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strategies for PET imaging of the receptor for advanced glycation endproducts(RAGE)

Journal of Pharmaceutical Analysis 2020年第5期10卷 452-465页

作者： Lindsey R.Drake Allen F.Brooks Jenelle stauff phillip s.sherman Janna Arteaga Robert A.Koeppe Aimee Reed Timothy J.Montavon Marc B.skaddan Peter J.H.scott Department of Radiology University of MichiganAnn ArborMI48109USA Department of Medicinal Chemistry University of MichiganAnn ArborMI48109USA AbbVie Process Chemistry North ChicagoIL60064USA AbbVie Centralized Medicinal Chemistry North ChicagoIL60064USA AbbVie Translational Imaging North ChicagoIL60064USA

The implication of the receptor for advanced glycation end-products(RAGE)in numerous diseases and neurodegenerative disorders makes it interesting both as a therapeutic target and as an inflammatory *** the context of investigating RAGE as a biomarker,there is interest in developing radiotracers that will enable quantification of RAGE using positron emission tomography(PET)*** have synthesized potential small molecule radiotracers for both the intracellular([18F]InRAGER)and extracellular([18F]RAGER)domains of *** we report preclinical evaluation of both using in vitro(lead panel screens)and in vivo(rodent and nonhuman primate PET imaging)*** radiotracers have high affinity for RAGE and show good brain uptake,but suffer from off-target *** source of the off-target PET signal is not attributable to binding to melatonin receptors,but remains *** have also investigated use of lipopolysaccharide(LPs)-treated mice as a possible animal model with upregulated RAGE for evaluation of new imaging *** of the mouse brain sections revealed increases in RAGE in the male cohorts,but no difference in the female ***,it proves challenging to quantify the changes in RAGE due to off-target binding of the ***,they are appropriate lead scaffolds for future development of 2nd generation RAGE PET radiotracers because of their high affinity for the receptor and good CNs penetration.

关键词： RAGE Neuroimaging Positron emission tomography Radiochemistry Neuroinflammation

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Understanding pediatric surgical needs in North Korea: a modeling analysis

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World Journal of Pediatric surgery 2024年第1期7卷 47-53页

作者： phillip J Hsu sangchul Yoon Kee B Park University of Michigan Ann ArborMichiganUSA Department of Global Health and social Medicine Harvard Medical SchoolBostonMassachusettsUSA Department of Medical Humanitiesand social sciences Yonsei University SeoulSouth Korea

Background sixty-five percent of children worldwide lack access to surgical care,the majority of whom live in low-income and middle-income countries(LMiCs).Developing surgical infrastructure requires information on surgical need;however,this information is often limited in *** Korea(Democratic People's Republic of Korea,DPRK)has a low amount of publicly available ***,we analyzed available modeled data to understand the causes of pediatric deaths due to conditions treatable with surgery in *** We used World Bank data and models from the Institute for Health Metrics and Evaluation to identify causes of pediatric deaths affecting pediatric patients(ages).We compared mortality of disease between DPRK and countries with similar economic *** Between 1990 and 2019,the number of overall pediatric deaths has *** 2019,32.2%of allpediatric deaths in DPRK were caused by surgical *** leading categories of surgical conditions were injuries(53.9%),congenital conditions(34.2%),tumors(8.8%),and abdominal conditions(3.2%).DPRK has a lower relative rate of pediatric deaths compared with other LMICs with similar gross domestic product per ***,it has a higher relative rate of pediatric deaths due to conditions requiring treatment with *** injuries contribute significantly to the high rate of pediatric deaths in *** Although DPRK may be allocating overall resources toward pediatric healthcare more efficiently than economic peers,DPRK may benefit from improvement in pediatric surgical *** availability of data and close international collaboration could be potential solutions to bridge this gap.

