Estimating the timing of velocity changes (break points) in Global Navigation Satellite System (GNSS) coordinate time series is required for understanding various Earth processes and how they may ...couple with each other. We jointly estimate break points, noise parameters and their uncertainties in GNSS time series using Bayesian interference. Synthetic data experiments demonstrate that time‐correlated noise can cause spurious estimates of break points for small velocity change and suggest the lower limits of velocity change for reliable estimates. A case study at the Krafla volcanic system shows increased rift‐perpendicular movementof 7.6–9.8 mm/yr, preceding by 23–77 days the 2014 Bárðarbunga rifting episode that occurred ∼120 km to the south (maximum likelihood estimates). These far‐field velocity anomalies occur in the same period as enhanced near‐field seismicity and deformation before the dike intrusion at Bárðarbunga, possibly indicating the coupling between the two volcanic systems through a deep partial melt zone.
Plain Language Summary
The velocity of ground movements can change due to Earth's activities. Satellite positioning techniques record these changes, while noise in the records may obscure their analyses. We developed a statistical method to detect velocity changes from these noisy records and give an estimate of uncertainty. Simulated data is used to examine the method, revealing the lower limits of velocity change for reliable estimates. Then the method is applied to detect velocity changes in the records at the Krafla volcanic system, Iceland. With maximum likelihood estimates, it is inferred that the ground moves 7.6–9.8 mm/yr faster, in rift‐perpendicular direction, before the start of the 2014 Bárðarbunga dike intrusion that occurred ∼120 km to the south. The ground movements resume to approximately the original velocities by a second velocity change in late 2014 or early 2015. The onset of the far‐field velocity anomalies occurs in the same period as enhanced near‐field seismicity and deformation rate before the dike intrusion at Bárðarbunga. In the context of enhanced seismicity at the Bárðarbunga volcano and rapid inflation at the Askja volcano before the Krafla rifting episode in 1975–1984, our result may again indicate coupling among the volcanic systems in Iceland.
Key Points
The lower limit of velocity change values, where reliable estimates can be derived, depends on noise characteristics of Global Navigation Satellite System time series
Increased rift‐perpendicular movement before the 2014 Bárðarbunga dike intrusion is inferred with 95% confidence, 120 km north of it
Concurrent far‐field velocity anomalies and near‐field precursors may indicate coupling between distant volcanic systems at a plate boundary
Abstract Nanobubbles (NBs), as novel ultrasound contrast agents (UCAs), have attracted increasing attention in the field of molecular ultrasound imaging for tumors. However, the preparation of ...uniform-sized NBs is considered to be controversial, and poor tumor selectivity in in vivo imaging has been reported. In this study, we fabricated uniform nano-sized NBs (478.2 ± 29.7 nm with polydispersity index of 0.164 ± 0.044, n = 3) using a thin-film hydration method by controlling the thickness of phospholipid films; we then conjugated the NBs with Affibody molecules to produce nano-sized UCAs referred to as NB–Affibody with specific affinity to human epidermal growth factor receptor type 2 (HER2)-overexpressing tumors. NB–Affibody presented good ultrasound enhancement, demonstrating a peak intensity of 104.5 ± 2.1 dB under ultrasound contrast scanning. Ex vivo experiments further confirmed that the NB–Affibody conjugates were capable of targeting HER2-expressing tumor cells in vivo with high affinity. The newly prepared nano-sized NB–Affibody conjugates were observed to be novel targeted UCAs for efficient and safe specific molecular imaging and may have potential applications in early cancer quantitative diagnosis and targeted therapy in the future.
