ASYMPTOTIC NORMALITY OF PARAMETERSESTIMATION IN EV MODEL WITH REPLICATEDOBSERVATIONS

This paper based on the essay [1], studies in case that replicated observations are available in some experimental points., the parameters estimation of one dimensional linear errors-in-variables (EV) models. Asymptotic normality is established.

Convergence Rate of Empirical Bayes for Two-parameter Exponential Distribution with Replicated Data

In this paper, empirical Bayes test for a parameter θ of two-parameter exponential distribution is investigated with replicated past data. Under some conditions, the asymptotically optimal property is obtained. It is indicated that the rate of convergence can be very close to O（N-2^-1） in this case that a parameter μ is known.

An analysis of quantitative PCR reliability through replicates using the C_(t)method

There is considerable interest in quantitatively measuring nucleic acids from single cells to small populations. The most commonly employed laboratory method is the real-time polymerase chain reaction (PCR) analyzed with the crossing point or crossing threshold (Ct) method. Utilizing a multiwell plate reader we have performed hundreds of replicate reactions each at a set of initial conditions whose initial number of copies span a concentration range of ten orders of magnitude. The resultant Ct value distributions are analyzed with standard and novel statistical techniques to assess the variability/reliability of the PCR process. Our analysis supports the following conclusions. Given sufficient replicates, the mean and/or median Ct values are statistically distinguishable and can be rank ordered across ten orders of magnitude in initial template concentration. As expected, the variances in the Ct distributions grow as the number of initial copies declines to 1. We demonstrate that these variances are large enough to confound quantitative classi?cation of the initial condition at low template concentrations. The data indicate that a misclassi?cation transition is centered around 3000 initial copies of template DNA and that the transition region correlates with independent data on the thermal wear of the TAQ polymerase enzyme. We provide data that indicate that an alternative endpoint detection strategy based on the theory of well mixing and plate ?lling statistics is accurate below the mis- classi?cation transition where the real time method becomes unreliable.

A New Primary Lazy Update Propagation Protocol for Replicated Databases

This paper proposes a new primary lazy update protocol, PTCS （Primary Transaction Commit Schedule）. In the PTCS protocol, a serializable primary transaction schedule is generated firstly and then the secondary transactions are committed according to the serializable primary transaction schedule. PTCS protocol can guarantee serializability if the data copy graph contains no directed circles. It can also be ex tended to eliminate all requirements on the data copy graph. Compared to earlier works, PTCS protocol not only imposes a much weaker requirement on the data placement, but also avoids the deadlock caused by transaction waits and extra message overhead. The performance experiments show that the degradation of the performance caused by the replica man- agement of the PTCS protocol is tolerable.

Replicated association of the single nucleotide polymorphism in PNLIP with marbling in Niigata population of Japanese Black beef cattle

Marbling is regarded as an economically important trait of beef cattle inJapan, and measured as a beef marbling score (BMS). Our previous study reported an association between a single nucleotide polymorphism (SNP), rs4164 8172, in the pancreatic lipase (PNLIP) gene and the BMS level, using the Japanese Black beef cattle population of Oita prefecture. Further, we showed that the T allele at the rs41648172 SNP is associated with a high level of the BMS. Thus, we suggested that the rs41648172 SNP seems to be a candidate marker for marker-assisted selection. Our present study was designed to investigate whether this association could be replicated in other independent Japanese Black cattle population and analyze the effect of the SNP genotypes on the carcass traits other than the BMS. We detected the marginally significant effect of the genotypes of the rs41648172 SNP on the BMS level by using the Japanese Black beef cattle population of Niigata prefecture (P = 0.0919), and obtained the result of the T allele associated with an increase in the BMS level, consistent with our previous data. In addition, we showed no significant association of the SNP with the subcutaneous fat thickness, carcass weight, rib eye area, rib thickness and yield estimate in the Japanese Black beef cattle population ofNiigataprefecture. Thus, we concluded that the rs41648172 SNP was useful for effective marker-assisted selection to increase the BMS level in Japanese Black beef cattle, based on the replicated association of the rs41648172 SNP with the BMS level in the other independent Japanese Black beef cattle population and no effect of the SNP genotypes on the carcass traits other than BMS.

