147 research outputs found

    Co-transcriptional R-loops are the main cause of estrogen-induced DNA damage.

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    The hormone estrogen (E2) binds the estrogen receptor to promote transcription of E2-responsive genes in the breast and other tissues. E2 also has links to genomic instability, and elevated E2 levels are tied to breast cancer. Here, we show that E2 stimulation causes a rapid, global increase in the formation of R-loops, co-transcriptional RNA-DNA products, which in some instances have been linked to DNA damage. We show that E2-dependent R-loop formation and breast cancer rearrangements are highly enriched at E2-responsive genomic loci and that E2 induces DNA replication-dependent double-strand breaks (DSBs). Strikingly, many DSBs that accumulate in response to E2 are R-loop dependent. Thus, R-loops resulting from the E2 transcriptional response are a significant source of DNA damage. This work reveals a novel mechanism by which E2 stimulation leads to genomic instability and highlights how transcriptional programs play an important role in shaping the genomic landscape of DNA damage susceptibility

    Search for Neutral Supersymmetric Higgs Bosons in ppˉp\bar{p} Collisions at s=1.8\sqrt{s}=1.8 TeV

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    We present the results of a search for neutral Higgs bosons produced in association with bb quarks in ppˉ→bbˉϕ→bbˉbbˉp\bar{p}\to b\bar{b} \phi\to b\bar{b}b\bar{b} final states with 91±791 \pm 7 pb−1^{-1} of ppˉp\bar{p} collisions at s=1.8\sqrt{s}=1.8 TeV recorded by the Collider Detector at Fermilab. We find no evidence of such a signal and the data is interpreted in the context of the neutral Higgs sector of the Minimal Supersymmetric extension of the Standard Model. With basic parameter choices for the supersymmetric scale and the stop quark mixing, we derive 95% C.L. lower mass limits for neutral Higgs bosons for \tb values in excess of 35.Comment: 2 tex files 3 figure

    Preparing construction supply chains for blockchain technology:An investigation of its potential and future directions

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    Blockchain, a peer-to-peer, controlled, distributed database structure, has the potential to profoundly affect current business transactions in the construction industry through smart contracts, cryptocurrencies, and reliable asset tracking. The construction industry is often criticized for being slow in embracing emerging technologies and not effectively diffusing them through its supply chains. Often, the extensive fragmentation, traditional procurement structures, destructive competition, lack of collaboration and transparency, low-profit margins, and human resources are shown as the main culprits for this. As blockchain technology makes its presence felt strongly in many other industries like finance and banking, this study investigates the preparation of construction supply chains for blockchain technology through an explorative analysis. Empirical data for the study were collected through semistructured interviews with 17 subject experts. Alongside presenting a strengths, weaknesses, opportunities, and threats analysis (SWOT), the study exhibits the requirements for and steps toward a construction supply structure facilitated by blockchain technology
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