The Influence of Various Structure Surface Boundary Conditions on Pressure Characteristics of Underwater Explosion

The shock wave of the underwater explosion can cause severe damage to the ship structure.The propagation characteristics of shock waves near the structure surface are complex,involving lots of complex phenomena such as reflection,transmission,diffraction,and cavitation.However,different structure surface boundaries have a significant effect on the propagation characteristics of pressure.This paper focuses on investigating the behavior of shock wave propagation and cavitation from underwater explosions near various structure surfaces.A coupled Runge–Kutta discontinuous Galerkin(RKDG)and finite elementmethod(FEM)is utilized to solve the problem of the complex waves of fluids and structure dynamic response,considering the fluid compressibility.The level set(LS)method and the ghost fluid(GF)method are combined to capture the moving interface and deal with the stability of the coupling between the shock wave and structure surface.Besides,a cut-off cavitation model is introduced to the RKDG method.The validation of the numerical calculation model is discussed by comparing it with the known solution to verify the numerical solutions.Then,crucial kinds of structure surface boundary conditions include shallow-water single layer elasticity plate,double-layer crevasse elasticity plate,single layer curved elasticity plate,and double-layer curved elasticity plates are analyzed and discussed.The results and analysis can provide references for underwater explosion pressure characteristics,the impacting response of different boundary structures,and designing structures.

Human adipose, placenta, and umbilical cord-derived mesenchymal stem cells ameliorate imiquimod-induced psoriatic mice via reducing T cells infiltration

Psoriasis is an autoimmune-related chronic inflammatory disease with an approximate prevalence of 2–3%around the world,involving increased keratinocyte proliferation.Indeed,Th17 cells and IL-17 play critical roles in the pathogenesis of psoriasis.The monoclonal antibodies against cytokines have been shown to have effectively immunosuppressive effects on human psoriasis.However,there are still some patients that have no response to these treatments.Some patients have even serious side-effects which may affect their life.Mesenchymal stem cells have the ability of immunosuppressive and anti-inflammatory effects,which may be an alternative therapy with more safety and efficacy for human psoriasis.Moreover,the underlying mechanisms by which the MSCs prevent or ameliorate psoriasis are still poorly understood.Here,we first isolated and characterized human adipose,placenta,and umbilical cord-derived mesenchymal stem cells(haMSCs,hpMSCs,and huMSCs).After that,the animal model of imiquimod(IMQ)-induced psoriasis in C57BL/6 mice was confirmed.We investigated the impact of haMSCs,hpMSCs,and huMSCs on this model by H&E staining,immunohistochemistry staining,and quantitative real-time PCR.Data analysis showed that mice subcutaneously injected with these MSCs had a significantly decreased epidermal thickness,which was caused by obviously reduced hyper-proliferation of keratinocytes.Furthermore,our findings revealed that the infiltration of T cells to psoriatic lesions in IMQ-induced psoriasis mice was markedly downregulated by intradermal administration of haMSCs,hpMSCs,and huMSCs,respectively.Consequently,the production of IL-17 from Th17 cells was reduced,which inhibits the proliferation of keratinocytes in lesioned skin of IMQ-induced psoriasis mice.These data suggest that haMSCs,hpMSCs,and huMSCs can inhibit the effects of proinflammatory Th17 cells on the development of psoriasis,which may be potential therapeutic candidates for skin inflammatory disease or other autoimmune diseases.

