The disease gonorrhea has plagued mankind at least as long as written records have been kept (Black and Sparling, 1985). N. gonorrhoeae is still an important cause of suffering, infertility, and occasional mortality despite the fact that treatment with antibiotics is relatively easy and highly effective, even with the recent increase in penicillin-resistant isolates (Jephcott, 1986). The continued existence of this public health problem is partly the result of a reservoir of asymptomatic carriers within the community who normally don't seek treatment and continue their usual sexual practices (Handsfield, 1983; Kavli et al., 1984). Asymptomatic carriers do not have the purulent discharge characteristic of gonococcal urethritis and cervicitis in which the neutrophil is such a prominent element. Since IgM is present in only trace amounts on genital mucosa (Schumacher, 1973), and this is the "naturally occurring" antibody against gonococci (Rich and Kasper, 1982); it is not unreasonable to assume that non-opsonic chemotaxis and non-opsonic phagocytosis by PMN may play important roles in initiating the inflammatory response and symptomatology seen with gonorrhea. Further, non-opsonic phagocytic killing may be important in eventually clearing gonococcal infection since the role of specific humoral immunity is limited by the ability of gonococcus to constantly vary its antigenic facade (Zak et al., 1984). I have found that three different gonococcal strains express certain outer membrane proteins of the protein II (P.II) family which stimulate neutrophil phagocytic killing and oxidative metabolism in a highly efficient, dose-dependent manner. Other P.IIs expressed by two of the strains are non-stimulatory. Since all P.IIs have very similar physicochemical properties, these results suggest that a specific receptor-ligand interaction occurs between the gonococcal P.II and some element of the neutrophil plasma membrane. The presence or absence of pili on the gonococcal surface has no apparent effect on the ability of certain P.IIs to stimulate neutrophils. Changes in gonococcal outer membrane protein I and lipopolysaccharide, which are thought to confer serum resistance, also have no apparent effect on P.II stimulation of human PMN. Therefore, gonococcal outer membrane P.II may be an important mediator in the inflammatory response to gonococcal infection. Once gonococci are phagocytized by human PMN killing occurs rapidly and there is no evidence of significant intracellular survival. Non-oxidative killing by human chronic granulomatous disease neutrophils is as effective as the killing seen with normal PMN. Extracellular killing of gonococci does not occur to any appreciable extent.

The specific research work described in this thesis forms part of a much larger research project that was funded by the Technology Programme of the UK Government. This larger project considered improving the design and efficiency of membrane bioreactor (MBR) plant by using modelling, simulation and laboratory methods. This research work uses phenomenological mechanistic models based on MBR filtration and biochemical processes to measure the effectiveness of alternative behavioural models based upon input-output system identification methods. Both model types are calibrated and validated using similar plant layouts and data sets derived for this purpose. Results prove that although both approaches have their advantages, they also have specific disadvantages as well. In conclusion, the MBR plant designer and/or operator who wishes to use good quality, calibrated models to gain a better understanding of their process, should carefully consider which model type is selected based upon on what their initial modelling objectives are (e.g. using either a physically mechanistic model or an input-output behaviourial model). Each situation usually proves unique. In this regard, this research work creates a "Model Conceptualisation Procedure" for a typical MBR which can be used by future researchers as a theoretical framework which underpins any newly created model type. There has been insufficient work completed to date on using a times series input-output approach in the model development of a wastewater treatment plant, so only general conclusions can be made from this research work. However, it can be stated that this novel approach seems to be applicable for a membrane filtration model if care it taken to select appropriate input-output model structures, such as those suggested in the "Model Conceptualisation Procedure". In the case of the development of a MBR biological model, it is thought that a conventional Activated Sludge model produced by the IWA could be coupled to a input-output model structure as suggested by this report to give a hybrid model structure that may have the advantages of both model types. Further research work is needed in this area. Future work that should follow on from this research study should focus on whether these input-output models could be used for predictive control purposes, whether an integrated model could be created, and whether a benchmark could be created for the three main MBR configurations.

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A metasurface or 2D metamaterial composed of a membrane array can support an interesting acoustic wave field. These waves are evanescent in the direction normal to the array and can propagate in the immersion fluid immediately above the metasurface. These waves are a result of the resonant membranes coupling to the fluid medium and propagate with a group and phase speed lower than that of the bulk waves in the surrounding fluid. This work examines and utilizes these evanescent surface waves using Capacitively Micromachined Ultrasonic Transducers (CMUT) as a specific example. CMUT arrays can generate and detect membrane displacement capacitively, and are shown to support the surface waves capable of subwavelength focusing and imaging. A model is developed that can solve for the modes of the membrane array in addition to transiently modeling the behavior of the array. It is found that the dispersive nature of the waves is dependent on the behavior of the modes of the membrane array. Two-dimensional dispersion analysis of the metasurface shows evidence of four distinct frequency bands of surface wave propagation: isotropic, anisotropic, directional band gap, and complete band gap around the first resonant frequency of the membrane. Some of the frequencies in the partial band gap show concave equifrequency contours capable of negative refraction. The dispersion and modal properties are also examined as to how they are affected by basic array parameters. Potential applications of this wave field are examined in the context of subwavelength focusing and imaging. Several methods of acoustic focusing are used on an array consisting of dense grid of membranes and several membranes spatially removed from the structure. Subwavelength acoustic focusing to a resolution of λ/5 is shown in simulations and verified with experiments. An imaging test is also performed in which a subwavelength defect is localized. This fundamental work in characterizing the waves above the membrane metasurfaces is expected to have impact and implications for transducer design, resonant sensors, 2D acoustic lenses, and subwavelength focusing and imaging.

published_or_final_version / Civil Engineering / Master / Master of Philosophy

<p>There are many types of membrane lipids throughout Nature. Still little is known about synthesizing pathways and how different lipids affect the embedded membrane proteins. The most common lipids are glycolipids since they dominate plant green tissue. Glycolipids also exist in mammal cells as well as in most Gram-positive bacteria. Glycosyltransferases (GTs) catalyze the final enzymatic steps for these glycolipids. In the bacteria <i>Acholeplasma laidlawii</i> and <i>Streptococcus pneumonie</i> and in the plant <i>Arabidopsis thaliana</i>, GTs for mono-/di-glycosyl-diacylglycerol (-DAG) are suggested to be regulated to keep a certain membrane curvature close to a bilayer/nonbilayer phase transition. The monoglycosylDAGs are nonbilayer-prone with small headgroups, hence by themselves they will not form bilayer structures.</p><p>Here we have determined the genes encoding the main glycolipids of <i>A. laidlawii</i> and <i>S. pneumonie</i>. We have also shown that these GTs belong to a large enzyme group widely spread in Nature, and that all four enzymes are differently regulated by membrane lipids. The importance of different lipid properties were traced in a lipid mutant of <i>Escherichia coli</i> lacking the major (75 %), nonbilayer-prone/zwitterionic, lipid phosphatidylethanolamine. Introducing the genes for the GTs of <i>A. laidlawii</i> and two analogous genes from <i>A. thaliana</i> yielded new strains containing 50 percent of glyco-DAG lipids. The monoglyco-DAG strains contain significant amounts of nonbilayer-prone lipids while the diglyco-DAG strains contain no such lipids. Comparing these new strains for viability and the state of membrane-associated functions made it possible to connect different functions to certain lipid properties. In summary, a low surface charge density of anionic lipids is important in <i>E.coli</i> membranes, but this fails to be supportive if the diluting species have a too large headgroup. This indicates that a certain magnitude of the curvature stress is crucial for the membrane bilayer <i>in vivo</i>.</p>

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