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β-funaltrexamine differentially modulates chemokine and cytokine expression in normal human astrocytes and C20 human microglial cells

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Neuroimmunology and Neuroinflammation 2020年第4期7卷 300-310页

作者： Randall L.Davis kelly mccracken Daniel J.Buck Department of Pharmacology/Physiology Oklahoma State University Center for Health SciencesTulsaOK 74107USA

Aim: Emerging evidence implicates astrocyte/microglia dysregulation in a range of brain disorders, thereby making glial cells potential therapeutic targets. The novel anti-inflammatory actions of beta-funaltrexamine (β-FNA) are of particular interest. β-FNA is a derivative of naltrexone, and recognized as a selective, irreversible antagonist at the mu-opioid receptor (MOR). However, we discovered that β-FNA has novel anti-inflammatory actions that seem to be mediated through a MOR-independent mechanism. Thus far, we have focused on the acute effects of β-FNA on inflammatory ***: The effect of β-FNA treatment on interleukin-1β (IL-1β)-induced inflammatory signaling in normal human astrocytes (NHA) and C20 human microglial cells. Cytokine/chemokine expression was measured using ELISA, and nuclear factor-kappaB (NF-κB) p65 activation was evaluated by immunoblot. Results: IL-1β-induced interferon-γ inducible protein-10 (CXCL10) production in NHA was more sensitive to chronic (3 day) β-FNA as indicated by an approximately 3-fold lower EC50 compared to that observed in acutely treated cells. Chronic β-FNA did not affect IL-1β-induced monocyte chemoattractant protein-1 (CCL2) or IL-6 production in NHA. β-FNA inhibited phosphorylation of NF-κB p65, suggesting that the inhibitory effects may be due in part to reduced NF-κB activation. We showed for the first time that C20 human microglial cells were insensitive to the anti-inflammatory actions of acute β-FNA. Conclusion: β-FNA differentially affects inflammatory cytokine/chemokine expression in human astrocytes and microglia. These findings warrant further investigation into the novel anti-inflammatory actions of β-FNA, with a particular focus on astrocytes. These insights should contribute to the development of strategies to treat brain disorders that involve neuroinflammation.

关键词： Neuroinflammation brain opioid nuclear factor-kappaB pro-inflammatory

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Interleukin-1β-induced inflammatory signaling in C20 human microglial cells

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Neuroimmunology and Neuroinflammation 2018年第12期5卷 60-70页

作者： Randall LDavis Daniel JBuck kelly mccracken Gary WCox Subhas Das Department of Pharmacology&Physiology Oklahoma State University Center for Health SciencesTulsaOK74107USA Department of Anatomy&Cell Biology Oklahoma State University Center for Health SciencesTulsaOK74107USA.

Aim: Increased inflammatory signaling in microglia is implicated in the pathogenesis of neurodegenerative diseases, trauma, psychiatric disorders, and anxiety/depression. Understanding inflammatory signaling in microglia is critical for advancing treatment options. Studying rodent-derived microglia has yielded substantial information, yet, much remains to better understand inflammatory signaling in human microglia. Hence, there is great interest in developing immortalized human microglial cell lines. The C20 human microglial cell line was recently developed and our primary objective was to advance our knowledge of inflammatory signaling in these cells. Methods: Expression of the microglia specific marker transmembrane protein 119 (TMEM119) was assessed by western blot analysis. Lipopolysaccharide (LPS)- and interleukin-1β (IL-1β)-induced cytokine/chemokine expression was determined by ELISA. Phosphorylation of inhibitory kappa B alpha (IκBα), nuclear factor (NF)-κB p65, and p38 mitogen-activated protein kinase (p38 MAPK) was measured by western blot analysis. Results: TMEM119 was expressed in unstimulated C20 cells, and to a greater extent in IL-1β-stimulated cells. IL-1βsignificantly induced IL-6, monocyte chemoattractant protein-1/CCL2, and interferon-γ inducible protein 10/CXCL10 expression. LPS induced CCL2 expression, but not IL-6 or CXCL10 expression. IL-1β induced inflammatory signaling as indicated by increased phosphorylation of IκBα, NF-κB p65 and p38 MAPK. Conclusion: We provide the first evidence that C20 microglia express TMEM119. This is the initial report of IL-1β-induced activation of IκBα, NF-κB p65, and p38 MAPK and subsequent CXCL10, CCL2 and IL-6 secretion in C20cells. These findings advance our understanding of inflammatory signaling in C20 cells and support the value of this cell line as a research tool.

