Synthesis of the tBuSATE pronucleotide of AZT by two different synthetic approaches.

A large scale synthesis of the tBuSATE pronucleotide of AZT was required for in vivo studies. A comparative synthesis of this derivative by phosphoramidite and monophosphate approaches is reported.     

A New Tiazofurin Pronucleotide: Synthesis and Biological Evaluation of CycloSaligenyl-Tiazofurin Monophosphate

Abstract

Synthesis and biological activities of cyclosaligenyl-tiazofurin monophosphate (CycloSal-TRMP), a new tiazofurin pronucleotide, are reported. CycloSal-TRMP proved to be active in vitro against human myelogenous leukemia K562 cell line and as A₁ adenosine receptor agonist.     

Methodological Quality of Systematic Reviews in Subfertility: A Comparison of Two Different Approaches

Background

Systematic reviews are used widely to guide health care decisions. Several tools have been created to assess systematic review quality. The measurement tool for assessing the methodological quality of systematic reviews known as the AMSTAR tool applies a yes/no score to eleven relevant domains of review methodology. This tool has been reworked so that each domain is scored based on a four point scale, producing R-AMSTAR.

Methods and Findings

We aimed to compare the AMSTAR and R-AMSTAR tools in assessing systematic reviews in the field of assisted reproduction for subfertility. All published systematic reviews on assisted reproductive technology, with the latest search for studies taking place from 2007–2011, were considered. Reviews that contained no included studies or considered diagnostic outcomes were excluded. Thirty each of Cochrane and non-Cochrane reviews were randomly selected from a search of relevant databases. Both tools were then applied to all sixty reviews. The results were converted to percentage scores and all reviews graded and ranked based on this. AMSTAR produced a much wider variation in percentage scores and achieved higher inter-rater reliability than R-AMSTAR according to kappa statistics. The average rating for Cochrane reviews was consistent between the two tools (88.3% for R-AMSTAR versus 83.6% for AMSTAR) but inconsistent for non-Cochrane reviews (63.9% R-AMSTAR vs. 38.5% AMSTAR). In comparing the rankings generated between the two tools Cochrane reviews changed an average of 4.2 places, compared to 2.9 for non-Cochrane.

Conclusion

R-AMSTAR provided greater guidance in the assessment of domains and produced quantitative results. However, there were many problems with the construction of its criteria and AMSTAR was much easier to apply consistently. We recommend that AMSTAR incorporates the findings of this study and produces additional guidance for its application in order to improve its reliability and usefulness.     

Synthetic Approaches to a Mononucleotide Prodrug of Cytarabine

Synthetic pathways to a mononucleotide prodrug of cytarabine (Ara-C) bearing S-pivaloyl-2-thioethyl (tBuSATE) groups, as biolabile phosphate protections, are reported. Using a common phosphoramidite approach, two different kinds of nucleoside protecting groups have been investigated. During this study, we observed an intermolecular migration of the Boc protecting group in the course of the tert-butyldimethylsilyl ether cleavage using tetrabutyl ammonium fluoride.     

The Pronucleotide Approach. II: Synthesis and Preliminary Stability Studies of Mononucleoside Glycosyl Phosphotriester Derivatives

Abstract

The synthesis and preliminary stability studies of mononucleoside phosphotriester derivatives of 3′-azido-2′,3′-dideoxythymidine (AZT) incorporating a new kind of phosphate protecting group, namely S-glycopyranosidyl-2-thioethyl (SGTE), are reported.     

The Autocovariance Function for Marked Point Processes: A Comparison between Two Different Approaches

Exploratory analysis of marked point patterns has previously been conducted using two disjoint techniques, namely the mark correlation function and spectral analysis. Our purpose here is to present two alternative autocovariance estimators to the mark correlation function which not only apply in both planar and lattice situations, but which in the lattice case can also be considered in terms of the inverse Fourier transform of the spectrum. Moreover, they can be applied to isotropic or anisotropic marked point patterns. Various examples are presented to show how these estimators perform when applied to data sets possessing different kinds of mark structure, and a rank test procedure is proposed to enable the construction of empirical tests of hypothesis.     

