Direct male-male competition can facilitate invasion of new colour types in Lake Victoria cichlids

The possibility that disruptive sexual selection alone can cause sympatric speciation is currently a subject of much debate. The initial difficulty for new and rare ornament phenotypes to invade a population, and the stabilisation of the resulting polymorphism in trait and preference make this hypothesis problematic. Recent theoretical work indicates that the invasion is facilitated if males with the new phenotype have an initial advantage in male-male competition. We studied a pair of sympatric incipient species of cichlids from Lake Victoria, in which the red (Pundamilia nyererei) and blue males (P. pundamilia) vigorously defend territories. Other studies suggested that red phenotypes may have repeatedly invaded blue populations in independent episodes of speciation. We hypothesised that red coloration confers an advantage in male-male competition, assisting red phenotypes to invade. To test this hypothesis, we staged contests between red and blue males from a population where the phenotypes are interbreeding morphs or incipient species. We staged contests under both white and green light condition. Green light effectively masks the difference between red and blue coloration. Red males dominated blue males under white light, but their competitive advantage was significantly diminished under green light. Contests were shorter when colour differences were visible. Experience of blue males with red males did not affect the outcome of a contest. The advantage of red over blue in combats may assist the red phenotype to invade blue populations. The apparently stable co-existence of red and blue incipient species in many populations of Lake Victoria cichlids is discussed.

The Hamburg-Model of Integrated Care for Patients with Psychosis: Part 2

Objective: Since the beginning of the integrated care model for severely ill patients with psychotic disorders ("Hamburg model") in 2007 different clinical parameters have been consecutively assessed within a naturalistic, observational, prospective study.Methods: Clinical outcome of the 2-year and 4-year follow-ups of n = 158 patients.Results: A significant and ongoing improvement of psychopathology, severity of illness, functional outcome, quality of life and satisfaction with care in this sample of severely ill and merely chronic patients with psychosis was shown. Moreover, medication adherence improved and quality and quantity of outpatient treatment increased.Conclusion: The ongoing psychosocial stabilisation of the patients most likely result from a combination of various factors: continuity of care, multimodal and individualized care, therapeutic specialisation and the multidisciplinary ACT team. Results provide clinical and scientific evidence for future implementations of the integrated care model "Hamburg Model" for the treatment of psychosis.

Analysis of the chlorophyll catabolism pathway in leaves of an introgression senescence mutant of Lolium temulentum

igments, proteins and enzyme activity related to chlorophyll catabolism were analysed in senescing leaves of wild-type (WT) Lolium temulentum and compared with those of an introgression line carrying a mutant gene from stay-green (SG) Festuca pratensis. During senescence of WT leaves chlorophylls a and b were continuously catabolised to colourless products and no other derivatives were observed, whereas in SG leaves there was an accumulation of dephytylated and oxidised catabolites including chlorophyllide a, phaeophorbide a and 132 OH-chlorophyllide a. Dephytylated products were absent from SG leaf tissue senescing under a light-dark cycle. Retention of pigments in SG was accompanied by significant stabilisation of light harvesting chlorophyll-proteins compared with WT, but soluble proteins such as Rubisco were degraded during senescence at a similar rate in the two genotypes. The activity of phaeophorbide a oxygenase measured in SG tissue at 3d was less than 12% of that in WT tissue at the same time-point during senescence and of the same order as that in young pre-senescent WT leaves, indicating that the metabolic lesion in SG concerns a deficiency at the ring-opening step of the catabolic pathway. In senescent L. temulentum tissue two terminal chlorophyll catabolites were identified with chromatographic characteristics that suggest they may represent hitherto undescribed catabolite structures. These data are discussed in relation to current understanding of the genetic and metabolic control of chlorophyll catabolism in leaf senescence.

Synthesis of arbitrary group delay responses with all-pass optical cavities structures

We propose a systematic method for the synthesis of arbitrary group delay responses by using allpass structures of coupled optical cavities. Optimum structure parameters design, in terms of filter order and accuracy, are obtained.

