支持复杂疾病的临床路径知识库平台的构建及应用

目的 为了提高医疗服务质量、降低医疗成本,建立临床路径知识库平台,为临床提供决策服务。方法 围绕临床路径知识库的构建,主要解决三个问题：临床规则库的建立、临床路径自适应及修复模型和HIS数据整合框架。结果 构建支持复杂疾病的临床路径知识库,并实现共享平台。结论 通过建立支持复杂疾病的临床知识库平台,为患者提供准确的医疗服务,为医院提供临床路径决策支持,具有良好的应用效果。     

Pyrazolo[3,4-d]pyrimidine Nucleic Acids: Adjustment of the dA-dT to the dG-dC Base Pair Stability

Abstract

The pyrazolo[3,4-d]pyrimidine-4,6-diamine nucleosides 2b-d stabilize the dA-dT base pair significantly when the dA-residue is replaced. Oligonucleotide duplexes incorporating 2b-d show a 4–6°C T _m increase per modification. The 7-bromo compound 2b harmonizes the stability of the dA-dT vs. the dG-dC pair. According to this the stability of such duplexes depends no longer on the base pair composition of a DNA molecule.     

NMR Investigation of Palindromic LAC Operator DNA Sequences of Varying Size: Influences of Complex Formation with the LAC Repressor Headpiece on the DNA 1H Resonances

Abstract

¹H-NMR studies on s3rmmetrical lac operators were performed to determine the minimum size of a lac operator for tight complex formation with the lac repressor headpiece. Four operators of varying size from 18 base pairs to 24 base pairs were chemically synthesized. The data obtained suggest that for a synthetic lac operator to form a tight complex with the lac headpiece it should be at least 22 base pairs long.     

基于注意力机制的RNA碱基关联图预测方法

目的 长链非编码RNA在遗传、代谢和基因表达调控等方面发挥着重要作用。然而，传统的实验方法解析RNA的三级结构耗时长、费用高且操作要求高。此外，通过计算方法来预测RNA的三级结构在近十年来无突破性进展。因此，需要提出新的预测算法来准确的预测RNA的三级结构。所以，本文发展可以用于提高RNA三级结构预测准确性的碱基关联图预测方法。方法 为了利用RNA理化特征信息，本文应用多层全卷积神经网络和循环神经网络的深度学习算法来预测RNA碱基间的接触概率，并通过注意力机制处理RNA序列中碱基间相互依赖的特征。结果 通过多层神经网络与注意力机制结合，本文方法能够有效得到RNA特征值中局部和全局的信息，提高了模型的鲁棒性和泛化能力。检验计算表明，所提出模型对序列长度L的4种标准（L/10、L/5、L/2、L）碱基关联图的预测准确率分别达到0.84、0.82、0.82和0.75。结论 基于注意力机制的深度学习预测算法能够提高RNA碱基关联图预测的准确率，从而帮助RNA三级结构的预测。     

Novel Synthesis of 4′C-Aryl-Branched Acyclic Nucleoside Using [3,3]-Sigmatropic Rearrangement

Abstract

A very efficient synthetic route for preparing a novel 4′-C-aryl branched-1′,2′-seco-2′,3′-dideoxy-2′,3′-didehydro-nucleoside is described. Mesylate 7 was successfully synthesized via a Horner-Wadsworth-Emmons reaction and a [3,3]-sigmatropic rearrangement, with which an adenine base was coupled by nucleophilic substitution conditions (K₂CO₃, 18-Crown-6, DMF) to give the target nucleoside 9.     

Transition Metal Ligands as Novel DNA-Base Substitutes

Abstract

The base modified nucleoside dBP, carrying a non-hydrogen-bonding non-shape complementary base was incorporated into oligonucleotides (Brotschi, C.; Häberli, A.; Leumann C.J. Angew. Chem. Int. Ed. 2001, 40, 3012–3014). This base was designed to coordinate transition metal ions into well defined positions within a DNA double helix. Melting experiments revealed that the stability of a dBP: dBP base couple in a DNA duplex is similar to a dG: dC base pair even in the absence of transition metal ions. In the presence of transition metal ions, melting experiments revealed a decrease in duplex stability which is on a similar order for all metal ions (Mn²⁺, Cu²⁺, Zn²⁺, Ni²⁺) tested.     

Nucleosides and Nucleotides. 192. Toward the Total Synthesis of Cyclic ADP-Carbocyclic-Ribose. Formation of the Intramolecular Pyrophosphate Linkage by a Conformation-Restriction Strategy in a Syn-form Using a Halogen Substitution at the 8-Position of the Adenine Ring

Abstract

The synthesis of cyclic ADP-carbocyclic-ribose (2), as a stable mimic for cyclic ADP-ribose, was investigated. Construction of the 18-membered backbone structure was successfully achieved by condensation of the two phosphate groups of 19, possibly due to restriction of the conformation of the substrate in a syn-form using an 8-chloro substituent at the adenine moiety. SN2 reactions between an optically active carbocyclic unit 8, which was constructed by a previously developed method, and 8-bromo-N ⁶-trichloroacetyl-2′,3′-O-isopropylideneadenosine 9c gave N-1-carbocyclic derivative, which was deprotected to give 5′,5′-diol derivatives 18. When 18 was treated with POCl₃ in PO(OEt)₃, the bromo group at the 8-position was replaced to give N-1-carbocyclic-8-chloroadenosine 5′,5′-diphosphate derivative 19 in 43% yield. Treatment of 19 with 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride gave the desired intramolecular condensation product 20 in 10% yield. This is the first chemical construction of the 18-membered backbone structure containing an intramolecular pyrophosphate linkage of a cADPR-related compound with an adenine base.     

