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The spike (S) protein of SARS-CoV-2 is delivered to the virion assembly site in the ER-Golgi Intermediate Compartment (ERGIC) from both the ER and cis-Golgi in infected cells. However, the relevance and modulatory mechanism of this bidirectional trafficking are unclear. Here, using structure-function analyses, we show that S incorporation into virus-like particles (VLP) and VLP fusogenicity are determined by coatomer-dependent S delivery from the cis-Golgi and restricted by S-coatomer dissociation. Although S mimicry of the host coatomer-binding dibasic motif ensures retrograde trafficking to the ERGIC, avoidance of the host-like C-terminal acidic residue is critical for S-coatomer dissociation and therefore incorporation into virions or export for cell-cell fusion. Because this C-terminal residue is the key determinant of SARS-CoV-2 assembly and fusogenicity, our work provides a framework for the export of S protein encoded in genetic vaccines for surface display and immune activation.

The nuclear reactor system is complex and the operating environment is harsh, resulting in the complex phenomena of multi-physics coupling. The multi-physics coupling codes developed in the early stage shows limitations on codes' scalability and generality. Therefore, it is of great significance to build a multi-physics coupling framework and conduct research on key technologies in coupling problems, which may accelerate the development process of autonomous multi-physics coupling platform in China. In this paper, the multi-dimensional and multi-physics coupling finite element analysis platform for nuclear reactor developed by XJTU-NuTHeL was introduced. The main work consisted of the development of thermal-hydraulic model, the research of fuel performance analysis technology and the establishment of multi-physics coupling framework. In terms of thermal-hydraulic calculation, XJTU-NuTHeL conducted a series of studies on pressurized water reactors and advanced reactors grounded in the advanced multi-physics coupling framework, and developed the nuclear reactor system safety analysis code, NUSAC. In addition, a subchannel analysis model tailored for liquid metal fast reactors was established, and the fully coupled subchannel transient analysis code, FLARE, was developed. NUSAC and FLARE were then verified against relevant codes and experimental data. In the realm of fuel performance analysis, considering the wide application of finite element method in solid mechanics and its versatile modeling capabilities, XJTU-NuTHeL developed a fuel performance analysis code, BEEs, based on finite element method. The code could not only conduct multi-physics coupling analysis for traditional rod fuels under steady and transient conditions, but also extends its applicability to accident tolerant fuels and other fuels with diverse geometric shapes. This paper focused on the study and analysis of coated particle dispersed fuel and plate type fuel. The multi-scale simulation results of coated particle dispersed fuels, as well as the thermomechanical and corrosion behavior of plate type fuels were shown. In the context of multi-physics coupling analysis, the efficiency and accuracy of different mesh grid mapping schemes were studied and a multi-physics coupling framework was established. An example of the framework was then presented, showcasing the integration of the fuel performance code BEEs, the Monte Carlo neutron physics code OpenMC, and reactor system safety analysis code NUSAC. The keys parameters of mechanics, thermal-hydraulic and neutronics were obtained and analyzed through the coupling different codes. The multi-dimensional and multi-physics coupling finite element analysis platform built in this paper can provide a strong support for the high-fidelity numerical simulation of nuclear reactor multi-scale and multi-physics coupling.

BackgroundHeat pipe cooled reactor (HPR) has many characteristics, such as reliability, inherent safety, small volume, modularity, and solid core. The nuclear fuel of solid core is seriously affected by high temperature, strong irradiation, and solid constraint when operating, which affect the heat transfer performance and mechanical properties of the core seriously. The stress and gap heat transfer caused by the contact between monolith and other components change nonlinearly with the increase of burnup, and they influence each other. Therefore, the coupled irradiation-thermal-mechanical behavior of the monolith is a complex multi-physics phenomena.PurposeThis study aims to develop a coupled irradiation-thermal-mechanical model to explore the characteristics of gap variation, heat transfer and mechanics during the lifetime of solid core.MethodsFirst of all, based on the geometric parameter and material of a typical solid core of HPR with fuel rod composed of UO2 pellets and 316 stainless steel cladding, a coupled irradiation-thermal-mechanical model was developed and applied to the finite element multi-physics field analysis software COMSOL. The calculation parameter settings mainly referred to the design parameters of the MegaPower reactor. Then, a thermal conductivity model changing with the increase of burnup for UO2, the gap heat transfer model and mechanical contact were introduced in the gaps in the solid core, and both irradiation-induced deformation effect including densification and fission product swelling, and creep effect of UO2 pellets and 316 stainless steel monolith were taken into account. Finally, the model was applied to calculating the typical HPR and the characteristics of gap variation, heat transfer and mechanics were analyzed.ResultsAnalysis results show that pellet temperature and creep of monolith and cladding increase after complete contact between monolith and cladding. A smaller average number of heat pipes around the fuel rod result in higher temperature and stress distribution in the nearby area, and the cladding in this area has a risk of creep failure during its lifetime caused by internal pressure of the fuel rod and contact pressure between the monolith and cladding.ConclusionsThe gap contact can affect the heat transfer and mechanical properties of the solid core of HPR, and even result in an increase in the risk of cladding failure.

