Pipeline is an important structure to transport oil and gas through long distances. However, pipeline also suffers from many threats especially corrosion and leakage. Therefore, it is necessary to ...conduct pipeline safety monitoring. With the advantage of high precision in distributed strain measurement, the optical frequency domain reflectometry (OFDR) technique is more suitable for pipeline monitoring. In this paper, a new application of the OFDR technique is introduced to monitor both corrosion and leakage. In order to verify this method, simulation tests of corrosion and leakage were conducted. In the corrosion test, several optical fiber sensors were bonded to the pipe surface with the same interval, forming a sensor array. Based on the sensor array, a hoop strain nephogram was created to show the corrosion level and corrosion location. In the leakage test, the results indicated that pipeline leakage can be detected by the distributed optical fiber sensor (DOFS). All the test results demonstrate that it is possible to monitor pipeline corrosion and leakage based on the hoop strain theory and the DOFS.
A general and mild strategy involving three-component carboarylation of unactivated alkenes with protic C(sp
)-H feedstocks via photoredox catalysis was reported. This catalytic system is compatible ...with a broad range of unactivated alkenes, cyano-substituted arenes, and diverse protic C(sp
)-H feedstocks. The synthetic value of this protocol was demonstrated by the late-stage functionalization of complex molecules and the synthesis of the antiallergies including pheniramine, chlorpheniramine, and brompheniramine.
A mathematical model was developed to study the effects of the flow control devices and the gas curtain on the steel cleanness in a single-strand tundish. The Eulerian–Lagrangian approach was applied ...to investigate the bubble flow and the behavior of the non-metallic inclusions in the system. Two modelling approaches were considered: (i) one-way coupling, where the influence of the micro-inclusion on the molten steel flow is neglected; and (ii) two-way coupling, where the momentum exchange between the molten steel and the bubbles is modelled. The model verification and validation (V&V) were carried out in order to establish confidence in the model predictions. Four different tundish configurations and the effect of various parameters, such as the inclusion size, the inclusion density and the gas flow rate, were investigated at the normal casting conditions. The results show that the flow control devices and the gas curtain reduce the extent of the dead volumes in the tundish and thus enhance the removal efficiency of the inclusions. Controlling the gas stirring intensity is important for tundish operation with the aim of removing the inclusions. Theoretical analysis suggests that small bubbles are preferable to increase the inclusion removal rate in industrial operations.
High-altitude adaptation of Tibetans represents a remarkable case of natural selection during recent human evolution. Previous genome-wide scans found many non-coding variants under selection, ...suggesting a pressing need to understand the functional role of non-coding regulatory elements (REs). Here, we generate time courses of paired ATAC-seq and RNA-seq data on cultured HUVECs under hypoxic and normoxic conditions. We further develop a variant interpretation methodology (vPECA) to identify active selected REs (ASREs) and associated regulatory network. We discover three causal SNPs of EPAS1, the key adaptive gene for Tibetans. These SNPs decrease the accessibility of ASREs with weakened binding strength of relevant TFs, and cooperatively down-regulate EPAS1 expression. We further construct the downstream network of EPAS1, elucidating its roles in hypoxic response and angiogenesis. Collectively, we provide a systematic approach to interpret phenotype-associated noncoding variants in proper cell types and relevant dynamic conditions, to model their impact on gene regulation.
