Plutonium oxide melt structure and covalency.

Advances in nuclear power reactors include the use of mixed oxide fuel, containing uranium and plutonium oxides. The high-temperature behaviour and structure of PuO above 1,800 K remain largely unexplored, and these conditions must be considered for reactor design and planning for the mitigation of severe accidents. Here, we measure the atomic structure of PuO through the melting transition up to 3,000 ± 50 K using X-ray scattering of aerodynamically levitated and laser-beam-heated samples, with O/Pu ranging from 1.

High-Temperature Raman Spectroscopy of UCl: A Combined Experimental and Theoretical Study.

Uranium trichloride (UCl) has received growing interest for its use in uranium-fueled molten salt reactors and in the pyrochemical processing of used fuel. In this paper, we report for the first time the experimentally determined Raman spectra of UCl, at both ambient condition and high temperatures up to 871 K. The frequencies of five of the Raman-active vibrational modes () of UCl exhibit a negative temperature derivative ((∂ν/∂)) with increasing temperature.

Topical Oxaliplatin Produces Gain- and Loss-of-Function in Multiple Classes of Sensory Afferents.

The platinum chemotherapeutic oxaliplatin produces dose-limiting pain, dysesthesia, and cold hypersensitivity in most patients immediately after infusion. An improved understanding of the mechanisms underlying these symptoms is urgently required to facilitate the development of symptomatic or preventative therapies. In this study, we have used skin-saphenous nerve recordings in vitro and behavioral experiments in mice to characterize the direct effects of oxaliplatin on different types of sensory afferent fibers.

AL4GAP: Active learning workflow for generating DFT-SCAN accurate machine-learning potentials for combinatorial molten salt mixtures.

Machine learning interatomic potentials have emerged as a powerful tool for bypassing the spatiotemporal limitations of ab initio simulations, but major challenges remain in their efficient parameterization. We present AL4GAP, an ensemble active learning software workflow for generating multicomposition Gaussian approximation potentials (GAP) for arbitrary molten salt mixtures. The workflow capabilities include: (1) setting up user-defined combinatorial chemical spaces of charge neutral mixtures of arbitrary molten mixtures spanning 11 cations (Li, Na, K, Rb, Cs, Mg, Ca, Sr, Ba and two heavy species, Nd, and Th) and 4 anions (F, Cl, Br, and I), (2) configurational sampling using low-cost empirical parameterizations, (3) active learning for down-selecting configurational samples for single point density functional theory calculations at the level of Strongly Constrained and Appropriately Normed (SCAN) exchange-correlation functional, and (4) Bayesian optimization for hyperparameter tuning of two-body and many-body GAP models.

Pain-causing stinging nettle toxins target TMEM233 to modulate Na1.7 function.

Voltage-gated sodium (Na) channels are critical regulators of neuronal excitability and are targeted by many toxins that directly interact with the pore-forming α subunit, typically via extracellular loops of the voltage-sensing domains, or residues forming part of the pore domain. Excelsatoxin A (ExTxA), a pain-causing knottin peptide from the Australian stinging tree Dendrocnide excelsa, is the first reported plant-derived Na channel modulating peptide toxin. Here we show that TMEM233, a member of the dispanin family of transmembrane proteins expressed in sensory neurons, is essential for pharmacological activity of ExTxA at Na channels, and that co-expression of TMEM233 modulates the gating properties of Na1.

Aftersensations and Lingering Pain After Examination in Patients with Fibromyalgia Syndrome.

Background: Fibromyalgia syndrome (FMS) is a chronic widespread pain condition with mixed peripheral and central contributions. Patients display hypersensitivities to a spectrum of stimuli. Patients' blunt pressure pain thresholds are typically reduced, and sometimes (∼15%) gentle brushstroke induces allodynia.

Passive transfer of fibromyalgia symptoms from patients to mice.

Fibromyalgia syndrome (FMS) is characterized by widespread pain and tenderness, and patients typically experience fatigue and emotional distress. The etiology and pathophysiology of fibromyalgia are not fully explained and there are no effective drug treatments. Here we show that IgG from FMS patients produced sensory hypersensitivity by sensitizing nociceptive neurons.

A Systematic Review Into the Influence of Temperature on Fibromyalgia Pain: Meteorological Studies and Quantitative Sensory Testing.

Fibromyalgia syndrome (FMS) is a chronic widespread pain condition of unknown aetiology. The role of temperature in FMS pain has not been reviewed systematically. The goal of this study was to review the influences of temperature on pain in FMS, from meteorological and quantitative sensory testing (QST) studies.

