438 research outputs found

    Improved quantification of Chinese carbon fluxes using CO2/CO correlations in Asian outflow

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    [1] We use observed CO2:CO correlations in Asian outflow from the TRACE-P aircraft campaign (February–April 2001), together with a three-dimensional global chemical transport model (GEOS-CHEM), to constrain specific components of the east Asian CO2 budget including, in particular, Chinese emissions. The CO2/CO emission ratio varies with the source of CO2 (different combustion types versus the terrestrial biosphere) and provides a characteristic signature of source regions and source type. Observed CO2/CO correlation slopes in east Asian boundary layer outflow display distinct regional signatures ranging from 10–20 mol/mol (outflow from northeast China) to 80 mol/mol (over Japan). Model simulations using best a priori estimates of regional CO2 and CO sources from Streets et al. [2003] (anthropogenic), the CASA model (biospheric), and Duncan et al. [2003] (biomass burning) overestimate CO2 concentrations and CO2/CO slopes in the boundary layer outflow. Constraints from the CO2/CO slopes indicate that this must arise from an overestimate of the modeled regional net biospheric CO2 flux. Our corrected best estimate of the net biospheric source of CO2 from China for March–April 2001 is 3200 Gg C/d, which represents a 45 % reduction of the net flux from the CASA model. Previous analyses of the TRACE-P data had found that anthropogenic Chinese C

    Informed finite element modelling for wire and arc additively manufactured metallics—a case study on modular building connections

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    The use of 3D printing in modular building connections is a novel and promising technique. However, the performance of 3D printed steel modular building connections has not been investigated adequately to date. Therefore, this paper presents a three-dimensional finite element model (FEM), using the multi-purpose software Abaqus, to study the effect of different geometrical and material parameters on the ultimate behaviour of modular building connections (herein named 3DMBC) using a wire and arc additive manufacturing (WAAM) method, as part of the UK’s 3DMBC (3D Modular Building Connections) project. The proposed model considers material and geometrical non-linearities, initial imperfections, and the contact between adjacent surfaces. The finite element results are compared with the currently available experimental results and validated to ensure developed FEM can be used to analyse the behaviour of 3DMBC with some adjustments. Case studies were investigated using the validated model to analyse the ultimate behaviour with different nominal and WAAM-produced materials under various loading arrangements. Based on the results, it is recommended to conservatively use the treated or untreated WAAM material properties obtained in θ = 90◦ print orientation in the finite element modelling of 3DMBCs considering the complex component arrangements and multi-directional loading in the modular connections. It is also noted that the thickness of beams and columns of fully 3D printed connections can be increased to achieve the same level of performance as traditional modular connections. For the 3DMBCs printed using untreated WAAM, the thickness increment was found to be 50% in this study

    COVID-19: UK frontline intensivists' emerging learning.

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    The Intensive Care Society held a webinar on 3 April 2020 at which representatives from 11 of the most COVID-19 experienced hospital trusts in England and Wales shared learning around five specific topic areas in an open forum. This paper summarises the emerging learning and practice shared by those frontline clinicians

    CD28 between tolerance and autoimmunity: The side effects of animal models [version 1; referees: 2 approved]

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    Regulation of immune responses is critical for ensuring pathogen clearance and for preventing reaction against self-antigens. Failure or breakdown of immunological tolerance results in autoimmunity. CD28 is an important co-stimulatory receptor expressed on T cells that, upon specific ligand binding, delivers signals essential for full T-cell activation and for the development and homeostasis of suppressive regulatory T cells. Many in vivo mouse models have been used for understanding the role of CD28 in the maintenance of immune homeostasis, thus leading to the development of CD28 signaling modulators that have been approved for the treatment of some autoimmune diseases. Despite all of this progress, a deeper understanding of the differences between the mouse and human receptor is required to allow a safe translation of pre-clinical studies in efficient therapies. In this review, we discuss the role of CD28 in tolerance and autoimmunity and the clinical efficacy of drugs that block or enhance CD28 signaling, by highlighting the success and failure of pre-clinical studies, when translated to humans

    Flexural Behaviour of Built-up Beams Made of Optimised Sections

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    The modular construction industry often seeks cost-effective, high-performing, and longer-span members in buildings to ensure efficiency and quality. Accordingly, the idea of built-up sections was brought into gain numerous benefits including higher structural capacity, improved torsional rigidity, and increased stiffness. While limited research studies have been carried out to study the structural performances of built-up sections, few innovative section profiles have been developed in the industry considering the structural benefits, including improved stiffness. Hence, the application of newly developed built-up sections could enhance the employment of built-up sections in the industry. On that note, this research is focused on the flexural behaviour of optimised section profiles named the LCB-benchmark (Lipped Channel Beam), the optimised-LCB, folded-flange and the super-sigma sections. In addition, different materials, namely cold-formed carbon steel (CFS), cold-formed (CF) aluminium and CF stainless steel, were considered for built-up sections, in order to provide recommendations based on their flexural performances. Numerical analysis was carried out on single sections as well as on built-up sections to the developed parametric plan after the successful validation of experimental studies. The results were compared for single and built-up sections. Finally, based on the comparisons, the folded-flange built-up section is recommended for all three materials as it displayed the highest bending capacity, and the capacity enhancement compared to the corresponding single section was a minimum of 131

    Characterization of a New Mouse Model for Peripheral T Cell Lymphoma in Humans

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    Peripheral T cell lymphomas (PTCLs) are associated with a poor prognosis due to often advanced disease at the time of diagnosis and due to a lack of efficient therapeutic options. Therefore, appropriate animal models of PTCL are vital to improve clinical management of this disease. Here, we describe a monoclonal CD8+ CD4− αβ T cell receptor Vβ2+ CD28+ T cell lymphoma line, termed T8-28. T8-28 cells were isolated from an un-manipulated adult BALB/c mouse housed under standard pathogen-free conditions. T8-28 cells induced terminal malignancy upon adoptive transfer into syngeneic BALB/c mice. Despite intracellular expression of the cytotoxic T cell differentiation marker granzyme B, T8-28 cells appeared to be defective with respect to cytotoxic activity as read-out in vitro. Among the protocols tested, only addition of interleukin 2 in vitro could partially compensate for the in vivo micro-milieu in promoting growth of the T8-28 lymphoma cells

    The anti-breast cancer stem cell properties of gold( i )-non-steroidal anti-inflammatory drug complexes

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    The anti-breast cancer stem cell (CSC) properties of a series of gold(i) complexes comprising various non-steroidal anti-inflammatory drugs (NSAIDs) and triphenylphosphine 1–8 are reported. The most effective gold(i)-NSAID complex 1, containing indomethacin, exhibits greater potency for breast CSCs than bulk breast cancer cells (up to 80-fold). Furthermore, 1 reduces mammosphere viability to a better extent than a panel of clinically used breast cancer drugs and salinomycin, an established anti-breast CSC agent. Mechanistic studies suggest 1-induced breast CSC death results from breast CSC entry, cytoplasm localisation, an increase in intracellular reactive oxygen species levels, cyclooxygenase-2 downregulation and inhibition, and apoptosis. Remarkably, 1 also significantly inhibits tumour growth in a murine metastatic triple-negative breast cancer model. To the best of our knowledge, 1 is the first gold complex of any geometry or oxidation state to demonstrate anti-breast CSC properties
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