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At GE Research, we are combining “physics” with artificial intelligence and machine learning to advance manufacturing design, processing, and inspection, turning innovative technologies into real products and solutions across our industrial portfolio. This article provides a snapshot of how this physical plus digital transformation is evolving at GE.
Nucleos(t)ide analogues (NAs) are widely used for antiviral therapy in patients with chronic hepatitis B (CHB), but real-world data on treatment patterns and long-term clinical outcomes are not always available. Using data from electronic medical records between January 2011 and December 2016 in Shanghai, China, we evaluated patient characteristics, treatment patterns and clinical outcomes in patients with CHB. There were 6688 patients in the study cohort. The incidences of cirrhosis and hepatocellular carcinoma (HCC) were 41.0‰ and 6.8‰ person-years, respectively. There were more cirrhosis and HCC cases among patients who had shorter NA treatment duration (<365 days), or who were less compliant (<80%). In addition, increased risk of cirrhosis and HCC was observed in patients who did not achieve hepatitis B surface antigen (HBsAg) loss/seroconversion. Moreover, patients with cirrhosis developed after antiviral treatments had a higher incidence of HCC (adjusted hazard ratio 15.86, 95% confidence interval 7.35–34.24). Good compliance with treatment and longer treatment duration significantly decreased the risk of developing cirrhosis and HCC. HBsAg loss seemed to be a protective factor for cirrhosis/HCC in NAs-treated patients with CHB, and cirrhosis was a confirmed risk factor for HCC development as expected.
Heading date (HD) and flowering date (FD) are critical for yield potential and stability, so understanding their genetic foundation is of great significance in wheat breeding. Three related recombinant inbred line populations with a common female parent were developed to identify quantitative trait loci (QTL) for HD and FD in four environments. In total, 25 putative additive QTL and 20 pairwise epistatic effect QTL were detected in four environments. The additive QTL were distributed across 17 wheat chromosomes. Of these, QHd-1A, QHd-1D, QHd-2B, QHd-3B, QHd-4A, QHd-4B and QHd-6D were major and stable QTL for HD. QFd-1A, QFd-2B, QFd-4A and QFd-4B were major and stable QTL for FD. In addition, an epistatic interaction test showed that epistasis played important roles in controlling wheat HD and FD. Genetic relationships between HD/FD and five yield-related traits (YRTs) were characterized and ten QTL clusters (C1–C10) simultaneously controlling YRTs and HD/FD were identified. The present work laid a genetic foundation for improving yield potential in wheat molecular breeding programmes.
A multi-scale strategy is employed in the paper to investigate the thermo-mechanical properties of 2.5D angle-interlock woven shape memory polymer composites (SMPCs). In the study, the mesoscopic model of 2.5D woven SMPCs and microscopic model of yarns are firstly developed. After that, the themo-viscoelastic constitutive relationship of the yarn is described in the form of hereditary integral and the parameters of relaxation moduli are obtained from nonlinear fitting of Prony series based on the results of finite element method (FEM). Based on the multi-scale models and the constitutive relationship, the effects of warp and weft arranged densities on viscoelastic properties of 2.5D woven SMPCs are studied in detail. Finally, the shape memory behavior along the warp direction in small strain region is also analyzed. The research in the paper lays a foundation for design and application of woven SMPCs in engineering.
The role that vitamin D plays in pulmonary function remains uncertain. Epidemiological studies reported mixed findings for serum 25-hydroxyvitamin D (25(OH)D)–pulmonary function association. We conducted the largest cross-sectional meta-analysis of the 25(OH)D–pulmonary function association to date, based on nine European ancestry (EA) cohorts (n 22 838) and five African ancestry (AA) cohorts (n 4290) in the Cohorts for Heart and Aging Research in Genomic Epidemiology Consortium. Data were analysed using linear models by cohort and ancestry. Effect modification by smoking status (current/former/never) was tested. Results were combined using fixed-effects meta-analysis. Mean serum 25(OH)D was 68 (sd 29) nmol/l for EA and 49 (sd 21) nmol/l for AA. For each 1 nmol/l higher 25(OH)D, forced expiratory volume in the 1st second (FEV1) was higher by 1·1 ml in EA (95 % CI 0·9, 1·3; P<0·0001) and 1·8 ml (95 % CI 1·1, 2·5; P<0·0001) in AA (Prace difference=0·06), and forced vital capacity (FVC) was higher by 1·3 ml in EA (95 % CI 1·0, 1·6; P<0·0001) and 1·5 ml (95 % CI 0·8, 2·3; P=0·0001) in AA (Prace difference=0·56). Among EA, the 25(OH)D–FVC association was stronger in smokers: per 1 nmol/l higher 25(OH)D, FVC was higher by 1·7 ml (95 % CI 1·1, 2·3) for current smokers and 1·7 ml (95 % CI 1·2, 2·1) for former smokers, compared with 0·8 ml (95 % CI 0·4, 1·2) for never smokers. In summary, the 25(OH)D associations with FEV1 and FVC were positive in both ancestries. In EA, a stronger association was observed for smokers compared with never smokers, which supports the importance of vitamin D in vulnerable populations.
