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

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journal of Pharmaceutical Analysis 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 *** 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 *** 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

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Neurological and neuropsychological consequences of electrical and lightning shock： review and theories of causation

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Neural Regeneration Research 2017年第5期12卷 677-686页

作者： christopher j.Andrews Andrew D.Reisner Faculty of Medicine-The University of Queensland HerstonAustraliaLightning and Electrical InjuriesMt Ommaney Family PracticeMt OmmaneyBrisbaneAustralia Forensic Diagnostic Center of District Nine CambridgeOHUSA

Injuries from lightning and electrical injuries involve multiple systems of the body, however neurological symptoms are very widely reported. A disabling neuropsychological syndrome is also noted. This paper presents a comprehensive review of neurological and neuropsychological symptoms. Partial theories of causation for these injuries have been advanced, however, there is no convincing explanation for both delay in onset of symptoms and also the genesis of the neuropsychological syndrome. A theory of causation is proposed which satisfies both these constraints. This theory suggests circulating hormones such as cortisol, together with nitric oxide and oxidant free radicals from glutamatergic hyper-stimulation, act on tissues remote from the injury path including the hippocampus. This theory opens a research path to explore treatment options.

关键词： electrical injury lightning injury neurology neuropsychology neuropsychiatry injury trauma

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White light endoscopy,narrow band imaging and chromoendoscopy with magnification in diagnosing colorectal neoplasia

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World journal of Gastrointestinal Endoscopy 2009年第1期1卷 45-50页

作者： Rajvinder Singh Victoria Owen Anthony Shonde Philip Kaye christopher hawkey Krish Ragunath Wolfson Digestive Diseases Centre Queens Medical Centre campusNottingham University Hospitals NHS TrustNG7 2UHNottinghamUnited Kingdom Trent Research Development Unit University of NottinghamNG7 2RDNottinghamUnited Kingdom

AIM:To evaluate the sensitivity(Sn),specificity(Sp),positive predictive value(PPV) and negative predictive value(NPV) of 3 different techniques:high resolution white light endoscopy(WLE),Narrow Band Imaging(NBI) and Chromoendoscopy(CHR),all with magnification in differentiating adenocarcinomas,adenomatous and hyperplastic colorectal ***:Each polyp was sequentially assessed first by WLE,followed by NBI and finally by *** images of each polyp with each modality were taken and *** or polypectomies were then performed followed by blinded histopathological *** image was blindly graded based on the Kudo's pit pattern(KPP).In the assessment with NBI,the mesh brown capillary network pattern(MBCN) of each polyp was also *** Sn,Sp,PPV and NPV of differentiating hyperplastic(Type Ⅰ & Ⅱ-KPP,Type Ⅰ-MBCN) adenomatous(Types Ⅲ,Ⅳ-KPP,Type Ⅱ-MBCN) and carcinomatous polyps(Type Ⅴ-KPP,Type Ⅲ-MCBN) was then compared with reference to the final histopathological ***:A total of 50 colorectal polyps(5 adenocarcinomas,38 adenomas,7 hyperplastic) were *** and NBI [KPP,MBCN or the combined classification(KPP & MBCN)] were superior to WLE in the prediction of polyp histology(P < 0.001,P=0.002,P=0.001 and P < 0.001,respectively).NBI,using the MBCN pattern or the combined classification showed higher numerical accuracies compared to CHR,but this was not statistically significant(P=0.625,0.250).CONCLUSION:This feasibility study demonstrated that this combined classification with NBI could potentially be useful in routine clinical practice,allowing the endoscopist to predict histology with higher accuracies using a less cumbersome and technically less challenging method.

