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This paper describes the context, motivation, and requirements behind the design and development of the first version of the Data Documentation Initiative 2 (DDI) metadata community specification, with an emphasis upon the process of creating the initial element set for the “study level” of DDI version 1. We also offer a framework for understanding the infrastructural changes that contributed to the establishment of the DDI. By taking a close look at the confluence of influences on the earliest efforts to design and build the DDI, we can better understand what essential elements of metadata are necessary to support independent use of social science data over time.

Many ovarian cancers have a chromosomal rearrangement that fuses two neighboring genes, ESRRA and c11orf20. Similar rearrangements may be common, important features of cancer genomes that have largely escaped detection., Every year, ovarian cancer kills approximately 14,000 women in the United States and more than 140,000 women worldwide. Most of these deaths are caused by tumors of the serous histological type, which is rarely diagnosed before it has disseminated. By deep paired-end sequencing of mRNA from serous ovarian cancers, followed by deep sequencing of the corresponding genomic region, we identified a recurrent fusion transcript. The fusion transcript joins the 5′ exons of ESRRA, encoding a ligand-independent member of the nuclear-hormone receptor superfamily, to the 3′ exons of C11orf20, a conserved but uncharacterized gene located immediately upstream of ESRRA in the reference genome. To estimate the prevalence of the fusion, we tested 67 cases of serous ovarian cancer by RT-PCR and sequencing and confirmed its presence in 10 of these. Targeted resequencing of the corresponding genomic region from two fusion-positive tumor samples identified a nearly clonal chromosomal rearrangement positioning ESRRA upstream of C11orf20 in one tumor, and evidence of local copy number variation in the ESRRA locus in the second tumor. We hypothesize that the recurrent novel fusion transcript may play a role in pathogenesis of a substantial fraction of serous ovarian cancers and could provide a molecular marker for detection of the cancer. Gene fusions involving adjacent or nearby genes can readily escape detection but may play important roles in the development and progression of cancer., Author Summary Serous ovarian cancer, the most common form of ovarian cancer, is especially lethal because it is usually only detected at a late stage in its progression, after the cancer has spread to other tissues. We searched for molecular markers of this cancer that might provide a better way to detect tumors at a curable stage and that might provide targets for new treatments. Chromosomal rearrangements that fuse two genes to produce a recombinant gene that enhances growth or spread of the cancer are particularly specific biomarkers and have been found in many cancers. By “deep” sequencing of the RNA molecules that carry genetic information in serous ovarian cancers, we discovered a rearrangement that fuses the same two neighboring genes in at least 15% of these tumors. The two fused genes are ESRRA, which encodes a key regulator of gene expression, and an essentially uncharacterized gene, C11orf20, that is normally adjacent to the ESRRA gene. Chromosomal rearrangements that recombine parts of two nearby genes or even parts of a single gene may be a common, important feature of the cancer genome that eludes detection by most approaches to characterizing cancer genomes.

The primary objective of this study is to demonstrate the activation and analyze the regulation of the MEK- S6 kinase pathway in high-grade ovarian cancer. Phospho-ERK (pERK), a direct substrate of MEK and two phosphorylation sites on the ribosomal protein, S6, Ser235/236 and Ser240/244, which are both targeted by the MEK and PI3-kinase/AKT pathways, were analyzed in 13 cell lines, 28 primary cancers and 8 cases of cancer cells from ascites. In primary cancers, ERK and S6 phosphorylation was measured by immunohistochemistry (IHC). pERK, pS6, pAKT and p4EBP1 were also measured by Western blotting (WB). The regulation of S6 phosphorylation by the MEK and PI3-kinase pathways was determined in ovarian cancer cell lines. We observed frequent pERK expression in primary ovarian cancers (100 % by WB, 75% by IHC) but not in ovarian cancer cells from ascites (25% of cases by WB). The activation of the AKT pathway, measured by pAKT expression occurred in 7 cases of primary ovarian cancer by WB, but in none of the ascites samples. In ovarian cancer cell lines, the MEK pathway had a greater effect on S6 phosphorylation in cells without hyperactive AKT signaling. Our data suggest that MEK is a potential drug target in high-grade ovarian cancer, however cancer cells with hyperactive AKT and cancer cells in ascites may be less responsive to MEK inhibition. The phosphorylation of S6 as a specific biomarker for either MEK or PI3-kinase pathway activation should be used with caution.

