Symbiotic Supramolecular Chemistry - The Development of Smart Soaps

Supramolecular chemistry is continually being explored, applied and expanded in many countries all overthe world. The complexity of this area of science means that it is continually researched.This study has demonstrated the importance of the self-assembly between surfactants structuresand supramolecular aggregation. Within this thesis the design, synthesis, characterization and bindingproperties of five amphiphilic molecules are discussed. These molecules were investigated in the gaseousphase, solid and solution states by a variety of complementary analytical techniques with the resultsdemonstrating that the anionic monomers have a propensity to self-associate into a variety of aggregatedspecies.A selection of 1H and DOSY NMR experiments were conducted in DMSO-d6, providing evidencethat these molecules tend to form dimeric rather than larger aggregated species. The presence ofhydrogen bonding was further confirmed by 1H NMR self-association studies, showing a down fieldchange in chemical shift due to both the urea NH. The data when fitted to dimerization/Equal K (EK)binding model showed that the dimerization constant increases in line with the increase of aromaticsubstituents. By direct observation it was established that the sulfonate-anion molecules self-associatedthrough intermolecular hydrogen bonds to form aggregated species of either irregular or spherical shapein solution. The size and type of these species was both concentration, and solute dependent. CMC valuesand dimerization constants correlated well with the computationally derived Emax and Emin values, givingpreliminary evidence that self-association properties may be predicted by low level computationalmodelling methods. This innovative, cohesive branch of supramolecular chemistry will revolutionise thestudy and scope of non-covalent interactions beyond the molecule

Supramolecular Self-associating Amphiphiles (SSAs)

This thesis reports the synthesis of 30 structurally related compounds, related by stepwise variation of a hydrogen bond donor-acceptor amphiphilic salt. The self-associative and corresponding global properties of these compounds were investigated in the solid state, solution state and gas phase to enable elucidation of any structure-activity relationships. In the solution state, it was established that the molecular self-association of these compounds could be controlled through modification of the solvent environment. In organic DMSO these compounds principally form dimeric species and in an aqueous environment, spherical aggregates were preferentially formed. The addition of salt to the aqueous solution resulted in the generation of a hydrogel. The physicochemical properties and antimicrobial properties of these gelated materials were then investigated, where it was shown that these hydrogels exhibit antimicrobial properties against both Gram-negative and Gram-positive bacteria. Finally, a tool-kit of novel high-throughput microplate reader technology was developed to assess the presence of dimers, spherical aggregates or fibres in the solution state

Hitting a Moving Target: A Model for Malaria Elimination in the Presence of Population Movement

South Africa is committed to eliminating malaria with a goal of zero local transmission by 2018. Malaria elimination strategies may be unsuccessful if they focus only on vector biology, and ignore the mobility patterns of humans, particularly where the majority of infections are imported. In the first study in Mpumalanga Province in South Africa designed for this purpose, a metapopulation model is developed to assess the impact of their proposed elimination-focused policy interventions. A stochastic, non-linear, ordinary-differential equation model is fitted to malaria data from Mpumalanga and neighbouring Maputo Province in Mozambique. Further scaling-up of vector control is predicted to lead to a minimal reduction in local infections, while mass drug administration and focal screening and treatment at the Mpumalanga-Maputo border are predicted to have only a short-lived impact. Source reduction in Maputo Province is predicted to generate large reductions in local infections through stemming imported infections. The mathematical model predicts malaria elimination to be possible only when imported infections are treated before entry or eliminated at the source suggesting that a regionally focused strategy appears needed, for achieving malaria elimination in Mpumalanga and South Africa

Fire management in a changing landscape: a case study from Lopé National Park, Gabon

A key management goal in Lopé National Park, Gabon, is to protect regionally-rare savannah ecosystems within the continuous rainforest block. In order to evaluate the impact of existing protection efforts, data on burning season environmental conditions, burning effort and current woody values for savannahs were examined between 1995 and 2008. Results showed (a) spatial heterogeneity in woody values to be correlated with grassy vegetation type (b) a negative relationship between woody vegetation and fire return frequency over the study, suggesting that decreased fire return frequency may favour savannah thickening and (c) that inconsistent burn effort by Park staff, and burns designed for reduced heat, may limit the efficiency of fire to prevent savannah thickening or forest expansion. Optimal humidity and fuel moisture conditions for burning are identified and recommendations made for improving the existing fire plan to achieve the management goal. Modifications will require significant investment of resources and training and require urgent experimental work to disentangle the direct impacts of fire from other processes of vegetation change. Lopé's fire policy should ultimately be a dynamic response to change in the local landscape driven by direct fire impacts or by global climate change

MicroRNA Analysis of ATM-Deficient Cells Indicate PTEN and CCDN1 as Potential Biomarkers of Radiation Response

