The iPlant Collaborative (iPlant) is a United States National Science Foundation (NSF) funded project that aims to create an innovative, comprehensive, and foundational cyberinfrastructure in support of plant biology research (PSCIC, 2006). iPlant is developing cyberinfrastructure that uniquely enables scientists throughout the diverse fields that comprise plant biology to address Grand Challenges in new ways, to stimulate and facilitate cross-disciplinary research, to promote biology and computer science research interactions, and to train the next generation of scientists on the use of cyberinfrastructure in research and education. Meeting humanity's projected demands for agricultural and forest products and the expectation that natural ecosystems be managed sustainably will require synergies from the application of information technologies. The iPlant cyberinfrastructure design is based on an unprecedented period of research community input, and leverages developments in high-performance computing, data storage, and cyberinfrastructure for the physical sciences. iPlant is an open-source project with application programming interfaces that allow the community to extend the infrastructure to meet its needs. iPlant is sponsoring community-driven workshops addressing specific scientific questions via analysis tool integration and hypothesis testing. These workshops teach researchers how to add bioinformatics tools and/or datasets into the iPlant cyberinfrastructure enabling plant scientists to perform complex analyses on large datasets without the need to master the command-line or high-performance computational services.
The Arabidopsis Information Portal (https://www.araport.org) is a new online resource for plant biology research. It houses the Arabidopsis thaliana genome sequence and associated annotation. It was conceived as a framework that allows the research community to develop and release ‘modules’ that integrate, analyze and visualize Arabidopsis data that may reside at remote sites. The current implementation provides an indexed database of core genomic information. These data are made available through feature-rich web applications that provide search, data mining, and genome browser functionality, and also by bulk download and web services. Araport uses software from the InterMine and JBrowse projects to expose curated data from TAIR, GO, BAR, EBI, UniProt, PubMed and EPIC CoGe. The site also hosts ‘science apps,’ developed as prototypes for community modules that use dynamic web pages to present data obtained on-demand from third-party servers via RESTful web services. Designed for sustainability, the Arabidopsis Information Portal strategy exploits existing scientific computing infrastructure, adopts a practical mixture of data integration technologies and encourages collaborative enhancement of the resource by its user community.
Purpose: PLX4032 (RG7204), an oncogenic BRAF kinase inhibitor undergoing clinical evaluation, has high response rates in early clinical trials in patients with advanced BRAF V600E mutant melanoma.Combining PLX4032 with immunotherapy may allow expanding the durability of responses. The effects of PLX4032 on immune cells were studied to explore the feasibility of future combinatorial approaches with immunotherapy for melanoma. Experimental Design: Peripheral blood mononuclear cells (PBMC) and BRAF V600E mutant melanoma cells were exposed to increasing concentrations of PLX4032 and the cell viability, proliferation, cell cycle, apoptosis, and phosphorylation of signaling proteins were analyzed. Effects of PLX4032 on antigenspecific T-cell function were analyzed by specific cytokine release and cytotoxicity activity.Results: The 50% inhibition concentration (IC 50 ) of PLX4032 for resting human PBMC was between 50 and 150 mmol/L compared with an IC 50 below 1 mmol/L for sensitive BRAF V600E mutant melanoma cell lines. Activated lymphocytes were even more resistant with no growth inhibition up to concentrations of 250 mmol/L. PLX4032 had a marginal effect on cell-cycle arrest, apoptotic cell changes or alteration of phosphorylated signaling molecules in lymphocytes. Functional analysis of specific antigen recognition showed preserved T-cell function up to 10-mmol/L concentration of PLX4032, whereas the cytotoxic activity of PLX4032 was maintained up to high concentrations of 50 mmol/L. Conclusions:The preserved viability and function of lymphocytes exposed to high concentrations of PLX4032 suggest that this agent could be a potential candidate for combining with immunotherapy strategies for the treatment of patients with BRAF V600E mutant melanoma.
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