46 research outputs found

    Stinking Foreshore to Tree Lined Avenue: Investigating the Riverine Lives Impacted by the Construction of the Thames Embankments in Victorian London

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    Victorian London saw dramatic physical changes along the river Thames. Large enclosed Docks and Thames Embankments were constructed as the city struggled to cope with its ballooning population and prospering shipping industry. Whilst the Thames Embankments have been hailed as engineering triumphs, the fate of those whose livelihood relied on access to the river in central London (such as wharf workers, barge, ferry and lighter men, and others) is unknown. In order to investigate the impact of the Embankment, a methodology has been developed which enables characterisation of a large swathe of urban riverside throughout the mid- to late 19th century, whilst also ensuring that the stories of individuals and communities are not lost. The approach combines and adapts established methodologies, such as Historic Landscape/Seascape Characterisation and Maritime Cultural Landscapes, to understand the nature and changes in the urban riverside landscape. This methodology forms the background for detailed research on smaller sites, such as a single street, housing block, or industrial site, in order to create ‘Ethnographies of Place’. These small-scale ‘Ethnographies’ have the potential to tell stories about how the social and economic circumstances of individuals and communities changed as a result of the landscape changes associated with the Embankment construction. This paper presents the initial work to establish the methodology and preliminary conclusions based on key sources

    Immunoparesis defined by heavy/light chain pair suppression in smoldering multiple myeloma shows initial isotype specificity and involves other isotypes in advanced disease

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    Smoldering multiple myeloma (SMM) is an asymptomatic and biologically heterogeneous plasma cell disorder, with a highly variable clinical course. Immunoparesis, defined by total immunoglobulin measurements, has been shown to be an independent risk factor for progression to symptomatic disease. The heavy/light chain (HLC) assay allows precise measurement of the polyclonal immunoglobulin of the same isotype, enabling the evaluation of isotype-matched immunoparesis (IMI). In this study, we prospectively characterized immunoparesis, as determined by HLC measurements, in 53 SMM patients. Severe IMI was present in 51% of patients, while severe IP of uninvolved isotypes (HLC IP) was present in 39%. Most of the patients with severe HLC IP presented with severe IMI, but not the other way around. Isotype specificity of immune suppression was suggested by lower relative values of isotype-matched HLC pairs, both for IgG and IgA SMM. Severe IMI was associated with other risk factors for progression while patients with severe IMI and severe HLC IP showed an even higher risk profile. Both severe IMI and severe IgM HLC IP showed a significantly shorter time to progression. Finally, gene expression analysis demonstrated differences in the bone marrow microenvironment between patients with IMI and IMI plus HLC IP, with an increased expression of genes associated with cytolytic cells. In conclusion, our data supports isotype specificity of early immunoglobulin suppression mechanisms. While suppression of both involved and uninvolved isotypes is associated with risk of progression, the later appears to develop with more advanced disease and could be mediated by different mechanisms.© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature

    Preliminary to the Intonation Study of Okayama Dialect of Japanese

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    application/pdfThe aim of this short paper is to report the results of the preliminary field research the author conducted into the intonation of Okayama dialect of Japanese, and thereby raising some related issues. The main points drawn from the discussion based on the research are summarized as follows: (i) both interrogative and non-interrogative sentences, including imperative ones, fundamentally have a global falling tonal pattern; (ii) interrogative sentences, both yes/no- and wh-questions, are formed by means of sentence-final particles‘ン’and‘ノン’, the latter of which is used in negative interrogative sentences; (iii) interrogative sentences/utterances may exceptionally have a global rising, non-falling tonal pattern in the following three cases: i) when an interrogative sentence lacks an interrogative particle for some reasons; ii) when a hearer intends to request a speaker to repeat what he or she has just uttered; iii) when a speaker intends to remind a hearer of something or to reconfirm something.journal articl

    Towards a Description of Danish Intonation: Its Basic Concepts and Issues

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    application/pdfThis paper aims at exploring further into Danish intonation from descriptive linguistic point of view. Although a large number of studies have been made on Danish intonation, little is known and we still lack enough data and knowledge to be utilized in an actual pedagogical situation. This ascribes to the fact that the primary interest of scholars lies in acoustic/experimental analysis and mathematical modeling of intonation. To deepen our knowledge and understanding about Danish intonation, the author conducted field researches and elicited the primary data of intonation. Based on the data, this paper discusses the relationship between several sentence types and terminal tonal patterns and reveals several important basic key concepts and mechanisms operative behind intonation.journal articl

    Historic Landscape Characterisation: Technical Approaches Beyond Theory

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    \ua9 2021 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group. This paper describes how Historic Landscape Characterisation (HLC) projects are implemented using Geographical Information Systems. Today, HLCs are still often considered simple thematic maps to visualise landscape histories, but they are more than that–spatial databases that serve more than one purpose and could be integrated in planning processes with different types of aims. By explaining how historic characterisation is carried out in GIS environments and how future methodological developments can unlock HLC’s potential in spatial analysis, this paper seeks to enhance the integration of HLC in various spatially driven projects and processes. While exploring the technical aspects of HLC a further purpose of the paper is to reach out towards other approaches (e.g. Landscape Character Assessment) to be better equipped in finding solutions to complement them

    The Isle of Wight in the English landscape: Medieval and Post-Medieval rural settlement and land use.

