Analysis of parameters of haemostasis in pre-eclamptic, normotensive pregnant and non-pregnant women.

Pregnancy is characterized by a state of heightened coagulation, which is exacerbated in pathological conditions such as pre-eclampsia (PET). PET is further associated with abnormal maternal inflammation and increased circulating microparticles (MP); however, a mechanistic link between these pathological features has never been established. It is proposed in this thesis that abnormal maternal inflammation is causally linked to pro-coagulant trophoblast MP shedding via a mechanism mediated by the pro-inflammatory cytokine tumour necrosis factor alpha (TNF), thereby contributing to maternal coagulopathies associated with PET. Using thromboelastography (TEG) and standard laboratory tests, haemostatic function was evaluated in PET and normotensive subjects at delivery and post-partum. Furthermore, the effects of the menstrual cycle and oral contraceptive (OC) use on haemostatic function were assessed in non-pregnant subjects in order to understand their influence on post-partum haemostasis. Plasma TNF and pro-coagulant MP levels were evaluated in the pregnant subjects. Using chorionic villi explants from human term placentas, MPs were quantified after TNF administration. The pro-coagulant potential of placental MPs was evaluated by TEG by spiking whole-blood with medium containing MPs from chorionic villi. TEG identified increased whole-blood coagulability in PET subjects at delivery, demonstrating its increased sensitivity over standard laboratory tests at identifying haemostatic alterations associated with PET. Haemostatic alterations were normalized by six weeks post-partum. TEG also identified cyclic haemostatic variations associated with OC use. Chorionic villi treated with TNF (1 ng/ml) shed significantly more MPs than untreated placentas. MPs from chorionic villi increased the coagulability of whole-blood. Together, results provide evidence supporting the concept that abnormal maternal inflammation is causally linked to the development of maternal coagulopathies in pregnancy complications. Moreover, TEG may be superior to standard laboratory tests in evaluating haemostasis in pregnant and non-pregnant subjects.

Modelling the correlation between processing parameters and properties of maraging steels using artificial neural network

An artificial neural network (ANN) model is developed for the analysis and simulation of the correlation between the properties of maraging steels and composition, processing and working conditions. The input parameters of the model consist of alloy composition, processing parameters (including cold deformation degree, ageing temperature, and ageing time), and working temperature. The outputs of the ANN model include property parameters namely: ultimate tensile strength, yield strength, elongation, reduction in area, hardness, notched tensile strength, Charpy impact energy, fracture toughness, and martensitic transformation start temperature. Good performance of the ANN model is achieved. The model can be used to calculate properties of maraging steels as functions of alloy composition, processing parameters, and working condition. The combined influence of Co and Mo on the properties of maraging steels is simulated using the model. The results are in agreement with experimental data. Explanation of the calculated results from the metallurgical point of view is attempted. The model can be used as a guide for further alloy development.

The atmospheric parameters and chemical composition of early B-type giants in h and chi Persei

Atmospheric parameters and surface chemical compositions are presented for eight stars, classified as B1 or B2 but with a range of luminosity classes, in the northern double cluster h and chi Persei. Echelle spectroscopy (covering the wavelength region 3900 to 4700 Ä) and grating spectroscopy (of the Balmer, H? and Hß lines) were analysed using non-LTE synthetic spectra based on LTE line-blanketed atmosphere structures. High microturbulences are found in our sample, and this quantity must be included in the computation of the non-LTE level populations; its effect is generally to decrease the derived metal abundances by typically 0.1 dex but by up to 0.4 dex. Our absolute abundances are in reasonable agreement with those previously found for main sequence B-type stars, while we find some evidence for small abundance variations (particularly for nitrogen) within our sample. One star (BD+56 678) appears to be a spectrum variable and at two epochs shows a highly enriched nitrogen spectrum. Our atmospheric parameters imply that two stars have previously been mis-identified as main sequence objects and a distance modulus, at the higher end of the values previously deduced. The observational HR diagram is consistent with stellar evolutionary models that explicitly include the effects of rotation.

Space and phase resolved plasma parameters in an industrial dual-frequency capacitively coupled radio-frequency discharge

The dynamics of high energetic electrons (>= 11.7 eV) in a modified industrial confined dual-frequency capacitively coupled RF discharge (Exelan, Lam Research Inc.), operated at 1.937 MHz and 27.118 MHz, is investigated by means of phase resolved optical emission spectroscopy. Operating in a He-O-2. plasma with small rare gas admixtures the emission is measured, with one-dimensional spatial resolution along the discharge axis. Both the low and high frequency RF cycle are resolved. The diagnostic is based on time dependent measurements of the population densities of specifically chosen excited rare gas states. A time dependent model, based on rate equations, describes the dynamics of the population densities of these levels. Based on this model and the comparison of the excitation of various rare gas states, with different excitation thresholds, time and space resolved electron temperature, propagation velocity and qualitative electron density as well as electron energy distribution functions are determined. This information leads to a better understanding of the dual-frequency sheath dynamics and shows, that separate control of ion energy and electron density is limited.

Spatial structures of plasma parameters in a magnetic neutral loop discharge

Spatial structures of plasma parameters in a radio-frequency inductively coupled magnetic neutral loop discharge are investigated under various parameter variations using spatially resolved Langmuir probe measurements. A strong coupling between the plasma production region, in the neutral loop (NL) plane, and the axially remote substrate region is observed. The two regions are connected through the separatrices and therefore, spatial profiles in the substrate region are strongly influenced by the plasma production region and the structure of the separatrices. The electron temperature in the plasma production region peaks in the centre of the NL while the maximum in electron density is shifted radially inwards due to diffusion. Details of the structures in both regions, the production region and the substrate region, are determined through the position of the NL and the gradient of the inhomogeneous magnetic field around the NL confinement region. Parameter combinations are found providing higher plasma densities and better uniformity than in common inductively coupled plasmas without applying an additional magnetic field. The uniformity can be further improved using temporal variations of the magnetic field structure.

