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Supplementary Data from TNFRSF19 Inhibits TGFβ Signaling through Interaction with TGFβ Receptor Type I to Promote Tumorigenesis

Genetic susceptibility underlies the pathogenesis of cancer. We and others have previously identified a novel susceptibility gene TNFRSF19, which encodes an orphan member of the TNF receptor superfamily known to be associated with nasopharyngeal carcinoma (NPC) and lung cancer risk. Here, we show that TNFRSF19 is highly expressed in NPC and is required for cell proliferation and NPC development. However, unlike most of the TNF receptors, TNFRSF19 was not involved in NFκB activation or associated with TRAF proteins. We identified TGFβ receptor type I (TβRI) as a specific binding partner for TNFRSF19. TNFRSF19 bound the kinase domain of TβRI in the cytoplasm, thereby blocking Smad2/3 association with TβRI and subsequent signal transduction. Ectopic expression of TNFRSF19 in normal epithelial cells conferred resistance to the cell-cycle block induced by TGFβ, whereas knockout of TNFRSF19 in NPC cells unleashed a potent TGFβ response characterized by upregulation of Smad2/3 phosphorylation and TGFβ target gene transcription. Furthermore, elevated TNFRSF19 expression correlated with reduced TGFβ activity and poor prognosis in patients with NPC. Our data reveal that gain of function of TNFRSF19 in NPC represents a mechanism by which tumor cells evade the growth-inhibitory action of TGFβ.Significance:TNFRSF19, a susceptibility gene for nasopharyngeal carcinoma and other cancers, functions as a potent inhibitor of the TGFβ signaling pathway.Graphical Abstract:http://cancerres.aacrjournals.org/content/canres/78/13/3469/F1.large.jpg. Cancer Res; 78(13); 3469–83. ©2018 AACR.

Supplementary Figure S4 from TNFRSF19 Inhibits TGFβ Signaling through Interaction with TGFβ Receptor Type I to Promote Tumorigenesis

Supplementary Table S1 from TNFRSF19 Inhibits TGFβ Signaling through Interaction with TGFβ Receptor Type I to Promote Tumorigenesis

A RELAP5 input model was established for a scaled-up facility simulating China's Advanced Passive Water Reactor with passive safety features. The simulation was performed to reproduce a Main Steam Line Break (MSLB) scenario at steam line connected to one Steam Generator. The figure of merit selected in this accident scenario includes the maximum containment pressure, mass and energy release to containment. Driving factors of this response function include Passive Residue Heat Removal material thermal conductivity, Pressurizer temperature, and broken steam line temperature.To achieve an adequately justified safety margin using a Best Estimate Plus Uncertainty analysis, dominant phenomena were selected from a reference Phenomenon Identification and Ranking Table. The calculation results were compared with the available reference data of similar Generation III Passive Water Reactor to assess the code's capability to predict the MSLB phenomena. The DAKOTA toolkit is used to drive both parameter sensitivity analysis and uncertainty propagation. The 95/95 uncertainty bands of key output parameters were obtained using the Wilks’ statistical methods.Compared with the reference data, the simulation results partially confirmed the stability and repeatability of the code model for initial and boundary condition perturbations. The uncertainty bands of important output parameters were demonstrated. The results indicated that the maximum containment pressure value was below the safety limit, and the passive safety system can mitigate the consequence of the MSLB. The mass and energy released into the containment were assessed according to the containment design.The parameter sensitivity analysis was performed with 34 input parameters, and the results were evaluated by Spearman's Simple Rank Correlation Coefficients.

Background Postoperative cognitive dysfunction is a common postoperative complication in elderly patients. In elderly patients, the decline of organ function and neuromuscular junction function make them more sensitive to muscle relaxants. They are more likely to experience residual muscle relaxation after surgery, which may cause various adverse events. Neostigmine, a commonly used muscle relaxant antagonist, can reduce the expression of inflammatory factors, thereby reducing the pro-inflammatory response and neurodegeneration of the cerebral cortex and hippocampus after surgery. The study aimed at observing the effect of different doses of neostigmine on postoperative cognitive function and peripheral inflammatory factors in elderly patients. Methods One hundred thirty-two elderly patients who underwent a radical section of gastrointestinal cancer at First Affiliated Hospital of Dalian Medical University were divided into neostigmine and saline groups at a 2:1 ratio. Neostigmine was intravenously injected in the post-anesthesia care unit (PACU) according to the train-of-four ratio (TOFR) T4/T1. When TOFR was ≤0.5, 0.04 mg/kg neostigmine was administered, whereas when TOFR was > 0.5, 0.02 mg/kg neostigmine was injected. The main observation indexes were cognitive function, interleukin 1 beta (IL-1β), tumor necrosis factor-alpha (TNF-α), and interleukin 6 (IL-6) in peripheral blood at the different times before and after the surgery. Secondary observation indicators include the number of atropine injection, extubating time, PACU residence time, incidence of hypoxemia, hypercapnia, and postoperative nausea and vomiting in PACU, time of exhaustion, and length of hospitalization. Results The extubating and PACU times in 0.04 mg/kg and 0.02 mg/kg groups were significantly shorter than those in the control group (P P = 0.013). Conclusion In elderly patients, 0.02–0.04 mg/kg neostigmine could significantly reduce the incidence of early postoperative cognitive decline without affecting peripheral inflammatory factors. Trial registration Trial registration: Chinese Clinical Trial Registry, ChiCTR2000031739. Registered 8 April 2020 - Retrospectively registered, http://www.medresman.org.cn.

