2, N6, and 5'-substituted adenosine derivatives were synthesized via alkylation of 2-oxypurine nucleosides leading to 2-arylalkylether derivatives. 2-(3-(Indolyl)ethyloxy)adenosine 17 was examined in both binding and cAMP assays and found to be a potent agonist of the human A2BAR. Simplification, altered connectivity, and mimicking of the indole ring of 17 failed to maintain A2BAR potency. Introduction of N6-ethyl or N6-guanidino substitution, shown to favor A2BAR potency, failed to enhance potency in the 2-(3-(indolyl)ethyloxy)adenosine series. Indole 5' '- or 6' '-halo substitution was favored at the A2BAR, but a 5'-N-ethylcarboxyamide did not further enhance potency. 2-(3' '-(6' '-Bromoindolyl)ethyloxy)adenosine 28 displayed an A2BAR EC50 value of 128 nM, that is, more potent than the parent 17 (299 nM) and similar to 5'-N-ethylcarboxamidoadenosine (140 nM). Compound 28 was a full agonist at A2B and A2AARs and a low efficacy partial agonist at A1 and A3ARs. Thus, we have identified and optimized 2-(2-arylethyl)oxo moieties in AR agonists that enhance A2BAR potency and selectivity.
The benefits of three simple modifications to the design of a Birkbeck bedload slot-sampling system that has been continuously operating in Nahal Eshtemoa, Israel, since the early 1990s are demonstrated. The modifications include the deployment of a removable slot cover which delays the accumulation of sediment, so allowing sampling at late stages of a flood and, in conjunction with other samplers, extending the period of sampling during a flood wave; inclusion of a slot the size of which is adjustable so that that the probability of sampling the largest clast sizes in transit as bedload can be increased post-installation, once knowledge is gained about the bedload grain-size distribution; and a sampler side-wall door that allows stratification and textural changes within the accumulated bedload to be identified, so promoting intelligent sampling of the deposit for grain-size determination. Results from seven flash-floods are presented and discussed, with recommendations for bedload monitoring, particularly in rivers where sediment flux is high and dynamic sediment records are inevitably short because of instrumental limitations. Figure 1. (a) Upstream view of the approach reach and the five Birkbeck samplers in Nahal Eshtemoa. The pecked line separates finer (A) and coarser (B) textural patches of the channel flat at the time of photography. C and L samplers were closed when the photograph was taken. Channel width is 6 m. (b) Downstream view of RC and C samplers, with slot openings of 165 and 110 mm, respectively. (c) Schematic diagram of the Birkbeck samplers and sediment monitoring station on Nahal Eshtemoa. This figure is available in colour online at www.interscience.wiley.com/journal/espl 320 N. Bergman et al.Figure 3. Relation between the largest clast size (D maxb ) in each time slice or facies and the contemporary average cross-sectional boundary shear stress. Pecked lines denote slot widths of 110 and 165 mm. L = left sampler, LC = left centre, C = centre, RC = right centre, R = right.
N. Bergman et al.interest in the entrainment of coarser fractions and an assessment of the hydraulic conditions under which the state of equal mobility of all grain sizes is reached (Parker and Klingeman, 1982).Deployment of a slot cover is useful in revealing bedload processes (e.g. bedload waves and other mobile bedforms) and bedload dynamics that occur at later stages of the flood hydrograph, processes that cannot be observed if sampling duration is shortened by the rate at which the sampler pit fills. A number of adjacent samplers could incorporate covers, the sequential release of which would allow consecutive operation at predetermined water stages and, hence, prolong the sampling period. Manual operation could be replaced by pre-programmed covers that automatically open without the need for an operator to be present at the site. The disadvantage of collecting data this way is that mean cross-sectional transport rates would not be calculable. Consequently, this option eliminates one of the Birkbeck system's virtues ...
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