神经网络宽度对燃烧室排放预测的影响

为研究神经网络宽度对航空发动机燃烧室排放预测的影响,基于录取的全环燃烧室排放试验数据,构建了以燃烧室进口空气温度、进口空气压力、供油流量和油气比为输入,CO和NOx排放指数为输出的神经网络预测模型,确定了最优网络宽度。结果表明,存在一个最优的网络宽度值,使得神经网络预测模型的拟合优度和预测精度达到最佳,本文最优的网络宽度为24。通过拟合优度、误差分析和敏感性分析验证了构建的神经网络模型的准确性和泛化性。基于最优网络宽度的神经网络预测模型能够很好地挖掘输入参数与排放指数之间的映射关系,可作为给定工况参数下燃烧室排放预测工具。最后,基于敏感性分析,结合燃烧物理机理和试验现象对构建的神经网络可解释性进行了探讨。

An Early-Stop Adjoint Transient Sensitivity Analysis Method for Objective Functions Associated with Many Time Points

Transient sensitivity analysis aims to obtain the gradients of objective functions(circuit performance)with respect to design or variation parameters in a simulator,which can be widely used in yield analysis and circuit optimization,among others.However,the traditional method has a computational complexity of O(N^(2))for objective functions containing circuit states at N time points.The computational complexity is too expensive for large N,especially in time-frequency transform.This paper proposes a many-time-point sensitivity method to reduce the computational complexity to O(N)in multiparameter many-time-point cases.The paper demonstrates a derivation process that improves efficiency by weighting the transfer chain and multiplexing the backpropagation process.We also proposed an early-stop method to improve efficiency further under the premise of ensuring accuracy.The algorithm enables sensitivity calculation of performances involving thousands of time points,such as signal-to-noise and distortion ratio and total harmonic distortion,with significant speed improvements.

PML–LRIF1 interactions form a novel link between promyelocytic leukemia bodies and centromeres

Dear Editor,Promyelocytic leukemia(PML)is the scaffold protein that organizes PML bod-ies,which are nuclear membraneless organelles involved in various biologi-cal processes,including tumor suppres-sion and antiviral responses(Ugge et al.,2022).Early electron microscopic analy-ses revealed contacts between the sur-face of PML bodies and chromatin struc-ture(Corpet et al.,2020).In fact,sev-eral chromatin and cell cycle regulators,such as TIP60,P300,and heterochro-matin protein 1(HP1),are localized in PML bodies in interphase cells(Corpet et al.,2020).

不同参数精子顶体酶活性与精子在IVF治疗中受精能力的关系研究

目的探讨不同参数精子的顶体酶活性与精子在体外受精(IVF)治疗中受精能力的关系。方法通过对75 例接受IVF或短时IVF治疗的少弱精子或正常精子病例进行术前精子顶体酶活性测定,不明原因和有受精不良史病例优先入组。比较顶体酶正常值组和低值组的精子参数差异和IVF受精结果;进一步比较精子高浓度组(>35×10^6/mL)和低浓度组[(10-35)×10^6/mL]的顶体酶活性值差异和IVF受精结果。结果顶体酶活性正常值组和低值组的精子浓度分别为(61.88±35.95)×10^6/mL和(32.89±12.94)×10^6/mL,两者差异具统计学意义(P<0.01),前向运动精子百分率分别为(48.76±12.60)%和(36.35±10.30)%,差异无统计学意义(P>0.05),快速前向运动精子百分率分别为(22.41 ±7.02)%和(16.35+5.23)%,差异无统计学意义(P>0.05), IVF或短时IVF总受精率分别为67.65%和41.74%,两者差异具统计学意义(P<0.01),不受精率分别为19.51%和38.24%,差异无统计学意义(P>0.05),低受精率0%VS14.71%(P<0.05)。精子高浓度组和低浓度组的精子顶体酶活性值分别为(76.55+32.65) VS (43.17±19.68)(M0.01), IVF或短时IVF总受精率 70.65% VS41.20%(P<0.01),不受精比例 17.95%(7/39) VS 3&89%(14/36)(P>0.05),低受精比例 0%(0/39)VS 13.89%(5/36)(P<0.05)。精子高浓度组完全不受精病例卵子数均大于6枚,没有低受精病例,顶体酶异常占12.8%(5/39),其中只有1例不受精;而精子低浓度组完全不受精病例大部分卵子数少于6枚,顶体酶异常占80.56%(29/36),其中不受精和低受精率为58.62%(17/29)。结论在IVF治疗中,粗子浓度与受精能力的相关性比活动力和顶体酶活性更强;在低浓度组通常伴有顶体酶活性的低下,提示低受精或不受精可能性增大;而高浓度精子顶体酶大多正常,呈现“全”或“无”的受精模式,其不受精原因可能与顶体酶活性无关。

