Object-based Information Flow Control in Peer-to-peer Publish/Subscribe Systems

Distributed systems are getting so scalable like IoT (Internet of Things) and P2P (Peer-to-Peer) systems that millions of devices are connected and support various types of applications. Here, distributed systems are required to be secure in addition to increasing the performance, reliability, and availability and reducing the energy consumption. In distributed systems, information in objects flows to other objects by transactions reading and writing data in the objects. Here, some information of an object may illegally flow to a subject which is not allowed to get the information of the object. Especially, a leakage of sensitive information is to be prevented from occurring. In order to keep information systems secure, illegal information flow among objects has to be prevented. Types of synchronization protocols are so far discussed based on read and write access rights in the RBAC (Role-Based Access Control) model to prevent illegal information flow.In this thesis, we newly propose a P2PPSO (P2P type of topic-based PS (Publish/Subscribe) with Object concept) model and discuss the models and protocols for information flow control. A P2PPSO model is composed of peer processes (peers) which communicate with one another by publishing and subscribing event messages. Each peer can both publish and receive event messages with no centralized coordinator compared with traditional centralized PS models. Each event message published by a source peer carries information to a target peer. The contents carried by an event message are considered to be composed of objects. An object is a unit of data resource. Objects are characterized by topics, and each event message is also characterized by topics named publication topics.In order to make a P2PPSO system secure, we first newly propose a TBAC (Topic-Based Access Control) model. Here, an access right is a pair ⟨t, op⟩ of a topic t and a publish or subscribe operation op. A peer is allowed to publish an event message with publication topics and subscribe interesting topics only if the publication and subscription access rights are granted to the peer, respectively. Suppose an event message e_j published by a peer p_j carries an object on some topics into a target peer p_i. Here, information in the peer p_j illegally flows to the peer p_i if the target peer p_i is not allowed to subscribe the topics. An illegal object is an object whose topics a target peer is not allowed to subscribe. Even if an event message is received by a target peer by checking topics, objects carried by the event message may be illegal at the target peer. Hence, first, we propose a TOBS (Topics-of-Objects-Based Synchronization) protocol to prevent target peers from being delivered illegal objects in the P2PPSO system. Here, even if an event message is received by a target peer, illegal objects in the event message are not delivered to the target peer.In the TOBS protocol, every event message is assumed to be causally delivered to every common target peer in the underlying network. Suppose an event message e_2 is delivered to a target peer p_i before another event message e_1 while the event message e_1 causally precedes the event message e_2 (e_1 →_c e_2). Here, the event message e_2 is premature at the peer p_i. Hence, secondly, we propose a TOBSCO (TOBS with Causally Ordering delivery) protocol where the function to causally deliver every pair of event messages is added to the TOBS protocol. Here, we assume the underlying network supports reliable communication among every pair of peers, i.e. no event message loss, no duplicate message, and the sending order delivery of messages. Every pair of event messages received by using topics are causally delivered to every common target peer by using the vector of sequence numbers.In the TOBS and TOBSCO protocols, objects delivered to target peers are held as replicas of the objects by the target peers. If a peer updates data of an object, the peer distributes event messages, i.e. update event messages, to update every replica of the object obtained by other peers. If a peer updates an object without changing topics, the object is referred to as altered. Here, an update event message for the altered object is meaningless since peers check only topics to exchange event messages. Hence, thirdly, we propose an ETOBSCO (Efficient TOBSCO) protocol where update event messages of objects are published only if topics of the objects are updated to reduce the network overhead.In the evaluation, first, we show how many numbers of event messages and objects are prevented from being delivered to target peers in the TOBS protocol. Next, we show every pair of event messages are causally delivered but it takes longer to deliver event messages in the TOBSCO protocol than the TOBS protocol. Finally, we show the fewer number of event messages are delivered while it takes longer to update replicas of altered objects in the ETOBSCO protocol than the TOBSCO protocol.博士(工学)法政大学 (Hosei University

Protocols to Prevent Illegal Information Flow in Peer-to-Peer Publish/Subscribe Systems

In a peer-to-peer (P2P) type of topic-based subscribe/publish (P2PPS) model, each peer (process) can be a publisher and subscriber. Here, a peer publishes an event message and then the event message is notified to a target peer which is interested in the event message. Publications and subscriptions are specified in terms of topics. In the topic-based access control (TBAC) model proposed in our previous studies,only a peer granted publication and subscription access rights is allowed to publish event messages with publication topics and subscribe events, respectively. In our previous studies, the illegal information flow relation among peers is defined and the subscription-based synchronization (SBS) protocol is proposed to prevent illegal information flow. Here, topics carried by event messages are just accumulated in the target peers and notification of event messages which may cause illegal information flow are banned in each target peer. The more number of event messages are published, the more number of event messages are not notified in the system. In this paper, we newly propose a subscription initialization (SI) protocol where topics accumulated in peers are removed to reduce the number of notifications banned. We show the number of notifications banned is reduced in the SI protocol compared with the SBS protocol in the evaluation.Key Words : Information flow control, Peer-to-peer (P2P) model, Publish/subscribe (PS) systems, Subscription initialization (SI) protocol, Implicit topics, Topic-based access control (TBAC) mode

