Immunity to nematode infections requires a host T helper 2 (Th2) response promoted by epithelial cell driven IL-33 induction of cytokine secretion of Interleukin (IL)-4, 5 and 13 by a range of immune cells including innate lymphoid cells type 2 (ILC2s) and CD4+ T cells. This induces effector responses such as goblet cell mucus secretion and mast cell activation driving disease resolution. Finding candidate molecules and discrete cell populations that enhance these responses would provide new targets for treating infection via specific host immune-modulation and would contribute to the development of effective vaccines against nematode infections. In this study we addressed how novel components of host adaptive and innate immunity can contribute to pulmonary control of Nippostrongylus brasiliensis infections. Murine reinfection studies with the parasitic nematode N. brasiliensis have shown development of a Th2 CD4+ T cell responses in the lung to be essential for immunity to secondary N. brasiliensis infection. To test if T cell recruitment from secondary lymphoid tissue contributed to this immunity, we used the drug Fingolimod (FTY720) to block T cell egress from lymph nodes (LN) to peripheral tissue. T cell egress from the LN was required for resolution of a primary infection but not for secondary infection. The presence of tissue-resident IL-4Rα responsive CD4+ T cells in the lung was sufficient for protective immunity to N. brasiliensis reinfection. These results demonstrated that effective CD4+ T cell Th2 immunity can be generated at peripheral sites by pre-existing T cell populations, independently of T cell recruitment from secondary lymphoid organs (SLO). Additionally, we identify that the pulmonary epithelial cell-secreted collectin, surfactant protein D (SP-D), is an important component of host immunity to N. brasiliensis infection. We demonstrate here that SP-D production is induced following N. brasiliensis infection in a Th2 dependent manner, it bound preferentially to lung stage L4 parasites and enhanced macrophage and ILC2 protective responses essential for controlling infection. vi Taken together the data presented in this thesis provides two new important insights into pulmonary host immunity to parasitic helminth infections.

Immunity to nematode infections requires a host T helper 2 (Th2) response promoted by epithelial cell driven IL-33 induction of cytokine secretion of Interleukin (IL)-4, 5 and 13 by a range of immune cells including innate lymphoid cells type 2 (ILC2s) and CD4+ T cells. This induces effector responses such as goblet cell mucus secretion and mast cell activation driving disease resolution. Finding candidate molecules and discrete cell populations that enhance these responses would provide new targets for treating infection via specific host immune-modulation and would contribute to the development of effective vaccines against nematode infections. In this study we addressed how novel components of host adaptive and innate immunity can contribute to pulmonary control of Nippostrongylus brasiliensis infections. Murine reinfection studies with the parasitic nematode N. brasiliensis have shown development of a Th2 CD4+ T cell responses in the lung to be essential for immunity to secondary N. brasiliensis infection. To test if T cell recruitment from secondary lymphoid tissue contributed to this immunity, we used the drug Fingolimod (FTY720) to block T cell egress from lymph nodes (LN) to peripheral tissue. T cell egress from the LN was required for resolution of a primary infection but not for secondary infection. The presence of tissue-resident IL-4Rα responsive CD4+ T cells in the lung was sufficient for protective immunity to N. brasiliensis reinfection. These results demonstrated that effective CD4+ T cell Th2 immunity can be generated at peripheral sites by pre-existing T cell populations, independently of T cell recruitment from secondary lymphoid organs (SLO). Additionally, we identify that the pulmonary epithelial cell-secreted collectin, surfactant protein D (SP-D), is an important component of host immunity to N. brasiliensis infection. We demonstrate here that SP-D production is induced following N. brasiliensis infection in a Th2 dependent manner, it bound preferentially to lung stage L4 parasites and enhanced macrophage and ILC2 protective responses essential for controlling infection. vi Taken together the data presented in this thesis provides two new important insights into pulmonary host immunity to parasitic helminth infections.

No description available.

Like much of the world, the United States is currently experiencing intense growth, especially in and around its cities. Unfortunately, this growth is often at odds with the natural environment. In order to reduce the demand of foreign energy resources designing with "green" or ecologically responsive design objectives in mind is vital. We may think of cars and factories as the most obvious enemies of the environment, but buildings consume half of the energy used world wide. The idea of this thesis project was to explore the possibilities of sustainable strategies.That is to develop an energy intensive building based on ecological principles as design tools that demonstrate the economic value of sustainability, and to highlight an energy intensive building type as an example of energy-responsive-living that actually 'looks good'. / Master of Architecture

Thesis (M.S.P.H.)--University of Michigan, 1941.

