1,145 research outputs found
Computational and Mathematical Modelling of the EGF Receptor System
This chapter gives an overview of computational and mathematical modelling of the EGF receptor system. It begins with a survey of motivations for producing such models, then describes the main approaches that are taken to carrying out such modelling, viz. differential equations and individual-based modelling. Finally, a number of projects that applying modelling and simulation techniques to various aspects of the EGF receptor system are described
Plasmalemmal Na+/Ca2+ exchanger modulates Ca2+-dependent exocytotic release of glutamate from rat cortical astrocytes
Astroglial excitability operates through increases in Ca2+cyt (cytosolic Ca2+), which can lead to glutamatergic gliotransmission. In parallel fluctuations in astrocytic Na+cyt (cytosolic Na+) control metabolic neuronal-glial signalling, most notably through stimulation of lactate production, which on release from astrocytes can be taken up and utilized by nearby neurons, a process referred to as lactate shuttle. Both gliotransmission and lactate shuttle play a role in modulation of synaptic transmission and plasticity. Consequently, we studied the role of the PMCA (plasma membrane Ca2+-ATPase), NCX (plasma membrane Na+/Ca2+ exchanger) and NKA (Na+/K+-ATPase) in complex and coordinated regulation of Ca2+cyt and Na+cyt in astrocytes at rest and upon mechanical stimulation. Our data support the notion that NKA and PMCA are the major Na+ and Ca2+ extruders in resting astrocytes. Surprisingly, the blockade of NKA or PMCA appeared less important during times of Ca2+ and Na+ cytosolic loads caused by mechanical stimulation. Unexpectedly, NCX in reverse mode appeared as a major contributor to overall Ca2+ and Na+ homoeostasis in astrocytes both at rest and when these glial cells were mechanically stimulated. In addition, NCX facilitated mechanically induced Ca2+-dependent exocytotic release of glutamate from astrocytes. These findings help better understanding of astrocyte-neuron bidirectional signalling at the tripartite synapse and/or microvasculature. We propose that NCX operating in reverse mode could be involved in fast and spatially localized Ca2+-dependent gliotransmission, that would operate in parallel to a slower and more widely distributed gliotransmission pathway that requires metabotropically controlled Ca2+ release from the ER (endoplasmic reticulum)
Phase-slip induced dissipation in an atomic Bose-Hubbard system
Phase slips play a primary role in dissipation across a wide spectrum of
bosonic systems, from determining the critical velocity of superfluid helium to
generating resistance in thin superconducting wires. This subject has also
inspired much technological interest, largely motivated by applications
involving nanoscale superconducting circuit elements, e.g., standards based on
quantum phase-slip junctions. While phase slips caused by thermal fluctuations
at high temperatures are well understood, controversy remains over the role of
phase slips in small-scale superconductors. In solids, problems such as
uncontrolled noise sources and disorder complicate the study and application of
phase slips. Here we show that phase slips can lead to dissipation for a clean
and well-characterized Bose-Hubbard (BH) system by experimentally studying
transport using ultra-cold atoms trapped in an optical lattice. In contrast to
previous work, we explore a low velocity regime described by the 3D BH model
which is not affected by instabilities, and we measure the effect of
temperature on the dissipation strength. We show that the damping rate of
atomic motion-the analogue of electrical resistance in a solid-in the confining
parabolic potential fits well to a model that includes finite damping at zero
temperature. The low-temperature behaviour is consistent with the theory of
quantum tunnelling of phase slips, while at higher temperatures a cross-over
consistent with the transition to thermal activation of phase slips is evident.
