2,878 research outputs found

    Modeling the human bone marrow niche in mice: From host bone marrow engraftment to bioengineering approaches

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    Xenotransplantation of patient-derived samples in mouse models has been instrumental in depicting the role of hematopoietic stem and progenitor cells in the establishment as well as progression of hematological malignancies. The foundations for this field of research have been based on the development of immunodeficient mouse models, which provide normal and malignant human hematopoietic cells with a supportive microenvironment. Immunosuppressed and genetically modified mice expressing human growth factors were key milestones in patient-derived xenograft (PDX) models, highlighting the importance of developing humanized microenvironments. The latest major improvement has been the use of human bone marrow (BM) niche-forming cells to generate human-mouse chimeric BM tissues in PDXs, which can shed light on the interactions between human stroma and hematopoietic cells. Here, we summarize the methods used for human hematopoietic cell xenotransplantation and their milestones and review the latest approaches in generating humanized BM tissues in mice to study human normal and malignant hematopoiesis

    The application of mHealth to mental health: opportunities and challenges

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    Recent advances in smartphones and wearable biosensors enable the gathering of ‘real-time’ psychological, behavioural and physiological data, in increasingly precise and unobtrusive ways. It is therefore now possible to collect moment-to-moment information about an individuals’ moods, cognitions and activities, as well as automated data about their whereabouts, behaviour and physiological states. In this paper, we discuss the potential of these new mobile digital technologies for transforming mental health research and clinical practice. By drawing on a recent research project, we illustrate how traditional boundaries between research and clinical practice are becoming increasingly blurred and how in turn, this is leading to exciting new developments in the assessment and management of common mental disorders. The potential risks and key challenges associated with applying mobile technology to mental health are also discussed

    Transient, unsettling and creative space: Experiences of liminality through the accounts of Chinese students on a UK-based MBA

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    This is the author's accepted manuscript. The final published article is available from the link below. Copyright @ The Author(s) 2009.This article explores the experiences of liminality through the accounts of Chinese students on a UK-based MBA programme. The transient nature of the MBA experience, as well as the international status of the Chinese student, is resonant with conceptualizations of liminality as ‘in between’ space. Based on semi-structured interviews with 20 MBA graduates who had subsequently returned to China with their qualification, we explored their perceptions of outcomes from the course and their experiences as international students on a programme imbued with western norms and values. Results support the unsettling yet creative implications of liminality, as well as the fragmented insecure nature of identities, as individuals pass through the MBA ‘rite of passage’ in terms of ‘becoming’ a manager and entering a new phase of career. Accounts suggest the creation of hierarchical structures within liminal space whereby Chinese students, through their positioning at the margin, have uncomfortable yet illuminating encounters with alterity. At the same time, they experience levels of ambiguity and uncertainty in the post-liminal phase of China-located employments, as new western-based managerial identities collide with dominant discourses of Chinese organization

    Vandetanib-eluting Radiopaque Beads: <i>In vivo</i> Pharmacokinetics, Safety and Toxicity Evaluation following Swine Liver Embolization.

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    To evaluate the plasma and tissue pharmacokinetics, safety and toxicity following intra-arterial hepatic artery administration of Vandetanib (VTB)-eluting Radiopaque Beads (VERB) in healthy swine. In a first phase, healthy swine were treated with hepatic intra-arterial administration of VERB at target dose loading strengths of 36 mg/mL (VERB36), 72 mg/mL (VERB72) and 120 mg/mL (VERB120). Blood and tissue samples were taken and analysed for VTB and metabolites to determine pharmacokinetic parameters for the different dose forms over 30 days. In a second phase, animals were treated with unloaded radiopaque beads or high dose VTB loaded beads (VERB100, 100 mg/mL). Tissue samples from embolized and non-embolized areas of the liver were evaluated at necropsy (30 and 90 days) for determination of VTB and metabolite levels and tissue pathology. Imaging was performed prior to sacrifice using multi-detector computed tomography (MDCT) and imaging findings correlated with pathological changes in the tissue and location of the radiopaque beads. The peak plasma levels of VTB (C &lt;sub&gt;max&lt;/sub&gt; ) released from the various doses of VERB ranged between 6.19-17.3 ng/mL indicating a low systemic burst release. The plasma profile of VTB was consistent with a distribution phase up to 6 h after administration followed by elimination with a half-life of 20-23 h. The AUC of VTB and its major metabolite N-desmethyl vandetanib (NDM VTB) was approximately linear with the dose strength of VERB. VTB plasma levels were at or below limits of detection two weeks after administration. In liver samples, VTB and NDM VTB were present in treated sections at 30 days after administration at levels above the &lt;i&gt;in vitro&lt;/i&gt; IC &lt;sub&gt;50&lt;/sub&gt; for biological effectiveness. At 90 days both analytes were still present in treated liver but were near or below the limit of quantification in untreated liver sections, demonstrating sustained release from the VERB. Comparison of the reduction of the liver lobe size and associated tissue changes suggested a more effective embolization with VERB compared to the beads without drug. Hepatic intra-arterial administration of VERB results in a low systemic exposure and enables sustained delivery of VTB to target tissues following embolization. Changes in the liver tissue are consistent with an effective embolization and this study has demonstrated that VERB100 is well tolerated with no obvious systemic toxicity

