检索结果-南通市图书馆

Chromatoprobe as a sample-sparing technique for residual solvent analysis of drug discovery candidates by gas chromatography

引用

药物分析学报：英文版 2017年第4期7卷 265-269页

作者： christopher j.Poronsky jingfang Qian Cutrone Bristol-Myers Squibb Research and DevelopmentWallingfordCT 06492USA

In drug discovery research, residual solvent measurement is an integral part of purity analysis for synthesis of a drug candidate before it is used for toxicity testing. This is usually carried out using gas chromatography(GC)with direct injection sample introduction. This method requires testing compounds to be soluble at high concentrations( > 50 mg/mL, usually in DMSO) to achieve acceptable sensitivity, a hurdle which is not always achievable for some samples such as cyclic peptides and oligonucleotides. To overcome the limitation associated with the direct injection approach, a new method using the Chromatoprobe thermal extraction device was developed for quantifying residual solvents of drug discovery compounds. This method not only consumes significantly less material(less than 1 mg), but also shows higher sensitivity than the direct injection approach.In addition, because no diluent is required with the Chromatoprobe thermal extraction, all residual solvents can be detected and measured without further method optimization. In our study, we compared data from GC residual solvent analysis using the Chromatoprobe solid sample introduction to those of the direct injection method for seven in-house samples. Our results showed a good agreement between the data from these two sample introduction methods. Thus, the Chromatoprobe sample introduction method provided a samplesparing alternative to the direct injection method for the measurement of residual solvents in drug discovery.This method can be particularly useful for residual solvent analysis in samples that are available only in limited amounts, poorly soluble, and/or unstable in the diluents used for the direct injection method.

关键词： Chromatoprobe Thermal extraction Gas chromatography Residual solvent Drug discovery

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

Enhanced recovery programme in colorectal surgery:Does one size fit all?

引用

World journal of Gastroenterology 2012年第40期18卷 5661-5663页

作者： Alison Lyon christopher j Payne Graham j MacKay Specialty Registrar in General Surgery West of Scotland RotationGlasgow G4 0SFUnited Kingdom Lister Department of Surgery Glasgow Royal InfirmaryGlasgow G4 0SFUnited Kingdom

Enhanced recovery after surgery(ERAS) employs a multimodal perioperative care pathway with the aim of attenuating the stress response to surgery and accelerating recovery.It has been difficult to determine the relative importance of some of the individual components of these pathways such as epidural analgesia and laparoscopic colorectal surgery.Some argue that only a rigid adherence to the published ERAS protocol can achieve the proposed benefits of fast-track surgery.In this article,we explore some of the areas where the evidence base may be changing and ask whether a more flexible and individualised approach should be considered.

关键词：围手术期结直肠癌恢复方案尺寸多式联运应激反应组成部分发生变化

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

Vitamin B_(12)-auxotrophy in dinoflagellates caused by incomplete or absent cobalamin-independent methionine synthase genes(metE)

引用

Fundamental Research 2022年第5期2卷 727-737页

作者： Siheng Lin Zhangxi Hu Xiaoying Song christopher jGobler Ying Zhong Tang CAS Key Laboratory of Marine Ecology and Environmental Sciences Institute of OceanologyChinese Academy of SciencesQingdao 266071China Laboratory for Marine Ecology and Environmental Science Qingdao National Laboratory for Marine Science and TechnologyQingdao 266237China Center for Ocean Mega-Science Chinese Academy of SciencesQingdao 266071China University of Chinese Academy of Sciences Beijing 100049China School of Marine and Atmospheric Sciences Stony Brook UniversityNY11790USA Department of Biological Sciences and Biotechnology Minnan Normal UniversityZhangzhou 363000China

Dinoflagellates are responsible for most marine harmful algal blooms (HABs) and play vital roles in many ocean processes.More than 90% of dinoflagellates are vitamin B_(12) auxotrophs and that B_(12) availability can control dinoflagellate HABs,yet the genetic basis of B_(12) auxotrophy in dinoflagellates in the framework of the ecology of dinoflagellates and particularly HABs,which was the objective of this work.Here,we investigated the presence,phylogeny,and transcription of two methionine synthase genes(B_(12)-dependent metH and B_(12)-independent metE)via searching and assembling transcripts and genes from transcriptomic and genomic databases,cloning 38 cDNA isoforms of the two genes from 14 strains of dinoflagellates,measuring the expression at different scenarios of B_(12),and comprehensive phylogenetic analyses of more than 100 organisms.We found that 1)metH was present in all 58 dinoflagellates accessible and metE was present in 40 of 58 species,2)all metE genes lacked N-terminal domains,3)metE of dinoflagellates were phylogenetically distinct from other known metE genes,and 4)expression of metH in dinoflagellates was responsive to exogenous B_(12) levels while expression of metE was not responding as that of genuine metE genes.We conclude that most,hypothetically all,dinoflagellates have either non-functional metE genes lacking N-terminal domain for most species,or do not possess metE for other species,which provides the genetic basis for the widespread nature of B_(12) auxotrophy in dinoflagellates.The work elucidated a fundamental aspect of the nutritional ecology of dinoflagellates.

