7,824 research outputs found

    A Graph-Based Approach to Address Trust and Reputation in Ubiquitous Networks

    Get PDF
    The increasing popularity of virtual computing environments such as Cloud and Grid computing is helping to drive the realization of ubiquitous and pervasive computing. However, as computing becomes more entrenched in everyday life, the concepts of trust and risk become increasingly important. In this paper, we propose a new graph-based theoretical approach to address trust and reputation in complex ubiquitous networks. We formulate trust as a function of quality of a task and time required to authenticate agent-to-agent relationship based on the Zero-Common Knowledge (ZCK) authentication scheme. This initial representation applies a graph theory concept, accompanied by a mathematical formulation of trust metrics. The approach we propose increases awareness and trustworthiness to agents based on the values estimated for each requested task, we conclude by stating our plans for future work in this area

    Charge mobility of discotic mesophases: A multiscale quantum/classical study

    Full text link
    A correlation is established between the molecular structure and charge mobility of discotic mesophases of hexabenzocoronene derivatives by combining electronic structure calculations, Molecular Dynamics, and kinetic Monte Carlo simulations. It is demonstrated that this multiscale approach can provide an accurate ab-initio description of charge transport in organic materials

    Molecular determinants of drug-specific sensitivity for epidermal growth factor receptor (EGFR) exon 19 and 20 mutants in non-small cell lung cancer.

    Get PDF
    We hypothesized that aberrations activating epidermal growth factor receptor (EGFR) via dimerization would be more sensitive to anti-dimerization agents (e.g., cetuximab). EGFR exon 19 abnormalities (L747_A750del; deletes amino acids LREA) respond to reversible EGFR kinase inhibitors (TKIs). Exon 20 in-frame insertions and/or duplications (codons 767 to 774) and T790M mutations are clinically resistant to reversible/some irreversible TKIs. Their impact on protein function/therapeutic actionability are not fully elucidated.In our study, the index patient with non-small cell lung cancer (NSCLC) harbored EGFR D770_P772del_insKG (exon 20). A twenty patient trial (NSCLC cohort) (cetuximab-based regimen) included two participants with EGFR TKI-resistant mutations ((i) exon 20 D770>GY; and (ii) exon 19 LREA plus exon 20 T790M mutations). Structural modeling predicted that EGFR exon 20 anomalies (D770_P772del_insKG and D770>GY), but not T790M mutations, stabilize the active dimer configuration by increasing the interaction between the kinase domains, hence sensitizing to an agent preventing dimerization. Consistent with predictions, the two patients harboring D770_P772del_insKG and D770>GY, respectively, responded to an EGFR antibody (cetuximab)-based regimen; the T790M-bearing patient showed no response to cetuximab combined with erlotinib. In silico modeling merits investigation of its ability to optimize therapeutic selection based on structural/functional implications of different aberrations within the same gene

    Recovery of a medieval Brucella melitensis genome using shotgun metagenomics

    Get PDF
    Shotgun metagenomics provides a powerful assumption-free approach to the recovery of pathogen genomes from contemporary and historical material. We sequenced the metagenome of a calcified nodule from the skeleton of a 14th-century middle-aged male excavated from the medieval Sardinian settlement of Geridu. We obtained 6.5-fold coverage of a Brucella melitensis genome. Sequence reads from this genome showed signatures typical of ancient or aged DNA. Despite the relatively low coverage, we were able to use information from single-nucleotide polymorphisms to place the medieval pathogen genome within a clade of B. melitensis strains that included the well-studied Ether strain and two other recent Italian isolates. We confirmed this placement using information from deletions and IS711 insertions. We conclude that metagenomics stands ready to document past and present infections, shedding light on the emergence, evolution, and spread of microbial pathogens
    • 

    corecore