No description available.

Thesis (Ph.D.)--Massachusetts Institute of Technology, Dept. of Biology, 1982. / MICROFICHE COPY AVAILABLE IN ARCHIVES AND SCIENCE / Vita. / Bibliography: leaves 211-223. / by Douglas Elliott Koshland. / Ph.D.

Kwan Ho-yuet. / "April 2004." / Thesis (Ph.D.)--Chinese University of Hong Kong, 2004. / Includes bibliographical references (p. 98-[103]). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Electronic reproduction. Ann Arbor, MI : ProQuest Information and Learning Company, [200-] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Mode of access: World Wide Web. / Abstracts in English and Chinese.

Dans le domaine du développement logiciel, le changement est la seule constante. Les logiciels évoluent parfois de façon substantielle et, pendant ce processus, des séquences de transformation de code (par exemple, créer une classe, puis surcharger une méthode) sont systématiquement appliquées dans le système (e.g. à certaines classes dans une même hiérarchie). De par la nature répétitive de ces transformations, il est nécessaire d’automatiser leur support afin d’assurer que ces séquences de transformations sont appliquées de façon consistante sur la globalité du système.Dans cette thèse, nous proposons d’améliorer les transformations de code pour mieux aider les développeurs dans l’application de transformation de code systématiques et complexes. Nous couvrons deux aspects:• Le support automatisé pour composer et appliquer des séquences de transformations de code. Nous réalisons une recherche de l’existence de telles séquences dans de vrais logiciels. Nous proposons un outil pour appliquer automatiquement ces séquences dans les systèmes que nous avons analysés. • La détection de violations de bons principes dans la conception lors d’efforts de transformation. Nous proposons un outil qui recommande des transformations additionnelles pour résoudre les violations de conception qui ont pu être détectées après avoir effectué les transformations de refactoring.Nous évaluons les approches proposées quantitativement et qualitativement sur des cas d’étude issus du monde réel, parfois avec l’aide des experts du système analysé. Les résultats obtenus montrent la pertinence de nos approches. / In software development, change is the only constant. Software systems sometimes evolve in a substantial way and, during this process, sequences of code transformations (e.g., create a class, then override a method) are systematically performed in the system (e.g., to some classes in the same hierarchy). Due to the repetitive nature of these transformations, some automated support is needed to ensure that these sequences of transformations are consistently applied to the entire system.In this thesis we propose to improve source code transformations to better sup- port developers performing more complex and systematic code transformations. We cover two aspects: • The automated support to compose and apply sequences of code transformations. We undergo an investigation on the existence of these sequences in real-world software systems. We propose a tool to automatically apply these sequences in the systems we analyzed. • The detection of design violations during a transformation effort. We undergo an investigation on cases of systematic application of refactoring transformations. We proposed a tool that recommends additional transformations to fix design violations that are detected after performing refactoring transformations.We evaluated the proposed approaches quantitatively and qualitatively in real-world case studies and, in some cases, with the help of experts on the systems under analysis. The results we obtained demonstrate the usefulness of our approaches.

Thesis (M.A (Translation studies and linguistics )) --University of Limpopo (Turfloop Campus), 2010. / This research is intended as a tool to survey the state of Sindebele, the speech variety that is predominantly spoken at Mokopane in the Limpopo Province of South Africa. The study will inform the reader, making use of a sociolinguistic approach, about the language situation at Mokopane. The study further provides a factual account as to what is happening at Mokopane concerning the two commonly spoken speech forms, that is, Sepedi and Sindebele. Furthermore, it presents ideas and insights in order to stimulate academic debates on the differences between isiNdebele and Sindebele and how the authorities are approaching the whole idea of Sindebele as a minority language. The researcher used the qualitative method to have more insight into the language situation of the area. The tool the researcher will use in this research will be the structured interview that will enable her to obtain the required sample of the respondents. The main aim of the researcher to conduct this research is to analyse the linguistic situation to understand the socio-political situation of the area. The researcher has found that the issue of Sindebele is more of a political nature than social. The Sindebele speakers’ concern about the revival of their speech form seems to have gone in one ear and out the other, as a result, Sindebele may totally not be given recognition as a subject in schools. Finally, the researcher gives general recommendations for improving the status of Sindebele.

