Vaccination with Human Induced Pluripotent Stem Cells Creates an Antigen-Specific Immune Response Against HIV-1 gp160

Induced pluripotent stem cells (iPSCs) are artificially derived from somatic cells that have been transduced with defined reprogramming factors. A previous report has indicated the possibility of using iPSCs as an immune stimulator to generate antigen-specific immunity. In our current study, we have investigated whether human iPSCs (hiPSCs) have the ability to enhance specific immune response against a human immunodeficiency virus type 1 (HIV-1) antigen in a xenogenic mouse model. Our results show that BALB/c mice immunized with hiPSCs transduced with an adenoviral vector encoding HIV-1 gp160 exhibited prominent antigen-specific cellular immune responses. We further found that pre-treatment of hiPSCs with ionizing radiation promotes the secretion of pro-inflammatory cytokines such as interleukin-1 alpha (IL-1α), IL-12, and IL-18. These cytokines might promote the activation of antigen-presenting cells and the effective induction of cellular immunity. Our present findings thus demonstrate that a hiPSCs-based vaccine has the potential to generate cellular immunity against viral antigens such as HIV-1 gp160 in a xenogenic condition

Name anomaly detection for ICN

International audience—Information leakages are one of the main security threats in today's Internet. As ICN is expected to become the core architecture for Future Internet, it is therefore mandatory to prevent this threat. This paper proves that some ICN configuration prevents information leakages via Data packets and shows that it is an open problem to prevent interest packets from carrying encoded crucial information in their names. Assuming that names in ICN will follow the current URL format commonly used in the Internet, we get the statistics of web URL based on extensive crawling experiments of main internet organizations. Then we propose a simple filtering technique based on these statistics for firewall to detect anomalous names in ICN. The experiment shows that our filtering technique recognizes 15% of names in our dataset as malicious. As the false positive rate is still high for this filter to be used in a real world operation, this work is an important step for detecting anomalous names and preventing information-leakage in ICN

Name Filter: A Countermeasure against Information Leakage Attacks in Named Data Networking

International audienceNamed Data Networking (NDN) has emerged as a future networking architecture having thepotential to replace the Internet. In order to do so, NDN needs to cope with inherent problems of the Internetsuch as attacks that cause information leakage from an enterprise. Since NDN has not yet been deployed ona large scale, it is currently unknown how such attacks can occur, let alone what countermeasures can betaken against them. In this study, we first show that information leakage in NDN, can be caused by malwareinside an enterprise, which uses steganography to produce malicious Interest names encoding confidentialinformation. We investigate such attacks by utilizing a content name dataset based on uniform resourcelocators (URLs) collected by a web crawler. Our main contribution is a name filter based on anomalydetection that takes the dataset as input and classifies a name in the Interest as legitimate or not. Ourevaluation shows that malware can exploit the path part in the URL-based NDN name to create maliciousnames, thus, information leakage in NDN cannot be prevented completely. However, we illustrate for thefirst time that our filter can dramatically choke the leakage throughput causing the malware to be 137 timesless efficient at leaking information. This finding opens up an interesting avenue of research that could resultin a safer future networking architecture

Risk analysis of information-leakage through interest packets in NDN

International audienceInformation-leakage is one of the most importantsecurity issues in the current Internet. In Named-Data Networking(NDN), Interest names introduce novel vulnerabilities thatcan be exploited. By setting up a malware, Interest names can beused to encode critical information (steganography embedded) andto leak information out of the network by generating anomalousInterest traffic. This security threat based on Interest names doesnot exist in IP network, and it is essential to solve this issue tosecure the NDN architecture. This paper performs risk analysisof information-leakage in NDN. We first describe vulnerabilitieswith Interest names and, as countermeasures, we propose a namebasedfilter using search engine information, and another filterusing one-class Support Vector Machine (SVM). We collectedURLs from the data repository provided by Common Crawland we evaluate the performances of our per-packet filters. Weshow that our filters can choke drastically the throughput ofinformation-leakage, which makes it easier to detect anomalousInterest traffic. It is therefore possible to mitigate informationleakagein NDN network and it is a strong incentive for futuredeployment of this architecture at the Internet scale

Self-assembling A6K peptide nanotubes as a mercaptoundecahydrododecaborate (BSH) delivery system for boron neutron capture t (BNCT)

Boron neutron capture therapy (BNCT) is a tumor selective therapy, the effectiveness of which depends on sufficient 10B delivery to and accumulation in tumors. In this study, we used self-assembling A6K peptide nanotubes as boron carriers and prepared new boron agents by simple mixing of A6K and BSH. BSH has been used to treat malignant glioma patients in clinical trials and its drug safety and availability have been confirmed; however, its contribution to BNCT efficacy is low. A6K nanotube delivery improved two major limitations of BSH, including absence of intracellular transduction and non-specific drug delivery to tumor tissue. Varying the A6K peptide and BSH mixture ratio produced materials with different morphologies—determined by electron microscopy—and intracellular transduction efficiencies. We investigated the A6K/BSH 1:10 mixture ratio and found high intracellular boron uptake with no toxicity. Microscopy observation showed intracellular localization of A6K/BSH in the perinuclear region and endosome in human glioma cells. The intracellular boron concentration using A6K/BSH was almost 10 times higher than that of BSH. The systematic administration of A6K/BSH via mouse tail vein showed tumor specific accumulation in a mouse brain tumor model with immunohistochemistry and pharmacokinetic study. Neutron irradiation of glioma cells treated with A6K/BSH showed the inhibition of cell proliferation in a colony formation assay. Boron delivery using A6K peptide provides a unique and simple strategy for next generation BNCT drugs

Localization of S100C immunoreactivity in various human tissues.

