Metformin sensitizes human breast cancer MDA-MB-231 cells to tamo-xifen through down-regulation of c-Myc

AIM: To investigate whether metformin enhances the sensitivity of human breast cancer MDA-MB-231 cells to tamoxifen by down-regulating c-Myc. METHODS: The cell viability, colony formation, apoptosis, and migration and invasion abilities of MDA-MB-231 cells were detected by CCK-8 assay, colony formation experiment, flow cytometry and Transwell assay. The expression level of c-Myc was quantified by Western blot and immunohistochemical analysis. The antitumor effects of metformin and tamoxifen were investigated in vivo in a MDA-MB-231 triple-negative breast cancer xenograft model in the SCID mice. RESULTS: Metformin in combination with tamoxifen exerted synergistic effects on inhibition of the viability, colony formation, migration and invasion, and induced the apoptosis compared with the controls and either agent treatment alone in the MDA-MB-231 cells. The levels of c-Myc was down-regulated in vitro by treatment with metformin and/or tamoxifen (P<0.01). Moreover, metformin or in combination with tamoxifen also reduced the growth of MDA-MB-231 breast cancer tumors in the SCID mice by down-regulation of c-Myc in vivo. CONCLUSION: Metformin in combination with tamoxifen exerts synergistic effects on inhibition of the proliferation, migration, invasion and tumor growth of human triple-negative breast cancer MDA-MB-231 cells by down-regulating c-Myc expression, suggesting that metformin in combination with tamoxifen merits further evaluation as a target.     

防治胡椒瘟病的生物农药和新型低毒化学农药筛选

胡椒瘟病是危害我国胡椒产业的首要病害，目前基本依赖使用化学农药防治。筛选应用生物农药是减少化学农药用量的有效途径。本文采用生长速率法测定胡椒瘟病病原菌对12种生物农药和新型低毒化学农药的敏感性。结果表明：70%烯酰?嘧菌酯WG、木霉菌WP和枯草芽孢杆菌WP对胡椒瘟病病原菌的抑菌效果好且敏感性高，EC50分别为0.211 3、0.49和0.78 μg/mL。     

Bayesian estimation of diagnostic accuracy of a new bead-based antibody detection test to reveal Toxoplasma gondii infections in pig populations

The success of a Toxoplasma gondii surveillance program in European pig production systems depends partly on the quality of the test to detect infection in the population. The test accuracy of a recently developed serological bead-based assay (BBA) was investigated earlier using sera from experimentally infected animals. In this study, the accuracy of the BBA was determined by the use of sera from animals from two field subpopulations. As no T. gondii infection information of these animals was available, test accuracy was determined through a Bayesian approach allowing for conditional dependency between BBA and an ELISA test. The priors for prevalence were based on available information from literature, whereas for specificity vague non-informative priors were used. Priors for sensitivity were based either on available information or specified as non-informative. Posterior estimates for BBA sensitivity and specificity were (mode) 0.855 (Bayesian 95% credibility interval (bCI) 0.702–0.960) and 0.913 (bCI 0.893–0.931), respectively. Comparing the results of BBA and ELISA, sensitivity was higher for the BBA while specificity was higher for ELISA. Alternative priors for the sensitivity affected posterior estimates for sensitivity of both BBA and ELISA, but not for specificity. Because the difference in prevalence between the two subpopulations is small, and the number of infected animals is small as well, the precision of the posterior estimates for sensitivity may be less accurate in comparison to the estimates for specificity. The estimated value for specificity of BBA is at least optimally defined for testing pigs from conventional and organic Dutch farms.     

A global sensitivity analysis of cultivar trait parameters in a sugarcane growth model for contrasting production environments in Queensland,Australia

