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As an alternative to spherical harmonics, mass concentration (mascon) parameters have been successfully applied to the recovery of time-varying gravity (TVG) fields from the GRACE satellite mission. However, before meaningful mass anomalies can be estimated, the noise and errors inherent in the solutions needs to be quantified and appropriate procedures adopted for mitigation. The uniqueness of the mascon methodology is the capability to mitigate noise and errors using spatial and temporal constraints, which can be adapted and tailored to any geophysical signal of interest. Therefore, in the first instance, this work was motivated by the need to improve the accuracy of GRACE TVG fields by understanding the effect of noise and errors. This study then aims to validate mascons for recovery of basin scale inter-annual mass variability at a 10 day temporal resolution. Newcastle University’s orbit determination software, Faust, was modified to allow for estimation of mascon parameters including: modelling of accelerometer bias values; mascon parameterisation; and processing based on short-arc gravity field recovery and KBRR data. Accuracy assessments were undertaken using simulations in the presence of realistic noise facilitating the comparison of mascons and spherical harmonic coefficients, including an assessment of potential limitations associated with each technique. Comparisons with time-series derived from CSR RL05 Level-2 data validated the mascon TVG field recovery, before estimation of the mass change of Antarctica, Greenland and Alaska. Several hydrological basins, including the Amazon and Indus were also assessed before the GRACE trends resulting from the Sumatra earthquake of 2004 were investigated. While only provided for validation, these comparisons provide confidence in the mascon mass estimates. Between January 2003 and December 2013 a mass change of -83 ± 12 Gt/year and -242 ± 7 Gt/year were estimated for Antarctica and Greenland respectively by linear regression using mascons with a 10 day temporal resolution. Overall, the work undertaken in this thesis provides evidence of the improved accuracy achievable when using mascon parameters to estimating TVG fields from Level-1B GRACE data. ii As part of this work a processing methodology to estimate mascon parameters from Level-1B GRACE data using Newcastle University’s orbit determination software Faust has been established and documented. This leaves the University well placed to continue processing mascon solutions from Level-1B GRACE data and to estimate mascon solutions from the GRACE-FO mission. Through simulations, mascon parameters were found to offer advantages over spherical harmonics for the mitigation of noise and for improving the temporal and spatial recovery of the TVG field from GRACE. The mascon constraint matrix allowed more signal to be preserved up to degree ~35. Using basin constraints, simulation revealed that the constraint matric can be tuned to recovery the gravity changes resulting from any geophysical phenomena of interest. Basin constraints were found to optimise the signal recovery of GLDAS and a known mass change signal over Antarctica and Greenland. A novel way to create realistic noise and errors in the KBRR measurement was also documented. Generating monthly and 10 day mascon solutions using real data revealed that the noise and errors in mascon solutions is comparably lower than in CRS RL05 solution while also validating the mascon methodology established here. Comparison to published mass trends to those estimated using mascon parameters showed that the estimation of mascon parameters has application in the study of mass change in the cryosphere, hydrological applications and for the study of the co-seismic mass changes resulting from earthquakes.

Adhesions following abdominal surgery remain a significant unresolved clinical problem causing a great deal of post-operative morbidity. To date adhesion prevention strategies have proven of limited effectiveness. Osteopontin COPN) is a cytokine up-regulated in cell injury and tissue repair. Previous studies have shown that blocking OPN expression in the cutaneous wound demonstrates reduced granulation tissue and scarring without compromising healing. I hypothesise that it might be possible to produce a similar effect on inflammation associated fibrosis that leads to inter-loop bowel adhesions after intra-peritoneal surgery using a murine model. My experimental work on OPN suppression using mRNA blockade by delivering OPN antisense oligodeoxynucleotides on to the surface of injured juxtaposed small bowel supports this hypothesis. There was a significant reduction in granulation tissue and subsequent adhesion size. Also demonstrated was a significant reduction of leukocyte flux, alpha smooth muscle actin expression and collagen density within developing adhesions. There was no impact on mortality or delay in wound healing. Inflammation triggered by expression of OPN was not essential for healing of serosal injury to bowel within the peritoneal cavity. Blocking OPN expression is a very interesting target for anti-adhesion therapeutics.

