The ascidian isolation artifact didemnaketal A is a highly oxygenated polyisoprenoid capable of inhibiting HIV-1 protease through an unusual dissociative mechanism. However, recent synthetic efforts have cast doubt on stereochemical assignments in the originally published structure. In the interest of elucidating the true structure of didemnaketal A through total synthesis, we present a strategy for rapidly accessing the putative spiroketal fragment by exploiting its latent symmetry. In a single step, double Sharpless asymmetric dihydroxylation reactions (SAD) allowed us to simultaneously set all seven stereogenic centers and assemble this complex fragment from non-chiral material. The precursor was obtainable through a racemic synthesis in which the geometric isomers of a nine-membered cyclic enone converged in a ring-opening cross metathesis reaction (ROCM). / Graduate / 0490 / jdavy@uvic.ca

No description available.

The use of living radical polymerization methods has shown significant potential to control grafting of polymers from inert polymeric substrates. The objective of this thesis is to create advanced substrates for use in combinatorial chemistry applications through the use of g-radiation as a radical source, and the use of RAFT, ATRP and RATRP living radical techniques to control grafting polymerization. The substrates grafted were polypropylene SynPhase lanterns from Mimotopes and are intended to be used as supports for combinatorial chemistry. ATRP was used to graft polymers to SynPhase lanterns using a technique where the lantern was functionalized by exposing the lanterns to gamma-radiation from a 60Co radiation source in the presence of carbon tetra-bromide, producing short chain polystyrene tethered bromine atoms, and also with CBr4 directly functionalizing the surface. Styrene was then grafted off these lanterns using ATRP. MMA was graft to the surface of SynPhase lanterns, using g-radiation initiated RATRP at room temperature. It was found that the addition of the thermal initiator, AIBN, successfully increased the concentration of radicals to a level where we could achieve proper control of the polymerization. RAFT was used to successfully control the grafting of styrene, acrylic acid and N,N???-dimethylacrylamide to polypropylene SynPhase Lanterns via a -initiated RAFT agent mediated free radical polymerization process using cumyl phenyldithioacetate and cumyl dithiobenzoate RAFT agents. Amphiphilic brush copolymers were produced with a novel combined RAFT and ATRP system. Polystyrene-co-poly(vinylbenzyl chloride) created using gamma-radiation and controlled with the RAFT agent PEPDA was used as a backbone. The VBC moieties were then used as initiator sites for the ATRP grafting of t-BA to give a P(t-BA) brush that was then hydrolyzed to produce a PAA brush polymer. FMOC loading tests were conducted on all these lanterns to assess their effectiveness as combinatorial chemistry supports. It was found that the loading could be controlled by adjusting the graft ratio of the lanterns and had a comparable loading to those commercially produced by Mimotopes.

Introduction of soft ionization techniques, such as electrospray ionization (ESI), has resulted in extensive use of mass spectrometry based techniques to study biomolecules in the gas phase. Despite thorough studies of the gas-phase chemistry of even-electron biomolecules, the examination of their odd-electron counterparts has to this point been much less extensive due to the inefficiency of ESI in generating such species. Among various methods that could be employed to generate and study odd-electron biomolecules in the gas phase, redox processes involving metal ions and homolytic cleavage of metallated amino acid or peptide derivatives would be attractive from a chemical perspective since, in principle, a wide range of metals and biomolecules or biomolecule derivatives could be explored. An important aspect of these approaches is that they can be carried out on a wide range of tandem mass spectrometers equipped with electrospray ionization and collision induced dissociation capabilities. (For complete abstract open document)

This thesis is an account of praxis: it examines Playback conceptually, and portrays a programme of practical work exploring the experience of workplace audiences of five Playback Theatre performances, delivered from 2002-2005. The aim of the performances was to assist multi-disciplinary teams of staff in community health centres in Auckland New Zealand to communicate and work together with more understanding of each other. The thesis describes Playback as a way not only to elicit complex narratives which allow for diverse points of view to be expressed, but also as an aesthetic reworking of these narratives using action, music, dance, gesture and speech, in ways which have been influenced by 20th century avant-garde forms such as surrealism, dada, collage, jazz and poetry. Unlike some forms of theatre, Playback calls on elements of ritual and group method, in that it relies on audience members taking an active part in the performance by contributing narratives from their own lives. The thesis interrogates the notion of audience in theatre, using the words audience, spectator, spectactor, participant, public and polis, and specifically investigates two moments of the theatre as polis, in the French and Russian revolutions, when the potential of theatre to engage with the widest cross-section of the nation led to influential experiments and innovations in theatrical practice, each of which influenced the succeeding century. Some Playback discourse and practice is found to contain simplistic, even nostalgic, concepts of personal narrative, and the potential for performers’ interpretations in Playback to reinscribe social privilege is noted. In spite of its simple structure, Playback demands extremely complex skills from all the performers, not only the facilitator. In addition, the complex setting of the practical work encompasses both local NZ health initiatives and developments in global health. The work in each Healthcare Centre is described in a complete chapter: each containing details of the Centre and the Playback, seen through the findings of the patient focus groups, through comments made in interviews by the staff and through the researcher’s observation and experience. In all three Centres, existential and emancipatory metanarratives surfaced in the performances and in interviews. Professionalism was seen as meaning different things: at Ngākau it was a measure by which people were found to be unsatisfactory; at Oranga, it referred to applying the lessons of the Playback to one’s own practice; while at Pātaka, professionalism was evident in narratives of self care, dedication and seeking clarification and support from peers. While the study revealed limitations of Playback, it also pointed to some unique contributions this form of improvisational theatre can make to a programme of staff or group development. In particular, Playback can open up spaces, people and topics, for non-dogmatic, pluralistic, embodied thinking and reflection, leading people to more nuanced understandings of themselves and each other, and can even affect attitudes and behaviours.

