Significance Analysis of Time Course Microarray Experiments

Characterizing the genome-wide dynamic regulation of gene expression is important and will be of much interest in the future. However, there is currently no established method for identifying differentially expressed genes in a time course study. Here we propose a significance method for analyzing time course microarray studies that can be applied to the typical types of comparisons and sampling schemes. This method is applied to two studies on humans. In one study, genes are identified that show differential expression over time in response to in vivo endotoxin administration. Using our method 7409 genes are called significant at a 1% FDR level, whereas several existing approaches fail to identify any genes. In another study, 417 genes are identified at a 10% FDR level that show expression changing with age in the kidney cortex. Here it is also shown that as many as 47% of the genes change with age in a manner more complex than simple exponential growth or decay. The methodology proposed here has been implemented in the freely distributed and open-source EDGE software package

Flight Team Development in Support of LCROSS - A Class D Mission

The LCROSS (Lunar Crater Observation and Sensing Satellite) project presented a number of challenges to the preparation for mission operations. A class D mission under NASA s risk tolerance scale, LCROSS was governed by a $79 million cost cap and a 29 month schedule from "authority to proceed" to flight readiness. LCROSS was NASA Ames Research Center s flagship mission in its return to spacecraft flight operations after many years of pursuing other strategic goals. As such, ARC needed to restore and update its mission support infrastructure, and in parallel, the LCROSS project had to newly define operational practices and to select and train a flight team combining experienced operators and staff from other arenas of ARC research. This paper describes the LCROSS flight team development process, which deeply involved team members in spacecraft and ground system design, implementation and test; leveraged collaborations with strategic partners; and conducted extensive testing and rehearsals that scaled in realism and complexity in coordination with ground system and spacecraft development. As a testament to the approach, LCROSS successfully met its full mission objectives, despite many in-flight challenges, with its impact on the lunar south pole on October 9, 2009

Flight Operations for the LCROSS Lunar Impactor Mission

The LCROSS (Lunar CRater Observation and Sensing Satellite) mission was conceived as a low-cost means of determining the nature of hydrogen concentrated at the polar regions of the moon. Co-manifested for launch with LRO (Lunar Reconnaissance Orbiter), LCROSS guided its spent Centaur upper stage into the Cabeus crater as a kinetic impactor, and observed the impact flash and resulting debris plume for signs of water and other compounds from a Shepherding Spacecraft. Led by NASA Ames Research Center, LCROSS flight operations spanned 112 days, from June 18 through October 9, 2009. This paper summarizes the experiences from the LCROSS flight, highlights the challenges faced during the mission, and examines the reasons for its ultimate success

Shifting perspectives on coastal impacts and adaptation

The Intergovernmental Panel on Climate Change reports reflect evolving attitudes in adapting to sea-level rise by taking a systems approach and recognizing that multiple responses exist to achieve a less hazardous coast.info:eu-repo/semantics/publishedVersio

FGF23 is elevated in multiple myeloma and increases heparanase expression by tumor cells

Multiply myeloma (MM) grows in and destroys bone, where osteocytes secrete FGF23, a hormone which affects phosphate homeostasis and aging. We report that multiple myeloma (MM) cells express receptors for and respond to FGF23. FGF23 increased mRNA for EGR1 and its target heparanase, a pro-osteolytic factor in MM. FGF23 signals through a complex of klotho and a classical FGF receptor (FGFR); both were expressed by MM cell lines and patient samples. Bone marrow plasma cells from 42 MM patients stained positively for klotho, while plasma cells from 8 patients with monoclonal gammopathy of undetermined significance (MGUS) and 6 controls were negative. Intact, active FGF23 was increased 2.9X in sera of MM patients compared to controls. FGF23 was not expressed by human MM cells, but co-culture with mouse bone increased its mRNA. The FGFR inhibitor NVP-BGJ398 blocked the heparanase response to FGF23. NVP-BGJ398 did not inhibit 8226 growth in vitro but significantly suppressed growth in bone and induction of the osteoclast regulator RANK ligand, while decreasing heparanase mRNA. The bone microenvironment provides resistance to some anti-tumor drugs but increased the activity of NVP-BGJ398 against 8226 cells. The FGF23/klotho/heparanase signaling axis may offer targets for treatment of MM in bone

Climate change 2014 : impacts, adaptation, and vulnerability

Current and future climate-related drivers of risk for small islands during the 21st century include sea level rise (SLR), tropical and extratropical cyclones, increasing air and sea surface temperatures, and changing rainfall patterns (high confidence; robust evidence, high agreement). Current impacts associated with these changes confirm findings reported on small islands from the Fourth Assessment Report (AR4) and previous IPCC assessments. The future risks associated with these drivers include loss of adaptive capacity and ecosystem services critical to lives and livelihoods in small islands.peer-reviewe

Characterization of an immediate-early gene induced in adherent monocytes that encodes IκB-like activity

We have cloned a group of cDNAs representing mRNAs that are rapidly induced following adherence of human monocytes. One of the induced transcripts (MAD-3) encodes a protein of 317 amino acids with one domain containing five tandem repeats of the cdc10/ankyrin motif, which is 60% similar (46% identical) to the ankyrin repeat region of the precursor of NF-κBKBF1 p50. The C-terminus has a putative protein kinase C phosphorylation site. In vitro translated MAD-3 protein was found to specifically inhibit the DNA-binding activity of the p50p65 NF-κB complex but not that of the p50p50 KBF1 factor or of other DNA-binding proteins. The MAD-3 cDNA encodes an IκB-like protein that is likely to be involved in regulation of transcriptional responses to NF-κB, including adhesion-dependent pathways of monocyte activation

The CCAP knowledgebase:Linking protistan and cyanobacterial biological resources with taxonomic and molecular data

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