We describe here a comprehensive study on the effect of cellular structure and melt pool boundary (MPB) condition on the mechanical properties, deformation and failure behavior of AlSi10Mg alloy ...processed by selective laser melting (SLM). The morphology of melt pool (MP) on the load bearing face of tensile samples was significantly different with build directions. It resulted in different mechanical properties of the samples with different build directions. Furthermore, the microstructure analysis revealed that the MP in the SLM AlSi10Mg alloy mainly consisted of columnar α-Al grains which were made of ultra-fine elongated cellular structure. Electron back-scatter diffraction (EBSD) analysis revealed that the long axis of cellular structure and columnar grains were parallel to < 100 >, which resulted in < 100 > fiber texture in SLM AlSi10Mg alloy. However, Schmid factor calculation demonstrated that the anisotropy of mechanical properties of the SLM AlSi10Mg alloy built with different direction was mainly dependent on the distribution of MPB on the load bearing face, and not texture. The defects including pores, residual stress and heat affected zone (HAZ) located at MPB made it the weakest part in the SLM AlSi10Mg. The sample built along horizontal direction exhibited good combination of strength and plasticity and is attributed to the lowest fraction of MPBs that withstand load during tensile. MPB had strong influence on the mechanical properties and failure behavior of SLM AlSi10Mg built with different directions.
Racial differences in molecular biomarkers for Alzheimer disease may suggest race-dependent biological mechanisms.
To ascertain whether there are racial disparities in molecular biomarkers for ...Alzheimer disease.
A total of 1255 participants (173 African Americans) were enrolled from January 1, 2004, through December 31, 2015, in longitudinal studies at the Knight Alzheimer Disease Research Center at Washington University and completed a magnetic resonance imaging study of the brain and/or positron emission tomography of the brain with Pittsburgh compound B (radioligand for aggregated amyloid-β) and/or cerebrospinal fluid (CSF) assays for the concentrations of amyloid-β42, total tau, and phosphorylated tau181. Independent cross-sectional analyses were conducted from April 22, 2016, to August 27, 2018, for each biomarker modality with an analysis of variance or analysis of covariance including age, sex, educational level, race, apolipoprotein E (APOE) ε4 allele status, and clinical status (normal cognition or dementia). All biomarker assessments were conducted without knowledge of the clinical status of the participants.
The primary outcomes were hippocampal volumes adjusted for differences in intracranial volumes, global cerebral amyloid burden as transformed into standardized uptake value ratios (partial volume corrected), and CSF concentrations of amyloid-β42, total tau, and phosphorylated tau181.
Of the 1255 participants (707 women and 548 men; mean SD age, 70.8 9.9 years), 116 of 173 African American participants (67.1%) and 724 of 1082 non-Hispanic white participants (66.9%) had normal cognition. There were no racial differences in the frequency of cerebral ischemic lesions noted on results of brain magnetic resonance imaging, mean cortical standardized uptake value ratios for Pittsburgh compound B, or for amyloid-β42 concentrations in CSF. However, in individuals with a reported family history of dementia, mean (SE) total hippocampal volumes were lower for African American participants than for white participants (6418.26 138.97 vs 6990.50 44.10 mm3). Mean (SE) CSF concentrations of total tau were lower in African American participants than in white participants (293.65 34.61 vs 443.28 18.20 pg/mL; P < .001), as were mean (SE) concentrations of phosphorylated tau181 (53.18 4.91 vs 70.73 2.46 pg/mL; P < .001). There was a significant race by APOE ε4 interaction for both CSF total tau and phosphorylated tau181 such that only APOE ε4-positive participants showed the racial differences.
The results of this study suggest that analyses of molecular biomarkers of Alzheimer disease should adjust for race. The lower CSF concentrations of total tau and phosphorylated tau181 in African American individuals appear to reflect a significant race by APOE ε4 interaction, suggesting a differential effect of this Alzheimer risk variant in African American individuals compared with white individuals.