Aurora B kinase activation requires survivin priming phosphorylation by PLK1

During cell division,chromosome segregation is orchestrated by the interaction of spindle microtubules with the centromere.Accurate attachment of spindle microtubules to kinetochore requires the chromosomal passenger of Aurora B kinase complex with borealin,INCENP and survivin(SUR).The current working model argues that SUR is responsible for docking Aurora B to the centromere whereas its precise role in Aurora B activation has been unclear.Here,we show that Aurora B kinase activation requires SUR priming phosphorylation at Ser20 which is catalyzed by polo-like kinase 1(PLK1).Inhibition of PLK1 kinase activity or expression of non-phosphorylatable SUR mutant prevents Aurora B activation and correct spindle microtubule attachment.The PLK1-mediated regulation of Aurora B kinase activity was examined in real-time mitosis using fluorescence resonance energy transfer-based reporter and quantitative analysis of native Aurora B substrate phosphorylation.We reason that the PLK1-mediated priming phosphorylation is critical for orchestrating Aurora B activity in centromere which is essential for accurate chromosome segregation and faithful completion of cytokinesis.

The Growth of China’s Private Sector: A Case Study of Zhejiang Province

Private capital is one of the main driving forces in China's initiatives towards stimulating the market economy. The development of private economy in China has always been based on integrating industrial and corporate structures with product composition and market structures. This paper explores the development of the private economy and how it integrates different industries with specific markets by analyzing the leading private sector in Zhejiang province. It also examines the trends of industrial cluster, the formation of the agglomerative economy and their effects on private economy development. Finally, the paper explains why Zhejiang people have profited much from the Wenzhou model and discusses some existing problems and future possibilities for development of the Wenzhou model.

Phosphorylation of CENP-R by Aurora B regulates kinetochore-microtubule attachment for accurate chromosome segregation

Error-free mitosis depends on accurate chromosome attachment to spindle microtubules via a fine structure called the centromere that is epigenetically specified by the enrichment of CENP-A nucleosomes.Centromere maintenance during mitosis requires CENP-A-mediated deposition of constitutive centromere-associated network that establishes the inner kinetochore and connects centromeric chromatin to spindle microtubules during mitosis.Although previously proposed to be an adaptor of retinoic acid receptor,here,we show that CENP-R synergizes with CENP-OPQU to regulate kinetochore-microtubule attachment stability and ensure accurate chromosome segregation in mitosis.We found that a phospho-mimicking mutation of CENP-R weakened its localization to the kinetochore,suggesting that phosphorylation may regulate its localization.Perturbation of CENP-R phosphorylation is shown to prevent proper kinetochore-microtubule attachment at metaphase.Mechanistically,CENP-R phosphorylation disrupts its binding with CENP-U.Thus,we speculate that Aurora B-mediated CENP-R phosphorylation promotes the correction of improper kinetochore-microtubule attachment in mitosis.As CENP-R is absent from yeast,we reasoned that metazoan evolved an elaborate chromosome stability control machinery to ensure faithful chromosome segregation in mitosis.

Modeling of COVID-19 disease disparity in gastric organoids reveals the spatiotemporal dynamics of SARS-CoV-2 infectivity

Dear Editor,The promptness and continuous expansion of the coronavirus disease 2019(COVID-19)pandemic,elicited by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)and its variants,has presented an unprecedented impact on human health(WHO Coronavirus(COVID-19)Dashboard,2021).Although vaccination has attenuated the severe symptoms,there is no specific antiviral medication available for preventing the viral spread(Drayman et al.,2021).

