2,667 research outputs found
High temperature measuring device
Ultrasonic pulse technique for measuring average gas temperature in nuclear rocket engine - sound propagation and environmental studie
Propofol inhibits prokaryotic voltage-gated Na+ channels by promoting activation-coupled inactivation
Propofol is widely used in the clinic for the induction and maintenance of general anesthesia. As with most general anesthetics, however, our understanding of its mechanism of action remains incomplete. Local and general anesthetics largely inhibit voltage-gated Na+ channels (Navs) by inducing an apparent stabilization of the inactivated state, associated in some instances with pore block. To determine the biophysical and molecular basis of propofol action in Navs, we investigated NaChBac and NavMs, two prokaryotic Navs with distinct voltage dependencies and gating kinetics, by whole-cell patch clamp electrophysiology in the absence and presence of propofol at clinically relevant concentrations (2-10 μM). In both Navs, propofol induced a hyperpolarizing shift of the pre-pulse inactivation curve without any significant effects on recovery from inactivation at strongly hyperpolarized voltages, demonstrating that propofol does not stabilize the inactivated state. Moreover, there was no evidence of fast or slow pore block by propofol in a non-inactivating NaChBac mutant (T220A). Propofol also induced hyperpolarizing shifts of the conductance-voltage relationships with negligible effects on the time constants of deactivation at hyperpolarized voltages, indicating that propofol does not stabilize the open state. Instead, propofol decreases the time constants of macroscopic activation and inactivation. Adopting a kinetic scheme of Nav gating that assumes preferential closed-state recovery from inactivation, a 1.7-fold acceleration of the rate constant of activation and a 1.4-fold acceleration of the rate constant of inactivation were sufficient to reproduce experimental observations with computer simulations. In addition, molecular dynamics simulations and molecular docking suggest that propofol binding involves interactions with gating machinery in the S4-S5 linker and external pore regions. Our findings show that propofol is primarily a positive gating modulator of prokaryotic Navs, which ultimately inhibits the channels by promoting activation-coupled inactivation. © 2018 Yang et al
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A general method for finding extremal states of Hamiltonian dynamical systems, with applications to perfect fluids
In addition to the Hamiltonian functional itself, non-canonical Hamiltonian dynamical systems generally possess integral invariants known as ‘Casimir functionals’. In the case of the Euler equations for a perfect fluid, the Casimir functionals correspond to the vortex topology, whose invariance derives from the particle-relabelling symmetry of the underlying Lagrangian equations of motion. In a recent paper, Vallis, Carnevale & Young (1989) have presented algorithms for finding steady states of the Euler equations that represent extrema of energy subject to given vortex topology, and are therefore stable. The purpose of this note is to point out a very general method for modifying any Hamiltonian dynamical system into an algorithm that is analogous to those of Vallis etal. in that it will systematically increase or decrease the energy of the system while preserving all of the Casimir invariants. By incorporating momentum into the extremization procedure, the algorithm is able to find steadily-translating as well as steady stable states. The method is applied to a variety of perfect-fluid systems, including Euler flow as well as compressible and incompressible stratified flow
Innovative MRI techniques in neuroimaging approaches for cerebrovascular diseases and vascular cognitive impairment
Cognitive impairment and dementia are recognized as major threats to public health. Many studies have shown the important role played by challenges to the cerebral vasculature and the neurovascular unit. To investigate the structural and functional characteristics of the brain, MRI has proven an invaluable tool for visualizing the internal organs of patients and analyzing the parameters related to neuronal activation and blood flow in vivo. Different strategies of imaging can be combined to obtain various parameters: (i) measures of cortical and subcortical structures (cortical thickness, subcortical structures volume); (ii) evaluation of microstructural characteristics of the white matter (fractional anisotropy, mean diffusivity); (iii) neuronal activation and synchronicity to identify functional networks across different regions (functional connectivity between specific regions, graph measures of specific nodes); and (iv) structure of the cerebral vasculature and its efficacy in irrorating the brain (main vessel diameter, cerebral perfusion). The high amount of data obtainable from multi-modal sources calls for methods of advanced analysis, like machine-learning algorithms that allow the discrimination of the most informative features, to comprehensively characterize the cerebrovascular network into specific and sensitive biomarkers. By using the same techniques of human imaging in pre-clinical research, we can also investigate the mechanisms underlying the pathophysiological alterations identified in patients by imaging, with the chance of looking for molecular mechanisms to recover the pathology or hamper its progression
