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Throughout biology, RNA molecules form complex networks of molecular interactions that are central to their function, but remain challenging to investigate. Here, we introduce Oligonucleotide-mediated proximity-interactome MAPping (O-MAP), a straightforward method for elucidating the biomolecules near an RNA of interest, within its native cellular context. O-MAP uses programmable oligonucleotide probes to deliver proximity-biotinylating enzymes to a target RNA, enabling nearby molecules to be enriched by streptavidin pulldown. O-MAP induces exceptionally precise RNA-localizedin situbiotinylation, and unlike alternative methods it enables straightforward optimization of its targeting accuracy. Using the 47S pre-ribosomal RNA and long noncoding RNAXistas models, we develop O-MAP workflows for unbiased discovery of RNA-proximal proteins, transcripts, and genomic loci. This revealed unexpected co-compartmentalization ofXistand other chromatin-regulatory RNAs and enabled systematic characterization of nucleolar-chromatin interactions across multiple cell lines. O-MAP is portable to cultured cells, organoids, and tissues, and to RNAs of various lengths, abundances, and sequence composition. And, O-MAP requires no genetic manipulation and uses exclusively off-the-shelf parts. We therefore anticipate its application to a broad array of RNA phenomena.

In this paper, the particle packing-based discrete element method is applied to study the correlations between the microstructural parameters and electrochemical performances of LSM-LSCF composite electrodes. Firstly, through the verification of domain size independence and the comparison with the percolation theory, the computational domain size and effectiveness of the particle packing are determined. Then, the changes of the electrochemical reaction sites in the composite electrode with the LSM volume fraction under two different ratios of particle radius are investigated, including the LSM-LSCF-pore three-phase boundaries (TPBs) per electrode volume, TPBs per electrolyte surface, and percolated LSCF-pore double phase boundaries (DPBs). The distribution characteristics of the LSM-LSCF-pore TPBs within and outside the threshold volume fraction zone at different particle size ratio cases are obtained. When the particles are of equal radius, the formation of both percolated e−, O2−, and O2 transport paths is in the LSM volume fraction range of 0 to 0.7, due to the electronic conducting path is fully connected. The distribution characteristics of the LSCF-pore DPBs within the electrode in the percolation area and outside the percolation area are obtained respectively. This work is of great significance for the follow-up study of the physical and electrochemical processes within porous composite electrodes based on large-scale complex morphology.

The increasing wealthy of high-resolution topography allows for remotely measuring and analysing offset features and their associated surface slip distributions at a very high resolution and along a significant length of a fault, hence providing important insights into many aspects of the fault behaviour. The West Helanshan Fault is a Holocene active fault located at the junction of the Tibetan Plateau, Alashan, and Ordos blocks. Despite its special tectonic location, it has rarely been studied before. In this study, a 2-m-resolution DEM of the West Helanshan Fault was built from the high-resolution (0.5 m) WorldView-3 stereo satellite imagery based on the photogrammetry method, and a total of 181 strike-slip offsets and 201 vertical displacements were acquired along different segments of the fault. By statistical analysis of the offset observations, we conclude that at least six large paleoearthquakes have ruptured the fault, producing a minimum rupture length of ∼50 km, and the paleoearthquakes have followed a characteristic slip pattern with a coseismic strike slip of ∼3 m and a vertical slip of ∼1 m, corresponding to a geologic moment magnitude of 7.1–7.5.

The incidence of oropharyngeal cancer induced by human papillomavirus (HPV) infection is steadily increasing in developed countries. These tumors are more chemoradiosensitive and have a better prognosis than HPV-negative one. In addition, they occur in younger and better-off patients with longer life expectancy. Current radiotherapy and chemotherapy protocols are currently being questioned as they may expose HPV-positive patients to excessive treatment and unnecessary toxic effects. Less intensive treatment regimens could possibly achieve similar efficacy with lower toxicity and improved quality of life. The aim of this work was to summarize the knowledge on these tumors and their implications for radiation oncologists. In this update, we will discuss ongoing de-escalation trials and highlight the issues raised by these studies. We will also comment on the results of recently published de-intensification studies. Three main strategies are analyzed in the present article: the de-escalation of the drug associated with radiotherapy, the de-escalation of the radiotherapy dose (in concomitant chemoradiotherapy, after induction chemotherapy, in a postoperative setting) and de-escalation of radiation target volumes. Our findings ultimately indicate that clinicians should not change the management of oropharyngeal cancer patients outside of clinical trials.

