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A new type of biocomposites – the polyaniline - deoxynucleic acid (PAN / DNA) and the poly-(o-phenylenediamine)-DNA (POPD-DNA) complexes can be synthesized electrochemically in acidic media in the potential range of –0.2V to 0.8 V vs. Ag/AgCl reference electrode, respectively. The ultraviolet-visible (UV-Vis) spectroscopy, the alternating-current impedance, the electrochemical quartz crystal microbalance (EQCM) and the voltammetry techniques have been used to characterize the above system. Results revealed that during the surface composite formation, DNA is incorporated into the polyaniline and the poly-o-phenylenediamine) networks, respectively. DNA also serves as a template to guide the surface synthesis of the oxidative polymerization. It provides a lower local pH environment that favors the protonation of aniline monomers, and subsequently minimizes the branching of the polymer network.

An unexpected biological removal of phosphorous in IVL Hammarby Sjöstadsverket pilot membrane bioreactor (MBR) wastewater treatment process was investigated by three distinct methods. a) Investigation and quantification of the biological phosphorous uptake (bio-P) capacity by phosphate release tests (PRT), b) validation of bio-P occurrence by granular polyphosphate (poly-P) staining and microscopy and c) metagenomic community structure analysis to map the sludge habitat. Validation of phosphate accumulating organisms (PAO) was successfully performed using the Neisser Methylene Blue Metachromatic staining protocol. Quantification by a novel staining protocol gave indications of the relative activity of bio-P in the bioreactor process line. The bio-P activity by PRT showed high capacity of phosphate accumulation in the treatment process. Furthermore, the use of ethylenediaminetetraacetic acid (EDTA) to induce stressful conditions was successfully shown to increase the release rate and depletion of intracellular poly-P of PAO. Finally, the impact of temperature dependency in PRT was investigated.A metagenomic community structure analysis by 16S rRNA successfully prepared 28 samples for sequencing and analysis. The project has successfully validated and quantified bio-P with an improved methodology as a foundation for upcoming studies of the treatment process. / En oväntad biologisk fosforrening (bio-P) i IVL Hammarby Sjöstadsverkets membranreaktorpilot undersöktes med tre distinkta metoder. Kvantifiering av det biologiska fosforupptaget undersöktes med fosforsläppstest (PRT). Validering av förekomsten av fosfatackumulerande organismer (PAO) via infärgning av polyfosfatgranuler med Neissers protokoll för infärgning med metylenblå. Ett nytt protokoll för kvantifiering av polyfosfatgranulkluster gav indikationer på relativ aktivitet av bio-P i reningsprocessens bioreaktorer. Bio-P aktiviteten som uppmättes med PRT visade på hög kapacitet av biologisk fosforackumulation. Vidare visades framgångsrikt att stresspåslag av PAO med etylendiamintetraättiksyra (EDTA) ökade fosfatsläppshastigheten och uttömningen av intracellulär poly-P. Slutligen undersöktes temperaturberoendet i PRT. En 16S rRNA metagenomikstudie gav 28 st prover redo att sekvensieras och analyseras. Projektet har framgångsrikt validerat och kvantifierat bio-P med en utvecklad metodologi som kan utgöra grunden för kommande studier vid reningsverket.

