Η Ωκυτοκίνη (ΟΤ) είναι ένα κυκλικό εννιαπεπτίδιο του υποθαλάμου, η οποία απελευθερώνεται στη γενική κυκλοφορία από τον οπίσθιο λοβό της υπόφυσης. Οι κύριες φυσιολογικές δράσης της είναι η επαγωγή συσπάσεων του μυομητρίου και η έκθλιψη του γάλακτος. Εν τούτοις, η μεγάλη διασπορά των υποδοχέων της ΟΤ στον εγκέφαλο αποδίδουν στην ορμόνη το ρόλο του νευροδιαβιβαστή, ο οποίο ρυθμίζει τις αναπαραγωγικές και κοινωνικές συμπεριφορές. Ο ρόλος της ΟΤ στην πρόκληση του πρόωρου τοκετού οδήγησε την έρευνα για το σχεδιασμό και τη σύνθεση πεπτιδικών ανταγωνιστών της ορμόνης ως δραστικούς τοκολυτικούς παράγοντες. Πλήθος τέτοιων αναλόγων συντέθηκε και εξετάστηκε, αλλά μόλις για ένα, το Atosiban, και μόνο στην Ευρώπη, επετράπη η κυκλοφορία για την πρόληψη του πρόωρου τοκετού με την εμπορική ονομασία Tractocile™. Ο σχεδιασμός νέων αναλόγων της ΟΤ βασίζεται στα συμπεράσματα δομής-δραστικότητας. Η ανταγωνιστική δράση εξαρτάται από τη διαμόρφωση και την υδροφοβικότητα του αμινοξέος στη θέση 2. Επιπρόσθετα, η απαλοιφή της τελικής αμινομάδας προσδίδει στο πεπτίδιο παράταση της δράσης. Ιδιαίτερη σημασία στην εκλεκτική πρόσδεση της ΟΤ στον υποδοχέα της έχει η Ιle στη θέση 3, μιας και είναι το μόνο αμινοξύ στο οποίο διαφέρει στον εικοσαμελή δακτύλιο η ΟΤ από το συγγενές μόριο της, τη Βασοπρεσίνη (VP). Βασιζόμενοι στα ανωτέρω συμπεράσματα και για διερεύνηση του ρόλου της θέσης 3 της ορμόνης, συνθέσαμε δεκατέσσερα νέα ανάλογα της ΟΤ. Όλα τα ανάλογα περιέχουν β-μερκαπτοπροπιονικό οξύ (Mpa) στη θέση 1 και D-O-αιθυλ-τυροσίνη [D-Tyr(Et)] ή D-1-ναφθυλ-αλανίνη [D-Nal(1)] στη θέση 2. Η ισολευκίνη (Ile) στη θέση 3 έχει υποκατασταθεί με γ-αμινοϊσοβουτυρικό οξύ (Aib), L- ή D-α-τερτβουτυλ-γλυκίνη [L-/D-Gly(But)], L- ή D-3-πυριδυλ-αλανίνη [L-/D-Pal(3)] και L- ή D-β-(2-θεϊενυλ)-αλανίνη (L-/D-Thi). Τα φάσματα μάζας των αναλόγων συμφωνούν με τα αναμενόμενα αποτελέσματα. Τα δεκατέσσερα ανάλογα εξετάστηκαν ως προς την ωκυτόκιο δράση σε απομονωμένο ιστό μήτρας αρουραίου, ως προς τη δράση επί της πίεσης και ως προς τη συγγένεια με τον ανθρώπινο ωκυτόκιο υποδοχέα. Επιπλέον, τα ανάλογα [Mpa1, D-Tyr(Et)2, Thi3]OT, [Mpa1, D-Tyr(Et)2, D- Thi3]OT], [Mpa1, D-Nal(1)2, Thi3]OT και [Mpa1, D-Nal(1)2, D- Thi3]OT] εξετάστηκαν και ως προς τη δράση τους επί του πολλαπλασιασμού των καρκινικών κυτταρικών σειρών MDA-MB-468 και MCF-7. Όλα τα ανάλογα δρουν ως ανταγωνιστές της φυσικής ορμόνης. Συγκεκριμένα, τα ανάλογα [Mpa1, D-Nal(1)2, Gly(But)3]OT και [Mpa1, D-Nal(1)2, Thi3]OT έχουν ισχυρή αντι-ωκυτόκιο δράση (pA2=8.34±0.30 και 8.50±0.24, αντίστοιχα). Όσο αφορά τα αποτελέσματα των βιολογικών δοκιμών επί του πολλαπλασιασμού των καρκινικών κυττάρων,αυτά δεν οδηγούν σε ασφαλή συμπεράσματα για τη δράση των αναλόγων. / Oxytocin (OT) is a cyclic nonapeptide hormone of hypothalamus that is released into the general circulation from the posterior lobe of the pituitary gland. Its major physiological roles are: a) the ability to induce uterine constructions and b) milk injection. However, widespread distribution of OT receptors in the brain and specific behavioral effects of centrally applied OT, have firmly established a role of OT as a neurotransmitter modulating reproductive and social behaviors. The role of OT in preterm labor led to the search for and design of synthetic peptide antagonists as potential tocolytic agents. A number of those OT analogues synthesized and studied. However, only Atosiban was approved, in Europe only, under the trade name Tractocile™ for the treatment of preterm labor. The design of new OT analogues is based on consequences from structure-activity studies. Antagonistic activity depends on the configuration and the hydrophobicity of the amino acid in position 2. Additionally, the deficiency of the amino-group in position 1 leads to prolongation of the activity. Furthermore, Ile3 is important for the selective binding of OT to its receptor. Based on these findings and for the investigation of the role of position 3 on biological activities, we synthesized by the Fmoc/But solid phase methodology fourteen new analogues of OT. All the analogues contain β-mercaptopropionic acid (Mpa) position 1 and D-O-ethyl-tyrosine [D-Tyr(Et)] or D-1-naphthyl-alanine [D-Nal(1)] in position 2. Isoleucine (Ile) in position 3 has substituted by γ-aminoisobutyric acid (Aib), L- or D-α-tertbutyl-glycine [L-/D-Gly(But)], L- or D-3-pyridyl-alanine [L-/D-Pal(3)] and L- or D-β-(2-thienyl)-alanine (L-/D-Thi). Electro-spray MS was in agreement with the expected results. The analogues were tested for uterotonic activity in the rat uterus in vitro test, for pressor activity in the rat pressor assay and for the affinity to human OT receptor using [3H]OT. Also, the analogues [Mpa1, D-Tyr(Et)2, Thi3]OT, [Mpa1, D-Tyr(Et)2, D- Thi3]OT], [Mpa1, D-Nal(1)2, Thi3]OT and [Mpa1, D-Nal(1)2, D- Thi3]OT] were tested for the activity on the proliferation of MDA-MB-468 and MCF-7 cells. All the new analogues are antagonists of the hormone. In particular, the analogues [Mpa1, D-Nal(1)2, Gly(But)3]OT and [Mpa1, D-Nal(1)2, Thi3]OT have potent anti-uterotonic activity (pA2=8.34±0.30 and 8.50±0.24, respectively). As regards the tests of proliferation, we are unable to come to a sfe conclusion as far as the activity of the analogues is concerned.