关键词： pediatric surgical injuries

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Identifying the validity domain of machine learning models in building energy systems

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Energy and AI 2024年第1期15卷 328-341页

作者： Martin Rätz Patrick Henkel phillip stoffel Rita streblow Dirk Müller RWTH Aachen University E.ON Energy Research CenterInstitute for Energy Efficient Buildings and Indoor ClimateMathieustraβe 10Aachen52074Germany

The building sector significantly contributes to climate *** improve its carbon footprint,applications like model predictive control and predictive maintenance rely on system ***,the high modeling effort hinders practical *** learning models can significantly reduce this modeling *** ensure a machine learning model’s reliability in all operating states,it is essential to know its validity *** states outside the validity domain might lead to extrapolation,resulting in unpredictable *** paper addresses the challenge of identifying extrapolation in data-driven building energy system models and aims to raise knowledge about *** that,a novel approach is proposed that calibrates novelty detection algorithms towards the machine learning *** novelty detection algorithms are identified through a literature review and a benchmark test with 15 candidates.A subset of five algorithms is then evaluated on building energy ***,on two-dimensional data,displaying the results with a novel visualization *** on more complex multi-dimensional use *** methodology performs well,and the validity domain could be *** visualization allows for a profound analysis and an improved understanding of the fundamental effects behind a machine learning model’s validity domain and the extrapolation regimes.

关键词： Extrapolation detection Validity domain Novelty detection Machine learning Artificial neural network Data-driven model predictive control Building energy systems

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The neglect of nonnative orthopterans as potential invaders:A call for awareness

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Insect science 2024年第4期31卷 994-1000页

作者： Anna K.Kulessa Paride Balzani Ismael soto Antonín Kouba David Renault Ali serhan Tarkan phillip J.Haubrock Ruhr University Bochum Faculty of Biology and BiotechnologyBochumGermany Faculty of Biology University of Duisburg-EssenUniversitätsstraße 5EssenGermany Faculty of Fisheries and Protection of Waters South Bohemian Research Center of Aquaculture and Biodiversity of HydrocenosesUniversity of South Bohemia in CˇeskéBudeˇjoviceVodnˇanyCzech Republic University of Rennes CNRSECOBIO(EcosystèmesBiodiversitéEvolution)UMRRennesFrance Faculty of Fisheries Department of Basic SciencesMu˘gla SıtkıKoçman UniversityMu˘glaTurkey Department of Life and Environmental sciences Bournemouth UniversityPooleDorsetUK Faculty of Biology and Environmental Protection Department of Ecology and Vertebrate ZoologyUniversity ofŁodzŁodzPoland Department of River Ecology and Conservation Senckenberg Research Institute and Natural History Museum FrankfurtGelnhausenGermany Center for Applied Mathematics and Bioinformatics Gulf University for Science and TechnologyMubarak Al-AbdullahKuwait

Despite the potential ecological and economic impacts of invasive species,there is a dearth of data on the presence,impacts,and management implications of potentially invasive Orthoptera *** lack of research and inconsistent data,including risk screenings and impact assessments,is especially evident in ***,assessing the status,distribution,and potential threats of nonnative Orthoptera in Europe remains challenging,impeding the development of effective management *** address this gap,we call for increased efforts to collect and curate data on non-native and possibly invasive Orthoptera in *** efforts will improve our understanding of this order’s invasion dynamics,facilitate the identification of priority areas for conservation,and support the development of effective management policies and preventive measures.

关键词： costs cricket damages grasshopper impact research

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Pre-operative visceral adipose tissue radiodensity is a potentially novel prognostic biomarker for early endoscopic post-operative recurrence in Crohn’s disease

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World Journal of Gastrointestinal surgery 2024年第3期16卷 740-750页

作者： phillip Gu shishir Dube Norman Gellada so Yung Choi susan Win Yoo Jin Lee shaohong Yang Talin Haritunians Gil Y Melmed Eric A Vasiliauskas Niru Bonthala Gaurav syal Andres J Yarur David Ziring shervin Rabizadeh phillip Fleshner Cindy Kallman suzanne Devkota stephan R Targan Dalin Li Dermot PB McGovern Department of Medicine Cedars-Sinai Medical CenterLos AngelesCA 90048United States Department of Imaging Cedars-Sinai Medical CenterLos AngelesCA 90048United States Department of Biostatistics shared Resource Cedars-Sinai Medical CenterLos AngelesCA 90048United States Department of Internal Medicine Keimyung University School of MedicineDaegu 42601South Korea Department of Medicine University of California at Los AngelesLos AngelesCA 90095United States Department of Medicine University of California at San DiegoSan DiegoCA 92093United States Department of Pediatrics Cedars-Sinai Medical CenterLos AngelesCA 90048United States Department of surgery Cedars-Sinai Medical CenterLos AngelesCA 90048United States

