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. Asymptot...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.展开更多
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...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.展开更多
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 w...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.展开更多
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 trans...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.展开更多
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 nucle...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.展开更多
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), r...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.展开更多
Geographically replicating objects across multiple data centers improves the performance and reliability of cloud storage systems.Maintaining consistent replicas comes with high synchronization costs,as it faces more ...Geographically replicating objects across multiple data centers improves the performance and reliability of cloud storage systems.Maintaining consistent replicas comes with high synchronization costs,as it faces more expensive WAN transport prices and increased latency.Periodic replication is the widely used technique to reduce the synchronization costs.Periodic replication strategies in existing cloud storage systems are too static to handle traffic changes,which indicates that they are inflexible in the face of unforeseen loads,resulting in additional synchronization cost.We propose quantitative analysis models to quantify consistency and synchronization cost for periodically replicated systems,and derive the optimal synchronization period to achieve the best tradeoff between consistency and synchronization cost.Based on this,we propose a dynamic periodic synchronization method,Sync-Opt,which allows systems to set the optimal synchronization period according to the variable load in clouds to minimize the synchronization cost.Simulation results demonstrate the effectiveness of our models.Compared with the policies widely used in modern cloud storage systems,the Sync-Opt strategy significantly reduces the synchronization cost.展开更多
Vertical Federated Learning(VFL),which draws attention because of its ability to evaluate individuals based on features spread across multiple institutions,encounters numerous privacy and security threats.Existing sol...Vertical Federated Learning(VFL),which draws attention because of its ability to evaluate individuals based on features spread across multiple institutions,encounters numerous privacy and security threats.Existing solutions often suffer from centralized architectures,and exorbitant costs.To mitigate these issues,in this paper,we propose SecureVFL,a decentralized multi-party VFL scheme designed to enhance efficiency and trustworthiness while guaranteeing privacy.SecureVFL uses a permissioned blockchain and introduces a novel consensus algorithm,Proof of Feature Sharing(PoFS),to facilitate decentralized,trustworthy,and high-throughput federated training.SecureVFL introduces a verifiable and lightweight three-party Replicated Secret Sharing(RSS)protocol for feature intersection summation among overlapping users.Furthermore,we propose a(_(2)^(4))-sharing protocol to achieve federated training in a four-party VFL setting.This protocol involves only addition operations and exhibits robustness.SecureVFL not only enables anonymous interactions among participants but also safeguards their real identities,and provides mechanisms to unmask these identities when malicious activities are performed.We illustrate the proposed mechanism through a case study on VFL across four banks.Finally,our theoretical analysis proves the security of SecureVFL.Experiments demonstrated that SecureVFL outperformed existing multi-party VFL privacy-preserving schemes,such as MP-FedXGB,in terms of both overhead and model performance.展开更多
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 err...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.展开更多
In case that replicated observations are available in someexperimental points, the parameters estimation of one-dimensional linear errors-in-variables (EV) models was studied. Weak and strong consistency was proved un...In case that replicated observations are available in someexperimental points, the parameters estimation of one-dimensional linear errors-in-variables (EV) models was studied. Weak and strong consistency was proved under mild conditions.展开更多
An in-memory storage system provides submillisecond latency and improves the concurrency of user applications by caching data into memory from external storage.Fault tolerance of in-memory storage systems is essential...An in-memory storage system provides submillisecond latency and improves the concurrency of user applications by caching data into memory from external storage.Fault tolerance of in-memory storage systems is essential,as the loss of cached data requires access to data from external storage,which evidently increases the response latency.Typically,replication and erasure code(EC)are two fault-tolerant schemes that pose different trade-offs between access performance and storage usage.To help make the best performance and space trade-off,we design ElasticMem,a hybrid fault-tolerant distributed in-memory storage system that supports elastic redundancy transition to dynamically change the fault-tolerant scheme.ElasticMem exploits a novel EC-oriented replication(EOR)that carefully designs the data placement of replication according to the future data layout of EC to enhance the I/O efficiency of redundancy transition.ElasticMem solves the consistency problem caused by concurrent data accesses via a lightweight table-based scheme combined with data bypassing.It detects correlated read and write requests and serves subsequent read requests with local data.We implement a prototype that realizes ElasticMem based on Memcached.Experiments show that ElasticMem remarkably reduces the time of redundancy transition,the overall latency of correlated concurrent data accesses,and the latency of single data access among them.展开更多
