2,314 research outputs found

    Recovery of caustic soda from the mercerization process

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    M.S.William L. Hyde

    Interactive effects of land use, river regulation, and climate on a key recreational fishing species in temperate and boreal streams

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    Numerous anthropogenic stressors, including river regulation, excess loadings of nutrients and sediment, channelisation, as well as thermal and hydrological stressors driven by climate change impact riverine ecosystems worldwide. In a time when freshwater degradation and the rate of global warming are faster than ever, understanding the potential interactive effects of local and catchment-scale stressors with large-scale climatic conditions is essential to enhance our ability to plan effective conservation, restoration, and mitigation measures. In this study we analysed a dataset spanning the whole of Sweden using a space-for-time approach to investigate interactive effects of land use, river regulation, and climate on brown trout (Salmo trutta) abundance in streams. We found that in warmer regions trout populations were negatively affected in catchments with more intense river regulation by hydropower dams (i.e. >= 10 m(3)/km(2) total reservoir storage volume). In such catchments, a 7 degrees C warmer mean summer air temperature was associated with an average between 44% and 83% decline in trout abundance. In catchments with less intense river regulation, trout abundance instead increased moderately with increasing temperature. We also found that brown trout abundance declined with increasing areal extent of urban areas when found in combination with >= 20% agricultural land use. When agricultural land use reached maximum values (84%), brown trout abundance decreased from an average of 13 individuals per 100 m(2) in catchments with no urban areas to values = 5% urban land use. Also, brown trout abundance declined with increasing agricultural land use in catchments with >= 3% urban land use. Our study brings innovative empirical evidence of interactive effects between river regulation, land use and climate on brown trout populations. From a management perspective our findings suggest that: (1) restoring natural flows (e.g. through dam removal) and riparian vegetation could mitigate adverse effects of climate change; and (2) restoration measures that minimise the effects of agriculture and urban land use (e.g. reduction of nutrient levels and restored riparian buffer zones) could help rehabilitate brown trout in catchments with high anthropogenic land use change. However, given the large observed variation between streams, we advise for bespoke management actions stemming from sound knowledge of local habitat conditions and target populations, whenever possible, using an ecosystem management-based approach

    Melancholia and conviviality in modern literary Scots : Sanghas, Sengas and Shairs

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    This paper considers the visions of Scottish identity projected in twenty-first century, post-devolution Scots literature, and seeks to read them against Paul Gilroy’s Postcolonial Melancholia (2005) which examines the protean identities of post-imperial Britain. Gilroy looks particularly at social and artistic manifestations of racial and cultural inequality, although conceding that there is also room for a ‘postcolonial conviviality’ that celebrates diversity. His critique of this ‘Britain’ is, however, selectively constructed, making only passing reference to the constituent nations of the United Kingdom, and no space is devoted to an evaluation of post-colonial Wales, Scotland or Northern Ireland. As yet, no comparable analysis is forthcoming for these ‘home nations’, so this paper attempts to outline the ways in which Scottish—and particularly Scots—literature may provide relevant comparable cultural commentary. Focus is given here to literature written in Scots because the choice to write in Scots is strongly politically motivated and speaks immediately to the question of cultural inequality and loss. Specific attention is paid to Matthew Fitt’s But n Ben A-Go-Go (2000), Suhayl Saadi’s Psychoraag (2004), and Anne Donovan’s Buddha Da (2003), which various engage with questions of personal and national identity as their main characters take part in their personal journeys

    HER2-enriched subtype and novel molecular subgroups drive aromatase inhibitor resistance and an increased risk of relapse in early ER+/HER2+ breast cancer

