1,131 research outputs found
James Bond: international man of gastronomy
No full textThis article is concerned with the representation of food and drink in Ian Fleming’s James Bond novels. In particular, it examines how the author uses Bond’s culinary knowledge and habits of consumption as an important constituent of his hero’s character. Similarly, the food choices of other characters, notably villains, are shown to be linked, by Fleming, to core aspects of their identity − principally their ethnicity. Bond’s impulse to observe and classify, very much in evidence in the novels’ food sequences, is examined in terms of the texts’ construction of Bond as a skilled identifier of signs
Molecular Logic of Spinocerebellar Tract Neuron Diversity and Connectivity
No full textCoordinated motor behaviors depend on feedback communication between peripheral sensory systems and central circuits in the brain and spinal cord. Relay of muscle- and tendon-derived sensory information to the CNS is facilitated by functionally and anatomically diverse groups of spinocerebellar tract neurons (SCTNs), but the molecular logic by which SCTN diversity and connectivity is achieved is poorly understood. We used single-cell RNA sequencing and genetic manipulations to define the mechanisms governing the molecular profile and organization of SCTN subtypes. We found that SCTNs relaying proprioceptive sensory information from limb and axial muscles are generated through segmentally restricted actions of specific Hox genes. Loss of Hox function disrupts SCTN-subtype-specific transcriptional programs, leading to defects in the connections between proprioceptive sensory neurons, SCTNs, and the cerebellum. These results indicate that Hox-dependent genetic programs play essential roles in the assembly of neural circuits necessary for communication between the brain and spinal cord. © 2019 The Author(s)Baek et al. show that Hox-transcription-factor-dependent programs govern the specification and connectivity of spinal interneurons that relay muscle-derived sensory information to the cerebellum. These findings shed light on the development of neural circuits required for proprioception—the perception of body position. © 2019 The Author(s)1
The role of the hydrophobic core in regulating protein stability: probing proteins with dielectric and electrodynamic driving forces
No full textThis thesis answers questions about how the design of proteins maintains dynamic stability. It begins with an investigation into how a globular protein, β -Lactoglobulin A, accommodates a small molecule into its hydrophobic core. These experiments examine the events of ligand binding, reporting the pico- to nanosecond motions that stabilize the ligand. The small molecule, Coumarin 153 (C153), is a dye whose fluorescence energy is modulated by the surrounding protein. Relaxation of the protein about the dye manifests as a time-dependent red shift in observed fluorescence energy. This red shift is successfully separated from the fluorescence of two other C153 dye binding sites with an analysis tool we develop. Using a model fluorescence spectrum, the total fluorescence is decomposed into its three components. binding locations are assigned based on temperature-dependent fluorescence data which reveal site specific thermodynamic changes in the protein consistent with previous reports. The high temperature denature of β -Lactoglobulin is also manifested as a change in fluctuation activation energies, which are calculated according to Arrhenius theory. The second part of the thesis establishes the ma jor driving force for the destabilization of an intrinsically disordered protein, an event which initiates its aggregation to amyloid. α-synuclein (αSyn) is the major protein component of pathological Lewy bodies found in Parkinsonian neural tissue. The majority of in vitro experiments accelerate kinetics with sample agitation in the presence of air or polytetrafluoroethylene (PTFE). Our experiments use controlled amounts of PTFE to demonstrate the accel- eration is due to the stabilization of monomeric αSyn at the hydrophobic-hydrophilic (PTFE-water) interface. This result disproves the widely held assumption that amyloid kinetics are primarily accelerated by mass transfer and/or fibril fragmentation and calls for a reevaluation of αSyn amyloid publications. It is determined that only the initial dimerization reaction is surface dependent and a fit of data to an explicit kinetic model allows information of solution phase reactions to be separated from it. A model is developed about a free energy landscape and the resulting kinetic parameters are translated into ∆G and ∆G‡ values for prenuclation, nucleation, and fibrillization reactions.Ph.D.Includes bibliographical referencesIncludes vitaby Jeremy Pronchi
Quantum profiles
No full textFor the prominent science writer Jeremy Bernstein, the profile is the most congenial way of communicating science. Here, in what he labels a "series of conversations carried on in the reader's behalf and my own," he evokes the tremendous intellectual excitement of the world of modern physics, especially the quantum revolution. Drawing on his well-known talent for explaining the most complex scientific ideas for the layperson, Bernstein gives us a lively sense of what the issues of quantum mechanics are and of various ways in which individual physicists approached them.The author begins this s
Freedom and the 'creative act' in the writings of Nikolai Berdiaev : an evaluation in light of Jürgen Moltmann's theology of freedom
No full textThis project revisits the work of Nikolai Berdiaev, one of the first Russian Silver Age religious philosophers to be widely read in the West. The focus of this research is his thought on freedom and the ‘creative act’. We will argue that Berdiaev’s vision of freedom contains two types of freedom – a freedom understood within the created order and a freedom ‘outside’ of creation. It will be shown that in the former type, the reader finds a nuanced and insightful multi-layered conception of human freedom, which offers intriguing possibilities for exploring freedom and its implications for humanity. It will also be demonstrated that this type of freedom is closely related to his innovative view of creativity. Berdiaev conceives of freedom and creativity as distinct concepts, and yet so integrally related that they are interdependent. In the latter type of freedom, the reader will encounter a highly speculative and original metaphysical view that attempts to explain freedom as non-determination and answer the challenges of theodicy, which, this research will maintain, fails to do.
