Search for substrate-based inhibitors fitting the S2' space of malarial aspartic protease plasmepsin II.

Plasmepsin (Plm) has been identified as an important target for the development of new antimalarial drugs, since its inhibition leads to the starvation of Plasmodium falciparum. A series of substrate-based dipeptide-type Plm II inhibitors containing the hydroxymethylcarbonyl isostere as a transition-state mimic were synthesized. The general design principle was provision of a conformationally restrained hydroxyl group (corresponding to the set residue at the P2' position in native substrates) and a bulky unit to fit the S2' pocket.     

优化肥料结构促进稻田土壤生态良性循环

１９８５￣１９９２年在福州、莆田两地,２次进行８年１６个稻作年次定位试验。结果表明,尿素分别与红萍、绿肥、厩肥、稻草配合施用,对稻田土壤物理性状、碳氮平衡、微生物区系、酶活性、供肥能力等生态良性循环有积极的影响;稻谷平均每公顷年产量比等氮量尿素为对照的,增产分别为１０．７％、１１．４％、９．６％、６．５％。取得显著的经济效益和土壤生态效益。     

北方稻田生态系统研究Ⅱ．稻萍结合系统细绿萍共生固N量研究

对稻萍结合系统细绿萍共生固Ｎ量研究表明,萍的固Ｎ力在整个生长季不同时期有所变化．最高固Ｎ率出现在６月初,萍固Ｎ量随其接种量和水稻行距增加而增加．５０～１０ｃｍ宽窄行交替的水稻行距和１５００ｋｇ·ｈｍ－２的萍接种量的稻萍结合系统的总固Ｎ量为１０７．１ｋｇ·ｈｍ－２,而３０ｃｍ等行距的３２５ｋｇ·ｈｍ－２的萍接种量的稻－萍结合系统的总固Ｎ量仅为３６．０ｋｇ·ｈｍ－２     

珍珠菜属的新组合和新异名──兼论此属植物在中国和日本的地理替代现象

本文对过去一直认为是日本特有的两种珍珠菜属植物作了归并和组合：将Ｌｙｓｉｍａｃｈｉａ,ｔａｓｈｉｒｏｉＭａｋｉｎｏ归并作Ｌ．ｐａｔｕｎｇｅｎｓｉｓＨａｎｄ．－Ｍａｚｚ．的异名,将Ｌ．ｔａｎａｋａｅＭａｘｉｍ．降级作Ｌ．ｃｈｒｉｓｔｉｎａｅＨａｎｃｅ的亚种处理．对此间植物在中国和日本的地理替代现象作了讨论．     

Thoughts on the origin and nature of life and intelligence on earth

Believing, for good reasons, that our Universe engenders the occurrence of Life, it is probable that Life appeared more than once on young planet Earth. The universality of our genetic code indicates though, that only one line produced a population that was cellular, autopoietic, responsive intelligently (i.e., to its advantage) to its environment, and capable of reproduction. Its evolution took time during which other intermediate or incipient forms of life disappeared. Trying to retrace ab initio the preceding chemical evolution on our young planet, we may not repeat the chemistry which led to our line. One can argue that it may be profitable to attempt to construct artificial life forms using the kind of building blocks that we learned to know through studying the chemistry of our life. Independently, computers are being built, or are planned, which possess memory that can be used appropriately (intelligently), and which to some extent can repair and reproduce themselves. Such Life does not depend on our biochemistry. However, these machines do perform as yet only partly along the lines of our human intelligence which is guided by self-awareness and a sense of individual integrity, and are thereby not equipped to search for Understanding and Self-expression.     

数理统计方法优化单细胞蛋白发酵培养基研究

采用正交试验和中心组合设计相结合的数理统计方法,在２Ｌ发酵罐中对紫云英汁液培养单细胞蛋白发酵培养基进行筛选、优化,试验结果表明较优培养基为：初糖２．３％,酵母粉０．１６％,ＫＨ_２ＰＯ_４０．２％,ＭｇＳＯ_４０．０５％。酵母浓度最高达１０．４６ｇ／Ｌ,基质生长得率为０．５５ｇ菌体／ｇ基质,基质转化率为８３％。研究结果同时说明采用数理统计方法设计实验,工作量小,效率高,结果准确。     

Approximate likelihood ratios for general estimating functions

The method of estimating functions (Godambe, 1991) is commonlyused when one desires to conduct inference about some parametersof interest but the full distribution of the observations isunknown. However, this approach may have limited utility, dueto multiple roots for the estimating function, a poorly behavedWald test, or lack of a goodness-of-fit test. This paper presentsapproximate likelihood ratios that can be used along with estimatingfunctions when any of these three problems occurs. We show thatthe approximate likelihood ratio provides correct large sampleinference under very general circumstances, including clustereddata and misspecified weights in the estimating function. Twomethods of constructing the approximate likelihood ratio, onebased on the quasi-likelihood approach and the other based onthe linear projection approach, are compared and shown to beclosely related. In particular we show that quasi-likelihoodis the limit of the projection approach. We illustrate the techniquewith two applications.     

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.