4,050 research outputs found

    Quantum dot emission from site-controlled ngan/gan micropyramid arrays

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    InxGa1−xN quantum dots have been fabricated by the selective growth of GaN micropyramid arrays topped with InGaN/GaN quantum wells. The spatially, spectrally, and time-resolved emission properties of these structures were measured using cathodoluminescence hyperspectral imaging and low-temperature microphotoluminescence spectroscopy. The presence of InGaN quantum dots was confirmed directly by the observation of sharp peaks in the emission spectrum at the pyramid apices. These luminescence peaks exhibit decay lifetimes of approximately 0.5 ns, with linewidths down to 650 me

    Effect of nickel on the microstructure and mechanical property of die-cast Al–Mg–Si–Mn alloy

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    The effect of nickel on the microstructure and mechanical properties of a die-cast Al–Mg–Si–Mn alloy has been investigated. The results show that the presence of Ni in the alloy promotes the formation of Ni-rich intermetallics. These occur consistently during solidification in the die-cast Al–Mg–Si–Mn alloy across different levels of Ni content. The Ni-rich intermetallics exhibit dendritic morphology during the primary solidification and lamellar morphology during the eutectic solidification stage. Ni was found to be always associated with iron forming AlFeMnSiNi intermetallics, and no Al3Ni intermetallic was observed when Ni concentrations were up to 2.06 wt% in the alloy. Although with different morphologies, the Ni-rich intermetallics were identified as the same AlFeMnSiNi phase bearing a typical composition of Al[100–140](Fe,Mn)[2–7]SiNi[4–9]. With increasing Ni content, the spacing of the α-Al–Mg2Si eutectic phase was enlarged in the Al–Mg–Si–Mn alloy. The addition of Ni to the alloy resulted in a slight increase in the yield strength, but a significant decrease in the elongation. The ultimate tensile strength (UTS) increased slightly from 300 to 320 MPa when a small amount (e.g. 0.16 wt%) of Ni was added to the alloy, but further increase of the Ni content resulted in a decrease of the UTS.The Engineering and Physical Sciences Research Council (EPSRC), Technology Strategy Board (TSB) and Jaguar Land Rover (JLR) in the United Kingdom

    Marek's disease virus-encoded miR-155 ortholog critical for the induction of lymphomas is not essential for the proliferation of transformed cell lines

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    MicroRNAs (miRNAs) are small noncoding RNAs with profound regulatory roles in many areas of biology, including cancer. MicroRNA 155 (miR-155), one of the extensively studied multifunctional miRNAs, is important in several human malignancies such as diffuse large B cell lymphoma and chronic lymphocytic leukemia. Moreover, miR-155 orthologs KSHV-miR-K12-11 and MDV-miR-M4, encoded by Kaposi's sarcoma-associated herpesvirus (KSHV) and Marek's disease virus (MDV), respectively, are also involved in oncogenesis. In MDV-induced T-cell lymphomas and in lymphoblastoid cell lines derived from them, MDV-miR-M4 is highly expressed. Using excellent disease models of infection in natural avian hosts, we showed previously that MDV-miR-M4 is critical for the induction of T-cell lymphomas as mutant viruses with precise deletions were significantly compromised in their oncogenicity. However, those studies did not elucidate whether continued expression of MDV-miR-M4 is essential for maintaining the transformed phenotype of tumor cells. Here using an in situ CRISPR/Cas9 editing approach, we deleted MDV-miR-M4 from the MDV-induced lymphoma-derived lymphoblastoid cell line MDCC-HP8. Precise deletion of MDV-miR-M4 was confirmed by PCR, sequencing, quantitative reverse transcription-PCR (qRT-PCR), and functional analysis. Continued proliferation of the MDV-miR-M4-deleted cell lines demonstrated that MDV-miR-M4 expression is not essential for maintaining the transformed phenotype, despite its initial critical role in the induction of lymphomas. Ability to examine the direct role of oncogenic miRNAs in situ in tumor cell lines is valuable in delineating distinct determinants and pathways associated with the induction or maintenance of transformation in cancer cells and will also contribute significantly to gaining further insights into the biology of oncogenic herpesviruses.IMPORTANCE Marek's disease virus (MDV) is an alphaherpesvirus associated with Marek's disease (MD), a highly contagious neoplastic disease of chickens. MD serves as an excellent model for studying virus-induced T-cell lymphomas in the natural chicken hosts. Among the limited set of genes associated with MD oncogenicity, MDV-miR-M4, a highly expressed viral ortholog of the oncogenic miR-155, has received extensive attention due to its direct role in the induction of lymphomas. Using a targeted CRISPR-Cas9-based gene editing approach in MDV-transformed lymphoblastoid cell lines, we show that MDV-miR-M4, despite its critical role in the induction of tumors, is not essential for maintaining the transformed phenotype and continuous proliferation. As far as we know, this was the first study in which precise editing of an oncogenic miRNA was carried out in situ in MD lymphoma-derived cell lines to demonstrate that it is not essential in maintaining the transformed phenotype

