Using the AHP to determine the correlation of product issues to profit

Analyzes the correlation between product issues and product profit using the analytic hierarchy process (AHP). Estimation on the effect of profit on product issues by AHP; failure of the AHP to determine the correlation factors; development of procedure for determining correlation factors

An experimental investigation into the constant velocity water entry of wedge-shaped sections

Constant velocity water entry is important in understanding planing and slamming of marine vessels. A test rig has been developed that drives a wedge section with end plates down guides to enter the water vertically at near constant velocity. Entry force and velocity are measured. Analysis of the test data shows that the wetting factor is about 1.6 at low deadrise angles and reduces nearly linearly to 1.3 at 451 deadrise angle. The added mass increases quadratically with immersed depth until the chines become wetted. It then continues to increase at a reducing rate, reaching a maximum value between 20% and 80% greater than at chine immersion. The flow momentum drag coefficient is estimated from the results to be 0.78 at 51 deadrise angle reducing to 0.41 at 451 deadrise angles. Constant velocity exit tests show that the momentum of the added mass is expended in driving the water above the surface level and that exit forces are low and equivalent to a drag coefficient of about 1.0-1.3. Considerable dynamic noise limits the accuracy of the results, particularly after chine immersion

The evaluation of manufacturing issues in the product development process

Many companies still do not achieve the success rates they desire with new product introductions to the market. A method has been developed to aid companies to self-evaluate their product development processes (PDP). The method meets an identified need for a non-prescriptive procedure to evaluate an existing or proposed PDP at a detailed level, both in the context of the company's own products, processes, procedures and markets, and in the context of accepted good practice. The specification and development of the process and facilities needed for the manufacture of a product are identified as fundamental generic issues within the PDP that must be handled effectively to achieve successful product outcomes. The paper describes the main constructs of the evaluation method in relation to manufacturing issues, and presents results and findings from trials conducted in industry. It is seen that great care is needed to ensure that company practitioners make objective assessments of the important factors. Further work is planned to develop the method as an interactive computer tool and to conduct more trials

Significance of cross-reactive antibody responses and isotype bias in malaria- helminth co-infection

The socio-economic and geographical distribution of malaria overlaps with that of many parasitic helminths and in these areas co-infections are common. Co-infection with helminths can influence disease outcome causing either exacerbation or amelioration of malaria. Understanding the complex host-parasite interactions that lead to these different disease outcomes is important for the success of control programmes aimed at these parasites. The immune system has evolved diverse types of response (e.g. T-helper 1 (Th1) and T-helper 2 (Th2)) to efficiently combat infection with ‘microparasites’ and helminths respectively. When faced with co-infection however, the need for the host to multitask means it must manage these counter-regulatory responses. In this study a murine model of malaria-hookworm (Plasmodium chabaudi- Nippostrongylus brasiliensis) co-infection was utilised to investigate how changes in T-helper bias affect malaria disease outcome. Antibody isotypes were used as indicators of Th1/Th2 bias and revealed that helminth co-infection reduced the malaria-specific Th1 response. Counter-intuitively this resulted in ‘protection’ from malaria with co-infected mice having reduced peak P. chabaudi parasitaemia and suffering less severe anaemia. In addition to providing a measure of Th1/Th2 bias, analysis of antibody responses revealed the occurrence of cross-reactive antibodies. The potential for these crossreactive antibodies to influence disease outcome was investigated but in this murine model resource-mediated mechanisms of parasite regulation appear to be responsible for the ‘protection’ that co-infection affords. The question of why cross-reactive antibodies are produced has important immunological and ecological implications. Cross-reactive responses may arise through some physiological constraint on the immune mechanisms that usually result in antibody-specificity. However experiments designed to investigate if the specificity of antibodies is constrained by availability of antigen suggest that this is not the case in the model system used here. There is also the possibility that production of cross-reactive antibodies represents an evolutionary optimal strategy for a host faced with unpredictable exposure to a variety of parasites. However a major finding of this study indicates these two taxonomically distinct parasite species share antigens, which in itself is crucial to understanding host-parasite interactions in a co-infection setting. The main findings of this thesis are relevant to co-infection studies in general and the implications for both evolutionary and applied biology are discussed

Role of IL-33 and ST2 signalling pathway in multiple sclerosis: expression by oligodendrocytes and inhibition of myelination in central nervous system

Recent research findings have provided convincing evidence indicating a role for Interleukin-33 (IL-33) signalling pathway in a number of central nervous system (CNS) diseases including multiple sclerosis (MS) and Alzheimer’s disease. However, the exact function of IL-33 molecule within the CNS under normal and pathological conditions is currently unknown. In this study, we have mapped cellular expression of IL-33 and its receptor ST2 by immunohistochemistry in the brain tissues of MS patients and appropriate controls; and investigated the functional significance of these findings in vitro using a myelinating culture system. Our results demonstrate that IL-33 is expressed by neurons, astrocytes and microglia as well as oligodendrocytes, while ST2 is expressed in the lesions by oligodendrocytes and within and around axons. Furthermore, the expression levels and patterns of IL-33 and ST2 in the lesions of acute and chronic MS patient brain samples are enhanced compared with the healthy brain tissues. Finally, our data using rat myelinating co-cultures suggest that IL-33 may play an important role in MS development by inhibiting CNS myelination

Experimental Evaluation of Mountain Bike Suspension Systems

A significant distinction between competitive mountain bikes is whether they have a suspension system. Research studies indicate that a suspension system gives advantages, but it is difficult to quantify the benefits because they depend on so many variables, including the physiology and psychology of the cyclist, the roughness of the track and the design of the suspension system. A laboratory based test rig has been built that allows the number of variables in the system to be reduced and test conditions to be controlled. The test rig simulates regular impacts of the rear wheel with bumps in a rolling road. The physiological variables of oxygen consumption and heart rate were measured, together with speeds and forces at various points in the system. Physiological and mechanical test results both confirm a significant benefit in using a suspension system on the simulated rough track, with oxygen consumption reduced by around 30 % and power transmitted through the pedals reduced by 30 % to 60 %

