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Elucidating the Degradation Pathways of Human Insulin in the Solid State

Journal of Analysis and Testing 2024年第03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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Global prevalence of hepatitis B virus serological markers among healthcare workers:A systematic review and meta-analysis

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World Journal of Hepatology 2021年第9期13卷 1190-1202页

作者： Gadji mahamat Sebastien kenmoe Etheline W Akazong Jean Thierry Ebogo-Belobo Donatien Serge mbaga Arnol Bowo-Ngandji Joseph Rodrigue Foe-Essomba marie Amougou-Atsama Chavely Gwladys monamele Chris Andre mbongue mikangue Ginette Irma kame-Ngasse Jeannette Nina magoudjou-Pekam Cromwel Zemnou-Tepap Dowbiss meta-Djomsi martin maidadi-Foudi Sabine Aimee Touangnou-Chamda Audrey Gaelle Daha-Tchoffo Abdel Aziz Selly-Ngaloumo Rachel Audrey Nayang-mundo Jacqueline Felicite Yengue Jean Bosco Taya-fokou lorraine k m fokou Raoul kenfack-momo Dimitri Tchami Ngongang Efietngab Atembeh Noura Herve Raoul Tazokong Cynthia Paola Demeni Emoh Cyprien kengne-Nde Jean Joel Bigna Onana Boyomo Richard Njouom Department of microbiology The University of Yaounde IYaounde 00237Cameroon Department Centre Pasteur of CameroonYaounde 00237Cameroon Department of Biochemistry University of DschangDschang 00237Cameroon medical Research Centre Institute of Medical Research and Medicinal Plants StudiesYaounde 00237Cameroon Department of mycobacteriology Centre Pasteur of CameroonYaounde 00237Cameroon Centre de Recherche sur les maladies Emergentes et Re-Emergentes Institut de Recherches Medicales et d'Etudes des Plantes MedicinalesYaounde 00237Cameroon Department of Biochemistry The University of Yaounde IYaounde 00237Cameroon Department of medical Biochemistry The University of Yaounde IYaounde 00237Cameroon Department of microbiology Protestant University of Central AfricaYaounde 00237Cameroon Department of Animals Biology and Physiology The University of Yaounde IYaounde 00237Cameroon Evaluation and Research Unit National AIDS Control CommitteeYaounde 00237Cameroon Department of Epidemiology and Public Health Centre Pasteur of CameroonYaounde 00237Cameroon

BACkGROUND The hepatitis B virus(HBV)infection is a global public health concern that affects about 2 billion people and causes 1 million people deaths *** is a bloodborne disease and healthcare workers(HCWs)are a high-risk group because of occupational hazard to patients’*** regions of the world show a highly variable proportion of HCWs infected and/or immunized against *** data on serologic markers of HBV infection and immunization in HCWs are very important to improve strategies for HBV *** To determine the worldwide prevalence of HBV serological markers among *** In this systematic review and meta–analyses,we searched Pubmed and Excerpta medica Database(Embase)to identify studies published between 1970 and 2019 on the prevalence of HBV serological markers in HCWs *** also manually searched for references of relevant *** independent investigators selected studies and included those on the prevalence of each of the HBV serological markers including hepatitis B surface antigen(HBsAg),hepatitis e antigen(HBeAg),immunoglobulin m anti-HBc,and *** quality of eligible studies was assessed and random-effect model meta-analysis resulted in the pooled prevalence of HBV serological markers HBV infection in ***(I²)was assessed using theχ²test on Cochran’s Q statistic and H ***’sources were explored through subgroup and metaregression *** study is registered with PROSPERO,number *** We reviewed 14059 references,out of which 227 studies corresponding to 448 prevalence data among HCWs(224936 HCWs recruited from 1964 to 2019 in 71 countries)were included in this *** pooled seroprevalences of current HBsAg,current HBeAg,and acute HBV infection among HCWs were 2.3%[95% confidence interval(CI):1.9-2.7],0.2%(95%CI:0.0-1.7),and 5.3%(95%CI:1.4-11.2),*** pooled seroprevalences of total immunity against HBV and immu

关键词： Healthcare workers Hepatitis B virus Seroprevalence Hepatitis B surface antigen Hepatitis e antigen

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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(Pkilled *** stimulation resulted in a4-5 fold increase in IL-8 compared to the unstimulated control cells at each time point(Pkilled *** and HkC stimulated 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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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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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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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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Drought events influence nutrient canopy exchanges and green leaf partitioning during senescence in a deciduous forest

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Forest Ecosystems 2024年第1期11卷 110-119页

作者： J.Touche C.Calvaruso P.De Donato m.-P.Turpault INRAE BEFF-54000NancyFrance UmR 7359 GeoRessourcesFaculte des Sciences-Campus des Aiguillettes54506Vandoeuvre Les NancyFrance EcoSustain Environmental Engineering OfficeResearch and DevelopmentKanfen57330France

