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151.
Concurrent inhibition of aromatase and steroid sulfatase (STS) may provide a more effective treatment for hormone‐dependent breast cancer than monotherapy against individual enzymes, and several dual aromatase–sulfatase inhibitors (DASIs) have been reported. Three aromatase inhibitors with sub‐nanomolar potency, better than the benchmark agent letrozole, were designed. To further explore the DASI concept, a new series of letrozole‐derived sulfamates and a vorozole‐based sulfamate were designed and biologically evaluated in JEG‐3 cells to reveal structure–activity relationships. Amongst achiral and racemic compounds, 2‐bromo‐4‐(2‐(4‐cyanophenyl)‐2‐(1H‐1,2,4‐triazol‐1‐yl)ethyl)phenyl sulfamate is the most potent DASI (aromatase: IC50=0.87 nM ; STS: IC50=593 nM ). The enantiomers of the phenolic precursor to this compound were separated by chiral HPLC and their absolute configuration determined by X‐ray crystallography. Following conversion to their corresponding sulfamates, the S‐(+)‐enantiomer was found to inhibit aromatase and sulfatase most potently (aromatase: IC50=0.52 nM ; STS: IC50=280 nM ). The docking of each enantiomer and other ligands into the aromatase and sulfatase active sites was also investigated. 相似文献
152.
A variety of human land uses involve the release of toxins into the environment. Wildlife live alongside humans across this array of land uses and thus, are exposed to varying chemical milieus. Kidneys are the principle excretory organs for vertebrates and excessive or chronic exposure to exogenous toxins can lead to renal pathology and renal failure. Although studies have linked chemical exposure to specific renal diseases across diverse taxa, none compare renal lesions occurring in wildlife living in different types of human-modified landscapes. We identify lesions characteristic of renal stress, including toxin exposure, in 82 giant toad (Bufo marinus) males living in habitats ranging from suburban to agricultural. In a previous study [McCoy K.A., Bortnick L.J., Campbell C.M., Hamlin H.J., Guillette L.J., Jr., St. Mary C.M. Agriculture Alters Gonadal Form and Function in Bufo marinus. Environ Health Persp; in press.], these individuals were examined for gonadal abnormalities, which were significantly and positively associated with percentage of agriculture at the collection site. Thus, we hypothesized the same association for renal abnormalities. We scored gross anatomical abnormalities and used light microscopy to identify tubular and interstitial lesions that have been associated with toxicant exposure in other organisms, including humans. Renal lesions indicative of tubular disease were observed at one suburban and two agricultural sites, whereas interstitial lesions were most severe at one agricultural site. Although there was no relationship between frequency of renal disease and proportion of agriculture in the collection vicinity, the renal lesions we identify are consistent with toxin exposure and are similar to those found in human drug abusers and patients suffering medication-induced nephropathy. This is the first study to describe renal lesions in a wild amphibian species and investigate the distribution of renal lesions across human altered landscapes. Indentifying the chemicals inducing renal lesions across these landscapes, their toxicological mechanisms, and their implications on wildlife health will help us devise strategies to mitigate the impacts of toxins on humans and animals living in human-modified environments. 相似文献
153.
As the number of robots in the market and their implementations increase, it becomes more difficult to find which robot is the most suitable for a particular application. Today, electronics assembly is one of the areas where robots are highly used. This is because of the advantages which robots offer in complex tasks of electronic assembly.
In this paper a decision making algorithm which uses utility theory was developed for the selection and evaluation of robots for electronics assembly. 相似文献
154.