Hepatic venous pressure gradient measurement via jugular vein catheterization is still currently the gold standard for evaluating portal hypertension. However, how to accurately and reproducibly assess whether there is portal hypertension has always been a concern in patients with liver cirrhosis. In recent years, imaging methods have made significant progress in the non-invasive diagnosis of portal hypertension. This paper reviews the current different diagnostic value of imaging methods and related research progress in an attempt to evaluate patients with cirrhotic portal hypertension.目前经颈静脉插管测量肝静脉压力梯度仍是评价门静脉高压的金标准，如何准确、可重复地无创评估肝硬化患者是否存在门静脉高压，一直备受关注。近年来，影像学方法无创诊断门静脉高压取得重要进展，现就不同影像方法在评价肝硬化患者门静脉高压的诊断价值及相关研究进展予以综述。.

Evidence-based interventional radiology is the result of the evolution and integration of evidence-based medicine and interventional radiology. It adopts the concepts and methods of evidence-based medicine to guide the best clinical practice in interventional radiology. We aim to systematically elaborate on the status quo of Clinical Research, Systematic Review/Meta-Analysis and Clinical Practice Guidelines in interventional radiology, analyze the existing problems, and put forward thoughts and suggestions on promoting the development of evidence-based interventional radiology in the future.循证介入放射学是循证医学和介入放射学学科演进交融的结果，其采用循证医学的理念和方法，指导介入放射学领域进行最佳的临床实践。本文将系统地阐述介入放射学中临床研究、系统评价/Meta分析和临床实践指南的现状，分析存在的问题，在此基础上提出我国未来推动循证介入放射学发展的思考与建议。.

原发于子宫的脂肪肉瘤罕见，该文报道1例原发于子宫、去分化成分与高分化脂肪肉瘤两种成分混杂生长的去分化脂肪肉瘤。该例发生于罕见部位子宫体，肿瘤的组织学生长模式亦为不常见模式，间质黏液样变，所以容易误导影像学诊断，而对子宫的活检和诊刮，病理学诊断亦具有一定挑战性。.

ABSTRACT: The Gotthard Base Tunnel (GBT), constructed between 2000 and 2011, is a 57 km long and up to 2.5 km deep high-speed railway tunnel located in the Swiss Alps. Significant ground surface displacements up to 10 cm were observed during and after the tunnel construction. To gain a better understanding of the physical mechanisms underpinning such conspicuous ground deformations, we develop a 3D fully-coupled hydro-mechanical model to simulate the excavation-induced groundwater drainage, stress perturbation, and poroelastic response in faulted rock masses over both space and time. First, we construct a geological model with topographical features, lithological units, and natural faults realistically represented. We constrain the material properties of faults and rock masses based on extensive laboratory testing results and site characterisation datasets. We then simulate the tunnelling process with the resulting coupled hydro-mechanical responses of the faulted rock captured and ground surface displacements analysed. The simulation results show a good agreement with the field monitoring data of both ground surface displacement and tunnel settlement. The research findings from our work have important implications for many groundwater drainage-related geoengineering activities such as underground excavation in alpine mountains and fluid withdrawal in subsurface reservoirs. 1 INTRODUCTION The Gotthard Base Tunnel (GBT) is a 57 km long and up to 2.5 km deep high-speed railway tunnel located in the Central Alps of Switzerland (Fig. 1). The excavation work of the two tunnel tubes started in 2000 and successfully completed in 2011. The Sedrun and Faido sections of the GBT are located in crystalline basement rocks of the Gotthard Massif, where three arch dams are located on the ground surface at the Nalps, Curnera and St. Maria hydropower lakes. Due to the significant concern regarding the safety of these nearby hydropower infrastructures during and after the GBT excavation, a comprehensive in-situ monitoring system was installed to closely monitor the surface displacement and tunnel inflow/settlement. According to the monitoring data, up to 10 cm surface displacements and 50L/s tunnel inflow took place during the construction period (Loew et al., 2015).