Single-stranded DNA-binding proteins(SSBs)play essential roles in the replication,recombination and repair processes of organellar DNA molecules.In Arabidopsis thaliana,SSBs are encoded by a small family of two genes(...Single-stranded DNA-binding proteins(SSBs)play essential roles in the replication,recombination and repair processes of organellar DNA molecules.In Arabidopsis thaliana,SSBs are encoded by a small family of two genes(SSB1 and SSB2).However,the functional divergence of these two SSB copies in plants remains largely unknown,and detailed studies regarding their roles in the replication and recombination of organellar genomes are still incomplete.In this study,phylogenetic,gene structure and protein motif analyses all suggested that SSB1 and SSB2 probably diverged during the early evolution of seed plants.Based on accurate long-read sequencing results,ssb1 and ssb2 mutants had decreased copy numbers for both mitochondrial DNA(mtDNA)and plastid DNA(ptDNA),accompanied by a slight increase in structural rearrangements mediated by intermediate-sized repeats in mt genome and small-scale variants in both genomes.Our findings provide an important foundation for further investigating the effects of DNA dosage in the regulation of mutation frequencies in plant organellar genomes.展开更多
Ultraviolet nanoimprint lithography(UV-NIL)is a versatile and cost-effective technique for the fabrication of micro-and nanostructures by copying master patterns in a planar or a roll-to-roll process through curing of...Ultraviolet nanoimprint lithography(UV-NIL)is a versatile and cost-effective technique for the fabrication of micro-and nanostructures by copying master patterns in a planar or a roll-to-roll process through curing of a liquid UV-sensitive precursor.For applications with a high pattern complexity,new UV-NIL process chains must be specified.Master fabrication is a challenging part of the development and often cannot be accomplished using a single master fabrication technique.Therefore,an approach combining different patterning fabrication techniques is developed here for polymer masters using laser direct writing and photolithography.The polymer masters produced in this way are molded into inverse silicone stamps that are used for roll-to-roll replication into an acrylate formulation.To fit the required roller size for large-area UV-NIL,several submasters with micrometer-sized dot and line gratings and prism arrays,which have been patterned by these different techniques,are assembled to final size of ~200×600 mm^(2) with an absolute precision of better than 50μm.The size of the submasters allows the use of standard laboratory equipment for patterning and direct writing,thus enabling the fabrication of micro-and even nanostructures when electron-beam writing is utilized.In this way,the effort,time,and costs for the fabrication of masters for UV-NIL processes are reduced,enabling further development for particular structures and applications.Using this approach,patterns fabricated with different laboratory tools are finally replicated by UV-NIL in an acrylate formulation,demonstrating the high quality of the whole process chain.展开更多
The 3CL protease, a highly conserved enzyme in the coronavirus, plays a crucial role in the viral life cycle by facilitating viral replication through precise cleavage of polyproteins. Beyond its proteolytic function,...The 3CL protease, a highly conserved enzyme in the coronavirus, plays a crucial role in the viral life cycle by facilitating viral replication through precise cleavage of polyproteins. Beyond its proteolytic function, the 3CL protease also engages in intricate interactions with host cell proteins involved in critical cellular processes such as transcription, translation, and nuclear-cytoplasmic transport, effectively hijacking cellular machinery to promote viral replication. Additionally, it disrupts innate immune signaling pathways, suppresses interferon activity and cleaves antiviral proteins. Furthermore, it modulates host cell death pathways including pyroptosis and apoptosis, interferes with autophagy and inhibits stress granule formation to maintain viral infection and exacerbate viral pathogenesis. This review highlights the molecular mechanisms by which the 3CL protease orchestrates virus-host interactions, emphasizing its central role in coronavirus pathogenesis and highlighting potential therapeutic targets for future interventions.展开更多
