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ABSTRACTAbout 9 wt.% Cr steels are widely used in the design and fabrication of thick section components in combined cycle or coal-fired applications for working temperatures of 600 ~ 650°C. This family of materials possesses a martensitic microstructure stabilised by precipitates. The presence of nitrides, inclusions or evolution of second-phase particles may increase the metallurgical risk to creep. The chemical composition and microstructural evolution of 9 wt.% Cr steels contribute to thermal stability and long-term performance. In some specialist alloys, Ta is added to the composition which causes the formation of fine MX precipitates which are only present at the nanometre scale in tempered martensite, which hinders the recovery of dislocations and the migration of laths to extend creep life. However, the presence of large Ta-containing particles or inclusions in the 9 wt.% Cr steels may have a detrimental effect on its creep performance, as they may act as preferred sites for cavity nucleation. To fully appreciate the development of damage in these steels, it is necessary to link the pre- and post-test conditions, evaluate damage in the parent metal, develop procedures that provide consistency of results, and obtain statistically relevant data. The evolution of the Ta-containing phase has been tracked and quantified using a variety of correlative characterisation approaches. Utilising focused ion beam microscopy and two-dimensional electron-based microscopic characterisation, three-dimensional tomography has identified a strong relationship between creep cavities and Ta-containing phases from the early stages of creep.

The results from an investigation into the physics of how fluid curtains can be applied to improve the aerodynamic performance of conventional turbomachinery shaft and rotor seals are described in this paper. Computational fluid dynamics and testing on two experimental facilities are used in the study. In the first part of the work, computational fluid dynamics simulations validated against experimental test data demonstrate the fundamental mechanism by which the presence of the curtain can act to reduce leakage flow through conventional seals. These results are consolidated into a single performance carpet map, showing how the leakage reduction performance and the curtain supply pressure needed to achieve it vary with changes in values of key geometrical parameters. In the second part of the work the effect of swirl in the seal inlet flow, as is often encountered in turbomachinery applications, on the performance of the fluid curtain is investigated experimentally. Test results show that if the swirl momentum in the inlet flow is greater than the momentum of the curtain flow, the performance benefit from applying the curtain is greatly diminished. Overall, the results provide some fundamental design rules for applying fluid curtains to enhance turbomachinery sealing performance for the general type of leakage path geometry (cylindrical channel, 45-deg jet angle, curtain upstream of a conventional seal) and working fluid type and conditions (air, ambient temperature, subsonic leakage channel flow) used in the study.

This paper reviews the differences between two nickel based alloys, Alloy 740 and Alloy 740H. Microstructural evolution models are used to forecast the changes in volume fraction and interparticle spacing of both grain boundary and intra-granular precipitates in the alloys. These data are then employed in continuum damage mechanics models to forecast creep curves, and in fracture mechanics models to forecast Charpy impact energies/energy. The results reveal the key microstructural features that control secondary and tertiary creep rate as well as the time dependence of Charpy impact energy after high temperature exposure.

In ultra-supercritical power plants, Ni-base alloys are candidate materials for long-term, high-temperature applications, operating at temperatures and pressures as high as 750°C and 35 MPa. Alloy IN740 and its modification, alloy IN740H, are considered for such applications. Their microstructural evolution, at 750°C for times ranging between 3000 and 5000 hours, has been investigated by means of scanning electron microscopy, electron back-scattered diffraction, energy dispersive X-ray analysis and phase quantification. All phases were identified and quantified allowing comparison between the two microstructures, their evolution and stability. Particular attention was paid to γ′, η and G phases. The results are used within a broader investigation aimed at improving and further developing a predictive creep model based on continuous damage mechanics.

