| 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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| 11. |
- Gifford, Katherine A, et al.
(författare)
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The 12-Word Philadelphia Verbal Learning Test Performances in Older Adults: Brain MRI and Cerebrospinal Fluid Correlates and Regression-Based Normative Data.
- 2018
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Ingår i: Dementia and geriatric cognitive disorders extra. - : S. Karger AG. - 1664-5464. ; 8:3, s. 476-491
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Tidskriftsartikel (refereegranskat)abstract
- This study evaluated neuroimaging and biological correlates, psychometric properties, and regression-based normative data of the 12-word Philadelphia Verbal Learning Test (PVLT), a list-learning test.Vanderbilt Memory and Aging Project participants free of clinical dementia and stroke (n = 230, aged 73 ± 7 years) completed a neuropsychological protocol and brain MRI. A subset (n = 111) underwent lumbar puncture for analysis of Alzheimer's disease (AD) and axonal integrity cerebrospinal fluid (CSF) biomarkers. Regression models related PVLT indices to MRI and CSF biomarkers adjusting for age, sex, race/ethnicity, education, APOE-ε4 carrier status, cognitive status, and intracranial volume (MRI models). Secondary analyses were restricted to participants with normal cognition (NC; n = 127), from which regression-based normative data were generated.Lower PVLT performances were associated with smaller medial temporal lobe volumes (p < 0.05) and higher CSF tau concentrations (p < 0.04). Among NC, PVLT indices were associated with white matter hyperintensities on MRI and an axonal injury biomarker (CSF neurofilament light; p < 0.03).The PVLT appears sensitive to markers of neurodegeneration, including temporal regions affected by AD. Conversely, in cognitively normal older adults, PVLT performance seems to relate to white matter disease and axonal injury, perhaps reflecting non-AD pathways to cognitive change. Enhanced normative data enrich the clinical utility of this tool.
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| 12. |
- Gifford, Katherine A, et al.
(författare)
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Validity and Normative Data for the Biber Figure Learning Test: A Visual Supraspan Memory Measure.
- 2020
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Ingår i: Assessment. - : SAGE Publications. - 1552-3489 .- 1073-1911. ; 27:6, s. 1320-1334
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Tidskriftsartikel (refereegranskat)abstract
- The Biber Figure Learning Test (BFLT), a visuospatial serial figure learning test, was evaluated for biological correlates and psychometric properties, and normative data were generated. Nondemented individuals ( n = 332, 73 ± 7, 41% female) from the Vanderbilt Memory & Aging Project completed a comprehensive neuropsychological protocol. Adjusted regression models related BFLT indices to structural brain magnetic resonance imaging and cerebrospinal fluid (CSF) markers of brain health. Regression-based normative data were generated. Lower BFLT performances (Total Learning, Delayed Recall, Recognition) related to smaller medial temporal lobe volumes and higher CSF tau concentrations but not CSF amyloid. BFLT indices were most strongly correlated with other measures of verbal and nonverbal memory and visuospatial skills. The BFLT provides a comprehensive assessment of all aspects of visuospatial learning and memory and is sensitive to biomarkers of unhealthy brain aging. Enhanced normative data enriches the clinical utility of this visual serial figure learning test for use with older adults.
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| 13. |
- Guo, Jing, et al.