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    The thesis is a local-scale study which aims to place the Isle of Wight in the English landscape. It examines the much discussed but problematic concept of ‘islandness’, identifying distinctive insular characteristics and determining their significance but also investigating internal landscape diversity. This is the first detailed academic study of Isle of Wight land use and settlement from the early medieval period to the nineteenth century and is fully referenced to national frameworks. The thesis utilises documentary, cartographic and archaeological evidence. It employs the techniques of historic landscape characterisation (HLC), using synoptic maps created by the author and others as tools of graphic analysis. An analysis of the Isle of Wight’s physical character and cultural roots is followed by an investigation of problems and questions associated with models of settlement and land use at various scales. Specifically, national-scale models by Oliver Rackham and by Brian Roberts and Stuart Wrathmell are critically assessed for their value as frameworks within which Isle of Wight data may be examined, as is the local-scale Isle of Wight HLC model. Historic Ordnance Survey maps, royal surveys, manorial surveys and other sources are used to define the Isle of Wight’s territorial units and patterns of land use, enclosure and settlement; to create a new model of 1790s HLC Areas; and to construct a database listing all settlements by size and form. Nucleation and dispersion densities are calculated from this database, compared with Isle of Wight densities mapped by Roberts & Wrathmell and discussed in relation to densities elsewhere in England. Regional-scale patterns of settlement and land-use within central southern England are considered and the relevance of national-scale models of settlement and land use to this region is discussed. The origins and evolution of Isle of Wight settlements are then explored, using evidence from early sources including place-names, Domesday Book, tax lists and surveys. Subsequent analysis defines discrete cultural zones within the Isle of Wight, confirming the diversity and ancient origins of its cultural landscapes. The final chapter provides a synoptic assessment of models, emphasising the value of the local-scale 1790s HLC Areas model and recognising the compatibility of Roberts & Wrathmell’s national-scale settlement model with detailed local data for the Isle of Wight. It is found that Rackham’s model of Ancient Countryside conforms partially with local attributes but that this model may now need some revision. The paradoxical status of the Solent as both a gateway and a cultural boundary is proposed, as is the Island’s affinity with other ‘peripheral’ areas of England

    The high-level committee and the ITU in the 21st century

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    The High-Level Committee (HLC) has made a series of carefully crafted, thoughtful proposals designed to help the ITU maintain its pre-eminent position in the field of telecommunications. In this article the author analyses the HLC's proposals in each of the major areas outlined in its mandate from the point of view of the rationale for change. Why is the change being discussed; who wants change; what sort of change is being proposed; and what will happen if change is not forthcoming?

    Microfabricated 3D Culture for Promoting Hepatic Differentiation of Stem Cell and Maintaining Hepatocyte Function for Liver Tissue Engineering