The increase in the frequency and intensity of drought events expected in the coming decades in Western Europe may disturb forest biogeochemical cycles and create nutrient deficiencies in *** possible origin of nutrient deficiency is the disturbance of the partitioning of the green leaf pool during the leaf senescence period between resorption,foliar leaching and senesced ***,the effects of drought events on this partitioning and the consequences for the maintenance of tree nutrition are poorly *** experiment in a beech forest in meuse(France)was conducted to assess the effect of drought events on nutrient canopy exchanges and on the partitioning of the green leaf pool during the leaf senescence *** aim was to identify potential nutritional consequences of droughts for *** nutrient dynamics,including resorption,chemistry of green and senesced leaves,foliar absorption and leaching in mature beech stands from 2012 to 2019 allowed us to compare the nutrient exchanges for three nondry and three dry years(i.e.,with an intense drought event during the growing season).During dry years,we observed a decrease by almost a third of the potassium(k)partitioning to resorption(*** efficiency),thus reducing the k reserve in trees for the next growing *** result suggests that with the increased drought frequency and intensity expected for the coming decades,there will be a risk of potassium deficiency in trees,as already observed in a rainfall exclusion experiment on the same study *** foliar leaching and higher parititioning to the senesced leaves for k and phosphorus(P)were also *** addition,a slight increase in nitrogen(N)resorption efficiency occurred during dry years which is more likely to improve tree *** calcium(Ca)negative resorption decreased,with no apparent consequence in our study *** results show that nutrient exchanges in the canopy and the partitioning of the green leaf

关键词： Natural drought Beech forest Canopy Resorption Foliar leaching Senesced leaves Nutrition

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Personalising pancreas cancer treatment:When tissue is the issue

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World Journal of Gastroenterology 2014年第24期20卷 7849-7863页

作者： katrin m Sjoquist Venessa T Chin lorraine A Chantrill Chelsie O'Connor Chris Hemmings David k Chang Angela Chou marina Pajic Amber L Johns Adnan m Nagrial Andrew V Biankin Desmond Yip NHmRC Clinical Trials Centre University of SydneySydney NSW 1450Australia Cancer Care Centre St George HospitalKogarah NSW 2217Australia The kinghorn Cancer Centre and the Cancer Research ProgramGarvan Institute of Medical ResearchSydney NSW 2010Australia macarthur Cancer Therapy Centre Campbelltown HospitalCampbelltown NSW 2560Australia St Vincents Hospital Clinical School Sydney UNSW 2010Australia Cancer Therapy Centre Liverpool HospitalLiverpool NSW 2170Australia St John of God Pathology Subiaco WA 6904Australia Department of Surgery Bankstown HospitalEldridge RoadBankstownSydney NSW 2200Australia Faculty of medicine South Western Sydney Clinical SchoolUniversity of NSWLiverpool NSW 2170Australia Wolfson Wohl Cancer Research Centre Institute of Cancer SciencesUniversity of GlasgowGlasgow G61 1BDUnited Kingdom Department of Anatomical Pathology St.Vincent’s HospitalDarlinghurstSydney NSW 2010Australia West of Scotland Pancreatic Unit Glasgow Royal InfirmaryGlasgow G4 0SFUnited Kingdom Department of medical Oncology The Canberra HospitalGarran ACT 2605Australia ANU medical School Australian National UniversityActon ACT 2601Australia

The treatment of advanced pancreatic cancer has not moved much beyond single agent gemcitabine until recently when protocols such as FOLFIRINOX(fluorouracil,leucovorin,irinotecan and oxaliplatin)and nab-paclitaxelgemcitabine have demonstrated some improved *** in technology especially in massively parallel genome sequencing has progressed our understanding of the biology of pancreatic cancer especially the candidate signalling pathways that are involved in tumourogenesis and disease *** has allowed identification of potentially actionable mutations that may be targeted by new biological *** heterogeneity of pancreatic cancer makes tumour tissue collection important with the aim of being able to personalise therapies for the individual as opposed to a one size fits all approach to treatment of the *** paper reviews the developments in this area of translational research and the ongoing clinical studies that will attempt to move this into the everyday oncology practice.

关键词： Pancreatic neoplasms molecular targeted therapy Genomics Tissue banks Chemotherapy

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Postpartum meloxicam administration alters plasma haptoglobin, polyunsaturated fatty acid, and oxylipid concentrations in postpartum ewes

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Journal of Animal Science and Biotechnology 2020年第4期11卷 1047-1060页

作者： katie EOlagaray Barry J.Bradford lorraine m.Sordillo Jeffery C.Gandy Laman k.mamedova Turner H.Swartz Trey D.Jackson Emma k.Persoon Caitlin S.Shugart Curtis R.Youngs Department of Animal Sciences and Industry Kansas State UniversityManhattan 66506USA College of Veterinary medicine Michigan State University2265K Anthony HallEast LansingMI 48824-1225USA Department of Animal Science Iowa State UniversityAmesIAUSA.

