810 research outputs found
Exploring volatile general anesthetic binding to a closed membrane-bound bacterial voltage-gated sodium channel via computation.
Despite the clinical ubiquity of anesthesia, the molecular basis of anesthetic action is poorly understood. Amongst the many molecular targets proposed to contribute to anesthetic effects, the voltage gated sodium channels (VGSCs) should also be considered relevant, as they have been shown to be sensitive to all general anesthetics tested thus far. However, binding sites for VGSCs have not been identified. Moreover, the mechanism of inhibition is still largely unknown. The recently reported atomic structures of several members of the bacterial VGSC family offer the opportunity to shed light on the mechanism of action of anesthetics on these important ion channels. To this end, we have performed a molecular dynamics flooding simulation on a membrane-bound structural model of the archetypal bacterial VGSC, NaChBac in a closed pore conformation. This computation allowed us to identify binding sites and access pathways for the commonly used volatile general anesthetic, isoflurane. Three sites have been characterized with binding affinities in a physiologically relevant range. Interestingly, one of the most favorable sites is in the pore of the channel, suggesting that the binding sites of local and general anesthetics may overlap. Surprisingly, even though the activation gate of the channel is closed, and therefore the pore and the aqueous compartment at the intracellular side are disconnected, we observe binding of isoflurane in the central cavity. Several sampled association and dissociation events in the central cavity provide consistent support to the hypothesis that the fenestrations present in the membrane-embedded region of the channel act as the long-hypothesized hydrophobic drug access pathway
Low temperature expansion for the 3-d Ising Model
We compute the weak coupling expansion for the energy of the three
dimensional Ising model through 48 excited bonds. We also compute the
magnetization through 40 excited bonds. This was achieved via a recursive
enumeration of states of fixed energy on a set of finite lattices. We use a
linear combination of lattices with a generalization of helical boundary
conditions to eliminate finite volume effects.Comment: 10 pages, IASSNS-HEP-92/42, BNL-4767
Asymmetric Fluid Criticality I: Scaling with Pressure Mixing
The thermodynamic behavior of a fluid near a vapor-liquid and, hence,
asymmetric critical point is discussed within a general ``complete'' scaling
theory incorporating pressure mixing in the nonlinear scaling fields as well as
corrections to scaling. This theory allows for a Yang-Yang anomaly in which
\mu_{\sigma}^{\prime\prime}(T), the second temperature derivative of the
chemical potential along the phase boundary, diverges like the specific heat
when T\to T_{\scriptsize c}; it also generates a leading singular term,
|t|^{2\beta}, in the coexistence curve diameter, where t\equiv
(T-T_{\scriptsize c}) /T_{\scriptsize c}. The behavior of various special loci,
such as the critical isochore, the critical isotherm, the k-inflection loci, on
which \chi^{(k)}\equiv \chi(\rho,T)/\rho^{k} (with \chi = \rho^{2}
k_{\scriptsize B}TK_{T}) and C_{V}^{(k)}\equiv C_{V}(\rho,T)/\rho^{k} are
maximal at fixed T, is carefully elucidated. These results are useful for
analyzing simulations and experiments, since particular, nonuniversal values of
k specify loci that approach the critical density most rapidly and reflect the
pressure-mixing coefficient. Concrete illustrations are presented for the
hard-core square-well fluid and for the restricted primitive model electrolyte.