No description available.

DNA is the pharmacological target for most platinum drugs; however, the majority of these drugs show little or no specificity for particular base pairs. Considerable progress has been made in the design of sequence selective compounds, such that an antiparallel association of a polyamide can have high affinity for selected DNA base pairs. Hairpin polyamides have distinct advantages as they achieve affinities and specificities that are comparable to that of DNA-binding proteins. Platinum(II) hairpin polyamides are expected to display antitumour activity and target specific sequences of DNA. Five DNA-sequence-selective hairpin polyamide platinum(II) complexes, containing pyrrole (Py) and imidazole (Im) heterocyclic rings, have been synthesised using a combination of solid and solution phase chemistry. One mononuclear sequence selective complex, β-Ala-PyPyPy-L4-ImImIm-L4-Pt (HLSP-6) [β-Ala is β-alanine, L4 is 4-(Fmoc-amino)butyric acid and Pt is transplatin], and two dinuclear sequence selective complexes, β-Ala-PyPyPy-L4-ImImIm-L6'-Pt-(Pt) (DNHLSP-6) [L6' is 2,6-Fmoc-Lysine-(Fmoc)-OH] and β-Ala-PyPyImImIm-L4'-PyPyPyPyPy-L6'-Pt-(Pt) (DNHLSP-10) (L4' is 2-Boc-4-Fmoc-L-diaminobutyric acid), were synthesised entirely using solid phase chemistry. Two mononuclear sequence selective complexes, Pt-L6-β-Ala-Py-L4-Im (HSP-2) and Pt-L6-β-Ala-PyPyPy-L4-ImImIm (HSP-6), were synthesised using a combination of solid and solution phase chemistry. The synthesis of a trinuclear sequence selective polyamide was also attempted using a combination of solid and solution phase chemistry. The polyamides were synthesised in a series of reaction steps. Each heterocyclic ring and linker was coupled through solid phase chemistry using 2-(1H-benzotriazole-1-y1)-1,1,3,3-tetramethyluronium hexafluorophosphate (HBTU). Once the organic components were assembled, the platinum(II) group/s was/were added using either solid or solution phase chemistry. The polyamide sequence of PyPyPy-L4-ImImIm was designed to target the guanine rich telomere region of DNA. The metal complexes reported in this study will span sequences between 2, 5 or 7 DNA base pairs (depending on their length), which include 5'-(A/T)GGG(A/T)-3' and 5'-(A/T)(A/T)(A/T)GGG(A/T)-3'. All complexes were characterised using 1H and 195Pt NMR, high resolution mass spectrometry and elemental analysis. The binding of HLSP-6 and DNHLSP-6 to guanosine was also monitored by 1H NMR. / Doctor of Philosophy (PhD)

The introduction of cellular wireless systems in the 1980s has resulted in a huge demand for personal communication services. This demand has made larger capacity systems necessary. This has been partially satisfied by the introduction of second generation digital systems. New third generation systems are now under going standardisation and will require even more efficient utilisation of the spectrum if the high bandwidth features and larger capacity are to become a reality. Motivated by these growing requirements we discuss methods of achieving large improvements in spectral efficiency and performance. Multiple-user communications over a channel can only be achieved with some form of diversity. In this work we point out that the efficient utilisation of the dimensions of space, time, and frequency will ultimately maximise the system capacity of a multiple-user system. We apply our receiver techniques solely to the base-station design where capacity limitations are currently present. We note however, that some of these techniques could also be applied at the mobile terminal receiver. We primarily focus our attention on the direct-sequence code-division multiple-access (DS/CDMA) channel, since this channel is inherently interference limited by other users in the cell of interest. We exploit a new powerful channel coding technique named " turbo coding" for its iterative decoding approach. We show how we can substitute the inner convolutional code of a turbo code encoder with the CDMA channel. By " iterative detection/decoding" or " turbo equalisation" at the receiver we achieve performance results which show the interference from other users to approach complete removal. We develop and analyse a new, low complexity, iterative interference canceller/decoder. This receiver has complexity per user linear with the memory of the channel and independent of the number of users in the system. We extend this receiver to more realistic channels that are asynchronous and include multi-path, and include spatial diversity by using an antenna array at the receiver. The CDMA channel we study exclusively uses randomly generated spreading codes. With this channel model we still achieve single user performance (no interference from other users) with a 10logL gain from L antenna elements and a gain of up to 10logP from P multi-path components. With any new receiver design, sensitivity to channel parameter errors is of paramount interest. We find that the sensitivity of our receiver is low with respect to the parameter errors induced. This is as we desire for a realisable receiver design. Finally we investigate the application of this new iterative interference canceller/decoder receiver to a number of other interference channels. These include the intersymbol interference (ISI) channel, partial response signalling (PRS), and continuous phase modulation (CPM). For these channels excellent performance improvement is generally achieved by the utilisation of the iterative interference canceller/decoder solution. / Thesis (PhD)--University of South Australia, 1999