Liuwei Dihuang Pill is widely used to treat tinnitus in China. However, the underlying mechanism of Liuwei Dihuang Pill in treating tinnitus still remains unclear.To explore the potential pharmacological mechanism of Liuwei Dihuang Pill in the treatment of tinnitus based on network pharmacology and molecular docking.The active components of the Liuwei Dihuang Pill were obtained from the traditional Chinese medicine systems pharmacology database and analysis platform (TCMSP) database. Cytoscape software was used to draw the active component-target network diagram of Liuwei Dihuang Pill, and obtain the core components. Then the corresponding targets were also obtained from the TCMSP database. Targets related to tinnitus were obtained from the GeneCards, DisGeNET, TTD and DrugBank databases. The String database was used to construct protein-protein interaction (PPI) network of common targets of drugs and diseases, then the core targets were screened out. The Annotation, Visualization and Integrated Discovery (DAVID) database was used for gene ontology (GO) enrichment and Kyoto encyclopedia of genes and genomes (KEGG) pathway analysis of common targets. Finally, the molecular docking between the core component and the core target was carried out by AutoDock.The core components of Liuwei Dihuang Pill in the treatment of tinnitus including quercetin, stigmasterol, kaempferol, β-sitosterol, tetrahydroalstonine, which may act on core targets such as STAT3, transcription factor AP-1 (JUN), tumor necrosis factor (TNF), interleukin-6 and MAPK3. HIF-1 signaling pathway, Influenza A, P53 signaling pathway, and Toll-like receptor signaling pathway play a role in anti-inflammatory, improving microcirculation in the blood-labyrinth barrier, increasing cochlear blood flow, and preventing hair cell damage. The molecular docking results showed that the affinity between core components and core targets was good.The potential mechanism of Liuwei Dihuang Pill in the treatment of tinnitus was preliminarily discussed in this study, which may provide a theoretical basis and evidence for further experimental research.

Long non-coding RNAs (LncRNAs) are vital in the treatment of laryngeal squamous cell carcinoma (LSCC). This study estimated the mechanism of lncRNA CCAT1 (CCAT1) in LSCC cells. The expression of CCAT1 in the human laryngeal mucosal epithelial cells (HLCs) and LSCC cells (Hep-2 and TU177) was detected. CCK-8 and Transwell assays were used to evaluate the cell proliferative, migrative, and invasive abilities, respectively. The subcellular localization of CCAT1 was verified by RNA-FISH and cytoplasmic isolation assays. The targeted relationship among CCAT1, miR-218-5p, and BMI1 was verified by dual-luciferase assay. Expressions of miR-218-5p and BMI1 were detected by RT-qPCR. Our results depicted that CCAT1 was highly-expressed in Hep-2 and TU177 cells. Silencing CCAT1 inhibited the proliferation, migration, and invasion of Hep-2 and TU177 cells. Mechanically, CCAT1 regulated the BMI1 expression by competitively binding to miR-218-5p as a competing endogenous RNA (ceRNA), and thus facilitated the growth of Hep-2 and TU177 cells. Downregulation of miR-218-5p or upregulation of BMI1 inhibited the inhibitory effect of silencing CCAT1 on Hep-2 and TU177 cell proliferation, invasion, and migration. In conclusion, our study elicited that lncRNA CCAT1 facilitated the proliferation, migration, and invasion of Hep-2 and TU177 cells by sponging miR-218-5p and regulating the downstream BMI1.