Optimal design of AC EMI filters with damping networks and effect on the systems power factor

The cutoff frequencies of an EMI filter are normally given by the noise attenuation requirements the filter has to fulfill. In order to select the component values of the filter elements, i.e. inductances and capacitances, an additional design criterium is needed. In this paper the effect of the EMI filter input and output impedances are considered. The input impedance influences the filters effect on the system displacement power factor and the output impedance plays a key role in the system stability. The effect of filter element values, the number of filter stages as well as additional damping networks are considered and a design procedure is provided. For this analysis a two-port description of the input filters employing ABCD-parameters is used.

Microstructural and mechanical characterization of tungsten based materials for fusion reactors

El wolframio (W) y sus aleaciones se consideran los mejores candidatos para la construcción del divertor en la nueva generación de reactores de fusión nuclear. Este componente va a recibir las cargas térmicas más elevadas durante el funcionamiento del reactor ya que estará en contacto directo con el plasma. En los últimos años, después de un profundo análisis y siguiendo una estrategia de reducción de costes, la Organización de ITER tomó la decisión de construir el divertor integramente de wolframio desde el principio. Por ello, el wolframio no sólo actuará como material en contacto con el plasma (PFM), sino que también tendría aplicaciones estructurales. El wolframio, debido a sus excelentes propiedades termo-físicas, cumple todos los requerimientos para ser utilizado como PFM, sin embargo, su inherente fragilidad pone en peligro su uso estructural. Por tanto, uno de los principales objetivos de esta tesis es encontrar una aleación de wolframio con menor fragilidad. Durante éste trabajo, se realizó la caracterización microstructural y mecánica de diferentes materiales basados en wolframio. Sin embargo, ésta tarea es un reto debido a la pequeña cantidad de material suministrado, su reducido tamaño de grano y fragilidad. Por ello, para una correcta medida de todas las propiedades físicas y mecánicas se utilizaron diversas técnicas experimentales. Algunas de ellas se emplean habitualmente como la nanoindentación o los ensayos de flexión en tres puntos (TPB). Sin embargo, otras fueron especificamente desarrolladas e implementadas durante el desarrollo de esta tesis como es el caso de la medida real de la tenacidad de fractura en los materiales masivos, o de las medidas in situ de la tenacidad de fractura en las láminas delgadas de wolframio. Diversas composiciones de aleaciones de wolframio masivas (W-1% Y2O3, W-2% V-0.5% Y2O3, W-4% V-0.5% Y2O3, W-2% Ti-1% La2O3 y W-4% Ti-1% La2O3) se han estudiado y comparado con un wolframio puro producido en las mismas condiciones. Estas aleaciones, producidas por ruta pulvimetalúrgica de aleado mecánico (MA) y compactación isostática en caliente (HIP), fueron microstructural y mecánicamente caracterizadas desde 77 hasta 1473 K en aire y en alto vacío. Entre otras propiedades físicas y mecánicas se midieron la dureza, el módulo elástico, la resistencia a flexión y la tenacidad de fractura para todas las aleaciones. Finalmente se analizaron las superficies de fractura después de los ensayos de TPB para relacionar los micromecanismos de fallo con el comportamiento macroscópico a rotura. Los resultados obtenidos mostraron un comportamiento mecánico frágil en casi todo el intervalo de temperaturas y para casi todas las aleaciones sin mejoría de la temperatura de transición dúctil-frágil (DBTT). Con el fin de encontrar un material base wolframio con una DBTT más baja se realizó también un estudio, aún preliminar, de láminas delgadas de wolframio puro y wolframio dopado con 0.005wt.