4,875 research outputs found

    Coexistence of amplitude and frequency modulations in intracellular calcium dynamics

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    The complex dynamics of intracellular calcium regulates cellular responses to information encoded in extracellular signals. Here, we study the encoding of these external signals in the context of the Li-Rinzel model. We show that by control of biophysical parameters the information can be encoded in amplitude modulation, frequency modulation or mixed (AM and FM) modulation. We briefly discuss the possible implications of this new role of information encoding for astrocytes.Comment: 4 pages, 4 figure

    Giant Alcohol: A Worthy Opponent for the Children of the Band of Hope

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    From its foundation in 1847, the temperance organisation the Band of Hope addressed its young members as consumers, victims, and agents. In the first two roles they encountered the effects of drink of necessity, but in the third role they were encouraged to seek it out, attempting to influence individuals and wider society against 'Giant Alcohol'. With an estimated membership of half the school-age population by the early twentieth century, well over three million, the Band of Hope also acted more directly to influence policy, and encouraged young people to consider issues of policy and politics. With its wide range of activities and material to educate, entertain and empower millions of children, and its radical view of the place of the child, the Band of Hope not only mobilised its child members to lobby for legal change, including prohibition, but took an active part in pointing out the cost of alcohol to society, particularly during the 14-18 war. The organisation began to decline post 1918, and this paper focuses on the address made to children by the Band of Hope in the late nineteenth and early twentieth centuries, at a time when its innovative view of children as able to understand and influence policy decisions reflected developments in the construction of childhood. This article draws on the archive of the British National Temperance League, over 50,000 items located in the Livesey Collection, University of Central Lancashire

    Wave nucleation rate in excitable systems in the low noise limit

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    Motivated by recent experiments on intracellular calcium dynamics, we study the general issue of fluctuation-induced nucleation of waves in excitable media. We utilize a stochastic Fitzhugh-Nagumo model for this study, a spatially-extended non-potential pair of equations driven by thermal (i.e. white) noise. The nucleation rate is determined by finding the most probable escape path via minimization of an action related to the deviation of the fields from their deterministic trajectories. Our results pave the way both for studies of more realistic models of calcium dynamics as well as of nucleation phenomena in other non-equilibrium pattern-forming processes

    A multiscale hybrid model for pro-angiogenic calcium signals in a vascular endothelial cell

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    Cytosolic calcium machinery is one of the principal signaling mechanisms by which endothelial cells (ECs) respond to external stimuli during several biological processes, including vascular progression in both physiological and pathological conditions. Low concentrations of angiogenic factors (such as VEGF) activate in fact complex pathways involving, among others, second messengers arachidonic acid (AA) and nitric oxide (NO), which in turn control the activity of plasma membrane calcium channels. The subsequent increase in the intracellular level of the ion regulates fundamental biophysical properties of ECs (such as elasticity, intrinsic motility, and chemical strength), enhancing their migratory capacity. Previously, a number of continuous models have represented cytosolic calcium dynamics, while EC migration in angiogenesis has been separately approached with discrete, lattice-based techniques. These two components are here integrated and interfaced to provide a multiscale and hybrid Cellular Potts Model (CPM), where the phenomenology of a motile EC is realistically mediated by its calcium-dependent subcellular events. The model, based on a realistic 3-D cell morphology with a nuclear and a cytosolic region, is set with known biochemical and electrophysiological data. In particular, the resulting simulations are able to reproduce and describe the polarization process, typical of stimulated vascular cells, in various experimental conditions.Moreover, by analyzing the mutual interactions between multilevel biochemical and biomechanical aspects, our study investigates ways to inhibit cell migration: such strategies have in fact the potential to result in pharmacological interventions useful to disrupt malignant vascular progressio

    The experience of long-term opiate maintenance treatment and reported barriers to recovery: A qualitative systematic review

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    Background/Aim: To inform understanding of the experience of long-term opiate maintenance and identify barriers to recovery. Methods: A qualitative systematic review. Results: 14 studies in 17 papers, mainly from the USA (65%), met inclusion criteria, involving 1,088 participants. Studies focused on methadone prescribing. Participants reported stability; however, many disliked methadone. Barriers to full recovery were primarily ‘inward focused'. Conclusion: This is the first review of qualitative literature on long-term maintenance, finding that universal service improvements could be made to address reported barriers to recovery, including involving ex-users as positive role models, and increasing access to psychological support. Treatment policies combining harm minimisation and abstinence-orientated approaches may best support individualised recovery
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