Phase stability, electronic structures and elastic properties of (U,Np)O2 and (Th,Np)O2 mixed oxides.

Mixing enthalpies (ΔHmix) of U1-xNpxO2 and Th1-xNpxO2 solid solutions are derived from atomic scale simulations based on density functional theory (DFT) employing the generalised gradient approximation corrected with an effective Hubbard parameter (Ueff). The variation of structural and electronic properties of UO2 and NpO2 with collinear ferromagnetic (FM), collinear anti-ferromagnetic (AFM) and non-collinear anti-ferromagnetic arrangements of the uranium and neptunium magnetic moments are investigated while ramping up Ueff from 0 eV to 4 eV (the Ueff-ramping method). A combination of the Ueff-ramping method to treat the presence of metastable magnetic states and special-quasirandom structures (SQS) for the random distribution of Np atoms in UO2 and ThO2 is employed to calculate ΔHmix of U1-xNpxO2 and Th1-xNpxO2 mixed oxides (MOX). The effect of collinear FM and AFM ordering is also considered in determining the ΔHmix. The calculated ΔHmix of Th1-xNpxO2 MOX were positive compared to the end members and nearly symmetric around x = 0.5 and ΔHmix of the AFM configuration were higher compared to the FM configuration maximum by 0.19 kJ mol-1. The ΔHmix of U1-xNpxO2 MOX were negative up to U0.50Np0.50O2 with a maximum value of -1.21 kJ mol-1 for U0.4375Np0.5625O2 whereas Np-rich (U,Np)O2 MOX compositions exhibited ΔHmix close to zero. Values of ΔHmix for (Th,Np)O2 are consistent with a simple miscibility-gap phase diagram while those for (U,Np)O2 suggest more complex behaviour. Nevertheless, lattice parameter variation with composition still follows a Vegard's law relationship. Finally, single crystal elastic constants of pure oxides and MOX are reported. The linear-elasticity models describe the mixing energies to within an accuracy of approximately 1 kJ mol-1 for the U1-xNpxO2 and Th1-xNpxO2 MOX systems.

A computational study on the superionic behaviour of ThO2.

This study reports the density functional theory (DFT) and classical molecular dynamics (MD) study of the lattice dynamical, mechanical and anionic transport behaviours of ThO2 in the superionic state. DFT calculations of phonon frequencies were performed at different levels of approximation as a function of isotropic dilation (ε) in the lattice parameter. With the expansion of the lattice parameter, there is a softening of B1u and Eu phonon modes at the X symmetry point of the Brillouin zone. As a result of the nonlinear decrease at the X point, the B1u and Eu phonon modes cross each other at ε = 0.03, which is associated with a sharp increase in the narrow peak of the phonon density of states, signifying a higher occupation and hence a higher coupling of these modes at high temperatures. The mode crossing also indicates anionic conductivity in the 〈001〉 direction leading to occupation of interstitial sites. Moreover, MD and nudged elastic band calculated diffusion barriers indicate that 〈001〉 is the easy direction for anion migration in the normal and superionic states. With a further increase in the lattice parameter, the B1u mode continues to soften and becomes imaginary at a strain (ε) of 0.036 corresponding to a temperature of 3430 K. The calculated temperature variation of single crystal elastic constants shows that the fluorite phase of ThO2 remains elastically stable up to the superionic regime, though the B1u phonon mode is imaginary in that state. This leads to anionic disorder at elevated temperatures. Tracking of anion positions in the superionic state as a function of time in MD simulations suggests a hopping model in which the oxygen ions migrate from one tetrahedral site to another via octahedral interstitial sites.

Genetics of superionic conductivity in lithium lanthanum titanates.