No replicated association of the c.-312A >G in<i>EDG</i>1 with marbling in Niigata population of Japanese Black beef cattle

Marbling, defined by the amount and the distribution of intramuscular fat and measured as beef marbling score (BMS), is an economically important trait of beef cattle in Japan. We recently reported that a single nucleotide polymorphism (SNP), namely, c.-312A > G, in the endothelial differentiation sphingolipid G-proteincoupled receptor, 1 (EDG1) gene was associated with the BMS level in the Japanese Black beef cattle population of Oita prefecture, with the G allele being associated with a high level of the BMS. Thus, the c.-312A > G SNP seems to be a candidate marker for marker-assisted selection. In this study, we investigated whether this association could be replicated in the Japanese Black beef cattle population of Niigata prefecture and analyzed the effect of the SNP genotypes on the carcass traits other than the BMS. No significant differences in the BMS level were detected among the genotypes of the c.-312A > G SNP in the Niigata Japanese Black beef cattle population. The SNP genotype had no significant effects on the carcass weight, rib eye area and rib thickness of the cattle population. These findings suggested that the association of the c.-312A > G SNP with the BMS level in the Japanese Black beef cattle population was not replicated in the Niigata population, and revealed no effects of the SNP genotype on the beef productivity in the Niigata population. Thus, we concluded that the c.-312A > G SNP is not useful for effective marker-assisted selection to increase meat quality and, additionally, meat productivity in Japanese Black beef cattle of Niigata prefecture.

Estimation in partial linear EV models with replicated observations

The aim of this work is to construct the parameter estimators in the partial linear errors-in-variables (EV) models and explore their asymptotic properties. Unlike other related References, the assumption of known error covariance matrix is removed when the sample can be repeatedly drawn at each designed point from the model. The estimators of interested regression parameters, and the model error variance, as well as the nonparametric function, are constructed. Under some regular conditions, all of the estimators prove strongly consistent. Meanwhile, the asymptotic normality for the estimator of regression parameter is also presented. A simulation study is reported to illustrate our asymptotic results.

Characterization of the infectivity of an Indonesian Zika virus strain in mammalian cell lines

Objective:To characterize the infection patterns and growth characteristics of the Zika virus(ZIKV)strain JMB-185 from Indonesia in various mammalian cell lines.Methods:ZIKV was grown in human(A549,HEK293,HepG2,Huh7,Jurkat,and THP-1)and non-human mammalian(RAW264.7,Vero,and Vero76)cell lines.Viral replication kinetics were measured using plaque assay,while intra-and extracellular viral RNA concentrations were assessed using RT-PCR.Flow cytometry was used to quantify the infected cells and cell viability was measured using an MTT assay.The ability of ZIKV to infect cell lines was visualized using a fluorescence immunostaining assay.Results:This ZIKV strain preferentially infected the lung,kidney,and liver cell lines A549,HEK293,Huh7,Vero,and Vero76,but not the immune cells Jurkat,RAW264.7,and THP-1.By contrast,the ZIKV showed no sign of infection in HepG2 cells,while maintaining viral titer over 3 days post-infection,with no infection recorded in immunostaining,no increase in viral RNA,and no indication of cell deterioration.Conclusions:The Indonesian ZIKV strain has a similar infection profile as other strains,except for its poor infectivity on HepG2 cells.Information on the growth characteristics of Indonesia ZIKV will help expand our understanding of the biology of ZIKV which will be useful for various applications including antiviral discovery.

Causal genetic regulation of DNA replication on immune microenvironment in colorectal tumorigenesis: Evidenced by an integrated approach of trans-omics and GWAS

The interplay between DNA replication stress and immune microenvironment alterations is known to play a crucial role in colorectal tumorigenesis,but a comprehensive understanding of their association with and relevant biomarkers involved in colorectal tumorigenesis is lacking.To address this gap,we conducted a study aiming to investigate this association and identify relevant biomarkers.We analyzed transcriptomic and proteomic profiles of 904 colorectal tumor tissues and 342 normal tissues to examine pathway enrichment,biological activity,and the immune microenvironment.Additionally,we evaluated genetic effects of single variants and genes on colorectal cancer susceptibility using data from genome-wide association studies(GWASs)involving both East Asian(7062 cases and 195745 controls)and European(24476 cases and 23073 controls)populations.We employed mediation analysis to infer the causal pathway,and applied multiplex immunofluorescence to visualize colocalized biomarkers in colorectal tumors and immune cells.Our findings revealed that both DNA replication activity and the flap structure-specific endonuclease 1(FEN1)gene were significantly enriched in colorectal tumor tissues,compared with normal tissues.Moreover,a genetic variant rs4246215 G>T in FEN1 was associated with a decreased risk of colorectal cancer(odds ratio=0.94,95%confidence interval:0.90–0.97,P_(meta)=4.70×10^(-9)).Importantly,we identified basophils and eosinophils that both exhibited a significantly decreased infiltration in colorectal tumors,and were regulated by rs4246215 through causal pathways involving both FEN1 and DNA replication.In conclusion,this trans-omics incorporating GWAS data provides insights into a plausible pathway connecting DNA replication and immunity,expanding biological knowledge of colorectal tumorigenesis and therapeutic targets.