BACKGROUND Evidence suggests inflammatory mesenteric fat is involved in post-operative recurrence(POR)of Crohn’s disease(CD).However,its prognostic value is INTRODUCTION Crohn’s disease(CD)is a debilitating chronic immune-mediated inflammatory disease(IMID)of the gastrointestinal tract that is increasing in incidence and prevalence globally[1].CD patients often undergo surgery for disease-related complic-ations and/or medically refractory ***,surgery is not curative,and many patients develop post-operative recurrence(POR)of CD with a significant proportion eventually requiring additional *** advances in early detection and therapeutics,the contemporary 10-year risk of surgery has improved from 50%to 26%,but the risk of recurrent surgery has remained unchanged at 30%,suggesting a need to improve post-operative management strategies[2].Presently,there are two accepted strategies to mitigate POR,but each have potential ***,patients start early post-operative pharmacologic prophylaxis within 4-6 wk after *** strategy can potentially overtreat a subset of patient who may not develop long-term disease recurrence off ***,these patients are at risk of medication-related adverse events and the direct and indirect costs associated with therapy with little or no benefit[3].The second strategy is performing early colonoscopy within 6-12 months after surgery and escalating therapy based on FOOTNOTEs Author contributions:Gu P is the guarantor of the article and was involved in concept and design,data collection,statistical analysis,drafting of manuscript,and final approval of manuscript;Dube s and Choi sY were involved in statistical analysis,drafting of the manuscript,and final approval of manuscript;Gellada N,Win s,Lee YJ and Yang s were involved in the data collection,drafting of the manuscript,and final approval of manuscript;Haritunians T and Li D were involved in data analysis and interpretation,drafting

关键词： Crohn’s disease surgery Visceral adipose tissue Mesenteric adipose tissue Creeping fat Computed tomography

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Key Performance Dimensions of the“Well-Tempered Musician”:A Framework for Artist Management

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艺术管理（中英文） 2024年第2期 76-90页

作者： [UsA]phillip A.Cartwright [Germany]Mats B.Küssner [UK]Aaron Williamon Paris school of Business Humboldt University Berlin the Royal College of Music

Artist management or mentoring is generally recognized as a fundamental challenge and contributing element in an artist’s *** article takes the position that artist management should go well beyond the narrow confines of standard business practice focused on traditional business management,marketing,accounting and finance,extending into seven dimensions of artist *** scope of artist management is broadened and *** management is considered more challenging,as there must be open sharing and evaluation of attributes and liabilities associated with professional and personal ***,it is unlikely that a manager has all of the expertise necessary to directly manage in all identity dimensions,so outside expertise might be *** examples of such cases are sub-optimal artist achievement owing to musical performance anxiety,the causes and consequences of such anxiety,and methods of alleviating severe problems and the shortened life expectancy of popular musicians.

关键词： Artist Management Artist Identity Performance science Performance Profiling Coaching

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Identification of meta-instable stress state based on experimental study of evolution of the temperature field during stick-slip instability on a 5° bending fault

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science China Earth sciences 2012年第6期55卷 869-881页

作者： MA Jin s I sherman GUO Yanshuang state Key Laboratory of Earthquake Dynamics Institute of Geology China Earthquake Administration Beijing 100029 China Institute of the Earth＇s Crust siberian Branch of Russian Academy of sciences lrkutsk 664033 Russia

Identification of the meta-instable stress state and study of its mechanism and evolution of relevant physical fields would be of great significance for determination of potential seismic risks and estimation of critical times. In laboratory experiments, that the specimen enters the meta-instable is marked by accelerated stress release. Could we use the experimental result to identify the earthquake in natural conditions? Because the observational data from one station can only reflect the stress state beneath this station, the key problem for identification of the meta-instability is how to recognize regional stress state through observational data from many stations. In this work, we choose the evolution of the temperature field over varied deformation stages during a stick-slip event on a 5 bending fault as an example, and attempt to find the response features of the physical quantity when the fault enters the meta-instable state. We discuss the characteristics of stages for the stress build-up, stress-time process deviating from linearity before instability, meta-instability, instability, and post-instability, respectively. The result shows that the fault instability slide is a conversion process from independent activities of each fault segment to synergism activity. The instability implies completion of the synergism. The stage deviating from linearity is the onset of stress release, and it is also the onset of the synergism. At the meta-instability stages, stress release becomes dominant, while the synergism tends to finish. Therefore, the analysis of the regional overall stress state should not start from individual stations, and instead it should begin with the evolution of the whole deformation field.