The response of soil microbial communities to soil quality changes is a sensitive indicator of soil ecosystem health. The current work investigated soil microbial communities under different fertilization treatments in a 31-year experiment using the phospholipid fatty acid (PLFA) profile method. The experiment consisted of five fertilization treatments: without fertilizer input (CK), chemical fertilizer alone (MF), rice (Oryza sativa L.) straw residue and chemical fertilizer (RF), low manure rate and chemical fertilizer (LOM), and high manure rate and chemical fertilizer (HOM). Soil samples were collected from the plough layer and results indicated that the content of PLFAs were increased in all fertilization treatments compared with the control. The iC15:0 fatty acids increased significantly in MF treatment but decreased in RF, LOM and HOM, while aC15:0 fatty acids increased in these three treatments. Principal component (PC) analysis was conducted to determine factors defining soil microbial community structure using the 21 PLFAs detected in all treatments: the first and second PCs explained 89.8% of the total variance. All unsaturated and cyclopropyl PLFAs except C12:0 and C15:0 were highly weighted on the first PC. The first and second PC also explained 87.1% of the total variance among all fertilization treatments. There was no difference in the first and second PC between RF and HOM treatments. The results indicated that long-term combined application of straw residue or organic manure with chemical fertilizer practices improved soil microbial community structure more than the mineral fertilizer treatment in double-cropped paddy fields in Southern China.
Pathogenesis of pregnancy toxemia (PT) is believed to be associated with the disruption of lipid metabolism. The present study aimed to explore the underlying mechanisms of lipid metabolism disorder in the livers of ewes with PT. In total, 10 pregnant ewes were fed normally (control group) whereas another 10 were subjected to 70% level feed restriction for 15 days to establish a pathological model of PT. Results showed that, as compared with the controls, the levels of blood β-hydroxybutyrate (BHBA), non-esterified fatty acids (NEFAs) and cholesterol were greater (P<0.05) and blood glucose level was lower (P<0.05) in PT ewes. The contents of NEFAs, BHBA, cholesterol and triglyceride were higher (P<0.05) and glycerol content was lower (P<0.05) in hepatic tissues of PT ewes than those of the controls. For ewes with PT, excessive fat vacuoles were observed in liver sections stained with hematoxylin–eosin; furthermore, inner structures of hepatocytes including nuclei, mitochondria and endoplasmic reticulum were damaged seriously according to the results of transmission electron microscope. Real-time PCR data showed that compared with the controls, the expression of hepatic genes involved in fatty acid oxidation (FAO) and triglyceride synthesis (TGS) was enhanced (P<0.05) whereas that related to acetyl-CoA metabolism (ACM) was repressed (P<0.05) in PT ewes. Generally, our results showed that negative energy balance altered the expression of genes involved in FAO, ACM and TGS, further caused lipid metabolism disorder in livers, resulting in PT of ewes. Our findings may provide the molecular basis for novel therapeutic strategies against this systemic metabolic disease in sheep.