Activating Ly-49d and Inhibitory Ly-49a Natural Killer Cell Receptors Demonstrate Distinct Requirements for Interaction with H2-Dd

The activating Ly-49D receptor and the inhibitory Ly-49A receptor mediate opposing effects on natural killer (NK) cell cytotoxicity after interaction with the same major histocompatibility complex ligand, H2-Dd. To compare Ly-49D and Ly-49A interactions with H2-Dd, we created mutations in H2-Dd and examined the functional ability of these mutants to activate lysis through Ly-49D or to inhibit lysis through Ly-49A. Specific single amino acid changes in either the H2-Dd α1 helix or the α2 helix abrogated Ly-49D–mediated cytotoxicity, but these changes had no significant effect on Ly-49A–dependent inhibition. Each of three α2 domain mutations in the floor of the peptide binding groove reduced functional recognition by either Ly-49D or Ly-49A, but all three were required to fully abrogate inhibition by Ly-49A. Our studies indicate that Ly-49D/H2-Dd interactions require distinct determinants compared with Ly-49A/H2-Dd interactions. These differences have important implications for the integration of activating and inhibitory signals in NK cells

The whole blood transcriptional regulation landscape in 465 COVID-19 infected samples from Japan COVID-19 Task Force

「コロナ制圧タスクフォース」COVID-19患者由来の血液細胞における遺伝子発現の網羅的解析 --重症度に応じた遺伝子発現の変化には、ヒトゲノム配列の個人差が影響する--. 京都大学プレスリリース. 2022-08-23.Coronavirus disease 2019 (COVID-19) is a recently-emerged infectious disease that has caused millions of deaths, where comprehensive understanding of disease mechanisms is still unestablished. In particular, studies of gene expression dynamics and regulation landscape in COVID-19 infected individuals are limited. Here, we report on a thorough analysis of whole blood RNA-seq data from 465 genotyped samples from the Japan COVID-19 Task Force, including 359 severe and 106 non-severe COVID-19 cases. We discover 1169 putative causal expression quantitative trait loci (eQTLs) including 34 possible colocalizations with biobank fine-mapping results of hematopoietic traits in a Japanese population, 1549 putative causal splice QTLs (sQTLs; e.g. two independent sQTLs at TOR1AIP1), as well as biologically interpretable trans-eQTL examples (e.g., REST and STING1), all fine-mapped at single variant resolution. We perform differential gene expression analysis to elucidate 198 genes with increased expression in severe COVID-19 cases and enriched for innate immune-related functions. Finally, we evaluate the limited but non-zero effect of COVID-19 phenotype on eQTL discovery, and highlight the presence of COVID-19 severity-interaction eQTLs (ieQTLs; e.g., CLEC4C and MYBL2). Our study provides a comprehensive catalog of whole blood regulatory variants in Japanese, as well as a reference for transcriptional landscapes in response to COVID-19 infection

DOCK2 is involved in the host genetics and biology of severe COVID-19

「コロナ制圧タスクフォース」COVID-19疾患感受性遺伝子DOCK2の重症化機序を解明 --アジア最大のバイオレポジトリーでCOVID-19の治療標的を発見--. 京都大学プレスリリース. 2022-08-10.Identifying the host genetic factors underlying severe COVID-19 is an emerging challenge. Here we conducted a genome-wide association study (GWAS) involving 2, 393 cases of COVID-19 in a cohort of Japanese individuals collected during the initial waves of the pandemic, with 3, 289 unaffected controls. We identified a variant on chromosome 5 at 5q35 (rs60200309-A), close to the dedicator of cytokinesis 2 gene (DOCK2), which was associated with severe COVID-19 in patients less than 65 years of age. This risk allele was prevalent in East Asian individuals but rare in Europeans, highlighting the value of genome-wide association studies in non-European populations. RNA-sequencing analysis of 473 bulk peripheral blood samples identified decreased expression of DOCK2 associated with the risk allele in these younger patients. DOCK2 expression was suppressed in patients with severe cases of COVID-19. Single-cell RNA-sequencing analysis (n = 61 individuals) identified cell-type-specific downregulation of DOCK2 and a COVID-19-specific decreasing effect of the risk allele on DOCK2 expression in non-classical monocytes. Immunohistochemistry of lung specimens from patients with severe COVID-19 pneumonia showed suppressed DOCK2 expression. Moreover, inhibition of DOCK2 function with CPYPP increased the severity of pneumonia in a Syrian hamster model of SARS-CoV-2 infection, characterized by weight loss, lung oedema, enhanced viral loads, impaired macrophage recruitment and dysregulated type I interferon responses. We conclude that DOCK2 has an important role in the host immune response to SARS-CoV-2 infection and the development of severe COVID-19, and could be further explored as a potential biomarker and/or therapeutic target