A significant fraction of ferrite has been identified in a 321 grade austenitic stainless steel in the solution heat treated condition. The microstructures were analysed using electron backscatter diffraction, energy dispersive X-ray spectroscopy and X-ray diffraction (XRD) and the stability of the ferrite investigated using heat treatments in a tube furnace, dilatometry and high temperature XRD. The ferrite dissolved ~800°C, then formed again on cooling at temperatures under 200°C. Thermodynamic predictions showed a significant ferrite content at room temperature under equilibrium conditions, and the DeLong diagrams predict an austenite+martensite microstructure in the cast condition. Sensitivity analysis on the DeLong diagram has shown that the nitrogen content had a large effect on the austenite stability. The instability of the austenite and the subsequent transformation to ferrite on cooling can be attributed to low nitrogen content measured in the as received material. It was found that thermal aging of the material caused further transformation of austenite to ferrite as well as the formation of sigma phase that appears higher in nitrogen than the matrix phases. The diffusion of nitrogen into sigma phase may cause instability of the austenite, which could cause further transformation of austenite to ferrite on cooling from the aging temperature. The transformation of austenite to ferrite is known to be accompanied by an increase in volume, which may be of relevance to components made with tight dimensional tolerances.

In the context of ultrasupercritical power plants, Ni base alloys are prime candidate materials for long term, high temperature applications, such as boilers, operating at temperatures and pressures as high as 750°C and 35 MPa. This necessitates the investigation of their microstructural evolution as a function of thermal treatment and simulated service conditions out to longer times at forecasted service temperatures, coupled with modelling activities able to predict the microstructural evolution under these new conditions. The lack of widespread microstructural data for most commercial nickel base alloys in these time–temperature regimes makes this type of investigation even more important. In this study, the microstructural evolution of IN740, a Ni–Cr–Co–Mo–Nb–Ti–Al superalloy, is characterised as a function of aging conditions. A method for phase identification is described that can be confidently used to gather relevant information for modelling activity, such as: phase identity, volume fraction, size distribution and interparticle spacing. The microstructural evolution of IN740 is investigated at temperatures of 700 and 750°C for aging times up to 10?000 h. The data obtained experimentally from the aged specimens as well as from literature are used both as input for and validation of a microstructurally based continuum damage mechanics (CDM) model for forecasting creep properties. Using this predictive model, discussion is made of possible approaches needed to optimize creep performance.

Samples of 321 stainless steel from both the parent and welded section of a thin section tube were subjected to accelerated ageing to simulate long term service conditions in an advanced gas cooled reactor (AGR) power plant. The initial condition of the parent metal showed a duplex microstructure with approximately 50 ferrite and 50 austenite. The weld metal showed three distinct matrix phases, austenite, delta ferrite and ferrite. This result was surprising as the initial condition of the parent metal was expected to be fully austenitic and austenite+delta ferrite in the weldment. The intermetallic sigma phase formed during the accelerated ageing was imaged using ion beam induced secondary electrons then measured using computer software which gave the particle size as a function of aging time. The measurements were used to plot particle size, area coverage against aging time and minimum particle spacing for the parent metal. During aging the amount of ferrite in the parent metal actually increased from ~50 to ~80 after aging for 15?000 h at 750°C. Sigma has been observed to form on the austenite/ferrite boundaries as they may provide new nucleation sites for sigma phase precipitation. This has resulted in small sigma phase particles forming on the austenite/ferrite boundaries in the parent metal as the ferrite transforms from the austenite.

