Etoposide: four decades of development of a topoisomerase II inhibitor

Podophyllin-containing materials have been used as folk medicines for centuries. In the 1950s, scientists began a search to identify a more effective podophyllotoxin derivative. These efforts eventually resulted in the development of a new class of antineoplastic agents which target the DNA unwinding enzyme, topoisomerase II. The history of the development of one of the first identified topoisomerase II inhibitors, etoposide, is reviewed in this paper. Critical developments in etoposide's mechanism of action, pharmacology and administration schedule are summarised. The clinical benefits of the recently marketed etoposide prodrug, etoposide phosphate (Etopophos) are also detailed. The current status of other clinically approved anticancer agents which target topoisomerase II is briefly reviewed.     

Clinical applications of anticancer drugs targeted to topoisomerase II

Agents which 'poison' the enzyme topoisomerase II, have proven to be useful drugs for cancer treatment. Six antineoplastic drugs, which target topoisomerase II (doxorubicin, daunorubicin, idarubicin, mitoxantrone, etoposide and teniposide) are currently approved for clinical use in the United States. In this paper, the strategies and goals of cancer chemotherapy are summarized for the non-clinician. The use, pharmacology and toxicity of each of the six currently approved topoisomerase II inhibiting agents are reviewed.     

Films formed from polystyrene latex/clay composites: A fluorescence study

This study reports a steady-state fluorescence (SSF) technique for studying film formation from surfactant-free polystyrene (PS) latex and Na-montmorillonite (SNaM) composites. The composite films were prepared from pyrene (P)-labeled PS particles and SNaM clay at room temperature and annealed at elevated temperatures in 10-min intervals above glass transition temperature (t₃) of polystyrene. During the annealing processes, the transparency of the film improved considerably. Scattered light (I_s) and fluorescence intensity (I_p) from P were measured after each annealing step to monitor the stages of film formation. Evolution of transparency of composite films was monitored by using photon transmission intensity, I_tr. Scanning electron microscopy (SEM) was used to detect the variation in physical structure of annealed composite films. Minimum film formation temperature, T_q, and healing temperatures, T_h, were determined. Void closure and interdiffusion stages were modeled and related activation energies were determined. It was observed that both activation energies increased as the percent of SNaM was increased in composite films.     

食糖市场营销战略分析

2005/06年制糖期全国食糖产量881.5万t,消费量估计达到1070万t,主产区白糖平均售价达到4500元/t,制糖企业取得很好效益.新形势下制糖行业将发生转变,一是食糖流通企业经过整合力量不断壮大,二是市场化、国际化程度逐步提高,三是食糖价格将总体走高,四是甜菜糖和淀粉糖将加速发展.在新形势下制糖企业必须努力提高市场竞争力,制定市场营销战略,重视销售网络渠道建设,不断扩大市场份额.     

Dark fermentative hydrogen production from sucrose and molasses

There are many factors affecting the dark fermentative hydrogen production. The interaction of these factors, that is, their combined effects, should be investigated for better design of the systems with stable and higher hydrogen yields. This study aimed to investigate the combined effects of initial substrate, pH, and biomass (or initial substrate to biomass) values on hydrogen production from sucrose and sugar‐beet molasses. Therefore, optimum initial chemical oxygen demand (COD), pH, and volatile suspended solids (VSS) or initial substrate to biomass (VSS) ratio (S/X_o) values leading to the highest dark fermentative hydrogen production were investigated in batch reactors. An experimental design approach (response surface methodology) was used. Results revealed that when sucrose was the substrate, maximum hydrogen production yield (HY) of 2.3 mol H₂/mol sucrose_added was obtained at initial pH of 7 and COD of 10 g/L. Initial S/X_o values studied (4–20 g COD/g VSS) had no effect on HY, while the initial pH was found as the parameter mostly affecting both HY and hydrogen production rate (HPR). When substrate was molasses, initial COD concentration was the only variable affecting HY and HPR. Maximum of both was achieved at 10 g/L initial COD. Initial VSS values studied (2.5–7.5 g/L) had no effect on HPR and HY. This study also indicated that molasses leads to homoacetogenesis for potentially containing intrinsic microorganism and/or natural constituents; thus, sucrose is more advantageous for hydrogen production via fermentation. Homoacetogenesis should be prevented for effective optimization via response surface methodology, if substrate is a natural carbon source potential to have intrinsic microorganisms. Copyright © 2017 John Wiley & Sons, Ltd.     

