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21.
Risks and benefit evaluation for controlled human infection studies, where healthy volunteers are deliberately exposed to infectious agents to evaluate vaccine efficacy, should be explicit, systematic, thorough, and non-arbitrary. Decision analysis promotes these qualities using four steps: (1) determining explicit criteria and measures for evaluation, (2) identifying alternatives to the study, (3) defining the models used to estimate the measures for each alternative, and (4) running the models to produce the estimates and compare the alternatives. In this paper, we describe how decision analysis might be applied by funders and regulators, as well as by others contemplating the use of novel controlled human infection studies for vaccine development and evaluation. 相似文献
22.
23.
Makoto Misono 《Molecular Engineering》1993,3(1-3):193-203
First, fundamental properties (structure, acid and redox properties) and advantages of solid polyoxometalate catalysts (catalyst design by acid and redox control, molecularity, unusual reaction field and unique basicity) are explained. Then, the mechanism of alcohol dehydration elucidated by direct observation of reaction intermediates by solid-state NMR and the very high activity of Cs2.5H0.5PW12O40 are described. Finally several industrial applications of polyoxometalate catalysts are briefly introduced placing stress on the role of unique chemical properties of polyoxometalates. 相似文献
24.
B. Singh 《Biometrical journal. Biometrische Zeitschrift》1993,35(7):823-831
The distribution and moments, of ANOVA estimator of heritability are given under unbalanced random model. These expressions are used to investigate the effect of unbalancedness on the bias and variance/MSE of the estimator and also the validity of certain approximations for its variance, numerically. The computed results reveal that the unbalancedness increases both the bias and variance/MSE of the estimator and the Smith-approximation for the variance of the estimator provides better accuracy. 相似文献
25.
Promotion of indole alkaloid production in Catharanthus roseus cell cultures by rare earth elements 总被引:3,自引:0,他引:3
Production of the indole alkaloids, ajmalicine or catharanthine, in cell suspension cultures of Catharanthus roseus was enhanced by cerium (CeO2 and CeCl3), yttrium (Y2O3) and neodymium (NdCl3). The yield of ajmalicine in these treated-cultures reached 51 mg l–1 (CeO2), 40 mg l–1 (CeCl3), 41 mg l–1 (Y2O3) and 49 mg l–1 (NdCl3) while catharanthine production reached to 36 mg l–1 (CeO2) and 31 mg l–1 (CeCl3). A major portion of increased alkaloids was released into medium in these treatments. But Sm2O3, SmCl3, La2O3, LaCl3, complex of chromium (III)-titanium (IV) and NaSeO4 treatments had little effect on alkaloid production of C. roseus cell cultures. 相似文献
26.
Predictivity of an in vitro model for acute and chronic skin irritation (SkinEthic) applied to the testing of topical vehicles 总被引:2,自引:0,他引:2
A. de Brugerolle de Fraissinette V. Picarles S. Chibout M. Kolopp J. Medina P. Burtin M.E. Ebelin S. Osborne F. K. Mayer A. Spake M. Rosdy B. De Wever R.A. Ettlin A. Cordier 《Cell biology and toxicology》1999,15(2):121-135
An in vitro human reconstructed epidermis model (SkinEthic) used for screening acute and chronic skin irritation potential
was validated against in vivo data from skin tolerability studies. The irritation potential of sodium lauryl sulfate (SLS),
calcipotriol and trans-retinoic acid was investigated. The in vitro epidermis-like model consists of cultures of keratinocytes
from human foreskin on a polycarbonate filter. The modulation of cell viability, the release and gene expression of proinflammatory
cytokines, interleukins 1α and 8, and morphological changes were evaluated during 3 days as endpoints representative for an
inflammatory reaction. The cumulative irritation potential of the topical products was evaluated in a human clinical study
by visual scoring and biophysical measurement of inflammatory skin reaction after repeated 24 h applications over 3 weeks
under Finn chamber patches. All topical products that were nonirritating in the human study were noncytotoxic and did not
induce cytokine expression in the in vitro acute model (day 1 exposure). All irritating controls exhibited specific cell viability
and cytokine patterns, which were predictive of the in vivo human data. The ranking of mild to moderate skin irritation potential
was based on the lack of cytotoxicity and the presence of cytokine patterns including gene expression specific for each irritant,
using the chronic in vitro model (up to 3 days exposure).
The human reconstructed epidermis model SkinEthic was shown to be a reliable preclinical tool predicting the irritation potential
of topical products. Moreover, it is a useful model in a two-step tiered strategy for screening acute and chronic irritation
potential for the selection of vehicles for new topical drugs.
This revised version was published online in July 2006 with corrections to the Cover Date. 相似文献
27.
Distribution of Ankyrin Isoforms and Their Proteolysis After Ischemia and Reperfusion in Rat Brain 总被引:1,自引:0,他引:1
Kazuki Harada Shiro Fukuda †Manabu Kunimoto Ken-ichi Yoshida 《Journal of neurochemistry》1997,69(1):371-376
Abstract: The distribution of brain-type ankyrin (ankyrinB , 212 kDa) and erythrocyte-type ankyrin (ankyrinR , 239 kDa) was investigated in the subcellular fractions of rat forebrain (P1, 1,000 g pellet; P2, 15,000 g pellet; P3, 100,000 g pellet; S, 100,000 g supernatant) by immunoblotting using specific antibodies. The P2 fraction contained ∼40% of the 212- and 163-kDa isoforms of ankyrinB and the 239-kDa isoform of ankyrinR . Further subfractionation of the P2 by Percoll gradient centrifugation followed by separation of myelin showed association of the three ankyrin isoforms with the synaptosome-rich fraction but not with the myelin-rich fraction. The plasma membrane-rich P3 fraction contained a concentration of ankyrin isoforms similar to that in the P2 fraction. In vitro proteolysis of ankyrin in the P2 fraction with calpain showed that the 212-kDa ankyrinB was more susceptible to calpain than was ankyrinR . In the two-vessel occlusion model, ischemia for 30 min generated the 160-kDa fragment of ankyrinR , and reperfusion for 60 min after 30 min of ischemia remarkably increased the 160-kDa fragment. The reperfusion also significantly decreased the 212-kDa isoform of ankyrinB . Both ischemia-reperfusion and in vitro proteolysis with calpain generated the 160-kDa fragment of ankyrinR , suggesting the involvement of calpain. 相似文献
28.