The phase III AXEPT study showed the noninferiority of modified capecitabine plus irinotecan (mXELIRI) with or without bevacizumab relative to fluorouracil, leucovorin, and irinotecan (FOLFIRI) with ...or without bevacizumab as a second‐line treatment for metastatic colorectal cancer. We evaluated the associations between the UGT1A1 genotype linked to adverse events—caused by irinotecan—and the efficacy and safety of mXELIRI and FOLFIRI. The UGT1A1 genotype was prospectively determined and patients were categorized into three groups according to WT (*1/*1), single heterozygous (SH; *28/*1 or *6/*1), and double heterozygous or homozygous (DHH; *28/*28, *6/*6, or *28/*6). Overall survival (OS), progression‐free survival, response rate, and safety were assessed. The UGT1A1 genotype was available in all 650 randomized patients (WT, 309 47.5%; SH, 291 44.8%; DHH, 50 7.7%). The median OS was 15.9, 17.7, and 10.6 months in the WT, SH, and DHH groups, respectively, with an adjusted hazard ratio (HR) of 1.53 (95% confidence interval CI, 1.12‐2.09; P = .008) for DHH vs WT or SH. The median OS in the mXELIRI and FOLFIRI arms was 18.1 vs 14.3 months (HR 0.80; 95% CI, 0.62‐1.03) in the WT group, 16.3 vs 18.3 months (HR 1.04; 95% CI, 0.79‐1.36) in the SH group, and 13.0 vs 9.1 months (HR 0.71; 95% CI, 0.39‐1.31) in the DHH group, respectively. Modified capecitabine plus irinotecan with or without bevacizumab could be a standard second‐line chemotherapy in terms of efficacy and safety regardless of the UGT1A1 genotype.
Capecitabine plus irinotecan (XELIRI) with or without bevacizumab is noninferior to fluorouracil, leucovorin, and irinotecan (FOLFIRI) with or without bevacizumab in terms of overall survival, regardless of UGT1A1 genotype. Additionally, modified XELIRI with or without bevacizumab showed a favorable tolerability profile that was comparable to that of FOLFIRI with or without bevacizumab among all UGT1A1 genotypes.
In this work, a kinetics‐integrated CFD model based on coupling computational fluid dynamics (CFD) and biokinetic was developed to guide the industrial scale‐up for fermentation of docosahexaenoic ...acid (DHA). Two‐substrate biokinetic equations for a 5 L bioreactor with oxygen and nitrogen source as limiting substrates were established, which were further coupled with CFD to simulate the biomass growth and lipid accumulation as well as flow field environment in the fermentation process. The coupled CFD‐biokinetic model can accurately reflect the changes of each relevant variable in the 50 L bioreactor under different operating conditions. The optimal working conditions of a 35 m3 bioreactor were predicted by this model and have secured the one‐step scale‐up of DHA fermentation, resulting in a biomass, lipid concentration, and DHA content in lipids of 99.2 g/L, 55.7 g/L, and 52.5%, respectively. This study thus provides an effective strategy for rapid industrial scale‐up of DHA production.
Spinal cord injury is linked to the interruption of neural pathways, which results in irreversible neural dysfunction. Neural repair and neuroregeneration are critical goals and issues for ...rehabilitation in spinal cord injury, which require neural stem cell repair and multimodal neuromodulation techniques involving personalized rehabilitation strategies. Besides the involvement of endogenous stem cells in neurogenesis and neural repair, exogenous neural stem cell transplantation is an emerging effective method for repairing and replacing damaged tissues in central nervous system diseases. However, to ensure that endogenous or exogenous neural stem cells truly participate in neural repair following spinal cord injury, appropriate interventional measures (e.g., neuromodulation) should be adopted. Neuromodulation techniques, such as noninvasive magnetic stimulation and electrical stimulation, have been safely applied in many neuropsychiatric diseases. There is increasing evidence to suggest that neuromagnetic/electrical modulation promotes neuroregeneration and neural repair by affecting signaling in the nervous system; namely, by exciting, inhibiting, or regulating neuronal and neural network activities to improve motor function and motor learning following spinal cord injury. Several studies have indicated that fine motor skill rehabilitation training makes use of residual nerve fibers for collateral growth, encourages the formation of new synaptic connections to promote neural plasticity, and improves motor function recovery in patients with spinal cord injury. With the development of biomaterial technology and biomechanical engineering, several emerging treatments have been developed, such as robots, brain-computer interfaces, and nanomaterials. These treatments have the potential to help millions of patients suffering from motor dysfunction caused by spinal cord injury. However, large-scale clinical trials need to be conducted to validate their efficacy. This review evaluated the efficacy of neural stem cells and magnetic or electrical stimulation combined with rehabilitation training and intelligent therapies for spinal cord injury according to existing evidence, to build up a multimodal treatment strategy of spinal cord injury to enhance nerve repair and regeneration.
