检索结果-南通市图书馆

Discovery of N-benzyl hydroxypyridone carboxamides as a novel and potent antiviral chemotype against human cytomegalovirus (HCMV)

引用

Acta Pharmaceutica Sinica B 2022年第4期12卷 1671-1684页

作者： Sameera Senaweera Tiffany C.edwards Jayakanth Kankanala Yan Wang Rajkumar Lalji Sahani Jiashu Xie Robert J.Geraghty Zhengqiang Wang Center for Drug Design College of PharmacyUniversity of MinnesotaMinneapolisMN 55455USA Translational Medicine R&D Center Shenzhen Institutes of Advanced TechnologyChinese Academy of SciencesShenzhen 518055China

Current drugs for treating human cytomegalovirus(HCMV)infections are limited by resistance and treatment-associated *** developing mechanistically novel HCMV antivirals,we discovered an N-benzyl hydroxypyridone carboxamide antiviral hit(8a)inhibiting HCMV in submicromolar *** describe herein the structure–activity relationship(SAR)for 8a,and the characterization of potent analogs for cytotoxicity/cytostatic property,the preliminary mechanism of action,and the absorption,distribution,metabolism and excretion(ADME)*** SAR revealed a few pharmacophore features conferring optimal antiviral profile,including the 5-OH,the N-1 benzyl,at least one–CH_(2)−in the linker,and a di-halogen substituted phenyl ring in the amide *** the end,we identified numerous analogs with sub-micromolar antiviral potency and good selectivity *** preliminary mechanism of action characterization used a pUL89-C biochemical endonuclease assay,a virus entry assay,a time-of-addition assay,and a compound withdrawal *** profiling measuring aqueous solubility,plasma and liver microsomal stability,and parallel artificial membrane permeability assay(PAMPA)permeability demonstrated largely favorable drug-like ***,these studies validate the N-benzyl hydroxypyridone carboxamide as a viable chemotype for potent and mechanistically distinct antivirals against HCMV.

关键词： Human cytomegalovirus N-Benzyl hydroxypyridone carboxamides Structureeactivity relationship Mechanism of action

来源：

维普期刊数据库

同方期刊数据库评论

在线全文

学校读者我要写书评

暂无评论

Showering in Flint, MI: Is there a DBP problem?

引用

Journal of Environmental Sciences 2017年第8期29卷 271-284页

作者： Joshua M.Allen Amy A.Cuthbertson Hannah K.Liberatore Susana Y.Kimura Anurag Mantha Marc A.edwards Susan D.Richardson Department of Chemistry and Biochemistry University of South Carolina the Department of Chemistry University of Calgary Civil and Environmental Engineering Virginia Tech

Lead contamination in the City of Flint, MI has been well documented over the past two years, with lead levels above the EPA Action Level until summer 2016. This resulted from an ill-fated decision to switch from Detroit water（Lake Huron） with corrosion control, to Flint River water without corrosion control. Although lead levels are now closer to normal,reports of skin rashes have sparked questions surrounding tap water in some Flint *** study investigated the presence of contaminants, including disinfection by-products（DBPs）, in the hot tap water used for showering in the homes of residents in Flint. Extensive quantitative analysis of 61 regulated and priority unregulated DBPs was conducted in Flint hot and cold tap water, along with the analysis of 50 volatile organic compounds and a nontarget comprehensive, broadscreen analysis, to identify a possible source for the reported skin rashes. For comparison, chlorinated hot and cold waters from three other cities were also sampled, including Detroit, which also uses Lake Huron as its source *** showed that hot water samples generally contained elevated levels of regulated and priority unregulated DBPs compared to cold water samples, but trihalomethanes were still within regulatory limits. Overall, hot shower water from Flint was similar to waters sampled from the three other cities and did not have unusually high levels of DBPs or other organic chemicals that could be responsible for the skin rashes observed by residents. It is possible that an inorganic chemical or microbial contaminant may be responsible.