Personal video recorders (PVRs) have altered the way users consume television (TV) content by allowing users to record programs and watch them at their convenience, overcoming the constraints of live broadcasting. How...Personal video recorders (PVRs) have altered the way users consume television (TV) content by allowing users to record programs and watch them at their convenience, overcoming the constraints of live broadcasting. However, standalone PVRs are limited by their individual storage capacities, restricting the number of programs they can store. While online catch-up TV services such as Hulu and Netflix mitigate this limitation by offering on-demand access to broadcast programs shortly after their initial broadcast, they require substantial storage and network resources, leading to significant infrastructural costs for service providers. To address these challenges, we propose a collaborative TV content recording system that leverages distributed PVRs, combining their storage into a virtual shared pool without additional costs. Our system aims to support all concurrent playback requests without service interruption while ensuring program availability comparable to that of local devices. The main contributions of our proposed system are fourfold. First, by sharing storage and upload bandwidth among PVRs, our system significantly expands the overall recording capacity and enables simultaneous recording of multiple programs without the physical constraints of standalone devices. Second, by utilizing erasure coding efficiently, our system reduces the storage space required for each program, allowing more programs to be recorded compared to traditional replication. Third, we propose an adaptive redundancy scheme to control the degree of redundancy of each program based on its evolving playback demand, ensuring high-quality playback by providing sufficient bandwidth for popular programs. Finally, we introduce a contribution-based incentive policy that encourages PVRs to actively participate by contributing resources, while discouraging excessive consumption of the combined storage pool. Through extensive experiments, we demonstrate the effectiveness of our proposed collaborative TV program recording system in terms of storage efficiency and performance.展开更多
When interpreting results,it is imperative to have some understanding of the degree to which the results are replicable.If the results cannot be replicated with independent data,then interpretations from the results b...When interpreting results,it is imperative to have some understanding of the degree to which the results are replicable.If the results cannot be replicated with independent data,then interpretations from the results become questionable.To minimize the potential for misinterpretations,the current study analyzes six time-series derived from globally sampled U-Pb zircon databases–of which,two are independent igneous databases,one being a quasi-independent igneous database,and three being independent detrital databases.These time-series are then analyzed with standard statistical methods to evaluate replicability.The methods include bandpass filtering to transform the raw time-series into stationary sequences,Student’s t-test,Monte Carlo simulations,periodograms from spectral analysis,correlation studies,and correlograms.Each test is designed to determine the replicability of a specific time-series,as well as the replicability of periodicities found from the time-series.The results show at least three key components to assessing replicability:(a)U-Pb igneous and detrital zircon age distributions are highly replicable,(b)time-series replicability gradually deteriorates with age,and(c)replicability is scale dependent,with low frequency cycles being more replicable than high frequency cycles.From the tests,we conclude that four harmonic cycles are highly replicable and statistically significant,these being periodicities of 810,270,90,and 67.5-myr.展开更多
Mitochondria provides adenosine triphosphate for multiple vital movements to ensure tumor cell proliferation.Compared to the broadly used method of inducing DNA replication arrest to kill cancer,inducing mitochondria ...Mitochondria provides adenosine triphosphate for multiple vital movements to ensure tumor cell proliferation.Compared to the broadly used method of inducing DNA replication arrest to kill cancer,inducing mitochondria damage to cause energy shortage is quite promising as it can inhibit tumor cell bioactivities,increase intracellular accumulation of toxic drugs,eventually sensitize chemotherapy and even reverse drug resistance.Breaking the balance of glutathione(GSH)and reactive oxygen species(ROS)contents have been proven efficient in destroying mitochondria respectively.Herein,apigenin,a GSH efflux reagent,and 2-deoxy-5-fluorouridine 5-monophosphate sodium salt(FdUMP)that could induce toxic ROS were co-delivered by constructed lipid nanoparticles,noted as Lip@AF.An immune-checkpoint inhibition reagent CD276 antibody was modified onto the surface of Lip@AF with high reaction specificity(noted asαCD276-Lip@AF)to enhance the recognition of immune cells to tumor.Results showed that the redox balancewas destroyed,leading to severe injury to mitochondria and cell membrane.Furthermore,synergistic DNA/RNA replication inhibition caused by inhibiting the function of thymidylate synthase were observed.Eventually,significantly enhanced cytotoxicity was achieved by combining multiple mechanisms including ferroptosis,apoptosis and pyroptosis.In vivo,strengthen tumor growth inhibitionwas achieved byαCD276-Lip@AF with high biosafety,providing new sights in enhancing chemotherapy sensitiveness and achieving high-performance chemo-immunotherapy.展开更多
