Using Copulas to Introduce Dependence in Dose-Response Modeling of Multiple Binary Endpoints

We propose a method for introducing dependence in the dose-response modeling of multiple dichotomous endpoints. The method uses a copula to define a joint multivariate distribution that is consistent with predetermined marginal distributions representing the individual dose-response functions for each endpoint. Use of copulas allows the marginal dose-response functions for each dose-endpoint combination to be unrestricted in form. An application of particular relevance to risk assessment is the dose-response modeling of multiple types of tumors in test animals exposed to a carcinogen, allowing for tumors at different sites in the same animal to be statistically dependent. In addition, the method can be used to address the possibility that different tissues/organs are subject to different internal doses and possibly different active moieties. These applications are illustrated with rodent cancer bioassay data from two example compounds.     

Immunoadjuvant activities of a recombinant chicken IL-12 in chickens vaccinated with Newcastle disease virus recombinant HN protein

Recombinant fowlpox virus (rFPV/HN) expressing Newcastle disease virus (NDV) HN gene and rFPV/HN/chIL-12 co-expressing chicken IL-12 (chIL-12) and HN (rHN/chIL-12) genes have been characterized. rHN/chIL-12 or rchIL-12, expressed by our previous construct rFPV/chIL-12, co-administered with rHN was assessed for adjuvant activities of chIL-12. Chickens were vaccinated with various amounts of rHN/chIL-12 mixed with mineral oil (MO), intramuscularly. Levels of hemagglutination-inhibition (HI) antibody production depended on the concentration of the injected rHN or rHN/chIL-12. The lower HI antibody titers were obtained in chicken groups rHN/chIL-12/7-rHN/chIL-12/9, receiving 60ng rHN/8ng chIL-12 with MO, 30ng rHN/4ng chIL-12 with MO or 15ng rHN/2ng chIL-12 with MO, respectively, compared to those in chicken groups rHN/7-rHN/9, receiving rHN with MO alone. However, chickens in group rHN/chIL-12/7 or rHN/chIL-12/8 and rHN with MO alone showed the same effective protection. Chicken group rHN/chIL-12/9 was even more protective than that in group rHN/9. When rchIL-12 was co-injected with 15ng rHN plus MO, chickens produced low levels of HI antibody titers; while higher levels of IFN-γ production and an effective protection rate (83%) were obtained. On the other hand, low levels of IFN-γ production and low protection response (50%) were obtained in chickens injected with rHN with MO alone. Taken together, when the concentration of rHN decreased to certain levels, rchIL-12 reduced HI antibody production. The increase in the induction of IFN-γ production might suggest the enhancement of the cell-mediated immunity which conferred the protection from the NDV challenge.     

Ellagic acid inhibits oxidized low-density lipoprotein (OxLDL)-induced metalloproteinase (MMP) expression by modulating the protein kinase C-α/extracellular signal-regulated kinase/peroxisome proliferator-activated receptor γ/nuclear factor-κB (PKC-α/ERK/PPAR-γ/NF-κB) signaling pathway in endothelial cells

Previous studies have shown that vascular endothelium-derived matrix metalloproteinases (MMPs) contribute to the destabilization of atherosclerotic plaques, a key event triggering acute myocardial infarction. In addition, studies have reported that the PKC-MEK-PPARγ signaling pathway is involved in oxidized low-density lipoprotein (oxLDL)-induced expression of MMPs. Ellagic acid, a phenolic compound found in fruits and nuts, has potent antioxidant, anti-inflammatory, and anticancerous properties. However, the molecular mechanisms underlying its antiatherogenic effects remain to be clarified. This study aimed to assess whether the effects of ellagic acid on the fibrotic markers MMP-1 and MMP-3 are modulated by the PKC-ERK-PPAR-γ signaling pathway in human umbilical vein endothelial cells (HUVECs) that have been exposed to oxLDL. It was found that ellagic acid significantly inhibited oxLDL-induced expressions of MMP-1 and MMP-3. Pretreatment with ellagic acid and DPI, a well-known ROS inhibitor, attenuated the oxLDL-induced expression and activity of PKC-α. In addition, ellagic acid as well as pharmacological inhibitors of ROS, calcium, and PKC strongly suppressed the oxLDL-induced phosphorylation of extracellular signal-regulated kinase (ERK) and NF-κB activation. Moreover, ellagic acid ameliorated the oxLDL-induced suppression of PPAR-γ expression. In conclusion, the data suggest that ellagic acid elicits its protective effects by modulating the PKC-α/ERK/PPAR-γ/NF-κB pathway, resulting in the suppression of ROS generation and, ultimately, inhibition of MMP-1 and MMP-3 expression in HUVECs exposed to oxLDL.     

