The design of biomaterials, historically initiated and developed by physicians and engineers, in the last decades has slowly shifted toward a more biochemical based approach. For the replacement, repair and regeneration of tissues scientists are now focusing on materials that stimulate specific biological response at the molecular level. These biomaterials have already shown interesting applications in cell proliferation, differentiation, and extracellular matrix production and organization when the material modifications are designed to elicit specific interactions with cell integrins. In the present work we propose the application of this strategy for the development of blood-compatible materials. We first identified, in the coagulation cascade a key enzyme that constitute a valuable biological target for the development of anti-thrombogenic compounds. Piperazinyl-amide derivatives of N-alfa-(3-trifluoromethyl-benzenesulfonyl)-L-arginine were synthesized as graftable thrombin inhibitors. These inhibitors provided a spacer arm for surface grafting and a fluorine tag for XPS (X-ray photoelectron spectroscopy) detection. The possible disturbance of biological activity due to a variable spacer-arm fixed on the N-4 piperazinyl position was evaluated in vitro against human alfa-thrombin, in silico by molecular modelling and via X-ray diffraction study. Selected inhibitors, having inhibition potency in the mM range, were grafted on polyesters surface via wet chemistry and photochemical activation treatments. Wet chemistry surface grafting was performed by specific hydroxyl chain-ends activation and resulted in bioactive molecules fixation of 20-300pmol/cm2. The photochemical grafting was performed using a molecular clip providing an aromatic azide, for nitrene insertion into a polymer, and an activated ester for grafting of tag compounds. This grafting technique resulted in a dramatic increase in fixed bioactive signals (up to nmol/cm2). The material blood-compatibilization induced by the surface fixation of the inhibitors, was measured by a static blood clot weight measurement test. The wet chemistry grafting technique resulted in moderate blood-compatibilization while by the photochemical grafting method important decrease in surface blood clot formation was observed. In the latter case, the blood response to material contact was found to be strongly affected by the polyester surface photo-degradation induced by the activation treatment.

The aim of the research study was to evaluate the levels of 14C and 3H radionuclides in Hartbeespoort Dam water and to determine if these radionuclides are within regulatory concerns. Water samples from Hartbeespoort Dam were prepared using the Sample Oxidiser Method and measurements of selected radionuclides were done using Liquid Scintillation Counter Quantulus 1220. The results evaluated suggest that water from Hartbeespoort Dam contains levels of 14C and 3H radionuclides that are within regulatory limits. The highest average concentration for 14C measured was 3.77E+01 (+/-2.47E-01) Bq/L, whereas the highest average concentration measured for 3H was 2.74E+01 (+/- 2.30E-01) Bq/L. The observations made regarding the impacts of climate on the 14C radionuclide were that, the concentration levels were higher during winter season when there was a rain than during rainy seasons. Tritium results showed that the climate conditions did not have any significant impacts on the concentration levels. When the concentrations of these radionuclides are above regulatory levels (14C is 100 Bq/L and 3H is10000 Bq/L), their impacts may cause harm to public`s health and the environment. Therefore, Necsa as a nuclear facility owner and National Nuclear Regulator (NNR) as a regulator are responsible for ensuring the public protection from radioactive effluents that contain not just 3H and 14C, but any radionuclide which may cause harm to public`s health. / Environmental Sciences / M. Sc. (Environmental Science)

Les cellules cancéreuses se multiplient de manière incontrôlée, se propagent dans le corps et constituent une menace significative à la santé publique, mettant en évidence la nécessité de traitements universels. Parmi les modalités thérapeutiques complémentaires, la radiothérapie est une des plus couramment utilisée pour éliminer ces cellules. L’introduction récente de la Radiothérapie par Émetteurs Alpha Diffusants (Alpha DaRT), une thérapie innovante contre le cancer, utilise des sources radioactives contenant des atomes de Ra-224 pour améliorer l'efficacité du traitement en exploitant les propriétés radiobiologiques des particules alpha. L'objectif de cette étude est de caractériser le spectre énergétique d’une source Alpha DaRT en distinguant les particules alpha et bêta, et d'évaluer les activités du Ra-224 et de ses descendants à l’aide d’un compteur à scintillation liquide moderne. Grâce à l'utilisation du compteur à scintillation liquide Hidex 600 SLe, équipé de trois PMT, et de la séparation alpha/bêta 2D/3D, il est possible de déterminer les activités absolues des radionucléides. La séparation alpha/bêta 2D/3D surmonte les limitations des études précédentes et offre une représentation visuelle unique des spectres, améliorant ainsi la caractérisation des sources Alpha DaRT. Le suivi sur plusieurs mois d’une source Alpha DaRT, avec la décroissance progressive de son activité, et la mesure par scintillation liquide de son facteur d’efficacité en excluant les traces de contamination au Th-228, supportent la faisabilité d’utiliser cette méthode de mesure sur une longue période. Pour ce faire, le compte des particules alpha et bêta a été séparés par le compteur et classifié en fonction de l’énergie émise des particules. Un programme maison en Python a été développé pour extraire les activités de chaque fille dans la chaîne de désintégration du Ra-224. Un résultat intéressant est qu’en raison de la décroissance rapide (demi-vie de 0,3 μs) du Po-212 (une descendante du Ra-224), une partie de l'activité alpha totale n’est pas mesurée par le compteur. Ce phénomène doit être pris en compte lors de l'évaluation des efficacités de la scintillation liquide pour les mesures quantitatives des sources Alpha DaRT. Les résultats ont ensuite été comparés à aux valeurs attendues de la littérature et des calculs numériques. / Cancer cells multiply uncontrollably, spread throughout the body, and pose a significant public health threat, requiring the need for universal treatments. Among the complementary therapeutic modalities, radiotherapy is one of the most commonly used to eliminate these cells. The recent introduction of Alpha DaRT (Diffusing Alpha-emitters Radiation Therapy), an innovative cancer therapy, involves the use of radioactive sources containing Ra-224 atoms to enhance treatment efficacy by exploiting the radiobiological properties of alpha particles. The aim of this study is to characterize an Alpha DaRT source by distinguishing alpha and beta particles, and to evaluate the activities of Ra-224 and its descendants using a modern liquid scintillation counter. With the use of the Hidex 600 SLe liquid scintillation counter, equipped with three PMTs, and the 2D/3D alpha/beta separation method, it is possible to determine the absolute activities of the radionuclides. The 2D/3D alpha/beta separation method overcomes the limitations of previous studies and provides a unique visual representation of spectra, thereby improving the characterization of Alpha DaRT sources. Monitoring an Alpha DaRT source over several months, with its progressively decaying activity, and measuring its efficiency excluding traces of Th-228 contamination, confirm the feasibility of using this method of measurement over a long period. Counts from alpha and beta particles were separated by the counter and binned according to their emitted energies. An in-house Python program was developed to extract the activities of each daughter in the Ra-224 decay chain. An interesting finding is due to the fast (0.3 μs half-life) decay of Po-212 (Ra-224 daughter), part of the alpha activity is missed by the counter. This phenomenon should be considered when assessing the efficiency of liquid scintillation for quantitative measurements of Alpha DaRT sources. These results were then compared to expected values from literature and numerical calculations.