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Particle elasticity influences polymeric artificial antigen presenting cell effectiveness in vivo via CD8+T cell activation,macrophage uptake,and the protein corona

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Nano Research 2024年第10期17卷 9052-9064页

作者： Savannah E.Est-Witte Sydney R.Shannon Dennis H.Gong Kaitlyn G.Calabresi Jawaun J.harris Kaitlyn Storm Edwin J.Yoo Ariel Isser Vivek P.Jani Natalie K.Livingston mary O.Omotoso Kelly Rhodes Elana Ben-Akiva Randall A.Meyer Zoe T.Hsieh Simone Sidoli Stephany Y.Tzeng Jonathan P.Schneck Jordan J.Green Translational Tissue Engineering Center Institute for NanobiotechnologyDepartment of Biomedical EngineeringJohns Hopkins School of Medicine400 N BroadwayBaltimoreMD 21231USA Institute for Cell Engineering Department of PathologyJohns Hopkins School of Medicine733 N BroadwayBaltimoreMD 21205USA Department of Biochemistry Albert Einstein College of MedicineThe BronxNew York CityNY 10461USA

Adoptive cell therapy(ACT)is an immunotherapy strategy for cancer that has seen widespread clinical *** ACT,patient-derived lymphocytes are stimulated with the antigen of interest ex vivo,proliferated,then returned to the patient to initiate an antigen-specific antitumor *** effective,this process is resource-intensive and logistically impossible for many *** artificial antigen presenting cells(aAPCs)offer a potential“off-the-shelf”alternative to ex vivo *** particulate aAPCs perform well in vitro,they have had limited success in vivo due to poor bioavailability after *** to bioavailability include rapid clearance,unfavorable biodistribution,and inadequate interactions with CD8+T cells at sites of *** properties such as elasticity have been shown to vastly impact the bioavailability and particle-cell interactions,but this has yet to be investigated in the context of aAPCs for in vivo T-cell *** literature likewise indicates that biomaterial properties,especially elasticity,can modulate T-cell activation in *** the goal of creating a more biomimetic,next-generation particulate aAPC,we developed a poly(ethylene)glycol hydrogel particle platform with tunable elasticity to investigate the impact of elasticity on antigen-specific T cell activation for in vivo adoptive *** this knowledge,we were able to gain more precise control over in vivo T cell activation and investigate possible mechanisms including the effects of aAPC elasticity on T cell binding,macrophage uptake,and the protein corona.

关键词： adoptive cell therapy artificial antigen presenting cells particle drug delivery elasticity protein corona poly(ethylene glycol)

Bone morphogenetic protein-2 gene controls tooth root development in coordination with formation of the periodontium

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International Journal of Oral Science 2013年第2期5卷 75-84页

作者： Audrey Rakian Wu-Chen Yang Jelica Gluhak-Heinrich Yong Cui Marie A harris Demitri Villarreal Jerry Q Feng mary MacDougall Stephen E harris Department of Periodontics University of Texas Health Science Center at San Antonio Baylor College of Dentistry Texas A&M System University of Alabama School of Dentistry

Formation of the periodontium begins following onset of tooth-root formation in a coordinated manner after birth. Dental follicle progenitor cells are thought to form the cementum, alveolar bone and Sharpey＇s fibers of the periodontal ligament （PDL）. However, little is known about the regulatory morphogens that control differentiation and function of these progenitor cells, as well as the progenitor cells involved in crown and root formation. We investigated the role of bone morphogenetic protein-2 （Bmp2） in these processes by the conditional removal of the Bmp2 gene using the Sp7-Cre-EGFP mouse model. Sp7-Cre-EGFP first becomes active at E18 in the first molar, with robust Cre activity at postnatal day 0 （PO）, followed by Cre activity in the second molar, which occurs after P0. There is robust Cre activity in the periodontium and third molars by 2 weeks of age. When the Bmp2gene is removed from Sp7＋（Osterix＋） cells, major defects are noted in root, cellular cementum and periodontium formation. First, there are major cell autonomous defects in root-odontoblast terminal differentiation. Second, there are major alterations in formation of the PDLs and cellular cementum, correlated with decreased nuclear factor IC （Nfic）, periostin and α-SMA＋ cells. Third, there is a failure to produce vascular endothelial growth factor A （VEGF-A） in the periodontium and the pulp leading to decreased formation of the microvascular and associated candidate stem cells in the Bmp2-cKOsp7-cre＇EGFe. Fourth, ameloblast function and enamel formation are indirectly altered in the Bmp2-cKOsp7-cre＇EGFe. These data demonstrate that the Bmp2 gene has complex roles in postnatal tooth development and periodontium formation.

