| 1. |
- Deng, Min, et al.
(författare)
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Genome-wide association analyses in Han Chinese identify two new susceptibility loci for amyotrophic lateral sclerosis
- 2013
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Ingår i: Nature Genetics. - : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 45:6, s. 697-
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Tidskriftsartikel (refereegranskat)abstract
- To identify susceptibility genes for amyotrophic lateral sclerosis (ALS), we conducted a genome-wide association study (GWAS) in 506 individuals with sporadic ALS and 1,859 controls of Han Chinese ancestry. Ninety top SNPs suggested by the current GWAS and 6 SNPs identified by previous GWAS were analyzed in an independent cohort of 706 individuals with ALS and 1,777 controls of Han Chinese ancestry. We discovered two new susceptibility loci for ALS at 1q32 (CAMK1G, rs6703183, P-combined = 2.92 x 10(-8), odds ratio (OR) = 1.31) and 22p11 (CABIN1 and SUSD2, rs8141797, P-combined = 2.35 x 10(-9), OR = 1.52). These two loci explain 12.48% of the overall variance in disease risk in the Han Chinese population. We found no association evidence for the previously reported loci in the Han Chinese population, suggesting genetic heterogeneity of disease susceptibility for ALS between ancestry groups. Our study identifies two new susceptibility loci and suggests new pathogenic mechanisms of ALS.
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| 2. |
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| 3. |
- Xu, An, et al.
(författare)
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Rewired m6A epitranscriptomic networks link mutant p53 to neoplastic transformation
- 2023
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Ingår i: Nature Communications. - : Springer Nature. - 2041-1723. ; 14:1
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Tidskriftsartikel (refereegranskat)abstract
- N6-methyladenosine (m6A), one of the most prevalent mRNA modifications in eukaryotes, plays a critical role in modulating both biological and pathological processes. However, it is unknown whether mutant p53 neomorphic oncogenic functions exploit dysregulation of m6A epitranscriptomic networks. Here, we investigate Li-Fraumeni syndrome (LFS)-associated neoplastic transformation driven by mutant p53 in iPSC-derived astrocytes, the cell-of-origin of gliomas. We find that mutant p53 but not wild-type (WT) p53 physically interacts with SVIL to recruit the H3K4me3 methyltransferase MLL1 to activate the expression of m6A reader YTHDF2, culminating in an oncogenic phenotype. Aberrant YTHDF2 upregulation markedly hampers expression of multiple m6A-marked tumor-suppressing transcripts, including CDKN2B and SPOCK2, and induces oncogenic reprogramming. Mutant p53 neoplastic behaviors are significantly impaired by genetic depletion of YTHDF2 or by pharmacological inhibition using MLL1 complex inhibitors. Our study reveals how mutant p53 hijacks epigenetic and epitranscriptomic machinery to initiate gliomagenesis and suggests potential treatment strategies for LFS gliomas.
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| 4. |
- Zhou, Xin, et al.
(författare)
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3D-imaging of selective laser melting defects in a Co-Cr-Mo alloy by synchrotron radiation micro-CT
- 2015
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Ingår i: Acta Materialia. - : Elsevier BV. - 1359-6454 .- 1873-2453. ; 98, s. 1-16
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Tidskriftsartikel (refereegranskat)abstract
- Microstructure defects set the mechanical property limits for solid Co-Cr-Mo alloy prepared by selective laser melting (SLM). Previous studies were mainly based on 2D SEM images and thus not able to provide information of the 3D morphologies of the complex defects. In this paper, the remaining porosities in Co-Cr-Mo alloy parts prepared by selective laser melting were presented in relation to the laser processing parameters. In order to understand the defect forming mechanism, accurate 3D images of defects inside SLM fabricated Co-Cr-Mo samples were provided by synchrotron radiation micro-CT imaging of 300 pm thick slices cut from a 10 mm cube. With 3D reconstructed images distinctive morphologies of SLM defects spanning across the consolidated powder layers were generated. The faults can be classified as single layer or multi-layers defects. The accidental single layer defects form as gaps between adjacent laser melt tracks or melt track discontinuousness caused by inherent fluid instability under various disturbances. The first formed single layer defect generates often a multi-layer defect spanning for 2-3 subsequent powder layers. By stabilizing the melt pool flow and by reducing the surface roughness through adjusting processing parameters it appears possible to reduce the defect concentrations.
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| 5. |
- Zhou, Xin, et al.