高龄食管下段癌患者两种不同手术路径治疗的临床效果观察

目的：比较高龄食管下段癌患者采用二切口和三切口两种不同手术路径手术治疗的临床效果。方法：回顾性分析高龄食管下段癌患者135例,其中73例患者采用二切口术式,分为A组;62例患者采用三切口术式,分为B组,比较两组患者术中出血量、手术时间、食管切除长度、淋巴结清扫数目及术后并发症、术后死亡率和1年后生存率、生活质量。结果：A组术中出血量、手术时间优于B组;B组食管切除长度、淋巴结清扫数目优于A组;A组术后并发症及死亡率低于B组、术后生活质量优于B组;术后1年生存率两组无显著性差异。结论：高龄食管下段癌患者手术治疗时,应首选二切口术式,可减少术后并发症的发生,并提高术后生活质量。     

Two Approaches to an Archaeology of the Social

Social Theory in Archaeology. Michael Brian Schiffer. ed. Salt Lake City: University of Utah Press, 2000. 235 pp.
Social Transformations In Archaeology: Global and Local Perspectives. Kristian Kristiansen and Michael Row. lands. London: Routledge, 1998. 438 pp.     

Synthesis and Anti-HIV Activity of a New Hexopyranoside Analogue of AZT

Abstract

The glycosylation of thymine (13) with 12 in the presence of trimethylsilyl triflate promoter afforded the α, β-L-ribo-hexopyranosy1-nucleoside analogue 14a,b. After removal of the protecting group 1-(3-azido-2,3,6-trideoxy-α and β-L-ribo-hexopyranosyl) -thymine (15a and 15b) were isolated in anomerically pure form in a ratio of 1:20. The anti-HIV activity of the major product 15b was examined, in comparison with AZT, on H9 lymphoid cell-line.     

高龄食管下段癌患者两种不同手术路径治疗的临床效果观察

目的:比较高龄食管下段癌患者采用二切口和三切口两种不同手术路径手术治疗的临床效果。方法:回顾性分析高龄食管下段癌患者135例,其中73例患者采用二切口术式,分为A组;62例患者采用三切口术式,分为B组,比较两组患者术中出血量、手术时间、食管切除长度、淋巴结清扫数目及术后并发症、术后死亡率和1年后生存率、生活质量。结果:A组术中出血量、手术时间优于B组;B组食管切除长度、淋巴结清扫数目优于A组;A组术后并发症及死亡率低于B组、术后生活质量优于B组;术后1年生存率两组无显著性差异。结论:高龄食管下段癌患者手术治疗时,应首选二切口术式,可减少术后并发症的发生,并提高术后生活质量。     

两种常用数量性状连锁分析方法的原理和进展

在复杂性状疾病的家系连锁研究中,Haseman-Elston回归分析和方差组成模型是常用的两种数量性状连锁分析方法。前者主要针对同胞对的性状值差或和的平方进行回归分析;后者引用方差组成模型,将数量性状分解为遗传方差和环境方差,可估计二者对表型的影响。两种方法可应用于同胞对、核心家系或扩展家系,定位数量性状基因座。本文对这两种模型的原理、算法及其进展进行了综述,并给出了常用的统计软件包。 Abstract：In this article, we discussed two model-free methods for detecting genetic linkage for quantitative traits, Haseman-Elston regression approach and variance components approach. The former is a regression approach for detecting linkage based on the squared difference or squared sums in quantitative trait values of sib-pairs and their estimated marker IBD scores. The latter can jointly model covariate effects along with variance components, including genetic component and non-genetic sources of variability. We have outlined the model assumption, the algorithm and the extensions for the both methods.     

Biotransformation of Natural and Synthetic Isoflavonoids by Two Recombinant Microbial Enzymes

