EELS: Autonomous snake-like robot with task and motion planning capabilities for ice world exploration.

Ice worlds are at the forefront of astrobiological interest because of the evidence of subsurface oceans. Enceladus in particular is unique among the icy moons because there are known vent systems that are likely connected to a subsurface ocean, through which the ocean water is ejected to space. An existing study has shown that sending small robots into the vents and directly sampling the ocean water is likely possible. To enable such a mission, NASA's Jet Propulsion Laboratory is developing a snake-like robot called Exobiology Extant Life Surveyor (EELS) that can navigate Enceladus' extreme surface and descend an erupting vent to capture unaltered liquid samples and potentially reach the ocean. However, navigating to and through Enceladus' environment is challenging: Because of the limitations of existing orbital reconnaissance, there is substantial uncertainty with respect to its geometry and the physical properties of the surface/vents; communication is limited, which requires highly autonomous robots to execute the mission with limited human supervision. Here, we provide an overview of the EELS project and its development effort to create a risk-aware autonomous robot to navigate these extreme ice terrains/environments. We describe the robot's architecture and the technical challenges to navigate and sense the icy environment safely and effectively. We focus on the challenges related to surface mobility, task and motion planning under uncertainty, and risk quantification. We provide initial results on mobility and risk-aware task and motion planning from field tests and simulated scenarios.

Sex-specific cognitive-behavioural profiles emerging from individual variation in numerosity discrimination in Gambusia affinis.

The relationship between an individual's cognitive abilities and other behavioural attributes is complex, yet critical to understanding how individual differences in cognition arise. Here we use western mosquitofish, Gambusia affinis, to investigate the relationship between individual associative learning performance in numerical discrimination tests and independent measures of activity, exploration, anxiety and sociability. We found extensive and highly repeatable inter-individual variation in learning performance (r = 0.89; ICC = 0.89). Males and females exhibited similar learning performance, yet differed in sociability, activity and their relationship between learning and anxiety/exploration tendencies. Sex-specific multivariate behaviour scores successfully predicted variation in individual learning performance, whereas combined sex analyses did not. Female multivariate behaviour scores significantly predict learning performance across females (ρ = 0.80, p = 0.005) with high-performing female learners differentiated from female non-learners and low-performing learners by significant contributions of activity and sociability measures. Meanwhile, males of different learning performance levels (high-, low- and non-learners) were distinguished from each other by unique behavioural loadings of sociability, activity and anxiety/exploration scores, respectively. Our data suggest that despite convergence on learning performance, the sexes diverge in cognitive-behavioural relationships that are likely products of different sexual selection pressures.

A dose proportionality study of eprosartan in healthy male volunteers.

The present study investigated the proportionality of exposure after single oral doses of 100, 200, 400, and 800 mg of eprosartan, a nonpeptide, nonbiphenyl angiotensin II receptor antagonist, in 23 healthy young men. Eprosartan was safe and well tolerated. Exposure to eprosartan increased with dose but in a less than proportional manner. For each two-fold dose increase, area under the concentration--time curve (AUC) increased an average of 1.6 to 1.8 times and maximum plasma drug concentration (Cmax) increased an average of 1.5 to 1.8 times. For both parameters, the greatest difference from the dose multiple was observed between the 400- and 800-mg doses. Dose proportionality of eprosartan, as assessed by an equivalence-type approach using the 100-mg dose as the reference and a 30% acceptance region (0.70, 1.43), was achieved for the 200- and 400-mg doses for AUC and the 200-mg dose for Cmax. The observed changes in the pharmacokinetics of eprosartan suggest slight saturation of absorption of eprosartan over the 100- to 800-mg dose range, most likely due to the physicochemical properties of the drug (pH-dependent aqueous solubility and lipophilicity).

Bioequivalence assessment of a single 5 mg/day testosterone transdermal system versus two 2.5 mg/day systems in hypogonadal men.

