多元方差分析中的单一自由度独立比较

本文根据一元方差分析的单一自由度比较原理提出了多元方差分析中的单一自由度比较方法,以用于各种平衡试验设计中具多个变量的处理间多重比较．     

巢式设计的多元分析

本文把经典巢式设计的统计分析方法由单变量推广到多变量,使得试验或调查的多性状数据能综合在一起进行分析,以得出考虑了性状间相关性在内的统计结论并用一烟草栽培试验数据示明具体步骤。     

鼠抗人纤维蛋白抗体单链Fv片断的三维结构模建

用Biosym公司开发的计算机辅助分子设计系统模建了鼠抗人纤维蛋白抗体Fv片断的三维结构。Fv是由重链可变区(Vh)和轻链可变区(Vl)两个结构域组成的具有抗原结合能力的最小抗体片断。先分别模建了Vh和Vl两个结构域,然后搭建出Fv片断的整体三维结构,并对模建的结构进行了分子力学和动力学优化。对结构的合理性验证显示模建结构是合理的。本研究为鼠抗人纤维蛋白抗体Fv片断的人源化的分子设计打下了基础。     

Genetics of size and growth rate through sexual maturity in freshwater-reared coho salmon (Oncorhynchus kisutch)

Genetic parameters of size through sexual maturity have been relatively unexplored for Pacific salmon. In this study, individually tagged coho salmon were raised in freshwater, and the heritabilities of size and growth rate were estimated at several intervals between 13 and 24 months of age (spawning). Heritability estimates for size were moderate to high from 13 to 19 months of age, ranging from 0.36 to 0.50, and lower from 21 months to spawning at 24 months, ranging from 0.17 to 0.32. Heritabilities of specific growth rates estimated over 3-month intervals were moderate from 16 to 21 months of age, ranging from 0.21 to 0.34. Genetic and phenotypic correlations between sizes measured at different ages were moderate to high, ranging from about 0.7 to 1.0. Correlations between growth rate and size indicated that the larger fish were the fastest growing between 16 and 19 months of age and were slower growing between 19 and 21 months of age.     

Modulated red blood cell survival by membrane protein clustering

Human and murine blood cells treated with ZnCl₂ and bis(sulfosuccinimidyl)suberate (BS³) (a cross linking agent) undergo band 3 clustering and binding of hemoglobin to red blood cell membrane proteins. These clusters induce autologous IgG binding and complement fixation, thus favouring the phagocytosis of ZnCl₂/BS³ treated cells by macrophages. The extension of red blood cell opsonization can be easily modulated by changing the ZnCl₂ concentration in the 0.1–1.0 mM range thus providing an effective way to affect blood cell recognition by macrophages. In fact, murine erythrocytes treated with increasing ZnCl₂ concentrations have proportionally reduced survivals when reinjected into the animal. Furthermore, the organ sequestration of ZnCl₂/BS³ treated cells strongly resembles the typical distribution of the senescent cells. Since the ZnCl₂/BS³ treatment can also be performed on red blood cells loaded with drugs or other substances, this procedure is an effective drug-targeting system to be used for the delivery of molecules to peritoneal, liver and spleen macrophages.     

Modulation of cisPlatin cytotoxicity by interleukin-1α and resident tumor macrophages

The modulation of cisPlatin cytotoxicity by interleukin-1 (IL-1α) was studied in cultures of SCC-7 tumor cells with and without tumor macrophages to examine potential mechanisms for the synergistic antitumor activity of cisPlatin and IL-1α in SCC-7 solid tumors. Neither IL-1α nor tumor macrophages affected the survival of clonogenic tumor cells and IL-1α had no direct effect on tumor cell growthin vitro. Macrophages had no direct effect on cisPlatin sensitivity (IC₉₀=6.0 μM), but, the addition of IL-1α (500–2000U/ml) to co-cultures of cisPlatin pretreated tumor cells and resident tumor macrophages increased cell killing (IC₉₀=3.1 μM). Similar responses were seen in primary cultures treated with cisPlatin before IL-1α. The modulation of cisPlatin cytotoxicity by IL-1α exhibited a biphasic dose response that paralleled the IL-1α dose dependent release of H₂O₂by resident tumor macrophages. Further, IL-1α modification of cisPlatin cytotoxicity was prompt and inhibited by catalase. CisPlatin and exogenous H₂O₂ (50 μM) produced more than additive SCC-7 clonogenic cell kill and hydroxyl radicals played an important role in the response. Interleukin-1 modulation of cisPlatin cytotoxicity was schedule dependent. IL-1α treatment for 24 hrs, before cisPlatin, produced drug resistance (IC₉₀=11.1 μM). Our study shows that IL-1α can stimulate tumor macrophages to release pro-oxidants that modify cellular chemosensitivity in a schedule and dose dependent fashion. Our findings may also provide a mechanistic explanation for the synergistic antitumor activity of cisPlatin and IL-1αin vivo.     

Engineering of zinc finger and MHC motifs to locked-in tertiary folds

The assembly of helical and -sheet peptide blocks containing reactive chain ends results inhighly branched chain architectures (locked-in folds) mimicking native tertiary structures.This molecular kit strategy allows to bypass the protein folding problem in protein de novodesign and gives access to protein mimetics of high thermodynamic stability. The validity ofthis concept is exemplified for the design and synthesis of locked-in folds mimicking the zincfinger and MHC folding motifs.