1,138 research outputs found

    Edge local complementation for logical cluster states

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    A method is presented for the implementation of edge local complementation in graph states, based on the application of two Hadamard operations and a single controlled-phase (CZ) gate. As an application, we demonstrate an efficient scheme to construct a one-dimensional logical cluster state based on the five-qubit quantum error-correcting code, using a sequence of edge local complementations. A single physical CZ operation, together with local operations, is sufficient to create a logical CZ operation between two logical qubits. The same construction can be used to generate any encoded graph state. This approach in concatenation may allow one to create a hierarchical quantum network for quantum information tasks.Comment: 15 pages, two figures, IOP styl

    The Transcription co-Repressors MTG8 and MTG16 Regulate Exit of Intestinal Stem Cells From Their Niche and Differentiation into Enterocyte vs Secretory Lineages

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    BACKGROUND & AIMS: Notch signaling maintains intestinal stem cells (ISCs). When ISCs exit the niche, Notch signaling among early progenitor cells at position +4/5 regulates their specification toward secretory vs enterocyte lineages (binary fate). The transcription factor ATOH1 is repressed by Notch in ISCs; its de-repression, when Notch is inactivated, drives progenitor cells to differentiate along the secretory lineage. However, it is not clear what promotes transition of ISCs to progenitors and how this fate decision is established. METHODS: We sorted cells from Lgr5-Gfp knock-in intestines from mice and characterized gene expression patterns. We analyzed Notch regulation by examining expression profiles (by quantitative reverse transcription PCR and RNAscope) of small intestinal organoids incubated with the Notch inhibitor DAPT, intestine tissues from mice given injections of the Îł-secretase inhibitor dibenzazepine, and mice with intestine-specific disruption of Rbpj. We analyzed intestine tissues from mice with disruption of the RUNX1 translocation partner 1 gene (Runx1t1, also called Mtg8) or CBFA2/RUNX1 partner transcriptional co-repressor 3 (Cbfa2t3, also called Mtg16), and derived their organoids, by histology, immunohistochemistry, and RNA sequencing. We performed chromatin immunoprecipitation and sequencing analyses of intestinal crypts to identify genes regulated by MTG16. RESULTS: The transcription co-repressors MTG8 and MTG16 were highly expressed by +4/5 early progenitors, compared with other cells along crypt-villus axis. Expression of MTG8 and MTG16 were repressed by Notch signaling via ATOH1 in organoids and intestine tissues from mice. MTG8- and MTG16-knockout intestines had increased crypt hyperproliferation and expansion of ISCs, but enterocyte differentiation was impaired, based on loss of enterocyte markers and functions. Chromatin immunoprecipitation and sequencing analyses showed that MTG16 bound to promoters of genes that are specifically expressed by stem cells (such as Lgr5 and Ascl2) and repressed their transcription. MTG16 also bound to previously reported enhancer regions of genes regulated by ATOH1, including genes that encode delta-like canonical Notch ligand and other secretory-specific transcription factors. CONCLUSIONS: In intestine tissues of mice and human intestinal organoids, MTG8 and MTG16 repress transcription in the earliest progenitor cells to promote exit of ISCs from their niche (niche exit) and control the binary fate decision (secretory vs enterocyte lineage) by repressing genes regulated by ATOH1

    Membrane Topology of the Lactococcal Bacteriocin ATP-binding Cassette Transporter Protein LcnC. Involvement of LcnC in Lactococcin A Maturation

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    Many non-lantibiotic bacteriocins of lactic acid bacteria are produced as precursors with N-terminal leader peptides different from those present in preproteins exported by the general sec-dependent (type II) secretion pathway. These bacteriocins utilize a dedicated (type I) secretion system for externalization. The secretion apparatus for the lactococcins A, B, and M/N (LcnA, B, and M/N) from Lactococcus lactis is composed of the two membrane proteins LcnC and LcnD. LcnC belongs to the ATP-binding cassette transporters, whereas LcnD is a protein with similarities to other accessory proteins of type I secretion systems. This paper shows that the N-terminal part of LcnC is involved in the processing of the precursor of LcnA. By making translational fusions of LcnC to the reporter proteins β-galactosidase (LacZ) and alkaline phosphatase (PhoA*), it was shown that both the N- and C-terminal parts of LcnC are located in the cytoplasm. As the N terminus of LcnC is required for LcnA maturation and is localized in the cytoplasm, we conclude that the processing of the bacteriocin LcnA to its mature form takes place at the cytosolic side of the cytoplasmic membrane.

