Behaviour of semi-rigid composite connections for steel framed buildings

During propped construction the steel-concrete composite action resists dead as well as imposed loads. Conversely, the steel section alone resists the floor self-weight in unpropped beams. The major difference between propped and unpropped composite beams lies in the ductility requirements rather than in the strength requirements. Relatively few studies have been carried out to assess the rotation requirements for unpropped semi-continuous composite beams. The outstanding critical factor in the case of unpropped construction is the dead load stress that must be carried by the steel beam alone prior to hardening of the concrete. This research overcomes the difficulties involved in modelling the composite and noncomposite stages by using a numerical integration technique developed from the basic principles of structural mechanics. The method incorporates the fully non-linear material properties and requires very little assumption. The technique was initially validated using the experimental results from plain steel beam bending tests. The subsequent comparison between the model predictions and the results from the large-scale frame test carried out for this research purpose, showed that the method is capable of predicting non-elastic load vs. end rotation behaviour within a high degree of accuracy. Thus the model can be used with confidence in order to predict the connection rotation requirements for a wider range of loading configurations than is practically possible from experimental testing alone. A parametric study is carried out using the numerical integration technique developed for the semi-continuous composite beam on a total of 2160 different beam configurations, utilising different steel grades and loading conditions. In this study the influence of dead load stress on the connection rotation requirement has been thoroughly evaluated along with several other factors including span to depth ratio, location within the building frame, ratio between the support (connection) moment capacity and span (beam) moment capacity, loading type, steel grade and percentage of the beam strength utilised during design. The connection rotation capacity requirements resulting from this study are assessed to establish the scope for extending the use of composite connections to unpropped beams. The large-scale experiment that has been carried out provided an opportunity to investigate the behaviour of a modified form of composite connection detail for use at perimeter columns (single-sided composite connections) with improved rebar anchorage. Additionally, another extensive parametric study is carried out using the numerical integration technique developed for the steel beam to establish the influence of strainhardening on elastic-plastic frame instability design.EThOS - Electronic Theses Online ServiceGBUnited Kingdo

Mice, men, mustard and methylated xanthines: the potential role of caffeine and related drugs in the sensitization of human tumours to alkylating agents.

The relationships between DNA damage from UV radiation, alkylating drugs and the methylated xanthines (MX) have been studied in normal and malignant rodent and human cells. A comparison of the level of DNA excision repair (repair replication and unscheduled DNA synthesis) confirms that some forms of alkylating-agent damage (probably mono-filar DNA adducts) are less completely removed by both normal and malignant rodent cells than by their human counterparts, rendering rodent cells more susceptible to the toxic potential of unexcised lesions. The toxicity of alkylating agents can be increased by the presence of several MXs during the period of DNA replication which follows infliction of the damage. Human cells appear capable of excising more DNA damage, rendering them somewhat less susceptible to enhancement of cytotoxicity by MX. This resistance of human cells is only quantitative, however, since 2 human cancer cell lines (HeLa and HT-29) could be sensitized to a variety of alkylating agents by appropriate concentrations of MX. Trimethylxanthine (caffeine) and the 2 clinically useful dimethylxanthines (theophylline and theobromine) appeared equally effective in sensitizing cells. The sensitization was dependent upon a slightly cytotoxic concentration of the MX and a suitably prolonged period of post-damage MX exposure. Of these 3 classic MXs, only theobromine might be clinically useful. The levels required for alkylating-agent sensitization exceed the clinically tolerable level of theophylline, and probably approach the tolerance of man to caffeine. The most likely mechanism by which MX sensitization is achieved is reversal of the inhibition of DNA replicon initiation which follows the infliction of significant DNA damage. Through the selection of suitable clinically useful alkylating agents (those dependent on active cellular transport for cell penetration) and appropriate MX scheduling, an enhanced therapeutic ratio might be achieved, potentially increasing the clinical usefulness of these alkylating agents. MX would thus form a useful class of agents adjuvant to conventional anti-cancer drugs

Genome-wide repeat dynamics reflect phylogenetic distance in closely related allotetraploid Nicotiana (Solanaceae)

Nicotiana sect. Repandae is a group of four allotetraploid species originating from a single allopolyploidisation event approximately 5 million years ago. Previous phylogenetic analyses support the hypothesis of N. nudicaulis as sister to the other three species. This is concordant with changes in genome size, separating those with genome downsizing (N. nudicaulis) from those with genome upsizing (N. repanda, N. nesophila, N. stocktonii). However, a recent analysis reflecting genome dynamics of different transposable element families reconstructed greater similarity between N. nudicaulis and the Revillagigedo Island taxa (N. nesophila and N. stocktonii), thereby placing N. repanda as sister to the rest of the group. This could reflect a different phylogenetic hypothesis or the unique evolutionary history of these particular elements. Here we re-examine relationships in this group and investigate genome-wide patterns in repetitive DNA, utilising high-throughput sequencing and a genome skimming approach. Repetitive DNA clusters provide support for N. nudicaulis as sister to the rest of the section, with N. repanda sister to the two Revillagigedo Island species. Clade-specific patterns in the occurrence and abundance of particular repeats confirm the original (N. nudicaulis (N. repanda (N. nesophila ? N. stocktonii))) hypothesis. Furthermore, overall repeat dynamics in the island species N. nesophila and N. stocktonii confirm their similarity to N. repanda and the distinctive patterns between these three species and N. nudicaulis. Together these results suggest that broad-scale repeat dynamics do in fact reflect evolutionary history and could be predicted based on phylogenetic distance