(författare)
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Balling phenomena in selective laser melted tungsten
- 2015
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Ingår i: Journal of Materials Processing Technology. - : Elsevier BV. - 0924-0136 .- 1873-4774. ; 222, s. 33-42
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Tidskriftsartikel (refereegranskat)abstract
- Selective laser melting (SLM) of pure tungsten was carried out and the relevant consolidation issues were investigated. It was observed that balling of melted droplets at the laser focal points and entrapped cavities hindered the preparation of fully dense parts. An analysis of the balling mechanism reveals that SLM of tungsten is a process where melt spreading and solidification compete with each other and the final result is determined by intrinsic tungsten properties and the set laser processing parameters. Melted tungsten droplets wetted its own solid substrate at a low speed driven by capillary force, but solidified simultaneous at a high speed driven by the existing steep temperature gradient. Melted droplets solidified before spreading completely and kept their globular geometry instead of creating a flat layer. Tungsten bodies reaching a density of 14.8-15.2 g/cm(3) were prepared with an open irregular porosity and surface roughness. With a second laser scanning the balling W droplets were remelted at the building surface resulting in a much smoother appearance with less porosity and indicated a way to further improve relative density, near 16 g/cm(3) (82.9% theoretical density). Oxidation must be avoided, as any oxide contamination enriched preferably around the melt pool edge, changing the surface tension gradient and the thermocapillary convection thereby increasing balling.
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| 6. |
- Zhou, Xin, et al.
(författare)
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Textures formed in a CoCrMo alloy by selective laser melting
- 2015
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Ingår i: Journal of Alloys and Compounds. - : Elsevier BV. - 0925-8388 .- 1873-4669. ; 631, s. 153-164
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Tidskriftsartikel (refereegranskat)abstract
- Unique crystal textures formed by selective laser melting of a CoCrMo alloy were characterized by electron backscattered diffraction. Preferred crystallographic orientations were found for individual grains in the solid alloy microstructure. Along the building or radial grain growth direction in the rapidly cooling melt pool the formed columnar grains were not purely < 001 > or < 111 >, as reported before, but a concurrence of < 001 > and < 011 >. Along the scanning direction, a (011) < 100 > texture was limited to the outmost surface whereas in the solid bulk the preferred orientation was a < 001 > fiber texture.
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| 7. |
- Bolton, Corey J, et al.
(författare)
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Sex and Education Modify the Association Between Subjective Cognitive Decline and Amyloid Pathology.
- 2023
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Ingår i: medRxiv : the preprint server for health sciences.
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Subjective cognitive decline (SCD) may be an early risk factor for dementia, particularly in highly educated individuals and women. This study examined the effect of education and sex on the association between SCD and Alzheimer's disease (AD) biomarkers in non-demented older adults.Vanderbilt Memory and Aging Project participants free of clinical dementia or stroke (n=156, 72±6 years, 37% mild cognitive impairment, 33% female) completed fasting lumbar puncture, SCD assessment, and Wide Range Achievement Test-III Reading subtest to assess reading level at baseline as a a proxy for educational quality. Cerebrospinal fluid (CSF) biomarkers for AD (β-amyloid 42 (Aβ42), Aβ42/40 ratio, phosphorylated tau (p-tau), tau, and neurofilament light (NfL)) were analyzed in batch. Linear mixed effects models related SCD to CSF AD biomarkers and follow-up models assessed SCD x sex, SCD x reading level , and SCD x education interactions on AD biomarkers.In main effect models, higher SCD was associated with lower Aβ42 and Aβ42/40 ratio (p-values<0.004). SCD was not associated with tau, p-tau, or NfL levels ( p- values>0.38). SCD score interacted with sex on Aβ42/40 ratio ( p =0.03) but no other biomarkers ( p -values>0.10). In stratified models, higher SCD was associated with lower Aβ42/40 ratio in men ( p =0.0003) but not in women ( p =0.48). SCD score interacted with education on Aβ42 ( p =0.005) and Aβ42/40 ratio ( p =0.001) such that higher education was associated with a stronger negative association between SCD and amyloid levels. No SCD score x reading level interaction was found (p-values> 0.51) though significant associations between SCD and amyloid markers were seen in the higher reading level group (p-values<0.004) but not the lower reading level group (p-values>0.12) when stratified by a median split in reading level.Among community-dwelling older adults free of clinical dementia, higher SCD was associated with greater cerebral amyloid accumulation, one of the earliest pathological AD changes. SCD appears most useful in detecting early AD-related brain changes in men and individuals with higher quantity and quality of education. SCD was not associated with CSF markers of tau pathology or neurodegeneration. These findings suggest that considering sex and education is important when assessing SCD in older adults.
