Taxadiene synthase structure and evolution of modular architecture in terpene biosynthesis

With more than 55,000 members identified so far in all forms of life, the family of terpene or terpenoid natural products represents the epitome of molecular biodiversity. A well-known and important member of this family is the polycyclic diterpenoid Taxol (paclitaxel), which promotes tubulin polymerization and shows remarkable efficacy in cancer chemotherapy. The first committed step of Taxol biosynthesis in the Pacific yew (Taxus brevifolia) is the cyclization of the linear isoprenoid substrate geranylgeranyl diphosphate (GGPP) to form taxa-4(5),11(12)diene, which is catalysed by taxadiene synthase. The full-length form of this diterpene cyclase contains 862 residues, but a roughly 80-residue amino-terminal transit sequence is cleaved on maturation in plastids. We now report the X-ray crystal structure of a truncation variant lacking the transit sequence and an additional 27 residues at the N terminus, hereafter designated TXS. Specifically, we have determined structures of TXS complexed with 13-aza-13,14-dihydrocopalyl diphosphate (1.82?? resolution) and 2-fluorogeranylgeranyl diphosphate (2.25?? resolution). The TXS structure reveals a modular assembly of three α-helical domains. The carboxy-terminal catalytic domain is a class?I terpenoid cyclase, which binds and activates substrate GGPP with a three-metal ion cluster. The N-terminal domain and a third 'insertion' domain together adopt the fold of a vestigial class?II terpenoid cyclase. A class?II cyclase activates the isoprenoid substrate by protonation instead of ionization, and the TXS structure reveals a definitive connection between the two distinct cyclase classes in the evolution of terpenoid biosynthesis.     

Modelling peak electricity demand

This paper estimates a forecasting equation for the hourly peak electricity demand one day in the future. The models incorporate deterministic influences such as holidays, stochastic influences such as average loads by building bivariate models, and exogenous influences such as the weather which is given a careful non-linear formulation. Out-of-sample comparisons are made using an additional year of data.     

A KELM-Based Ensemble Learning Approach for Exchange Rate Forecasting

In this paper, a KELM-based ensemble learning approach, integrating Granger causality test, grey relational analysis and KELM(Kernel Extreme Learning Machine), is proposed for the exchange rate forecasting. The study uses a set of sixteen macroeconomic variables including, import,export, foreign exchange reserves, etc. Furthermore, the selected variables are ranked and then three of them, which have the highest degrees of relevance with the exchange rate, are filtered out by Granger causality test and the grey relational analysis, to represent the domestic situation. Then, based on the domestic situation, KELM is utilized for medium-term RMB/USD forecasting. The empirical results show that the proposed KELM-based ensemble learning approach outperforms all other benchmark models in different forecasting horizons, which implies that the KELM-based ensemble learning approach is a powerful learning approach for exchange rates forecasting.     

A Systemic Evaluation of the State of Affairs Following the Negative Outcome of the Referendum in Cyprus Using the Structured Dialogic Design Process

This paper reports the results of the first of a series of co-laboratories organized by Cypriot peace pioneers 30 months after the negative outcome of the referendum concerning UN General Secretary’s plan for reunification of the island. The purpose of this co-laboratory was to support a diverse group of disengaged and disappointed peace pioneers and activists representing Turkish and Greek communities of Cyprus develop a shared understanding of factors contributing to the perceived widening of the gap between the two divided communities in Cyprus. The co-laboratory was organized using the structured dialogic design process (SDDP) approach within the context of a rich web-based communication environment. The root causes contributing to the widening of the gap are discussed and are also compared with those identified during a similar co-laboratory employing the Interactive Management methodology 12 years earlier.

Exploring Options for Enhancement of Social Dialogue Between the Turkish and Greek Communities in Cyprus Using the Structured Dialogic Design Process

This paper summarizes results of a co-laboratory that took place 33 months after the negative outcome of the referendum on the UN’s proposal for the solution of the Cyprus problem, and which was a follow-up (3 months later) of a previous co-laboratory. The earlier co-laboratory explored factors contributing to the increasing gap between the two conflicting communities. The co-laboratory reported here engaged relevant stakeholders (peace pioneers, academics, business people, activists and others representing the Turkish and Greek speaking communities of Cyprus) to come up with options aiming to enhance the social dialogue between the two communities. The Structured Dialogic Design Process was used to structure 27 proposed options and develop an influence map. The deep drivers, i.e., most influential factors, determined decisions taken by the participating peace pioneers regarding their future interventions. The results are also discussed within the framework of current (analysis reflects the political situation during the period reported here) political developments.     

一种新的体细分格式

近二十年来,对曲线和曲面的细分方法(Subdivision)的研究和应用在计算机图形学和造型领域中相当流行,然而对于实体的细分方法却研究得较少.在本文中,我们设计了一种基于六面体的逼近细分格式在张量积网格上表现为张量积格式,在体网格上生成光滑的极限实体,并能在实体上引入边界和折痕.根据已有的在简单六面体网格上的基于六面体的逼近格式,如果不采用一些特殊规则,设计者很难得到实体模型.我们设计了一套针对实体模型的细分规则来简化细分过程.大体上,我们的细分过程结合了简单线性细分和二层平均,对网格的局部拓扑结构没有严格要求.特别地,我们的格式可以不加修改地应用到非流形拓扑网格上.同时,我们引入了用于控制模型形状的自由参数,使模型设计更具弹性.     

T-cell conditioned media reverse T-cell unresponsiveness in lepromatous leprosy

In some subjects the infective agent of leprosy, Mycobacterium leprae, causes disseminated (lepromatous) disease. Such subjects have a major role in the transmission of the disease and show deficient T-cell responses both in vivo and in vitro to M. leprae, but not to other antigens. Numerous studies have recently shown that T cells with functional capabilities after initial triggering with antigen can be maintained in a state of continuous proliferation in vitro when cultured in medium containing interleukin 2 (IL-2). Here we have studied the effect of IL-2 rich T-cell conditioned medium on lepromatous peripheral blood mononuclear cells. Our results show that although lepromatous T cells fail to produce IL-2 after exposure to M. leprae they can respond by proliferation to M. leprae in the presence of T-cell conditioned medium, suggesting that the unresponsiveness in lepromatous leprosy results from a deficiency in the production of IL-2 or related factors and not a lack of M. leprae-reactive T cells.