MULTISPECIES AND SINGLE‐SPECIES MODELS OF FISH POPULATION DYNAMICS: COMPARING PARAMETER ESTIMATES

Abstract Population features inferred from single‐species, age‐structured models are compared to those inferred from a multispecies, age‐structured model that includes predator‐prey interactions among three commercially harvested fish species—walleye pollock, Atka mackerel, and Pacific cod—on the Aleutian Shelf, Alaska. The multispecies framework treats the single‐species models and data as a special case of the multispecies model and data. The same data from fisheries and surveys are used to estimate model parameters for both single‐species and multispecies configurations of the model. Additionally, data from stomach samples and predator rations are used to estimate the parameters of the multispecies model. One form of the feeding functional response, predator pre‐emption, was selected using AIC from seven alternative models for how the predation rate changes with the densities of prey and possibly other predators. Differences in estimated population dynamics and productivity between the multispecies and single‐species models were observed. The multispecies model estimated lower mackerel population sizes from 1964–2003 than the single‐species model, while the spawning biomass of pollock was estimated to have declined more than three times faster since 1964 by the multispecies model. The variances around the estimates of spawning biomass were smaller for mackerel and larger for pollock in the multispecies model compared to the single‐species model.     

中国股市和债市波动溢出效应的MV-GARCH分析

股市和债市的波动溢出效应是研究金融市场信息流动、风险传递的重要内容。在估计了股市和债市候选MV-GARCH模型参数基础上,通过AIC准则等拟合优度方法选择了t分布型BEKK为最优模型,因为它更好的捕捉到了金融时序尖峰、厚尾的特征.结果显示,中国股市和债市波动溢出具有明显时变特征,波动影响不对称,股市对债市影响大于债市对股市影响。动态相关系数偏弱说明两个市场在资源配置能力、信息流动等方面存在显著的缺陷.     

Development of small molecules designed to modulate protein–protein interactions

Summary Protein–protein interactions are ubiquitous, essential to almost all known biological processes, and offer attractive opportunities for therapeutic intervention. Developing small molecules that modulate protein–protein interactions is challenging, owing to the large size of protein-complex interface, the lack of well-defined binding pockets, etc. We describe a general approach based on the “privileged-structure hypothesis” [Che, Ph.D. Thesis, Washington University, 2003] – that any organic templates capable of mimicking surfaces of protein-recognition motifs are potential privileged scaffolds as protein-complex antagonists – to address the challenges inherent in the discovery of small-molecule inhibitors of protein–protein interactions.This paper is adapted from a presentation at the 230th National Meeting of the American Chemical Society, Washington DC, August 28 – September 1, 2005, Abstract COMP-136.     

A validated new method for nevirapine quantitation in human plasma via high-performance liquid chromatography

A fully validated and clinically relevant assay was developed for the assessment of nevirapine concentrations in neonate blood plasma samples. Solid-phase extraction with an acid-base wash series was used to prepare subject samples for analysis. Samples were separated by high performance liquid chromatography and detected at 280 nm on a C8 reverse-phase column in an isocratic mobile phase. The retention times of nevirapine and its internal standard were 5.0 and 6.9 min, respectively. The method was validated by assessment of accuracy and precision (statistical values <15%), specificity, and stability. The assay was linear in the range 25-10,000 ng/mL (r2 > 0.996) and the average recovery was 93% (n = 18). The lower limit of quantification (relative standard deviation <20%) was determined to be 25 ng/mL for 50 microL of plasma, allowing detection of as little as 1.25 ng of nevirapine in a sample. This value represents an increase in sensitivity of up to 30-fold over previously published methods.     

Applicability of bioanalysis of multiple analytes in drug discovery and development: review of select case studies including assay development considerations

The development of sound bioanalytical method(s) is of paramount importance during the process of drug discovery and development culminating in a marketing approval. Although the bioanalytical procedure(s) originally developed during the discovery stage may not necessarily be fit to support the drug development scenario, they may be suitably modified and validated, as deemed necessary. Several reviews have appeared over the years describing analytical approaches including various techniques, detection systems, automation tools that are available for an effective separation, enhanced selectivity and sensitivity for quantitation of many analytes. The intention of this review is to cover various key areas where analytical method development becomes necessary during different stages of drug discovery research and development process. The key areas covered in this article with relevant case studies include: (a) simultaneous assay for parent compound and metabolites that are purported to display pharmacological activity; (b) bioanalytical procedures for determination of multiple drugs in combating a disease; (c) analytical measurement of chirality aspects in the pharmacokinetics, metabolism and biotransformation investigations; (d) drug monitoring for therapeutic benefits and/or occupational hazard; (e) analysis of drugs from complex and/or less frequently used matrices; (f) analytical determination during in vitro experiments (metabolism and permeability related) and in situ intestinal perfusion experiments; (g) determination of a major metabolite as a surrogate for the parent molecule; (h) analytical approaches for universal determination of CYP450 probe substrates and metabolites; (i) analytical applicability to prodrug evaluations-simultaneous determination of prodrug, parent and metabolites; (j) quantitative determination of parent compound and/or phase II metabolite(s) via direct or indirect approaches; (k) applicability in analysis of multiple compounds in select disease areas and/or in clinically important drug-drug interaction studies. A tabular representation of select examples of analysis is provided covering areas of separation conditions, validation aspects and applicable conclusion. A limited discussion is provided on relevant aspects of the need for developing bioanalytical procedures for speedy drug discovery and development. Additionally, some key elements such as internal standard selection, likely issues of mass detection, matrix effect, chiral aspects etc. are provided for consideration during method development.     