Drug-induced interstitial lung disease (DI-ILD) is a rare adverse event associated with targeted therapies that inhibit the anaplastic lymphoma kinase (ALK) protein. Although newer-generation ALK inhibitors such as alectinib significantly improve survival in metastatic ALK-rearranged non-small cell lung cancer (NSCLC), the risk of DI-ILD is similar to that of earlier-generation therapies. Lorlatinib is a third-generation ALK inhibitor that is active in patients with metastatic NSCLC whose tumors have developed secondary resistance to alectinib. While it is associated with low rates of DI-ILD in initial phase 1/2 clinical trials, the safety of lorlatinib in patients with a history of DI-ILD has not been well-described. In this case series, we therefore report two patients with metastatic ALK-rearranged NSCLC who each tolerated lorlatinib following recovery from alectinib-related DI-ILD. Both cases were notable for the acute onset of dyspnea, hypoxia, and diffuse ground-glass opacities within one month of initiating alectinib. With no alternative etiology of pneumonitis identified, both patients were treated empirically for grade 3 DI-ILD with corticosteroids and discontinuation of alectinib. Following rapid clinical recovery and eventual radiographic resolution of opacities, each patient was started on lorlatinib at the time of cancer progression, with neither person developing symptoms or radiographic findings consistent with recurrent DI-ILD. In the following series, we describe these two cases in greater detail and discuss their significance within the context of the prior literature. While further descriptions are needed, our experience suggests that lorlatinib may be a safe therapeutic option in some patients who have recovered from DI-ILD.

To investigate the effects of the downregulation of AGER by miRNA-185-3p on renal function in diabetic nephropathy (DN) mice.Mice were divided into normal, model, NC, miR-185-3p mimic, si-AGER, and miR-185-3p mimic + si-AGER groups. Eight weeks following the establishment of the model, various indicators were assessed.Compared to control groups, miR-185-3p expression, body weight, superoxide dismutase (SOD) content, catalase (CAT) content, proliferation, S-phase ratios, and proliferating cell nuclear antigen (PCNA) expression were significantly lower in all experimental groups, whilst AGER expression, water intake, food intake, urine volume, urine protein content, serum creatinine (Scr), Blood Urea Nitrogen (BUN), MDA content, G0/G1 status, and rates of apoptosis were significantly higher (all p0.05). Compared to the model group, miR-185-3p mimics, si-AGER, and miR-185-3p mimic + si-AGER groups had a significantly higher SOD content, CAT content, proliferation, S phase ratios, PCNA expression and lower AGER expression, water intake, food intake, urine output, urine protein, Scr, BUN, MDA content, G0/G1 ratios, and apoptosis rates (all p0.05). In addition, the effects of the miR-185-3p mimics + si-AGER were superior to miR-185-3p mimics and si-AGER monotherapy groups (both p0.05).MiR-185-3p inhibits AGER, downregulates AGER expression, and improves renal function in DN mice.

The effects of plant essential oil (PEO) on the production performance and immune function of laying hens were evaluated to provide theoretical basis for promoting the natural plant extracts. Eight thousand 1-day-old healthy laying hens were randomly divided into a control group or PEO group, with four replicates per treatment and 1000 hens per replicate. The PEO diet was supplemented with 3g/kg plant extract. Diets were fed for 56 days. The tibia length and keel length were detected on an empty stomach at the end of the trial. Blood samples were collected on the 28th and 56th days to detect the level of C3, C4, IL-1, IL-2, IL-17 and immunoglobulin in the serum. The results showed that, compared with the control, PEO supplementation significantly increased the weight gain rate (WGR) at the 2nd, 4th, 5th and 7th week (p

It is reported that the flooding rate in low permeability sandstones is low and the oil recovery is hard to increase after water breakthrough. Understanding characteristics of waterflood is hence i...

