Evaluation and design of function for tracing diffusion of classified information for file operations with KVM

Cases of classified information leakage have become increasingly common. To address this problem, we have developed a function for tracing the diffusion of classified information within an operating system. However, this function suffers from the following two problems: first, in order to introduce the function, the operating system's source code must be modified. Second, there is a risk that the function will be disabled when the operating system is attacked. Thus, we have designed a function for tracing the diffusion of classified information in a guest operating system by using a virtual machine monitor. By using a virtual machine monitor, we can introduce the proposed function in various environments without modifying the operating system's source code. In addition, attacks aimed at the proposed function are made more difficult, because the virtual machine monitor is isolated from the operating system. In this paper, we describe the implementation of the proposed function for file operations and child process creation in the guest operating system with a kernel-based virtual machine. Further, we demonstrate the traceability of diffusing classified information by file operations and child process creation. We also report the logical lines of code required to introduce the proposed function and performance overheads

Population-level transition of capsular polysaccharide types among sequence type 1 group B Streptococcus isolates with reduced penicillin susceptibility during a long-term hospital epidemic

Over a 35-month period, group B Streptococcus isolates with reduced penicillin susceptibility (PRGBS) were detected from elderly patients at a regional hospital in Japan, accompanying population-level transition of PRGBS serotypes. The genetic relatedness of 77 non-duplicate PRGBS from 73 patients was analysed. Serotype III PRGBS predominated (16 serotype III/1 serotype Ib) in the first 9 months (period I), then 3 serotype Ib isolates appeared transiently for the next 3 months (period II), which was replaced predominantly by serotype Ia (20 serotype Ia/1 serotype III/1 non-typeable) for 9 months (period III). In the last 14 months (period IV), besides 25 serotype Ia isolates, 10 serotype III were also identified. Serotypes III and Ia isolates, belonging to ST1, shared G329V, G398A, V405A and G429D substitutions in penicillin-binding protein 2X. Of three strains subjected to whole-genome sequencing, serotype III strain SU12 (period I) had a higher degree of genomic similarity with serotype Ia strain SU97 (period III) than serotype Ib strain SU67 (period II) based on average nucleotide identity and single nucleotide polymorphisms. Analysis of the cps gene clusters and the upstream and downstream flanking sequences revealed that disruption of the hyaluronidase gene located upstream of cpsY by insertion of IS 1548 was found in strain SU12, whereas Delta ISSag8 was inserted between tRNA-Arg and rpsA genes located downstream of cpsL in strain SU97. Interestingly, most serotype III PRGBS re-emerging in period IV had this tRNA-Arg-Delta ISSag8-rpsA region. Capsular switching and nosocomial transmission may possibly contribute to population-level serotype replacement among ST1 PRGBS isolates. (c) 2018 Elsevier B.V. and International Society of Chemotherapy. All rights reserved.ArticleINTERNATIONAL JOURNAL OF ANTIMICROBIAL AGENTS.53(3):203-210(2019)journal articl

MRP3 as a novel resistance factor for sorafenib in hepatocellular carcinoma

The mechanism of resistance of hepatocellular carcinoma (HCC) to sorafenib is unknown and no useful predictive biomarker for sorafenib treatment has been reported. Accordingly, we established sorafenib-resistant HCC cells and investigated the underlying mechanism of resistance to sorafenib. Sorafenib-resistant cell lines were established from the HCC cell line PLC/PRF5 by cultivation under continuous exposure to increasing concentration of sorafenib. The IC50 values of the 2 resistant clones PLC/PRF5-R1 and PLC-PRF5-R2 were 9.2±0.47 μM (1.8-fold) and 25±5.1 μM (4.6-fold) respectively, which were significantly higher than that of parental PLC/PRF5 cells (5.4±0.17 μM) (p<0.01 respectively), as determined by MTT assay. Western blot analysis of signal transduction-related proteins showed no significant differences in expression of AKT/pAKT, mTOR/pmTOR, or ERK/pERK between the 2 resistant clones versus parent cells, suggesting no activation of an alternative signal transduction pathway. Likewise, when expression of membrane transporter proteins was determined, there were no significant differences in expression levels of BSEP, MDR1, MRP2, BCRP, MRP4 and OCT1 between resistant clones and parent cells. However, the expression levels of MRP3 in the 2 resistant clones were significantly higher than that of parent cells. When MRP3 gene was knocked down by siRNA in PLC-PRF5-R2 cells, the sensitivity of the cells to sorafenib was restored. In the analysis of gene mutation, there was no mutation in the activation segment of Raf1 kinase in the resistant clones. Our data clearly demonstrate that the efflux transporter MRP3 plays an important role in resistance to sorafenib in HCC cells

CD153/CD30 signaling promotes age-dependent tertiary lymphoid tissue expansion and kidney injury

高齢者腎臓病を悪化させる原因細胞・分子の同定に成功. 京都大学プレスリリース. 2021-11-30.A new drug target for kidney disease. 京都大学プレスリリース. 2021-11-30.Tertiary lymphoid tissues (TLTs) facilitate local T- and B-cell interactions in chronically inflamed organs. However, the cells and molecular pathways that govern TLT formation are poorly defined. Here we identify TNF superfamily CD153-CD30 signaling between two unique age-dependent lymphocyte subpopulations, CD153⁺PD-1⁺CD4⁺ senescence-associated T (SAT) cells and CD30+T-bet+ age-associated B cells (ABCs), as a driver for TLT expansion. SAT cells, which produced ABC-inducing factors IL21 and IFNγ, and ABCs progressively accumulated within TLTs in aged kidneys after injury. Notably, in kidney injury models, CD153 or CD30 deficiency impaired functional SAT cell induction, which resulted in reduced ABC numbers and attenuated TLT formation with improved inflammation, fibrosis and renal function. Attenuated TLT formation after transplantation of CD153-deficient bone marrow further supported the importance of CD153 in immune cells. Clonal analysis revealed that SAT cells and ABCs in the kidneys arose from both local differentiation and recruitment from the spleen. In the synovium of aged rheumatoid arthritis patients, T peripheral helper/T follicular helper cells and ABCs also expressed CD153 and CD30, respectively. Together, our data reveal a previously unappreciated function of CD153-CD30 signaling in TLT formation and propose targeting CD153-CD30 signaling pathway as a therapeutic target for slowing kidney disease progression