The integral thermal-hydraulic test facility is an important part of the design certification and safety review of nuclear power plants. During the past few decades, a considerable number of resources and efforts have been devoted to establishing integral test facilities and carrying out experimental programs throughout the world. These test facilities provide a large database for computer code assessments and a better understanding of thermal-hydraulic phenomena for postulated accident transients. In this paper, some main integral thermal-hydraulic test facilities are summarized from the perspective of scaling design and applicability evaluation. Scaling analysis methods are presented for the rational design of scaled-down test facilities. The main characteristics of these thermal-hydraulic test facilities are illustrated, including their construction history, scaling design, test matrix, verified codes and related research works. The scaling distortion and experimental applicability of different integral test facilities are compared and evaluated. This review is expected to provide the reference guidance for the rational design and application evaluation of integral thermal-hydraulic test facilities.

The RELAP5/MOD3.3 code was used to simulate a Main Steam Line Break (MSLB) Loss of Coolant Accident (LOCA) on a Generation III type Reactor with passive safety features. The MSLB is a hypothetical multi-failure large break LOCA accident scenario. The results of the base case calculation have been compared with the available integral testing data to assess the code’s capability to predict the large break LOCA phenomena in this generic reactor, particularly with passive safety systems. Various flows such as break flow and gravity injection flow were simulated with a high level of accuracy. In addition, both sensitivity cases and uncertainty analysis were carried out to build the best estimate plus uncertainty practice. The sensitivity study was performed with different initial conditions and adjusted containment cooling capacities. The results confirmed that the code model held its stability and repeatability against a few variations of initial and boundary conditions. In the uncertainty quantification process, the 95/95 uncertainty bands of key output parameters were obtained using the Wilks statistic methods. Ten input parameters were selected with imposed uncertainty distribution to perform uncertainty propagation analysis. The contribution weight of input parameters for the uncertainty of minimum core level were identified with the Spearman rank correlation coefficient in sensitivity analysis.

CAP1400 has been developed as a new passive nuclear power plant in China based on AP1000 technique. In order to support the CAP1400 licensing, a scale-down integral test facility named ACME (Advanced Core-cooling Mechanism Experiment) has been designed and constructed. In this study, best-estimate calculation using RELAP5/MOD3.4 code plus uncertainty quantification and sensitivity analysis of the small break loss of coolant accident (SBLOCA) transient were carried out for the ACME test facility. The important thermal-hydraulic phenomena during the SBLOCA transient were investigated through the comparing calculations between the ACME and CAP1400. Thereafter, uncertainty quantification process was demonstrated including the selection of input uncertain parameters, the application of Wilks’ nonparametric statistics and the propagation of uncertainty through the SNAP interface coupling RELAP5 and DAKOTA codes. Furthermore, the results of uncertainty and sensitivity analysis were discussed. Through the comparison of the thermal-hydraulic modeling results between ACME and CAP1400, the results show that the ACME test facility is able to reproduce the important thermal-hydraulic phenomena of CAP1400 by reasonable scaling design. The 95/95 uncertainty bands of some key output parameters are obtained through uncertainty quantification. The lower band of the minimum core level is maintained still above the top of the active core section, thus the core uncover will not occur with 95% confidence level. Important input uncertain contributors for the minimum core level are identified through the measure of Spearman rank correlation coefficients in sensitivity analysis. The demonstration of best-estimate plus uncertainty analysis (BEPU) application will provide some guidance for the safety analysis of advanced passive nuclear power plants.

Exploring the mechanism of interfacial thermal transport and reducing the interfacial thermal resistance are of great importance for thermal management and modulation. Herein, the interfacial thermal resistance between overlapped graphene nanoribbons is largely reduced by adding bonded carbon chains as shown by molecular dynamics simulations. And the analytical model (phonon weak couplings model, PWCM) is utilized to analyze and explain the two-dimensional thermal transport mechanism at the cross-interface. An order of magnitude reduction of the interfacial thermal resistance is found as the graphene nanoribbons are bonded by just one carbon chain. Interestingly, the decreasing rate of the interfacial thermal resistance slows down gradually with the increasing number of carbon chains, which can be explained by the proposed theoretical relationship based on analytical model. Moreover, by the comparison of PWCM and the traditional simplified model, the accuracy of PWCM is demonstrated in the overlapped graphene nanoribbons. This work provides a new way to improve the interfacial thermal transport and reveal the essential mechanism for low-dimensional materials applied in thermal management.