A severe dust storm event originated from the Gobi Desert in Central and East Asia during 2–7 May 2017. Based on Moderate Resolution Imaging Spectroradiometer (MODIS) satellite products, hourly environmental monitoring measurements from Chinese cities and East Asian meteorological observation stations, and numerical simulations, we analysed the spatial and temporal characteristics of this dust event as well as its associated impact on the Asia-Pacific region. The maximum observed hourly PM10 (particulate matter with an aerodynamic diameter ≤ 10 µm) concentration was above 1000 µg m−3 in Beijing, Tianjin, Shijiazhuang, Baoding, and Langfang and above 2000 µg m−3 in Erdos, Hohhot, Baotou, and Alxa in northern China. This dust event affected over 8.35 million km2, or 87 % of the Chinese mainland, and significantly deteriorated air quality in 316 cities of the 367 cities examined across China. The maximum surface wind speed during the dust storm was 23–24 m s−1 in the Mongolian Gobi Desert and 20–22 m s−1 in central Inner Mongolia, indicating the potential source regions of this dust event. Lidar-derived vertical dust profiles in Beijing, Seoul, and Tokyo indicated dust aerosols were uplifted to an altitude of 1.5–3.5 km, whereas simulations by the Weather Research and Forecasting with Chemistry (WRF-Chem) model indicated 20.4 and 5.3 Tg of aeolian dust being deposited respectively across continental Asia and the North Pacific Ocean. According to forward trajectory analysis by the FLEXible PARTicle dispersion (FLEXPART) model, the East Asian dust plume moved across the North Pacific within a week. Dust concentrations decreased from the East Asian continent across the Pacific Ocean from a magnitude of 103 to 10−5 µg m−3, while dust deposition intensity ranged from 104 to 10−1 mg m−2. This dust event was unusual due to its impact on continental China, the Korean Peninsula, Japan, and the North Pacific Ocean. Asian dust storms such as those observed in early May 2017 may lead to wider climate forcing on a global scale.

BACKGROUND The aim of this study was to evaluate the dispersal effects of 3,5-dicaffeoylquinic acid (3,5-DCQA) against the preformed biofilm of Aspergillus fumigatus and to investigate its potential mechanism. MATERIAL AND METHODS Aspergillus fumigatus biofilms of laboratory strain AF293 and clinical strain GXMU04 were generated in 24- or 96-well polystyrene microtiter plates in vitro. Crystal violet assay and XTT reduction assay were performed to evaluate the effects of 3,5-DCQA on biofilm biomass, extracellular matrix, and metabolic activity alteration of cells in biofilms. Real-time PCR was performed to quantify the expression of hydrophobin genes. The cytotoxicity of 3,5-DCQA on human erythrocytes was evaluated by a hemolytic assay. RESULTS The results indicated that 3,5-DCQA in subminimum inhibitory concentrations (256 to 1024 mg/L) elicited optimal A. fumigatus biofilm dispersion activity and improved the efficacy of VRC and AMB in minimal fungicidal concentrations (MFCs) to combat fungal cells embedded in biofilms. The results of scanning electron microscope (SEM) and confocal laser scanning microscopy (CLSM) revealed 3,5-DCQA facilitated the entry of antifungal agents into the A. fumigatus biofilm through eliminating the hydrophobic extracellular matrix (ECM) without affecting fungal growth. Real-time PCR indicated that 3,5-DCQA down-regulated the expression of hydrophobin genes. Hemolytic assay confirmed that 3,5-DCQA exhibited a low cytotoxicity against human erythrocytes. CONCLUSIONS Subminimum inhibitory concentrations of 3,5-DCQA can disperse A. fumigatus biofilm and enhance fungicidal efficacy of VRC and AMB through down-regulating expression of the hydrophobin genes. The study indicated the anti-biofilm potential of 3,5-DCQA for the management of A. fumigatus biofilm-associated infection.

Forecasting landslide displacement is an important issue in engineering geology. In this field, it is difficult to accurately forecast the displacement of the step point of a step-type landslide. In this study, a novel grey multivariate model is proposed for forecasting landslide displacement. The proposed model transforms the original sequence by using the Hausdorff derivative operator, determines the model parameters by using the particle swarm optimization algorithm, and uses the trapezoidal integral formula to calculate the predicted value. Two numerical examples show that the average absolute relative error and mean squared error of the proposed model are smaller than those of the recursive discrete multivariate grey model and the multivariable grey model with structure compatibility. The proposed model is used to forecast the displacement of the Bazimen landslide in the Three Gorges Reservoir area of China. The previous month’s displacement, precipitation, and change in the reservoir water level are used as input variables. The results show that the performance of the proposed model is superior to that of the extreme learning machine model. This paper provides an effective method for forecasting displacement of the step point of a step-type landslide.