% potasio (K). Éstas láminas fueron fabricadas industrialmente mediante sinterizado y laminación en caliente y en frío y se sometieron posteriormente a un tratamiento térmico de recocido desde 1073 hasta 2673 K. Se ha analizado la evolución de su microestructura y las propiedades mecánicas al aumentar la temperatura de recocido. Los resultados mostraron la estabilización de los granos de wolframio con el incremento de la temperatura de recocido en las láminas delgadas de wolframio dopado con potasio. Sin embargo, es necesario realizar estudios adicionales para entender mejor la microstructura y algunas propiedades mecánicas de estos materiales, como la tenacidad de fractura. Tungsten (W) and tungsten-based alloys are considered to be the best candidate materials for fabricating the divertor in the next-generation nuclear fusion reactors. This component will experience the highest thermal loads during the operation of a reactor since it directly faces the plasma. In recent years, after thorough analysis that followed a strategy of cost reduction, the ITER Organization decided to built a full-tunsgten divertor before the first nuclear campaigns. Therefore, tungsten will be used not only as a plasma-facing material (PFM) but also in structural applications. Tungsten, due to its the excellent thermo-physical properties fulfils the requirements of a PFM, however, its use in structural applications is compromised due to its inherent brittleness. One of the objectives of this phD thesis is therefore, to find a material with improved brittleness behaviour. The microstructural and mechanical characterisation of different tunsgten-based materials was performed. However, this is a challenging task because of the reduced laboratory-scale size of the specimens provided, their _ne microstructure and their brittleness. Consequently, many techniques are required to ensure an accurate measurement of all the mechanical and physical properties. Some of the applied methods have been widely used such as nanoindentation or three-point bending (TPB) tests. However, other methods were specifically developed and implemented during this work such as the measurement of the real fracture toughness of bulk-tunsgten alloys or the in situ fracture toughness measurements of very thin tungsten foils. Bulk-tunsgten materials with different compositions (W-1% Y2O3, W-2% V- 0.5% Y2O3, W-4% V-0.5% Y2O3, W-2% Ti-1% La2O3 and W-4% Ti-1% La2O3) were studied and compared with pure tungsten processed under the same conditions. These alloys, produced by a powder metallurgical route of mechanical alloying (MA) and hot isostatic pressing (HIP), were microstructural and mechanically characterised from 77 to 1473 K in air and under high vacuum conditions. Hardness, elastic modulus, flexural strength and fracture toughness for all of the alloys were measured in addition to other physical and mechanical properties. Finally, the fracture surfaces after the TPB tests were analysed to correlate the micromechanisms of failure with the macroscopic behaviour. The results reveal brittle mechanical behaviour in almost the entire temperature range for the alloys and micromechanisms of failure with no improvement in the ductile-brittle transition temperature (DBTT). To continue the search of a tungsten material with lowered DBTT, a preliminary study of pure tunsgten and 0.005 wt.% potassium (K)-doped tungsten foils was also performed. These foils were industrially produced by sintering and hot and cold rolling. After that, they were annealed from 1073 to 2673 K to analyse the evolution of the microstructural and mechanical properties with increasing annealing temperature. The results revealed the stabilisation of the tungsten grains with increasing annealing temperature in the potassium-doped tungsten foil. However, additional studies need to be performed to gain a better understanding of the microstructure and mechanical properties of these materials such as fracture toughness.