Motion-induced features reminiscent of vortices and vortex rings associated
with phase slips are also observed in time-of-flight imaging.Comment: published in Nature 453, 76 (2008
Evaluating Depressive Symptoms in Schizophrenia: A Psychometric Comparison of the Calgary Depression Scale for Schizophrenia and the Hamilton Depression Rating Scale
Background: The aim of this study was to compare two measures of depression in patients with schizophrenia and schizophrenia spectrum disorder, including patients with delusional and schizoaffective disorder, to conclude implications for their application. Sampling and Methods: A total of 278 patients were assessed using the Calgary Depression Scale for Schizophrenia (CDSS) and the Hamilton Depression Rating Scale (HAMD-17). The Positive and Negative Syndrome Scale (PANSS) was also applied. At admission and discharge, a principal component analysis was performed with each depression scale. The two depression rating scales were furthermore compared using correlation and regression analyses. Results: Three factors were revealed for the CDSS and HAMD-17 factor component analysis. A very similar item loading was found for the CDSS at admission and discharge, whereas results of the loadings of the HAMD-17 items were less stable. The first two factors of the CDSS revealed correlations with positive, negative and general psychopathology. In contrast, multiple significant correlations were found for the HAMD-17 factors and the PANSS sub-scores. Multiple regression analyses demonstrated that the HAMD-17 accounted more for the positive and negative symptom domains than the CDSS. Conclusions:The present results suggest that compared to the HAMD-17, the CDSS is a more specific instrument to measure depressive symptoms in schizophrenia and schizophrenia spectrum disorder, especially in acutely ill patients. Copyright (c) 2012 S. Karger AG, Base
Study protocol: developing a decision system for inclusive housing: applying a systematic, mixed-method quasi-experimental design
Background Identifying the housing preferences of people with complex disabilities is a much needed, but under-developed area of practice and scholarship. Despite the recognition that housing is a social determinant of health and quality of life, there is an absence of empirical methodologies that can practically and systematically involve consumers in this complex service delivery and housing design market. A rigorous process for making effective and consistent development decisions is needed to ensure resources are used effectively and the needs of consumers with complex disability are properly met. Methods/Design This 3-year project aims to identify how the public and private housing market in Australia can better respond to the needs of people with complex disabilities whilst simultaneously achieving key corporate objectives. First, using the Customer Relationship Management framework, qualitative (Nominal Group Technique) and quantitative (Discrete Choice Experiment) methods will be used to quantify the housing preferences of consumers and their carers. A systematic mixed-method, quasi-experimental design will then be used to quantify the development priorities of other key stakeholders (e.g., architects, developers, Government housing services etc.) in relation to inclusive housing for people with complex disabilities. Stakeholders randomly assigned to Group 1 (experimental group) will participate in a series of focus groups employing Analytical Hierarchical Process (AHP) methodology. Stakeholders randomly assigned to Group 2 (control group) will participate in focus groups employing existing decision making processes to inclusive housing development (e.g., Risk, Opportunity, Cost, Benefit considerations). Using comparative stakeholder analysis, this research design will enable the AHP methodology (a proposed tool to guide inclusive housing development decisions) to be tested. Discussion It is anticipated that the findings of this study will enable stakeholders to incorporate consumer housing preferences into commercial decisions. Housing designers and developers will benefit from the creation of a parsimonious set of consumer-led housing preferences by which to make informed investments in future housing and contribute to future housing policy. The research design has not been applied in the Australian research context or elsewhere, and will provide a much needed blueprint for market investment to develop viable, consumer directed inclusive housing options for people with complex disability
The cometary composition of a protoplanetary disk as revealed by complex cyanides
Observations of comets and asteroids show that the Solar Nebula that spawned
our planetary system was rich in water and organic molecules. Bombardment
brought these organics to the young Earth's surface, seeding its early
chemistry. Unlike asteroids, comets preserve a nearly pristine record of the
Solar Nebula composition. The presence of cyanides in comets, including 0.01%
of methyl cyanide (CH3CN) with respect to water, is of special interest because
of the importance of C-N bonds for abiotic amino acid synthesis. Comet-like
compositions of simple and complex volatiles are found in protostars, and can
be readily explained by a combination of gas-phase chemistry to form e.g. HCN
and an active ice-phase chemistry on grain surfaces that advances
complexity[3]. Simple volatiles, including water and HCN, have been detected
previously in Solar Nebula analogues - protoplanetary disks around young stars
- indicating that they survive disk formation or are reformed in situ. It has
been hitherto unclear whether the same holds for more complex organic molecules
outside of the Solar Nebula, since recent observations show a dramatic change
in the chemistry at the boundary between nascent envelopes and young disks due
to accretion shocks[8]. Here we report the detection of CH3CN (and HCN and
HC3N) in the protoplanetary disk around the young star MWC 480. We find
abundance ratios of these N-bearing organics in the gas-phase similar to
comets, which suggests an even higher relative abundance of complex cyanides in
the disk ice. This implies that complex organics accompany simpler volatiles in
protoplanetary disks, and that the rich organic chemistry of the Solar Nebula
was not unique.Comment: Definitive version of the manuscript is published in Nature, 520,
7546, 198, 2015. This is the author's versio
Direct activation of KCC2 arrests benzodiazepine refractory status epilepticus and limits the subsequent neuronal injury in mice
Hyperpolarizing GABAAR currents, the unitary events that underlie synaptic inhibition, are dependent upon efficient Cl− extrusion, a process that is facilitated by the neuronal specific K+/Cl− co-transporter KCC2. Its activity is also a determinant of the anticonvulsant efficacy of the canonical GABAAR-positive allosteric: benzodiazepines (BDZs). Compromised KCC2 activity is implicated in the pathophysiology of status epilepticus (SE), a medical emergency that rapidly becomes refractory to BDZ (BDZ-RSE). Here, we have identified small molecules that directly bind to and activate KCC2, which leads to reduced neuronal Cl− accumulation and excitability. KCC2 activation does not induce any overt effects on behavior but prevents the development of and terminates ongoing BDZ-RSE. In addition, KCC2 activation reduces neuronal cell death following BDZ-RSE. Collectively, these findings demonstrate that KCC2 activation is a promising strategy to terminate BDZ-resistant seizures and limit the associated neuronal injury
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