    The Role of Modelling and Simulation in the Preparations for Flight Trials Aboard the Queen Elizabeth Class Aircraft Carriers

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    This paper provides a brief overview of how modelling and simulation has been used to inform preparations for First of Class Flight Trials (FOCFT) aboard HMS Queen Elizabeth, the first of the United Kingdom’s two new Queen Elizabeth Class aircraft carriers, from the perspective of a collaborative research programme undertaken by industry and academia to develop high-fidelity simulations of the carrier’s ‘airwake’.  Computer modelling of the unsteady air flow over the carrier, and of the aircraft flight dynamics, have been integrated into high-fidelity flight simulators at BAE Systems Warton, and at the University of Liverpool.  The Queen Elizabeth Class (QEC) carriers have primarily been designed to operate the Short Take-Off and Vertical Landing (STOVL) variant of the Lockheed Martin F-35 Lightning II multirole fighter aircraft and will also operate a range of rotary-wing assets.  Computational Fluid Dynamics (CFD) has been used to compute the time-varying air flow over and around the 280m long ship, along the F-35B landing approach path and up to 400m astern of the ship.  The paper shows a selection of results from the full-scale CFD analysis, and the results from a small-scale experiment that was conducted to provide confidence in the validity of the computed airwakes.  The QEC airwakes have been employed by BAE Systems in its fixed-wing flight simulator at Warton, where test pilots have conducted simulated deck landings for a variety of wind over deck conditions, so providing experience for F-35B test pilots and the ship’s Flying Control (FLYCO) crew ahead of FOCFT, which will be conducted later this year.  Airwakes have also been implemented in the HELIFLIGHT-R flight simulator at the University of Liverpool, where helicopter landings to the QEC have been simulated using a generic medium-weight maritime-helicopter model. A selection of results from the helicopter flight simulator trials is presented in terms of the workload ratings reported by test pilots, and these are related to the characteristics of the computed airwake at the landing spots tested.  The paper demonstrates how modelling and simulation can be used to reduce both the risk and cost of flight trials, by informing the FOCFT planning process, and by highlighting, in advance of the trials, which wind speed and azimuth combinations may require more focus.  </jats:p

    Relation of gallbladder function and Helicobacter pylori infection to gastric mucosa inflammation in patients with symptomatic cholecystolithiasis

