200 research outputs found

    Octopus: A Secure and Anonymous DHT Lookup

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    Distributed Hash Table (DHT) lookup is a core technique in structured peer-to-peer (P2P) networks. Its decentralized nature introduces security and privacy vulnerabilities for applications built on top of them; we thus set out to design a lookup mechanism achieving both security and anonymity, heretofore an open problem. We present Octopus, a novel DHT lookup which provides strong guarantees for both security and anonymity. Octopus uses attacker identification mechanisms to discover and remove malicious nodes, severely limiting an adversary's ability to carry out active attacks, and splits lookup queries over separate anonymous paths and introduces dummy queries to achieve high levels of anonymity. We analyze the security of Octopus by developing an event-based simulator to show that the attacker discovery mechanisms can rapidly identify malicious nodes with low error rate. We calculate the anonymity of Octopus using probabilistic modeling and show that Octopus can achieve near-optimal anonymity. We evaluate Octopus's efficiency on Planetlab with 207 nodes and show that Octopus has reasonable lookup latency and manageable communication overhead

    Phenylboronic ester-modified polymeric nanoparticles for promoting TRP2 peptide antigen delivery in cancer immunotherapy

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    The tremendous development of peptide-based cancer vaccine has attracted incremental interest as a powerful approach in cancer management, prevention and treatment. As successful as tumor vaccine has been, major challenges associated with achieving efficient immune response against cancer are (1) drainage to and retention in lymph nodes; (2) uptake by dendritic cells (DCs); (3) activation of DCs. In order to overcome these barriers, here we construct PBE-modified TRP2 nanovaccine, which comprises TRP2 peptide tumor antigen and diblock copolymer PEG-b-PAsp grafted with phenylboronic ester (PBE). We confirmed that this TRP2 nanovaccine can be effectively trapped into lymph node, uptake by dendritic cells and induce DC maturation, relying on increased negative charge, ROS response and pH response. Consistently, this vehicle loaded with TRP2 peptide could boost the strongest T cell immune response against melanoma in vivo and potentiate antitumor efficacy both in tumor prevention and tumor treatment without any exogenous adjuvant. Furthermore, the TRP2 nanovaccine can suppress the tumor growth and prolong animal survival time, which may result from its synergistic effect of inhibiting tumor immunosuppression and increasing cytotoxic lymphocyte (CTL) response. Hence this type of PBE-modified nanovaccine would be widely used as a simple, safe and robust platform to deliver other antigen in cancer immunotherapy

    Time valid one-time signature for time-critical multicast data authentication

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    Abstract-It is challenging to provide authentication to timecritical multicast data, where low end-to-end delay is of crucial importance. Consequently, it requires not only efficient authentication algorithms to minimize computational cost, but also avoidance of buffering packets so that the data can be immediately processed once being presented. Desirable properties for a multicast authentication scheme also include small communication overhead, tolerance to packet loss, and resistance against malicious attacks. In this paper, we propose a novel signature model -Time Valid One-Time Signature (TV-OTS) -to boost the efficiency of regular one-time signature schemes. Based on the TV-OTS model, we design an efficient multicast authentication scheme "TV-HORS" to meet the above needs. TV-HORS combines one-way hash chains with TV-OTS to avoid frequent public key distribution. It provides fast signing/verification and buffering-free data processing, which make it one of the fastest multicast authentication schemes to date in terms of end-to-end computational latency (on the order of microseconds). In addition, TV-HORS has perfect tolerance to packet loss and strong robustness against malicious attacks. The communication overhead of TV-HORS is much smaller than regular OTS schemes, and even smaller than RSA signature. The only drawback of TV-HORS is a relatively large public key of size 8KB to 10KB, depending on parameters

    MiR-23a Regulates Skin Langerhans Cell Phagocytosis and Inflammation-Induced Langerhans Cell Repopulation