Efficient high-resolution genetic mapping of mouse interspersed repetitive sequence PCR products, toward integrated genetic and physical mapping of the mouse genome.

The ability to carry out high-resolution genetic mapping at high throughput in the mouse is a critical rate-limiting step in the generation of genetically anchored contigs in physical mapping projects and the mapping of genetic loci for complex traits. To address this need, we have developed an efficient, high-resolution, large-scale genome mapping system. This system is based on the identification of polymorphic DNA sites between mouse strains by using interspersed repetitive sequence (IRS) PCR. Individual cloned IRS PCR products are hybridized to a DNA array of IRS PCR products derived from the DNA of individual mice segregating DNA sequences from the two parent strains. Since gel electrophoresis is not required, large numbers of samples can be genotyped in parallel. By using this approach, we have mapped > 450 polymorphic probes with filters containing the DNA of up to 517 backcross mice, potentially allowing resolution of 0.14 centimorgan. This approach also carries the potential for a high degree of efficiency in the integration of physical and genetic maps, since pooled DNAs representing libraries of yeast artificial chromosomes or other physical representations of the mouse genome can be addressed by hybridization of filter representations of the IRS PCR products of such libraries.

Le role des politiques monétaires et la convergence macroeconomique sur le développement des systèmes financiers dans les pays du sud de la Méditerranée. = The role of monetary policies and macroeconomic convergence in the development of financial systems in south Mediterranean countries. MEDPRO Technical Report No. 12/April 2012

This MEDPRO Technical Report shows that the monetary and exchange rate policies conducted by central banks in the South Mediterranean region display apparent homogeneity in their operational frameworks, albeit with some specificities and differing degrees of advancement. While central banks state that price stability is their ultimate objective, failures to control interest rates as operational objectives of monetary policy result in monetary authorities resorting to quantitative approaches to monetary policy, meaning that monetary aggregates and credit targets are being used as intermediate targets of monetary policy. An econometric exercise limited to Maghreb countries (Algeria, Morocco, and Tunisia) has been conducted to analyse the potential scenarios of convergence and monetary policy coordination. Given the high structural heterogeneity and the slow pace of real convergence due to weak commercial integration in the Maghreb, results nevertheless show alternative dynamics in the integration of effective nominal exchange rates, as well as a complete convergence dynamic in exchange rate policies. Partial convergence of monetary policies regarding the stabilisation of inflation rates remains an open option for a transitional phase where financial integration is low.

Blur adaptation explained by a norm-based model of contrast adaptation

Adapting to blurred images makes in-focus images look too sharp, and vice-versa (Webster et al, 2002 Nature Neuroscience 5 839 - 840). We asked how such blur adaptation is related to contrast adaptation. Georgeson (1985 Spatial Vision 1 103 - 112) found that grating contrast adaptation followed a subtractive rule: perceived (matched) contrast of a grating was fairly well predicted by subtracting some fraction k(~0.3) of the adapting contrast from the test contrast. Here we apply that rule to the responses of a set of spatial filters at different scales and orientations. Blur is encoded by the pattern of filter response magnitudes over scale. We tested two versions - the 'norm model' and 'fatigue model' - against blur-matching data obtained after adaptation to sharpened, in-focus or blurred images. In the fatigue model, filter responses are simply reduced by exposure to the adapter. In the norm model, (a) the visual system is pre-adapted to a focused world and (b) discrepancy between observed and expected responses to the experimental adapter leads to additional reduction (or enhancement) of filter responses during experimental adaptation. The two models are closely related, but only the norm model gave a satisfactory account of results across the four experiments analysed, with one free parameter k. This model implies that the visual system is pre-adapted to focused images, that adapting to in-focus or blank images produces no change in adaptation, and that adapting to sharpened or blurred images changes the state of adaptation, leading to changes in perceived blur or sharpness.

The antioxidant role of vitamin E in polyolefins

Polymers are subject to oxidation throughout their lifecycle. Antioxidants are generally incorporated in polymers to inhibit or minimise oxidative degradation. Hindered phenolic antioxidants are important stabilisers for polyolefins. However, hindered phenols undergo chemical transformations while performing their antioxidant function during processing and fabrication. In addition, antioxidants are subject to loss from polymers during processing, or subsequently in-service. Migration of antioxidants is a major concern in applications involving polymers in direct contact with food and human environment. This concern is compounded by the realisation that very little is known about the nature and the migration behaviour of antioxidant transformation products. In this work, the antioxidant role of the biological antioxidant -tocopherol (Vitamin E) , which is structurally similar to many synthetic hindered phenols, is investigated in low density polyethylene (LDPE) and polypropylene (PP). The melt stabilising effectiveness of -tocopherol (Toc) was found to be very high, higher than that of commercial hindered phenol antioxidants, such as Irganox 1076 (Irg 1076) and Irganox 1010 (Irg 1010), after multiple extrusions, especially at very low concentrations. The high antioxidant activity of Toc was shown to be due, at least in part, to the formation of transformation products during processing. The main products formed are stereoisomers of dimers and trimers, as well as aldehydes and a quinone - the relative concentration of each was shown to depend on the processing severity, the initial antioxidant concentration and oxygen availability. These transformation products are shown to impart better, similar or lower melt stability to the polymer than the parent antioxidant. The nature of the products formed from Toc during processing was compared with those formed during processing of Irg 1076 and Irg 1010 with LDPE and a mechanism for the melt stabilisation of Toc was proposed and compared with the stabilisation mechanisms of the synthetic antioxidants Irg 1076 and Irg 1010.