New insights into ATR inhibition in muscle invasive bladder cancer:The role of apolipoprotein B mRNA editing catalytic subunit 3B

Background:Apolipoprotein B mRNA editing catalytic polypeptide(APOBEC),an endogenous mutator,induces DNA damage and activates the ataxia telangiectasia and Rad3-related(ATR)-checkpoint kinase 1(Chk1)pathway.Although cisplatin-based therapy is the mainstay for muscle-invasive bladder cancer(MIBC),it has a poor survival rate.Therefore,this study aimed to evaluate the efficacy of an ATR inhibitor combined with cisplatin in the treatment of APOBEC catalytic subunit 3B(APOBEC3B)expressing MIBC.Methods:Immunohistochemical staining was performed to analyze an association between APOBEC3B and ATR in patients with MIBC.The APOBEC3B expression in MIBC cell lines was assessed using real-time polymerase chain reaction and western blot analysis.Western blot analysis was performed to confirm differences in phosphorylated Chk1(pChk1)expression according to the APOBEC3B expression.Cell viability and apoptosis analyses were performed to examine the anti-tumor activity of ATR inhibitors combined with cisplatin.Results:There was a significant association between APOBEC3B and ATR expression in the tumor tissues obtained from patients with MIBC.Cells with higher APOBEC3B expression showed higher pChk1 expression than cells expressing low APOBEC3B levels.Combination treatment of ATR inhibitor and cisplatin inhibited cell growth in MIBC cells with a higher APOBEC3B expression.Compared to cisplatin single treatment,combination treatment induced more apoptotic cell death in the cells with higher APOBEC3B expression.Conclusion:Our study shows that APOBEC3B’s higher expression status can enhance the sensitivity of MIBC to cisplatin upon ATR inhibition.This result provides new insight into appropriate patient selection for the effective application of ATR inhibitors in MIBC.

Accurate and efficient follower log repair for Raft-replicated database systems

State machine replication has been widely used in modern cluster-based database systems.Most commonly deployed configurations adopt the Raft-like consensus protocol,which has a single strong leader which replicates the log to other followers.Since the followers can handle read requests and many real workloads are usually read-intensive,the recovery speed of a crashed follower may significantly impact on the throughput.Different from traditional database recovery,the recovering follower needs to repair its local log first.Original Raft protocol takes many network round trips to do log comparison between leader and the crashed follower.To reduce network round trips,an optimization method is to truncate the follower’s uncertain log entries behind the latest local commit point,and then to directly fetch all committed log entries from the leader in one round trip.However,if the commit point is not persisted,the recovering follower has to get the whole log from the leader.In this paper,we propose an accurate and efficient log repair(AELR)algorithm for follower recovery.AELR is more robust and resilient to follower failure,and it only needs one network round trip to fetch the least number of log entries for follower recovery.This approach is implemented in the open source database system OceanBase.We experimentally show that the system adopting AELR has a good performance in terms of recovery time.

Estimation of Parameters of Partially Linear Errors-in-variables Models with Replicated Net Points of Observation

A kind of partially linear errors-in-variables models with replicated net points of observation are studied in this paper. Estimators of unknown parameters are given. Under certain regular conditions, it is shown that the estimators of the unknown parameters are strongly consistent and their a.s. convergence rates are achieved.

Trees species’ dispersal mode and habitat heterogeneity shape negative density dependence in a temperate forest

Conspecific negative density dependence(CNDD)is a potentially important mechanism in maintaining species diversity.While previous evidence showed habitat heterogeneity and species’dispersal modes affect the strength of CNDD at early life stages of trees(e.g.,seedlings),it remains unclear how they affect the strength of CNDD at later life stages.We examined the degree of spatial aggregation between saplings and trees for species dispersed by wind and gravity in four topographic habitats within a 25-ha temperate forest dynamic plot in the Qinling Mountains of central China.We used the replicated spatial point pattern(RSPP)analysis and bivariate paircorrelation function(PCF)to detect the spatial distribution of saplings around trees at two scales,15 and 50 m,respectively.Although the signal was not apparent across the whole study region(or 25-ha),it is distinct on isolated areas with specific characteristics,suggesting that these characteristics could be important factors in CNDD.Further,we found that the gravity-dispersed tree species experienced CNDD across habitats,while for wind-dispersed species CNDD was found in gully,terrace and low-ridge habitats.Our study suggests that neglecting the habitat heterogeneity and dispersal mode can distort the signal of CNDD and community assembly in temperate forests.

