7,359 research outputs found
Structural synthesis of a stiffened cylinder
Structural synthesis of cylindrical shell reinforced with rectangular cross section stiffener
An analytical approach to solution of two- point boundary condition problems in optimal guidance Summary report, May 1965 - Apr. 1966
Analytical approaches to path-adaptive guidance functions, circular orbit trajectories, and use of Fortran-compiled program
How to validate machine-learned interatomic potentials
Machine learning (ML) approaches enable large-scale atomistic simulations
with near-quantum-mechanical accuracy. With the growing availability of these
methods there arises a need for careful validation, particularly for physically
agnostic models - that is, for potentials which extract the nature of atomic
interactions from reference data. Here, we review the basic principles behind
ML potentials and their validation for atomic-scale materials modeling. We
discuss best practice in defining error metrics based on numerical performance
as well as physically guided validation. We give specific recommendations that
we hope will be useful for the wider community, including those researchers who
intend to use ML potentials for materials "off the shelf"
Ethanol Regulation of Synaptic GABAA 4 Receptors Is Prevented by Protein Kinase A Activation
Ethanol alters GABAA receptor trafficking and function through activation of protein kinases, and these changes may underlie ethanol dependence and withdrawal. In this study, we used subsynaptic fraction techniques and patch-clamp electrophysiology to investigate the biochemical and functional effects of protein kinase A (PKA) and protein kinase C (PKC) activation by ethanol on synaptic GABAAα4 receptors, a key target of ethanol-induced changes. Rat cerebral cortical neurons were grown for 18 days in vitro and exposed to ethanol and/or kinase modulators for 4 hours, a paradigm that recapitulates GABAergic changes found after chronic ethanol exposure in vivo. PKA activation by forskolin or rolipram during ethanol exposure prevented increases in P2 fraction α4 subunit abundance, whereas inhibiting PKA had no effect. Similarly, in the synaptic fraction, activation of PKA by rolipram in the presence of ethanol prevented the increase in synaptic α4 subunit abundance, whereas inhibiting PKA in the presence of ethanol was ineffective. Conversely, PKC inhibition in the presence of ethanol prevented the ethanol-induced increases in synaptic α4 subunit abundance. Finally, we found that either activating PKA or inhibiting PKC in the presence of ethanol prevented the ethanol-induced decrease in GABA miniature inhibitory postsynaptic current decay τ1, whereas inhibiting PKA had no effect. We conclude that PKA and PKC have opposing effects in the regulation of synaptic α4 receptors, with PKA activation negatively modulating, and PKC activation positively modulating, synaptic α4 subunit abundance and function. These results suggest potential targets for restoring normal GABAergic functioning in the treatment of alcohol use disorders
Differential regulation of synaptic and extrasynaptic α4 GABA(A) receptor populations by protein kinase A and protein kinase C in cultured cortical neurons
The GABAA α4 subunit exists in two distinct populations of GABAA receptors. Synaptic GABAA α4 receptors are localized at the synapse and mediate phasic inhibitory neurotransmission, while extrasynaptic GABAA receptors are located outside of the synapse and mediate tonic inhibitory transmission. These receptors have distinct pharmacological and biophysical properties that contribute to interest in how these different subtypes are regulated under physiological and pathological states. We utilized subcellular fractionation procedures to separate these populations of receptors in order to investigate their regulation by protein kinases in cortical cultured neurons. Protein kinase A (PKA) activation decreases synaptic α4 expression while protein kinase C (PKC) activation increases α4 subunit expression, and these effects are associated with increased β3 S408/409 or γ2 S327 phosphorylation respectively. In contrast, PKA activation increases extrasynaptic α4 and δ subunit expression, while PKC activation has no effect. Our findings suggest synaptic and extrasynaptic GABAA α4 subunit expression can be modulated by PKA to inform the development of more specific therapeutics for neurological diseases that involve deficits in GABAergic transmission
Imaging geometry through dynamics: the observable representation
For many stochastic processes there is an underlying coordinate space, ,
with the process moving from point to point in or on variables (such as
spin configurations) defined with respect to . There is a matrix of
transition probabilities (whether between points in or between variables
defined on ) and we focus on its ``slow'' eigenvectors, those with
eigenvalues closest to that of the stationary eigenvector. These eigenvectors
are the ``observables,'' and they can be used to recover geometrical features
of
Perceived barriers towards healthy eating and their association with fruit and vegetable consumption
Acknowledgements The authors would like to thank the anonymous reviewer, staff at the Health Economics Research Unit and the Rowett Institute of Nutrition and Health for helpful comments on the manuscript. Funding This work was supported by the Scottish Government Rural and Environment Science and Analytical Services (RESAS) division.Peer reviewedPostprin
Implications of ocean acidification for marine microorganisms from the free-living to the host-associated
Anthropogenic CO2 emissions are causing oceans to become more acidic, with consequences for all marine life including microorganisms. Studies reveal that from the microbes that occupy the open ocean to those intimately associated with their invertebrate hosts changing ocean chemistry will alter the critical functions of these important organisms. Our current understanding indicates that bacterial communities associated with their host will shift as pH drops by another 0.2–0.4 units over the next 100 years. It is unclear what impacts this will have for host health, however, increased vulnerability to disease seems likely for those associated with reef corals. Natural CO2 seeps have provided a unique setting for the study of microbial communities under OA in situ, where shifts in the bacterial communities associated with corals at the seep are correlated with a decline in abundance of the associated coral species. Changes to global biogeochemical cycles also appear likely as photosynthesis and nitrogen fixation by pelagic microbes becomes enhanced under low pH conditions. However, recent long-term studies have shown that pelagic microbes are also capable of evolutionary adaptation, with some physiological responses to a decline in pH restored after hundreds of generations at high pCO2 levels. The impacts of ocean acidification (OA) also will not work in isolation, thus synergistic interactions with other potential stressors, such as rising seawater temperatures, will likely exacerbate the microbial response to OA. This review discusses our existing understanding of the impacts of OA on both pelagic and host-associated marine microbial communities, whilst highlighting the importance of controlled laboratory studies and in situ experiments, to fill the current gaps in our knowledge
Characterization of body weight and composition changes during the sophomore year of college
<p>Abstract</p> <p>Background</p> <p>Years spent in college represents a critical time for obesity development though little information is known regarding how body weight and composition changes beyond the first year of college. The aim of this study was to investigate changes in body weight and composition and the factors influencing those changes among sophomore females.</p> <p>Methods</p> <p>Body composition by dual energy X-ray absorptiometry was obtained in participants beginning during their freshman year and continued through their sophomore year.</p> <p>Results</p> <p>No difference was observed between sophomore year fall and spring visits for body weight (60.4 versus 60.6 kg) or fat mass (19.3 versus 18.7 kg). However, a significant (<it>P </it>≤ 0.05) decrease was observed for body fat (31.9 versus 30.9 %fat) and a significant increase was observed for fat-free mass (37.7 versus 38.4 kg). Participants living off campus significantly (<it>P </it>≤ 0.05) declined in body fat (33.0 versus 31.0 %fat) and fat mass (19.4 versus 18.2 kg) and increased in fat-free mass (36.1 versus 37.2 kg) with no differences in those living on campus.</p> <p>Conclusion</p> <p>No change in body weight was observed in females during their sophomore year. However, an increase in fat-free mass accompanied with a decrease in fat mass resulted in a decrease in body fat. Participants living off campus had favorable changes in their body composition by means of decreasing %fat and fat mass while increasing fat-free mass. Participants living on campus did not demonstrate these favorable changes.</p
- …