In order to develop high strength metal–matrix composites with acceptable ductility, bulk nanostructured aluminum–matrix composites reinforced with graphene nanoflakes were fabricated by cryomilling ...and hot extrusion processes. Microstructure and mechanical properties were characterized and determined using transmission electron microscopy, electron dispersion spectroscopy, as well as static tensile tests. The results show that, with an addition of only 0.5wt% graphene nanoflakes, the bulk nanostructured aluminum/graphene composite exhibited increased strength and unsubdued ductility over pure aluminum. Besides, the mechanical properties of the composites with higher content of graphene nanoflakes were also measured and investigated. Above 1.0wt% of graphene nanoflakes, however, this strengthening effect sharply dropped due to the clustering of graphene nanoflakes. Furthermore, the optimal addition of graphene nanoflakes into the nanocrystalline aluminum matrix was calculated and discussed.
The order and magnitude of pathologic processes in Alzheimer's disease are not well understood, partly because the disease develops over many years. Autosomal dominant Alzheimer's disease has a ...predictable age at onset and provides an opportunity to determine the sequence and magnitude of pathologic changes that culminate in symptomatic disease.
In this prospective, longitudinal study, we analyzed data from 128 participants who underwent baseline clinical and cognitive assessments, brain imaging, and cerebrospinal fluid (CSF) and blood tests. We used the participant's age at baseline assessment and the parent's age at the onset of symptoms of Alzheimer's disease to calculate the estimated years from expected symptom onset (age of the participant minus parent's age at symptom onset). We conducted cross-sectional analyses of baseline data in relation to estimated years from expected symptom onset in order to determine the relative order and magnitude of pathophysiological changes.
Concentrations of amyloid-beta (Aβ)(42) in the CSF appeared to decline 25 years before expected symptom onset. Aβ deposition, as measured by positron-emission tomography with the use of Pittsburgh compound B, was detected 15 years before expected symptom onset. Increased concentrations of tau protein in the CSF and an increase in brain atrophy were detected 15 years before expected symptom onset. Cerebral hypometabolism and impaired episodic memory were observed 10 years before expected symptom onset. Global cognitive impairment, as measured by the Mini-Mental State Examination and the Clinical Dementia Rating scale, was detected 5 years before expected symptom onset, and patients met diagnostic criteria for dementia at an average of 3 years after expected symptom onset.
We found that autosomal dominant Alzheimer's disease was associated with a series of pathophysiological changes over decades in CSF biochemical markers of Alzheimer's disease, brain amyloid deposition, and brain metabolism as well as progressive cognitive impairment. Our results require confirmation with the use of longitudinal data and may not apply to patients with sporadic Alzheimer's disease. (Funded by the National Institute on Aging and others; DIAN ClinicalTrials.gov number, NCT00869817.).
We propose a new method for determining the target genes of transcriptional enhancers in specific cells and tissues. It combines global trends across many samples and sample-specific information, and ...considers the joint effect of multiple enhancers. Our method outperforms existing methods when predicting the target genes of enhancers in unseen samples, as evaluated by independent experimental data. Requiring few types of input data, we are able to apply our method to reconstruct the enhancer-target networks in 935 samples of human primary cells, tissues and cell lines, which constitute by far the largest set of enhancer-target networks. The similarity of these networks from different samples closely follows their cell and tissue lineages. We discover three major co-regulation modes of enhancers and find defense-related genes often simultaneously regulated by multiple enhancers bound by different transcription factors. We also identify differentially methylated enhancers in hepatocellular carcinoma (HCC) and experimentally confirm their altered regulation of HCC-related genes.
Individuals in the presymptomatic stage of Alzheimer disease (AD) are increasingly being targeted for AD secondary prevention trials. How early during the normal life span underlying AD pathologies ...begin to develop, their patterns of change over time, and their relationship with future cognitive decline remain to be determined.
To characterize the within-person trajectories of cerebrospinal fluid (CSF) biomarkers of AD over time and their association with changes in brain amyloid deposition and cognitive decline in cognitively normal middle-aged individuals.