The separation of secondary oil-water dispersions in particulate beds

The literature relating to haze formation, methods of separation, coalescence mechanisms, and models by which droplets <100 μm are collected, coalesced and transferred, have been reviewed with particular reference to particulate bed coalescers. The separation of secondary oil-water dispersions was studied experimentally using packed beds of monosized glass ballotini particles. The variables investigated were superficial velocity, bed depth, particle size, and the phase ratio and drop size distribution of inlet secondary dispersion. A modified pump loop was used to generate secondary dispersions of toluene or Clairsol 350 in water with phase ratios between 0.5-6.0 v/v%.Inlet drop size distributions were determined using a Malvern Particle Size Analyser;effluent, coalesced droplets were sized by photography. Single phase flow pressure drop data were correlated by means of a Carman-Kozeny type equation. Correlations were obtained relating single and two phase pressure drops, as (ΔP2/μc)/ΔP1/μd) = kp Ua Lb dcc dpd Cine A flow equation was derived to correlate the two phase pressure drop data as, ΔP2/(ρcU2) = 8.64*107 [dc/D]-0.27 [L/D]0.71 [dp/D]-0.17 [NRe]1.5 [e1]-0.14 [Cin]0.26  In a comparison between functions to characterise the inlet drop size distributions a modification of the Weibull function provided the best fit of experimental data. The general mean drop diameter was correlated by: q_p q_p p_q /β      Γ ((q-3/β) +1) d qp = d fr  .α        Γ ((P-3/β +1 The measured and predicted mean inlet drop diameters agreed within ±15%. Secondary dispersion separation depends largely upon drop capture within a bed. A theoretical analysis of drop capture mechanisms in this work indicated that indirect interception and London-van der Waal's mechanisms predominate. Mathematical models of dispersed phase concentration m the bed were developed by considering drop motion to be analogous to molecular diffusion.The number of possible channels in a bed was predicted from a model in which the pores comprised randomly-interconnected passage-ways between adjacent packing elements and axial flow occured in cylinders on an equilateral triangular pitch. An expression was derived for length of service channels in a queuing system leading to the prediction of filter coefficients. The insight provided into the mechanisms of drop collection and travel, and the correlations of operating parameters, should assist design of industrial particulate bed coalescers.

The microbial ecology of cow slurry in vermiculture beds

The suitability of cow slurry as a substrate for vermicomposting by Eisenia fetida was investigated. Particular attention was given to the effects of the earthworm on the decomposition and stabilisation of the slurry; and to the interactions between E. fetida and the microflora of the substrate. Assessment of the chemical and microbiological changes in cow slurry stored under forced aeration, and subsequently in shallow trays, showed that neither method was suitable for the treatment of slurry. A comparison of two methods of vermicomposting showed that top-feeding of slurry was more efficient in promoting earthworm growth and cocoon production than the mixing of slurry with solid materials. Management practices were found to have an important influence on the efficiency of the process. An investigation o:f the effect of E. fetida. on the decomposition of slurry indicated that the presence of this earthworm enhanced the stabilisation of the substrate and increased the plant-available nitrogen content. Specific nutritional interactions were observed between E. fetida and micro-organisms in sand/cellulose microcosms. The earthworms were found to be feeding directly upon the cells of certain micro-organisms. Other species were found to be toxic to E. fetida.. A technique was developed :for the production of axenic E. fetida., and the use of such earthworms in :feeding experiments confirmed the importance of some micro-organisms in earthworm nutrition. The seeding of vermiculture beds with one such micro-organism stimulated earthworm growth and consumption of the substrate. Vermicomposted mixtures of cow slurry and spent mushroom compost were shown to have potential application as casing materials in mushroom cultivation. The findings of this study indicate the suitability of vermicomposting as a method for the stabilisation of intensively-produced cow slurry, and give some indication of the importance of micro-organisms in the nutrition of E. fetida.

