Byzantine-Resistant Total Ordering Algorithms

AbstractMulticast group communication protocols are used extensively in fault-tolerant distributed systems. For many such protocols, the acknowledgments for individual messages define a causal order on messages. Maintaining the consistency of information, replicated on several processors to protect it against faults, is greatly simplified by a total order on messages. We present algorithms that incrementally convert a causal order on messages into a total order and that tolerate both crash and Byzantine process faults. Varying compromises between latency to message ordering and resilience to faults yield four distinct algorithms. All of these algorithms use a multistage voting strategy to achieve agreement on the total order and exploit the random structure of the causal order to ensure probabilistic termination

End-To-End Latency of a Fault-Tolerant CORBA Infrastructure

This paper presents an evaluation of the end-to-end latency of a fault-tolerant CORBA infrastructure that we have implemented. The fault-tolerant infrastructure replicates the server applications using active, passive and semi-active replication, and maintains strong replica consistency of the server replicas. By analyses and by measurements of the running fault-tolerant infrastructure, we characterize the end-to-end latency under fault-free conditions. The main determining factor of the run-time performance of the fault-tolerant infrastructure is the Totem group communication protocol, which contributes to the end-to-end latency primarily in two ways: the delay in sending messages and the processing cost of the rotating token. To reduce the delay in sending messages for passive and semi-active replication, the position of the primary server replica on the Totem ring, the token rotation time, the processing time at the client, and the processing time at the server must be considered. For active replication, the presence of duplicate messages adversely affects the performance. However, if an effective sending-side duplicate suppression mechanism is implemented, active replication is more advantageous than both passive and semi-active replication because of the automatic selection of the most favorable position of the server replica that sends the first non-duplicate reply

Unification of Transactions and Replication in Three-Tier Architectures Based on CORBA

In this paper, we describe a software infrastructure that unifies transactions and replication in three-tier architectures and provides data consistency and high availability for enterprise applications. The infrastructure uses transactions based on the CORBA object transaction service to protect the application data in databases on stable storage, using a roll-backward recovery strategy, and replication based on the fault tolerant CORBA standard to protect the middle-tier servers, using a roll-forward recovery strategy. The infrastructure replicates the middle-tier servers to protect the application business logic processing. In addition, it replicates the transaction coordinator, which renders the two-phase commit protocol nonblocking and, thus, avoids potentially long service disruptions caused by failure of the coordinator. The infrastructure handles the interactions between the replicated middle-tier servers and the database servers through replicated gateways that prevent duplicate requests from reaching the database servers. It implements automatic client-side failover mechanisms, which guarantee that clients know the outcome of the requests that they have made, and retries aborted transactions automatically on behalf of the clients

Are Women Who Work in Bars, Guesthouses and Similar Facilities a Suitable Study Population for Vaginal Microbicide Trials in Africa?

BACKGROUND: A feasibility study was conducted to investigate whether an occupational at-risk cohort of women in Mwanza, Tanzania are a suitable study population for future phase III vaginal microbicide trials. METHODOLOGY/PRINCIPAL FINDINGS: 1573 women aged 16-54 y working in traditional and modern bars, restaurants, hotels, guesthouses or as local food-handlers were enrolled at community-based reproductive health clinics, provided specimens for HIV/STI and pregnancy testing, and asked to attend three-monthly clinical follow-up visits for 12-months. HIV positive and negative women were eligible to enter the feasibility study and to receive free reproductive health services at any time. HIV prevalence at baseline was 26.5% (417/1573). HIV incidence among 1156 sero-negative women attending at baseline was 2.9/100PYs. Among 1020 HIV sero-negative, non-pregnant women, HIV incidence was 2.0/100PYs, HSV-2 incidence 12.7/100PYs and pregnancy rate 17.8/100PYs. Retention at three-months was 76.3% (778/1020). Among 771 HIV sero-negative, non-pregnant women attending at three-months, subsequent follow-up at 6, 9 and 12-months was 83.7%, 79.6%, and 72.1% respectively. Older women, those who had not moved home or changed their place of work in the last year, and women working in traditional bars or as local food handlers had the highest re-attendance. CONCLUSIONS/SIGNIFICANCE: Women working in food outlets and recreational facilities in Tanzania and other parts of Africa may be a suitable study population for microbicide and other HIV prevention trials. Effective locally-appropriate strategies to address high pregnancy rates and early losses to follow-up are essential to minimise risk to clinical trials in these settings

Dissecting the Shared Genetic Architecture of Suicide Attempt, Psychiatric Disorders, and Known Risk Factors

Background Suicide is a leading cause of death worldwide, and nonfatal suicide attempts, which occur far more frequently, are a major source of disability and social and economic burden. Both have substantial genetic etiology, which is partially shared and partially distinct from that of related psychiatric disorders. Methods We conducted a genome-wide association study (GWAS) of 29,782 suicide attempt (SA) cases and 519,961 controls in the International Suicide Genetics Consortium (ISGC). The GWAS of SA was conditioned on psychiatric disorders using GWAS summary statistics via multitrait-based conditional and joint analysis, to remove genetic effects on SA mediated by psychiatric disorders. We investigated the shared and divergent genetic architectures of SA, psychiatric disorders, and other known risk factors. Results Two loci reached genome-wide significance for SA: the major histocompatibility complex and an intergenic locus on chromosome 7, the latter of which remained associated with SA after conditioning on psychiatric disorders and replicated in an independent cohort from the Million Veteran Program. This locus has been implicated in risk-taking behavior, smoking, and insomnia. SA showed strong genetic correlation with psychiatric disorders, particularly major depression, and also with smoking, pain, risk-taking behavior, sleep disturbances, lower educational attainment, reproductive traits, lower socioeconomic status, and poorer general health. After conditioning on psychiatric disorders, the genetic correlations between SA and psychiatric disorders decreased, whereas those with nonpsychiatric traits remained largely unchanged. Conclusions Our results identify a risk locus that contributes more strongly to SA than other phenotypes and suggest a shared underlying biology between SA and known risk factors that is not mediated by psychiatric disorders.Peer reviewe

Identification of regulatory variants associated with genetic susceptibility to meningococcal disease.

Non-coding genetic variants play an important role in driving susceptibility to complex diseases but their characterization remains challenging. Here, we employed a novel approach to interrogate the genetic risk of such polymorphisms in a more systematic way by targeting specific regulatory regions relevant for the phenotype studied. We applied this method to meningococcal disease susceptibility, using the DNA binding pattern of RELA - a NF-kB subunit, master regulator of the response to infection - under bacterial stimuli in nasopharyngeal epithelial cells. We designed a custom panel to cover these RELA binding sites and used it for targeted sequencing in cases and controls. Variant calling and association analysis were performed followed by validation of candidate polymorphisms by genotyping in three independent cohorts. We identified two new polymorphisms, rs4823231 and rs11913168, showing signs of association with meningococcal disease susceptibility. In addition, using our genomic data as well as publicly available resources, we found evidences for these SNPs to have potential regulatory effects on ATXN10 and LIF genes respectively. The variants and related candidate genes are relevant for infectious diseases and may have important contribution for meningococcal disease pathology. Finally, we described a novel genetic association approach that could be applied to other phenotypes

Author correction : roadmap for naming uncultivated archaea and bacteria

Correction to: Nature Microbiology https://doi.org/10.1038/s41564-020-0733-x , published online 8 June 2020. In the version of this Consensus Statement originally published, Pablo Yarza was mistakenly not included in the author list. Also, in Supplementary Table 1, Alexander Jaffe was missing from the list of endorsees. These errors have now been corrected and the updated Supplementary Table 1 is available online