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Th1 cytokines promote T-cell binding to antigen-presenting cells via enhanced hyaluronan production and accumulation at the immune synapse

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Cellular & Molecular Immunology 2010年第3期7卷 211-220页

作者： Paul l Bollyky Stephen P Evanko rebecca P Wu Susan Potter-Perigo S Alice long Brian Kinsella Helena Reijonen Kelly Guebtner Brandon Teng Christina K Chan Kathy R Braun John A Gebe Gerald T Nepom Thomas N Wight Benaroya Research Institute SeattleWAUSA

Hyaluronan(HA)production by dendritic cells(DCs)is known to promote antigen presentation and to augment T-cell activation and *** hypothesized that pericellular HA can function as intercellular‘glue’directly mediating T cell–DC *** primary human cells,we observed HA-dependent binding between T cells and DCs,which was abrogated upon pre-treatment of the DCs with 4-methylumbelliferone(4-MU),an agent which blocks HA ***,T cells regulate HA production by DCs via T cell-derived cytokines in a T helper(Th)subset-specific manner,as demonstrated by the observation that cell-culture supernatants from Th1 but not Th2 clones promote HA *** effects were seen upon the addition of exogenous Th1 cytokines,Il-2,interferon c(IFN-c)and tumor necrosis factor a(TNF-a).The critical factors which determined the extent of DC–T cell binding in this system were the nature of the pre-treatment the DCs received and their capacity to synthesize HA,as T-cell clones which were pre-treated with monensin,added to block cytokine secretion,bound equivalently irrespective of their Th *** data support the existence of a feedforward loop wherein T-cell cytokines influence DC production of HA,which in turn affects the extent of DC–T cell *** also document the presence of focal deposits of HA at the immune synapse between T-cells and APC and on dendritic processes thought to be important in antigen *** data point to a pivotal role for HA in DC–T cell interactions at the IS.

关键词： dendritic cell hyaluronan immune synapse pericellular matrix Th1

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

The Potential Risk Associated with Foodborne Pathogens in Watersheds: <i>Salmonellap</i>spp. in Dairy Cattle

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Journal of Water Resource and Protection 2015年第6期7卷 476-484页

作者： rebecca Bordonaro Patrick l. McDonough Yung-Fu Chang Hussni O. Mohammed Section of Epidemiology Department of Population Medicine and Diagnostic Sciences College of Veterinary Medicine Cornell University Ithaca NY USA

Salmonella spp. is one of the most important food- and waterborne pathogens implicated in human and animal disease. A repeat cross-sectional study was performed to assess the occurrence of Salmonella in dairy herds in a watershed and determine the factors that play a role in the likelihood of perpetuation of this organism among animals on these farms. A convenience sample of herds in the Delaware County watershed was selected based on farmers’ willingness to participate. Fecal samples were collected per rectum from a representative sample of cattle in these herds and tested for the presence of Salmonella using a combination of culturing and molecular detection methods. The significance of association between the putative risk factors and the likelihood of Salmonella spp. was evaluated using the logistic regression analysis. A total of 34 dairy farms were enrolled in the study and 1987 samples were collected coinciding with seasonal variation. Salmonella spp. was detected in 44% (15/34) of the herds in the study population (i.e., from at least one animal in these herds). However, only a small fraction of the entire sampling population (1.7%) was found to be shedding Salmonella. Risk factors that were found to be associated with the presence of the pathogen on the farm in the final multivariable model included concrete flooring for calves, prevention of calf access to the dam, and the lack of a designated calving pen. Two serovars, Salmonella enterica serovar Infantis and Salmonella enterica serovar Oranienburg, were identified among the isolates recovered in this study. Our study demonstrated that there was a potential risk of watershed degradation from Salmonella associated with cattle.