关键词： Bmp2 gene cementum dentinogenesis periodontium development root formation

Patient perceptions of stool DNA testing for pan-digestive cancer screening:A survey questionnaire

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World Journal of Gastroenterology 2014年第17期20卷 4972-4979页

作者： Dennis Yang Shauna L Hillman Ann M harris Pamela S Sinicrope mary E Devens David A Ahlquist Department of Internal Medicine Mayo ClinicRochesterMN 55902United States Division of Biostatistics Mayo ClinicRochesterMN 55902United States Survey Research Center Mayo ClinicRochesterMN 55902United States Division of Gastroenterology and Hepatology Mayo ClinicRochesterMN 55902United States

AIM: To explore patient interest in a potential multi-organ stool-DNA test (MUST) for pan-digestive cancer screening.

关键词： Stool-DNA testing Colorectal cancer screening Gastrointestinal cancer screening Patient perceptions

Maternal Supplementation of Vitamin D During Lactation to Support Infant Vitamin D Needs: A Systematic Review

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Open Journal of Pediatrics 2018年第3期8卷 255-272页

作者： Kelly Schossow Alena M. Clark mary A. harris Jefferson County Public Health Lakewood CO USA Department of Nutrition and Dietetics University of Northern Colorado Greeley CO USA Department of Food Science and Human Nutrition Colorado State University Fort Collins CO USA

Human milk is generally considered to be insufficient in vitamin D. However, research completed in the 1980s showed that the vitamin D content of human milk is directly related to maternal serum vitamin D levels and therefore may potentially be adequate if the mother’s vitamin D levels are sufficient. Approximately one-third of the adult population, which includes breastfeeding women, in the United States have vitamin D insufficiency or deficiency. Among infants, 90.4% of breastfed infants are vitamin D deficient compared to 15.4% of formula fed infants. The American Academy of Pediatrics (AAP) has therefore recommended all breastfed infants be directly supplemented with 400 IU per day of vitamin D to decrease the risk of vitamin D insufficiency and rickets. According to the AAP, compliance rates with this recommendation ranges between 2% - 36%. Because the recommendation to supplement may undermine breastfeeding, many pediatricians do not inform their patients of the need to supplement. Additionally, some parents are concerned about directly supplementing their infant as risks may include allergic reactions to the ingredients, aspiration pneumonia, accidental overdose, and changes in intestinal flora and pH which may compromise the immune benefits of human milk. A literature review was conducted to examine the effect of maternal supplementation with vitamin D during lactation on human milk vitamin D content and maternal and infant serum vitamin D levels. Although there is no current consensus regarding dosage and timing of maternal vitamin D supplementation, the literature suggests that high-dose vitamin D supplementation of the lactating mother is as effective at maintaining infant vitamin D levels as direct infant supplementation, while also correcting the mother’s vitamin D deficiency.

关键词： vitamin D vitamin supplements infant breastfeeding human milk

Effectively Using the QRFM to Model Truck Trips in Medium-Sized Urban Communities

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Journal of Transportation Technologies 2013年第3期3卷 185-189页

作者： Michael D. Anderson mary C. Dondapati Gregory A. harris Center for Management and Economic Research University of Alabama in Huntsville Huntsville USA Department of Civil and Environmental Engineering University of Alabama in Huntsville Huntsville USA

This paper analyses the effectiveness of applying the Quick Response Freight Manual (QRFM) to model freight transportation. Typically, freight transportation is indirectly modeled or as an after-thought. Increasing freight volumes, coupled with cost saving strategies such as just-in-time delivery systems, require that transportation policymakers analyze infrastructure needs and make investment decisions that explicitly include freight volumes as a component. This paper contains a case study using a medium sized urban area travel model and the QRFM trip generation and a distribution methodology to provide a framework for freight planning that can be used to improve resource allocation decisions.