L'exposition aux rayons ultraviolets (UV) est essentielle à la vie et bénéfique pour la santé humaine. Cependant, la surexposition aux UV solaires, en particulier aux UVB, rayons les plus énergétiques atteignant la surface terrestre, peut entrainer des cancers de la peau chez l'être-humain comme les cancers de la peau de type non-mélanome (NMSC). La capacité des UVB à initier des NMSC provient principalement de leurs habilités à causer des dommages directs à l'ADN, tels que les dimères cyclobutyliques de pyrimidine (CPD) et les produits pyrimidine-pyrimidone (6-4PP), qui sont pris en charge par le mécanisme de réparation par excision de nucléotide (NER). L'incidence croissante de NMSC chez les patients déficients pour l'une des protéines de la NER souligne l'importance d'un processus fonctionnel. Par conséquent, une meilleure compréhension des mécanismes moléculaires de la NER permettrait de mettre en évidence de nouvelles cibles thérapeutiques pour la prévention ou le traitement des cancers de la peau. L'une des premières réponses cellulaires aux dommages CPD/6-4PP induits par UVB dans la peau des mammifères est l'activation de l'enzyme nucléaire poly(ADP-ribose) polymérase-1 (PARP1) qui catalyse la formation de polymères d'ADP-ribose. Les précédents travaux de notre laboratoire et d'autres équipes ont démontré que PARP1 et son activité enzymatique facilitent la NER en collaboration avec la protéine UV-damaged DNA binding protein 2 (DDB2), qui va aussi s'accumuler rapidement aux sites CPD/6-4PP pendant la phase de reconnaissance des dommages à l'ADN de la NER. Cependant, plusieurs aspects des interactions de PARP1 avec DDB2 et avec les dommages directs à l'ADN sont inconnus. Ainsi, le premier objectif de mon projet de doctorat a été de caractériser précisément la nature de la liaison de PARP1 aux dommages CPD/6-4PP induits par UV vis-à-vis la protéine DDB2. Mes recherches ont mis en évidence l'empreinte asymétrique formée par PARP1 de -12 à +9 nucléotides de chaque côté des dommages CPD/6-4PP en présence ou en absence de DDB2. Nous avons également démontré que PARP1 augmente l'affinité de DDB2 pour les dommages CPD/6-4PP. De plus, les résultats de notre étude indiquent un rôle de PARP1 indépendant de DDB2 pendant la phase de reconnaissance des dommages à l'ADN. Cibler PARP1 et son rôle dans les voies de réparation des dommages à l'ADN est l'une des stratégies les plus efficaces développées ces dernières années pour le traitement des cancers des ovaires et du sein. L'application translationnelle de mon projet de doctorat a alors été de comprendre le rôle de PARP1 dans la NER dans le contexte des NMSC. À cet égard, nous avons développé un modèle PARP1-KO dans la lignée de souris SKH-1, qui est un modèle largement adopté pour étudier les NMSC induits par UVB. Puisque les souris SKH-1 développent principalement des carcinomes spinocellulaires (CSC) cutanés après une exposition chronique aux UVB, notre étude rapporte le rôle de PARP1 dans le développement des CSC. En utilisant les souris nouvellement créées SKH-1 PARP1-KO et les souris SKH-1 PARP1-WT avec ou sans application topique d'inhibiteurs de PARP, nous avons mis en évidence que l'absence de PARP1 ou de son activité dans la peau des souris SKH-1 mâles et femelles réduit significativement le fardeau tumoral des CSC et prolonge la période de latence du développement tumoral. L'étude hebdomadaire de l'apparition et de la croissance de tumeurs tout au long du protocole révèlent aussi que cibler PARP1 est très efficace pour ralentir, à l'étape pré-maligne, le développement de CSC. Nos résultats sont surprenants à la lumière des propriétés onco-suppressives rapportées de PARP1 et de son activité catalytique dans des cas de cancérogenèse induits par des dommages à l'ADN causés par des agents alkylants, ainsi que de la susceptibilité croissante des souris knock-out pour d'autres protéines de la NER à développer des CSC induits par UVB. Le rôle de PARP1 dans les mécanismes cellulaires induits par UVB autres que la NER, comme la mort cellulaire et les modulations immunes, pourrait expliquer nos observations. Alors que d'autres analyses sont nécessaires pour comprendre le rôle de PARP1 dans ces mécanismes, notre étude met en avant l'utilisation potentielle d'inhibiteurs de PARP comme nouvel agent chimiopréventif contre les CSC induits par UVB. / The exposure to solar ultraviolet radiation (UV) is essential to life and beneficial to human health. However, an overexposure to terrestrial solar UV, especially its most energetic component UVB, can cause skin cancers including the non-melanoma skin cancers (NMSC) in humans. The NMSC initiating properties of UVB arise predominantly from their ability to cause direct DNA damage such as cyclobutane pyrimidine dimers (CPD) and 6-4photoproducts (6-4PP), which are repaired via nucleotide excision repair (NER) pathway. The increased incidence of NMSC in patients with hereditary defects in NER pathway proteins underscores the importance of efficient NER in humans. Therefore, detailed understanding of the molecular operation of NER pathway can provide novel therapeutic targets for the prevention or treatment of skin cancers. One of the earliest responses of the mammalian skin cells to UVB-induced CPD or 6-4PP is the activation of the nuclear enzyme poly(ADP-ribose) polymerase-1 (PARP1), which catalyzes the formation of polymers of ADP-ribose (PAR). The previous work from other teams and our laboratory have shown that PARP1 and its enzymatic activity facilitate NER in collaboration with UV-damaged DNA binding protein 2 (DDB2), which also rapidly accumulates at the CPD/6-4PP site during the DNA damage recognition stage of NER. However, many aspects of interaction of PARP1 with DDB2 and direct DNA damage are not understood. Therefore, the first aim of my doctoral project was to characterize the precise nature of binding of PARP1 vis-à-vis DDB2 at UV-induced CPD/6-4PP. My doctoral research demonstrates that PARP1 casts asymmetric footprint from −12 to +9 nucleotides on either side of the CPD/6-4PP in presence or absence of DDB2. We also demonstrated that PARP1 facilitates the binding of DDB2 to CPD/6-4PP. Moreover, our study reports DDB2-independent role of PARP1 during the DNA damage recognition phase in NER. Targeting the role of PARP1 in DNA strand break repair pathways has emerged as one of the successful strategies for the treatment of ovarian and breast cancers in last decade. Consequently, the ultimate translational goal of my doctoral project was to understand the implication of NER facilitating role of PARP1 in NMSC. In this regard, we first developed a PARP1-KO model in the albino hairless SKH-1 mouse strain, which is a widely adopted mouse model to study UVB-induced NMSC. Since SKH-1 mice mainly develop cutaneous squamous cell carcinoma (SCC) upon chronic UVB-exposure, our present study reports the role of PARP1 in development of SCC. Using the newly developed PARP1-KO and PARP1-WT SKH-1 mice with or without topical application of PARP inhibitor, we report that the absence of PARP1 or its activity in skin of both male and female SKH-1 mice significantly reduces the SCC tumor burden and prolongs the tumor latency period. The analyses of appearance and growth of individual tumors on a weekly basis during this protocol also revealed that targeting of PARP1 was most effective in suppressing the premalignant stage of the SCC development. Our results are surprising in light of the reported onco-suppressive property of PARP1 and its catalytic activity in alkylating DNA damage-induced tumorigenesis and the increased susceptibility of other NER protein knock-out mice to UVB-induced SCC. We reason that the roles of PARP1 in UVB-induced cellular processes other than NER, such as cell death and immune modulations, can account for our observation. While further studies are required to understand these roles of PARP1 in UVB-induced cellular processes, our study underscores the potential for use of PARP inhibitors as a novel chemopreventive agents against UVB-induced SCC.