Synthesis of triplex-forming oligonucleotide conjugates of the anticancer drug temodal

Covalent attachment of the anticancer drugs temozolomide (Temodal) and mitozolomide to triplex-forming oligonucleotides (TFOs) is a potential way of targeting these alkylating agents to specific gene sequences to maximise site-selectivity. In this work, polypyrimidine TFO conjugates of both drugs were synthesised and targeted to duplex DNA in an attempt to effect site-specific alkylation of guanine residues. Concurrently, in an attempt to enhance the triple helix stability of TFOs at neutral pH, the thermal stabilities of triplexes formed from TFOs containing isoguanine, 2-O-benzyl- and 2-O-allyl-adenine were evaluated. A novel cleavage and deprotection procedure was developed which allowed for the solid phase synthesis of the base-sensitive TFO-drug conjugates using a recently developed silyl-linked controlled pore glass (SLCPG) support. Covalent attachment of either temozolomide or mitozolomide at the 5'-end of TFO conjugates caused no destabilisation of the triplexes studied. The synthesis of a phosphoramidite derivative of mitozolomide enabled direct incorporation of this reagent into a model sequence during DNA synthesis. After cleavage and deprotection of the TFO-drug conjugate, the 5'-end mitozolomide residue was found to have decomposed presumably as a result of ring-opening of the tetrazinone ring. The base-sensitive antibacterial and antitumour agent, metronidazole, was also successfully incorporated at the 5'-end of the oligonucleotide d(T8) using conventional methods. Two C2-substituted derivatives of 2'-deoxyadenosine containing 2-O-benzyl and 2-O-allyl groups were synthesised. Hydrogenolysis of the 2-O-benzyl analogue provided a useful route, amenable to scale-up, for the synthesis of the rare nucleoside 2'-deoxyisoguanosine (isoG). Both the 2-O-allyl and 2-O-benzyl derivatives were incorporated into TFO sequences using phosphoramidite methodology. Thermal melting experiments showed that the 2-O-allyl and 2-O-benzyl groups caused marked destabilisation of the triple helices studied, in contrast to hexose-DNA duplexes, where aralkyl substituents caused significant stabilisation of duplexes. TFOs containing isoG were synthesised by Pd(O)-catalysed deallylation of 2-0-allyl adenine residues. These sequences containing isoG, in its N3- or 02-H tautomeric form, formed triple helices which were equally as stable as those containing adenine.

Prodrugs of antiviral phosphonates

Phosphonoformate and phosphonoacetate are effective antiviral agents, however they are charged at physiological pH and as such penetration into cells and diffusion across the blood-brain bamer is limited. In an attempt to increase the lipophilicity and improve the transport properties of these molecules, prodrugs were synthesised and their stabilities and reconversion to the parent compound subsequently investigated by the techniques of 31P nuclear magnetic resonance spectroscopy and high performance liquid Chromatography. A series of 4-substituted dibenzyl (methoxycarbonyl)phosphonates were prepared and found to be hydrolytically unstable giving predominantly the diesters, benzyl (methoxycarbonyl)phosphonates. This instability arose from the electron-withdrawing effect of the carbonyl group promoting nucleophilic attack at phosphorus. It was possible to influence the mechanism and, to some extent, the rate of hydrolysis of the phosphonoformate triesters to the diesters by varying the electronic nature of the substituent in the 4-position of the aromatic ring. Strongly electron-withdrawing groups increased the sensitivity of phosphorus to nucleophilic attack, thus promoting P-O .bond cleavage and rapid hydrolysis. Conversely, weakly electron-withdrawing substituents encouraged C-O bond fission, presumably through resonance stabilisation of the benzyl carbonium ion. The loss of the protecting group on phosphorus was in competition with nucleophilic attack at the carbonyl group, resulting in P-C bond cleavage with dibenzyl phosphite formation. The high instability and P-C bond fission make triesters unsuitable prodrug forms of phosphonoformate. A range of chemically stable triesters of phosphonoacetate were synthesised and their bioactivation investigated. Di(benzoyloxymethyl) (methoxycarbonylmethyl)phosphonates degraded to the relevant benzoyloxymethyl (methoxycarbonylmethyl)phosphonate in the presence of esterase. The enzymatic activation was restricted to the removal of only one protecting group from phosphorus, most likely due to the close proximity of the benzoyloxy ester function to the anionic charge on the diester. However, in similar systems di(4-alkanoyloxybenzyl) (methoxycarbonylmethyl)phosphonates degraded in the presence of esterase with the loss of both protecting groups on phosphorus to give the monoester, (methoxycarbonylmethyl)phosphonate, via the intermediary of the unstable 4-hydroxy benzyl esters. The methoxycarbonyl function remained intact. The rate of enzymatic hydrolysis and subsequent removal of the protecting groups on phosphorus was dependent on the nature of the alkanoyl group and was most rapid for the 4-nbutanoyloxybenzyl and 4-iso-butanoyloxybenzyl esters of phosphonoacetate. This provides a strategy for the design of a prodrug with sufficient stability in plasma to reach the central nervous system in high concentration, wherein rapid metabolism to the active drug by brain-associated enzymes occurs.