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| 8. |
- Chen, Baowei, et al.
(författare)
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Methylation mechanism of tin(II) by methylcobalamin in aquatic systems
- 2007
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Ingår i: Chemosphere. - : Elsevier BV. - 0045-6535 .- 1879-1298. ; 68:3, s. 414-419
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Tidskriftsartikel (refereegranskat)abstract
- The methylation reaction of tin(II) with methylcobalamin (CH(3)B(12)) in aquatic systems was modeled in the laboratory. The products were detected by a sensitive gas chromatography-flame photometric detector (GC-FPD), and further identified by gas chromatography-mass spectrometry (GC-MS). Both monomethyltin (MMT) and dimethyltin (DMT) were found as methylation products. Three important effecting factors during the methylation reaction, salinity, pH and aerobic or anaerobic, were studied. The results showed that methyl group can be transferred from CH(3)B(12) to tin in aquatic solutions as a radical or carbonium, as well as a carbanion. Two explanations for the pH-dependency of the methylation reaction between tin(II) and CH(3)B(12) were proposed: pH-dependency of the equilibrium states of CH(3)B(12), and pH-dependency of inorganic tin(II) species whose reactivity vary with the redox potential in the solution. Salinity can influence the activity of the methyl donor, which cause changes in the methylation efficiency. Kinetic experiments showed that the methylation reaction was pseudo-first-order for CH(3)B(12).
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| 9. |
- Chen, Yundai, et al.
(författare)
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Treatment Trends, Effectiveness, and Safety of Statins on Lipid Goal Attainment in Chinese Percutaneous Coronary Intervention Patients : a Multicenter, Retrospective Cohort Study
- 2017
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Ingår i: Clinical Therapeutics. - : ELSEVIER. - 0149-2918 .- 1879-114X. ; 39:9, s. 1827-1839
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: Limited data exist on the use of statins in Chinese patients with coronary artery disease (CAD) treated with percutaneous coronary intervention (PCI). We therefore conducted this study to observe the usage trend and the effectiveness of statins on LDL-C goal attainment and other lipid parameters among PCI-treated patients.Methods: This multicenter, retrospective, observational, longitudinal cohort study was conducted in PCI-treated patients with CAD between July 1, 2011, and February 28, 2015. Primary study outcomes included statin treatment pattern after PCI and proportion of patients achieving target (LDL-C) levels 1 month after PCI and initiating statin therapy.Findings: Data were analyzed for 2708 patients (mean age, 59 [10] years; median body mass index, 25.6 [4.0] kg/m(2)). From baseline to the end of 1 month, atorvastatin and rosuvastatin were the most prescribed statins; 20 mg and 10 mg were the most prescribed doses and therefore chosen for efficacy comparisons. In patients without dose changes, LDL-C reduction with rosuvastatin 10 mg was significantly greater compared with atorvastatin 20 mg (-0.67 mmol/L [from 2.44 mmol/L to 1.77 mmol/L] vs 0.54 mmol/L [from 2.40 mmol/L to 1.86 mmol/L]; P = 0.008). However, there was no difference in HDL-C, triglyceride, or total cholesterol values between groups. Age and LDL-C levels at baseline were significantly associated with target LDL-C achievement.
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| 10. |
- Eilert, Johan, 1980-, et al.
(författare)
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Complexity Reduction of Matrix Manipulation for Multi-User STBC-MIMO Decoding
- 2007
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Ingår i: IEEE Sarnoff Symmposium,2007. - 9781424424832 ; , s. 1-5
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Konferensbidrag (refereegranskat)abstract
- This paper studies efficient complex valued matrix manipulations for multi-user STBC-MIMO decoding. A novel method called Alamouti blockwise analytical matrix inversion (ABAMI) is proposed for the inversion of large complex matrices that are based on Alamouti sub-blocks. Another method using a variant of Givens rotation is proposed for fast QR decomposition of this kind of matrices. Our solutions significantly reduce the number of operations which makes them more than 4 times faster than several other solutions in the literature. Furthermore, compared to fixed function VLSI implementations, our solution is more flexible and consumes less silicon area because the hardware is programmable and it can be reused for many other operations such as filtering, correlation and FFT/IFFT. Besides the analysis of the general computational complexity based on the number of basic operations, the computational latency is also measured in clock cycles based on the conceptual hardware for real-time matrix manipulations.
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