关键词： Salmonellap Risk Dairy Cows Watershed Polymerase Chain Reaction (PCR)

Tumor-intrinsic metabolic reprogramming and how it drives resistance to anti-PD-1/PD-l1 treatment

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Cancer Drug Resistance 2023年第3期6卷 611-641页

作者： Kyra laubach Tolga Turan rebecca Mathew Julie Wilsbacher John Engelhardt Josue Samayoa Computational Oncology AbbVieSouth San FranciscoCA 94080USA Immuno-Oncology AbbVieSouth San FranciscoCA 94080USA Immuno-Oncology AbbVieLake CountyIL 60064USA

The development of immune checkpoint blockade (ICB) therapies has been instrumental in advancing the field of immunotherapy. Despite the prominence of these treatments, many patients exhibit primary or acquired resistance, rendering them ineffective. For example, anti-programmed cell death protein 1 (anti-PD-1)/anti-programmed cell death ligand 1 (anti-PD-l1) treatments are widely utilized across a range of cancer indications, but the response rate is only 10%-30%. As such, it is necessary for researchers to identify targets and develop drugs that can be used in combination with existing ICB therapies to overcome resistance. The intersection of cancer, metabolism, and the immune system has gained considerable traction in recent years as a way to comprehensively study the mechanisms that drive oncogenesis, immune evasion, and immunotherapy resistance. As a result, new research is continuously emerging in support of targeting metabolic pathways as an adjuvant to ICB to boost patient response and overcome resistance. Due to the plethora of studies in recent years highlighting this notion, this review will integrate the relevant articles that demonstrate how tumor-derived alterations in energy, amino acid, and lipid metabolism dysregulate anti-tumor immune responses and drive resistance to anti-PD-1/PD-l1 therapy.

关键词： Immunotherapy resistance tumor-immune microenvironment immune checkpoint blockade energy metabolism amino acid metabolism lipid metabolism

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营销专业技术成功销售的实战秘笈

Evaluation of a Pulse Width Modulated Bypass Nozzle for the Development of a Variable load Residential Oil Burner

丛书名：课里播企业培训课程，营销实务学习方案

2001年

作者：（美）rebecca l.Morgan 万君宝王晖译

本书包括：成功销售人员所必备的个人条件、如何找到潜在客户、销售面谈的技巧、根据顾客不同的性格采取不同的销售技巧，最后教你如何组织策划合理的销售过程，最终达到最好的销售效果。

ISBN: (纸本)7810495933

关键词：企业管理学科:市场营销学市场营销学

来源：汇雅图书（南通市图书馆... 评论

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Engineering（科研） 2018年第10期10卷 643-654页

作者： Mebougna l. Drabo Narinder K. Tutu Thomas Butcher George Wei rebecca Trojanowski Department of Mechanical & Civil Engineering and Construction Management Alabama A & M University Normal AL USA Sustainable Energy Technology Department Brookhaven National Laboratory Upton NY USA

Due to the need for energy conservation in buildings and the simultaneous benefit of cost savings, the development of a low firing rate load modulating residential oil burner is very desirable. One of the two main requirements of such a burner is the development of a burner nozzle that is able to maintain the particle size distribution of the fuel spray in the desirable (small) size range for efficient and stable combustion. The other being the ability to vary the air flow rate and air distribution around the fuel nozzle in the burner for optimal combustion at the current fuel firing rate. In this paper, which deals with the first requirement, we show that by using pulse width modulation in the bypass channel of a commercial off-the-shelf bypass nozzle, this objective can be met. Here we present results of spray patterns and particle size distribution for a range of fuel firing rates. The results show that a desirable fuel spray pattern can be maintained over a fuel firing rate turndown ratio (Maximum Fuel Flow Rate/Minimum Fuel Flow Rate) of 3.7. Thus here we successfully demonstrate the ability to electronically vary the fuel firing rate by more than a factor of 3 while simultaneously maintaining good atomization.

关键词： Residential Oil Burner Variable load Pulse Width Modulated Burner Nozzle Bypass Nozzle Droplet Spray Size Distribution Variable Fuel Firing Rate

SlC11A1 polymorphisms in inflammatory bowel disease and Mycobacterium avium subspecies paratuberculosis status

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World Journal of Gastroenterology 2010年第45期16卷 5727-5731页

作者： lucy C Stewart Andrew S Day John Pearson Murray l Barclay Richard B Gearry rebecca l Roberts Robert W Bentley Department of Paediatrics University of OtagoChristchurch 8140New Zealand Department of Paediatrics Christchurch HospitalChristchurch 8140New Zealand Department of Pathology University of OtagoChristchurch 8140New Zealand Department of Medicine University of OtagoChristchurch 8140New Zealand Department of Gastroenterology Christchurch HospitalChristchurch 8140New Zealand Department of Biochemistry University of OtagoDunedin 9054New Zealand

