3,255 research outputs found

    The role of the epidermis in pathogenesis of systemic sclerosis

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    Studies into the pathogenesis of systemic sclerosis (SSc) skin fibrosis to date have concentrated on dermal changes in the disease. Little attention has been paid to the epidermis in SSc. Epithelial-fibroblast interactions are believed to regulate wound healing and contribute to a number of fibrotic diseases. Recent proteomic data from our laboratory reveals altered keratinocyte (KC) specific proteins in SSc skin consistent with a wound healing phenotype of the disease epidermis. I therefore studied SSc KCs focusing on differentiation and KC-fibroblast interaction. I found that KC maturation is altered in SSc with abnormal persistence of cytokeratins 1, 10 and 14 into suprabasal layers. Cytokeratins 6 and 16, induced in wound healing KCs, were shown to be expressed in SSc epidermis. In addition, IL-1, a pivotal cytokine involved in KC and fibroblast events post epidermal injury, and its downstream signalling phosphoproteins p38 and JNK were elevated in SSc epidermis. I went on to study the effect of SSc epidermis on normal human fibroblasts. I found that SSc epidermis promoted fibroblast activation in an ET-1, TGF-ÎČ, and IL-1 dependent fashion. I suggest a double paracrine loop initiated by KC-derived IL-1 as a mechanism for epidermal-dermal co-activation in the disease, similar to that previously demonstrated for wound healing. There is a need for developing antifibrotic agents targeting epithelium-derived factors and their signalling pathways. I went on to study normal epidermal wound healing. A paradox during epithelial repair is that KCs proliferate despite a TGF-ÎČ dominated environment, which is known to be anti-proliferative. Our laboratory previously showed that prostanoids antagonise TGF-ÎČ-dependent events in human cells. The induction of prostanoids following injury could transiently free KCs from the anti-proliferative effects of TGF-ÎČ. I test this hypothesis by confirming transient induction of epidermal COX II and PGE2 following injury. I also show that PGE2 antagonises the anti-proliferative and pro-migratory effects of TGF-ÎČ on KCs. My work supports a model where induction of epidermal wound edge COX II leads to antagonism of TGF-ÎČ and allows KCs to proliferate prior to migration over the wound

    Fur, fangs and feathers: colonial and counter-colonial portrayals of American Indians in young adult fantasy literature

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    Although there have been many postcolonial studies of the portrayals of Native American characters in children’s and young adult literature, the majority of these have focused on historical novels, rather than analysing fantasy literature. Additionally, I have found no direct comparisons between texts by Native and non-Native authors, and the impact of authorship on the representations of American Indian characters. I believe that a study of this area of literature is important, as it will serve to examine how the portrayal of Native characters in texts varies depending on the insider or outsider experience of the author. In my thesis, using critical theory around Gothic, gender and queer studies, I analyse three examples of young adult fantasy literature; the Twilight saga by Stephenie Meyer, the Tantalize series by Cynthia Leitich Smith, and the novel Wolf Mark by Joseph Bruchac. In the first chapter, I study the texts’ portrayals of Native American spiritual beliefs, comparing Meyer’s use of Quileute legends to bolster her series’ mythology with Bruchac’s reinterpretation of Abenaki beliefs in Wolf Mark. In the next chapter, I focus on the role of Christianity in the novels, considering historical contexts of missionary movements and colonisation. Chapter Three analyses the novels from a gender studies perspective, considering the racialised representations of masculinity and femininity in the texts, while Chapter Four studies the theme of sexuality in the novels. Finally, in the fifth chapter, I look at postcolonial Gothic space in the novels, and its connections to frontiers and borders, both physical and psychic. ii As a result of my research, I discovered that the Quileute characters in Meyer’s novels correspond with images of Native peoples as ‘savage’ and animalistic, with Native men portrayed as violent and sexually threatening, and Native women as pitiable and subordinate. Her focus on the ‘treaty line’ established by the vampires, and the ‘civilising process’ the main Quileute character Jacob undergoes during his time with the Cullen family, perpetuate colonialist narratives. By contrast, Leitich Smith and Bruchac write against these stereotypes. Bruchac focuses directly on Abenaki characters, writing from an insider perspective that allows him to create a nuanced, non-stereotypical portrayal of a Native protagonist. Although Leitich Smith does not write directly about Native characters or cultures, her representations of gender, sexuality and race correspond with a counter-colonialist perspective. My direct comparison of texts by Native and non-Native authors shows that an author writing from an outsider perspective is far more likely to use stereotypical portrayals of American Indian characters and cultures than an author with an insider perspective of a Native culture. It also indicates that young adult fantasy literature, with its emphasis on the boundaries between childhood and adulthood, can be used as a site for both conservative and radical narratives on colonialism and postcolonialism

    Dynamic Normalization for Compact Binary Coalescence Searches in Non-Stationary Noise