The PIM1 protein is an important regulator of cell proliferation, the cell cycle, apoptosis, and metabolism in various human cancers. MicroRNAs (miRNAs) are powerful post‐transcriptional gene ...regulators that function through translational repression or transcript destabilization. Therefore, we aimed to identify whether a close relationship exists between PIM1 and miRNAs. PIM1 protein levels and mRNA levels were significantly upregulated in astrocytoma tissues, indicating the oncogenic role of PIM1 in astrocytoma. Further bioinformatics analysis indicated that miR‐124‐3p targeted the 3′‐UTR of PIM1. We also observed an inverse correlation between the miR‐124‐3p levels and PIM1 protein or mRNA levels in astrocytoma samples. Next, we experimentally confirmed that miR‐124‐3p directly recognizes the 3′‐UTR of the PIM1 transcript and regulates PIM1 expression at both the protein and mRNA levels. Furthermore, we examined the biological consequences of miR‐124‐3p targeting PIM1 in vitro. We showed that the repression of PIM1 in astrocytoma cancer cells by miR‐124‐3p suppressed proliferation, invasion, and aerobic glycolysis and promoted apoptosis. We observed that the restoration or inhibition of PIM1 activity resulted in effects that were similar to those induced by miR‐124‐3p inhibitors or mimics in cancer cells. Finally, overexpression of PIM1 rescued the inhibitory effects of miR‐124‐3p. In summary, these findings aid in understanding the tumor‐suppressive role of miR‐124‐3p in astrocytoma pathogenesis through the inhibition of PIM1 translation.
miR‐124‐3p inhibits astrocytoma cancer cell proliferation, invasion and aerobic glycolysis, and promotes apoptosis in vitro.
The emerging pathogen severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused social and economic disruption worldwide, infecting over 9.0 million people and killing over 469 000 by ...24 June 2020. Unfortunately, no vaccine or antiviral drug that completely eliminates the transmissible disease coronavirus disease 2019 (COVID-19) has been developed to date. Given that coronavirus nonstructural protein 1 (nsp1) is a good target for attenuated vaccines, it is of great significance to explore the detailed characteristics of SARS-CoV-2 nsp1. Here, we first confirmed that SARS-CoV-2 nsp1 had a conserved function similar to that of SARS-CoV nsp1 in inhibiting host-protein synthesis and showed greater inhibition efficiency, as revealed by ribopuromycylation and Renilla luciferase (Rluc) reporter assays. Specifically, bioinformatics and biochemical experiments showed that by interacting with 40S ribosomal subunit, the lysine located at amino acid 164 (K164) was the key residue that enabled SARS-CoV-2 nsp1 to suppress host gene expression. Furthermore, as an inhibitor of host-protein expression, SARS-CoV-2 nsp1 contributed to cell-cycle arrest in G0/G1 phase, which might provide a favourable environment for virus production. Taken together, this research uncovered the detailed mechanism by which SARS-CoV-2 nsp1 K164 inhibited host gene expression, laying the foundation for the development of attenuated vaccines based on nsp1 modification.
Multidrug resistance (MDR) is a major impediment to successful cancer chemotherapy. Co-delivery of novel MDR-reversing agents and anticancer drugs to cancer cells holds great promise for cancer ...treatment. MicroRNA-21 (miR-21) overexpression is associated with the development and progression of MDR in breast cancer, and it is emerging as a novel and promising MDR-reversing target. In this study, a multifunctional nanocomplex, composed of polyethylenimine (PEI)/poly(sodium 4-styrenesulfonates) (PSS)/graphene oxide (GO) and termed PPG, was prepared using the layer-by-layer assembly method to evaluate the reversal effects of PPG as a carrier for adriamycin (ADR) along with miR-21 targeted siRNA (anti-miR-21) in cancer drug resistance. ADR was firstly loaded onto the PPG surface (PPGADR) by physical mixing and anti-miR-21 was sequentially loaded onto PPGADR through electric absorption to form (anti-miR-21)PPGADR. Cell experiments showed that PPG significantly enhanced the accumulation of ADR in MCF-7/ADR cells (an ADR resistant breast cancer cell line) and exhibited much higher cytotoxicity than free ADR, suggesting that PPG could effectively reverse ADR resistance of MCF-7/ADR. Furthermore, the enhanced therapeutic efficacy of PPG could be correlated with effective silencing of miR-21 and with increased accumulation of ADR in drug-resistant tumor cells. The endocytosis study confirmed that PPG could effectively carry drug molecules into cells via the caveolae and clathrin-mediated endocytosis pathways. These results suggest that this PPG could be a potential and efficient non-viral vector for reversing MDR, and the strategy of combining anticancer drugs with miRNA therapy to overcome MDR could be an attractive approach in cancer treatment.
