How to Do Things with Words: Tolkien’s Theory of Fantasy in Practice

After his St Andrews lecture on ‘Fairy Stories’ Tolkien projected his theory of sub-creation into his legendarium. In this projection the theory of what the human sub-creator does with thought and words became a model for what miraculous and magical beings can do with spirit and matter. For example, Fëanor’s making of the Silmarils and Sauron’s forging of the Ring were conceived (or in the first case, re-conceived) as acts analogous to human fantasy. Middle-earth thus became a world in which the magical potential of human words is revealed in the visible being of magical things

Fantasy Incarnate: Of Elves and Men

This essay proposes the idea of incarnation as a key to unlocking Tolkien’s conception of fantasy as set out in the \u27Origins\u27 section of On Fairy Stories. Tolkien\u27s intellectual context is explored and his conception of mythology as a blending of imagination and history examined. The essay also establishes the differences between mortal and Elvish fantasy and argues that Tolkien\u27s Elves engage in a different kind of incarnational art than do mortals. In conclusion it is claimed that in ‘Origins’ Tolkien reworked the speculations of mid-Victorian comparative philology into an aesthetic theory of artistic creation grounded upon the notion of incarnation

Oncogenic K-Ras suppresses IP₃-dependent Ca²⁺ release through remodeling of IP₃Rs isoform composition and ER luminal Ca²⁺ levels in colorectal cancer cell lines

The GTPase Ras is a molecular switch engaged downstream of G-protein coupled receptors and receptor tyrosine inases that controls multiple cell fate-determining signalling athways. Ras signalling is frequently deregulated in cancer underlying associated changes in cell phenotype. Although Ca2+ signalling pathways control some overlapping functions with Ras, and altered Ca2+ signalling pathways are emerging as important players in oncogenic transformation, how Ca2+ signalling is remodelled during transformation and whether it has a causal role remains unclear. We have investigated Ca2+ signalling in two human colorectal cancer cell lines and their isogenic derivatives in which the mutated K-Ras allele (G13D) has been deleted by homologous recombination. We show that agonist-induced Ca2+ release from intracellular stores is enhanced by loss of K-RasG13D through an increase in the ER store content and a modification of IP3R subtype abundance. Consistently, uptake of Ca2+ into mitochondria and sensitivity to apoptosis was enhanced as a result of KRasG13D loss. These results suggest that suppression of Ca2+ signalling is a common response to naturally occurring levels of K-RasG13D that contributes to a survival advantage during oncogenic transformation

Origin and significance of 'dispersed facies' basal ice: Svínafellsjökull, Iceland

Dispersed facies basal ice - massive (i.e. structureless) ice with dispersed debris aggregates - is present at the margins of many glaciers and, as a product of internal glacial processes, has the potential to provide important information about the mechanisms of glacier flow and the nature of the subglacial environment. The origin of dispersed facies is poorly understood, with several hypotheses having been advanced for its formation, and there is disagreement as to whether it is largely a sedimentary or a tectonic feature. We test these established hypotheses at the temperate glacier Svfnafellsjokull, Iceland, and find that none fully account for dispersed facies characteristics at this location. Instead, dispersed facies physical, sedimentological and stable-isotope (5180, 8D) characteristics favour a predominantly tectonic origin that we suggest comprises the regelation and straininduced metamorphism of debris-rich basal ice that has been entrained into an englacial position by tectonic processes operating at the base of an icefall. Further thickening of the resultant dispersed facies may also occur tectonically as a result of ice flow against the reverse bed slope of a terminal overdeepening. Lack of efficient subglacial drainage in the region of the overdeepening may limit basal melting and thus favour basal ice preservation, including the preservation of dispersed facies. Despite the relatively low sediment content of dispersed facies (~1.6% by volume), its thickness (up to 25 m) and ubiquity at Svfnafellsjokull results in a significant contribution to annual sediment discharge (1635-3270 m3 a"1) that is ~6.5 times that contributed by debris-rich stratified facies basal ice

Assessment of climate change effects on vegetation and river hydrology in a semi-arid river basin