Doctor of Philosophy (PhD) / This thesis primarily details the application of high-level ab initio quantum chemistry techniques in order to understand aspects of free-radical mediated protein oxidation. Traditionally, product analysis and electron paramagnetic resonance (EPR) spectroscopy are the primary means for elucidating the chemistry of protein oxidation. However, in experiments involving relatively small proteins reacting with a controlled radical-flux, a vast array of compounds can be produced, which are often difficult to analyse. Quantum chemical techniques on the other hand, can calculate the properties of any particular species directly, without suffering from the problems associated with experiment, such as side-reactions and chain processes. The results presented in this thesis are aimed at elucidating mechanistic details of protein oxidation, which might otherwise be difficult to probe experimentally. Chapter 1 gives an overview of the free-radical hypothesis of disease and ageing. Protein-derived radicals can undergo a variety of reactions, with the particular reaction that occurs depending on numerous aspects. Many types of reactions have been identified through radiolysis experiments of amino acids, and these are detailed in this chapter. In addition, the key reactive species are characterized and their different chemistries explained. Chapter 2 details the theoretical tools used throughout this thesis. Species with unpaired electrons (radicals) present unique problems for quantum chemistry to handle, thus an appropriate choice of theoretical technique is needed. The approach taken in this thesis is to use high-level compound methods, many of which have been directly formulated to give improved results for radical species, to provide benchmark quality results by which other less demanding techniques can be assessed. During the course of this study, it became apparent there was a void in the armoury of tools that could be used for the theoretical chemistry calculations. Chapter 3 details the formulation of a new tool in an attempt to fill this gap. Historically, the formulation of this new procedure came after much of the work in this thesis had been carried out. Thus, for the study of many of the reactions of this thesis the new method has not been used. However, it is most appropriate to place its formulation after summarizing the current status of techniques in common use today. Chapters 4 and 5 detail computations carried out on models of peptides containing backbone carbon- and nitrogen-centered radicals. A number of different theoretical techniques are used in these chapters, ranging from the highly accurate and computationally intensive to the less reliable and less demanding. The highly accurate techniques are used to gauge the accuracy of the other less demanding theoretical techniques so that the latter can be used with confidence in larger systems. Not only is the choice of theoretical technique important but also the judicious choice of model is essential. With this in mind, models are incrementally built until convergence of the particular property of interest is reached. Chapters 6 and 7 detail the calculations of β-scission reactions of alkoxyl radicals, which are a particular class of reaction known to occur on peptide backbones. Alkoxyl radicals are particularly difficult for theory to describe correctly. Therefore, Chapter 6 extensively assesses and then identifies the theoretical methods needed to portray them. Chapter 7 uses the techniques identified in the previous chapter in order to predict how the preference for a particular type of β-scission reaction changes.

Thesis (Ph.D.)--McMaster University (Canada), 1992. / Source: Dissertation Abstracts International, Volume: 54-12, Section: B, page: 6173. Adviser: J. Warkentin.

Thesis (Ph.D)--Earth and Atmospheric Sciences, Georgia Institute of Technology, 2010. / Committee Chair: Wine, Paul; Committee Member: Huey, Greg; Committee Member: Mulholland, James; Committee Member: Nenes, Athanasios; Committee Member: Weber, Rodney. Part of the SMARTech Electronic Thesis and Dissertation Collection.

Th.--Sci. phys.--Grenoble 1, 1981. N°: 2.