College English Listening and Speaking Teaching Guided by Memetics

Memetics confirms the importance of recitation and imitation in college English teaching.Starting with the explanation of the replication cycle of language memes,this paper discusses how to use the memetic perspective in college English listening and speaking teaching,effectively transform the input language information into language output,and improve the classroom effect of college English listening and speaking teaching.

Statistical Method for Block in Replication Design and Its SAS Program

Large-scale genetic population used for genetic breeding researches covers a large area in the field experiment,and the effect of local control would be gradually weakened.The block in replication(BIR)design is suitable for large population,which is applied to the field experiment of genetic population.The statistical methods of analysis of variance(ANOVA)and heritability estimation in single and multiple environments were derived and implemented using the statistical analysis system(SAS)program for the analysis of BIR.As a work example,a comparison of statistical analysis between BIR design and the completely random block(CRB)design were conducted for the protein content from a panel containing 455 soybean germplasms.The results indicated the different estimates of average heritability in multiple environments.The research results provided technical support for the application of BIR design in genetics and breeding studies.

Replication Strategy with Comprehensive Data Center Selection Method in Cloud Environments

As the amount of data continues to grow rapidly,the variety of data produced by applications is becoming more affluent than ever.Cloud computing is the best technology evolving today to provide multi-services for the mass and variety of data.The cloud computing features are capable of processing,managing,and storing all sorts of data.Although data is stored in many high-end nodes,either in the same data centers or across many data centers in cloud,performance issues are still inevitable.The cloud replication strategy is one of best solutions to address risk of performance degradation in the cloud environment.The real challenge here is developing the right data replication strategy with minimal data movement that guarantees efficient network usage,low fault tolerance,and minimal replication frequency.The key problem discussed in this research is inefficient network usage discovered during selecting a suitable data center to store replica copies induced by inadequate data center selection criteria.Hence,to mitigate the issue,we proposed Replication Strategy with a comprehensive Data Center Selection Method(RS-DCSM),which can determine the appropriate data center to place replicas by considering three key factors:Popularity,space availability,and centrality.The proposed RS-DCSM was simulated using CloudSim and the results proved that data movement between data centers is significantly reduced by 14%reduction in overall replication frequency and 20%decrement in network usage,which outperformed the current replication strategy,known as Dynamic Popularity aware Replication Strategy(DPRS)algorithm.

Transcriptional regulation of secondary metabolism and autophagy genes in response to DNA replication stress in Setosphaeria turcica

The fungal pathogen Setosphaeria turcica causes northern corn leaf blight(NCLB),which leads to considerable crop losses.Setosphaeria turcica elaborates a specialized infection structures called appressorium for maize infection.Previously,we demonstrated that the S.turcica triggers an S-phase checkpoint and ATR(Ataxia Telangiectasia and Rad3 related)-dependent self-protective response to DNA genotoxic insults during maize infection.However,how the regulatory mechanism works was still largely unknown.Here,we report a genome wide transcriptional profile analysis during appressorium formation in the present of DNA replication stress.We performed RNA-Seq analysis to identify S.tuicica genes responsive to DNA replication stress.In the current work,we found that appressorium-mediated maize infection by S.turcica is significantly blocked by S-phase checkpoint.A large serial of secondary metabolite and melanin biosynthesis genes were blocked in appressorium formation of S.turcica during the replication stress.The secondary metabolite biosynthesis genes including alcohol dehydrogenase GroES-like domain,multicopper oxidase,ABCtransporter families,cytochrome P450 and FAD-containing monooxygenase were related to plant pathogen infection.In addition,we demonstrated that autophagy in S.turcica is up-regulated by ATR as a defense response to stress.We identified StATG3,StATG4,StATG5,StATG7 and StATG16 genes for autophagy were induced by ATR-mediated S-phase checkpoint.We therefore propose that in response to genotoxic stress,S.turcica utilizes ATR-dependent pathway to turn off transcription of genes governing appressorium-mediated infection,and meanwhile inducing transcription of autophagy genes likely as a mechanism of self-protection,aside from the more conservative responses in eukaryotes.