A novel, nonscrotal, transdermal delivery system for testosterone therapy has been marketed for treatment of hypogonadal men. The usual dose of this system is two 2.5 mg/day systems applied daily. A new system has been developed that administers a dose of 5 mg/day using a single patch rather than two patches. A randomized, steady-state, four-period, replicate-design, open-label, crossover study was conducted to assess the bioequivalence of the two testosterone transdermal delivery systems in postpubertal, hypogonadal men: two 2.5 mg/day patches as the reference regimen (R) and one 5 mg/day patch as the test regimen (T). 21 men were enrolled, and 20 completed the study. Each subject was randomly assigned to one of four sequences (R1-R2-T1-T2, T1-T2-R1-R2, R1-T1-T2-R2, T1-R1-R2-T2), such that each subject received each regimen during two study sessions. Two subjects were inadvertently treated according to the sequence T1-R1-T2-R2. Patches were applied to the upper arm, thigh, and back in the evening on days 1, 2, and 3, respectively, of each study session. Serial blood samples were obtained for pharmacokinetic analysis of testosterone for 24 hours after patch application on day 3 of each study session. The two formulations would be considered bioequivalent if the 90% confidence intervals (CI) for the ratios of the adjusted geometric means for T:R for both area under the concentration--time curve from 0 to 24 hours (AUC0-24) and maximum concentration (Cmax) were completely contained in the interval (0.80, 1.25). Mean values for AUC0-24 and Cmax were similar for the two formulations. The T and R formulations were found to be bioequivalent based on both AUC0-24 (90% CI 0.96, 1.08) and Cmax (90% CI 0.92, 1.07). The median time to Cmax was also similar, indicating comparable rates of testosterone absorption for both formulations. Based on this analysis, the testosterone transdermal system 5 mg/day patch is bioequivalent to two of the 2.5 mg/day patches. Both systems were safe and well tolerated in hypogonadal men.

Paroxetine does not affect the cardiac safety and pharmacokinetics of terfenadine in healthy adult men.

Potent CYP3A4 inhibitors such as ketoconazole can cause dangerous increases in plasma concentrations of the H-1 antagonist terfenadine. In light of recent reports that the selective serotonin reuptake inhibitor antidepressants may be weak CYP3A4 inhibitors, this study was designed to investigate the effects of paroxetine on the pharmacodynamic and pharmacokinetic profile of terfenadine. Twelve healthy male volunteers participated in a randomized open-label, two-period, steady-state crossover study. Terfenadine (60 mg twice daily for 8 days) was administered alone and with paroxetine at steady state (20 mg once daily for 15 days, with terfenadine on days 8 through 15). Extensive electrocardiogram monitoring was conducted throughout, and terfenadine and carboxyterfenadine pharmacokinetics were assessed at the end of each treatment period. One subject withdrew because of adverse experiences related to paroxetine, but the other 11 subjects completed the study uneventfully. On the final day of coadministration, the rate-corrected QT interval (QTc) was unaltered compared with terfenadine dosed alone; maximum QTc values (mean [SEM]) were 404 (4) and 405 (5) msec, respectively. Terfenadine pharmacokinetics were also unchanged; geometric mean steady-state area under the curve (AUC)tau values were 30.0 ng.hr/mL during coadministration compared with 30.8 ng.hr/mL when dosed alone (p > 0.05). The corresponding Cmax values were 3.68 and 3.64 ng/mL (p > 0.05). There was, however, a small (on average 17-20%), unexplained reduction in the steadystate Cmax and AUCtau of carboxyterfenadine during coadministration with paroxetine. In conclusion, paroxetine does not affect the pharmacokinetics or cardiovascular effects of terfenadine. The small reduction in carboxyterfenadine plasma concentrations is unlikely to be important clinically.

Effect of fluconazole on the pharmacokinetics of eprosartan and losartan in healthy male volunteers.

OBJECTIVE: To investigate the effect of steady-state fluconazole administration on the disposition of eprosartan, losartan, and E-3174. METHODS: Sixteen healthy male subjects received 300 mg eprosartan every 12 hours, and 16 received 100 mg losartan every 24 hours on study days 1 to 20. All 32 subjects received 200 mg fluconazole every 24 hours beginning on day 11 and continuing through day 20. Serial blood samples were collected over one dosing interval on study days 10 and 20 for measurement of plasma concentrations of eprosartan, losartan, and E-3174 (the active metabolite of losartan). RESULTS: There was no significant difference in eprosartan area under the concentration-time curve from time 0 to time of last quantifiable concentration [AUC(0-t)] or maximum concentration (Cmax) when administered alone and with fluconazole. After concomitant administration with fluconazole, losartan AUC(0-t) and Cmax were significantly increased 66% and 30%, respectively, compared with those values for losartan alone. The AUC(0-t) and Cmax for E-3174 were significantly decreased 43% and 56%, respectively, after administration of losartan with fluconazole. CONCLUSIONS: Fluconazole significantly increases the steady-state AUC of losartan and inhibits the formation of the active metabolite of losartan, E-3174. In contrast, fluconazole administration has no effect on the steady-state pharmacokinetics of eprosartan.

Dust emissions in cattle feedlots.

