基于GenePANDA算法的精神分裂症药物靶基因预测

精神分裂症是常见的精神障碍类疾病.目前,治疗精神分裂症的药物存在疗效差、副作用大和耐药性的问题,迫切需要开发新的药物,而发现新的药物靶基因是开发新药的重要环节.为了预测精神分裂症药物的靶基因,我们首先基于DrugBank中药物已知的靶基因,使用网络算法GenePANDA预测出候选靶基因;之后,我们对药物已知靶基因进行功能富集分析,使用富集出的生物学通路筛选候选靶基因,最终得到48个候选靶基因.其中,29个基因被报道和精神分裂症直接相关,13个基因被报道为精神分裂症药物的靶基因.此外,在DrugBank中共有54种药物靶向预测出的基因,其中17种药物被研究报道可用于治疗精神分裂症.     

阿尔茨海默症靶基因及其药物的预测研究

阿尔茨海默症(AD)是一种起病隐匿的进行性发展的神经系统退行性疾病.目前用于治疗AD的药物主要改善患者的认知功能,延缓疾病的进展.目前,这类药物的研制和开发方兴未艾,新药层出不穷.遗憾的是,几乎所有的药物都未能使患者广泛受益.本文一方面从现有用于治疗AD的药物出发,利用DrugBank数据库挖掘AD的靶基因,通过使用DAVID、GenePANDA等数据资源和生物工具,预测得到30个用于治疗AD的靶基因或与AD直接相关的基因,如目前未被充分研究的AD靶基因GPER1、SSTR4、GALR2等.另一方面,基于预测靶基因方法,通过DrugBank数据库预测的可潜在用于AD治疗的药物,如神经类治疗药物中的阿米替林、奥氮平、氯氮平、阿莫沙平、α-氨基异丁酸和组胺6种药物,在非神经类治疗药物中有地塞米松、吲哚美辛、舒林酸和酮洛芬4种药物.     

采用偏最小二乘法的基因-药物共模块识别

首先,将药物二维化学结构转化为数值序列,计算药物之间的皮尔逊相关系数,进而构建药物关联网络;然后,在带有基因网络约束的稀疏偏最小二乘算法的基础上,加入药物关联网络信息,提出伴有基因和药物关联网络正则约束的稀疏偏最小二乘(SGDPLS)算法;最后,将SGDPLS算法应用于基因-药物共模块识别.结果表明:药物关联网络信息的加入能够有效提高所识别的共模块中基因模块与药物模块的相关性,增加共模块的生物可解释性.     

电化学DNA传感器研究进展

电化学DNA传感器是一种新型的生物传感器,对其基本原理、组成及其在基因检测、基因疾病诊断药物机理研究等方面作了介绍,并对其发展趋势进行了展望.     

宁夏地区162株大肠杆菌临床分离株对磺胺类药物的耐药性分析

分析宁夏地区大肠杆菌临床分离株对磺胺类药物的耐药性,为指导临床合理用药提供参考.用PCR技术和药敏实验对宁夏地区临床分离的162株大肠杆菌进行了磺胺类药物耐药基因sul1,sul2,sul3的分子检测和耐药性研究.结果表明,在162株大肠杆菌临床分离株中,127株检测出了耐药基因,阳性率为78.4%.其中,sul1基因的阳性率最高,为65.4%,sul2,sul3基因的阳性率分别为48.1%,1.9%;106株对磺胺类药物的耐药率为65.4%,耐药菌株中有5株未检测到sul1,sul2,sul3耐药基因.药敏实验结果与基因检测结果的符合率为95.3%.宁夏地区大肠杆菌临床分离株对磺胺类药物具有较高的耐药性,应予以足够重视.     

ATP-TCA结合MDR水平检测在临床乳腺癌化疗药物筛选中的应用

目的建立乳腺癌个体化疗体系,减少滥用药物或过度用药给患者带来的副作用,提高化疗药物的有效率.方法分离、培养乳腺癌患者新鲜组织细胞,加入临床常用化疗药物,体外培养一定时间后,按ATP-TCA试剂盒说明书进行细胞ATP含量检测,根据荧光强度计算药物半数致死量及细胞生长增殖抑制率;提取切除的手术标本及癌旁组织RNA,RT-PCR,检测MDR基因表达水平;根据细胞敏感程度及MDR基因水平检测优化对患者的化疗方案.结果 142例患者对常见的化疗药物敏感程度各有不同;在这些耐受病例中约有50%~80%病例MDR基因高表达.结论 ATP-TCA配合MDR基因水平检测有利于建立个体化化疗体系,提高临床化疗药物的有效性.     

肿瘤基因治疗

在单基因缺陷遗传病的基因治疗取得重要研究进展的同时,涉及多基因异常的肿瘤基因治疗研究也取得了令人瞩目的突破.从五个方面考虑肿瘤的基因治疗:信息药物法,导入反意核酸或核酸代酶信息药物抑制肿瘤恶性基因的表达;遗传免疫调节法,导入细胞因子基因刺激对肿瘤细胞毒的免疫反应;正常组织保护法,导入外源基因增强正常细胞对化疗和放疗的抗性,最大限度减小化疗和放疗对正常组织的损伤;药物打靶法,导入外源病毒特殊酶的基因,使这个基因选择性地在肿瘤细胞中表达,进而把一些低毒的原药转化为高毒药物,有针对性地杀伤肿瘤细胞;基因取代疗法,导入外源基因纠正抑癌基因的缺陷,恢复抑癌功能.     

