On the Judgement of Full-Period Sequences and a Novel Congruential Map with Double Modulus on Z(p^n)

This paper studies the judgement problem of full-period maps on Z(p^n) and proposes a novel congruential map with double modulus on Z(p^n). The full-period properties of the sequences generated by the novel map are studied completely. We prove some theorems including full-period judgement theorem on Z(p^n) and validate them by some numerical experiments. In the experiments, full-period sequences are generated by a full-period map on Z(p^n). By the binarization, full-period sequences are transformed into binary sequences. Then, we test the binary sequences with the NIST SP 800-22 software package and make the poker test. The passing rates of the statistical tests are high in NIST test and the sequences pass the poker test. So the randomness and statistic characteristics of the binary sequences are good. The analysis and experiments show that these full-period maps can be applied in the pseudo-random number generation(PRNG), cryptography, spread spectrum communications and so on.

Zika virus non-structural protein 4B interacts with DHCR7 to facilitate viral infection

Zika virus(ZIKV)evolves non-structural proteins to evade immune response and ensure efficient replication in the host cells.Cholesterol metabolic enzyme 7-dehydrocholesterol reductase(DHCR7)was recently reported to impact innate immune responses in ZIKV infection.However,the vital non-structural protein and mechanisms involved in DHCR7-mediated viral evasion are not well elucidated.In this study,we demonstrated that ZIKV infection facilitated DHCR7 expression.Notably,the upregulated DHCR7 in turn facilitated ZIKV infection and blocking DHCR7 suppressed ZIKV infection.Mechanically,ZIKV non-structural protein 4B(NS4B)interacted with DHCR7 to induce DHCR7 expression.Moreover,DHCR7 inhibited TANK-binding kinase 1(TBK1)and interferon regulatory factor 3(IRF3)phosphorylation,which resulted in the reduction of interferon-beta(IFN-β)and interferon-stimulated genes(ISGs)productions.Therefore,we propose that ZIKV NS4B binds to DHCR7 to repress TBK1 and IRF3 activation,which in turn inhibits IFN-βand ISGs,and thereby facilitating ZIKV evasion.This study broadens the insights on how viral non-structural proteins antagonize innate immunity to facilitate viral infection via cholesterol metabolic enzymes and intermediates.

SARS-CoV-2 N protein enhances the anti-apoptotic activity of MCL-1 to promote viral replication

Viral infection in respiratory tract usually leads to cell death,impairing respiratory function to cause severe disease.However,the diversity of clinical manifestations of SARS-CoV-2 infection increases the complexity and difficulty of viral infection prevention,and especially the high-frequency asymptomatic infection increases the risk of virus transmission.Studying how SARS-CoV-2 affects apoptotic pathway may help to understand the pathological process of its infection.Here,we uncovered SARS-CoV-2 imployed a distinct anti-apoptotic mechanism via its N protein.We found SARS-CoV-2 virus-like particles(trVLP)suppressed cell apoptosis,but the trVLP lacking N protein didn’t.Further study verified that N protein repressed cell apoptosis in cultured cells,human lung organoids and mice.Mechanistically,N protein specifically interacted with anti-apoptotic protein MCL-1,and recruited a deubiquitinating enzyme USP15 to remove the K63-linked ubiquitination of MCL-1,which stabilized this protein and promoted it to hijack Bak in mitochondria.Importantly,N protein promoted the replications of IAV,DENV and ZIKV,and exacerbated death of IAV-infected mice,all of which could be blocked by a MCL-1 specific inhibitor,S63845.Altogether,we identifed a distinct anti-apoptotic function of the N protein,through which it promoted viral replication.These may explain how SARS-CoV-2 effectively replicates in asymptomatic individuals without cuasing respiratory dysfunction,and indicate a risk of enhanced coinfection with other viruses.We anticipate that abrogating the N/MCL-1-dominated apoptosis repression is conducive to the treatments of SARS-CoV-2 infection as well as coinfections with other viruses.