(författare)
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Pulmonary toxicity and adjuvant effect of di-(2-exylhexyl) phthalate in ovalbumin-immunized BALB/c mice
- 2012
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Ingår i: PLOS ONE. - : PLOS. - 1932-6203. ; 7:6
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Asthma is a complex pulmonary inflammatory disease, which is characterized by airway hyperresponsiveness, variable airflow obstruction and inflammation in the airways. The majority of asthma is allergic asthma, which is a disease caused by type I hypersensitivity mediated by IgE. Exposures to a number of environmental chemicals are suspected to lead to asthma, one such pollutant is di-(2-ethylheyl) phthalate (DEHP). DEHP is a manufactured chemical that is commonly added in plastic products to make them flexible. Epidemiological studies have revealed a positive association between DEHP exposure and asthma prevalence.METHODOLOGY/PRINCIPAL FINDINGS: The present study was aimed to determine the underlying role of DEHP exposure in airway reactivity, especially when combined with allergen exposure. The biomarkers include pulmonary histopathology, airway hyperresponsiveness (lung function), IgE, IL-4, IFN-γ and eosinophils. Healthy balb/c mice were randomly divided into eight exposure groups (n = 8 each): (1) saline control, (2) 30 µg/(kg•d) DEHP, (3) 300 µg/(kg•d) DEHP, (4) 3000 µg/(kg•d) DEHP, and (5) ovalbumin (OVA)-sensitized group, (6) OVA-combined with 30 µg/(kg•d) DEHP, (7) OVA-combined with 300 µg/(kg•d) DEHP, and (8) OVA-combined with 3000 µg/(kg•d) DEHP. Experimental tests were conducted after 52-day DEHP exposure and subsequently one week of challenge with aerosolized OVA. The principal findings include: (1) Strong postive associations exist between OVA-combined DEHP exposure and serum total IgE (T-IgE), as well as histological findings. These positive associations show a dose-dependent low dose sensitive effect of DEHP. (2) IL-4, eosinophil recruitment and lung function are also indicators for adjuvant effect of DEHP.CONCLUSIONS/SIGNIFICANCE: Our results suggest that except the significant changes of immunological and inflammatory biomarkers (T-IgE, IL-4, IFN-γ and eosinophils), the pulmonary histological (histopathological examination) and physiological (lung function) data also support that DEHP may promote and aggravate allergic asthma by adjuvant effect.
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| 14. |
- Han, Mengying, et al.
(författare)
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ChemHub: a knowledgebase of functional chemicals for synthetic biology studies
- 2021
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Ingår i: Bioinformatics. - : Oxford University Press (OUP). - 1367-4803 .- 1367-4811 .- 1460-2059. ; 37:22, s. 4275-4276
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Tidskriftsartikel (refereegranskat)abstract
- The field of synthetic biology lacks a comprehensive knowledgebase for selecting synthetic target molecules according to their functions, economic applications and known biosynthetic pathways. We implemented ChemHub, a knowledgebase containing >90 000 chemicals and their functions, along with related biosynthesis information for these chemicals that was manually extracted from >600 000 published studies by more than 100 people over the past 10 years.
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| 15. |
- Kresge, Hailey A, et al.
(författare)
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Lower Left Ventricular Ejection Fraction Relates to Cerebrospinal Fluid Biomarker Evidence of Neurodegeneration in Older Adults.
- 2020
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Ingår i: Journal of Alzheimer's disease : JAD. - 1875-8908. ; 74:3, s. 965-974
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Tidskriftsartikel (refereegranskat)abstract
- Subclinical cardiac dysfunction is associated with decreased cerebral blood flow, placing the aging brain at risk for Alzheimer's disease (AD) pathology and neurodegeneration.This study investigates the association between subclinical cardiac dysfunction, measured by left ventricular ejection fraction (LVEF), and cerebrospinal fluid (CSF) biomarkers of AD and neurodegeneration.Vanderbilt Memory & Aging Project participants free of dementia, stroke, and heart failure (n=152, 72±6 years, 68% male) underwent echocardiogram to quantify LVEF and lumbar puncture to measure CSF levels of amyloid-β42 (Aβ42), phosphorylated tau (p-tau), and total tau (t-tau). Linear regressions related LVEF to CSF biomarkers, adjusting for age, sex, race/ethnicity, education, Framingham Stroke Risk Profile, cognitive diagnosis, and apolipoprotein E ɛ4 status. Secondary models tested an LVEF x cognitive diagnosis interaction and then stratified by diagnosis (normal cognitive (NC), mild cognitive impairment (MCI)).Higher LVEF related to decreased CSF Aβ42 levels (β=-6.50, p=0.04) reflecting greater cerebral amyloid accumulation, but this counterintuitive result was attenuated after excluding participants with cardiovascular disease and atrial fibrillation (p=0.07). We observed an interaction between LVEF and cognitive diagnosis on CSF t-tau (p=0.004) and p-tau levels (p=0.002), whereas lower LVEF was associated with increased CSF t-tau (β=-9.74, p=0.01) and p-tau in the NC (β=-1.41, p=0.003) but not MCI participants (p-values>0.13).Among cognitively normal older adults, subclinically lower LVEF relates to greater molecular evidence of tau phosphorylation and neurodegeneration. Modest age-related changes in cardiovascular function may have implications for pathophysiological changes in the brain later in life.