Self‐Assembled Micelles Based on PEG‐Polypeptide Hybrid Copolymers for Drug Delivery

A series of amphiphilic poly(L ‐leucine)‐block‐poly(ethylene glycol)‐block‐poly(L ‐leucine) (PLL‐PEG‐PLL) hybrid triblock copolymers have been synthesized. All the blocks in this system have good biocompatibility and low toxicity. The PLL‐PEG‐PLL copolymers could self‐assemble into micelles with PLL blocks as the hydrophobic core and PEG blocks as the hydrophilic shell, which were characterized by FT‐IR, ¹H NMR, and transmission electron microscopy analysis. The critical micellar concentration of the copolymer was 95.0 mg · L⁻¹. The circular dichroism spectrum shows that the PLL segments adopt a unique α‐helical conformation, which is found to play an important role in controlling the drug release rate. The drug release could be effectively sustained by encapsulation in the micelles. The copolymers may have potential applications in drug delivery.

     

使用T-20治疗HIV-1患者的不同策略的数学建模与研究

通过建立数学模型,描述了HIV-1感染者使用抗病毒治疗药物——融合酶抑制剂(T-20)的治疗效果．使用脉冲微分方程描述了T-20的使用过程,并考虑了两种不同的药物消除动力学:一级消除动力学与米-曼(Michaelis-Menten)消除动力学．此模型是个非自治微分方程系统,主要关注其无病平衡态,并研究当接受治疗者在服药完全依从的治疗过程中无病平衡态的稳定性．分别针对药物剂量与服药间隔得到了使得无病平衡态稳定的阈值条件．此外,还研究了间歇治疗的效果．研究表明,间歇治疗的效果甚至可以比完全不治疗还要糟糕．     

两亲嵌段共聚物胶束用作医用材料

两亲嵌段共聚物可以在水溶液中自组装形成亲水性链段为外壳、疏水性链段为内核的胶束,这种胶束能够用作药物载体而引起人们极大的关注。本文综述了两亲嵌段共聚物胶束用作医用材料的研究进展,主要内容包括医用两亲嵌段共聚物的种类,胶束化,以及用作诊断试剂载体、药物缓释载体、靶向载体等。两亲嵌段共聚物胶束用作磁共振造影剂载体有利于肿瘤的诊断,用作药物缓释载体可以有效增溶难溶性抗肿瘤药物,延长药物在体内的血液循环时间。此外,通过对胶束表面进行修饰或者施加外场,还可以实现靶向功能。因此,两亲嵌段共聚物胶束在医用材料领域有着广阔的发展前景。     

沪深股市相关结构之谜:基于贝叶斯Copula的研究

目前沪深股市相关结构的Copula模型选择差异很大,并没有形成统一的认识。在指出现有Copula检验要受到模型参数估计影响后,引入了贝叶斯估计方法将模型参数估计与拟合优度检验有效的分开。接着,沪深股市相关性的贝叶斯实证结果发现两市相关结构Copula模型具有时变特征,势必导致当前研究结果的不一致;同时也反映了Copula对样本区间选择有很强的依赖性。     

喜树碱/氧化石墨烯/类水滑石纳米杂化物的制备及表征

采用共组装法成功制备了电中性疏水抗癌药物喜树碱（CPT）/氧化石墨烯（GO）/Mg-Al类水滑石（HTlc）纳米杂化物. 先将CPT负载于荷负电的GO纳米片表面上制备成CPT/GO复合物,再与荷正电的HTlc纳米片（HNS）共组装,形成CPT/GO/HTlc纳米杂化物,其中GO纳米片和HNS相间叠加,CPT负载于层间. 采用X-射线衍射、透射电子显微镜、原子力显微镜、扫描电子显微镜-能量色谱仪、傅里叶变换红外光谱、紫外-可见分光光度计和热重/差示扫描量热分析等技术对纳米杂化物进行了表征. 37 ℃下分别在pH 7.4和4.0的磷酸缓冲液中,考察了CPT/GO/HTlc纳米杂化物的药物释放行为. 结果表明,CPT/GO/HTlc纳米杂化物的药物释放过程符合准二级动力学方程,且具pH响应性,在酸性（pH 4.0）介质中的释放速率和释放率明显高于中性（pH 7.4）介质. 共组装法是构筑药物/ GO/HTlc纳米杂化物的简便方法,该纳米杂化物在药物输送领域具有良好的应用前景.