Unmanned and uncontrolled: The commingling theory and the legality of unmanned aircraft system operations

In 2002 Australia became the first nation to promulgate certification standards for the commercial use of drones or unmanned aircraft systems (UAS). Since that time the Australian Civil Aviation Safety Authority (CASA) has played a key role both domestically and internationally through the International Civil Aviation Organization (ICAO) in assisting to develop technical guidance materials that will enable contracting states to develop UAS regulations. An arduous component of this task is the fact that all existing aircraft are capable of being unmanned. Moreover, given the unbounded nature of aircraft operations, UAS regulations necessarily require international harmonisation. But the objective of developing universal UAS standards is still far from being finalised while the accelerating pace of UAS technological development continues to challenge traditional regulatory regimes and legal systems throughout the world. This paper considers the broader legal issues associated with civilian UAS operations and their integration into unsegregated civilian airspace. The Australian UAS regulatory experience is examined with some unique constitutional limitations identified in relation to the application of the so-called ‘commingling theory’. It is contended that such limitations may render void existing UAS regulation in certain situations – many of which are related to the operation of small UAS and may have significant privacy implications. In particular this paper finds that the regulations purporting to control the operation of systems that are not capable of commingling with aircraft operating within navigable airspace are ultra vires and hence of no legal effect. In concluding this paper strongly asserts that if the commercial benefits attendant to UAS operations is to be fully realised then their risks to society must be controlled through domestic legislation that is harmonised and consistent with internationally agreed guidelines

Endothelins regulate Mrp2-mediated transport in killifish (fundulus hetroclitus) renal proximal tubules

Item does not contain fulltext2 p

Contribution of multidrug resistance protein 2 (MRP2/ABCC2) to the renal excretion of p-aminohippurate (PAH) and identification of MRP4 (ABCC4) as a novel PAH transporter.

Contains fulltext : 58753.pdf (publisher's version ) (Closed access)p-Aminohippurate (PAH) is the classical substrate used in the characterization of organic anion transport in renal proximal tubular cells. Although basolateral transporters for PAH uptake from blood into the cell have been well characterized, there is still little knowledge on the apical urinary efflux transporters. The multidrug resistance protein 2 (MRP2/ABCC2) is localized to the apical membrane and mediates ATP-dependent PAH transport, but its contribution to urinary PAH excretion is not known. In this report, we show that renal excretion of PAH in isolated perfused kidneys from wild-type and Mrp2-deficient (TR(-)) rats is not significantly different. Uptake of [(14)C]PAH in membrane vesicles expressing two different MRP2 clones isolated from Sf9 and MDCKII cells exhibited a low affinity for PAH (Sf9, 5 +/- 2 mM; MDCKII, 2.1 +/- 0.6 mM). Human MRP4 (ABCC4), which has recently been localized to the apical membrane, expressed in Sf9 cells had a much higher affinity for PAH (K(m) = 160 +/- 50 microM). Various inhibitors of MRP2-mediated PAH transport also inhibited MRP4. Probenecid stimulated MRP2 at low concentrations but had no effect on MRP4; but at high probenecid concentrations, both MRP2 and MRP4 were inhibited. Sulfinpyrazone only stimulated MRP2, but inhibited MRP4. Real-time PCR and Western blot analysis showed that renal cortical expression of MRP4 is approximately fivefold higher as compared with MRP2. MRP4 is a novel PAH transporter that has higher affinity for PAH and is expressed more highly in kidney than MRP2, and may therefore be more important in renal PAH excretion

Human organic anion transporter MRP4 (ABCC4) is an efflux pump for the purine end metabolite urate with multiple allosteric substrate binding sites.

Contains fulltext : 47658.pdf (publisher's version ) (Closed access)The end product of human purine metabolism is urate, which is produced primarily in the liver and excreted by the kidney through a well-defined basolateral blood-to-cell uptake step. However, the apical cell-to-urine efflux mechanism is as yet unidentified. Here, we show that the renal apical organic anion efflux transporter human multidrug resistance protein 4 (MRP4), but not apical MRP2, mediates ATP-dependent urate transport via a positive cooperative mechanism (K(m) of 1.5 +/- 0.3 mM, V(max) of 47 +/- 7 pmol x mg(-1) x min(-1), and Hill coefficient of 1.7 +/- 0.2). In HEK293 cells overexpressing MRP4, intracellular urate levels were lower than in control cells. Urate inhibited methotrexate transport (IC50 of 235 +/- 8 microM) by MRP4, did not affect cAMP transport, whereas cGMP transport was stimulated. Urate shifted cGMP transport by MRP4 from positive cooperativity (K(m) and V(max) value of 180 +/- 20 microM and 58 +/- 4 pmol x mg(-1) x min(-1), respectively, Hill coefficient of 1.4 +/- 0.1) to single binding site kinetics (K(m) and V(max) value of 2.2 +/- 0.9 mM and 280 +/- 50 pmol x mg(-1) x min(-1), respectively). Finally, MRP4 could transport urate simultaneously with cAMP or cGMP. We conclude that human MRP4 is a unidirectional efflux pump for urate with multiple allosteric substrate binding sites. We propose MRP4 as a candidate transporter for urinary urate excretion and suggest that MRP4 may also mediate hepatic export of urate into the circulation, because of its basolateral expression in the liver

Urinary Content of Aquaporin-1 and Aquaporin-2 in Nephrogenic Diabetes-Insipidus

Item does not contain fulltex

Urinary content of aquaporin 1 and 2 in nephrogenic diabetes insipidus

Item does not contain fulltext6 p

Endothelin B receptor-mediated regulation of ATP-driven drug secretion in renal proximal tubule

Item does not contain fulltext9 p