The application of low-dimensional materials for heat dissipation requires a comprehensive understanding of thermal transport at cross-interfaces, which widely exist in various composite materials and electronic devices. In this work, an analytical model is proposed, named as the cross-interface model (CIM), to accurately reveal the essential mechanism of the two-dimensional thermal transport at cross-interfaces. The applicability of CIM is validated through a comparison of the analytical results with molecular dynamics simulations for a typical cross-interface between two overlapped boron nitride nanoribbons. Besides, it is found that both the thermal resistances and the factor, η, has an important influence on the thermal transport. These investigations would deepen the understanding of the thermal transport at cross-interfaces and also facilitate the application of low-dimensional materials in thermal management.

In the scaled-down test facilities that simulate the accident transient process of the prototype nuclear power plant, the stored energy release in the metal structures has an important influence on the accuracy and effectiveness of the experimental data. Three methods of stored energy analysis are developed, and the mechanism behind stored energy distortion in the test facilities is revealed. Moreover, the application of stored energy analysis is demonstrated for the ACME test facility newly built in China. The results show that the similarity requirements of three methods analyzing the stored energy release decrease gradually. The physical mechanism of stored energy release process can be characterized by the dimensionless numbers including Stanton number, Fourier number and Biot number. Under the premise of satisfying the overall similarity of natural circulation, the stored energy release process in the scale-down test facilities cannot maintain exact similarity. The results of the application of stored energy analysis illustrate that both the transient release process and integral total stored energy of the reactor pressure vessel wall of CAP1400 power plant can be well reproduced in the ACME test facility.

There has been an increasing demand for materials with special thermal properties, whereas experimental discovery is high-cost and time-consuming. The emerging discipline `Materials Informatics' is an effective approach that can accelerate materials development by combining material science and big data technique. Recently materials informatics has been applied to the design of novel materials such as thermal interface materials for heat-dissipation, and thermoelectric materials for power generation. This mini-review summarized the research progress on the applications of materials informatics for the thermal transport properties prediction and discovery of materials with special thermal properties, including optimal thermal conductivity, interfacial thermal conductance and thermoelectricity efficiency. In addition, some perspectives are given for the outlook of materials informatics in the field of thermal transport.

With the rapid growth of personal loan applications, credit risk assessment has become very crucial both in academic and industrial domain. Research literatures show that besides “hard” information, such as individual socio-demographic information and loan application information, “soft” information such as social relationships of the borrowers is a key factor to the credit risk assessment as social capital. In social networks, a user’s position and its influence are affected not only by the direct relationships (its friends) but also the indirect relationships (friends’ friends). A user’s importance and influence in his communities are attractive and valuable for credit assessment. But due to data deficiency in real life, social relationships are rarely considered in lending markets. By leveraging data from various sources, we proposed a social relationship enhanced credit risk assessment system, by building a social network from users’ geolocation data, extracting social relationship features at three different levels: ego, community and global level to capture a user’s position and influence from direct relationships, community and whole network perspectives. A real-life loan granting dataset is utilized for verifying the performance of the system. The experiment results show that, by combining the conventional financial indicators along with the proposed social network features, our system outperforms benchmark methods. Novel social network features we proposed make a good contribution to the loan default prediction. The research highlights the power of social relationships in detecting the default loans.

The thermal management on low-dimensional materials requires a fundamental understanding of phonon couplings, which dominates thermal transport. In this mini-review, recent studies on weak couplings between phonon and other energy carriers are reviewed firstly. Then, a generalized analytical model, phonon weak couplings model, is proposed based on Boltzmann transport equation. When applying this model to describe recent works on weak couplings of phonons, it is classified as “implicit couplings” and “explicit couplings”, corresponding to couplings within a single structure and between two structures, respectively. Furthermore, perspectives and limitations of phonon weak couplings model are summarized, and potential research prospects are given to inspire future investigations and applications.

In order to investigate the performance of a Generation III BWR safety system, an Integral test facility was designed and conducted, and several integral tests were performed. The best estimate safety analysis of Main Steam Line Break (MSLB) accident using RELAP5/MOD3.3 and RELAP/SCDAPSIM/MOD3.4 (from now on referred as RELAP/SCDAP3.4) was performed. By comparing the simulation results with the test results, the prediction capability of the RELAP5/MOD3.3 and the RELAP/SCDAP3.4 was compared and analyzed. The RELAP/SCDAP3.4 code was selected to perform the uncertainty study. According to the Phenomenon Identification and Ranking Table, 12 input treatable parameters and 29 source code coefficients were selected with imposed uncertainty distribution to conduct uncertainty analysis. The 95/95 uncertainty band of the minimum core collapsed level were obtained and analyzed. In addition, the contribution weight of input treatable parameters and source code coefficients for the minimum core collapsed level were identified with the Spearman rank correlation coefficient.