The study of the motion of manoeuvring aircraft has traditionally considered the aircraft to be rigid. This simplifying assumption has been shown to give quite accurate results for the flight dynamics of many aircraft types. As modern transport aircraft have developed however, there has been a marked increase in the size and weight of these aircraft. This trend is likely to continue with the development of future blended-wing-body and supersonic transport aircraft. This increase in size and weight has brought about a unique set of aeroelastic and handling quality issues. The aerodynamic forces and moments acting on an aeroplane have traditionally been represented using the aerodynamic derivative approach. It has been shown that this quasisteady aerodynamic model inadequately predicts the aircraft’s stability characteristics, and that the inclusion of unsteady aerodynamics “greatly improves the fidelity” of aircraft models. This thesis thus presents a novel numerical simulation of an aeroelastic aeroplane for real-time analysis. The model is built around the standard six degree-of-freedom equations of motion for a rigid aeroplane using the mean-axes system, and includes unsteady aerodynamics and structural dynamics. This is suitable for pilot-in-the-loop simulation, handling qualities and flight loads analysis, and control law development. The dynamics of the structure are modelled as a set of normal modes, and the equations of motion are realised in state-space form. The unsteady aerodynamic forces acting on the aeroplane are described by an indicial state-space model, including unsteady tailplane downwash and compressibility effects. An implementation of the model is presented in the MATLAB/ Simulink environment. The interaction between the flight control system, the aeroelastic system and the rigidbody motion of the aeroplane can result in degraded handling qualities, excessive actuator control, and fatigue problems. The introduction of load alleviation systems for the management of loads due to manoeuvres and gusts is also likely to result in the handling qualities of the aeroplane being degraded. This thesis presents a number of studies into the impact of structural dynamics, unsteady aerodynamics, and load alleviation on the handling qualities of a flexible civil transport aeroplane. The handling qualities of the aeroplane are assessed against a number of different handling qualities criteria and flying specifications, including the Neal-Smith, Bandwidth, and CAP criterion. It is shown that aeroelastic effects alter the longitudinal and lateral-directional characteristics of the aeroplane, resulting in degraded handling qualities. Manoeuvre and gust load alleviation are similarly found to degrade handling qualities, while active mode control is shown to offer the possibility of improved handling qualities.

Histones are proteins required for packaging of DNA in the nucleus.  Metazoan replication-dependent histone genes are expressed only during S-phase, intronless, and their mRNAs do not end in a poly(A) tail but rather a highly conserved hairpin structure.  Hairpin binding protein (HBP or Stem-Loop Binding Protein) specifically binds to the hairpin structure of histone pre-mRNA.  This interaction is important during the endonucleolytic cleavage reaction to generate the mature histone mRNA.  I have performed preliminary work to identify nucleotides in the hairpin structure that are involved in the interaction with HBP. HBP expression occurs concurrently with expression of histone genes during S-phase.  A hairpin RNA binding activity, presumed to be HBP has been previously demonstrated in both nuclear and cytoplasmic extracts.  I have used a specific antibody to show that hHBP has a histone RNA-independent localisation in both the nucleus and cytoplasm only during S-phase.  Also, I have examined the localisation of an exclusively nuclear alternative splice variant of HBP which arises from skipping of exon 3 of mouse and human HBP mRNA. Efficient translation of histone mRNA is dependent on HBP.  I show that a minor fraction of cytoplasmic hHBP associates with ribosomes in an RNA-dependent manner and show that HBP stimulates translation.  I further participated in mapping of the HBP region required for the translation stimulation by a motif encoded by xSLBP1 exon 3 found in xSLBP1-Nt and characterised interactions between HBP and translation initiation factors, eIF3h and PAIP1, mediated by hHBP RBD and Ct, respectively.