BackgroundThe enrichment of nuclear fuel may significantly influence the fuel performance of a reactor.PurposeThis study aims to explore the effect of U3Si2-Al plate-type fuel enrichment on its performance,MethodsThe fuel performance analysis code BEEs-Plates, neutronics Monte Carlo code OpenMC, and the one-dimensional system analysis code ZEBRA were coupled together within the MOOSE (Multiphysics Object-Oriented Simulation Environment) framework. Then the coupling code was employed to conduct the multiphysics coupling calculation for JRR-3 (Japanese Research Reactor No.3) fuel assembly enriched at 15%, 20%, and 25%. The data exchange among the three codes were realized with the help of interpolation transfer method implemented in MOOSE. Additionally, neutron physical parameters and fuel performance parameters after 231 d of operation were analyzed when the average fuel consumption of the module was 125.71 GWd∙tU-1.ResultsThe calculation results indicate that the max power density of fuel assembly enriched at 25% is 18% higher than the assembly enriched at 15%. Due to the high thermal conductivity of aluminum, the temperature difference in the fuel assembly is almost negligible whilst there is a significant difference in the fast neutron fluence. The results of fuel temperature and fast neutron fluence show that the volumetric strain is more obviously affected by the fuel temperature. Specifically, the plastic strain of the assembly with 25% enrichment is approximately 40% higher than that of the assembly with 15% enrichment.ConclusionThe analysis results of this study suggest that the assembly with a higher enrichment is more prone to failure.

Blistering usually occurs in plate-type fuels because of the absence of the gap between the cladding and the fuel meat. It can narrow coolant channels and deteriorate the local heat transfer, resulting in the increase of cladding temperature and plastic deformation, which threatens the integrity of fuel elements. Much research work mainly focuses on the causes of blistering and its effect on fuel elements, while few measures to reduce blistering were proposed. In view of the effect that Cr coating can effectively reduce the ballooning of fuel rod cladding during loss of coolant accident (LOCA), a design to apply Cr coating to plate-type fuels to restrain their blistering was proposed. In order to study the effect of Cr coating on the blistering of plate-type fuel elements, the simulation of a blistering test was conducted based on the MOOSE framework. The material properties of Zr and Cr were added, and the thermal creep, as well as plastic behavior after irradiation hardening was considered according to the characteristics of blistering. In addition, the effect of temperature and thickness of Cr coating on blistering were also analyzed and some important results were obtained. The simulation of the blistering test indicates that the reduction of blistering for the plate-type fuel cladding by Cr coating is not as significant as that of ballooning for the fuel rod cladding. The reason for the difference and the difference between the two phenomena were analyzed. The results also show that due to its low yield stress, Cr coating is likely to enter the plastic stage when the cladding blisters, which cannot effectively prevent the occurrence of blistering. However, owing to the low creep rate of Cr even at a relatively high temperature, the height of blistering can be reduced, and the higher the temperature, the more obvious the reduction effect. Under the premise of keeping the overall thickness of the cladding and the coating unchanged, even if the presence of Cr coating will reduce the thickness of cladding and thus reduce its mechanical strength, it can still effectively reduce the blistering height at high temperatures, and the thicker the coating, the more obvious the reduction effect. Nevertheless, adding Cr coating to the cladding of the original thickness has the most significant effect. From the results above, the main conclusion can be drawn: The thin coating can hardly affect the overall mechanical properties of the cladding, but it can effectively inhibit the creep, thereby reducing the blistering height.

The development and application of machine translation cannot be separated from the evaluation of its quality. Correct evaluation is a correct lead to its development direction, and the translation direction respected by mainstream evaluation can be said to be the development direction of machine translation in research. In this paper, the Transformer model of the multi-head attention mechanism is constructed, and the optimization and improvement schemes in both model architecture and training data are proposed for the mBERT and XLM models to form the XLM-R model. Based on the predictor-evaluator QE model and the pre-trained model-evaluator QE two models, the XLM-R translation quality assessment baseline is proposed. A CLS pooling method is proposed for the baseline system, which ensures similarity at a finer-grained subword level. Meanwhile, the subword similarity scoring index is embodied using a simple splicing method, taking into account the global semantic quality. Simulation experiments are set up to evaluate the quality of translation tasks at the sentence and system levels, respectively. There was a 7.92% improvement in the Pearson correlation coefficient of the model with similarity characterization when compared to the one without the model in the sentence-level QE task development set, which was 0.0379 higher. The model’s translation fluency also showed an increasing trend in the interval of 0.15 to 0.5 with the growth of the manual score, indicating that the model proposed in this paper is effective in baseline system evaluation.

