Review of Nuclear Thermal Propulsion Ground Test Options

High efficiency rocket propulsion systems are essential for humanity to venture beyond the moon. Nuclear Thermal Propulsion (NTP) is a promising alternative to conventional chemical rockets with relatively high thrust and twice the efficiency of highest performing chemical propellant engines. NTP utilizes the coolant of a nuclear reactor to produce propulsive thrust. An NTP engine produces thrust by flowing hydrogen through a nuclear reactor to cool the reactor, heating the hydrogen and expelling it through a rocket nozzle. The hot gaseous hydrogen is nominally expected to be free of radioactive byproducts from the nuclear reactor; however, it has the potential to be contaminated due to off-nominal engine reactor performance. NTP ground testing is more difficult than chemical engine testing since current environmental regulations do not allow/permit open air testing of NTP as was done in the 1960's and 1970's for the Rover/NERVA program. A new and innovative approach to rocket engine ground test is required to mitigate the unique health and safety risks associated with the potential entrainment of radioactive waste from the NTP engine reactor core into the engine exhaust. Several studies have been conducted since the ROVER/NERVA program in the 1970's investigating NTP engine ground test options to understand the technical feasibility, identify technical challenges and associated risks and provide rough order of magnitude cost estimates for facility development and test operations. The options can be divided into two distinct schemes; (1) real-time filtering of the engine exhaust and its release to the environment or (2) capture and storage of engine exhaust for subsequent processing

Energy expenditure estimation using accelerometry and heart rate for multiple sclerosis and healthy older adults

Accurate estimation of Energy Expenditure (EE) in ambulatory settings provides greater insight into the underlying relation between different human physical activity and health. This paper describes the development and validation of energy expenditure estimation algorithms. A total of 4 healthy subjects and 3 suffering from multiple sclerosis were monitored using a gold-standard energy expenditure measurement system, a heart rate monitor and accelerometry. We demonstrated that greater improvements can be achieved by estimating energy expenditure during normal activities of daily living by combining both whole body acceleration estimates, vertical body acceleration estimates, body posture and heart rate data as part of a flex heart rate algorithm in subject specific models when compared to using accelerometry or heart rate data alone. This will allow more accurate EE estimation during normal activities of daily living

Discovery of a novel chemotype of potent human ENaC blockers using a bioisostere approach. Part 2: α-Branched quaternary amines

We report the synthesis and biological evaluation of a series of novel α-branched pyrazinoyl quaternary amines for their ability to block ion transport via the epithelial sodium channel (ENaC) in human bronchial epithelial cells (HBECs). Compound 12g has an IC50 of 37 nM and is highly efficacious in the Guinea-pig tracheal potential difference (TPD) model of ENaC blockade with an ED50 of 1 μgkg-1 at 1 h. In addition the SAR results demonstrate for the first time the chiral nature of the binding site of human ENaC. As such, pyrazinoyl quaternary amines represent a promising new class of ENaC blockers for the treatment of cystic fibrosis that are structurally distinct from the pyrazinoyl guanidine chemotype found in prototypical ENaC blockers such as amiloride

Discovery of a novel chemotype of potent human ENaC blockers using a bioisostere approach. Part 1: Quaternary amines

We report the identification of a novel series of human epithelial sodium channel (ENaC) blockers that are structurally distinct from the pyrazinoyl guanidine chemotype found in prototypical ENaC blockers such as amiloride. Following a rational design hypothesis a series of quaternary amines were prepared and evaluated for their ability to block ion transport via ENaC in human bronchial epithelial cells (HBECs). Compound 11 has an IC50 of 200 nM and is efficacious in the Guinea-pig tracheal potential difference (TPD) model of ENaC blockade with an ED50 of 44 μg kg−1 at 1 h. As such, pyrazinoyl quaternary amines represent the first examples of a promising new class of human ENaC blockers

Inhibition of PAD4 activity is sufficient to disrupt mouse and human NET formation

PAD4 has been strongly implicated in the pathogenesis of autoimmune, cardiovascular and oncological diseases through clinical genetics and gene disruption in mice. New selective PAD4 inhibitors binding a calcium-deficient form of the PAD4 enzyme have validated the critical enzymatic role of human and mouse PAD4 in both histone citrullination and neutrophil extracellular trap formation for, to our knowledge, the first time. The therapeutic potential of PAD4 inhibitors can now be explored