Comparison of the replication and neutralization of different SARS-CoV-2 Omicron subvariants in vitro

Background:New Omicron subvariants are emerging rapidly from BA.1 to BA.4 and BA.5.Their pathogenicity has changed from that of wild-type(WH-09)and Omicron variants have over time become globally dominant.The spike proteins of BA.4 and BA.5 that serve as the target for vaccine-induced neutralizing antibodies have also changed compared to the previous subvariants,which is likely to cause immune es-cape and the reduction of the protective effect of the vaccine.Our study addresses the above issues and provides a basis for formulating relevant prevention and control strategies.Methods:We collected cellular supernatant and cell lysates and measured the viral titers,viral RNA loads,and E subgenomic RNA(E sgRNA)loads in different Omicron subvariants grown in Vero E6 cells,using WH-09 and Delta variants as a reference.Additionally,we evaluated the in vitro neutralizing activity of different Omicron sub-variants and compared it to the WH-09 and Delta variants using macaque sera with different types of immunity.Results:As the SARS-CoV-2 evolved into Omicron BA.1,the replication ability in vitro began to decrease.Then with the emergence of new subvariants,the replication ability gradually recovered and became stable in the BA.4 and BA.5 subvariants.In WH-09-inactivated vaccine sera,geometric mean titers of neutralization antibodies against different Omicron subvariants declined by 3.7~15.4-fold compared to those against WH-09.In Delta-inactivated vaccine sera,geometric mean titers of neutrali-zation antibodies against Omicron subvariants declined by 3.1~7.4-fold compared to those against Delta.Conclusion:According to the findings of this research,the replication efficiency of all Omicron subvariants declined compared with WH-09 and Delta variants,and was lower in BA.1 than in other Omicron subvariants.After two doses of inactivated(WH-09 or Delta)vaccine,cross-neutralizing activities against various Omicron subvariants were seen despite a decline in neutralizing titers.

RMCARTAM For DDoS Attack Mitigation in SDN Using Machine Learning

The impact of a Distributed Denial of Service(DDoS)attack on Soft-ware Defined Networks(SDN)is briefly analyzed.Many approaches to detecting DDoS attacks exist,varying on the feature being considered and the method used.Still,the methods have a deficiency in the performance of detecting DDoS attacks and mitigating them.To improve the performance of SDN,an efficient Real-time Multi-Constrained Adaptive Replication and Traffic Approximation Model(RMCARTAM)is sketched in this article.The RMCARTAM considers different parameters or constraints in running different controllers responsible for handling incoming packets.The model is designed with multiple controllers to handle net-work traffic but can turn the controllers according to requirements.The multi-con-straint adaptive replication model monitors different features of network traffic like rate of packet reception,class-based packet reception and target-specific reception.According to these features,the method estimates the Replication Turn-ing Weight(RTW)based on which triggering controllers are performed.Similarly,the method applies Traffic Approximation(TA)in the detection of DDoS attacks.The detection of a DDoS attack is performed by approximating the incoming traf-fic to any service and using various features like hop count,payload,service fre-quency,and malformed frequency to compute various support measures on bandwidth access,data support,frequency support,malformed support,route sup-port,and so on.Using all these support measures,the method computes the value of legitimate weight to conclude the behavior of any source in identifying the mal-icious node.Identified node details are used in the mitigation of DDoS attacks.The method stimulates the network performance by reducing the power factor by switching the controller according to different factors,which also reduces the cost.In the same way,the proposed model improves the accuracy of detecting DDoS attacks by estimating the features of incoming traffic in different corners.

A novel method for geometric quality assurance of rock joint replicas in direct shear testing-Part 2:Validation and mechanical replicability

Each rock joint is unique by nature which means that utilization of replicas in direct shear tests is required in experimental parameter studies.However,a method to acquire knowledge about the ability of the replicas to imitate the shear mechanical behavior of the rock joint and their dispersion in direct shear testing is lacking.In this study,a novel method is presented for geometric quality assurance of replicas.The aim is to facilitate generation of high-quality direct shear testing data as a prerequisite for reliable subsequent analyses of the results.In Part 1 of this study,two quality assurance parameters,smf and V_(Hp100),are derived and their usefulness for evaluation of geometric deviations,i.e.geometric reproducibility,is shown.In Part 2,the parameters are validated by showing a correlation between the parameters and the shear mechanical behavior,which qualifies the parameters for usage in the quality assurance method.Unique results from direct shear tests presenting comparisons between replicas and the rock joint show that replicas fulfilling proposed threshold values of σ_(mf)<0.06 mm and
|V_(Hp100)|
<0.2 mm have a narrow dispersion and imitate the shear mechanical behavior of the rock joint in all aspects apart from having a slightly lower peak shear strength.The wear in these replicas,which have similar morphology as the rock joint,is in the same areas as in the rock joint.The wear is slightly larger in the rock joint and therefore the discrepancy in peak shear strength derives from differences in material properties,possibly from differences in toughness.It is shown by application of the suggested method that the quality assured replicas manufactured following the process employed in this study phenomenologically capture the shear strength characteristics,which makes them useful in parameter studies.