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"

Imaging geometry through dynamics: the observable representation

For many stochastic processes there is an underlying coordinate space, $V$, with the process moving from point to point in $V$ or on variables (such as spin configurations) defined with respect to $V$. There is a matrix of transition probabilities (whether between points in $V$ or between variables defined on $V$) 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 $V$

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

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

Adsorption and two-body recombination of atomic hydrogen on 3^3He-4^4He mixture films

We present the first systematic measurement of the binding energy $E_a$ of hydrogen atoms to the surface of saturated $^3$He-$^4$He mixture films. $E_a$ is found to decrease almost linearly from 1.14(1) K down to 0.39(1) K, when the population of the ground surface state of $^3$He grows from zero to $6\times10^{14}$ cm$^{-2}$, yielding the value $1.2(1)\times 10^{-15}$ K cm$^2$ for the mean-field parameter of H-$^3$He interaction in 2D. The experiments were carried out with overall $^3$He concentrations ranging from 0.1 ppm to 5 % as well as with commercial and isotopically purified $^4$He at temperatures 70...400 mK. Measuring by ESR the rate constants $K_{aa}$ and $K_{ab}$ for second-order recombination of hydrogen atoms in hyperfine states $a$ and $b$ we find the ratio $K_{ab}/K_{aa}$ to be independent of the $^3$He content and to grow with temperature.Comment: 4 pages, 4 figures, all zipped in a sigle file. Submitted to Phys. Rev. Let