Indicators of landscape condition should be selected based on their sensitivity to environmental changes and their capacity to provide early warning detection of those changes. We assessed the performance of a suite of spatial-pattern metrics selected to quantify the condition of the ridge-slough landscape in the Everglades (South Florida, USA). Spatial pattern metrics (n = 14) that describe landscape composition, geometry and hydrologic connectivity were enumerated from vegetation maps of twenty-five 2 × 2 km primary sampling units (PSUs) that span a gradient of hydrologic and ecological condition across the greater Everglades ecosystem. Metrics were assessed in comparison with field measurements from each PSU of landscape condition obtained from regional surveys of soil elevation, which have previously been shown to capture dramatic differences between conserved and degraded locations. Elevation-based measures of landscape condition included soil elevation bi-modality (BISE), a binary measure of landscape condition, and also the standard deviation of soil elevation (SDSE), a continuous measure of condition. Metric performance was assessed based on the strength (sensitivity) and shape (leading vs. lagging) of the relationship between spatial pattern metrics and these elevation-based measures. We observed significant logistic regression slopes with BISE for only 4 metrics (slough width, ridge density, directional connectivity index – DCI, and least flow cost – LFC). More significant relationships (n = 8 metrics) were observed with SDSE, with the strongest associations for slough density, mean ridge width, and the average length of straight flow, as well as for a suite of hydrologic connectivity metrics (DCI, LFC and landscape discharge competence – LDC). Leading vs. lagging performance, inferred from the curvature of the association obtained from the exponent of fitted power functions, suggest that only DCI was a leading metric of the loss of soil elevation variation; most metrics were indeterminate, though some were clearly lagging. Our findings support the contention that soil elevation changes from altered peat accretion dynamics precede changes in landscape pattern, and offer insights that will enable efficient monitoring of the ridge-slough landscape as part of the ongoing Everglades restoration effort. 相似文献
29.
Shuanxi Fan 《人类与生态风险评估》2017,23(5):1099-1120
Soil heavy metal pollution from mining activities is potentially harmful to human health through the food chain. In this study, a total of 43 soil samples were collected from a depth of 0–20 cm from fields close to a Pb and Zn smelter. The samples were used to: 1) analyze the pollution level of heavy metals (Pb, Zn, Cr, and Cu) and spatial distribution pattern; 2) evaluate the degree of accumulation and enrichment, potential ecological risk, and human health risk; and 3) perform source apportionment in Fengxiang County, Shaanxi Province of China. The results showed that the concentration ranged from 43.67 to 189.55, 131.43 to 239.53, 74.77 to 112.25, and 24.69 to 37.71 mg·kg?1 for Pb, Zn, Cr, and Cu, respectively, and the mean concentration for Pb, Zn, Cr, and Cu was 129.46, 192.85, 91.98 and 31.67 mg·kg?1, respectively. The concentrations were greater than the Shaanxi Province background values, while they were lower than the second-level limits of Environmental Quality Standard for Soils of China (EQSS). The spatial distribution of heavy metal contents showed a banded in soil except Cu. The spatial distribution pattern and pollution assessment indexes (Igeo, EF) indicated that the investigated metals had been accumulated in the study areas, and implied significant influences from anthropogenic activities, local meteorological situation, and soil properties. The ecological risk assessment showed that the risks were relatively low (RI<150). Compared with the exposure risk for adults, that for children was significantly greater. The ingestion of heavy metals in the soils by humans was the main exposure pathway compared with the dermal exposure. There may be a risk of noncarcinogenic adverse health effects (HQ < 1, 0.377 ≤ HI≤1.553) on children, but the adults were unlikely to experience obvious adverse health effects (HQ < 1, HI < 1). The carcinogenic risk of Cr for adults and children was at an unacceptable level. The carcinogenic and noncarcinogenic risks were in the order of children > adults. The correlation analysis showed that Pb, Cr, and Cu have identical anthropogenic and natural sources, while Zn has another identical source. This study could provide a basis for the sustainable management of this region by reducing metal inputs and to protect soils from long-term heavy metal accumulation. 相似文献
30.
K. Sasikala Ch.V. Ramana P. Raghuveer Rao M. Subrahmanyam 《FEMS microbiology letters》1990,72(1-2):23-28
Abstract Photoproduction of hydrogen, nitrogenase activity (acetylene reduction) and hydrogenase activity (methylene blue dye reduction) were studied in free and alginate immobilized whole cells of a purple non-sulfur photosynthetic bacterium Rhodobacter sphaeroides O.U. 001. Four-fold increase in hydrogen production, two-fold increase in nitrogenase activity and 1.2-fold increase in the hydrogenase activity were observed in immobilized cells compared to free cells. Effect of various inhibitors (CO and C2 H2 ) and electron donor (H2 ) on the above three functions by free and immobilized cells has also been studied. 相似文献