关键词： Harmful algal blooms(HABs)Dinoflagellates Vitamin B_(12) (cobalamin) Auxotrophy Methionine synthase genes Phytoplankton ecology

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

法律对裸统计及其他差错的反感

引用

证据科学 2024年第3期32卷 287-308页

作者：罗纳德·j·艾伦克里斯托弗·K·斯米克莱斯张嘉源西北大学普利兹克法学院国际证据科学协会中国政法大学证据科学研究院外国专家咨询委员会美国西北大学普利兹克法学院中国政法大学证据科学研究院

有大量文献抒发了法律对统计/概率证据的厌烦，尤其是对裸统计证据的排斥。这类文献都是基于错误的前提才持有这样的态度。至少就美国法律而言，人们对统计形式的证明并没有普遍反感，当证据的提供满足了可采性（其中最重要的是可靠性... 详细信息

有大量文献抒发了法律对统计/概率证据的厌烦，尤其是对裸统计证据的排斥。这类文献都是基于错误的前提才持有这样的态度。至少就美国法律而言，人们对统计形式的证明并没有普遍反感，当证据的提供满足了可采性（其中最重要的是可靠性）正常标准时，即使裸统计数据也是可采的，并足以支持裁决。相反的信念是建立在一系列差错基础上的：最重要的是，对法律制度的结构和普通法裁决性质的错误建模。造成这些错误的原因是，这些文献常见的方法论依赖于奇怪的假设，这些假设错误模拟了潜在法律关系，并包含了不可能的认识论要求。总的来说，这些现象分散了人们对影响法律制度的真问题的注意力。

关键词：裸统计概率可采性糟糕证据错误风险

来源：

同方期刊数据库评论

在线全文

同方期刊数据库

学校读者我要写书评

暂无评论

Growth trends and environmental drivers of major tree species of the northern hardwood forest of eastern North America

引用

journal of Forestry Research 2023年第1期34卷 37-50页

作者： Rebecca L.Stern Paul G.Schaberg Shelly A.Rayback christopher F.Hansen Paula F.Murakami Gary j.Hawley Rubenstein School of Environment and Natural Resources The University of VermontBurlingtonVT 05405USA ERM MalvernPA 19355USA Forest Service United States Department of AgricultureNorthern Research StationBurlingtonVT 05405USA Department of Geography The University of VermontBurlingtonVT 05405USA

The future health and productivity of tree species in the northern hardwood forest of eastern North America are uncertain considering changes in climate and pollution loading there.To better understand the trajectory of the northern hardwood forest,we studied the growth of three tree species emblematic of it:sugar maple(Acer saccharum Marsh),American beech(Fagus grandifolia Ehrh.),and yellow birch(Betula alleghaniensis Britton),plus a fourth species,red maple(Acer rubrum L.),whose abundance has increased in the region.We also analyzed the link between growth and several factors for690 trees in 45 plots throughout Vermont,USA:tree age and size,site elevation,and climate and acid deposition variables.Throughout their chronologies(1945-2014),all four species exhibited increasing growth followed by plateaued growth indicative of a maturing forest.For all species,summer moisture was positively correlated with growth,summer temperature was negatively associated with growth,and winter moisture or snow were positively correlated with growth.This last association was expected for sugar maple.However,our data suggest that winter snowpack may be more broadly relevant in sustaining tree growth in a region where snow has historically insulated the soil from freezing that can damage roots and lead to reduced aboveground growth.Measures of pollution deposition were also correlated with growth for all species except American beech—a species with documented tolerance to pollutant inputs.Of the four species studied,red maple had the fewest associations with environmental variables,which suggests that it may be less susceptible to growth reductions as the climate changes.