Background: Postpartum inflammation is a natural and necessary response;however, a dysfunctional inflammatory response can be detrimental to animal productivity. The objective of this study was to determine the effects of a non-steroidal anti-inflammatory drug(meloxicam) on ewe postpartum inflammatory response, ewe plasma polyunsaturated fatty acid and oxylipid concentrations, and lamb ***: After lambing, 36 Hampshire and Hampshire × Suffolk ewes were sequentially assigned within type of birth to control(n = 17) or meloxicam orally administered on d 1 and 4 of lactation(mEL;90 mg, n = 19). milk and blood samples were collected on d 1(prior to treatment) and d 4. milk glucose-6-phosphate was not affected by mEL. Plasma haptoglobin(Hp) concentrations were less for mEL ewes;control ewes with greater d 1 Hp concentrations had elevated Hp on d 4, but this was not the case for mEL-treated ewes. Treatment with mEL increased plasma arachidonic acid concentration by more than 4-fold in ewes rearing singles but decreased concentrations of 9,10-dihydroxyoctadecenoic acid, prostaglandin F2α, 8-iso-prostaglandin E2, and 8,9-dihydroxyeicosatetraenoic acid. Nine oxylipids in plasma had interactions of treatment with d 1 Hp concentration,all of which revealed positive associations between d 1 Hp and d 4 oxylipid concentrations for CON, but neutral or negative relationships for mEL. mEL decreased 13-hydroxyoctadecadienoic acid:13-oxooctadecadienoic acid ratio and tended to increase 9-hydroxyoctadecadienoic acid:9-oxooctadecadienoic acid ratio(both dependent on d 1 values), indicating progressive metabolism of linoleic acid-derived oxylipids occurred by enzymatic oxidation after mEL treatment. meloxicam reduced oxylipids generated across oxygenation pathways, potentially due to an improved redox ***: Postpartum mEL treatment of ewes decreased plasma concentrations of Hp and several oxylipids,with the greatest impact in ewes with biomarkers reflecting a greate

关键词： Eicosanoid Inflammation Lactation Nonsteroidal anti-inflammatory drug Sheep

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Intelligent Solution System for Cloud Security Based on Equity Distribution:model and Algorithms

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Computers, materials & Continua 2024年第1期78卷 1461-1479页

作者： Sarah mustafa Eljack mahdi Jemmali mohsen Denden mutasim Al Sadig Abdullah m.Algashami Sadok Turki Department of Computer Science and Information College of Science at ZulfiMajmaah UniversityAl-Majmaah11952Saudi Arabia Department of Computer Science College of Computing and InformaticsUniversity of SharjahSharjahUnited Arab Emirates Higher Institute of Computer Science and mathematics University of MonastirMonastir5000Tunisia mars Laboratory University of SousseSousseTunisia Department of Logistic and maintenance UFR MIM at MetzUniversity of LorraineMetzFrance Department of Computer and Information Technologies College of Telecommunicationand Information Riyadh CTITechnical and Vocational Training Corporation TVTCRiyadh12464Saudi Arabia Department of Computer Science Higher Institute of Applied Sciences of SousseSousse UniversitySousse4000Tunisia

In the cloud environment,ensuring a high level of data security is in high *** planning storage optimization is part of the whole security process in the cloud *** enables data security by avoiding the risk of data loss and data *** development of data flow scheduling approaches in the cloud environment taking security parameters into account is *** our work,we propose a data scheduling model for the cloud *** is made up of three parts that together help dispatch user data flow to the appropriate *** first component is the Collector Agent whichmust periodically collect information on the state of the network *** second one is the monitoring agent which must then analyze,classify,and make a decision on the state of the link and finally transmit this information to the *** third one is the scheduler who must consider previous information to transfer user data,including fair distribution and reliable *** should be noted that each part of the proposedmodel requires the development of its *** this article,we are interested in the development of data transfer algorithms,including fairness distribution with the consideration of a stable link *** algorithms are based on the grouping of transmitted files and the iterative *** proposed algorithms showthe performances to obtain an approximate solution to the studied problem which is an NP-hard(Non-Polynomial solution)*** experimental results show that the best algorithm is the half-grouped minimum excluding(HmE),with a percentage of 91.3%,an average deviation of 0.042,and an execution time of 0.001 s.

关键词： Cyber-security cloud computing cloud security algorithms heuristics

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