Thesis (M.S.P.H.)--University of Michigan, 1941.

The anti-estrogenic properties of birdsfoot trefoil (Lotus corniculatus) and yellow pine (Pinus ponderosa) needles were studied. Oral administration of a water-soluble fraction of an acetone extract of birdsfoot trefoil was found to decrease uterine weight of immature female mice. The estrous cycles of rats receiving this extract in the ration, were not disturbed. Specially prepared aqueous fractions of an acetone extract of yellow pine needles decreased the uterine weight of mice. In further experiments, immature female mice were fed 0.040 mcgms. and 0.020 mcgms. diethylstilbestrol (D.E.S.) per gram of feed. When a water-soluble fraction of pine needle extract was administered, it did not affect uterine weight significantly in the 0.040 mcgm. D.E.S. group, but markedly and significantly decreased uterine weight in the 0.020 mcgm. D.E.S. group. This pine needle extract also interrupted the estrous cycles of mature rats, causing a prolonged diestrus. Chromatographic studies indicated that the pine extracts probably do not owe their anti-estrogenic activity to pinosylvin or its mono-methyl ether. / Land and Food Systems, Faculty of / Graduate

Background: Measuring CD4 levels is the key laboratory investigation for decision making when initiating HAART, a tertiary prevention measure to reduce HIV/AIDS mortality and morbidity. Inherent biological and analytical variability is common during CD4 enumeration. We cannot control biological variation but how significant is analytical variation to clinical decision making. Objectives: To quantify inter and intra laboratories analytical variation of CD4 counts and percentages and to determine the degree to which time lapse after sample collection contributes to the analytical coefficient of variation (CV%).To estimate the extent of disease misclassification due to CD4 variability if CD4 < 350cells/mm3. Setting: This study was conducted at the HIV clinics of RSSC Hospital, a sugar-cane estate health institution located on the north-east of Swaziland, in Lubombo district, the worst affected by HIV/AIDS in Swaziland. The laboratories involved were Lancet, Good Shepherd (GSH) and National Reference (NRL) laboratories. Study design and method: An analytical diagnostic, cross-sectional (observational) study was used in this study. Using a convenience sampling technique and after obtaining consent from participants, blood was collected in EDTA tubes and sub-divided into three samples, each for Lancet, GSH and NRL. The samples were further split into two at each respective laboratory, one of which was run at 12hours and the other at 24hours from the time of sample collection. Main outcome measures: Student t-test; analytical coefficient of variation (CV%); Bland and Altman (BA) method bias and limits of confidence; BA plots and percentage difference plots; concordance correlation, Pearson and Kappa coefficients; McNemar test for comparison of paired proportion. Results: Fifty three participants consented for participation and of these twenty eight participants were male. The mean CD4 was 373.4 cells/mm3 for Lancet, 395.9 cells/mm3 for NRL and 439.2 cells/mm3 for GSH and subsequent paired t-test revealed some inherent variability. The CV% for CD4 count was 3.5%, 8.4% and 20.1 whilst bias was 7.0, 13.5 and 8.2 for NRL, Lancet and GSH respectively. CD4% had even stronger CV% for all three laboratories. Inter-laboratory bias for Lancet/NRL was -31.5; -64.3 for Lancet/GSH and -38.2 for NRL/GSH at 12hours for CD4 count with only Lancet/GSH having a clinically interchangeable limit of agreement. At 24hours, the trends were similar, possibly confirming stability of CD4 between 12 and 24hours. An assessment of disease misclassification at HAART initiation threshold was performed. The agreement was 81.1% for Lancet/NRL, 88.7% for Lancet/GSH and 77.4% for NRL/GSH corresponding to Kappa values of 0.64, 0.77 and 0.55 respectively. McNemar test for paired proportions revealed that there were no differences between the laboratories when it came to initiating HAART. Conclusions: whilst intra-laboratory variability is minimal, there is some significant inter-laboratory variation of CD4 count and CD4% at the laboratories used in Swaziland. Swaziland should ensure standard SOPs, on -going training and continuous quality improvements for all national laboratories and ensure standards are on par with international recommendations. The national HIV guidelines should possibly enforce two different CD4 counts in decision making to reduce systematic errors. Meanwhile, clinicians should continue to use their clinical judgment in cases of suspicious CD4 count results. / Dissertation (MSc)--University of Pretoria, 2011. / School of Health Systems and Public Health (SHSPH) / Unrestricted

