Rh phenotype prediction by DNA typing and its application to practice

The complexity of the RHD and RHCE genes, which is the greatest of all blood group systems, confounds analysis at the molecular level. RH DNA typing was introduced in 1993 and has been applied to prenatal testing. PCR-SSP analysis covering multiple polymorphisms was recently introduced for the screening and initial characterization of partial D. Our objective is to summarize the accrued knowledge relevant to the approaches to Rh phenotype prediction by DNA typing, their possible applications beyond research laboratories and their limitations. The procedures, results and problems encountered are highly detailed. It is recommended that DNA typing comprises an analysis of more than one polymorphism. We discuss future directions and propose a piecemeal approach to improve reliability and cost-efficiency of blood group genotyping that may eventually replace the prevalent serology-based techniques even for many routine tasks. Transfusion medicine is in the unique position of being able to utilize the most extensive phenotype databases available to check and develop genotyping strategies.     

缓和加氢裂化动力学模型

参考缓和加氢裂化（ＭＨＣ）反应机理，开发了一种既能预测产品产率，又能预测产品性质的ＭＨＣ动力学网络模型。以文献上发表的ＭＨＣ实验数据为例，进行了参数估计，确定了动力学参数，给出了模型的标准差。本模型所预测的ＭＨＣ结果，与文献数据吻合良好，具有良好的预测性能。     

Serum digoxin and beta-methyldigoxin in elderly patients on hospital admission: correlation with home compliance and clinical variables

Summary Serum digoxin and beta-methyldigoxin (BMD) were measured in 165 elderly patients (age >60 years) admitted to hospital, of whom 109 had been treated at home with digoxin and 56 with BMD.The mean BMD level was significantly lower than that of digoxin (1.1 vs. 1.4 ng/ml). Creatinine clearance and daily dose were the variables most strongly associated with digoxin level, and the prescribed dose and serum albumin were the best predictors of the BMD concentration. Compliance was assessed by a compliance index (CI), namely the ratio of the measured glycoside concentration, corrected for creatinine clearance, over the expected steady-state dose, calculated from a hospitalized reference group. Compliant individuals in both treatment groups, i.e. those with a CI > the median value, were characterized by a lower daily dose and dosage frequency.Toxicity, whether clinical or electrocardiographic, was present in 9% of the patients and was associated only with a significantly higher mean serum level of the drug.     

Sequence analysis of L RNA of Lassa virus

The L RNA of three Lassa virus strains originating from Nigeria, Ghana/Ivory Coast, and Sierra Leone was sequenced and the data subjected to structure predictions and phylogenetic analyses. The L gene products had 2218-2221 residues, diverged by 18% at the amino acid level, and contained several conserved regions. Only one region of 504 residues (positions 1043-1546) could be assigned a function, namely that of an RNA polymerase. Secondary structure predictions suggest that this domain is very similar to RNA-dependent RNA polymerases of known structure encoded by plus-strand RNA viruses, permitting a model to be built. Outside the polymerase region, there is little structural data, except for regions of strong alpha-helical content and probably a coiled-coil domain at the N terminus. No evidence for reassortment or recombination during Lassa virus evolution was found. The secondary structure-assisted alignment of the RNA polymerase region permitted a reliable reconstruction of the phylogeny of all negative-strand RNA viruses, indicating that Arenaviridae are most closely related to Nairoviruses. In conclusion, the data provide a basis for structural and functional characterization of the Lassa virus L protein and reveal new insights into the phylogeny of negative-strand RNA viruses.     

Synthetic MRI improves radiomics-based glioblastoma survival prediction

Glioblastoma is an aggressive and fast-growing brain tumor with poor prognosis. Predicting the expected survival of patients with glioblastoma is a key task for efficient treatment and surgery planning. Survival predictions could be enhanced by means of a radiomic system. However, these systems demand high numbers of multicontrast images, the acquisitions of which are time consuming, giving rise to patient discomfort and low healthcare system efficiency. Synthetic MRI could favor deployment of radiomic systems in the clinic by allowing practitioners not only to reduce acquisition time, but also to retrospectively complete databases or to replace artifacted images. In this work we analyze the replacement of an actually acquired MR weighted image by a synthesized version to predict survival of glioblastoma patients with a radiomic system. Each synthesized version was realistically generated from two acquired images with a deep learning synthetic MRI approach based on a convolutional neural network. Specifically, two weighted images were considered for the replacement one at a time, a T2w and a FLAIR, which were synthesized from the pairs T1w and FLAIR, and T1w and T2w, respectively. Furthermore, a radiomic system for survival prediction, which can classify patients into two groups (survival >480 days and $\le$ 480 days), was built. Results show that the radiomic system fed with the synthesized image achieves similar performance compared with using the acquired one, and better performance than a model that does not include this image. Hence, our results confirm that synthetic MRI does add to glioblastoma survival prediction within a radiomics-based approach.     