Frequency multipliers and mixers based on Schottky barrier diodes (SBDs) are widely used in terahertz (THz) imaging applications. However, they still face obstacles, such as poor performance ...consistency caused by discrete flip-chip diodes, as well as low efficiency and large receiving noise temperature. It is very hard to meet the requirement of multiple channels in THz imaging array. In order to solve this problem, 12-μm-thick gallium arsenide (GaAs) monolithic integrated technology was adopted. In the process, the diode chip shared the same GaAs substrate with the transmission line, and the diode’s pads were seamlessly connected to the transmission line without using silver glue. A three-dimensional (3D) electromagnetic (EM) model of the diode chip was established in Ansys High Frequency Structure Simulator (HFSS) to accurately characterize the parasitic parameters. Based on the model, by quantitatively analyzing the influence of the surface channel width and the diode anode junction area on the best efficiency, the final parameters and dimensions of the diode were further optimized and determined. Finally, three 0.34 THz triplers and subharmonic mixers (SHMs) were manufactured, assembled, and measured for demonstration, all of which comprised a waveguide housing, a GaAs circuit integrated with diodes, and other external connectors. Experimental results show that all the triplers and SHMs had great performance consistency. Typically, when the input power was 100 mW, the output power of the THz tripler was greater than 1 mW in the frequency range of 324 GHz to 352 GHz, and a peak efficiency of 6.8% was achieved at 338 GHz. The THz SHM exhibited quite a low double sideband (DSB) noise temperature of 900~1500 K and a DSB conversion loss of 6.9~9 dB over the frequency range of 325~352 GHz. It is indicated that the GaAs monolithic integrated process, diodes modeling, and circuits simulation method in this paper provide an effective way to design THz frequency multiplier and mixer circuits.
Abstract
Acute appendicitis is one of the common acute abdominal diseases in pediatrics. However, the implementation of radiological examination guided endoscopic retrograde appendicitis therapy ...(ERAT) in adults is limited in children. Our previous research explored the non-invasive guidance of high-frequency ultrasound (HFUS) for ERAT and achieved good therapeutic effects. This study mainly focuses on exploring the application value of HFUS in the feasibility assessment of ERAT in children with appendicitis. 163 children with appendicitis received ERAT guided by HFUS were analyzed retrospectively. According to the parameters evaluated by HFUS before and during ERAT, the results indicated that the distance between the appendix orifice and the ileocecal valve significantly affected the time required for the guidewire to enter the appendix cavity (P < 0.05). The diameter and the texture of the fecalith, the thickness of the intestinal wall of the appendiceal orifice all had significant effects on the successful removal of the fecalith (P < 0.05). The success rate, treatment time and final flushing effect of the guidewire to reach the blind end of the appendix were significantly affected by the tortuosity of the appendix and whether there was adhesion with surrounding tissues (P < 0.05). HFUS can accurately assess the feasibility of ERAT in children with appendicitis.
The free‐piston Stirling linear generation system has tremendous applications in space power supply, biomass generation, solar thermal generation, factory waste heat generation, and other industrial ...fields. However, the free‐piston Stirling linear generation system suffered from the disadvantages of fluctuation of output electric energy and self‐starting. To solve the aforesaid problems, a two‐level electric energy conversion control mode which combines three‐phase AC/DC and bidirectional buck/boost DC to DC converter is proposed in this paper to make the generation system with stable output DC power. Then, both the linear and non‐linear mathematical model of the free‐piston Stirling engine are established. Additionally, to improve the performance of frequency and displacement tracking, the traditional proportional‐integral (PI) in the position loop is replaced by Proportional Resonance (PR) controller. Moreover, the Hysteresis‐SVPWM current control strategy with high robustness and dynamic response is applied to the rectifier to realize the unit power factor control of the AC side of the generator and the stability and controllability of the DC side voltage. Finally, the three‐phase voltage Source Rectifier (VSR) and Bi‐directional DC/DC with an appropriate inductance and capacitance for energy storage are modelled. The effectiveness of the proposed system is validated using theoretical analysis and simulations in Matlab.
Background
To investigate the application of ultrasound elastography in monitoring the effects of the transforming growth factor (TGF)-β1 signaling pathway-targeted combination therapy for hepatic ...fibrosis.