Effect of suspension systems on the physiological and psychological responses to sub-maximal biking on simulated smooth and bumpy tracks

The aim of this study was to compare the physiological and psychological responses of cyclists riding on a hard tail bicycle and on a full suspension bicycle. Twenty males participated in two series of tests. A test rig held the front axle of the bicycle steady while the rear wheel rotated against a heavy roller with bumps (or no bumps) on its surface. In the first series of tests, eight participants (age 19 – 27 years, body mass 65 – 82 kg) were tested on both the full suspension and hard tail bicycles with and without bumps fitted to the roller. The second series of test repeated the bump tests with a further six participants (age 22 – 31 years, body mass 74 – 94 kg) and also involved an investigation of familiarization effects with the final six participants (age 21 – 30 years, body mass 64 – 80 kg). Heart rate, oxygen consumption (VO<sub>2</sub>), rating of perceived exertion (RPE) and comfort were recorded during 10 min sub-maximal tests. Combined data for the bumps tests show that the full suspension bicycle was significantly different (P < 0.001) from the hard tail bicycle on all four measures. Oxygen consumption, heart rate and RPE were lower on average by 8.7 (s = 3.6) ml · kg<sup>-1</sup> · min<sup>-1</sup>, 32.1 (s = 12.1) beats · min<sup>-1</sup> and 2.6 (s = 2.0) units, respectively. Comfort scores were higher (better) on average by 1.9 (s = 0.8) units. For the no bumps tests, the only statistically significant difference (P = 0.008) was in VO<sub>2</sub>, which was lower for the hard tail bicycle by 2.2 (s = 1.7) ml · kg-1 · min<sup>-1</sup>. The results indicate that the full suspension bicycle provides a physiological and psychological advantage over the hard tail bicycle during simulated sub-maximal exercise on bumps

Plasmodium chabaudi limits early Nippostrongylus brasiliensis-induced pulmonary immune activation and Th2 polarization in co-infected mice

<p>Abstract</p> <p>Background</p> <p>Larvae of several common species of parasitic nematodes obligately migrate through, and often damage, host lungs. The larvae induce strong pulmonary Type 2 immune responses, including T-helper (Th)2 cells as well as alternatively activated macrophages (AAMφ) and associated chitinase and Fizz/resistin family members (ChaFFs), which are thought to promote tissue repair processes. Given the prevalence of systemic or lung-resident Type 1-inducing pathogens in geographical areas in which nematodes are endemic, we wished to investigate the impact of concurrent Type 1 responses on the development of these Type 2 responses to nematode larval migration. We therefore infected BALB/c mice with the nematode <it>Nippostrongylus brasiliensis</it>, in the presence or absence of <it>Plasmodium chabaudi chabaudi </it>malaria parasites. Co-infected animals received both infections on the same day, and disease was assessed daily before immunological measurements were taken at 3, 5, 7 or 20 days post-infection.</p> <p>Results</p> <p>We observed that the nematodes themselves caused transient loss of body mass and red blood cell density, but co-infection then slightly ameliorated the severity of malarial anaemia. We also tracked the development of immune responses in the lung and thoracic lymph node. By the time of onset of the adaptive immune response around 7 days post-infection, malaria co-infection had reduced pulmonary expression of ChaFFs. Assessment of the T cell response demonstrated that the Th2 response to the nematode was also significantly impaired by malaria co-infection.</p> <p>Conclusion</p> <p><it>P. c. chabaudi </it>co-infection altered both local and lymph node Type 2 immune activation due to migration of <it>N. brasiliensis </it>larvae. Given recent work from other laboratories showing that <it>N. brasiliensis</it>-induced ChaFFs correlate to the extent of long-term lung damage, our results raise the possibility that co-infection with malaria might alter pulmonary repair processes following nematode migration. Further experimentation in the co-infection model developed here will reveal the longer-term consequences of the presence of both malaria and helminths in the lung.</p

Quantifying variation in the potential for antibody-mediated apparent competition among nine genotypes of the rodent malaria parasite Plasmodium chabaudi

Within-host competition among parasite genotypes affects epidemiology as well as the evolution of virulence. In the rodent malaria Plasmodium chabaudi, competition among genotypes, as well as clone-specific and clone-transcending immunity are well documented. However, variation among genotypes in the induction of antibodies is not well understood, despite the important role of antibodies in the clearance of malaria infection. Here, we quantify the potential for antibodies induced by one clone to bind another (i.e., to cause antibody-mediated apparent competition) for nine genetically distinct P. chabaudi clones. We hypothesised that clones would vary in the strength of antibody induction, and that the propensity for clone-transcending immunity between a pair of clones would increase with increasing genetic relatedness at key antigenic loci. Using serum collected from mice 35 days post-infection, we measured titres of antibody to an unrelated antigen, Keyhole Limpet Haemocyanin (KLH), and two malaria antigens: recombinant Apical Membrane Antigen-1 (AMA-1) and Merozoite Surface Protein-119 (MSP-119). Amino acid sequence homology within each antigenic locus was used as a measure of relatedness. We found significant parasite genetic variation for the strength of antibody induction. We also found that relatedness at MSP-119 but not AMA-1 predicted clone-transcending binding. Our results help explain the outcome of chronic-phase mixed infections and generate testable predictions about the pairwise competitive ability of P. chabaudi clones