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| 16. |
- Li, Xiaojuan, et al.
(författare)
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Climate and soil properties drive soil organic and inorganic carbon patterns across a latitudinal gradient in southwestern China
- 2023
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Ingår i: Journal of Soils and Sediments. - : Springer Science and Business Media LLC. - 1614-7480 .- 1439-0108. ; 23:1, s. 91-102
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Tidskriftsartikel (refereegranskat)abstract
- PurposeDrylands account for 47.2% of land area and contain 15.5% of global carbon (C). However, the variation in organic and inorganic C stocks across latitudinal gradients in arid and semiarid shrubland ecosystems remains understudied, and we lack in-depth understanding of the main drivers of C variation at this spatial scale.MethodsHere, we sampled soils from 95 sites across a latitudinal gradient to explore both the latitudinal patterns and potential drivers of soil organic carbon density (SOCD) and soil inorganic carbon density (SICD). We also assessed variation in SOCD and SICD down the soil profile, by sampling soils at four depths (0 – 10 cm, 10 – 20 cm, 20 – 30 cm, and 30 – 50 cm).ResultBoth SOCD and SICD exhibited a binomial relationship with latitude (P < 0.01). Soil properties accounted for the greatest variation in SOCD, with the most important explanatory factor being exchangeable calcium, followed by mean annual temperature, pH, plant diversity, and silt content. Soil pH and plant diversity were more important in explaining variation in SOCD in the subsoil (> 20 cm depth) than the topsoil. For SICD, soil properties explained the greatest variation at all depths. Soil pH explained the most variance in SICD, followed by exchangeable calcium and mean annual temperature in the topsoil (i.e., 0 – 10 cm and 10 – 20 cm). In the subsoil (i.e., 20 – 30 cm and 30 – 50 cm), exchangeable calcium was the most important predictor, followed by soil organic carbon, mean annual temperature, and pH.ConclusionOur study shows that soil properties are a strong predictor of latitudinal patterns of soil organic and inorganic C in arid and semiarid shrubland ecosystems. We also identified differences in potential drivers of SOCD and SICD with depth, advancing our understanding of large-scale patterns of C storage in arid and semiarid soils.
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| 17. |
- Li, Xiaojuan, et al.
(författare)
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Latitudinal patterns of light and heavy organic matter fractions in arid and semi-arid soils
- 2022
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Ingår i: Catena. - : Elsevier BV. - 0341-8162. ; 215
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Tidskriftsartikel (refereegranskat)abstract
- Semi-arid and arid ecosystems are important for the global C cycle. Despite this, it remains unclear how organic matter fractions vary across latitudinal gradients, and what drives this variation, in dry ecosystems. In this study, we sampled soils from 100 sites across a latitudinal gradient in the dry valleys of southwestern China to explore the latitudinal patterns of light fraction organic matter (LFOM) and heavy fraction organic matter (HFOM) at two soil depths (0–10 cm and 10–20 cm). Across the studied gradient, HFOM accounted for a larger fraction of soil organic matter than LFOM. LFOM increased exponentially with increasing latitude at both 0–10 cm and 10–20 cm depths. Heavy fraction organic C increased linearly with increasing latitude at both depths, while heavy fraction organic N only increased with latitude in soils from 10 to 20 cm depth. Latitudinal patterns of LFOM were mainly explained by climate, with the most important driver being mean annual temperature, followed by mean annual precipitation. Soil physicochemical factors – in particular cation exchange capacity and silt content – explained the most variation in HFOM. Total microbial biomass was also important in explaining variation in HFOM, especially in the 10–20 cm soil layer. Overall, our results shed light on the spatial distribution of organic matter fractions in arid and semi-arid regions. We also identify candidate drivers of the variation in LFOM and HFOM in arid and semi-arid regions, finding that climate primarily explains variation in LFOM while soil physiochemistry primarily explains variation in HFOM.
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| 18. |
- Meng, Weida, et al.