1-[2-(2,4-Dimethylphenyl-sulfanyl)-phenyl]-piperazine (Lu AA21004) is a human (h) serotonin (5-HT)(3A) receptor antagonist (K(i) = 3.7 nM), h5-HT(7) receptor antagonist (K(i) = 19 nM), h5-HT(1B) receptor partial agonist (K(i) = 33 nM), h5-HT(1A) receptor agonist (K(i) = 15 nM), and a human 5-HT transporter (SERT) inhibitor (K(i) = 1.6 nM) (J Med Chem 54:3206-3221, 2011). Here, we confirm that Lu AA21004 is a partial h5-HT(1B) receptor agonist [EC(50) = 460 nM, intrinsic activity = 22%] using a whole-cell cAMP-based assay and demonstrate that Lu AA21004 is a rat (r) 5-HT(7) receptor antagonist (K(i) = 200 nM and IC(50) = 2080 nM). In vivo, Lu AA21004 occupies the r5-HT(1B) receptor and rSERT (ED(50) = 3.2 and 0.4 mg/kg, respectively) after subcutaneous administration and is a 5-HT(3) receptor antagonist in the Bezold-Jarisch reflex assay (ED(50) = 0.11 mg/kg s.c.). In rat microdialysis experiments, Lu AA21004 (2.5-10.0 mg/kg s.c.) increased extracellular 5-HT, dopamine, and noradrenaline in the medial prefrontal cortex and ventral hippocampus. Lu AA21004 (5 mg/kg per day for 3 days; minipump subcutaneously), corresponding to 41% rSERT occupancy, significantly increased extracellular 5-HT in the ventral hippocampus. Furthermore, the 5-HT(3) receptor antagonist, ondansetron, potentiated the increase in extracellular levels of 5-HT induced by citalopram. Lu AA21004 has antidepressant- and anxiolytic-like effects in the rat forced swim (Flinders Sensitive Line) and social interaction and conditioned fear tests (minimal effective doses: 7.8, 2.0, and 3.9 mg/kg). In conclusion, Lu AA21004 mediates its pharmacological effects via two pharmacological modalities: SERT inhibition and 5-HT receptor modulation. In vivo, this results in enhanced release of several neurotransmitters and antidepressant- and anxiolytic-like profiles at doses for which targets in addition to the SERT are occupied. The multimodal activity profile of Lu AA21004 is distinct from that of current antidepressants.

Low density Al4Mg1.3Li0.4Zr and Al6Mg1.6Li0.4Zr alloys were spray formed and the billets extruded under a range of conditions. The alloy compositions were selected to provide an attractive balance of tensile strength and elongation, without relying on complex postprocessing and heat treatments – and are therefore suitable for complex cross section extrusions and free from quench distortion. The asspray formed microstructures showed fine homogeneous, equiaxed grains with an average size of 10–15 μm. Firstly, a laboratory scale extrusion was carried out to extrude 30 mm diameter billets into 7.5 mm diameter crosssection and to investigate the effects of temperature and ram speeds on microstructural development. The microstructure after extrusion at 400°C was partially dynamically recrystallised with a 0.5 area fraction of 1 μm grains and the remainder were unrecrystallised elongated grains. Electron backscatter diffraction showed a mixed <111> + <100> double fibre texture. After peak age hardening at 150°C for 96 h, the Al6Mg1.6Li0.4Zr alloy showed a 0.2 proof strength of 495 MPa, a tensile strength of 553 MPa and elongation to failure of 8.5; Al4Mg1.3Li0.4Zr showed a 0.2 proof strength of 392 MPa, a tensile strength of 476 MPa and an elongation of 10. Subsequently, largescale complex crosssection were extruded at 400°C. Due to the complexity of the crosssections and the nonaxisymetric deformation, the fibre texture was distorted to FCC rolled Copper and Brass orientations. After a dualstep age hardening treatment of 130°C for 8h followed by 160°C for 8h, the proof strength, ultimate strength and elongations were 340 MPa, 470 MPa and 16 respectively. The combination of relatively simple process steps, high strength and ductilityformability, and low distortion in complex sections demonstrated the strong potential for these low density alloys in aerospace and autosport applications.

