The long terminal repeat (LTR) regulates gene expression of HIV-1 by interacting with multiple host and viral factors. Cross-sectional studies in the pre-HAART era demonstrated that single nucleotide polymorphisms (SNPs) in peripheral blood-derived LTRs (a C-to-T change at position 3 of C/EBP site I (3T) and at position 5 of Sp site III (5T)) increased in frequency as disease severity increased. Additionally, the 3T variant correlated with HIV-1-associated dementia. LTR sequences derived by longitudinal sampling of peripheral blood from a single patient in the DrexelMed HIV/AIDS Genetic Analysis Cohort resulted in the detection of the 3T and 5T coselected SNPs before the onset of neurologic impairment, demonstrating that these SNPs may be useful in predicting HIV-associated neurological complications. The relative fitness of the LTRs containing the 3T and/or 5T co-selected SNPs as they evolve in their native patient-derived LTR backbone structure demonstrated a spectrum of basal and Tat-mediated transcriptional activities using the IIIB-derived Tat and colinear Tat derived from the same molecular clone containing the 3T/5T LTR SNP. In silico predictions utilizing colinear envelope sequence suggested that the patient's virus evolved from an X4 to an R5 swarm prior to the development of neurological complications and more advanced HIV disease. These results suggest that the HIV-1 genomic swarm may evolve during the course of disease in response to selective pressures that lead to changes in prevalence of specific polymorphisms in the LTR, env, and/or tat that could predict the onset of neurological disease and result in alterations in viral function.
Sharply reduced catchment inflows across Australia around the end of the twentieth Century led to a sequence of water restrictions followed, as the drought persisted, by approximately $10 billion of investments in desalination plants near Perth, Adelaide, Melbourne, Sydney and Brisbane. This Deakin University project jointly with Griffith University, for the National Centre of Excellence in Desalination (NCEDA), follows these new investments. We ask how best to manage bulk water supply and retail supply given the facts and fears of uncertain rainfall, modelled over a 100 year simulation period. We use Monte Carlo style studies aiming to capture the new tensions and trade-offs regarding uncertain climate, rainfall and water supply. There are presently no comprehensive life-cycle approaches to model city water balances that incorporate economic feedbacks, such as tariff adjustment, which can in turn create a financing capacity for such investment responses to low catchment levels, models that could provide significant policy implications for water planners. This project addresses the gap, and presents excerpt from a system dynamics model that augments the usual water utility representation of the physical linkages and water grids. We add interconnected feedback loops in tariff structures, demand levels and financing capacity. Tariffs are reset in association with drought and the modelling of responses both in terms of reduced consumption and increased revenue of the utility, depending on the elasticity's of demand responses to higher tariffs, both short and long term, while also allowing
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