Studies on the Biosynthesis of the Stephacidin and Notoamide Natural Products: A Stereochemical and Genetic Conundrum

The stephacidin and notoamide natural products belong to a group of prenylated indole alkaloids containing a bicyclo[2.2.2]diazaoctane core. Biosynthetically, this bicyclic core is believed to be the product of an intermolecular Diels–Alder (IMDA) cycloaddition of an achiral azadiene. Since all of the natural products in this family have been isolated in enantiomerically pure form to date, it is believed that an elusive Diels–Alderase enzyme mediates the IMDA reaction. Adding further intrigue to this biosynthetic puzzle is the fact that several related Aspergillus fungi produce a number of metabolites with the opposite absolute configuration, implying that these fungi have evolved enantiomerically distinct Diels–Alderases. We have undertaken a program to identify every step in the biogenesis of the stephacidins and notoamides, and by combining the techniques of chemical synthesis and biochemical analysis we have been able to identify the two prenyltransferases involved in the early stages of the stephacidin and notoamide biosyntheses. This has allowed us to propose a modified biosynthesis for stephacidin A, and has brought us closer to our goal of finding evidence for, or against, the presence of a Diels–Alderase in this biosynthetic pathway.     

Redirecting effector T cells through their IL-2 receptors

Fusion proteins constructed of a tumor-specific Ab joined to IL-2 (Ab-IL-2) have been used in the past to deliver cytokine directly to the site of tumor cells in vivo. These molecules mimic the activity of IL-2 and assist in activating and expanding antitumor effector cells. To enhance the cytolytic activity of CTL specific for peptide epitopes of the Her-2/neu tumor Ag presented by HLA-A*0201 molecules, a fusion protein was constructed consisting of a single chain Ab specific for Her-2/neu, linked to IL-2 (neu-Ab-IL-2). When added to a mixture of tumor cells and Her-2/neu-specific CTL, the protein was found to augment lysis of tumor cells. In addition, the hybrid molecule also promoted lysis of Her-2/neu expressing tumors by non-tumor-specific cloned T cell lines, including Th1 CD4 cells. Analysis of the mechanism of cytotoxicity revealed that the fusion protein mediates the formation of stable conjugates between T cells expressing IL-2R and tumor cells expressing Her-2/neu, resulting in lysis through the Fas-Fas ligand pathway. Lysis induction was independent of specific engagement by the TCR. When tested for its ability to enhance tumor cell eradication by Her-2/neu-specific CD8+ T cells in an adoptive transfer model in SCID mice, neu-Ab-IL-2 facilitated the elimination of tumor cells in vivo. Surprisingly, the combination of non-tumor-specific CD8+ T cells and fusion protein also induced a significant delay of tumor growth. This represents a novel approach for redirecting non-tumor-specific T cells to eliminate tumors.     

Formulation and characterization of ultra-thick electrodes for high energy lithium-ion batteries employing tailored metal foams

Increasing the thickness of a battery electrode without comprising cell electrochemical performance, such as power density and cycling stability, is very challenging. In this work, we demonstrate the utility of 3D (three dimensional) Cu foam framework as a current collector for building carbon negative electrodes as thick as 1.2 mm. When tested in a bipolar configuration, electrodes of 1.2 and 0.6 mm thick delivered capacities of over 350 mAh g⁻¹ (>95% of theoretical capacity) up to a C/5 rate. We have also assembled a full cell composed of a 1.2 mm thick negative electrode with Cu foam as the current collector and a 1.2 mm thick L333 (LiNi_1/3Mn_1/3Co_1/3O₂) positive electrode with Al foam as the current collector. The cell exhibited good capacity retention at low rates. These results underscore the promise of 3D foam structures in terms of enabling ultra-thick electrodes for high energy density battery applications.     

深圳华侨城会所

“深圳华侨城会所不仅仅是理查德·迈耶第一次涉足中国的代表项目，同时还是周边地区一个质量非常高的建设项目。”这点也是香港龚书楷建筑师事务所有限公司在项目起初设定的使命，并引领项目团队克服在施工过程中所遇到的全部挑战。     

Studies on the Biosynthesis of the Stephacidin and Notoamide Natural Products: A Stereochemical and Genetic Conundrum

The stephacidin and notoamide natural products belong to a group of prenylated indole alkaloids containing a bicyclo[2.2.2]diazaoctane core. Biosynthetically, this bicyclic core is believed to be the product of an intermolecular Diels- Alder (IMDA) cycloaddition of an achiral azadiene. Since all of the natural products in this family have been isolated in enantiomerically pure form to date, it is believed that an elusive Diels-Alderase enzyme mediates the IMDA reaction. Adding further intrigue to this biosynthetic puzzle is the fact that several related Aspergillus fungi produce a number of metabolites with the opposite absolute configuration, implying that these fungi have evolved enantiomerically distinct Diels-Alderases. We have undertaken a program to identify every step in the biogenesis of the stephacidins and notoamides, and by combining the techniques of chemical synthesis and biochemical analysis we have been able to identify the two prenyltransferases involved in the early stages of the stephacidin and notoamide biosyntheses. This has allowed us to propose a modified biosynthesis for stephacidin A, and has brought us closer to our goal of finding evidence for, or against, the presence of a Diels-Alderase in this biosynthetic pathway.     

Palliative care: pain and symptom management in persons with HIV/AIDS

As patients with HIV/AIDS are living longer with the illness, pain and symptom management are increasingly important health issues. This article will discuss the assessment and management of such common problems as pain, fatigue and weakness, dyspnea and cough, anorexia and weight-loss, nausea and vomiting, sleep disorders, dry mouth, diarrhea, itching, and fever and night sweats.     

The effect of omega-3 polyunsaturated fatty acids in the diet on the indices of lipid metabolism in patients with ischemic heart disease

To study the dietetic effect of canned natural Ivasi herring, containing up to 10% of eicosopentenic acid, the blood serum was analyzed in 37 patients with coronary heart disease at Vladivostok City Hospital and in 73 patients at the Regional Cardiological Sanatorium. Lipid characteristics of the blood serum (total cholesterol, alpha- and beta-cholesterol, beta-lipoproteins) were comparatively studied in 5 groups of subjects: normal subjects, two control groups (who did not receive the dietetic product) and two groups who received Ivasi herring. A favourable effect on all above parameters was recorded in more than 50% of patients in the sanatorium. The frequency of favourable shifts was higher in patients who received Ivasi herring than in the controls, the highest changes concerned beta-cholesterol. No significant improvement was recorded in coronary patients during the acute period (the group at the City Hospital). The results of the investigation have evidenced the expediency of using canned Ivasi herring in the diet therapy and prevention of coronary heart disease during the rehabilitation period.     

用于战术制导与导航应用的一种微机械振梁多敏感器的研制

基尔福特(Kearfott)制导与导航公司已经开发出用于战术惯性制导与导航应用的一种微机械振梁多敏感器(MVBM).这种MVBM是一种固态石英(硅Si)器件,它测量运动共轴的线加速度和角速率.这是通过单个柔性放置的检测质量来实现的,其中检测质量起到一种耦合模式的哥里奥利(Coriolis-哥氏)敏感器和加速度计的作用.位置敏感器是固定的,以使这两种测量在双级输出中有所不同,这样增加了标度因数,且相对于单极器件而言降低了共模而引起的热、振动以及老化误差.