Properties of Oligonucleotides Containing the Transition Bases P and K

Abstract

The properties of the degenerate nucleosides dP and dK, in templates and primers were determined. dP was copied as either pyrimidine, dK as either purine. In primers, an equimolar mixture of the two nucleosides functioned as a universal base equivalent in both sequencing and the polymerase chain reactions. Cloning of DNA containing dP or dK produced transition mutations in vivo.     

Regioselective N1-Alkylation of Guanosine Derivatives Protected at N 2 by an N,N-Dialkyl Amidine Group

Abstract

Under Mitsunobu reaction conditions or in the presence of eiectrophilic alkylating reagents, alkylation of guanosine derivatives protected by an N,N-dialkyl amidine at the exocyclic amino group occurs selectively on nitrogen N ¹ of the purine base.     

Végétation marine de l'Ile de Port-Cros (Parc National). XII: Sur Acrochaetium molinieri sp. nov. et Lophosiphonia cristata Falkenberg

Abstract

Marine vegetation of Port-Cros Island (National park). XII: on Acrochaetium molinieri sp. nov. and Lophosiphonia cristata Falkenberg. – Acrochaetium molinieri sp. nov. is characterized by its bicellular base; only one of these cells originates an erect filament. Lophosiphonia cristata, rarely mentioned from the Mediterranean, is richly illustrated and described in detail     

360度评价法在住培学员岗位胜任能力评价中

目的 运用360度评价法对2015级住培学员岗位胜任力进行评价,对2015级住培学员岗位胜任力现状进行探讨分析。方法 采用问卷调查评价表分别从专业基地主任、学员指导教师、轮转带教教师、同学、自我评价5个角度,对202名住培学员岗位胜任力进行360度反馈评价,岗位胜任力评价内容包含基本能力、职业素养、医患沟通、医学知识等8个方面核心能力;应用EpiData3.02建立数据库,采用SPSS19.0软件进行统计分析,统计分析方法主要为描述性统计分析、单因素方差分析。结果 5类评价主体在基本能力和医学知识2项能力打分较高,在职业精神、沟通能力、职业道德、团队合作、学术研究等其他几项能力打分偏低;在基本能力、职业精神与素质、沟通能力、团队合作和学术研究几方面能力评分,差异均有统计学意义（P＜0.05）;本人各方面打分均偏高,轮转带教教师和同专业基地同学打分居中,专业基地主任、指导导师在各方面打分偏低 结论 360度评价法客观公正地评价住培学员岗位胜任能力,有助于提高住培学员岗位胜任能力,有利于加强团队意识,增强团队建设。     

Three new species of Philocorydoras Suriano, 1986 (Monogenoidea: Dactylogyridae) infecting the gills of callichthyids (Actinopterygii: Callichthyidae) from the Peruvian Amazonia

During a research on gill ectoparasites of callichthyids fishes from the Peruvian Amazonia, the following monogenoideans were found: Philocorydoras peruensis n. sp. from Corydoras splendens (Castelnau); Philocorydoras multiradiatus n. sp. and Philocorydoras jumboi n. sp. from Brochis multiradiatus (Orcés, V.). All new species described herein are mainly differentiated from their congeners based on the morphology of the copulatory complex. In P. peruensis n. sp. the cirrus is “J”-like shaped tube slightly tilted to one side, while in P. jumboi n. sp. is “J”-like shaped tube in a straight position and in P. multiradiatus n. sp. the cirrus is an arced tube with inflated base and distally narrow. Brochis (Orcés, V.) represents a new genus hosting species of Philocorydoras. All new species presented in this work represent the first species of Philocorydoras reported for Peru.

     

Una especie nueva de <Emphasis Type="Italic">Lepechinia</Emphasis> sección <Emphasis Type="Italic">Glomeratae</Emphasis> (Lamiaceae) de México

During the study of the Lamiaceae from Guerrero, Mexico, specimens of Lepechinia sect. Glomeratae were found, similar to L. glomerata, but different in having larger flowers that are orange at the base and red at the apex, with a tubular corolla that is invaginated at the base, and widely ovate bracts that are acuminate at the apex. The new species, Lepechinia flammea, is described and illustrated. A key to distinguish the species is included.