The development of new drug therapies traditionally requires mass screening of thousands if not millions of substances to identify lead compounds. They are then further optimised to increase potency. The screening of the large pharmaceutical compound libraries can be incredibly expensive, with the industry responding by miniaturising the assays to smaller formats, enabling the compound screening to be automated and, importantly, eliminating assay reagents that are a major contributing cost for running large screens. A potential target for such an approach is the genetic recoding site of viruses like HIV-1 and SARS. They use programmed recoding of the genetic code to regulate the translation of necessary proteins required for viable virus production. For example HIV-1 uses a -1 frameshift mechanism to regulate the ratio of the Gag to the Pol proteins, crucial for viable virus formation. The study of recoding, including readthrough of premature termination codons have most recently used bicistronic reporters with different combinations of enzymes. The most widely used plasmid bicistronic reporter utilises a dual luciferase arrangement comprised of firefly luciferase and Renilla luciferase reporters flanking the DNA being studied. Both of the luciferase enzymatic reporters emit light in response to their respective substrates. The cost of these substrates is the major issue to using luciferase reporters for high throughput screening. My study aimed at designing and developing a bicistronic assay suitable for genetic recoding that was amenable to high throughput screening. The luciferase reporters were replaced with Green Fluorescent Protein (GFP) reporters that do not require the addition of substrates. The development of a dual GFP assay required the appropriate selection of GFP fluorophores, the best arrangement of the GFPs to maximise the ratio of relative fluorescence intensity signal to background, the optimisation of the cells and growth conditions, DNA transfection, plate reader selection, and optical filter sets. Cassettes encoding protein linkers were also incorporated into the design of the constructs to separate the fluorescent proteins spatially to facilitate unimpaired folding into their functional units within the fusion protein. The assay was further improved by moving from transient transfection to stably expressing cell lines. A viable assay was almost achieved for 96 (and 384) well plates with a Z� factor compatible with the assay being suitable for high throughput screening. The assay was used to test a small collection of compounds known to interact with the ribosome and compounds known in the literature to affect frameshifting. This proof of concept was important, since it showed that the assay, with the various modifications, optimisations and miniaturisation steps, still retained the capability of correctly measuring the -1 frameshifting efficiency at the HIV-1 recoding site, and recording compound-induced modulations to the frameshifting efficiency. The compounds cycloheximide and anisomycin, for example, were shown to decrease -1 frameshifting albeit at some expense to overall protein synthesis. The dual GFP assay was also shown to be able to measure accurately changes in the frameshift efficiency brought about by mutations to the frameshift element, and additionally, it would be suitable for the detection and study of compounds, like the recently reported PTC-124 (currently undergoing phase II clinical trial for Duchenne Muscular Dystrophy and cystic fibrosis) that increases readthrough of a UGA premature stop codon mutation. The dual GFP assay developed in this study is at most only 1/10th of the cost of a comparable dual luciferase assay, largely due to removal of assay substrates and transfection reagents. The assay has a robust Z� factor comparable to that of the dual luciferase assay, and would substantially decrease the costs of high throughput screening in situations where a bicistronic reporter is required. The HIV-1 frameshift element is such a site.

Thesis (M. A.)--University of Hong Kong, 2006. / Title proper from title frame. Also available in printed format.