Hypoxia signaling in human health and diseases:implications and prospects for therapeutics

Molecular oxygen(O2)is essential for most biological reactions in mammalian cells.When the intracellular oxygen content decreases,it is called hypoxia.The process of hypoxia is linked to several biological processes,including pathogenic microbe infection,metabolic adaptation,cancer,acute and chronic diseases,and other stress responses.The mechanism underlying cells respond to oxygen changes to mediate subsequent signal response is the central question during hypoxia.Hypoxia-inducible factors(HIFs)sense hypoxia to regulate the expressions of a series of downstream genes expression,which participate in multiple processes including cell metabolism,cell growth/death,cell proliferation,glycolysis,immune response,microbe infection,tumorigenesis,and metastasis.Importantly,hypoxia signaling also interacts with other cellular pathways,such as phosphoinositide 3-kinase(PI3K)-mammalian target of rapamycin(mTOR)signaling,nuclear factor kappa-B(NF-κB)pathway,extracellular signal-regulated kinases(ERK)signaling,and endoplasmic reticulum(ER)stress.This paper systematically reviews the mechanisms of hypoxia signaling activation,the control of HIF signaling,and the function of HIF signaling in human health and diseases.In addition,the therapeutic targets involved in HIF signaling to balance health and diseases are summarized and highlighted,which would provide novel strategies for the design and development of therapeutic drugs.

MicroRNA-548 down-regulates host antiviral response via direct targeting of IFN-λ1

Interferon(IFN)-mediated pathways are a crucial part of the cellular response against viral infection.Type III IFNs,which include IFN-λ1,2 and 3,mediate antiviral responses similar to Type I IFNs via a distinct receptor complex.IFN-λ1 is more effective than the other two members.Transcription of IFN-λ1 requires activation of IRF3/7 and nuclear factor-kappa B(NF-κB),similar to the transcriptional mechanism of Type I IFNs.Using reporter assays,we discovered that viral infection in-duced both IFN-λ1 promoter activity and that of the 3′-untranslated region(UTR),indicating that IFN-λ1 expression is also regulated at the post-transcriptional level.After analysis with microRNA(miRNA)prediction programs and 3′UTR targeting site assays,the miR-NA-548 family,including miR-548b-5p,miR-548c-5p,miR-548i,miR-548j,and miR-548n,was identified to target the 3′UTR of IFN-λ1.Further study demonstrated that miRNA-548 mimics down-regulated the expression of IFN-λ1.In contrast,their inhibitors,the complemen-tary RNAs,enhanced the expression of IFN-λ1 and IFN-stimulated genes.Furthermore,miRNA-548 mimics promoted infection by enterovirus-71(EV71)and ve-sicular stomatitis virus(VSV),whereas their inhibitors significantly suppressed the replication of EV71 and VSV.Endogenous miRNA-548 levels were suppressed during viral infection.In conclusion,our results sug-gest that miRNA-548 regulates host antiviral response via direct targeting of IFN-λ1,which may offer a poten-tial candidate for antiviral therapy.

Hepatitis B virus X protein suppresses virus-triggered IRF3 activation and IFN-β induction by disrupting the VISA-associated complex

Viral RNAs produced during viral infection are recognized by the cytoplasmic RNA helicases retinoic acid-inducible gene-I(RIG-I)and melanoma differentiation-associated gene 5(MDA5).A central adapter protein downstream of RIG-I and MDA5 is the mitochondrial membrane protein virus-induced signaling adaptor(VISA),which mediates the induction of type I interferons(IFNs)through the activation of transcription factors such as nuclear factor-kappaB(NF-kB)and IFN-regulatory factor-3(IRF3).Here we found that hepatitis B virus(HBV)-encoded X protein(HBx)acts as an inhibitor of virus-triggered IRF3 activation and IFN-b induction.Reporter and plaque assays indicate that HBx inhibits signaling by components upstream but not downstream of VISA.Immunoprecipitation experiments indicate that HBx interacts with VISA and disrupts the association of VISA with its upstream and downstream components.These findings suggest that HBx acts as a suppressor of virus-triggered induction of type I IFNs,which explains the observation that HBV causes transient and chronic infection in hepatocytes but fails to activate the pattern recognition receptor-mediated IFN induction pathways.

