2,366 research outputs found

    Exclusive development of T cell neoplasms in mice transplanted with bone marrow expressing activated Notch alleles

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    Notch is a highly conserved transmembrane protein that is involved in cell fate decisions and is found in organisms ranging from Drosophila to humans. A human homologue of Notch, TAN1, was initially identified at the chromosomal breakpoint of a subset of T-cell lymphoblastic leukemias/lymphomas containing a t(7;9) chromosomal translocation; however, its role in oncogenesis has been unclear. Using a bone marrow reconstitution assay with cells containing retrovirally transduced TAN1 alleles, we analyzed the oncogenic potential of both nuclear and extranuclear forms of truncated TAN1 in hematopoietic cells. Although the Moloney leukemia virus long terminal repeat drives expression in most hematopoietic cell types, retroviruses encoding either form of the TAN1 protein induced clonal leukemias of exclusively immature T cell phenotypes in approximately 50% of transplanted animals. All tumors overexpressed truncated TAN1 of the size and subcellular localization predicted from the structure of the gene. These results show that TAN1 is an oncoprotein and suggest that truncation and overexpression are important determinants of transforming activity. Moreover, the murine tumors caused by TAN1 in the bone marrow transplant model are very similar to the TAN1-associated human tumors and suggest that TAN1 may be specifically oncotropic for T cells

    Improving the accuracy of protein secondary structure prediction using structural alignment

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    BACKGROUND: The accuracy of protein secondary structure prediction has steadily improved over the past 30 years. Now many secondary structure prediction methods routinely achieve an accuracy (Q3) of about 75%. We believe this accuracy could be further improved by including structure (as opposed to sequence) database comparisons as part of the prediction process. Indeed, given the large size of the Protein Data Bank (>35,000 sequences), the probability of a newly identified sequence having a structural homologue is actually quite high. RESULTS: We have developed a method that performs structure-based sequence alignments as part of the secondary structure prediction process. By mapping the structure of a known homologue (sequence ID >25%) onto the query protein's sequence, it is possible to predict at least a portion of that query protein's secondary structure. By integrating this structural alignment approach with conventional (sequence-based) secondary structure methods and then combining it with a "jury-of-experts" system to generate a consensus result, it is possible to attain very high prediction accuracy. Using a sequence-unique test set of 1644 proteins from EVA, this new method achieves an average Q3 score of 81.3%. Extensive testing indicates this is approximately 4–5% better than any other method currently available. Assessments using non sequence-unique test sets (typical of those used in proteome annotation or structural genomics) indicate that this new method can achieve a Q3 score approaching 88%. CONCLUSION: By using both sequence and structure databases and by exploiting the latest techniques in machine learning it is possible to routinely predict protein secondary structure with an accuracy well above 80%. A program and web server, called PROTEUS, that performs these secondary structure predictions is accessible at . For high throughput or batch sequence analyses, the PROTEUS programs, databases (and server) can be downloaded and run locally

    Sloan Digital Sky Survey Spectroscopic Lens Search. I. Discovery of Intermediate-Redshift Star-Forming Galaxies Behind Foreground Luminous Red Galaxies

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    We present a catalog of 49 spectroscopic strong gravitational lens candidates selected from a Sloan Digital Sky Survey sample of 50996 luminous red galaxies. Potentially lensed star-forming galaxies are detected through the presence of background oxygen and hydrogen nebular emission lines in the spectra of these massive foreground galaxies. This multiline selection eliminates the ambiguity of single-line identification and provides a very promising sample of candidate galaxy-galaxy lens systems at low to intermediate redshift, with foreground redshifts ranging from 0.16 to 0.49 and background redshifts from 0.25 to 0.81. Any lenses confirmed within our sample would be important new probes of early-type galaxy mass distributions, providing complementary constraints to those obtained from currently known lensed high-redshift quasars.Comment: 23 pages; to appear in The Astronomical Journal, 2004 April. Version with full-resolution figures available at http://web.mit.edu/bolton/www/speclens.ps.gz (PostScript) or http://web.mit.edu/bolton/www/speclens.pdf (PDF

    A first-principles study of oxygen vacancy pinning of domain walls in PbTiO3

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    We have investigated the interaction of oxygen vacancies and 180-degree domain walls in tetragonal PbTiO3 using density-functional theory. Our calculations indicate that the vacancies do have a lower formation energy in the domain wall than in the bulk, thereby confirming the tendency of these defects to migrate to, and pin, the domain walls. The pinning energies are reported for each of the three possible orientations of the original Ti-O-Ti bonds, and attempts to model the results with simple continuum models are discussed.Comment: 8 pages, with 3 postscript figures embedded. Uses REVTEX and epsf macros. Also available at http://www.physics.rutgers.edu/~dhv/preprints/lh_dw/index.htm

    Interpreting core-level spectra of oxidizing phosphorene: Theory and experiment

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    We combine ab initio density functional theory calculations with the equivalent cores approximation to determine core-level binding-energy shifts at phosphorus sites caused by oxidation of phosphorene. We find that presence of oxygen increases the core-level binding energies of P atoms and expect binding-energy shifts of up to 6 eV in highly defective geometries. We have identified likely binding geometries of oxygen that help to interpret the observed core-level photoemission spectra in samples at different stages of oxidation and allow us to determine the fractions of specific local geometries

    Pro-neural transcription factors as cancer markers.