As part of a cohort study, cognitively normal (Clinical Dementia Rating CDR of 0) middle-aged research volunteers (n = 169) enrolled in the Adult Children Study at Washington University, St Louis, Missouri, had undergone serial CSF collection and longitudinal clinical assessment (mean, 6 years; range, 0.91-11.3 years) at 3-year intervals at the time of analysis, between January 2003 and November 2013. A subset (n = 74) had also undergone longitudinal amyloid positron emission tomographic imaging with Pittsburgh compound B (PiB) in the same period. Serial CSF samples were analyzed for β-amyloid 40 (Aβ40), Aβ42, total tau, tau phosphorylated at threonine 181 (P-tau181), visinin-like protein 1 (VILIP-1), and chitinase-3-like protein 1 (YKL-40). Within-person measures were plotted according to age and AD risk defined by APOE genotype (ε4 carriers vs noncarriers). Linear mixed models were used to compare estimated biomarker slopes among middle-age bins at baseline (early, 45-54 years; mid, 55-64 years; late, 65-74 years) and between risk groups. Within-person changes in CSF biomarkers were also compared with changes in cortical PiB binding and progression to a CDR higher than 0 at follow-up.
Changes in Aβ40, Aβ42, total tau, P-tau181, VILIP-1, and YKL-40 and, in a subset of participants, changes in cortical PiB binding.
While there were no consistent longitudinal patterns in Aβ40 (P = .001-.97), longitudinal reductions in Aβ42 were observed in some individuals as early as early middle age (P ≤ .05) and low Aβ42 levels were associated with the development of cortical PiB-positive amyloid plaques (area under receiver operating characteristic curve = 0.9352; 95% CI, 0.8895-0.9808), especially in mid middle age (P < .001). Markers of neuronal injury (total tau, P-tau181, and VILIP-1) dramatically increased in some individuals in mid and late middle age (P ≤ .02), whereas the neuroinflammation marker YKL-40 increased consistently throughout middle age (P ≤ .003). These patterns were more apparent in at-risk ε4 carriers (Aβ42 in an allele dose-dependent manner) and appeared to be associated with future cognitive deficits as determined by CDR.
Longitudinal CSF biomarker patterns consistent with AD are first detectable during early middle age and are associated with later amyloid positivity and cognitive decline. Such measures may be useful for targeting middle-aged, asymptomatic individuals for therapeutic trials designed to prevent cognitive decline.
Context.
Despite over 50 years of research, many open questions remain about the origin and nature of gamma-ray bursts (GRBs). Linear polarization measurements of the prompt emission of these extreme ...phenomena have long been thought to be key to answering a range of these questions. The POLAR detector was designed to produce the first set of detailed and reliable linear polarization measurements in the 50 − 500 keV energy range. During late 2016 and early 2017, POLAR detected a total of 55 GRBs. The analysis results of 5 of these GRBs have been reported, and were found to be consistent with a low or unpolarized flux. However, previous reports by other collaborations found high levels of linear polarization, including some as high as 90%.
Aims.
We study the linear polarization for the 14 GRBs observed by POLAR for which statistically robust inferences are possible. Additionally, time-resolved polarization studies are performed on GRBs with sufficient apparent flux.
Methods.
A publicly available polarization analysis tool, developed within the Multi-Mission Maximum Likelihood framework (
3ML
), was used to produce statistically robust results. The method allows spectral and polarimetric data from POLAR to be combined with spectral data from the
Fermi
Gamma-ray Burst Monitor (
Fermi
-GBM) and the
Neil Gehrels Swift
Observatory to jointly model the spectral and polarimetric parameters.
Results.
The time-integrated analysis finds all results to be compatible with low or zero polarization with the caveat that, when time-resolved analysis is possible within individual pulses, we observe moderate linear polarization with a rapidly changing polarization angle. Therefore, time-integrated polarization results, while pointing to lower polarization, are potentially an artifact of summing over the changing polarization signal and thus washing out the true moderate polarization. We therefore caution against overinterpretation of any time-integrated results inferred herein and encourage the community to wait for more detailed polarization measurements from forthcoming missions such as POLAR-2 and LEAP.