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Building reliable genetic devices in synthetic biology is still a major challenge despite the various advances that have been made in the field since its inception. In principle, genetic devices with matching input and output expression levels can be assembled from well-characterized genetic parts. In practice, a priori genetic circuit design continues to be difficult in synthetic biology due to the lack of foundational work in this area. Currently, a successful genetic device is typically created by manually building and testing many combinatorial variants of the target device and then picking the best one. While this process is slow and error-prone, as synthetic genetic devices grow in complexity, this approach also becomes unmanageable and impractical. Fluctuations in genetic context have been identified as a major cause of rational genetic circuit design failures. Promoter elements often behave unpredictably as they are moved from the context in which they were originally characterized. Thus, the ordered location of parts in a synthetic device impacts expected performance. Synthetic spacer DNA sequences have been reported to successfully buffer promoters from their neighboring DNA sequence but design rules for these sequences are lacking. I address this problem with a novel method based on a randomized insulator library. I have developed a high-throughput, flow cytometry-based screen that randomly samples from a library of 4^36 potential insulators created in a single cloning step. This method provides precise control over genetic circuit expression. I further show that insulating the promoters in a genetic NOT-gate improves circuit performance and nearly eliminates the effect of the order in which the promoters are organized in the device. This foundational work will help improve the design of reliable genetic devices in E. coli. Finally, automated DNA assembly using liquid-handling robots can help increase the speed at which combinatorial synthetic device variants are assembled. However, these systems require significant investment in optimizing the handling parameters for handling very small volumes of the various liquids in DNA assembly protocols. I have optimized and validated these liquid-handling parameters on the Tecan EVO liquid handling robotic platform. These materials have been made available to the larger community. / 2017-12-03T00:00:00Z

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The patellazoles are a family of marine polyketide natural products first isolated from Lissoclinum patella in 1988 by both the Moore and Ireland groups. They exhibit significant cytotoxicity against the HCT 116 human colon tumour cells. To date however, their full 3D stereostructure have yet to be elucidated, which has hindered their development as potential drugs, and hampered full investigation into their biological mechanism of action and has deterred total synthesis efforts. This thesis describes synthetic efforts towards Patellazole B, which exhibits the highest potency of the three main congeners. To fully elucidate the structure and renew interest in the patellazoles as anticancer compounds, we have developed a flexible and modular synthesis that aims to define the unknown stereocentres within the pertinent region and allow for rapid fragment union. Compound 36 has been chosen as an initial target for NMR comparison studies. The synthesis of all eight diastereomers of this macrocycle should aid determination of the four unknown stereocentres. Chapter 2 describes the synthesis of the C1–C12 fragment, focusing on the configuring of the C5 methyl stereocentre and the construction of the C7-C10 stereotetrad via a boron-mediated anti aldol with an in-situ reduction. In the third chapter, the synthesis of the C13-C19 fragment is outlined. A boron-mediated glycolate aldol has been used to install the C16-C17 anti stereochemistry and a substrate-controlled reduction at C15 delivered the hydroxyl with high diastereoselectivity. Studies into the C¬17¬ methylation are also described. Chapter 4 describes the synthesis of one possible diastereomer of the C20-C25 fragment, as a template for the preparation of the other 7 possible diastereomers. The route therefore employs only catalyst based control methods to install the three stereocentres, utilising a Sharpless asymmetric epoxidation and Evans aldol to construct the stereotriad. The 22R, 23S, 24S diastereomer has been initially chosen to investigate the later chemistry. Chapter 5 contains discussion of the ongoing work investigating fragment union and formation of the macrocycle. A Heck coupling reaction has been employed to construct the C19-C20 bond and a Suzuki coupling reaction has been developed to facilitate the C12-C13 bond formation. These two cross couplings have delivered the C1 - C25 fragment, 360, the final compound reported in this thesis, which is three steps away from the completed macrocycle and six from compound 36. The experimental procedures and spectroscopic characterisation of the synthesised intermediates can be found in Chapter 6 and the Appendix.