    Superstructure and Correlated Na+ Hopping in a Layered Mg-Substituted Sodium Manganate Battery Cathode are Driven by Local Electroneutrality

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    Acknowledgments ARTICLE SECTIONSJump To E.N.B. acknowledges funding from the Engineering Physical Sciences Research Council (EPSRC) via the National Productivity Interest Fund (NPIF) 2018 (EP/S515334/1). J.D.B. acknowledges funding from the Faraday Institution (EP/S003053/1, FIRG016). The authors also thank the Science and Technology Facilities Council (STFC) and ISIS Neutron and Muon source for neutron data (experiment no.: RB2010350). Additional thanks are given to the staff scientists at beamline I11 of the Diamond Light Source for synchrotron data using block allocation group time under proposal CY34243. This work also utilized the ARCHER UK National Supercomputing Service via our membership in the UK’s HEC Materials Chemistry Consortium, funded by the EPSRC (EP/L000202). The research was also carried out at the Center for Functional Nanomaterials, Brookhaven National Laboratory, through the U.S. Department of Energy, Office of Basic Energy Sciences, Contract DE-AC02-98CH10866. E.N.B. would also like to thank A. Van der Ven and M.A. Jones for illuminating discussions.Peer reviewedPublisher PD

    Structural evolution in synthetic, Ca-based sorbents for carbon capture

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    The carbonation of CaO-based materials at high temperatures (e.g. > 600°C) is a promising method of capturing CO₂ emitted from, e.g. the combustion of carbonaceous fuels. The resulting CaCO₃ can be regenerated by calcination at a temperature at which the equilibrium partial pressure exceeds that of the local partial pressure of CO₂ (e.g. 950°C). A process involving repeated cycles of carbonation and calcination of a calcareous material is called calcium looping. The capacity of a CaO-based sorbent to accept and reject CO₂ over many cycles is governed by a number of factors, such as chemical composition, surface morphology and pore structure, all of which often evolve with cycling. The present paper investigates the underlying mechanisms controlling the evolution of the micro-structures of a series of synthetic sorbents consisting of CaO mixed with the inert supports Ca₁₂Al₁₄O₃₃ and MgO. These sorbents were subjected to cycles of calcination and carbonation and were characterised using a variety of in situ and ex situ techniques. It was found that the balance between the degree of surface cracking during calcination and the extent of sintering during carbonation was responsible for changes in uptake during cycling, giving an increase in uptake for the supported CaO and a decrease for the unsupported CaO.The authors would like to thank the Australian Synchtrotron for the award of beamtime, and Justin Kimpton and Qinfen Gu for their help with the design and operation of the in situ gas flow capillary XRD cell. Mr Zlatko Zaracevic is acknowledged for the BET measurements. W.L acknowledges funding from the National Research Foundation (NRF), Prime Minister’s Office, Singapore under its Campus for Research Excellence and Technological Enterprise (CREATE) programme. B.G acknowledges the EU Research Fund for Coal and Steel (project number RFCR-CT-2012-00008). M.T.D acknowledges funding from the Cambridge Commonwealth Trusts and Trinity College, Cambridge and the EU ERC for an advanced fellowship for CPG. D.S.S acknowledges financial support by Engineering and Physical Sciences Research Council (EPSRC). C.D.L acknowledges funding by the Australian Research Council (Discovery Projects).This is the final version of the article. It first appeared from Elsevier via http://dx.doi.org/10.1016/j.ces.2015.09.01

    Massively parallel landscape-evolution modelling using general purpose graphical processing units

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    As our expectations of what computer systems can do and our ability to capture data improves, the desire to perform ever more computationally intensive tasks increases. Often these tasks, comprising vast numbers of repeated computations, are highly interdependent on each other – a closely coupled problem. The process of Landscape-Evolution Modelling is an example of such a problem. In order to produce realistic models it is necessary to process landscapes containing millions of data points over time periods extending up to millions of years. This leads to non-tractable execution times, often in the order of years. Researchers therefore seek multiple orders of magnitude reduction in the execution time of these models. The massively parallel programming environment offered through General Purpose Graphical Processing Units offers the potential for multiple orders of magnitude speedup in code execution times. In this paper we demonstrate how the time dominant parts of a Landscape-Evolution Model can be recoded for a massively parallel architecture providing two orders of magnitude reduction in execution time
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