New sugarcane cultivars are continuously developed to improve sugar industry productivity. Despite this sugarcane crop models such as the ‘Sugar’ module in the Agricultural Productions System sIMulator (APSIM-Sugar) have not been updated to reflect the most recent cultivars. The implications of misrepresenting cultivar parameters in APSIM-Sugar is difficult to judge as little research has been published on the likely values of these parameters and how uncertainty in parameter values may affect model outputs. A global sensitivity analysis can be used to better understand how cultivar parameters influence simulated yields. A Gaussian emulator was used to perform a global sensitivity analysis on simulated biomass and sucrose yield at harvest for two contrasting sugarcane-growing regions in Queensland, Australia. Biomass and sucrose yields were simulated for 42 years to identify inter-annual variability in output sensitivities to 10 parameters that represent physiological traits and can be used to simulated differences between sugarcane cultivars. Parameter main effect (S_i) and total effect (ST_i) sensitivity indices and emulator accuracy were calculated for all year-region-output combinations. When both regions were considered together parameters representing radiation use efficiency (rue), number of green leaves (green_leaf_no) and a conductance surrogate parameter (k_L) were the most influential parameters for simulated biomass in APSIM-Sugar. Simulated sucrose yield was most sensitive to rue, sucrose_fraction (representing the fraction of biomass partitioned as sucrose in the stem) and green_leaf_no. However, climate and soil differences between regions changed the level of influence cultivar parameters had on simulation outputs. Specifically, model outputs were more sensitive to changes in the transp_eff_cf and k_L parameters in the Burdekin region due to lower rainfall and poor simulated soil conditions. Collecting data on influential traits that are relatively simple to measure (e.g. number of green leaves) during cultivar development would greatly contribute to the simulation of new cultivars in crop models. Influential parameters that are difficult to measure directly such as transp_eff_cf and sucrose_fraction are ideal candidates for statistical calibration. Calibrating crop models either through direct observation or statistical calibration would allow crop modellers to better test how new cultivars will perform in a range of production environments.     

Neural network prediction of performance parameters of an inclined plate seed metering device and its reverse mapping for the determination of optimum design and operational parameters

Seed planting equipment with inclined plate seed metering devices is the most commonly used equipment for planting of peanut crop in India. For obtaining the high yield, it is very essential to drop the peanut seeds in rows maintaining accurate seed rate and seed spacing with minimum damage to seeds during metering. This mainly depends on forward speed of the planting equipment, rotary speed of the metering plate and area of cells on the plate. The relationship between these factors and the performance parameters viz., seed rate, seed spacing and percent seed damage can be established using regression analysis. But they may not be very accurate and may pose difficulty in the determination of inputs for a set of desired outputs (reverse mapping). Hence, an attempt has been made in this paper to develop the feed forward artificial neural network (ANN) models for the prediction of the performance parameters of an inclined plate seed metering device. The data were generated in the laboratory by conducting experiments on a sticky belt test stand provided with a seed metering device and an opto-electronic seed counter. The generated data was used to develop both statistical and neural network models. The performance of the developed models was compared among themselves for 4 randomly generated test cases. The results show that the ANN model predicted the performance parameters of the seed metering device better than the statistical models. In order to determine the optimum forward speed of the planting equipment, peripheral speed of the metering plate and the area of cells on the plate to obtain the recommended seed rate of 33.33 seeds/m², seed spacing of 100 mm and percent seed damage of 0.2% with 100% fill of the cells, a novel technique of reverse mapping using ANN model was followed. It was observed that the optimum forward speed of the planting equipment and optimum area of cells on the metering plate had good correlation with size of seed. Linear regression equations were developed to predict the optimum forward speed of the planting equipment and optimum area of cells on the metering plate using the size of seeds as independent parameter. The peripheral speed of the metering plate of 0.237 m/s was found to be optimum for the size of seeds in the range of 95.42-123.01 mm². However, the results need to be verified by conducting planting operation under actual field conditions.     

Sensitivity of Botryosphaeria dothidea from apple to tebuconazole in China

The white rot disease caused by Botryosphaeria dothidea threatens apple production in Bohai bay area and along the Yellow River of China, where disease control is largely dependent on fungicides such as tebuconazole. A total of 146 isolates of B. dothidea obtained from different apple orchards in six provinces were tested for their sensitivity to tebuconazole, carbendazim and iprodione. The EC₅₀ values of all tested isolates for tebuconazole were from 0.035 to 1.415 μg/mL. The broad range of EC₅₀ values of tebuconazole suggests an obvious variation among the 146 isolates. Isolate HB13 (EC₅₀ = 1.415 μg/mL) showed reduced sensitivity to tebuconazole, with an EC₅₀ value significantly higher than those of the other 145 isolates tested. The low sensitivity of HB13 was stable after 15 generations, and this isolate showed similar pathogenicity as susceptible strains. EC₅₀ correlation analysis indicates no cross resistance between tebuconazole and carbendazim and iprodione. Field efficacy trials showed that tebuconazole remains very effective for apple white rot control in China.     