Building a Post-Layout Simulation Performance Model with Global Mapping Model Fusion Technique

Building a post-layout simulation performance model is essential in closing the loop of analog circuits, but it is a challenging task because of the high-dimensional space and expensive simulation cost. To facilitate efficient modeling, this paper proposes a Global Mapping Model Fusion(GMMF) technique. The key idea of GMMF is to reuse the schematic-level model trained by the Artificial Neural Network(ANN) algorithm, and combine it with few mapping coefficients to build the post-simulation model. Furthermore, as an efficient global optimization algorithm,differential evolution is applied to determine the optimal mapping coefficients with few samples. In GMMF, only a small number of mapping coefficients are unknown, so the number of post-layout samples needed is significantly reduced. To enhance practical utility of the proposed GMMF technique, two specific mapping relations, i.e., linear or weakly no-linear and nonlinear, are carefully considered in this paper. We conduct experiments on two topologies of two-stage operational amplifier and comparator in different commercial processes. All the simulation data for modeling are obtained from a parametric design framework. A more than 5 runtime speedup is achieved over ANN without surrendering any accuracy.

Diverse bacterial populations of PM_(2.5) in urban and suburb Shanghai,China

Airborne bacteria play key roles in terrestrial and marine ecosystems and human health,yet our understanding of bacterial communities and their response to the environmental variables lags significantly behind that of other components of PM_(2.5).Here,atmospheric fine particles obtained from urban and suburb Shanghai were analyzed by using the qPCR and Illumina Miseq sequencing.The bacteria with an average concentration of 2.12× 10^(3 )cells/m^(3),were dominated by Sphingomonas,Curvibacter,Acinetobacter,Bradyrhizobium,Methylobacterium,Halomonas,Aliihoeflea,and Phyllobacterium,which were related to the nitrogen,carbon,sulfur cycling and human health risk.Our results provide a global survey of bacterial community across urban,suburb,and high-altitude sites.In Shanghai(China),urban PM2.5 harbour more diverse and dynamic bacterial populations than that in the suburb.The structural equation model explained about 27%,41%,and 20%^78%of the variance found in bacteria diversity,concentration,and discrepant genera among urban and suburb sites.This work furthered the knowledge of diverse bacteria in a coastal Megacity in the Yangtze river delta and emphasized the potential impact of environmental variables on bacterial community structure.

Protein phosphatase 6 (Pp6) is crucial for regulatory T cell function and stability in autoimmunity

Regulatory T(T_(reg))cells constitute a dynamic population that is critical in autoimmunity.T_(reg) cell therapies for autoimmune diseases are mainly focused on enhancing their suppressive activities.However,recent studies demonstrated that certain inflammatory conditions induce T_(reg) cell instability with diminished FoxP3 expression and convert them into pathogenic effector cells.Therefore,the identification of novel targets crucial to both T_(reg) cell function and plasticity is of vital importance to the development of therapeutic approaches in autoimmunity.In this study,we found that conditional Pp6 knockout(cKO)in T_(reg) cells led to spontaneous autoinflammation,immune cell activation,and diminished levels of FoxP3 in CD4^(+)T cells in mice.Loss of Pp6 in T_(reg) cells exacerbated two classical mouse models of T_(reg)-related autoinflammation.Mechanistically,Pp6 deficiency increased CpG motif methylation of the FoxP3 locus by dephosphorylating Dnmt1 and enhancing Akt phosphorylation at Ser473/Thr308,leading to impaired FoxP3 expression in T_(reg) cells.In summary,our study proposes Pp6 as a critical positive regulator of FoxP3 that acts by decreasing DNA methylation of the FoxP3 gene enhancer and inhibiting Akt signaling,thus maintaining T_(reg) cell stability and preventing autoimmune diseases.

