Systematic assessment of reduced representation bisulfite sequencing to human blood samples: A promising method for large-sample-scale epigenomic studies

Complementary to the time- and cost-intensive direct bisulfite sequencing, we applied reduced representation bisulfite sequencing (RRBS) to the human peripheral blood mononuclear cells (PBMC) from YH, the Asian individual whose genome and epigenome has been deciphered in the YH project and systematically assessed the genomic coverage, coverage depth and reproducibility of this technology as well as the concordance of DNA methylation levels measured by RRBS and direct bisulfite sequencing for the detected CpG sites. Our result suggests that RRBS can cover more than half of CpG islands and promoter regions with a good coverage depth and the proportion of the CpG sites covered by the biological replicates reaches 80-90%, indicating good reproducibility. Given a smaller data quantity, RRBS enjoys much better coverage depth than direct bisulfite sequencing and the concordance of DNA methylation levels between the two methods is high. It can be concluded that RRBS is a time and cost-effective sequencing method for unbiased DNA methylation profiling of CpG islands and promoter regions in a genome-wide scale and it is the method of choice to assay certain genomic regions for multiple samples in a rapid way.     

Terrorist Radiological Dispersive Device (RDD) Scenario and Cancer Risk Assessment

Terrorist attacks using radiological dispersal devices (RDD) are important threats that can lead to major environmental, economic, and public health concerns. In a simulation using a Gaussian model, we sought to determine dose curves as a function of distance from the explosion core site and from these data to determine the relative risk of developing tumors as well as the probability of causation (i.e., the statistical correlation between occurrence of malignancies and previous exposure to radiation). Calculation confirmed the cause dependence on age at exposure and the probability of tumor causation. This study aimed at emphasizing the importance of responding rapidly and efficiently, with a user-friendly user methodology that initially may help to guide the response from basic actions to the complete decision process.     

The working of a pulsatory liposome

Under positive osmotic stress, a greater lipid vesicle swells to a critical diameter, when suddenly a transbilayer pore appears and grows to a maximum radius, then decreases and finally disappears. An amount of liquid was leaked out through the pore and the vesicle returns to the initial state and can start another cycle. This is a pulsatory lipid liposome. In this paper, we have considered the problem of such liposomes. We have obtained the condition that a pulsatory liposome to run an a priori settled number of cycles. The length time of each cycle and its activity life was calculated. Also, we have calculated the quantities of solute leaked out through a pore in each cycle. The pulsatory liposome may be regarded as a biotechnological device to dose drugs at fixed intervals time.     

Entamoeba histolytica: lipid rafts are involved in adhesion of trophozoites to host extracellular matrix components

Adhesion is an important virulence function for Entamoeba histolytica, the causative agent of amoebic dysentery. Lipid rafts, cholesterol-rich domains, function in compartmentalization of cellular processes. In E. histolytica, rafts participate in parasite-host cell interactions; however, their role in parasite-host extracellular matrix (ECM) interactions has not been explored. Disruption of rafts with a cholesterol extracting agent, methyl-β-cyclodextrin (MβCD), resulted in inhibition of adhesion to collagen, and to a lesser extent, to fibronectin. Replenishment of cholesterol in MβCD-treated cells, using a lipoprotein-cholesterol concentrate, restored adhesion to collagen. Confocal microscopy revealed enrichment of rafts at parasite-ECM interfaces. A raft-resident adhesin, the galactose/N-acetylgalactosamine-inhibitable lectin, mediates interaction to host cells by binding to galactose or N-acetylgalactosamine moieties on host glycoproteins. In this study, galactose inhibited adhesion to collagen, but not to fibronectin. Together these data suggest that rafts participate in E. histolytica-ECM interactions and that raft-associated Gal/GalNAc lectin may serve as a collagen receptor.     