AIM: To test for association of SlC11A1 with inflammatory bowel disease (IBD) and Mycobacterium avium subspecies paratuberculosis (MAP) status in a Caucasian cohort. METHODS: Five hundred and seven Crohn's disease (CD) patients, 474 ulcerative colitis (UC) patients, and 569 healthy controls were genotyped for SlC11A1 1730G>A and SlC11A1 469+14G>C using pre-designed TaqMan  SNP assays. χ 2 tests were applied to test for association of single nucleotide polymorphisms (SNPs) with disease, and the presence of MAP ***:SlC11A1 1730G>A and SlC11A 1469+14G>C were not associated with CD, UC, or IBD. The SlC11A1 1730A minor allele was over-represented in patients who did not require immunomodulator therapy (P = 0.002, OR: 0.29, 95% CI: 0.13-0.66). The frequency of the SlC11A1 469+14C allele was higher in the subset of study participants who tested positive for MAP DNA (P = 0.02, OR: 1.56, 95% CI: 1.06-2.29). No association of SlC11A1 1730G>A with MAP was ***: Although SlC11A1 was not associated with IBD, association with MAP suggests that SlC11A1 is important in determining susceptibility to bacteria implicated in the etiology of CD.

关键词： NRAMP1 Crohn’s disease Ulcerative colitis IS900 polymerase chain reaction

Web-Based Spatial Decision Support System andWatershed Management with a Case Study

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International Journal of Geosciences 2011年第3期2卷 195-203页

作者： Yanli Zhang Ramanathan Sugumaran Matthew McBroom John DeGroote rebecca l Kauten Paul K Barten 不详

In order to maintain a proper balance between development pressure and water resources protection, and also to improve public participation, efficient tools and techniques for soil and water conservation projects are needed. This paper describes the development and application of a web-based watershed management spatial decision support system, WebWMPI. The WebWMPI uses the Watershed Management Priority Indices (WMPI) approach which is a prioritizing method for watershed management planning and it integrates land use/cover, hydrological data, soils, slope, roads, and other spatial data. The land is divided into three categories: Conservation Priority Index (CPI) land, Restoration Priority Index (RPI) land, and Stormwater Management Priority Index (SMPI) land. Within each category, spatial factors are rated based on their influence on water resources and critical areas can be identified for soil conservation, water quality protection and improvement. The WebWMPI has user-friendly client side graphical interfaces which enable the public to interactively run the server side Geographic Information System to evaluate different scenarios for watershed planning and management. The system was applied for Dry Run Creek watershed (Cedar Falls, Iowa, US) as a demonstration and it can be easily used in other watersheds to prioritize crucial areas and to increase public participation for soil and water conservation projects.

关键词： Web-Based SDSS Watershed Management GIS

Urban health and ecology： the promise of an avian biomonitoring tool

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Current Zoology 2017年第2期63卷 205-212页

作者： lea POllACK Naomi R. ONDRASEK rebecca CAlISI Department of Environmental Science and Policy University of California Davis CA 95616 USA Department of Neurobiology Physiology and Behavior University of California Davis CA 95616 USA

Urban-dwelling birds have the potential to serve as powerful biomonitors that reveal the impact of environmental change due to urbanization. Specifically, urban bird populations can be used to sur- vey cities for factors that may pose both public and wildlife health concerns. Here, we review evi- dence supporting the use of avian biomonitors to identify threats associated with urbanization, including bioaccumulation of toxicants and the dysregulation of behavior and physiology by related stressors. In addition, we consider the use of birds to examine how factors in the urban en- vironment can impact immunity against communicable pathogens. By studying the behavior, physiology, and ecology of urban bird populations, we can elucidate not only how avian popula- tions are responding to environmental change, but also how unintended consequences of urban- ization affect the well-being of human and non-human inhabitants.

关键词： avian biomonitor pollutant bioaccumulation urban ecology zoonotic disease.