Histone Methylation Marks on Circulating Nucleosomes as Novel Blood-Based Biomarker in Colorectal Cancer

Circulating nucleic acids (CNAs) are under investigation as a liquid biopsy in cancer as potential non-invasive biomarkers, as stable structure in circulation nucleosomes could be valuable sources for detection of cancer-specific alterations in histone modifications. Our interest is in histone methylation marks with a focus on colorectal cancer, one of the leading cancers respective the incidence and mortality. Our previous work included the analysis of trimethylations of lysine 9 on histone 3 (H3K9me3) and of lysine 20 on histone 4 (H4K20me3) by chromatin immuno- precipitation-related PCR in circulating nucleosomes. Here we asked whether global immunologic measurement of histone marks in circulation could be a suitable approach to show their potential as biomarkers. In addition to H3K9me3 and H4K20me3 we also measured H3K27me3 in plasma samples from CRC patients (n = 63) and cancer free individuals (n = 40) by ELISA-based methylation assays. Our results show that of three marks, the amounts of H3K27me3 (p = 0.04) and H4K20me3 (p < 0.001) were significantly lower in CRC patients than in healthy controls. For H3K9me3 similar amounts were measured in both groups. Areas under the curve (AUC) in receiver operating characteristic (ROC) curves indicating the power of CRC detection were 0.620 for H3K27me3, 0.715 for H4K20me3 and 0.769 for the combination of both markers. In conclusion, findings of this preliminary study reveal the potential of blood-based detection of CRC by quantification of histone methylation marks and the additive effect of the marker combination.     

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.     

Chemical,thermal, and mechanical properties and ultraviolet transmittance of novel nano-hydroxyapatite/polyethylene terephthalate milk bottles

Polyethylene terephthalate (PET)/nano-hydroxyapatite (nHAp) composite granules were obtained using twin-screw extruder. Preforms were prepared by injection molding and then PET/nHAp bottles were produced by blow molding. For PET bottles with nHAp, the migration amounts of carboxylic acid (COOH), acetaldehyde (AA), diethylene glycol (DEG), and isophthalic acid (IPA); glass transition temperature (T_g); melting temperature (T_m); and the maximum crystallization temperature (T_cry) were measured. The load-carrying capacity, burst strength, stress cracking, and regional material distribution tests were carried out on the bottles. X-ray diffraction, scanning electron microscopy, Fourier transform infrared spectroscopy, differential scanning calorimetry, and ultraviolet transmittance analyses were conducted to explain the changes in mechanical, chemical, physical properties, and light transmission of bottles. It was found out that the COOH amount increased and the AA content decreased with increasing nHAp amount. On the other hand, no change was observed in the amounts of DEG and IPA. Although the mechanical properties such as load-carrying capacity and burst strength of the bottles have improved, it has been determined that the standard environmental stress crack resistance test procedure cannot be applied to such a composite. Experimental findings indicate that nHAp disrupts the chemical structure of PET and it isolates harmful chemicals such as AA by forming intermolecular bonds. Moreover, with the addition of up to 0.8% nHAp, PET bottles block the light transmission approximately 80% within 400–700 nm wave length zone. The study demonstrates that the PET/nHAp composite bottles can be used in the food industry, particularly in the packaging of milk and milk products which are vulnerable to light exposure.     

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.     

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。     

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.     

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.