Microbial distribution and function across wheat rhizosphere with oxamide and ammonium sulfate as N sources

Analysis of the effect of slow-releasing N fertilizers on microbial parameters of the rhizosphere soil is essential for their effective use. This investigation revealed the comparative effects of oxamide and ammonium sulfate as different N sources on some selected microbial parameters as well as the pH in the rhizosphere of wheat (Triticum aestivum cv. Nourin No. 61). The study was conducted on a Japanese upland alluvial soil using a rhizobox system. In the central compartment (CC) of the rhizoboxes treated with oxamide and ammonium sulfate, four wheat seedlings were grown for 53 d. In either of the treatments, the pH of the rhizosphere soil increased with the increase in the distance from the CC. In contrast, nitrate production, bacterial and fungal numbers, microbial biomass nitrogen, and β-acetylglucosaminidase activity decreased with the increase in the distance, with the highest values of the respective parameters being recorded in the CC. However, remarkable changes of these microbial parameters were found within a distance of 1–2 mm from the CC to the distant compartments. Thus the results indicated that pH, bacterial number, and nitrate production were high in the oxamide treatment. In contrast, higher fungal number, microbial biomass N, and .B-acetylglucosaminidase activity were associated with the ammonium sulfate treatment. It was assumed that the significant (p<O.05) effect of the rhizosphere on microbial activities varied with the treatments.     

Electroacupuncture-induced neural activation detected by use of manganese-enhanced functional magnetic resonance imaging in rabbits

OBJECTIVE: To investigate the effects of acupuncture on neural activity detected by use of manganese-enhanced functional magnetic resonance imaging (fMRI) and elucidate the relationship between somatic acupoint stimulation and brain activation. ANIMALS: 40 New Zealand White rabbits. PROCEDURE: Manganese-enhanced fMRI was performed in anesthetized rabbits manipulated with electroacupuncture (EA) on Zusanli (ST-36) and Yanglingquan (GB-34) acupoints. Image acquisition was performed on a 1.5T superconductive clinical scanner with a circular polarized extremity coil. T1-weighted images were acquired sequentially as follows: baseline, after mannitol injection, after manganese infusion, and 5 and 20 minutes after initiation of EA. RESULTS: Changes in focal neural activity were detected by use of manganese-enhanced fMRI. Stimulation on Zusanli (ST-36) for 5 minutes resulted in activation of the hippocampus, whereas stimulation on Yanglingquan (GB-34) resulted in activation of the hypothalamus, insula, and motor cortex. Activation became less specific after 20 minutes of EA. Furthermore, stimulation on ipsilateral acupoints led to bilateral brain activation. CONCLUSIONS AND CLINICAL RELEVANCE: Each acupoint has a corresponding cerebral linkage, and stimulation on these points resulted in time-dependent neural activation. Understanding the linkage between peripheral acupoint stimulation and central neural pathways may provide a useful guide for clinical applications of acupuncture.     

苦豆子种子抽提物对两种蔬菜害虫的活性

在害虫防治中,面对化学防治出现的一些问题,本文采集广泛分布于我国西北地区的野生豆科植物苦豆子Sophora alopecuroida(L.),采取有机溶剂制备提取物,测定了对两种蔬菜害虫的生物活性,结果简报如下。 1.1 苦豆子提取物制备及试验方法将苦豆子种子用植物粉碎机粉碎并过40目筛,在实验室以索氏抽提器进行抽提,然后将提取物在旋转蒸发器内蒸干,将此提取物稀释后进行毒力测定。供试虫为萝卜蚜Li-     

光活化农药的研究与应用

结合作者近期的研究工作，对光活化农药的研究现状、作用机理、应用前景及其与新农药创 制的关系进行了综述。