Using 2-dimensional gel electrophoresis, we previously demonstrated that the S100C protein remarkably decreased after immortalization of normal human fibroblasts, and that this protein caused growth inhibition of human tumor cells when forcibly expressed in these cells, suggesting that S100C plays a significant role in tumor suppression. The present study was carried out to determine what type of human tissues express S100C protein, and, subsequently, whether the S100C content in these tissues changes after normal cells have been transformed into cancer cells. We found that ductal cells in various tissues were positively stained with the S100C protein. In comparison, epithelial cells in digestive organs such as the stomach, small intestine, and colon were not stained as strongly. When 14 pairs of human normal and cancerous tissues were stained with the antibody, decreases in the staining levels of S100C were observed in 6 kinds of cancerous tissues--from the bronchus, mammary duct, renal tubule, prostate, uterus, and testis--in comparison with staining in their normal counterparts. These results suggest that S100C is a new tumor marker protein, the expression of which significantly decreases after malignant transformation of human tissues.</p

Circadian production of melatonin in cartilage modifies rhythmic gene expression

Endochondral ossification, including bone growth and other metabolic events, is regulated by circadian rhythms. Herein, we provide evidence that melatonin has a direct effect on the circadian rhythm of chondrocytes. We detected mRNA expression of the genes which encode the melatonin-synthesizing enzymes AANAT (arylalkylamine N-acetyltransferase) and HIOMT (hydroxyindole O-methyltransferase), as well as the melatonin receptors MT1 and MT2 in mouse primary chondrocytes and cartilage. Production of melatonin was confirmed by mass spectrometric analysis of primary rat and chick chondrocytes. Addition of melatonin to primary mouse chondrocytes caused enhanced cell growth and increased expression of Col2a1, Aggrecan, and Sox9, but inhibited Col10a1 expression in primary BALB/c mouse chondrocytes. Addition of luzindole, an MT1 and MT2 antagonist, abolished these effects. These data indicate that chondrocytes produce melatonin, which regulates cartilage growth and maturation via the MT1 and MT2 receptors. Kinetic analysis showed that melatonin caused rapid upregulation of Aanat, Mt1, Mt2, and Pthrp expression, followed by Sox9 and Ihh. Furthermore, expression of the clock gene Bmal1 was induced, while that of Per1 was downregulated. Chronobiological analysis of synchronized C3H mouse chondrocytes revealed that melatonin induced the cyclic expression of Aanat and modified the cyclic rhythm of Bmal1, Mt1, and Mt2. In contrast, Mt1 and Mt2 showed different rhythms from Bmal1 and Aanat, indicating the existence of different regulatory genes. Our results indicate that exogenous and endogenous melatonin work in synergy in chondrocytes to adjust rhythmic expression to the central suprachiasmatic nucleus clock

Comparison of cellular characteristics between human hepatoma cell lines with wild-type p53 and those with mutant-type p53 gene

Characteristics of human hepatoma cell lines with the wild-type p53 were compared with those of human hepatoma cell lines with the mutant-type p53. The p21 protein located downstream of p53 was expressed in cell lines with the wild-type p53 but was not expressed in cell lines with the mutant-type p53. As to other tumor suppressor genes such as p16 and p27, there was no difference in their expression between both types of cell lines. In addition, no marked difference was observed in the activities of CDK2 and CDK4 between cell lines with the wild-type and the mutant-type p53. Phosphorylated Rb protein was detected in all cell lines except the HLE line, indicating that this cell line may have a deletion of and/or a mutation of the Rb gene. These results indicate that abnormalities of tumor suppressor genes other than p53, p16, p27, and Rb may be involved in hepatocarcinogenesis. The population doubling time of the wild-type p53 cells was significantly longer than that of the mutant p53 cells. Neither type of cell line showed a specific chromosome distribution which would indicate karyotype instability. The cell lines expressing the wild-type p53 produced tumors at lower frequency than those with the mutant p53 gene. Although there was no significant difference in effects of TGF-&#946;1, EGF, cholera toxin, and db-cAMP on cell growth between the two types of cells, all three cell lines with the wild-type p53 were resistant to cytotoxicity of TNF-&#945;, while two of the three with the mutant p53 were very sensitive to its cytotoxic effects.</p

『分類語彙表』と『岩波国語辞典第五版タグ付きコーパス2004』の対応表

University of TsukubaUniversity of TokyoTsuda University / National Institute for Japanese Language and LinguisticsTsuda University / National Institute for Japanese Language and LinguisticsNational Institute for Japanese Language and Linguistics/National Institute for Japanese Language and Linguistics会議名: 言語資源活用ワークショップ2019, 開催地: 国立国語研究所, 会期: 2019年9月2日−4日, 主催: 国立国語研究所 コーパス開発センター『分類語彙表』の見出し語と『岩波国語辞典第五版タグ付きコーパス2004』に含まれる国語辞典見出し語との対応表を作成した。分類語彙表は統語・意味に基づいて見出し語を分類したシソーラスであるが、その語義を規定する語釈文を含んでいない。そこで、岩波国語辞典の見出し語と対照させることで対応表を構築し、統語・意味分類と語釈文を結びつける作業を行った。作業は、見出し語表記による2部グラフを構成し、対応する見出し語対を抽出することによる。本作業は5人の作業者により平行して進めた。本作業結果により、『現代日本語書き言葉均衡コーパス』に付与された2種類の語義情報（分類語彙表番号・岩波語義タグ）との対照比較ができるようになった。本発表では、情報付与作業の方法と基礎情報を報告する