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    Langerhans cells (LCs) are skin-resident macrophage that act similarly to dendritic cells for controlling adaptive immunity and immune tolerance in the skin, and they are key players in the development of numerous skin diseases. While TGF-Ī² and related downstream signaling pathways are known to control numerous aspects of LC biology, little is known about the epigenetic signals that coordinate cell signaling during LC ontogeny, maintenance, and function. Our previous studies in a total miRNA deletion mouse model showed that miRNAs are critically involved in embryonic LC development and postnatal LC homeostasis; however, the specific miRNA(s) that regulate LCs remain unknown. miR-23a is the first member of the miR-23a-27a-24-2 cluster, a direct downstream target of PU.1 and TGF-b, which regulate the determination of myeloid versus lymphoid fates. Therefore, we used a myeloid-specific miR-23a deletion mouse model to explore whether and how miR-23a affects LC ontogeny and function in the skin. We observed the indispensable role of miR-23a in LC antigen uptake and inflammation-induced LC epidermal repopulation; however, embryonic LC development and postnatal homeostasis were not affected by cells lacking miR23a. Our results suggest that miR-23a controls LC phagocytosis by targeting molecules that regulate efferocytosis and endocytosis, whereas miR-23a promotes homeostasis in bone marrow-derived LCs that repopulate the skin after inflammatory insult by targeting Fas and Bcl-2 family proapoptotic molecules. Collectively, the context-dependent regulatory role of miR-23a in LCs represents an extra-epigenetic layer that incorporates TGF-b- and PU.1-mediated regulation during steady-state and inflammation-induced repopulation

    Mannoseā€Modified Multiā€Walled Carbon Nanotubes as a Delivery Nanovector Optimizing the Antigen Presentation of Dendritic Cells

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    Dendritic cells (DCs) based cancer immunotherapy is largely dependent on adequate antigen delivery and efficient induction of DCs maturation to produce sufficient antigen presentation and ultimately lead to substantial activation of tumorā€specific CD8+ T cells. Carbon nanotubes (CNTs) have attracted great attention in biomedicine because of their unique physicochemical properties. In order to effectively deliver tumor antigens to DCs and trigger a strong antiā€tumor immune response, herein, a specific DCs target delivery system was assembled by using multiā€walled carbon nanotubes modified with mannose which can specifically bind to the mannose receptor on DCs membrane. Ovalbumin (OVA) as a model antigen, could be adsorbed on the surface of mannose modified multiā€walled carbon nanotubes (Manā€MWCNTs) with a large drug loading content. This nanotubeā€antigen complex showed low cytotoxicity to DCs and was efficiently engulfed by DCs to induce DCs maturation and cytokine release inā€…vitro, indicating that it could be a potent antigenā€adjuvant nanovector of efficient antigen delivery for therapeutic purpose.Perfectly delivered! Mannoseā€modified multiā€walled carbon nanotubes (Manā€MWCNTs) could efficiently deliver a large amount of antigen to bone marrow derived dendritic cells (DCs) through ligand/receptor interactions of mannose, inducing enhanced BMDCs maturation and cytokines secretion.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/150607/1/open201900126-sup-0001-misc_information.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/150607/2/open201900126.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/150607/3/open201900126_am.pd

    DDT-RELATED PROTEIN4-IMITATION SWITCH alters nucleosome distribution to relieve transcriptional silencing in Arabidopsis

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    DNA methylation is a conserved epigenetic modification that is typically associated with silencing of transposable elements and promoter methylated genes. However, some DNA-methylated loci are protected from silencing, allowing transcriptional flexibility in response to environmental and developmental cues. Through a genetic screen in Arabidopsis (Arabidopsis thaliana), we uncovered an antagonistic relationship between the MICRORCHIDIA (MORC) protein and the IMITATION SWITCH (ISWI) complex in regulating the DNA-methylated SUPPRESSOR OF DRM1 DRM2 CMT3 (SDC) reporter. We demonstrate that components of the plant-specific ISWI complex, including CHROMATIN REMODELING PROTEIN11 (CHR11), CHR17, DDT-RELATED PROTEIN4 (DDR4), and DDR5, function to partially de-repress silenced genes and transposable elements (TEs), through their function in regulating nucleosome distribution. This action also requires the known transcriptional activator DNAJ proteins, providing a mechanistic link between nucleosome remodeling and transcriptional activation. Genome-wide studies revealed that DDR4 causes changes in nucleosome distribution at numerous loci, a subset of which is associated with changes in DNA methylation and/or transcription. Our work reveals a mechanism for balancing transcriptional flexibility and faithful silencing of DNA-methylated loci. As both ISWI and MORC family genes are widely distributed across plant and animal species, our findings may represent a conserved eukaryotic mechanism for fine-tuning gene expression under epigenetic regulation
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