Wave loading on marine structures is the major external force to be considered in the design of such structures. The accurate prediction of the nonlinear high-order components of the wave loading has been an unresolved challenging problem. In this paper, the nonlinear harmonic components of hydrodynamic forces on a bottom-mounted vertical cylinder are investigated experimentally. A large number of experiments were conducted in the Danish Hydraulic Institute shallow water wave basin on the cylinder, both on a flat bed and a sloping bed, as part of a European collaborative research project. High-quality data sets for focused wave groups have been collected for a wide range of wave conditions. The high-order harmonic force components are separated by applying the ‘phase-inversion’ method to the measured force time histories for a crest focused wave group and the same wave group inverted. This separation method is found to work well even for locally violent nearly-breaking waves formed from bidirectional wave pairs. It is also found that the
th-harmonic force scales with the
th power of the envelope of both the linear undisturbed free-surface elevation and the linear force component in both time variation and amplitude. This allows estimation of the higher-order harmonic shapes and time histories from knowledge of the linear component alone. The experiments also show that the harmonic structure of the wave loading on the cylinder is virtually unaltered by the introduction of a sloping bed, depending only on the local wave properties at the cylinder. Furthermore, our new experimental results reveal that for certain wave cases the linear loading is actually less than 40 % of the total wave loading and the high-order harmonics contribute more than 60 % of the loading. The significance of this striking new result is that it reveals the importance of high-order nonlinear wave loading on offshore structures and means that such loading should be considered in their design.
Group-3 medulloblastoma (MBL) is highly resistant to radiation (IR) and chemotherapy and has the worst prognosis. Hence, there is an urgent need to elucidate targets that sensitize these tumors to chemotherapy and IR. Employing standard assays for viability and sensitization to IR, we identified PRDX1 as a therapeutic target in Group-3 MBL. Specifically, targeting PRDX1 by RNAi or inhibition by Adenanthin led to specific killing and sensitization to IR of Group-3 MBL cells. We rescued sensitization of Daoy and UW228 cells by hypermorphic expression of PRDX1. PRDX1 knockdown caused oxidative DNA damage and induced apoptosis. We correlated PRDX1 expression to patient outcomes in a validated MBL tumor-microarray. Whole genome sequencing identified pathways/genes that were dysregulated with PRDX1 inhibition or silencing. Our in vivo studies in mice employing flank/orthotopic tumors from patient derived xenografts/Group-3 MBL cells confirmed in vitro observations. Animals with tumors in which PRDX1 was targeted by RNAi or Adenanthin (using mini osmotic pumps) showed decreased tumor burden and increased survival when compared to controls. Since, Adenanthin does not cross the blood brain barrier (BBB) we used HAV6 peptide to transiently disrupt the BBB and deliver Adenanthin to the tumor. Immunohistochemistry confirmed that targeting PRDX1 resulted in increased oxidative DNA damage, apoptosis and decreased proliferation. In summary, we have validated PRDX1 as a therapeutic target in group-3 MBL, identified Adenanthin as a potent chemical inhibitor of PRDX1 and confirmed the role of HAV peptide (in the transient modulation of BBB permeability) in an orthotopic model of group-3 MBL.
Introduction: The prevalence of pulmonary embolism (PE) among patients with syncope is understudied. Based on a recent study with an exceptionally high PE prevalence, some advocate investigating all syncope patients for PE, including those with another clear cause for their syncope. We sought to evaluate the PE prevalence among emergency department (ED) patients with syncope. Methods: We combined data from two large prospective studies enrolling adults with syncope from 17 EDs in Canada and the United States. Each study collected the results of investigations related to PE (i.e. D-dimer or ventilation-perfusion (VQ) scan, or computed tomography pulmonary angiogram (CTPA)), and 30-day adjudicated outcomes including diagnosis of PE, arrhythmia, myocardial infarction, serious hemorrhage and/or death. Results: Of the 9,091 patients (median age 66 years, 51.9% females, 39.1% hospitalized) with 30-day follow-up, 546 (6.0%) were investigated for PE: 278 (3.1%) had D-dimer, 39 (0.4%) had VQ and 347 (3.8%) patients had CTPA performed. 30-day outcomes included: 874 (9.6%) patients with any serious outcome; 0.9% deaths; and 818 (9.0%) patients with non-PE serious outcomes. Overall, 56 patients (prevalence 0.6%; 95% CI 0.5% 0.8%) were diagnosed with PE, including 8 (0.1%) of those admitted to hospital at the index presentation. Only 11 patients (0.1%) with a non-PE serious condition had a concomitant underlying PE identified. Conclusion: The prevalence of PE is very low among ED patients with syncope, including those hospitalized following syncope. While acknowledging syncope may be caused by an underlying PE, clinicians should be cautious against indiscriminate over-investigations for PE.