关键词： Climate change Sugar maple Yellow birch American beech Red maple

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

Chromophobe renal cell carcinoma: Novel molecular insights and clinicopathologic updates

引用

Asian journal of Urology 2022年第1期9卷 1-11页

作者： Reza Alaghehbandan G.Przybycin christopher Virginie Verkarre Rohit Mehra Department of Pathology Faculty of MedicineUniversity of British ColumbiaRoyal Columbian HospitalVancouverBCCanada Robert j Tomsich Pathology and Laboratory Medicine Institute Cleveland ClinicClevelandOHUSA Department of Pathology Georges Pompidou European HospitalAP-HPParis UniversityINSERM UMR 970PARCCParisFrance Department of Pathology University of Michigan Medical SchoolAnn ArborMIUSA Michigan Center for Translational Pathology Ann ArborMIUSA Rogel Cancer Center Michigan MedicineAnn ArborMIUSA

Chromophobe renal cell carcinoma(ChRCC)is the third most common renal cell carcinoma(RCC)subtype,which predominantly occurs in sporadic setting.ChRCCs are considered to originate from the intercalated cell of distal tubules with two main morphological variants,classic and eosinophilic.Most ChRCCs carry a favorable clinical outcome.Histology alone is limited in predicting the behavior of ChRCCs that do not have overtly aggressive morphologic findings such as necrosis and sarcomatoid features.Along with positive CD117 expression,classic ChRCCs generally express diffuse and uniform CK7,while eosinophilic variant demonstrates more heterogeneous CK7 expression(rare or patchy).Multiple losses of chromosomes 1,2,6,10,13,17,and 21 are considered to be the genetic hallmarks of classic and eosinophilic ChRCCs,while chromosomal gains are known to be associated with sarcomatoid ChRCCs.TP53 and PTEN are the two most frequently mutated genes in ChRCCs.The major challenge in the differential diagnosis of ChRCCs includes considerations around the eosinophilic variant(of ChRCCs),where it may share overlapping features with oncocytoma or other recent emergent oncocytic tumors.Most eosinophilic ChRCCs share expression of the recently described biomarkers,LINC01187 and FOXI1,with classic ChRCCs,however,a subset of eosinophilic-like ChRCCs with lower biomarker expression have been demonstrated to harbor MTOR gene mutations.Overall,the morphologic features of ChRCCs and genetic profile with combinations of chromosomal losses and gains suggest this tumor entity to represent a distinct,yet heterogeneous group of renal neoplasms.

关键词： Renal cell carcinoma Chromophobe Immunohisto-chemistry RNA in situ hybridization Next-generation sequencing Oncocytic tumors Molecular

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

Structural subgrid-scale modeling for large-eddy simulation: A review

引用

Acta Mechanica Sinica 2016年第4期32卷 567-578页

作者： Hao Lu christopher j.Rutland School of Energy and Power Engineering Huazhong University of Science and Technology Engine Research Center Mechanical EngineeringUniversity of Wisconsin-Madison

Accurately modeling nonlinear interactions in turbulence is one of the key challenges for large-eddy simulation（LES） of turbulence. In this article, we review recent studies on structural subgrid scale modeling, focusing on evaluating how well these models predict the effects of small scales. The article discusses a priori and a posteriori test results. Other nonlinear models are briefly discussed, and future prospects are noted.

关键词： turbulence turbulent viscosity priori dissipation posteriori scalar A review scales Reynolds

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

Approaches to identifying drug resistance mechanisms to clinically relevant treatments in childhood rhabdomyosarcoma

引用

Cancer Drug Resistance 2022年第1期5卷 80-89页

作者： Samson Ghilu christopher L.Morton Angelina V.Vaseva Siyuan Zheng Raushan T.Kurmasheva Peter j.Houghton Department of Molecular Medicine Greehey Children’s Cancer Research InstituteUT HealthSan AntonioTX 78229USA Department of Surgery St.Jude Children’s Research HospitalMemphisTN 38105USA Department of Epidemiology and Biostatistics Greehey Children’s Cancer Research InstituteUT HealthSan AntonioTX 78229USA

