Discovery of Adamantyl Ethanone Derivatives as Potent 11β‐Hydroxysteroid Dehydrogenase Type 1 (11β‐HSD1) Inhibitors

11β‐Hydroxysteroid dehydrogenases (11β‐HSDs) are key enzymes regulating the pre‐receptor metabolism of glucocorticoid hormones. The modulation of 11β‐HSD type 1 activity with selective inhibitors has beneficial effects on various conditions including insulin resistance, dyslipidemia and obesity. Inhibition of tissue‐specific glucocorticoid action by regulating 11β‐HSD1 constitutes a promising treatment for metabolic and cardiovascular diseases. A series of novel adamantyl ethanone compounds was identified as potent inhibitors of human 11β‐HSD1. The most active compounds identified ( 52 , 62 , 72 , 92 , 103 and 104 ) display potent inhibition of 11β‐HSD1 with IC₅₀ values in the 50–70 nM range. Compound 72 also proved to be metabolically stable when incubated with human liver microsomes. Furthermore, compound 72 showed very weak inhibitory activity for human cytochrome P450 enzymes and is therefore a candidate for in vivo studies. Comparison of the publicly available X‐ray crystal structures of human 11β‐HSD1 led to docking studies of the potent compounds, revealing how these molecules may interact with the enzyme and cofactor.     

Caloric beverage consumption patterns in Mexican children

Background  

Mexico has seen a very steep increase in child obesity level. Little is known about caloric beverage intake in this country as well as all other countries outside a few high income countries. This study examines overall patterns and trends in all caloric beverages from two nationally representative surveys from Mexico.     

Iron porphyrin-based cathode catalysts for polymer electrolyte membrane fuel cells: Effect of NH3 and Ar mixtures as pyrolysis gases on catalytic activity and stability

Ten different catalysts were prepared by loading 66 wt% ClFeTMPP on N330, a furnace grade carbon black, and pyrolyzing this catalyst precursor for 10 min at 950 °C in a NH₃/Ar gas mixture with various NH₃ volume fractions (from 0% to 100%). The activity and stability of these catalysts were measured in a fuel cell and compared. The only stable catalyst, although the least active, among these was the one pyrolyzed in pure Ar. A notable leap in catalytic activity, but drop in stability, was observed for all catalysts pyrolyzed in gas mixtures containing NH₃, even with a mere volume fraction of 1.3% NH₃ in the pyrolysis gas mixture. Catalytic activities increased, while stability decreased with increasing volume fraction of NH₃. The physicochemical properties of these catalysts were correlated with their electrochemical behaviour observed in fuel cell tests. It was found that a volume fraction of only 1.3% NH₃ was enough to double the micropore surface area, the surface nitrogen and iron concentrations in the resulting catalyst. Since the active sites are believed to be of the Fe/N/C type, the sharp increase in catalytic activity with as little as 1.3% NH₃ is attributed to the concurrent increase in microporous surface area, N and Fe surface contents in these catalysts. The only property that apparently correlates with stability is the degree of graphitization of the catalyst, which was estimated either from either X-ray diffraction and Raman spectroscopy measurements. Lastly, it was found that the catalysts’ peroxide yield, resulting from the partial reduction of O₂, does not correlate with their degree of stability.     

Impact of dams on point bar habitat: a case for the extirpation of the Sacramento Valley Tiger Beetle,C. hirticollis abrupta

Quantitative analyses of flow and stage data, remote sensing and geographic information systems analysis, and field studies were used to assess the impact of dams and diversions on the point bar habitat of the Sacramento Valley Tiger Beetle (Cicindela hirticollis abrupta). The reaches of interest include sites of known historic populations of C. h. abrupta along the Sacramento River from approximately 8 km north of Colusa southward to the confluence with the Feather River and along the Feather River between Yuba City and its confluence with the Sacramento River. The results from this study show that construction of two major dams has altered flows such that prolonged and increased flows during summer, fall, and early winter have most likely disrupted life cycles, flooded larvae, drowned overwintering adults and led to high mortality. Additionally, habitat availability has decreased over time because point bars have decreased in number and area causing increased distances between populations and isolation of populations. Moreover, point bar armouring, channel scouring, altered flows, redirected flows through weirs, and lithologic controls have produced a bimodal distribution of mean grain sizes in the Sacramento River in which the more northern bars contain gravel deposits and more southern bars possess fine sands. These conditions negatively alter moisture retention and sediment compaction and, consequently, burrowing conditions needed by this tiger beetle. Additionally, more stabilized flows (reduced variability) and increased fine‐grained deposition have enabled development and encroachment of vegetation onto the sand bars. Finally, human stresses, such as foot traffic and vehicular traffic may have interfered with burrowing, ovipositing, and foraging. The combination of these stress factors has most likely led to a reduction in source populations and, ultimately, the apparent extirpation of the entire metapopulation. Copyright © 2006 John Wiley & Sons, Ltd.     

Micro-organisms and manganese cycling in a seasonally stratified freshwater dam

This work describes investigations into the role that biotic and abiotic mechanisms play in the manganese redox cycle in a freshwater dam over a twelve month period. Enzymatic control of manganese oxidation was taking place with a temperature optimum of approx. 30°C. Manganese oxidation was only significant above about 19°C. The temperature and season play vital roles in determining the extent to which abiotic and microbial mechanisms contribute to manganese oxidation. Results showed that microbial catalysis is overwhelmingly responsible for manganese oxidation in the lower epilimnion from November to May. Significant abiotic catalysis (up to 25%) can occur in late summer/autumn when the water temperature is greatest. Mn(II) oxidation, pseudo-first order rate constants to 1.12 × 10²² M⁻⁴ · d⁻¹ were measured while poisoned sample experiments confirmed the role of biological mediation. In winter, biological control could not occur because of the lower temperature of the water column. The measurement of “x” in MnO_x showed that higher manganese oxidation states were expected when the manganese oxidation rate was at a maximum and therefore when microbial activity was greatest. Direct microbial reduction of MnO_x in the water column was of much less significance. However, indirect reduction may have taken place through the reaction of MnO_x with sulfide. The results of this work have important implications for the design and operation of artificial destratification units for the control of manganese speciation.     