关键词： Disinfection by-products Disinfection byproducts DBPs Flint Hot water Showering Bathing Drinking water

来源：

维普期刊数据库

同方期刊数据库评论

在线全文

学校读者我要写书评

暂无评论

Beyond monogenetic rare variants:tackling the low rate of genetic diagnoses in predominantly antibody deficiency

引用

Cellular & Molecular Immunology 2021年第3期18卷 588-603页

作者： Emily S.J.edwards Julian J.Bosco Samar Ojaimi Robyn E.O’Hehir Menno C.van Zelm Department of Immunology and Pathology Central Clinical SchoolMonash UniversityMelbourneVICAustralia The Jeffrey Modell Diagnostic and Research Centre for Primary Immunodeficiencies MelbourneVICAustralia Department of Allergy Immunology and Respiratory MedicineCentral Clinical SchoolMonash University and AllergyAsthma and Clinical Immunology ServiceAlfred HospitalMelbourneVICAustralia Department of Infectious Diseases Monash HealthClaytonVICAustralia Centre for Inflammatory Diseases Monash HealthClaytonVICAustralia Department of Allergy and Immunology Monash HealthClaytonVICAustralia

Predominantly antibody deficiency(PAD)is the most prevalent form of primary immunodeficiency,and is characterized by broad clinical,immunological and genetic *** the current gold standard of whole exome sequencing for diagnosis,pathogenic gene variants are only identified in less than 20% of *** elucidation of the causal genes underlying PAD has provided many insights into the cellular and molecular mechanisms underpinning disease pathogenesis,many other genes may remain as yet undefined to enable definitive diagnosis,prognostic monitoring and targeted therapy of *** that many patients display a relatively late onset of disease presentation in their 2^(nd) or 3^(rd) decade of life,it is questionable whether a single genetic lesion underlies disease in all ***,combined effects of other gene variants and/or non-genetic factors,including specific infections can drive disease *** this review,we define(1)the clinical and immunological variability of PAD,(2)consider how genetic defects identified in PAD have given insight into B-cell immunobiology,(3)address recent technological advances in genomics and the challenges associated with identifying causal variants,and(4)discuss how functional validation of variants of unknown significance could potentially be translated into increased diagnostic rates,improved prognostic monitoring and personalized medicine for PAD patients.A multidisciplinary approach will be the key to curtailing the early mortality and high morbidity rates in this immune disorder.

关键词： Predominantly antibody deficiency Genetic diagnosis Genomics Functional validation

来源：

维普期刊数据库评论

在线全文

维普期刊数据库

学校读者我要写书评

暂无评论

Role of coronary angiogram before transcatheter aortic valve implantation

引用

World Journal of Cardiology 2021年第8期13卷 361-371页

作者： Benjamin Beska Divya Manoharan Ashfaq Mohammed Rajiv Das Richard edwards Azfar Zaman Mohammad Alkhalil Cardiothoracic Centre Freeman HospitalNewcastle-upon-Tyne NE77DNUnited Kingdom

BACKGROUND Coexistent coronary artery disease is commonly seen in patients undergoing transcatheter aortic valve implantation(TAVI).Previous studies showed that pre-TAVI coronary revascularisation was not associated with improved outcomes,challenging the clinical value of routine coronary angiogram(CA).AIM To assess whether a selective approach to perform pre-TAVI CA is safe and *** This was a retrospective non-randomised single-centre analysis of consecutive patients undergoing TAVI.A selective approach for performing CA tailored to patient clinical need was *** outcomes were compared based on whether patients underwent *** primary endpoint was a composite of allcause mortality,myocardial infraction,repeat CA,and re-admission with heart *** Of 348 patients(average age 81±7 and 57%male)were included with a median follow up of 19(9-31)*** hundred and fifty-four(44%)patients,underwent CA before TAVI *** who underwent CA were more likely to have previous myocardial infarction(MI)and previous percutaneous *** primary endpoint was comparable between the two group(22.6%vs 22.2%;hazard ratio 1.05,95%CI:0.67-1.64,P=0.82).Patients who had CA were less likely to be readmitted with heart failure(P=0.022),but more likely to have repeat CA(P=0.002)and MI(P=0.007).In those who underwent CA,the presence of flow limiting lesions did not affect the incidence of primary endpoint,or its components,except for increased rate of repeat *** Selective CA is a feasible and safe *** clinical value of routine CA should be challenged in future randomised trials.