This thesis constitutes a general survey and a study of significant extensions to the usual conventional satellite radar altimetry. Historically radar altimeter has been configured to the measurement of mean sea level. It is well known that other statistics such as Significant Wave Height (SWH) and wind speed are in principle recoverable from the radar echo and these are currently of great interest. It has been the aim in this thesis to optimize such measurements, for a general meteorological application, with less interest shown in absolute measurement of sea level. Current technology makes possible a total Earth survey using a constellation of small satellites, covering the entire Earth sea surface with short revisit time. Such solutions necessitate less cost, lower power, and less precise attitude control than the scientific satellites used hitherto. The purpose of this thesis is to present a novel two mode radar altimeter for sea state monitoring. SWH is still measured by conventional high-resolution mode, which is not sensitive to off-nadir pointing. An additional novel low-resolution mode is proposed for wind speed measurement. By using this mode, wind speed measurement is much more robust to pointing error than by using conventional high-resolution mode. An improved wind speed measurement can be achieved by using a cost effective small satellite. Some considerable time was also spent on incorporating SAR (Synthetic Aperture Radar) into altimetry techniques to improve the signal to noise ratio. For sea state monitoring the improvements are relatively disappointing, although greater improvement are expected for ice sheet monitoring.

Thesis (MTech (Chemical Engineering))--Cape Peninsula University of Technology, 2017. / One of the very promising synthetic fuel production strategies is the Fischer-Tropsch process, founded on the Fischer-Tropsch Synthesis, which owes its discovery to the namesake researchers Franz Fischer and Hans Tropsch. The Fischer-Tropsch Synthesis (FTS) converts via complex polymerisation reaction a mixture of CO and H2 over transition metal catalysts to a complex mixture of hydrocarbons and oxygen containing compounds with water as major by-product. The mixture of CO and H2 (termed syngas) may be obtained by partial oxidation of carbon containing base feedstocks such as coal, biomass or natural gas via gasification or reforming. The Fischer-Tropsch (FT) process thus presents the opportunity to convert carbon containing feedstocks to liquid fuels, chemicals or hydrocarbon waxes, which makes, for instance, the monetisation of stranded gas or associated gas a possibility. The FT-process is typically carried out in two modes of operation: low temperature Fischer-Tropsch (LTFT) and high temperature Fischer-Tropsch (HTFT). LTFT is normally operated at temperatures of 200 – 250 °C and pressures of 10 – 45 bar to target production of high molecular weight hydrocarbons, while HTFT is operated at 300 – 350 °C and 25 bar to target gasoline production. The catalytically active metals currently used commercially are iron and cobalt, since product selectivity over nickel is almost exclusively to methane and ruthenium is highly expensive in addition to requiring very high pressures to perform optimally. Fe is much cheaper, but tends to deactivate more rapidly than Co due to oxidation in the presence of high H2O partial pressures. One of the major drawbacks to using Fe as FT catalyst is the requirement of lower per pass conversion which necessitates tail gas recycle to extend catalyst life and attain acceptable overall conversions. A more active or similarly active but more stable Fe-catalyst would thus be advantageous. For this reason promotion of a self-prepared typical LTFT Fe-catalyst with Ru was investigated. A precipitated K-promoted Fe-catalyst was prepared by combination of co-precipitation and incipient wetness impregnation and a ruthenium containing catalyst prepared from this by impregnation with Ru3(CO)12. The catalysts, which had a target composition of 100 Fe/30 Al2O3/5 K and 100 Fe/30 Al2O3/5 K/3 Ru, were characterised using XRD, SEMEDX, ICP-OES, TPR and BET N2-physisorption, before testing at LTFT conditions of 250 °C and 20 bar in a continuously stirred slurry phase reactor.