关键词： earthquake risk stress state meta-instable state evolution of the temperature field synergism bending fault

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Interactions between hepatic iron and lipid metabolism with possible relevance to steatohepatitis

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World Journal of Gastroenterology 2012年第34期18卷 4651-4658页

作者： Umbreen Ahmed Patricia s Latham phillip s Oates Department of Physiology Army Medical CollegeNational University of Sciences and TechnologyRawalpindi 46000Pakistan Department of Pathology The George Washington School of Medicine and Health SciencesWashingtonDC 20037United States Physiology M311 AnatomyPhysiology and Human BiologyUniversity of Western AustraliaPerthWA 6009 Australia

The liver is an important site for iron and lipid metabolism and the main site for the interactions between these two metabolic pathways. Although conflicting results have been obtained, most studies support the hypothesis that iron plays a role in hepatic lipogenesis. Iron is an integral part of some enzymes and transporters involved in lipid metabolism and, as such, may exert a direct effect on hepatic lipid load, intrahepatic metabolic pathways and hepatic lipid secretion. On the other hand, iron in its ferrous form may indirectly affect lipid metabolism through its ability to induce oxidative stress and inflammation, a hypothesis which is currently the focus of much research in the field of nonalcoholic fatty liver disease/non-alcoholic steatohepatitis (NAFLD/NAsH). The present review will first discuss how iron might directly interact with the metabolism of hepatic lipids and then consider a new perspective on the way in which iron may have a role in the two hit hypothesis for the progression of NAFLD via ferroportinand the iron regulatory molecule hepcidin. The review concludes that iron has important interactions with lipid metabolism in the liver that can impact on the development of NAFLD/NAsH. More defined studies are required to improve our understanding of these effects.

关键词： Lipids Iron Non-alcoholic fatty liver dis-ease/non-alcoholic steatohepatitis Hepcidin Oxidativestress

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Mechanisms of heme iron absorption:Current questions and controversies

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World Journal of Gastroenterology 2008年第26期14卷 4101-4110页

作者： Adrian R West phillip s Oates M311 Physiology School of BiomedicalBiomolecular and Chemical SciencesThe University of Western Australia35 Stirling HighwayCrawley 6009 Australia

Iron is a critical micronutrient, and iron derived from heme contributes a large proportion of the total iron absorbed in a typical Western diet. Heme iron is absorbed by different mechanisms than non-heme iron, but despite considerable study over many years these mechanisms remain poorly understood. This review provides an overview of the importance of heme iron in the diet and discusses the two prevailing hypotheses of heme absorption; namely receptor mediated endocytosis of heme, and direct transport into the intestinal enterocyte by recently discovered heme transporters. A specific emphasis is placed on the questions surrounding the site of heme catabolism and the identity of the enzyme that performs this task. Additionally, we present the hypothesis that a non-heme iron transport protein may be required for heme iron absorption and discuss the experiences of our laboratory in examining this hypothesis.

关键词： Iron Heme absorption Receptor mediatedendocytosis Heine transporter Heine oxygenase

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Heme in intestinal epithelial cell turnover, differentiation, detoxification, inflammation, carcinogenesis, absorption and motility

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World Journal of Gastroenterology 2006年第27期12卷 4281-4295页

作者： phillip s Oates Adrian R West Physiology M311 School of Biomedical Biomolecular and Chemical SciencesUniversity of Western Australia35 Stirling HighwayNedlands 6009Australia

The gastrointestinal tract is lined by a simple epithelium that undergoes constant renewal involving cell division, differentiation and cell death. In addition, the epithelial lining separates the hostile processes of digestion and absorption that occur in the intestinal lumen from the aseptic environment of the internal milieu by defensive mechanisms that protect the epithelium from being breached. Central to these defensive processes is the synthesis of heme and its catabolism by heme oxygenase （HO）. Dietary heme is also an important source of iron for the body which is taken up intact by the enterocyte. This review describes the recent literature on the diverse properties of heme/HO in the intestine tract. The roles of heme/HO in the regulation of the cell cycle/ apoptosis, detoxification of xenobiotics, oxidative stress, inflammation, development of colon cancer, hemeiron absorption and intestinal motility are specifically examined.

关键词： Absorption Heme Uptake Release Heme oxygenase Oxidant Cytoprotection Inflammation Cancer Detoxification

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