Aim:Despite aggressive multiagent protocols,patients with metastatic rhabdomyosarcoma(RMS)have poor prognosis.In a recent high-risk trial(ARST0431),25% of patients failed within the first year,while on therapy and 80% had tumor progression within 24 months.However,the mechanisms for tumor resistance are essentially unknown.Here we explore the use of preclinical models to develop resistance to complex chemotherapy regimens used in ARST0431.Methods:A Single Mouse Testing(SMT)protocol was used to evaluate the sensitivity of 34 RMS xenograft models to one cycle of vincristine,actinomycin D,cyclophosphamide(VAC)treatment.Tumor response was determined by caliper measurement,and tumor regression and event-free survival(EFS)were used as endpoints for evaluation.Treated tumors at regrowth were transplanted into recipient mice,and the treatment was repeated until tumors progressed during the treatment period(i.e.,became resistant).At transplant,tumor tissue was stored for biochemical and omics analysis.Results:The sensitivity to VAC of 34 RMS models was determined.EFS varied from 3 weeks to>20 weeks.Tumor models were classified as having intrinsic resistance,intermediate sensitivity,or high sensitivity to VAC therapy.Resistance to VAC was developed in multiple models after 2-5 cycles of therapy;however,there were examples where sensitivity remained unchanged after 3 cycles of treatment.Conclusion:The SMT approach allows for in vivo assessment of drug sensitivity and development of drug resistance in a large number of RMS models.As such,it provides a platform for assessing in vivo drug resistance mechanisms at a“population”level,simulating conditions in vivo that lead to clinical resistance.These VAC-resistant models represent“high-risk”tumors that mimic a preclinical phase 2 population and will be valuable for identifying novel agents active against VAC-resistant disease.

关键词： Rhabdomyosarcoma patient-derived xenografts combination therapy intrinsic drug resistance acquired drug resistance

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

An In Vivo Experimental Validation of a Computational Model of Human Foot

引用

journal of Bionic Engineering 2009年第4期6卷 387-397页

作者： christopher j.Nester David Howard Centre for Health Sport and Rehabilitation Sciences ResearchUniversity of Salford Salford M5 4WTUK

Reliable computational foot models offer an alternative means to enhance knowledge on the biomechanics of human foot. Model validation is one of the most critical aspects of the entire foot modeling and analysis process.This paper presents an in vivo experiment combining motion capture system and plantar pressure measure platform to validate a three-dimensional finite element model of human foot.The Magnetic Resonance Imaging(MRI)slices for the foot modeling and the experimental data for validation were both collected from the same volunteer subject.The validated components included the comparison of static model predictions of plantar force,plantar pressure and foot surface deformation during six loading conditions,to equivalent measured data.During the whole experiment,foot surface deformation,plantar force and plantar pressure were recorded simultaneously during six different loaded standing conditions.The predictions of the current FE model were in good agreement with these experimental results.

关键词： human foot computational model plantar pressure

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

Lessons learned from hepatocellular carcinoma may cause a paradigm shift in intraductal papillary mucinous neoplasms:a narrative review and discussion of conceptual similarities in tumor progression and recurrence

引用

journal of Pancreatology 2022年第1期5卷 36-40页

作者： Georgios Antonios Margonis Nikolaos Andreatos jane Wang Matthew j.Weiss christopher L.Wolfgang Department of Surgery Memorial Sloan Kettering Cancer CenterNew YorkNY Department of Internal Medicine and Taussig Cancer Institute Cleveland ClinicClevelandOH Department of Surgery University of California San FranciscoSan FranciscoCA Department of Surgery Northwell Health Cancer Institute and Zucker School of Medicine at HofstraL ake Success Department of Surgery NYU Grossman School of MedicineNew YorkNYUSA

Although the natural history of recurrence/progression in patients with intraductal papillary mucinous neoplasms (IPMN) of the pancreas has not been studied thoroughly, the three principal mechanisms have been identified: (a) presence of residual disease at the transection margin, (b) presence of intraductal/intraparenchymal metastases and (c) development of new primary lesions. Mechanisms (a) and (b) result in metastatic lesions that are genetically related to the primary, while new primary lesions (mechanism c) are genetically distinct. Interestingly, recurrence/progression in IPMN displays conceptual parallels with the well-established paradigm of disease recurrence in patients with hepatocellular carcinoma (HCC). Specifically, patients with HCC may also develop recurrent tumors due to microscopic residual disease/intrahepatic metastasis which are genetically similar to the primary while the development of genetically unrelated, de novo HCC after curative-intent resection is also common. The latter has been attributed to the presence of a widespread genetic abnormality ( "field defect" ) in the liver (ie, cirrhosis). Given the conceptual similarities between IPMN and HCC, a pancreatic "field defect" may also be hypothesized to exist. This review does not suggest that HCC and IPMN have identical pathogeneses, but rather that they have conceptual similarities in tumor recurrence/progression;thus, lessons learned from HCC could be applied to IPMN research and subsequent management. Conceptual similarities in tumor progression and recurrence may also be observed between IPMN and other malignancies. However, HCC was selected because it is well studied and can serve as a paradigm.

关键词： Field defect Hepatocellular carcinoma Intraductal papillary mucinous neoplasm Progression Recurrence

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

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：