Made available in DSpace on 2014-06-12T15:52:31Z (GMT). No. of bitstreams: 1 license.txt: 1748 bytes, checksum: 8a4605be74aa9ea9d79846c1fba20a33 (MD5) Previous issue date: 2009 / Atores Sintéticos são agentes inteligentes que possuem personalidade, atuam em ambientes multimídias ou virtuais e são representados graficamente por avatares. Estas entidades são utilizadas em sistemas de simuladores como forma de enriquecer a interação entre a aplicação e seus usuários, proporcionando assim aumento da credibilidade do projeto. Com a sua popularização sugiram vários projetos que os utilizam. Estes projetos têm diversos aspectos em comum. Por exemplo, neles seus atores se comunicam e possuem modelos de personalidade. Contudo, apesar das similaridades os projetos encontrados na literatura foram implementados de forma independente. Ou seja, tiveram seu código fonte desenvolvido do zero. Porém, no âmbito dos sistemas multiagentes tal problema não ocorre devido à existência de diversos frameworks multiagentes que agrupam as funcionalidades comuns a tais sistemas, fazendo com que o desenvolvedor implemente apenas o que é relativo ao seu contexto de simulação. Porém, estes frameworks não são utilizados em sistemas multiarores, pois não suportam as peculiaridades dos sistemas multiatores. Buscando solucionar esse problema, este trabalho apresenta o FAct (Framework for Actors), um projeto criado especificamente para auxiliar na construção sistemas multiatores. Ele focado nas características peculiares destes sistemas e tem como principal objetivo reduzir o custo e tempo de desenvolvimento para os projetos baseados nesta tecnologia. Como forma de exemplificar o uso do FAct e avaliar o seu impacto no desenvolvimento de simuladores multiatores, serão apresentados dois simuladores implementados com base no framework

M.Phil. (Energy Studies) / South Africa has no commercially proven indigenous crude oil deposits. The country therefore follows a well formulated longterm energy policy to ensure a continuous and uninterrupted supply of transport fuels. The development of a very successful synfuel industry contributes to the national desire of maintaining a minimum level of self sufficiency in transport fuels. The Government also plays a supportive role in financing synthetic fuel projects from the Central Energy Fund. South Africa has abundant coal resources at a reasonable cost, as well as the offshore gas field near the coast of Mosselbay. The objective of this study is therefore to evaluate and compare the re1athe economics of certain direct and indirect coal liquefaction process routes, as well as the conversion of natural gas to transport fuels. The methanol option as a transport fuel is also addressed. Information for this study was collected mainly from the literature on this subject as well as Government institutions and private companies that are actively involved in the production of synthetic transport fuels. The primary conclusions of this study are: Synthetic fuel projects are capital intensive. The number of commercially proven options for the production of synfuels are limited to the well proven technology of the Sasol process, conventional methanol synthesis technology and to a lessor extent the Mobil methanol-to-gasoline technology. Accurate costs comparisons will therefore only be possible when more of the direct liquefaction options have been commercially demonstrated. Commercial realisat ion of the unproven technologies also involve enormous financial resources and a high risk. The Sasol synfuel option with the lowest thermal efficiency of approximately 42% requires the highest capital investment per ton or barrel of final product. The high severity direct processes (H-coal, Exxon-Donor-Solvent or EDS and the German Technology) as well as the Mobil-MTG capital investment follows, with the low severity and high thermal efficiency SRC-1 and SRC-2 process capital requirements the lowest, except for the very low,capital investment for a methanol synthesis plant...