The self-diffusion of ions is a fundamental mass transport process in solids and has a profound impact on the performance of electrochemical devices such as the solid oxide fuel cell, batteries and electrolysers. The perovskite system lithium lanthanum titanate, La2/3-xLi3xTiO3 (LLTO) has been the subject of much academic interest as it displays very high lattice conductivity for a solid state Li conductor; making it a material of great technological interest for deployment in safe durable mobile power applications. However, so far, a clear picture of the structural features that lead to efficient ion diffusion pathways in LLTO, has not been fully developed. In this work we show that a genetic algorithm in conjunction with molecular dynamics can be employed to elucidate diffusion mechanisms in systems such as LLTO. Based on our simulations we provide evidence that there is a three-dimensional percolated network of Li diffusion pathways. The present approach not only reproduces experimental ionic conductivity results but the method also promises straightforward investigation and optimisation of the properties relating to superionic conductivity in materials such as LLTO. Furthermore, this method could be used to provide insights into related materials with structural disorder.

Point defect engineering strategies to retard phosphorous diffusion in germanium.

The diffusion of phosphorous in germanium is very fast, requiring point defect engineering strategies to retard it in support of technological application. Density functional theory corroborated with hybrid density functional calculations are used to investigate the influence of the isovalent codopants tin and hafnium in the migration of phosphorous via the vacancy-mediated diffusion process. The migration energy barriers for phosphorous are increased significantly in the presence of oversized isovalent codopants. Therefore, it is proposed that tin and in particular hafnium codoping are efficient point defect engineering strategies to retard phosphorous migration.

Defect processes in orthorhombic LnBaCo2O5.5 double perovskites.

Static atomistic simulations based on the Born model were used to investigate intrinsic defect processes in orthorhombic LnBaCo(2)O(5.5) (Ln = Y, La, Pr, Nd, Sm, Gd, Dy, Ho, Er, and Yb) double perovskites. It was found that Ln/Ba antisite disorder is the lowest energy defect reaction, with the large Ln cations giving rise to smaller antisite energies. On the oxygen sublattice the oxygen Frenkel disorder dominates and also decreases in energy with increasing Ln cation size. The lowest energy oxygen vacancy and interstitial positions are in the LnO(0.5) and CoO(2) layers respectively. Interestingly, the calculations indicate that oxygen vacancies cluster with Ba antisite defects (occupying Ln sites). This suggests that the transport of oxygen vacancies will be influenced not only by the oxygen Frenkel energy but also the antisite energy. We propose that PrBaCo(2)O(5.5) most efficiently balances these two competing effects as it has an oxygen Frenkel energy of just 0.24 eV per defect combined with a high antisite energy (0.94 eV), which ensures that the A cation sublattice will remain more ordered.

A theoretical study of intrinsic point defects and defect clusters in magnesium aluminate spinel.

Point and small cluster defects in magnesium aluminate spinel have been studied from a first principles viewpoint. Typical point defects that occur during collision cascade simulations are cation anti-site defects, which have a small formation energy and are very stable, O and Mg split interstitials and vacancies. Isolated Al interstitials were found to be energetically unfavourable but could occur as part of a split Mg-Al pair or as a three atom-three vacancy Al 'ring' defect, previously observed in collision cascades using empirical potentials. The structure and energetics of the defects were investigated using density functional theory (DFT) and the results compared to simulations using empirical fixed charge potentials. Each point defect was studied in a variety of supercell sizes in order to ensure convergence. It was found that empirical potential simulations significantly overestimate formation energies, but that the type and relative stability of the defects are well predicted by the empirical potentials both for point defects and small defect clusters.

High temperature measurements and condensed matter analysis of the thermo-physical properties of ThO2.

Values are presented for thermal conductivity, specific heat, spectral and total hemispherical emissivity of ThO2 (a potential nuclear fuel material) in a temperature range representative of a nuclear accident - 2000 K to 3050 K. For the first time direct measurements of thermal conductivity have been carried out on ThO2 at such high temperatures, clearly showing the property does not decrease above 2000 K. This could be understood in terms of an electronic contribution (arising from defect induced donor/acceptor states) compensating the degradation of lattice thermal conductivity. The increase in total hemispherical emissivity and visible/near-infrared spectral emissivity is consistent with the formation of donor/acceptor states in the band gap of ThO2. The electronic population of these defect states increases with temperature and hence more incoming photons (in the visible and near-infrared wavelength range) can be absorbed. A solid state physics model is used to interpret the experimental results. Specific heat and thermal expansion coefficient increase at high temperatures due to the formation of defects, in particular oxygen Frenkel pairs. Prior to melting a gradual increase to a maximum value is predicted in both properties. These maxima mark the onset of saturation of oxygen interstitial sites.