关键词： Interleukin-1β chemokine microglia p38 nuclear factor-κB p65 neuroinflammation

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INVESTIGATION OF THE ATRP OF n-BUTYL METHACRYLATE USING THE Cu(I)/N,N,N',N",N"-PENTAMETHYLDIETHYLENETRIAMINE CATALYST SYSTEM

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Chinese Journal of Polymer Science 2004年第2期22卷 195-204页

作者： kelly A. Davis Krzysztof Matyjaszewski Center for Macromolecular Engineering Department of Chemistry Carnegie Mellon University 4400 Fifth Ave.Pittsburgh Pennsylvania 15213 USACenter for Macromolecular Engineering Department of Chemistry Carnegie Mellon University 4400 Fifth Ave.Pittsburgh Pennsylvania 15213 USA

The polymerization of n-butyl methacrylate was investigated using the Atom Transfer Radical Polymerization technique with CuBr and CuCl/N,N,N',N',N'-pentamethyldiethylenetriamine catalytic systems. Various combinations of catalyst systems and initiators were utilized in order to optimize the polymerization conditions and to obtain well-defined polymers (i.e. controlled molecular weights and low polydispersities). It has been found that the optimal initiator for this system is a chlorine-based initiator, when the catalyst used is a salt in conjunction with the N,N,N',N',N'- pentamethyldiethylenetriamine ligand. Bromine-based initiators tend to result in large amounts of initial termination, leading to polymers with less than ideal chain end functionality, even if CuCl is used as the species to invoke the halogen exchange. Additionally, the effects of the polymerization temperature, species and the initiator structure were determined.

关键词： ATRP Atom transfer radical polymerization Controlled/living radical polymerization Butyl methacrylate Pentamethyldiethylenetriamine

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Optimization designed large-stroke MEMS micromirror for adaptive optics

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Chinese Optics Letters 2010年第12期8卷 1163-1166页

作者：孙全 kelly He Edmond Cretu College of Optoelectronics Science and Engineering National University of Defense Technology Department of Electrical and Computer Engineering University of British Columbia

A novel micromirror based on the PolyMUMPs process is designed and presented. The hexagonal micromirror with a diameter of 450 μm consists of three supporting bilayer cantilevers and a mirror plate. The bilayer cantilevers, formed with a polysilicon layer and a gold layer, elevate the mirror plate according to residual stress-induced bending. Both analytical and finite element analysis （FEA） models are built to calculate the elevated height of the free end of the cantilever. The analytical solution is in accordance with the FEA simulation results, with longitudinal stresses applied only. Results of a three-dimensional （3D） simulation with two direction stresses applied also show the elevated height to be proportional to the width of the cantilever and the length of the gold layer. Due to the torque of the joint, the elevated heights of the two kinds of cantilevers assembled with the mirror plates are much smaller than those of the free end of the cantilevers. Both micromirrors with different cantilevers are fabricated. The elevated heights of the fabricated micromirrors are measured using Veeco optical profiler, which show good coincidence with simulation results.

关键词： Finite element method Microelectromechanical devices Mirrors Polysilicon Three dimensional Three dimensional computer graphics

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The impact of increased flooding caused by climate change on heritage in England and North Wales, and possible preventative measures: what could/should be done?

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Built Heritage 2023年第1期7卷 44-58页

作者： kelly Anderson Independent Consultant ManchesterEngland

Despite 30 years of discussion,adaptation work is not routinely being carried out at heritage sites to minimise future impacts of climate change,particularly increased flooding *** understand barriers to essential work being carried out,interviews were carried out with six heritage sites that have already experienced river flooding to understand levels of preparation both before and after the flooding *** results prove that despite funding,or lack of,being an important contributor,it is not the sole barrier to *** flooded sites still do not have a flood plan in place,outside agencies are preventing work being carried out,measures which have been put in place through listing status are prohibiting necessary work and delays in decision making about what is acceptable are all delaying adaptation while allowing more damage to be caused from weather *** responsibility for adaptation lies locally this situation will not improve;responsibility needs to lie more *** the principle of replacing like for like is a sound one with the best of intentions behind it,this is also contributing to losses in heritage and must be reconsidered when big decisions are finally made about what will be acceptable if impacts to heritage from future climate change are to be minimised.

