Meteorological influences on coastal sea levels west of Port Phillip and their engineering significance

This report presents the results of an analysis of three years of tide and meteorological data aimed at delineating the influences of atmospheric pressure, waves, onshore winds and longshore winds on coastal sea levels West of Port Phillip Bay, Victoria« The data was used to develop predictive and hindcasting techniques for meteorological tides on the Otway Coast, using statistical methods, an empirical method and a mathematical model. The nature and magnitude of contributions of the various components of the meteorological tide, and the general variability of monthly and seasonal variations were also studied. It was found that meteorological tides on the Otway Coast can account for significant sea level changes, with the main factors being wind and atmospheric pressure. The wind component of the meteorological tide was found to be approximately twice the pressure component, and longshore winds were found to be more significant than onshore winds for wind setup on the Otway Coast. The meteorological tide models developed enable estimates of wind setup and atmospheric pressure setup on the Otway Coast to be readily computed using data from synoptic charts. The wave setup component could not be separated from the meteorological tide and is included in the wind setup component. The results of the investigation are relevant to the design and maintenance of coastal engineering works, and point to the need for the establishment and operation of coastal management schemes on the Otway Coast

Fast acting allosteric phosphofructokinase inhibitors block trypanosome glycolysis and cure acute African trypanosomiasis in mice

The parasitic protist Trypanosoma brucei is the causative agent of Human African Trypanosomiasis, also known as sleeping sickness. The parasite enters the blood via the bite of the tsetse fly where it is wholly reliant on glycolysis for the production of ATP. Glycolytic enzymes have been regarded as challenging drug targets because of their highly conserved active sites and phosphorylated substrates. We describe the development of novel small molecule allosteric inhibitors of trypanosome phosphofructokinase (PFK) that block the glycolytic pathway resulting in very fast parasite kill times with no inhibition of human PFKs. The compounds cross the blood brain barrier and single day oral dosing cures parasitaemia in a stage 1 animal model of human African trypanosomiasis. This study demonstrates that it is possible to target glycolysis and additionally shows how differences in allosteric mechanisms may allow the development of species-specific inhibitors to tackle a range of proliferative or infectious diseases