89 research outputs found

    Discriminating DRDoS Packets using Time Interval Analysis

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    Distributed Reflection Denial of Service (DRDoS) attack is one of the critical security threats. As the attack generates unidirectional traffic, it is not easy for the targets of the attack to protect themselves. To mitigate the attack, we need a defense mechanism installed at backbone networks, i.e., detecting and blocking the attack traffic before they reach to the destinations. A conventional approach is to monitor the traffic volume of the attack, i.e., an attack is detected if the observed traffic volume exceeds a certain threshold. However, such a simple approach may not work when an attacker adjusts the traffic volume to evade the detection. This paper proposes a novel method that can detect the DRDoS attacks accurately. The key idea is to leverage the characteristics of time intervals between the packets. We make use of the K-means clustering algorithm to find the best threshold values used to distinguish packets associated with DRDoS attacks. We implement the proposed algorithm into an equipment at a data center and demonstrate that our approach attains high accuracy

    Pituitary Volume and Socio-Cognitive Functions in Individuals at Risk of Psychosis and Patients With Schizophrenia

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    Objectives: Increased pituitary volume, which probably reflects hypothalamic-pituitary-adrenal (HPA) hyperactivity, has been reported in patients with schizophrenia and individuals at risk of psychosis. On the basis of potential role of abnormal HPA axis function on cognitive impairments in psychosis, we aimed to examine possible relations between the pituitary volume and socio-cognitive impairments in these subjects.Methods: This magnetic resonance imaging study examined the pituitary gland volume in 38 subjects with at-risk mental state (ARMS) [of whom 4 (10.5%) exhibited the transition to schizophrenia], 63 patients with schizophrenia, and 61 healthy controls. Social and cognitive functions of the ARMS and schizophrenia groups were assessed using the Brief Assessment of Cognition in Schizophrenia (BACS), the Schizophrenia Cognition Rating Scale (SCoRS), and the Social and Occupational Functioning Assessment Scale (SOFAS).Results: Both the ARMS and schizophrenia groups had a significantly larger pituitary volume compared to controls. In the schizophrenia group, the pituitary volume was negatively associated with the BACS working memory score. No association was found between the pituitary volume and clinical variables (medication, symptom severity) in either clinical group.Conclusion: Our findings support the notion of common HPA hyperactivity in the ARMS and schizophrenia groups, but abnormal HPA axis function may contribute differently to cognitive deficits according to the illness stages of schizophrenia

    Ultra-multiplex CARS spectroscopic imaging with 1-millisecond pixel dwell time

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    We performed ultra-multiplex coherent anti-Stokes Raman scattering (CARS) spectroscopic imaging by using a CCD camera with a fast readout time (<1 ms). The ultra-multiplex CARS signal of a polystyrene bead was detected in the range 600–3600 cm-1 with resolution <10 cm-1. The pixel dwell time was approximately 1 ms, which was limited by the readout time of the CCD camera rather than the exposure time. CARS images of 161 × 161 pixels were obtained of the polymer beads with a total data-acquisition time of approximately 28 s even with the use of a cost-effective microchip laser source. Label-free and ultra-multiplex (18 colors) imaging of living cells was also performed with an effective exposure time of 1.8 ms based on the molecular fingerprint as well as the C-H and O-H stretching vibrational modes using a master oscillator fiber amplifier laser source

    Infantile Pain Episodes Associated with Novel Nav1.9 Mutations in Familial Episodic Pain Syndrome in Japanese Families