关键词： climate change adaptation barriers heritage flooding site interviews

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Antibiotic use in early childhood and risk of obesity: longitudinal analysis of a national cohort

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World Journal of Pediatrics 2019年第4期15卷 390-397页

作者： Dervla kelly Alan kelly Tom O'Dowd Catherine B.Hayes Department of Public Health and Primary Care Trinity College DublinRussell CenterTallaght CrossDublin 24Ireland

Background Taking oral antibiotics during childhood has been linked with an increased risk of childhood *** study assessed any potential association in number of courses of antibiotics taken between 2-3 and 4-5 years of age and body mass trajectory up to age *** The study was a secondary analysis of 8186 children and their parents from the infant cohort of the Irish National Longitudinal Study of *** use was measured by parental recall between ages 2-3 and *** models described the relationship between antibiotic exposure and body mass index (BMI) standard deviation scores andbinary outcomes,and examined interactions between covariates,which included socioeconomic status,diet assessed by food frequency questionnaires and maternal *** Any antibiotic usage between 2 and 3 years did not predict risk of overweight or obesity at age *** or more courses of antibiotics between 2 and 3 years were independently associated with obesity at age 5 (odds ratio 1.6,95% confidence interval 1.11-2.31).Effect size was modest (coefficient + 0.09 body mass SD units,standard error 0.04,P =0.037).Maternal BMI modified the relationship:≥ 4 courses of antibiotics between 2 and 3 years were associated with a + 0.12 body mass SD units increase in weight at age 5 among children of normal-weight mothers (P=0.035),but not in children of overweight *** Number of antibiotic courses,rather than antibiotic use,may be an important factor in any link between early antibiotic exposure and subsequent childhood *** is needed to confirm differential effects on babies of normal versus overweight/obese mothers independent of socioeconomic factors.

关键词： Antibiotics Body mass index Early childhood Infants Obesity

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Multilayer network analyses as a toolkit for measuring social structure

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Current Zoology 2021年第1期67卷 81-99页

作者： kelly R.FINN Neukom Institute Dartmouth CollegeHanoverNH 03755USA

The formalization of multilayer networks allows for new ways to measure sociality in complex social systems,including groups of *** same mathematical representation and methods are widely applicable across fields and study systems,and a network can represent drastically different types of *** such,in order to apply analyses and interpret the results in a meaningful way the researcher must have a deep understanding of what their network is representing and what parts of it are being measured by a given *** social networks can represent social structure with more detail than is often present in single layer networks,including multiple"types"of individuals,interactions,or relationships,and the extent to which these types are *** networks can also encompass a wider range of social scales,which can help overcome complications that are inherent to measuring *** this paper,I dissect multilayer networks into the parts that correspond to different components of social structures.I then discuss common pitfalls to avoid across different stages of multilayer network analyses-some novel and some that always exist in social network analysis but are magnified in multi-layer *** paper serves as a primer for building a customized toolkit of multilayer network analyses,to probe components of social structure in animal social systems.

关键词： animal behavior multilayer networks relationships sociality social networks social structure subgroups

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Parking reservation techniques:A review of research topics,considerations,and optimization methods

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Journal of Traffic and Transportation Engineering(English Edition) 2023年第6期10卷 1099-1117页

作者： Xinying Zhang kelly Pitera Yuanqing Wang Department of Transportation Engineering School of Transportation EngineeringChang'an UniversityXi'an 710064China Department of Civil and Environmental Engineering Norwegian University of Science and Technology(NTNU)Trondheim 7491Norway

Growing private vehicle use and a limited supply of parking resources have increased competition for parking *** searching for parking spaces is a significant barrier to smooth traffic *** technology-generated parking reservations are regarded as an excellent way to increase parking efficiency and lessen *** there is increased attention on smart parking research and parking reservation optimization,a scoping review is currently ***,the purpose of this paper is to provide a comprehensive review of the research literature related to parking *** of the original 438 publications identified in this search,99 were eventually chosen for *** review categorized parking reservations into four research topics:inventory control,allocation decisions,pricing strategies,and performance *** elements considered in these research themes,modeling techniques,and evaluation criteria are explored in *** addition,the challenges and further enhancements of parking reservation optimization are *** is believed that the findings from this study will be beneficial in further research on parking reservations.