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    Background. Inflammatory alterations of the gastric mucosa are commonly caused by Helicobacter pylori (Hp) infection in patients with symptomatic gallstone disease. However, the additional pathogenetic role of an impaired gallbladder function leading to an increased alkaline duodenogastric reflux is controversially discussed. Aim:To investigate the relation of gallbladder function and Hp infection to gastric mucosa inflammation in patients with symptomatic gallstones prior to cholecystectomy. Patients: Seventy-three patients with symptomatic gallstones were studied by endoscopy and Hp testing. Methods: Gastritis classification was performed according to the updated Sydney System and gallbladder function was determined by total lipid concentration of gallbladder bile collected during mainly laparoscopic cholecystectomy. Results: Fifteen patients revealed no, 39 patients mild, and 19 moderate to marked gastritis. No significant differences for bile salts, phospholipids, cholesterol, or total lipids in gallbladder bile were found between these three groups of patients. However, while only 1 out of 54 (< 2%) patients with mild or no gastritis was found histologically positive for Hp, this infection could be detected in 14 (74%) out of 19 patients with moderate to marked gastritis. Conclusion: Moderate to marked gastric mucosa inflammation in gallstone patients is mainly caused by Hp infection, whereas gallbladder function is not related to the degree of gastritis. Thus, an increased alkaline duodenogastric reflux in gallstone patients seems to be of limited pathophysiological relevance. Copyright (c) 2006 S. Karger AG, Basel

    Multilevel Deconstruction of the In Vivo Behavior of Looped DNA-Protein Complexes

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    Protein-DNA complexes with loops play a fundamental role in a wide variety of cellular processes, ranging from the regulation of DNA transcription to telomere maintenance. As ubiquitous as they are, their precise in vivo properties and their integration into the cellular function still remain largely unexplored. Here, we present a multilevel approach that efficiently connects in both directions molecular properties with cell physiology and use it to characterize the molecular properties of the looped DNA-lac repressor complex while functioning in vivo. The properties we uncover include the presence of two representative conformations of the complex, the stabilization of one conformation by DNA architectural proteins, and precise values of the underlying twisting elastic constants and bending free energies. Incorporation of all this molecular information into gene-regulation models reveals an unprecedented versatility of looped DNA-protein complexes at shaping the properties of gene expression.Comment: Open Access article available at http://www.plosone.org/article/fetchArticle.action?articleURI=info%3Adoi%2F10.1371%2Fjournal.pone.000035

    The Interstellar Medium In Galaxies Seen A Billion Years After The Big Bang

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    Evolution in the measured rest frame ultraviolet spectral slope and ultraviolet to optical flux ratios indicate a rapid evolution in the dust obscuration of galaxies during the first 3 billion years of cosmic time (z>4). This evolution implies a change in the average interstellar medium properties, but the measurements are systematically uncertain due to untested assumptions, and the inability to measure heavily obscured regions of the galaxies. Previous attempts to directly measure the interstellar medium in normal galaxies at these redshifts have failed for a number of reasons with one notable exception. Here we report measurements of the [CII] gas and dust emission in 9 typical (~1-4L*) star-forming galaxies ~1 billon years after the big bang (z~5-6). We find these galaxies have >12x less thermal emission compared with similar systems ~2 billion years later, and enhanced [CII] emission relative to the far-infrared continuum, confirming a strong evolution in the interstellar medium properties in the early universe. The gas is distributed over scales of 1-8 kpc, and shows diverse dynamics within the sample. These results are consistent with early galaxies having significantly less dust than typical galaxies seen at z<3 and being comparable to local low-metallicity systems.Comment: Submitted to Nature, under review after referee report. 22 pages, 4 figures, 4 Extended Data Figures, 5 Extended Data table

    Benefits and risks of the hormetic effects of dietary isothiocyanates on cancer prevention

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    The isothiocyanate (ITC) sulforaphane (SFN) was shown at low levels (1-5 µM) to promote cell proliferation to 120-143% of the controls in a number of human cell lines, whilst at high levels (10-40 µM) it inhibited such cell proliferation. Similar dose responses were observed for cell migration, i.e. SFN at 2.5 µM increased cell migration in bladder cancer T24 cells to 128% whilst high levels inhibited cell migration. This hormetic action was also found in an angiogenesis assay where SFN at 2.5 µM promoted endothelial tube formation (118% of the control), whereas at 10-20 µM it caused significant inhibition. The precise mechanism by which SFN influences promotion of cell growth and migration is not known, but probably involves activation of autophagy since an autophagy inhibitor, 3-methyladenine, abolished the effect of SFN on cell migration. Moreover, low doses of SFN offered a protective effect against free-radical mediated cell death, an effect that was enhanced by co-treatment with selenium. These results suggest that SFN may either prevent or promote tumour cell growth depending on the dose and the nature of the target cells. In normal cells, the promotion of cell growth may be of benefit, but in transformed or cancer cells it may be an undesirable risk factor. In summary, ITCs have a biphasic effect on cell growth and migration. The benefits and risks of ITCs are not only determined by the doses, but are affected by interactions with Se and the measured endpoint