Climate change plays a key role in changing vegetation productivity dynamics, which ultimately affect the hydrological cycle of a watershed through evapotranspiration (ET). Trends and correlation analysis were conducted to investigate vegetation responses across the whole Upper Jhelum River Basin (UJRB) in the northeast of Pakistan using the normalized difference vegetation index (NDVI), climate variables, and river flow data at inter-annual/monthly scales between 1982 and 2015. The spatial variability in trends calculated with the Mann-Kendall (MK) trend test on NDVI and climate data was assessed considering five dominant land use/cover types. The inter-annual NDVI in four out of five vegetation types showed a consistent increase over the 34-year study period; the exception was for herbaceous vegetation (HV), which increased until the end of the 1990s and then decreased slightly in subsequent years. In spring, significant (p<0.05) increasing trends were found in the NDVI of all vegetation types. Minimum temperature (Tmin) showed a significant increase during spring, while maximum temperature (Tmax) decreased significantly during summer. Average annual increase in Tmin (1.54°C) was much higher than Tmax (0.37°C) over 34 years in the UJRB. Hence, Tmin appears to have an enhancing effect on vegetation productivity over the UJRB. A significant increase in NDVI, Tmin and Tmax during spring may have contributed to reductions in spring river flow by enhancing evapotranspiration observed in the watershed of UJRB. These findings provide valuable information to improve our knowledge and understanding about the interlinkages between vegetation, climate and river flow at a watershed scale

Inhibitory feedback control of NF-κB signalling in health and disease.

Cells must adapt to changes in their environment to maintain cell, tissue and organismal integrity in the face of mechanical, chemical or microbiological stress. Nuclear factor-κB (NF-κB) is one of the most important transcription factors that controls inducible gene expression as cells attempt to restore homeostasis. It plays critical roles in the immune system, from acute inflammation to the development of secondary lymphoid organs, and also has roles in cell survival, proliferation and differentiation. Given its role in such critical processes, NF-κB signalling must be subject to strict spatiotemporal control to ensure measured and context-specific cellular responses. Indeed, deregulation of NF-κB signalling can result in debilitating and even lethal inflammation and also underpins some forms of cancer. In this review, we describe the homeostatic feedback mechanisms that limit and 're-set' inducible activation of NF-κB. We first describe the key components of the signalling pathways leading to activation of NF-κB, including the prominent role of protein phosphorylation and protein ubiquitylation, before briefly introducing the key features of feedback control mechanisms. We then describe the array of negative feedback loops targeting different components of the NF-κB signalling cascade including controls at the receptor level, post-receptor signalosome complexes, direct regulation of the critical 'inhibitor of κB kinases' (IKKs) and inhibitory feedforward regulation of NF-κB-dependent transcriptional responses. We also review post-transcriptional feedback controls affecting RNA stability and translation. Finally, we describe the deregulation of these feedback controls in human disease and consider how feedback may be a challenge to the efficacy of inhibitors

First evidence of cryptotephra in palaeoenvironmental records associated with Norse occupation sites in Greenland

The Norse/Viking occupation of Greenland is part of a dispersal of communities across the North Atlantic coincident with the supposed Medieval Warm Period of the late 1st millennium AD. The abandonment of the Greenland settlements has been linked to climatic deterioration in the Little Ice Age as well as other possible explanations. There are significant dating uncertainties over the time of European abandonment of Greenland and the potential influence of climatic deterioration. Dating issues largely revolve around radiocarbon chronologies for Norse settlements and associated mire sequences close to settlement sites. Here we show the potential for moving this situation forward by a combination of palynological, radiocarbon and cryptotephra analyses of environmental records close to three ‘iconic’ Norse sites in the former Eastern Settlement of Greenland – Herjolfsnes, Hvalsey and Garðar (the modern Igaliku). While much work remains to be undertaken, our results show that palynological evidence can provide a useful marker for both the onset and end of Norse occupation in the region, while the radiocarbon chronologies for these sequences remain difficult. Significantly, we here demonstrate the potential for cryptotephra to become a useful tool in resolving the chronology of Norse occupation, when coupled with palynology. For the first time, we show that cryptotephra are present within palaeoenvironmental sequences located within or close to Norse settlement ruin-groups, with tephra horizons detected at all three sites. While shard concentrations were small at Herjolfsnes, concentrations sufficient for geochemical analyses were detected at Igaliku and Hvalsey. WDS-EPMA analyses of these tephra indicate that, unlike the predominantly Icelandic tephra sources reported in the Greenland ice core records, the tephra associated with the Norse sites correlate more closely with volcanic centres in the Aleutians and Cascades. Recent investigations of cryptotephra dispersal from North American centres, along with our new findings, point to the potential for cryptotephra to facilitate hypothesis testing, providing a key chronological tool for refining the timing of Norse activities in Greenland (e.g. abandonment) and of environmental contexts and drivers (e.g. climate forcing)