Small dams for hydropower have caused widespread alteration of Central American rivers, yet much of recent development has gone undocumented by scientists and conservationists. We examined the ecological effects of a small hydropower plant (Doña Julia Hydroelectric Center) on two low‐order streams (the Puerto Viejo River and Quebradon stream) draining a mountainous area of Costa Rica. Operation of the Doña Julia plant has dewatered these streams, reducing discharge to ~10% of average annual flow. This study compared fish assemblage composition and aquatic habitat upstream and downstream of diversion dams on two streams and along a ~4 km dewatered reach of the Puerto Viejo River in an attempt to evaluate current instream flow recommendations for regulated Costa Rican streams. Our results indicated that fish assemblages directly upstream and downstream of the dam on the third order Puerto Viejo River were dissimilar, suggesting that the small dam (< 15 m high) hindered movement of fishes. Along the ~4 km dewatered reach of the Puerto Viejo River, species count increased with downstream distance from the dam. However, estimated species richness and overall fish abundance were not significantly correlated with downstream distance from the dam. Our results suggested that effects of stream dewatering may be most pronounced for a subset of species with more complex reproductive requirements, classified as equilibrium‐type species based on their life‐history. In the absence of changes to current operations, we expect that fish assemblages in the Puerto Viejo River will be increasingly dominated by opportunistic‐type, colonizing fish species. Operations of many other small hydropower plants in Costa Rica and other parts of Central America mirror those of Doña Julia; the methods and results of this study may be applicable to some of those projects. Copyright © 2006 John Wiley & Sons, Ltd. 相似文献
155.
Lynnette D. Madsen Louise Weaver Henrik Ljungcrantz Alison J. Clark 《Journal of Electronic Materials》1998,27(5):418-426
The microstructure of the Pt/Ti/SiO2/Si structure has been investigated by scanning and transmission electron microscopy. Pt films of 100 nm thickness deposited
by sputtering or evaporation onto unheated substrates gave complete coverage of the underlying Ti layer and showed a granular
and faceted structure with grains ∼20 nm in diameter. They did not exhibit hillocks or surface TiOx formation. X-ray diffraction was used to examine the film stress through use of the sin2ψ method with bulk values for the elastic constants (v=0.39, E=162 GPa). The as-deposited sputtered film had a compressive
stress of ∼540 MPa, while the evaporated films had tensile stresses of ∼630 MPa. The films then received a 400°C rapid thermal
anneal (RTA) for 90 s and a subsequent RTA of 650°C for 30s. Further investigation of the film stresses and microstructure
were made after each annealing step. After the low temperature anneal, the film stress for the sputtered film became tensile.
Plan-view sections examined by transmission electron microscopy (TEM) showed that the as-deposited sputtered films were dense
but became porous after annealing. Initially, the evaporated films had a less dense microstructure, but were more stable with
annealing. Little change in the stress for the evaporated film was observed after this initial low temperature annealing step.
Additional annealing of the evaporated and sputtered samples caused complete consumption of the Ti layer including some TiOx formation from the underlying SiO2 layer and marked interaction with the Pt; however, little change in the stress was found. The surface of the Pt film revealed
larger grains, but otherwise remained unaffected. The underlying phase changes were minimized once the Ti layer had reacted
with the Pt. Due to the ratio of the layers, Pt:Ti of 2:1, the surface of the Pt was unaffected. 相似文献
156.
Brenda Long Mary Manning Micheal Burke Bartholomaeus N. Szafranek Giuseppe Visimberga Damien Thompson James C. Greer Ian M. Povey John MacHale Guaylord Lejosne Daniel Neumaier Aidan J. Quinn 《Advanced functional materials》2012,22(4):717-725
A simple, versatile method for non‐covalent functionalization of graphene based on solution‐phase assembly of alkane‐amine layers is presented. Second‐order Møller–Plesset (MP2) perturbation theory on a cluster model (methylamine on pyrene) yields a binding energy of ≈220 meV for the amine–graphene interaction, which is strong enough to enable formation of a stable aminodecane layer at room temperature. Atomistic molecular dynamics simulations on an assembly of 1‐aminodecane molecules indicate that a self‐assembled monolayer can form, with the alkane chains oriented perpendicular to the graphene basal plane. The calculated monolayer height (≈1.7 nm) is in good agreement with atomic force microscopy data acquired for graphene functionalized with 1‐aminodecane, which yield a continuous layer with mean thickness ≈1.7 nm, albeit with some island defects. Raman data also confirm that self‐assembly of alkane‐amines is a non‐covalent process, i.e., it does not perturb the sp2 hybridization of the graphene. Passivation and adsorbate n‐doping of graphene field‐effect devices using 1‐aminodecane, as well as high‐density binding of plasmonic metal nanoparticles and seeded atomic layer deposition of inorganic dielectrics using 1,10‐diaminodecane are also reported. 相似文献
157.