Advances in the development of a dissolution method for the attribution of iridium source materials.

To assist in nuclear forensic investigations, new techniques are required to evaluate radioactive materials that may be discovered outside of regulatory control. Using a recently developed pressure digestion method for iridium powder, assessments have been made of this techniques suitability for undertaking iridium target material evaluations. In addition to determining the reaction conditions necessary for total dissolution, these investigations have provided an insight into the elemental impurities that are present within unirradiated iridium targets that are used in QSA Global radiography sources, and established the speciation of the iridium solutions that are formed during this process.

Thermophysical properties and oxygen transport in (Thx,Pu1-x)O2.

Using Molecular Dynamics, this paper investigates the thermophysical properties and oxygen transport of (Thx,Pu1-x)O2 (0 ≤ x ≤ 1) between 300-3500 K. In particular, the superionic transition is investigated and viewed via the thermal dependence of lattice parameter, linear thermal expansion coefficient, enthalpy and specific heat at constant pressure. Oxygen diffusivity and activation enthalpy are also investigated. Below the superionic temperature an increase of oxygen diffusivity for certain compositions of (Thx,Pu1-x)O2 compared to the pure end members is predicted. Oxygen defect formation enthalpies are also examined, as they underpin the superionic transition temperature and the increase in oxygen diffusivity. The increase in oxygen diffusivity for (Thx,Pu1-x)O2 is explained in terms of lower oxygen defect formation enthalpies for (Thx,Pu1-x)O2 than PuO2 and ThO2, while links are drawn between the superionic transition temperature and oxygen Frenkel disorder.

Development of Xe and Kr empirical potentials for CeO2, ThO2, UO2 and PuO2, combining DFT with high temperature MD.

The development of embedded atom method (EAM) many-body potentials for actinide oxides and associated mixed oxide (MOX) systems has motivated the development of a complementary parameter set for gas-actinide and gas-oxygen interactions. A comprehensive set of density functional theory (DFT) calculations were used to study Xe and Kr incorporation at a number of sites in CeO2, ThO2, UO2 and PuO2. These structures were used to fit a potential, which was used to generate molecular dynamics (MD) configurations incorporating Xe and Kr at 300 K, 1500 K, 3000 K and 5000 K. Subsequent matching to the forces predicted by DFT for these MD configurations was used to refine the potential set. This fitting approach ensured weighted fitting to configurations that are thermodynamically significant over a broad temperature range, while avoiding computationally expensive DFT-MD calculations. The resultant gas potentials were validated against DFT trapping energies and are suitable for simulating combinations of Xe and Kr in solid solutions of CeO2, ThO2, UO2 and PuO2, providing a powerful tool for the atomistic simulation of conventional nuclear reactor fuel UO2 as well as advanced MOX fuels.

Pipe and grain boundary diffusion of He in UO2.

Molecular dynamics simulations have been conducted to study the effects of dislocations and grain boundaries on He diffusion in [Formula: see text]. Calculations were carried out for the {1 0 0}, {1 1 0} and {1 1 1} [Formula: see text] edge dislocations, the screw [Formula: see text] dislocation and Σ5, Σ13, Σ19 and Σ25 tilt grain boundaries. He diffusivity as a function of distance from the dislocation core and grain boundaries was investigated for the temperature range 2300-3000 K. An enhancement in diffusivity was predicted within 20 Å of the dislocations or grain boundaries. Further investigation showed that He diffusion in the edge dislocations follows anisotropic behaviour along the dislocation core, suggesting that pipe diffusion occurs. An Arrhenius plot of He diffusivity against the inverse of temperature was also presented and the activation energy calculated for each structure, as a function of distance from the dislocation or grain boundary.

Insulin and insulin-like growth factors (IGFs) stimulate production of IGF-binding proteins by ovarian granulosa cells.