Isolation and synthesis of isoflavonoids has become a frequent endeavor, due to their interesting biological activities. The introduction of hydroxyl groups into isoflavonoids by the use of enzymes represents an attractive alternative to conventional chemical synthesis. In this study, the capabilities of biphenyl-2,3-dioxygenase (BphA) and biphenyl-2,3-dihydrodiol 2,3-dehydrogenase (BphB) of Burkholderia sp. strain LB400 to biotransform 14 isoflavonoids synthesized in the laboratory were investigated by using recombinant Escherichia coli strains containing plasmid vectors expressing the bphA1A2A3A4 or bphA1A2A3A4B genes of strain LB400. The use of BphA and BphB allowed us to biotransform 7-hydroxy-8-methylisoflavone and 7-hydroxyisoflavone into 7,2′,3′-trihydroxy-8-methylisoflavone and 7,3′,4′-trihydroxyisoflavone, respectively. The compound 2′-fluoro-7-hydroxy-8-methylisoflavone was dihydroxylated by BphA at ortho-fluorinated and meta positions of ring B, with concomitant dehalogenation leading to 7,2′,3′,-trihydroxy-8-methylisoflavone. Daidzein (7,4′-dihydroxyisoflavone) was biotransformed by BphA, generating 7,2′,4′-trihydroxyisoflavone after dehydration. Biotransformation products were analyzed by gas chromatography-mass spectrometry and nuclear magnetic resonance techniques.     

Two Approaches to Study of the Perception of Time

From the standpoint of psychology, study of man's perception of the world around him presupposes study of the process and the result of the development of a subjective reflection of the objective world. The objects of perception are the concrete objects in the surrounding world, and empirical investigation is designed to seek and find lawful correspondences between the physical characteristics (properties) of those objects and the psychological characteristics (properties) of the image of that world. In such an approach, the question of the object of perception is the key to resolving the problem of time perception.     

Two Approaches to the Study of the Origin of Life

This paper compares two approaches that attempt to explain the origin of life, or biogenesis. The more established approach is one based on chemical principles, whereas a new, yet not widely known approach begins from a physical perspective. According to the first approach, life would have begun with—often organic—compounds. After having developed to a certain level of complexity and mutual dependence within a non-compartmentalised organic soup, they would have assembled into a functioning cell. In contrast, the second, physical type of approach has life developing within tiny compartments from the beginning. It emphasises the importance of redox reactions between inorganic elements and compounds found on two sides of a compartmental boundary. Without this boundary, “life” would not have begun, nor have been maintained; this boundary—and the complex cell membrane that evolved from it—forms the essence of life.     

Two Different High Throughput Sequencing Approaches Identify Thousands of De Novo Genomic Markers for the Genetically Depleted Bornean Elephant

High throughput sequencing technologies are being applied to an increasing number of model species with a high-quality reference genome. The application and analyses of whole-genome sequence data in non-model species with no prior genomic information are currently under way. Recent sequencing technologies provide new opportunities for gathering genomic data in natural populations, laying the empirical foundation for future research in the field of conservation and population genomics. Here we present the case study of the Bornean elephant, which is the most endangered subspecies of Asian elephant and exhibits very low genetic diversity. We used two different sequencing platforms, the Roche 454 FLX (shotgun) and Illumina, GAIIx (Restriction site associated DNA, RAD) to evaluate the feasibility of the two methodologies for the discovery of de novo markers (single nucleotide polymorphism, SNPs and microsatellites) using low coverage data. Approximately, 6,683 (shotgun) and 14,724 (RAD) SNPs were detected within our elephant sequence dataset. Genotyping of a representative sample of 194 SNPs resulted in a SNP validation rate of ∼ 83 to 94% and 17% of the loci were polymorphic with a low diversity (H _o = 0.057). Different numbers of microsatellites were identified through shotgun (27,226) and RAD (868) techniques. Out of all di-, tri-, and tetra-microsatellite loci, 1,706 loci had sufficient flanking regions (shotgun) while only 7 were found with RAD. All microsatellites were monomorphic in the Bornean but polymorphic in another elephant subspecies. Despite using different sample sizes, and the well known differences in the two platforms used regarding sequence length and throughput, the two approaches showed high validation rate. The approaches used here for marker development in a threatened species demonstrate the utility of high throughput sequencing technologies as a starting point for the development of genomic tools in a non-model species and in particular for a species with low genetic diversity.     

Synthesis and In Vitro Antiviral Activity of Some Symmetrical Phosphoramidate Dimers of AZT

Abstract

The synthesis of some symmetrical phosphoramidate dimers of AZT is presented. The synthetic scheme includes the formation of the symmetrical H-phosphonate diester of AZT, followed by its conversion to several dinucleoside phosphoramidate analogues. The compounds were evaluated for their anti-retroviral activity.