PolyHIPE composite based-form stable phase change material for thermal energy storage

A novel shape-stabilized n-hexadecane/polyHIPE composite phase change material (PCM) was designed and thermal energy storage properties were determined. Porous carbon-based frameworks were produced by polymerization of styrene-based high internal phase emulsions (HIPEs) in existence of the surface modified montmorillonite nanoclay. The morphological and mechanical properties of the obtained polyHIPEs were investigated by scanning electron microscopy analysis and the compression test, respectively. The polyHIPE composite with the best pore morphology and the highest compression modulus was determined as a framework to prepare the form stable n-hexadecane/polyHIPE composite phase change material using the one-step impregnation method. The chemical structure and morphologic property of composite PCM was investigated by FT-IR and polarized optical microscopy analysis. Thermal stability of the form-stable PCM (FSPCM) was examined by TG analysis. The n-hexadecane fraction engaged into the carbon foam skeleton was found of as 55 wt% from TG curve. differential scanning calorimetry analysis was used for determining melting temperature and latent heat storage capacity of FSPCM and these values were determined as (26.36°C) and (143.41 J/g), respectively. The results indicated that the obtained composite material (FSPCM) has a considerable potential for low temperature (18°C-30°C) thermal energy storage applications with its thermal energy storage capacity, appropriate phase change temperatures and high thermal stability.     

Induction of telomerase activity by UV-irradiation in Chinese hamster cells

Telomerase is a ribonucleoprotein whose activity has been detected in germline cells and in neoplastic and immortal cells. Telomerase compensates the telomere loss arising by the end replication problem by synthesizing telomeric repeats at the 3' end of the eukaryotic chromosomes. Telomerase is reactivated during cancer progression in human and mice. In order to determine whether the telomerase activity can be upregulated in vitro in response to DNA damaging agents, we examined the telomerase activity in five Chinese hamster cell lines following exposure to 5 J/m2 or 40 J/m2 UV-C radiation. All the cell lines tested showed an increase in telomerase activity in the PCR-based telomeric repeat amplification protocol (TRAP) in a dose dependent manner. This increase in telomerase activity correlated well with the number of cells being in the S and G2/M phase after UV exposure. However, in unirradiated control cells, similar levels of telomerase activity were observed in different phases of the cell cycle. Furthermore, telomeric signals were clustered in one or more parts of the disintegrating nuclear particles of the apoptotic cell as detected by fluorescence in situ hybridization (FISH). This is the first study to demonstrate the induction of telomerase activity following exposure to DNA-damaging agents like UV radiation in Chinese hamster cells in vitro.     

纳秒级d－T聚变反应的16．7MeVγ测量

ｄ－Ｔ聚变反应产生的１６７ＭｅＶγ射线很弱，必须从很强的γ、中于混合场中筛选出来，故要求探测系统有高的信噪比，快的时间响应和宽的动态范围。利用高能γ与介质相互作用的康普顿效应及其定量对应关系，由扇形聚焦磁场一次偏转，用ＣＯ２气体切连科夫探测器（ＧＣＤ）探测电子束，或由扇形聚焦磁场（ＳＣＤ）二次偏转，用有机玻璃切连科夫探测器测电子束。仔细考虑了探测装置的辐射屏蔽和探测系统的电磁屏蔽。分别在“闪光－１”装置、ＤＨＪ－２５回旋加速器和２ＭＶ直线加速器上对探测装置进行了模拟检验实验和标定实验。在实际测试中，首次获得了纳秒级ｄ－Ｔ聚变反应产生的１６７ＭｅＶγ波形。     

An artificial neural network model for virtual Superpave asphalt mixture design

This study presents an artificial neural network (ANN) model to predict the asphalt mixture volumetrics at Superpave gyration levels. The input data-set needed by the algorithm is composed of gradation of the mix, bulk specific gravity of aggregates, low- and high-performance grade of the binder, binder content of the mix and the target number of gyrations (i.e. N_ini, N_des and N_max). The proposed ANN model uses a three-layer scaled conjugate gradient back-propagation (feed-forward) network. The ANN was trained using data obtained from numerous roads with a total of 1817 different mix designs. Results revealed that the ANN was able to predict V_a within V_a (measured) ± 1.0% range 85–93% of the time and within V_a (measured) ± 0.5% range 60–70% of the time. Currently with the developed ANN model, Superpave mix design can take approximately between 1.5 and 4.5 days, which corresponds to 3–6 days of savings.