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    BACKGROUND: Oestrogen receptor positive/ human epidermal growth factor receptor positive (ER+/HER2+) breast cancers (BCs) are less responsive to endocrine therapy than ER+/HER2- tumours. Mechanisms underpinning the differential behaviour of ER+HER2+ tumours are poorly characterised. Our aim was to identify biomarkers of response to 2 weeks’ presurgical AI treatment in ER+/HER2+ BCs. METHODS: All available ER+/HER2+ BC baseline tumours (n=342) in the POETIC trial were gene expression profiled using BC360™ (NanoString) covering intrinsic subtypes and 46 key biological signatures. Early response to AI was assessed by changes in Ki67 expression and residual Ki67 at 2 weeks (Ki672wk). Time-To-Recurrence (TTR) was estimated using Kaplan-Meier methods and Cox models adjusted for standard clinicopathological variables. New molecular subgroups (MS) were identified using consensus clustering. FINDINGS: HER2-enriched (HER2-E) subtype BCs (44.7% of the total) showed poorer Ki67 response and higher Ki672wk (p<0.0001) than non-HER2-E BCs. High expression of ERBB2 expression, homologous recombination deficiency (HRD) and TP53 mutational score were associated with poor response and immune-related signatures with High Ki672wk. Five new MS that were associated with differential response to AI were identified. HER2-E had significantly poorer TTR compared to Luminal BCs (HR 2.55, 95% CI 1.14–5.69; p=0.0222). The new MS were independent predictors of TTR, adding significant value beyond intrinsic subtypes. INTERPRETATION: Our results show HER2-E as a standardised biomarker associated with poor response to AI and worse outcome in ER+/HER2+. HRD, TP53 mutational score and immune-tumour tolerance are predictive biomarkers for poor response to AI. Lastly, novel MS identify additional non-HER2-E tumours not responding to AI with an increased risk of relapse

    Neurogenic inflammation after traumatic brain injury and its potentiation of classical inflammation

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    Background: The neuroinflammatory response following traumatic brain injury (TBI) is known to be a key secondary injury factor that can drive ongoing neuronal injury. Despite this, treatments that have targeted aspects of the inflammatory pathway have not shown significant efficacy in clinical trials. Main body: We suggest that this may be because classical inflammation only represents part of the story, with activation of neurogenic inflammation potentially one of the key initiating inflammatory events following TBI. Indeed, evidence suggests that the transient receptor potential cation channels (TRP channels), TRPV1 and TRPA1, are polymodal receptors that are activated by a variety of stimuli associated with TBI, including mechanical shear stress, leading to the release of neuropeptides such as substance P (SP). SP augments many aspects of the classical inflammatory response via activation of microglia and astrocytes, degranulation of mast cells, and promoting leukocyte migration. Furthermore, SP may initiate the earliest changes seen in blood-brain barrier (BBB) permeability, namely the increased transcellular transport of plasma proteins via activation of caveolae. This is in line with reports that alterations in transcellular transport are seen first following TBI, prior to decreases in expression of tight-junction proteins such as claudin-5 and occludin. Indeed, the receptor for SP, the tachykinin NK1 receptor, is found in caveolae and its activation following TBI may allow influx of albumin and other plasma proteins which directly augment the inflammatory response by activating astrocytes and microglia. Conclusions: As such, the neurogenic inflammatory response can exacerbate classical inflammation via a positive feedback loop, with classical inflammatory mediators such as bradykinin and prostaglandins then further stimulating TRP receptors. Accordingly, complete inhibition of neuroinflammation following TBI may require the inhibition of both classical and neurogenic inflammatory pathways.Frances Corrigan, Kimberley A. Mander, Anna V. Leonard and Robert Vin

    HIV Replication Enhances Production of Free Fatty Acids, Low Density Lipoproteins and Many Key Proteins Involved in Lipid Metabolism: A Proteomics Study