The discovery of the first electromagnetic counterpart to a gravitational wave signal has generated follow-up observations by over 50 facilities world-wide, ushering in the new era of multi-messenger astronomy. In this paper, we present follow-up observations of the gravitational wave event GW170817 and its electromagnetic counterpart SSS17a/DLT17ck (IAU label AT2017gfo) by 14 Australian telescopes and partner observatories as part of Australian-based and Australian-led research programs. We report early- to late-time multi-wavelength observations, including optical imaging and spectroscopy, mid-infrared imaging, radio imaging, and searches for fast radio bursts. Our optical spectra reveal that the transient source emission cooled from approximately 6 400 K to 2 100 K over a 7-d period and produced no significant optical emission lines. The spectral profiles, cooling rate, and photometric light curves are consistent with the expected outburst and subsequent processes of a binary neutron star merger. Star formation in the host galaxy probably ceased at least a Gyr ago, although there is evidence for a galaxy merger. Binary pulsars with short (100 Myr) decay times are therefore unlikely progenitors, but pulsars like PSR B1534+12 with its 2.7 Gyr coalescence time could produce such a merger. The displacement (~2.2 kpc) of the binary star system from the centre of the main galaxy is not unusual for stars in the host galaxy or stars originating in the merging galaxy, and therefore any constraints on the kick velocity imparted to the progenitor are poor.
Fatigue cracking in polycrystalline NiTi was investigated using a multiscale experimental framework for average grain sizes (GS) from 10 to 1500 nm for the first time. Macroscopic fatigue crack growth rates, measured by optical digital image correlation, were connected to microscopic crack opening and closing displacements, measured by scanning electron microscope DIC (SEM-DIC) using a high-precision external SEM scan controller. Among all grain sizes, the 1500 nm GS sample exhibited the slowest crack growth rate at the macroscale, and the largest crack opening level (stress intensity at first crack opening) and minimum crack opening displacements at the microscale. Smaller GS samples (10, 18, 42, and 80 nm) exhibited nonmonotonic trends in their fatigue performance, yet the correlation was strong between macroscale and microscale behaviors for each GS. The samples that exhibited the fastest crack growth rates (42 and 80 nm GS) showed a small crack opening level and the largest crack opening displacements. The irregular trends in fatigue performance across the nanocrystalline GS samples were consistent with nonmonotonic values in the elastic modulus reported previously, both of which may be related to the presence of residual martensite only evident in the small GS samples (10 and 18 nm).
Lead is one of the environmental pollutants with cardiovascular toxicity. The embryos are particularly sensitive to lead exposure, because it can move through the blood-placental barrier and the blood-brain barrier easily during embryonic development. Cerebral cavernous malformations 3 (CCM3) gene plays an important role in cardiovascular development, mainly affecting cell proliferation, differentiation and apoptosis. In this study, we established a blood vessel development model of mouse embryos in order to imitate human people with CCM3 genes defects and exposing to environment toxin Pb in utero. We would like to determine the interaction of Pb and CCM3 gene on vascular development, and to explore the mechanisms. We found that the yolk sac of CCM3 heterozygous mice embryo showed abnormal morphology at E11.5 after lead treatment comparing with wild type (WT) mice without lead exposure, meanwhile it showed more angiogenesis and vascular remodeling in the hematoxylin and eosin stained sections of the CCM3+/− yolk sac with lead exposure. We also found that the similar effect of Pb and CCM3 gene on mitochondrial DNA (mtDNA) copy number in vivo and in vitro. Mitochondrial morphology and function also changed in primary human umbilical vein endothelial cells after lead exposure. Besides, it was found that the HIF-1α and TFAM which have close relationship with mtDNA biogenesis showed similarly increasing messenger RNA expression in both human and mouse-derived primary cells with lead treated and CCM3 gene knockout. All of the above results indicated that lead and CCM3 might damage endothelial cells through mitochondria pathway and eventually both affected angiogenesis.
