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Layered double hydroxides (LDHs) or hydrotalcite-like compounds (HTLcs) are classified as anionic clays in which their structure is based upon brucite and are represented by the following general chemical formula: [MII1-xMIII x(OH)2]x+(An-)x/y.yH2O where MII and MIII represent various possible divalent cations, e.g., Mg2+, Zn2+, Ni2+, Co2+ and Fe2+ and trivalent cations, e.g., Al3+, Fe3+ and Cr3+ respectively. The value x is equal to the stoichiometric ratio of MIII/(MII+MIII) and An- represents exchangeable anions such as CO32-, Cl- and SO42-. It is these exchangeable interlayer anions, which make layered double hydroxide compounds excellent carriers of negatively charged or anionic containing biomolecules, such as DNA and hence can be exploited in their use in gene therapy. In this study, a variety of Mg-Al hydrotalcites (HTs), Zn-Al, Zn-Fe and Mg-Fe LDHs were synthesized using co-precipitation. The synthesized compounds were characterized by X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), Raman spectroscopy, Inductively coupled plasma-optical emission spectroscopy (ICP-OES), Transmission electron microscopy (TEM), Scanning electron microscopy (SEM) and Scanning electron microscopy-energy dispersive X-ray spectroscopy (SEM-EDX). XRD patterns for the synthesized HTs and LDHs exhibited characteristic features indicative of an ordered layered material. Elemental analysis of the compounds revealed a measured value of x in the range of 0.25-0.33 for Mg-Al HTs and Zn-Fe LDHs, 0.11-0.16 for Zn-Al LDHs and 0.55-0.58 for Mg-Fe LDHs. FTIR and Raman spectroscopy confirmed the presence of characteristic functional groups and interlayer anions. From electron microscopy, the compounds exhibited classical morphologies typical of HT and LDH compounds and had a lateral size range of 200-300 nm. These compounds were studied in their ability to bind DNA with the use of a gel retardation or band shift assay. This assay confirmed that these compounds are indeed able to bind DNA. The binding mechanism of DNA to the HT and LDH compounds was evaluated and plausible mechanisms were proposed. Furthermore, nuclease digestion assays were carried out in order to evaluate the potential protecting ability that these compounds afford towards the bound DNA in the presence of serum. It was observed that all compounds protected most of the bound DNA. The cytotoxicity of the compounds was evaluated in the HEK293, HepG2 and HeLa mammalian cell lines using the MTS (3-(4,5-dimethylthiazol-2yl)-5(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium, inner salts) assay with a concentration range of 20-100 μg of respective HT/LDH compound. For most of the compounds, cell viability was observed in excess of 80 %. Finally, transfection studies were carried out utilizing green fluorescent protein (GFP) analysis and luciferase gene expression using the same mammalian cells in culture. It was noted that all HTs and LDHs were able to release DNA in a controlled prolonged manner over a period of three days. Green fluorescent protein gene expression commenced after 27 hours and reached a maximum at 72 hours. Efficient luciferase gene expression was observed with luciferase activities for DNA: HTs ranging from 0.05 x 106 - 2.0 x 106 RLU / mg protein and DNA: LDHs ranging from 0.05 x 106 - 16.7 x 106 RLU / mg protein. Highest luciferase activity was recorded as 16.7 x 106 RLU / mg protein. / Thesis (M.Sc.)-University of KwaZulu-Natal, Westville, 2010.

Thesis (Master of Science)--University of the Witwatersrand, Faculty of Health Sciences, 1963. / The rapid progress of the last decade has made possible the synthesis of the molar and molecular approaches to the mechanism of muscle contraction. It is now possible to offer a molecular explanation for many of the gross mechanical properties of muscle. As a result there is a necessity to re-examine the validity of the classical terminology used to describe these properties, and to define them more accurately. Since Pick (1882), various "types” of contraction have been ascribed to muscle, according to the changes in length and tension of the activated muscle. These are dependent upon the load opposing the muscle. If the load is less than the force developed in the muscle, shortening occurs at a constant tension just exceeding the load. This process is termed isotonic contraction. If, on the other hand, the load is equal to the tension developed in the muscle,there is no overall change in length, although tension in the system rises. This constitutes an isometric contraction. Recently, studies of the ultra-structure and mechanical properties of muscle have revealed inherent difficulties in the classical terminology. / WHSLYP2017

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To prevent re-replication of DNA in a single cell cycle, the licensing of replication origins by Mcm2-7 is prevented during S and G2 phases. Metazoans achieve this by cell cycle regulated proteolysis of the essential licensing factor Cdt1 and formation of an inhibitory heterohexameric complex of Cdt1 with a small protein called geminin. The consequences of either stabilising Cdt1 or ablating geminin in synchronised human U2OS cells are investigated in this PhD Thesis to elucidate the possible contribution of re-replication in gene amplifications or rearrangements commonly seen in human tumours. I show that following geminin loss, cells complete an apparently normal S-phase, but a proportion arrests at the G2/M boundary. When Cdt1 starts to accumulate in these cells, DNA re-replicates, suggesting that the key role of geminin is to prevent re-licensing in G2. Inhibition of cell cycle checkpoints in cells lacking geminin promotes progression through mitosis without detectable levels of re-replication. Checkpoint kinases thereby amplify re-replication into an all-or-nothing response by delaying geminin depleted cells in G2 phase. Comparative Genomic Hybridisation (CGH) array and Solexa Deep DNA sequencing revealed that re-replication after geminin depletion does not appear at preferential genomic regions within the human genome. This is consistent with a recent observation that G2 cells have lost their replication timing information and reduplicate their genome stochastically. In contrast, when Cdt1 is stabilised by the neddylation inhibitor MLN4924, re-replication starts directly from within S-phase raising the question whether alternative mechanisms of may cause distinct genomic consequences.

"July 2004" / Bibliography: leaves 108-144. / v, 187 leaves : ill. ; 30 cm. / Title page, contents and abstract only. The complete thesis in print form is available from the University Library. / Thesis (Ph.D.)--University of Adelaide, School of Earth and Environmental Sciences, Discipline of Environmental Biology, 2004