预测蛋白质相互作用位点的计算方法研究(一)

许多重要的细胞过程如信号转导、转运、细胞运动以及多数调节机制均由蛋白-蛋白之间的相可作用介导，蛋白质之间的相互作用在物理上是通过在两个相互作用蛋白之间形成接触面的短残基序列来实现。识别蛋白-蛋白相互作用位点，以及检测相互作用氨基酸残基之间的特异性与强度特异性，是一个具有重要应用前景的课题，它的应用范围从理性的药物设计到代谢和信号转导网络的分析。虽然有不少准确度不断提高的实验技术和计算方法来检测蛋白质之间的相互作用，但很少有方法能够精确地指出参与蛋白质相互作用的特定残基及其位置，而这些信息是将相互作用数据直接应用于药物开发所必需的。随着生物信息学和计算生物学的发展，通过研究已知蛋白-蛋白相互作用位点的这些不同特征．出现了一些利用序列与结构信息顶测蛋白-蛋白相互作用位点的计算方法。本文简要介绍了近年来在顶测蛋白-蛋白的相互作用位点方面取得一定进展的计算方法，包括基于基因组信息的计算方法、基于蛋白质初级序列的计算方法以及基于蛋白复合物结构信息的计算方法。虽然这些方法在过去儿年里取得了显著的进展，但是大多数在这方面的研究仍处于起步阶段．而现在数据库的不足和实验技术的缺陷对计算预测方法的进一步发展和公平性评价也存在着较大的影响，要提高蛋白-蛋白相巨作用位点预测的鲁棒性与可靠性，仍要有很多的工作要做。（发表在这里的是第一部分）     

A pattern search method for putative anchor residues in T cell epitopes

The binding affinity between an antigenic peptide and its particular major histocompatibility complex (MHC) molecule seems to be largely determined by only a few residues. These residues have been called “anchors” because of their property of fitting into “pockets” inside the groove of the MHC molecule. To predict natural antigenic epitopes within a longer sequence, it therefore appears to be important to know the motif or pattern describing the anchors, i.e. the anchors amino acid residue preference and the distance between anchor residues. A large set of MHC class I-restricted peptides has been described. Peptide sequences vary in length and lack an obvious common sequence motif. For a list of peptides belonging to one type of MHC class I molecule, we describe a method to find the most prominent sequence motif with at least two anchor residues. Briefly, antigenic sequences are aligned, and two anchor positions are searched for, where all anchor residues share a high similarity. The alignments are scored according to the similarity of their anchor residues. We show that the motifs predicted for the MHC alleles A2.1, B27, K^b, K^d, D^b are in substantial agreement with experimental data. We derive binding motifs for the MHC class I alleles HLA-A1, All, B8, B14, H-2L^d and for the MHC class II alleles I-A^b and I-A^s. In some cases, higher scores were obtained by allowing a slight variation in the number of residues between anchors. Therefore, we support the view that the length of epitopes belonging to a particular class I MHC is not uniform. This method can be used to predict the natural short epitope inside longer antigenic peptides and to predict the epitopes anchor residues. Anchor motifs can be used to search for antigenic regions in sequences of infectious viruses, bacteria and parasites.     

B族链球菌C5a肽酶蛋白表位的克隆、表达和免疫学分析

目的应用生物信息学方法预测B族链球菌C5a肽酶蛋白表位，结合基因工程手段进行表位重组、表达和免疫原性分析。方法用预测程序ProPred和ANTIGENIC预测B族链球菌C5a肽酶蛋白的表位，应用PCR技术扩增出编码该表位基因片段，克隆PCR产物构建重组质粒，测序验证。在大肠杆菌BL21（DE3）中诱导表达融合蛋白。表达的蛋白经质谱分析和Western blot鉴定。纯化该融合蛋白并免疫C57／BL小鼠，萃取GBS表面蛋白，双向琼脂扩散试验检测抗体水平。结果在SCPB中预测到1个既具有MHC结合肽特性又具有B细胞表位特征的肽段。重组和表达了这一肽段，质谱得出与SCPB蛋白的相似性分数为79，Western-blot证实能与抗SCPB的抗体反应，纯化后融合蛋白纯度〉90％。动物实验证实融合蛋白能产生特异性的抗GBS抗体。结论重组表位具有一定免疫原性。为相关蛋白的毒力机制研究和亚单位疫苗等方面的研究打下了良好的基础。     

Morphological evaluation of human embryos and derivation of an embryo quality scoring system specific for day 3 embryos: a preliminary study

A scoring system specific for day 3 embryos has not been extensively explored. Most IVF laboratories continue to grade embryos solely on the basis of cell number and percentage fragmentation as was traditionally done for day 2 embryos. Additional morphological features, some unique to day 3 embryos, may be useful in selecting embryos most likely to blastulate and implant. The objective of this study was to derive an embryo scoring system for day 3 transfers which is predictive of positive pregnancy outcomes. A total of 316 transferred embryos from 93 patients was recorded on videotape and evaluated. The following parameters were used to grade the embryos: cell number, fragmentation pattern (FP), cytoplasmic pitting, compaction, equal sized blastomeres, blastomere expansion and absence of vacuoles. The clinical pregnancy rate was 41.9%, with an implantation rate of 18% per embryo transferred. The mean number of embryos transferred per patient was 3.4. Three formulae were derived to score embryo quality in each transfer based on the average score of individual embryos transferred. In the first scoring system, cell number alone was used to predict pregnancy outcome. The second scoring system was based on blastomere number and the observed FP. The third scoring system utilized both blastomere number and FP but also combined this with five morphological criteria to yield a final day 3 embryo quality (D3EQ) score. We found the D3EQ score to be prognostic of pregnancy outcome. This study suggests that although cell number and FP are certainly predictors of positive pregnancy outcomes, additional parameters specific to day 3 embryos should be used to stratify a cohort of embryos further.