(författare)
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Genotype-dependent epigenetic regulation of DLGAP2 in alcohol use and dependence
- 2021
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Ingår i: Molecular Psychiatry. - : Springer Nature. - 1359-4184 .- 1476-5578. ; 26:8, s. 4367-4382
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Tidskriftsartikel (refereegranskat)abstract
- Alcohol misuse is a major public health problem originating from genetic and environmental risk factors. Alterations in the brain epigenome may orchestrate changes in gene expression that lead to alcohol misuse and dependence. Through epigenome-wide association analysis of DNA methylation from human brain tissues, we identified a differentially methylated region, DMR-DLGAP2, associated with alcohol dependence. Methylation within DMR-DLGAP2 was found to be genotype-dependent, allele-specific and associated with reward processing in brain. Methylation at the DMR-DLGAP2 regulated expression of DLGAP2 in vitro, and Dlgap2-deficient mice showed reduced alcohol consumption compared with wild-type controls. These results suggest that DLGAP2 may be an interface for genetic and epigenetic factors controlling alcohol use and dependence.
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| 19. |
- Moore, Elizabeth E, et al.
(författare)
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Axonal Injury Partially Mediates Associations Between Increased Left Ventricular Mass Index and White Matter Damage.
- 2021
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Ingår i: Stroke. - 1524-4628. ; 53:3, s. 808-816
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Tidskriftsartikel (refereegranskat)abstract
- Left ventricular (LV) mass index is a marker of subclinical LV remodeling that relates to white matter damage in aging, but molecular pathways underlying this association are unknown. This study assessed if LV mass index related to cerebrospinal fluid (CSF) biomarkers of microglial activation (sTREM2 [soluble triggering receptor expressed on myeloid cells 2]), axonal injury (NFL [neurofilament light]), neurodegeneration (total-tau), and amyloid-β, and whether these biomarkers partially accounted for associations between increased LV mass index and white matter damage. We hypothesized higher LV mass index would relate to greater CSF biomarker levels, and these pathologies would partially mediate associations with cerebral white matter microstructure.Vanderbilt Memory and Aging Project participants who underwent cardiac magnetic resonance, lumbar puncture, and diffusion tensor imaging (n=142, 72±6 years, 37% mild cognitive impairment [MCI], 32% APOE-ε4 positive, LV mass index 51.4±8.1 g/m2, NFL 1070±588 pg/mL) were included. Linear regressions and voxel-wise analyses related LV mass index to each biomarker and diffusion tensor imaging metrics, respectively. Follow-up models assessed interactions with MCI and APOE-ε4. In models where LV mass index significantly related to a biomarker and white matter microstructure, we assessed if the biomarker mediated white matter associations.Among all participants, LV mass index was unrelated to CSF biomarkers (P>0.33). LV mass index interacted with MCI (P=0.01), such that higher LV mass index related to increased NFL among MCI participants. Associations were also present among APOE-ε4 carriers (P=0.02). NFL partially mediated up to 13% of the effect of increased LV mass index on white matter damage.Subclinical cardiovascular remodeling, measured as an increase in LV mass index, is associated with neuroaxonal degeneration among individuals with MCI and APOE-ɛ4. Neuroaxonal degeneration partially reflects associations between higher LV mass index and white matter damage. Findings highlight neuroaxonal degeneration, rather than amyloidosis or microglia, may be more relevant in pathways between structural cardiovascular remodeling and white matter damage.
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| 20. |
- Osborn, Katie E, et al.
(författare)
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Cerebrospinal fluid and plasma neurofilament light relate to abnormal cognition.
- 2019
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Ingår i: Alzheimer's & dementia. - : Wiley. - 2352-8729. ; 11:C, s. 700-709
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Tidskriftsartikel (refereegranskat)abstract
- Neuroaxonal damage may contribute to cognitive changes preceding clinical dementia. Accessible biomarkers are critical for detecting such damage.Plasma and cerebrospinal fluid (CSF) neurofilament light (NFL) were related to neuropsychological performance among Vanderbilt Memory & Aging Project participants (plasma n=333, 73±7years; CSF n=149, 72±6years) ranging from normal cognition (NC) to mild cognitive impairment (MCI). Models adjusted for age, sex, race/ethnicity, education, apolipoprotein E ε4 carriership,and Framingham Stroke Risk Profile.Plasma NFL was related to all domains (P values ≤ .008) except processing speed (P values ≥ .09). CSF NFL was related to memory and language (P values ≤ .04). Interactions with cognitive diagnosis revealed widespread plasma associations, particularly in MCI participants, which were further supported in head-to-head comparison models.Plasma and CSF NFL (reflecting neuroaxonal injury) relate to cognition among non-demented older adults albeit with small to medium effects. Plasma NFL shows particular promise as an accessible biomarker with relevance to cognition in MCI.