Following the successful launch of CP3 and CP4, the PolySat team noticed an unreliable uplink to both satellites. A significant problem with the PolySat COMM system is poor receive sensitivity of the communications system. Efforts have been made to improve the uplink margin, but without proper characterization of the receiver sensitivity, the problem cannot be fully addressed. By developing an accurate method of measuring receive sensitivity, a methodical approach can be used to properly diagnose the communication system and link budget. Two revisions of the PolySat COMM system will be measured and compared. An in-depth study of the PolySat COMM system will be performed, providing an interesting look at possible causes of the inconsistent uplink and methods of improving the COMM system. For future bus development, this test setup can be used to accurately measure the receive sensitivity.

Yes / Highly-oriented poly(l-lactic acid) (PLLA) with fibrillar structure and micro-grooves was fabricated through solid hot drawing technology for further improving the mechanical properties and blood biocompatibility of PLLA as blood-contacting medical devices. In order to enhance the melt strength and thus obtain high orientation degree, PLLA was first chain extended with ethylene glycol diglycidyl ether (EGDE). The extending degree as high as 25.79 mol% can be obtained at 0.7 wt% EGDE content. The complex viscosity, storage and viscous modulus for chain extended PLLA were improved resulting from the enhancement of molecular entanglement, and consequently higher draw ratio can be achieved during the subsequent hot stretching. The tensile strength and modulus of PLLA were improved dramatically by stretching. The stress-induced crystallization of PLLA occurred during drawing. The interfacial tension (γs·blood) between PLLA surface and blood decreased by chain extension and molecular orientation, indicating the weakened interaction between bioactive substance in the blood and the surface of PLLA. Modification and orientation could significantly enhance the blood compatibility of PLLA by prolonging clotting time and decreasing hemolysis ratio, protein adsorption and platelet activation. The bionic character of oriented PLLA and its anti-coagulation mechanism were tried to be explored. / This research was supported by National Natural Science Foundation of China (Grant No. 51303109)

This research studied Ho166/PLLA microspheres, a promising treatment for tumours in the liver. The Ho166 is generated through a neutron capture reaction during irradiation in a nuclear reactor. Previous work has found that neutron-irradiation in-core causes damage to microspheres and causes additional degradation to progress once suspended in media. The cause of this damage was not well understood and is the focus of this research. This research studied factors present in-core such as heat, gamma radiation, and impacts of lead shielding, for their impact on microsphere quality. Additionally, this research looked at the potential of reactive oxygen species causing damage once microspheres are suspended in liquid. Thresholds for damage were identified to correlate with the glass transition temperature of poly- l-lactic acid. Exposure to gamma radiation induces heating, as well as structural changes to the polymer which shifts the temperature where the glass transition occurs. Damage formed from gamma radiation, independent of other variables, was seen at extreme accumulated doses. Notably, exposure to gamma radiation and heat did not cause a progression of damage over time. Samples exposed only to these factors remained stable in solution for extended periods. A theory was proposed that reactive oxygen species formed by the interaction of ionizing radiation with the suspending media may be causing the progression of damage over time. This factor would only be present for microspheres having undergone neutron capture reactions, forming radioactive holmium. Testing confirmed a potential impact of radiation interactions with the suspending media contributing to damage progression. Several thicknesses of lead shielding surrounding the sample chamber were tested in-core. There were significant impacts on temperature, neutron flux, and microsphere quality. / Thesis / Master of Science (MSc) / This research studied Ho166/PLLA microspheres, a promising treatment for tumours in the liver. The preparation of this treatment includes microspheres being neutron irradiated in the core of a nuclear reactor. Irradiation in-core leads to damage of microspheres. This research studied factors present in-core such as heat, gamma radiation, and thickness of lead shielding, for their impact on microsphere quality. Additionally, this research looked at the potential of reactive oxygen species causing damage once microspheres are suspended in liquid. Thresholds for damage were identified for temperature and gamma radiation exposure. Radiation interactions in liquid suggest possible damaging effects over time. Finally changing the thickness of lead shielding in core had significant impact on temperature, neutron flux, and microsphere quality.