---

Resumen  Durante el estudio de la familia Lamiaceae en el Guerrero, México, se encontraron algunos ejemplares de Lepechinia sección Glomeratae, cercanamente relacionados con L. glomerata, pero que difieren por presentar flores más grandes, anaranjadas en la base y rojas en el ápice, corola tubular, el tubo invaginado en la base y brácteas ampliamente ovadas, con el ápice acuminado. Se presenta una descripción de la nueva especie, Lepechinia flammea, así como ilustraciones y una clave para separar ambas especies.

     

Synthesis and Antiviral Activity of Carbocyclic Nucleosides Incorporating a Modified Cyclopentane Ring. Part 3: Adenosine and Uridine Analogues

Abstract

Six new carbocyclic nucleosides were prepared by mounting a purine (compounds 4–6), 8-azapurine (7 and 8) or undine (9) base on the ammo group of (1S,3R)-3-amino-2,2,3-trimethylcyclopentylmethanol (10). At subtoxic concentrations, compounds 5-9 showed at best marginal antiviral activity.     

Interactions of Quinoxaline Antibiotic and DNA.: The Molecular Structure of a Triostin A—d(GCGTACGC) Complex

Abstract

The crystal structure of a DNA. octamer d(GCGTA.CGC) complexed to an antitumor antibiotic, triostin A, has been solved and refined to 2.2 Å resolution by x-ray diffraction analysis. The antibiotic molecule acts as a true bis intercalator surrouding the d(CpG) sequence at either end of the unwound right-handed DNA. double helix. A.s previously observed in the structure of triostin A.—d(CGTA.CG) complex (A.H.-J. Wang, et. al., Science, 225,1115–1121 (1984)), the alanine amino acid residues of the drug molecule form sequence-specific hydrogen bonds to guanines in the minor groove. The two central A · T base pairs are in Hoogsteen configuration with adenine in the syn conformation. In addition, the two terminal G · C base pairs flanking the quinoxaline rings are also held together by Hoogsteen base pairing. This is the first observation in an oligonucleotide of. Hoogsteen G · C base pairs where the cytosine is protonated. The principal functional components of a bis-intercalative compound are discussed.     

Synthesis of the Oligoribonucleotides Incorporating 8-Oxo-Guanosine and Evaluation of their Base Pairing Properties

6-O-7-N-Bis(diphenylcarbamoyl)-2-N-phenoxyacetyl-5′-O-dimethoxytrityl-2′-O-{[(triisopropyl- silyl)oxy]methyl}-8-oxoguanosine-3′-yl-β-cyanoethyl-N,N-diisopropylphosphoramidite (5) was synt- hesized as a new phosphoramidite precursor unit for the synthesis of RNA. Compound 5 was successfully incorporated into the middle of the RNA sequences, and the synthesized RNAs were identified by MALDI-TOF mass measurements. Their properties were evaluated for formation of the RNA duplex and RNA/DNA heteroduplex. ORNs 1 and 4 containing 8-oxo-G can form base pairs with rC or dC in an anti conformation, while it can also interact with rA or dA in a syn conformation in the RNA duplex or RNA/DNA heteroduplex. The described synthetic method is therefore a useful procedure for the synthesis of ORN containing 8-oxo-G and contributes to the study of 8-oxo-G in RNA.     

Reinstatement of Ocyroe (Compositae: Astereae)

Nardophyllum armatum, a species from the Puna region of Argentina, Bolivia, and Chile is here transferred to genus Ocyroe, which in turn is resurrected from the synonymy under Nardophyllum. Ocyroe is characterized by thorny branches, discoid capitula, naked receptacles, glandular corollas with a globose swelling at the base, and a profuse 3- to 5-seriate pappus. The new combination Ocyroe armata and a lectotype for Dolichogyne armata are here presented.     

甘肃省青年医生职业倾向实证研究

???? 目的 通过对青年医生职业倾向的调查研究,为医院人力资源管理提供依据。方法 以甘肃18个市州468位青年医生为样本,以职业锚理论为基础对他们职业倾向状况进行实证分析。结果 青年医生在各种职业倾向上均有一定比例,且职业倾向因个体人口学特征的不同而存在差异。结论 青年医生的职业倾向呈现多元化,并受管理环境等多种因素的影响,是变化发展的。

     

The 1,1-Dianisyl-2,2,2-trichloroethyl Moiety as a New Protective Group for the Synthesis of Dinucleostde Trifluoromethylphosphonates

Abstract

The new 1,1-Dianisyl-2,2,2-trichloroethyl moiety (DATE) is used as an acid and base stable protective group for nucleosides. 5′-O-DATE-thymidine and 3′-O-acetyl-thymidine are phosphorylated with CF₃P(NR₂)₂ to the corresponding thymidine trifluoromethylphosphonous amidites. These building blocks are coupled with appropriate protected thymidines to a dinucleotide trifluoromethylphosphonate.

     

SYNTHESIS AND EVALUATION OF ANTIVIRAL ACTIVITY OF HIGHER HOMOLOGUES OF XYLO-CARBOCYCLIC NUCLEOSIDES

New carbocyclic nucleosides with purine (compounds 3a and 3b), and 8-azapurine (compounds 3c and 3d) as base were prepared and assayed for in vitro activity.