Solar steam generation technology can utilize abundant and renewable solar energy for many applications. In this work, we proposed a low-cost high-efficiency solar steam generator by using wick materials with wrapped graphene nanoparticles, and the energy efficiency can reaches up to 80%. Instead of traditional smearing method, the chemical wrapping method was used for better coating the graphene nanoparticles on the wick materials. Through the SEM morphological results, the graphene nanoparticles are shown to be evenly wrapped across the fibres of the wick material, which have better dispersity and stability. The evaporation rate, instantaneous energy efficiency and the solar absorptivity of three wick materials with/without nanoparticles under different conditions were compared and analyzed. Among the three different wick materials, the fine fluffy cloth can provide more three-dimensional contact area for wrapping graphene nanoparticles and thus contribute to better evaporation. Additionally, the influence of two different reduction methods and different concentrations of graphene oxide solution on the energy efficiency was also analyzed. Our work offers a simple and effective way of using nanotechnology in practical application for better solar-to-heat conversion.

The van der Waals (vdW) interactions exist in reality universally and play an important role in physics. Here, we show the study on the mechanism of vdW interactions on phonon transport in atomic scale, which would boost developments in heat management and energy conversion. Commonly, the vdW interactions are regarded as a hindrance in phonon transport. Here, we propose that the vdW confinement will enhance phonon transport. Through molecular dynamics simulations, it shows that the vdW confinement makes more than two-fold enhancement on thermal conductivity of both polyethylene single chain and graphene nanoribbon. The quantitative analyses of morphology, local vdW potential energy and dynamical properties are carried out to reveal the underlying physical mechanism. It is found that the confined vdW potential barriers reduce the atomic thermal displacement magnitudes, thus lead to less phonon scattering and facilitate thermal transport. Our study offers a new strategy to modulate the heat transport.

Since best-estimate plus uncertainty analysis was approved by Nuclear Regulatory Commission for nuclear reactor safety evaluation, several uncertainty assessment methods have been proposed and applied in the framework of best-estimate code validation in nuclear industry. Among them, the Wilks’ method and Bayesian approach are the two most popular statistical methods for uncertainty quantification. This study explores the inherent relation between the two methods using the Beta distribution function as the prior in the Bayesian analysis. Subsequently, the Wilks’ method can be considered as a special case of Beta-Bayesian approach, equivalent to the conservative case with Wallis’ “pessimistic” prior in the Bayesian analysis. However, the results do depend on the choice of the pessimistic prior function forms. The analysis of mean and variance through Beta-Bayesian approach provides insight into the Wilks’ 95/95 results with different orders. It indicates that the 95/95 results of Wilks’ method become more accurate and more precise with the increasing of the order. Furthermore, Bayesian updating process is well demonstrated in the code validation practice. The selection of updating prior can make use of the current experience of the code failure and success statistics, so as to effectively predict further needed number of numerical simulations to reach the 95/95 criterion.

A new way was proposed to enhance the interfacial thermal conductance (ITC) of silicon carbide (SiC) composite through the overlapped carbon nanotubes (CNTs) and intertube atoms. By nonequilibrium molecular dynamics (NEMD) simulations, the dependence of ITC on both the number of intertube atoms and the temperature was studied. It is indicated that the ITC can be significantly enhanced by adding intertube atoms and finally becomes saturated with the increase of the number of intertube atoms. And the mechanism is discussed by analyzing the probability distributions of atomic forces and vibrational density of states (VDOS). This work may provide some guidance on enhancing the ITC of CNT-based composites.

In this paper, computer software is employed to simulate the temperature-field and flow-field of AP1000 PRHR HX, and investigate its heat-transferring and flow characteristic. Through comparative analysis of the distribution of temperature-field and flow-field in different locations at the same time, and the change of temperature-field and flow-field in the same location at different times, heat-transferring process and natural convection situation of PRHR HX are deeply understand. It contributes to analyze the natural circulation capacity of PRHR HX, and provides some references for the effective operation of passive residual heat removal system.

The widely used topological map is quite essential to localization and navigation for mobile robot, especially in large-scale environment. In this paper, a new structure of topological map is presented and applied in robot navigation. This kind of map, compared to occupancy grid map and conventional topological map, can better represent the environment with certain features, such as multi-floor and multi-type, and reduce time and space complexity to a degree. In this case, it will be more convenient for the creation and maintenance of topological map, and the navigation based on this kind of map become more efficient and robust. Finally, certain experiments demonstrate that this approach is very effective.