This study was initiated to identify biomarkers with potential value for the early detection of poor-outcome breast cancer. Two sets of well-characterized tissues were utilized: one from breast cancer patients with favorable vs. poor outcome and the other from healthy women undergoing reduction mammaplasty. Over 46 differentially expressed genes were identified from a large list of potential targets by a) mining publicly available expression data (identifying 134 genes for quantitative PCR) and b) utilizing a commercial PCR array. Three genes show elevated expression in cancers with poor outcome and low expression in all other tissues, warranting further investigation as potential blood markers for early detection of cancers with poor outcome. Twelve genes showed lower expression in cancers with poor outcome than in cancers with favorable outcome but no differential expression between aggressive cancers and most healthy controls. These genes are more likely to be useful as prognostic tissue markers than as serum markers for early detection of aggressive disease. As a secondary finding was that, when histologically normal breast tissue was removed from a distant site in a breast with cancer, 7 of 38 specimens displayed a cancer-like expression profile, while the remaining 31 were genetically similar to the reduction mammaplasty control group. This finding suggests that some regions of ipsilateral histologically 'normal' breast tissue are predisposed to becoming malignant and that normal-appearing tissue with malignant signature might warrant treatment to prevent new primary tumors. © 2010 Schummer et al.

Background Elucidation of the repertoire of secreted and cell surface proteins of tumor cells is relevant to molecular diagnostics, tumor imaging and targeted therapies. We have characterized the cell surface proteome and the proteins released into the extra-cellular milieu of three ovarian cancer cell lines, CaOV3, OVCAR3 and ES2 and of ovarian tumor cells enriched from ascites fluid. Methodology and Findings To differentiate proteins released into the media from protein constituents of media utilized for culture, cells were grown in the presence of [13C]-labeled lysine. A biotinylation-based approach was used to capture cell surface associated proteins. Our general experimental strategy consisted of fractionation of proteins from individual compartments followed by proteolytic digestion and LC-MS/MS analysis. In total, some 6,400 proteins were identified with high confidence across all specimens and fractions. Conclusions and Significance Protein profiles of the cell lines had substantial similarity to the profiles of human ovarian cancer cells from ascites fluid and included protein markers known to be associated with ovarian cancer. Proteomic analysis indicated extensive shedding from extra-cellular domains of proteins expressed on the cell surface, and remarkably high secretion rates for some proteins (nanograms per million cells per hour). Cell surface and secreted proteins identified by in-depth proteomic profiling of ovarian cancer cells may provide new targets for diagnosis and therapy.

AL s service-learning scholarship enters its second generation, the writing on service-learningl must begin to reflect our own-and our institutions'complex relationship to "doing good." Since service-learning is a widely accepted part of many college curriculums, those who write about servicelearning must go beyond the pragmatics of when and how to integrate service into composition courses and begin to theorize who participates in servicelearning programs and why they do so. I hope, as Cynthia Rosenberger writes, that service-learning can create a "more just and humane society," and believe that in order to do this service-learning must "generate a thoughtful and critical consciousness in all stakeholders" (39). We must begin theorizing how service-learning is experienced differently by those from different groups and look closely at the gaps between our theories of service-learning and our theories of subject position(s), of race, class, gender, sexuality, and writing. Recent work

When we read Michael Murphy's article, "New Faculty for a New University," we were surprised and troubled by the story about adjuncts that Murphy purports to tell. Murphy's argument, that a teaching substructure in rhetoric and composition exists but remains invisible and that to recognize such a substructure would cost universities "very little," is based on a notion of universities that has not existed in most places for a very long time, if ever. Murphy's idea of a "teaching track" that supports full-time faculty research is based on a conception of a university at a handful of research institutions. Schools that train graduate students, produce the bulk of scholarship in the field of rhetoric and composition, and grant PhDs are about 7 percent of the total number of universities in this country (Phelan 76). To make an argument about adjunct work and adjunct labor without considering the other 93 percent of us seems to us to be thoughtless, at best, and unethical, at worst. The other aspect of adjuncting that Murphy leaves out is, of course, gender. As Theresa Enos writes, "When a field has been feminized and when a disproportionate number of its workers are female, that field is devalued and is subject to both disciplinary and gender bias" (43). As the latest report on Women in the Profession indicates, women are still "more likely than white men ... to obtain jobs in lower-paying institutions .., and they tend to linger

The effects of seven antineoplastic agents (dacarbazine, procarbazine. hexamethylmelamine. carmustine, lomustine, chlorozotocin, p -carbmethoxyphenyldimethyltriazene) on oxidative drug metabolism were studied. With the exception of dacarbazine and chlorozotocin they inhibited p -nitroanisol O -demethylase in vitro in liver 9000 g supernatant of CBALac mice. The inhibition mode was mixed for procarbazine and hexamethylmelamine, apparent K i values for these drugs were 1.9 and O.8mM. Carmustine and p -carbmethoxyphenyldimethyltriazene (CMPDT) showed uncompetitive inhibition. Procarbazine inhibition is mediated by a metabonate and the inhibition by CMPDT is reduced by non-specific binding. The administration of these agents at tumour curative doses in vivo lead only to weak to negligible depression of O - and N -demethylase activities 10 min, l day and 3 days after cessation of drug administration.