At times, total dissolved gas concentrations in the Columbia and Snake rivers have been elevated due to involuntary spill from high spring runoff and voluntary spill used as a method to pass juvenile salmonids over dams. The goal of this project was to determine if acute exposure to total dissolved gas supersaturation (TDGS) affects the reproductive performance of female chinook salmon late in their maturation. During this study, adult female spring chinook salmon were exposed to mean TDGS levels of 114.1% to 125.5%. We ended exposures at first mortality, or at the appearance of impending death. Based on this criterion, exposures lasted from 10 to 68 h and were inversely related to TDGS. There was no effect of TDGS on pre‐spawning mortality or fecundity when comparing treatment fish to experimental controls or the general hatchery population four to six weeks after exposures. Egg quality, based on egg weight and egg diameter, did not differ between treatment and control fish. Fertilization rate and survival to eyed‐stage was high ( > 94%) for all groups. With the exception of Renibacterium salmoninarum (the causative agent of bacterial kidney disease; BKD), no viral or bacterial fish pathogens were isolated from experimental fish. The prevalence (about 45%) and severity of R. salmoninarum did not differ among the groups or the general hatchery population. We conclude that these acute exposures to moderate levels of gas‐supersaturated water—perhaps similar to that experienced by immigrating adult salmon as they approach and pass a hydropower dam on the Columbia River—did not affect reproductive success of female chinook salmon late in their maturation. These results are most applicable to summer and fall chinook salmon, which migrate in the summer/fall and spawn shortly after reaching their natal streams. Published in 2004 by John Wiley & Sons, Ltd. 相似文献
158.
159.
160.
Amar A. DESAI Allen NISSENSON Glenn M. CHERTOW Mary FARID Inder SINGH Martijn G. H. VAN OIJEN Eric ESRAILIAN Matthew D. SOLOMON Brennan M. R. SPIEGEL 《Hemodialysis international. International Symposium on Home Hemodialysis》2009,13(3):347-359
Despite data that traditional laboratory-based outcome measures in dialysis are improving over time, population-based data indicate that mortality rates are not improving in parallel. With increased focus on performance measures based on laboratory-based outcomes (e.g., hematocrit, albumin, and parathyroid hormone), less emphasis has been placed on other markers, some of which may be stronger predictors of mortality. We performed a systematic review to interpret the predictive value of laboratory-based outcome measures in dialysis. We identified studies with data regarding the predictive value of laboratory-based outcomes for mortality in dialysis. We calculated the sample size-weighted pooled relative risk of death with dichotomized "high" vs. "low" levels of each measure. We rank-ordered predictors by scaling the pooled relative risk of each measure by its pooled standard deviation. There were 5171 titles, of which 128 (representing 44 laboratory-based outcomes) were selected. Nine were significantly associated with mortality, in order of decreasing scaled effect size: (1) tumor necrosis factor-α, (2) hematocrit, (3) interleukin-6, (4) troponin T, (5) Kt/Vurea , (6) prealbumin, (7) urea reduction ratio, (8) serum albumin, and (9) C-reactive protein. Other oft-cited measures such as calcium phosphate product and parathyroid hormone were not significantly associated with mortality in pooled analysis. Quality improvement efforts to improve traditional laboratory-based outcomes in end-stage renal disease are necessary, but likely insufficient, to improve overall mortality in dialysis. Renewed consideration of cardiovascular, inflammatory, and nutritional markers that are especially strong predictors of mortality may have important implications for risk stratification and targeted therapeutic interventions. 相似文献