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Background/Objectives:: Our objective was to assess the sustained, low-dose and constant administration of the thyroid receptor-ß (TRß)-selective agonist GC-1 (sobetirome) from a novel nanochannel membrane device (NMD) for drug delivery. As it known to speed up metabolism, accomplish weight loss, improve cholesterol levels and possess anti-diabetic effects, GC-1 was steadily administered by our NMD, consisting of an implantable nanochannel membrane, as an alternative to conventional daily administration, which is subject to compliance issues in clinical settings. Subjects/Methods:: Diet-induced obese C57BL/J6 male mice were fed a very high-fat diet (VHFD) and received NMD implants subcutaneously. Ten mice per group received capsules containing GC-1 or phosphate-buffered saline (control). Weight, lean and fat mass, as well as cholesterol, triglycerides, insulin and glucose, were monitored for 24 days. After treatment, plasma levels of thyroid-stimulating hormone (TSH) and thyroxine were compared. mRNA levels of a panel of thermogenic markers were examined using real-time PCR in white adipose tissue (WAT) and brown adipose tissue (BAT). Adipose tissue, liver and local inflammatory response to the implant were examined histologically. Pancreatic islet number and ß-cell area were assessed. Results:: GC-1 released from the NMD reversed VHFD-induced obesity and normalized serum cholesterol and glycemia. Significant reductions in body weight and fat mass were observed within 10 days, whereas reductions in serum cholesterol and glucose levels were seen within 7 days. The significant decrease in TSH was consistent with TRß selectivity for GC-1. Levels of transcript for Ucp1and thermogenic genes PGC1a, Cidea, Dio2and Cox5ashowed significant upregulation in WAT in NMD–GC-1-treated mice, but decreased in BAT. Although mice treated by NMD–GC-1 showed a similar number of pancreatic islets, they exhibited significant increase in ß-cell area. Conclusions:: Our data demonstrate that the NMD implant achieves steady administration of GC-1, offering an effective and tightly controlled molecular delivery system for treatment of obesity and metabolic disease, thereby addressing compliance.

Methods of analysing the response of germination to constant temperature are extended to alternating temperatures. The analysis is illustrated for seeds of pearl millet (Pennisetum typhoides S. & H.) germinated on a thermal gradient plate in pairs of alternating temperatures ranging from 15�C to 47�C. Alternating temperatures had a small but systematic effect on germination rate such that below 42 �C, alternations in temperature had no effect on the maximum fraction of seeds which germinated in the population, but increases in temperature amplitude from zero to �8 �C caused a small but systematic increase in the rate of germination.

The germination of pearl millet (Pennisetum typhoides S. & H.) seeds was investigated at constant temperatures between 12 �C and 47 �C on a thermal gradient plate. The rate of germination increased linearly with temperature from a base Tb to a sharply defined optimum To beyond which the rate decreased linearly with temperature, reaching zero at Tm. The linearity of the response both above and below To allowed time and temperature to be combined in a thermal time at which a specified fraction of the seeds germinated. Within the population Tb and Tm were constant.

Seeds of pearl millet were germinated on wet filter paper at temperatures up to 50 �C. In one experiment, the temperature was held at 50 �C during imbibition and was then lowered to 32 �C or 25 �C. Germination rate and the maximum fraction of seeds germinating (Gm) both decreased as the time of exposure to 50 �C increased. In contrast, exposure to 50 �C after imbibition for 8 h slowed germination but did not significantly reduce Gm. When the ‘high’ temperature imposed after imbibition was reduced from 50 �C to 45 �C, there was a small reduction in the rate of germination but not in Gm. The responses have implications for the optimum time of sowing in the tropics when maximum daytime soil temperature at the depth of sowing is in the range of 45–50 �C.