Aurora B promotes the CENP-T–CENP-W interaction to guide accurate chromosome segregation in mitosis

Accurate chromosome segregation in mitosis depends on kinetochores that connect centromeric chromatin to spindle microtubules.Centromeres are captured by individual microtubules via a kinetochore constitutive centromere-associated network(CCAN)during chromosome segregation.CCAN contains 16 subunits,including CENP-W and CENP-T.However,the molecular recognition and mitotic regulation of the CCAN assembly remain elusive.Here,we revealed that CENP-W binds to the histone fold domain and an uncharacterized N-terminal region of CENP-T.Aurora B phosphorylates CENP-W at threonine 60,which enhances the interaction between CENP-W and CENP-T to ensure robust metaphase chromosome alignment and accurate chromosome segregation in mitosis.These findings delineate a conserved signaling cascade that integrates protein phosphorylation with CCAN integrity for the maintenance of genomic stability.

Sgo1 interacts with CENP-A to guide accurate chromosome segregation in mitosis

Shugoshin-1(Sgo1)is necessary for maintaining sister centromere cohesion and ensuring accurate chromosome segregation during mitosis.It has been reported that the localization of Sgo1 at the centromere is dependent on Bub1-mediated phosphorylation of histone H2A at T120.However,it remains uncertain whether other centromeric proteins play a role in regulating the localization and function of Sgo1 during mitosis.Here,we show that CENP-A interacts with Sgo1 and determines the localization of Sgo1 to the centromere during mitosis.Further biochemical characterization revealed that lysine and arginine residues in the C-terminal domain of Sgo1 are critical for binding CENP-A.Interestingly,the replacement of these basic amino acids with acidic amino acids perturbed the localization of Sgo1 and Aurora B to the centromere,resulting in aberrant chromosome segregation and premature chromatid separation.Taken together,these findings reveal a previously unrecognized but direct link between Sgo1 and CENP-A in centromere plasticity control and illustrate how the Sgo1–CENP-A interaction guides accurate cell division.

Organization of microtubule plus-end dynamics by phase separation in mitosis

In eukaryotes,microtubule polymers are essential for cellular plasticity and fate decisions.End-binding(EB)proteins serve as scaffolds for orchestrating microtubule polymer dynamics and are essential for cellular dynamics and chromosome segregation in mitosis.Here,we show that EB1 forms molecular condensates with TIP150 and MCAK through liquid–liquid phase separation to compartmentalize the kinetochore–microtubule plus-end machinery,ensuring accurate kinetochore–microtubule interactions during chromosome segregation in mitosis.Perturbation of EB1–TIP150 polymer formation by a competing peptide prevents phase separation of the EB1-mediated complex and chromosome alignment at the metaphase equator in both cultured cells and Drosophila embryos.Lys220 of EB1 is dynamically acetylated by p300/CBP-associated factor in early mitosis,and persistent acetylation at Lys220 attenuates phase separation of the EB1-mediated complex,dissolves droplets in vitro,and harnesses accurate chromosome segregation.Our data suggest a novel framework for understanding the organization and regulation of eukaryotic spindle for accurate chromosome segregation in mitosis.

CSPP1 stabilizes microtubules by capping both plus and minus ends

Although the dynamic instability of microtubules(MTs)is fundamental to many cellular functions,quiescent MTs with unattached free distal ends are commonly present and play important roles in various events to power cellular dynamics.However,how these free MT tips are stabilized remains poorly understood.Here,we report that centrosome and spindle pole protein 1(CSPP1)caps and stabilizes both plus and minus ends of static MTs.Real-time imaging of laser-ablated MTs in live cells showed deposition of CSPP1 at the newly generated MT ends,whose dynamic instability was concomitantly suppressed.Consistently,MT ends in CSPP1-overexpressing cells were hyper-stabilized,while those in CSPP1-depleted cells were much more dynamic.This CSPP1-elicited stabilization of MTs was demonstrated to be achieved by suppressing intrinsic MT catastrophe and restricting polymerization.Importantly,CSPP1-bound MTs were resistant to mitotic centromere-associated kinesin-mediated depolymerization.These findings delineate a previously uncharacterized CSPP1 activity that integrates MT end capping to orchestrate quiescent MTs.