By combining numerical simulation and experimental investigation, this paper intensively investigated the influence rules of adding three active agents (SiO2, TiO2 and NaF) on the dynamic behaviors of flow field in the laser welding 304 stainless steel thick plate pool. First of all, the mathematical model of the activating laser welding stainless steel thick plate was constructed to numerically investigate the impact of active agents on the fluid flow in the pool. Secondly, based on the tungsten particle tracing principle test, the high speed camera system was adopted for real-time monitoring to investigate the mechanism of action of the active agents on the flow field in the pool. The results suggested that, the active agents partially affected the mode of fluid flow. The velocity vector from both sides of the pool to the center occurred on the pool surface, while vortex from the pool margin to the center occurred on the pool cross section. The phenomenon that the tracing tungsten particles moving from the pool margin to the center, it shows that the flow direction of the fluid changed after coating with the active agent, the fluid flew from the pool margin to the center. At the same time, the coating of active agents changed the flow velocity of fluid inside the pool, and SiO2 active agent has the most significant increase effect, the maximum velocity of fluid flow on the upper surface, the longitudinal and cross sections at the same position of the SiO2 active agent coated specimen increased by 25.8%, 8% and 33.8%, respectively, compared with that without the active agents.

A 2-D generalized Maxwell fish-eye lens has been fabricated with all-dielectric polymer/ceramic composite materials and evaluated numerically and experimentally. The graded refractive index profile of the lens was discretized into a concentric-ring structure and functioned as a two-way beam splitter. Epoxy composites, with a broad dielectric constant range that can be precisely controlled, were used to cast the lens using a low-cost manufacturing method that can readily accommodate different geometries. The lens was tested with a near-field microwave imaging system to demonstrate its capability of controlling waves at an operating frequency of 18 GHz. The measured results had some differences from the expected behavior, which are considered in detail and provided some insights into the practical manufacturing and measurement constraints for graded dielectric composites. Possible routes to increase the number of output beams are discussed.

Previous reports show increased incidence of venous thromboembolism [VTE, deep-vein thrombosis (DVT) and pulmonary embolus (PE)] in sickle cell disease (SCD) patients but did not account for frequency of hospitalization. We determined the incidence of VTE in a SCD cohort versus matched controls. For SCD patients, risk factors for incident VTE, recurrence and the impact on mortality were also determined. Among 6237 patients with SCD, 696 patients (11·2%) developed incident-VTE: 358 (51·6%) had PE (±DVT); 179 (25·7%) had lower-extremity DVT only and 158 (22·7%) had upper-extremity DVT. By 40 years of age, the cumulative incidence of VTE was 17·1% for severe SCD patients (hospitalized ≥3 times a year) versus 8·0% for the matched asthma controls. Amongst SCD patients, women (Hazard ratio [HR] = 1·22; 95% confidence interval [CI]: 1·05-1·43) and those with severe disease (HR = 2·86; 95% CI: 2·42-3·37) had an increased risk of VTE. Five-year recurrence was 36·8% in patients with severe SCD. VTE was associated with increased risk of death (HR = 2·88, 95% CI: 2·35-3·52). In this population-based study, the incidence of VTE was higher in SCD patients than matched controls and was associated with increased mortality. The high incidence of recurrent VTE in patients with severe SCD suggests that extended anticoagulation may be indicated.

The incidence of oropharyngeal cancer induced by human papillomavirus (HPV) infection is steadily increasing in developed countries. These tumors are more chemoradiosensitive and have a better prognosis than HPV-negative one. In addition, they occur in younger and better-off patients with longer life expectancy. Current radiotherapy and chemotherapy protocols are currently being questioned as they may expose HPV-positive patients to excessive treatment and unnecessary toxic effects. Less intensive treatment regimens could possibly achieve similar efficacy with lower toxicity and improved quality of life. The aim of this work was to summarize the knowledge on these tumors and their implications for radiation oncologists. In this update, we will discuss ongoing de-escalation trials and highlight the issues raised by these studies. We will also comment on the results of recently published de-intensification studies. Three main strategies are analyzed in the present article: the de-escalation of the drug associated with radiotherapy, the de-escalation of the radiotherapy dose (in concomitant chemoradiotherapy, after induction chemotherapy, in a postoperative setting) and de-escalation of radiation target volumes. Our findings ultimately indicate that clinicians should not change the management of oropharyngeal cancer patients outside of clinical trials.

