Response experiments, dose

Lowcst-Obsciwcd-Advcrsc-El fcct-Lcvel (LOAEL) In dose-response experiments, the lowest exposure level at which there are statistically or biologically significant increases in frequency or severity of adverse effects between the exposed population and its appropriate control group. 

FIGURE 3.4 Results from the May 2000 dose-response experiment conducted in situ within mesocosms installed at 4 sites in the Florida Everglades and using isotopically labeled Hg. Experimental conditions called for dosing at 0.5, 1.0, and 2.0 times the ambient loading rate... 

SAR). In addition, small molecules have the advantage of being suitable for dose response experiments that are helpful in validating borderline hits from the kinome siRNA libraries. 

Polyacetylenes are toxic to a broad range of organisms (39) but are especially toxic to insects. At 0.5 ppm, 9 of 14 compounds tested were toxic to first instar mosquito larvae (Aedes aegypti) in 30 min treatments with sources of near UV (15 W/m ) (40). The compounds were more active in sunlight. For example CX-T killed second instar larvae Instantaneously at 4 ppm. Compounds VTI, Ct-T and PHT were especially active and were selected for further testing in dose response experiments (41). For similar near UV treatments, the LC50 for a-T was 19 ppb,... 

For example, in the two largest laboratory-controlled dose-response experiments conducted to date on the neurobehavioral effects of chronic sleep restriction, cumulative increases were evident in the average number of PVT lapses per 24 hr across days of sleep restricted to 3, 4, 5, and 6 hr per night... 

Scytonemin-containing cyanobacterial sheaths are estimated to attenuate more than 88% of incident UVA radiation (at 370 nm).194 Several studies have demonstrated the ability of scytonemin to prevent UV-induced damage in cells, and these results have generally demonstrated that the presence of scytonemin does increase the UV tolerance of cyanobacteria. Dose response experiments with strains of the terrestrial/freshwater cyanobacterium Tolypothrix, with and without scytonemin in the filament sheaths, show that a nonpigmented sheath results in greater UV... 

Laboratory iron-addition dose-response experiment... 

Moreover, to ensure that the drug effects observed are not due to intrinsic effects of the test substance on social exploration, it is desirable to precede the main social recognition experiment by a prior dose-response experiment to ensure that the selected doses do not affect baseline social investigation. 

In the second experiment, mice were irradiated with the highest dose from the dose-response experiment. Concentrations of lipid hydroperoxides and lipophilic antioxidants were measured simultaneously on single skin samples from irradiated and non-irradiated sides of each mouse. The lipid hydroperoxide assay directly measured lipid peroxidation and thus was superior to the TBARS assay, which is indirect. Lipid-peroxyl radicals have been linked to chemically induced cutaneous carcinogenesis [31] as well as to UV-light-induced cutaneous carcinogenesis [32],... 

It is now clear that an LDP line that is not straight may represent a resistant population. This may not be as obvious as it may seem. In the normal dose-response experiment with perhaps five groups of insects, there may be only three or four points with which the line is based (e.g., if one of the dose results in either 0% or 100% mortality). In this case, a real break or plateau in the curve could be overlooked. Tsukamoto (1963) discusses this problem and suggests that such experiments include more groups of insects, up to 8 to 10, in order that the direction of the line is more easily seen. 

Caprifoliaceae In a dose-response experiment, the IC50 value of ginkgetin (7) was estimated at 7.5 pM, suggesting it eould be a strong NF-kB inhibitor and worthy of study in vivo. ... 

Dose-response experiments typically use 10-20 doses, approximately spaced on a logarithmic scale. For example. 

We recommend performing two different immunoblot experiments First, a dose response experiment to determine an optimal dose of inhibitor, i.e., the lowest concentration that yields maximal response and second, a time course experiment that captures the effects of inhibitors (used at optimal dose) at various time points after TCR stimulation. Efficacious PTP inhibitors not only are expected to augment phosphorylation levels of substrates, but also to induce a sustained effect on these molecules, compared to the vehicle control. For instance, treatment of Jmkat T cells with the chemical probe MLl 19 [21 ] resulted in augmented and sustained phosphorylation of the MAP kinases ERKl/2 and p38 [22]. This effect was due to direct inhibition of HePTP PTPN7), a classical PTP that specifically dephosphorylates the phosphotyrosine residue in the activation loop of ERKl/2 andp38. 

In addition, these positives where confirmed in a competition assay with a positive control leaving 80 compounds for further characterization. The next validation step consisted of the determination of the K s via 10 point dose response experiments. This left 36 substances with well defined dose response in an affinity range from 10 to 60 iM for further characterization in X-ray crystallographic experiments. 

All specific primary positives were confirmed in a competition assay using a known high affinity active site binder as competitor compound followed by dose response experiments to determine the KD values. 

Hormetic dose responses often have been overlooked or dismissed incorrecdy or prematurely because the low-dose stimulation may not have achieved statistical significance. Given the mUd limits of enhancement of the (hormetic) stimulatory responses, the low-dose end of dose-response experiments should be sufficiently powered to affirm or deny the existence of hormesis. 

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