New tools and specification languages for biophysically detailed neuronal network modelling

Increasingly detailed data are being gathered on the molecular, electrical and anatomical properties of neuronal systems both in vitro and in vivo. These range from the kinetic properties and distribution of ion channels, synaptic plasticity mechanisms, electrical activity in neurons, and detailed anatomical connectivity within neuronal microcircuits from connectomics data. Publications describing these experimental results often set them in the context of higher level network behaviour. Biophysically detailed computational modelling provides a framework for consolidating these data, for quantifying the assumptions about underlying biological mechanisms, and for ensuring consistency in the explanation of the phenomena across scales. Such multiscale biophysically detailed models are not currently in wide- spread use by the experimental neuroscience community however. Reasons for this include the relative inaccessibility of software for creating these models, the range of specialised scripting languages used by the available simulators, and the difficulty in creating and managing large scale network simulations. This thesis describes new solutions to facilitate the creation, simulation, analysis and reuse of biophysically detailed neuronal models. The graphical application neuroConstruct allows detailed cell and network models to be built in 3D, and run on multiple simulation platforms without detailed programming knowledge. NeuroML is a simulator independent language for describing models containing detailed neuronal morphologies, ion channels, synapses, and 3D network connectivity. New solutions have also been developed for creating and analysing network models at much closer to biological scale on high performance computing platforms. A number of detailed neocortical, cerebellar and hippocampal models have been converted for use with these tools. The tools and models I have developed have already started to be used for original scientific research. It is hoped that this work will lead to a more solid foundation for creating, validating, simulating and sharing ever more realistic models of neurons and networks

Ferroelectric Smectic Liquid Crystals as Electrocaloric Materials

The 1980s saw the development of ferroelectric chiral smectic C (SmC*) liquid crystals (FLCs) with a clear focus on their application in fast electro-optic devices. However, as the only known fluid ferroelectric materials, they also have potential in other applications, one of which is in heat-exchange devices based on the electrocaloric effect. In particular, ferroelectric liquid crystals can be both the electrocaloric material and the heat exchanging fluid in an electrocaloric device, significantly simplifying some of the design constraints associated with solid dielectrics. In this paper, we consider the electrocaloric potential of three SmC* ferroelectric liquid crystal systems, two of which are pure materials that exhibit ferroelectric, antiferroelectric, and intermediate phases and one that was developed as a room-temperature SmC* material for electro-optic applications. We report the field-induced temperature changes of these selected materials, measured indirectly using the Maxwell method. The maximum induced temperature change determined, 0.37 K, is currently record-breaking for an FLC and is sufficiently large to make these materials interesting candidates for the development for electrocaloric applications. Using the electrocaloric temperature change normalised as a function of electric field strength, as a function of merit, the performances of FLCs are compared with ferroelectric ceramics and polymers

Early signs of tinnitus in a simulation of the mammalian primary auditory cortex

© 2011 Metzner et al; licensee BioMed Central Ltd. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited[Poster presentation] The majority of tinnitus cases are related to cochlear dysfunction, leading to altered peripheral input to the central auditory system. These alterations are believed to increase the basic level of neural activity during off-conditions of sound and to diminish the increase in neural activity when sound is presented. As a compensatory means the affected region of primary auditory cortex tries to maximize the difference between basic level activity and sound-induced activity by adapting inhibitory and excitatory influences towards less GABAergic inhibition. This adaptation in turn triggers unmasking of dormant synapses and creation of new connections through axonal sprouting and finally results in a reorganization of tonotopic receptive fields and the manifestation of tinnitusPeer reviewe

Liquid crystal blue phases: stability, field effects and alignment

The blue phases are fascinating structures in liquid crystals, fluids that exhibit cubic structures that have true crystalline order. The blue phases were discovered in the 1970s and were the subject of extensive research in the 1980s, when a deep understanding of many of their properties was established. The discovery that the blue phases could be stabilised to exist over wide temperature ranges meant that they became more than scientific curiosities and led to a recent resurgence in research into them as they offer some promise in applications. This paper considers some important aspects of the blue phases that are recurrent topics in their research. It describes factors affecting blue phase stability, demonstrating on the role of the bend elastic constant; field effects, including the Kerr effect, electrostriction and relaxation phenomena; and alignment, in particular production and control of blue phase monodomains. The dependence of these phenomena on the physical properties of the liquid crystalline system, including the twist and bend elastic constants and the dielectric anisotropy, is emphasised wherever possible. The paper links work carried out in the 1980s with contemporary research, using a few key examples to show how there is still much to understand in this beautiful topic

Liquid Crystal Elastomers for Biological Applications

The term liquid crystal elastomer (LCE) describes a class of materials that combine the elastic entropy behaviour associated with conventional elastomers with the stimuli responsive properties of anisotropic liquid crystals. LCEs consequently exhibit attributes of both elastomers and liquid crystals, but additionally have unique properties not found in either. Recent developments in LCE synthesis, as well as the understanding of the behaviour of liquid crystal elastomers—namely their mechanical, optical and responsive properties—is of significant relevance to biology and biomedicine. LCEs are abundant in nature, highlighting the potential use of LCEs in biomimetics. Their exceptional tensile properties and biocompatibility have led to research exploring their applications in artificial tissue, biological sensors and cell scaffolds by exploiting their actuation and shock absorption properties. There has also been significant recent interest in using LCEs as a model for morphogenesis. This review provides an overview of some aspects of LCEs which are of relevance in different branches of biology and biomedicine, as well as discussing how recent LCE advances could impact future applications