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| 21. |
- Wang, Dandan, et al.
(författare)
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Porcine ZBED6 regulates growth of skeletal muscle and internal organs via multiple targets
- 2021
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Ingår i: PLOS Genetics. - : Public Library of Science (PLoS). - 1553-7390 .- 1553-7404. ; 17:10
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Tidskriftsartikel (refereegranskat)abstract
- ZBED6 (zinc finger BED domain containing protein 6) is a transcription factor unique to placental mammals and its interaction with the IGF2 (insulin-like growth factor 2) locus plays a prominent role in the regulation of postnatal skeletal muscle growth. Here, we generated lean Bama miniature pigs by generating ZBED6-knockout (ZBED6(-/-)) and investigated the mechanism underlying ZBED6 in growth of muscle and internal organs of placental mammals. ZBED6(-/-) pigs show markedly higher lean mass, lean mass rate, larger muscle fiber area and heavier internal organs (heart and liver) than wild-type (WT) pigs. The striking phenotypic changes of ZBED6(-/-) pigs coincided with remarkable upregulation of IGF2 mRNA and protein expression across three tissues (gastrocnemius muscle, longissimus dorsi, heart). Despite a significant increase in liver weight, ZBED6(-/-) pigs show comparable levels of IGF2 expression to those of WT controls. A mechanistic study revealed that elevated methylation in the liver abrogates ZBED6 binding at the IGF2 locus, explaining the unaltered hepatic IGF2 expression in ZBED6(-/-) pigs. These results indicate that a ZBED6-IGF2-independent regulatory pathway exists in the liver. Transcriptome analysis and ChIP-PCR revealed new ZBED6 target genes other than IGF2, including cyclin dependent kinase inhibitor 1A (CDKN1A) and tsukushi, small leucine rich proteoglycan (TSKU), that regulates growth of muscle and liver, respectively. Author summary The lean meat rate is an important economic trait for the swine industry and it is determined by muscle growth and development. A single base change in intron 3 of the insulin-like growth factor 2 (IGF2) gene increases meat production in pigs by disrupting a binding site for zinc finger BED domain containing protein 6 (ZBED6). Chinese indigenous pig breeds carrying the homozygous IGF2 wild-type allele produce low lean meat. We thus generate a lean pig model in Chinese Bama pig by knocking out ZBED6. In this model, we demonstrate that ZBED6 KO increases muscle and internal organ growth through ZBED6-IGF2 axis and other target genes. These results not only open new strategies for lean meat breeding in Chinese indigenous pigs, but also provide new insights to the global function of ZBED6 in organ growth and development.
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| 22. |
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| 23. |
- Wu, Di, 1979-, et al.
(författare)
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Fast Complex Valued Matrix Inversion for Multi-User STBC-MIMO Decoding
- 2007
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Ingår i: IEEE Computer Society Annual Aymposium on VLSI, ISVLSI,2007. - : IEEE. - 0769528961 ; , s. 325-330
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Konferensbidrag (refereegranskat)abstract
- This paper studies the efficient complex matrix inversion for multi-user STBC-MIMO decoding. A novel method called Alamouti blockwise analytical matrix inversion (ABAMI) and its programmable VLSI implementation are proposed for the inversion of (in this context) large complex matrices with Alamouti sub-blocks. Our solution significantly reduces the number of operations which makes it more than 4 times faster than several other solutions in the literature. Furthermore, compared to these fixed function VLSI implementations, our solution is more flexible and consumes less silicon area because the hardware can be reused for many other operations. In addition to the routine 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 inversion.
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| 24. |
- Zhang, Dachuan, et al.
(författare)
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FRCD: A comprehensive food risk component database with molecular scaffold, chemical diversity, toxicity, and biodegradability analysis
- 2020
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Ingår i: Food Chemistry. - : Elsevier BV. - 0308-8146 .- 1873-7072. ; 318
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Tidskriftsartikel (refereegranskat)abstract
- The presence of natural toxins, pesticide residues, and illegal additives in food products has been associated with a range of potential health hazards. However, no systematic database exists that comprehensively includes and integrates all research information on these compounds, and valuable information remains scattered across numerous databases and extensive literature reports. Thus, using natural language processing technology, we curated 12,018 food risk components from 152,737 literature reports, 12 authoritative databases, and numerous related regulatory documents. Data on molecular structures, physicochemical properties, chemical taxonomy, absorption, distribution, metabolism, excretion, toxicity properties, and physiological targets within the human body were integrated to afford the comprehensive food risk component database (FRCD, http://www.rxnfinder.org/frcd/). We also analyzed the molecular scaffold and chemical diversity, in addition to evaluating the toxicity and biodegradability of the food risk components. The FRCD could be considered a highly promising tool for future food safety studies.