关键词： Freight Modeling Travel Demand Modeling

Human dNK cell function is differentially regulated by extrinsic cellular engagement and intrinsic activating receptors in first and second trimester pregnancy

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Cellular & Molecular Immunology 2017年第2期14卷 203-213页

作者： Jianhong Zhang Caroline E Dunk Melissa Kwan Rebecca L Jones Lynda K harris Sarah Keating Stephen J Lye Research Centre for Women's and Infants' Health Lunenfeld-Tanenbaum Research Institute Mount Sinai Hospital Toronto ON M5T 3H7 Canada Department of Obstetrics & Gynaecology University of Toronto Toronto ON M5G 1 L4 Canada Department of Physiology University of Toronto Toronto ON M5G 1L4 Canada Institute of Human Development University of Manchester Manchester M 13 9WL UK St. mary's Hospital Central Manchester University Hospitals NHS Foundation Trust Manchester Academic Health Science Centre Manchester M13 9WL UK Department of Pathology University of Toronto Toronto ON M5G 1L4 Canada

Decidual natural killer （dNK） cells express an array of activation receptors to regulate placental immunity and development during early pregnancy. We investigated the functional character of human dNK cells during the first and second trimester of gestation and the interaction between dNK and trophoblast cells. Although the frequency of CD56＋CD16-dNK among the total CD45＋ leukocytes did not change over this period, the expression of the activating receptors, NKp80 and NKG2D, was greatly upregulated. We observed a significantly higher number of extravillous trophoblast cells in proximity to the dNK cells in the first trimester in comparison with the second trimester decidua. NKG2D expression by first trimester dNK cells was decreased when co-cultured with the HTR-8 trophoblast cell line. In the second trimester, functional markers of dNK activation, i.e., angiogenic factor production （e.g., vascular endothelial growth factor, interleukin-8, interferon-gamma）, remained stable despite an increase in NKp80 or NKG2D surface expression. Furthermore, the degranulation capacity of dNK cells, as assessed by CD107a, was decreased in the second trimester. We suggest that in the first trimester, trophoblast-dNK interactions generate a population of dNK cells with a suppressed activating phenotype. In the second trimester, the loss of trophoblast-dNK interactions led to the inhibition of dNK cell function, although their activating receptor expression was increased. We speculate that during pregnancy, two mechanisms operate to modulate the dNK cell activation：suppression of activating receptor levels in the first trimester by trophoblasts and disengagement of receptor-ligand coupling in the second trimester.

关键词： decidual NK cells IFN-gamma NKG2D NKp80 pregnancy

Inferring the Tree of Life of the order Cypriniformes, the earth＇s most diverse clade of freshwater fishes： Implications of varied taxon and character sampling

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植物分类学报 2008年第3期46卷 424-438页

作者： Richard L. MAYDEN Kevin L. TANG Robert M. WOOD Wei-Jen CHEN mary K. AGNEW Kevin W. CONWAY Lei YANG Andrew M. SIMONS Henry L. BART Phillip M. harris Junbing LI Xuzhen WANG Kenji SAITOH Shunping HE Huanzhang LIU Yiyu CHEN Mutstmi NISHIDA Masaki MIYA Department of Biology Saint Louis University St. Louis MO 63103 USA Department of Fisheries Wildlife and Conservation Biology Bell Museum of Natural History University of Minnesota St. Paul MN 55108 USA Department of Ecology and Evolutionary Biology Tulane University New Orleans LA 70118 USA Department of Biological Sciences The University of Alabama Tuscaloosa AL 35487 USA Laboratory ofFish Phylogenetics and Biogeography Institute of Hydrobiology Chinese Academy of Sciences Wuhan 430072 China Tohoku National Fisheries Research Institute Fisheries Research Agency Miyagi 985-0001 Japan Ocean Research Institute University of Tokyo Tokyo 164-8639 Japan Department of Zoology Natural History Museum ＆ Institute Chiba 260-8682 Japan