Ligand blot analysis of granulosa cell (GC)-conditioned culture medium revealed several easily measurable insulin-like growth factor (IGF)-binding proteins (IGFBPs), including IGFBP-3 [40-44 kilodaltons (kDa)] and IGFBP-2 (34 kDa). In the present study, IGF-I, in a dose-dependent manner, significantly stimulated the production of these IGFBPs. Insulin, but not IGF-II, mimicked IGF-I's action on IGFBP-3 and -2 production, but was less potent. The synthetic IGF, long R3-IGF-I, which has very low affinity for IGFBPs and only slightly reduced affinity for the IGF-I (type I) receptor, had significantly greater potency in stimulating IGFBP-3 and -2 production compared to IGF-I. Des-(1-3)-IGF-I had similar effects. IGF-I, IGF-II, and the IGF-I analogs, but not insulin, also induced production of an unidentified 30-kDa IGFBP not normally detectable in these cultures. However, in the presence of epidermal growth factor (which was without independent effect on the 30-kDa IGFBP), insulin also induced this 30-kDa IGFBP. By Northern analysis the expression of IGFBP-3 mRNA was found to be significantly stimulated by IGF-I. In summary, insulin stimulated IGFBP-3 and -2 production in a manner that mimics that of IGF-I and the more potent long R3-IGF-I. However, its low potency suggested that IGFBP production is regulated via the IGF-I (type I) receptor. The much higher potency of long R3-IGF-I compared to that of IGF-I suggests that the IGFBPs themselves modulate the action of IGFs by sequestering exogenous IGFs. Thus, one cellular response to IGF stimulation is the production of IGFBPs, which, in turn, reduce or negate the biological activity of the IGFs. The effects of insulin-like peptides are exerted at least in part by increasing levels of mRNA for specific BPs.

Proteolytic degradation of insulin-like growth factor (IGF)-binding protein-3 by porcine ovarian granulosa cells in culture: regulation by IGF-I.

Porcine ovarian granulosa cells in culture secrete glycosylated insulin-like growth factor (IGF)-binding protein-3 (IGFBP-3), which inhibits gonadotropin and IGF action in the ovary. Synthesis of IGFBP-3 is stimulated by IGF-I and attenuated by gonadotropin. The purpose of the present study was to determine whether IGFBP-3 levels were also regulated via proteolysis. Exogenously added nonglycosylated recombinant human IGFBP-3 (rhIGFBP-3) was significantly degraded over time by a soluble serine-specific protease, similar to plasmin, in control cultures and those treated with FSH, insulin, or several other classes of hormones. In contrast, degradation was greatly attenuated by the IGFs. Degraded rhIGFBP-3 exhibited much reduced affinity for [125I]IGF-II, suggesting that degradation could make available IGFs for cellular interaction. The mechanism of IGFBP-3 protease inhibition by IGFs is unclear. Mediation by IGF receptors is unlikely, as insulin at a dose that activated both insulin and type I IGF receptors did not alter intrinsic degradation of IGFBP-3 (as does IGF). Additionally, IGF-I attenuation of IGFBP-3 degradation was not inhibited by antagonism of receptor action with a tyrosine kinase inhibitor. Further, IGF-I inhibited degradation in cell-free conditioned medium. Direct stabilization of IGFBP-3 via binding of IGFs was suggested from these results. However, long R3 IGF-I attenuated IGFBP-3 degradation even though it has low affinity for IGFBPs. Inhibition of the protease by IGFs is also possible. We conclude that IGFs inhibit the degradation of exogenous nonglycosylated rhIGFBP-3. If active in vivo, this may serve to increase endogenous IGFBP-3 levels in follicular fluid.

Divergent actions of prostaglandins-E2 and -F2 alpha on the regulation of insulin-like growth factor-binding protein-3 in luteinized granulosa cells.

