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Elucidating the Degradation Pathways of Human Insulin in the Solid State

Journal of Analysis and Testing 2024年第3期8卷 288-299页

作者： Andrew Fagan lorraine m.Bateman Joseph P.O'Shea Abina m.Crean SSPC the SFI Centre for Pharmaceutical Research School of Pharmacy University College Cork School of Pharmacy University College Cork Analytical and Biological Chemistry Research Facility (ABCRF) University College Cork School of Chemistry University College Cork

While there have been significant advances in the development of peptide oral dosage forms in recent years, highlighted by the clinical and commercial success of approved peptides such as Rybelsus?, there remain several barriers in the way of broad range applicability of this approach to peptide delivery. One such barrier includes the poor physical and chemical stability inherent to their structures, which persists in the solid state although degradation typically occurs at different rates and via different pathways in comparison to the solution state. Using insulin as a model peptide, this work sought to contribute to the development of analytical techniques for investigating common insulin degradation pathways. Chemically denatured,deamidated and aggregated samples were prepared and used to benchmark circular dichroism spectroscopy, reverse phase HPLC and size exclusion chromatography methods for the investigation of unfolding, chemical modifications and covalent aggregation of the insulin molecule respectively. Solid state degraded samples were prepared by heating insulin powder at 60 °C and 75% relative humidity for 1, 3, 5 and 7 d, and the degradation profiles of the samples were evaluated and compared with those observed in solution. While no unfolding was observed to occur, significant deamidation and covalent aggregation were detected. Reductive disulfide bond cleavage using dithiothreitol allowed for separation of the insulin A-and B-chains,offering a facile yet novel means of assessing the mechanisms of deamidation and covalent aggregation occurring in the solid state.

关键词： Biopharmaceutical analysis Covalent aggregation Deamidation Disulfide cleavage Insulin Solid state Stability

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A cluster-randomized trial comparing two SWITCH implementation support strategies for school wellness intervention effectiveness

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Journal of Sport and Health Science 2023年第1期12卷 87-96页

作者： Richard R.Rosenkranz Philip m.Dixon David A.Dzewaltowski Gabriella m.mcLoughlin Joey A.Lee Senlin Chen Spyridoula Vazou lorraine m.lanningham.foster Doug A.Gentile Gregory J.Welk Department of Food NutritionDietetics&HealthKansas State UniversityManhattanKS 66506USA Department of Statistics Snedecor HallIowa State UniversityAmesIA 50011-1210USA Department of Health Promotion University of NebraskaOmahaNE 68198-4365USA Implementation Science Center for Cancer Control and Prevention Research Center Brown SchoolWashington University in St.LouisSt.LouisMO 63130USA Division of Public Health Sciences(Department of Surgery) Washington University School of MedicineWashington University in St.LouisSt.LouisMO 63130USA Department of Health Sciences University of Colorado Colorado SpringsColorado SpringsCO 80918USA Department of Kinesiology Iowa State UniversityAmesIA 50011-4008USA Department of Food Science&Human Nutrition Iowa State UniversityAmesIA 50011USA Department of Psychology Iowa State UniversityAmesIA 50011-1041USA

Background:The School Wellness Integration Targeting Child Health(SWITCH)intervention has demonstrated feasibility as an implementation approach to help schools facilitate changes in students’physical activity(PA),sedentary screen time(SST),and dietary intake(DI).This study evaluated the comparative effectiveness of enhanced(individualized)implementation and standard(group-based)***:Twenty-two Iowa elementary schools participated,with each receiving standardized training(wellness conference and webinars).Schools were matched within region and randomized to receive either individualized or group implementation *** PA,SST,and DI outcomes of 1097 students were assessed at pre-and post-intervention periods using the Youth Activity *** mixed models evaluated differential change in outcomes by condition,for comparative effectiveness,and by ***:Both implementation conditions led to significant improvements in PA and SST over time(pmprove commensurately(p value range:0.02‒0.05).There were no differential changes between the group and individualized conditions for PA(p=0.51),SST(p=0.19),or DI(p=0.73).There were no differential effects by gender(i.e.,non-significant condition-by-gender interactions)for PA(p_(for interaction)=0.86),SST(p_(for interaction)=0.46),or DI(p_(for interaction)=0.15).Effect sizes for both conditions equated to approximately 6 min more PA per day and approximately 3 min less sedentary ***:The observed lack of difference in outcomes suggests that group implementation of SWITCH is equally effective as individualized implementation for building capacity in school wellness ***,the lack of interaction by gender suggests that SWITCH can be beneficial for both boys and *** research is needed to understand the school-level factors that influence implementation(and outcomes)of SWITCH.