The VLT-FLAMES survey of massive stars: atmospheric parameters and rotational velocity distributions for B-type stars in the Magellanic Clouds

Aims.We aim to provide the atmospheric parameters and rotational velocities for a large sample of O- and early B-type stars, analysed in a homogeneous and consistent manner, for use in constraining theoretical models. Methods: Atmospheric parameters, stellar masses, and rotational velocities have been estimated for approximately 250 early B-type stars in the Large (LMC) and Small (SMC) Magellanic Clouds from high-resolution VLT-FLAMES data using the non-LTE TLUSTY model atmosphere code. This data set has been supplemented with our previous analyses of some 50 O-type stars (Mokiem et al. 2006, 2007) and 100 narrow-lined early B-type stars (Hunter et al. 2006; Trundle et al. 2007) from the same survey, providing a sample of ~400 early-type objects. Results: Comparison of the rotational velocities with evolutionary tracks suggests that the end of core hydrogen burning occurs later than currently predicted and we argue for an extension of the evolutionary tracks. We also show that the large number of the luminous blue supergiants observed in the fields are unlikely to have directly evolved from main-sequence massive O-type stars as neither their low rotational velocities nor their position on the H-R diagram are predicted. We suggest that blue loops or mass-transfer binary systems may populate the blue supergiant regime. By comparing the rotational velocity distributions of the Magellanic Cloud stars to a similar Galactic sample, we find that (at 3s confidence level) massive stars (above 8 M?) in the SMC rotate faster than those in the solar neighbourhood. However there appears to be no significant difference between the rotational velocity distributions in the Galaxy and the LMC. We find that the v sin i distributions in the SMC and LMC can modelled with an intrinsic rotational velocity distribution that is a Gaussian peaking at 175 km s-1 (SMC) and 100 km s-1 (LMC) with a 1/e half width of 150 km s-1. We find that in NGC 346 in the SMC, the 10-25 M? main-sequence stars appear to rotate faster than their higher mass counterparts. It is not expected that O-type stars spin down significantly through angular momentum loss via stellar winds at SMC metallicity, hence this could be a reflection of mass dependent birth spin rates. Recently Yoon et al. (2006) have determined rates of GRBs by modelling rapidly rotating massive star progenitors. Our measured rotational velocity distribution for the 10-25 M? stars is peaked at slightly higher velocities than they assume, supporting the idea that GRBs could come from rapid rotators with initial masses as low as 14 M? at low metallicities.

Acoustic, volumetric, compressibility and refractivity properties and Flory’s reduction parameters of some homologous series of alkyl alkanoates from 298.15 to 333.15 K

The speeds of sound u in, densities ? and refractive indices nD of some homologous series, such as n-alkyl ethanoates, n-alkyl propionates, methyl alkanoates, ethyl alkanoates, dialkyl malonates, and alkyl haloalkanoates, were measured in the temperature range from 298.15 to 333.15 K. Molar volume V, isentropic and isothermal compressibilities ?S and ?T, molar refraction Rm, Eykman’s constant Cm, molecular radius r, Rao’s molar function R, thermal expansion coefficient a, thermal pressure coefficient ?, and Flory’s characteristic parameters image, P*, V*, and T* have been calculated from the measured experimental data. Applicability of Rao theory and Flory–Patterson–Pandey (FPP) theory have been examined and discussed for these alkanoates.

Acoustic, volumetric, compressibility and refractivity properties and reduction parameters for the ERAS and Flory models of some homologous series of amines from 298.15 to 328.15 K

The speeds of sound u, densities ? and refractive indices nD of homologous series of mono-, di-, and tri-alkylamines were measured in the temperature range from 298.15 to 328.15 K. Isentropic and isothermal compressibilities ?S and ?T, molar refraction Rm, Eykman’s constant Cm, Rao’s molar sound function R, thermal expansion coefficient a, thermal pressure coefficient ?, and reduction parameters P*, V*, and T* in frameworks of the ERAS model for associated amines and Flory model for tertiary amines have been calculated from the measured experimental data. Applicability of the Rao theory and the ERAS and Flory models have been examined and discussed for the alkyl amines.

Proteasome inhibitors: a therapeutic strategy for haematological malignancy

The proteasome is a multicatalytic enzyme complex responsible for the regulated degradation of intracellular proteins. In recent years, inhibition of proteasome function has emerged as a novel anti-cancer therapy. Proteasome inhibition is now established as an effective treatment for relapsed and refractory multiple myeloma and offers great promise for the treatment of other haematological malignancies, when used in combination with conventional therapeutic agents. Bortezomib is the first proteasome inhibitor to be used clinically and a second generation of proteasome inhibitors with differential pharmacological properties are currently in early clinical trials. This review summarises the development of proteasome inhibitors as therapeutic agents and describes how novel assays for measuring proteasome activity and inhibition may help to further delineate the mechanisms of action of different proteasome inhibitors. This will allow for the optimized use of proteasome inhibitors in combination therapies and provide the opportunity to design more potent and therapeutically efficacious proteasome inhibitors.