    Changes in the Activities, Functions, and Roles of Public Health Educators

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    Accounts of early activities of public health educators, statements of the American Public Health Association on the qualifications and functions of these educators, and studies concerned with their responsibilities, functions, work, or roles are reviewed. These point up the three major foci in public health education over time in the U.S., viz, dissemination of information, community organization, and health behavior and program planning. Functions of public health educators in emerging settings for practice are presented and the implications of this movement (i.e., movement of health educators into non-traditional settings) for the public health education profession are discussedPeer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/66927/2/10.1177_109019817600400304.pd

    Empty forest or empty rivers? A century of commercial hunting in Amazonia

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    The Amazon basin is the largest and most species-rich tropical forest and river system in the world, playing a pivotal role in global climate regulation and harboring hundreds of traditional and indigenous cultures. It is a matter of intense debate whether the ecosystem is threatened by hunting practices, whereby an “empty forest” loses critical ecological functions. Strikingly, no previous study has examined Amazonian ecosystem resilience through the perspective of the massive 20th century international trade in furs and skins. We present the first historical account of the scale and impacts of this trade and show that whereas aquatic species suffered basin-wide population collapse, terrestrial species did not. We link this differential resilience to the persistence of adequate spatial refuges for terrestrial species, enabling populations to be sustained through source-sink dynamics, contrasting with unremitting hunting pressure on more accessible aquatic habitats. Our findings attest the high vulnerability of aquatic fauna to unregulated hunting, particularly during years of severe drought. We propose that the relative resilience of terrestrial species suggests a marked opportunity for managing, rather than criminalizing, contemporary traditional subsistence hunting in Amazonia, through both the engagement of local people in community-based comanagement programs and science-led conservation governance

    Deep learning for prediction of colorectal cancer outcome: a discovery and validation study

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    Background Improved markers of prognosis are needed to stratify patients with early-stage colorectal cancer to refine selection of adjuvant therapy. The aim of the present study was to develop a biomarker of patient outcome after primary colorectal cancer resection by directly analysing scanned conventional haematoxylin and eosin stained sections using deep learning. Methods More than 12 000 000 image tiles from patients with a distinctly good or poor disease outcome from four cohorts were used to train a total of ten convolutional neural networks, purpose-built for classifying supersized heterogeneous images. A prognostic biomarker integrating the ten networks was determined using patients with a non-distinct outcome. The marker was tested on 920 patients with slides prepared in the UK, and then independently validated according to a predefined protocol in 1122 patients treated with single-agent capecitabine using slides prepared in Norway. All cohorts included only patients with resectable tumours, and a formalin-fixed, paraffin-embedded tumour tissue block available for analysis. The primary outcome was cancer-specific survival. Findings 828 patients from four cohorts had a distinct outcome and were used as a training cohort to obtain clear ground truth. 1645 patients had a non-distinct outcome and were used for tuning. The biomarker provided a hazard ratio for poor versus good prognosis of 3·84 (95% CI 2·72–5·43; p<0·0001) in the primary analysis of the validation cohort, and 3·04 (2·07–4·47; p<0·0001) after adjusting for established prognostic markers significant in univariable analyses of the same cohort, which were pN stage, pT stage, lymphatic invasion, and venous vascular invasion. Interpretation A clinically useful prognostic marker was developed using deep learning allied to digital scanning of conventional haematoxylin and eosin stained tumour tissue sections. The assay has been extensively evaluated in large, independent patient populations, correlates with and outperforms established molecular and morphological prognostic markers, and gives consistent results across tumour and nodal stage. The biomarker stratified stage II and III patients into sufficiently distinct prognostic groups that potentially could be used to guide selection of adjuvant treatment by avoiding therapy in very low risk groups and identifying patients who would benefit from more intensive treatment regimes
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