关键词： Children Implementation science Obesity prevention Physical activity School health

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IT-Software SmEs in China, Technology Transfer from Universities and Entrepreneurship, a Successful Nexus？

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Frontiers of Business Research in China 2014年第1期8卷 18-48页

作者： Jianghong Cao m. John foster lorraine Watkins-mathys Kingston-Business School Kingston University Kingston Upon Thames KT2 7LB UK

Drawing on the empirical work of a broader study, this paper examines whether technology is being successfully transferred from universities to the IT-sottware SmEs present in China, and the effectiveness of entrepreneurship in effecting such transfers. A conceptual framework was generated to guide the investigation. Data were elicited using a detailed questionnaire which generated 53 usable responses; follow-up interviews with 17 of the 53 respondents; and four interviews with relevant government officials （civil servants from the ministry of Science and Technology and state-owned banks）. There were three main fmdings. Chinese software SmEs tend to be reluctant to adopt new technologies from local tmiversities; there is a lack of common purpose between the parties; and entrepreneurs who did undertake such technology transfer felt the process was badly impeded by the lack of available finance, and expressed fears about poor protection of intellectual property rights in China. The majority of the sample firms acted opportunistically, taking advantage of the benefits offered under government schemes to earn rapid returns mainly using extant technologies. These conclusions suggest that the Chinese government＇s policies in this area of technology transfer have had only limited success.

关键词： entrepreneurship technology transfer universities IT-software,SmE China

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Oxidative stress-induced mitochondrial dysfunction in a normal colon epithelial cell line

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World Journal of Gastroenterology 2017年第19期23卷 3427-3439页

作者： Nandakumar Packiriswamy Kari F Coulson Susan J Holcombe lorraine m Sordillo Department of Large Animal Clinical Sciences College of Veterinary Medicine Michigan State University

AIm To determine how a normal human colon cell line reacts to microbial challenge as a way to study oxidative stress-induced responses associated with inflammatory bowel *** Normal human colon epithelial cells(ATCC?CRL.1790?)were stimulated with either heat killed *** or heat killed murine cecal contents(HKC)and examined for several relevant biomarkers associated with inflammation and oxidative stress including cytokine production,mitochondrial autophagy and oxidant ***α,IL-1βand IL-8 protein concentrations were measured within the *** microscopy was performed to quantify the production of reactive oxygen species(ROS)using an oxidation responsive fluorogenic *** morphology and mitochondrial membrane potential was assessed by dual staining using COXIV antibody and a dye concentrating in active *** ROS scavenger was used to determine the source of ROS in stimulated *** was detected by staining for the presence of autophagic *** controls for autophagy and ROS/RNS experiments were treated with rapamycin and *** morphology,ROS production and autophagy microscopy experiments were analyzed using a custom acquisition and analysis microscopy software(Image J).RESULTS Exposing CRL.1790 cells to microbial challenge stimulated cells to produce several relevant biomarkers associated with inflammation and oxidative *** killed cecal contents treatment induced a 10-12fold increase in IL-8 production by CRL.1790 cells compared to unstimulated controls at 6 and 12 h(Pmulation resulted in a4-5 fold increase in IL-8 compared to the unstimulated control cells at each time point(Pmulated robust ROS production at 6(Pmitochondrial morphologic abnormalities were detected at 6 and12 h based on reduced mitochondrial circularity and decreased mitochondrial membr

关键词： Colon cancer cell line CRL.1790 cells Inflammation mitochondria microbial stimulation Interleukin-8 Autophagy

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Tesco Strikes Out into Asia

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Frontiers of Business Research in China 2013年第2期7卷 289-310页

作者： m J foster ToJ Noh Kingston Business School Kingston Upon Thames KT2 7LB UK Department of management Kumoh National Institute of Technology Gyongbuk 730-701Korea

The case looks at the internationalisation of Tesco PLC, a successful UK retailing business, and in particular how and why it has gone about developing its business in Southeast/East Asia. The case is suitable for use with final year undergraduate and especially postgraduate students, in either corporate strategy or international business modules. The case follows Tesco＇s moves into Thailand, South Korea, and most recently China. It is found that the methods of entry to the new markets/countries and strategies used post-entry have varied country by country, culture by culture. The strategies adopted are found not to have been universally successful, which raises questions as to why that may be. It is expected that students will be able to identify the entry methods and reasons for their use; determine the business strategies adopted country by country, explore why they may differ, and locate the influences of the varying cultures. They will be expected to assess how successful Tesco has been in these processes. Finally, they should explore the question whether the giant China market can indeed be ＂an ultimate prize＂ and if so how it should best be tackled. For the time being, South Korea is arguably the most successful part of the company＇s Asian push.