As revealed recently by the modeling of the multiwavelength data of the emission following GW170817/GRB 170817A, there was an off-axis energetic relativistic outflow component launched by this ...historic double neutron star merger event. In this work we use the results of this model to examine the energy extraction process of the central engine. We show that the magnetic process (i.e., the Blandford-Znajek mechanism) is favored, while the neutrino process usually requires an accretion disk that is too massive if the duration of the central engine activity Tact is comparable to the observed T90 of GRB 170817A. If Tact is less than ∼0.2 s, the two models are indistinguishable. We propose that the GRB observations are helpful to constrain the combined tidal parameter , and by adopting the accretion disk mass distribution estimated in the BZ mechanism, the 90% credible interval of for the progenitor of GW170817 is inferred as 309 − 954.
Studies investigating the impact of chocolate consumption on cardiovascular disease (CVD) have reached inconsistent conclusions. As such, a quantitative assessment of the dose-response association ...between chocolate consumption and incident CVD has not been reported. We performed a systematic review and meta-analysis of studies assessing the risk of CVD with chocolate consumption.
PubMed and EMBASE databases were searched for articles published up to 6 June 2018. Restricted cubic splines were used to model the dose-response association.
Fourteen publications (23 studies including 405 304 participants and 35 093 cases of CVD) were included in the meta-analysis. The summary of relative risk (RR) per 20 g/week increase in chocolate consumption was 0.982 (95% CI 0.972 to 0.992, I
=50.4%, n=18) for CVD (heart failure: 0.995 (0.981 to 1.010, I
=36.3%, n=5); total stroke: 0.956 (0.932 to 0.980, I
=25.5%, n=7); cerebral infarction: 0.952 (0.917 to 0.988, I
=0.0%, n=4); haemorrhagic stroke: 0.931 (0.871 to 0.994, I
=0.0%, n=4); myocardial infarction: 0.981 (0.964 to 0.997, I
=0.0%, n=3); coronary heart disease: 0.986 (0.973 to 0.999, n=1)). A non-linear dose-response (p
=0.001) indicated that the most appropriate dose of chocolate consumption for reducing risk of CVD was 45 g/week (RR 0.890;95%CI 0.849 to 0.932).
Chocolate consumption may be associated with reduced risk of CVD at <100 g/week consumption. Higher levels may negate the health benefits and induce adverse effects associated with high sugar consumption.
Supramolecular chemotherapy is currently a new strategy to improve the therapeutic efficacy as well as overcome the side effects of traditional chemotherapy. Herein, a supramolecular chemotherapy ...platform based on the pegylated guanidinium-modified calix5arene pentadodecyl ether (GC5A-12C) nanoassembly was prepared. Three commercially available antitumor drugs: oxaliplatin, methotrexate and chlorambucil, all showed strong binding to this GC5A-12C nanocarrier. The supramolecular nanodrugs achieved higher anticancer performances compared with free drugs in cell experiments. Furthermore, the cellular uptake mechanisms and efficacy are confirmed by fluorescence imaging.
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•A host-guest drug delivery nanosystem is fabricated for supramolecular chemotherapy.•The GC5A-12C nanocarrier as a universal platform can load various drugs via the host-guest complexation.•GC5A-12C nanocarriers’ drug loading and encapsulation efficiency are higher than liposomes due to host-guest interactions•GC5A-12C nanocarriers promote the cellular uptake of drugs, leading to higher cytotoxicity to cancer cells than free drug.
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