Stepwise confidence intervals for monotone dose-response studies

Summary .   In dose–response studies, one of the most important issues is the identification of the minimum effective dose (MED), where the MED is defined as the lowest dose such that the mean response is better than the mean response of a zero-dose control by a clinically significant difference. Dose–response curves are sometimes monotonic in nature. To find the MED, various authors have proposed step-down test procedures based on contrasts among the sample means. In this article, we improve upon the method of Marcus and Peritz (1976, Journal of the Royal Statistical Society, Series B 38 , 157–165) and implement the dose–response method of Hsu and Berger (1999, Journal of the American Statistical Association 94 , 468–482) to construct the lower confidence bound for the difference between the mean response of any nonzero-dose level and that of the control under the monotonicity assumption to identify the MED. The proposed method is illustrated by numerical examples, and simulation studies on power comparisons are presented.     

Simple example of structure versus property relationship applied to a reduced-friction biosystem, a quite personal opinion

Structure versus property (small-scale) relationship enters when something interesting is going to happen in a biosystem. This special-type "happening" is actually appearing to be manifested at both micro- and mesoscopic levels of always productive soft-matter organization under dynamic response, especially the one characteristic of the articular cartilage--an efficient, designed-by-nature multi-membrane, and virtually, with-ion-channels equipped, absorber and load relaxor.     

低剂量率下高线性能量转移碳离子束辐照人类唾液腺细胞的存活效应

利用日本千叶重离子医用加速器 HIMAC 提供的碳离子束,对人类唾液腺细胞 (HSG) 在剂量率为 0.5 Gy/h 的低剂量率条件下进行了辐照,运用标准的克隆形成法得到了 3 种不同剂量平均线性能量转移 (LET) 碳离子束辐照 HSG 细胞的剂量存活效应 . 与先前 HSG 细胞在治癌剂量率 (1~5 Gy/min) 下对相近剂量平均 LET 碳离子束辐照的剂量存活效应数据相比, HSG 细胞对高 LET 碳离子束辐射表现出明显的剂量率效应 . 为在相同条件下得到碳离子束对 HSG 细胞的相对生物学效应 (RBE) ,利用 60Co-γ射线在剂量率为 0.5 Gy/h 的条件下辐照了 HSG 细胞,得到该细胞系对低 LET 射线响应的剂量存活效应 . 与先前在治癌剂量率下得到的 RBE 值相比,低剂量率条件下得到的 RBE 值总体减小 . 由实验发现的剂量率效应及低剂量率条件下 RBE 值的减小,表明由高 LET 碳离子束造成的辐射损伤在低剂量率条件下也存在着显著的修复效应 . 据此,对辐射造成细胞致死的原因进行了探讨 .     

多层螺旋CT低剂量扫描在小儿胸部的应用探讨

目的:评价小儿胸部多层螺旋CT低剂量与常规剂量扫描的图像质量,探讨低剂量扫描在小儿胸部应用的可行性。材料与方法:(1)随机选择肺部感染的患儿30例,先常规剂量(150mAs)扫描,再在感染灶局部加作低剂量扫描,剂量为50,35及15mAs。其他参数为:120kV,床进28.8mm/圈,0.5s/圈,16×1.5mm准直,重建层厚及间隔均为3mm。分别记录不同剂量扫描时的CT权重剂量指数(CTDIw)及剂量长度乘积(DLP)。(2)由2位高年资医师按优、良、合格及不合格的等级盲法评价不同剂量的图像质量,结果进行统计学处理。结果:(1)小儿胸部35mAs和15mAs的CTDIw与常规剂量150mAs的比值分别为23.0%及10.0%,其DLP与常规剂量比值为23.3%和10.0%。(2)图像质量评价结果:150,50,35,15mAs的可诊断图像χ2检验,肺窗P>0.05,纵膈窗P<0.05,提示上述剂量肺窗图像差异无显著性意义,纵膈窗图像差异有显著性意义。用150,50,35mAs的可诊断图像进行χ2检验,P>0.05,提示其差异亦无显著性意义。结论:多层螺旋CT低剂量扫描适用于小儿胸部检查,在保证图像质量的前提下,采用35mAs左右的扫描条件较为适宜。