Insulin-like growth factor (IGF)-I synergizes with gonadotropin to further stimulate ovarian steroidogenesis. In contrast, the IGF-binding proteins (IGFBPs) produced by granulosa cells have been shown to antagonize the stimulatory actions of the IGFs and gonadotropins. The purpose of the present study was to examine the effects on IGFBP-3 production of prostaglandin (PG)-E2, a compound known to stimulate luteal function and prevent/delay luteal regression (a luteotropic compound), and PGF2 alpha, a compound known to be luteolytic. PGF2 alpha significantly stimulated IGFBP-3 production to 2.6-fold of control (P < 0.05) while PGE2 attenuated its production to half of control (P < 0.05). In contrast to the effects of IGFBP-3, PGE2 stimulated progesterone production to 8-fold of control (P < 0.05) while PGF2 alpha had no effect. Possible mechanisms of action of PGE2 and PGF2 alpha were also examined. PGE2, but not PGF2 alpha, stimulated cAMP accumulation which has been previously shown to inhibit IGFBP-3 production. PGF2 alpha is suspected to act via activation of protein kinase-C. However, a phorbol ester did not mimic PGF2 alpha's action toward IGFBP-3. This study demonstrated that PGE2 and PGF2 alpha conversely modulate IGFBP-3 production. Since IGFBPs have been shown to antagonize gonadotropin and IGF actions, this action of the prostaglandins may impact on the synergism between IGFs and gonadotropin necessary for follicular growth and luteal function.

Insulin-like growth factor-binding protein-2 and -3 are correlated with atresia and preovulatory maturation in the porcine ovary.

We compared insulin-like growth factor-binding protein (IGFBP) levels with indicators of follicular maturation and atresia in individual follicles of the porcine ovary. Follicular development was synchronized with the progestin, altrenogest, and progestin withdrawal was used to initiate the growth of an ovulatory cohort of follicles, which is accompanied by atresia of noncohort follicles. Individual follicles were isolated on days 1, 3, 5, and 7 after progestin withdrawal. Atretic follicles were identified by the presence of low hypodiploid levels of DNA in 10% or more of their granulosa cells using flow cytometry. The follicular fluid (FF) level of IGFBP-3 did not differ significantly between healthy and atretic medium-sized (3- to 6-mm) follicles and was not significantly correlated with the percentage of granulosa cells containing hypodiploid levels of DNA (r = 0.181) or with endocrine parameters such as FF concentrations of estradiol or androstenedione. However, among healthy follicles (atretic follicles removed from analyses to better examine follicular maturation), IGFBP-3 increased (P < 0.01) between days 1 and 7 and was positively correlated with follicle diameter (r = 0.514; P < 0.05) and the FF concentration of progesterone (r = 0.556; P < 0.01), indicators of the degree of follicular maturation. FF IGFBP-2 levels were 3-fold greater (P < 0.01) in atretic than in healthy follicles, and IGFBP-2 was correlated with percentage of granulosa cells containing hypodiploid levels of DNA (r = 0.729; P < 0.001). Among healthy follicles, FF IGFBP-2 did not differ significantly among days and was not significantly correlated with follicle diameter. These data suggest that the content of IGFBP-2 is related to the state of follicular health/atresia, whereas IGFBP-3 is related to preovulatory follicular development.

Regulation of human placental trophoblast low-density lipoprotein uptake in vitro by estrogen.

In the present study, human trophoblast cells were studied in culture to determine the effect of estrogen on low-density lipoprotein (LDL) uptake and progesterone formation. Cytotrophoblasts were obtained from term human placentas and incubated for 72 h with 10% FBS to stimulate formation of syncytia. Syncytiotrophoblasts were then incubated for an additional 48 h with estradiol and/or LDL protein. Estradiol plus LDL stimulated progesterone to a level that was 133% greater (P < 0.05) than control (314 +/- 69 ng/mg protein) or LDL alone, suggesting that estrogen stimulated progesterone formation via an increase in LDL uptake and utilization. To examine this possibility, trophoblast cells were cultured with estradiol for 48 h as above, then incubated for 12 h with 6-200 micrograms/mL [125I]LDL. Mean (+/- SE) specific uptake of [125I]LDL (ng/mg cell protein) was approximately 50% greater (P < 0.01) with estradiol (638 +/- 23) than with vehicle (429 +/- 54). Scatchard analysis demonstrated that the dissociation constant for LDL uptake was similar in the presence (2.9 +/- 0.4 x 10(-6)M) and absence (2.8 +/- 0.6 x 10(-8)M) of estradiol, indicating that estrogen increased LDL receptor number without affecting affinity. LDL uptake was increased (P < 0.05) by incubating trophoblast with as little as 0.10 ng/mL estradiol (approximately 10(-9) M). We conclude that estrogen regulates placental trophoblast cell uptake of LDL and, thus, the availability of cholesterol for progesterone bio-synthesis during human pregnancy.