A calibration protocol of a one-dimensional moving bed bioreactor (MBBR) dynamic model for nitrogen removal

This work suggests a procedure to correctly calibrate the parameters of a one-dimensional MBBR dynamic model in nitrification treatment. The study deals with the MBBR configuration with two reactors in series, one for carbon treatment and the other for nitrogen treatment. Because of the influence of the first reactor on the second one, the approach needs a specific calibration strategy. Firstly, a comparison between measured values and simulated ones obtained with default parameters has been carried out. Simulated values of filtered COD, NH(4)-N and dissolved oxygen are underestimated and nitrates are overestimated compared with observed data. Thus, nitrifying rate and oxygen transfer into the biofilm are overvalued. Secondly, a sensitivity analysis was carried out for parameters and for COD fractionation. It revealed three classes of sensitive parameters: physical, diffusional and kinetic. Then a calibration protocol of the MBBR dynamic model was proposed. It was successfully tested on data recorded at a pilot-scale plant and a calibrated set of values was obtained for four parameters: the maximum biofilm thickness, the detachment rate, the maximum autotrophic growth rate and the oxygen transfer rate.     

Satellite ocean color algorithms: A review of applications to the Great Lakes

We review the literature dealing with retrievals of chlorophyll concentrations in the Great Lakes from satellite observations. Most studies show that the satellite estimates of chlorophyll concentrations are linearly related to the observed concentrations, though they tend to overestimate concentrations at lower values and underestimate them at higher values. Deviations from a consistent, accurate, linear relationship can be attributed to temporal and spatial variations in the inherent optical properties of the color producing agents in the water as well as to varying concentrations of non-algal substances that interfere with the retrievals. We confirmed these results by using a simple optical model to examine the sensitivity of the retrieved chlorophyll values to the concentrations of interfering substances and to differences in model parameters. Because the spatial and temporal optical properties of the Great Lakes are unpredictable, no retrieval method is likely to produce accurate results all the time. The papers we reviewed show that simple band ratio algorithms can provide chlorophyll estimates that are proportional to in situ concentrations. The published literature suggests that the band ratio methods will be of most value in regions where the concentrations of non-algal interfering substances are minimal. Because of these limitations we recommend that future papers presenting chlorophyll analysis based on satellite data provide confirming field observations that include measurements of chlorophyll, suspended particles and dissolved organic carbon. We also recommend that Great Lakes scientists explore novel methods for retrieving chlorophyll concentrations from satellite observations that have proven useful in other optically complex waters.     

Toxicity of waters from the St. Lawrence River at Massena Area-of-Concern to the plankton species Selenastrum capricornutum and Ceriodaphnia dubia

In 1972, the US and Canada committed to restore the chemical, physical, and biological integrity of the Great Lakes Ecosystem under the first Great Lakes Water Quality Agreement. During subsequent amendments, part of the St. Lawrence River at Massena NY, and segments of three tributaries, were designated as one Area of Concern (AOC) due to various beneficial use impairments (BUIs). Plankton beneficial use was designated impaired within this AOC because phytoplankton and zooplankton population data were unavailable or needed “further assessment”. Contaminated sediments from industrial waste disposal have been largely remediated, thus, the plankton BUI may currently be obsolete. The St. Lawrence River at Massena AOC remedial action plan established two criteria which may be used to assess the plankton BUI; the second states that, “in the absence of community structure data, plankton bioassays confirm no toxicity impact in ambient waters”. This study was implemented during 2011 to determine whether this criterion was achieved. Acute toxicity and chronic toxicity of local waters were quantified seasonally using standardized bioassays with green alga Selenastrum capricornutum and water flea Ceriodaphnia dubia to test the hypothesis that waters from sites within the AOC were no more toxic than were waters from adjacent reference sites. The results of univariate and multivariate analyses confirm that ambient waters from most AOC sites (and seasons) were not toxic to both species. Assuming both test species represent natural plankton assemblages, the quality of surface waters throughout most of this AOC should not seriously impair the health of resident plankton communities.     

Potential for electrification from biomass gasification in Vanuatu

At least 170,000 rural people in the Pacific-island nation Vanuatu (approximately 70% of the country’s population) live without reliable access to electricity. The few rural households that do consume electricity incur high prices for imported diesel fuel ($2-3/liter). Thus, there is an important role in Vanuatu for expanding cost-competitive, non-diesel alternatives for electricity generation.Informed by an interdisciplinary data synthesis and an extensive series of field interviews in Vanuatu, this paper analyzes the potential for converting reportedly obsolete timber plantation land into a dedicated feedstock supply system for new small-scale biomass gasifiers. The analysis draws upon geographic mapping of electricity demand and feedstock supply, a historical assessment of Vanuatu’s forest plantations, a techno-economic evaluation of investment in 10 kW and 30 kW gasifiers, and a discussion of important social-institutional factors.This analysis identifies up to 13 geographic matches between areas of rural electricity demand and potential feedstock supply. In addition, financial modeling suggests that the levelized cost of electricity from gasification is competitive (relative to diesel systems) given capacity factors of 15-40% or greater (corresponding to a cost of $1.60/kWh or less). Further research is recommended to examine the socioeconomic and ecological aspects of feedstock plantation establishment in Vanuatu.