Folded proteins show a high degree of structural order and undergo (fairly constrained) collective motions related to their functions. On the other hand, intrinsically disordered proteins (IDPs), while lacking a well-defined three-dimensional structure, do exhibit some structural and dynamical ordering, but are less constrained in their motions than folded proteins. The larger structural plasticity of IDPs emphasizes the importance of entropically driven motions. Many IDPs undergo function-related disorder-to-order transitions driven by their interaction with specific binding partners. As experimental techniques become more sensitive and become better integrated with computational simulations, we are beginning to see how the modest structural ordering and large amplitude collective motions of IDPs endow them with an ability to mediate multiple interactions with different partners in the cell. To illustrate these points, here, we use Prostate-associated gene 4 (PAGE4), an IDP implicated in prostate cancer (PCa) as an example. We first review our previous efforts using molecular dynamics simulations based on atomistic AWSEM to study the conformational dynamics of PAGE4 and how its motions change in its different physiologically relevant phosphorylated forms. Our simulations quantitatively reproduced experimental observations and revealed how structural and dynamical ordering are encoded in the sequence of PAGE4 and can be modulated by different extents of phosphorylation by the kinases HIPK1 and CLK2. This ordering is reflected in changing populations of certain secondary structural elements as well as in the regularity of its collective motions. These ordered features are directly correlated with the functional interactions of WT-PAGE4, HIPK1-PAGE4 and CLK2-PAGE4 with the AP-1 signaling axis. These interactions give rise to repeated transitions between (high HIPK1-PAGE4, low CLK2-PAGE4) and (low HIPK1-PAGE4, high CLK2-PAGE4) cell phenotypes, which possess differing sensitivities to the standard PCa therapies, such as androgen deprivation therapy (ADT). We argue that, although the structural plasticity of an IDP is important in promoting promiscuous interactions, the modulation of the structural ordering is important for sculpting its interactions so as to rewire with agility biomolecular interaction networks with significant functional consequences.

This study aimed to investigate radiation safety in patients with ureteral stent implantation undergoing radiotherapy. We enrolled 15 patients with ureteral stents undergoing postoperative radiotherapy for cervical cancer at the Chongqing University Cancer Hospital from November 2016 to April 2018. Computed tomography localization, target delineation, and radiotherapy planning were performed. The treatment group was the stent group, and the control group was the stent-free group. The high radiodensity HU value of ureteral stents on computed tomography was replaced by liquid radiodensity using density-filling technology, and the stent-free group was optimized with the same parameters. The Monte Carlo method was used to calculate the γ passing rate of the planning target volume and organs at risk (OARs). The conformal index, homogeneity index, and OAR receiver were compared between the two groups. The results showed that the γ passing rate of both groups met the clinical requirements. The target conformal index results were 0.88±0.03 and 0.90±0.03 in the stent and stent-free groups, respectively (p0.05). D2%, D98%, Dmean, and OARs in the stenting group were significantly higher than those in the stent-free group, and only the small intestine and ureter showed significant differences (p

Objective To determine if the cardiac function and "endocrinium" of Chinese patients are associated with dopamine D2 (DRD2) (rs6276) and DRD3 (rs6280, rs963468) genetic polymorphisms when treated with amisulpride. Methods This study enrolled 148 patients with schizophrenia who took amisulpride orally for 8 weeks. DRD2 (rs6276) and DRD3 (rs6280, rs963468) genetic polymorphisms were detected with TaqMan-MGB allelic discrimination. Results Analysis by multivariate covariance analysis (MANCOVA) showed that after adjusting for age, gender, and the baseline level, the increase in the level of aspartate aminotransferase (AST) and creatine kinase (CK) in the rs6276 AG group was higher than that in the AA and GG groups. Similarly, the changed estradiol (E2) level in rs6276 GG and rs963468 GG groups was higher than that in the other two groups. Adjusting for covariates, the increased triglyceride (TG) level in rs6276 GG and rs963468 GG groups was the highest among their different genotype groups. The increase in the level of "AST" in the rs6280 TT group was higher than that in the CC and CT groups upon adjusting for covariates. Similarly, MANCOVA showed that the increase in the level of "CK" in the rs6280 CT group was higher than that in the CC and CT groups. Besides, the increased level of "PRL" in the rs6280 CC group and rs963468 GG group was higher than that in their other two genotypes groups. ConclusionDRD2 (rs6276) and DRD3 (rs6280, rs963468) polymorphisms can affect amisulpride tolerability since they are associated with the observed adverse reactions, including cardiac dysfunction and endocrine disorders in Chinese patients with schizophrenia. [ABSTRACT FROM AUTHOR]