We present techniques developed to calibrate and correct Murchison Widefield Array low-frequency (72–300 MHz) radio observations for polarimetry. The extremely wide field-of-view, excellent instantaneous (u, v)-coverage and sensitivity to degree-scale structure that the Murchison Widefield Array provides enable instrumental calibration, removal of instrumental artefacts, and correction for ionospheric Faraday rotation through imaging techniques. With the demonstrated polarimetric capabilities of the Murchison Widefield Array, we discuss future directions for polarimetric science at low frequencies to answer outstanding questions relating to polarised source counts, source depolarisation, pulsar science, low-mass stars, exoplanets, the nature of the interstellar and intergalactic media, and the solar environment.
An outbreak of acute hepatitis recently occurred in a nursing home in Zhejiang Province, China. The objectives of this study were to confirm the outbreak and identify the aetiology, source and transmission patterns. All residents and staff in or near the nursing home during the period from 1 October 2014 to 21 May 2015 were investigated regarding hygiene and for epidemiological information including water and food (eating meat especially pork products). Serum and stool specimens were collected for detection of hepatitis E virus (HEV) antibodies using ELISA and RNA using RT–PCR. Samples that were RNA positive were genotyped. Of 185 senior residents and 24 staff in the nursing home, there were 37 laboratory-confirmed cases during the outbreak. Of these cases, 12 patients (three deaths) were symptomatic with jaundice, a common clinical symptom for hepatitis E infection. HEV strains were isolated from three cases and they formed a single cluster within genotype 4d. A case-control study was conducted to investigate potential risk factors for the outbreak and the results revealed that cases more often washed their dishes and rinsed their mouths using tap water than the controls (P < 0·05). Based on hygiene investigation and meteorological information, it is likely that HEV-infected sewage and faeces contaminated the water network on rainy days. Collectively, these results suggest that the outbreak of HEV genotype 4 infection was most likely caused by contaminated tap water rather than food.
The objective of this study was to determine if a moderate or high reduction of dietary CP, supplemented with indispensable amino acids (IAA), would affect growth, intestinal morphology and immunological parameters of pigs. A total of 40 barrows (initial BW=13.50±0.50 kg, 45±2 day of age) were used in a completely randomized block design, and allocated to four dietary treatments containing CP levels at 20.00%, 17.16%, 15.30% and 13.90%, respectively. Industrial AA were added to meet the IAA requirements of pigs. After 4-week feeding, blood and tissue samples were obtained from pigs. The results showed that reducing dietary CP level decreased average daily gain, plasma urea nitrogen concentration and relative organ weights of liver and pancreas (P<0.01), and increased feed conversion ratio (P<0.01). Pigs fed the 13.90% CP diet had significantly lower growth performance than that of pigs fed higher CP at 20.00%, 17.16% or 15.30%. Moreover, reducing dietary CP level decreased villous height in duodenum (P<0.01) and crypt depth in duodenum, jejunum and ileum (P<0.01). The reduction in the dietary CP level increased plasma concentrations of methionine, alanine (P<0.01) and lysine (P<0.05), and decreased arginine (P<0.05). Intriguingly, reducing dietary CP level from 20.00% to 13.90% resulted in a significant decrease in plasma concentration of IgG (P<0.05), percentage of CD3+T cells of the peripheral blood (P<0.01), also down-regulated the mRNA abundance of innate immunity-related genes on toll-like receptor 4, myeloid differentiation factor 88 (P<0.01) and nuclear factor kappa B (P<0.05) in the ileum. These results indicate that reducing dietary CP level from 20.00% to 15.30%, supplemented with IAA, had no significant effect on growth performance and had a limited effect on immunological parameters. However, a further reduction of dietary CP level up to 13.90% would lead to poor growth performance and organ development, associated with the modifications of intestinal morphology and immune function.
Research in Celestial Mechanics, for the past three years, has mainly focused on the understanding of Chaos on all its aspects. The always larger number of potential applications (meteors, KBO, NEA, asteroids of the main belt but also exoplanets or galactic motions) and the development of new efficient tools, like the symplectic integrators, have allowed the passage from QUALITATIVE models (for example the transfer mechanisms) to real QUANTITATIVE results (like the calculation of lifetimes). This important step has contributed to (re)create collaborations between theoreticians and observers (for example, in the prediction of catastrophic impacts) and to situate the Celestial Mechanics in a wider scientific context.