"The unity of the spirit": the trinity, the church and love in Saint Augustine of Hippo

"The unity ofthe Spirit": the Trinity, the Church and love in Saint Augustine of Hippo. Augustine of Hippo spent most of his career contending for the cause of the unity of the Church. His passion for Church unity has frequently been portrayed as a consequence of his north African heritage, but one important theological basis has generally been overlooked. This thesis locates his ecclesiology firmly in the context of his trinitarian theology, particularly his emphasis on the unity of God. Many scholars have considered his theology of the Trinity; others have explored his theology of the Church; but this thesis draws out the connections between the two. Augustine is not the first theologian to discuss the unity of the three persons of the Trinity. However, he is the first to develop the doctrine that the Holy Spirit is the bond of love and unity between the Father and the Son. This principle has important implications for his theology of the Church, since it means that discussions of the Holy Spirit and of love in the context of ecclesiology have an explicitly Trinitarian dimension. The thesis consists of three chapters. In the first, Augustine's unique doctrine of the Holy Spirit and of love is set out. It is demonstrated that he locates the image of God not so much in the individual human soul, as in human beings in relation with one another. In the second chapter, attention moves to the Church, and it is shown that Augustine sees the fellowship itself as the analogy of God the Trinity. Love is the characteristic mark of the Church, and those who do not have love and the Holy Spirit have excluded themselves from communion with one another and with God. The third and final chapter is a case study of how these ideas were worked out in practice in the controversies with Manicheism, Donatism and Pelagianism

Early focus development effort, ultrasonic inspection of fixed housing metal-to-adhesive bondline

An ultrasonic technique was developed for the fixed housing metal-to-adhesive bondline that will support the Flight 15 time frame and subsequent motors. The technique has the capability to detect a 1.0 inch diameter unbond with a 90 percent probability of detection (POD) at a 95 percent confidence level. The technique and support equipment will perform within the working envelope dictated by a stacked motor configuration

A new Rossby Wave-breaking interpretation of the North Atlantic Oscillation

This paper proposes the hypothesis that the low-frequency variability of the North Atlantic Oscillation (NAO) arises as a result of variations in the occurrence of upper-level Rossby wave–breaking events over the North Atlantic. These events lead to synoptic situations similar to midlatitude blocking that are referred to as high-latitude blocking episodes. A positive NAO is envisaged as being a description of periods in which these episodes are infrequent and can be considered as a basic, unblocked situation. A negative NAO is a description of periods in which episodes occur frequently. A similar, but weaker, relationship exists between wave breaking over the Pacific and the west Pacific pattern. Evidence is given to support this hypothesis by using a two-dimensional potential-vorticity-based index to identify wave breaking at various latitudes. This is applied to Northern Hemisphere winter data from the 40-yr ECMWF Re-Analysis (ERA-40), and the events identified are then related to the NAO. Certain dynamical precursors are identified that appear to increase the likelihood of wave breaking. These suggest mechanisms by which variability in the tropical Pacific, and in the stratosphere, could affect the NAO

Remotely triggered scaffolds for controlled release of pharmaceuticals

Fe3O4-Au hybrid nanoparticles (HNPs) have shown increasing potential for biomedical applications such as image guided stimuli responsive drug delivery. Incorporation of the unique properties of HNPs into thermally responsive scaffolds holds great potential for future biomedical applications. Here we successfully fabricated smart scaffolds based on thermo-responsive poly(N-isopropylacrylamide) (pNiPAM). Nanoparticles providing localized trigger of heating when irradiated with a short laser burst were found to give rise to remote control of bulk polymer shrinkage. Gold-coated iron oxide nanoparticles were synthesized using wet chemical precipitation methods followed by electrochemical coating. After subsequent functionalization of particles with allyl methyl sulfide, mercaptodecane, cysteamine and poly(ethylene glycol) thiol to enhance stability, detailed biological safety was determined using live/dead staining and cell membrane integrity studies through lactate dehydrogenase (LDH) quantification. The PEG coated HNPs did not show significant cytotoxic effect or adverse cellular response on exposure to 7F2 cells (p < 0.05) and were carried forward for scaffold incorporation. The pNiPAM-HNP composite scaffolds were investigated for their potential as thermally triggered systems using a Q-switched Nd:YAG laser. These studies show that incorporation of HNPs resulted in scaffold deformation after very short irradiation times (seconds) due to internal structural heating. Our data highlights the potential of these hybrid-scaffold constructs for exploitation in drug delivery, using methylene blue as a model drug being released during remote structural change of the scaffold

Carboplatin/taxane-induced gastrointestinal toxicity: a pharmacogenomics study on the SCOTROC1 trial

Carboplatin/taxane combination is first-line therapy for ovarian cancer. However, patients can encounter treatment delays, impaired quality of life, even death because of chemotherapy-induced gastrointestinal (GI) toxicity. A candidate gene study was conducted to assess potential association of genetic variants with GI toxicity in 808 patients who received carboplatin/taxane in the Scottish Randomized Trial in Ovarian Cancer 1 (SCOTROC1). Patients were randomized into discovery and validation cohorts consisting of 404 patients each. Clinical covariates and genetic variants associated with grade III/IV GI toxicity in discovery cohort were evaluated in replication cohort. Chemotherapy-induced GI toxicity was significantly associated with seven single-nucleotide polymorphisms in the ATP7B, GSR, VEGFA and SCN10A genes. Patients with risk genotypes were at 1.53 to 18.01 higher odds to develop carboplatin/taxane-induced GI toxicity (P&#60;0.01). Variants in the VEGF gene were marginally associated with survival time. Our data provide potential targets for modulation/inhibition of GI toxicity in ovarian cancer patients

