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1.
CI-994 (acetyldinaline) is an orally active anticancer drug currently in Phase 1 clinical trials. To assess its preclinical toxicity, CI-994 was administered orally as suspensions to Wistar rats (10/sex/dose) and in capsules to beagle dogs (3/sex/dose) once daily for two weeks. Doses were 1.5, 5, and 15 mg/kg for rats (9, 30, and 90 mg/m2, respectively), and 0.5, 2, and 5 mg/kg for dogs (10, 40, and 100 mg/m2, respectively). Systemic exposure was dose-proportional based on toxicokinetic analysis in dogs. Severe clinical signs and mortality occurred at the highest dose in both species beginning on Day 10. Neutropenia, lymphocytopenia, thrombocytopenia, lymphoid depletion, bone marrow hypocellularity, and testicular degeneration were observed in both species, primarily at the mid- and high-doses. Despite continued treatment, neutrophil counts in dogs returned to control levels in Week 2. Other microscopic findings in rats included splenic hematopoietic depletion at all doses and epithelial cell necrosis in various tissues at 15 mg/kg. Additional bone marrow changes in dogs involved myeloid and megakaryocyte hyperplasia at 2 mg/kg and abnormal myeloid and megakaryocyte maturation at 2 and 5 mg/kg. Except for the testicular effects in both species, all changes were reversible within a 4-week (rat) or 9-week (dog) recovery period. The results of these studies show that target organ effects of CI-994 principally involve tissues with rapidly dividing cell populations and that bone marrow suppression is the dose-limiting toxicity. CI-994 also seems to interfere with the release and/or maturation of cells in the bone marrow.  相似文献   
2.
ROI-based Watermarking Scheme for JPEG 2000   总被引:1,自引:0,他引:1  
A new region of interest (ROI)-based watermarking method for JPEG 2000 is presented. The watermark is embedded into the host image based on the characteristics of the ROI to protect rights to the images. This scheme integrates the watermarking process with JPEG 2000 compression procedures. Experimental results have demonstrated that the proposed watermark technique successfully survives JPEG 2000 compression, progressive transmission, and principal attacks.  相似文献   
3.
The differential effectiveness of group psychotherapy was estimated in a meta-analysis of 111 experimental and quasi-experimental studies published over the past 20 years. A number of client, therapist, group, and methodological variables were examined in an attempt to determine specific as well as generic effectiveness. Three different effect sizes were computed: active versus wait list, active versus alternative treatment, and pre- to posttreatment improvement rates. The active versus wait list overall effect size (0.58) indicated that the average recipient of group treatment is better off than 72% of untreated controls. Improvement was related to group composition, setting, and diagnosis. Findings are discussed within the context of what the authors have learned about group treatment, meta-analytic studies of the extant group literature, and what remains for future research. (PsycINFO Database Record (c) 2010 APA, all rights reserved)  相似文献   
4.
Deriving the optimal policies of hydropower multi-reservoir systems is a nonlinear and high-dimensional problem which makes it difficult to achieve the global or near global optimal solution. In order to optimally solve the problem effectively, development of optimization methods with the purpose of optimizing reservoir operation is indispensable as well as inevitable. This paper introduces an enhanced differential evolution (EDE) algorithm to enhance the exploration and exploitation abilities of the original differential evolution (DE) algorithm. The EDE algorithm is first applied to minimize two benchmark functions (Ackley and Shifted Schwefel). In addition, a real world two-reservoir hydropower optimization problem and a large scale benchmark problem, namely ten-reservoir problem, were considered to indicate the effectiveness of the EDE. The performance of the EDE was compared with the original DE to solve the three optimization problems. The results demonstrate that the EDE would have a powerful global ability and faster convergence than the original DE to solve the two benchmark functions. In the 10-reservoir optimization problem, the EDE proved to be much more functional to reach optimal or near optimal solution and to be effective in terms of convergence rate, standard deviation, the best, average and worst values of objective function than the original DE. Also, In the case of two-reservoir system, the best values of the objective function obtained 93.86 and 101.09 for EDE and DE respectively. Based on the results, it can be stated that the most important reason to improve the performance of the EDE algorithm is the promotion of local and global search abilities of the DE algorithm using the number of novel operators. Also, the results of these three problems corroborated the superior performance, the high efficiency and robustness of the EDE to optimize complex and large scale multi-reservoir operation problems.  相似文献   
5.
Increasing concentrations of methane (CH4) in the atmosphere are projected to account for about 25% of the net radiative forcing. Biospheric emissions of CH4 to the atmosphere total approximately 400 Tg C y-1. An estimated 300 Tg of CH4-C y-1 is oxidized in the atmosphere by hydroxyl radicals while about 40 Tg y-1 remains in the atmosphere. Approximately 40 Tg y-1 of the atmospheric burden is oxidized in aerobic soils. Research efforts during the past several years have focused on quantifying CH4 sources while relatively less effort has been directed toward quantifying and understanding the soil sink for atmospheric CH4. Recent research has demonstrated that land use change, including agricultural use of native forest and grassland systems has decreased the soil sink for atmospheric methane. Some agricultural systems consume atmospheric CH4 at rates less than 10% of those found in comparable undisturbed soils. While it has been necessary to change land use practices over the past centuries to meet the required production of food and fiber, we need to recognize and account for impacts of land use change on the biogeochemical nutrient cycles in the biosphere. Changes that have ensued in these cycles have and will impact the atmospheric concentrations of CH4 and N2O. Since CH4 and N2O production and consumption are accomplished by a variety of soil microorganisms, the influence of changing agricultural, forest, and, demographic patterns has been large. Existing management and technological practices may already exist to limit the effect of land use change and agriculture on trace gas fluxes. It is therefore important to understand how management and land use affect trace gas fluxes and to observe the effect of new technology on them. This paper describes the role of aerobic soils in the global CH4 budget and the impact of agriculture on this soil CH4 sink. Examples from field studies made across subarctic, temperate and tropical climate gradients in grasslands are used to demonstrate the influence of nutrient cycle perturbations on the soil consumption of atmospheric CH4 and in increased N2O emissions. This revised version was published online in August 2006 with corrections to the Cover Date.  相似文献   
6.