关键词： Traffic engineering Parking reservation optimization Capacity control Allocation decision Dynamic pricing Performance evaluation

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Investigating bee dietary preferences along a gradient of floral resources:how does resource use align with resource availability?

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Insect Science 2021年第2期28卷 555-565页

作者： Tyler T.kelly Elizabeth Elle Evolutionary and Behavioural Ecology Research Group Department of Biological SciencesSimon Fraser UniversityBurnabyCanada

Bee dietary preferences,or the floral resources that they consistently collect,likely impact where a species can *** this reason it is likely that bee dietary preferences are dependent upon the composition of the plant *** this study,we evaluated floral visits and pollen loads of the mining bee,Andrena angustitarsata Viereck,across a 630 km north-south range to understand dietary preferences along a floral resource *** research,in a more geographically limited area,suggested this species was an eclectic oligolege on predominantly Apiaceae and in part *** the present study we found the species predominately visited and collected pollen from Apiaceae and Rosaceae,but visited 12 flower families and collected pollen from 32,distinguishing them as generalist *** frequency of Apiaceae pollen on the bees and the species-level specialization index(a measure of visit specialization)were higher in regions with higher Apiaceae *** addition Apiaceae and Rosaceae were the only plant families significantly preferred for pollen collection,regardless of floral *** conclude that across our study region *** has a generalist dietary breadth,but also has dietary preference for Apiaceae and *** study indicates that while bees may overall make generalist foraging decisions they may still prefer and likely benefit from selecting fewer flower taxa.

关键词： andrenidae dietary breadth ecoregions oak-savanna pollen specialization

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Mapping the quality of prenatal and postnatal care and demographic differences on child mortality in 26 low to middle-income countries

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World Journal of Pediatrics 2023年第9期19卷 835-850页

作者： kelly Lin Serena Chern Jing Sun School of Medicine and Dentistry Griffith UniversityParkland DriveGold CoastQLD4215Australia Institute for Integrated and Intelligent Systems Griffith UniversityGold Coast4222Australia Menzies Health Institute Queensland Griffith UniversityGold CoastAustralia

Background Closing the gap between child mortality in low-and middle-income countries(LMICs)and high-income countries is a priority set by the WHO in sustainable development goals(SDGs).We aimed to examine poor nutrition and prenatal and postnatal care that could increase the risk of child mortality in *** The Demographic and Health Survey(DHS)was used to examine data from 26 countries to compare prenatal,postnatal,nutritional,and demographic factors across *** of child death was classified into death before one month of age,between 1 to 11 months,between one to two years,between three to five years,and overall death before five ***-square analyses identified differences in prenatal care,postnatal care,nutrition,and demographic factors between children who died and those who *** regression identified factors that increased child mortality *** The majority of deaths occurred before the ages of one month and one *** poorer quality of prenatal care,postnatal care,and nutrition were found in low-income and low-middle-income countries in the contemporary *** child mortality and poor quality of prenatal and postnatal care coincide with low *** in LMICs were exposed to less vitamin A-rich foods than children in higher-middle-income *** use of intestinal parasite drugs and the absence of postpartum maternal vitamin A supplementation significantly increased child mortality *** socio-demographic risk factors were associated with an increased mortality rate in children,including lack of education,maternal marital status,family wealth index,living rurally,and financial problems hindering access to *** Poor nutrition remains a vital factor across all LMICs,with numerous children being exposed to foods low in iron and vitamin ***,most deaths occur in neonates and infants,indicating an urgent need to address risk factors associated with early chil

关键词： Child mortality Low-and middle-income countries Postnatal care Prenatal care

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