关键词： Transcatheter aortic valve implantation Angiogram Revascularisation Coronary angiogram

来源：

维普期刊数据库评论

在线全文

维普期刊数据库

学校读者我要写书评

暂无评论

Complicated responses of stalagmite δ ^(13)C to climate change during the last glaciation from Hulu Cave, Nanjing,China

引用

Science China Earth Sciences 2005年第12期48卷 2174-2181页

作者： R. L. edwards Department of Geology and Geophysics University of Minnesota MN 55455 USA

We present a record on carbon stable isotopic composition (δ 13C), covering 75 through 10 thousands years ago (ka B.P.), from Hulu Cave, Nanjing. The overlapping δ 13C pro-files are very similar in pattern and range, indicating that they mainly record climatic signal. Dur-ing the last glacial-interglacial transition, the >6‰ change of δ 13C values implies different con-tributions of C3 vs. C4 type plants in soils. On millennial scale, however, the increased calcite δ 13C during the warm Dansgaard-Oeschger (DO) events suggests a decrease of dissolved bio-genic CO2 when water flux rate through soil is large. This correlation between heavier δ 13C and higher precipitation is consistent with our previous report on the samples’ stable oxygen isotope records (Wang et al., 2001). Comparison of coeval δ 13C and δ 18O of stalagmites indicates that kinetic fractionation of carbon isotope is closely related to growth rate of stalagmites. This study also shows that local vegetation changes may lag behind precipitation changes by ~700 years during the deglaciation.

关键词： Hulu Cave stalagmite δ 13C last glacial period.

来源：

维普期刊数据库

同方期刊数据库评论

在线全文

学校读者我要写书评

暂无评论

Gene body demethylation increases expression and is associated with self-pruning during grape genome duplication

引用

Horticulture Research 2020年第1期7卷 1572-1583页

作者： Luming Zou Wenwen Liu Zhan Zhang Everard J.edwards Elias Kirabi Gathunga Peige Fan Wei Duan Shaohua Li Zhenchang Liang Beijing Key Laboratory of Grape Science and Enology and CAS Key Laboratory of Plant Resources Institute of BotanyChinese Academy of SciencesBeijing 100093PR China University of the Chinese Academy of Sciences Beijing 100049PR China College of Life Science Shanxi Normal UniversityShanxi 041004PR China CSIRO Agriculture&Food Locked Bag 2Glen OsmondSA 5064Australia Sino-Africa Joint Research Center Chinese Academy of SciencesWuhan 430074PR China

A colchicine-induced autotetraploid grapevine exhibiting potentially valuable agronomic traits for grape production and breeding,including self-pruning,was *** study investigated DNA methylation variation and its role in gene expression during self-pruning in the autotetraploid *** used RNA-Seq to estimate differentially expressed genes between diploid and autotetraploid grapevine shoot *** genes showing increases in the autotetraploid were mainly related to stress response pathways,whereas those showing decreases in the autotetraploid were related to biological metabolism and ***-genome bisulfite sequencing was performed to produce single-base methylomes for the diploid and autotetraploid *** between the methylomes revealed that they were conserved in CG and CHG *** the autotetraploid grapevine,hypodifferentially methylated regions(DMRs)and hyper-DMRs in the gene body increased or decreased gene expression,*** results indicated that a hypo-DMR in the ACO1 gene body increased its expression and might promote *** study reports that hypo-DMRs in the gene body increase gene expression in plants and reveals the mechanism underlying the changes in the modifications affecting gene expression during genome ***,our results provide valuable information for understanding the relationships between DNA methylation,gene expression,and autotetraploid breeding in grape.