This paper determined the effects of mulching time for double furrows and ridges using plastic film on soil water status, grain yield of maize, soil quality, and economic benefits. The study was ...conducted in a typical semiarid area during two growing seasons of 2006–2007 with the following three treatments: (i) plastic film mulching at maize sowing with conventional tillage, and the film was removed at harvest (CK); (ii) mulching applied 30
d before sowing with conventional tillage, and the film was removed at harvest (T1); and (iii) mulching at sowing with no-tillage, and the film left on the field after harvest in the first season and used for mulching in the second season (T2). The T1 in both years and T2 in the second year (2007) improved soil water content (in the 0–60
cm layer) and temperature (10
cm) at sowing compared with CK. After the two seasons, the soil water content was significantly higher in the 0–80
cm soil layer in CK and T1, and in the 0–120
cm soil layer in T2; however, it decreased significantly in 140–200
cm soil layer in CK and T1, compared to their initial values at sowing in April 2006, and there was no significant change in T2. The rainfall storage in the 0–200
cm soil layer during the non-growing season (late September 2006 to late April 2007) was 18.2
mm in CK, 34.0
mm in T1, and 59.7
mm in T2, and the rainfall storage in 100–200
cm soil layer was 16.5 and 18.6
mm higher in T2 than in CK and T1, respectively. In 2006, there were no significant differences in yield and water use efficiency (WUE) in all treatments. In 2007, the yield in T1 was significantly higher than in T2, but yields in T2 and CK were not significantly different, and there was no significant difference in WUE among treatments. Soil organic carbon (SOC) (0–20
cm) decreased in CK and T1, but increased (by 2.7%) in T2 at harvesting in September 2007 from the initial value of sowing in April 2006. The ratio of output to input was 1.32:1 for CK, 1.40:1 for T1, and 1.67:1 for T2 averaged across the two seasons. Therefore, T2 was a more sustainable model for increasing water storage, producing greater economic benefit and maintaining SOC balance for maize production in semiarid area.
Dapsone is used in the treatment of infections and inflammatory diseases. The dapsone hypersensitivity syndrome, which is associated with a reported mortality of 9.9%, develops in about 0.5 to 3.6% ...of persons treated with the drug. Currently, no tests are available to predict the risk of the dapsone hypersensitivity syndrome.
We performed a genomewide association study involving 872 participants who had received dapsone as part of multidrug therapy for leprosy (39 participants with the dapsone hypersensitivity syndrome and 833 controls), using log-additive tests of single-nucleotide polymorphisms (SNPs) and imputed HLA molecules. For a replication analysis, we genotyped 24 SNPs in an additional 31 participants with the dapsone hypersensitivity syndrome and 1089 controls and performed next-generation sequencing for HLA-B and HLA-C typing at four-digit resolution in an independent series of 37 participants with the dapsone hypersensitivity syndrome and 201 controls.
Genomewide association analysis showed that SNP rs2844573, located between the HLA-B and MICA loci, was significantly associated with the dapsone hypersensitivity syndrome among patients with leprosy (odds ratio, 6.18; P=3.84×10(-13)). HLA-B*13:01 was confirmed to be a risk factor for the dapsone hypersensitivity syndrome (odds ratio, 20.53; P=6.84×10(-25)). The presence of HLA-B*13:01 had a sensitivity of 85.5% and a specificity of 85.7% as a predictor of the dapsone hypersensitivity syndrome, and its absence was associated with a reduction in risk by a factor of 7 (from 1.4% to 0.2%). HLA-B*13:01 is present in about 2 to 20% of Chinese persons, 1.5% of Japanese persons, 1 to 12% of Indians, and 2 to 4% of Southeast Asians but is largely absent in Europeans and Africans.
HLA-B*13:01 was associated with the development of the dapsone hypersensitivity syndrome among patients with leprosy. (Funded by the National Natural Science Foundation of China and others.).
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