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    Painful peripheral neuropathy has been correlated with various voltage-gated sodium channel mutations in sensory neurons. Recently Nav1.9, a voltage-gated sodium channel subtype, has been established as a genetic influence for certain peripheral pain syndromes. In this study, we performed a genetic study in six unrelated multigenerational Japanese families with episodic pain syndrome. Affected participants (n = 23) were characterized by infantile recurrent pain episodes with spontaneous mitigation around adolescence. This unique phenotype was inherited in an autosomal-dominant mode. Linkage analysis was performed for two families with 12 affected and nine unaffected members, and a single locus was identified on 3p22 (LOD score 4.32). Exome analysis (n = 14) was performed for affected and unaffected members in these two families and an additional family. Two missense variants were identified: R222H and R222S in SCN11A. Next, we generated a knock-in mouse model harboring one of the mutations (R222S). Behavioral tests (Hargreaves test and cold plate test) using R222S and wild-type C57BL/6 (WT) mice, young (8-9 weeks old; n = 10-12 for each group) and mature (36-38 weeks old; n = 5-6 for each group), showed that R222S mice were significantly (p < 0.05) more hypersensitive to hot and cold stimuli than WT mice. Electrophysiological studies using dorsal root ganglion neurons from 8-9-week-old mice showed no significant difference in resting membrane potential, but input impedance and firing frequency of evoked action potentials were significantly increased in R222S mice compared with WT mice. However, there was no significant difference among Nav1.9 (WT, R222S, and R222H)-overexpressing ND7/23 cell lines. These results suggest that our novel mutation is a gain-of-function mutation that causes infantile familial episodic pain. The mouse model developed here will be useful for drug screening for familial episodic pain syndrome associated with SCN11A mutations

    Hepatitis C Virus Infection Suppresses the Interferon Response in the Liver of the Human Hepatocyte Chimeric Mouse

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    BACKGROUND AND AIMS: Recent studies indicate that hepatitis C virus (HCV) can modulate the expression of various genes including those involved in interferon signaling, and up-regulation of interferon-stimulated genes by HCV was reported to be strongly associated with treatment outcome. To expand our understanding of the molecular mechanism underlying treatment resistance, we analyzed the direct effects of interferon and/or HCV infection under immunodeficient conditions using cDNA microarray analysis of human hepatocyte chimeric mice. METHODS: Human serum containing HCV genotype 1b was injected into human hepatocyte chimeric mice. IFN-α was administered 8 weeks after inoculation, and 6 hours later human hepatocytes in the mouse livers were collected for microarray analysis. RESULTS: HCV infection induced a more than 3-fold change in the expression of 181 genes, especially genes related to Organismal Injury and Abnormalities, such as fibrosis or injury of the liver (P = 5.90E-16∼3.66E-03). IFN administration induced more than 3-fold up-regulation in the expression of 152 genes. Marked induction was observed in the anti-fibrotic chemokines such as CXCL9, suggesting that IFN treatment might lead not only to HCV eradication but also prevention and repair of liver fibrosis. HCV infection appeared to suppress interferon signaling via significant reduction in interferon-induced gene expression in several genes of the IFN signaling pathway, including Mx1, STAT1, and several members of the CXCL and IFI families (P = 6.0E-12). Genes associated with Antimicrobial Response and Inflammatory Response were also significantly repressed (P = 5.22×10(-10)∼1.95×10(-2)). CONCLUSIONS: These results provide molecular insights into possible mechanisms used by HCV to evade innate immune responses, as well as novel therapeutic targets and a potential new indication for interferon therapy

    On the origin and evolution of the asteroid Ryugu: A comprehensive geochemical perspective

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    Presented here are the observations and interpretations from a comprehensive analysis of 16 representative particles returned from the C-type asteroid Ryugu by the Hayabusa2 mission. On average Ryugu particles consist of 50% phyllosilicate matrix, 41% porosity and 9% minor phases, including organic matter. The abundances of 70 elements from the particles are in close agreement with those of CI chondrites. Bulk Ryugu particles show higher δ18O, Δ17O, and ε54Cr values than CI chondrites. As such, Ryugu sampled the most primitive and least-thermally processed protosolar nebula reservoirs. Such a finding is consistent with multi-scale H-C-N isotopic compositions that are compatible with an origin for Ryugu organic matter within both the protosolar nebula and the interstellar medium. The analytical data obtained here, suggests that complex soluble organic matter formed during aqueous alteration on the Ryugu progenitor planetesimal (several 10’s of km), <2.6 Myr after CAI formation. Subsequently, the Ryugu progenitor planetesimal was fragmented and evolved into the current asteroid Ryugu through sublimation

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

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    「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
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