Methods
1. Short hairpin RNA (shRNA) constructs targeted towards
TβR1
were designed, synthesized, and packaged using an adeno-associated virus (AAV), and the effective target shRNA was selected based on transfection results. 2. Fifty rats were randomly allocated (n = 10 per group) to the (A) control group, (B) model group, (C) 0-week therapy group, (D) 4-week therapy group, and (E) combination therapy group. At weeks 2, 4, 6, 8, 10, and 12, acoustic radiation force impulse (ARFI) elastography was used to measure the liver stiffness, inner diameter of the portal vein diameter, and blood velocity; radio frequency ultrasound imaging was used to measure the abdominal aortic elasticity parameter and pulse wave velocity (PWV) of the rats. 3. At week 12, portal vein puncture was performed to measure the portal venous pressure, and rat liver specimens were obtained for the pathological measurement of the degree of hepatic fibrosis.
Results
1. An shRNA interference sequence targeted towards
TβR1
was successfully designed, screened, and packaged using an AAV, and small-animal imaging results indicated expression of the specific shRNA in the liver. 2. At week 12, the ultrasound elastography results were significantly different between the experimental groups and the control group (p < 0.01); among the experimental groups, differences were significant between the therapy groups and the model group (p < 0.01). For groups C and E, the therapeutic effects on hepatic fibrosis in rats were significant, with the pathological results indicating a significant reduction in the degree of hepatic fibrosis (p < 0.01). The therapeutic effectiveness of group D was less than that of group C (p < 0.05). Significant differences existed between the portal venous pressure of the experimental groups and of the control group (p < 0.01). For the abdominal aortic elasticity parameter measured by radio frequency ultrasound imaging, differences existed between the values obtained from the experimental groups and from that of the control group (p < 0.05), while statistically significant differences were not found among the various experimental groups. 3. Continuous ultrasound examination results indicated that the elasticity value of group A was significantly different from those of the other groups after 2 weeks of model establishment (p < 0.01); after 6 weeks, the elasticity values of groups C and E were significantly different compared with those of groups B and D (p < 0.01). For the abdominal aortic elasticity parameter and pulse wave velocity (PWV), there were no significant differences among the various groups (p > 0.05).
Conclusion
CCl4-induced hepatic fibrosis can be treated through shRNA silencing of TβR1. Ultrasound ARFI elastography is superior to external force-assisted elastography as it can reflect the degree of fibrosis in moderate to severe hepatic fibrosis and the variations in the degree of fibrosis after treatment. Portal venous pressure was positively correlated with the degree of fibrosis; with early combination therapy, both the degree of fibrosis and portal venous pressure could be effectively reduced.
•COVID-19 has greatly changed travel demand, trip purposes and mode choices.•Socially disadvantaged groups are more likely to experience transport-related exclusion.•Policymakers and urban planners ...should pay greater attention to social inequities.•Public transport systems should be further developed through network expansion.
During the COVID-19 crisis, a series of measures were taken to restrict travel and social activities outside the home in order to curb the pandemic and ameliorate its negative effects. These unprecedented measures have had a profound impact on the number and purposes of trips and modes of travel. In China, although the pandemic is now generally under control and transport availability has returned to nearly normal, the extent of the changes in travel behaviour wrought during and after the pandemic still remains unclear. Therefore, the aim of this paper is to investigate the differences in individual travel behaviours during and after the COVID-19 pandemic, using Huzhou as an example. Semi-structured interviews were used to examine the influence of COVID-19 on the travel behaviour and perceptions of different groups. The results indicate that, initially, travel demand was greatly reduced. Second, decreased travel reduced participation in activities, which can have adverse effects on people’s health as well as their subjective well-being. Third, the degree and duration of such impacts varied from person to person. Students, lower income cohorts, groups living in small communities with insufficient green spaces, and those working in tourism, catering, informal businesses and transport-related sectors were more vulnerable than others. Policymakers, urban and transport planners should therefore pay attention to the social inequities that arise from unequal access to transport and heterogeneity between individuals. Additionally, public transport systems require further development to promote social cohesion.
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