关键词： retailing internationalisation FDI joint venture (JV) businessstrategies East Asia China

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Genetic variability of the stable fly assessed on a global scale using amplified fragment length polymorphism

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Insect Science 2016年第5期23卷 695-703页

作者： Kathleen m Kneeland Steven R. Skoda John E. foster Department of Entomology 103 Entomology Haft University of Nebraska-Lincoln Lincoln NE 68583 USDA-ARS-KBUSLIRL Screwworm Research Unit 2700 Fredericksburg Road Kern/ille TX 78028 USA

The stable fly, Stomoxys calcitrans （L.）（Diptera： muscidae）, is a blood-feeding, economically important pest of animals and humans worldwide. Improved management strategies are essential and their development would benefit from studies on genetic di- versity of stable flies. Especially if done on a global scale, such research could generate information necessary for the development and application of more efficient control meth- ods. Herein we report on a genetic study of stable flies using amplified fragment length polymorphism, with samples of 10-40 individuals acquired from a total of 25 locations in the Nearctic, Neotropic, Palearctic, Afrotropic and Australasian biogeographical regions. We hypothesized that genetic differentiation would exist across geographical barriers. Although Fsx （0.33） was moderately high, the Gsx （0.05; representing genetic diversity between individuals） was very low; Nm values （representing gene flow） were high （9.36）. The mismatch distribution and tests of neutrality suggested population expansion, with no genetic differentiation between locations. The analysis of molecular variance （AmOVA） results showed the majority of genetic diversity was within groups. The mantel test showed no correlation between geographic and genetic distance; this strongly supports the AmOVA results. These results suggest that stable flies did not show genetic differentiation but are panmictic, with no evidence of isolation by distance or across geographical barriers.

关键词： AFLP biting flies external parasites genetic diversity livestock pests Stomoxys calcitrans

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Downscaling future climate scenarios to fine scales for hydrologic and ecological modeling and analysis

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Ecological Processes 2012年第1期1卷 109-123页

作者： lorraine E Flint Alan L Flint U.S.Geological Survey Placer Hall6000 J St.SacramentoCA 95819USA

Introduction:Evaluating the environmental impacts of climate change on water resources and biological components of the landscape is an integral part of hydrologic and ecological investigations,and the resultant land and resource management in the twenty-first *** of both climate and simulated hydrologic parameters on ecological processes are relevant at scales that reflect the heterogeneity and complexity of *** present,simulations of climate change available from global climate models[GCms]require downscaling for hydrologic or ecological ***:Using statistically downscaled future climate projections developed using constructed analogues,a methodology was developed to further downscale the projections spatially using a gradient-inverse-distancesquared approach for application to hydrologic modeling at 270-m spatial ***:This paper illustrates a methodology to downscale and bias-correct national GCms to subkilometer scales that are applicable to fine-scale environmental *** scenarios were chosen to bracket the range of future emissions put forth by the Intergovernmental Panel on Climate ***-scale applications of downscaled datasets of ecological and hydrologic correlations to variation in climate are ***:The methodology,which includes a sequence of rigorous analyses and calculations,is intended to reduce the addition of uncertainty to the climate data as a result of the downscaling while providing the fine-scale climate information necessary for ecological *** results in new but consistent data sets for the US at 4 km,the southwest US at 270 m,and California at 90 m and illustrates the utility of fine-scale downscaling to analyses of ecological processes influenced by topographic complexity.