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    Many factors (such as alcohol and toxins) can cause acute and chronic liver diseases, which can further develop into liver failure. End-stage liver failure is associated with high rates of morbidity and mortality and liver transplantation is the only effective treatment. However, due to limited number of donors, at least 15% patients die while being on the waiting list for liver transplant. Liver regenerative medicine, including hepatocyte transplantation, bioartificial livers and bioengineered grafts, can be an alternative for liver transplantation. In vitro culture of hepatocytes can serve as a cell source for liver regenerative medicine. However, in most cases, the isolated primary hepatocytes rapidly dedifferentiate and lose their functions in vitro, which leads to a shortage of available hepatocytes for liver regenerative medicine. Consequently, developing a strategy to improve hepatocyte functions in vitro or supply hepatocyte or hepatocyte-like cell (HLC) derived from stem cells will advance our understanding of liver regenerative medicine and facilitate end-stage liver diseases therapy using hepatocyte and stem cells.Liver extracellular matrix (ECM) regulates the specification of liver progenitors and hepatocyte functions in vivo. Previous studies showed that decellularized ECM scaffold and liver derived-ECM hydrogel can maintain the functions of isolated hepatocyte in vitro. However, given that native ECM is composed of various component(s) that assemble into a complex structure, the effect of individual and combination of ECM component on hepatic function should be determined in order to optimize the scaffold properties. In addition, understanding the role of individual ECM component can facilitate liver regenerative medicine using hepatocyte and stem cells. Here, we explore the effects of different ECM components (i.e. type I collagen, type IV collagen, laminin, fibronectin) on hepatocyte cell polarity and hepatic function maintenance, as well as the basis of the ECM effects. However, no significant difference in terms of hepatic functions was observed in traditional monolayer culture when different ECM molecules were applied. Previous studies suggested hepatocytes in spheroids culture can better mimic their in vivo state. Thus, we try to aggregate hepatocytes to form hepatocyte spheroids, and our results suggest that spheroids culture can restore the polarity of hepatocytes. Alginate encapsulation can further enhance cell-cell interaction and improve hepatic functions. Moreover, differential effects of ECM molecules were observed in 3D spheroid encapsulation (when ECM was mixed with alginate) but not so much in other configurations. LM displayed the best individual effect on hepatocyte hepatic function maintenance in 3D culture. When ECM components were mixed in combinatorial screening, a strong positive effect of CI and a negative interaction effect of CI*LM on some hepatic functions were observed. In addition, we found that the effect of LM relies on the activation of integrin α1 and integrin α6 signals. These findings on ECM effect on hepatocyte culture have broad applications in optimizing ECM microenvironments for liver regenerative medicine.To expand the source of available hepatocytes, stem cell-derived HLC has been generated by researchers. HLC can be potential cell sources for liver tissue engineering. Nevertheless, traditional 2D differentiation methods produce HLC similar to fetal hepatocytes rather than mature hepatocytes. Therefore, promoting functional maturation of HLC is necessary. Some studies have reported 3D differentiation could promote differentiated HLC mature. However, there are also some challenges associated with 3D culture, such as insufficient oxygen and nutrient supply due to the large size of hydrogel, non-uniform spheroids size and non-uniform distributions of embryonic bodies (EB). Microfluidics technique allows high throughput generation of size-controllable microgels. Here, we utilized microfluidics technique to encapsulate ESC into CI microgels for 3D differentiation. Our results suggested uniform-sized EB were formed after ESC were encapsulated in collagen microgels that were later differentiated to HLC with high efficiency. Compared with 3D encapsulation in a bulk collagen hydrogel and 2D differentiation, our approach resulted in HLC with higher ALB gene expression and lower AFP gene expression, indicating HLC in CI microgel was more mature. Our studies on ESC hepatic differentiation can provide relatively mature and available HLC and facilitate the development of liver tissue engineering.In conclusion, our results provide a method to maintain liver function in vitro and supply functional HLC derived from stem cells. Our research can potentially help develop cell-based treatment for end-stage liver diseases.許多因素(例如酒精和毒素)都會導致急性和慢性肝病的發生,並可能進一步發展為肝衰竭。肝衰竭具有高發病率和高死亡率。目前,肝移植是肝衰竭唯一有效的治療方法。然而由於肝臟供體有限,每年至少有15%的患者在等待肝移植的過程中死亡。肝再生醫學,包括肝細胞移植,人工肝和組織工程肝組織移植,是潛在的肝移植的替代療法,而體外培養肝細胞是肝再生醫學的基礎。然而,從人體中分離的原代肝細胞在體外會迅速退分化並喪失增殖能力和肝功能,這導致了可用于肝再生醫學的肝細胞的短缺。因此,研究改善體外培養的肝細胞功能以及擴大可用肝細胞或類肝細胞樣細胞的方法將增進我們對肝再生醫學的理解,並促進利用肝細胞和幹細胞來源的類肝細胞樣細胞進行終末期肝病治療的發展。肝細胞外基質(ECM)可以調節體內肝祖細胞的分化和肝細胞功能。研究表明,脫細胞的ECM支架和肝臟來源的ECM水凝膠可以幫助分離的肝細胞維持它們的功能。然而天然ECM支架的成分十分複雜,研究具體ECM成分對於肝細胞功能的影響可以幫助我們優化出有助於肝細胞功能維持的生物材料支架,而瞭解不同ECM成分的作用也可以促進肝再生醫學的發展。本研究中,我們研究了不同ECM成分( I型膠原(CI),IV型膠原(CIV),層粘連蛋白(LM),纖連蛋白(FN))對肝細胞極性和肝功能維持的影響。然而在2D培養中,不同的ECM成分對肝細胞功能沒有明顯影響。而有研究表明,細胞團培養中的肝細胞可以更好地類比其在體狀態。因此,我們將肝細胞聚集為肝細胞團並研究不同ECM成分對於肝細胞團的肝功能的影響。結果表明,細胞團培養可以幫助肝細胞恢復細胞極性,而藻酸鹽封裝可以增強細胞間的相互作用並促進肝細胞的功能。我們的研究表明,不同ECM成分對於3D培養的肝細胞團的功能提升有著不同作用,LM能夠全方位地提升肝細胞團的肝功能,這與ITGA1和ITGA6信號的轉導有關。然而當不同ECM成分組合在一起時,CI有著明顯的促進肝功能的作用,而CI*LM的組合則有著明顯的抑制肝功能的作用。人胚胎幹細胞(hESC)衍生的類肝細胞樣細胞(HLC)是肝再生醫學潛在的細胞來源。然而,傳統的2D分化方法產生的HLC與胎兒肝細胞相似,與成熟的肝細胞相去甚遠。因此,產生成熟的具有肝功能的HLC是肝細胞再生醫學的第一步。有研究表明3D分化可以促進分化的HLC成熟,然而,3D培養中的一些困難可能會阻礙分化的肝細胞的成熟,例如傳統方法產生水凝膠過大,而其中的細胞團分佈不均勻從而導致的氧氣和營養供應不足不利於肝細胞的成熟。而微流控技術可以產生大量直徑相似的微凝膠(microgel)。因此,我們利用微流控技術將hESC封裝在CI微凝膠中然後再進行肝細胞方向分化,希望這能產生大量可用的成熟有功能的肝細胞。而我們的結果表明,hESC被包裹在膠原微凝膠可以成功分化為HLC,並且與CI水凝膠和2D分化的HLC相比微凝膠分化的HLC具有更高的ALB表達和更低的AFP表達,這表明微凝膠產生的HLC更加成熟。我們利用微流控技術包裹hESC並進行分化的方法可以產生大量成熟可用的類肝細胞樣細胞,這可能會促進肝組織工程的發展。總之,我們關於利用ECM成分幫助分離的肝細胞維持肝功能和利用微流控技術包裹hESC從而產生大量成熟可用的類肝細胞樣細胞可能有助於肝再生醫學的發展和晚期肝病的治療。DENG, Shuai.Ph.D. Chinese University of Hong Kong 2021.Includes bibliographical references (leaves )Abstracts in English and Chinese.Title from PDF title page (viewed on ...