海南不同地区香蕉假茎象甲对几种杀虫剂的敏感性测定

采用虫体浸渍法，测定了海南澄迈和儋州两地的香蕉假茎象甲成虫对480克/升毒死蜱EC、77.5%敌敌畏EC、40%辛硫磷EC、40%丙溴磷EC、25%丙溴?辛硫磷EC、20%三唑磷EC等6种杀虫剂对的敏感性。结果表明，6种药剂对澄迈和儋州两地区的香蕉假茎象甲的毒力大小顺序相同，毒死蜱＞丙溴?辛硫磷＞丙溴磷＞三唑磷＞敌敌畏＞辛硫磷；儋州地区的香蕉假茎象甲对6种药剂的敏感性均高于澄迈地区。     

Comparative diagnostic test characteristics of oscillometric and Doppler ultrasonographic methods in the detection of systolic hypertension in dogs

Comparison of test characteristics allows a clinician to choose the optimal diagnostic test method for an individual patient. This study assessed the comparative test characteristics of noninvasive (NI) blood pressure measurement methods (oscillometric and Doppler) and used this information to develop optimal cutoff values for diagnosis of systolic hypertension in dogs by these NI methods. Simultaneous NI (oscillometric or Doppler methods) and invasive (arterial puncture [AP]) systolic blood pressure (SBP) measurements were obtained prospectively from normal dogs and dogs suspected of having systemic hypertension based on clinical signs. Oscillometric SBP readings were obtained from the distal hind limb (Osc-L, n = 54) or the proximal tail (T. n = 27). Doppler BP measurements were obtained using a forelimb cuff (n = 57). AP-SBP was categorized as hypertensive if > or = 160 mmHg, and sensitivity (Se). specificity (Sp), and likelihood ratios (LR) were calculated for diagnostic cutoff values ranging from 130 to 220 mmHg. Receiver operator characteristic (ROC) curves were analyzed to determine optimal cutoff values for diagnosis of AP-SBP > or = 160 mmHg. Optimal NI SBP cutoff values considered to reflect AP values > or = 160 mmHg were: Osc-L = 160 mmHg (Se: 65%, Sp: 85%. LR = 4.33: 1), Osc-T = 150 mmHg (Se: 84%, Sp: 75%, LR = 3.36: 1), and Doppler = 160 mmHg (Se: 71%,     

A Bayesian approach to the accuracy of clinical observations

The accuracy of clinical observations was estimated using Bayesian latent-class models with two or more independent tests. Four veterinarians carried out systematic independent clinical examinations on 155 pigs in three herds. Based on the results of binary recordings of clinical observations on dullness, poor body condition (PBC), skin lesions, lameness, respiratory disease, and diarrhea, a latent disease state for each clinical disease was estimated using Gibbs sampling.

The accuracy of the clinical observations differed for the four observers and for different clinical signs. Population parameters were estimated from a Bayesian hierarchical model, and the accuracy of a random observer was calculated. We concluded that the accuracy of the veterinarians in this study substantiated the need to pursue more-precise definitions of the clinical findings and that larger sample sizes would be needed to provide reasonable variance estimates. Finally, we concluded that the uncertainty in the clinical decision-making process (starting with the clinical examination) needs to be represented fully.     

连续流粮食干燥控制系统变量分析与结构设

针对粮食干燥影响因素多且不确定,以及测量结果存在滞后的问题,提出了连续流粮食干燥被控变量和控制变量的选择方法,通过实验数据对影响粮食干燥过程的各因素及各因素对粮食出口含水率的灵敏度进行了分析.结果表明,影响较大的因素有排粮电动机转速、热风温度、粮食初始含水率,影响较小的因素有环境温度、热风和冷却风风量、粮食初始温度.设计了连续流粮食干燥过程自动控制系统的控制结构,引入微分环节可有效抑制因测量而造成的滞后现象.