Promiscuous G-Protein-Coupled Receptor Inhibition of Transient Receptor Potential Melastatin 3 Ion Channels by Gβγ Subunits.

Transient receptor potential melastatin 3 (TRPM3) is a nonselective cation channel that is inhibited by Gβγ subunits liberated following activation of Gα protein-coupled receptors. Here, we demonstrate that TRPM3 channels are also inhibited by Gβγ released from Gα and Gα Activation of the G-coupled adenosine 2B receptor and the G-coupled muscarinic acetylcholine M1 receptor inhibited the activity of TRPM3 heterologously expressed in HEK293 cells. This inhibition was prevented when the Gβγ sink βARK1-ct (C terminus of β-adrenergic receptor kinase-1) was coexpressed with TRPM3.

Autoantibodies produce pain in complex regional pain syndrome by sensitizing nociceptors.

Complex regional pain syndrome (CRPS) is a posttraumatic pain condition with an incompletely understood pathophysiological basis. Here, we have examined the cellular basis of pain in CRPS using behavioral and electrophysiological methods in mice treated with IgG from CRPS patients, in combination with a paw incision. Mice were subjected to a hind paw skin-muscle incision alone, or in combination with administration of IgG purified from either healthy control subjects or patients with persistent CRPS.

Impaired Nociception in the Diabetic Mouse.

The mechanisms responsible for painful and insensate diabetic neuropathy are not completely understood. Here, we have investigated sensory neuropathy in the mouse, a hereditary model of diabetes. Akita mice become diabetic soon after weaning, and we show that this is accompanied by an impaired mechanical and thermal nociception and a significant loss of intraepidermal nerve fibers.

G protein βγ subunits inhibit TRPM3 ion channels in sensory neurons.

Transient receptor potential (TRP) ion channels in peripheral sensory neurons are functionally regulated by hydrolysis of the phosphoinositide PI(4,5)P and changes in the level of protein kinase mediated phosphorylation following activation of various G protein coupled receptors. We now show that the activity of TRPM3 expressed in mouse dorsal root ganglion (DRG) neurons is inhibited by agonists of the G-coupled µ opioid, GABA-B and NPY receptors. These agonist effects are mediated by direct inhibition of TRPM3 by Gβγ subunits, rather than by a canonical cAMP mediated mechanism.

Structure-Pungency Relationships and TRP Channel Activation of Drimane Sesquiterpenes in Tasmanian Pepper (Tasmannia lanceolata).

Sensory-guided fractionation of extracts of Tasmanian pepper berries revealed 20 drimane sesquiterpens, among which polygodial, warburganal, and 1β-acetoxy-9-deoxy-isomuzigadial exhibited the lowest pungency threshold concentrations on the tongue surface (0.6-2.8 nmol/cm) and elicited a dose-dependent calcium influx into mTRPA1 expressing CHO cells with the lowest EC values (4.

Determination of Krypton Diffusion Coefficients in Uranium Dioxide Using Atomic Scale Calculations.

We present a study of the diffusion of krypton in UO using atomic scale calculations combined with diffusion models adapted to the system studied. The migration barriers of the elementary mechanisms for interstitial or vacancy assisted migration are calculated in the DFT+U framework using the nudged elastic band method. The attempt frequencies are obtained from the phonon modes of the defect at the initial and saddle points using empirical potential methods.

Local Symmetry Effects in Actinide 4f X-ray Absorption in Oxides.

A systematic X-ray absorption study at actinide N6,7 (4f → 6d transitions) edges was performed for light-actinide oxides including data obtained for the first time for NpO2, PuO2, and UO3. The measurements were supported by ab initio calculations based on local-density-approximation with added 5f-5f Coulomb interaction (LDA+U). Improved energy resolution compared to common experiments at actinide L(2,3) (2p → 6d transitions) edges allowed us to resolve the major structures of the unoccupied 6d density of states (DOS) and estimate the crystal-field splittings in the 6d shell directly from the spectra of light-actinide dioxides.

Possible Demonstration of a Polaronic Bose-Einstein(-Mott) Condensate in UO2(+x) by Ultrafast THz Spectroscopy and Microwave Dissipation.

Bose-Einstein condensates (BECs) composed of polarons would be an advance because they would combine coherently charge, spin, and a crystal lattice. Following our earlier report of unique structural and spectroscopic properties, we now identify potentially definitive evidence for polaronic BECs in photo- and chemically doped UO2(+x) on the basis of exceptional coherence in the ultrafast time dependent terahertz absorption and microwave spectroscopy results that show collective behavior including dissipation patterns whose precedents are condensate vortex and defect disorder and condensate excitations. That some of these signatures of coherence in an atom-based system extend to ambient temperature suggests a novel mechanism that could be a synchronized, dynamical, disproportionation excitation, possibly via the solid state analog of a Feshbach resonance that promotes the coherence.