Toward In Silico Design of Highly Tunable Liquid Crystal Elastomers

In this work, a two-component acrylate liquid crystal elastomer, with varying composition and templating phase, is synthesized in the laboratory and investigated in parallel using atomistic molecular dynamics simulations. The anisotropic nature of both the mono- and bifunctional acrylates used in this study enables a large tunability in the compositional range while still retaining liquid crystalline properties in the final elastomer. The use of simulations allows important evaluation and comparison of physical properties such as glass transition temperature, nematic to isotropic phase transition temperature, and order parameter. The dependence of physical properties (glass transition, nematic to isotropic transition, order parameter, coefficient of thermal expansion, and mechanical properties) is established as a function of chemical composition, showing a high degree of tunability. Interestingly, the templating phase (nematic or isotropic) is also shown to impact the subsequent elastomer properties, with excellent agreement shown here between experiments and simulations. The in silico approach to polymerization, coupled with excellent comparison with the experimental system, represents a new methodology for the targeted design of liquid crystal elastomers with specific physical properties

Duodenal enteroglucagonoma revealed by differential comparison of serum and tissue glucagon reactivity with Siemens' Double Glucagon Antibody and DakoCytomation's Polyclonal Rabbit Anti-Human Glucagon: a case report

<p>Abstract</p> <p>Introduction</p> <p>This case report demonstrates that the differential immunohistochemical reactivities of Siemens' <it>Double Antibody Glucagon </it>compared to DakoCytomation's <it>Polyclonal Rabbit Anti-Human Glucagon </it>allow for pathologic distinction of enteral versus pancreatic glucagonoma.</p> <p>Case presentation</p> <p>A 64-year-old Caucasian man was diagnosed with a duodenal enteroglucagonoma following presentation with obstructive jaundice. He had a low serum glucagon level using Siemens' <it>Double Antibody Glucagon</it>, a clinical syndrome consistent with glucagon hypersecretion. A periampullary mass biopsy proved to be a neuroendocrine tumor, with positive immunohistochemical reactivity to DakoCytomation's <it>Polyclonal Rabbit Anti-Human Glucagon</it>.</p> <p>Conclusions</p> <p>Differential comparison of the immunohistochemical reactivities of Siemens' <it>Double Antibody Glucagon </it>and DakoCytomation's <it>Polyclonal Rabbit Anti-Human Glucagon </it>discerns enteroglucagon from pancreatic glucagon.</p

Integrated groundwater management: An overview of concepts and challenges

Managing water is a grand challenge problem and has become one of humanity’s foremost priorities. Surface water resources are typically societally managed and relatively well understood; groundwater resources, however, are often hidden and more difficult to conceptualize. Replenishment rates of groundwater cannot match past and current rates of depletion in many parts of the world. In addition, declining quality of the remaining groundwater commonly cannot support all agricultural, industrial and urban demands and ecosystem functioning, especially in the developed world. In the developing world, it can fail to even meet essential human needs. The issue is: how do we manage this crucial resource in an acceptable way, one that considers the sustainability of the resource for future generations and the socioeconomic and environmental impacts? In many cases this means restoring aquifers of concern to some sustainable equilibrium over a negotiated period of time, and seeking opportunities for better managing groundwater conjunctively with surface water and other resource uses. However, there are many, often-interrelated, dimensions to managing groundwater effectively. Effective groundwater management is underpinned by sound science (biophysical and social) that actively engages the wider community and relevant stakeholders in the decision making process. Generally, an integrated approach will mean “thinking beyond the aquifer”, a view which considers the wider context of surface water links, catchment management and cross-sectoral issues with economics, energy, climate, agriculture and the environment. The aim of the book is to document for the first time the dimensions and requirements of sound integrated groundwater management (IGM). The primary focus is on groundwater management within its system, but integrates linkages beyond the aquifer. The book provides an encompassing synthesis for researchers, practitioners and water resource managers on the concepts and tools required for defensible IGM, including how IGM can be applied to achieve more sustainable socioeconomic and environmental outcomes, and key challenges of IGM. The book is divided into five parts: integration overview and problem settings; governance; socioeconomics; biophysical aspects; and modelling and decision support. However, IGM is integrated by definition, thus these divisions should be considered a convenience for presenting the topics rather than hard and fast demarcations of the topic area

Decaying Dark Matter in Supersymmetric Model and Cosmic-Ray Observations

We study cosmic-rays in decaying dark matter scenario, assuming that the dark matter is the lightest superparticle and it decays through a R-parity violating operator. We calculate the fluxes of cosmic-rays from the decay of the dark matter and those from the standard astrophysical phenomena in the same propagation model using the GALPROP package. We reevaluate the preferred parameters characterizing standard astrophysical cosmic-ray sources with taking account of the effects of dark matter decay. We show that, if energetic leptons are produced by the decay of the dark matter, the fluxes of cosmic-ray positron and electron can be in good agreements with both PAMELA and Fermi-LAT data in wide parameter region. It is also discussed that, in the case where sizable number of hadrons are also produced by the decay of the dark matter, the mass of the dark matter is constrained to be less than 200-300 GeV in order to avoid the overproduction of anti-proton. We also show that the cosmic gamma-ray flux can be consistent with the results of Fermi-LAT observation if the mass of the dark matter is smaller than nearly 4 TeV.Comment: 24 pages, 5 figure