A dissertation submitted in fulfilment of the requirements for the degree of Master of Science to the Faculty of Science, University of the Witwatersrand, Johannesburg, 2017 / Transcription factors are proteins that are involved in the regulation of gene expression and are responsible for the tight control of transcription allowing a cell to react to changes in its environment. Transcription factors are thus highly regulated by a variety of mechanisms which include phosphorylation. Forkhead box P2 (FOXP2) is a transcription factor expressed in multiple tissues during embryonic development. FOXP2 like other FOX proteins contains a DNA binding domain known as the forkhead domain (FHD). The effect of phosphorylation of serine 557 in the FHD on the structure and DNA binding was done using a glutamate mutant (to mimic phosphorylation) and an alanine mutant (as a control). Structural characterisation was performed using size exclusion chromatography (SEC), intrinsic fluorescence and far-UV circular dichroism. The effect of phosphorylation on DNA binding was observed using electrophoretic mobility shift assay (EMSA) and isothermal titration calorimetry (ITC). Far-UV circular dichroism and intrinsic fluorescence of the mutants and wild type did not reveal any significant secondary or tertiary structural changes. SEC however revealed a decrease in dimerisation propensity in the Ser557 mutants when compared the wild type (WT). EMSA revealed that DNA binding of S557E is only observed at protein concentrations 40 times in excess of the DNA. DNA binding of the WT and S557A mutants is observed at 5 times and 20 times excess protein respectively. However, using ITC no DNA binding is observed for either S557E or S557A FOXP2 FHD. Thus, it is possible that phosphorylation of serine 557 in the FOXP2 FHD could be a mechanism for inactivation of FOXP2. / XL2017

Chemical and biological agents can cause serious adverse occupational health effects, and can adversely impact environmental health. Adverse incidents occur in laboratories using chemical, biological and radiologic agents, and laboratories pose a number of dangers to workers. Adverse incidents occur more frequently in teaching and research institutions when compared to industrial laboratories. Good laboratory safety practices, including the use of personal protective equipment, can reduce the number and severity of laboratory accidents, thus reducing the risk of chemical, biological and radiologic exposure for workers and for the public. Improving laboratory safety training should also result in fewer lab accidents. This study was conducted at a mid-sized Midwestern research university. The study population consisted of people who had attended a laboratory safety training session in 2010, 2011 or 2012. Following administration of a pilot survey and development of additional items, a sample (N=451) of the total population (N=936) received a survey inquiring about the use of personal protective equipment, and about laboratory safety training. 143 completed surveys were returned. The survey was based on the Theory of Planned Behavior (Ajzen, 1991). Theoretical constructs investigated included personal protective equipment attitude, subjective norm, behavioral control, behavioral intention, past self-reported behavior, and safety training attitude. Multiple regression showed that the overall model accounted for 56% of the variability in the study population. Subjective norm was the theoretical construct most strongly predictive of behavioral intention (B=.653, p=.001). Attitude was next most strongly predictive of intention (B=.343, p=.001). Behavioral control was not significantly correlated with behavioral intention. There was a positive significant correlation between training attitude and behavioral intention (Pearson's r = 0.233, p=.006, 2-tailed). There was also a positive significant correlation between attitude toward personal protective equipment, and attitude toward training (Pearson's correlation coefficient was 0.332, p=.001, 2-tailed). Self-reported behavior was regressed on the three theoretical constructs. Subjective norm was most significantly predictive of self-reported behavior (B = .523, p= .001), followed by attitude (B = .281, p= .034). Behavioral control was not significantly predictive of self-reported behavior. The study determined that about 80% of respondents felt that their lab was usually or always a safe place to work, although 40% reported having been injured in a lab. Training can be improved by emphasizing the importance of subjective norm, by clarifying the responsibilities of lab supervisors, and by providing additional information regarding how to obtain, use, and care for personal protective equipment. Use of personal protective equipment may be increased by emphasizing the importance of subjective norm during training.