This paper presents all-dielectric materials used to 3D print coupons with spatially varying dielectric permittivity and possessing high dielectric anisotropy. The coupons were directly printed through a dual-filament fused deposition modelling technique utilizing bespoke feedstock filament comprised a polymer-based micro-ceramic composite with controlled permittivity and loss. By designing the arrangement of both high and low permittivity filament materials in the printed coupons, the microwave operating frequency and magnitude of Mie-type resonances could be manipulated to provide metamaterial-like characteristics. Keywords: Additive manufacturing, Fusion deposition, Dielectric composites, Metamaterials

The effects of displacement damage due to 1 MeV electron radiation on 680 nm and 850 nm vertical-cavity surface-emitting lasers (VCSELs) were experimentally investigated. The displacement damage dose was calculated using the MULASSIS tool, where it was found that radiation significantly affects the threshold current of VCSELs. The threshold current damage factor is 2.46 × 10−18 cm2/e for 680 nm VCSELs and 1.48 × 10−18 cm2/e for 850 nm VCSELs. In addition, the power intensity distribution and light output power degradation were characterized to evaluate the radiation hardness of VCSELs. An understanding of the performance degradation of VCSELs under electron exposure would be useful in optimizing their applications in hostile environments.

On the 29th and 30th of August 2012, more than 100 geological disasters occurred near the dam area of Jinping I Hydropower Station, Xichang, China due to local intense rainstorm. The upper part of the left valley slope, which is 500 m upstream of the dam, failed and slid, exposing the C-pile of the G1006 electricity pylon and threatening the entire power transmission lines. Therefore, ensuring the stability of the residual rock masses in the rear of the main scarp and the safety of the G1006 electricity pylon became a primary emergency task. Field geological survey, topographic mapping, and the instability mechanism study of the G1006 electricity pylon landslide were conducted. Results revealed that the G1006 electricity pylon landslide (here after represented as the G1006 EPL) occurred in the middle block cut by two faults, and the rock masses had inferior mechanical properties. Intense unloading effects and frequent microseism events during the dam construction relaxed the rock mass structural planes and reduced the geotechnical parameters. Under the influence of intense rainfall, the failure mechanisms of the slope were a combination of slope surface effect from rainfall and lateral erosion and undercutting of the slope toe by high flooding. The residual rock masses and landslide deposits around the pylon foundation were unstable under natural conditions and during the rainstorm. To prevent the continuous damage and exposure of C-pile foundation and ensure the stability of pylon foundation, the mitigation measure of “retaining piles + platform + retaining wall” was arranged. Moreover, a check dam was added to stabilize the slope toe and prevent the landslide deposits, which are the starting material source of debris flow that threatens the safety of the arch dam.

The degradation characteristics of MOCVD grown InGaAsP/InGaAs dual junction solar cells, irradiated by 1 MeV electron, 3 MeV and 10 MeV proton, have been investigated. Main electrical and optical properties of solar cell degraded seriously with the increase of irradiation fluences due to the irradiation induced defects which are acting as non-radiative recombination centers in the active layers of the solar cell. The remaining factor of P m a x is 0.67, 0.53 and 0.51 for 1 MeV electron, 10 MeV proton, and 3 MeV proton irradiation, respectively, when the displacement damage dose (DDD) is 3 . 16 × 1 0 10 MeV/g. The degradation of external quantum efficiency (EQE) of each subcell mainly occurred in the long wavelength region, the integrated current density J s c of InGaAsP and InGaAs subcells degraded more seriously upon 3 MeV and 10 MeV proton irradiation comparing to 1 MeV electron irradiation. The InGaAsP subcell turned out to be the current limiting unit due to the lower J s c before and post irradiation. By applying equivalent displacement damage dose model, the relative damage coefficient for 3 MeV proton to 10 MeV proton and 1 MeV electron to 10 MeV proton have been calculated.