    SentiBench - a benchmark comparison of state-of-the-practice sentiment analysis methods

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    In the last few years thousands of scientific papers have investigated sentiment analysis, several startups that measure opinions on real data have emerged and a number of innovative products related to this theme have been developed. There are multiple methods for measuring sentiments, including lexical-based and supervised machine learning methods. Despite the vast interest on the theme and wide popularity of some methods, it is unclear which one is better for identifying the polarity (i.e., positive or negative) of a message. Accordingly, there is a strong need to conduct a thorough apple-to-apple comparison of sentiment analysis methods, \textit{as they are used in practice}, across multiple datasets originated from different data sources. Such a comparison is key for understanding the potential limitations, advantages, and disadvantages of popular methods. This article aims at filling this gap by presenting a benchmark comparison of twenty-four popular sentiment analysis methods (which we call the state-of-the-practice methods). Our evaluation is based on a benchmark of eighteen labeled datasets, covering messages posted on social networks, movie and product reviews, as well as opinions and comments in news articles. Our results highlight the extent to which the prediction performance of these methods varies considerably across datasets. Aiming at boosting the development of this research area, we open the methods' codes and datasets used in this article, deploying them in a benchmark system, which provides an open API for accessing and comparing sentence-level sentiment analysis methods

    Evaluation of serum glycoprotein biomarker candidates for detection of esophageal adenocarcinoma and surveillance of Barrett’s esophagus

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    Esophageal adenocarcinoma (EAC) is thought to develop from asymptomatic Barrett’s esophagus (BE) with a low annual rate of conversion. Current endoscopy surveillance for BE patients is probably not cost-effective. Previously, we discovered serum glycoprotein biomarker candidates which could discriminate BE patients from EAC. Here, we aimed to validate candidate serum glycoprotein biomarkers in independent cohorts, and to develop a biomarker candidate panel for BE surveillance. Serum glycoprotein biomarker candidates were measured in 301 serum samples collected from Australia (4 states) and USA (1 clinic) using previously established lectin magnetic bead array (LeMBA) coupled multiple reaction monitoring mass spectrometry (MRM-MS) tier 3 assay. The area under receiver operating characteristic curve (AUROC) was calculated as a measure of discrimination, and multivariate recursive partitioning was used to formulate a multimarker panel for BE surveillance. Complement C9 (C9), gelsolin (GSN), serum paraoxonase/arylesterase 1 (PON1) and serum paraoxonase/lactonase 3 (PON3) were validated as diagnostic glycoprotein biomarkers in lectin pull-down samples for EAC across both cohorts. A panel of 10 serum glycoprotein biomarker candidates discriminated BE patients not requiring intervention [BE+/- low grade dysplasia] from those requiring intervention [BE with high grade dysplasia (BE-HGD) or EAC] with an AUROC value of 0.93. Tissue expression of C9 was found to be induced in BE, dysplastic BE and EAC. In longitudinal samples from subjects that have progressed towards EAC, levels of serum C9 were significantly (P\u3c0.05) increased with disease progression in EPHA (erythroagglutinin from Phaseolus vulgaris) and NPL (Narcissus pseudonarcissus lectin) pull-down samples. The results confirm alteration of complement pathway glycoproteins during BE-EAC pathogenesis. Further prospective clinical validation of the confirmed biomarker candidates in a large cohort is warranted, prior to development of a first-line BE surveillance blood test
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