Objetivo: Analisar a casuística de prostatovesiculectomias radicais com linfadenectomia ilíaca avaliando a validade das Tabelas de Partin versão 2001. Estudar variáveis que possam interferir no confinamento ou não da neoplasia como retardo cirúrgico, peso prostático, resultados referentes à biópsia e ano da cirurgia. Material e Métodos: Avaliação retrospectiva de 568 prontuários de pacientes submetidos à cirurgia para câncer de próstata clinicamente localizado entre 1995 até agosto de 2005 no Hospital de Clínicas de Porto Alegre. Foram excluidos quem tivesse feito hormonioterapia neoadjuvante ou com diagnóstico feito por ressecção endoscópica da próstata e aqueles com insuficiência dos dados no prontuário. Estágio clínico pelo toque retal , valores de PSA e dados da biópsia que diagnosticou a neoplasia, assim como dos dados da peça da prostatectomia radical foram coletados. Os valores preditivos das Tabelas de Partin, versão 2001 foram comparados com os do espécime cirúrgico e analisados através de Curvas R.OC. Foram também avaliados tempo de espera para cirurgia, peso da próstata, ano da cirurgia, uni ou bilateralidade tumoral na biópsia e qual a biópsia que diagnosticou (primeira ou ulterior) e analisados como fatores preditivos para confinamento ou não da neoplasia. Resultados: A idade média do pacientes foi 63 (42-77). A percentagem de estágio T1c foi de 63 %. Pacientes com escore de Gleason 2-4 na biópsia constituiram 20,2 %, notadamente antes de 2000. O percentual de pacientes com níveis de PSA menores de 4,0 ng/ml foi de 8,3 % e acima de 10,0 ng/ml foi de 35 %. Os percentuais de doença confinada ao órgão, extensão extra-prostática, invasão de vesículas seminais e metástases linfonodais foram 48,2 %, 35,3%, 13,9% e 2,6% , respectivamente. A área sob a curva calculada para doença confinada ao órgão foi de 0,65 , enquanto as áreas sob as curvas para extensão extra-prostática, invasão de vesículas seminais e metástases linfonodais foi respectivamente 0,54; 063 e 0,77. Pacientes que tiveram o diagnóstico já na primeira biópsia, ou com biópsias bilateralmente comprometidas e aqueles operados antes de 2000 tinham tendência ao não confinamento. Biópsias realizadas a partir de 2000 que já foram positivas na primeira tentativa tiveram maior tendência ao confinamento do que até 1999. Conclusão: As Tabelas de Partin tiveram valor preditivo marginal para as características patológicas finais como doença confinada ao órgão e invasão de vesículas seminais e valor preditivo importante para metástases linfonodais. Não mostraram valor preditivo para extensão extra-prostática. Bilateralidade tumoral na biópsia, diagnóstico na primeira biópsia (especialmente até 1999) e cirurgia antes de 2000 configuraram situações com tendência a tumores não confinados. / Objective: The predictive value of current Partin tables (2001) has been not validated in most of the countries as well Brazil. Therefore, we evaluated the validity of 2001 Partin tables for the ability to predict the pathological stage in specimens of radical prostatectomy. Also, we analysed how biopsies can predict results for organ confinement or not and as well what the year of the surgery can make in organ confinement issue . Materials and methods: The clinical and pathological findings of 568 patients who have had radical prostatectomy and iliac lymphadenectomy from 1995 to 2005 at Hospital de Clínicas de Porto Alegre were assessed. Those with missing information, patients who had neoadjuvant endocrine treatment and those who had the diagnosis by transurethral ressection of prostate were excluded. Serum PSA, clinical stage, biopsy characteristics and the pathological features of the specimens were collected. The predictive value of Partin tables and pathological findings of prostatectomy specimens were compared and analyzed according to Receiver Operating Characteristics curves. The delay of the surgery, prostate weight, year of the surgery, bilaterality of the biopsies and if the diagnostic biopsy was the first or not were important for the organ confined disease were also tested. Results: Median age of the patients was 63(42-77). The percentage of patients with clinical stage T1c was 63%. Gleason score 2-4 in biopsy constituted 20,2 %, at mainly before 2000. The ratio of patients with serum PSA above 4,0 ng/ml was 8,3% and higher than 10,0 ng/ml was 35%.Organ confined disease, extra-prostatic extension, seminal vesicle involvement and lymph node metastasis were 48,2%; 35,3%; 13,9 % and 2,6% respectively. Area under curve (AUC) values for organ confined disease, extra-prostatic extension, seminal vesicle invasion and lymph node involvement were 0,65 ; 0,54; 0,63 and 0,77. Tumor bilaterallity at biopsy and positive biopsy at the first procedure (at least until 1999) as well radical prostatectomy before 2000 were predictors for non organ confined prostate cancer. Conclusion: Partin tables have a marginally predictive value for the pathological features like organ confined disease and seminal vesicle involvement and a good predictive value for lymph node metastasis prediction. They don’t have predictive value for extra-prostatic extension. Positive first biopsy, bilateral tumor at biopsy and radical prostatectomy before 2000 were predictive for non organ confined disease.