关键词： downscaling climate change spatial scale scenarios

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Kingfisher Attacks the China market

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Frontiers of Business Research in China 2012年第1期6卷 156-168页

作者： m J foster C S Tseng Kingston Business School Kingston Upon Thames KT2 7LB UK Department of marketing City University of Hong Kong Hong Kong China

This article examines the entry to the Chinese market of Kingfisher plc under its B＆Q brand, operating in the DIY or home improvement market. It is a pedagogically oriented case in the international strategy area, which deals with both the mode of market development by the company in China and some of the softer issues arising from that process relating to HR in the company and the inevitable cultural challenges it faced. The story begins in the mid-1990s and goes through to the early summer of 2010. On the one hand, the entry has been successful： B＆Q is now a significant presence in China, holding number one position in their chosen market, which is primarily highly fragmented; there is some concentration in four key cities in the wealthy east coast region; and it has made profits over a fair portion over the last decade. Lessons were learned from the initial mistakes and the core sales proposition in China has been crafted to differ from that in the original UK home base. However, for the last three completed financial years, losses have been booked and significant changes have been made or were planned at the time of writing. Some changes were inevitable, but which were they （other than those where the Chinese government changed its rules）？

关键词： multinational Corporation (mNC) retailing do-it-yourself (DIY) China regulation market development

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Characterizing drought in California:new drought indices and scenario-testing in support of resource management

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Ecological Processes 2018年第1期7卷 1-13页

作者： lorraine E.Flint Alan L.Flint John mendoza Julie Kalansky F.m.Ralph U.S.Geological Survey 6000 J.StSacramentoCA 95819USA Sonoma County Water Agency 404 Aviation Dr.Santa RosaCA 95403USA Scripps Institution of Oceanography 9500 Gilman Dr.La JollaCA 92093USA

Introduction:California’s recent drought(2012–2016)has implications throughout the state for natural resource management and adaptation planning and has generated many discussions about drought characterization and *** study characterizes drought conditions with two indices describing deficits in natural water supply and increases in landscape stress developed on the basis of water balance modeling,at a fine spatial scale to assess the variation in conditions across the entire state,and provides an in-depth evaluation for the Russian River basin in northern California to address local resource management by developing extreme drought scenarios for consideration in planning and ***:We employed the USGS Basin Characterization model to characterize drought on the basis of water supply(a measure of recharge plus runoff)and landscape stress(climatic water deficit).These were applied to the state and to the Russian River basin where antecedent soil moisture conditions were evaluated and extreme drought scenarios were developed and run through a water management and reservoir operations model to further explore impacts on water ***:Drought indices indicated that as of the end of water year 2016 when reservoirs were full,additional water supply and landscape replenishment of up to three average years of precipitation in some locations was needed to return to normal *** soil conditions in the Russian River were determined to contribute to very different water supply results for different years and were necessary to understand to anticipate proper watershed response to *** drought scenarios manifested very different kinds of drought and recovery and characterization helps to guide the management response to ***:These scenarios and indices illustrate how droughts differ with regard to water supply and landscape stress and how long warm droughts recover much more slowly than short very dry dro

关键词： California drought Russian River Water supply Basin Characterization model

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The First Stegosaur (Dinosauria, Ornithischia) from the Upper Jurassic Shishugou Formation of Xinjiang, China

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Acta Geologica Sinica(English Edition) 2007年第3期81卷 351-356页

作者： JIA Chengkai Catherine A. foster XU Xing James m. CLARK Institute of Vertebrate Paleontology Paleoanthropology Chinese Academy of Sciences Beijing 100044 China Research Institute of Exploration and Development Xinjiang Oilfield Company Karamay Xinjiang 834000 China Graduate University of the Chinese Academy of Sciences Beijing 100039 China Department of Anatomical Sciences Stony Brook University Stony Brook New York 11794 USA Department of Biological Sciences George Washington University Washington DC 20052 USA

A new stegosaur species, Jiangjunosaurusjunggarensis, gen. et sp. nov., is erected based on a specimen collected from the Upper Jurassic upper section of the Shishugou Formation in the Junggar Basin, Xinjiang, China. It represents the first stegosaur from the Jurassic of Xinjiang and increases the diversity of the dinosaur fauna in the Shishugou Formation. The new genus is characterized by symmetrical and proportionally wide tooth crowns, a sub-rectangular axial neural spine seen in lateral view, and large openings on the lateral surfaces of the cervical centra. A preliminary character analysis suggests that this new taxon is more derived than the middle Jurassic stegosaur Huayangosaurus but more primitive than most other known stegosaur species.

关键词： Dinosauria Stegosauria Upper Jurassic Shishugou Formation Xinjiang

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