Local and systemic delivery of a novel group of inhibitors of transglutaminase enzyme: A potential approach for treating of catheter-related complications and liver fibrosis

The present thesis investigates targeted (locally and systemically) delivery of a novel group of inhibitors of enzyme transglutaminases (TGs). TGs are a widely distributed group of enzymes that catalyse the formation of isopeptide bonds between the y-carboxamide group of protein-bound glutamines and the a-amino group of protein-bound lysines or polyamines. The first group of the novel inhibitors tested were the tluorescently labelled inhibitors of Factor XIIIa (FXIIIa). These small, non-toxic inhibitors have the potential to prevent stabilisation of thrombi by FXIIIa and consequently increase the natural rate of thrombolysis, in addition it reduces staphylococcal colonisation of catheters by inhibiting their FXIIIa¬mediated cross-linking to blood clot proteins on the central venous catheter (CVCs) surface. The aim of this work was to incorporate the FXIIIa inhibitor either within coating of polyurethane (PU) catheters or to integrate it into silicone catheters, so as to reduce the incidence of thrombotic occlusion and associated bacterial infection in CVCs. The initial work focused on the incorporation of FXIIIa inhibitors within polymeric coatings of PU catheters. After defining the key characteristics desired for an effective polymeric-coating, polyvinylpyrrolidone (PVP), poly(lactic-co-glycolic acid) (PLGA) or their combination were studies as polymers of choice for coating of the catheters_ The coating was conducted by dip-coating method in a polymer solution containing the inhibitor. Upon incubation of the inhibitor-and polymer-coated strips in buffer, PVP was dissolved instantly, generating fast and significant drug release, whilst PLGA did not dissolve, yielding a slow and an insufficient amount of drug release. Nevertheless, the drug release profile was enhanced upon employing a blend solution of PVP and PLGA. The second part of the study was to incorporate the FXIIIa inhibitor into a silicone elastomer; results demonstrated that FXIIIa inhibitor can be incorporated and released from silicone by using citric acid (CA) and sodium bicarbonate (SB) as additives and the drug release rate can be controlled by the amount of incorporated additives in the silicone matrix. Furthermore, it was deemed that the inhibitor was still biologically active subsequent to being released from the silicone elastomer strips. Morphological analysis confirmed the formation of channels and cracks inside the specimens upon the addition of CA and SB. Nevertheless, the tensile strength, in addition to Young's modulus of silicone elastomer strips, decreased constantly with an increasing amount of amalgamated CA/ SB in the formulations. According to our results, incorporation of FXIIIa inhibitor into catheters and other medical implant devices could offer new perspectives in preventing bio-material associated infections and thrombosis. The use of tissue transglutaminase (T02) inhibitor for treating of liver fibrosis was also investigated. Liver fibrosis is characterized by increased synthesis and decreased degradation of the extracellular matrix (ECM). Transglutaminase-mediated covalent cross-linking is involved in the stabilization of ECM in human liver fibrosis. Thus, TG2 inhibitors may be used to counteract the decreased degradation of the ECM. The potential of a liposome based drug delivery system for site specific delivery of the fluorescent TG2 inhibitor into the liver was investigated; results indicated that the TG2 inhibitor can be successfully integrated into liposomes and delivered to the liver, therefore demonstrating that liposomes can be employed for site-specific delivery of TG2 inhibitors into the liver and TG2 inhibitor incorporating liposomes could offer a new approach in treating liver fibrosis and its end stage disease cirrhosis.