PI3kinases in diabetes mellitus and its related complications
Recent studies have shown that phosphoinositide 3-kinases (PI3Ks) have become the target of many pharmacological treatments, both in clinical trials and in clinical practice. PI3Ks play an important role in glucose regulation, and this suggests their possible involvement in the onset of diabetes mellitus. In this review, we gather our knowledge regarding the effects of PI3K isoforms on glucose regulation in several organs and on the most clinically-relevant complications of diabetes mellitus, such as cardiomyopathy, vasculopathy, nephropathy, and neurological disease. For instance, PI3K α has been proven to be protective against diabetes-induced heart failure, while PI3K γ inhibition is protective against the disease onset. In vessels, PI3K γ can generate oxidative stress, while PI3K β inhibition is anti-thrombotic. Finally, we describe the role of PI3Ks in Alzheimer’s disease and ADHD, discussing the relevance for diabetic patients. Given the high prevalence of diabetes mellitus, the multiple effects here described should be taken into account for the development and validation of drugs acting on PI3Ks
The Miocene vertebrate-bearing deposits of Scontrone (Abruzzo, Central Italy): Stratigraphic and paleoenvironmental analysis.
The Miocene carbonate deposits of Scontrone (Abruzzo, Central Italy) are well known among
palaeontologists because of their fossil vertebrate content that exhibits striking similarities to those of
the remarkable ‘‘Terre Rosse’’ faunal complex of the Gargano region, defining the existence of the
Miocene Central Mediterranean Apulia paleobioprovince. The main goal of this paper is to establish the
age and environment of the Scontrone vertebrate bonebeds. The vertebrate remains are embedded in the
basal portion of the Lithothamnion Limestone, a widespread carbonate-ramp lithosome representative of
the Tortonian-early Messinian transgression over the entire Apulia Platform. The bonebeds belong to
marginal-marine deposits (here called ‘‘Scontrone calcarenites’’) preserved in a small area below
transgressive ravinement surfaces. The rapid vertical and lateral facies variations displayed by the
‘‘Scontrone calcarenites’’, together with paleoenvironmental considerations deriving from the vertebrate
association, document a complex wave-dominated river-mouth depositional setting developed over a
large, flat and semi-arid carbonate ramp. The ‘‘Scontrone calcarenites’’ have been split herein into five
facies associations representing the stratigraphic response to a discontinuous or punctuated
transgression within an overall rise of the relative sea level. Because of the absence of age-diagnostic
fossils, the age of the ‘‘Scontrone calcarenites’’ cannot be directly defined through their paleontological
content. However, a regional stratigraphic correlation between the Lithothamnion Limestone of
Scontrone and the Lithothamnion Limestone of northern Majella, which is biostratigraphically well
constrained, allows the attribution of the ‘‘Scontrone calcarenites’’ to the Tortonian
Flow over the Mid Adriatic Pit
The influence of the Mid Adriatic Pit (MAP) on the general circulation of the Adriatic is explored through numerical simulations. The numerical code used is the DieCAST model specifically modified for application to the Adriatic Sea. A ten-year simulation is performed and the ability of the model to capture important features of the Adriatic circulation is demonstrated. A series of numerical
experiments on the importance of the MAP on the general circulation is performed. It is demonstrated that the current over the northern flank of the MAP, which flows
from the Croatian toward the Italian coast, is primarily a topographic current and that such a current would reverse direction if the gradient of the bathymetry were
reversed
Flow over the Mid Adriatic Pit
The influence of the Mid Adriatic Pit (MAP) on the general circulation of the Adriatic is explored through numerical simulations. The numerical code used is the DieCAST model specifically modified for application to the Adriatic Sea. A ten-year simulation is performed and the ability of the model to capture important features of the Adriatic circulation is demonstrated. A series of numerical
experiments on the importance of the MAP on the general circulation is performed. It is demonstrated that the current over the northern flank of the MAP, which flows
from the Croatian toward the Italian coast, is primarily a topographic current and that such a current would reverse direction if the gradient of the bathymetry were
reversed
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