The DNA replication stress(RS)response is crucial for maintaining cellular homeostasis and promoting physiological longevity.However,the mechanisms by which long-lived species,such as bats,regulate RS to maintain geno...The DNA replication stress(RS)response is crucial for maintaining cellular homeostasis and promoting physiological longevity.However,the mechanisms by which long-lived species,such as bats,regulate RS to maintain genomic stability remain unclear.Also,recent studies have uncovered noncanonical roles of ribosome-associated factors in maintaining genomic stability.In this study,somatic skin fibroblasts from the long-lived big-footed bat(Myotis pilosus)were examined,with results showing that bat cells exhibited enhanced RS tolerance compared to mouse cells.Comparative transcriptome analysis under RS conditions revealed pronounced species-specific transcriptional differences,including robust up-regulation of ribosome biogenesis genes in bat cells and a markedly reduced activation of the P53 signaling pathway.These features emphasize a distinct homeostatic strategy in bat cells.Nuclear fragile X mental retardation-interacting protein 1(Nufip1),a ribosome-associated factor highly expressed in bat fibroblasts,was identified as a potential integrator of ribosomal and P53 signaling via its association with ribosomal protein S27-like(Rps27l).These findings provide direct cellular and molecular evidence for a noncanonical RS response in bats,highlighting a deeper understanding of the biological characteristics and genomic maintenance mechanisms of long-lived species.展开更多
BACKGROUND Whether rtS106C+H126Y+D134E/rtS106C+H126Y+D134E+L269I(rtCYE/rtCYEI)mutations in the hepatitis B virus(HBV)reverse-transcriptase(RT)region are associated with tenofovir disoproxil fumarate(TDF)resistance is ...BACKGROUND Whether rtS106C+H126Y+D134E/rtS106C+H126Y+D134E+L269I(rtCYE/rtCYEI)mutations in the hepatitis B virus(HBV)reverse-transcriptase(RT)region are associated with tenofovir disoproxil fumarate(TDF)resistance is controversial.AIM To evaluate the presence of the rtCYE/rtCYEI mutations in a large cohort of Chinese patients with chronic HBV infection.METHODS A total of 28236 patients who underwent drug resistance testing at the Fifth Medical Center of Chinese PLA General Hospital from 2007 to 2019 were enrolled.All patients received nucleoside/nucleotide analogues(NAs)therapy,and serum samples were collected for sequence analysis of the HBV RT domain with mutation analysis.RESULTS The detection rates of a single mutation of rtS106C,rtH126Y,rtD134E,and rtL269I were 8.21%,3.20%,2.55%and 61.49%in 23718 genotype C patients,and 1.31%,1.76%,0.21%,and 92.33%in 4266 genotype B patients,respectively.The combined mutations of rtCYE/rtCYEI were only detected in 12 genotype C patients,accounting for 0.042%of all patients.These 12 patients had received NA treatments except TDF before testing.Among them,6 patients had coexisting rtCYE/rtCYEI and lamivudine-resistance mutations,and 2 patients had coexisting rtCYE/rtCYEI and adefovir-resistance mutations.Compared with the wild-type(WT)strain,the replication capacity of rtCYE/rtCYEI mutants from representative patients decreased by 41.1%-71.8%,and TDF susceptibility reduced by less than 2-fold,but rtCYEI+rtA181V/N236T mutants exhibited a 6.2-/9.9-fold decrease in TDF susceptibility.Molecular modeling showed that rtCYE/rtCYEI mutants had a slight decrease in binding energy to TDF compared to the WT strain.In the clinic,emergence of the rtCYE/rtCYEI mutations was not specifically associated with TDF treatment.CONCLUSION HBV rtCYE/rtCYEI mutations have a limited effect on TDF susceptibility and are not sufficient to cause TDF resistance.展开更多
Cloud computing has become an essential technology for the management and processing of large datasets,offering scalability,high availability,and fault tolerance.However,optimizing data replication across multiple dat...Cloud computing has become an essential technology for the management and processing of large datasets,offering scalability,high availability,and fault tolerance.However,optimizing data replication across multiple data centers poses a significant challenge,especially when balancing opposing goals such as latency,storage costs,energy consumption,and network efficiency.This study introduces a novel Dynamic Optimization Algorithm called Dynamic Multi-Objective Gannet Optimization(DMGO),designed to enhance data replication efficiency in cloud environments.Unlike traditional static replication systems,DMGO adapts dynamically to variations in network conditions,system demand,and resource availability.The approach utilizes multi-objective optimization approaches to efficiently balance data access latency,storage efficiency,and operational costs.DMGO consistently evaluates data center performance and adjusts replication algorithms in real time to guarantee optimal system efficiency.Experimental evaluations conducted in a simulated cloud environment demonstrate that DMGO significantly outperforms conventional static algorithms,achieving faster data access,lower storage overhead,reduced energy consumption,and improved scalability.The proposed methodology offers a robust and adaptable solution for modern cloud systems,ensuring efficient resource consumption while maintaining high performance.展开更多
基金the National Natural Science Foundation of China (Grant No. 19631040)
文摘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.
基金The NSF (10661003) of Chinathe NSF (1012138,0612163) of Guangdong Ocean University
文摘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.
基金partially supported through NSF-DMS 0443855NSF ECS 0601528+1 种基金NIH EB009235the short-lived W.M.Keck Foundation Grant#062014.
文摘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.