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    BACKGROUND: The aberrant transcription in cancer of genes normally associated with embryonic tissue differentiation at various organ sites may be a hallmark of tumour progression. For example, neuroendocrine differentiation is found more commonly in cancers destined to progress, including prostate and lung. We sought to identify proteins which are involved in neuroendocrine differentiation and differentially expressed in aggressive/metastatic tumours. RESULTS: Expression arrays were used to identify up-regulated transcripts in a neuroendocrine (NE) transgenic mouse model of prostate cancer. Amongst these were several genes normally expressed in neural tissues, including the pro-neural transcription factors Ascl1 and Hes6. Using quantitative RT-PCR and immuno-histochemistry we showed that these same genes were highly expressed in castrate resistant, metastatic LNCaP cell-lines. Finally we performed a meta-analysis on expression array datasets from human clinical material. The expression of these pro-neural transcripts effectively segregates metastatic from localised prostate cancer and benign tissue as well as sub-clustering a variety of other human cancers. CONCLUSION: By focussing on transcription factors known to drive normal tissue development and comparing expression signatures for normal and malignant mouse tissues we have identified two transcription factors, Ascl1 and Hes6, which appear effective markers for an aggressive phenotype in all prostate models and tissues examined. We suggest that the aberrant initiation of differentiation programs may confer a selective advantage on cells in all contexts and this approach to identify biomarkers therefore has the potential to uncover proteins equally applicable to pre-clinical and clinical cancer biology.RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are

    Using the affective priming paradigm to explore the attitudes underlying walking behaviour

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    Objectives. Walking is poorly represented in memory, making it difficult to measure using self-report and even harder to predict. To circumvent this, we used the affective priming paradigm (Fazio, Sanbonmatsu, Powell, & Kardes, 1986) to assess implicit attitudes towards walking. Methods. Royal Air Force trainee aircraftsmen (N ¼ 188) wore pedometers for 1 week prior to completing the affective priming paradigm, questionnaire and interview. The affective priming paradigm involved a computer-based response latency task containing physical activity words as primes followed by adjectives as targets to be evaluated. Targets were drawn from two bipolar dichotomies, good–bad (the original Fazio et al. items) and happy–sad (mood). Results. Priming for mood items was related to levels of physical activity with high frequency participants priming for the positive (happy) pole and low frequency participants priming for the negative (sad). Both groups primed for the negative element of the Fazio (good–bad) dichotomy. Regarding walking and running, there was no differentiation on the basis of participation level. Instead, facilitated responses to happy targets contrasted with inhibited responses to sad targets for both types of locomotion. There was weak evidence that intentions to run were associated with priming of positive target items, irrespective of category. Conclusions. The relationship between implicit attitudes and behaviour is complex. Whereas implicit attitudes were related to overall exercise participation, they were not related to the specific activity of walking, despite the behaviour being mainly under automatic control.</p

    Discontinuities in soil strength contribute to destabilization of nutrient-enriched creeks

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    In a whole-ecosystem, nutrient addition experiment in the Plum Island Sound Estuary (Massachusetts), we tested the effects of nitrogen enrichment on the carbon and nitrogen contents, respiration, and strength of marsh soils. We measured soil shear strength within and across vegetation zones. We found significantly higher soil percent organic matter, carbon, and nitrogen in the long-term enriched marshes and higher soil respiration rates with longer duration of enrichment. The soil strength was similar in magnitude across depths and vegetation zones in the reference creeks, but showed signs of significant nutrient-mediated alteration in enriched creeks where shear strength at rooting depths of the low marsh-high marsh interface zone was significantly lower than at the sub-rooting depths or in the creek bank vegetation zone. To more closely examine the soil strength of the rooting (10-30 cm) and sub-rooting (40-60 cm) depths in the interface and creek bank vegetation zones, we calculated a vertical shear strength differential between these depths. We found significantly lower differentials in shear strength (rooting depth \u3c sub-rooting depths) in the enriched creeks and in the interface zones. The discontinuities in the vertical and horizontal shear strength across the enriched marshes may contribute to observed fracturing and slumping occurring in the marsh systems. Tide gauge data also showed a pattern of rapid sea level rise for the period of the study, and changes in plant distribution patterns were indicative of increased flooding. Longer exposure times to nutrient-enriched waters and increased hydraulic energy associated with sea level rise may exacerbate creek bank sloughing. Additional research is needed, however, to better understand the interactions of nutrient enrichment and sea level rise on soil shear strength and stability of tidal salt marshes

    Impact of a novel surgical wound protection device on observed versus expected surgical site infection rates after colectomy using the National Surgical Quality Improvement Program Risk Calculator

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    Surgical site infection (SSI) remains a persistent and morbid problem in colorectal surgery. A novel surgical device that combines barrier surgical wound protection and continuous surgical wound irrigation was evaluated in a cohort of elective colorectal surgery patients. A retrospective analysis was performed comparing rates of SSI observed in a prospective cohort study with the predicted rate of SSI using the American College of Surgeons (ACS) National Surgical Quality Improvement Program (NSQIP) Risk Calculator.A prospective multi-center study of colectomy patients was conducted using a study device for surgical site retraction and protection, as well as irrigation of the incision. Patients were followed for 30 days after the surgical procedure to assess for SSI. After completion of the study, patients' characteristics were inserted into the ACS-NSQIP Risk Calculator to determine the predicted rate of SSI for the given patient population and compared with the observed rate in the study.A total of 108 subjects were enrolled in the study. The observed rate of SSI in the prospective study using the novel device was 3.7% (4/108). The predicted rate of SSI in the same patient population utilizing the ACS-NSQIP Risk Calculator was estimated to be 9.5%. This demonstrated a 61% difference (3.7% vs. 9.5%, p = 0.04) in SSI from the NSQIP predicted rate with the use of the irrigating surgical wound protection and retraction device.These data suggest the use of a novel surgical wound protection device seems to reduce the rate of SSIs in colorectal surgery
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