关键词： metabolism breeding showing

来源：

维普期刊数据库评论

在线全文

维普期刊数据库

学校读者我要写书评

暂无评论

CONSERVATION-A BROAD CONCEPT!

CONSERVATION-A BROAD CONCEPT!

引用

亚洲民族建筑保护与发展学术研讨会

作者： John edwards Cardiff Castle Surveyor to the Fabric

This paper will examine why conservation needs to be a broad concept if it is to be sustainable, and uses Cardiff Castle as a case study to illustrate the points to be made. Cardiff Castle is a 2,000 year old site situated in Cardiff, the capital city of Wales, part of the United Kingdom of Great Britain. Here, many diverse conservation challenges are being met, with due consideration of all issues. These range from physical conservation work to the building fabric and decoration, to issues concerning visitor access, education, interpretation, tourism and those concerning economic sustainability. The paper will also examine the necessity to put in place processes that will ensure that all issues are properly and consistently dealt with, based upon the utmost understanding of the issues and the site. The need to start with the analysis of cultural significance will be raised, and a methodology that starts with the understanding of legal protection and subsequently, the production of a conservation plan, management plan, a research and analysis programme, to the specification of detailed requirements.

关键词： ancient building Cardiff Castle cultural meaning

来源： cnki会议评论

在线全文

cnki会议

学校读者我要写书评

暂无评论

Preliminary Studies of Speleothem in Central Asia

引用

Acta Geologica Sinica(English Edition) 2016年第6期90卷 2279-2280页

作者： TAN Liangcheng SONG Yougui CAI Yanjun AN Zhisheng Rustam OROZBAEV Yunus MAMADJANOV Lawrence R.edwards CHENG Hai LI Dong LI Yue State Key Laboratory of Loess and Quaternary Geology Institute of Earth EnvironmentChinese Academy of Sciences Institute of Global Environmental Change Xi’an Jiaotong University Research Center for Ecology and Environment of Central Asia (Bishkek) Chinese Academy of Sciences Institute of Geology National Academy of Sciences of Kyrgyz Republic Institute of Geology Earthquake Engineering and SeismologyAcademy of Sciences of the Republic of Tajikistan Department of Earth Sciences University of Minnesota

The Westerlies is important in linking the Northem high latitude, North Atlantic and East Asian monsoon. The location and intensity of the Westerly jet can not only control the climate of central Asia （including northwest arid China）, but also significantly influence the climate of the East Asian monsoon region. However, it remains unclear of the variability of the Westerlies in Asia on multiple timeseales and their global linkage.

关键词： Preliminary Studies of Speleothem in Central Asia

来源：

维普期刊数据库

同方期刊数据库评论

在线全文

学校读者我要写书评

暂无评论

Expanding public health professionals’ roles in promoting and supporting breastfeeding as optimal infant feeding: A pilot study with online tutorial implications

引用

Open Journal of Preventive Medicine 2013年第2期3卷 184-190页

作者： Amna Umer Roger A. edwards Department of Health Sciences Bouvé College of Health Sciences Northeastern University Boston USA Department of Pharmacy Practice School of Pharmacy Bouvé College of Health Sciences Northeastern University Boston USA