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    The output of gravitational-wave interferometers, such as LIGO and Virgo, can be highly non-stationary. Broadband detector noise can affect the detector sensitivity on the order of tens of seconds. Gravitational-wave transient searches, such as those for colliding black holes, estimate this noise in order to identify gravitational-wave events. During times of non-stationarity we see a higher rate of false events being reported. To accurately separate signal from noise, it is imperative to incorporate the changing detector state into gravitational-wave searches. We develop a new statistic which estimates the variation of the interferometric detector noise. We use this statistic to re-rank candidate events identified during LIGO-Virgo's second observing run by the PyCBC search pipeline. This results in a 7% improvement in the sensitivity volume for low mass binaries, particularly binary neutron stars mergers

    Wonders of tick saliva

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    Saliva of ticks is arguably the most complex saliva of any animal. This is particularly the case for ixodid species that feed for many days firmly attached to the same skin site of their obliging host. Sequencing and spectrometry technologies combined with bioinformatics are enumerating ingredients in the saliva cocktail. The dynamic and expanding saliva recipe is helping decipher the wonderous activities of tick saliva, revealing how ticks stealthily hide from their hosts while satisfying their gluttony and sharing their individual resources. This review takes a tick perspective on the composition and functions of tick saliva, covering water balance, gasket and holdfast, control of host responses, dynamics, individuality, mate guarding, saliva-assisted transmission, and redundancy. It highlights areas sometimes overlooked – feeding aggregation and sharing of sialomes, and the contribution of salivary gland storage granules – and questions whether the huge diversity of tick saliva molecules is ‘redundant’ or more a reflection on the enormous adaptability wonderous saliva confers on ticks

    Nuclear Power: a Hedge against Uncertain Gas and Carbon Prices?

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    High fossil fuel prices have rekindled interest in nuclear power. This paper identifies specific nuclear characteristics making it unattractive to merchant generators in liberalised electricity markets, and argues that non-fossil fuel technologies have an overlooked à ±à  à  option valueà ±à  à  given fuel and carbon price uncertainty. Stochastic optimisation estimates the company option value of keeping open the choice between nuclear and gas technologies. This option value decreases sharply as the correlation between electricity, gas, and carbon prices rises, casting doubt on whether private investorsà ±à  à  fuel-mix diversification incentives in electricity markets are aligned with the social value of a diverse fuel-mix

    Improving the Sensitivity of Advanced LIGO Using Noise Subtraction

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    This paper presents an adaptable, parallelizable method for subtracting linearly coupled noise from Advanced LIGO data. We explain the features developed to ensure that the process is robust enough to handle the variability present in Advanced LIGO data. In this work, we target subtraction of noise due to beam jitter, detector calibration lines, and mains power lines. We demonstrate noise subtraction over the entirety of the second observing run, resulting in increases in sensitivity comparable to those reported in previous targeted efforts. Over the course of the second observing run, we see a 30% increase in Advanced LIGO sensitivity to gravitational waves from a broad range of compact binary systems. We expect the use of this method to result in a higher rate of detected gravitational-wave signals in Advanced LIGO data.Comment: 15 pages, 6 figure

    Discharge and suspended sediment dynamics in an Indian Himalayan river system

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    A pure, clean and reliable water supply is of paramount importance in India where meeting the requirements of a rising population is one of the big challenges of the 21st century. Climate change in the Indian subcontinent, identified by the Intergovernmental Panel on Climate Change (IPCC, 2013) as the region with the highest level of climate instability, is of major concern (Immerzeel et al., 2010; Morton, 2011). In 2010 the ïŹ‚oods in the Indus basin were the worst in history (Hobley et al., 2012). Two thousand people died in Pakistan and in the high-altitude desert of Ladakh, intense rain and ïŹ‚oods centred around Leh, washed away homes and villages and killed 200 people. At present, 10 % of the earth’s land-mass is covered with snow. Of this total area, 84.16 % is in the Antarctic, 13.9 % in Greenland, 0.77 % in the Himalaya, 0.51 % in North America, 0.37 % in Africa, 0.15 % in South America, and 0.06 % in Europe. Outside the Polar Regions, the Himalaya has the maximum concentration of glaciers – 9.04 % of its area. An additional 30-to-40 % is covered with snow. The glaciers of the Himalaya are the Third Pole (Dyhrenfurth, 2011). They feed the giant rivers of Asia, support half of humanity and can have a significant influence on regional water availability (Immerzeel et al., 2009). Recent studies have confirmed the important role of high mountain areas of the world as sources of freshwater for the population living in the adjacent lowlands (eg. Bandyopadhyay et al., 1997; Viviroli &Weingartner, 2004; Barnett et al., 2005; Viviroli et al., 2007; Thayyen & Gergan, 2010) Despite the hydrological importance of glaciers for the adjoining lowlands, data on the glaciers of the Himalaya, Karakorum, and Hindu Kush ranges are sparse and inconsistent. There is a lack of long-term series and field investigations, especially for glaciers at higher altitudes (Armstrong, 2010; Schmidt & NĂŒsser, 2012)

    Statistical Communication Theory

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    Contains reports on three research projects
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