering level in these alloys can facilitate the optimal tuning of their mechanical performance while keeping the density almost unchanged. The study presented here further predicts that these alloys possess high specific stiffness, low thermal expansion, and large elastic softening resistance. It is demonstrated that the considered alloys have thermal and mechanical properties that compete with superalloys and other high temperature structural materials.
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| 7. |
- Huang, Shuo, et al.
(författare)
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Mechanical performance of FeCrCoMnAlx high-entropy alloys from first-principle
- 2018
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Ingår i: Materials Chemistry and Physics. - : Elsevier. - 0254-0584 .- 1879-3312. ; 210, s. 37-42
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Tidskriftsartikel (refereegranskat)abstract
- The elastic parameters and ideal tensile strength in the 10011 direction for the body-centered cubic solid solution phase of FeCrCoMnAlx (0.6 <= x <= 1.5) high-entropy alloys are determined using first-principle alloy theory. Based on the estimated theoretical Curie temperatures, all alloys considered here are predicted to order ferromagnetically at room temperature. The mechanical behaviors are analyzed through the single-crystal and polycrystalline elastic moduli, Pugh ratio, and Debye temperature by making use of a series of phenomenological models. High ideal tensile strength is found for the equiatomic FeCrCoMnAl system, and the intrinsic strength increases with decreasing Al content.
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| 8. |
- Huang, Shuo, et al.
(författare)
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Phase-transition assisted mechanical behavior of TiZrHfTax high-entropy alloys
- 2018
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Ingår i: Scientific Reports. - : Nature Publishing Group. - 2045-2322. ; 8
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Tidskriftsartikel (refereegranskat)abstract
- Recent developments of high-entropy alloys with high strength and high ductility draw attention to the metastability-engineering strategy. Using first-principle theory, here we demonstrate that reducing the Ta level in the refractory TiZrHfTax system destabilizes the body-centered cubic (bcc) phase and leads to the appearance of the hexagonal close-packed (hcp) phase embedded in the bcc matrix. The alloying-induced features of the elastic parameters for the cubic and hexagonal structures are mapped out in details, and strong sensitivity to the crystal lattice and chemistry is revealed. Results show softening of the bcc matrix with decreasing Ta concentration which ensures ductile behavior. However, the elastically nearly isotropic hcp precipitates possess enhanced resistance against shear which promotes strengthening of the TiZrHfTax dual-phase system. The present atomic-level insight provides strong evidence to the experimental observation, and emphasizes the significance of quantum-design for advanced multi-phase high-entropy alloys with excellent strength-ductility combinations.
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| 9. |
- Huang, Shuo, et al.
(författare)
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Strengthening Induced by MagnetoChemical Transition in Al-Doped Fe-Cr-Co-Ni High-Entropy Alloys
- 2018
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Ingår i: Physical Review Applied. - : American Physical Society. - 2331-7019. ; 10:6
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Tidskriftsartikel (refereegranskat)abstract
- Alloys with adjustable mechanical performance are of fundamental interest in material designs. Here, we investigate the magnetic- and chemical-ordering behavior of the ferromagnetic Fe-Cr-Co-Ni-Al-x (1 <= x <= 2.5) high-entropy alloys with the help of first-principle alloy theory. The lattice constants and the single- and polycrystalline elastic parameters for partially ordered and random structures are considered. In contrast to the trend found for the completely disordered phase, we demonstrate that ordering driven primarily by Al results in an enhanced Young's modulus, especially at high-Al concentrations, which is in line with the observed increase of the hardness for systems with a body-centered-cubic underlying lattice. The results suggest that outstanding strength and ductility can be realized by proper control of the ordering level in single- and multiphase high-entropy alloys.
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| 10. |
- Huang, Shuo, et al.
(författare)
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Temperature dependent stacking fault energy of FeCrCoNiMn high entropy alloy
- 2015
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Ingår i: Scripta Materialia. - : Elsevier BV. - 1359-6462 .- 1872-8456. ; 108, s. 44-47
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Tidskriftsartikel (refereegranskat)abstract
- The stacking fault energy (SFE) of paramagnetic FeCrCoNiMn high entropy alloy is investigated as a function of temperature via ab initio calculations. We divide the SFE into three major contributions: chemical, magnetic and strain parts. Structural energies, local magnetic moments and elastic moduli are used to estimate the effect of temperature on each term. The present results explain the recently reported twinning observed below room-temperature and predict the occurrence of the hexagonal phase at cryogenic conditions.
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