Background: Their knowledge of preventive health, coupled with their dynamic roles in the community, puts public health professionals in a key position to expand their roles in the health promotion and support of breastfeeding as optimal infant feeding. This online tutorial was created to increase public health professionals’ knowledge about breastfeeding and to assess their attitudes in supporting healthy behaviors related to infant feeding as a health promotion strategy. Method: The study utilized an online breastfeeding tutorial based on the US Breast-feeding Committee recommendations for minimum breastfeeding knowledge for health professionals. Pre- and post-tutorial questionnaires assessed breastfeeding knowledge, and an attitudinal survey evaluated attitudes of public health professionals after the tutorial. Exposing public health students to this information can facilitate the early shaping of their attitudes and understanding about the importance of breastfeeding. Results: Fifty-two Northeastern University MPH students and alumni (62% response rate) completed the study. There was an overall gain in participants’ fundamental knowledge regarding breastfeeding as assessed by pre- (77%) to post-tutorial (97%) correct responses (p = 0.00001). The post-tutorial attitudinal survey showed that 92% of participants were comfortable in answering questions about breastfeeding as part of their professional responsibilities. Conclusion: This pilot study highlights the important role that a short online tutorial can play in expanding public health professionals’ knowledge about breastfeeding. Greater use of online methods can enhance awareness of critical health behaviors, such as breastfeeding, that have not received adequate attention in public health curricula. This pilot study provides the foundation for a larger study. Integration of breastfeeding into public health professionals’ core training could support broader social change.

关键词： Breastfeeding Health Promotion Public Health Online Tutorial

来源：

维普期刊数据库评论

在线全文

维普期刊数据库

学校读者我要写书评

暂无评论

Breast Cancer Therapies Present and Future

引用

Journal of Cancer Therapy 2012年第6期3卷 1140-1150页

作者： Jessica Kalra Lincoln A. edwards Experimental Therapeutics Department of Pathology and Laboratory Medicine BC Cancer Agency Vancouver Canada&Department of Biology Langara College Vancouver Canada Neuro-Oncology Branch National Cancer Institute National Institute of Neuro- logical Disorders and Stroke National Institutes of Health Bethesda USA.

Significant advances in breast cancer treatment have been made where it is now possible to treat localized disease to a curable state. However, for approximately 30% of women with primary disease, metastatic breast cancer (MBC) or recurrent disease, treatment has remained challenging. Major obstacles in the effective treatment of breast cancer in these populations include: 1) the molecular heterogeneity of the disease;2) treatment of MBC and more specifically brain metastasis;and 3) defining combination therapies that address the evolution of resistance with disease relapse. The acknowledgement of these difficulties has led to an effort to further understand the roadblocks to therapy with the anticipation that more appropriate treatments will result. Here we describe the current state of breast cancer treatment, and the potential for improved therapy.

关键词： Breast Cancer Brain Metastasis Drug Combinations

来源：

维普期刊数据库评论

在线全文

维普期刊数据库

学校读者我要写书评

暂无评论

欢迎您,

建议与咨询留下您的常用邮箱和电话号码，以便我们向您反馈解决方案和替代方法

时间限定

文献类型

馆藏选择

核心期刊

语言

文献类型

帮助

文字说明：

检索规则说明：

检索范例：

分类表

所选分类

限定检索结果

文献类型

馆藏范围

日期分布

学科分类号

主题

机构

作者

语言

在线全文

在线全文

在线全文

在线全文

在线全文

在线全文

在线全文

在线全文

在线全文

在线全文

请选择保存的检索档案：

请选择收藏分类：

通借通还

欢迎您,

建议与咨询 留下您的常用邮箱和电话号码，以便我们向您反馈解决方案和替代方法

时间限定

文献类型

馆藏选择

核心期刊

语言

文献类型

帮助

文字说明：

检索规则说明：

检索范例：

分类表

所选分类

限定检索结果

文献类型

馆藏范围

日期分布

学科分类号

主题

机构

作者

语言

在线全文

在线全文

在线全文

在线全文

在线全文

在线全文

在线全文

在线全文

在线全文

在线全文

请选择保存的检索档案： 新增检索档案 确定 取消

请选择收藏分类： 新增自定义分类 确定 取消

通借通还

建议与咨询留下您的常用邮箱和电话号码，以便我们向您反馈解决方案和替代方法

请选择保存的检索档案：

请选择收藏分类：