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    BACKGROUND: HIV-infected patients develop multiple metabolic abnormalities including insulin resistance, lipodystrophy and dyslipidemia. Although progression of these disorders has been associated with the use of various protease inhibitors and other antiretroviral drugs, HIV-infected individuals who have not received these treatments also develop lipid abnormalities albeit to a lesser extent. How HIV alters lipid metabolism in an infected cell and what molecular changes are affected through protein interaction pathways are not well-understood. RESULTS: Since many genetic, epigenetic, dietary and other factors influence lipid metabolism in vivo, we have chosen to study genome-wide changes in the proteomes of a human T-cell line before and after HIV infection in order to circumvent computational problems associated with multiple variables. Four separate experiments were conducted including one that compared 14 different time points over a period of >3 months. By subtractive analyses of protein profiles overtime, several hundred differentially expressed proteins were identified in HIV-infected cells by mass spectrometry and each protein was scrutinized for its biological functions by using various bioinformatics programs. Herein, we report 18 HIV-modulated proteins and their interaction pathways that enhance fatty acid synthesis, increase low density lipoproteins (triglycerides), dysregulate lipid transport, oxidize lipids, and alter cellular lipid metabolism. CONCLUSIONS: We conclude that HIV replication alone (i.e. without any influence of antiviral drugs, or other human genetic factors), can induce novel cellular enzymes and proteins that are significantly associated with biologically relevant processes involved in lipid synthesis, transport and metabolism (p = <0.0002-0.01). Translational and clinical studies on the newly discovered proteins may now shed light on how some of these proteins may be useful for early diagnosis of individuals who might be at high risk for developing lipid-related disorders. The target proteins could then be used for future studies in the development of inhibitors for preventing lipid-metabolic anomalies. This is the first direct evidence that HIV-modulates production of proteins that are significantly involved in disrupting the normal lipid-metabolic pathways

    Identification of unique neoantigen qualities in long-term survivors of pancreatic cancer

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    Pancreatic ductal adenocarcinoma is a lethal cancer with fewer than 7% of patients surviving past 5 years. T-cell immunity has been linked to the exceptional outcome of the few long-term survivors1,2, yet the relevant antigens remain unknown. Here we use genetic, immunohistochemical and transcriptional immunoprofiling, computational biophysics, and functional assays to identify T-cell antigens in long-term survivors of pancreatic cancer. Using whole-exome sequencing and in silico neoantigen prediction, we found that tumours with both the highest neoantigen number and the most abundant CD8+ T-cell infiltrates, but neither alone, stratified patients with the longest survival. Investigating the specific neoantigen qualities promoting T-cell activation in long-term survivors, we discovered that these individuals were enriched in neoantigen qualities defined by a fitness model, and neoantigens in the tumour antigen MUC16 (also known as CA125). A neoantigen quality fitness model conferring greater immunogenicity to neoantigens with differential presentation and homology to infectious disease-derived peptides identified long-term survivors in two independent datasets, whereas a neoantigen quantity model ascribing greater immunogenicity to increasing neoantigen number alone did not. We detected intratumoural and lasting circulating T-cell reactivity to both high-quality and MUC16 neoantigens in long-term survivors of pancreatic cancer, including clones with specificity to both high-quality neoantigens and predicted cross-reactive microbial epitopes, consistent with neoantigen molecular mimicry. Notably, we observed selective loss of high-quality and MUC16 neoantigenic clones on metastatic progression, suggesting neoantigen immunoediting. Our results identify neoantigens with unique qualities as T-cell targets in pancreatic ductal adenocarcinoma. More broadly, we identify neoantigen quality as a biomarker for immunogenic tumours that may guide the application of immunotherapies

    Discourse and religion in educational practice

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    Despite the existence of long-held binaries between secular and sacred, private and public spaces, school and religious literacies in many contemporary societies, the significance of religion and its relationship to education and society more broadly has become increasingly topical. Yet, it is only recently that the investigation of the nexus of discourse and religion in educational practice has started to receive some scholarly attention. In this chapter, religion is understood as a cultural practice, historically situated and embedded in specific local and global contexts. This view of religion stresses the social alongside the subjective or experiential dimensions. It explores how through active participation and apprenticeship in culturally appropriate practices and behaviors often mediated intergenerationally and the mobilisation of linguistic and other semiotic resources but also affective, social and material resources, membership in religious communities is constructed and affirmed. The chapter reviews research strands that have explored different aspects of discourse and religion in educational practice as a growing interdisciplinary field. Research strands have examined the place and purpose of religion in general and evangelical Christianity in particular in English Language Teaching (ELT) programmes and the interplay of religion and teaching and learning in a wide range of religious and increasingly secular educational contexts. They provide useful insights for scholars of discourse studies to issues of identity, socialisation, pedagogy and language policy
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