This paper reports a study on the distribution of dinitrogen between the atmosphere, floodwater and porewater of the soil in a flooded rice field after addition of15N-labelled urea into the floodwater.Microplots (0.086 m2) were established in a rice field near Griffith, N.S.W., and labelled urea (80 kg N ha–1 containing 79.25 atoms %15N) was added to the floodwater when the rice was at the panicle initiation stage. Emission of nitrous oxide and dinitrogen was measured directly during the day and overnight, using a cover collection method and gas chromatographic and mass spectrometric analytical methods. Ammonia volatilization was calculated with a bulk aerodynamic method from measurements of wind speed and floodwater pH, temperature and ammoniacal nitrogen concentration. Seven days after urea application the15N2 content of the floodwater and soil porewater was determined and total fertilizer nitrogen loss was calculated from an isotopic balance.Throughout the experimental period gas fluxes were low; nitrous oxide, ammonia and dinitrogen flux densities were less than 5, 170 and 720 g N ha–1 d–1, respectively. The greatest dinitrogen flux density was observed two days after urea addition and this declined to ~ 100 g ha–1 d–1 after seven days.The data indicate that, of the urea nitrogen added, 0.02% was lost to the atmosphere as nitrous oxide, 0.9% was lost by ammonia volatilization, and 3.6% was lost as dinitrogen gas during the 7 days of measurement. At the end of this period 0.028% and 0.002% of the added nitrogen was retained as dinitrogen gas in the floodwater and soil porewater respectively. Recovery of the15N applied as nitrogen gases, plant uptake, and soil and floodwater constituents totaled about 94% of the nitrogen added.  相似文献   
7.
This paper is focused on the effects of sharing knowledge and collaboration of multiple heterogeneous, intelligent agents (hardware or software) which work together to learn a task. As each agent employs a different machine learning technique, the system consists of multiple knowledge sources and their respective heterogeneous knowledge representations. Collaboration between agents involves sharing knowledge to both speed up team learning, as well as refine the team's overall performance and group behavior. Experiments have been performed that vary the team composition in terms of machine learning algorithms, learning strategies employed by the agents, and sharing frequency for a predator‐prey cooperative pursuit task. For lifelong learning, heterogeneous learning teams were more successful than homogeneous learning counterparts. Interestingly, sharing increased the learning rate, but sharing with higher frequency showed diminishing results. Lastly, knowledge conflicts are reduced over time the more sharing takes place. These results support further investigation of the merits of heterogeneous learning. © 2008 Wiley Periodicals, Inc.  相似文献   
8.
Electrode biasing system was designed, constructed, and installed on the IR-T1 tokamak, and then biasing experiments were carried out. Also, using a Mach probes the effects of radial electric field (produced by biased electrode) on the poloidal and toroidal components of the edge plasma velocity were investigated. The results showed an increase in both toroidal and poloidal components of the edge plasma velocity during biasing regime. Results compared and discussed. During positive biasing, increased Er tends to slow the poloidal rotation in the electron diamagnetic drift direction, i.e., to speed up rotation in the ion diamagnetic drift direction. An increased toroidal rotation velocity has the opposite effect on the poloidal rotation.  相似文献   
9.
This study focuses on the analysis of group scheduling heuristics in a dual-constrained, automated manufacturing cell, where labour utilization is limited to setups, tear-downs and loads/unloads. This scenario is realistic in today's automated manufacturing cells. The results indicate that policies for allocating labour to tasks have very little impact in such an environment. Furthermore, the performance of efficiency oriented, exhaustive, group scheduling heuristics deteriorated while the performance of the more complex, non-exhaustive heuristics improved. Thus, it is recommended that production managers use the simplest labour scheduling policy, and instead focus their efforts to activities such as job scheduling and production planning in such environments.  相似文献   
10.
We report the anti-osteosarcoma and anti-osteosarcoma stem cell (OSC) properties of a nickel(II) complex, 1 . Complex 1 displays similar potency towards bulk osteosarcoma cells and OSCs, in the micromolar range. Notably, 1 displays similar or better OSC potency than the clinically approved platinum(II) anticancer drugs cisplatin and carboplatin in two- and three-dimensional osteosarcoma cell cultures. Mechanistic studies revealed that 1 induces osteosarcoma cell death by necroptosis, an ordered form of necrosis. The nickel(II) complex, 1 triggers necrosome-dependent mitrochondrial membrane depolarisation and propidium iodide uptake. Interestingly, 1 does not evoke necroptosis by elevating intracellular reactive oxygen species (ROS) or hyperactivation of poly ADP ribose polymerase (PARP-1). ROS elevation and PARP-1 activity are traits that have been observed for established necroptosis inducers such as shikonin, TRAIL and glutamate. Thus the necroptosis pathway evoked by 1 is distinct. To the best of our knowledge, this is the first report into the anti-osteosarcoma and anti-OSC properties of a nickel complex.  相似文献   
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