关键词： High-resolution magnification endoscopy Narrow band imaging with magnification Chromoendoscopy with magnification Colorectal polyp Colorectal neoplasia

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The floristic relationship between the upland and lowland Carboniferous wetlands of Variscan Euramerica——Evidence from some medullosalean pteridosperm fronds

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journal of Palaeogeography 2019年第2期8卷 130-141页

作者： christopher j.Cleal Borja Cascales-Mi?ana Department of Natural Sciences National Museum Wales CNRS University of Lille

Alethopteris grandinii represents remains of fronds of a medullosalean pteridosperm(probably a small tree) that rapidly migrated across the lowland wetland habitats of Variscan Euramerica in middle Asturian(late Moscovian)*** was probably caused by changing drainage patterns within the lowland coal swamps,in response to climate and landscape ***,these medullosaleans had first appeared rather earlier,in early Bolsovian(early Moscovian) times,in upland wetland *** upland habitats may have pre-adapted these plants to the changed condition in the lowland coal swamps.

关键词： Carboniferous Coal swamps Medullosales Upland Migration

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The information content of financial survey response data

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Financial Innovation 2015年第1期1卷 131-150页

作者： j christopher Westland University of Illinois

Market data for financial studies typically derives from either historical transactions or contemporaneous surveys of sentiment and *** research communities analyzing data from these opposing categories of source data see themselves as distinct,with advantages not shared by the *** research investigates these latter claims in an information theoretic context,and suggests where methods and controls can be *** current research develops a Fisher Information metric for Likert scales,and explores the effect of particular survey design decisions or results on the information content.A Fisher Information metric outperforms earlier metrics by converging reliably to values that are intuitive in the sense that they suggest that information captured from subjects is fairly *** results of the analysis suggest that varying bias and response dispersion inherent in specific surveys may require increases of sample size by several orders of magnitude to compensate for information loss and in order to derive valid conclusions at a given significance and power of tests.A prioritization of quality of design,and the factors relevant to survey design are presented in the conclusions,and illustrative examples provide insight and guidance to the assessment of information content in a survey.

关键词： Financial transactions Information theory Survey Economics Mathematical models

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Edible hybrid microbial-electronic sensors for bleeding detection and beyond

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Hepatobiliary Surgery and Nutrition 2019年第2期8卷 157-160页

作者： christopher j.Bettinger Department of Materials Science and Engineering Carnegie Mellon UniversityPittsburghPAUSA Department of Biomedical Engineering Carnegie Mellon UniversityPittsburghPAUSA

Introduction to edible electronics Edible electronic devices are orally deployable electrified medical devices that have great potential to diagnose and treat many types of *** in edible electronic devices has accelerated in recent years for several ***,the role of gut health on overall health is becoming *** composition influences metabolism,immunity,and cognitive *** gut microbiome is also a valuable biomarker for distinguishing between healthy and diseased *** and longitudinal surveillance may could detect disorders such as inflammatory bowel disease(IBD),Crohn's disease,colorectal cancer,or ***,the availability of computing platforms and genomic information are becoming more prevalent,cost-effective,and *** and low-cost electronics serve as a core technology for designing and fabricating edible electronic *** computing platforms can provide a complementary monitoring network to interrogate ingestible medical devices in ambulatory ***,there have been critically enabling advances in materials,non-conventional fabrication,and device ***,Mimee et *** many of these capabilities to create an edible electronic device to detect bleeding in clinically relevant animal *** key innovation is the use of genetically engineered bacteria that transduce biochemical markers for bleeding into optical signals that can be measured,quantified,recorded,and communicated to external devices outside the body.

关键词： metabolism immunity becoming

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Enhancing sintering resistance of atomically dispersed catalysts in reducing environments with organic monolayers

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Green Energy & Environment 2022年第6期7卷 1263-1269页

作者： jing Zhang Chithra Asokan Gregory Zakem Phillip christopher j.Will Medlin Department of Chemical and Biological Engineering University of ColoradoBoulderCOUSA Department of Chemical Engineering University of CaliforniaSanta BarbaraSanta BarbaraCAUSA