    Decoupling the heat loss coefficient of an in-use office building into its transmission and infiltration heat loss coefficients

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    [EN]The actual building energy performance essentially depends on the building occupant's behaviour, the real performance of the installed energy systems and the in-use performance of the building envelope. The thermal performance characterization of in-use building envelopes, based on monitored data, represents a crucial step towards bridging the gap between the designed and as-built energy performance of buildings. The main indicator to analyse the performance gap of building envelopes is the Heat Loss Coefficient (HLC); when measured, it commonly shows considerable differences when compared with the design value. This research goes further and proposes a method, based on monitored data from in-use buildings, for the decoupling of the HLC of in-use buildings into its transmission (UA) and infiltration (C-v) heat loss coefficients, in order to identify the origin of the heat losses. The identification of this origin will facilitate the reduction of the performance gap. Therefore, a multi-storey occupied office building of the University of the Basque Country has been monitored and analysed, where the in-use HLC for each floor and for the whole building have already been estimated using an average method. Then, based on the ASTM D6245-18 Standard, the decay method of the metabolic CO2 of the building's occupants has been successfully applied in this paper to obtain the Air Change per Hour (ACH) rates due to infiltrations. These ACH values have been used to decouple the estimated HLC values into their transmission and infiltration parts.This work was supported by the Spanish Ministry of Science, Inno-vation and Universities and the European Regional Development Fund (grant number RTI2018-096296-B-C22) through the MONITHERM project 'Investigation of monitoring techniques of occupied buildings for their thermal characterization and methodology to identify their key performance indicators', project reference: RTI2018-096296-B-C22 (MCIU/AEI/FEDER, UE) . The corresponding author also acknowledges the support provided by the Education Department of the Basque Gov-ernment through a scholarship granted to her to complete her PhD degree

    Simulating Change in Cultural Landscapes: The Integration of Historic Landscape Characterisation and Computer Modelling

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    More than 80 per cent of the world's landscapes are influenced significantly by human activities, and current land-use and land cover trends are likely to increase the rate of landscape change at a significant rate in the near future. To manage and guide landscape change, and an advocacy of positive landscape change–rather than attempts to stop change as in traditional preservationist approaches–requires the identification of threats and opportunities. Tools to do this will need to be based on well-investigated evidence for the long-term past evolution of landscapes and the understanding of possible future scenarios for change. Historic landscape characterisation (HLC) is a GIS-based method employed to interpret and study landscapes with a particular focus on representing and mapping the aspects of landscape character which result from past cultural processes. This paper introduces a new protocol which uses HLC data to model future landscape evolution and to simulate scenarios of landscape change. It describes a computer-based simulation framework derived from landscape ecology and used with HLC datasets during research on a region in southern Turkey. Such integrated modelling protocols have the potential to assist landscape planners to develop holistic and informative approaches to managing landscape change. © 2021 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.Research Councils UK, RCUK, (AH/P005829/1); Türkiye Bilimsel ve Teknolojik Araştirma Kurumu, TÜBITAK, (116K829
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