基金Supported by Visiting Scholar Foundation of KeyLabin University and National Lab of Switching Technology and Tele-communication Networks ([2000]123)
文摘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.
文摘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.
文摘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.
基金This work was supported by the National Natural Science Foundation of China(Grant Nos.62272026 and 62104014)the fund of the State Key Laboratory of Software Development Environment(No.SKLSDE-2022ZX-07)the Iluvatar CoreX semiconductor Co.,Ltd.
文摘Geographically replicating objects across multiple data centers improves the performance and reliability of cloud storage systems.Maintaining consistent replicas comes with high synchronization costs,as it faces more expensive WAN transport prices and increased latency.Periodic replication is the widely used technique to reduce the synchronization costs.Periodic replication strategies in existing cloud storage systems are too static to handle traffic changes,which indicates that they are inflexible in the face of unforeseen loads,resulting in additional synchronization cost.We propose quantitative analysis models to quantify consistency and synchronization cost for periodically replicated systems,and derive the optimal synchronization period to achieve the best tradeoff between consistency and synchronization cost.Based on this,we propose a dynamic periodic synchronization method,Sync-Opt,which allows systems to set the optimal synchronization period according to the variable load in clouds to minimize the synchronization cost.Simulation results demonstrate the effectiveness of our models.Compared with the policies widely used in modern cloud storage systems,the Sync-Opt strategy significantly reduces the synchronization cost.
基金supported by Open Research Projects of Zhejiang Lab(No.2022QA0AB02)Natural Science Foundation of Sichuan Province(2022NSFSC0913)Sichuan Province Selected Funding for Postdoctoral Research Projects(TB2022032).
文摘Vertical Federated Learning(VFL),which draws attention because of its ability to evaluate individuals based on features spread across multiple institutions,encounters numerous privacy and security threats.Existing solutions often suffer from centralized architectures,and exorbitant costs.To mitigate these issues,in this paper,we propose SecureVFL,a decentralized multi-party VFL scheme designed to enhance efficiency and trustworthiness while guaranteeing privacy.SecureVFL uses a permissioned blockchain and introduces a novel consensus algorithm,Proof of Feature Sharing(PoFS),to facilitate decentralized,trustworthy,and high-throughput federated training.SecureVFL introduces a verifiable and lightweight three-party Replicated Secret Sharing(RSS)protocol for feature intersection summation among overlapping users.Furthermore,we propose a(_(2)^(4))-sharing protocol to achieve federated training in a four-party VFL setting.This protocol involves only addition operations and exhibits robustness.SecureVFL not only enables anonymous interactions among participants but also safeguards their real identities,and provides mechanisms to unmask these identities when malicious activities are performed.We illustrate the proposed mechanism through a case study on VFL across four banks.Finally,our theoretical analysis proves the security of SecureVFL.Experiments demonstrated that SecureVFL outperformed existing multi-party VFL privacy-preserving schemes,such as MP-FedXGB,in terms of both overhead and model performance.
基金This work was partially supported by the National Natural Science Foundation of China(Grant No.10071009)Research Foundation of Doctorial Programme(Grant No.20020027010)the Excellent Young Teacher Programme of the Ministry of Educatioin of China
文摘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.
基金This work was supported by the National Natural Science Foundation of China (Grant No. 19631040) .
文摘In case that replicated observations are available in someexperimental points, the parameters estimation of one-dimensional linear errors-in-variables (EV) models was studied. Weak and strong consistency was proved under mild conditions.
基金supported by the Fundamental Research Funds for the Central Universities(WK2150110022)Anhui Provincial Natural Science Foundation(2208085QF189)National Natural Science Foundation of China(62202440).
文摘An in-memory storage system provides submillisecond latency and improves the concurrency of user applications by caching data into memory from external storage.Fault tolerance of in-memory storage systems is essential,as the loss of cached data requires access to data from external storage,which evidently increases the response latency.Typically,replication and erasure code(EC)are two fault-tolerant schemes that pose different trade-offs between access performance and storage usage.To help make the best performance and space trade-off,we design ElasticMem,a hybrid fault-tolerant distributed in-memory storage system that supports elastic redundancy transition to dynamically change the fault-tolerant scheme.ElasticMem exploits a novel EC-oriented replication(EOR)that carefully designs the data placement of replication according to the future data layout of EC to enhance the I/O efficiency of redundancy transition.ElasticMem solves the consistency problem caused by concurrent data accesses via a lightweight table-based scheme combined with data bypassing.It detects correlated read and write requests and serves subsequent read requests with local data.We implement a prototype that realizes ElasticMem based on Memcached.Experiments show that ElasticMem remarkably reduces the time of redundancy transition,the overall latency of correlated concurrent data accesses,and the latency of single data access among them.