The phylogenetic relationships of species are fundamental to any biological investigation, including all evolutionary studies. Accurate inferences of sister group relationships provide the researcher with an historical framework within which the attributes or geographic origin of species (or supraspecific groups) evolved. Taken out of this phylogenetic context, interpretations of evolutionary processes or origins, geographic distributions, or speciation rates and mechanisms, are subject to nothing less than a biological experiment without controls. Cypriniformes is the most diverse clade of freshwater fishes with estimates of diversity of nearly 3,500 species. These fishes display an amazing array of morphological, ecological, behavioral, and geographic diversity and offer a tremendous opportunity to enhance our understanding of the biotic and abiotic factors associated with diversification and adaptation to environments. Given the nearly global distribution of these fishes, they serve as an important model group for a plethora of biological investigations, including indicator species for future cli-matic changes. The occurrence of the zebrafish, Danio rerio, in this order makes this clade a critical component in understanding and predicting the relationship between mutagenesis and phenotypic expressions in vertebrates, including humans. With the tremendous diversity in Cypriniformes, our understanding of their phylogenetic relationships has not proceeded at an acceptable rate, despite a plethora of morphological and more recent mo-lecular studies. Most studies are pre-Hennigian in origin or include relatively small numbers of taxa. Given that analyses of small numbers of taxa for molecular characters can be compromised by peculiarities of long-branch attraction and nodal-density effect, it is critical that significant progress in our understanding of the relationships of these important fishes occurs with increasing sampling of species to mitigate these potential p

关键词：进化系统生命科学淡水鱼分类单元

Ten questions concerning future buildings beyond zero energy and carbon neutrality

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建筑节能 2017年第7期45卷 27-27页

作者： Na Wang Patrick E. Phelan Jorge G onzalez Chioke harris G regor P. Henze Robert Hutchinson Jared Langevin mary Ann Lazarus Brent Nelson Chris Pyke Kurt Roth David Rouse Karma Sawyer Stephen Selkowitz 侯恩哲 <建筑节能>杂志社

Architects and planners have been at the forefront of envisioning a future built environment for millennia. How ever,fragmental view s that emphasize one facet of the built environment,such as energy,environment,or groundbreaking technologies,often do not achieve expected outcomes. Buildings are responsible for approximately one-third of w orldw ide carbon emissions and account for about 40% of primary energy consumption in the U. S. In addition to achieving the very ambitious goal of reducing building-associated greenhouse gas emissions by75% by 2050,buildings must improve their functionality and performance to meet current and future human,societal,and environmental needs in a changing w orld. In this article,w e introduce a new framew ork to guide potential evolution of the building stock in the next century,based on greenhouse gas emissions as the common thread to investigate the potential implications of new design paradigms,innovative operational strategies,and disruptive technologies. This framew ork emphasizes integration of multidisciplinary know ledge,scalability for mainstream buildings,and proactive approaches considering constraints and unknow *** framew ork integrates the interrelated aspects of the built environment through a series of quantitative metrics that aim to improve environmental outcomes w hile optimizing building performance to achieve healthy,adaptive,and productive buildings.

关键词：建筑节能建筑设计建筑风格建筑材料

黑山学院:欧洲现代主义、实验精神和美国先锋

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艺术学研究（辑刊） 2010年第2期 185-192页

作者： [美]玛丽·埃玛·哈里斯朱天(译) 不详南京艺术学院美术学院

黑山学院于1933年创立于美国北卡罗来纳州艾西维尔市附近,是美国一所以引领革新而著名的学校,为60年代的美国造就了数位非凡的前卫派先锋艺术家。该校以拥有在视觉、文学与表演艺术上非凡的教程而自豪,该校的精神也持续地影响著美国现... 详细信息

黑山学院于1933年创立于美国北卡罗来纳州艾西维尔市附近,是美国一所以引领革新而著名的学校,为60年代的美国造就了数位非凡的前卫派先锋艺术家。该校以拥有在视觉、文学与表演艺术上非凡的教程而自豪,该校的精神也持续地影响著美国现代艺术的发展。

关键词：黑山学院现代主义实验精神