HIF-1α promotes SARS-CoV-2 infection and aggravates inflammatory responses to COVID-19

Cytokine storm induced by Severe Acute Respiratory Syndrome Coronavirus 2(SARS-CoV-2)is a major pathological feature of Coronavirus Disease 2019(COVID-19)and a crucial determinant in COVID-19 prognosis.Understanding the mechanism underlying the SARS-CoV-2-induced cytokine storm is critical for COVID-19 control.Here,we identify that SARS-CoV-2 ORF3a and host hypoxia-inducible factor-1α(HIF-1α)play key roles in the virus infection and pro-inflammatory responses.

Grasping institutional complexity in infrastructure megaprojects through the multi-level governance system： A case study of the Hong Kong-Zhuhai-Macao Bridge construction

This study analyzes the design and operation of multi-level governance system for the smooth delivery of infrastructure mega-projects with high institutional complexity caused by market transition. From an institutional perspective, this study scrutinizes the structure,elements, and dynamics of the governance system of infrastructure mega-projects and then proposes an integrative framework based on the inductive case study of the Hong Kong-Zhuhai-Macao Bridge mega-project. Multiple evidences of archives, field studies, and interviews related to the case project are triangulated to further analyze the institutional effects, specifically those with government logics and market structures, on the design and operation of the three-level governance system. Results reveal that the co-evolution between governments and markets in China has shaped the vertical levels of the mega-project governance system and has further affected their evolution and operation across various stages of project development. This study contributes to the rapidly emerging research on complex system governance by proposing a systematic model of three-level mega-project governance to enhance the timely delivery of infrastructure megaprojects within budget.

Microstructure and Mechanical Properties of Simulated Heat-affected Zones of EP-823 Steel for ADS/LFR

EP-823 steel is one of the candidate materials for accelerator-driven systems/lead-cooled fast reactors （ADS/LFR）. Its weldability was investigated by mechanical property tests and microstructure analysis on the enlarged heat-affected zones （HAZs） made by numerical and physical simulation. The finite element numerical simulation could simulate the welding thermal cycle of the characteristic regions in HAZs with extremely high accuracy, The physical simulation performed on a Gleeble simulator could enlarge the characteristic regions to easily investigate the relationship between the microstructure evolution and the mechanical properties of the HAZs. The results showed that the simulated partially normalized zone comprising tempered martensite, newly formed martensite and more tiny carbides has the highest impact energy. The fully normalized zone exhibits the highest hardness because of the quenched martensite and large carbides. The ductile property of the overheated zone is poor for the residual delta- ferrite phases and the quenched martensite.

Impact Toughness of Heat-Affected Zones of 11Cr Heat-Resistant Steels

Aiming at the requirements of structural steel in Gen-IV nuclear reactor, the high-chromium martensitic heat-resistant steels containing 10–12% chromium were developed. The toughness of heat-affected zones(HAZs) is one of the important factors for evaluating the weldability of steels. In this paper, the simulated HAZs were fabricated using tempered SIMP steels. The effects of microstructures on the impact toughness of materials were analyzed using Vickers hardness tester, optical microscope, transmission electron microscope. Experimental results demonstrated that the HAZs of weldment were poor in toughness, much lower than that of the base metal. However, after experiencing post-weld heat treatment, the toughness of the HAZs increased greatly. The toughness became better in terms of CG-HAZ, FG-HAZ and IC-HAZ for the two steels, regardless of as-welded or after PWHT. Compared with SIMP7 steel, chemical compositions, such as C, Si, Mn and Cr, were adjusted to a lower content;the toughness of base metal and simulated HAZs was better in the case of SIMP11. The conjunct roles of dislocation density and carbon contents retained in the martensite led to poor impact toughness of the aswelded HAZs, because dislocations and carbon atoms affected the inner stresses within lattices.

Project management maturity in construction consulting services: Case of Expo in China

For many years,project management maturity models(PMMM)derived from the software industry have brought immeasurable benefits.However,the adoption and investigation of PMMM in the construction field have been weak and insufficient,particularly in construction consulting services(CCS).Moreover,professionals have gradually realized the importance of non-process factors(e.g.,teamwork,culture,leadership)in the evaluation of PMMM.This study describes the construction of PMMM for CCS that considers non-process factors and combines them with CCS-specific process factors.To verify the effectiveness of the proposed model,we conduct a case study on the overall project management consultancy for China’s 2010 Winter Expo.The results would fill in the PMMM research gap in CCS and provide practitioners with ideas to improve their performance.