基金supported by grants from the National Natural Science Foundation of China(32170238,32400191)Guangdong Basic and Applied Basic Research Foundation(2023A1515111029)+2 种基金the Science,Technology and Innovation Commission of Shenzhen Municipality(RCYX20200714114538196)the Chinese Academy of Agricultural Sciences Elite Youth Program(grant 110243160001007)the Guangdong Pearl River Talent Program(2021QN02N792)。
文摘Single-stranded DNA-binding proteins(SSBs)play essential roles in the replication,recombination and repair processes of organellar DNA molecules.In Arabidopsis thaliana,SSBs are encoded by a small family of two genes(SSB1 and SSB2).However,the functional divergence of these two SSB copies in plants remains largely unknown,and detailed studies regarding their roles in the replication and recombination of organellar genomes are still incomplete.In this study,phylogenetic,gene structure and protein motif analyses all suggested that SSB1 and SSB2 probably diverged during the early evolution of seed plants.Based on accurate long-read sequencing results,ssb1 and ssb2 mutants had decreased copy numbers for both mitochondrial DNA(mtDNA)and plastid DNA(ptDNA),accompanied by a slight increase in structural rearrangements mediated by intermediate-sized repeats in mt genome and small-scale variants in both genomes.Our findings provide an important foundation for further investigating the effects of DNA dosage in the regulation of mutation frequencies in plant organellar genomes.
文摘Ultraviolet nanoimprint lithography(UV-NIL)is a versatile and cost-effective technique for the fabrication of micro-and nanostructures by copying master patterns in a planar or a roll-to-roll process through curing of a liquid UV-sensitive precursor.For applications with a high pattern complexity,new UV-NIL process chains must be specified.Master fabrication is a challenging part of the development and often cannot be accomplished using a single master fabrication technique.Therefore,an approach combining different patterning fabrication techniques is developed here for polymer masters using laser direct writing and photolithography.The polymer masters produced in this way are molded into inverse silicone stamps that are used for roll-to-roll replication into an acrylate formulation.To fit the required roller size for large-area UV-NIL,several submasters with micrometer-sized dot and line gratings and prism arrays,which have been patterned by these different techniques,are assembled to final size of ~200×600 mm^(2) with an absolute precision of better than 50μm.The size of the submasters allows the use of standard laboratory equipment for patterning and direct writing,thus enabling the fabrication of micro-and even nanostructures when electron-beam writing is utilized.In this way,the effort,time,and costs for the fabrication of masters for UV-NIL processes are reduced,enabling further development for particular structures and applications.Using this approach,patterns fabricated with different laboratory tools are finally replicated by UV-NIL in an acrylate formulation,demonstrating the high quality of the whole process chain.
基金supported by the National Natural Science Foundation of China(grant no.82370015).
文摘The 3CL protease, a highly conserved enzyme in the coronavirus, plays a crucial role in the viral life cycle by facilitating viral replication through precise cleavage of polyproteins. Beyond its proteolytic function, the 3CL protease also engages in intricate interactions with host cell proteins involved in critical cellular processes such as transcription, translation, and nuclear-cytoplasmic transport, effectively hijacking cellular machinery to promote viral replication. Additionally, it disrupts innate immune signaling pathways, suppresses interferon activity and cleaves antiviral proteins. Furthermore, it modulates host cell death pathways including pyroptosis and apoptosis, interferes with autophagy and inhibits stress granule formation to maintain viral infection and exacerbate viral pathogenesis. This review highlights the molecular mechanisms by which the 3CL protease orchestrates virus-host interactions, emphasizing its central role in coronavirus pathogenesis and highlighting potential therapeutic targets for future interventions.
基金supported by the National Research Foundation of Korea(NRF)grant funded by the Korea government(MSIT)(Nos.2019R1A2C1002221 and RS-2023-00252186)Institute of Information&Communications Technology Planning&Evaluation(IITP)grant funded by the Korea government(MSIT)(Nos.2021-0-00590,RS-2021-II210590Decentralized High Performance Consensus for Large-Scale Blockchains).