Expression of the IGF system in primary and immortalized porcine ovarian granulosa cells.

We have established a novel granulosa cell line derived from porcine ovarian follicles (4-6 mm in diameter). This cell line, MDG2.1, was obtained by transfection of freshly cultured cells with the plasmid pSV3neo. Doubling time for MDG2.1 cells is 24-36 h. Northern analysis for RNAs of the insulin-like growth factor (IGF) regulatory system indicates that RNAs for IGF-I, IGF-I receptor, and IGF binding proteins (IGFBP) 2-6, but not IGFBP-1, are expressed in MDG2.1 cells. The secretion of IGFBPs from MDG2.1 cells shows > 10-fold levels of the 24 kDa form, reduced secretion of other IGFBPs, with no change in the total amount of IGFBP secreted, as compared to primary cells cultured under identical conditions. Use of endoglycosidase F indicated that several IGFBPs are posttranslationally modified. This cell line is a useful model and plasmid transfection target system to investigate IGFBP action in ovarian granulosa cells.

IGF-binding proteins are differentially regulated in an ovarian granulosa cell line.

We have recently established an immortalized granulosa cell line as a model system to investigate ovarian function, with particular emphasis on the insulin-like growth factor (IGF) regulatory system. Previous results have shown that these cells express mRNAs for IGF-binding proteins (IGFBPs)-2 to -5. These IGFBPs are also detected by ligand blots. The current work evaluated the regulation by the IGFs and cAMP on the IGFBPs and their mRNAs and compared the findings to that in primary culture. Our results indicate that levels of the IGFBPs are controlled, in part, by expression of the mRNAs. However, evidence for post-transcriptional regulation was also discovered. IGFBP-3 was stimulated by IGF-I, IGFBP-4 by forskolin, and IGFBP-5 by IGF-I. IGFBP-2, -3, and -4 are expressed under basal conditions whereas IGFBP-5 is only detectable after IGF-I induction. An alteration in the biphasic actions of cAMP in this cell line, as compared to primary culture, was evident.

Single nerve capsaicin: effects on pain and morphine analgesia in the formalin and foot-flick tests.

Application of capsaicin to the sciatic nerve reduces responsiveness to pain in the foot-flick test which examines brief, threshold-level pain. The purpose of the present study was to determine if a similar reduction occurs in the formalin test which examines suprathreshold, deep pain that persists for several hours. The sciatic nerve on one side in the rat was exposed and soaked for 15 min in a solution of capsaicin and the saphenous nerve was ligated and cut. The operated foot was tested for sensitivity to pain in the formalin and foot-flick tests 2 days to 12 weeks later both with and without morphine. The capsaicin treatment produced a substantial reduction in sensitivity to foot-flick heat pain at all times after surgery. In the formalin test, the effects were small and tended to suggest that the rats felt more rather than less pain. The capsaicin treatment markedly reduced the sensitivity of formalin test pain to morphine. This effect appeared about one week after surgery and persisted for 12 weeks. The results suggest that capsaicin-sensitive unmyelinated afferents play a role in the threshold-level, non-damaging heat pain, but are not involved in pain resulting from tissue damage. However, these afferents appear to be important for the spinal action of morphine on this type of pain.

Autotomy after nerve sections in the rat is influenced by tonic descending inhibition from locus coeruleus.

This study examined the role of descending brainstem inhibition on autotomy (self-mutilation) produced by neurectomy, and on the enhancement of autotomy by an injury prior to denervation. Autotomy after sciatic and saphenous nerve sections was examined following lesions of the locus coeruleus (or sham lesions) in rats which were either uninjured or previously injured by an injection of formalin into the hindpaw. The prior injury of the paw produced a significant increase in autotomy which occurred earlier in rats with lesions of the locus coeruleus than in the sham controls. The locus coeruleus lesion by itself also produced an enhancement of autotomy. These results suggest that self-mutilation following neurectomy, and possibly its enhancement by prior injury, are subject to tonic inhibition due to descending controls from the locus coeruleus.