Atomically dispersed precious metal catalysts maximize atom efficiency and exhibit unique ***,they are susceptible to *** reactions occurring in reducing environments tend to result in atomically dispersed metals sintering at lower temperatures than in oxidative or inert atmospheres due to the formation of mobile metal-H or metal-CO ***,we develop a new approach to mitigate sintering of oxide supported atomically dispersed metals in a reducing atmosphere using organophosphonate self-assembled monolayers(SAMs).We demonstrate this for the case of atomically dispersed Rh on Al_(2)O_(3) and TiO_(2) using a combination of CO probe molecule FTIR,temperature programmed desorption,and alkene hydrogenation rate *** suggests that SAM functionalization of the oxide provides physical diffusion barriers for the metal and weakens the interactions between the reducing gas and metal,thereby discouraging the adsorbate-promoted diffusion of metal atoms on oxide *** results show that support functionalization by organic species can provide improved resistance to sintering of atomically dispersed metals with maintained catalytic reactivity.

关键词： Atomically dispersed catalysts Organic monolayers Rh Single atom catalysis Sintering

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Protecting miners from coal bursts during development above historic mine workings in Harlan County,KY

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International journal of Mining Science and Technology 2021年第1期31卷 111-116页

作者： christopher Mark Mine Safety and Health Administration PittsburghPA 15236USA

In order to reach a large,untapped reserve of high-quality coal,D8 Cloverlick Mine proposed to mine a corridor nearly 600 m deep beneath the Benham Spur of Black Mountain,Kentucky’s highest peak.D8 Cloverlick Mine was extracting the Owl seam,but the corridor’s route lay approximately 20 m above century-old mine workings in the C–(Darby)*** to the concern,three serious coal bursts had recently occurred in nearby Owl seam *** of the old workings seemed to indicate that the underlying C–seam had been fully ***,two of the coal bursts had occurred above areas where the C–Seam was also shown as mined *** Safety and Health Administration(MSHA)Technical Support therefore investigated the records of past mining to better understand the old mine *** conditions observed in current Owl seam workings were also compared with the maps of the old C–seam *** study concluded that the presence of hazardous underlying remnants could not be ruled *** mitigate the burst risk,D8 Cloverlick Mine adopted a strategy of stress probe drilling.A self-propelled coal drill was used to auger 11.5-m-long,small diameter holes in advance of *** each hole was drilled,the cuttings were measured to detect the presence of highly stressed *** the crossing was successfully completed without incident.

关键词： Coal bursts Underground mining Room-and-pillar Destressing

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An updated empirical model for ground control in *** coal mines

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International journal of Mining Science and Technology 2021年第2期31卷 163-174页

作者： christopher Mark Mine Safety and Health Administration PittsburghPA 15217USA

Multiple seam interactions are a major source of ground instability in several *** methods are well suited for this problem,because while the mechanics multiple seam interactions are very complex and poorly understood,many mining case histories are available for *** study makes use of an updated database that includes 356 multiseam case histories,including 67 unsuccessful *** paper describes in detail the process used to design the study,collect the data,conduct the statistical analysis,and develop the quantitative *** model can be used for mine planning in multiple seam situations,and has been made available as a module within the Analysis of Coal Pillar Stability(ACPS)computer program.

关键词： Underground Coal Multiseam Ground control Pillar design Empirical

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Himalayan Tectonics:Preface

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Geoscience Frontiers 2019年第3期10卷 791-792页

作者： Kyle Larson christopher j. Spencer Tectonics and Geodynamics Earth Environmental and Geographical Sciences IKBSAS University of British Columbia Earth Dynamics Research Group The Institute for Geoscience Research (TIGeR) Department of Applied Geology Curtin University

The Himalayan-Tibetan orogen system serves as the modern paradigm for understanding convergence-related processes in orogenic belts. The advancements made studying the region have been applied to other ancient orogenic belts leading not only to a better understanding of their development, but also of secular changes in collisional processes. As more advanced methodologies are introduced and utilized in geological research, the type, scale, and quality of data available enable quantification of geological processes not previously possible. These complex and robust datasets now form the core of many of the research projects undertaken across the Himalaya and continue to provide unprecedented insight into the myriad different aspects of the evolution of the collisional system.

关键词： Himalayan-Tibetan system evolution

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