Modulated extrusion for textured 3D printing

This research utilises a Fused Deposition Modelling 3D Printer to investigate the aesthetics of 3D printing and it's broader applications. The presented research re-evaluates the 3D printer as a tool to manipulate materials, as opposed to a machine that discretely reproduces digital models at a fine resolution. The research questions the utility of automation, and attempts to find a level that permits materially expressive modes of fabrication. The exploration of aesthetics has uncovered a variety of unexpected textures and interesting material properties that may have wider use. For instance, rigid plastic has been extruded and manipulated finer than the extrusion nozzle diameter, which confers flexibility and fabric like qualities to the printed object. The discovered techniques for 3D printed aesthetics are reproducibly reliable and can be incorporated back into orthodox digital-model driven fabrication

Carboplatin/taxane-induced gastrointestinal toxicity: a pharmacogenomics study on the SCOTROC1 trial

Carboplatin/taxane combination is first-line therapy for ovarian cancer. However, patients can encounter treatment delays, impaired quality of life, even death because of chemotherapy-induced gastrointestinal (GI) toxicity. A candidate gene study was conducted to assess potential association of genetic variants with GI toxicity in 808 patients who received carboplatin/taxane in the Scottish Randomized Trial in Ovarian Cancer 1 (SCOTROC1). Patients were randomized into discovery and validation cohorts consisting of 404 patients each. Clinical covariates and genetic variants associated with grade III/IV GI toxicity in discovery cohort were evaluated in replication cohort. Chemotherapy-induced GI toxicity was significantly associated with seven single-nucleotide polymorphisms in the ATP7B, GSR, VEGFA and SCN10A genes. Patients with risk genotypes were at 1.53 to 18.01 higher odds to develop carboplatin/taxane-induced GI toxicity (P<0.01). Variants in the VEGF gene were marginally associated with survival time. Our data provide potential targets for modulation/inhibition of GI toxicity in ovarian cancer patients

The use of nano polymeric self-assemblies based on novel amphiphilic polymers for oral hydrophobic drug delivery.

Purpose: To investigate the use of nano self-assemblies formed by polyallylamine (PAA) modified with 5 or 10% mole fluorenylmethoxy carbonyl (Fmoc5/10), dimethylamino-1-naphthalenesulfonyl (Dansyl5/10) and 5% mole cholesteryl group (Ch5) for oral hydrophobic drug delivery. Methods: Propofol, griseofulvin and prednisolone were loaded into amphiphilic PAAs. Particle size and morphology of drug-loaded self-assemblies were determined using photon correlation spectroscopy and transmission electron microscopy. Solubilising capacity, in vitro drug release and formulation stability were analysed by HPLC, and in vitro biocompatibility studies (haemolysis and cytotoxicity) were carried out on bovine erythrocytes and Caco-2 cells, respectively. Dansyl10 and Ch5 griseofulvin formulations were administered intra-gastrically to rats, and drug plasma levels were analysed by HPLC. Results: Drug-encapsulated self-assemblies typically have hydrodynamic size of 300–400 nm. Dansyl10 exhibited universal drug solubiliser property and had significantly improved prednisolone, griseofulvin and propofol solubility by 145, 557 and 224-fold, respectively. Fmoc polymers resulted in modest drug solubility improvement. These polymers were non-haemolytic, did not enhance cytotoxicity compared to unmodified PAA, and demonstrated significant increase in griseofulvin plasma concentration compared to griseofulvin in water after oral administration. Conclusions: Ch5 and Dansyl10 showed promising potential as nano-carriers for oral hydrophobic drug delivery

A novel PAA derivative with enhanced drug efficacy in pancreatic cancer cell lines.

Nanoparticles have been shown to be effective drug carriers in cancer therapy. Pancreatic cancer forms dense tumours which are often resistant to drug molecules. In order to overcome such multidrug resistance, new drug entities, novel delivery systems and combination therapy strategies are being explored. In this paper, we report the design and synthesis of a poly(allylamine)-based amphiphile modified with hydrophobic naphthalimido pendant groups. Bisnaphthalimide compounds have been shown to possess anticancer activity. The potential of this polymer to encapsulate, solubilize and enhance drug (5-fluorouricil and bis-(naphthalimidopropyl)-diaminooctane) cytotoxicity in BxPC-3 cells was evaluated. Our studies showed that the insoluble drugs could be formulated up to 4.3 mg mL−1 and 2.4 mg mL−1 inside the amphiphiles, respectively. Additionally, the novel poly(allylamine)-naphthalimide carrier resulted in an amplification of cytotoxic effect with drug treatment after 24 h, and was capable of reduction of 50% cell population at concentrations as low as 3 μg mL−1

Thermally triggered theranostics for pancreatic cancer therapy.

Hybrid iron oxide-gold nanoparticles (HNPs) are capable of drug binding onto their surface with a triggered release at elevated temperatures. The iron oxide core allows for diagnostic imaging whilst heating of the gold shell upon laser irradiation reverses drug binding. This study exploits the reversible binding of novel polyamine based drugs in order to provide specific and effective method for pancreatic cancer treatment. Here we used novel bisnaphthalamido (BNIP) based drug series. Our hybrid nanoparticles (50 nm) were capable of drug loading onto their surface (3:1:0.25, Drug:Fe:Au). By exploiting the surface-to-drug electrostatic interaction of a range of BNIP agents, heat triggered drug release was achieved. 12-fold reduction in IC50 after 24 h in vitro and 5-fold reduction of tumour retardation in vivo compared with free drug in pancreatic models after treatment with the HNP-formulation and laser irradiation. This heat activated system could provide a key platform for future therapy strategies