用纳米技术诊断与治疗恶性肿瘤的进展

利用纳米技术进行恶性肿瘤早期诊断和治疗是目前国际生物技术领域中最前沿的研究课题,迄今实验室细胞模型(in vitro)研究和临床前动物模型(in vivo)研究已取得了重大进展.纳米生物技术将成为继放疗、化疗和手术治疗后治疗基因疾病的更有效的方法.纳米生物技术涵盖纳米材料科学,构成纳米药物载体平台的纳米材料与药物或基因结合的组装技术以及随后与靶向物质结合的组装技术.目前,实现了纳米生物传感器在肿瘤细胞上的表达,纳米基因药物能够抑制肿瘤细胞的增殖、诱导肿瘤细胞凋亡,但在临床治疗之前为了确保安全、有效,首先应该研制出针对癌细胞表面配位子特意性更强的靶向物质,以减少对正常组织的损害;此外,还需提高纳米材料药物的装载量和稳定性,并研制出适宜的纳米材料以及相应的制备技术.     

GenCenter:一个基因综合信息数据集成系统

GenCenter集成了已被实验验证以及功能已经明确了的基因信息,增加了基因相关的核酸序列、蛋白质结构、专利以及与该基因相关的疾病、药物与文献等信息.描述了GenCenter的体系结构、数据库构成、关键技术、功能.     

蛇毒及其基因克隆研究进展

对蛇素及其基因克隆研究进行了综述.蛇毒是一种天然蛋白质,蛇毒制剂可抗凝、去纤、溶 栓、扩血管、降血压、治疗神经性疾病和各种中、晚期癌症,是目前治疗疾病的理想药物.随着分子生 物学技术的迅猛发展,克隆蛇毒基因的方法也日臻成熟.通过基因工程技术使获得大量的高纯度的 蛇毒各组分成为可能.     

Markedness and its Interpretation in Language Use

Language markedness is a common phenomenon in languages, and is reflected from hearing, vision and sense, i.e. the variation in the three aspects such as phonology, morphology and semantics. This paper focuses on the interpretation of markedness in language use following the three perspectives, i.e. pragmatic interpretation, psychological interpretation and cognitive interpretation, with an aim to define the function of markedness.     

Lower Paleozoic oil relationships within Williston Basin, Canada

The Williston Basin is a significant petroleum province, containing oil production zones that include the Middle Cambrian to Lower Ordovician, Upper Ordovician, Middle Devonian, Upper Devonian and Mississippian and within the Jurassic and Cretaceous. The oils of the Williston Basin exhibit a wide range of geochemical characteristics defined as "oil families", although the geochemical signature of the Cambrian Deadwood Formation and Lower Ordovician Winnipeg reservoired oils does not match any "oil family". Despite their close stratigraphic proximity, it is evident that the oils of the Lower Palaeozoic within the Williston Basin are distinct. This suggests the presence of a new "oil family" within the Williston Basin. Diagnostic geochemical signatures occur in the gasoline range chromatograms, within saturate fraction gas chromatograms and biomarker fingerprints. However, some of the established criteria and cross-plots that are currently used to segregate oils into distinct genetic families within the basin do not always meet with success, particularly when applied to the Lower Palaeozoic oils of the Deadwood and Winnipeg Formation.     

An Analysis of Catherine＇s Character——Wuthering Heights

Wuthering Heights, Emily Bronte＇s only novel, was published in December of 1847 under the pseudonym Ellis Bell. The book did not gain immediate success, but it is now thought one of the finest novels in the English language. Catherine is the key character of this masterpiece, because everybody and everything center on her though she had a short life. We can understand this masterpiece better if we know Catherine well.     

Characterization of Ordovician carbonate reservoirs, southeastern Saskatchewan, Canada

The discovery of the prolific Ordovician Red River reservoirs in 1995 in southeastern Saskatchewan was the catalyst for extensive exploration activity which resulted in the discovery of more than 15 new Red River pools. The best yields of Red River production to date have been from dolomite reservoirs. Understanding the processes of dolomitization is, therefore, crucial for the prediction of the connectivity, spatial distribution and heterogeneity of dolomite reservoirs.The Red River reservoirs in the Midale area consist of 3～4 thin dolomitized zones, with a total thickness of about 20 m, which occur at the top of the Yeoman Formation. Two types of replacement dolomite were recognized in the Red River reservoir: dolomitized burrow infills and dolomitized host matrix. The spatial distribution of dolomite suggests that burrowing organisms played an important role in facilitating the fluid flow in the backfilled sediments. This resulted in penecontemporaneous dolomitization of burrow infills by normal seawater. The dolomite in the host matrix is interpreted as having occurred at shallow burial by evaporitic seawater during precipitation of Lake Almar anhydrite that immediately overlies the Yeoman Formation. However, the low δ18O values of dolomited burrow infills (-5.9‰～ -7.8‰, PDB) and matrix dolomites (-6.6‰～ -8.1‰, avg. -7.4‰ PDB) compared to the estimated values for the late Ordovician marine dolomite could be attributed to modification and alteration of dolomite at higher temperatures during deeper burial, which could also be responsible for its 87Sr/86Sr ratios (0.7084～0.7088) that are higher than suggested for the late Ordovician seawaters (0.7078～0.7080). The trace amounts of saddle dolomite cement in the Red River carbonates are probably related to "cannibalization" of earlier replacement dolomite during the chemical compaction.     