文摘Personal video recorders (PVRs) have altered the way users consume television (TV) content by allowing users to record programs and watch them at their convenience, overcoming the constraints of live broadcasting. However, standalone PVRs are limited by their individual storage capacities, restricting the number of programs they can store. While online catch-up TV services such as Hulu and Netflix mitigate this limitation by offering on-demand access to broadcast programs shortly after their initial broadcast, they require substantial storage and network resources, leading to significant infrastructural costs for service providers. To address these challenges, we propose a collaborative TV content recording system that leverages distributed PVRs, combining their storage into a virtual shared pool without additional costs. Our system aims to support all concurrent playback requests without service interruption while ensuring program availability comparable to that of local devices. The main contributions of our proposed system are fourfold. First, by sharing storage and upload bandwidth among PVRs, our system significantly expands the overall recording capacity and enables simultaneous recording of multiple programs without the physical constraints of standalone devices. Second, by utilizing erasure coding efficiently, our system reduces the storage space required for each program, allowing more programs to be recorded compared to traditional replication. Third, we propose an adaptive redundancy scheme to control the degree of redundancy of each program based on its evolving playback demand, ensuring high-quality playback by providing sufficient bandwidth for popular programs. Finally, we introduce a contribution-based incentive policy that encourages PVRs to actively participate by contributing resources, while discouraging excessive consumption of the combined storage pool. Through extensive experiments, we demonstrate the effectiveness of our proposed collaborative TV program recording system in terms of storage efficiency and performance.
基金supported by the French Agence Nationale de la Recherche(19-CE31-0002 AstroMeso)the European Research Council under the European Union’s Horizon 2020 Research and Innovation Program(Advanced Grant AstroGeo-885250).
文摘When interpreting results,it is imperative to have some understanding of the degree to which the results are replicable.If the results cannot be replicated with independent data,then interpretations from the results become questionable.To minimize the potential for misinterpretations,the current study analyzes six time-series derived from globally sampled U-Pb zircon databases–of which,two are independent igneous databases,one being a quasi-independent igneous database,and three being independent detrital databases.These time-series are then analyzed with standard statistical methods to evaluate replicability.The methods include bandpass filtering to transform the raw time-series into stationary sequences,Student’s t-test,Monte Carlo simulations,periodograms from spectral analysis,correlation studies,and correlograms.Each test is designed to determine the replicability of a specific time-series,as well as the replicability of periodicities found from the time-series.The results show at least three key components to assessing replicability:(a)U-Pb igneous and detrital zircon age distributions are highly replicable,(b)time-series replicability gradually deteriorates with age,and(c)replicability is scale dependent,with low frequency cycles being more replicable than high frequency cycles.From the tests,we conclude that four harmonic cycles are highly replicable and statistically significant,these being periodicities of 810,270,90,and 67.5-myr.
基金financially supported by the National Natural Science Foundation of China(82173769)Tianjin Science Foundation for Distinguished Young Scholars(24JCJQJC00050)+2 种基金Applied Basic Research Multi-Investment Foundation of Tianjin(21JCYBJC01540)the National Natural Science Foundation of China(82300336)the Science&Technology Development Fund of Tianjin Education Commission for Higher Education(2019KJ178).
文摘Mitochondria provides adenosine triphosphate for multiple vital movements to ensure tumor cell proliferation.Compared to the broadly used method of inducing DNA replication arrest to kill cancer,inducing mitochondria damage to cause energy shortage is quite promising as it can inhibit tumor cell bioactivities,increase intracellular accumulation of toxic drugs,eventually sensitize chemotherapy and even reverse drug resistance.Breaking the balance of glutathione(GSH)and reactive oxygen species(ROS)contents have been proven efficient in destroying mitochondria respectively.Herein,apigenin,a GSH efflux reagent,and 2-deoxy-5-fluorouridine 5-monophosphate sodium salt(FdUMP)that could induce toxic ROS were co-delivered by constructed lipid nanoparticles,noted as Lip@AF.An immune-checkpoint inhibition reagent CD276 antibody was modified onto the surface of Lip@AF with high reaction specificity(noted asαCD276-Lip@AF)to enhance the recognition of immune cells to tumor.Results showed that the redox balancewas destroyed,leading to severe injury to mitochondria and cell membrane.Furthermore,synergistic DNA/RNA replication inhibition caused by inhibiting the function of thymidylate synthase were observed.Eventually,significantly enhanced cytotoxicity was achieved by combining multiple mechanisms including ferroptosis,apoptosis and pyroptosis.In vivo,strengthen tumor growth inhibitionwas achieved byαCD276-Lip@AF with high biosafety,providing new sights in enhancing chemotherapy sensitiveness and achieving high-performance chemo-immunotherapy.