Genetic and epigenetic profile changes associated with individual radiation sensitivity are well documented and have led to enhanced understanding of the mechanisms of the radiation-induced DNA damage response. However, the search continues to identify reliable biomarkers of individual radiation sensitivity. Herein, we report on a multi-biomarker approach using traditional cytogenetic biomarkers, DNA damage biomarkers and transcriptional microRNA (miR) biomarkers coupled with their potential gene targets to identify radiosensitivity in ataxia-telangiectasia mutated (ATM)-deficient lymphoblastoid cell lines (LCL); ATM-proficient cell lines were used as controls. Cells were 0.05 and 0.5 Gy irradiated, using a linear accelerator, with sham-irradiated cells as controls. At 1 h postirradiation, cells were fixed for γ-H2AX analysis as a measurement of DNA damage, and cytogenetic analysis using the G2 chromosomal sensitivity assay, G-banding and FISH techniques. RNA was also isolated for genetic profiling by microRNA (miR) and RT-PCR analysis. A panel of 752 miR were analyzed, and potential target genes, phosphatase and tensin homolog (PTEN) and cyclin D1 (CCND1), were measured. The cytogenetic assays revealed that although the control cell line had functional cell cycle checkpoints, the radiosensitivity of the control and AT cell lines were similar. Analysis of DNA damage in all cell lines, including an additional control cell line, showed elevated γ-H2AX levels for only one AT cell line. Of the 752 miR analyzed, eight miR were upregulated, and six miR were downregulated in the AT cells compared to the control. Upregulated miR-152-3p, miR-24-5p and miR-92-15p and all downregulated miR were indicated as modulators of PTEN and CCDN1. Further measurement of both genes validated their potential role as radiation-response biomarkers. The multi-biomarker approach not only revealed potential candidates for radiation response, but provided additional mechanistic insights into the response in AT-deficient cells

An interactive application for malaria elimination transmission and costing in the Asia-Pacific

Leaders in the Asia-Pacific have endorsed an ambitious target to eliminate malaria in the region by 2030. The emergence and spread of artemisinin drug resistance in the Greater Mekong Subregion makes elimination urgent and strategic for the global goal of malaria eradication. Mathematical modelling is a useful tool for assessing and comparing different elimination strategies and scenarios to inform policymakers. Mathematical models are especially relevant in this context because of the wide heterogeneity of regional, country and local settings, which means that different strategies are needed to eliminate malaria. However, models and their predictions can be seen as highly technical, limiting their use for decision making. Simplified applications of models are needed to allow policy makers to benefit from these valuable tools. This paper describes a method for communicating complex model results with a user-friendly and intuitive framework. Using open-source technologies, we designed and developed an interactive application to disseminate the modelling results for malaria elimination. The design was iteratively improved while the application was being piloted and extensively tested by a diverse range of researchers and decision makers. This application allows several target audiences to explore, navigate and visualise complex datasets and models generated in the context of malaria elimination. It allows widespread access, use of and interpretation of models, generated at great effort and expense as well as enabling them to remain relevant for a longer period of time. It has long been acknowledged that scientific results need to be repackaged for larger audiences. We demonstrate that modellers can include applications as part of the dissemination strategy of their findings. We highlight that there is a need for additional research in order to provide guidelines and direction for designing and developing effective applications for disseminating models

Using Ripple Effects Maps to Identify Story Threads: A Framework to Link Private to Public Value

Extension professionals must demonstrate organizational value to garner public awareness and support. Measuring and communicating outcomes that have public value can be challenging. In this study, Ripple Effects Mapping incorporating the Community Capitals Framework was used to evaluate a childhood obesity prevention study, iCook 4-H, of youth-adult pairs in Maine. The objective was to describe the process of generating impact statements through story threads about program benefits to the participants and the potential benefits to nonparticipants, such as family members, friends, and other community members. Extension professionals can use storylines, or story threads, as a qualitative research technique to generate stories about private and public value from participants’ actions, experiences, and emotions following community programs. The story threads process can be used across disciplines to leverage community program data into public value messaging

Malaria elimination transmission and costing in the Asia-Pacific: developing an investment case

Background:; The Asia-Pacific region has made significant progress against malaria, reducing cases and deaths by over 50% between 2010 and 2015. These gains have been facilitated in part, by strong political and financial commitment of governments and donors. However, funding gaps and persistent health system challenges threaten further progress. Achieving the regional goal of malaria elimination by 2030 will require an intensification of efforts and a plan for sustainable financing. This article presents an investment case for malaria elimination to facilitate these efforts.; Methods:; A transmission model was developed to project rates of decline of; Plasmodium falciparum; and; Plasmodium vivax; malaria and the output was used to determine the cost of the interventions that would be needed for elimination by 2030. In total, 80 scenarios were modelled under various assumptions of resistance and intervention coverage. The mortality and morbidity averted were estimated and health benefits were monetized by calculating the averted cost to the health system, individual households, and society. The full-income approach was used to estimate the economic impact of lost productivity due to premature death and illness, and a return on investment was computed.; Results; : The study estimated that malaria elimination in the region by 2030 could be achieved at a cost of USD 29.02 billion (range: USD 23.65-36.23 billion) between 2017 and 2030. Elimination would save over 400,000 lives and avert 123 million malaria cases, translating to almost USD 90 billion in economic benefits. Discontinuing vector control interventions and reducing treatment coverage rates to 50% will result in an additional 845 million cases, 3.5 million deaths, and excess costs of USD 7 billion. Malaria elimination provides a 6:1 return on investment.; Conclusion:; This investment case provides compelling evidence for the benefits of continued prioritization of funding for malaria and can be used to develop an advocacy strategy

Prediction of DNA Damage and G2 Chromosomal Radio-Sensitivity Ex-vivo in Peripheral Blood Mononuclear Cells with Label-Free Raman Microspectroscopy

Liquid biopsies are a potentially rich store of biochemical information that can be linked to an individual’s response to therapeutic treatments, including radiotherapy, and which may ultimately play a role in the individualization of treatment regimens. Peripheral blood mononuclear cells (PBMCs) can be used for the biochemical profiling of the individual, but also, being living cells, can provide insights into the individuals response to ionizing radiation exposure

2020 American College of Rheumatology Guideline for the Management of Reproductive Health in Rheumatic and Musculoskeletal Diseases

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/154675/1/art41191.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/154675/2/art41191_am.pd