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| 25. |
- Zhang, Xueyi, et al.
(författare)
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Synthesis of Self-Pillared Zeolite Nanosheets by Repetitive Branching
- 2012
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 336:6089, s. 1684-1687
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Tidskriftsartikel (refereegranskat)abstract
- Hierarchical zeolites are a class of microporous catalysts and adsorbents that also contain mesopores, which allow for fas transport of bulky molecules and thereby enable improved performance in petrochemical and biomass processing. We used repetitive branching during one-step hydrothermal crystal growth to synthesize a new hierarchical zeolite made of orthogonally connected microporous nanosheets. The nanosheets are 2 nanometers thick and contain a network of 0.5-nanometer micropores. The house-of-cards arrangement of the nanosheets creates a permanent network of 2- to 7-nanometer mesopores, which, along with the high external surface area and reduced micropore diffusion length, account for higher reaction rates for bulky molecules relative to those of other mesoporous and conventional MFI zeolites.
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| 26. |
- Zhao, Dandan, et al.
(författare)
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Investigation of ion irradiation hardening behaviors of tempered and long-term thermal aged T92 steel
- 2018
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Ingår i: Journal of Nuclear Materials. - : Elsevier BV. - 0022-3115. ; 511, s. 191-199
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Tidskriftsartikel (refereegranskat)abstract
- 9Cr ferritic/martensitic steels are promising materials for in-core components in advanced Gen-IV reactors. In these applications, their long-term microstructural stability under thermal exposure and resistance to neutron irradiation are essential. Tempered (unaged) and long-term thermal aged T92 samples were used to evaluate the effects of thermal aging and ion irradiation on the microstructure and micromechanical properties of the steel. Both the tempered and aged samples were irradiated with 3 MeV Fe11+ions to 0.25, 0.50, 1.00 and 5.00 dpa at room temperature. Using the nanoindentation technique, the irradiation hardening behaviors of T92 steel were investigated. The irradiation hardening effect was observed in both the tempered and aged T92 samples. To eliminate the soft substrate effect, the critical indentation depth was determined using the ratio of the average hardness of irradiated and unirradiated samples at the same depth. Under the same irradiation conditions, the macroscopic hardness values of the aged T92 samples after irradiation were lower than those of the tempered samples. The irradiation hardening effect was more significant in the aged T92 due to the decreased dislocation density and the coarsened martensitic lath after long-term thermal aging.
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| 27. |
- Zhao, Dandan, et al.
(författare)
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Proton irradiation induced defects in T92 steels: An investigation by TEM and positron annihilation spectroscopy
- 2019
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Ingår i: Nuclear Instruments and Methods in Physics Research, Section B: Beam Interactions with Materials and Atoms. - : Elsevier BV. - 0168-583X. ; 442, s. 59-66
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Tidskriftsartikel (refereegranskat)abstract
- In order to investigate proton irradiation damage on ferritic/martensitic T92 steels, both the unaged and aged (650 °C for 15,000 h) T92 steels were irradiated with 250 keV protons to 0.01, 0.05 and 0.20 dpa at room temperature due to the lower dose rate of protons compared with heavy-ions. The microstructural evolution induced by thermal aging and proton irradiation was studied by transmission electron microscopy and positron annihilation spectroscopy, and the corresponding micromechanical property changes were investigated by nano-indentation. After 0.20 dpa proton irradiation, the dominant irradiation-induced dislocation loops were a0100 type loops for both the unaged and aged samples. The dislocation-type defects in the aged T92 sample were larger in size and higher in number density, compared with those in the unaged samples. Less vacancy-type defects induced by protons were detected in the aged than the unaged T92 samples under the same irradiation conditions. The higher number density of dislocation-type defects led to more severe irradiation hardening in the aged T92 samples.
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