This research will contend (contrary to Berdiaev’s own statements) that his thought is most comprehensible from a broadly theological perspective. This perspective will underscore the significant tension within his work that arises from his speculative metaphysics. Unlike earlier works on Berdiaev that glossed over this tension, we will attempt to ameliorate it by engaging Jürgen Moltmann’s theology of freedom. Moltmann’s theology will provide a number of ideas and concepts for an analysis, critique, and reconfiguration of Berdiaev’s vision. This reconfiguration will seek to remain faithful to Berdiaev’s core concerns, while providing a new interpretation of his thought that is relevant for a contemporary dialogue concerning the significance of freedom and creativity for the person and community in relation to God
Climate change and the eco‐hydrology of fire: Will area burned increase in a warming western USA?
No full textSelective anticancer activity of a hexapeptide with sequence homology to a non-kinase domain of Cyclin Dependent Kinase 4
No full textBackground: cyclin-dependent kinases 2, 4 and 6 (Cdk2, Cdk4, Cdk6) are closely structurally homologous proteins which are classically understood to control the transition from the G1 to the S-phases of the cell cycle by combining with their appropriate cyclin D or cyclin E partners to form kinase-active holoenzymes. Deregulation of Cdk4 is widespread in human cancer, CDK4 gene knockout is highly protective against chemical and oncogene-mediated epithelial carcinogenesis, despite the continued presence of CDK2 and CDK6; and overexpresssion of Cdk4 promotes skin carcinogenesis. Surprisingly, however, Cdk4 kinase inhibitors have not yet fulfilled their expectation as 'blockbuster' anticancer agents. Resistance to inhibition of Cdk4 kinase in some cases could potentially be due to a non-kinase activity, as recently reported with epidermal growth factor receptor. Results: a search for a potential functional site of non-kinase activity present in Cdk4 but not Cdk2 or Cdk6 revealed a previously-unidentified loop on the outside of the C'-terminal non-kinase domain of Cdk4, containing a central amino-acid sequence, Pro-Arg-Gly-Pro-Arg-Pro (PRGPRP). An isolated hexapeptide with this sequence and its cyclic amphiphilic congeners are selectively lethal at high doses to a wide range of human cancer cell lines whilst sparing normal diploid keratinocytes and fibroblasts. Treated cancer cells do not exhibit the wide variability of dose response typically seen with other anticancer agents. Cancer cell killing by PRGPRP, in a cyclic amphiphilic cassette, requires cells to be in cycle but does not perturb cell cycle distribution and is accompanied by altered relative Cdk4/Cdk1 expression and selective decrease in ATP levels. Morphological features of apoptosis are absent and cancer cell death does not appear to involve autophagy. Conclusion: these findings suggest a potential new paradigm for the development of broad-spectrum cancer specific therapeutics with a companion diagnostic biomarker and a putative functional site for kinase-unrelated activities of Cdk4
The Whitsun Wedding Video: a journey into British poetry
No full textA hundred years after the publication of T S Eliot’s ‘The Love Song of J Alfred Prufrock’ one of Britain’s brightest and sharpest poetry critics, Jeremy Noel-Tod, takes contemporary British poetry to task for its failure to match the ambition of the great modernists such as Eliot. This witty and incisive book ‘about how reputations have been made in modern British poetry and may be remade’ challenges received opinion about contemporary verse. ‘Rumours persist that excellent poetry is being written by poets who are not venerable names rehearsing old themes,’ the author reports in an essay certain to create controversy in the world of poetry. Jeremy Noel-Tod lives in Norwich where he teaches Literature and Creative Writing at the University of East Anglia. Since 2000 he has reviewed poetry for a wide range of national publications, including the Guardian, the Daily Telegraph, the New Statesman, and The Sunday Times. He is the editor of R.F. Langley’s Complete Poems (Carcanet, 2015) and was the revising editor of the Oxford Companion to Modern Poetry (2013), previously published as the Oxford Companion to Twentieth Century Poetry (1994), ed. Ian Hamilton
Climatic Water Balance and Regional Fire Years in the Pacific Northwest, USA: Linking Regional Climate and Fire at Landscape Scales
No full textRECONSTRUCTING THE S. CEREVISIAE GROWTH CONTROL NETWORK IN STRESS CONDITIONS
No full textRights Copyright © is held by the author. Digital access to this material is made possible by the University Libraries, University of Arizona. Further transmission, reproduction or presentation (such as public display or performance) of protected items is prohibited except with permission of the author. Downloaded 13-Sep-2016 12:15:21 Link to ite
- …