Design and analysis of generic LBS application developing platform

Location based services is promising due to its novel working style and contents.A software platform is proposed to provide application programs of typical location based services and support new applications developing efficiently. The analysis shows that this scheme is easy implemented, low cost and adapt to all kinds of mobile nework system.     

橡胶颗粒沥青混合料低温抗裂性试验研究

以AC-13级配为基础,将橡胶颗粒代替部分集料掺入混合料中,以低温弯曲试验为评价方法对不同橡胶颗粒掺量下沥青混合料的低温抗裂性进行研究,并引入应变能密度值对混合料的低温抗裂性进行综合评价.试验结果表明:橡胶颗粒沥青混合料试件的破坏微应变均超过2 300,满足冬寒区的技术指标;无论是否掺加橡胶颗粒,随着温度的下降,沥青混合料破坏时的最大弯拉强度增大,弯拉应变降低,劲度模量增大;弯曲应变能密度在胶粒掺量为1%左右时具有较大的弯曲应变能密度值,此时橡胶颗粒沥青混合料具有较好的低温抗裂性.     

A computer generator for randomly layered structures

AcomputergeneratorforrandomlylayeredstructuresYUJia shun1,2,HEZhen hua2(1.TheInstituteofGeologicalandNuclearSciences,NewZealand;2.StateKeyLaboratoryofOilandGasReservoirGeologyandExploitation,ChengduUniversityofTechnology,China)Abstract:Analgorithmisintrod…     

低渗透非均质砂岩油藏启动压力梯度研究

理论推导与室内实验相结合,建立了低渗透非均质砂岩油藏启动压力梯度确定方法。首先借助油藏流场与电场相似的原理,推导了非均质砂岩油藏启动压力梯度计算公式。其次基于稳定流实验方法,建立了非均质砂岩油藏启动压力梯度测试方法。结果表明:低渗透非均质砂岩油藏的启动压力梯度确定遵循两个等效原则。平面非均质油藏的启动压力梯度等于各级渗透率段的启动压力梯度关于长度的加权平均;纵向非均质油藏的启动压力梯度等于各渗透率层的启动压力梯度关于渗透率与渗流面积乘积的加权平均。研究成果可用于有效指导低渗透非均质砂岩油藏的合理井距确定,促进该类油藏的高效开发。     

Quantitative trait loci （QTLs） for quality traits related to protein and starch in wheat

Quality traits in wheat （Triticum aestirum L.） were studied by quantitative trait locus （QTL） analysis in a recombinant inbred line （RIL） population, a set of 131 lines derived from Chuan 35050 × Shannong 483 cross （ChSh）. Grains from RILs were assayed for 21 quality traits related to protein and starch. A total of 35 putative QTLs for 19 traits with a single QTL explaining 7.99-40.52% of phenotypic variations were detected on 10 chromosomes, 1D, 2A, 2D, 3B, 3D, 5A, 6A, 6B, 6D, and 7B. The additive effects of 30 QTLs were positive, contributed by Chuan 35050, the remaining 5 QTLs were negative with the additive effect contributed by Shannong 483. For protein traits, 15 QTLs were obtained and most of them were located on chromosomes 1 D, 3B and 6D, while 20 QTLs for starch traits were detected and most of them were located on chromosomes 3D, 6B and 7B. Only 7 QTLs for protein and starch traits were co-located in three regions on chromosomes 1D, 2A and 2D. These protein and starch trait QTLs showed a distinct distribution pattern in certain regions and chromosomes. Twenty-two QTLs were clustered in 6 regions of 5 chromosomes. Two QTL clusters for protein traits were located on chromosomes 1D and 3B, respectively, three clusters for starch traits on chromosomes 3D, 6B and 7B, and one cluster including protein and starch traits on chromosome 1D.     

On Tragic Consciousness In The Works By Ernest Hemingway

As an American modern novelist who were famous in the literary world, Hemingway was not a person who always followed the trend but a sharp observer. At the same time, he was a tragedy maestro, he paid great attention on existence, fate and end-result. The dramatis personae's tragedy of his works was an extreme limit by all means tragedy on the meaning of fearless challenge that failed. The beauty of tragedy was not produced on the destruction of life, but now this kind of value was in the impact activity. They performed for the reader about the tragedy on challenging for the limit and the death.