采用惩罚函数法的立体定向放疗方案的优化

γ－刀的全称是“γ－射线立体定向放射治疗系统”。随着近十多年来计算机技术及ＣＴ、ＭＲＩ等先进成象技术的飞速发展，γ－刀在临床中的应用也越来越广泛。而其中治疗规划方案的设计是一项非常庞杂的过程，均需涉及到大量的临床参数和计算，一般是由医生反复调试各参数后确定的，不仅费时，而且难以获得最佳结果。本文据此提出一种数学模型，并以该模型为基础，给出解决该问题的一种方法，即惩罚函数法，计算数据结果表明了这一方     

Bankruptcy prediction using a discrete‐time duration model incorporating temporal and macroeconomic dependencies

The purpose of this paper is to build an alternative method of bankruptcy prediction that accounts for some deficiencies in previous approaches that resulted in poor out‐of‐sample performances. Most of the traditional approaches suffer from restrictive presumptions and structural limitations and fail to reflect the panel properties of financial statements and/or the common macroeconomic influence. Extending the work of Shumway (2001), we present a duration model with time‐varying covariates and a baseline hazard function incorporating macroeconomic dependencies. Using the proposed model, we investigate how the hazard rates of listed companies in the Korea Stock Exchange (KSE) are affected by changes in the macroeconomic environment and by time‐varying covariate vectors that show unique financial characteristics of each company. We also investigate out‐of‐sample forecasting performances of the suggested model and demonstrate improvements produced by allowing temporal and macroeconomic dependencies. Copyright © 2008 John Wiley & Sons, Ltd.     

Time-qualified reference intervals — chronodesms

Summary Methods are presented for qualifying clinical reference intervals, for individuals as well as peer groups, according to circadian and other rhythms, using chronobiologically-defined single samples or time series.Supported by the Hoechst Italia Foundation, US Environmental Protection Agency (R804512-01-0), US Public Health Service (5-K6-GM-13, 981), National Cancer Institute (1R01-CA-14446-01), Cancer Supplement (CA-14445-01S1), National Institute of Aging (A6-00158) and National Institute of Occupational Safety and Health (OH 00631).     

SPIN90 dephosphorylation is required for cofilin-mediated actin depolymerization in NMDA-stimulated hippocampal neurons

Actin plays a fundamental role in the regulation of spine morphology (both shrinkage and enlargement) upon synaptic activation. In particular, actin depolymerization is crucial for the spine shrinkage in NMDAR-mediated synaptic depression. Here, we define the role of SPIN90 phosphorylation/dephosphorylation in regulating actin depolymerization via modulation of cofilin activity. When neurons were treated with NMDA, SPIN90 was dephosphorylated by STEP61 (striatal-enriched protein tyrosine phosphatase) and translocated from the spines to the dendritic shafts. In addition, phosphorylated SPIN90 bound cofilin and then inhibited cofilin activity, suggesting that SPIN90 dephosphorylation is a prerequisite step for releasing cofilin so that cofilin can adequately sever actin filaments into monomeric form. We found that SPIN90 YE, a phosphomimetic mutant, remained in the spines after NMDAR activation where it bound cofilin, thereby effectively preventing actin depolymerization. This led to inhibition of the activity-dependent redistribution of cortactin and drebrin A, as well as of the morphological changes in the spines that underlie synaptic plasticity. These findings indicate that NMDA-induced SPIN90 dephosphorylation and translocation initiates cofilin-mediated actin dynamics and spine shrinkage within dendritic spines, thereby modulating synaptic activity.     

Anti-adipogenesis by 6-thioinosine is mediated by downregulation of PPAR γ through JNK-dependent upregulation of iNOS

Adipocyte dysfunction is associated with the development of obesity. This study shows that 6-thioinosine inhibits adipocyte differentiation. The mRNA levels of PPAR γ and C/EBPα, but not C/EBPβ and δ, were reduced by 6-thioinosine. Moreover, the mRNA levels of PPAR γ target genes (LPL, CD36, aP2, and LXRα) were down-regulated by 6-thioinosine. We also demonstrated that 6-thioinosine inhibits the transactivation activity and the mRNA level of PPAR γ. Additionally, attempts to elucidate a possible mechanism underlying the 6-thioinosine-mediated effects revealed that 6-thioinosine induced iNOS gene expression without impacting eNOS expression, and that this was mediated through activation of AP-1, especially, JNK. In addition, 6-thioinosine was found to operate upstream of MEKK-1 in JNK activation signaling. Taken together, these findings suggest that the inhibition of adipocyte differentiation by 6-thioinosine occurs primarily through the reduced expression of PPAR γ, which is mediated by upregulation of iNOS via the activation of JNK.     

Extraction and analysis of polyunsaturated fatty acid from Asterina pectinifera in Huanghai Sea

The full fats of Asterina pectinifera in Huanghai Sea were extracted and refined using solvent extraction combined with silica gel colmnn chromatography with yield of 1.64%. The full fats were analyzed by gas chromatography and the result indicated that the full fats from Asterina pectinifera contained abundant Polyunsaturated Fatty Acid （PUFA） with a total of 25 kinds, especially rich in EPA and DHA. After enrichment by silica gel colmnn chromatography, the total PUFA content in ligarine fraction is 42.20%, in which EPA and DHA account for 12.50% and 10.33% respectively. The total PUFA content in acetic ether fraction is 48.98%, in which EPA and DHA take up 17.53% and 6.59% respectively. The total amount of EPA and DHA in both fractions all exceeded that of the fish oil from deep sea. In conclusion, the Asterina pectinifera in Huanghai Sea is a favorable source of PUFA.     

Long term toxicity studies with endotoxoid in monkeys

Zusammenfassung Vor dem Hintergrund der vielfältigen Endotoxoidwirkung wurde diese Substanz in chronischen Toxizitätsstudien beiMacaca mulatta geprüft. Endotoxoid wurdeMacaca mulatta in einer Dosierung von jeweils 100/kg in insgesamt 51 Injektionen innerhalb von 12 Wochen injiziert. Dabei zeigte sich, dass diese Substanz keinen Einfluss auf die geprüften klinischchemischen Parameter hatte und bei makroskopischer und histologischer Untersuchung keine Veränderungen auftraten.

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Kindly supported by a grant from the Deutsche Forschungsgemeinschaft to Dr.Fritsch.     

In vivo priming of virus-specific cytotoxic T lymphocytes with synthetic lipopeptide vaccine

Cytotoxic T lymphocytes (CTL) constitute an essential part of the immune response against viral infections. Such CTL recognize peptides derived from viral proteins together with major histocompatibility complex (MHC) class I molecules on the surface of infected cells, and usually require in vivo priming with infectious virus. Here we report that synthetic viral peptides covalently linked to tripalmitoyl-S-glycerylcysteinyl-seryl-serine (P3CSS) can efficiently prime influenza-virus-specific CTL in vivo. These lipopeptides are able to induce the same high-affinity CTL as does the infectious virus. Our data are not only relevant to vaccine development, but also have a bearing on basic immune processes leading to the transition of virgin T cells to activated effector cells in vivo, and to antigen presentation by MHC class I molecules.