Dust emissions were measured at three Texas cattle feedlots on 15 occasions in 1987 to determine concentrations of total suspended particulate matter (TSP) and dust with 10 microns or less aerodynamic particle size (PM-10). Net feedlot dust concentrations (downwind minus upwind) ranged from 15.7 to 1,700.1 micrograms per m3 and averaged 412.4 +/- 271.2 micrograms per m3, which is about 37 per cent less than was determined in feedlot dust research in California approximately 17 years earlier. Upwind concentrations averaged 22 per cent of the downwind concentrations. Feedlot dust concentrations were generally highest in early evening and lowest in early morning. Using the Wedding and Andersen-321A PM-10 samplers, the PM-10 dust concentrations were 19 and 40 per cent, respectively, of mean TSP concentrations in direct comparisons. There was good correlation between PM-10 and TSP concentrations. Although dust concentrations decreased with increasing moisture, the correlation coefficients were relatively low. Odor intensity appeared to increase with decreasing net dust concentrations, perhaps due to moisture influences. Mean particle sizes of feedlot dust were 8.5 to 12.2 microns on a particle volume basis and 2.5 to 3.4 microns on a population basis. Respirable dust (below 2 microns) represented only 2.0 to 4.4 per cent of total dust on a particle volume basis. Under conditions of these experiments, the feedlots often exceeded both state and federal (U.S. Environmental Protection Agency) standards for TSP concentrations and for PM-10 concentrations measured using the Andersen-321A sampler. However, feedlots were below the new U.S. Environmental Protection Agency standards when the Wedding PM-10 sampler was used for measuring dust emissions.

Resolution and identification of O-phosphoserine, O-phosphothreonine, O-phosphotyrosine, and gamma-carboxyglutamic acid as their fluorescent o-phthalaldehyde derivatives by high performance liquid chromatography.

High performance liquid chromatography was used to resolve O-phosphoserine, O-phosphothreonine, and O-phosphotyrosine as their fluorescent o-phthalaldehyde derivatives. By adjusting the buffer system, very small amounts of O-phosphothreonine could be detected and quantitated in the presence of very large amounts of O-phosphoserine. In addition, gamma-carboxyglutamic acid and glutamic acid were also separated and quantitated. Depending on the buffer used, various combinations of these amino acids could be resolved in a single run.

Identification and quantitation of O-phosphoserine in human plasma fibronectin.

O-Phosphoserine was positively identified as the phosphorylated moiety in human plasma fibronectin by 31P-NMR of intact peptides. These data correlated completely with chemical analyses which demonstrated the presence of O-phosphoserine at a concentration of 2 residues/molecule. Neither O-phosphothreonine nor O-phosphotyrosine was detected in partial acid and partial alkaline hydrolysates, respectively.

Changes in the hexosamine content and swelling ratio of articular cartilage as functions of depth from the surface.

The hexasamine content and swelling ratio of adult bovine articular cartilage were determined as functions of depth. Progressing from the surface downward, the hexosamine content increased rapidly to a depth equivalent to approximately 30 to 35 per cent of the total thickness of the uncalcified portion of the tissue, and thereafter decreased at a less rapid rate. The swelling ratio was relatively constant throughtout the first quarter of the tissue but diminished thereafter. At depths below 35 per cent, the curve for the decrease in swelling ratio with depth was similar in form to that for the decrease in hexosamine content. Considering the factors that determine the swelling ratio of polyelectrolyte gels, it is proposed that progressing down from the surface, the interaction between the macromolecular components of the tissue is increased to a depth equivalent to about one-third of the total thickness of the cartilage.

In vitro wear of articular cartilage.

Seeking a reliable chemical index of the wear of articular cartilage during in vitro experiments, the contents of hydroxyproline, hexosamine, and the amino acid composition of adult bovine articular cartilage were determined as functions of depth from the surface. The hydroxyproline content, expressed as per cent of dry weight of tissue, was constant throughout the thickness of the tissue except in a surface region approximately twenty-five micrometers thick; the hexosamine content in this region was less than in the interior of the tissue; the collagen content was higher and the amino acid composition was less like that of pure collagen here than in the interior, indicating that the content of noncollagenous protein in the superficial layer of cartilage was greater than that in the interior. It was also evident that adult bovine articular cartilage contains significant amounts of collagen with a low hydroxylysine content, presumably Type I as well as Type II. Since the content of hydroxyproline is constant throughout the cartilage and the collagen and proteoglycan constituents of the intact tissue are relatively insoluble, the hydroxyproline content of the lubricant and the wear debris can be used to measure the extent of wear of articular cartilage during in vitro experiments. However, approximately 10 per cent of the hydroxyproline and 50 to 60 per cent of the glycosaminoglycans of the wear debris are dissolved in the lubricating fluid. Therefore, both the lubricant (solvent) and the solid wear debris must be analyzed to determine the amount of cartilage wear.