Serotonin re-uptake inhibitors (SSRIs) can affect the basal activity of the hypothalamic–pituitary–adrenal (HPA) axis in rats. A single injection of citalopram has been shown to stimulate the HPA axis while repeated administration leads to attenuation of the corticosterone response to the SSRI. The purpose of this work was to investigate the rodent HPA axis response to restraint stress, following acute and chronic treatment with the SSRI citalopram. We have demonstrated that a single injection of citalopram is able to prolong acute restraint-induced increases in plasma levels of corticosterone and adrenocorticotrophin (ACTH). This is possibly mediated by arginine vasopressin (AVP) in the parvocellular cells of the paraventricular nucleus (pPVN), as treatment with citalopram or restraint alone did not increase AVP mRNA in pPVN while the combination of treatments resulted in a significant increase in AVP mRNA in the pPVN. In contrast, the increase in corticotrophin-releasing factor (CRF) mRNA in the pPVN in response to acute restraint stress was not altered by citalopram. Oxytocin (OT) mRNA was also increased in the magnocellular PVN (mPVN) by the solo treatments of citalopram and restraint, and was not further enhanced by the dual treatment of restraint and citalopram. Chronic treatment with citalopram did not alter basal plasma levels of corticosterone or ACTH. However, the ACTH response to acute restraint was attenuated following chronic citalopram treatment. AVP mRNA in the pPVN was significantly elevated in response to chronic citalopram compared with saline controls suggesting an effect mediated through the AVP subset of pPVN neurones. The CRF mRNA response to acute restraint was not altered in rats treated chronically with citalopram. OT mRNA was not enhanced in the mPVN following chronic infusion of citalopram but was increased by acute restraint stress. We conclude from these data that both acute and chronic citalopram treatment has the potential to alter the rodent response to acute restraint stress. These effects appear to be regulated by the AVP-containing subset of CRF neurons in the pPVN and thus suggest that parvocellular AVP may have an important role in mediating the actions of SSRIs.

Abstract: Shaping of metals by thixoforming relies on the unusual flow behavior of semisolid slurries containing nondendritic solid phase. The microstructure of an alloy stirred during freezing consists of rounded particles of solid, as opposed to the dendrites associated with conventional solidification. In the semisolid state, these slurries are thixotropic, in that their apparent viscosity is dependent on shear rate and time. Here, a technique of rapid compression testing is outlined, carried out under conditions similar to normal industrial thixoforming, to assess slurry flow behavior and to examine the correlation between feedstock production routes, microstructure, and resistance to flow. Samples are heated to the desired temperature in the semisolid state with various soaking times and rammed at constant velocity against a platen backed by a load cell. The load-displacement curves produced from the tests may show an initial peak, believed to originate from a skeletal structure which rapidly breaks down under shear. The load signal during flow decreases with increasing soaking time and with temperature, and the initial peak eventually disappears in all alloys investigated. Quantitative metallography indicates that the lower loads correspond to greater spheroidicity of the solid particles within the slurry. The curves have been analyzed to derive the viscosity as a function of average shear rate and demonstrate that the semisolid slurries exhibit pseudoplastic flow behavior which is dependent on the compression velocity and is far removed from steady-state conditions.

Antibodies to double-stranded DNA (dsDNA), generally regarded as highly specific for systemic lupus erythematosus (SLE), have also been reported in chronic active hepatitis (CAH). Using the Farr assay and E. coli DNA, fractionated by benzoylated-naphthoylated-DEAE cellulose chromatography into dsDNA and dsDNA containing single-stranded regions, we compared the serum DNA binding of CAH and SLE patients. Although CAH sera were found to have dsDNA binding significantly above the normal control group such binding was of low level and we could find no evidence of markedly elevated dsDNA binding in CAH. However 12 of the 20 CAH sera studied did bind preferentially to dsDNA containing single-stranded regions suggesting the presence of anti-single-stranded DNA antibodies. We conclude that the description of elevated anti-dsDNA antibodies, as measured by the Farr assay, in CAH is due to the interaction of anti-single-stranded DNA antibodies or other serum components with single-stranded DNA contaminating dsDNA preparations.

A competitive ELISA is described for the measurement of lipoteichoic acid. The assay was used to determine the wall associated lipoteichoic acid ofStreptococcus sanguis which was found to represent only 2–4% of the phenol extractable content. Extracellular lipoteichoic acid was detected even after exhaustive cell washing. This material was not the result ofde novo synthesis because membrane de-polarization had no effect on the amount detected. Since extracellular lipoteichoic acid interfered with the measurement of cell surface antigen, cells were fixed with glutaraldehyde prior to assay. Lipoteichoic acid was demonstrated on the surface of fixed cells which did not leak antigen. The relevance of fixation used in antigen location studies by electron microscopy of immune-labelled cells is discussed.

Infective endocarditis (IE) is a life-threatening disease of the heart which, before the discovery of penicillin, was nearly always fatal. Although the use of antibiotics and, more recently, cardiac surgery have greatly improved survival, mortality remains high at 30 per cent.11