For comparison, a discussion of the classical (or Landau) theory is presented
briefly and various interesting loci are determined explicitly and illustrated
quantitatively for a van der Waals fluid.Comment: 21 pages in two-column format including 8 figure
Invaded cluster algorithm for critical properties of periodic and aperiodic planar Ising models
We demonstrate that the invaded cluster algorithm, recently introduced by
Machta et al, is a fast and reliable tool for determining the critical
temperature and the magnetic critical exponent of periodic and aperiodic
ferromagnetic Ising models in two dimensions. The algorithm is shown to
reproduce the known values of the critical temperature on various periodic and
quasiperiodic graphs with an accuracy of more than three significant digits. On
two quasiperiodic graphs which were not investigated in this respect before,
the twelvefold symmetric square-triangle tiling and the tenfold symmetric
T\"ubingen triangle tiling, we determine the critical temperature. Furthermore,
a generalization of the algorithm to non-identical coupling strengths is
presented and applied to a class of Ising models on the Labyrinth tiling. For
generic cases in which the heuristic Harris-Luck criterion predicts deviations
from the Onsager universality class, we find a magnetic critical exponent
different from the Onsager value. But also notable exceptions to the criterion
are found which consist not only of the exactly solvable cases, in agreement
with a recent exact result, but also of the self-dual ones and maybe more.Comment: 15 pages, 5 figures; v2: Fig. 5b replaced, minor change
Crack determination from boundary measurementsāReconstruction using experimental data
In this work we assess the effectiveness of Electrical Impedance Tomography for determining the presence and the location of an interior crack from boundary measurements. Electrical Impedance Tomography uses boundary voltages and currents to image the interior of a region. We collect the data needed for this nondestructive evaluation technique by laboratory experiments and apply two numerical inversion algorithms to the data. Our experiments show that the data collected are sufficient to give good estimates of crack locations and crack sizes.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/45002/1/10921_2004_Article_BF00567084.pd
Casimir forces in binary liquid mixtures
If two ore more bodies are immersed in a critical fluid critical fluctuations
of the order parameter generate long ranged forces between these bodies. Due to
the underlying mechanism these forces are close analogues of the well known
Casimir forces in electromagnetism. For the special case of a binary liquid
mixture near its critical demixing transition confined to a simple parallel
plate geometry it is shown that the corresponding critical Casimir forces can
be of the same order of magnitude as the dispersion (van der Waals) forces
between the plates. In wetting experiments or by direct measurements with an
atomic force microscope the resulting modification of the usual dispersion
forces in the critical regime should therefore be easily detectable. Analytical
estimates for the Casimir amplitudes Delta in d=4-epsilon are compared with
corresponding Monte-Carlo results in d=3 and their quantitative effect on the
thickness of critical wetting layers and on force measurements is discussed.Comment: 34 pages LaTeX with revtex and epsf style, to appear in Phys. Rev.
In vitro assessment of the combined effect of eicosapentaenoic acid, green tea extract and curcumin C3 on protein loss in C2C12 myotubes
EPA has been clinically shown to reduce muscle wasting during cancer cachexia. This study investigates whether curcumin or green tea extract (GTE) enhances the ability of low doses of eicosapentaenoic acid (EPA) to reduce loss of muscle protein in an in vitro model. A low dose of EPA with minimal anti-cachectic activity was chosen to evaluate any potential synergistic effect with curcumin or GTE. Depression of protein synthesis and increase in degradation was determined in C2C12 myotubes in response to tumour necrosis factor-Ī± (TNF-Ī±) and proteolysis-inducing factor (PIF). EPA (50 Ī¼M) or curcumin (10 Ī¼g mlā1) alone had little effect on protein degradation caused by PIF but the combination produced complete inhibition, as did the combination with GTE (10 Ī¼g mlā1). In response to TNF-Ī± (25 ng mlā1)-induced protein degradation, EPA had a small, but not significant effect on protein degradation; however, when curcumin and GTE were combined with EPA, the effect was enhanced. EPA completely attenuated the depression of protein synthesis caused by TNF-Ī±, but not that caused by PIF. The combination of EPA with curcumin produced a significant increase in protein synthesis to both agents. GTE alone or in combination with EPA had no effect on the depression of protein synthesis by TNF-Ī±, but did significantly increase protein synthesis in PIF-treated cells. Both TNF-Ī± and PIF significantly reduced myotube diameter from 17 to 13 Ī¼m for TNF-Ī± (23.5%) and 15 Ī¼m (11.8%) for PIF However the triple combination of EPA, curcumin and GTE returned diameters to values not significantly different from the control. These results suggest that either curcumin or GTE or the combination could enhance the anti-catabolic effect of EPA on lean body mass
Nature-Based Interventions for Improving Health and Wellbeing : The Purpose, the People and the Outcomes
Engagement with nature is an important part of many people's lives, and the health and wellbeing benefits of nature-based activities are becoming increasingly recognised across disciplines from city planning to medicine. Despite this, urbanisation, challenges of modern life and environmental degradation are leading to a reduction in both the quantity and the quality of nature experiences. Nature-based health interventions (NBIs) can facilitate behavioural change through a somewhat structured promotion of nature-based experiences and, in doing so, promote improved physical, mental and social health and wellbeing. We conducted a Delphi expert elicitation process with 19 experts from seven countries (all named authors on this paper) to identify the different forms that such interventions take, the potential health outcomes and the target beneficiaries. In total, 27 NBIs were identified, aiming to prevent illness, promote wellbeing and treat specific physical, mental or social health and wellbeing conditions. These interventions were broadly categorized into those that change the environment in which people live, work, learn, recreate or heal (for example, the provision of gardens in hospitals or parks in cities) and those that change behaviour (for example, engaging people through organized programmes or other activities). We also noted the range of factors (such as socioeconomic variation) that will inevitably influence the extent to which these interventions succeed. We conclude with a call for research to identify the drivers influencing the effectiveness of NBIs in enhancing health and wellbeing.Peer reviewe
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