TRPA1 mediates the hypothermic action of acetaminophen.

Acetaminophen (APAP) is an effective antipyretic and one of the most commonly used analgesic drugs. Unlike antipyretic non-steroidal anti-inflammatory drugs, APAP elicits hypothermia in addition to its antipyretic effect. Here we have examined the mechanisms responsible for the hypothermic activity of APAP.

TRPM8 is a neuronal osmosensor that regulates eye blinking in mice.

Specific peripheral sensory neurons respond to increases in extracellular osmolality but the mechanism responsible for excitation is unknown. Here we show that small increases in osmolality excite isolated mouse dorsal root ganglion (DRG) and trigeminal ganglion (TG) neurons expressing the cold-sensitive TRPM8 channel (transient receptor potential channel, subfamily M, member 8). Hyperosmotic responses were abolished by TRPM8 antagonists, and were absent in DRG and TG neurons isolated from Trpm8(-/-) mice.

Streptozotocin Stimulates the Ion Channel TRPA1 Directly: INVOLVEMENT OF PEROXYNITRITE.

Streptozotocin (STZ)-induced diabetes is the most commonly used animal model of diabetes. Here, we have demonstrated that intraplantar injections of low dose STZ evoked acute polymodal hypersensitivities in mice. These hypersensitivities were inhibited by a TRPA1 antagonist and were absent in TRPA1-null mice.

TRPV1.

TRPV1 is a well-characterised channel expressed by a subset of peripheral sensory neurons involved in pain sensation and also at a number of other neuronal and non-neuronal sites in the mammalian body. Functionally, TRPV1 acts as a sensor for noxious heat (greater than ~42 °C). It can also be activated by some endogenous lipid-derived molecules, acidic solutions (pH < 6.

Monoacylglycerols activate TRPV1--a link between phospholipase C and TRPV1.

Phospholipase C-mediated hydrolysis of phosphatidylinositol 4,5-bisphosphate generates diacylglycerol, inositol 1,4,5-trisphosphate and protons, all of which can regulate TRPV1 activity via different mechanisms. Here we explored the possibility that the diacylglycerol metabolites 2-arachidonoylglycerol and 1-arachidonoylglycerol, and not metabolites of these monoacylglycerols, activate TRPV1 and contribute to this signaling cascade. 2-Arachidonoylglycerol and 1-arachidonoylglycerol activated native TRPV1 on vascular sensory nerve fibers and heterologously expressed TRPV1 in whole cells and inside-out membrane patches.

Methylglyoxal evokes pain by stimulating TRPA1.

Diabetic neuropathy is a severe complication of long-standing diabetes and one of the major etiologies of neuropathic pain. Diabetes is associated with an increased formation of reactive oxygen species and the electrophilic dicarbonyl compound methylglyoxal (MG). Here we show that MG stimulates heterologously expressed TRPA1 in CHO cells and natively expressed TRPA1 in MDCK cells and DRG neurons.

Mixing and non-stoichiometry in Fe-Ni-Cr-Zn-O spinel compounds: density functional theory calculations.

Density functional theory (DFT) calculations have been performed on A(2+)B2(3+)O4(2-) (where A(2+) = Fe, Ni or Zn, and B(3+) = Fe or Cr) spinel oxides in order to determine some of their thermodynamic properties. Mixing energies were calculated for Fe3O4-NiFe2O4, Fe3O4-ZnFe2O4, Fe3O4-FeCr2O4, NiFe2O4-ZnFe2O4, NiFe2O4-NiCr2O4, FeCr2O4-NiCr2O4, FeCr2O4-ZnCr2O4 and ZnCr2O4-ZnFe2O4 pseudo-binaries based on special quasi random (SQS) structures to account for cationic disorder. The results generally agree with available experimental data and the rule that two normal or two inverse spinel compounds easily form solid solutions, while inverse-normal spinel mixtures exhibit positive deviation from solid solution behavior (i.

Parthenolide inhibits nociception and neurogenic vasodilatation in the trigeminovascular system by targeting the TRPA1 channel.

Although feverfew has been used for centuries to treat pain and headaches and is recommended for migraine treatment, the mechanism for its protective action remains unknown. Migraine is triggered by calcitonin gene-related peptide (CGRP) release from trigeminal neurons. Peptidergic sensory neurons express a series of transient receptor potential (TRP) channels, including the ankyrin 1 (TRPA1) channel.