基金supported by the Applied Basic Research Programs of Science and Technology Commission Foundation of Yunnan Province(202401AT070186 to K.Q.L.,202201AS070044 to B.Z.)Yunnan Province(202305AH340006 to B.Z.)Kunming Science and Technology Bureau(2022SCP007 to B.Z.)。
文摘The DNA replication stress(RS)response is crucial for maintaining cellular homeostasis and promoting physiological longevity.However,the mechanisms by which long-lived species,such as bats,regulate RS to maintain genomic stability remain unclear.Also,recent studies have uncovered noncanonical roles of ribosome-associated factors in maintaining genomic stability.In this study,somatic skin fibroblasts from the long-lived big-footed bat(Myotis pilosus)were examined,with results showing that bat cells exhibited enhanced RS tolerance compared to mouse cells.Comparative transcriptome analysis under RS conditions revealed pronounced species-specific transcriptional differences,including robust up-regulation of ribosome biogenesis genes in bat cells and a markedly reduced activation of the P53 signaling pathway.These features emphasize a distinct homeostatic strategy in bat cells.Nuclear fragile X mental retardation-interacting protein 1(Nufip1),a ribosome-associated factor highly expressed in bat fibroblasts,was identified as a potential integrator of ribosomal and P53 signaling via its association with ribosomal protein S27-like(Rps27l).These findings provide direct cellular and molecular evidence for a noncanonical RS response in bats,highlighting a deeper understanding of the biological characteristics and genomic maintenance mechanisms of long-lived species.
基金Supported by The National Natural Science Foundation of China,No.82470632.
文摘BACKGROUND Whether rtS106C+H126Y+D134E/rtS106C+H126Y+D134E+L269I(rtCYE/rtCYEI)mutations in the hepatitis B virus(HBV)reverse-transcriptase(RT)region are associated with tenofovir disoproxil fumarate(TDF)resistance is controversial.AIM To evaluate the presence of the rtCYE/rtCYEI mutations in a large cohort of Chinese patients with chronic HBV infection.METHODS A total of 28236 patients who underwent drug resistance testing at the Fifth Medical Center of Chinese PLA General Hospital from 2007 to 2019 were enrolled.All patients received nucleoside/nucleotide analogues(NAs)therapy,and serum samples were collected for sequence analysis of the HBV RT domain with mutation analysis.RESULTS The detection rates of a single mutation of rtS106C,rtH126Y,rtD134E,and rtL269I were 8.21%,3.20%,2.55%and 61.49%in 23718 genotype C patients,and 1.31%,1.76%,0.21%,and 92.33%in 4266 genotype B patients,respectively.The combined mutations of rtCYE/rtCYEI were only detected in 12 genotype C patients,accounting for 0.042%of all patients.These 12 patients had received NA treatments except TDF before testing.Among them,6 patients had coexisting rtCYE/rtCYEI and lamivudine-resistance mutations,and 2 patients had coexisting rtCYE/rtCYEI and adefovir-resistance mutations.Compared with the wild-type(WT)strain,the replication capacity of rtCYE/rtCYEI mutants from representative patients decreased by 41.1%-71.8%,and TDF susceptibility reduced by less than 2-fold,but rtCYEI+rtA181V/N236T mutants exhibited a 6.2-/9.9-fold decrease in TDF susceptibility.Molecular modeling showed that rtCYE/rtCYEI mutants had a slight decrease in binding energy to TDF compared to the WT strain.In the clinic,emergence of the rtCYE/rtCYEI mutations was not specifically associated with TDF treatment.CONCLUSION HBV rtCYE/rtCYEI mutations have a limited effect on TDF susceptibility and are not sufficient to cause TDF resistance.
文摘Cloud computing has become an essential technology for the management and processing of large datasets,offering scalability,high availability,and fault tolerance.However,optimizing data replication across multiple data centers poses a significant challenge,especially when balancing opposing goals such as latency,storage costs,energy consumption,and network efficiency.This study introduces a novel Dynamic Optimization Algorithm called Dynamic Multi-Objective Gannet Optimization(DMGO),designed to enhance data replication efficiency in cloud environments.Unlike traditional static replication systems,DMGO adapts dynamically to variations in network conditions,system demand,and resource availability.The approach utilizes multi-objective optimization approaches to efficiently balance data access latency,storage efficiency,and operational costs.DMGO consistently evaluates data center performance and adjusts replication algorithms in real time to guarantee optimal system efficiency.Experimental evaluations conducted in a simulated cloud environment demonstrate that DMGO significantly outperforms conventional static algorithms,achieving faster data access,lower storage overhead,reduced energy consumption,and improved scalability.The proposed methodology offers a robust and adaptable solution for modern cloud systems,ensuring efficient resource consumption while maintaining high performance.
